Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Factors Associated with Suicidal Behaviors and Alcohol Use Disorders in an American Indian Population

American Indians (AI) demonstrate the highest rates of both suicidal behaviors (SB) and alcohol use disorders (AUD) among all ethnic groups in the US. Rates of suicide and AUD vary substantially between tribal groups and across different geographical regions, underscoring a need to delineate more specific risk and resilience factors. Using data from over 740 AI living within eight contiguous reservations, we assessed genetic risk factors for SB by investigating: (1) possible genetic overlap with AUD, and (2) impacts of rare and low frequency genomic variants. Suicidal behaviors included lifetime history of suicidal thoughts and acts, including verified suicide deaths, scored using a ranking variable for the SB phenotype (range 0-4). We identified five loci significantly associated with SB and AUD, two of which are intergenic and three intronic on genes AACSP1, ANK1, and FBXO11. Nonsynonymous rare mutations in four genes including SERPINF1 (PEDF), ZNF30, CD34, and SLC5A9, and non-intronic rare mutations in genes OPRD1, HSD17B3 and one lincRNA were significantly associated with SB. One identified pathway related to hypoxia-inducible factor (HIF) regulation, whose 83 nonsynonymous rare variants on 10 genes were significantly linked to SB as well. Four additional genes, and two pathways related to vasopressin-regulated water metabolism and cellular hexose transport, also were strongly associated with SB. This study represents the first investigation of genetic factors for SB in an American Indian population that has high risk for suicide. Our study suggests that bivariate association analysis between comorbid disorders can increase statistical power; and rare variant analysis in a high-risk population enabled by whole-genome sequencing has the potential to identify novel genetic factors. Although such findings may be population specific, rare functional mutations relating to PEDF and HIF regulation align with past reports and suggest a biological mechanism for suicide risk and a potential therapeutic target for intervention.
Applications of CRISPR technologies to the development of gene and cell therapy

Advancements in gene and cell therapy have resulted in novel therapeutics for diseases previously considered incurable or challenging to treat. Among the various contributing technologies, genome editing stands out as one of the most crucial for the progress in gene and cell therapy. The discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and the subsequent evolution of genetic engineering technology have markedly expanded the field of target-specific gene editing. Originally studied in the immune systems of bacteria and archaea, the CRISPR system has demonstrated wide applicability to effective genome editing of various biological systems including human cells. The development of CRISPR-based base editing has enabled directional cytosine-to-thymine and adenine-to-guanine substitutions of select DNA bases at the target locus. Subsequent advances in prime editing further elevated the flexibility of the edit multiple consecutive bases to desired sequences. The recent CRISPR technologies also have been actively utilized for the development of in vivo and ex vivo gene and cell therapies. We anticipate that the medical applications of CRISPR will rapidly progress to provide unprecedented possibilities to develop novel therapeutics towards various diseases.
Average Horizontal Crustal Strain Ratesin Japan during Interseismic Period Deduced from Geodetic Surveys (Part2)

This is a revision of Hashimoto's (1990) study on average horizontal crustal strain rates in Japan derived from geodetic data collected during the past 100 years. This new study includes Hokkaido since the completion of the latest nationwide trilateration enables us to apply the methods of the previous study and obtain strain rates there. In this method, side lengths of triangulation networks are calculated using adjusted coordinates for different epochs and then the rate of change of each side length is estimated by regression. Finally the principal strain rate in each triangular region is obtained. In order to avoid the effects of large earthquakes or volcanic eruptions, data before or after these events are simply discarded. Unfortunately, due to frequent occurrence of large events in northern Japan, we can use data from only two epochs for most of Hokkaido, which causes large uncertainties in the estimated strain rates. Hokkaido appears to be divided into four provinces according to the characteristics of the horizontal strain rates, although the uncertainties are too large to be definitive. Eastern Hokkaido is characterized by large WNW-ESE contraction. In northern Hokkaido E-W contraction is prevailing, while extension is dominant in southwestern Hokkaido. In other regions the directions of principal axes of strain rates are not noticeably different from those of the previous study. In the Tohoku region, tensile strain rates in a N-S direction are prevailing. A NNW-SSE or NW-SE trending contraction is dominant along the coast from southern Kanto to Shikoku, though it is smaller in the Tokai area and Kui peninsula than in southern Kanto and Shikoku. In the same Shikoku region, there is a remarkable region of NE-SW extension that is as large as contraction. In central Japan, there is a NE-SW trending region of contraction. An E-W oriented contraction is dominant west or northwest of this region, such as in the Kinki and eastern Chugoku districts, while a NW-SE trending contraction is prevailing in the southeast. Kyushu is under an extensional regime with tensional directions of N-S and NW-SE in central and southern Kyushu, respectively. Magnitude of strain rates obtained in this study ranges from 1 to 3 •~ 10-7/yr in most regions except in the Shikoku, southern Kanto and Fukui areas where it reaches 6 •~ 10-7/yr. Over all, magnitude of strain rates are as large as or slightly larger than those derived from continuous GPS observations, but are larger than geological or seismological strain rates by a factor of 10.
ExEmPLAR (Extracting, Exploring, and Embedding Pathways Leading to Actionable Research): a user-friendly interface for knowledge graph mining

