Miracle-dz/UniFAR-FTUs huggingface dataset:
A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients

ABSTRACT Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4+CD25+ leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN + AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (TSCM) Fashi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied. In this study, we found significant ex vivo antiproliferative, antiviral and immunomodulatory effects of IFN-α treatment in short-term culture of primary mononuclear cells from ATL patients (n = 25). Bayesian Network analysis allowed us to integrate ex vivo IFN-α response with clinical, genetic and immunological data from ATL patients, thereby revealing a central role for FAS -670 polymorphism and apoptosis in the coordinated mechanism of action of IFN-α. FAS genotype-dependence of IFN-induced apoptosis was experimentally validated in an independent cohort of healthy controls (n = 20). The same FAS -670 polymorphism also determined CD4 TSCM levels in a genome-wide twin study (p = 7 × 10−11, n = 460), confirming a genetic link between apoptosis and TSCM levels. Transcriptomic analysis and cell type deconvolution confirmed the FAS genotype/TSCM link and IFN-α-induced downregulation of CD4 TSCM-specific genes in ATL patient cells. In conclusion, ex vivo IFN-α treatment exerts a pleiotropic effect on primary ATL cells, with a genetic IFN/STAT1/Fas axis determining apoptosis vs. proliferation and underscoring the CD4 TSCM model of ATL leukemogenesis.
Animacy and attentional processes: Evidence from the Stroop task

In visual perception, evidence has shown that attention is captured earlier and held longer by animate than inanimate stimuli. The former are also remembered better than the latter. Thus, as far as attentional processes are concerned, animate entities have a privileged status over inanimate entities. We tested this hypothesis further using an adaptation of the Stroop paradigm. Adults had to categorise the colours of words that referred to either animate or inanimate concepts. In two experiments, we found that it took longer to process the ink colour of animate than inanimate words. Indeed, this effect was found when the words were presented in an oral animacy Stroop task (Experiment 1) and in a manual animacy Stroop task (Experiment 2). Using ex-Gaussian analyses and examining the distribution of RTs as a function of vincentiles per animacy condition, we did not find a specific localisation of the animacy effect. The findings are interpreted as providing further evidence that animates are prioritised in processing because their fitness value is higher than that of inanimates.
Association Between Midwall Late Gadolinium Enhancement and Sudden Cardiac Death in Patients With Dilated Cardiomyopathy and Mild and Moderate Left Ventricular Systolic Dysfunction

Background: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. Methods: We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ≥40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. Results: Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9–21.8; P<0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8–13.5; P=0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6–266.6; P<0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9–22.3; P<0.0001), SCD (HR, 4.8; 95% CI, 1.7–13.8; P=0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8–271.4; P<0.001). Estimated HRs for the primary end point for patients with an LGE extent of 0% to 2.5%, 2.5% to 5%, and >5% compared with those without LGE were 10.6 (95% CI, 3.9–29.4), 4.9 (95% CI, 1.3–18.9), and 11.8 (95% CI, 4.3–32.3), respectively. Conclusions: Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ≥40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00930735.
Sensitivity and linearity analysis of ozone in East Asia: The effects of domestic emission and intercontinental transport

