Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Defects of SKAP-55-Deﬁcient T Cells Identify a Regulatory Role for the Adaptor in LFA-1 Adhesion (cid:1)

The ADAP–SKAP-55 module regulates T-cell receptor (TCR)-induced integrin clustering and adhesion in T cells. However, it has been unclear whether ADAP and/or SKAP-55 is an effector of the response. ADAP controls SKAP-55 expression such that ADAP (cid:1) / (cid:1) T cells are also deﬁcient in SKAP-55 expression. In this study, we report the phenotype of the SKAP-55-deﬁcient mouse. SKAP-55 (cid:1) / (cid:1) T cells retain ADAP expression yet show defects in (cid:2) 1 and (cid:2) 2 integrin adhesion, leukocyte function-associated antigen 1 (LFA-1) clustering, production of the cytokines interleukin-2 and gamma interferon, and proliferation. This dependency was also reﬂected in more-transient conjugation times in response to the superantigen staphylococcal enterotoxin A on dendritic cells and a reduced number of cells with TCR/CD3 microcluster localization at the immunological synapse. SKAP-55 (cid:1) / (cid:1) T cells showed the same general impairment of function as ADAP (cid:1) / (cid:1) T cells, indicating that SKAP-55 is an effector of the ADAP–SKAP-55 module. At the same time, the requirement for ADAP and SKAP-55 was not absolute, since a subset of peripheral T cells adhered with loss of expression of either adaptor. Further, dependency on SKAP-55 or ADAP differed with the strength of the TCR signal. As with the ADAP (cid:1) / (cid:1) mouse, SKAP-55-deﬁcient mice showed no major effects on lymphoid development or the appearance of peripheral T cells, B cells, and NK cells. Our ﬁndings identify a clear effector role for SKAP-55 in LFA-1 adhesion in peripheral T cells and demonstrate that dependency on SKAP-55 and ADAP differs among T cells and differs with the strength of the TCR signal. and SKAP-55-deﬁcient T cells inﬂuence the activation of other pathways linked to the regulation of T-cell adhesion.
Longitudinal Chemical Gradients and the Functional Responses of Nutrients, Organic Matter, and Other Parameters to the Land Use Pattern and Monsoon Intensity

: River water quality degradation is one of the hottest environmental issues worldwide. Therefore, monitoring water quality longitudinally and temporally is crucial for effective water management and contamination control. The main aim of this study was to assess the longitudinal variations in water quality in the mainstream of the Han River, Korea, from 2015 to 2019. The trophic state classiﬁcation (TSC), microbial pollution indicator (MPI), and river pollution index (RPI) were calculated to characterize river water quality and revealed more serious pollution toward the downstream zone (Dz) due to agricultural and urban-dominated areas. The biodegradability index (BI) indicated that non-biodegradable organic pollutants are increasing in the water body from the urban and animal wastewater treatment plants. Nutrients, organic matter contents, total suspended solids, ionic factors, and algal chlorophyll were higher in the Dz than in any other zones and were markedly inﬂuenced by the summer monsoon. Empirical analysis showed that nutrients and organic matter had positive linear functional relations with agricultural and urban coverage and negative linear relations with forest coverage. The pollutant-transport function suggested that suspended solids act as TP and TN carriers. Regression analysis indicated that TP (R 2 = 0.47) has more positive functional relations with algal growth than TN (R 2 = 0.22). Our ﬁndings suggest that a combination of empirical models and pollution indices might be utilized to assess river water quality and that the resulting information could aid policymakers in managing the Han River.
(2015). Freshwater reservoir effect and the radiocarbon chronology of the cemetery in Zabie, Poland. Journal of Archaeological Science, 53, 264-276.

