Journal articles on the topic 'Qu 17'

e15656 Background: To evaluate safety and efficacy of supportive treatment with fermented mistletoe extract Iscador Qu (from oak tree, quercus) (ISC-Qu) in a cohort of patients that received conventional adjuvant chemo- and/or radiotherapy (conv-th) alone (control) or additionally ISC-Qu (test group). Methods: Multicenter, comparative, non- interventional cohort study with parallel groups. Unselected, standardized, anonymized data from medical records meeting the eligibility criteria were followed until last visit or death. All endpoints were adjusted to baseline imbalance, therapy regimen and other confounders. Results: 270 patients (75 ISC-Qu/195 control) from 17 oncological centers. The treatment with ISC-Qu started before (16.7%), during (75.0%), or after (8.3%) the conv-th (mainly with gemcitabine) and usually lasted until last visit or death. The period of aftercare was median 20.3 (test group) and 10.1 months (control). Isc-Qu was applied by sequential dose escalation from 0.01 mg up to 20 mg, 2–3 injections per week (s.c.). Safety: Only 14.7% of the patients developed local ADR to ISC-Qu, there was no life- threatening ADR. Efficacy: There was a significant and relevant prolongation of overall survival: hazard ratio, HR (95% CI) = 0.35 (0.21- 0.58), p < 0.001; estimated relative risk reduction = 65%. The number of ADR to conv-th (odds ratio, OR = 0.20, p = 0.006, risk reduction 80%) and the estimated risk for disease or therapy related symptom persistence were significantly reduced in the test group with ISC-Qu. Conclusions: The results show reliable safety and an important effect of supportive ISC-Qu treatment on overall survival in patients with pancreatic cancer of any stage. [Table: see text]

Abstract Background The Bronx (BX) is an urban city with the most poverty, least educated population and poorest health outcomes among 62 counties in New York State. Unsurprisingly, BX has the highest rates of COVID-19 diagnoses across New York City (NYC). Lincoln Medical Center (LMC) is part of the NYC health and hospital system (NYC H+H) and has the highest COVID-19 admissions in BX and the second-highest across NYC. Herein we report our preliminary data on mortality rate (MR) of hospitalized COVID-19 patients and discuss the disproportionate of MR across NYC. Methods On 26 April 2020, we acquired the total number of hospitalized COVID-19 and deaths and mechanically ventilated (MV) COVID-19 and death from LMC and all other NYC H+H. Scheffe test was used to determine MR differences. The P-value (p) &lt; 0.005 was set as a statistically significant threshold. Results MR of our hospitalized COVID-19 patients was 31%, which is higher than that of Man (24%, p 0.001). However, LMC has a high proportion of MV COVID-19 (local and transferred cases). Sub-group analysis of non-MV COVID-19 showed LMC MR (6%) is lower than Brooklyn (BL) (17%, p 0.00) and Queens (Qu) (17%, p 0.00) and didn’t differ from Man NYC H+H centers (8%, p 0.68). Analysis of MR among MV patients between LMC and other NYC H+H centers across four boroughs did not discover any differences. Hospitalized COVID-19 MR from all NYC H+H centers in BX (28%) did not differ from Man (24%, p 0.7) and Qu (28%, p 0.99). Interestingly, we found that MR is the highest in BL (33%). Moreover, MR of non-MV COVID-19 was higher in BL (17%) and Qu (17%) than BX (10%) and Man (8%) NYC H+H centers. We hypothesize this may result partly from the tense and shortage of health care resources in these two boroughs, especially, at the beginning of pandemic so some critical patients may not receive adequate care such as delaying intubation. Further research investigating reasons for this disproportion will help in developing the best available care plan for the ongoing crisis. Percentage of COVID-19 Mortality in each group Multiple comparison by Scheffe Test of MR of hospitalized patients with COVID-19 at LMC and across 4 NYC boroughs Multiple comparison by Scheffe Test of MR of non-MV patients with COVID-19 at LMC and across 4 NYC boroughs Conclusion Despite the high COVID-19 incidence and poor epidemiologic health risks of the population in BX, MR of hospitalized COVID-19 seemed to be the same as Man and Qu, and surprisingly lower than BL. MR of non-MV COVID-19 in BX is lower than BL and Qu. The studies determining the reasons underlying this disproportionate would be worthwhile. Disclosures All Authors: No reported disclosures

Persuad&#233;e que l&#8217;avenir du prol&#233;tariat r&#233;side dans l&#8217;&#233;ducation de ses enfants, Madeleine Vernet (1878-1949) fonde en 1906 un orphelinat o&#249; elle recueille les enfants des classes populaires, qu&#8217;elle ne peut se r&#233;signer &#224; abandonner &#224; la charit&#233; catholique ou &#224; l&#8217;Assistance publique. D&#232;s les premiers mois d&#8217;existence de l&#8217;Avenir social, Louis Tribier (1884-1954), un militant qu&#8217;elle a rencontr&#233; dans une universit&#233; populaire parisienne, se propose de l&#8217;aider dans sa t&#226;che quotidienne. Venu pour l&#8217;&#233;t&#233;, il y restera 17 ans et fondera une famille avec celle qui, de compagne de lutte, est devenue sa compagne de vie. Victimes de la guerre fratricide entre socialistes et communistes, Madeleine Vernet et Louis Tribier quittent l&#8217;orphelinat en 1923 et poursuivent par d&#8217;autres moyens leur lutte commune jusqu&#8217;au seuil de la Deuxi&#232;me Guerre mondiale, au croisement du pacifisme, de la libre-pens&#233;e, du f&#233;minisme et du socialisme.

This research is motivated by the results of the Kurious survey from the Katadata Insight Center (KIC), Acer is the second most popular laptop in Indonesia, which is 79.2% of the total respondents. Based on the top brand award in 2022, Acer laptops are ranked first in the notebook or laptop category with a score of 27.1%. However, in 2023 there was a significant decrease in the Acer brand laptop, which was 5.90% compared to 2022. This indicates a decrease in repurchase interest in Acer brand laptops. This study aims to analyze the effect of product quality, price perception, and brand image on repurchase interest in Acer laptops in Bandung City. The d|at|a collection technique used is nonprob|ability s|ampling with convenience s|ampling rese|arch with |a tot|al of 120 respondents of |Acer l|aptop users who live in B|andung City with |an |age r|ange of 17 ye|ars |and over. The d|at|a |an|alysis technique used is multiple regression test using SPSS version 26. The results showed th|at product qu|ality h|as |a positive |and signific|ant effect on repurch|ase interest. Price perception h|as |a positive |and signific|ant effect on repurch|ase intention. Br|and im|age h|as |a positive |and signific|ant effect on repurch|ase intention. Then, product qu|ality, price perception, |and br|and im|age simult|aneously |affect repurch|ase intention.

We examined 70 women who were 22-40 weeks pregnant and their newborns. Of these, 15 women with moderate PE made up group 1, 22 women with severe PE-group 2, and 55 women with uncomplicated pregnancy without hypertensive disorders - the control group. Blood was collected from women when they were admitted to the clinic, and blood was taken from newborns for 3-5 days of life. The concentration of hydrogen sulfide was determined by the method of K. Qu et al [17]. There was a decrease in the level of hydrogen sulfide in the blood serum of women whose pregnancy was complicated by severe preeclampsia. In newborns born to mothers with preeclampsia, an increase in the concentration of hydrogen sulfide was detected in the blood, which is probably a compensatory reaction aimed at restoring vascular homeostasis during early postnatal adaptation.

Geothermal energy pile (GEP) foundation is a new type of sustainable geostructure that can be used as an alternative solution to the energy demand for heating and cooling of built structures. However, due to limited information of this system, the installed piles have generally been over-designed to lower the risk of the system failing. This paper presents the findings of the research carried out to evaluate the performance of laboratory scaled GEP model (model pile) under the effects of the cyclic thermal loads on the settlement behaviour of the model pile with and without the application of axial load. A small-scale model pile of 19 mm diameter and 300 mm length (150 mm embedded length) was used in the experimental work while kaolin was chosen as the model soil. The model soil was compacted at 90% maximum dry density (1.4625 Mg/m3) with optimum moisture content (17%) to obtain ‘firm’ consistency, in a container of 450 mm height and 270 mm diameter. Strain gauges were installed along the pile to monitor the temperature. The ultimate load, Qu of model pile was determined as 480 N. It is found that two cycles of thermal load decreased the settlement; the higher the values, the lower the settlement due to pile expansion and soil heaves. For thermo-axially loaded pile with two cycles of thermal load, the reduction was not significant as the effect of settlement due to axial load had caused much more settlement. For the thermo-axial loads of 50°C-100 N, 17% of the settlement at failure, sf occurred after the application of axial load. When two cycles of thermal load were applied from 29°C to 50°C, the settlement occurred reduced to 16%sf. From this study it can be concluded that the effect of two cycles of cyclic thermal loads from 29°C to 50°C on pile subjected to 21% of Qu in firm clay, is negligible. The pile could function satisfactorily as designed. However, the application of higher axial loads and cycles of thermal load may need to be studied as it could potentially cause hazard to the building due to the excessive pile settlement.

Pondasi Bored pile merupakan jenis pondasi yang di bangun dengan cara pengeboran tanah terlebih dahulu, kemudian diisi dengan tulangan dan dicor. Pembangunan rumah susun universitas muhammadiyah sorong menggunakan pondasi tiang bor yang terletak di Jl. Watem Kilo Meter 17, Kota Sorong. Berdasarkan hasil penyelidikan Standard Penetration Test (SPT) dilapangan tanah keras berada pada kedalaman 12 m dan bangunan terdiri dari 3 lantai. Penelitian ini difokuskan pada tinjauan ulang pondasi bored pile type 1 dan type 2. Data yang digunakan berupa data sekunder yang diperoleh kemudian dianalisis berdasarkan data Standart Penetration Test (SPT) menggunakan perhitungan manual dan software GEO5. Dari hasil perhitungan manual didapatkan nilai Tahanan ujung ultimit (Qb) pada type pondasi 1 dan 2 menggunakan metode O'Neil dan Reese (1989) yakni 1.085,73 kN dan 1.930,19 kN, Tahanan gesek ultimit (Qs) yakni 3.403,89 kN dan 4.538,52 kN, Kapasitas dukung ultimit neto (Qu) menggunakan persamaan umum yakni 4.416,42 kN dan 6.338,58 kN dan Penurunan (S) menggunakan metode Poulos dan Davis (1980) yakni 3,98 mm dan 6,22 mm. Perhitungan kapasitas dukung dengan software GEO5 didapatkan 4.619,83 kN dan 5.035,76 kN

Abstract. Land-surface albedo plays a critical role in the earth's radiant energy budget studies. Satellite remote sensing provides an effective approach to acquire regional and global albedo observations. Owing to cloud coverage, seasonal snow and sensor malfunctions, spatiotemporally continuous albedo datasets are often inaccessible. The Global LAnd Surface Satellite (GLASS) project aims at providing a suite of key land surface parameter datasets with high temporal resolution and high accuracy for a global change study. The GLASS preliminary albedo datasets are global daily land-surface albedo generated by an angular bin algorithm (Qu et al., 2013). Like other products, the GLASS preliminary albedo datasets are affected by large areas of missing data; beside, sharp fluctuations exist in the time series of the GLASS preliminary albedo due to data noise and algorithm uncertainties. Based on the Bayesian theory, a statistics-based temporal filter (STF) algorithm is proposed in this paper to fill data gaps, smooth albedo time series, and generate the GLASS final albedo product. The results of the STF algorithm are smooth and gapless albedo time series, with uncertainty estimations. The performance of the STF method was tested on one tile (H25V05) and three ground stations. Results show that the STF method has greatly improved the integrity and smoothness of the GLASS final albedo product. Seasonal trends in albedo are well depicted by the GLASS final albedo product. Compared with MODerate resolution Imaging Spectroradiometer (MODIS) product, the GLASS final albedo product has a higher temporal resolution and more competence in capturing the surface albedo variations. It is recommended that the quality flag should be always checked before using the GLASS final albedo product.

La investigación tiene el objetivo de hallar el efecto y proporción adecuada de la fibra de cáñamo de 4 cm de longitud, en las propiedades de resistencia y resistividad de una arcilla. Las propiedades investigadas incluyen la humedad óptima (wópt); el peso unitario seco máximo (γdmáx), cohesión (c); ángulo de fricción (Φ), resistencia a la compresión inconfinada (qu), y resistividad eléctrica (ρ). Los ensayos de compactación Proctor modificado (ASTM D 1557-12), corte directo consolidado no drenado (CU) para suelos cohesivos (ASTM 6528-17), resistencia a la compresión inconfinada (ASTM D2166-16) y del ensayo de los cuatro electrodos de Wenner (ASTM G57-01l), se aplicaron en tres muestras de arcilla con diferentes proporciones de fibra de cáñamo; muestra patrón, Ap, de 100 % arcilla de la ciudad de Tunja, Colombia, muestra con 0.5 % y 0.75 % de fibra de cáñamo, A0.5 %, y A0.75 %, con relación al peso seco del material. Los resultados del presente estudios indican que el porcentaje óptimo de cáñamo es 0.5 %, evidenciando disminución en las propiedades de compactación, y aumento de las propiedades de resistencia al corte, resistencia a la compresión inconfinada, y de resistividad eléctrica, sin embrago, ante mayor presencia de fibra, se presenta destrucción de la matriz arcillosa.

(francuski) Les ?uvres de Dejan Despic (1930), inspir?es par Dubrovnik: Jadranski soneti op. 17 (1951-1954), Dubrovacki divertimento op. 18 (1952) et Dubrovacki kanconijer op. 96 (1989), r?v?lent, outre leur th?me commun, une parent? suppl?mentaire importante. Elles sont incit?es et, d'une mani?re essentielle, m?diatis?es par la po?sie: soit par les vers de Jovan Ducic (1871-1943), po?te du Parnasse et symbolisme serbe, soit par la po?sie p?trarquiste ragusaine. Or, ces compositions ne se montrent pas seulement en tant qu` issues de l`inspiration par la po?sie sur Dubrovnik, mais aussi d'un conditionnement spirituel plus profond: de l`inspiration po?tique du compositeur lui-m?me par Dubrovnik. C`est le sentiment po?tique du monde, en tant que constante de la vision cr?atrice de Dejan Despic, qui provient de cette inspiration particuli?re. Ce monde ragusain du compositeur est le monde classique dans une signification universelle du concept, selon la nature m?me du milieu ?voqu?. Or, cela n implique pas une monochromie stylistique des compositions consid?r?es. Au contraire, les perspectives musicales de l`impressionnisme, du n?oclassicisme, voire, de la n?orennaissance, varient ce cadre stylistique g?n?ral, tout en marquant les traits distincts d'une po?tique de composition tr?s individualis?e.

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide. Hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), which was newly identified as a liver lipid droplet associated protein, was recently found to be down-regulated in HCC. However, the effects of HSD17B13 on the underlying mechanisms of HCC have not yet been fully explored. For this purpose, HSD17B13 gene was knockdown with CRISPER/Cas9 technique in several HCC cell lines. HSD17B13 expression was detected by Flow cytometry and Western blotting with recombinant rabbit monoclonal antibodies (clone OTIR3G2 and OTIR5C10) against HSD17B13 which were screened for use in immunohistochemistry, western blot, and ELISA application. Overexpressed HSD17B13 induces hepatic cell line G1 capture and increases several G1 arrest-related protein expression, including p21, p27, MMP2 and MMP3. Then the proliferation and cell cycle were suppressed. HSD17B13 gene knockdown will reverse the suppression. These data indicated that HSD17B13 play important roles in the progression of HCC lesions. HSD17B13 might be a potential immune-oncology marker for HCC. Citation Format: Tianli Qu, Lipeng Wu, Jina Yom, Zhaoying Guo, Xiaomin Hu, Qi Ren, Qian Niu, Ruei-Shiuan Lin, Dezhong Yin, Xuan Liu, Fu Wei. Overexpression of HSD17B13 induced G1 arrest in hepatic cell lines detected by anti-HSD17B13 recombinant rabbit monoclonal antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3695.

Abstract An early step in breast cancer progression is invasion of tumor cells into surrounding tissues. In many breast cancers, particularly ductal carcinomas, this invasion is accomplished by tumor cells migrating as a cohesive group. This often involves cells that take on heterogeneous roles as either leader or follower cells. Studies in common mouse and human breast cancer models have established that leader cells express high levels of keratin-14 (K14) and other basal epithelial markers. The presence of these K14+ cells promote metastasis and predict poor prognosis. The molecular mechanisms regulating K14+ leader cell identity and the methods for targeted depletion of these cells remain obscure. Here we performed time-sampled single cell RNA-sequencing in 3D type I collagen-embedded tumor organoids isolated from the MMTV-PyMT luminal B model of breast cancer. 11 distinct cellular transcriptional states were identified, and through correlation with K14 expression and invasive strand formation we classified one of the states as leader cells. Having confirmed the leader cell cluster markers spatially localize to the invasive front, we next asked which transcription factors were enriched, reasoning that transcription factors could be master regulators of leader cell fate. Three different shRNAs targeting ten genes were systematically evaluated for their effects on collective invasion and keratin-14 transcription. Each transcription factor was designated as either an invasion promoter or invasion suppressor depending on the correlation between transcription factor expression and organoid invasion. Studies are ongoing investigating the impact of invasion-promoting and invasion-suppressing transcription factors on cellular transcriptional states and metastatic dissemination in-vivo. We propose that targeting invasion-suppressing pathways could be combined with therapies that specifically target and eliminate K14+ invasive cells. To this end, we have identified multiple candidate druggable targets and specific surface markers expressed in K14+ invasive cells. Citation Format: Andrea E. Doak, Rose Qu, Kevin J. Cheung. Transcriptional regulation of basal leader cell identity during collective breast cancer invasion [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A014.

