Artykuły w czasopismach: „813/.6 b”

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WILLIAMS, NICOLE C., i STEVEN C. INGHAM. "Thermotolerance of Escherichia coli O157:H7 ATCC 43894, Escherichia coli B, and an rpoS-Deficient Mutant of Escherichia coliO157:H7 ATCC 43895 Following Exposure to 1.5% Acetic Acid". Journal of Food Protection 61, nr 9 (1.09.1998): 1184–86. http://dx.doi.org/10.4315/0362-028x-61.9.1184.

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On a beef carcass, Escherichia coli may sequentially encounter acid- and heat-intervention steps. This study tested whether acid stress (1.5% [vol/vol] acetic acid, pH 4.0, 37°C, 15 min) would enhance subsequent heat resistance of E. coli. Initially, cells (E. coli O157:H7 ATCC 43894, nonpathogenic E. coli B [strain FRIK-124], and rpoS-deficient mutant 813-6 [derived from E. coli O157:H7 ATCC 43895]) were acid stressed and transferred to 54°C tiypticase soy broth (TSB), and survivors were immediately enumerated after at least three intervals of 12, 2, and 6 min, respectively, by plating. The ATCC 43894 and 813-6 strains survived the acid stress but strain FRIK-124 did not. Acid-stressed ATCC 43894 had significantly lower D values than the non-acid-stressed controls. Strain 813-6 had significantly lower D values than strain ATCC 43894, with no significant difference between acid-stressed and non-acid-stressed cells. In a second experiment, cooling of cells prior to plating resulted in an increased D value for acid-stressed ATCC 43894 cells, such that it was not significantly different from the D value for non-acid-stressed Controls. Using this protocol, there was no significant difference in D values between acid-stressed and non-acid-stressed ATCC 43894 cells in prewarmed TSB (54, 58, and 62°C), in prewarmed ground beef slurry (GBS; 58°C), or in TSB and GBS inoculated at 5°C and heated to 58°C. The acid stress tested does not enhance subsequent heat resistance of E. coli.

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Eisner, N. L., O. Barragán, S. Aigrain, C. Lintott, G. Miller, N. Zicher, T. S. Boyajian i in. "Planet Hunters TESS I: TOI 813, a subgiant hosting a transiting Saturn-sized planet on an 84-day orbit". Monthly Notices of the Royal Astronomical Society 494, nr 1 (23.01.2020): 750–63. http://dx.doi.org/10.1093/mnras/staa138.

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ABSTRACT We report on the discovery and validation of TOI 813 b (TIC 55525572 b), a transiting exoplanet identified by citizen scientists in data from NASA’s Transiting Exoplanet Survey Satellite (TESS) and the first planet discovered by the Planet Hunters TESS project. The host star is a bright (V = 10.3 mag) subgiant ($R_\star =1.94\, R_\odot$, $M_\star =1.32\, M_\odot$). It was observed almost continuously by TESS during its first year of operations, during which time four individual transit events were detected. The candidate passed all the standard light curve-based vetting checks, and ground-based follow-up spectroscopy and speckle imaging enabled us to place an upper limit of $2\, M_{\rm Jup}$ (99 per cent confidence) on the mass of the companion, and to statistically validate its planetary nature. Detailed modelling of the transits yields a period of $83.8911 _{ - 0.0031 } ^ { + 0.0027 }$ d, a planet radius of 6.71 ± 0.38 R⊕ and a semimajor axis of $0.423 _{ - 0.037 } ^ { + 0.031 }$ AU. The planet’s orbital period combined with the evolved nature of the host star places this object in a relatively underexplored region of parameter space. We estimate that TOI 813 b induces a reflex motion in its host star with a semi-amplitude of ∼6 m s−1, making this a promising system to measure the mass of a relatively long-period transiting planet.

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Kustin, Talia, Noam Harel, Uriah Finkel, Shay Perchik, Sheri Harari, Maayan Tahor, Itamar Caspi i in. "Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals". Nature Medicine 27, nr 8 (14.06.2021): 1379–84. http://dx.doi.org/10.1038/s41591-021-01413-7.

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AbstractThe BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.

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Hernández Espinal, Luis Alberto, i Tomás Moreno Gallegos. "Análisis de las generaciones F1 y F2 de híbridos experimentales y comerciales de sorgo". Revista Mexicana de Ciencias Agrícolas 5, nr 1 (14.03.2018): 49–59. http://dx.doi.org/10.29312/remexca.v5i1.981.

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El precio de la semilla híbrida F1 de sorgo [Sorghum bicolor (L.) Moench.] es de alto costo, los productores de temporal principalmente, siembran semilla de generación avanzada o F2. El objetivo del presente estudio fue evaluar el rendimiento de grano de sorgo de la generación F2, respecto a la F1. Se estimó la relación beneficio costo (B/C) de 20 híbridos experimentales y 14 comerciales de sorgo, bajo condiciones de riego, en el CEVACU, Culiacán, Sinaloa, México. De 2010 a 2012, se establecieron dos experimentos, con un diseño de bloques completos al azar con tres repeticiones. En promedio el rendimiento de grano se redujo 50.79% en F2 con respecto a F1. El mayor rendimiento de grano en la F1, se obtuvo en el híbrido experimental SHS-23 x 43 (7 109 kg ha-1) y el híbrido comercial G STAR 7304 (6 813 kg ha-1). La relación B/C promedio de la generación F2 fue menor con 45.61% con respecto a F1. Los resultados obtenidos, indican que el uso de semilla de la generación avanzada o F2, no es recomendable ya que en promedio en más de 90% de los híbridos de sorgo la relación B/C es negativa, siendo no rentable para la producción de grano.

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Ferrari, Silvia Martina, Giusy Elia, Simona Piaggi, Enke Baldini, Salvatore Ulisse, Mario Miccoli, Gabriele Materazzi, Alessandro Antonelli i Poupak Fallahi. "CCL2 is Modulated by Cytokines and PPAR-γ in Anaplastic Thyroid Cancer". Anti-Cancer Agents in Medicinal Chemistry 18, nr 3 (4.06.2018): 458–66. http://dx.doi.org/10.2174/1871520617666170719152349.

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Background and Objective: Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. Methods: We tested in “primary human anaplastic thyroid carcinoma (ATC) cells” (ANA) versus “normal thyroid follicular cells” (TFC): a) CCL2 secretion basally, after IFN-γ and/or TNF-α stimulation; b) PPARγ activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA. Results: ANA produced basally CCL2, at a higher level versus TFC. IFN-γ or TNF-α dose-dependently induced the CCL2 release in 3/6 or 5/6 ANA, respectively, but in all TFC. IFN-γ+TNF-α induced a synergistic release of CCL2 in all TFC, but only in 1/6 ATC. TZDs exerted an inhibition of CCL2 release in 3/6 ANA, while had no effect in TFC. Pioglitazone inhibition of ANA proliferation was not associated with the effect on CCL2; NF-κB and ERK1/2 were basally activated in ANA, increased by IFN-γ+TNF-α, and pioglitazone inhibited IFN- γ+TNF-α activation. CCL2 serum levels were higher in 6 ATC patients than in 5 controls (813±345 versus 345±212, pg/mL; respectively; P<0.01, ANOVA). Conclusion: ANA produce CCL2 basally and after cytokines stimulation, with an extremely variable pattern of modulation, suggesting different types of deregulation in the chemokine modulation. Serum CCL2 is increased in ATC patients. Further studies will be necessary to evaluate if CCL2 might be used as a marker in the followup of ATC patients.

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Zhang, Liangjun, Huixiu Zhong, Bin Wei, Jiwen Fan, Jingyuan Huang, Yi Li i Weiping Liu. "Establishing Reference Values for Peripheral Blood Lymphocyte Subsets of Healthy Children in China Using a Single Platform". Journal of Immunology Research 2022 (17.08.2022): 1–10. http://dx.doi.org/10.1155/2022/5603566.

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Lymphocyte subsets significantly change during childhood; thus, age-matched reference values derived from healthy children are crucial. We established reference values for lymphocyte subsets, including T cells (CD3+), CD4 T cells (CD3 + CD4+), CD8 T cells (CD3 + CD8+), double negative T (DNT) cells (CD3 + CD4-CD8-), B cells (CD3-CD19+), NK cells (CD3-CD56+), and NKT-like cells (CD3 + CD56+) in the peripheral blood of 813 healthy children. We used the method of the international standard document (Clinical Laboratory Standard Institute C28-A3) to establish reference intervals with a single platform. First, we used the Skewness and Kurtosis test to analyze the normality of the data. The nonnormally distributed data was transformed into approximately normal distribution by the Box-Cox transformation. Second, we used the Tukey’s method to eliminate outliers. Further, all the subjects were grouped into subgroups according to sex (male and female) and age (0–1 month, 2–12 months, 1–3 years, 4–6 years, and 7–18 years). We used the standard normal deviation test ( Z -test) to evaluate whether age and sex were possible grouping factors. The analyses indicated age to be an important factor associated with changes in lymphocyte subsets. The absolute number of lymphocyte subsets and total number of lymphocytes, T cells, CD4 T cells, CD8 T cells, and B cells gradually increase from birth to 12 months and then gradually decrease with age. Furthermore, CD4 T cells and the ratio of CD4+/CD8+ gradually decrease with age. In contrast, CD8 T and DNT cells gradually increase with age. The percentage and number of NK and NKT-like cells gradually increase with age and remain stable between 1 and 18 years of age. In conclusion, the age-related reference intervals established in healthy children in this study can aid in monitoring and assessing the changes in immune levels in diseased conditions.

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Burden, Eleanor G., Timothy J. Batten, Christopher D. Smith i Jonathan P. Evans. "Reverse total shoulder arthroplasty". Bone & Joint Journal 103-B, nr 5 (1.05.2021): 813–21. http://dx.doi.org/10.1302/0301-620x.103b.bjj-2020-2101.

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Aims This systematic review asked which patterns of complications are associated with the three reverse total shoulder arthroplasty (RTSA) prosthetic designs, as classified by Routman et al, in patients undergoing RTSA for the management of cuff tear arthropathy, massive cuff tear, osteoarthritis, and rheumatoid arthritis. The three implant design philosophies investigated were medial glenoid/medial humerus (MGMH), medial glenoid/lateral humerus (MGLH), and lateral glenoid/medial humerus (LGMH). Methods A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on complication occurrence and patient-reported outcome measures (PROMs). Meta-analysis was conducted on the reported proportion of complications, weighted by sample size, and PROMs were pooled using the reported standardized mean difference (SMD). Quality of methodology was assessed using Wylde’s non-summative four-point system. The study was registered with PROSPERO (CRD42020193041). Results A total of 42 studies met the inclusion and exclusion criteria. Rates of scapular notching were found to be significantly higher in MGMH implants (52% (95% confidence interval (CI) 40 to 63)) compared with MGLH ((18% (95% CI 6 to 34)) and LGMH (12% (95% CI 3 to 26)). Higher rates of glenoid loosening were seen in MGMH implants (6% (95% CI 3 to 10)) than in MGLH implants (0% (95% CI 0 to 2)). However, strength of evidence for this finding was low. No significant differences were identified in any other complication, and there were no significant differences observed in PROMs between implant philosophies. Conclusion This systematic review has found significant improvement in PROMS and low complication rates across the implant philosophies studied. Scapular notching was the only complication found definitely to have significantly higher prevalence with the MGMH implant design. Cite this article: Bone Joint J 2021;103-B(5):813–821.

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Halkes, Constantijn J. M., Inge Jedema, Judith Olde Wolbers, Esther M. van Egmond, Peter A. Von Dem Borne, Erik W. A. F. Marijt i J. H. Frederik Falkenburg. "Low Incidence of Post-Transplant EBV-Related Disease After Alemtuzumab-Mediated T Cell Depletion Is Explained by the Differential Susceptibility to Alemtuzumab of B Cells and Protective CD8 and CD4 T Cells". Blood 116, nr 21 (19.11.2010): 2330. http://dx.doi.org/10.1182/blood.v116.21.2330.2330.

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Abstract Abstract 2330 In vivo T cell depletion with anti-thymocyte globulin (ATG) or alemtuzumab (anti-CD52) before reduced intensity allogeneic stem cell transplantation (alloSCT) in combination with in vitro T cell depletion with alemtuzumab reduces the risk of GVHD. Detectable levels of circulating antibodies are present up to several months after the alloSCT, leading to a delayed immune reconstitution which is associated with an increased incidence of opportunistic infections and early relapses. Prior to 2007, combined in vitro (Alemtuzumab 20 mg added “to the bag”) and in vivo T cell depletion with horse-derived ATG (h-ATG) resulted in good engraftment without GVHD in the absence of GVHD prophylaxis after reduced intensity alloSCT using conditioning with fludarabine and busulphan. Due to the unavailability of h-ATG, rabbit-derived ATG (r-ATG) 10–14 mg/kg was introduced in the conditioning regimen in 2007. Strikingly, in this cohort of patients, early EBV reactivation and EBV-associated post-transplantation lymphoproliferative disease (PTLD) was observed in 10 out of 18 patients at a median time of 6 weeks after alloSCT (range 5 to 11 weeks) in the absence of GVHD or immunosuppressive treatment. Analysis of T and B cell recovery early after transplantation revealed preferential depletion of T cells as compared to B cells, thereby allowing unrestricted proliferation of EBV infected B cells. Due to this unacceptable high incidence of EBV-related complications, in the conditioning regimen r-ATG was replaced by low dose alemtuzumab (15 mg i.v. day -4 and -3) in 2008. In this cohort of 60 patients, only 2 patients experienced transient EBV reactivation during the first 3 months after alloSCT and one patient developed an EBV-associated lymphoma 4 weeks after alloSCT. To investigate the mechanisms underlying the low incidence of EBV reactivation using alemtuzumab for T cell depletion, we studied the in vivo and in vitro effects of alemtuzumab on different lymphocyte subsets. First, lineage-specific reconstitution was studied in 20 patients from the alemtuzumab cohort with known CD52 negative diseases (11 AML and 9 multiple myeloma) to exclude the confounding effect of antibody absorption by malignant cells. Whereas at 3 weeks after alloSCT detectable numbers of circulating NK cells and T cells were observed (medians 71 (range 6–378), and 12 (range 1–1164)E6/L, respectively), no circulating B cells could be detected (median 0, range 0–1 E6/L). At 6 weeks after alloSCT, NK and T cell numbers further increased (medians 212 (52-813), and 130 (range 25–1509)E6/L, respectively), whereas B cell numbers still remained low in the majority of patients (median 15, range 0–813E6/L). In all patients, T cells were detectable before the appearance of circulating B cells. Furthermore, the expression of CD52 and the sensitivity to alemtuzumab-mediated complement-dependent cell lysis (CDC) of B cells, T cells and NK cells was measured in vitro. The highest CD52 expression was observed on B cells (mean fluorescence intensity (MFI) 120), resulting in 95% lysis after incubation with 10ug/mL alemtuzumab and rabbit complement. NK cells showed a significantly lower CD52 expression (MFI 41), which was also reflected by a lower susceptibility to alemtuzumab-mediated CDC (62% lysis). Interestingly, differential expression of CD52 was observed on CD4 and CD8 T cells (MFI 120 and 101, respectively). Cytotoxicity analysis revealed relative protection of CD8 compared to CD4 T cells against alemtuzumab-mediated CDC, resulting in 52% and 90% lysis, respectively. Based on these results, we investigated in detail the presence and phenotype of the CD4 and CD8 subsets and EBV-specific CD8 T cells using tetramer staining at 6 weeks after alloSCT. In accordance with the in-vitro expression and susceptibility data, circulating CD52+ CD8 T cells including EBV-specific T cells were detectable. Interestingly, the majority of circulating CD4 T cells (64-93%, n=4) lacked CD52 expression, explaining their capacity to persist in the presence of alemtuzumab. We conclude that in vivo and in vitro T cell depletion with alemtuzumab is associated with a relatively low risk of EBV-associated PTLD because of efficient B cell depletion and persistent EBV immunity allowed by the relative insusceptibility for alemtuzumab of CD8 T cells and the development of CD52 negative escape variants of CD4 T cells. Disclosures: No relevant conflicts of interest to declare.