In the 3 rd millennium BC an island on the Łańskie Lake in north-eastern Poland was seasonally settled by a group of people practicing a syncretic burial ritual, exhibiting indigenous and foreign patterns. They left behind a small cemetery consisting of at least six graves. 14 C dates made for samples of human bones until 2009 did not coincide with the expected age of the graves. Under a new pilot program in 2010-2013, a series of radiocarbon measurements was made for the human bones and an artefact of red deer antler, along with analyses of the stable isotopes ratios of carbon (δ 13 C) and nitrogen (δ 15 N) in the collagen. The results indicate a significant proportion of freshwater food in the diet, which caused the radiocarbon dates to be too old due to the freshwater reservoir effect (FRE). Based on the dating of the antler, unaffected by FRE, and comparative analysis, the reservoir offset for one of the graves was estimated to 740 radiocarbon years. The results, although limited by a low number of investigated humans and animals, indicate indirectly a specialization in the exploitation of local water resources. Such an economic strategy seems to be characteristic for the societies inhabiting the coasts of the Baltic Sea and littoral zones of large lakes in the Final Neolithic and at the beginning of the Early Bronze Age.
DMSO_A_302207 1473..1483

1Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; 3Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan Purpose: To examine the association between different phenotypes of obesity or metabolic syndromes and liver fibrosis score in a Taiwanese elderly population with fatty liver. Patients and Methods: This cross-sectional study included 1817 participants aged ≥65 years with fatty liver diagnosed by sonography. We used ethnicity-specific criteria for body mass index and metabolic syndrome, and to define obesity phenotypes as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Correlated fibrosis severity was calculated using the nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) and Fibrosis-4 (FIB-4). Fibrosis severity was divided into two categories according to NFS (no-to-mild fibrosis and advanced fibrosis, defined as NFS ≤ 0.676 and >0.676, respectively) and FIB-4 score (no-to-mild fibrosis and advanced fibrosis, defined as FIB-4 score ≤2.67 and >2.67, respectively). Results: Compared with that in the MHNO group, the associated risk (odds ratio [OR], 95% confidence interval [CI]) of advanced fibrosis by NFS was 2.43 (1.50–3.93), 2.35 (1.25–4.41), and 6.11 (3.90–9.59), whereas that of advanced fibrosis by FIB-4 score was 1.34 (0.83–2.18), 2.37 (1.36–4.13), and 1.38 (0.82–2.31) in the MUNO, MHO, and MUO groups, respectively. Conclusion: Both metabolic syndrome and obesity were positively associated with more advanced fibrosis according to NFS. The detrimental effect of obesity appears to be more than metabolic abnormalities per se in the elderly with more advanced fibrosis severity according to the FIB-4 score.
Delay-Conscious Defense Against Fingerprinting Attacks

—In the past few years, many defense mechanisms have been proposed against website ﬁngerprinting attacks. Walkie-Talkie (WT) built on top of Tor network is known to be one of the most effective and efﬁcient defense mechanisms. However, we observed that WT signiﬁcantly increases page loading times (time overhead) while adding little bandwidth overhead compared to other approaches. We analyze the cause of the increased page loading time and present a defending approach called Tail Timeout (TT), which addresses the problem, by introducing a timeout mechanism limiting the maximum time for which a pending request can block subsequent requests. Our experimental results indicate that the proposed TT defense can signiﬁcantly reduce the page loading time while keeping similar defense performance in terms of true positive and true negative ratios achieved by WT.
XPERIENCE OF R ESIDENTIAL C ARE FROM THE P ERSPECTIVE OF A DOLESCENTS AND C AREGIVERS

/Izvleček Aim of the study is to provide an insight into the experience of residential care from the perspective of beneficiaries and experts. The data was collected in two male residential units. The results show that adolescents and caregivers tend to have a negative attitude toward residential care. Adolescents are even more skeptical about the purpose of treatment s ince they experience shortcomings in the activities and the methods of treatment, as well as monotony and stigmatization by the local community. Caregivers highlight their disappointment regarding the inadequate intervention system and the complexity of working with children with multiple risks and problems.
Loneliness and Social Networks in Europe

