Letteratura scientifica selezionata sul tema "Li shan ta"

Abstract Modern Chinese Pseudo-Possessive-Object Constructions (shortened as Modern Chinese PPO constructions; e.g. ta shuo le wo de haohua (他说了我的好话) ‘he has put in a good word for me’ and ta chi le wo de doufu (他吃了我的豆腐) ‘he has taken advantage of me’) are actually constructions displaying possessor-affectee syncretism. They derive from Early Modern Chinese Real-Possessive-Object constructions in bridging contexts, some examples being wo ye quande liewei daren de jiu (我也劝得列位大人的酒), ‘I also urged all the magistrates here to finish drinking your wine’ and shi nage zai jie wo de duan li (是那个在揭我的短哩) ‘who is uncovering my demerits’. Di-transitive constructions in Middle Chinese and Early Modern Chinese (e.g. Changxing! quan er yibei jiu (长星，劝尔一杯酒) ‘Comet! I urge you (to finish drinking) a cup of wine’ and shuru gan jie wu duanchu (竖儒敢揭吾短处) ‘how dare the Confucius scholar uncover my demerits’) have provided structural templates for the formation of Modern Chinese PPO constructions. They also have led to a condition in which there are more examples of a maleficiary Modern Chinese PPO construction than examples of a beneficiary Modern Chinese PPO construction (e.g. ta chi le wo de doufu (他吃了我的豆腐) ‘he has taken advantage of me’ vs. ta shuo le wo de haohua (他说了我的好话) ‘he has put in a good word for me’). The grammaticalization pathway can also explain the formation of other constructions including another Modern Chinese PPO construction (e.g. ta chi le wo de kui (他吃了我的亏) ‘he has suffered the loss caused by me’), a Modern Chinese pseudo-object construction (e.g. wo ganxie ni de haoxin (我感谢你的好心) ‘I thank you for your kindness’), and a Modern Chinese pseudo-modifier construction (e.g. wo pa le yi xiawu de shan (我爬了一下午的山) ‘I did mountain-climbing for the whole afternoon’).

The purpose of this study was to know the student's Arabic vocabulary mastery in the class that did not use simulation methods and classes that used simulation methods, and to what degree the effectiveness of the methods used to increase student's Arabic vocabulary mastery of the XI class in Pondok Pesantren Modern Ta 'dib al-Syakirin, Medan Johor. The research method used is an ex post facto quantitative study method. The results of this study indicate that for mastery of the student's Arabic vocabulary when not using the practice of simulation are obtained with an average of 64.72, where 4 students are "excellent", 2 people who are "good",7 people who are predicated "enough", and 5 people who are predicated "less". While the student's Arabic vocabulary mastery when using simulation methods is obtained with an average value of 83.61, which are 5 students on a "satisfactory" predicate, 10 on "excellent", 2 on a "good" predicate, and 1 person on a "less" predicate. As well as analysis of data, it has been found that the use of simulated methods is effective to increase student's Arabic vocabulary mastery with a level of effectiveness given by 0.54 based on n - gain tests by "moderate" since n-gain values are in the range of 0.30. < g < 0.70.