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Grant, H. Roger. "The Sunshine Economy: An Economic History of Florida since the Civil War. By William B. Stronge. Gainesville: University Press of Florida, 2008. xxi + 334 pp. Figures, maps, bibliography, notes, index. Cloth $34–95. ISBN: 978–0–813–03201–6." Business History Review 82, nr 4 (2008): 856–58. http://dx.doi.org/10.1017/s0007680500063285.

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McDonald, L. Clifford, Hui Tzu Yu, Hsiao Chun Yin, Chao Agnes Hsiung, Chien-Ching Hung i Monto Ho. "Correlates of Antibiotic Use in Taiwan Hospitals". Infection Control & Hospital Epidemiology 22, nr 9 (wrzesień 2001): 565–71. http://dx.doi.org/10.1086/501953.

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AbstractObjective:To determine factors that correlate with increased antibiotic use among adult inpatients in Taiwan.Design:Retrospective survey of medical records.Setting:14 acute-care hospitals (8 regional hospitals, 6 medical centers) in Taiwan.Participants:A systematic probability sample from each hospital, totaling 663 adult inpatients who were discharged or had died in early 1999.Measurements:Infectious disease physicians at the 14 hospitals collected data from medical records regarding patient demographics, hospitalization, discharge diagnosis, and antibiotics received.Results:A total of 447 (67%) patients received antibiotics for an overall rate of 813 antibiotic-days (number of days patients received each antibiotic)/1,000 patient-days. Both the proportion of beds in intensive care units ([ICUs] Pearson correlation coefficient [r], 0.67; 95% confidence interval [CI95], 0.36-0.89;P<.01) and the proportion of patients admitted to surgical services (r,0.66; CI95, 0.20-0.88;P=.01) correlated with the mean patient rate of antibiotic-days/hospital-day (MPAUD). In contrast, we found no correlation between the proportion of patients who received antibiotics and the MPAUD. Using multiple linear regression, medical center status was the only independent predictor for increased MPAUD (regression coefficient [b], 0.15; CI95, 0.05-0.24;P<.01). There was no correlation between pooled rates of antibiotic-days/hospital-day and any hospital demographic factors. First-generation cephalosporin (39%) and aminoglycoside (24%) use accounted for the majority of antibiotic-days.Conclusions:Antibiotic use is greater in medical centers than in regional hospitals and appears to be independent of surgical case mix or the proportion of ICU beds. Determination of multiple, independent measures of antibiotic use may be necessary to understand the relation between antibiotic use and resistance in hospitals.

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Cavallo-Perin, P., A. Bruno, P. Nuccio, A. M. Dall'omo, G. R. Fronda, P. Avagnina, G. Molino, C. Bozzo i G. Pagano. "Insulin resistance in human liver cirrhosis is not modified by porto-systemic surgical shunt". Acta Endocrinologica 112, nr 3 (lipiec 1986): 377–82. http://dx.doi.org/10.1530/acta.0.1120377.

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Abstract. Cirrhosis of the liver is characterized by glucose intolerance and hyperinsulinaemia. It is considered an insulin resistant state with both a receptor and a post-receptor defect of insulin activity. It would appear that reduced hepatic degradation rather than increased B-cell production is responsible for hyperinsulinaemia. The effect of surgical portosystemic shunt on insulin resistance was studied in 18 cirrhotics with impaired glucose tolerance (12 males, 6 females; mean age 46.9 ± 0.7 years) by measuring: glucose production (3H-glucose infusion), glucose utilisation (euglycaemic clamp at ~ 100, ~ 1000 and ~ 10000 μU/l), plasma insulin and C-peptide levels, and liver function indices (serum bilirubin, albumin, ALT, GGT) before and 2 months after surgery. Liver sorbitol clearance was also employed to measure variations in the functional liver plasma flow induced by the shunt. No significant changes were noted in: glucose production (1.94 ± 0.17 sem vs 1.96 ± 0.17 mg/kg/min), glucose utilisation (metabolic clearance rate: 3.32 ± 0.48 vs 3.42 ± 0.43 at ~ μU/ml; 9.70 ± 1.0 vs 9.16 ± 0.9 at~ 1000 μU/ml; 10.92 ± 1.1 vs 11.07 ± 0.8 ml/kg/min at ~ 10000 μU/ml), fasting plasma insulin, C-peptide and C-peptide/insulin molar ratio (4.66 ± 0.47 vs 5.50 ± 0.54), and the liver function indices. By contrast, there was a significant decrease in functional liver plasma flow (813 ± 34 vs 604 ± 34 ml/min, P < 0.001). These results suggest that surgical shunt does not modify the mechanisms and the degree of insulin resistance in human liver cirrhosis and that hyperinsulinaemia can not be primarily referred to change of liver perfusion, but is most probably related to liver cell damage.

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Gutierrez, J., J. Balladares, G. Suarez, M. Pugliese, F. Rigali, L. Cané, M. Panarace i M. Medina. "32 FIRST SHEEP CLONES BORN IN SOUTH AMERICA". Reproduction, Fertility and Development 20, nr 1 (2008): 96. http://dx.doi.org/10.1071/rdv20n1ab32.

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Since the birth of the first animal produced by nuclear transfer using adult somatic cells (Wilmut et al. 1997 Nature 385, 810–813), cloning has been used in many species. Although sheep were the first species to be cloned, the limited data available from different research groups indicate sheep to be among the lowest in terms of efficiency (0.5–2%), mainly due to high losses during pregnancy and the postnatal period. Since there were no previous reports on cloning of small ruminants in South America, the aims of the present study were to perform a larger scale sheep cloning program to evaluate the efficiency under local conditions in Argentina and describe the main postmortem findings observed in fetuses and extraembrionary membranes. Male adult fibroblast cell lines from different animals were used. Matured oocytes were recovered by flushing the oviducts of synchronized and superovulated donor ewes. From 437 ewes, 4720 oocytes were recovered (10.8 oocytes/ewe). Enucleation and nuclear transfer were performed as described previously, with modifications. Cell fusion was induced by a double electrical pulse in sorbitol medium (1.20 kV cm–1, 30 μs). Fused couplets were activated using ionomycin for 5 min and then cycloheximide and cytochalasin B for 5 h. Embryo culture was performed at 38.5°C in a 5% O2, 5% CO2, 90% N2 atmosphere, in KSOM supplemented with 2% FCS and 0.2 mm glucose on Day 3 of culture. After 6 to 7 days in culture, embryos were graded and then surgically transferred into synchronized recipients. Pregnancy rate was checked 23 days after embryo transfer and then weekly until 60 days, using a transrectal 5-MHz probe (Toshiba, Tokyo, Japan). From 70 to 150 days, a 3-MHz convex probe was used to perform monthly transabdominal scans. Most of the losses (70%) occurred within the first 90 days of pregnancy, and 15% of the fetuses were aborted late in gestation. Main ultrasound findings were fetal and placental hydrops and bilateral hydronefrosis. In addition, 6 of the ewes developed hydrallantois. Ewes beyond 148 days of gestation were induced for parturition using four IM injections of betamethasone 12 h apart (3.96 mg each). If labor did not commence, a C-section was performed (9/11). Eleven cloned lambs were born; two of them are still alive (6 months). All newborns were clinically evaluated after birth and their health assessed. Of the newborns, 80% died in the first 24 h after birth; they were depressed, with severe respiratory distress that developed into acidosis. At necropsy, fetuses were found with: collapsed lungs (9/9), fatty liver (6/9), ascitis (7/9), hydronefrosis (6/9), and placental edema with partial degeneration of placentomes (8/9). The final efficiency obtained in this large-scale cloning program (0.6%) was very similar to that reported by others in a smaller trials. Many studies on gene expression of cloned embryos and placental development have partially explained why this technique has a particular low efficiency in the sheep species; therefore further studies should be done in order to improve the outcome. Table 1. Efficiency of sheep cloning

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Atsumi, Tatsuya, Tomonori Sekizaki, Hiraku Kameda, Akinobu Nakamura, Aika Miya, Hiroshi Nomoto, Kyu Yong Cho, Hiroaki Motegi i Hideaki Miyoshi. "ODP338 Neuromedin B Receptor Antagonist Suppresses ACTH Secretion and Cell Proliferation in Human and Mouse Corticotroph Adenoma". Journal of the Endocrine Society 6, Supplement_1 (1.11.2022): A503—A504. http://dx.doi.org/10.1210/jendso/bvac150.1047.

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Abstract Objective We previously reported that Neuromedin B (NMB) is expressed in murine pituitary corticotrophs under adrenal insufficiency (1). Because NMB is also expressed in several cancer cells and stimulates ACTH secretion, we hypothesized that NMB is related to corticotroph adenoma cell proliferation and hormone secretion. To examine this hypothesis, we investigated the effects of a NMB receptor (NMBR) antagonist on AtT-20 cells, a tumor xenograft model and patient-derived corticotroph adenoma cells. Methods 1. NMB and NMBR expression in human pituitary adenoma: We performed real-time qPCR and immunostaining on human pathological specimens of corticotroph and non-functioning pituitary adenomas to investigate NMB and NMBR expression. 2. Experiments in AtT-20 cells: We extracted RNAs, proteins and mediums from AtT-20 cells after incubation with NMBR antagonist PD168368, and performed real-time qPCR, western blotting and ELISA analyses. We also performed WST-1 assay to investigate cell proliferation. 3. Experiments in a tumor xenograft model: AtT-20 cells in Matrigel were injected subcutaneously into BALB/c-nu mice. A week after inoculation, we administered 1.2 mg/kg PD168368 intraperitoneally once daily for 14 days. Upon completion of treatment, tumors were measured and cardiac blood was collected. 4. Experiments in patient-derived corticotroph adenoma cells: We isolated surgically resected human corticotroph adenoma cells from patients who underwent trans-sphenoidal surgery and investigated mRNA expression and medium ACTH secretion after incubation with PD168368. Statistical analysis: Comparisons between two groups were made by unpaired Student t test. Multiple groups were compared using one-way ANOVA followed by Dunnett's test for comparison with control group. Statistical significance was defined as p < 0. 05. Results 1. NMB and NMBR expression levels were significantly higher in human corticotroph adenomas (13 and 33 times higher, respectively) than in non-functioning adenomas in the qPCR analyses. Immunostaining confirmed higher expression of NMB and NMBR in corticotroph adenoma. 2. Treatment with 100 nM PD168368 significantly suppressed Pomc mRNA and protein expression in AtT-20 cells by 22% and 25% respectively compared control group. Medium ACTH secretion, mRNA and protein expression of cyclin E1 and cell proliferation were also suppressed by PD168368. 3. Mice treated with PD168368 had significantly lower tumor growth rate, plasma ACTH and corticosterone than control group (70 vs 161%, 97 vs 180 pg/ml, 813 vs 1045 ng/ml, respectively). 4. Treatment with PD168368 significantly suppressed POMC mRNA expression (12-31%) in 4 out of 6 patient-derived corticotroph adenoma cells. Medium ACTH secretion was also suppressed (14-53%) in 3 out of 4 cases which could be evaluated. Cyclin E mRNA expression were also suppressed in 3 out of 4 cases in which POMC mRNA expression were suppressed. Conclusions NMBR antagonist may represent a potential treatment for Cushing disease, which effect may be mediated by decreased cyclin E expression. Reference: (1) Kameda H et al., Endocrinology 2014;155(7): 2492–9. Presentation: No date and time listed

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Cecil, Audrey L., Jesse M. Smotherman, Kathryn Glayat, Beth Arredondo, Anneliese Boettcher i Emily Brickell. "A-297 Analysis of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Cortical-Subcortical Deviation Index and Subtest Scores in Differentiating Between Cortical and Subcortical Dementia Profiles". Archives of Clinical Neuropsychology 37, nr 6 (17.08.2022): 1451. http://dx.doi.org/10.1093/arclin/acac060.297.

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Abstract Objective: This study examines the utility, both broadly and at the subtest level, of the cortical-subcortical index (CSI) of the RBANS in classifying cortical and subcortical cognitive profiles. Methods: Outpatients in a southeast hospital were grouped by diagnosis: Alzheimer’s Disease (AD, n=33; age=77.03[6.04], ed=13.55[2.58], 88% female, 91% Caucasian), Subcortical (n=36, age=72.17[11.51], ed=12.63[3.70], 50% female, 75% Caucasian) and No Diagnosis (n=30, age=71.97[5.59], ed=13.24[3.04], 80% female, 70% Caucasian). The CSI formula ([visuospatial construction + attention]/2]–[delayed memory + language]/2)) was calculated for patients. Groups were compared on CSI score using one-way analysis of variance (ANOVA) and Tukey’s HSD. ROC analysis was used to identify CSI cutoff that optimizes classification. Independent t-tests for subtests comprising the CSI were run comparing Cortical/Subcortical groups, with stepwise regression to evaluate significant subtests. Results: CSI differed significantly between groups (F[2, 96]=30.58, p<.001]). Tukey’s HSD found CSI was significantly different between Cortical/Subcortical (p<.001, 95% CI=16.38, 31.27) and Cortical/No Diagnosis (p<.001, 95% CI=9.62, 25.20), but not Subcortical/No Diagnosis (p=.118, 95% CI=-14.04, 1.22). ROC yielded a CSI cutoff of <-1 for optimal classification (AUC=.888, SE .039, p<.001, 95%CI .813-.964, Sensitivity=.750, Specificity=.909). Independent t-tests resulted in significance in 6 subtests. Stepwise regression using significant subtests revealed the best CSI-prediction model explained 28% of the variance (F[1,111]=44.06, p<.001) and included only List Recall (B=-2.96, p<.001). Conclusions: CSI’s accuracy in classifying Cortical from Subcortical profiles was 81.6% using a cut score of -1. List Recall accounted for most of the variance in the CSI. Limitations included small sample size and using RBANS scores to determine original diagnostic category.

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Тileubek, N., N. Shamsutdinova, V. Mukhamadieva, D. Abdulganieva, R. Abdrakipov i S. Lapshina. "AB1299 THE INCIDENCE OF POST-COVID SYNDROME IN PATIENTS WITH RHEUMATIC DISEASES". Annals of the Rheumatic Diseases 82, Suppl 1 (30.05.2023): 1879.1–1879. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5712.

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BackgroundPost-COVID Syndrome occurs in people after coronavirus infection with confirmed SARS-CoV-2 infection or in people with suspected coronavirus infection, usually 3 months after the onset of COVID-19, with symptoms that last at least 2 months and cannot be explained by an alternative diagnosis. Although post-COVID manifestations have been previously studied in the general population, they have not been studied in a specific population of patients with inflammatory rheumatic diseases. The list of post-covid syndromes includes arthralgia, arthritis, myalgia, vasculitis with damage to vessels of various sizes, antiphospholipid syndrome, as well as a number of immunological markers that are characteristic of a wide range of rheumatic diseases [1]Objectivesto study the incidence of post-COVID syndrome in patients with rheumatic diseases (RD).MethodsFrom March 2020 to September 2022, 271 patients with RD who had a novel coronavirus infection (NCI) with a confirmed SARS-CoV-2 PCR result and/or X-ray computed tomography (CT) of the lungs were under observation. Among the patients, 68 (25%) were males, 203 (75%) were females. The median age was 56 [46.65] years. The average duration of RD at the time of NCI was 10.9 [5.15] years. The distribution of patients was as follows: rheumatoid arthritis (RA) - 186 people (68.6%), ankylosing spondylitis (AS) - 46 people (16.9%), psoriatic arthritis (PsA) - 38 people (14%). The results of clinical and laboratory examinations for RD were assessed before the NCI and 3 and 6 months after the NCI. A survey of patients was conducted as part of an in-depth medical examination 3 and 6 months after undergoing NCI for the presence of post-COVID manifestations.Results90.4% of patients noted the persistence or appearance of symptoms after undergoing NCI, and all of them had a combination of at least 3 different groups of symptoms. The most common increase/appearance of pain in the joints was 91.1%. Among the respondents, the second symptom in terms of frequency of occurrence, in 52.9% of cases, were asthenic manifestations in the form of the appearance and intensification of fatigue, muscle pain, headaches. A decrease in working capacity and quality of life was noted by 52.9%. Complaints about a significant increase in dyspnea and a decrease in exercise tolerance were noted by 35.3% of the respondents, while there was no connection with the severity of NCI, and half of the patients had a mild course of NCI. Increased chest pain and/ or palpitations - in 23.5% of people. Half of the patients noticed hair loss and skin rash at 3-6 months after NCI: significant 35.2%, insignificant 20.5%. A slight persistence of elevated temperature since recovery from NCI was recorded in 17.6% of patients. RD stage of remission before NCI was in 9 (3.3%), low degree of activity 58 (21.4%), moderate degree of activity 140 (51.6%), high degree of activity 21 (7.7%), 43 (15.8%) people - no data. Moderate and high degrees of RD activity before NCI influenced the increase in joint pain (p<0.023), unstable course of diabetes mellitus (p<0.032) by 3 after recovery.ConclusionIn patients with RD, post-covid manifestations persist, primarily due to articular (91.1%) and general constitutional symptoms (85.3%) from 3 to 6 months after undergoing NCI. Moderate and high degrees of RD activity before NCI significantly affect the severity of the articular syndrome and the unstable course of diabetes mellitus. Therapy for post-COVID syndrome in patients with rheumatological diseases should be personalized and determined by the characteristics of this patient’s condition.Reference[1]Lapostolle F., Schneider E., Vianu I., Dollet G., Roche B., Berdah J., Michel J., Goix L., Chanzy E., Petrovic T., Adnet F. Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study// Intern. Emerg. Med. 2020. Vol. 15 (5). P. 813–817.https://doi.org/10.1007/s11739-020-02379-zAcknowledgements:NIL.Disclosure of InterestsNone Declared.