The paper analyses social causes of loneliness in Europe using cross-national data from the 2017 International Social Survey Programme (ISSP) module “Social Networks and Social Resources” from 13 countries categorised as Northern Europe, Continental Europe, and Central and Eastern Europe. The paper aims to examine loneliness with regard to three specific groups of predictors, related to network, sociocultural and sociostructural aspects. The results suggest that sociability patterns and personal networks are the most important predictors of loneliness. While the frequency of contacts with family members and close friends and the overall number of contacts showed significance, loneliness was primarily related to the quality of personal relationships. Considering sociocultural factors, the obtained findings showed that social trust is consistently associated with lower levels of loneliness. Furthermore, people from Continental Europe were, in general, less lonely than North and East Europeans. Age was an important factor here as respondents from younger age groups were lonelier in Nordic countries than in the other two blocs of countries, while older respondents were lonelier in Central and East European countries. Finally, sociostructural indicators in general showed less predictive value compared to sociability patterns and sociocultural variables. However, when it came to socioeconomic exclusion, this aspect showed a stronger connection with loneliness for the individuals from the Nordic group of countries. The findings of this paper contribute to the vibrant field of contemporary scholarship on loneliness with a fresh perspective based on comparing three large blocs of European countries and an integrated approach to various predictors of loneliness.
The Critical Role of Zinc in a New Murine Model of Enterotoxigenic E. coli

Enterotoxigenic E. coli are major causes of traveler’s diarrhea as well as 25 endemic diarrhea and stunting in children in developing areas. However a small 26 mammal model has been badly needed to better understand and assess 27 mechanisms, vaccines and interventions. We report a murine model of ETEC 28 diarrhea, weight loss and enteropathy, and investigate the role of zinc on the 29 outcomes. LT+ST producing enterotoxigenic E. coli (ETEC) given to weaned 30 C57BL/6 mice after antibiotic disruption of normal microbiota cause growth 31 impairment, watery diarrhea, heavy stool shedding and mild to moderate 32 intestinal inflammation, the latter worse with zinc deficiency. Zinc treatment 33 promoted growth in zinc deficient infected mice, and subinhibitory zinc reduced 34 expression of ETEC virulence genes cfa1 , cexE , sta2 and degP , but not eltA in 35 vitro. Zinc supplementation increased shedding and ileal burden of WT ETEC, 36 but decreased shedding and tissue burden of LTKO ETEC. LTKO ETEC infected 37 mice had delayed disease onset and also had less inflammation by fecal MPO 38 assessment These findings provide a new murine model of ETEC infection that 39 can help elucidate mechanisms of growth, diarrhea and inflammatory responses 40 as well as potential vaccines and interventions. 41 42 43 44 45 46
Entrepreneurial Skills' Training Packages on Disinfectant Production among Universities Chemistry Students in North Central, Nigeria

This study developed and determined the effect of entrepreneurial skill training package on disinfectant for undergraduate chemistry students’ skill acquisition in North Central Zone, Nigeria. To guide the study, two research questions and two hypotheses were stated and formulated respectively. The design of the study was non randomized post-test only quasi experimental. The population of the study comprised 1,640 consisting of Chemistry Lecturers and Undergraduate Chemistry Students from four Universities within the Study Area. Sample of Two Hundred and Ninety Six (296) respondents were used for the study. The instruments for data collection were structured questionnaires which were developed by the researcher from literature. Five specialists validated the items of the instruments. The reliability coefficients of the instruments were computed using Cronbach Alpha method. The coefficients of 0.83 and 0.77 was established. The data collected were analyzed using mean (X), standard deviation (SD), and percentage (%) to answer the research questions, while the two hypotheses were tested at 0.05 level of significance using t-test statistic. The result of the finding revealed that 16 skills are required for disinfectant production. All the skills were accepted by respondents as necessary and required for the development of entrepreneurial skill training package in disinfectant production for undergraduate chemistry students. Hypotheses tested showed that there was no significant difference in the performance mean scores of male and female Undergraduate Chemistry Students hence were accepted not rejected p>0.05 while result from the second hypothesis revealed that there was significant difference between the mean scores of state and federal undergraduate chemistry students , hence were rejected p˂0.05. Some recommendations were made among others as a result of the study findings which were that: of the developed skill training package to teach chemistry so as to understand its concepts and at the same time get the economic relevance and benefits of chemistry for self-reliance and sustainable economic development. Nigerian government should integrate the developed entrepreneurial skill training package on chemical product production for youths who wish to go into chemical products production on short term basis so as to enable them acquire the required entrepreneurial skills in chemical products production for employment.
A Multi-Center Randomized Comparison of High-Intensity Interval Training and Moderate-Intensity Exercise to Recover Walking Post-Stroke: Results of the HIT-Stroke Trial

