Miracle-dz/UniFAR-FTUs huggingface dataset:
Opioid Treatment Deserts: Concept development and application in a US Midwestern urban county

Objectives An Opioid Treatment Desert is an area with limited accessibility to medication-assisted treatment and recovery facilities for Opioid Use Disorder. We explored the concept of Opioid Treatment Deserts including racial differences in potential spatial accessibility and applied it to one Midwestern urban county using high resolution spatiotemporal data. Methods We obtained individual-level data from one Emergency Medical Services (EMS) agency (Columbus Fire Department) in Franklin County, Ohio. Opioid overdose events were based on EMS runs where naloxone was administered from 1/1/2013 to 12/31/2017. Potential spatial accessibility was measured as the time (in minutes) it would take an individual, who may decide to seek treatment after an opioid overdose, to travel from where they had the overdose event, which was a proxy measure of their residential location, to the nearest opioid use disorder (OUD) treatment provider that provided medically-assisted treatment (MAT). We estimated accessibility measures overall, by race and by four types of treatment providers (any type of MAT for OUD, Buprenorphine, Methadone, or Naltrexone). Areas were classified as an Opioid Treatment Desert if the estimate travel time to treatment provider (any type of MAT for OUD) was greater than a given threshold. We performed sensitivity analysis using a range of threshold values based on multiple modes of transportation (car and public transit) and using only EMS runs to home/residential location types. Results A total of 6,929 geocoded opioid overdose events based on data from EMS agencies were used in the final analysis. Most events occurred among 26–35 years old (34%), identified as White adults (56%) and male (62%). Median travel times and interquartile range (IQR) to closest treatment provider by car and public transit was 2 minutes (IQR: 3 minutes) and 17 minutes (IQR: 17 minutes), respectively. Several neighborhoods in the study area had limited accessibility to OUD treatment facilities and were classified as Opioid Treatment Deserts. Travel time by public transit for most treatment provider types and by car for Methadone-based treatment was significantly different between individuals who were identified as Black adults and White adults based on their race. Conclusions Disparities in access to opioid treatment exist at the sub-county level in specific neighborhoods and across racial groups in Columbus, Ohio and can be quantified and visualized using local public safety data (e.g., EMS runs). Identification of Opioid Treatment Deserts can aid multiple stakeholders better plan and allocate resources for more equitable access to MAT for OUD and, therefore, reduce the burden of the opioid epidemic while making better use of real-time public safety data to address a public health epidemic that has turned into a public safety crisis.
Flexible pivoting of dynamin pleckstrin homology domain catalyzes fission: insights into molecular degrees of freedom

The neuronal dynamin1 functions in the release of synaptic vesicles by orchestrating the process of GTPase-dependent membrane fission. Dynamin1 associates with the plasma membrane–localized phosphatidylinositol-4,5-bisphosphate (PIP2) through the centrally located pleckstrin homology domain (PHD). The PHD is dispensable as fission (in model membranes) can be managed, even when the PHD-PIP2 interaction is replaced by a generic polyhistidine- or polylysine-lipid interaction. However, the absence of the PHD renders a dramatic dampening of the rate of fission. These observations suggest that the PHD-PIP2–containing membrane interaction could have evolved to expedite fission to fulfill the requirement of rapid kinetics of synaptic vesicle recycling. Here, we use a suite of multiscale modeling approaches to explore PHD–membrane interactions. Our results reveal that 1) the binding of PHD to PIP2-containing membranes modulates the lipids toward fission-favoring conformations and softens the membrane, and 2) PHD associates with membrane in multiple orientations using variable loops as pivots. We identify a new loop (VL4), which acts as an auxiliary pivot and modulates the orientation flexibility of PHD on the membrane—a mechanism that we believe may be important for high-fidelity dynamin collar assembly. Together, these insights provide a molecular-level understanding of the catalytic role of PHD in dynamin-mediated membrane fission.
Journal of Reproduction and Development