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Willenbrock, F., i K. Brocklehurst. "Chemical evidence for the pH-dependent control of ion-pair geometry in cathepsin B. Benzofuroxan as a reactivity probe sensitive to differences in the mutual disposition of the thiolate and imidazolium components of cysteine proteinase catalytic sites". Biochemical Journal 238, nr 1 (15.08.1986): 103–7. http://dx.doi.org/10.1042/bj2380103.

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Benzofuroxan reacts with the catalytic-site thiol group of cathepsin B (EC 3.4.22.1) to produce stoichiometric amount of the chromophoric reduction product, o-benzoquinone dioxime. In a study of the pH-dependence of the kinetics of this reaction, most data were collected for the bovine spleen enzyme, but the more limited data collected for the rat liver enzyme were closely similar both in the magnitude of the values of the second-order rate constants (k) and in the shape of the pH-k profile. In acidic and weakly alkaline media, the reaction is faster than the reactions of benzofuroxan with some other cysteine proteinases. For example, in the pH region around 5-6, the reaction of cathepsin B is about 10 times faster than that of papain, 15 times faster than that of stem bromelain and 6 times faster than that of ficin. The pH-dependence of k for the reaction of cathepsin B with benzofuroxan was determined in the pH range 2.7-8.3. In marked contrast with the analogous reactions of papain, ficin and stem bromelain [reported by Shipton & Brocklehurst (1977) Biochem. J. 167, 799-810], the pH-k profile for the cathepsin B reaction contains a sigmoidal component with pKa 5.2 in which k increases with decrease in pH. This modulation of the reactivity of the catalytic-site -S-/-ImH+ ion-pair state of cathepsin B (produced by protonic dissociation from -SH/-ImH+ with pKa approx. 3) towards a small, rigid, electrophilic reagent, in a reaction that appears to involve both components of the ion-pair for efficient reaction, suggests that the state of ionization of a group associated with a molecular pKa of approx. 5 may control ion-pair geometry. This might account for the remarkable finding [reported by Willenbrock & Brocklehurst (1984) Biochem. J. 222, 805-814] that, although the ion-pair appears to be generated in cathepsin B as the pH is increased across pKa 3.4, catalytic competence is not generated until the pH is increased across pKa 5-6.

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Siddiqui, Mustaqeem A., Svetomir N. Markovic, Wendy K. Nevala, Cindy B. Uhl, William G. Morice i Luis F. Porrata. "Day 15 Natural Killer (NK) Cell Recovery Predicts Progression Free Survival after Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma." Blood 108, nr 11 (16.11.2006): 2914. http://dx.doi.org/10.1182/blood.v108.11.2914.2914.

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Abstract The peripheral blood absolute lymphocyte count (ALC) on day 15 after autologous stem cell transplantation (ASCT) has been shown to be an independent predictor for overall survival (OS) for many malignancies including acute myelogenous leukemia (AML), breast cancer, multiple myeloma (MM), primary systemic amyloidosis, and Hodgkin’s and non-Hodgkin’s lymphoma (NHL). However, due to the retrospective nature of previous studies, the peripheral blood lymphocyte subpopulations that predict survival are unknown. To prospectively correlate peripheral blood lymphocyte subpopulations after ASCT and progression free survival, peripheral blood lymphocytes collected from patients before and on day 15 after ASCT were analyzed by four color flow cytometry for CD3, CD4, CD8, CD16, CD 19, and CD56. Patients were then dichotomized into two groups: patients achieving normal numbers of lymphocyte subset (i.e. CD4, CD8, CD19, CD16/56) count versus those who did not. Progression free survival was then analyzed by the Kaplan-Mier method. In our cohort of 14 patients, 9 were male and 5 were female. Nine patients were diagnosed with diffuse large cell B cell lymphoma, two with mantle cell, two with follicular, and one with peripheral T cell lymphoma. On presentation, one patient had stage I, four patients had stage II, four had stage III, and five patients had stage IV disease. The median age at ASCT was 53 years (range: 26–70). The preliminary data from this ongoing prospective study of 14 patients shows that on day 15 after ASCT, 4/14 (29%) of patients achieved a normal CD3 count (median 321, range: 69–2069 cells/ml) 3/14 (21%) achieved a normal CD4 count (median 206, range: 31–1091 cells/ml), 6/14 (43%) achieved a normal CD 8 count (median 88.5, range: 13–813 cells/ml) 1/14 (7%) achieved a normal CD19 count (median 2, range:0–227 cells/ml), and 8/14 (57%) achieved a normal CD16/56 count (median 85.5, range: 10–744 cells/ml). The median follow-up was 12 months (range: 3–45 months). On univariate analysis, patients achieving an absolute NK cell count of ≥ 80 cells/μ on day 15 had significantly improved progression free survival compared to those who did not (not reached vs 3 months, p<0.006, respectively). Similar analysis evaluating the absolute CD3, CD4, CD8, and CD 19 count was not significant (p=0.1, p=0.258, p= 0.06, and p=0.55, respectively). To our knowledge, this is the first report detailing the critical role of NK cell immune reconstitution after ASCT in progression free survival. Figure Figure

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Li, Yi Ying Regina, Soo Jin Seung, Stephanie Y. Cheng, Matthew Cheung i Nicole Mittman. "Resource Utilization and Costs in the Care of Patients with Hematologic Malignancies". Blood 134, Supplement_1 (13.11.2019): 4745. http://dx.doi.org/10.1182/blood-2019-131407.

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Background: Patients with hematologic malignancies (HMs) make up a significant portion of the healthcare cost burden. To help understand how patients are managed and to guide allocation of public funds, the utilization of healthcare resources in various phases of disease should be investigated. We examined resource utilization and cost patterns during the pre-diagnosis, treatment, follow-up, and end-of-life phases of patients with specific HMs. Methods: We used the Cancer Care Ontario to identify patients with a diagnosis of HMs, including diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL) between 2006 and 2014. For phase-based analysis, we defined the following four phases of care: Pre-diagnosis: 90 days prior to Ontario Cancer Registry (OCR) diagnosis to index dateInitial treatment: index date to 6 months from OCR diagnosis dateFollow-up: from end of treatment phase to beginning of end-of-life (or completion of cohort follow-up)End-of-life: last 6 months of life We characterized resource utilization by determining overall and disaggregated health system costs for DLBCL and HL. Descriptive statistics were used to characterize the population, with continuous variables presented as medians (with interquartile ranges); costs ($CAN 2014) and resource utilization were normalized to 30-days and presented as means +/- standard deviation. Results: A total of 35,556 patients were diagnosed between 2006 and 2014 with a HM. Of these, 15% were diagnosed with DLBCL, and 7% with HL. There were 5,392 patients diagnosed with DLBCL, [53% male, median age 64 years (IQR 53-74)]. The median follow-up was 1,903 days (IQR 1,194-2,882) from diagnosis, and the median age at death was 72 (IQR 61-82). Mean overall 30-day cost was $1,175 (±2,267) in pre-diagnosis; $9,166 (±5,581) during initial treatment; $1,462 (±2,756) during follow-up; and $7,965 (±7,104) during end-of-life. Mean 30-day cost of cancer medication was 80.20 (±454.98) in pre-diagnosis, 3,115.03 (±1,235.76) during initial treatment, 232.48 (±711.93) during follow-up, and 304.63 (±694.28) during end-of-life. There were 2,367 patients with HL [53% male, median age 37 years (IQR 26-53)]. The median follow-up was 2,419 days (IQR 1,581-3,318) from diagnosis, and the median age at death was 62 (IQR 44-75). In HL, mean overall 30-day cost in Canadian dollars was $813 (±1,541) in pre-diagnosis, $5,473 (±3,485) during initial treatment, $895 (±1,619) during follow-up, and $8,678 (±9,086) during end-of-life. Mean 30-day cost of cancer medication was 91.08 (±368.25) in pre-diagnosis, 1,131.91 (±765.85) during initial treatment, 102.86 (±341.69) during follow-up, and 371.05 (±1,612.73) during end-of-life. Conclusions: Total cost per 30 days was highest in the initial treatment phase and at end-of-life. The highest costs are generally associated with inpatient care across all phases. This suggests that patients require significantly more health care resources during end-of-life and while on active treatment. Results can be used to guide allocation of health care dollars to ensure appropriate patient care throughout a patient's cancer journey. Disclosures No relevant conflicts of interest to declare.

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Oo, Thein H., Sumit Gaur, Janet Tierney, Alan Ashare i Robert Weinstein. "Hematocrit-Driven Referrals for Measurement of RBC Mass. Is the Natural History of Polycythemia Vera Changing?." Blood 106, nr 11 (16.11.2005): 4960. http://dx.doi.org/10.1182/blood.v106.11.4960.4960.

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Abstract Red blood cell mass (RCM) elevation is the sine qua non for diagnosis of polycythemia vera (pvera). The Polycythemia Vera Study Group (PVSG) employed therapeutic phlebotomy to lower the HCT to <55% as initial therapy. In the current era of frequent blood testing, RCM is usually requested based only on a high HCT often <55%. Thus the natural history of pvera may be changing if it is being diagnosed at an earlier stage. We reviewed 101 consecutive patients referred in 2002–2003 for RCM testing to characterize RCM requests from a large community referral base. There were 61 men and 40 women with mean HCT<55% (Table 1). 20 had lung disease or were smokers, 3 presented with arterial or venous thrombosis, 7 had cancer, 2 had renal cysts. HCT of men was higher than HCT of women if RCM was normal, but HCT were equivalent between genders if RCM was elevated. HCT was higher in men (p=0.0010) and women (p<0.0001) if RCM was elevated versus normal. HCT elevation was similar in secondary polycythemia vs pvera in men (51.0±4.02 vs 54.3±6.23; p=0.3397) or women (50.5±4.80 vs 49.3±2.12; p=0.4762). Table 1. HCT of patients referred for RCM measurement Gender Whole Group Normal RCM High RCM n HCT n HCT n HCT HCT shown as Mean (Median) ±SD Male 61 48.3 (47.8) ±4.89 45 46.9 (47.2) ±4.0 16 52.1 (51.3) ±5.16 Female 40 45.0 (43.8)± 4.72 32 43.3 (42.5) ±3.69 10 50.0 (50.0) ±3.84 p value 0.0001 <0.0001 0.4932 We examined whether, despite a lower presenting HCT, those with normal RCM demonstrated PVSG criteria that justified referral to our Nuclear Medicine department. Only 7 of the 75 patients with normal RCM met at least 2 of the PVSG “B” criteria or had splenomegaly, thus might have been diagnosed with pvera had RCM been high (Table 2). Table 2. 2 PVSG “B” criteria or splenomegaly and normal RCM Gender WBC ≥12K PLT ≥400K B12 ≥900 ≥ LAP 100 Splenomegaly M 14.4 413 640 158 “normal” M 12.1 585 1336 53 “normal” M 9.4 428 1139 68 “normal” M 8.6 132 1343 15 cm M 8.2 312 492 186 17 cm F 18.2 582 719 23 “normal” F 6.3 226 318 “enlarged” F 7.1 146 813 15.3 cm Overall, 10 of 40 women and 16 of 61 men had an elevated RCM: 4 women and 5 men with polycythemia vera; 6 women and 11 men with secondary polycythemia. One other man was diagnosed with polycythemia vera on the basis of a borderline elevated RCM (33.8 ml/kg), normal O2 Sat on room air, popliteal artery thrombosis, and 3 “B” criteria. Serum erythropoietin (EPO) was low at 2.6 mU/ml (ref range 4–16). He was receiving therapeutic phlebotomy for hereditary hemochromatosis when his RCM was measured. He was the only patient with pvera whose EPO was low (three others had normal EPO levels). The 11 patients with secondary polycythemia who had EPO measured had normal levels. In summary, the HCT was the primary criterion for RCM testing for 2/3 of these patients. Only 5 presented with HCT>55%; mean HCT was ~50% in patients with elevated RCM. The bottom quartile HCT of women with elevated RCM in our patient population was 48.7%. This is a sensitive “cut-off” for finding an elevated RCM (p<0.0001, Chi square with Yates correction). We conclude that patients are referred for RCM testing when a high HCT is found, but at HCT far below the original PVSG parameters. Therefore polycythemia vera is now diagnosed earlier and in mostly asymptomatic patients. A normal EPO level does not rule out a diagnosis of pvera. A HCT < 48.7% may not warrant the measurement of RBC mass.

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Ma, Hong, Ting Tan, Jie Wu, Juan Chen i Xiaohong Zhang. "Predisposition to Hyperthyroidism May Be Influenced by Functional TNF-α, IL-1, IL-6, and IL-10 Polymorphisms: A Meta-Analysis". International Archives of Allergy and Immunology 181, nr 12 (2020): 956–65. http://dx.doi.org/10.1159/000508284.

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Background: Predisposition to hyperthyroidism may be influenced by functional gene polymorphisms in tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). However, the results of the studies published so far remain discrepant, so we conducted a meta-analysis to more robustly investigate relationships between TNF-α/IL-1/IL-4/IL-6/IL-10 polymorphisms and predisposition to hyperthyroidism. Methods: A comprehensive literature retrieval from PubMed, Embase, Web of Science, WanFang, VIP, and CNKI was endorsed by the authors, and 38 studies were found to be eligible for pooled meta-analyses. Results: We found that genotypic frequencies of TNF-α −308 G/A, IL-1A −889 C/T, IL-6 −174 G/C, IL-6 −572 G/C, IL-10 −819 C/T, and IL-10 −1082 A/G polymorphisms among cases were significantly different from those among controls. Moreover, we also found that genotypic frequencies of TNF-α −308 G/A and IL-6 −174 G/C polymorphisms among cases of Caucasian origin were significantly different from those among Caucasian controls, and genotypic frequencies of IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −174 G/C, IL-6 −572 G/C, and IL-10 −1,082 A/G polymorphisms among cases of Asian origin were also significantly different from those among Asian controls. Conclusions: This meta-analysis suggests that TNF-α −308 G/A, IL-1A −889 C/T, IL-1B −511 C/T, IL-6 −174 G/C, IL-6 −572 G/C, IL-10 −819 C/T, and IL-10 −1,082 A/G polymorphisms may influence predisposition to hyperthyroidism in certain ethnic groups.

