Miracle-dz/UniFAR-FTUs huggingface dataset:
Fast Approach to Build an Automatic Sentiment Annotator for Legal Domain using Transfer Learning

This study proposes a novel way of identifying the sentiment of the phrases used in the legal domain. The added complexity of the language used in law, and the inability of the existing systems to accurately predict the sentiments of words in law are the main motivations behind this study. This is a transfer learning approach which can be used for other domain adaptation tasks as well. The proposed methodology achieves an improvement of over 6% compared to the source model’s accuracy in the legal domain.
CD44 is overexpressed and correlated with tumor progression in gallbladder cancer

Background Gallbladder cancer (GBC) is a highly lethal disease and the most common biliary tract malignant tumor with poor prognosis. Accumulating evidence indicates that cluster of differentiation 44 (CD44) is overexpressed in several malignancies and has a crucial role in the development of cancer. However, its expression and function in GBC are unclear. The aim of this study was to explore CD44 expression and its role in GBC. Materials and methods The expression of CD44 was measured by immunohistochemistry. Tissue microarray analysis was used to confirm the relationship between CD44 expression and clinical outcomes of GBC patients. EDU assay, colony formation assay, cell migration and invasion assay were performed to detect the functions of CD44 in GBC-SD and NOZ transfected with si-RNA. Results CD44 was overexpressed and associated with poor outcomes in GBC patients. The univariate and multivariate analyses confirmed that elevated CD44 was an independent prognostic factor for the OS of GBC patients. Silencing CD44 could suppress the GBC cell proliferation, migration and invasion in vitro, as well as attenuated cancer stem cell functions. Conclusion CD44 markedly correlated with aggressive tumor behaviors and contributed to the progression of GBC, which could represent a novel prognostic marker and potential therapeutic target for GBC patients.
Neural Networks for Cross-lingual Negation Scope Detection

Negation scope has been annotated in several English and Chinese corpora, and highly accurate models for this task in these languages have been learned from these annotations. Unfortunately, annotations are not available in other languages. Could a model that detects negation scope be applied to a language that it hasn't been trained on? We develop neural models that learn from cross-lingual word embeddings or universal dependencies in English, and test them on Chinese, showing that they work surprisingly well. We find that modelling syntax is helpful even in monolingual settings and that cross-lingual word embeddings help relatively little, and we analyse cases that are still difficult for this task.
Lon recognition of the replication initiator DnaA requires a bipartite degron

DnaA initiates chromosome replication in bacteria. In Caulobacter crescentus, the Lon protease degrades DnaA to coordinate replication with nutrient availability and to halt the cell cycle during acute stress. Here, we characterize the mechanism of DnaA recognition by Lon. We find that the folded state of DnaA appears crucial for its degradation, in contrast to the well‐known role of Lon in degrading misfolded proteins. We fail to identify a single degradation motif (degron) sufficient for DnaA degradation, rather we show that both the ATPase domain and a species‐specific N‐terminal motif are important for productive Lon degradation of full‐length DnaA. Mutations in either of these determinants disrupt DnaA degradation in vitro and in vivo. However, analysis of truncation products reveals that appending other extensions to the ATPase domain is sufficient to trigger degradation, suggesting plasticity in Lon recognition. Our final working model is that Lon engages DnaA through at least two elements, one of which anchors DnaA to Lon and the other acting as an initiation site for degradation.
Impacts of species richness on productivity in a large-scale subtropical forest experiment