Introduction: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. This trial aimed to determine the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8 or 12 weeks) needed to maximize immediate improvement in walking capacity in chronic stroke. Methods: Persons with chronic post-stroke gait dysfunction at three centers were randomized to high-intensity interval training (HIT) or moderate intensity aerobic training (MAT), each involving 45 minutes of treadmill and overground walking exercise with a physical therapist, 3 times per week for 12 weeks. The HIT protocol used repeated 30 second bursts of walking at maximum safe speed, alternated with 30-60 second recovery periods, targeting an average aerobic intensity above 60% heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40 {+/-} 5% HRR, progressing by 5% HRR every 2 weeks, up to 60% HRR as tolerated. Blinded assessment at baseline and after 4, 8 and 12 weeks of training included the 6-minute walk test (6MWT) as the primary measure of walking capacity. Results: Randomized participants (N=55) attended 1,675 (85%) of 1,980 planned treatment sessions and 197 (90%) of 220 planned testing sessions. No serious adverse events related to study procedures occurred. Compared with MAT, HIT involved significantly higher training speeds (161% vs 96% baseline fastest 10-meter speed, p<0.0001) and mean aerobic intensity (61% vs 46% HRR, p<0.0001) across treatment visits. There was no significant between-group difference in 6MWT changes after 4 weeks of training (HIT +27 meters [95% CI: 6-48], MAT +12 meters [-9-33], p=0.28), but randomization to HIT resulted in significantly greater gains than MAT after 8 weeks (+58 [39-76] vs +29 [9-48] meters, p=0.02) and 12 weeks (+71 [49-94] vs +27 [3-50] meters, p=0.005) of training. HIT also showed significantly greater improvements than MAT on some measures of gait speed, fatigue and exercise capacity. Discussion: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In chronic stroke, vigorous walking exercise can produce significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks are needed to maximize immediate gains.
Why does left ventricular distension usually not occur in veno-arterial extracorporeal membrane oxygenation?

Objectives: Using a lumped parameter-based theoretical circulatory model, we sought to examine the potential effects of veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support on coronary blood flow and resultant left ventricular (LV) contractility. Background: Previous theoretical studies have suggested that V-A ECMO support results in markedly increased left ventricular intracavity pressures and volumes, i.e., not only inadequate unloading, but exacerbated loading. However, this phenomenon of LV distension occurs only uncommonly in clinical scenarios. This discrepancy between previous theoretical work and clinical experience requires explanation. Methods: We defined a piecewise linear relation between the end-systolic pressure and volume of the ventricles to simulate ascending and descending limbs of the Frank-Starling relationship. A linear relationship between coronary blood flow rate and left ventricular contractility was added, defining the so-called Gregg effect. Results: LV systolic dysfunction resulted in reduced coronary blood flow; V-A ECMO support augmented coronary blood flow, proportionally to the circuit flow rate. On V-A ECMO support, a weak or absent Gregg effect resulted in increased LV end-diastolic pressures and volumes, and increased end-systolic volume with decreased LV ejection fraction (LVEF), consistent with LV distension. In contrast, a more robust Gregg effect resulted in unaffected and/or even reduced LV end-diastolic pressure and volume, end-systolic volume, and unaffected or even increased LVEF. Conclusions: In this lumped parameter model-based theoretical study, V-A ECMO support was found to augment coronary arterial blood flow. A resultant proportional augmentation of LV contractility may be an important contributory mechanism underlying why LV distension is uncommon in the setting of V-A ECMO support.
Cardiovascular Image-Derived Phenotypes from Abdominal MRI at a Population Scale