Ferroportin (FPN), the only known vertebrate iron exporter, transports iron from intestinal, splenic, and hepatic cells into the blood to provide iron to other tissues and cells in vivo. Most of the circulating iron is consumed by erythroid cells to synthesize hemoglobin. Recently, we found that erythroid cells not only consume large amounts of iron, but also return significant amounts of iron to the blood. Erythroblast-specific Fpn knockout (Fpn KO) mice developed lower serum iron levels in conjunction with tissue iron overload and increased FPN expression in spleen and liver without changing hepcidin levels. Our results also showed that Fpn KO mice, which suffer from mild hemolytic anemia, were sensitive to phenylhydrazine-induced oxidative stress but were able to tolerate iron deficiency upon exposure to a low-iron diet and phlebotomy, supporting that the anemia of Fpn KO mice resulted from erythrocytic iron overload and resulting oxidative injury rather than a red blood cell (RBC) production defect. Moreover, we found that the mean corpuscular volume (MCV) values of gain-of-function FPN mutation patients were positively associated with serum transferrin saturations, whereas MCVs of loss-of-function FPN mutation patients were not, supporting that erythroblasts donate iron to blood through FPN in response to serum iron levels. Our results indicate that FPN of erythroid cells has an unexpectedly essential role in maintaining systemic iron homeostasis and protecting RBCs from oxidative stress, providing insight into the pathophysiology of FPN diseases. When malaria parasites invade red blood cells (RBCs), they consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. We recently found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation,Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPNQ248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection. Zhang DL, Wu J, Shah BN et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018;359 (6383):1520-1523. Zhang DL, Ghosh MC, Ollivierre H, Li Y, Rouault TA. Ferroportin deficiency in erythroid cells causes serum iron deficiency and promotes hemolysis due to oxidative stress. Blood. 2018;132 (19):2078-2087. Zhang DL, Rouault TA. How does hepcidin hinder ferroportin activity. Blood. 2018;131 (8):840-842. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: CG0070, is an Ad5-based oncolytic vaccine engineered to express GM-CSF and replicate selectively in tumor cells with mutated or deficient RB. The CG0070 mechanism of action includes cell lysis and immunogenic cell death which is enhanced in the presence of GM-CSF. In an open label ph. 2 study, an overall CR rate of 62% and a CR at 12 months (m) of 29% have been observed in patients with high risk NMIBC previously treated with BCG. IV pembrolizumab, was recently approved by the FDA for patients with BCG-unresponsive CIS (with or without papillary tumors) with an overall complete RR of 41% and a 12 m CR rate of ~20%.This ph. 2 study will assess the potential synergy of the two agents in the treatment of BCG-unresponsive NMIBC. Methods:35 pts with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravescical CG0070 (1x1012 vp) in combination with pembrolizumab at a dose of 400 mg IV q6 weeks. CG0070 will be administered weekly x 6 as induction followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Pts with persistent CIS or HG Ta at 3 m may receive re-induction with weekly x 6 of CG0070. Pembrolizumab will be administered up to 24 m. Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping biopsies at 12 m. Recurrence of HG disease will be enumerated as disease recurrence. The primary endpoint of the study is CR at 12 m. Secondary endpoints will include CR at any time, progression free survival, duration of response, cystectomy free survival and the safety of the combination. Correlate assessments will include changes in the tumor immune microenvironment, systemic immune induction, viral replication and transgene expression. Baseline expression of PD-L1, coxsackie adenovirus receptor, E2F transcription factor as well as anti-Ad5 Ab titer will be correlated with tumor response. Results: Thus far, 10 patients are evaluable at the 3 m timepoint for efficacy. Assessment of these 10 pts demonstrates 100% CR at 3 mos. Six of the 10 pts have also reached the 6 m hallmark in a CR as well as 2 at the 12 mos timepoint. Treatment related AE have been limited to transient grade 1-2 local-regional genitourinary adverse events with no grade 3 or 4 treatment related AE reported date. Conclusions: This initial data on the efficacy and safety of CG0070 plus pembrolizumab for the treatment of BCG unresponsive NMIBC is encouraging. An update on the study will be provided at the time of presentation. Citation Format: Roger Li, Gary Steinberg, Paras Shah, Ed Uchio, Donald Lamm, Trinity Bivalacqua, Vignesh Packiam, Ashish Kamat, Michael Chisamore, John McAdory, Paola Grandi, Jee-Hyun Kim, James Burke. CORE1: Phase 2, single arm study of CG0070 combined with pembrolizumab in patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG) [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 CT036.