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Koide, Yasuo. "(Invited) Leading-Edge Diamond FET, MEMS, and Photodetector Devices". ECS Meeting Abstracts MA2023-02, nr 30 (22.12.2023): 1541. http://dx.doi.org/10.1149/ma2023-02301541mtgabs.

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Diamond is a candidate material for next-generation power electronics, micro-electro mechanical systems (MEMS), and solar-blind deep-ultraviolet (DUV) photodetector devices with excellent thermal stability and radiation hardness, which operate under extreme environment. In order to use an advantage of high-density hole channel of hydrogenated diamond (H-diamond) surface, we have developed the high-k stack gate dielectrics and AlN heterojuction gate for H-diamond FETs, such as HfO2/HfO2, LaAlO3/Al2O3 Ta2O5/Al2O3, and ZrO2/Al2O3, AlN/Al2O3 prepared by a combination of sputter-deposition (SD) and atomic layer deposition (ALD) techniques [1,2]. We also demonstrated the artificial diamond Fin-FETs with high-current level [3] and the nanolaminate insulator gate metal-oxide-gate FETs (MOSFETs) with k value as high as 100 [4], and the new transistor concept named by metal-insulator-metal-semiconductor field-effect transistor (MIMS-FET) to achieve normally-off operation by combining the advantages of MOSFET and metal-semiconductor FET [5]. In addition, we developed the routine ion-implantation process for preparing the diamond cantilever with a resonant frequency quality factor as high as one million [6,7]. We have also developed thermally stable Schottky barrier photodiode (SPD), metal-semiconductor-metal photodetector (MSMPD), and MSM-type SPD (IDF-SPD) with a large photoconductivity gain in DUV wavelength and a large discrimination ratio between DUV/visible light responsivity [8,9]. In this presentation, we will review the comprehensive our work on the diamond FET, MEMS, and photodetector devices. Acknowledgements: This work was in collaboration with J-W. Liu, M. Imura, M-Y. Liao, J. Alvarez in NIMS and A. Ouchiero and E. Obaldia in University of Taxes, Dallas, and partly supported by JSPS KAKENHI Grant Number 20H00313. References [1] Liu, M-Y. Liao, M. Imura, A. Tanaka, H. Iwai, Y. Koide, “Low on-resistance diamond field effect transistor with high-k ZrO2 as dielectric,” Sci. Reports, vol. 4, 6395-1 (2014). [2] Liu and Y. Koide, “An overview of high-k oxides on hydrogenated-diamond for metal-oxide-semiconductor capacitors and field-effect transistors.” SENSORS, 18, No.6, 813 (2018). [3] Liu, H. Ohsato, Bo Da, Y. Koide, "High Current Output Hydrogenated Diamond Triple-Gate MOSFETs," IEEE J. Electron Devices Society. 7, 561 (2019). [4] Liu, O. Auciello, E. de Obaldia, B. Da, Y. Koide, “Science and Technology of Integrated Super-High Dielectric Constant AlOx/TiOy Nanolaminates / Diamond for MOS Capacitors and MOSFETs,” Carbon. 172 112 (2021). [5] Liao, L. Sang, T. Shimaoka, M. Imura, S. Koizumi, Y. Koide, "Energy‐Efficient Metal–Insulator–Metal‐Semiconductor Field‐Effect Transistors Based on 2D Carrier Gases," Advanced Electronic Materials. 5 [5] (2019). [6] Liao, S. Hishita, E. Watanabe, S. Koizumi, Y. Koide, "Suspended single-crystal diamond nanowires for high-performance nanoelectro- mechanical switches." Adv. Mater. 22, 5393 (2010). [7] Wu, L. Sang, T. Teraji, T. Li, K. Wu, M. Imura, J. You, Y. Koide, M. Liao, "Reducing energy dissipation and surface effect of diamond nanoelectromechanical resonators by annealing in oxygen ambient," Carbon. 124, 281 (2017). [8] M. Liao, Y. Koide, and J. Alvarez, “Thermally Stable visible-blind Diamond Photodiode Using WC Schottky Contact,” Appl. Phys. Lett., 87, p. 0221051 (2005). [9] Liao and Y. Koide, "High-performance metal-semiconductor-metal deep-ultraviolet photodetectors based on homoepitaxial diamond thin film." Appl. Phys. Lett. 89, 113509 (2006).

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Sadek, Kamal Usef, Ramadan Ahmed Mekheimer, Tahany Mahmoud Mohamed, Moustafa Sherief Moustafa i Mohamed Hilmy Elnagdi. "Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating". Beilstein Journal of Organic Chemistry 8 (4.01.2012): 18–24. http://dx.doi.org/10.3762/bjoc.8.3.

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The multicomponent reaction of 5-aminopyrazole derivatives with cyclic 1,3-dicarbonyl compounds and dimethylformamide dimethylacetal (DMFDMA) in DMF at 150 °C under controlled microwave heating afforded regioselectively 8,9-dihydropyrazolo[1,5-a]quinazolin-6(7H)-ones 6 rather than the corresponding dihydropyrazolo[5,1-b]quinazolin-8(5H)-ones 4.

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Maya, Ram, M. Eric Gershwin i Yehuda Shoenfeld. "Hepatitis B Virus (HBV) and Autoimmune Disease". Clinical Reviews in Allergy & Immunology 34, nr 1 (18.09.2007): 85–102. http://dx.doi.org/10.1007/s12016-007-8013-6.

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Kotlyakov, V. M., i Yu Ya Macheret. "Fifty years of geophysical researches of glaciers in Institute of Geography, the Russian Academy of Sciences, 1966–2016". Ice and Snow 56, nr 4 (21.12.2016): 561–74. http://dx.doi.org/10.15356/2076-6734-2016-4-561-574.

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In 1967‑2015, Institute of Geography of the USSR/Russian Academy of Sciences together with other organizations carried out field expeditions in different areas of mountain and polar glaciations in many regions: the Polar Urals, Caucasus, Pamir, Zailiysky and Jungar Alatau, Tien‑Shan, Pamir‑Alai, the Kamchatka Peninsula, the Pyrenees, the Arctic – Spitsbergen, Novaya Zemlya, Franz Josef and Severnaya Zemlya, and Antarctica – on the ice flow B, and in the sub‑Antarctic – Islands King George, Galindez, and Livingston. The gravimetric and ground and aerial radar observations were made in these expeditions. About 300 glaciers of different morphological types and sizes with cold, subpolar and temperate thermal regime were studied. Basic results of these studies are the following: (1) the new data on the ice thicknesses, ice volumes, subglacial relief, internal structure, and thermal state of the glaciers were obtained; (2) the two‑layered (polythermal) glaciers consisting of the upper layer of cold ice and the lower layer of temperate water‑filled ice had been revealed in Svalbard for the first time; spatial distribution of cold, polythermal and temperate glaciers had been determined; (3) the evidences were obtained that measured changes in thickness of the upper cold ice layer in polythermal glaciers can be used to estimate the long‑period variations of regional climates and serve as regional paleothermometers; (4) methods for estimating the water content in temperate and polythermal glaciers from the RES data were developed; and its space‑time variations in temperate ices of the Svaldbald glaciers were estimated since even small water content inside of them can noticeably change their dynamic behavior; (5) methods for estimating the ice volume within glaciers in large regions of mountain and polar glaciations had been created; the ice storages were estimated in Svalbard, Franz Josef Land, Dzhungrsky Alatau, the Great Caucasus, and Mt. Elbrus; (6) detailed data on the ice thicknesses and the subglacial relief had been obtained for 40 glaciers in framework of different national and international programs and projects; the data can be used to solve a wide range of practical and theoretical problems, including numerical modeling. These studies demonstrated the following: (1) the use of monopulse radars VIRL‑6 and VIRL‑7 of decameter range (the central frequency is 20 MHz) with digital recording of the radar and GPS data is quite efficient for ground‑based and airborne (from helicopters) radio‑echo sounding of mountain and polar glaciers with their ice thicknesses up to 500–600 m; (2) it was found that thicknesses of glaciers in the Caucasus and Tien Shan can reach 330–430 m, while in regions of mountain, ice‑sheet and transitional glaciation on the Spitsbergen Archipelago – 300, 560 and 600 m, respectively, on the ice caps of the Franz‑Josef Land and Severnaya Zemlya – 450 and 813 m, and on King George and Livingston Islands (Sub‑Antarctica) – 330 and 500 m; (3) large parts of ice caps and outlet glaciers in Svalbard, Franz Josef Land, Severnaya Zemlya which beds were located below the sea level were found. Precisely these parts can be undergone quick shortening due to climate warming, and, thus, cause formation of icebergs making threats for ships and gas‑oil marine platforms in the Barents and Kara seas; (4) data of the measurements made possible to calculate volumes of a number of investigated glaciers and ice caps and to estimate the ice storages in large areas of mountain and polar glaciations (the Jungar Alatau, Great Caucasus, Spitsbergen, Franz Josef Land); (5) decreasing of glacier volumes on the Franz Josef Land and some Spitsbergen glaciers for the last decades had been estimated. Analysis of the data obtained had shown that considerable part of polythermal glaciers in Spitsbergen belong to type of surging glaciers; they have the winter englacial runoff and form the near‑glacier icings. It allows considering such glaciers as dynamically unstable, predisposed to surges as well as possible sources of winter water supply and additional sources of paleoinformation about long‑period variations of regional climate.

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Afonin, Nikolay N., i Vera A. Logachova. "Reactive Interdiffusion of Components in a Non-Stoichiometric Two‑Layer System of Polycrystalline Titanium and Cobalt Oxides". Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 22, nr 4 (26.11.2020): 430–37. http://dx.doi.org/10.17308/kcmf.2020.22/3058.

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We demonstrated the possibility of using the mathematical form of Darken's theory, applied to the description of the Kirkendall effect in binary systems, to the description of reactive interdiffusion in non-stoichiometric polycrystalline film oxide systems with limited solubility. The aim of the study was the simulation of reactive interdiffusion under vacuum annealing of a thin film system consisting of two non-stoichiometric polycrystalline titanium and cobalt oxides. The nonstoichiometric nature of the system assumes the presence of mobile components, free interstitial cobalt and titanium cations in it. Phase formation occurs as a result of reactive interdiffusion and trapping of mobile components of the systemon inter-grain traps. The proposed mechanism describes the formation of complex oxide phases distributed over the depth of the system.A complex empirical research technique was used, involving Rutherford backscattering spectrometry, X-ray phase analysis and modelling methods. The values of the characteristic parameters of the process were determined by numerical analysis of the experimentally obtained distributions of the concentrations of the components within the developed model. During vacuum annealing of a thin film two-layer system of non-stoichiometric TiO2–x–Co1–уO oxides in temperature range T = 773 – 1073 К, the values of the individual diffusion coefficients of cobalt DCo = 5.1·10–8·exp(–1.0 eV/(kT) cm2/s and titaniumDTi = 1.38·10–13·exp(–0.31 eV/(kT) cm2/s were determined.It was shown that for T = 1073 K, the phase formation of CoTiO3 with a rhombohedral structure occurs. The extension of the phase formation region of complex cobalt and titanium oxides increases with an increase in the vacuum annealing temperature and at 1073 K it is comparable with the total thickness of the film system.The model allows predicting the distribution of the concentrations of the components over the depth of multilayer nonstoichiometric systems in which reactive interdiffusion is possible. References1. Chebotin V. N. Fizicheskaya khimiya tverdogo tela[Physical chemistry of a solid state]. Moscow: KhimiyaPubl.; 1982. 320 p. (in Russ.)2. Tretyakov Yu. D. Tverdofaznye reaktsii [Solidphase reactions]. Moscow: Khimiya Publ.; 1978. 360 p.(in Russ.)3. Afonin N. N., Logacheva V. A. Interdiffusion andphase formation in the Fe–TiO2 thin-film system.Semiconductors. 2017;51(10): 1300–1305. DOI: https://doi.org/10.1134/S10637826171000254. Afonin N. N., Logacheva V. A. Cobalt modificationof thin rutile films magnetron-sputtered in vacuumtechnical. Technical Physics, 2018;63(4): 605–611. DOI:https://doi.org/10.1134/S10637842180400235. Afonin N. N., Logacheva V. A. Modeling of thereaction interdiffusion in the polycrystalline systemswith limited component solubility. IndustrialLaboratory. Diagnostics of Materials. 2019;85(9): 35–41.DOI: https://doi.org/10.26896/1028-6861-2019-85-9-35-41diffusion (In Russ., abstract in Eng.)6. Afonin N. N., Logacheva V. A. Modeling ofinterdiffusion and phase formation in the thin-filmtwo-layer system of polycrystalline oxides titaniumand cobalt. Kondensirovannye sredy i mezhfaznyegranitsy = Condensed Matter and Interphases.2019;21(3): 358–365. DOI: https://doi.org/10.17308/kcmf.2019.21/1157 (In Russ., abstract in Eng.)7. Darken L. S. Diffusion, mobility and theirinterrelation through free energy in binary metallicsystems. Trans. AMIE.1948;175: 184–190.8. Gurov K. P., Kartashkin B. A., Ugaste Yu. E.Vzaimnaya diffuziya v mnogofaznykh metallicheskikhsistemakh [Interdiffusion in multiphase metallicsystems]. Moscow: Nauka Publ.; 1981. 350 p. (In Russ.)9. Kulkarni N. S., Bruce Warmack R. J., RadhakrishnanB., Hunter J. L., Sohn Y., Coffey K. R., …Belova I. V. Overview of SIMS-based experimentalstudies of tracer diffusion in solids and application toMg self-diffusion. Journal of Phase Equilibria andDiffusion. 2014;35(6): 762–778. DOI: https://doi.org/10.1007/s11669-014-0344-410. Aleksandrov O. V., Kozlovski V. V. Simulationof interaction between nickel and silicon carbideduring the formation of ohmic contacts. Semiconductors.2009;43(7): 885–891. DOI: https://doi.org/10.1134/S106378260907010011. Kofstad P. Nonstoichiometry, diffusion, andelectrical conductivity in binary metal oxides. Wiley-Interscience; 1972. 382 p.12. Bak T., Nowotny J., Rekas M., Sorrell C. C. Defectchemistry and semiconducting properties of titaniumdioxide: II. Defect diagrams. Journal of Physics andChemistry of Solids. 2003;64(7): 1057–1067. DOI:https://doi.org/10.1016/s0022-3697(02)00480-813. Iddir H., Öğüt,S., Zapol P., Browning N. D.Diffusion mechanisms of native point defects in rutileTiO2: Ab initio total-energy calculations. PhysicalReview B. 2007;75(7): DOI: https://doi.org/10.1103/physrevb.75.07320314. Hoshino K., Peterson N. L., Wiley C. L. Diffusionand point defects in TiO2–x. Journal of Physics and Chemistry of Solids. 1985;46(12): 1397-1411. DOI:https://doi.org/10.1016/0022-3697(85)90079-415. Fiebig J., Divinski S., Rösner H., Estrin Y.,Wilde G. Diffusion of Ag and Co in ultrafine-graineda-Ti deformed by equal channel angular pressing.Journal of Applied Physics. 2011;110(8): 083514. DOI:https://doi.org/10.1063/1.365023016. Straumal P. B. Stakhanova S. V., Wilde G.,Divinski S. V. 44Ti self-diffusion in nanocrystalline thinTiO2 films produced by a low temperature wet chemicalprocess. Scripta Materialia. 2018;149: 31–35. DOI:https://doi.org/10.1016/j.scriptamat.2018.01.02217. Patrick R. Cantwell, Ming Tang, Shen J. Dillon,Jian Luo, Gregory S. Rohrer, Martin P. Harmer. Grainboundary complexions. Acta Materialia. 2014;62: 1–48.DOI: https://doi.org/10.1016/j.actamat.2013.07.03718. Dillon S. J., Tang M., Carter W. C., Harmer M. P.Complexion: A new concept for kinetic engineering inmaterials science. Acta Materialia, 2007;55(18):6208–6218. DOI: https://doi.org/10.1016/j.actamat.2007.07.02919. Grain boundary complexion transitions inWO3- and CuO-doped TiO2 bicrystals. Acta Materialia.2013;61(5); 1691–1704. DOI: https://doi.org/10.1016/j.actamat.2012.11.04420. Nie J., Chan J. M., Qin M., Zhou N., Luo J.Liquid-like grain boundary complexion and subeutecticactivated sintering in CuO-doped TiO2. ActaMaterialia. 2017;130: 329–338. DOI: https://doi.org/10.1016/j.actamat.2017.03.037

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Abudoukelimu, Abulajiang, Xinhui Yang, Lei Ge, Xiangyue Zeng, Yin Shu i Zeliang Zhao. "Effects of Amygdalin on TLR4/NF-αB Signaling Pathway-Mediated Proliferation and Apoptosis of Gastric Cancer Cells". Current Topics in Nutraceutical Research 20, nr 1 (29.07.2021): 153–58. http://dx.doi.org/10.37290/ctnr2641-452x.20:153-158.