Tree diversity improves forest productivity Experimental studies in grasslands have shown that the loss of species has negative consequences for ecosystem functioning. Is the same true for forests? Huang et al. report the first results from a large biodiversity experiment in a subtropical forest in China. The study combines many replicates, realistic tree densities, and large plot sizes with a wide range of species richness levels. After 8 years of the experiment, the findings suggest strong positive effects of tree diversity on forest productivity and carbon accumulation. Thus, changing from monocultures to more mixed forests could benefit both restoration of biodiversity and mitigation of climate change. Science, this issue p. 80 In a replicated experiment in a subtropical forest, higher tree species diversity promoted productivity and carbon storage. Biodiversity experiments have shown that species loss reduces ecosystem functioning in grassland. To test whether this result can be extrapolated to forests, the main contributors to terrestrial primary productivity, requires large-scale experiments. We manipulated tree species richness by planting more than 150,000 trees in plots with 1 to 16 species. Simulating multiple extinction scenarios, we found that richness strongly increased stand-level productivity. After 8 years, 16-species mixtures had accumulated over twice the amount of carbon found in average monocultures and similar amounts as those of two commercial monocultures. Species richness effects were strongly associated with functional and phylogenetic diversity. A shrub addition treatment reduced tree productivity, but this reduction was smaller at high shrub species richness. Our results encourage multispecies afforestation strategies to restore biodiversity and mitigate climate change.
Black-White Cardiovascular Disease Disparities After Target-Based Versus Personalized Benefit–Based Lipid and Blood Pressure Treatment

Background: Cardiovascular disease (CVD) remains the leading cause of black-white morbidity and mortality disparities in the United States. Objectives: We sought to compare black-white CVD morbidity and mortality if lipid and blood pressure treatments were prescribed to achieve targeted lipid and blood pressure levels (treat-to-target [TTT]) or personalized CVD risk and treatment benefit estimates (benefit-based tailored treatment [BTT]). Methods: We utilized a microsimulation model of statin and blood pressure treatment based on a TTT approach (Joint National Commission 7; Adult Treatment Panel III) or a BTT approach (treating those with 10-year CVD risk ≥10%, a modification and extension of recent American College of Cardiology/American Heart Association guidelines). We input data from the National Health and Nutrition Examination Survey, isolating adults 40 to 75 years of age without prior CVD events. Results: We observed that TTT would prevent fewer CVD events (17.0 events prevented per 1,000 whites, 22.2 per 1,000 blacks) than the BTT approach (25.9 events prevented per 1,000 whites, 45.4 per 1,000 blacks). TTT could lower the national black-white CVD event rate disparity from 23.1 excess events per 1,000 blacks to 17.9 excess events (−23%), while BTT could lower the disparity to 3.6 excess events (−84% overall). The inferiority of TTT to BTT remained consistent in sensitivity analyses testing alternative treatment targets and either over- or underestimation of risk by commonly used equations. Conclusions: A BTT approach to lipid and blood pressure treatment would be expected to prevent more CVD events in the overall population and more effectively reduce national black-white CVD disparities than a traditional TTT approach.
The frequency of TP53 R72P and MDM2 309T>G polymorphisms in Iranian infertile men with spermatogenetic failure: A case-control study

Background: Tumor protein p53 (TP53) is a tumor suppressor transcriptional regulator protein which plays a critical role in the spermatogenesis. One of the most important regulators of p53 is Murine double minute 2 (MDM2), which acts as a negative regulator of the p53 pathway. Based on the key role of p53 and MDM2 in germ cell apoptosis, polymorphisms that cause a change in their function might affect germ cell apoptosis and the risk of male infertility. Objective: This study was designed to examine associations of TP53 72 Arg>Pro (rs1042522), and MDM2 309 T>G (rs937283) polymorphisms with spermatogenetic failure in Iranian population. Materials and Methods: A case-control study was conducted with 150 nonobstructive azoospermia or severe oligozoospermia and 150 fertile controls. The two polymorphisms, 72 Arg>Pro in TP53 and 309 T>G in MDM2, were genotyped using PCR-RFLP and ARMS-PCR respectively. Results: Our analyses revealed that the allele and genotype frequencies of the TP53 R72P polymorphism were not significantly different between the cases and controls (p=0.41, p=0.40 respectively). Also, no significant differences were found in the allelic (p=0.46) and genotypic (p=0.78) distribution of MDM2 309 T>G polymorphism between patients and controls. Conclusion: The results of this study indicate that polymorphisms of TP53 and MDM2 genes are unlikely to contribute to the pathogenesis of male infertility with spermatogenetic failure.
Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor

ABSTRACT The tumor suppressor p53 responds to genotoxic and oncogenic stresses by inducing cell cycle arrest and apoptosis. Recent studies suggest that p53 also participates in the regulation of cellular immune responses. Here, we have investigated the potential of p53 gene therapy to augment immune checkpoint inhibition by combining an anti-programmed cell death protein 1 (PD1) antibody with SGT-53, our investigational nanomedicine carrying a plasmid encoding human wild-type p53. In three syngeneic mouse tumor models examined including a breast cancer, a non-small cell lung carcinoma, and a glioblastoma, SGT-53 sensitized otherwise refractory tumors to anti-PD1 antibody. The involvement of p53 in enhancing anti-PD1 immunotherapy appears to be multifaceted, since SGT-53 treatment increased tumor immunogenicity, enhanced both innate and adaptive immune responses, and reduced tumor-induced immunosuppression in a 4T1 breast tumor model. In addition, SGT-53 alleviates a fatal xenogeneic hypersensitivity associated with the anti-PD1 antibody in this model. Our data suggest that restoring p53 function by SGT-53 is able to boost anti-tumor immunity to augment anti-PD1 therapy by sensitizing tumors otherwise insensitive to anti-PD1 immunotherapy while reducing immune-related adverse events.
Own-Age Bias and Positivity Effects in Facial Recognition

ABSTRACT Background/Study Context - In the current study, we evaluated two age-related differences in recognition memory: the own-age bias, wherein older and younger adults best recognize those of their own age group, and an age-related positivity effect, wherein older adults recall positive emotional information better than negative information relative to younger adults. We sought to extend previous research that jointly investigated these variables in recognition memory. Methods - Younger (age 18 – 27) and older (age 62 – 80) adults completed an incidental encoding task on a sequence of 50 positive, negative, or neutrally valenced images of older and younger adult faces. After a distractor task, participants made forced-choice recognition judgments and rated their decision confidence for images that were repeated with the same or a different emotional expression, and for novel, previously unseen faces. Results – Older and younger adults’ recognition discriminability did not differ significantly between age groups. Notably, the data indicated an own-age bias in young adults, but not in older adults, and both age groups’ recognition accuracy was greatest for faces that had originally been shown with a positive emotional expression. Conclusion - To our knowledge, this research is the first to demonstrate an own-age recognition bias in younger adults for emotional faces. Although our predictions of a differential impact by emotional faces on recognition of same and other-age faces were not supported, we identify a number of factors that contextualize these findings in the recent literature.
White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies

Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural underpinnings of alcohol teratogenesis. This technique can detect alterations in white matter in neurodevelopmental disorders, such as fetal alcohol spectrum disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted on individuals with prenatal alcohol exposure (PAE). These studies confirm the widespread nature of brain damage in PAE by reporting diffusivity alterations in commissural, association, and projection fibers; and in relation to increasing cognitive impairment. Reduced integrity in terms of lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported more consistently in the corpus callosum, cerebellar peduncles, cingulum, and longitudinal fasciculi connecting frontal and temporoparietal regions. Although these interesting results provide insight into FASD neuropathology, it is important to investigate the clinical diversity of this disorder for better treatment options and prediction of progression. The aim of this review is to provide a summary of different patterns of neural structure between PAE and typically developed individuals. We further discuss the association of alterations in diffusivity with demographic features and symptomatology of PAE. With the accumulated knowledge of the neural correlates of FASD presenting symptoms, a comprehensive understanding of the heterogeneity in FASD will potentially improve the disease management and will highlight the diagnostic challenges and potential areas of future research avenues, where neural markers may be beneficial.
The Role of the Immunological Synapse in Differential Effects of APC Subsets in Alloimmunization to Fresh, Non-stored RBCs

Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantibodies can be a problem as they may mediate hemolysis or pose barriers to future transfusion support. While there is currently no reliable way to predict which RBC recipients will make an alloantibody response, risk factors such as inflammation have been shown to correlate with increased rates of RBC alloimmunization. The underlying mechanisms behind how inflammation mediates alloantibody production are incompletely defined. Methods: To assess erythrophagocytosis, mice were treated with PBS or inflammatory stimuli followed by a transfusion of allogeneic RBCs labeled with a lipophilic dye. At multiple time points, RBC consumption and expression of activation makers by leukocytes was evaluated. To determine which antigen presenting cell (APC) subset(s) were capable of promoting allogeneic T cell activation, sorted leukocyte populations (which had participated in erythrophagocytosis) were co-cultured in vitro with allogeneic CD4+ T cells; T cell proliferation and ability to form immunological synapses with APCs were determined. Results: Upon transfusion of fresh allogeneic RBCs, multiple APCs consumed transfused RBCs. However, only CD8+ and CD11b+ dendritic cells formed productive immunological synapses with allogeneic T cells and stimulated proliferation. Importantly, allogeneic T cell activation and RBC alloantibody production occurred in response to RBC transfusion alone, and transfusion in the context of inflammation enhanced RBC consumption, the number of immune synapses, allogeneic T cell proliferation, and the rate and magnitude of alloantibody production. Conclusions: These data demonstrate that regardless of the ability to participate in RBC consumption, only a subset of APCs are capable of forming an immune synapse with T cells thereby initiating an alloantibody response. Additionally, these data provide mechanistic insight into RBC alloantibody generation.
DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder

So far, genetic studies of treatment response in schizophrenia, bipolar disorder, and major depression have returned results with limited clinical utility. A gene × environment interplay has been proposed as a factor influencing not only pathophysiology but also the treatment response. Therefore, epigenetics has emerged as a major field of research to study the treatment of these three disorders. Among the epigenetic marks that can modify gene expression, DNA methylation is the best studied. We performed a systematic search (PubMed) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines for preclinical and clinical studies focused on genome-wide and gene-specific DNA methylation in the context of schizophrenia, bipolar disorders, and major depressive disorder. Out of the 112 studies initially identified, we selected 31 studies among them, with an emphasis on responses to the gold standard treatments in each disorder. Modulations of DNA methylation levels at specific CpG sites have been documented for all classes of treatments (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the models and methodologies used complicate the interpretation of results. Although few studies in each disorder have assessed the potential of DNA methylation as biomarkers of treatment response, data support this hypothesis for antipsychotics, mood stabilizers and antidepressants.
Actual and simulated weather data to evaluate wet bulb globe temperature and heat index as alerts for occupational heat-related illness

Abstract Heat stress occupational exposure limits (OELs) were developed in the 1970s to prevent heat-related illnesses (HRIs). The OELs define the maximum safe wet bulb globe temperature (WBGT) for a given physical activity level. This study’s objectives were to compute the sensitivity of heat stress OELs and determine if Heat Index could be a surrogate for WBGT. We performed a retrospective analysis of 234 outdoor work-related HRIs reported to the Occupational Safety and Health Administration in 2016. Archived NOAA weather data were used to compute each day’s maximum WBGT and Heat Index. We defined the OELs’ sensitivity as the percentage of incidents with WBGT > OEL. Sensitivity of the OELs was between 88% and 97%, depending upon our assumption about acclimatization status. In fatal cases, the OELs’ sensitivity was somewhat higher (92–100%). We also computed the sensitivity of each possible Heat Index discrimination threshold. A Heat Index threshold of 80 °F (26.7 °C) was exceeded in 100% of fatalities and 99% of non-fatal HRIs. In a separate analysis, we created simulated weather data to assess associations of WBGT with Heat Index over a range of realistic outdoor heat conditions. These simulations demonstrated that for a given Heat Index, when radiant heat was included, WBGT was often higher than previously reported. The imperfect correlation between WBGT and Heat Index precluded a direct translation of OELs from WBGT into Heat Index. We conclude that WBGT-based heat stress exposure limits are highly sensitive and should be used for workplace heat hazard assessment. When WBGT is unavailable, a Heat Index alert threshold of approximately 80 °F (26.7 °C) could identify potentially hazardous workplace environmental heat.
Molecular genetic advances in pituitary tumor development