Abstract Background: The recommended standard of care treatment for nonmetastatic muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC). Even with urinary diversion, radical cystectomy has a major impact on patients' quality of life. Although high rates of overall and disease-specific survival were observed in patients managed with bladder preservation, who achieved a clinically complete response to neoadjuvant therapy. Frequent evaluation of tumor response based cystoscopy implementing personalized bladder-sparing treatment paradigms. Case Presentation: Here, we report on a case of urine-based dynamically monitoring during neoadjuvant immunotherapy in a MIBC patient treated with RC. A 57-year-old male presented macrohematuria and was diagnosed with bladder urothelial carcinoma by transurethral resection of bladder tumor (TURBT) with clinical stage IIIA (high-grade, multiple, cT2N0M0). He received 3 cycles of Tislelizumab monotherapy and sequential radical cystectomy. The RC specimen showed a complete pathological response (pCR). Four urine samples were collected prior to TURBT, on a day after TURBT, at beginning of neoadjuvant immunotherapy, and on the day of CR. Mutations status in 17 genes and methylation level of ONECUT2 were analyzed by a high-throughput sequencing-based urine test panel (genetron-uro-V1). In urine sediment DNA, which was collected before TURBT, the TERT promoter mutations C228T, TP53 D281H, and ERBB2 D277Y were detected in urine sediment DNA at variant allele frequencies (VAF) of 31.8%, 10.5%, and 0.5%, respectively. After removing in most parts of tumor, the VAF of TERT C228T decreased to 19.6% and mutation in TP53 and ERBB2 could not be detected. Without neoadjuvant immunotherapy, the VAF of TERT C228T still stayed above 12%. After 3 cycles of Tislelizumab monotherapy on the day of CR, all mutation was below the detection limit in urine sediment DNA, which was consistent with pCR in the pathological report of RC specimen. Conclusions: This case suggested that urine-based dynamically monitoring reflected pathologic response, which could support personalized care and help select patients for bladder-sparing treatment. Citation Format: Xiao Yang, Lingkai Cai, Qiang Cao, Min Shi, Yiming Liang, Yurong Qu, Qiang Lu. Urine based dynamically monitoring reflect pathologic response in MIBC patients with neoadjuvant immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5101.

The oxygen evolution reaction (OER) is a key process that enables the storage of renewable energies in the form of chemical fuels.[1] Unraveling the catalytic mechanism is of paramount significance for the rational design of efficient electrocatalysts.[1] Here, we use well-defined crystalline cobalt oxyhydroxides CoOOH nanorods and nanosheets as model catalysts to investigate the geometric catalytic active sites.[2] We disclose a linear correlation of catalytic activities with their lateral surface areas, suggesting that the active sites are exclusively located at lateral facets rather than basal facets. Theoretical calculations show that the coordinatively unsaturated cobalt sites of lateral facets upshift the O 2p-band center closer to the Fermi level, thereby enhancing the covalency of Co-O bonds to yield the reactivity. Following this, we develop a eutectic dealloying strategy to activate the porous spinel NiFe2O4 nanowires with up to four metal cation substitutions.[3] Spinel oxide of NiFeXO4 (X= Fe, Ni, Al, Mo, Co, Cr, ~195 mV@10mA·cm-2) outperforms most spinel phase OER electrocatalysts and comparable to the state-of-the-art NiFe hydroxides. This work elucidates the geometrical catalytic active sites and enlightens the surface engineering for efficient OER catalysts. Besides, we studied the dependence of catalytic performances on electrical conductivities and unveils that charge transportability, to our surprise, regulates the reaction kinetics of the electronically accessible active sites.[4] Remarkably, the regulation extent correlates with the electrical conductivities, suggesting the strong coupling of the electrocatalytic process with electronic transport. Furthermore, we argue the origin of Ov-promoted catalytic activities of NiFe-based (oxy)hydroxides.[5] We uncover the pivotal role of charge transport for their electrocatalytic OER and propose that the superficial Ov imposes electron donation to the conductive band of NiFeOOH and therefore enables the regulation of electronic transport to switch on/off OER catalysis. The work highlights the pivotal role of electronic transportability in unfolding catalytic potential, holding both fundamental and technical implications for electrocatalysts. Fang Song, ..., and Xile Hu*. Am. Chem. Soc. 2018, 140, 7748; Fang Song, Xile Hu*. Nat. Commun. 2014, 5, 4477; Fang Song, Xile Hu*, J. Am. Chem. Soc. 2014, 136, 16481-16484; Fang Song, ..., Hao Ming Chen,* Clemence Corminboeuf,* Xile Hu *. ACS Cent. Sci. 2019, 5, 558; Chen, Wenshu; Gu, Jiajun*; Du, Yongping*; Song, Fang*; ...; Zhang, Di. Adv. Funct. Mater. 2019, 30, 2000551; Bowen Liu, ..., Fang Song,* Qinglei Liu.* ACS Nano 2022, 16, 9, 14121. Sihong Wang, Qu Jiang, ..., and Fang Song,* Commun. 2022, 13, 6650; Qiwen Zhang, ..., Fang Song*, Mingwei Chen, and Pan Liu*. ACS Nano 2023, 17, 1485. Haoyue Zhang,# Lingling Wu,# ..., and Fang Song*., ACS Appl. Mater. Interfaces, In revision. Haoyue Zhang,# Lingling Wu,# ..., and Fang Song*. ACS Catal. In press.

Abstract Obviously, breast cancer cells that disseminated from the primary tumor before surgical resection are responsible for metastasis. However, detection of disseminated cancer cells (DCC) in breast cancer patients during minimal residual disease is still difficult, impeding the study of early systemic cancer and the extraction of clinically relevant diagnostic or therapeutic information. Others and we have shown previously that EpCAM is a suitable DCC detection marker, however not entirely specific in bone marrow. To improve DCC detection, we here compared different methods to enrich DCC exploiting information from our ongoing single cell RNA-seq study. Based on our ongoing scRNA-seq study (see poster of Elia Raya), we generated a qPCR assay to classify candidate DCC based on an expression signature of four genes. This assay categorizes plasma cell-like EpCAM+ cells from healthy donors and candidate DCC from breast cancer patients with high fidelity. With this assay at hand, we compared two enrichment strategies: depletion of CD11b, CD319 and Glycophorin A positive cells from density gradient enriched mononuclear cells (MNC) vs. positive selection of EpCAM+ cells and subsequent addition of markers that separate out DCC among EpCAM+ cells. For this we applied 10x genomics profiling of EpCAM+ cells from bone marrow. We depleted and screened the bone marrow of 221 patients suffering from non-metastatic early breast cancer for EpCAM-positive cells. From 87 patient samples we could isolate EpCAM-positive cells. We performed single cell RNA-sequencing on 64 EpCAM-positive cells from 54 patients of which 84% were classified as cancer cells and 16% of bone marrow origin. Applying the selected gene signature, 76% of isolated cells were classified as DCC, 16% were undefined and 8% as non-cancer bone marrow cell (NCC). Upon positive selection of EpCAM+ cells implementing additional markers, we isolated 53 cells from 14 patients. Of these, 68% showed a DCC or DCC-like-signature, 15 % a NCC and 17% an undefined profile. To get a better understanding of these EpCAM-positive confounder populations we currently perform a scRNA-seq profiling using 10X on the enriched EpCAM+ cells. Our data shows that EpCAM is a promising marker to identify DCCs in the bone marrow of early cancer patients, but it also indicates that we find several groups of confounder cells. To differentiate between these cell types during staining and in our qPCR assay we are currently testing additional markers. Citation Format: Jonas Roth, Elia Raya, Sarah Hücker, Huiqin Koerkel-Qu, Stephan Seitz, Christoph Klein. Characterization of EpCAM-positive cells for specific detection of disseminated cancer cells in bone marrow of early breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3708.

BackgroundPAH is a well-recognized but infrequent manifestation of SLE. Often insidious in onset, PAH may have progressed for a while, before symptoms manifest. Prediction of clinical risk of PAH may have clinical benefit during the follow-up of a patient with SLE.ObjectivesThe aim of the study was to develop a prediction algorithm for PAH in patients with SLE using clinical and auto-antibody variables.MethodsThe study included patients from the INSPIRE cohort which is, a national multi-center study enrolling patients with disease duration of less than three years. Lupus patients with symptomatic PAH confirmed by a transthoracic 2D ECHO right ventricular systolic pressure of more than 40 mm Hg were enrolled as cases. Controls were age, sex and date of enrolment matched patients from the same cohort without any clinical evidence of PAH. We excluded patients with underlying known heart disease and critical illness. The clinical variables and antibody data was retrieved from records. Outcome of death if any was noted. Using supervised learning, a logistic regression model was built for the prediction of SLE-PAH. The final Prediction model included one clinical variable (RP), sixteen autoantibodies (Sm-RNP, Smith, SS-A, Ro-52, SS-B, SCL-70, PM-SCL, Centromere, Jo1, PCNA, Nucleosome, dsDNA, histone, Ribosomal P and AMA, anticardiolipin antibody) and complement level. To ensure accuracy of the model, a confusion matrix using python was performed. The proportion of right predictions (ρ) is a measure of accuracy of the model. If the model is good, ρ must be close to 1.ResultsA total of 69 patients with symptomatic PAH, confirmed by 2D echo-cardiography were enrolled as cases. Raynaud phenomenon (RP), Interstitial lung disease (ILD) and ischemic stroke were significantly higher in cases than control (p= 0.026,0.001, 0.05 respectively). There was no difference in the prevalence of individual auto-antibodies between the groups except high prevalence of anti-cardiolipin antibody in cases (39% vs 23% p= 0.048). Mortality rate was higher in cases (17% vs 0.06%, p=0.003) during a follow up of 3 years with all the deaths occurring within one year of PAH diagnosis. Ten repetitions of the confusion matrix analysis using Python for this prediction model (both derivation and validation) yielded the following ρ scores 0.60, 0.47, 0.57, 0.63, 0.50, 0.60, 0.57, 0.43, 0.50, 0.57. which exhibited wide variability.ConclusionA prediction model using RP and commonly assayed autoantibodies failed to be informative for PAH in Indian lupus patients.References[1]Qu J, Li M, Wang Y, Duan X, Luo H et al. Predicting the Risk of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus: A Chinese Systemic Lupus Erythematosus Treatment and Research Group Cohort Study. Arthritis Rheumatol. 2021 Oct;73(10):1847-1855AcknowledgementsI want to acknowledge INSPIRE cohort investigators,I want to acknowledge Government of India, Ministry of Science & Technology,Department of Biotechnology (No. BT /PR23111/MED/30/1852/2017)Disclosure of InterestsNone declared

Children's school readiness is important to discuss because learning loss is an obstacle in preparing early childhood to enter elementary school. This study aims to look at parents' perceptions of their children's readiness for school during and after the COVID-19 pandemic. This study uses a quantitative descriptive survey research design to collect measurable data for statistical analysis from a population sample. The results show that preparing children for school during and after the COVID-19 pandemic is very different from the usual practice. Parents are required to provide appropriate stimulation to children at home to replace the role of teachers at school and restore the motivation and willingness of children to enter elementary school. The perception of parents is certainly very influential on the stimulation that will be given to children. Keywords: early childhood education, parents’ perceptions, school readiness References: Alexander, K. L., Entwisle, D. R., & Olson, L. S. (2007). Lasting Consequences of the Summer Learning Gap. American Sociological Review, 72(2), 167–180. https://doi.org/10.1177/000312240707200202 Araújo, L. A. de, Veloso, C. F., Souza, M. de C., Azevedo, J. M. C. de, & Tarro, G. (2021). The potential impact of the COVID-19 pandemic on child growth and development: A systematic review. Jornal de Pediatria, 97(4), 369–377. https://doi.org/10.1016/j.jped.2020.08.008 Atkinsonová, R. L., Atkinson, R. C., SMITH, E. E., Herman, E., Bem, D. J., & Petržela, M. (1995). Psychologies. Victoria Publishing. https://books.google.co.id/books?id=Tj9OAAAACAAJ Bao, X., Qu, H., Zhang, R., & Hogan, T. P. (2020). Modeling Reading Ability Gain in Kindergarten Children during COVID-19 School Closures. International Journal of Environmental Research and Public Health, 17(17). https://doi.org/10.3390/ijerph17176371 Benner, A. D., & Mistry, R. S. (2020). Child Development During the COVID-19 Pandemic Through a Life Course Theory Lens. Child Development Perspectives, 14(4), 236–243. https://doi.org/10.1111/cdep.12387 Brown, S. M., Doom, J. R., Lechuga-Peña, S., Watamura, S. E., & Koppels, T. (2020). Stress and parenting during the global COVID-19 pandemic. Child Abuse & Neglect, 110, 104699. https://doi.org/10.1016/j.chiabu.2020.104699 Colizzi, M., Sironi, E., Antonini, F., Ciceri, M. L., Bovo, C., & Zoccante, L. (2020). Psychosocial and Behavioral Impact of COVID-19 in autism spectrum disorder: An Online Parent Survey. Brain Sciences, 10(6). https://doi.org/10.3390/brainsci10060341 Creswell, J. W. (2015). Educational research: Planning, conducting, and evaluating quantitative and qualitative research (Fifth edition). Pearson. Cushon, J. A., Vu, L. T. H., Janzen, B. L., & Muhajarine, N. (2011). Neighborhood Poverty Impacts Children’s Physical Health and Well-Being Over Time: Evidence from the Early Development Instrument. Early Education and Development, 22(2), 183–205. https://doi.org/10.1080/10409280902915861 Duncan, R. J., Duncan, G. J., Stanley, L., Aguilar, E., & Halfon, N. (2020). The kindergarten Early Development Instrument predicts third grade academic proficiency. Early Childhood Research Quarterly, 53, 287–300. https://doi.org/10.1016/j.ecresq.2020.05.009 Engzell, P., Frey, A., & Verhagen, M. D. (2021). Learning loss due to school closures during the COVID-19 pandemic. Proceedings of the National Academy of Sciences, 118(17), e2022376118. https://doi.org/10.1073/pnas.2022376118 Friedman, M. M., Bowden, V. R., & Jones, E. (2003). Family Nursing: Research, Theory & Practice. Prentice Hall. https://books.google.co.id/books?id=mkBtAAAAMAAJ Gobbi, E., Maltagliati, S., Sarrazin, P., di Fronso, S., Colangelo, A., Cheval, B., Escriva-Boulley, G., Tessier, D., Demirhan, G., Erturan, G., Yüksel, Y., Papaioannou, A., Bertollo, M., & Carraro, A. (2020). Promoting Physical Activity during School Closures Imposed by the First Wave of the COVID-19 Pandemic: Physical Education Teachers’ Behaviors in France, Italy and Turkey. International Journal of Environmental Research and Public Health, 17(24). https://doi.org/10.3390/ijerph17249431 Griffith, A. K. (2020). Parental Burnout and Child Maltreatment During the COVID-19 Pandemic. Journal of Family Violence. https://doi.org/10.1007/s10896-020-00172-2 Hevia, F. J., Vergara-Lope, S., Velásquez-Durán, A., & Calderón, D. (2022). Estimation of the fundamental learning loss and learning poverty related to COVID-19 pandemic in Mexico. International Journal of Educational Development, 88, 102515. https://doi.org/10.1016/j.ijedudev.2021.102515 Jandrić, P. (2020). Postdigital Research in the Time of Covid-19. Postdigital Science and Education, 2(2), 233–238. https://doi.org/10.1007/s42438-020-00113-8 Kuhfeld, M., Tarasawa, B., Johnson, A., Ruzek, E., & Lewis, K. (2020). Initial findings on students’ reading and math achievement and growth. 12. Maldonado, J. E., & De Witte, K. (2022). The effect of school closures on standardised student test outcomes. British Educational Research Journal, 48(1), 49–94. https://doi.org/10.1002/berj.3754 McDowell, K., Jack, A., & Compton, M. (2018). Parent Involvement in Pre-Kindergarten and the Effects on Student Achievement. The Advocate, 23(6). https://doi.org/10.4148/2637-4552.1004 Nevid, J. S. (2012). Psychology: Concepts and Applications. Wadsworth Cengage Learning. https://books.google.co.id/books?id=TpxZXwAACAAJ Skulmowski, A., & Rey, G. D. (2020). COVID-19 as an accelerator for digitalization at a German university: Establishing hybrid campuses in times of crisis. Human Behavior and Emerging Technologies, 2(3), 212–216. https://doi.org/10.1002/hbe2.201 Spinelli, M., Lionetti, F., Pastore, M., & Fasolo, M. (2020). Parents’ Stress and Children’s Psychological Problems in Families Facing the COVID-19 Outbreak in Italy. Frontiers in Psychology, 11, 1713. https://doi.org/10.3389/fpsyg.2020.01713 Yoshikawa, H., Wuermli, A. J., Britto, P. R., Dreyer, B., Leckman, J. F., Lye, S. J., Ponguta, L. A., Richter, L. M., & Stein, A. (2020). Effects of the Global Coronavirus Disease-2019 Pandemic on Early Childhood Development: Short- and Long-Term Risks and Mitigating Program and Policy Actions. The Journal of Pediatrics, 223, 188–193. https://doi.org/10.1016/j.jpeds.2020.05.020