In this study, ozone (O3) sensitivity and linearity over East Asia (EA) and seven urban areas are examined with an integrated air quality modeling system under two categories of scenarios: (1) The effects of domestic emission are estimated under local emission reduction scenarios, as anthropogenic NOx and volatile organic compounds (VOC) emissions are reduced by 20%, 50%, and 100%, respectively and independently; and (2) the influence of intercontinental transport is evaluated under Task Force on Hemispheric Transport of Air Pollution (TF HTAP) emission reduction scenarios, as anthropogenic NOx emission is reduced by 20% in Europe (EU), North America (NA), and South Asia (SA), respectively. Simulations are conducted for January and July 2001 to examine seasonal variation. Through the domestic O3 sensitivity investigation, we find O3 sensitivity varies dynamically depending on both time and location: North EA is VOC limited in January and NOx limited in July, except for the urban areas Beijing, Shanghai, Tokyo, and Seoul, which are VOC limited in both months; south EA is NOx limited in both January and July, except for the urban areas Taipei, which is VOC-limited in both months, and Pearl River Delta, which is VOC limited in January. Surface O3 change is found to be affected more by NOx than by VOC over EA in both January and July. We also find different O3 linearity characteristics among urban areas in EA: O3 at Beijing, Tokyo, and Seoul shows a strong negative linear response to NOx emission in January; O3 at Shanghai, Pearl River Delta, and Taipei shows a strong positive response to VOC emission in both January and July. Through the long-range transport investigation, monthly O3 changes over EA resulting from different source regions indicate the largest source contribution comes from NA (0.23 ppb), followed by SA (0.11 ppb) and EU (0.10 ppb). All of the three regions show higher impacts in January than in July. Implications: This study examine O3 sensitivities and linear response of NOx and VOC emission over EA and seven urban areas based on regional air quality modeling system MM5/CMAQ. We also quantify the intercontinental transport effect from EU, SA, and NA over EA. The result provide a theoretical basis for emission control strategy design in EA, and also reveal the O3 special nonlinearity features for further related studies that are applicable to other continents. The HTAP multimodel experiments need to examine the potential impacts on ground-level O3 of changes in meteorology and transport patterns expected as a result of the regional scale.
Strategies to Increase Human Immunodeficiency Virus Testing Among Men to Reach UNAIDS 90-90-90 Targets.

mortality because of imprecision and the small number of events [2]. The 95% confidence interval for the summary odds ratio for mortality (.46–1.21) included clinically relevant benefit as well as clinically relevant harm, not allowing for strong conclusions either way. However, as mentioned in our article, at least 5 ongoing eligible randomized clinical trials [2, supplementary materials] will help clarify the effect of corticosteroids on mortality in patients with CAP in the next few years. Our IPDMA was based on the currently available evidence, and we found no significant effect of corticosteroids on mortality, possibly owing to limited statistical power. Stern et al [1] further state that they cannot follow our concerns with subgroup analyses of severe CAP in an aggregate data meta-analysis by Siemieniuk et al [3]. However, Siemieniuk et al themselves argue that “established criteria for evaluating subgroup analyses suggest that the apparent effect is probably spurious” because the effect is “based on differences between rather than within studies,” among other reasons [3]. Aggregate data meta-analyses typically classify the trials reported by Blum et al [4], Meijvis et al [5], and Snijders et al [6] as trials in patients with less severe pneumonia, ignoring the fact that these trials included up to 49% patients with severe CAP (pneumonia severity index class IV or V). For credible subgroup analyses, it is crucial to use standardized definitions across trials and to consider effects within rather than between studies, which is mostly possible only with IPDMA. Finally, we agree with Stern et al that one should evaluate any intervention with a potential impact on mortality with great caution. However, this is why it is important to carefully consider the limitations of recent aggregate data meta-analyses and carefully consider benefits and harms, including our finding of an increased risk of CAP-related rehospitalization with corticosteroids, before jumping to recommendations. A substantial proportion of the body of evidence on corticosteroids for CAP is still in the making.
Loss of the Cyclin-Dependent Kinase Inhibitor 1 in the Context of Brachyury-Mediated Phenotypic Plasticity Drives Tumor Resistance to Immune Attack

The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells. Here, we investigated the mechanism involved in the immune resistance of carcinoma cells that express very high levels of the transcription factor brachyury, a molecule previously shown to drive the acquisition of mesenchymal features by carcinoma cells. Our results demonstrate that very high levels of brachyury expression drive the loss of the cyclin-dependent kinase inhibitor 1 (p21CIP1, p21), an event that results in decreased tumor susceptibility to immune-mediated lysis. We show here that reconstitution of p21 expression markedly increases the lysis of brachyury-high tumor cells mediated by antigen-specific CD8+ T cells, NK, and LAK cells, TNF-related apoptosis-inducing ligand, and chemotherapy. Several reports have now demonstrated a role for p21 loss in cancer as an inducer of the epithelial–mesenchymal transition. The results from the present study situate p21 as a central player in many of the aspects of the phenomenon of brachyury-mediated mesenchymalization of carcinomas, including resistance to chemotherapy and immune-mediated cytotoxicity. We also demonstrate here that the defects in tumor cell death described in association with very high levels of brachyury could be alleviated via the use of a WEE1 inhibitor. Several vaccine platforms targeting brachyury have been developed and are undergoing clinical evaluation. These studies provide further rationale for the use of WEE1 inhibition in combination with brachyury-based immunotherapeutic approaches.
Hierarchical RNN for Information Extraction from Lawsuit Documents