The diameters of the pre-ovulatory follicles (PF) and the largest follicle during the subsequent first follicular wave (W1LF), and plasma estradiol-17β (E2) concentrations were monitored on Days 0, 1, 3, 5, and 7 (ovulation = Day 1). Pregnancy was diagnosed on Day 30. Cows were classified into two groups according to the location of the dominant follicle ipsilateral (IG) or contralateral (CG) to the corpus luteum on Day 7. From Days 3 to 7, some follicles that had been determined as the subordinate in the previous examination exceeded the W1LF located in the opposite ovary in terms of the diameter. These were defined as switching (SW), whereas others were defined as non-switching (NSW). The diameter of PF was significantly smaller in pregnant (P) animals than in non-pregnant (NP) animals. The plasma E2 concentration on Day 0 was significantly higher in P animals than in NP animals and tended to be higher in NSW than in SW. In addition, plasma E2 concentrations around Days 3 to 7 tended to be higher in P animals of NSW than in NP animals of SW. The conception rates did not differ between IG and CG but were significantly higher in NSW than in SW. In the IG group, the conception rate tended to be higher in NSW than in SW.
Using social network analysis to examine inter-governmental relations in the implementation of the Ideal Clinic Realisation and Maintenance programme in two South African provinces

Background Within the context of universal health coverage (UHC), South Africa has embarked on a series of health sector reforms. The implementation of the Ideal Clinic Realisation and Maintenance (ICRM) programme is a major UHC reform. Cooperative governance is enshrined in South Africa’s Constitution, with health a concurrent competency of national and provincial government. Hence, effective inter-governmental relations (IGR) are essential for the ICRM programme implementation. Aim The aim of the study was to measure the cohesion of IGR, specifically consultation, support and information sharing, across national, provincial and local government health departments in the ICRM programme implementation. Materials and methods Using Provan and Milward’s theory on network effectiveness, this study was a whole network design social network analysis (SNA). The study was conducted in two districts in Gauteng (GP) and Mpumalanga (MP) provinces of South Africa. Following informed consent, we used both an interview schedule and a network matrix to collect the social network data from health policy actors in national, provincial and local government. We used UCINET version 6.619 to analyse the SNA data for the overall network cohesion and cohesion within and between the government spheres. Results The social network analysis revealed non-cohesive relationships between the different spheres of government. In both provinces, there was poor consultation in the ICRM programme implementation, illustrated by the low densities of seeking advice (GP = 15.6%; MP = 24.4%) and providing advice (GP = 14.1%; MP = 25.1%). The most cohesive relationships existed within the National Department of Health (density = 66.7%), suggesting that national policy actors sought advice from one another, rather than from the provincial health departments. A density of 2.1% in GP, and 12.5% in MP illustrated the latter. Conclusion The non-cohesive relationships amongst policy actors across government spheres should be addressed in order to realise the benefits of cooperative governance in implementing the ICRM programme.
Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis

Objectives To report the neuropsychiatric features and frequency of NMDA receptor (NMDAR) and other neuronal immunoglobulin G antibodies in patients with first episode psychosis (FEP) and to assess the performance of reported warning signs and criteria for autoimmune psychosis (AP). Methods This was a prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed. Results One hundred five patients were included; their median age was 30 (range 14–75) years, and 44 (42%) were female. None had neuronal antibodies. Two of 105 (2%) had CSF pleocytosis, 4 of 100 (4%) had brain MRI abnormalities, and 3 of 73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled 2 sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and nonpsychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1,159 reported patients with FEP, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features). Conclusions NMDAR antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurologic symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.
Assembly processes lead to divergent soil fungal communities within and among twelve forest ecosystems along a latitudinal gradient.

Latitudinal gradients provide opportunities to better understand soil fungal community assembly and its relationship with vegetation, climate, soil and ecosystem function. Understanding the mechanisms underlying community assembly is essential for predicting compositional responses to changing environments. We quantified the relative importance of stochastic and deterministic processes in structuring soil fungal communities using patterns of community dissimilarity observed within and between twelve natural forests and related these to environmental variation within and among sites. The results revealed that whole fungal communities and communities of arbuscular and ectomycorrhizal fungi consistently exhibited divergent patterns but with less divergence for ectomycorrhizal fungi at most sites. Within those forests, no clear relationships were observed between the degree of divergence within fungal and plant communities. When comparing communities at larger spatial scales, among the twelve forests, we observed distinct separation in all three fungal groups among tropical, subtropical and temperate climatic zones. Soil fungal β-diversity patterns between forests were also greater when comparing forests exhibiting high environmental heterogeneity. Taken together, although large-scale community turnover could be attributed to specific environmental drivers, the differences among fungal communities in soils within forests was high even at local scales.
Blood-Based Biomarkers and Long-term Risk of Frailty—Experience From the Swedish AMORIS Cohort