Pituitary adenomas are a heterogeneous group of tumors that may occur as part of a complex syndrome or as an isolated endocrinopathy and both forms can be familial or non-familial. Studies of syndromic and non-syndromic pituitary adenomas have yielded important insights about the molecular mechanisms underlying tumorigenesis. Thus, syndromic forms, including multiple endocrine neoplasia type 1 (MEN1), MEN4, Carney Complex and McCune Albright syndrome, have been shown to be due to mutations of the tumor-suppressor protein menin, a cyclin-dependent kinase inhibitor (p27Kip1), the protein kinase A regulatory subunit 1-α, and the G-protein α-stimulatory subunit (Gsα), respectively. Non-syndromic forms, which include familial isolated pituitary adenoma (FIPA) and sporadic tumors, have been shown to be due to abnormalities of: the aryl hydrocarbon receptor-interacting protein; Gsα; signal transducers; cell cycle regulators; transcriptional modulators and miRNAs. The roles of these molecular abnormalities and epigenetic mechanisms in pituitary tumorigenesis, and their therapeutic implications are reviewed.
Infection risk with alemtuzumab decreases over time: pooled analysis of 6-year data from the CAMMS223, CARE-MS I, and CARE-MS II studies and the CAMMS03409 extension study

Background: Reduced MS disease activity with alemtuzumab versus subcutaneous interferon beta-1a (SC IFNB-1a) in core phase 2/3 studies was accompanied by increased incidence of infections that were mainly nonserious and responsive to treatment. Alemtuzumab efficacy was durable over 6 years. Objective: To evaluate infections over 6 years in alemtuzumab-treated patients. Methods: Three randomized trials (CAMMS223, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I, and CARE-MS II) compared two courses of alemtuzumab 12 mg with SC IFNB-1a 44 μg in patients with active relapsing-remitting MS. An extension study (CAMMS03409) provided further evaluation and as-needed alemtuzumab retreatment. Results: Infections occurred more frequently with alemtuzumab 12 mg than SC IFNB-1a during Years 1 (58.7% vs 41.3%) and 2 (52.6% vs 37.7%), but declined for alemtuzumab-treated patients in Years 3 (46.6%), 4 (42.8%), 5 (40.9%), and 6 (38.1%). Serious infections were uncommon (1.0%–1.9% per year). Infections were predominantly (>95%) mild to moderate and included upper respiratory tract infections, urinary tract infections, and mucocutaneous herpetic infections. Prophylactic acyclovir reduced herpetic infections. Lymphocyte counts after alemtuzumab therapy did not predict infection risk. Conclusion: Infections with alemtuzumab were mostly mild to moderate and decreased over time, consistent with preservation of components of protective immunity.
Crystal structure of the full Swi2/Snf2 remodeler Mot1 in the resting state

Swi2/Snf2 ATPases remodel protein:DNA complexes in all of the fundamental chromosome-associated processes. The single-subunit remodeler Mot1 dissociates TATA box-binding protein (TBP):DNA complexes and provides a simple model for obtaining structural insights into the action of Swi2/Snf2 ATPases. Previously we reported how the N-terminal domain of Mot1 binds TBP, NC2 and DNA, but the location of the C-terminal ATPase domain remained unclear (Butryn et al., 2015). Here, we report the crystal structure of the near full-length Mot1 from Chaetomium thermophilum. Our data show that Mot1 adopts a ring like structure with a catalytically inactive resting state of the ATPase. Biochemical analysis suggests that TBP binding switches Mot1 into an ATP hydrolysis-competent conformation. Combined with our previous results, these data significantly improve the structural model for the complete Mot1:TBP:DNA complex and suggest a general mechanism for Mot1 action.