BackgroundSystemic sclerosis (SSc) is a rare autoimmune disease characterized by progressive microvascular damage, collagen deposition and subsequent fibrosis of the skin and internal organs which contributes to substantial morbidity and premature death.1-2ObjectivesThe objective was to evaluate the disease burden of SSc patients prior to their SSc diagnosis.MethodsPatients with SSc were identified in a claims dataset (IBM MarketScan Commercial Database, 2015-2019) using ICD 10 diagnosis codes for SSc. Eligible subjects were required to have > 1 inpatient or >2 outpatient/office claims with a scleroderma diagnosis code on separate days and > 24 months of continuous health plan enrollment without a SSc diagnosis before the first SSc claim (‘index date’) and > 12 months of enrollment after the index date. Overall comorbid disease burden was assessed via the Charlson Comorbidity Index (CCI) 13-24 and 12 months before and 12 months after index date. The prevalence of SSc-related complications for atherosclerosis, pulmonary arterial hypertension (PAH), pulmonary fibrosis (PF), Raynaud’s Phenomenon (RP), and gastrointestinal (GI) complications (e.g., GERD, dysphagia, etc.) were identified using ICD codes and reported as percentages for the aforementioned time intervals relative to patients’ index dates.Results902 eligible SSc patients were identified for analysis. The mean age at index SSc diagnosis was 54.3 years and 84.7% of patients were female. Mean CCI scores 13-24 months before, 12 months before, and 12 months after index SSc diagnosis were 0.84, 1.13 and 1.30, respectively. From the time points 13-24 months before, 12 months before, and 12 months after index SSc diagnosis, increasing rates were also observed of atherosclerosis, PAH, PF, RP, and GI complications (Table 1).Table 1.Charlson Comorbidity Index (CCI) and systemic sclerosis-related complications by time-intervalClinical characteristic13-24 months before Index12 months before Index12 months after IndexMean CCI (std dev)0.84 (1.58)1.13 (1.71)1.30 (1.75)Systemic sclerosis-related complicationsAtherosclerosis7%9%14%Pulmonary arterial hypertension (PAH)1%4%12%Pulmonary fibrosis (PF)5%8%16%Raynaud’s Phenomenon (RP)13%29%43%GI complications23%32%46%ConclusionResults from this analysis suggests that SSc-related sequalae are present at least two years prior to SSc diagnosis and rates of these complications increased markedly over time. Patients’ overall comorbid disease burden also worsened substantially over this period, likely because of these complications. The internal organ involvement is likely under reported due to requirements to link each diagnosis with an ICD-10 code. These data indicate the significant burden of SSc, prior to and after diagnosis, highlighting the need for awareness, prompt diagnosis, and effective therapies for SSc and its related complications.References[1]Cutolo M, et al. Expert Rev Clin Immunol. 2019;15(7):753-764.[2]Steen VD, Medsger TA. Ann Rheum Dis. 2007;66(7):940-944.Disclosure of InterestsDinesh Khanna Consultant of: Horizon Therapeutics, Daniel Furst Consultant of: Horizon Therapeutics, Justin W. Li Grant/research support from: Horizon Therapeutics, Saloni Shah Grant/research support from: Horizon Therapeutics, Tamara Lesperance Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Farah Ali Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Stephanie Taylor Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics

BackgroundMultiple genomics-based biomarkers of response to immune checkpoint inhibition have been reported or proposed, including tumor mutation/neoantigen frequency, PD-L1 expression, T cell receptor repertoire clonality, interferon gene signature expression, HLA expression, and others.1 Although genomics associations of response have been reported, the primary studies have used a variety of data generation and processing techniques. There is a need for data harmonization and assessment of generalizability of potential biomarkers across multiple datasets.MethodsWe acquired patient-level RNA sequencing FASTQ data files from 10 data sets reported in seven pan-cancer PD-1 and CTLA-4 immune checkpoint inhibition trials with matched clinical annotations.2–7 We applied a common bioinformatics workflow for quality control, mapping to reference (STAR), generating gene expression matrices (SALMON), T cell receptor repertoire inference (MiXCR), extraction of immune gene signatures and immune subtypes,8 and differential