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the sacroiliac joints and the spine, resulting in decline in quality of life[1,2]. Poor QoL is significantly related to high disease activity[3]. However, there is no systematic report on which prognosis indicators are affected by disease activity in AS patients.Objectives:This study aimed to evaluate the patient-reported outcome measures and health-related quality of life (HR-QoL) in AS patients defined on the basis of the Bath Spondylitis Ankylosing Disease Activity Index (BASDAI).Methods:204 AS patients were involved in this study. A serious of questionnaires were used to overall assess AS patients, which include: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), the 10 cm Visual Analog Scale (VAS), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Fatigue Severity Scale(FSS) and the Short Form 36 Health Survey (SF-36). Independent samples t-test, Mann–Whitney U-test, Chi-square analysis and Pearson /Spearman correlation were used to analyze the data.Results:The results demonstrated 31.4% AS patients were in active disease activity stage. Active AS patients were older, unemployed, and had less exercise therapy than stable AS patients. Besides, AS patients with active disease activity presented more severe pain(P<0.001), poor physical function(P<0.001) and spinal mobility(P<0.001). They were more anxious(P<0.001), depressed(P<0.001) and had more sleep disturbance(P=0.001). Compared with active AS patients, stable AS patients had more leukocytes(P=0.040), lymphocytes(P=0.002), erythrocytes(P=0.001) and hemoglobin(P<0.001). Active disease activity had a significant impact on all dimensions of quality of life in AS patients(P<0.001).Conclusion:These findings suggested that medical personnel should pay more attention to active AS patients and make effective interventions to improve quality of life.References:[1]Exarchou S, Lindstrom U, Askling J, Eriksson JK, Forsblad-d’Elia H, Neovius M, Turesson C, Kristensen LE, Jacobsson LT (2015) The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study. Arthritis research & therapy 17:118. doi:10.1186/s13075-015-0627-0[2]Qian Q, Xu X, He H, Ji H, Zhang H, Ding Y, Dai SM, Zou Y, Zhu Q, Yang C, Ye S, Jiang L, Tang JP, Tong Q, He D, Zhao D, Li Y, Ma Y, Zhou J, Yuan Z, Zhang J, Jin L, Zhou X, Reveille JD, Zou H, Wang J (2017) Clinical patterns and characteristics of ankylosing spondylitis in China. Clinical rheumatology 36 (7):1561-1568. doi:10.1007/s10067-017-3660-3[3]Huang JC, Qian BP, Qiu Y, Wang B, Yu Y, Zhu ZZ, Hu J, Qu Z (2017) Quality of life and correlation with clinical and radiographic variables in patients with ankylosing spondylitis: a retrospective case series study. BMC musculoskeletal disorders 18 (1):352. doi:10.1186/s12891-017-1711-1Acknowledgments:Thanks to all the authors for their efforts and thanks to all members of the Department of Rheumatology of Affiliated Hospital of Nantong University for their helpfulness in the acquisition of data.Disclosure of Interests:None declared

Abstract Background: MET gene amplification is associated with poor prognosis in gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ). Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor. Here we reported the preliminary efficacy and safety from a phase 2 trial of savolitinib monotherapy in patients (pts) with MET-amplified advanced or metastatic GC/GEJ. (NCT04923932). Methods: Eligible pts had 2L+ GEJ or GC, with MET amplification and measurable lesions. Pts received savolitinib at 600 mg QD for body weight (BW) ≥50 kg, while 400 mg QD for BW &lt;50 kg in 21-day cycles until disease progression or meeting other criteria for end of treatment. Savolitinib BID regimen has also been additionally explored. The primary endpoint was objective overall response rate (ORR) evaluated by Independent Review Committee (IRC). One interim analysis (IA) was pre-defined at the first 20 QD pts who had at least 2 tumor assessments. Results: As of IA, 20 pts were enrolled for QD regimen. Demographics and clinical outcomes are shown in table 1. The mean relative dose intensity of 93.07%. Median duration of exposure was 2.09 months. Confirmed ORR by IRC was 45%, and reached 50% in 16 patients with MET GCN (high) while only 1 PR was observed in 4 patients with MET GCN (low). Duration of response rate at 4-month was 85.7% with median follow up time of 5.5 months. The most common Gr≥3 TRAE (≥5%) were platelet count decreased, hypersensitivity, anemia, neutropenia and hepatic function abnormal. In all pts, only 1 patient discontinued treatment due to grade 4 liver function abnormal (TRAE) and no patient died due to TRAE. Conclusion: Savolitinib monotherapy had manageable safety and showed promising efficacy in pts with MET-amplified GEJ or GC, particularly in pts with MET high GCN. BID regimen is being investigated to further evaluate the efficacy and safety of savolitinib in pts with MET high GCN. Table 1. Pts baseline characteristics and clinical efficacy Baseline Characteristics ITT in IA (n=20) Median age (min, max), yearsSex (male/female), nECOG (0/1/2)Median BMI (min, max), (kg/m2)Primary location of tumor (GC/GEJ)Tumor stage (IV)Prior line of therapy (1/2/≥3)MET GCN (high/low) 57.00 (39.5, 76.8)17/33/15/220.8 (14.9, 25.8)16/4205/10/516/4 Clinical Efficacy By IRC By Investigator Confirmed objective response rateDisease control rate4m-DoR rate,% (95% CI) 45%65%85.7 (33.4, 97.9) 40%55%71.4 (25.8, 92.0) Citation Format: Zhi Peng, Hua Wang, Baorui Liu, Huiting Xu, Zhenyang Liu, Tianshu Liu, Jun Zhang, Yuxian Bai, Ying Yuan, Tao Wu, Feng Ye, Qinghua Pan, Jufeng Wang, Enxiao Li, Diansheng Zhong, Yueyin Pan, Yanru Qin, Yan Yang, Yusheng Wang, Aiping Zhou, Yongshun Chen, Dianbao Zhang, Hongli Liu, Xiujuan Qu, Shubin Wang, Ning Liu, Jinsheng Wu, Wei Li, Kejun Nan, Hongming Pan, Jianming Xu, Chunmei Bai, Heling Liu, Jia Wei, Runzhi Chen, Rongrong Li, Wei Li, Jinghong Zhou, Hongyan Yin, Qian Xu, Songhua Fan, Yongxin Ren, Weiguo Su, Lin Shen. A multicenter Phase II study of savolitinib in patients with MET-amplified gastroesophogeal junction adenocarcinomas or gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT152.

200 numéros d’exercer… Dans le numéro 80 de janvier 2008, premier numéro en ligne, l’éditorial signé par Pierre-Louis Druais, Patrick Chevalier et Denis Pouchain se terminait par : « Bonne lecture, mais critique s’il vous plaît. Toute l’équipe est à votre écoute pour que vive et grandisse exercer, la revue française de médecine générale. » La citation accolée à cette conclusion était « les étoiles naissent dans l’espace ». Dans ce numéro, la rédaction vous propose de découvrir d’autres citations, évoquées par ce numéro 200, celles de membres du comité de lecture et de relecteurs, qui entourent le premier éditorial de la revue. Pour ce numéro 200, l’éditorial vous propose 20 citations de films de tous les genres, et contrairement à l’habitude, aucune référence. Et comme « une citation sans référence est à peu près aussi utile qu’une horloge sans aiguilles »0, la mission pour les lecteurs est simple : trouver la référence ! Alors la revue exercer a-t-elle grandi ? Oui, simultanément à la filière universitaire de médecine générale, et ce n’est pas fini. Les utopistes de la rédaction veulent l’emmener « Vers l’infini et au-delà »1. Notre maître mot est « N’aie pas peur de rêver plus gros »2, en atteste la dernière plénière exercer au congrès de Lyon où « Je peux vous dire que Johnny Hallyday au stade de France, à côté c’est un Playmobil dans un évier »3. Comment faisons-nous pour rêver la suite ? Eh bien « La maison n’accepte pas l’échec »4 et nous savons que « les records sont faits pour être battus »5. Nous sommes conscients de notre mission : fournir aux soignants de soins de santé primaires des données indépendantes et EBM pour, in fine, améliorer l’état de santé des usagers : « à grand pouvoir, grandes responsabilités »6. Comment faisons-nous pour assurer cette mission ? « Force de frappe, esprit d’équipe »7. Cet esprit d’équipe insufflé par Jean-Pierre Lebeau « O captain, my captain »8 a été rapidement perçu par la dernière arrivée, Karolina Griffiths, autrice de podcasts, et elle peut déjà témoigner qu’« on ne laisse pas Bébé dans un coin »9. De quelle suite rêvons-nous ? Vous en avez peut-être entendu parler et « Quand une rumeur ne meurt pas, c’est que ce n’est pas une rumeur »10, nous travaillons à l’indexation dans Medline pour 2024, après Clarivate Analytics (ex-Web of Science) en 2018. Parallèlement, nous allons aussi travailler à un archivage HAL science ouverte : « HAL, ouvre la porte, s’il te plaît »11. Vous doutez ? « Votre manque de foi me consterne »12, ayez confiance, « l’union fait la force ! La foi fait l’union ! »13, notre équipe sait que « Seule compte la volonté, la volonté d’agir »14 et « rien n’est plus fort que le coeur d’un volontaire »15. Souvent l’éditorial présente le contenu du numéro, et à ce stade de la lecture vous vous demandez quel est ce contenu ? D’autant plus qu’exercer « C’est comme une boîte de chocolats, on ne sait jamais sur quoi on va tomber »16. Ce numéro contient des réponses à des questions issues de notre pratique, et il contient aussi des réponses à des questions que nous ne nous étions pas encore posées…Superflu, vous pensez ? « Rien n’est plus nécessaire que le superflu »17. Avec ce numéro 200, vous savez désormais que l’étoile exercer est née dans l’espace, et cet espace « C’est votre espace. Vous le possédez »18. Une étoile, mais pas une star, conservons notre humilité, car nous savons que « l’arrogance et l’introspection font rarement bon ménage »19. Soyons optimistes et forces de proposition, car « Peu importe ce qu’on pourra vous dire, les mots et les idées peuvent changer le monde »20.

Las redes sociales y el internet soy hoy en día un potencial para las empresas, para el fortalecimiento de su imagen y su forma rápida de llegar a los clientes. En este trabajo se analiza el impacto del marketing digital en las PYMES de la provincia de Chimborazo en el Ecuador. Los resultados revelaron que las PYMES tienen una participación del 8,72% en las redes sociales, donde las microempresas llevan el 90,81%. La provincia de Chimborazo obtuvo una participación del 3,18%, donde Pichincha y Guayas obtienen 23,75% y 18,95% respectivamente. En el año 2015 las PYMES invirtieron alrededor de 15 millones de dólares en redes sociales. Finalmente se concluye que las ventas han ido creciendo en los últimos años, en un total de 116 millones y en las PYMES en 774 miles de dólares en el año 2018. Palabras Clave: análisis financiero, marketing digital, redes sociales. Referencias [1]M. Vega y G. Romero, Salvador; Guzman, “Marketing Digital Y Las Finanzas De Las Pymes Digital Marketing and the Finances of Smes,” RITI J., vol. 6, 2018. [2]J. L. Colvée, “Estrategias de marketing digital para pymes.,” Fimal Cent. S. L., pp. 13–196, 2013, [En línea]. Disponible: https://www.antoniovchanal.com/wp-content/uploads/2012/09/ANETCOM-Estrategias- de-mk-digital-para-pymes1.pdf. [3]Observatorio Regional de ia Sociedad de la Información de Castilla y León, “Marketing digital para Pymes,” Man. eCommerce, vol. 67, no. 11, p. 02, 2012,doi: CIF B85208577. [4]S. Cortés, “MARKETING DIGITAL Como Herramienta de Negocios para PyMES,” Univ. Chile Fac. Econ. y Negocios Ing. Comer., p. 147, 2011, [En línea]. Disponible:http://repositorio.uchile.cl/bitstream/handle/2250/116571/ec-cortes_v.pdf?sequence=1&isAllowed=y. [5]Á. Sustaeta, “La importancia del SEO y el SEM en el emprendimiento,” p. 97, 2014, [En línea]. Disponible: https://repositorio.unican.es/xmlui/bitstream/handle/10902/6459/SUSTAETANAVARROANGELMANUEL. pdf?sequence=1. [6]F. Bilello, “Plan de social media adaptado a la empresa Queen ’ s,” 2016. [7]M. Mora, “Facebook Como Medio Publicitario,” Esc. Comun. Soc., vol. 1, pp. 1–137, 2009. [8]F. Meunier Rosas, “El uso de la red social Twitter como herramienta para la difusión de la información pública,” Razón y palabra, no. 81, pp. 48–8, 2012. [9]J. Martínez, “Guia empezar en linkedin,” pp. 1–22, 2012. [10]J. López, “Youtube Como Herramienta Para La Construcción De La Sociedad Del Conocimiento,” Publicación cuatrimestral. Edición continúa. Año, vol. 3, no. 1, pp. 1–16, 2018. [11]G. Villanueva, Julián; Aced, Cristina; Armelini, “Cuadernos Del,” pp. 1–24, 2013. [12]R. E. Ron Amores y V. A. Sacoto Castillo, “Las PYMES ecuatorianas: Su impacto en el empleo como contribución del PIB PYMES al PIB total,” Espacios, vol. 38, no. 53, 2017. [13]G. S. Peña, Y. Caicedo, y S. A. Delgado, “Importancia de implementar el marketing digital en las pymes Colombianas frente al tratado de libre comercio con Estados Unidos,” Doc. Trab. ECACEN, vol. 0, no. 1, 2017, [En línea]. Disponible: http://hemeroteca.unad.edu. co/index.php/working/article/view/2558. [14]D. J. Baños, J. M. Oleas, y P. E. Ricaurte, “Evolución de las PYMES de la ciudad de RIOBAMABA mediante análisis multivariado en las competencias dela destión empresarial,” pp. 47–60, 2017. [15]R. A. Fornero, “Análisis Financiero con Información Contable,” p. 20, 2016, [En línea]. Disponible: http://www.unsa.edu.ar/afinan/dfe/trabajos_practicos/afic/AFIC Cap 1 Bases An%E1lisis financiero.pdf. [16]M. Maranto, Marisol; González, “Fuentes de Información Fuentes de Información,” pp. 1–17, 2015. [17]R. I. J. Andino, “Directorio de empresas y establecimientos 2018,” pp. 1–15, 2018, [En línea]. Disponible: http://www.ecuadorencifras.gob.ec/documentos/webinec/Inflacion/2018/Enero-2018/01 ipc Presentacion_IPC_enero2018.pdf. [18]INEC, “Módulo de Tecnologías de la Información y Comunicación (TIC) de las Encuestas de Manufactura y Minería, Comercio Interno y Servicios.” QU, 2015, [En línea]. Disponible: https://www.ecuadorencifras.gob.ec/tecnologias-de-la-informacion-y-comunicacion-empresas/. [19]J. P. Del Alcázar Ponce, “Ecuador Estado Digital Ene/19,” Mentinno, p. 37, 2019, [En línea]. Disponible: https://drive.google.com/file/d/116eZRcn-FH-cLVWm-GGlt3jAn_SdG1aTL/view. [20]K. Bricio Samaniego, J. Calle Mejía, y M. Zambrano Paladines, “El marketing digital como herramienta en el desempeño laboral en el entorno ecuatoriano: estudio de caso de los egresados de la Universidad de Guayaquil,” Rev. Univ. y Soc., vol. 10, no. 4, pp. 103–109, 2018.

Abstract Background: Overexpression of EGFR and MET has been observed in wild-type (WT) adenocarcinoma and squamous non-small cell lung cancer (NSCLC; Huang L. J Thorac Oncol. 2014). Amivantamab (ami), an EGFR-MET bispecific antibody with immune cell-directing activity, demonstrated pre-clinical activity against WT tumors overexpressing EGFR and MET. We examined ami monotherapy activity in WT-NSCLC after disease progression on platinum-based chemotherapy and anti-PD-1 or PD-L1 therapy. Methods: The WT-Ad and WT-Sq cohorts of the CHRYSALIS study enrolled pateints (pts) with adenocarcinoma or squamous cell carcinoma histology, respectively, without evidence of EGFR, ALK, and MET Exon 14 skipping activating mutations. Pts received ami monotherapy at the approved dose (1050 mg; 1400 mg if ≥80 kg) weekly for the first 4 weeks and biweekly thereafter. Response was assessed by the investigator per RECIST v1.1. Plasma samples were collected pre-treatment, with ctDNA analyzed by Guardant Health (Redwood City, CA). Results: In the WT-Ad cohort, 41 pts received ami (30 with ≥1 post-baseline disease assessment; 11 discontinued due to adverse events [AEs], disease progression, or physician decision), with a median follow-up of 6.2 mo. The median age was 62 years, 63% were men, and 37% were Asian. The objective response rate (ORR) was 7% (3/41), the clinical benefit rate (CBR) was 29%, and the median duration of response (DoR) was 4.2 mo (95% CI, 4.1-not estimable [NE]). Among pts with detectable ctDNA (n=24), 9 pts had KRAS/HER2 mutations. The ORR for pts with and without KRAS/HER2 mutations was 0% (0/9) and 20% (3/15), respectively. The corresponding median PFS for pts with and without KRAS/HER2 mutations was 1.4 mo (95% CI, 1.4-NE) and 4.2 mo (95% CI, 1.6-NE), respectively. In the WT-Sq cohort, 14 pts received ami (12 with ≥1 post-baseline disease assessment; 2 discontinued), with a median follow-up of 6.3 mo. Median age in the WT-Sq cohort was 71 years, 57% were men, and 43% were Asian. ORR was 21% (3/14) with a median DoR that was NE and 2 pts with a DoR ≥6 mo. The overall CBR was 43% (6/14), median PFS was 4.0 mo (95% CI, 2.2-7.3), and median OS was NE. Most common treatment-emergent AEs in both cohorts were rash (grouped term; 66% for WT-Ad, 57% for WT-Sq) and infusion-related reactions (63% WT-Ad and 57% WT-Sq). Grade ≥3 treatment-related AEs (TRAEs) were reported in 17% of pts in the WT-Ad cohort and 21% the WT-Sq cohort. One (2%) pt in the WT-Ad cohort experienced grade 2 interstitial lung disease. Four pts in WT-Ad and 2 pts in WT-Sq cohort discontinued due to TRAEs. Conclusions: Ami demonstrated preliminary antitumor activity in pts with refractory WT squamous and adenocarcinoma NSCLC, particularly in those lacking KRAS/HER2 activating mutations. Safety profile was consistent with the previously reported monotherapy experience, and no new signals were identified. Citation Format: Byoung Chul Cho, Jonathan Goldman, Natasha Leighl, Filippo De Braud, Ki Hyeong Lee, François Ghiringhelli, Pilar Garrido, Julio Peguero, Benjamin Besse, Philippe Cassier, Nicolas Girard, Maria de Miguel, Rosa Alvarez, Alastair Greystroke, Yuichiro Ohe, Te-Chun Hsia, Joshua C. Curtin, Sanjib Chowdhury, Xuesong Lyu, Grace Gao, Siyang Qu, Patricia Lorenzini, Aastha Kapoor, Priya Kim, Mahadi Baig, Meena Thayu, Roland E. Knoblauch, Sandrine Hiret, Pascale Tomasini. Amivantamab in wild-type advanced non-small cell lung cancer after disease progression on checkpoint inhibition and chemotherapy: Results from the phase 1b CHRYSALIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT054.