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Gastric cancer is a highly malignant tumor of the digestive tract with high incidence rate and mortality. In the present study, we have shown decreased cell proliferation, increased apoptosis, and expression of proinflammatory cytokines (Interleukin-6, Interleukin-1β, and Tumor necrosis factor-α) in gastric cancer cells MGC-803 by amygdalin. Also, amygdalin treatment significantly reduced expression of the mRNA and protein for B-cell lymphoma 2 protein, CyclinD1, toll-like receptor 4, and REL-associated protein involved in NF-κB heterodimer formation in MGC-803 cells. In summary, amygdalin inhibits the proliferation of gastric cancer cells MGC-803 and promotes cell apoptosis by regulating the toll-like receptor 4/ nuclear factor-kappa B signaling pathway.

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Ma, Xiao, Xiaoyi Li, Danyue Peng, Huifang Wang, Lei Li, Hao Zhou, Daohong Zhou, Yi Luo i Lingbo Liu. "Inhibition of Both Activated p38 Mapkα and mTORC1 Potentiates the Effect of SR1 on Promoting Hematopoietic Reconstitution of Ex Vivo Expanded Human Umbilical Cord Blood Hematopoietic Stem Cells". Blood 128, nr 22 (2.12.2016): 2173. http://dx.doi.org/10.1182/blood.v128.22.2173.2173.

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Abstract Hematopoietic stem cells (HSCs) transplantation is a curative treatment for various hematological disorders. However, its use has been limited in part by the difficulty to obtain sufficient numbers of transplantable HSCs, especially from human umbilical cord bloods (hUCBs). Ex vivo expansion of cord blood HSCs can potentially mitigate the shortfall if the expanded HSCs can maintain their stemness for long-term hematopoietic reconstitution. Our previous studies have shown that some hUCB HSCs lose their "stemness" during ex vivo expansion in part due to induction of cellular senescence via p38MAPKα(p38) or mTORC1 activation and inhibition of p38 and mTOR C1 promotes HSCs expansion (Ann Hematol. 2012; 91:813-823; Transplantation. 2014; 97:20-29). Recently, it was shown that StemRegenin 1 (SR1), an antagonist of the aryl hydrocarbon receptor (AHR), could significantly promote ex vivo expansion of HSCs, primarily via inhibition of HSCs differentiation. Therefore, we investigated whether the combination of SR1 with LY2228820 (LY) and rapamycin (Rapa) to inhibit p38 and mTOR C1, respectively, can enhance ex vivo expansion of hUBC HSCs by inhibiting HSCs differentiation and senescence. Next, we confirmed that co-inhibition of activated p38 and mTORC1 promotes SR1 induced HSCs expansion ex vivo through inhibition of senescence.Our combined culture system in 7 days led to a 16.2-fold increase for CD34+CD90+ subpopulation and a 6.1-fold increase for CD34+CD45RA- subpopulation compared to input cells (Blood,126(23):381-381) .To determine the hematopoietic reconstitution ability of the progeny of hUCB CD34+ cells expanded with inhibitors of p38, mTORC1, and AHR, we transplanted 1000 to 30000 uncultured hUCB CD34+ cells or a fraction of the final culture equivalent to 1000 to 10000 starting hUCB CD34+ cells into sub-lethally irradiated 6 to 10-week-old NOD-Prkdcscid Il2rgnull (NOG) mice. Donor cell engraftment was analyzed at 8 and 13 weeks after the transplantation. The results showed that the progeny of 10,000 hUCB CD34+ cells cultured with LY, Rapa and SR1 produced significant greater donor cell engraftment in the recipients' peripheral blood compared with the same number of un-cultured hUCB CD34+ cells (2.19-fold, p<0.01), the progeny of 10,000 hUCB CD34+ cells cultured with vehicle (2.76-fold, p<0.01), or the progeny of 10,000 hUCB CD34+ cells cultured with SR1 alone (1.72-fold, p<0.05). The similar results were also found in the recipients' bone marrow and spleen. In addition, the progeny of 3,000 hUCB CD34+ cells cultured with LY, Rapa and SR1 generated the levels of peripheral blood donor cell engraftment that similar to these produced by 30,000 un-cultured hUCB CD34+ cells and the progeny of 10,000 hUCB CD34+ cells cultured with SR1 alone. More importantly, the hUCB CD34+ cells cultured with LY, Rapa and SR1 retained multi-lineage differentiation potential as they were able to produce human B cells, myeloid cells, red blood cell progenitors, megakaryocytes, and NK cells in the recipients' bone marrow. Furthermore, hUCB CD34+ cells cultured with LY, Rapa and SR1 produced the highest levels of human HSCs (CD34+CD38-/CD34+CD90+/CD34+CD45RA- cells) engraftment compared to all other cells. Collectively, these findings suggest that the combined inhibition of p38, mTORC1 and AHR is more effective in promoting the expansion and hematopoietic reconstitution of hUBC HSCs than inhibition of p38, mTORC1 or ARH alone probably via inhibition of HSCs senescence and differentiation. This new strategy may alleviate the limitation of hUBC for transplantation in adult patients. Disclosures No relevant conflicts of interest to declare.

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Fa'ak, Faisal, Chrystia M. Zobniw, Maryam Buni, Linda Lu, Adewunmi Falohun, VanAnh Trinh, Muhammad Osama Awiwi i in. "816 Selective immune suppression using interleukin-6 blockade in immune related adverse events". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (listopad 2021): A853. http://dx.doi.org/10.1136/jitc-2021-sitc2021.816.

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BackgroundManaging immune-related adverse events (irAEs) has become a critical challenge with the increasing implementation of immune-checkpoint inhibitors (ICIs) in cancer treatment. IrAEs may cause treatment interruption or discontinuation, the rate of which is higher with multi-agent ICI regimen needed to overcome resistant tumor microenvironment. Herein, we describe our clinical experience using interleukin-6 receptor antagonists (IL-6RA) to manage irAEs in cancer patients receiving ICIs.MethodsWe conducted a retrospective, multi-center study to evaluate the safety and efficacy of IL-6RA for irAE management. Eligible patients were identified from the institutional databases (pharmacy records, tumor registries, oncology and specialty clinic records for diagnosis and management of irAEs). The primary objective was assessing changes in irAE symptoms. The secondary objective was assessing overall response rate (ORR) before and after IL-6RA treatment.ResultsA total of 81 patients received an IL-6RA (tocilizumab or sarilumab); median age was 66 years, 41% were females, 70% received single-agent anti-PD-1 and 23% received nivolumab plus ipilimumab. Cancer types were primarily melanoma (44%), genitourinary cancer (37%), and lung cancer (8.6%). Indications for using IL-6RA were inflammatory arthritis (74%), polymyalgia rheumatica (6%), myositis/myocarditis/myasthenia gravis (5%) encephalitis (5%), and 1% each with pneumonitis, colitis, hepatitis, central nervous system vasculitis, oral mucositis, and flare of pre-existing myasthenia gravis, psoriasis, and Crohn's disease. Notably, 83 % of patients received corticosteroids as first-line therapy, and 29% received disease-modifying antirheumatic drugs, without improvement. After initiation of IL-6RA, improvement of irAEs was observed in 78% after a median of 2.1 months. Of evaluable patients with inflammatory arthritis, the median clinical disease activity index (CDAI) at IL-6RA initiation was 28, indicating high disease activity, and dropped to 6 after treatment, indicating low disease activity. The median CRP level at IL-6RA initiation was 59.5 mg/L and dropped to 1.5 mg/L within 10 weeks of treatment. Seventy-two patients tolerated IL-6RA, and nine stopped treatment due to side effects. Thirty-eight patients were evaluated for tumor response by RECIST 1.1 criteria; the ORR was 58% prior to IL-6RA and 66% after treatment. Of 21 evaluable melanoma patients, the ORR was 62% prior to IL-6RA compared to 71% after treatment (figure 1).ConclusionsOur study demonstrated that targeting IL-6R could be an effective approach to mitigate autoimmunity while maintaining and possibly boosting tumor immunity. Clinical trials are currently evaluating the safety and efficacy of tocilizumab in combination with ICIs in patients with melanoma, non-small cell lung cancer, and urothelial carcinoma (NCT04940299, NCT03999749).Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition's Ethics Board, approval number PA19-0089Abstract 816 Figure 1A patient with sinonasal malignant melanoma involving the ethmoid air cells. (A) Baseline maximum intensity projection (MIP) PET image at 1 month before initiation of ICI (ipilimumab and nivolumab) shows avid FDG uptake of the tumor at the ethmoid air cells (arrow). (B) MIP PET image at 7 months after ICI initiation shows resolution of the FDG uptake at the site of the tumor, consistent with complete response. (C) Concurrent MIP PET and corresponding fused PET-CT images 7 months after initiation of ICI show avid radiotracer uptake at the knee joints, suggestive of arthritis. (D) MIP PET image at 10 months after concomitant therapy with IL6R antagonist and nivolumab shows persistent absence of hypermetabolic radiotracer activity at the paranasal sinuses, consistent with complete response. (E) Concurrent MIP PET and corresponding fused PET-CT images show physiologic radiotracer uptake at the knee joints, consistent with resolving arthritis.

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Fuentes-Pananá, Ezequiel M., i John G. Monroe. "Ligand-dependent and -independent processes in B-cell-receptor-mediated signaling". Springer Seminars in Immunopathology 23, nr 4 (grudzień 2001): 333–50. http://dx.doi.org/10.1007/s281-001-8163-6.

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Kim, Jin Hong, i Hee Kwon Lee. "On the classification of positive quaternionic Kähler manifolds with b 4 = 1". Acta Mathematica Sinica, English Series 26, nr 5 (15.04.2010): 875–84. http://dx.doi.org/10.1007/s10114-010-8131-6.

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PAI, Chih-Hung, Kuo-Min KO i Troy SANTOS. "A Study of the Effect of Service Recovery on Customer Loyalty Based On Marketing Word Of Mouth in Tourism Industry". Revista de Cercetare si Interventie Sociala 64 (6.03.2019): 74–84. http://dx.doi.org/10.33788/rcis.64.6.

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Akamavi, R K., Mohamed, E., Pellmann, K., & Xu, Y. (2015). Key determinants of passenger loyalty in the low-cost airline business. Tourism Management, 46, 528-545. Baldus, B.J., Voorhees, C., & Calantone, R. (2015). Online brand community engagement: Scale development and validation. Journal of Business Research, 68(5), 978-985. Boo, H.V. (2017). Service Environment of Restaurants: Findings from the youth customers. Journal of Asian Behavioural Studies, 2(2), 67-77. Bowen, T.J., & Chen, S.L. (2015). Transitioning Loyalty Programs: A Commentary on the Relationship Between Customer Loyalty & Customer Satisfaction. International Journal of Contemporary Hospitality Management, 27(3), 415-430. Casidy, R., & Shin, H. (2015). The effects of harm directions and service recovery strategies on customer forgiveness and negative word-of-mouth intentions. Journal of Retailing and Consumer Services, 27, 103-112. Chang, J.H. (2017). The role of relationship on time and monetary compensation. The Service Industries Journal, 37, 915-935. Fan, A., Mattila, A.S., & Zhao, X. (2015). How does social distance impact customers’ complaint intentions? A cross-cultural examination. International Journal of Health Policy and Management, 47, 35-42. Gohary, A., Hamzelu, B., & Alizadeh, H. (2016). Please explain why it happened! How perceived justice and customer involvement affect post co-recovery evaluations: a study of Iranian online shoppers. Journal of Retailing and Consumer Services, 31, 127-142. Guo, L., Lotz, S.L., Tang, C., & Gruen, T.W. (2015). The role of perceived control in customer value cocreation and service recovery evaluation. Journal of Service Research, 19(1), 39-56. Heidenreich, S., Wittkowski, K., Handrich, M., & Falk, T. (2015). The dark side of customer co-creation: exploring the consequences of failed co-created services. The Journal of the Academy of Marketing Science, 43(3), 279-296. Hsu, C.L., & Lin, J.C.C. (2016). Effect of perceived value and social influences onmobile app stickiness and in-app purchase intention.Technological Forecasting and Social Change, 108, 42-53. Kashif, M., Zarkada, A., & Ramayah, T. (2016).The impact of attitude, subjective norms, and perceived behavioural control on managers’ intentions to behave ethically. Total Quality Management & Business Excellence, 29(5-6), 1-21. Li, M., Qiu, S.C., & Liu, Z., (2016). The Chinese way of response to hospitality service failure: The effects of face and guanxi. International Journal Hospital Management, 57, 18-29. Liu, S.Q., & Mattila, A.S. (2015). “I Want to Help” versus “I Am Just Mad” how affective commitment influences customer feedback decisions. Cornell Hospitality Quarterly, 56(2), 213-222. Oman, B., Pepur, M., & Arneric, J. (2016). The impact of service quality and sport-team identification on the repurchase intention. Journal of Contemporary Management Issues, 21(1), 19-46. Ozuem, W., Patel, A., Howell, K.E. & Lancaster, G. (2016). An Exploration of Consumers' Response to Online Service Recovery Initiatives. International Journal of Market Research, 59(1), 97-115. Park, J., & Ha, S. (2016). Co-creation of service recovery: Utilitarian and hedonic value and post-recovery responses. Journal of Retailing and Consumer Services, 28, 310-316. Rezaei, S., Shahijan, M.K., Amin, M., & Ismail, W.K.W. (2016). Determinants ofapp stores continuance behavior: A pls path modellingapproach. Journal of Internet Commerce, 15(4), 408-440. Sengupta, S.A., Balaji, M., & Krishnan, B.C. (2015). How customers cope with service failure? A study of brand reputation and customer satisfaction. Journal of Business Research, 68(3), 665-674. Sloan, S., Bodey, K., & Gyrd-Jones, R. (2015). Knowledge sharing in online brand communities. Qualitative Market Research: An International Journal, 18(3), 320-345. Tan, C., Benbasat, I. & Cenfetelli, R.T. (2016). An Exploratory Study of the Formation and Impact of Electronic Service Failures. MIS Quarterly, 40(1), 1-31. Van Vaerenbergh, Y., & Orsingher, C. (2016). Service Recovery: An Integrative Framework and Research Agenda. The Academy of Management Perspectives, 30(3), 328-346. Varela, J.C.S., Svensson, G., Brambilla, F.R., & Oliveros, M.E.G. (2015) Perceived Justice & Emotions in a Negative Service Encounter: A Latin American Perspective. In: Kubacki K. (eds). Ideas in Marketing: Finding the New and Polishing the Old. Developments in Marketing Science: Proceedings of the Academy of Marketing Science. Cham: Springer. Vyas, V. & Raitani, S. (2015). A Study of the Impact of Relationship Marketing on Cross-Buying. Journal of Relationship Marketing, 14(2), 79-108. Weber, K., Sparks, B., & Hsu, C.H. (2016). The effects of acculturation, social distinctiveness, and social presence in a service failure situation. International Journal Hospital Management, 56, 44-55. Wu, J., Huang, L., Zhao, J.L., & Hua, Z. (2015).The deeper, the better? Effect of online brand community activity on customer purchase frequency. Information & Management, 52(7), 813-823. Yang, A., Chen, Y., & Huang, Y. (2017). Enhancing customer loyalty in tourism services: the role of customer-company identification and customer participation. Asia Pacific Journal of Tourism Research, 22(7), 735-746. Zhang, H., Zhang, K.Z., Lee, M.K., & Feng, F. (2015). Brand loyalty in enterprise microblogs: Influence of community commitment, IT habit, and participation. Information Technology & People, 28(2), 304-326.