gene expression analysis (DESeq2). We analyzed i) immunogenomics features proposed as biomarkers, and ii) gene expression signatures built from each trial for association with overall survival across the set of trials using univariable Cox proportional hazards regression. In all, we assessed 9 total immunogenomics features/signatures. P-values were adjusted for multiple testing using the Benjamini-Hochberg method.ResultsOf the 9 immunogenomics features assessed, cytolytic activity score and expression of the Follicular Dendritic Cell Secreted Protein gene (FDCSP) were associated with survival in two of seven studies, respectively (adjusted p < 0.05) (figure 1). No proposed biomarkers were significantly associated with survival in more than two studies. The sets of genes significantly associated with clinical benefit across the studies were highly disjoint, with only three genes significant in three studies and thirteen genes significant in two studies (figure 2). No genes were significantly associated with clinical benefit in more than three of seven studies.Abstract 75 Figure 1Association of immunogenomics features and proposed biomarkers with survival in 10 publicly available datasets from 7 clinical trials with immune checkpoint blockade. Nine immunogenomics features were tested in 10 publicly available RNAseq data sets from 7 published clinical trials with immune checkpoint blockade for their correlation with outcome. SKCM, skin cutaneous melanoma; BLCA, bladder cancer; Kidney, kidney cancer; Ureter, ureteral cancer; GBM, glioblastomaAbstract 75 Figure 2Association of gene expression of single genes with survival in 10 publicly available datasets from 7 clinical trials with immune checkpoint inhibitorsConclusionsNo proposed biomarkers were highly generalizable across studies. We expect that integrated modeling incorporating multiple immunogenomics features will be required to build a robust and generalizable biomarker for ICI response. Further work is needed to analyze determinants of response and clinical benefit.AcknowledgementsWe would like to thank SITC for funding for this work as part of the Sparkathon TimIOS collaborative project.ReferencesZappasodi R, Wolchok JD, Merghoub T. 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The influence of family, school and peers on students' emotional social development is very important as a starting point for the design of school activities that will also improve student development in an integral way. The Star of the Week program was developed with the aim of helping students apply the knowledge, attitudes, and skills needed to socialize and understand and manage emotions. This study uses the Thiagarajan model stages, namely define, design, develop, and disseminate (4D). The results of the validity test from the experts show that this program has workable value with 91.1% material aspects, 90% emotional development aspects and 92% presentation aspects. For the practicality test results through teacher questionnaires obtained scores of 90%, and 88.67% through teacher observations of children who are in the high practical category. The results of the program effectiveness test showed a value of 89.08% on children's social-emotional development, because it showed an increase in values ​​before and after the intervention. The implication of further research is that it is hoped that various kinds of learning methods will develop aspects of child development based on cooperation and peer relationships. Keywords: Early Childhood, Peer Relationships, Star of the Week Program, Social Emotional References Acar, I. H., Hong, S. Y., & Wu, C. R. (2017). Examining the role of teacher presence and scaffolding in preschoolers’ peer interactions. European Early Childhood Education Research Journal, 25(6), 866–884. https://doi.org/10.1080/1350293X.2017.1380884 Acar, I. H., Rudasill, K. M., Molfese, V., Torquati, J., & Prokasky, A. (2015). Temperament and preschool children’s peer interactions. Early Education and Development, 26(4), 479–495. https://doi.org/10.1080/10409289.2015.1000718 Akhir, K., & Wisz, M. S. (2018). 