Abstract Background The combination of an aromatase inhibitor with a CDK4/6 inhibitor is the mainstay of first-line endocrine therapy (ET) for locally advanced or metastatic HR+/HER2− breast cancer (LA/mBC). Management of recurrent disease in the post-CDK4/6 inhibitor setting includes additional lines of ET single agent or in combination with a targeted agent. For patients with HR+/HER2− LA/mBC tumors, fulvestrant monotherapy as the second- or third-line therapy has limited activity with a median PFS of 1.9-3.6 months. Effective targeted treatments for these patients are needed to maintain quality of life, improve survival, and delay the initiation of cytotoxic chemotherapy. Methods This ongoing single arm, open-label global study (NCT04851613) is to evaluate the efficacy and safety of the combination therapy of afuresertib (a pan-AKT inhibitor) plus fulvestrant in patients with HR+/HER2− LA/mBC. Eligible patients must have received 1-2 prior lines of ET. Patients may have prior treatment of CDK4/6 inhibitors (up to 1 therapy), and/or up to 1 line of chemotherapy. Patients received afuresertib (125 mg PO, QD) in combination with fulvestrant (500 mg IM; Day 1 and 15 in Cycle 1, and Day 1 in subsequent 28-day cycles). The safety of the initial treatment doses of the combination therapy was evaluated in the first 6 patients during the Cycle 1 safety run-in period. Radiographic assessment per RECIST 1.1 was performed every 8 weeks for the first 6 cycles and every 12 weeks thereafter. The primary endpoint was the investigator-assessed objective response rate (ORR). The secondary endpoints included safety and tolerability of the combination therapy and pharmacokinetic characterization. Results Twenty patients (1 male and 19 females, 3 in the US and 17 in China) were enrolled between May 2022 and April 2023. As of the data cut-off date of May 26th, 2023, 10 patients had discontinued the study treatment (9 due to disease progression, 1 due to patient’s withdrawal of consent) and 10 patients were still in treatment. Of the 19 patients who had at least one post-baseline tumor assessment, 4 patients observed confirmed Partial Response (cPR), 12 had best overall response of Stable Disease, and 3 had Progressive Disease (PD). The Disease Control Rate is 84%. Of the 15 patients who had at least 2 tumor assessments or who discontinued treatment early due to PD, the confirmed ORR is 26.7% (4 cPR). No dose modification was required during the safety run-in. The most common treatment-emergent adverse events (TEAEs, &gt; 20% of patients) of all grades were hyperglycemia (50%), diarrhea (45%), ALT/AST increase (40%), nausea (35%), rash (35%), hypercholesterolemia (35%), and anemia (30%), the majority of which were Grade 1. Grade 3 AEs were reported in 4 patients, including diarrhea (1 patient), WBC increase (1 patient), creatine phosphokinase increase (1 patient), and ALT/AST increase and rash (1 patient). No SAE or TEAE &gt;= Grade 4 were reported. No patient discontinued treatment due to TEAE. Conclusions The preliminary data from the combination therapy of afuresertib plus fulvestrant has shown promising efficacy with a well-tolerated safety profile in patients with HR+/HER2− LA/mBC who progressed on 1-2 prior lines of standard of care therapies. These results support further evaluation of this combination therapy in this patient population in an upcoming phase III study. Citation Format: Binghe Xu, Pin Zhang, Tao Sun, Ying Wang, Zhongsheng Tong, Sneha Phadke, Trevor Feinstein, Pengfei Guo, Jing Qu, Xiaoyu Wang. A Phase Ib Study to Evaluate the Efficacy and Safety of Afuresertib Plus Fulvestrant in Patients with Locally Advanced or Metastatic HR+/HER2- Breast Cancer Who Failed Standard of Care Therapies [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS17-08.

Abstract Background: CHASE001 (NCT05544123), a prospective, non-interventional multicenter study exploring real-world treatment and referral behavior of Chinese county patients (pts) with HER2+ or HR+/HER2– breast cancer is ongoing since September 2022. A prespecified interim analysis (IA) on 750 HER2+ and HR+/HER2- early breast cancer (eBC) was reported at the ESMO Congress 2023. In the 2nd IA from CHASE001, adjuvant treatment selection for patients with HR+/HER2- eBC will be evaluated. Methods: The study was designed to enroll 2500 pts, including four cohorts (HER2+ eBC, HR+/HER2-eBC, HER2+ advanced BC, and HR+/HER2- aBC). In this IA, HR+/HER2- eBC pts after surgery were included. Descriptive statistics reported patient demographics, clinical and disease characteristics and treatment patterns. To investigate the factors associated with chemotherapy-free regimen, non-anthracycline chemotherapy regimen and ovarian function suppression (OFS), univariate and multivariate logistic regression analyses were conducted. Results: At data cutoff (May 17, 2023), 697 HR+/HER2- eBC pts (median age 52 years, 45.77% pT2, 50.93% pN0, 56.10% G2) were included from 26 institutions in China county areas, 338 (48.49%) were premenopausal. 584 (83.79%) received adjuvant chemotherapy, with a few (47/584, 8.05%) initially developing their treatment plan at a higher level hospital (national or provincial tertiary hospital). AC-T (309/584, 52.91%) was the most commonly used regimen. 181 (30.99%) pts received non-anthracycline chemotherapy regimen (mainly TC), and pts with N0, age≥65 years and ki67 &lt; 20% had the strongest association to this regimen (multivariate OR=0.082, 95%CI [0.037,0.179], OR=0.463, 95%CI [0.250,0.859], and OR=0.642, 95%CI [0.418,0.985], respectively). Interestingly, on univariate analysis pts initially diagnosed in a higher level hospital were significantly associated with non-anthracycline regimen (P=0.0109), however on multivariate analysis it was no longer significant. 483 pts received endocrine therapy, including 234 (48.45%) premenopausal pts. The most commonly used endocrine regimen for premenopausal pts was OFS/OFS+ (122/234, 52.14%) ,of which half (61, 50%) were prescribed OFS+TAM/TOR; followed by TAM/TOR monotherapy (69/234, 29.49%). The proportions of patients classified as low, intermediate, and high clinical risk for recurrence (investigator assessed)were 33.62%, 42.67% and 23.71%. The OFS rate were 39.74% in low, 61.62% in intermediate and 70.91% in high risk pts, respectively. Multivariable analyses found that high clinical risk, age &lt; 45 years and ki67 &lt; 20% were strongly associated with the use of OFS (OR=0.210, 95%CI [0.066,0.674], OR=0.327, 95%CI [0.165,0.649], and OR=0.405, 95%CI [0.194,0.845], respectively). For postmenopausal pts, AI monotherapy (84.74%) was the most commonly used endocrine regimen. Conclusions: To our knowledge, this is the first real-world study evaluating the treatment patterns and referral behavior of BC pts in China counties. The 2nd IA results presented showed the current systemic adjuvant treatment preferences and influence factors from a large sample of HR+/HER2- eBC pts in China counties, which were generally consistent with China BC treatment guidelines. Table 1. Utilization of adjuvant systemic therapy regimens in 697 HR+/HER2− eBC pts, China counties AC-T: (dd)doxorubicin/epirubicin, cyclophosphamide, followed by (dd)paclitaxel/docetaxel; TC: paclitaxel/docetaxel, cyclophosphamide; AC: doxorubicin/epirubicin, cyclophosphamide; TAC: docetaxel, doxorubicin/epirubicin, cyclophosphamide; TAM: tamoxifen; OFS: ovarian function suppression; AI: aromatase inhibitors; TOR: toremifene; CDK4/6i: cyclin-dependent kinase 4/6 inhibitors; “Other” category includes various therapies used in &lt;1% of patients each Citation Format: Yinghua Ji, Honglan Qu, Feidu Zhou, Juan Wang, Qianfu Wu, Guohua Dai, Mengyou Liu, Wenbo He, Wei Liang, Qiuli Meng, Yun Ren, Guoxiang Luo, Hongjian Wang, Hui Liu, Zien Qin, Yingguo Tian, Huali Tang, Hongmei Liu, Jun Luo, Zengfeng Yu, Guinv Hu, Jianzhi Gao, Xiang Tan, Yi Liu, Yuanjiang Zhang, Ming Wang, Min Zhang, Ping Lu. Adjuvant Treatment Selection for County-Level Patients with HR+/HER2- Early Breast Cancer in a Real-Life Setting in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-08.

Metal Organic Frameworks (MOFs) are a class of highly porous crystalline materials that are constructed from zero- or one-dimensional inorganic chains in combination with multitopic organic ligands.1 They have received great attention recently due to their large surface area, tunable porosity, and easy preparation, which lead to their versatile applications including gas storage2 and separation3, sensing4, catalysis5 and drug delivery6. The versatility of MOFs is further entrenched in the vast available design space offered by the enormous number of metal-linker combinations7, 8. However, majority of MOFs are insulators with very few of them showing appreciable electrical conductivity. The insulating nature of MOFs can be traced back to the starting materials used in constructing these hybrid materials9. Although conductive MOFs have been reported, very little information about the mechanism of charge transport is available.10-12 There are mainly two types of charge transport mechanism reported in such materials, hopping and band transport.13 Hopping mechanism is dominated by movement of charges from donor to acceptor moieties due to charge localization which exists at specific sites within the MOF.13 Band transport relies on delocalization of carriers throughout the valence and conduction bands.14 These mechanisms require low energy pathways for charge transport which are not present in MOFs. Recently, researchers have focused on two synthetic approaches from a chemical perspective to achieve such low energy pathways; through bond approach and through space approach.13 Ideally, both pathways can either lead to band or hopping transport. The through space mechanism utilizes non-covalent interactions like π-π stacking between organic linkers, which creates an extended pathway for charge delocalization usually pronounced in 2D MOFs.15, 16 Recent studies which have successfully quantified and identified charge carrier types in MOFs17 show that conductivity increases mainly with chemical oxidation signifying hole formation18, but mobility and directional charge transfer is still limited by geometry.19 Although the field of electrically conductive MOFs has experienced tremendous expansion in the last decade and yielded a variety of MOFs with high mobility and conductivity, majority of these works focus on material design principle and conductivity measurement, leaving the fundamental understanding of CT mechanism underexplored; yet the latter is essential for the further development of this class of materials to be exploited in optoelectronics, solar cells, and photocatalysis. I will present my progress in exploring CT mechanisms in 2D MOFs using advanced spectroscopic techniques. References C. Janiak and J. K. Vieth, New J. Chem., 2010, 34, 2366-2388. M. Latroche, S. Surble, C. Serre, C. Mellot-Draznieks, P. L. Llewellyn, J. H. Lee, J. S. Chang, S. H. Jhung and G. Ferey, Angewandte Chemie-International Edition, 2006, 45, 8227-8231. Z. J. Zhang, Y. G. Zhao, Q. H. Gong, Z. Li and J. Li, Chem. Commun., 2013, 49, 653-661. E. A. Dolgopolova, A. M. Rice, C. R. Martin and N. B. Shustova, Chem. Soc. Rev., 2018, 47, 4710-4728. Y. X. Zhou, W. H. Hu, S. Z. Yang, Y. B. Zhang, J. Nyakuchena, K. Duisenova, S. Lee, D. H. Fan and J. Huang, Journal of Physical Chemistry C, 2020, 124, 1405-1412. I. A. Lazaro and R. S. Forgan, Coord. Chem. Rev., 2019, 380, 230-259. C. Muschielok and H. Oberhofer, J. Chem. Phys., 2019, 151. L. Sun, M. G. Campbell and M. Dinca, Angewandte Chemie-International Edition, 2016, 55, 3566-3579. P. F. Li and B. Wang, Isr. J. Chem., 2018, 58, 1010-1018. K. W. Nam, S. S. Park, R. dos Reis, V. P. Dravid, H. Kim, C. A. Mirkin and J. F. Stoddart, Nature Communications, 2019, 10, 10. T. Chen, J.-H. Dou, L. Yang, C. Sun, N. J. Libretto, G. Skorupskii, J. T. Miller and M. Dincă, J. Am. Chem. Soc., 2020, 142, 12367-12373. S. S. Park, E. R. Hontz, L. Sun, C. H. Hendon, A. Walsh, T. Van Voorhis and M. Dincă, J. Am. Chem. Soc., 2015, 137, 1774-1777. M. Ko, L. Mendecki and K. A. Mirica, Chem. Commun., 2018, 54, 7873-7891. R. Dong, P. Han, H. Arora, M. Ballabio, M. Karakus, Z. Zhang, C. Shekhar, P. Adler, P. St Petkov, A. Erbe, S. C. B. Mannsfeld, C. Felser, T. Heine, M. Bonn, X. L. Feng and E. Canovas, Nature Materials, 2018, 17, 1027-+. L. Y. Qu, H. Iguchi, S. Takaishi, F. Habib, C. F. Leong, D. M. D'Alessandro, T. Yoshida, H. Abe, E. Nishibori and M. Yamashita, J. Am. Chem. Soc., 2019, 141, 6802-6806. L. S. Xie, E. V. Alexandrov, G. Skorupskii, D. M. Proserpio and M. Dinca, Chemical Science, 2019, 10, 8558-8565.A. C. Hinckley, J. Park, J. Gomes, E. Carlson and Z. Bao, J. Am. Chem. Soc., 2020, 142, 11123-11130. S.

Abstract Downsizing metal nanoparticle catalysts to form single-atom catalysts (SACs) has proven to be one of the best ways to enhance the catalysts’ activity and selectivity1-2 due to their unique characteristics such as nearly 100% atom utilization and well-defined active sites.3 However, the broad application of SACs in catalytic reactions is limited by their poor stability as they possess high surface energy and thus tend to aggregate and form nanoclusters or nanoparticles.4 To address this challenge, various supports such as metal oxides, carbon materials, and porous materials are widely used to stabilize the SACs.5 Metal organic frameworks (MOFs), a class of porous crystalline materials, have proven to be an ideal candidate to support SACs owing to their high surface area, high porosity, and abundant potential anchoring sites.6 It has been shown that immobilizing SACs on MOFs, which forms MOF supported SACs, can integrate the unique properties of SACs and MOFs and led to remarkable catalytic activity, selectivity, and stability toward various catalytic reactions.6-8 Application of MOF supported SACs in photocatalysis, organic linkers of metal-organic frameworks act as photosensitive units,9 However most pristine metal-organic frameworks possesses poor light absorption properties due to wide band gap.9To enhance the light harvesting properties of the metal organic framework its organic linker is functionalized.10-11 In my poster presentation, I will present my work where post-synthetic modification of UiO-66-NH2 MOF linker with 3,4,9,10 perylene tetracarboxylic dianhydride (PDA) an organic molecule with broad absorption edge,12and immobilization of Ni single atom catalyst on the zirconium cluster of the MOF was done. This resulted in enhanced optical properties and charge separation efficiency which was proved by a combination of UV-visible spectroscopy (UV-Vis), photoelectrochemical techniques, and X-ray absorption spectroscopy (XAS). Observed photophysical effects posed by the modifications of the UiO-66-NH2 were evaluated by photocatalytic hydrogen generation. References Yan, J.; Kong, L.; Ji, Y.; White, J.; Li, Y.; Zhang, J.; An, P.; Liu, S.; Lee, S.-T.; Ma, T., Single atom tungsten doped ultrathin α-Ni (OH) 2 for enhanced electrocatalytic water oxidation. Nature communications 2019, 10 (1), 1-10. Jiao, L.; Jiang, H.-L., Metal-organic-framework-based single-atom catalysts for energy applications. Chem 2019, 5 (4), 786-804. Qiao, B.; Wang, A.; Yang, X.; Allard, L. F.; Jiang, Z.; Cui, Y.; Liu, J.; Li, J.; Zhang, T., Single-atom catalysis of CO oxidation using Pt1/FeO x. Nature chemistry 2011, 3 (8), 634-641. Xia, C.; Qiu, Y.; Xia, Y.; Zhu, P.; King, G.; Zhang, X.; Wu, Z.; Kim, J. Y.; Cullen, D. A.; Zheng, D., General synthesis of single-atom catalysts with high metal loading using graphene quantum dots. Nature chemistry 2021, 13 (9), 887-894. Wu, J.; Xiong, L.; Zhao, B.; Liu, M.; Huang, L., Densely populated single atom catalysts. Small Methods 2020, 4 (2), 1900540. Huang, H.; Shen, K.; Chen, F.; Li, Y., Metal–organic frameworks as a good platform for the fabrication of single-atom catalysts. ACS Catalysis 2020, 10 (12), 6579-6586. Qu, W.; Chen, C.; Tang, Z.; Wen, H.; Hu, L.; Xia, D.; Tian, S.; Zhao, H.; He, C.; Shu, D., Progress in metal-organic-framework-based single-atom catalysts for environmental remediation. Coordination Chemistry Reviews 2023, 474, 214855. Szilágyi, P.; Rogers, D.; Zaiser, I.; Callini, E.; Turner, S.; Borgschulte, A.; Züttel, A.; Geerlings, H.; Hirscher, M.; Dam, B., Functionalised metal–organic frameworks: a novel approach to stabilising single metal atoms. Journal of Materials Chemistry A 2017, 5 (30), 15559-15566. He, J.; Wang, J.; Chen, Y.; Zhang, J.; Duan, D.; Wang, Y.; Yan, Z., A dye-sensitized Pt@ UiO-66 (Zr) metal–organic framework for visible-light photocatalytic hydrogen production. Chemical communications 2014, 50 (53), 7063-7066. Elcheikh Mahmoud, M.; Audi, H.; Assoud, A.; Ghaddar, T. H.; Hmadeh, M., Metal–Organic Framework Photocatalyst Incorporating Bis(4′-(4-carboxyphenyl)-terpyridine)ruthenium(II) for Visible-Light-Driven Carbon Dioxide Reduction. Journal of the American Chemical Society 2019, 141 (17), 7115-7121. Hendrickx, K.; Joos, J. J.; De Vos, A.; Poelman, D.; Smet, P. F.; Van Speybroeck, V.; Van Der Voort, P.; Lejaeghere, K., Exploring lanthanide doping in UiO-66: a combined experimental and computational study of the electronic structure. Inorganic Chemistry 2018, 57 (9), 5463-5474. Yu, H.; Joo, P.; Lee, D.; Kim, B. S.; Oh, J. H., Photoinduced Charge‐Carrier Dynamics of Phototransistors Based on Perylene Diimide/Reduced Graphene Oxide Core/Shell p–n Junction Nanowires. Advanced Optical Materials 2015, 3 (2), 241-247.