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Istina, Ida Nur. "Peningkatan Produksi Bawang Merah Melalui Teknik Pemupukan NPK". Jurnal Agro 3, nr 1 (31.07.2016): 36–42. http://dx.doi.org/10.15575/810.

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Bawang merah merupakan salah satu komoditas hortikultura strategis yang penyebarannya hampir di seluruh wilayah Indonesia. Permasalahan pengembangan komoditas ini adalah masih rendahnya produktivitas sebagai akibat adaptasi dan kecukupan asupan hara tanaman. Penelitian yang bertujuan untuk mendapatkan jenis pupuk NPK yang efektif dan efisien telah dilakukan di desa Langensari Kecamatan Lembang Kabupaten Bandung Barat dari Maret sampai Mei 2014 menggunakan Rancangan Acak kelompok (RAK) dengan 6 perlakuan dan 3 kali ulangan. Pupuk NPK yang digunakan adalah A= NPK 18+9+10+Te, B=NPK 15+15+sulfat 10, C=NPK 12+11+18z+(S) z +3 Mg+3,8S+Te, D= NPK 15+9+20(S)+2 MgO+3,8 S+Te, E= NPK 25+7+7 dan F=kontrol. Parameter yang diamati meliputi: tinggi tanaman, jumlah umbi, jumlah daun, panjang umbi (cm), diameter umbi (cm), bobot basah (g) dan bobot kering brangkasan (g). Hasil penelitian menunjukkan bahwa NPK 12+11+18z+(S)z+3 Mg+3,8S+Te menghasilkan bobot umbi terbaik. The shallot is one of the strategic and valuable horticultural commodities which is spreaded almost all over Indonesia area. Commodity development constrain by the low productivity as a result of adaptation and inadequate intake of plant nutrients. The research purposed to get the kind of NPK fertilizers that was efective and efficient on shallot production had been done in the Langensari village Langensari Lembang district, West Bandung regency from March till May 2014, using Randomized Block Design (RBD) with 6 treatments and 3 repplications. NPK fertilizer used were: A = NPK 18+9+10+Te, B = NPK 15+15+sulfate 10, C = NPK 12+11+18z+(S) z + 3 Mg+3,8S+Te, D = NPK 15+9+20(S)+2MgO+3,8 S+Te, E = NPK 25+7+7 and F = control. The observed parameters were plant height (cm), number of tubers, leaf number, tuber length, tuber diameter, fresh weight and dry weight tuber. The results showed that NPK 12+11+18z+ (S)z+3 Mg+3,8S+Te gave the best growth and production.

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P.Badiger, Naveen, i I. M. Khazi. "Synthesis & Evaluation of Antitubercular Activity of Novel Mannich Bases of imidazo[2,1-b][1,3,4]thiadiazoles". Advanced Materials Research 816-817 (wrzesień 2013): 1197–201. http://dx.doi.org/10.4028/www.scientific.net/amr.816-817.1197.

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A series of 2-(4-methoxybenzyl)-6-aryl-5-pyrrolidin/piperidin/morpholin-1-ylmethyl-imidazo [2,1-[1,3, thiadiazoles (3a-e, 4a-e & 5a-e) were synthesized by Mannich reaction by condensing 2-(4-methoxybenzyl)-6-arylimidazo [2,1-[1,3,thiadiazoles with pyrrolidine, piperidine and morpholine. The title compounds were screened for antitubercular activity againstMycobacterium tuberculosisH37Rv using the BACTEC 460 radiometric assay. Mannich bases with pyrrolidine substitution were found to be most active antitubercular agents. It proves that as the ring size decreases it becomes much potent in its activity. Pyrrolidine being 5 membered ring structure & further combined with imidazothiadiazole nucleus enhances the pharmacological activity.

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Yeo, J., E. A. Park, E. B. Lee, Y. W. Song i J. K. Park. "POS1386 ANGIOGRAPHIC CHARACTERISTICS OF VASCULOPATHY IN PATIENTS WITH CONNECTIVE TISSUE DISEASES". Annals of the Rheumatic Diseases 80, Suppl 1 (19.05.2021): 976.1–976. http://dx.doi.org/10.1136/annrheumdis-2021-eular.245.

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Background:Vasculopathies are a heterogeneous group of morphologically and pathogenetically distinct vascular diseases. They include both non-inflammatory and inflammatory vasculopathies. Patients with connective tissue disease (CTD), including systemic sclerosis (SSc), dermatomyositis (DM), and polymyositis (PM), can develop a non-thrombotic proliferative vasculopathy (NTPV), a distinctive disease entity characterized by vascular wall proliferation without overt evidence of vascular inflammation and intraluminal thrombosis.Objectives:This study aimed to analyze the angiographic features of NTPV in patients with CTD, including SSc, DM, and PM in comparison to polyarteritis nodosa (PAN).Methods:Angiograms of 47 extremities (24 upper and 23 lower extremities) of 11 patients with CTD (6 SSc, 4 DM, and 1 PM), and 12 patients with PAN who presented with critical digital ischemia between January 2001 and May 2020 were analyzed. The degree and pattern of stenosis, occlusion, aneurysms, and neovascularization in proximal arteries (defined as arteries above the wrist and ankle) and distal arteries (defined as those at or below the wrist and ankle) were compared between CTD-vasculopathy and PAN.Results:Diffuse narrowing was significantly more frequent (66.1% vs. 38.0%; p=0.001), whereas multifocal stenosis was significantly less frequent (6.5% vs. 26.8%, p=0.002) in the CTD group than in the PAN group. All patients with CTD and 72.0% with PAN had diffuse narrowing in the distal arteries (p =0.010). Tapered occlusion was more frequent than abrupt occlusion in patients with CTD (43.5% vs. 11.3%). Abrupt occlusion (11.3% vs. 29.6%, p=0.010) and aneurysm formation (1.6% vs. 11.3%; p=0.037) were significantly less frequent in the CTD than in the PAN group. After 1 year, three patients (27.3%) in the CTD group and seven (58.3%) in the PAN group showed improvements in digital ischemia. Moreover, four patients (36.4%) in the CTD group and two (16.7%) in the PAN group underwent auto- or surgical amputation.Conclusion:Patients with CTD-vasculopathy exhibit more frequently diffuse smooth narrowing, tapered occlusion and delayed distal blood flow on conventional angiograms and worse outcomes than with PAN patients. Larger studies are needed to confirm the current findings.References:[1]Kahaleh MB. Vascular involvement in systemic sclerosis (SSc). Clin Exp Rheumatol. 2004;22(3 Suppl 33):S19-23.[2]Lee JS, Kim H, Lee EB, Song YW, Park JK. Nonthrombotic proliferative vasculopathy associated with antiphospholipid antibodies: A case report and literature review. Mod Rheumatol. 2019;29(2):388-92.Figure 1.Angiographic features of CTD-vasculopathy and PAN.Arteries in the (A) upper extremities and (B) lower extremities of patients with CTD-vasculopathy and PAN. Diffuse narrowing is indicated by white arrowheads; tapered occlusion by white arrows; multifocal stenosis by black arrowheads; abrupt occlusion by black arrows; aneurysmal changes by empty arrows; grade 2 tortuosity by white stars; and grade 3 tortuosity by black stars. CTD, connective tissue disease; PAN, polyarteritis nodosa.Table 1.Comparison of angiographic parameters between CTD-vasculopathy and PAN.CTD (upper 14, lower 8)PAN (upper 10, lower 15)p-valueTotal number of images6271Shoulder/elbow/wrist and hand11/14/148/10/10Femoral/knee/ankle and foot7/8/813/15/15Stenosis Diffuse narrowing41/62 (66.1%)27/71 (38.0%)0.001 Focal stenosis13/62 (21.0%)10/71 (14.1%)0.295 Multifocal stenosis4/62 (6.5%)19/71 (26.8%)0.002Occlusion Tapered occlusion27/62 (43.5%)23/71 (32.4%)0.185 Abrupt occlusion7/62 (11.3%)21/71 (29.6%)0.010Aneurysm1/62 (1.6%)8/71 (11.3%)0.037Neovascularization in muscular branchTortuosity Grade 145/62 (72.6%)30/68 (39.1%)0.002 Grade 211/62 (17.7%)14/68 (23.9%) Grade 36/62 (9.7%)24/68 (37.0%)Tortuosity grade 1, normal; grade 2, mild to moderate; grade 3, severe (hypertortuosity). CTD, connective tissue disease; PAN, polyarteritis nodosa.Disclosure of Interests:Jina Yeo: None declared, Eun-Ah Park: None declared, Eun Bong Lee Consultant of: Pfizer, Grant/research support from: GC Pharma and Handok Inc., Yeong Wook Song: None declared, Jin Kyun Park: None declared

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Marin, Virna, Giovanna D’Amico, Harumi Kakuda, Erica Dander, Dario Campana i Andrea Biondi. "Cytokine Induced Killer (CIK) Cells Transduced with an Anti-CD19 Chimeric Receptor Containing 4-1BB Acquire Powerful Anti-Leukemic Activity." Blood 108, nr 11 (16.11.2006): 3264. http://dx.doi.org/10.1182/blood.v108.11.3264.3264.

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Abstract CIK cells are ex-vivo expanded cells with MHC-unrestricted cytotoxicity against several tumors, except B-lineage Acute Lymphoblastic Leukemia (ALL). Transduction of an anti-CD19-ζ chimeric receptor (cTCR) in CIK cells renders them efficient killers of ALL cells. However, in order to be fully effective for ALL immunotherapy, CIK cells should be able to exert a prolonged anti-leukemic activity after infusion, proliferating and secreting cytokines which amplify the anti-tumoral immune response following ALL encounter. Since it has been shown that incorporation of costimulatory molecules into cTCRs markedly enhances target-cell stimulated proliferation and cytotoxicity in T lymphocytes and NK cells, our aim was to identify costimulatory molecules able to increase the anti-leukemic properties of anti-CD19-ζ cTCR transduced CIK cells. CIK cells were efficiently transduced with the retroviral vectors carrying different types of cTCRs: anti-CD19-ζ, anti-CD19-DAP10, anti-CD19-4-1BB-ζ and anti-CD19-CD28-ζ (average expression of GFP and cTCR, 55% for all vectors tested; n=5 each). CIK cells expressing anti-CD19-ζ, anti-CD19-DAP10, anti-CD19-4-1BB-ζ and anti-CD19-CD28-ζ cTCRs were all strongly cytotoxic against OP-1 cells after 4 hours of incubation (>60% of lysis at E: T ratio 2:1 for all receptors tested). The benefit of adding the costimulatory molecules 4-1BB or CD28 to the cTCR was evident in long-term co-coltures (6days) on a mesenchimal cells layer, with low percentages of CIK cells (E:T ratio 0.01:1). In these assays, CIK cells expressing anti-CD19-4-1BB-ζ or anti-CD19-CD28-ζ cTCRs had more potent cytotoxicity than cells expressing the anti-CD19-ζ cTCR: average cell killing was 93% (range, 89–98%), 93% (87–97%), and 14% (3–24%), respectively (n=4, each; p=0.001). By contrast, addition of DAP10 to the cTCR did not improve cytotoxicity (average cell killing, 2%). Notably, CIK cells transduced with the anti-CD19-4-1BB-ζ cTCR had higher proliferative capacity in cocultures with irradiated OP1 cells and low dose IL-2. The average fold increase after 2 weeks of colture was 2.6 (range, 2.4–3.0) for these cells, while expansion of cells transduced with anti-CD19-ζ or anti-CD19-CD28-ζ was 1.4 (1.3–1.5) and 1.7 (1.2–2.7), respectively (p=0.01). Moreover, inclusion of 4-1BB or CD28 in the cTCR caused a significant increase in cytokines release (Multiplex Flow Cytomix assay) from transduced CIK cells after 48h stimulation with irradiated OP-1 cells: in 3 different experiments, CIK cells expressing anti-CD19-4-1BB-ζ or anti-CD19-CD28-ζ cTCR, secreted respectively, 2- and 3-fold more IL-2 (2040 and 2980 pg/ml, p=0.05), 3- and 4-fold more TNF-α (2000 and 2555 pg/ml, p=0.05), 4- and 3-fold more TNF-β (813 and 578 pg/ml, p=0.005), 4- and 3-fold more IL-6 (325 and 230 pg/ml, p=0.05), 3- and 4-fold more IL-8 (1962 and 2480 pg/ml, p=0.05) compared to cells expressing anti-CD19-ζ cTCR. However, OP-1 stimulation of anti-CD19-CD28-ζ cTCR transduced CIK cells resulted in the release of significant higher amount of the immunosuppressive cytokine IL-10 than CIK cells expressing the anti-CD19-4-1BB-ζ cTCR (880 and 85 pg/ml, p=0.05). In conclusion, our results suggest that anti-CD19-4-1BB-ζ cTCR represents the best tool to improve anti-leukemic activity of CIK cells for ALL immunotherapy, as it strenghtens their cytotoxicity against leukemic cells and notably, it induces transduced cell proliferation and secretion of immuno-stimulatory cytokines.

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Desai, Gauri, Marie Vahter, Elena I. Queirolo, Fabiana Peregalli, Nelly Mañay, Amy E. Millen, Jihnhee Yu, Richard W. Browne i Katarzyna Kordas. "Vitamin B-6 Intake Is Modestly Associated with Arsenic Methylation in Uruguayan Children with Low-Level Arsenic Exposure". Journal of Nutrition 150, nr 5 (8.01.2020): 1223–29. http://dx.doi.org/10.1093/jn/nxz331.

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ABSTRACT Background Detoxification of inorganic arsenic (iAs) occurs when it methylates to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of urinary iAs and MMA, and higher proportions of DMA indicate efficient methylation. The role of B-vitamins in iAs methylation in children with low-level arsenic exposure is understudied. Objectives Our study objective was to assess the association between B-vitamin intake and iAs methylation in children with low-level arsenic exposure (<50 µg/L in water; urinary arsenic 5–50 µg/L). Methods We conducted a cross-sectional study in 290 ∼7-y-old children in Montevideo. Intake of thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12 was calculated by averaging 2 nonconsecutive 24-h recalls. Total urinary arsenic concentration was measured as the sum of urinary iAs, MMA, and DMA, and adjusted for urinary specific gravity; iAs methylation was measured as urinary percentage As, percentage MMA, and percentage DMA. Arsenic concentrations from household water sources were assessed. Linear regressions tested the relationships between individual energy-adjusted B-vitamins and iAs methylation. Results Median (range) arsenic concentrations in urine and water were 9.9 (2.2–48.7) and 0.45 (0.1–18.9) µg/L, respectively. The median (range) of urinary percentage iAs, percentage MMA, and percentage DMA was 10.6% (0.0–33.8), 9.7% (2.6–24.8), and 79.1% (58.5–95.4), respectively. The median (range) intake levels of thiamin, riboflavin, niacin, and vitamin B-6 were 0.81 (0.19–2.56), 1.0 (0.30–2.24), 8.6 (3.5–23.3), and 0.67 (0.25–1.73) mg/1000 kcal, respectively, whereas those of folate and vitamin B-12 were 216 (75–466) and 1.7 (0.34–8.3) µg/1000 kcal, respectively. Vitamin B-6 intake was inversely associated with urinary percentage MMA (β = −1.60; 95% CI: −3.07, −0.15). No other statistically significant associations were observed. Conclusions Although vitamin B-6 intake was inversely associated with urinary percentage MMA, our findings suggest limited support for a relation between B-vitamin intake and iAs methylation in children exposed to low-level arsenic.

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Mutia, Liza, Karolina br Surbakti i Selamat Riadi. "Hubungan Polimorfisme Gen Interleukin 10 - 819 C/T Pada Kejadian Preeklampsia Ibu Hamil di Puskesmas Dalu X B Tanjung Morawa Deli Serdang". Jurnal Ners 7, nr 2 (21.10.2023): 1665–71. http://dx.doi.org/10.31004/jn.v7i2.18813.