Every lawsuit document contains the information about the party's claim, court's analysis, decision and others, and all of this information are helpful to understand the case better and predict the judge's decision on similar case in the future. However, the extraction of these information from the document is difficult because the language is too complicated and sentences varied at length. We treat this problem as a task of sequence labeling, and this paper presents the first research to extract relevant information from the civil lawsuit document in China with the hierarchical RNN framework.
Evaluation of Noncardiac Chest Pain: Toward a Positive Diagnosis

INSTRUCTIONS The following case study, “Evaluation of Noncardiac Chest Pain: Toward a Positive Diagnosis,” is accompanied by a continuing medical education (CME) evaluation that consists of 5 multiple-choice questions. After reading the case study, carefully consider each of the questions in the CME evaluation on page 52. Then, circle your selected answer to each question on the CME evaluation form on page 53. In order to receive one CME credit, at least 3 of the 5 questions must be answered correctly. The estimated time for this CME activity is 1 hour.
Measuring psychometric characteristics of the elderly sensory responsivity questionnaire– A tool for screening sensory processing difficulties in elderly adults

Background: The function of the sensory systems decreases in the elderly. This may negatively impact the person's performance and independence in daily living. Most studies refer to the decrease in specific modalities and to sensory acuity rather than to general sensory processing in all modalities. Moreover, there is a lack of evaluation tools that focus on these general sensory processing abilities with functional daily life perspective in the elderly population. Objectives: To examine the psychometric characteristics of the Elderly Adult Sensory Sensitivity Questionnaire (ESRQ) - an adapted version of the Sensory Responsiveness Questionnaire (SRQ) version II. The ESRQ aims to screen sensory processing difficulties among elderly adults, as expressed in daily living situations. Methods: The sample consisted of 361 participants, aged 50-86 years, who were and in good health and functionally independent. Participants were divided into three age groups: 50-59; 60-69 and 70-86. All participants completed a demographic and health status questionnaire and the ESRQ. Results: Analysis of ESRQ scales revealed five factors, which explained 45.66% of the total variance. Internal consistency was high for the full questionnaire and moderate to high for each factor. No significant differences were found between the age groups. Women showed significantly higher sensitivity than men in several modalities. Implications and conclusions: ESRQ may serve as a suitable tool for screening sensory processing difficulties in the elderly. Gender may play a role in sensory processing changes in the elderly. Further studies should examine the psychometric properties of the ESRQ among elderly people with disabilities. Establishing the prevalence of sensory processing difficulties in the elderly may be beneficial for developing and improving intervention strategies to overcome functional deficits.
Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage

Background The understanding of ovarian cancer pathogenesis has recently shifted to recognize distinct changes in how ovarian cancer histotypes are defined. Using the 2014 World Health Organization (WHO) diagnostic guidelines, we classified ovarian cancer histotypes in Surveillance, Epidemiology, and End Results (SEER) cancer registry data and examined survival patterns by histotype and disease stage. Methods We extracted data on 28 118 incident epithelial ovarian cancer cases diagnosed in 2004-2014 from SEER and defined histotype using the 2014 WHO guidelines (high-grade serous, low-grade serous, endometrioid, clear cell, mucinous, carcinosarcoma, and malignant Brenner tumors). By histotype and disease stage, we estimated Kaplan-Meier survival curves and calculated age-adjusted overall and cause-specific survival estimates. Cox proportional hazards regression models were used to estimate histotype-specific hazard ratios (HRs) and 95% confidence intervals (CIs) by disease stage while adjusting for age at diagnosis, region, race/ethnicity, and receipt of surgery. Results Within two years after diagnosis, localized/regional-stage carcinosarcoma and distant-stage mucinous, clear cell, and carcinosarcoma had a higher risk of mortality compared with high-grade serous, with the most pronounced association for localized/regional carcinosarcoma (>1-2-year time period: HR = 3.81, 95% CI = 2.74 to 5.30) and distant-stage mucinous (0-1-year time period: HR = 3.87, 95% CI = 3.45 to 4.34). In the time period more than four to 10 years after diagnosis, hazard ratios for all histotypes relative to high-grade serous, irrespective of disease stage, were less than 1.00. Cumulatively, both localized/regional and distant-stage low-grade serous and endometrioid carcinomas had the most favorable outcomes. Conclusions Our large study, which is representative of the United States population and incorporates the most current knowledge of ovarian cancer pathogenesis, highlights the need to recognize ovarian cancer as a set of distinct diseases and not a single entity. Only then will we be able to effectively target the unique features of each histotype to reduce ovarian cancer mortality.
ANCHOR: web server for predicting protein binding regions in disordered proteins

Summary: ANCHOR is a web-based implementation of an original method that takes a single amino acid sequence as an input and predicts protein binding regions that are disordered in isolation but can undergo disorder-to-order transition upon binding. The server incorporates the result of a general disorder prediction method, IUPred and can carry out simple motif searches as well. Availability: The web server is available at http://anchor.enzim.hu. The program package is freely available for academic users. Contact: zsuzsa@enzim.hu
The content and structure of laypeople's concept of pleasure

Five studies were conducted to map the content and structure of laypeople's conceptions of pleasure. Instances of the pleasure concept collected in Study 1 consisted predominantly of objects, events or persons described as sources of pleasure. Content analysis suggested that the pleasure category, like emotional response categories, might be formed at an implicit level where various pleasure antecedents are grouped based on common phenomenological qualities of the affective experience. Studies 2 and 3a showed that the pleasure category possesses a graded structure and fuzzy boundaries. Results further revealed that, either when explicitly presented with labels (Study 3b) or left to their own implicit categories during a sorting task (Study 4), laypeople represented pleasure as a hierarchical concept in which differentiated pleasure types (i.e., intellectual, emotional, social and physical) were subsumed under a higher level unitary form of pleasure. In this structure, unitary and differentiated pleasures shared a set of common affective qualities but were also distinguishable by unique and distinctive affective characteristics (Study 5). Ties to prior theories of pleasure and implications for decision making and behavioural research are discussed.
Collective Representation as a Mobilizer

Prior research has found that descriptive representation by race, ethnicity, or gender increases political action, but it has paid less attention to how the intersection of these identities influences participation. We extend this literature by assessing the effects on voter turnout of collective descriptive representation in U.S. state legislatures on the basis of race, ethnicity, gender, and their intersections. We argue that members of historically excluded groups respond to the overall composition of their state’s legislature. We test this proposition in seven elections (2000, 2002, 2004, 2006, 2008, 2010, and 2012). Our results are consistent with the minority empowerment literature, as overall collective representation does substantially increase turnout among previously excluded groups. However, the impact varies intersectionally. For white women, gender trumps race, as higher collective gender representation, regardless of race or ethnicity, increases voter turnout. For African Americans, race trumps gender, as both black men and women respond most consistently to higher levels of collective racial representation. For Latinos, we find less consistent results, but note a collective ethnic turnout effect for 2002 and 2006. We conclude that collective representation, especially at the intersection of identities, is an important factor influencing levels of turnout among previously excluded groups.
Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy—one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (Acadm) to display daily rhythms with peak values during daytime in preparations of the whole retina and microdissected photoreceptors. The cycling of both enzymes persisted in constant darkness, was dampened in mice deficient for dopamine D4 (D4) receptors and was altered in db/db mice—a model of diabetic retinopathy. The data of the present study are consistent with circadian clock-dependent and dopaminergic regulation of fatty acid oxidation in retina and its putative disturbance in diabetic retina.