With the aim of understanding the insertion of higher education into a new context of organization of society and State, which is managed according to the New Public Management, this work presents a comparative historical study of the organization of French and Brazilian higher education. It is concluded that the French adherence to the New Public Management is based on the knowledge economy, while the Brazilian one is based on State size reduction along the lines of the Washington Consensus; in addition, higher education institutions in both countries are organized to participate in competitions: in France, the international competition promoted by rankings, and in Brazil, the market competition.ResumoCom o objetivo de compreender a inserção do ensino superior dentro de um novo contexto de organização da sociedade e do Estado, gerido pela Nova Gestão Pública, o trabalho apresenta um estudo histórico comparativo da organização do ensino superior brasileiro e o francês. Conclui-se que a adesão francesa à Nova Gestão Pública tem como norte a economia do conhecimento, e a brasileira, a redução do Estado nos moldes do Consenso de Washington; e que as instituições de ensino superior nos dois países são organizadas para participarem de concorrências: na França, a internacional promovida pelos ranqueamentos, no Brasil, a mercantil.Palavras-chave: Ensino superior brasileiro, Ensino superior francês, Nova gestão pública, Universidade.Keywords: Brazilian higher education, French higher education, New public management, University.ReferencesAEBISCHER, S. Réinventer l'école, réinventer l'administration. Une loi pédagogique et managériale au prisme de ses producteurs. Politix, n. 98, n.2 p. 57-83 2012/2.AERES. Repères historiques. Agence d’évaluation de la recherche et de l’enseignement supérieur. Disponível em: <www.aeres-evaluation.fr/Agence/Presentation/Reperes-historiques>. Acesso em: 17 nov. 2016.AMARAL, N. C. 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La obesidad y la diabetes mellitus tipo II (DMT2) han sido declaradas pandemias del nuevo siglo, en virtud de su acelerado crecimiento y presencia en la población mundial. Sin embargo, el enfoque empleado en los tratamientos de estas condiciones ha radicado en la atención farmacológica de las comorbilidades asociadas, sin conseguir efectos positivos en la enfermedad en el largo plazo. En tal sentido, la investigación tuvo como objetivo determinar los parámetros básicos de atención de la obesidad y la DMT2, a través de la atención nutricional no farmacológica mediante una revisión bibliográfica en bases de datos atendiendo el contenido científico de cada estudio analizado. La evidencia científica es consistente es señalar que un tipo de alimentación con unaporte bajo en grasa, contenido moderadamente alto en proteínas, hidratos de carbono de bajo índice glucémico es adecuada para mantener y/o restablecer las condiciones de salud en este tipo de paciente. Palabras Clave: Diabetes, Obesidad, Diabesidad, Nutrición. Referencias [1]M. Mangas, A. Martínez y P. García, «“Tratamiento Farmacológico de la Diabesidad”,» Nutr. Clín. Med, vol. VI, nº 1, pp. 34-4, 2012. [2]L. Altamiro, M. Vásquez, G. Cordero, R. Álvarez, R. Añez, J. Rojas y V. Bermúdez, «Prevalencia de la diabetes mellitus tipo 2 y sus factores de riesgo en individuos adultos de la ciudad de Cuenca- Ecuador,» Avances en Biomedicina, vol. 6, nº 1, pp. 10-21, 2017. [3]A. Forero, J. Hernández, S. Rodríguez, J. Romero, G. Morales y G. Ramírez, «La alimentación para pacientes con diabetes mellitus de tipo 2 en tres hospitalespúblicos de Cundinamarca, Colombia,» Biomédica, nº38, pp. 355-362, 2018. [4]S. Durán, E. Carrasco y M. Araya, «Alimentación y diabetes,» Nutrición Hospitalaría, vol. 27, nº 4, pp. 1031-1036, 2012. [5]J. Hernandez, «Recomendaciones para el tratamiento médico de la obesidad exógena en el nivel primario de atención,» Rev cuba med gen integr, vol. 34, nº 3, pp. 123-144, 2018. [6]M. Acebo, «Obesidad y Salud: ¿En realidad existe el paciente obeso metabólicamente sano?,» Respyn, vol. 16, nº 2, p. 44–55, 2017. [7]T. Suarez, J. Sandoval, M. Galván, G. López, A.Olivo, A. J y M. González, «Nutracéuticos: usos potenciales en el tratamiento de la diabetes,» Educacióny Salud Boletín Científico de Ciencias de la Salud del ICSa, vol. 6, nº 12, p. doi: https://doi.org/10.29057/icsa.v6i12.3101, 2018. [8]R. Orellana, E. Salinas, D. Sánchez, J. Guajardo, E. Díaz y F. Rodríguez, «Tratamiento farmacológico de la diabetes mellitus tipo 2 dirigido a pacientes con sobrepeso y obesidad,» Medicina Interna México, vol. 35, nº4, pp. 525-536, 2019. [9]O. Pereira, «Diabesidad: una epidemia del siglo XXI,» Medisan , vol. 16, nº 2, pp. 295-299, 2012. [10]S. Andino, «Evolución de la diabetes mellitus tipo 2 en pacientes obesos mórbidos después del by pass gástrico. Tesis para la obtención del título de posgrado de Doctor en Medicina,» Universidad Católica de Córdoba , Córdoba- Argentina , 2016. [11]A. Muñoz, M. Jiménez, R. Mora, A. Hidalgo y D. Montoya, «Glucosa: amiga o enemiga,» de Diabetes mellitus: el reto a vencer, vol. 44, México, EditorialesFT, S. A., 2013, pp. 9-24. [12]H. Bays, L. Mandarino y R. DeFronzzo, «Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach,» J Clin Endocrinol Metab, vol.89, nº 2, pp. 463-478, 2014. [13]C. Quintanilla y S. Zúñiga, «El efecto incretina y su participación en la diabetes mellitus tipo 2,» Rev Med Inst Mex Seguro Soc, vol. 48, nº 5, pp. 509-520, 2013. [14]L. Baggio y D. Drucker, «Biology of incretins: GLP-1 and GIP,» Gastroenterology, vol. 132, nº 6, pp. 2131-2157, 2014. [15]Z. Cabrera y J. Díaz, «Sobrepeso - obesidad como factor de riesgo a la nefropatía en pacientes diabéticos del Hospital Víctor Lazarte Echegaray.2015,» Cientifi-k , vol. 5, nº 2, pp. 155-201, 2017. [16]F. Abbasi, J. Chu, C. Lamendola, T. McLaughlin, J. Hayden, G. Reaven y et al, «Discrimination between obesity and insulin resistance in the relationship withadiponectin,» Diabetes, vol. 53, nº 3, pp. 585-590, 2014. [17]M. Navarro, I. Jáuregui y G. Herrero, «Trastornos de la conducta alimentaria y diabetes mellitus: Tratamiento nutricional,» vol. 5, nº 9, pp. 914-1066, 2020. [18]A. Forero, J. Hernández, M. Rodríguez, J. Romero, G. Morales y G. Ramirez, «“La alimentación para pacientes con diabetes mellitus de tipo 2 en tres hospitales públicos de Cundinamarca, Colombia,» Biomédica, vol. 38, pp. 355-62, 2018. [19]S. Ramón y G. Medina, «Conocimientos, actitudes y prácticas nutricionales en diabéticos tipo 2 que integran los clubes de diabéticos urbanos, Cuenca, 2015,» Recimundo, vol. 2, pp. 595-610, 2018. [20]A. Prado, M. Mazacón y T. Estrada, «Aspectos nutricionales en la atención del paciente con diabetes,» Universidad, Ciencia y Tecnología, nº 02, pp. 132-139,2019. [21]D. Cárdenas, C. Bermúdez, S. Echeverri, A. Pérez, M. Puentes, L. López, M. Correia, J. Ochoa, A. Ferreira, M. Texeira, D. Arenas, H. Arenas, M. León y D. Rodríguez, «Declaración de Cartagena. declaración internacional sobre el derecho al cuidado nutricional y la lucha contra la malnutrición Cartagena,» Nutr Hosp, vol. 36, nº 4, pp. 974-980, 2019. [22]M. Manrique, M. de la Maza, F. Carrasco, M. Moreno, C. Albala, J. García, J. Díaz y C. Liberman, «Diagnóstico, evaluación y tratamiento no farmacológicodel paciente con sobrepeso u obesidad,» Rev Méd Chile, vol. 137, pp. 963-971, 2009. [23]A. Laparra, «Revisión sistemática y metaanálisis de los diferentes enfoques dietéticos para el tratamiento de la diabetes tipo 2: Lectura Crítica DARE,» Revista española de nutrición humana y dietética , vol. 21, nº 4, pp. 393-396, 2017. [24]F. Represa, «Comorbilidad, control metabólico y calidad de vida en los pacientes diabéticos tipo 2,» Biblioteca Lascasas, 2016. [25]P. Riobó Serván, «“Pautas dietéticas en la diabetes y en la obesidad”,» Nutr. Hosp., vol. 35, nº 4, pp. 109-115, 2018. [26]M. Hernández, M. Batle, B. Martínez, R. San Cristobal, S. Pérez, S. Navas y J. Martínez, «Cambios alimentarios y de estilo de vida como estrategia en la prevención del síndrome metabólico y la diabetes mellitus tipo 2: hitos y perspectivas,» Anales Sis San Navarra , vol. 39, nº 2, pp. 269-289, 2016. [27]R. Li, S. QU , P. Zhang, S. Chattopadhyay , E. Gregg , A. Albright , D. Hopkins y N. Pronk, «Economic evaluation of combined diet and physical activitypromotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the Community Preventive Services,» Ann Intern Med, vol. 163, nº 6, pp. 452-460, 2016. [28]J. López, Envejecimiento y nutrición. Intervención nutricional en pacientes diabéticos, Madrid: Sociedad Española de Geriatría y Gerontología , 2015. [29]I. Brajkovich, M. Izquierdo, R. Nieto y M. Cordero , «Tratamiento no farmacológico: aspectos nutricionales, estilo de vida y actividad física. Cirugía bariátrica,»Revista Venezolana de Endocrinología y Metabolismo, vol. 1, nº 1, pp. 47-57, 2012. [30]O. González, «Manejo nutricional en la diabetes mellitus tipo 2 y obesidad,» Revista Médica, vol. 4, nº1, pp. 22-31, 2014.

Can Gio mangrove forest (CGM) is located downstream of Ho Chi Minh City (HCMC), situated between an estuarine system of Dong Nai - Sai Gon river and a part of Vam Co river. The CGM is the largest restored mangrove forest in Vietnam and the UNESCO’s Mangrove Biosphere Reserve. The CGM has been gradually facing to numeric challenges of global climate change, environmental degradation and socio-economic development for the last decades. To evaluate sediment quality in the CGM, we collected 13 cores to analyze for sediment grain size, organic matter content, and trace element concentration of Cd, Cr, Cu, Ni, Pb, Zn. Results showed that trace element concentrations ranged from uncontaminated (Cd, Cu, and Zn) to very minor contaminated (Cr, Ni, and Pb). The concentrations were gradually influenced by suspended particle size and the mangrove plants.ReferencesAnh M.T., Chi D.H., Vinh N.N., Loan T.T., Triet L.M., Slootenb K.B.-V., Tarradellas J., 2003. 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This paper presents some results of rainfall forecast in the monsoon onset period in South Vietnam, with the use of ensemble Kalman filter to assimilate observation data into the initial field of the model. The study of rainfall forecasts are experimented at the time of Southern monsoon outbreaks for 3 years (2005, 2008 and 2009), corresponding to 18 cases. In each case, there are five trials, including satellite wind data assimilation, upper-air sounding data assimilation, mixed data (satellite wind+upper-air sounding data) assimilation and two controlled trials (one single predictive test and one multi-physical ensemble prediction), which is equivalent to 85 forecasts for one trial. Based on the statistical evaluation of 36 samples (18 meteorological stations and 18 trials), the results show that Kalman filter assimilates satellite wind data to forecast well rainfall at 48 hours and 72 hours ranges. With 24 hour forecasting period, upper-air sounding data assimilation and mixed data assimilation experiments predicted better rainfall than non-assimilation tests. The results of the assessment based on the phase prediction indicators also show that the ensemble Kalman filter assimilating satellite wind data and mixed data sets improve the rain forecasting capability of the model at 48 hours and 72 hour ranges, while the upper-air sounding data assimilation test produces satisfactory results at the 72 hour forecast range, and the multi-physical ensemble test predicted good rainfall at 24 hour and 48 hour forecasts. The results of this research initially lead to a new research approach, Kalman Filter Application that assimilates the existing observation data into input data of the model that can improve the quality of rainfall forecast in Southern Vietnam and overall country in general.References Bui Minh Tuan, Nguyen Minh Truong, 2013. 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BackgroundThe experience of art offers an emerging field in healthcare staff development, much of which is appropriate to the practice of palliative care. The workings of aesthetic learning interventions such as interactive theatre in relation to palliative and end of-life care staff development programmes are widely uncharted.AimTo investigate the use of aesthetic learning interventions used in palliative and end-of-life care staff development programmes.DesignScoping review.Data sourcesPublished literature from 1997 to 2015, MEDLINE, CINAHL and Applied Social Sciences Index and Abstracts, key journals and citation tracking.ResultsThe review included 138 studies containing 60 types of art. Studies explored palliative care scenarios from a safe distance. Learning from art as experience involved the amalgamation of action, emotion and meaning. Art forms were used to transport healthcare professionals into an aesthetic learning experience that could be reflected in the lived experience of healthcare practice. The proposed learning included the development of practical and technical skills; empathy and compassion; awareness of self; awareness of others and the wider narrative of illness; and personal development.ConclusionAesthetic learning interventions might be helpful in the delivery of palliative care staff development programmes by offering another dimension to the learning experience. As researchers continue to find solutions to understanding the efficacy of such interventions, we argue that evaluating the contextual factors, including the interplay between the experience of the programme and its impact on the healthcare professional, will help identify how the programmes work and thus how they can contribute to improvements in palliative care.References. 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The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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A cross-sectional observational study was undertaken in Qu‚bec dairy herds to evaluate regional and provincial prevalences of herds with gastrointestinal nematode (GIN) infections in lactating cows, and to determine risk factors associated with level of herd infection. The 5 most recently calved first-lactation cows from each of 208 randomly selected farms in 7 pre-defined regions of Qu‚bec were sampled for faeces collection in July to August 1995. On the same occasion, a bulk tank milk sample was collected. A questionnaire on replacement and grazing practices was filled out for each farm. Faecal samples were examined and faecal egg counts were determined for trichostrongylids, Capillaria, Nematodirus, Trichuris, Strongyloides, and total GIN eggs. Weighted provincial estimates for prevalence of herds with positive coprologies to these parasites ranged from 4 to 93%. Median faecal egg count per herd was low (17 eggs per 5 g of faeces). Milk samples were submitted for an indirect ELISA test to detect antibodies against Ostertagia and Cooperia. Level of herd infection, as estimated by Ostertagia and Cooperia bulk tank milk ELISA titres (BTTs), varied (P<0.05) among regions. Questionnaire-derived risk factors most significantly associated with an increased bulk tank Ostertagia titre were exposure of lactating cows to pasture, intensive grazing of heifers on farm, contamination history of heifers' pasture, and incomplete pasture rotation for heifers. Very high stocking rates for cows and heifers and mechanical mowing during the grazing season of heifer pastures were associated with decreased ELISA titres. The results of this study indicate that the prevalence of nematode infections in first-lactation cows is very high in Qu‚bec herds, with trichostrongylid infections being the most frequently observed. The association between bulk tank milk ELISA titres for Ostertagia and herd-level management practices capable of having an impact on exposure of cows to parasites suggest that BTTs could be a valuable indicator of herd infection level. Proper knowledge of regional prevalences, differences among mean regional titres, and the association between titres and of herd-level risk factors can help veterinarians with their decisions regarding parasite prevention and treatment.

Abstract Background The impact of COVID-19 towards psychology and mental health is anticipated to be significant and may affect the population disproportionately, especially adolescent as the vulnerable category. We aimed to analyze the impact of COVID-19 towards adolescents’ mental health. Main body A systematic search was conducted from Cochrane, Google Scholar, Scielo, and PubMed. Inclusion criteria included all types of studies which observed the effect of COVID-19 and its related causes, such as lockdown, on adolescents’ mental health. All studies were assessed for its level of evidence according to Oxford 2011 criteria and Newcastle Ottawa Scale (NOS). Three studies (Seçer and Ulaş, Int J Ment Health Addict: 1–14, 2020; Zhou et al., Eur Child Adolesc Psychiatry 29:749–58, 2020; Qu et al., Lancet: 1–17, 2020) showed that COVID-19 was a risk factor for mental health problems in adolescents while Oosterhoff et al. (J Adolesc Health 67: 179–185, 2020) showed that adolescents who preferred to stay at home during this pandemic reported less anxiety and depressive symptoms Conclusion COVID-19 has been found to be associated with mental health changes in adolescents which meant management of COVID-19 should also focus on mental health as well.