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Preeclampsia is one of the disorders during pregnancy, characterized by increased blood pressure and proteinuria, causing an increase in morbidity and mortality in the mother and fetus. Interleukin 10 (IL10) is called a T helper type 2 (Th2) cytokine which is important because it acts as an anti-inflammatory which functions for the maintenance and development of pregnancy and forms immunity to inhibit the secretion of T helper 1 (Th1) cytokines such as IL 6, TNF alpha and INF Gamma. Genotypic variation can provide information about individual differences in the secretion of IL-10 and the tendency to the incidence of preeclampsia. The IL 10 - 819 C/T gene polymorphism is located on chromosome 1q32.2 distal to the promoter area and is a transcription factor of the IL 10 gene. The aim of this study was to determine the relationship between 10-819 C/T Interleukin Gene Polymorphisms in the incidence of preeclampsia in pregnant women. The method used to determine the IL 10 819 C/T polymorphism with RFLP PCR. Results. The distribution of IL 10-819 C/T genotypes in the control group had 5 people (23.73%) of TT genetic variation, 15 people with CT (65.21%) and 3 people with CC genetic variation (13.04%). ). In the Preeclampsia group, there were 7 people (30.43%) with genetic variation of TT and there were 10 people (43.47%) with genetic variation of CT as many as 6 people (26.08%) with CC variation. There was no correlation between interleukin gene polymorphism 10-891 C/T with the incidence of preeclampsia in pregnant women at Dalu X B Health Center Tanjung Morawa, Deli Serdang

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Matsukawa, M. "A Screening System of Prodrugs Selective for MAO-A or MAO-B". NeuroToxicology 25, nr 1-2 (styczeń 2004): 293–302. http://dx.doi.org/10.1016/s0161-813x(03)00108-6.

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Paterson, Donald. "B. Huntley & T. Web III (eds). 1988. Vegetation history. Dr W. Junk, Dordrecht. 803 pages. ISBN 90-6193-188-6. Price: £116.00." Journal of Tropical Ecology 6, nr 2 (maj 1990): 238. http://dx.doi.org/10.1017/s0266467400004387.

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ПУШКАРЕВ, И. А. "EFFECT OF THE TISSUE BIO-STIMULANT ON PROLIFERATIVE ACTIVITY OF T- AND B-LYMPHOCYTES IN HEIFERS". Molochnoe i miasnoe skotovodstvo, nr 3 (14.06.2022): 50–53. http://dx.doi.org/10.33943/mms.2022.48.70.010.

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Изучено влияние применения различных схем тканевого биостимулятора на профилиративную активность Т- и В-лимфоцитов крови телок в возрасте 18 мес. Эксперимент проводился в условиях Алтайского края на 4-х группах телочек Приобского типа черно-пестрой породы (с живой массой 51,3±1,48 кг в возрасте 1 мес), в каждой из них было по 10 голов. При подборе животных учитывались возраст (1 мес) и живая масса. Продолжительность опыта составила 18 мес. Животным контрольной группы ежемесячно вводили подкожно физиологический раствор: с 1 до 5 мес — в дозе 3,0 мл/гол., с 6 до 11 — 6 мл/гол., с 12 до 15 — 12,0 мл/гол. и с 16 до 18 мес — 15,0 мл/гол. Телкам опытных групп делали инъекции тканевого биостимулятора по следующим схемам: в I группе — с 1 до 5 мес — в дозе 2,0 мл/гол., с 6 до 11 — 4 мл/гол., с 12 до 15 — 8,0 мл/гол. и с 16 до 18 мес — 10,0 мл/гол.; во II — с 1 до 5 мес — в дозе 3,0 мл/гол., с 6 до 11 — 6 мл/гол., с 12 до 15 — 12,0 мл/гол. и с 16 до 18 мес — 15,0 мл/гол.; в III опытной группе — с 1 до 5 мес. — в дозе 4,0 мл/гол., с 6 до 11 — 8,0 мл/гол., с 12 до 15 — 16,0 мл/гол. и с 16 до 18 мес — 20,0 мл/гол. Тканевый биостимулятор изготовили из субпродуктов и боенских отходов пантовых оленей. Схема его применения, использовавшаяся во II опытной группе животных, оказалась наиболее эффективной и способствовала увеличению в крови ремонтных телок 18-месячного возраста количества субпопуляции активированных лейкоцитов на 5,6% (P≤0,001), В-лимфоцитов — на 2,1—3,5% (P≤0,05) и уменьшению количества тотальных лейкоцитов — на 4,6—8,3% (P≤0,01), «киллеров-супрессоров» — на 4,1—5,8% (P≤0,05) в сравнении с аналогичными значениями в контроле. The effect of various dosing schedules of the tissue bio-stimulant on proliferative activity of T- and B-lymphocytes in heifers at the age of 18 months was studied. The experiment was carried out under the conditions of the Altai Region in 4 groups of 10 Black-Pied heifers of the Priobsky type (live weight of 51.3 ± 1.48 kg at the age of 1 month). When selecting the animals, their age (1 month) and live weight were taken into account. The experiment lasted 18 months. In the control group, physiological salt solution was injected subcutaneously monthly: from 1 to 5 months — at a dose of 3.0 mL per head, from 6 to 11 months — 6 mL head, from 12 to 15 months — 12.0 mL head, and from 16 to 18 months — 15.0 mL head. In the trial groups, the tissue bio-stimulant was injected to the heifers according to the following dosing schedules: in the 1st group, from 1 to 5 months — at a dose of 2.0 mL head; from 6 to 11 months — 4 mL head; from 12 to 15 months — 8.0 mL head, and from 16 to 18 months — 10.0 mL head; in the 2nd trial group, from 1 to 5 months — at a dose of 3.0 mL head; from 6 to 11 months — 6 mL head; from 12 to 15 months — 12.0 mL head; and from 16 to 18 months — 15.0 mL head; in the 3rd trial group, from 1 to 5 months — at a dose of 4.0 mL head; from 6 to 11 months — 8.0 mL head; from 12 to 15 months — 16.0 mL head; and from 16 to 18 months — 20.0 mL head. The tissue bio-stimulant was made from velvet antler deer by-products and slaughterhouse offal. The dosing schedule used in the 2nd trial group proved to be the most effective one; in 18-month-old replacement heifers, it contributed to the increased counts of activated leukocyte subpopulation by 5.6% (P≤0.001), B-lymphocytes — by 2.1—3.5% (P≤0.05), and decreased the total leukocyte count by 4.6-8.3% (P≤0.01), “killer-suppressor” cells — by 4.1—5.8% (P≤0.05) as compared to those in the control group.

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Thete A. M., Dahat D. V., Jambhale V. M. i Chaudhari S. R. "Molecular Characterization of Rice Genotypes Using Molecular Markers". International Journal of Plant & Soil Science 35, nr 20 (20.09.2023): 284–301. http://dx.doi.org/10.9734/ijpss/2023/v35i203809.

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Rice, (Oryza sativa L. 2n=24) belongs to the family Gramineae and subfamily Oryzoideae. Oryza has two cultivated species: Oryza sativa and Oryza glaberrima. Breeding for good-quality traits requires the selection of parents with a wider genetic diversity. Molecular markers are used in molecular biology and biotechnology to identify a sequence of DNA. Molecular markers have played an increasing role in rice breeding for cultivar improvement, screening, selection, and germplasm collections. The present investigation is undertaken to study the genetic diversity among thirty rice genotypes using the ISSR marker. Out of 40 ISSR primers, 9 amplified and showed polymorphism, viz., ISSR 807, ISSR 808, ISSR 809, ISSR 811, ISSR 816, ISSR 823, ISSR 826, ISSR 827 and ISSR 829. A total of 76 loci were generated by amplification with 9 polymorphic primers, out of which 66 loci were polymorphic with an average of 86.84 percent polymorphism. Among ISSR primers, ISSR 807 produced the maximum number of 11 loci. A dendrogram constructed using NTSYSpc 2.02i software grouped all 30 genotypes into two major clusters (clusters A and B). Cluster A Kalbhat alone is present in one sub-cluster at 69.2% similarity with Karjat 2, Jaya, Sairam, Saubhagya Dhan, RPBIO 226, Karjat 6, Ratnagiri 1, DRR Dhan 44, DRR Dhan 45, DRR Dhan 46, MTU 10010, Karjat 7, Swarna Shreya, Sugandha, and Madhumati. In Cluster B Karjat 3 alone forms one sub- cluster and has 70 % similarity with MTU 1001, PKVHMT, JGL 1798, Indrayani, Phule Samruddhi, Phule Maval, Sonsal, Pavana, DRR Dhan 41, kundalika, Bhogawati, Ambemohar, and Phule Radha.

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De Silva, Anushika L., Wiebke Kämper, Helen M. Wallace, Steven M. Ogbourne, Shahla Hosseini Bai, Joel Nichols i Stephen J. Trueman. "Boron Effects on Fruit Set, Yield, Quality and Paternity of Macadamia". Agronomy 12, nr 3 (11.03.2022): 684. http://dx.doi.org/10.3390/agronomy12030684.

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Many tree crops experience sub-optimal yields and low fruit quality due to inadequate pollination, low fruit set, and poor crop nutrition. Boron (B) is a critical crop nutrient for fruit set because B levels affect pollen germination and pollen tube growth. However, the relationship between floral B concentration and fruit set is not well understood. The aim of this study was to determine the effect of B applications on the initial fruit set, yield, quality, and paternity of macadamia (Macadamia integrifolia). Cultivar ‘816’ trees received one of three treatments: (a) 0 g, (b) 15 g, or (c) 30 g B per tree prior to flowering. Boron application increased the B concentration of macadamia flowers. Application of 15 g B increased fruit set at 3 weeks after peak anthesis, but this higher initial fruit set was not translated into higher fruit set at 6 or 10 weeks after peak anthesis or higher yield. Boron application increased B concentrations in kernels but did not affect nut-in-shell (NIS) mass, kernel mass, kernel recovery, kernel oil concentration or incidence of whole kernels. Cultivar ‘816’ was highly outcrossing, with 97–98% cross-paternity among kernels from all treatments. Our results indicate that higher B concentration in macadamia flowers can be associated with an increased initial fruit set. However, high B levels did not affect yield, nut quality, or the proportion of self-pollinated fruit at maturity. The heavy dependence on outcrossing highlights the importance of inter-planting different cultivars and managing bee hives to sustain the productivity of macadamia orchards.

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Chamie, Karim, John H. Lee, Amy Rock, Peter R. Rhode i Patrick Soon-Shiong. "Preliminary phase 2 clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients." Journal of Clinical Oncology 37, nr 15_suppl (20.05.2019): 4561. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.4561.

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4561 Background: Patients with non-muscle-invasive bladder cancer (NMIBC) unresponsive to BCG therapy have limited treatment options. N-803 (also known as ALT-803) is an IL-15-based immunostimulatory protein complex (IL-15RαFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase Ib data in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. Methods: An open-label, single-arm multicenter Phase 2 study of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. The study has two cohorts: Cohort A, patients with BCG-unresponsive carcinoma in situ (CIS) [with or without Ta or T1 disease] and Cohort B, patients with BCG-unresponsive high-grade Ta/T1 disease. All treated patients receive intravesical N-803 plus BCG, similar to a standard induction and maintenance treatment schedule. The primary endpoint for Cohort A is incidence of complete response (CR) of CIS at any time, and the primary endpoint for Cohort B is disease-free rate at 12 months. Results: To date, forty-six patients have enrolled in this phase 2 trial (Cohort A (CIS), n = 23, Cohort B (Papillary), n = 23). Of eleven evaluable patients in Cohort A, nine patients (82%) have a reported CR. In addition, seven out of nine (78%) patients in Cohort A demonstrated CR at their 6-month response assessment. Of thirteen evaluable patients in Cohort B, ten patients (77%) showed no evidence of recurrence at their 3-month response assessment; of these, none (0/8) evaluated past 3 months have had disease recurrence. Three serious adverse events (AEs) have been reported (E coli infection, anemia, and bacteremia), with no immune-related AEs. Conclusions: Nine out of eleven (82%) patients with BCG-unresponsive CIS of the bladder demonstrated a complete response. Ten out of thirteen patients with BCG-unresponsive papillary NMIBC show no evidence of disease at first assessment. Intravesical N-803 plus BCG was well-tolerated and no patients experienced immune-related AEs. Clinical trial information: NCT03022825.

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DI Mario, C., V. Varriano, L. Petricca, A. Paglionico, M. R. Gigante, B. Tolusso i E. Gremese. "AB0649 PERIPHERAL B CELLS IMMUNOPHENOTYING IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS". Annals of the Rheumatic Diseases 82, Suppl 1 (30.05.2023): 1527.1–1527. http://dx.doi.org/10.1136/annrheumdis-2023-eular.5395.

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BackgroundB cells play a central role in systemic lupus erythematosus (SLE) pathogenesis connecting innate with adaptative immunity.ObjectivesTo investigate the peripheral blood B cell phenotype in a cohort of SLE patients with renal (LN-SLE) and non-renal (NR-SLE) involvement compared to healthy controls.MethodsNinety-nine SLE patients, 76 with active renal involvement (30 at disease onset-Early and 46 in whom LN occurred after the disease onset-Long) and 23 with non-renal disease (articular and/or cutaneous) were enrolled. Thirty-seven healthy controls were included. Clinical, laboratory and demographic data were collected at baseline and at 6 and 12 months of follow-up. Disease activity was recorded using SLEDAI-2K. The memory B cells immunophenotyping (IgD/CD27 classification) was analyzed in peripheral blood through flow cytometry. To clarify the role of key molecules in the B cells activation, IL-6 and BAFF serum levels were assayed by Enzyme-linked immunosorbent assay (ELISA).ResultsStudying the B cell subsets, a lower percentage of CD19posand unswitched memory (IgDposCD27pos) in the whole SLE cohort compared to controls (8.7±6.8%vs10.5±3.5%;p=0.002and 10.7±13.7%vs15.3±8.0%;p<0.01,respectively) was observed. In addition, we found higher levels of double-negative memory B cells (IgDnegCD27neg) and plasmablasts (CD27posCD38pos) in SLE than in controls [(CD27negIgDneg10.3±8.3%vs4.1±1.9%;p<0.01) (CD27posCD38pos6.1±7.9%vs1.0±0.5%;p<0.01)]. Furthermore, CD19posnegatively correlated with BAFF (R=-0.322;p=0.01). No correlation was found between B cell subsets and the disease activity parameters. According to the organ involvement, LN-SLE and RN-SLE showed a lower percentage of CD19pos, IgDposCD27posand plasmacells and higher levels of IgDnegCD27negthan controls [(CD19pos: LN-SLE:9.1±7.4%vs10.5±4.6%;p=0.005;NR-SLE: 7.7±4.6%;p=0.008)(IgDposCD27pos:LN-SLE 10.4±14.9%vs15.3±8.0%;p<0.001;NR-SLE: 11.8±8.6%;p=0.006) (CD27posCD38pos: LN-SLE 7.5±8.4%vs0.9±0.5%;p<0.001;NR-SLE: 1.6±2.2%;p=0.001)(IgDnegCD27neg: LN-SLE 10.6±8.5%vs4.1±1.9%;p<0.001;NR-SLE: 9.6±7.3%;p=0.006]. According to the onset of renal symptoms, there were no differences in the distribution of the renal classes and in activity and chronicity indexes in the two groups. Analyzing the B cells subsets the Long-LN-SLE showed a lower percentage of CD19posand unswitched memory (IgDposCD27pos) compared to controls (8.6±6.5%vs10.5±3.5%;p=0.004and 9.7±6.9%vs15.3±8.0%;p=0.001,respectively) and higher levels of IgDnegCD27neg(12.1±8.4%) than Early LN-SLE (8.3±8.3%;p=0.027), NR-SLE (9.6±7.3%;p=0.001) and controls(4.1±1.9%;p<0.001). Furthermore, a direct correlation was observed between serum IL-6 levels and SLEDAI in Long-LN-SLE patients (r=0.380; p=0.004).ConclusionData on memory B cells immunophenotyping reveals a distinct B cells subset of SLE patients when compared to healthy controls, confirming an alteration of B cells subsets in SLE patients and strengthening the hypothesis of the pathogenetic role played by B lymphocytes in the course of LN. In particular, the higher levels of DN B cells observed in patients in which renal damage occurs after the onset of SLE reinforcing the data that these cells represents a B memory subsets characteristic of immune system overactivation conditions.Reference[1]Sang A, Zheng YY, Morel L Contributions of B cells to lupus pathogenesis.Mol Immunol2014; 62 (2): 329–338Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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Durner, Edward F., i E. Barclay Poling. "Comparison of Three Methods for Determining the Floral or Vegetative Status of Strawberry Plants". Journal of the American Society for Horticultural Science 111, nr 1 (styczeń 1986): 158. http://dx.doi.org/10.21273/jashs.111.1.158.