Abstract Background Frailty is associated with reduced quality of life, poor health outcomes, and death. Past studies have investigated how specific biomarkers are associated with frailty but understanding biomarkers in concert with each other and the associated risk of frailty is critical for clinical application. Methods Using a sample aged ≥59 years at baseline from the Swedish AMORIS (Apolipoprotein MOrtality RISk) cohort (n = 19 341), with biomarkers measured at baseline (1985–1996), we conducted latent class analysis with 18 biomarkers and used Cox models to determine the association between class and frailty and all-cause mortality. Results Four classes were identified. Compared to the largest class, the Reference class (81.7%), all other classes were associated with increased risk of both frailty and mortality. The Anemia class (5.8%), characterized by comparatively lower iron markers and higher inflammatory markers, had hazard ratio (HR) = 1.54, 95% confidence interval (CI) 1.38, 1.73 for frailty and HR = 1.76, 95% CI 1.65, 1.87 for mortality. The Diabetes class (6.5%) was characterized by higher glucose and fructosamine, and had HR = 1.59, 95% CI 1.43, 1.77 for frailty and HR = 1.74, 95% CI 1.64, 1.85 for mortality. Finally, the Liver class (6.0%), characterized by higher liver enzyme levels, had HR = 1.15, 95% CI 1.01, 1.30 for frailty and HR = 1.40, 95% CI 1.31, 1.50 for mortality. Sex-stratified analyses did not show any substantial differences between men and women. Conclusions Distinct sets of commonly available biomarkers were associated with development of frailty and monitoring these biomarkers in patients may allow for earlier detection and possible prevention of frailty, with the potential for improved quality of life.
Collective Emotion During Collective Trauma: A Metaphor Analysis of the COVID-19 Pandemic

This study provides insight into lived experiences of the COVID-19 pandemic in the United States. Participant metaphors of the pandemic were collected by conducting in-depth semi-structured interviews (N = 44). Participants were asked to compare the pandemic with an animal and with a color, and to provide contextual sensemaking about their metaphors. A metaphor analysis revealed four convergent mental models of participants’ pandemic experiences (i.e., uncertainty, danger, grotesque, and misery) as well as four primary emotions associated with those mental models (i.e., grief, disgust, anger, and fear). Through metaphor, participants were able to articulate deeply felt, implicit emotions about their pandemic experiences that were otherwise obscured and undiscussable. Theoretical and practical implications of these collective mental models and associated collective emotions related to the unprecedented collective trauma of the COVID-19 pandemic are discussed.
Profiling of Primary and Mature miRNA Expression in Atherosclerosis-Associated Cell Types

Supplemental Digital Content is available in the text. Objective: Atherosclerosis is the underlying cause of most cardiovascular diseases. The main cell types associated with disease progression in the vascular wall are endothelial cells, smooth muscle cells, and macrophages. Although their role in atherogenesis has been extensively described, molecular mechanisms underlying gene expression changes remain unknown. The objective of this study was to characterize microRNA (miRNA)-related regulatory mechanisms taking place in the aorta during atherosclerosis. Approach and Results: We analyzed the miRNA expression changes in primary human aortic endothelial cells and human umbilical vein endothelial cells, human aortic smooth muscle cells, and macrophages (CD14+) under various proatherogenic stimuli by integrating GRO-seq, miRNA-seq, and RNA-seq data. Despite the highly cell-type-specific expression of multi-variant primary miRNAs, the majority of mature miRNAs were found to be common to all cell types and dominated by 2 to 5 abundant miRNA species. We demonstrate that transcription contributes significantly to the mature miRNA levels although this is dependent on miRNA stability. An analysis of miRNA effects in relation to target mRNA pools highlighted pathways and targets through which miRNAs could affect atherogenesis in a cell-type-dependent manner. Finally, we validate miR-100-5p as a cell-type specific regulator of inflammatory and HIPPO-YAP/TAZ-pathways. Conclusions: This integrative approach allowed us to characterize miRNA dynamics in response to a proatherogenic stimulus and identify potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.
Brain-derived Neurotrophic Factor in the Aqueous Humor of Glaucoma Patients.