Enforcers are State officials, assigned tasks and powers in the process of executing legally effective judgments and decisions of courts and competent agencies. In order to ensure impartiality and objectivity in the course of performing their duties and powers, the Law on enforcement of Civil Judgments provides for things that enforcers must not do. This article analyzes some inadequacies and proposes to amend and supplement the provisions of Article 21 of the Law on enforcement of civil judgments on things that enforcers must not do. Keywords: enforcers; law on enforcement of civil judgments, impartial, objective, relatives. References: [1]. Điều 17 Luật Thi hành án dân sự 2008[2]. Điều 2 Luật Thi hành án dân sự 2008[3]. Điều 21 Luật Thi hành án dân sự 2008[4]. Hoàng Thảo Hà – Nghề Chấp hành viênhttps://thads.moj.gov.vn/quangninh/noidung/tintuc/lists/nghiencuutraodoi/viewdetail.aspx?itemid=40[5]https://dantri.com.vn/ban-doc/sau-loat-bai-dieu-tra-cua-dan-tri-hai-nguyen-can-bo-thi-hanh-an-chuan-bi-hau-toa-20180806081141529.htm[6]https://dantri.com.vn/ban-doc/binh-dinh-can-bo-thi-hanh-an-bi-to-hien-ke-de-bi-don-tau-tan-tai-san-20160608083218809.htm[7] Khoản 1 Điều 10, Nghị định số 62/2015/NĐ-CP ngày 18/7/2015[8]https://baophapluat.vn/tu-phap/lung-tung-ap-dung-quyen-yeu-cau-thay-doi-chap-hanh-vien-cua-nguoi-duoc-thi-hanh-an-387078.html[9] Khoản 1 Điều 651 Bộ luật dân sự 2015[10] Khoản 1 Điều 13, Nghị quyết 03/2012/NQ-HĐTP - Hướng dẫn thi hành một số quy định trong phần thứ nhất “Những quy định chung” của Bộ luật tố tụng dân sự đã được sửa đổi, bổ sung theo Luật sửa đổi, bổ sung một số điều của Bộ luật tố tụng dân sự: [11]https://vietnam.unfpa.org/vi/news/k%E1%BA%BFt-qu%E1%BA%A3-t%E1%BB%95ng-%C4%91i%E1%BB%81u-tra-d%C3%A2n-s%E1%BB%91-v%C3%A0-nh%C3%A0-%E1%BB%9F-n%C4%83m-2019

This study uses an in silico screening docking model to evaluate the ACE2 inhibitory activity of natural compounds and drugs. The study collected 49 compounds and evaluated the ACE2 inhibitory effect in silico. The study results show that 11 out of the 49 compounds had stronger inhibitory activity on ACE2 than MLN-4760. Lipinski’s rule of five criteria and predictive pharmacokinetic-toxicity analysis show that eight compounds including quercetin, galangin, quisinostat, fluprofylline, spirofylline, RS 504393, TNP and GNF-5 had drug-likeness. These compounds could be potential drug for the Covid-19 treatment. Keywords SARS-CoV-2S, Covid-19, ACE2, molecular docking, in silico. References [[1] C. Wang, P.W. Horby, F.G. Hayden, G.F. Gao. A novel coronavirus outbreak of global health concern. The Lancet 395(10223) (2020) 470.[2] WHO. WHO Coronavirus Disease (COVID-19) Dashboard. WHO, 2020.[3] N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 395(10223) (2020) 507.[4] J. Yang, Y. Zheng, X. Gou, K. Pu, Z. Chen, Q. Guo, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International Journal of Infectious Diseases 94 (2020) 91.[5] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 395(10224) (2020) 565.[6] R. Hilgenfeld. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS journal 281(18) (2014) 4085.[7] D. Wrapp, N. Wang, K.S. Corbett, J.A. Goldsmith, C.L. Hsieh, O. Abiona, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, NY) 367(6483) (2020) 1260.[8] P.A. Rota, M.S. Oberste, S.S. Monroe, W.A. Nix, R. Campagnoli, J.P. Icenogle, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science (New York, NY) 300(5624) (2003) 1394.[9] M. Donoghue, F. Hsieh, E. Baronas, K. Godbout, M. Gosselin, N. Stagliano, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation research 87(5) (2000) E1.[10] H. Zhang, Z. Kang, H. Gong, D. Xu, J. Wang, Z. Li, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv (2020) 2020.01.30.927806.[11] Y. Zhao, Z. Zhao, Y. Wang, Y. Zhou, Y. Ma, W. Zuo. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv (2020) 2020.01.26.919985.[12] E.I. Bahbah, A. Negida, M.S. Nabet. Purposing Saikosaponins for the treatment of COVID-19. Med Hypotheses 140 (2020) 109782.[13] I.W. Cheung, S. Nakayama, M.N. Hsu, A.G. Samaranayaka, E.C. Li-Chan. Angiotensin-I converting enzyme inhibitory activity of hydrolysates from oat (Avena sativa) proteins by in silico and in vitro analyses. Journal of agricultural and food chemistry 57(19) (2009) 9234.[14] T. Joshi, T. Joshi, P. Sharma, S. Mathpal, H. Pundir, V. Bhatt, et al. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. European review for medical and pharmacological sciences 24(8) (2020) 4529.[15] S. Shahid, A. Kausar, M. Khalid, S. Tewari, T. Alghassab, T. Acar, et al. analysis of binding properties of angiotensin-converting enzyme 2 through in silico molecular docking, 2018.[16] K. Teralı, B. Baddal, H.O. Gülcan. Prioritizing potential ACE2 inhibitors in the COVID-19 pandemic: Insights from a molecular mechanics-assisted structure-based virtual screening experiment. J Mol Graph Model 100 (2020) 107697.[17] M. Muchtaridi, M. Fauzi, N.K. Khairul Ikram, A. Mohd Gazzali, H.A. Wahab. Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2. Molecules 25(17) (2020) 3980.[18] M.J. Huentelman, J. Zubcevic, J.A. Hernández Prada, X. Xiao, D.S. Dimitrov, M.K. Raizada, et al. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension (Dallas, Tex : 1979) 44(6) (2004) 903.[19] S. Choudhary, Y.S. Malik, S. Tomar. Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Front Immunol 11((2020) 1664.[20] C.A. Lipinski. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies 1(4) (2004) 337.[21] B. Jayaram, T. Singh, G. Mukherjee, A. Mathur, S. Shekhar, V. Shekhar, Eds. Sanjeevini: a freely accessible web-server for target directed lead molecule discovery. Proceedings of the BMC bioinformatics; 2012. Springer (Year).[22] D.E. Pires, T.L. Blundell, D.B. Ascher. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry 58(9) (2015) 4066.[23] P. Towler, B. Staker, S.G. Prasad, S. Menon, J. Tang, T. Parsons, et al. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. The Journal of biological chemistry 279(17) (2004) 17996.[24] N.A. Dales, A.E. Gould, J.A. Brown, E.F. Calderwood, B. Guan, C.A. Minor, et al. Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. Journal of the American Chemical Society 124(40) (2002) 11852.[25] P. Pandey, J.S. Rane, A. Chatterjee, A. Kumar, R. Khan, A. Prakash, et al. Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development. Journal of Biomolecular Structure and Dynamics (2020) 1.[26] C.A. Lipinski. Lead- and drug-like compounds: the rule-of-five revolution. Drug discovery today Technologies 1(4) (2004) 337.[27] R.O. Barros, F.L. Junior, W.S. Pereira, N.M. Oliveira, R.M. Ramos. Interaction of drug candidates with various SARS-CoV-2 receptors: An in silico study to combat COVID-19. Journal of Proteome Research (2020).

Angiogenesis plays a crucial role in the proliferation, invasion and metastasis of cancer cells. Unlike conventional chemotherapy, anti-angiogenesis drugs inhibit the formation of new blood vessels, reduce the nutrition and oxygen supply to the tumour, thus halting disease progression. In the last fifteen years, Food and Drug Administration of the United States has approved more than ten anti-cancer drugs of this group, namely the monoclonal antibody bevacizumab and small molecules drugs such as temsirolimus, sunitinib, axitinib and sorafenib. Other anti-angiogenesis agents are currently undergoing clinical trials. In addition to treating cancer, these agents have also potential applications in the treatment of complications related to angiogenesis in diabetes, arthritis, psoriasis and collagen-related diseases. Keywords Anti-angiogenesis, angiogenesis, cancer, metastasis, treatment. References [1] International Agency for Research on Cancer WHO, International agency for research on cancer – world health organization. https://www.iarc.fr/featured-news/latest-global-cancer-data-cancer-burden-rises-to-18-1-million-new-cases-and-9-6-million-cancer-deaths-in-2018 (accessed 19 February 2019).[2] International Agency for Research on Cancer France, Cancer today - International agency for research on cancer – world health organization. https://gco.iarc.fr(accessed 19 February 2019).[3] D.W. Siemann, M.C. Bibby, G.G. Dark, A.P. Dicker, FALM. Eskens, et al. Differentiation and Definition of Vascular-Targeted Therapies. Clinical Cancer Research. 11(2) (2005) 416–420.[4] J. Folkman, Tumor angiogenesis: therapeutic implications, The New England Journal of Medicine. 285(21) (1971) 1182-1186.[5] D. Hanahan, J. Folkman. Patterns of emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 86(3) (1996) 353–64.[6] G. Gasparini. The rationale and future potential of angiogenesis inhibitors in neoplasia. Drugs. 58(1) (1999) 17-38.[7] J. Folkman, E. Braunwald, A.S. Fauci, D.L. Kasper, S.L. Hauser, D.L. Longo, J.L. Jameson, editors. Angiogenesis. Harrison’s textbook of internal medicine. fifteen ed. McGraw-Hill, New York, 2001. pp. 517–530.[8] J. Folkman. Angiogenesis research: From Laboratory to clinic. Forum Genova. 9(3) (1999) 59–62.[9] S. Liekens, E. De Clercq, J. Neyts. Angiogenesis: Regulators and clinical applications. Biochemical Pharmacology. 61(3) (2001) 253–270.[10] L. Rosen. Clinical experience with angiogenesis signaling inhibitors: Focus on vascular endothelial growth factor (VEGF) blockers, Cancer Control. 9(2) (2002) 36-44.[11] A.L. Harris. Angiogenesis as a new target for cancer control. European Journal of Cancer Supplements. 1(2) (2003) 1-12.[12] D.W. Siemann. Vascular Targeting Agents. horizons in cancer therapeutics from bench to bedside. 3(2) (2002) 4–15.[13] B.G. Wouters, S.A. Weppler, M. Koritzinsky, W. Landuyt, S. Nuyts, et al. Hypoxia as a target for combined modality treatments, European Journal of Cancer. 38(2) (2002) 240–257.[14] P. Carmeliet, R.K. Jain. Angiogenesis in cancer and other diseases. Nature. 407(6801) (2000) 249-257.[15] J.W. Rak, B.D. St. Croix, R.S. Kerbel. Consequences of angiogenesis for tumor progression, metastasis and cancer therapy. Anticancer Drugs. 6(1) (1995) 3–18.[16] J. Hamada, P.G. Cavanaugh, O. Lotan, G.L. Nicolson. Separable growth and migration factors for large-cell lymphoma cells secreted by microvascular endothelial cells derived from target organs for metastasis. British Journal of Cancer. 66(2) (1992) 349-54.[17] J. Denekamp. Vascular attack as a therapeutic strategy for cancer. Cancer and Metastasis Reviews. 9(3) (1990) 267–282.[18] J. Denekamp. Angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. The British Institute of Radiology. 66(783) (1993) 181–186.[19] H.P. Eikesdal, H. 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The geometries, stabilities of VGen0/- (n = 9 - 13) clusters were systematically studied by the density functional theory (DFT) using the BP86 functional and LANL2DZ basis set. Several possible multiplicities of each cluster were tested to determine the most stable structure among the isomers. The average binding energy per atom, fragmentation energy, second order energy difference and HOMO-LUMO gaps were evaluated. The results indicated that the neutral and anionic clusters possess higher stability when n = 10 and 12. The vertical detachment energy (VDE) and adiabatic detachment energy (ADE) were also calculated for anionic cluster to investigate their stabilities. Among neutral clusters, VGe10 had both the highest vertical ionization potential (VIP) and chemical hardness. Keywords BP86/LANL2DZ, binding energy, VGen0/- clusters, structure of clusters References [1] Shunping Shi, Yiliang Liu, Chuanyu Zhang, Banglin Deng, Gang Jiang (2015). A Computational Investigation of Aluminum-doped Germanium Clusters by Density Functional Theory Study. Computational and Theoretical Chemistry, 1054, pp. 8-15[2] Wen-Jie Zhao, Yuan-Xu Wang (2009). Geometries, stabilities, and Magnetic Properties of MnGen (n = 2 – 16) Clusters: Density-functional Theory Investigations. Journal of Molecular Structure: THEOCHEM, 901 (1–3), pp. 18-23.[3] Shi Shun-Ping, Liu Yi-Liang, Deng Bang-Lin, Zhang Chuan-Yu, and Jiang Gang (2016). Density Functional Theory Study of The Geometrical and Electronic Structures of (n = 1 - 9) clusters. World Scientific Publishing Company, 30, pp. 1750022-1750039.[4] J.Stato, H.Kobayashi, K. Ikarashi, N.Saito, H.Nishiyama, and Y. Inoue (2004). Photocatalitic Activity for Water Decomposition of RuO2-Dispersed Zn2GeO4 with d10 Configuration. The Journal of Physical Chemistry B, 108 (14), pp. 4369-4375.[5] Daoxin Dai, Molly Piels, and John E. Bowers (2014). Monolithic Germanium/Silicon Photodetectors With Decoupled Structures: Resonant APDs and UTC Photodiodes. IEEE Journal of Selected Topics in Quantum Electronics, 20 (6), pp. 3802214-3802227.[6] Chia-Yun Chou, Gyeong S. Hwang (2014). On The Origin of The Significant Difference in Lithiation Behavior Between Silicon and Germanium. Journal of Power Sources, 263, pp. 252-258.[7] Siwen Zhang, Bosi Yin, Yang Jiao, Yang Liu, Xu Zhang, Fengyu Qu, Ahmad Umar, Xiang Wu (2014). Ultra-long Germanium Oxide Nanowires: Structures and Optical Properties. Journal of Alloys and Compounds, 606, pp. 149-153.[8] T. Herrmannsdörfer, V. Heera, O. Ignatchik, M. Uhlarz, A. Mücklich, M. Posselt, H. Reuther, B. Schmidt, K.-H. Heinig, W. Skorupa, M. Voelskow, C. Wündisch, R. Skrotzki, M. Helm, and J. Wosnitza (2009).Superconducting State in a Gallium-Doped Germanium Layer at Low Temperatures. Physical Review Letters, 102, pp. 217003-217006.[9] Vijay Kumar, and Yoshiyuki Kawazoe (2002). Metal-Encapsulated Caged Clusters of Germanium with Large Gaps and Different Growth Behavior than Silicon. Physical Review Letters, 88, pp. 235504-235507.[10] Xiao-Jiao Deng, Xiang-Yu Kong, Hong-Guang Xu, Xi-Ling Xu, Gang Feng, and Wei-Jun Zheng (2015). Photoelectron Spectroscopy and Density Functional Calculations of VGen- (n = 3 − 12) Clusters. The Journal of Physical Chemistry C, 119 (20), pp. 11048-11055.[11] John P. Perdew, Kieron Burke, and Matthias Ernzerhof (1996).Generalized Gradient Approximation Made Simple. Physical Review Letters, 77, pp. 3865-3868.[12] Chaouki Siouani, Sofiane Mahtout, Sofiane Safer, and Franck Rabilloud (2017).Structure, Stability and Electronic and Magnetic Properties of VGen (n = 1 - 19) Clusters. 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Medicinal plants are a potential source of enzyme acetylcholinesrerase (AChE) inhibitors, a key target in the treatment of Alzheimer’s disease. This paper studies the AChE inhibitory activity and the antioxidant effect of Persea Americana Mill extract. The sample leave, seed, exocarp and mesocarp of avocado were extracted with 50% ethanol and subsequently fractionated with n-hexane, ethyl acetate (EtOA) and n-butanol (n-BuOH) solvents. The AChE inhibitory activity was evaluated by Ellman’s colorimetric method and the antioxidant activity by screening DPPH free radicals. The results show that the seed of Persea Americana extract had the strongest AChE inhibitory activity and antioxidant effect, followed by the leave extract, and the exocarp extract and mesocarp extract were the weakest. The Persea Americana seed extract inhibited AChE activity in a dose-dependent manner with an IC50 value of 47.43 ± 0.5 μg/mL and the antioxidant effect with an IC50 value of 68.7 ± 0.35 µg/mL. The results also show that n–BuOH fraction of Persea Americana seed extract had strong AChE inhibitory and antioxidant activities with an IC50 value of 15.24 ± 0.52 µg/ml and 15.73 ± 0.42 μg/mL, respectively. The study results suggest that the Persea Americana Mill is a promising ingredient in Alzheimer’s disease prevention and treatment. Keywords Persea Americana Mill, Acetylcholinesrerase inhibitors (AChE), Alzheimer, DPPH. References [1] M.M. Essa et al., Neuroprotective effect of natural products against Alzheimer's disease, Neurochem Res. 37(9) (2012) 1829.[2] B. McGleenon, K. Dynan, A. Passmore,. Acetylcholinesterase inhibitors in Alzheimer's disease, British journal of clinical pharmacology. 48 (1999) 471.[3] P. B. Watkins et al, Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease, In: Jama. pp. 992 (1994).[4] O. Adeyemi, S. Okpo, O. Ogunti,. 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Olufemi, Antioxidant properties of Persea americana M. seed as affected by different extraction solvent, Journal of Advances in Food Science & Technology. 3(2) (2016) 101.[18] C.A. Alagbaoso, I.I. Tokunbo, O.S. Osakwe, Comparative study of antioxidant activity and mineral composition of methanol extract of seeds of ripe and unripe avocado pear (Persea americana, Mill.). NISEB Journal. 15(4) (2017).[19] G. Oboh, V.O. Odubanjo, F. Bello, A.O. Ademosun, S.I. Oyeleye, E.E. Nwanna et al. Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro, Journal of basic and clinical physiology and pharmacology. 27(2) (2016) 131.[20] H. Cavdar, M. Senturk, M. Guney , S. Durdagi, G. Kayik, C.T. Supuran, et al. Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies, Journal of enzyme inhibition and medicinal chemistry. 34(1) (2019) 429.