Abstract Summary Knowledge graphs are being increasingly used in biomedical research to link large amounts of heterogenous data and facilitate reasoning across diverse knowledge sources. Wider adoption and exploration of knowledge graphs in the biomedical research community is limited by requirements to understand the underlying graph structure in terms of entity types and relationships, represented as nodes and edges, respectively, and learn specialized query languages for graph mining and exploration. We have developed a user-friendly interface dubbed ExEmPLAR (Extracting, Exploring, and Embedding Pathways Leading to Actionable Research) to aid reasoning over biomedical knowledge graphs and assist with data-driven research and hypothesis generation. We explain the key functionalities of ExEmPLAR and demonstrate its use with a case study considering the relationship of Trypanosoma cruzi, the etiological agent of Chagas disease, to frequently associated cardiovascular conditions. Availability and implementation ExEmPLAR is freely accessible at https://www.exemplar. mml.unc. edu/. For code and instructions for the using the application, see: https://github.com/beasleyjonm/AOP-COP-Path-Extractor.
Iron role paradox in nerve degeneration and regeneration

Iron accumulates in the neural tissue during peripheral nerve degeneration. Some studies have already been suggested that iron facilitates Wallerian degeneration (WD) events such as Schwann cell de‐differentiation. On the other hand, intracellular iron levels remain elevated during nerve regeneration and gradually decrease. Iron enhances Schwann cell differentiation and axonal outgrowth. Therefore, there seems to be a paradox in the role of iron during nerve degeneration and regeneration. We explain this contradiction by suggesting that the increase in intracellular iron concentration during peripheral nerve degeneration is likely to prepare neural cells for the initiation of regeneration. Changes in iron levels are the result of changes in the expression of iron homeostasis proteins. In this review, we will first discuss the changes in the iron/iron homeostasis protein levels during peripheral nerve degeneration and regeneration and then explain how iron is related to nerve regeneration. This data may help better understand the mechanisms of peripheral nerve repair and find a solution to prevent or slow the progression of peripheral neuropathies.
Democratising the design and delivery of large-scale randomised, controlled clinical trials in primary care: A personal view

Abstract Background Rapid identification of effective treatments for use in the community during a pandemic is vital for the well-being of individuals and the sustainability of healthcare systems and society. Furthermore, identifying treatments that do not work reduces research wastage, spares people unnecessary side effects, rationalises the cost of purchasing and stockpiling medication, and reduces inappropriate medication use. Nevertheless, only a small minority of therapeutic trials for SARS-CoV-2 infections have been in primary care: most opened too late, struggled to recruit, and few produced actionable results. Participation in research is often limited by where one lives or receives health care, and trial participants may not represent those for whom the treatments are intended. Innovative trials The ALIC4E, PRINCIPLE and the ongoing PANORAMIC trial have randomised over 40,500 people with COVID-19. This personal view describes how these trials have innovated in: trial design (by using novel adaptive platform designs); trial delivery (by complementing traditional site-based recruitment (‘the patient comes to the research’) with mechanisms to enable sick, infectious people to participate without having to leave home (‘taking research to the people’), and by addressing the ‘inverse research participation law,’ which highlights disproportionate barriers faced by those who have the most to contribute, and benefit from, research, and; in transforming the evidence base by evaluating nine medicines to support guidelines and care decisions world-wide for COVID-19 and contribute to antimicrobial stewardship. Conclusion The PRINCIPLE and PANORAMIC trials represent models of innovation and inclusivity, and exemplify the potential of primary care to lead the way in addressing pressing global health challenges.
Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia

ABSTRACTPurpose of Review: This article provides an overview of the clinical features, neuropathologic findings, diagnostic criteria, and management of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the Lewy body dementias.Recent Findings: DLB and PDD are common, clinically similar syndromes that share characteristic neuropathologic changes, including deposition of &agr;-synuclein in Lewy bodies and neurites and loss of tegmental dopamine cell populations and basal forebrain cholinergic populations, often with a variable degree of coexisting Alzheimer pathology. The clinical constellations of DLB and PDD include progressive cognitive impairment associated with parkinsonism, visual hallucinations, and fluctuations of attention and wakefulness. Current clinical diagnostic criteria emphasize these features and also weigh evidence for dopamine cell loss measured with single-photon emission computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep behavior disorder, a risk factor for the synucleinopathies. The timing of dementia relative to parkinsonism is the major clinical distinction between DLB and PDD, with dementia arising in the setting of well-established idiopathic Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while earlier cognitive impairment relative to parkinsonism denotes DLB. The distinction between these syndromes continues to be an active research question. Treatment for these illnesses remains symptomatic and relies on both pharmacologic and nonpharmacologic strategies.Summary: DLB and PDD are important and common dementia syndromes that overlap in their clinical features, neuropathology, and management. They are believed to exist on a spectrum of Lewy body disease, and some controversy persists in their differentiation. Given the need to optimize cognition, extrapyramidal function, and psychiatric health, management can be complex and should be systematic.
Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa

Supplemental Digital Content is Available in the Text. Background: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. Methods: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. Results: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15–39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15–29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%–11.7%), both much lower than the 25% reported by UNAIDS. Conclusion: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.
Inhibitory and synergistic effects during biodegradation of mixed contaminants at an industrial site in South America

ii DEDICATION . vi ACKNOWLEDGMENTS . vii LIST OF TABLES . xi LIST OF FIGURES . xiii LIST OF ABBREVIATIONS . xx 1.0 INTRODUCTION AND OBJECTIVES . 1 1.1 Interactions during Biodegradation of Contaminants Found at Area P . 2 1.1.1 Interactions during Biodegradation of Chlorobenzenes . 3 1.1.2 Interactions during Biodegradation of Nitrotoluenes . 6 1.1. 3 Interactions during Biodegradation of Anilines, 1,2-DCA, and Other Compounds . 8 1.1. 4 Impacts Resulting from Source Zone Chemical Oxidation. 8 1.2 Objectives . 9 2.0 MATERIALS AND METHODS. 11 2.1 Sample Locations . 11 2.2 Chemicals and Medium . 12 2.3 Experimental Design and Microcosm Preparation . 13 2.3. 1 Preparation and Evaluation of the Soil and Groundwater . 13 2.3. 2 Chemical Oxidation Laboratory Scale Test . 15 2.3. 3 Preparation of the Aerobic Microcosms . 17 2.3. 4 Preparation of the Anaerobic Microcosms . 19 2.4 Preparation of Enrichment Cultures . 20 2.4. 1 Aerobic Enrichment Culture . 20 2.4. 2 Anaerobic Enrichment Culture . 22 2.5 Inhibition Tests . 23 2.5. 1 Chlorobenzene Inhibition . 23 2.5. 2 1,2-Dichlorobenzene Inhibition. 25 2.5. 3 2,6-Dinitrotoluene Inhibition. 26 2.5. 4 4-Nitrotoluene Inhibition . 27 2.6 Analytical Procedures . 28 2.6. 1 VOCs and Oxygen. 28 2.6. 2 1,4-Dioxane . 30 2.6. 3 HPLC Methods . 31 2.6. 4 Other Methods . 33
Demystifying Hidden Privacy Settings in Mobile Apps

Mobile apps include privacy settings that allow their users to configure how their data should be shared. These settings, however, are often hard to locate and hard to understand by the users, even in popular apps, such as Facebook. More seriously, they are often set to share user data by default, exposing her privacy without proper consent. In this paper, we report the first systematic study on the problem, which is made possible through an in-depth analysis of user perception of the privacy settings. More specifically, we first conduct two user studies (involving nearly one thousand users) to understand privacy settings from the user’s perspective, and identify these hard-to-find settings. Then we select 14 features that uniquely characterize such hidden privacy settings and utilize a novel technique called semantics- based UI tracing to extract them from a given app. On top of these features, a classifier is trained to automatically discover the hidden privacy settings, which together with other innovations, has been implemented into a tool called Hound. Over our labeled data set, the tool achieves an accuracy of 93.54%. Further running it on 100,000 latest apps from both Google Play and third-party markets, we find that over a third (36.29%) of the privacy settings identified from these apps are “hidden”. Looking into these settings, we observe that they become hard to discover and hard to understand primarily due to the problematic categorization on the apps’ user interfaces and/or confusing descriptions. Further importantly, though more privacy options have been offered to the user over time, also discovered is the persistence of their usability issue, which becomes even more serious, e.g., originally easy-to-find settings now harder to locate. And among all such hidden privacy settings, 82.16% are set to leak user privacy by default. We provide suggestions for improving the usability of these privacy settings at the end of our study.
It Is Smart to Set Treatment Goals, But Are Set Treatment Goals SMART? A Qualitative Assessment of Goals Described in the Assessment of the Burden of COPD Tool