MRI measurements of heart volumes and vessel dimensions typically require specialised cardiac MRI examinations, which can be time consuming and resource intensive. Simpler scans covering the heart and major blood vessels of the abdomen may potentially provide useful clinical information. We used deep learning to segment cardiovascular structures from UK Biobank (UKBB) abdominal MRI scans and extracted six image-derived phenotypes (heart volume, and cross-sectional areas of the aorta and vena cava at key anatomical locations) from 44,541 participants. We found strong correlations between our measurements and those acquired using conventional cardiac MRI (CMR), with the strength of the association reflecting the degree of anatomical similarity between the measurements. We replicated previous findings related to gender differences and age-related changes in heart and vessel dimensions, and identified a significant association between infrarenal descending aorta cross-sectional area and incident aneurysm, and between heart volume and several cardiovascular disorders. In a genome-wide association study we identified 72 associations at 59 loci, of which 15 had not been previously associated with CMR IDPs. Furthermore, we demonstrated substantial genetic correlation with cardiovascular traits including varicose veins, aneurysms, dysrhythmia and cardiac failure. Our heritability enrichment implicated vascular tissue in the heritability of these traits. We derived a polygenic risk score for each trait and demonstrated an association with aneurysm diagnosis, pointing to a potential screening method for individuals at high-risk of this condition. Our work highlights the rich information content of abdominal MRI and the high degree of overlap with CMR.
MULTI-OMICS TEMPORAL PROFILING OF AXIAL SPONDYLOARTHRITIS PATIENTS REVEALS AN ASSOCIATION OF THERAPEUTIC RESPONSE TO ADALIMUMAB WITH DISEASE ACTIVITY AND INNATE / ADAPTIVE IMMUNITY

Background: Axial Spondyloarthritis can lead to significant disability and impairment in quality of life. TNF inhibitors are recommended to patients enduring active disease despite conventional treatment. Nonetheless, up to 40% of patients of patients fail to respond to TNF inhibitors. In this context, it is important to identify as early as possible patients highly likely to respond. This study aims at identifying, among axial spondyloarthritis patients undergoing treatment with the TNF inhibitor adalimumab, early molecular biomarkers differentiating good responders from non-responders after 14 weeks of treatment, as measured by ASAS20. Methods: Peripheral blood RNA sequencing and serum proteins measured by mass spectrometry were evaluated in a cohort of biologic naive axial spondyloarthritis patients (n = 35), before (baseline) and after (3-5 days, 2 weeks and 14 weeks) treatment with adalimumab. Results from differential expression analysis were used in combination with clinical data to build logistic regression models and random forest models to predict response to adalimumab at baseline. Results: Responders to adalimumab presented higher levels of markers of innate immunity at baseline, mostly related with neutrophils, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP and AFF3, the top differentially expressed gene between responders and non-responders at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC=0.96), with random forest models suggesting 80% predictive accuracy. A treatment-associated signature suggests a reduction in inflammatory activity, with C-reactive protein and Haptoglobin showing strong and early decrease in the serum of axial spondyloarthritis patients, while a cluster of apolipoproteins showed increased expression at week 14. Conclusions: Differences in disease activity and/or blood innate/adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axial spondyloarthritis, where a model including clinical and blood gene expression variables shows high predictive power. Our results suggest novel molecular biomarkers of response to adalimumab at baseline. Trial registration: Axial spondyloarthritis patients were selected from participants of the Bioefficacy study - Biomarkers Identification of Anti-TNF Agent's Efficacy in Ankylosing Spondylitis Patients Using a Transcriptome Analysis and Mass Spectrometry (clinical trials.gov identifier NCT02492217).