Alloys used in engines are subjected to challenging environments characterized by thermal and mechanical cyclic loadings during start-up and shut-down processes. These conditions can significantly increase the occurrence of fatigue failure mechanisms. Therefore, this study focuses on investigating the low cycle fatigue (LCF) behavior of directionally-solidified alloy at two distinct temperatures, namely 600 °C and 800 °C. Strain-controlled LCF tests were conducted at the specified temperatures, utilizing constant total strain amplitudes of 0.4%, 0.6%, 0.8%, and 1% under a totally reversed loading ratio (R = -1). The Coffin-Manson model, based on plastic deformation, along with a hysteresis energy-based criterion model, were employed to predict and evaluate fatigue life and LCF behavior. Notably, the hysteresis energy and Coffin-Manson models exhibited superior capability in predicting LCF life at 800 °C compared to 600 °C. REFERENCES Salehnasab, J. Marzbanrad, E. 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Babies and toddlers are amassing huge followings on social media, achieving microcelebrity status, and raking in five figure sums. In East Asia, many of these lucrative “micro­-microcelebrities” rise to fame by inheriting exposure and proximate microcelebrification from their social media Influencer mothers. Through self-branding techniques, Influencer mothers’ portrayals of their young’ children’s lives “as lived” are the canvas on which (baby) products and services are marketed to readers as “advertorials”. In turning to investigate this budding phenomenon, I draw on ethnographic case studies in Singapore to outline the career trajectory of these young children (under 4yo) including their social media presence, branding strategies, and engagement with their followers. The chapter closes with a brief discussion on some ethical considerations of such young children’s labour in the social media age.Influencer MothersTheresa Senft first coined the term “microcelebrity” in her work Camgirls as a burgeoning online trend, wherein people attempt to gain popularity by employing digital media technologies, such as videos, blogs, and social media. She describes microcelebrities as “non-actors as performers” whose narratives take place “without overt manipulation”, and who are “more ‘real’ than television personalities with ‘perfect hair, perfect friends and perfect lives’” (Senft 16), foregrounding their active response to their communities in the ways that maintain open channels of feedback on social media to engage with their following.Influencers – a vernacular industry term albeit inspired by Katz & Lazarsfeld’s notion of “personal influence” that predates Internet culture – are one type of microcelebrity; they are everyday, ordinary Internet users who accumulate a relatively large following on blogs and social media through the textual and visual narration of their personal lives and lifestyles, engage with their following in “digital” and “physical” spaces, and monetize their following by integrating “advertorials” into their blog or social media posts and making physical appearances at events. A pastiche of “advertisement” and “editorial”, advertorials in the Influencer industry are highly personalized, opinion-laden promotions of products/services that Influencers personally experience and endorse for a fee. Influencers in Singapore often brand themselves as having “relatability”, or the ability to persuade their followers to identify with them (Abidin). They do so by make consciously visible the backstage (Goffman) of the usually “inaccessible”, “personal”, and “private” aspects of mundane, everyday life to curate personae that feel “authentic” to fans (Marwick 114), and more accessible than traditional celebrity (Senft 16).Historically, the Influencer industry in Singapore can be traced back to the early beginnings of the “blogshop” industry from the mid-2000s and the “commercial blogging” industry. Influencers are predominantly young women, and market products and services from diverse industries, although the most popular have been fashion, beauty, F&B, travel, and electronics. Most prominent Influencers are contracted to management agencies who broker deals in exchange for commission and assist in the production of their vlogs. Since then, the industry has grown, matured, and expanded so rapidly that Influencers developed emergent models of advertorials, with the earliest cohorts moving into different life stages and monetizing several other aspects of their personal lives such as the “micro-microcelebrity” of their young children. What this paper provides is an important analysis of the genesis and normative practices of micro-microcelebrity commerce in Singapore from its earliest years, and future research trajectories in this field.Micro-Microcelebrity and Proximate MicrocelebrificationI define micro-microcelebrities as the children of Influencers who have themselves become proximate microcelebrities, having derived exposure and fame from their prominent Influencer mothers, usually through a more prolific, deliberate, and commercial form of what Blum-Ross defines as “sharenting”: the act of parents sharing images and stores about their children in digital spaces such as social networking sites and blogs. Marwick (116-117), drawing from Rojek’s work on types of celebrity – distinguishes between two types of microcelebrity: “ascribed microcelebrity” where the online personality is made recognizable through the “production of celebrity media” such as paparazzi shots and user-produced online memes, or “achieved microcelebrity” where users engage in “self-presentation strateg[ies]”, such as fostering the illusion of intimacy with fans, maintaining a persona, and selective disclosure about oneself.Micro-microcelebrities lie somewhere between the two: In a process I term “proximate microcelebrification”, micro-microcelebrities themselves inherit celebrity through the preemptive and continuous exposure from their Influencer mothers, many beginning even during the pre-birth pregnancy stages in the form of ultrasound scans, as a form of “achieved microcelebrity”. Influencer mothers whose “presentational strategies” (cf. Marshall, “Promotion” 45) are successful enough (as will be addressed later) gain traction among followers, who in turn further popularize the micro-microcelebrity by setting up fan accounts, tribute sites, and gossip forums through which fame is heightened in a feedback loop as a model of “ascribed microcelebrity”.Here, however, I refrain from conceptualizing these young stars as “micro-Influencers” for unlike Influencers, these children do not yet curate their self-presentation to command the attention of followers, but instead are used, framed, and appropriated by their mothers for advertorials. In other words, Influencer mothers “curate [micro-microcelebrities’] identities into being” (Leaver, “Birth”). Following this, many aspects of their micro-microcelebrities become rapidly commodified and commercialized, with advertisers clamoring to endorse anything from maternity hospital stays to nappy cream.Although children of mommybloggers have the prospect to become micro-microcelebrities, both groups are conceptually distinct. Friedman (200-201) argues that among mommybloggers arose a tension between those who adopt “the raw authenticity of nonmonetized blogging”, documenting the “unglamorous minutiae” of their daily lives and a “more authentic view of motherhood” and those who use mommyblogs “primarily as a source of extra income rather than as a site for memoir”, focusing on “parent-centered products” (cf. Mom Bloggers Club).In contrast, micro-microcelebrities and their digital presence are deliberately commercial, framed and staged by Influencer mothers in order to maximize their advertorial potential, and are often postured to market even non-baby/parenting products such as fast food and vehicles (see later). Because of the overt commerce, it is unclear if micro-microcelebrity displays constitute “intimate surveillance”, an “almost always well-intentioned surveillance of young people by parents” (Leaver, “Born” 4). Furthermore, children are generally peripheral to mommybloggers whose own parenting narratives take precedence as a way to connect with fellow mothers, while micro-microcelebrities are the primary feature whose everyday lives and digital presence enrapture followers.MethodologyThe analysis presented is informed by my original fieldwork with 125 Influencers and related actors among whom I conducted a mixture of physical and digital personal interviews, participant observation, web archaeology, and archival research between December 2011 and October 2014. However, the material presented here is based on my digital participant observation of publicly accessible and intentionally-public digital presence of the first four highly successful micro-microcelebrities in Singapore: “Baby Dash” (b.2013) is the son of Influencer xiaxue, “#HeYurou” (b.2011) is the niece of Influencer bongqiuqiu, “#BabyElroyE” (b.2014) is the son of Influencer ohsofickle, and “@MereGoRound” (b.2015) is the daughter of Influencer bongqiuqiu.The microcelebrity/social media handles of these children take different forms, following the platform on which their parent/aunt has exposed them on the most. Baby Dash appears in all of xiaxue’s digital platforms under a variety of over 30 indexical, ironic, or humourous hashtags (Leaver, “Birth”) including “#pointylipped”, #pineappledash”, and “#面包脸” (trans. “bread face”); “#HeYurou” appears on bongqiuqiu’s Instagram and Twitter; “#BabyElroyE” appears on ohsofickle’s Instagram and blog, and is the central figure of his mother’s new YouTube channel; and “@MereGoRound” appears on all of bongqiuqiu’s digital platforms but also has her own Instagram account and dedicated YouTube channel. The images reproduced here are screenshot from Influencer mothers’ highly public social media: xiaxue, bongqiuqiu, and ohsofickle boast 593k, 277k, and 124k followers on Instagram and 263k, 41k, and 17k followers on Twitter respectively at the time of writing.Anticipation and Digital EstatesIn an exclusive front-pager (Figure 1) on the day of his induced birth, it was announced that Baby Dash had already received up to SGD25,000 worth of endorsement deals brokered by his Influencer mother, xiaxue. As the first micro-microcelebrity in his cohort (his mother was among the pioneer Influencers), Baby Dash’s Caesarean section was even filmed and posted on xiaxue’s YouTube channel in three parts (Figure 2). xiaxue had announced her pregnancy on her blog while in her second trimester, following which she consistently posted mirror selfies of her baby bump.Figure 1 & 2, screenshot April 2013 from ‹instagram.com/xiaxue›In her successful attempt at generating anticipation, the “bump” itself seemed to garner its own following on Twitter and Instagram, with many followers discussing how the Influencer dressed “it”, and how “it” was evolving over the weeks. One follower even compiled a collage of xiaxue’s “bump” chronologically and gifted it to the Influencer as an art image via Twitter on the day she delivered Baby Dash (Figure 3 & 4). Followers also frequently speculated and bantered about how her baby would look, and mused about how much they were going to adore him. Figure 3 & 4, screenshot March 2013 from ‹twitter.com/xiaxue› While Lupton (42) has conceptualized the sharing of images that precede birth as a “rite of passage”, Influencer mothers who publish sonograms deliberately do so in order to claim digital estates for their to-be micro-microcelebrities in the form of “reserved” social media handles, blog URLs, and unique hashtags for self-branding. For instance, at the 3-month mark of her pregnancy, Influencer bongqiuqiu debuted her baby’s dedicated hashtag, “#MereGoRound” in a birth announcement on her on Instagram account. Shortly after, she started an Instagram account, “@MereGoRound”, for her baby, who amassed over 5.5k followers prior to her birth. Figure 5 & 6, screenshot March 2015 from instagram.com/meregoround and instagram.com/bongqiuqiuThe debut picture features a heavily pregnant belly shot of bongqiuqiu (Figure 5), creating much anticipation for the arrival of a new micro-microcelebrity: in the six months leading up to her birth, various family, friends, and fans shared Instagram images of their gifts and welcome party for @MereGoRound, and followers shared congratulations and fan art on the dedicated Instagram hashtag. During this time, bongqiuqiu also frequently updated followers on her pregnancy progress, not without advertising her (presumably sponsored) gynecologist and hospital stay in her pregnancy diaries (Figure 6) – like Baby Dash, even as a foetus @MereGoRound was accumulating advertorials. Presently at six months old, @MereGoRound boasts almost 40k followers on Instagram on which embedded in the narrative of her growth are sponsored products and services from various advertisers.Non-Baby-Related AdvertorialsPrior to her pregnancy, Influencer bongqiuqiu hopped onto the micro-microcelebrity bandwagon in the wake of Baby Dash’s birth, by using her niece “#HeYurou” in her advertorials. Many Influencers attempt to naturalize their advertorials by composing their post as if recounting a family event. With reference to a child, parent, or partner, they may muse or quip about a product being used or an experience being shared in a bid to mask the distinction between their personal and commercial material. bongqiuqiu frequently posted personal, non-sponsored images engaging in daily mundane activities under the dedicated hashtag “#HeYurou”.However, this was occasionally interspersed with pictures of her niece holding on to various products including storybooks (Figure 8) and shopping bags (Figure 9). At first glance, this might have seemed like any mundane daily update the Influencer often posts. However, a close inspection reveals the caption bearing sponsor hashtags, tags, and campaign information. For instance, one Instagram post shows #HeYurou casually holding on to and staring at a burger in KFC wrapping (Figure 7), but when read in tandem with bongqiuqiu’s other KFC-related posts published over a span of a few months, it becomes clear that #HeYurou was in fact advertising for KFC. Figure 7, 8, 9, screenshot December 2014 from ‹instagram.com/bongqiuqiu›Elsewhere, Baby Dash was incorporated into xiaxue’s car sponsorship with over 20 large decals of one of his viral photos – dubbed “pineapple Dash” among followers – plastered all over her vehicle (Figure 10). Followers who spot the car in public are encouraged to photograph and upload the image using its dedicated hashtag, “#xiaxuecar” as part of the Influencer’s car sponsorship – an engagement scarcely related to her young child. Since then, xiaxue has speculated producing offshoots of “pineapple Dash” products including smartphone casings. Figure 10, screenshot December 2014 from ‹instagram.com/xiaxue›Follower EngagementSponsors regularly organize fan meet-and-greets headlined by micro-microcelebrities in order to attract potential customers. Photo opportunities and the chance to see Baby Dash “in the flesh” frequently front press and promotional material of marketing campaigns. Elsewhere on social media, several Baby Dash fan and tribute accounts have also emerged on Instagram, reposting images and related media of the micro-microcelebrity with overt adoration, no doubt encouraged by xiaxue, who began crowdsourcing captions for Baby Dash’s photos.Influencer ohsofickle postures #BabyElroyE’s follower engagement in a more subtle way. In her YouTube channel that debut in the month of her baby’s birth, ohsofickle produces video diaries of being a young, single, mother who is raising a child (Figure 11). In each episode, #BabyElroyE is the main feature whose daily activities are documented, and while there is some advertising embedded, ohsofickle’s approach on YouTube is much less overt than others as it features much more non-monetized personal content (Figure 12). Her blog serves as a backchannel to her vlogs, in which she recounts her struggles with motherhood and explicitly solicits the advice of mothers. However, owing to her young age (she became an Influencer at 17 and gave birth at 24), many of her followers are teenagers and young women who respond to her solicitations by gushing over #BabyElroyE’s images on Instagram. Figure 11 & 12, screenshot September 2015 from ‹instagram.com/ohsofickle›PrivacyAs noted by Holloway et al. (23), children like micro-microcelebrities will be among the first cohorts to inherit “digital profiles” of their “whole lifetime” as a “work in progress”, from parents who habitually underestimate or discount the privacy and long term effects of publicizing information about their children at the time of posting. This matters in a climate where social media platforms can amend privacy policies without user consent (23), and is even more pressing for micro-microcelebrities whose followers store, republish, and recirculate information in fan networks, resulting in digital footprints with persistence, replicability, scalability, searchability (boyd), and extended longevity in public circulation which can be attributed back to the children indefinitely (Leaver, “Ends”).Despite minimum age restrictions and recent concerns with “digital kidnapping” where users steal images of other young children to be re-posted as their own (Whigham), some social media platforms rarely police the proliferation of accounts set up by parents on behalf of their underage children prominently displaying their legal names and life histories, citing differing jurisdictions in various countries (Facebook; Instagram), while others claim to disable accounts if users report an “incorrect birth date” (cf. Google for YouTube). In Singapore, the Media Development Authority (MDA) which governs all print and digital media has no firm regulations for this but suggests that the age of consent is 16 judging by their recommendation to parents with children aged below 16 to subscribe to Internet filtering services (Media Development Authority, “Regulatory” 1). Moreover, current initiatives have been focused on how parents can impart digital literacy to their children (Media Development Authority, “Empowered”; Media Literacy Council) as opposed to educating parents about the digital footprints they may be unwittingly leaving about their children.The digital lives of micro-microcelebrities pose new layers of concern given their publicness and deliberate publicity, specifically hinged on making visible the usually inaccessible, private aspects of everyday life (Marshall, “Persona” 5).Scholars note that celebrities are individuals for whom speculation of their private lives takes precedence over their actual public role or career (Geraghty 100-101; Turner 8). However, the personae of Influencers and their young children are shaped by ambiguously blurring the boundaries of privacy and publicness in order to bait followers’ attention, such that privacy and publicness are defined by being broadcast, circulated, and publicized (Warner 414). In other words, the publicness of micro-microcelebrities is premised on the extent of the intentional publicity rather than simply being in the public domain (Marwick 223-231, emphasis mine).Among Influencers privacy concerns have aroused awareness but not action – Baby Dash’s Influencer mother admitted in a national radio interview that he has received a death threat via Instagram but feels that her child is unlikely to be actually attacked (Channel News Asia) – because privacy is a commodity that is manipulated and performed to advance their micro-microcelebrities’ careers. As pioneer micro-microcelebrities are all under 2-years-old at present, future research warrants investigating “child-centred definitions” (Third et al.) of the transition in which they come of age, grow an awareness of their digital presence, respond to their Influencer mothers’ actions, and potentially take over their accounts.Young LabourThe Ministry of Manpower (MOM) in Singapore, which regulates the employment of children and young persons, states that children under the age of 13 may not legally work in non-industrial or industrial settings (Ministry of Manpower). However, the same document later ambiguously states underaged children who do work can only do so under strict work limits (Ministry of Manpower). Elsewhere (Chan), it is noted that national labour statistics have thus far only focused on those above the age of 15, thus neglecting a true reflection of underaged labour in Singapore. This is despite the prominence of micro-microcelebrities who are put in front of (video) cameras to build social media content. Additionally, the work of micro-microcelebrities on digital platforms has not yet been formally recognized as labour, and is not regulated by any authority including Influencer management firms, clients, the MDA, and the MOM. Brief snippets from my ethnographic fieldwork with Influencer management agencies in Singapore similarly reveal that micro-microcelebrities’ labour engagements and control of their earnings are entirely at their parents’ discretion.As models and actors, micro-microcelebrities are one form of entertainment workers who if between the ages of 15 days and 18 years in the state of California are required to obtain an Entertainment Work Permit to be gainfully employed, adhering to strict work, schooling, and rest hour quotas (Department of Industrial Relations). Furthermore, the Californian Coogan Law affirms that earnings by these minors are their own property and not their parents’, although they are not old enough to legally control their finances and rely on the state to govern their earnings with a legal guardian (Screen Actors Guild). However, this similarly excludes underaged children and micro-microcelebrities engaged in creative digital ecologies. Future research should look into safeguards and instruments among young child entertainers, especially for micro-micrcocelebrities’ among whom commercial work and personal documentation is not always distinct, and are in fact deliberately intertwined in order to better engage with followers for relatabilityGrowing Up BrandedIn the wake of moral panics over excessive surveillance technologies, children’s safety on the Internet, and data retention concerns, micro-microcelebrities and their Influencer mothers stand out for their deliberately personal and overtly commercial approach towards self-documenting, self-presenting, and self-publicizing from the moment of conception. As these debut micro-microcelebrities grow older and inherit digital publics, personae, and careers, future research should focus on the transition of their ownership, engagement, and reactions to a branded childhood in which babies were postured for an initimate public.ReferencesAbidin, Crystal. “Communicative Intimacies: Influencers and Perceived Interconnectedness.” Ada: A Journal of Gender, New Media, & Technology. Forthcoming, Nov 2015.Aiello, Marianne. “Mommy Blog Banner Ads Get Results.” Healthcare Marketing Advisor 17 Nov. 2010. HealthLeaders Media. 