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We review our recent work on optical biosensors based on microring resonators (MRR) integrated with 4x4 multimode interference (MMI) couplers for multichannel and highly sensitive chemical and biological sensors. The proposed sensor structure has advantages of compactness, high sensitivity compared with the reported sensing structures. By using the transfer matrix method (TMM) and numerical simulations, the designs of the sensor based on silicon waveguides are optimized and demonstrated in detail. We applied our structure to detect glucose and ethanol concentrations simultaneously. A high sensitivity of 9000 nm/RIU, detection limit of 2x10-4 for glucose sensing and sensitivity of 6000nm/RIU, detection limit of 1.3x10-5 for ethanol sensing are achieved. Keywords Biological sensors, chemical sensors, optical microring resonators, high sensitivity, multimode interference, transfer matrix method, beam propagation method (BPM), multichannel sensor References [1] Vittorio M.N. 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Abstract: Low density systems or adaptively coordinated systems that has enough buoyancy to float on over contents of the stomach for a significant length of time without noticeably decelerating the rate of gastric emptying are known as floating systems. To accomplish stomach retention, the principle process of flotation was specifically examined in this drug delivery system. It is advantageous to construct medications in an oral sustained release gastro-retentive dose form for those that are absorbed in the upper portions of the GIT. The development of dynamically controlled systems depends on the rate at which the stomach empties. The most recent FDDS advancements are strategies to reduce the variability that lengthens the drug delivery system's retention period to more than 12 hours. This paper also contains an overview of several contemporary in-vitro methods that demonstrate the correct. This review on floating drug delivery systems (FDDS) was written with the intention of gathering the most recent research with a particular focus on the main mechanism of flotation to induce stomach retention. The most recent changes in A detailed discussion of FDDS is provided, covering the physiological and formulation factors impacting stomach retention, design methods for single-unit and multiple-unit floating systems, and their classification and formulation characteristics. The techniques used in vitro, the in vivo tests used to gauge the effectiveness and use Sharma N, Agarwal D, Gupta MK, Khinchi M. A Comprehensive Review On Floating Drug Delivery System. Int J Res Pharm Biomed Sci. 2011;2:428-41. Gohel MC, Mehta PR, Dave RK, Bariya NH. A More Relevant Dissolution Method For Evaluation Of A Floating Drug Delivery System. Diss Technol. 2004;11(4):22-5. Doi: 14227/DT110404P22. Yeole PG, Khan S, Patel VF. Floating Drug Delivery Systems: Need And Development. 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Floating Drug Delivery Of Nevirapine As A Gastroretentive System. J Young Pharm JYP. 2010;2(4):350-5. Doi: 4103/0975-1483.71622, PMID 21264092. Upadhye AA, Ambike AA, Mahadik KR, Paradkar A. Application Of Ion Exchange Resin In Floating Drug Delivery System. Drug Dev Ind Pharm. 2008;34(10):1117-24. Doi: 1080/03639040801973982, PMID 18777244. Jiménez-Castellanos MR, Zia H, Rhodes CT. Design And Testing In Vitro Of A Bioadhesive And Floating Drug Delivery System For Oral Application. Int J Pharm. 1994;105(1):65-70. Doi: 1016/0378-5173(94)90236-4. Adibkia K, Hamedeyazdan S, Javadzadeh Y. Drug Release Kinetics And Physicochemical Characteristics Of Floating Drug Delivery Systems. Expert Opin Drug Deliv. 2011;8(7):891-903. Doi: 1517/17425247.2011.574124, PMID 21506906. Singh BN, Kim KH. Floating Drug Delivery Systems: An Approach To Oral Controlled Drug Delivery Via Gastric Retention. J Control Release. 2000;63(3):235-59. Doi: 1016/S0168-3659(99)00204-7, PMID 10601721. Seth SD. 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Regional Gastrointestinal Transit And Ph Studied In 215 Healthy Volunteers Using The Wireless Motility Capsule: Influence Of Age, Gender, Study Country And Testing Protocol. Aliment Pharmacol Ther. 2015;42(6):761-72. Doi: 1111/Apt.13329, PMID 26223837. Feldman M, Barnett C. Fasting Gastric Ph And Its Relationship To True Hypochlorhydria In Humans. Dig Dis Sci. 1991;36(7):866-9. Doi: 1007/BF01297133, PMID 2070698. Deshpande AA, Shah NH, Rhodes CT, Malick W. Development Of A Novel Cont Rolled Release System For Gastric Retention. P Harm Res. 1997;14(6):815-9. of floating systems, and the applications of these systems are all summarised in this paper. These systems are helpful for a number of issues that arise during the creation of a pharmaceutical dosage form.