BACKGROUND Brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of glaucoma. BDNF concentrations reported in previous studies have varied widely, and the concentration of BDNF in aqueous humor is unknown. In this study, BDNF concentrations in the aqueous humor of glaucoma patients and control patients were measured with ELISA kits. METHODS This prospective, observational study examined BDNF levels in aqueous humor in 62 eyes of 43 patients who underwent cataract surgery or trabeculectomy (11 glaucoma patients and 32 non-glaucoma cataract patients as controls). BDNF concentrations were examined by 4 different enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS The mean ± SD patient age was 72.0 ± 10.1 (range 35 to 87) years. Two of the techniques detected no BDNF in aqueous humor in any samples (n=3 and n=9, respectively); the average value was less than zero. An ultrasensitive ELISA kit did not yield reliable measurements. Finally, in an even more sensitive ELISA (Simoa-HD1), performed by an outside contractor, 25 (54.3%) eyes were below the detection limit, including 20 (55.6%) control and 5 (50%) glaucoma cases. For eyes with detectable BDNF, the overall BDNF concentration was 0.158 pg/mL (n=21): 0.196 pg/mL (n=16) in controls and 0.034 pg/mL (n=5) in glaucoma cases. CONCLUSIONS BDNF level in aqueous humor varies widely.
The Role of Nutrition in COVID-19 Susceptibility and Severity of Disease: A Systematic Review

Background Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. Objective The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19. Methods We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020. Results Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials. Conclusions Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.
Effects of ferrous iron supplementation on reductive dechlorination of tetrachloroethene and on methanogenic microbial community

ABSTRACT Chloroethenes are common soil and groundwater pollutants. Their dechlorination is impacted by environmental factors, such as the presence of metal ions. We here investigated the effect of ferrous iron on bacterial reductive dechlorination of chloroethenes and on methanogen community. Reductive dechlorination of tetrachloroethene was assayed with a groundwater sample originally containing 6.3 × 103 copies mL−1 of Dehalococcoides 16S rRNA gene and 2 mg L−1 of iron. Supplementation with 28 mg L−1 of ferrous iron enhanced the reductive dechlorination of cis-dichloroethene (cis-DCE) and vinyl chloride in the presence of methanogens. The supplementation shortened the time required for complete dechlorination of 1 mg L−1 of tetrachloroethene to ethene and ethane from 84 to 49 d. Methanogens, such as Candidatus ‘Methanogranum’, Methanomethylovorans and Methanocorpusculum, were significantly more abundant in iron-supplemented cultures than in non-supplemented cultures (P < 0.01). Upon methanogen growth inhibition by 2-bromoethanesulfonate and in the absence of iron supplementation, cis-DCE was not dechlorinated. Further, iron supplementation induced 71.3% dechlorination of cis-DCE accompanied by an increase in Dehalococcoides 16S rRNA and dehalogenase vcrA gene copies but not dehalogenase tceA gene copies. These observations highlight the cooperative effect of iron and methanogens on the reductive dechlorination of chloroethenes by Dehalococcoides spp.
S100B gene polymorphisms are associated with the S100B level and Alzheimer’s disease risk by altering the miRNA binding capacity

To examine the role of S100B in genetic susceptibility to Alzheimer’s disease (AD), we conducted a case-control study to analyze four polymorphism loci (rs2839364, rs1051169, rs2300403, and rs9722) of the S100B gene and AD risk. We found an independent increased risk of AD in ApoE ε4(-) subjects carrying the rs9722 AA-genotype (OR = 2.622, 95% CI = 1.399–4.915, P = 0.003). Further investigation revealed the serum S100B levels to be lower in rs9722 GG carriers than in rs9722 AA carriers (P = 0.003). We identified three miRNAs (miR-340-3p, miR-593-3p, miR-6827-3p) in which the seed match region covered locus rs9722. Luciferase assays indicated that the rs9722 G allele has a higher binding affinity to miR-6827-3p than the rs9722 A allele, leading to a significantly decreased fluorescence intensity. Subsequent western blot analysis showed that the S100B protein level of SH-SY5Y cells, which carry the rs9722 G allele, decreased significantly following miR-6827-3p stimulation (P = 0.009). The present study suggests that the rs9722 polymorphism may upregulate the expression of S100B by altering the miRNA binding capacity and may thus increase the AD risk. This finding would be of great help for the early diagnosis of AD.