16 Aug. 2015 ‹http://healthleadersmedia.com/content/MAR-259215/Mommy-Blog-Banner-Ads-Get-Results›.Azzarone, Stephanie. “When Consumers Report: Mommy Blogging Your Way to Success.” Playthings 18 Feb. 2009. 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Le terme violence qualifie un certain nombre de manifestations allant de l’altercation verbale jusqu’aux destructions de masse, en passant par l’agression physique, le viol, le meurtre, la torture, les mutilations, etc. Infligées ou subies, discontinues ou constantes, localisées ou endémiques, accidentelles ou motivées, ces expressions de la violence se compliquent encore par leur caractère tantôt privé, tantôt public, assumé et revendiqué ou dissimulé et renié. La violence est si protéiforme qu’elle ne cesse de voir les discriminants de sa catégorisation et les grilles de classification se démultiplier. Le critère est tantôt spatial (violence urbaine), tantôt social (violence conjugale, ouvrière), tantôt politique (répression, coercition, guerre, assassinat politique, terrorisme), économique (exploitation, injustice), sexuel (viol, maltraitance), ou encore psychologique (automutilations et autres actes pervers). Englober toutes ces manifestations dans une même perspective relève de la gageure (Michaud 2004 ; Crettiez 2008). Comment approcher pareils phénomènes aux formes et motivations aussi diversifiées selon les mêmes grilles théorico-méthodologiques? D’autant plus qu’à ces expressions physiques de la violence s’ajoutent toutes celles qui relèvent de la « violence symbolique ». Consentie (plus que subie), cette violence impose un certain ordre dans les manières d'être. Elle englobe tous les dispositifs dont usent les dominants pour que les dominés intériorisent et acceptent leur statut et leur état de dominés (Bourdieu & Wacquant 1992). Elle participe de cette violence structurelle inhérente à tout pouvoir, qu’il soit celui du pater familias ou du chef élu ou imposé. Elle peut être liée à la forme même de l'organisation sociale à laquelle on adhère et qu’elle tend à malmener. Le politiste norvégien Johan Galtung (1969) est sans doute le premier à l’évoquer, faisant remarquer que dans cette forme de violence il n’y a pas de lien évident et apparent entre les sujets. Inscrite dans des structures sociales, cette violence est plus insidieuse mais non moins destructrice. Outre ces violences dévastatrices du lien, l’anthropologie a mis en évidence un autre genre de violences, celles destinées précisément à instaurer le lien, à le suturer ou à le raffermir. Ces violences fondatrices qui ponctuent les rites de passage (tatouages, circoncisions, excisions, scarifications et autres marquages corporels), souvent violentes et non exemptes de douleur, ont pour finalité d’agréger les individus à des communautés. Initiatique, cette violence qui laisse une marque distinctive (du rang, du sexe, etc.), n’est jamais perçue comme telle par ceux qui l’adoptent (Bodiou et Briand 2015). Malgré la variété de ses expressions et de ses modes d’effectuation, l’acte de violence demeure aisément identifiable. En revanche, il en est tout autrement quand il s’agit de définir ce qu’est la violence. Tous les dictionnaires la mettent en rapport avec l’exercice d’une force brutale ou excessive en vue de soumettre, contraindre ou obtenir quelque chose. Pour la majorité des approches, la violence a été longtemps conçue comme un « usage délibéré de la force pour blesser ou détruire physiquement » (Gurr, 1970). Au milieu des années 1990, la définition de l’OMS en élargit l’acception. Se voulant exhaustive, elle intègre à la fois les actes individuels et communautaires, commis contre autrui ou auto-infligés; qu’ils soient interpersonnels ou collectifs. Elle couvre tout aussi bien les actes de violence que les menaces et intimidations de tous ordres, induisant des atteintes physiques, psychologiques, ou affectives. Toutefois, cette définition demeure encore fortement associée aux violences physiques et n'évoque pas clairement et suffisamment les violences psychologiques et morales découlant d’actes verbaux, d'attitudes et autres conduites symboliques. Plus largement, F. Héritier (1996 : 17) appelle « violence toute contrainte de nature physique ou psychique susceptible d'entraîner la terreur, le déplacement, le malheur, la souffrance ou la mort d'un être animé; tout acte d'intrusion qui a pour effet volontaire ou involontaire la dépossession d'autrui, le dommage ou la destruction d'objets inanimés (…) ». Complète et exhaustive, cette définition souligne, une fois encore, la difficulté à parler de la violence de manière générale. La violence est une force dont l’exercice s’inscrit immanquablement dans le cadre de normes partagées. Ce sont de telles normes qui caractérisent, in fine, ce qui relève ou non de la violence. Celle-ci est justement le plus souvent un dépassement de la règle ou de la norme admise, une démesure. Elle est ce qui remet en cause l’existence de ce qu’Hanna Arendt (1989 : 283) appelle « un monde commun ». Yves Michaud (1978 : 101) le dit avec ses mots : la violence « tient plus à la dissolution des règles qui unifient le regard social qu’à la réalité qu’elle peut avoir ». À ce titre, la manifestation de la violence est l’indice d’une rupture de consensus, dont la finalité est de contraindre et de faire mal, de manière volontaire et apparemment gratuite. Elle est tantôt une infraction, tantôt un outrage. Chaque société désigne ce qu’elle considère comme violent en tentant de le réduire par l’éthique, la culture, le droit, la contrainte et en lui opposant… de la violence. Ce sont les logiques qui président à ces choix que l’anthropologue ne cesse de pointer dans leur singularité pour tenter de comprendre le phénomène dans son universalité. Même si le catalogue des actes de violence semble infini, et l’imagination des bourreaux individuels et collectifs incommensurablement fertiles, il n’en demeure pas moins que cette violence s’exerce toujours ou du moins le plus souvent selon des logiques inscrites dans un contexte historico-culturel. La « violence » est enchâssée dans une matrice éthique et obéit à une échelle de valeurs qui rend sa perception et, partant, sa signification variables selon les normes de référence en usage. Polymorphe, elle est également et nécessairement polysémique; et sa perception culturellement et sociohistoriquement déterminée. Des châtiments tolérés naguère (sectionner la langue des blasphémateurs, noyer des femmes adultères), sont décriés par des sociétés contemporaines pratiquant d’autres formes de violence (chaise électrique ou injection létale), estimées moins cruelles à leurs yeux. Ce sont en général les actes et conduites jugés illégitimes qui sont qualifiés de violents; tous ceux, tout aussi violents, mais exercés au nom d’une règle partagée ou par un pouvoir considéré comme légitime, ne sont pas tenus pour de la violence; ils sont perçus comme une coercition, une contrainte. Que ce soit pour Hobbes (2000) ou Weber (1959), l’usage légitime de la violence prévient la violence. Dès lors, il n’est plus de la violence. Loin d’être un phénomène débridé, la violence est souvent un outil savamment orchestré destiné à faire obéir ou à punir. Qu’elle soit privée ou publique, la violence est toujours inscrite dans une matrice symbolique qui structure ses modes d’effectuation et lui donne sens aux yeux de ses protagonistes. Ainsi devient-elle légitime pour son auteur; et parfois même pour celui qui la subit, la vivant comme une fatalité ou se considérant comme victime expiatoire. Ainsi, est-elle une « configuration » (Elias, 1989) où les adversaires sont aussi des partenaires agissant selon des règles partagées. Une propension devenue routinière consiste à toujours considérer la violence comme une réactivité instinctive, motivée par une pure répétition pavlovienne et paresseuse. Les études des violences urbaines ont pu montrer que celles-ci peuvent être un indicateur d’inégalité ou de défiance vis-à-vis des institutions; et, partant, l’expression d’une volonté de négociation. La manifestation de la violence est un « signal de danger » nous dit Lewis Coser (1982). Autrement dit, la violence fait à la fois signe et sens. Elle n’est pas que l’expression du chaos et du désordre. L’exercice de la violence (notamment politique) a le souci à la fois de l’efficacité et de la légitimité. Le plus souvent, la violence n’est ainsi qualifiée qu’en rapport aux seuls faits concrets, quantifiables et mesurables. Or, d’un point de vue anthropologique, la violence intègre à la fois l’éthique, les valeurs partagées, les sentiments, etc. La rumeur, l’ironie ou la satire peuvent être ressenties comme plus violentes que des coups. Physique, psychologique ou symbolique, la violence est toujours un fait « construit » à partir d’une culture partagée; dont la perception et l’intensité sont étroitement en rapport avec les normes communément admises. Quelle que soit la forme de son expression, la violence demeure un « fait social total »; car elle est toujours enchâssée dans d’autres faits sociaux qui démultiplient ses logiques et ses univers de sens (politique, religieux, économique, social etc.) (Clastres, 1977 ; Kilani, 2006). Instinct naturel, moyen d’imposer l’ordre social ou vecteur du changement social? La violence est une des catégories les plus discutées dans les sciences humaines et sociales; mobilisant terrains et théories pour saisir un phénomène en passe de figurer parmi les universaux et ne cessant de réinventer ses formes d’expression. Pour Thomas Hobbes (2000), l’une des références inévitables dans ces débats, l’homme est un être « duplice », naturellement violent mais socialement dans l’obligation de rechercher la répression de son agression en acceptant de se conformer aux règles d’une instance qui lui permettrait de vivre en société. Pour Hobbes, c’est l’égalité primordiale entre les hommes qui serait à l’origine des affrontements. Jean-Jacques Rousseau (1971) reproche au philosophe britannique d’avoir attribué à l’homme vivant dans l’état de nature les attributs et les passions propres à l’homme vivant dans la société. Ces deux postures spéculatives vont constituer dans une large mesure le cadre de pensée dans lequel seront débattues thèse et contre-thèse sur la nature violente ou non de l’homme. La première défend le caractère inné de la violence, tandis que la seconde la considère comme un acquis culturel. En anthropologie, l’intérêt pour la violence comme phénomène, est présent dès les premiers travaux qui ont pu montrer que toutes les sociétés contiennent de la violence, la produisent, l’utilisent et la gèrent. Mise en avant par Max Weber (1959) dans sa théorie de l’État comme monopole de la violence légitime, elle est popularisée par les travaux de René Girard (1972, 1978). Pour ce philosophe et anthropologue, les désirs de l’homme sont mimétiques et engendrent une violence fondée sur la « rivalité ». L’homme désire les mêmes objets que son prochain, et son désir augmente en fonction de celui de l’autre. Ce désir mimétique débouche sur la violence qui, de proche en proche, devient générale et concerne toute la société. Pour y remédier, Girard s’écarte des thèses wébériennes qui préconisent l’instauration d’une violence légitime confiée à l’État. Il postule que les hommes déplacent leur hostilité sur une victime émissaire (Girard, 1972). C’est le sens du sacrifice présent dans toutes les sociétés humaines. C’est le « désir mimétique » à l’origine de la violence qui caractérise l’être humain en société. Pour empêcher le saccage de cette violence réciproque, présente dans l’essentiel des rapports humains et dans toutes les sociétés dès le début de leur formation, la communauté sacrifie une victime arbitraire consensuelle. La haine de chacun est transférée sur cette victime émissaire dont la mise à mort est expiatoire. Elle sauve la communauté et lui permet de survivre. En évitant la violence destructrice de la communauté, cette violence sacrificielle et pacificatrice se transforme en une violence fondatrice. Les anthropologues se sont également intéressés à la forme institutionnelle de la violence. Ainsi, la guerre mobilisera l’essentiel des théories. Une approche naturaliste développée notamment par André Leroi-Gourhan (1965), postule que la guerre (comme violence institutionnelle) est la conséquence de l'évolution naturelle de l'Homme, qui de chasseur devient guerrier. Pour cet ethnologue et penseur des techniques et de la culture, la violence humaine relèverait du biologique. Postulant que la guerre est une extension de la chasse, il considère que l’homme, à l’instar de l’animal, est un être prédateur et donc violent par nécessité. Le social et l'institutionnel sont ainsi naturalisés. La violence permet de se procurer les rares ressources disponibles. Une telle approche rejoint celle qui met en rapport la guerre et les pénuries de nourriture dans les sociétés primitives. D’autres thèses, plus répandues, estiment certains modèles culturels, comme la virilité, l'autoritarisme culturel et la religion, à l'origine immédiate et exclusive de cette violence. Ce courant culturaliste considère la violence comme un phénomène culturel. Une de ses premières figures, Ruth Benedict (1950), a tenté d’opposer la culture apollinienne des Indiens Pueblos, qu’elle considère comme communautaire et pacifique, à celle des Indiens des plaines, qu’elle définit comme passionnés et agressifs et dont elle qualifie la culture de dionysiaque. Une autre approche culturaliste, celle de Claude Lévi-Strauss, voit dans la violence un mode d’échange, un « échange malheureux ». Pour le théoricien du structuralisme, la guerre est l’expression d’un échec dans l'échange entre communautés, lequel échange est à ses yeux fondateur des sociétés. L’anthropologie Pierre Clastres (1977) réfutera toutes ces théories pour soutenir que la guerre est constitutive de la société primitive. Elle n’est, selon lui, ni un instinct animal, ni la conséquence d’un manque, ni l’expression d’un ethos culturel, ni un échange raté. Elle est au fondement même de l’être ensemble. Étant sans hiérarchie, la société primitive use de la guerre contre l’Autre comme moyen de raffermir son unité. Depuis Thomas Hobbes, la violence hors d'un cadre prescrit par l'État est considérée comme une pathologie sociale. Contre cette vision, Pierre Clastres soutient que les violences (apparemment déviantes ou criminelles) s'inscrivent dans un univers social, culturel et symbolique pour faire sens. Poussée à ses limites, cette approche compréhensive risque de conduire à soutenir des légitimations au nom du relativisme culturel. Dans un monde où génocides, guerres, terrorismes et autres destructions de masse sont devenus une réalité quotidienne, plusieurs auteurs soutiennent la thèse de Norbert Elias (1989) sur le recul de la violence et la domestication de l’animal humain. Contre-intuitive, cette thèse est défendue par plusieurs historiens sur la base de travaux sur des archives judiciaires, dont l'historien Jean-Claude Chesnais (1981 : 14) qui estime qu' « il y a au cours des derniers siècles une régression considérable de la violence criminelle ». Si aujourd’hui on parle de son omniprésence, c’est parce que le seuil de tolérance aurait baissé. Nous serions devenus plus sensibles à la violence, subjectivement. Ceux qui rejettent une telle thèse préfèrent souligner le nombre et la diversification des formes des violences : génocides, attentas, terrorismes, etc. (Wieviorka, 2004). En effet, la violence a pris des formes inédites en rapport avec la complexification de notre organisation sociale. La technologie a contribué à une certaine sophistication de la violence et à sa mise à distance. Sa « domestication » s’opère par sa taylorisation. L’acte de tuer ou de perpétrer un génocide est noyé dans les échelons de la décision (du général qui décide au soldat qui exécute) et dans une « chaîne opératoire » plus ou moins longue. Grâce à cette « taylorisation », la violence se trouve aujourd’hui « domestiquée ». L’euphémisation par la technologie (écrans) la rend supportable par celui qui l’exécute; tout comme le sacré l’avait déjà rendue acceptable et supportable aux yeux, à la fois, de celui qui la donne et de celui qui la subit (Matthew, 2017 ; Blaya, 2011). Quoi qu’il en soit, le développement vertigineux de la technologie, et de l’organisation bureaucratique, contribue à cette « banalisation du mal » (Arendt 1991) en rendant moins perceptibles et plus insidieuses ces violences. Les armes biologiques sont moins spectaculaires dans leur usage mais plus dévastatrices dans leurs effets, tout comme les drones tuent de façon aussi chirurgicale que silencieuse (Chamayou 2013). Il suffit également de penser à toutes les formes de cyberviolence qui se développent dans le monde virtuel des réseaux sociaux, à l’instar du « revenge porn » ou « cyber-rape » (Blaya, 2011). Ce type de violence s’effectue en général sans échange verbal direct. Le registre du langage et l’émotion qu’il produit sont ainsi annulés, privant la victime de repères et d’alertes. Le « bourreau » est également protégé puisqu’il ne voit pas et il n’entend pas la réaction que produit son acte sur la victime. Dans cette nouvelle configuration que produit la cyberviolence, l‘agresseur n’est pas nécessairement plus fort, mais dispose de plus de latitude pour nuire. La thèse du recul de la violence ne tient pas suffisamment compte de sa sophistication, qui arrive à l’occulter. En revanche, la montée de la violence, souvent signalée, peut n’être que le signe d’un abaissement du seuil de tolérance face à des conduites plus ou moins agressives. En réalité, la notion de violence renvoie à deux dimensions, l’une factuelle et l’autre normative. Elle qualifie les effets de la force physique au regard de la transgression des normes socialement établies (Robert & al. 2008 ; Mucchielli, 2008).