Abstract The Assessment of the Burden of COPD (ABC) tool facilitates shared decision-making and goal setting to develop a personalized care plan. In a previous trial (RCT), the ABC tool was found to have a significant effect on patients’ Health-related Quality of Life (HRQoL). In this exploratory study we used data from the intervention group of the RCT to investigate if patients with health-related goals had an improved HRQoL compared to those without goals, and if the quality and types of goals differed for those who have a clinically meaningful improvement in HRQoL. We hypothesized that the quality and the type of the goal described in the ABC tool, relates to an improved HRQoL. We assessed the quality of the goals according to the Specificity, Measurability, Achievability, Relevance and Timeliness (SMART) criteria, and coded and counted each type of goal. We found that having a goal or not, did not differ significantly for those who had a clinically meaningful improved HRQoL versus those who had not, nor was the quality or type of goal significantly different. The most common types of goals were exercise more, smoke less, and improve weight. Based on the results, we speculate that when a clinically meaningful improvement in HRQoL is achieved, it is not related to a single component (i.e. goal setting as part of shared decision-making) but that the different components of the ABC tool (visualization of burden, shared decision making, utilization of tailored evidence based interventions, and regular monitoring of progress) may have a synergistic effect on disease cognition and/or behavior change. Noteworthy, the sample size was small while the calculated effect size was moderate, making it unlikely to find a significant effect.
Non-breeding season movements of six North American Roseate Terns Sterna dougallii tracked with geolocators

Little is known of the endangered and declining western North Atlantic population of the Roseate Tern Sterna dougallii outside the breeding season, when most mortality probably occurs. We used geolocators to track Roseate Terns in 2007 and 2009 and retrieved six units with useful data. In the post-breeding period in July-August, all six birds staged around Cape Cod, close to the breeding site. They started southward migration from 28 August to 14 September and flew directly across the western North Atlantic Ocean to staging areas around Puerto Rico and the Dominican Republic. We identified five major areas and four minor areas in the West Indies and along the north and east coasts of South America where birds stopped over for 2-24 d during southward and northward migrations. Birds arrived at (Northern Hemisphere) wintering areas from Guyana/Suriname on the north coast of South America to eastern Brazil between 3 October and 2 November. They left wintering areas from 7-23 April and arrived back at the breeding area from 5-30 May. Although this study is based on data for only six birds, it identifies several stopover and wintering areas that should receive priority for future studies and potential conservation measures. Geolocators did not impair Roseate Terns' ability to raise young in the year the devices were attached, but lower than expected rates of return suggest that the geolocators reduced survival, and most of the birds that returned had lost body-mass and did not breed in the year of return.
A protocol for systematic review and meta-analysis

Background:Growing interest on the effects of telemonitoring on patients with chronic heart failure (CHF) has led to a rise in the number of trials addressing the same or very similar research questions with a concomitant increase in discordant findings. Therefore, we conducted a protocol for systematic review and meta-analysis to compare the effects of different telemonitoring strategies on clinical outcomes in patients with CHF. Methods: Two individual researchers conducted the platform searches on the PubMed, Cochrane Library, and Embase databases from inception to February 2022. Literature retrieving was carried out through a combined searching of subject terms (“MeSH” on PubMed and “Emtree” on “Embase”) and free terms on the platforms of PubMed and Embase, and through keywords searching on platform of Cochrane Library. Systematic review and meta-analysis of the data will be performed in STATA13.0 software according to the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two authors independently performed the literature searching, data extraction, and quality evaluation. Risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized controlled trials (RCTs). Results: The results will be submitted to a peer-reviewed journal. Conclusion: This meta-analysis will provide a comprehensive analysis and synthesis that can be used as an evidence map to inform practitioners and policy makers about the effectiveness of telemonitoring interventions for patients with CHF. Abbreviations: CHF = chronic heart failure, CI = confidence interval, GRADE = Grading of Recommendations Assessment, Development, and Evaluation, MD = mean difference, RCT = randomized controlled trial, RR = risk ratio.