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Abstract In the article “Comparison of Three Methods for Determining the Floral or Vegetative Status of Strawberry Plants” by Edward F. Dumer and E. Barclay Poling [Journal 110(6):808–811, Nov. 1985], the Fig. 2 caption was incorrect. The correct caption should read: Representative central longitudinal section of A. Questionable meristem (bar = 10 μ), B. Vegetative apex (bar = 10 μ), and C. Reproductive meristems (bar = 20 μ).

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Billaudel, B. J., A. G. Faure i B. C. Sutter. "Effect of 1,25 dihydroxyvitamin D3 on isolated islets from vitamin D3-deprived rats". American Journal of Physiology-Endocrinology and Metabolism 258, nr 4 (1.04.1990): E643—E648. http://dx.doi.org/10.1152/ajpendo.1990.258.4.e643.

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Insulin release is impaired by vitamin D3 deficiency but can be restored by in vivo administration of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. A direct influence of 1,25(OH)2D3 on the B-cell was studied in vitro with islets from 5-wk vitamin D3-deprived rats. This hormone (10(-12) to 10(-6) mol/l) added to the incubation medium had a stimulatory dose-dependent effect on insulin response to 8.3 mmol/l glucose 6 h later. Moreover, perifusion experiments performed after different times of incubation demonstrated that after 6 h 1,25(OH)2D3 increased in particular the first phase of insulin response to 16.7 mmol/l glucose. The 45Ca fluxes, followed in parallel, were never modified by 1,25(OH)2D3 in the absence of glucose but were enhanced during the glucose stimulus, whereas 86Rb fluxes were never affected by 1,25(OH)2D3. These results demonstrated that 1,25(OH)2D3 acts in vitro on B-cells, but with a 6-h delay to potentiate the glucose-induced insulin release, concomitant with intracellular calcium redistribution.

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Ravindranathan, Sruthi, Passang Tenzin, Sanjay Chandrasekaran, Brandon Ware, Mohammad Zaidi, Shuhua Wang, Rohan Dhamsania i in. "819 Targeting vasoactive intestinal peptide receptor signaling: a novel approach to enhance anti-tumor response in pancreatic ductal adenocarcinoma". Journal for ImmunoTherapy of Cancer 8, Suppl 3 (listopad 2020): A867—A869. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0819.

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BackgroundPancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer related death in the U.S, has a 5-year survival rate of only 10%.1 The paucity of T cells in the immune privileged tumor microenvironment (TME) is a major limitation in developing an effective immunotherapy against PDAC.2The cancer genome atlas (TCGA) shows that human PDAC tumors express high levels of vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide (figure 1A), that inhibits effector T cell responses.3 4 We hypothesized that paracrine secretion of VIP in the TME is a targetable mediator of immune paralysis in PDAC, and that pharmacological inhibition of VIP receptor signaling could enhance anti-tumor responses in PDAC.MethodsVIP levels in plasma or cell culture supernatant was determined via VIP-specific enzyme immunoassay. Luciferase transfected KPC (KPC.luc) cells were injected subcutaneously or orthotopically into the pancreas of C57BL/6, CD4KO, or CD8KO mice from Jackson Laboratories. C57BL/6 mice T cell subsets in were depleted post tumor implantation with anti-CD4 and/or anti-CD8 antibodies. Tumor-bearing mice were treated daily with ANT008, a novel VIP receptor antagonist peptide, and/or anti-PD1 monoclonal antibody (MoAb) for 10 days, starting 7-10 days after implantation. T cells isolated from peripheral blood of PDAC patients were expanded 9 days ex vivo in anti-CD3 MoAb coated plates with 30U/ml IL-2 and either control peptide (scrambled VIP sequence) or ANT008. Survival by VIP and VIP receptor expression from the TCGA was clinically correlated.ResultsIncreased human and mouse PDAC expression correlates with elevated blood levels (figure 1). While the PDAC cancer cell lines express VIP receptors, ANT008 does not have direct cytotoxic effect on cell growth in vitro (figure 2). However, in orthotopic KPC model, treatment with ANT008 & anti-PD-1 significantly decreased tumor growth rate and burden (figure 3) while increasing the intratumoral levels of CD4 and CD8 proliferating T cells (figure 4) via a T cell dependent mechanism (figure 5). Additionally, in ex vivo cultures of T cells isolated from PDAC patients, ANT008 improved the effector properties of T cells via decreasing expression levels of co-inhibitory molecules and decreasing frequency of regulatory T cells (figure 6). Clinically, VIPR1 receptor expression, but not VIP, provides a survival benefit (figure 7).Abstract 819 Figure 1Overexpression of VIP in PDAC tumors(A) VIP mRNA expression in several solid malignancies, with red arrow pointing at the levels in pancreatic cancer, as obtained from The Cancer Genome Atlas. (B) Blood collected from healthy volunteers (n=26) and consented untreated pancreatic cancer patients before surgery/chemotherapy (n=41) were quantified for levels of VIP. (C) Cell free supernatant collected from B16F10, SM1 and D4M (murine melanoma cell lines) or KPC, MT5 or Panc02 (murine PDAC cell lines) or BXPC3 and Panc1 (human PDAC cell lines), were quantified for VIP (D) C57BL/6 mice were implanted with 1 million B16F10 cells (n=4), D4M cells (n=4) or MT5 cells (n=3) subcutaneously, or with KPC cells in the tail of the pancreas after laparotomy (n=3). When tumor volumes reached 500mm3 for subcutaneous tumors or the tumor flux reached 2 x 1010 photons/sec for orthotopic KPC tumors, mice were sacrificed and the concentration of VIP in the blood was determined. P value for B was calculated using student t test and C and D were calculated by one-way ANOVA followed by Tukey’s post-test. Error bars show mean with standard deviation. *p<0.0001Abstract 819 Figure 2PDAC cell lines express receptors for VIP(A) Western blot analysis showing constitutive expression of VPAC1, VPAC2 and PACAP receptors in murine and human PDAC cell lines and B16F10, a murine melanoma cell line. GAPDH was used as the loading control. (B) Percentage viability of KPC and Capan02 cells treated with varying concentrations of ANT008 (0.5-5µM) relative to cells treated with 0µM ANT008 for 24, 48 and 72 hours as measured by MTT assay.Abstract 819 Figure 3Efficacy of ANT008+aPD-1 therapy in in-vivo model5x105 KPC.luc cells on a matrigel were implanted in the tail of pancreas of C57BL/6 mice. Seven days after tumor implantation, mice were randomized and treated with ANT008 and/or aPD-1 until day 25, when they were sacrificed. (A) From each treatment group, one mouse with biggest non-ulcerated tumor was imaged via IVIS imaging (top), sacrificed and imaged with 9.4T MRI scanning (MRI) and their paraffin embedded pancreatic tissues were stained via H&E (bottom). (B) The tumor flux measured via IVIS imaging is plotted with respect to days after tumor implantation. ‘o’ represent mice that were imaged via MRI on day 28 and ‘+’ represent mice that were sacrificed before day 25 due to ulceration. (C) On day 25 mice were sacrificed and the weight of the pancreas was plotted. The brown dashed line represent average weight of pancreas from naïve age matched mice. P value was calculated using one-way ANOVA followed by Tukey’s post-test. Error bars show mean with standard deviation with **p<0.01.Abstract 819 Figure 4ANT008+aPD-1 therapy increases T cell infiltration5x105 KPC.luc cells were implanted in the tail of the pancreas following laparotomy. Once the tumors were detectable via bioluminescent imaging, mice were randomized into four treatment groups and treated with isotype antibody and scrambled peptide or ANT008 and/or anti-PD-1 until day 25, when the mice were sacrificed, tumor tissues harvested, and formalin fixed. The tissues were stained for nucleus, CD4, CD8 and Ki67 via multiplex immunohistochemistry (A) A representative multiplex IHC image showing T cell infiltration in the different treatment groups .(B) Numbers of CD4, CD8, Ki67+ CD4 and Ki67+ CD8 T cells/mm2 with respect to weight of the pancreas is shown.Abstract 819 Figure 5ANT008+aPD-1 therapy is T cell dependent5x105 KPC.luc cells were subcutaneously implanted in C57BL/6 or CD4KO (A) and C57BL/6 or CD8KO (B) mice and treated with scrambled+IgG (control) or ANT008+aPD-1 (treated) for 10 days from day 5 or 7 when the tumors were palpable. Mice were monitored for tumor growth and sacrificed when the tumor volume reached 500mm3 or when the tumors ulcerated. P values were calculated using Log rank test. *p<0.0001.Abstract 819 Figure 6ANT008 improves effector properties of T cellsCryopreserved PBMCs from peripheral blood of consented PDAC patients were thawed and rested overnight at 37°C in a CO2 incubator followed by T cell isolated via negative magnetic sorting. Isolated T cells were seeded on human anti-CD3 coated plates and cultured in media supplemented with 30U/ml human recombinant IL-2 and 3uM of scrambled peptide (SCRAM) or ANT008 for 9 days. On day 9 the cells were counted and stained for CD3, CD4, CD8, Tim-3, Lag-3, PD-1, CD25, FoxP3 and with aqua live/dead viability stain and analyzed via flow cytometry. (A) The gating strategy, (B) yield on da 9 with respect to number of cells seeded on day 0 and C) the percentage of T cells expressing co-inhibitory molecules are shown. P values were calculated by student t test . *p<0.001.Abstract 819 Figure 7Survival correlates with VPAC1 expression (TCGA)Survival probability analysis and the respective Kaplan Meier curves from TCGA data sets for pancreatic ductal adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and colorectal adenocarcinoma (CAAD). (A) Combined survival analysis of multiple GI malignancies (PAAD, STAD and COAD) demonstrates increased VPAC1 expression is associated with a 1-year 50% survival benefit (75 vs 50%) (n=560 (high) & 557 (low)), (B) while VIP expression is not (n=540 (high) and 540 (low)). (C) In pancreatic adenocarcinoma, increased VIP receptor (VIPR1) expression trends toward an overall survival benefit (n=91 (high) & 92 (low)), while (D) VIP expression does not.ConclusionsVIP is a targetable mechanism of immune escape in PDAC. Inhibiting VIP receptor signaling improves effector properties of T cells and synergistically improves the anti-tumor response to checkpoint inhibitors in mouse PDAC models.ReferencesSiegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin2020;70(1):7-30.Sahin IH, et al. Immunotherapy in pancreatic ductal adenocarcinoma: an emerging entity?Ann Oncol 2017;28(12):2950-2961.Gonzalez-Rey E, Anderson P, Delgado M. Emerging roles of vasoactive intestinal peptide: a new approach for autoimmune therapy. Ann Rheum Dis 2007;66(Suppl 3):iii70-6.Anderson P, Gonzalez-Rey E. Vasoactive intestinal peptide induces cell cycle arrest and regulatory functions in human T cells at multiple levels. Mol Cell Biol 2010;30(10):2537-51.

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Milsan, Lili Rahimayasari, Gde Putu Arya Oka i Andi Nafsia. "PENGEMBANGAN VIDEO ANIMASI 2D PEMBELAJARAN “SALUT” TEMA TRANSPORTASI UNTUK ANAK USIA 5-6 TAHUN". Jurnal Citra Pendidikan Anak 1, nr 4 (30.12.2022): 373–84. http://dx.doi.org/10.38048/jcpa.v1i4.1132.

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Penelitian ini bertujuan untuk mengetahui desain dan tingkat kelayakan media video animasi 2D pembelajaran Salut tema transportasi. Penelitian ini dilakukan di TKN Nazareth Were kelompok B, Kabupaten Ngada, Nusa Tenggara Timur. Media Video Animasi yang dikembangkan adalah model ADDIE. Model ini terdiri atas lima bagian yaitu: (1) analyze, 2) design, 3) development, (4) implementation, (5) evaluation. Metode yang digunakan adalah metode observasi, metode angket, metode wawancara dan metode dokumentasi. Hasil penelitian pengembangan media Video Animasi berdasarkan hasil uji coba ahli dan anak usia dini sebagai pengguna produk adalah sebagai berikut: (1) uji coba ahli media memperoleh rata- rata 76% pada kategori valid, (2) uji coba ahli materi 91,7% dengan kategori sangat valid Penelitian, (3) uji coba ahli desain 81,3% dengan kategori valid, (4) uji coba kelompok kecil 75% dengan kategori valid, (5) uji coba perorangan 73% dengan kategori valid. Dengan kesimpulan bahwa media Video Animasi untuk Anak Usia Dini oleh ahli dan anak usia dini sebagai pengguna produk dinyatakan layak untuk digunakan dalam proses pembelajaran.

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Albiser, G., i S. Prémilat. "B-Z conformational transition and hydration of poly (dC-dG).poly (dC-dG) in fibres". International Journal of Biological Macromolecules 14, nr 3 (czerwiec 1992): 161–65. http://dx.doi.org/10.1016/s0141-8130(05)80006-6.

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Rocha, Sónia, Sandra Tejo, Eugénia Ferreira, Luís Trindade, Eduardo Rabadão, Nuno Marques i José Saraiva da Cunha. "Seroprevalência do Anticorpo do Vírus na Hepatite A em Viajantes Portugueses: Um Novo Paradigma". Acta Médica Portuguesa 30, nr 7-8 (31.08.2017): 534. http://dx.doi.org/10.20344/amp.8130.

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Introduction: In Portugal, the prevalence of hepatitis A virus infection has decreased in the past decades, especially in young adults. The aim of this study was to detect the prevalence of antibody to hepatitis A virus in a population observed in our Travel Clinic.Material and Methods: Antibodies against hepatitis A, hepatitis B, hepatitis C and human immunodeficiency virus were tested using standard enzyme immunoassay in patients older than 18. The exclusion criteria were: prior vaccination for hepatitis A virus, previous diagnosis of infection with hepatitis B virus, hepatitis C virus and/or human immunodeficiency virus, foreign travelers and long-term expatriates. We applied an epidemiological survey and data was statistically analyzed with SPSS® 18.0.Results: In the 665 travelers studied, natural immunity to hepatitis A virus was present in 57.6% (n = 383). They were stratified into 8 age groups and for each one hepatitis A immunity was clarified: 5.0% (n = 1) in 18 - 25 years, 32.3% (n = 21) in 26 - 30 years, 40.9% (n = 47) in 31 - 35 years, 45.8% (n = 54) in 36 - 40 years, 68.7% (n = 79) in 41 - 45 years, 70.1% (n = 68) in 46 - 50 years, 80.8% (n = 63) in 51 - 55 years and 87.7% (n = 50) over 56 years old. In those who accepted further screening, positivity for hepatitis B core antibody was found in 0.6% (n = 3) travelers, hepatitis C virus infection in 1.1% (n = 6) and human immunodeficiency virus infection in 0.5% (n = 3) whose previous status was unknown. The most frequent travel destination was sub-Saharan Africa (72.6%; n = 483).Discussion: We found 49.1% (n = 260) travelers under 50 years old susceptible to hepatitis A virus infection and for those between 40 and 50 years, 30.7% (n = 65) still need vaccine protection.Conclusion: Across age groups there is a trend towards lower prevalence of hepatitis A virus antibody, in particular among youngsters, when compared with older Portuguese studies.

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