Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Associated with Opioid Initiation in OEF/OIF/OND Veterans with Traumatic Brain Injury

Objective These analyses examined opioid initiation and chronic use among Iraq (OIF) and Afghanistan (OEF/OND) veterans with a new diagnosis of traumatic brain injury (TBI) in the Veterans Health Administration (VHA). Methods Data were obtained from national VHA data repositories. Analyses included OEF/OIF/OND veterans with a new TBI diagnosis in 2010-2012 who used the VHA at least twice, had not received a VHA opioid prescription in the 365 days before diagnosis, and had at least 365 days of data available after TBI diagnosis. Results Analyses included 35,621 veterans. Twenty-one percent initiated opioids; among new initiators, 23% used chronically. The mean dose was 24.0 mg morphine equivalent dose (MED) daily (SD = 24.26); mean days supplied was 60.52 (SD = 74.69). Initiation was significantly associated with age 36-45 years (odds ratio [OR] = 1.09, 95% CI = 1.01-1.17, P = 0.04), female gender (OR = 1.22, P < 0.001), having back pain (OR = 1.38, P < 0.0001), arthritis/joint pain (OR = 1.24, P < 0.0001), or neuropathic pain (OR = 1.415, P < 0.02). In veterans age 36-45 years, those living in small rural areas had higher odds of chronic opioid use (OR = 1.31, P < 0.0001, and OR = 1.33, P = 0.006, respectively) and back pain (OR = 1.36, P = 0.003). Headache/migraine pain was associated with decreased odds of chronic opioid use (OR = 0.639, P = 0.003). Conclusions Prevalence of opioid use is relatively low among OEF/OIF/OND veterans with newly diagnosed TBI who are using VHA. Among those who initiated opioids, about 25% use them chronically. Prescribing was mostly limited to moderate doses, with most veterans using opioids for approximately two months of the 12-month study period.
New extension software modules to enhance searching and display of transcriptome data in Tripal databases

Abstract Tripal is an open source software package for developing biological databases with a focus on genetic and genomic data. It consists of a set of core modules that deliver essential functions for loading and displaying data records and associated attributes including organisms, sequence features and genetic markers. Beyond the core modules, community members are encouraged to contribute extension modules to build on the Tripal core and to customize Tripal for individual community needs. To expand the utility of the Tripal software system, particularly for RNASeq data, we developed two new extension modules. Tripal Elasticsearch enables fast, scalable searching of the entire content of a Tripal site as well as the construction of customized advanced searches of specific data types. We demonstrate the use of this module for searching assembled transcripts by functional annotation. A second module, Tripal Analysis Expression, houses and displays records from gene expression assays such as RNA sequencing. This includes biological source materials (biomaterials), gene expression values and protocols used to generate the data. In the case of an RNASeq experiment, this would reflect the individual organisms and tissues used to produce sequencing libraries, the normalized gene expression values derived from the RNASeq data analysis and a description of the software or code used to generate the expression values. The module will load data from common flat file formats including standard NCBI Biosample XML. Data loading, display options and other configurations can be controlled by authorized users in the Drupal administrative backend. Both modules are open source, include usage documentation, and can be found in the Tripal organization’s GitHub repository. Database URL: Tripal Elasticsearch module: https://github.com/tripal/tripal_elasticsearch Tripal Analysis Expression module: https://github.com/tripal/tripal_analysis_expression
A Personalized and Learning Approach for Identifying Drugs with Adverse Events

Purpose Adverse drug events (ADEs) are associated with high health and financial costs and have increased as more elderly patients treated with multiple medications emerge in an aging society. It has thus become challenging for physicians to identify drugs causing adverse events. This study proposes a novel approach that can improve clinical decision making with recommendations on ADE causative drugs based on patient information, drug information, and previous ADE cases. Materials and Methods We introduce a personalized and learning approach for detecting drugs with a specific adverse event, where recommendations tailored to each patient are generated using data mining techniques. Recommendations could be improved by learning the associations of patients and ADEs as more ADE cases are accumulated through iterations. After consulting the system-generated recommendations, a physician can alter prescriptions accordingly and report feedback, enabling the system to evolve with actual causal relationships. Results A prototype system is developed using ADE cases reported over 1.5 years and recommendations obtained from decision tree analysis are validated by physicians. Two representative cases demonstrate that the personalized recommendations could contribute to more prompt and accurate responses to ADEs. Conclusion The current system where the information of individual drugs exists but is not organized in such a way that facilitates the extraction of relevant information together can be complemented with the proposed approach to enhance the treatment of patients with ADEs. Our illustrative results show the promise of the proposed system and further studies are expected to validate its performance with quantitative measures.
Deep Learning Methods for Personnel Recognition based on Micro-Doppler Features

In this paper, we investigate the use of human gait micro-Doppler features for personnel recognition with a deep learning approach. Compared with conventional methods for radar-based human recognition, most existing schemes remain in discussing the distinction of different human motions. The proposed method employs a deep convolutional neural network (DCNN), which combines the inception parallel structure, to learn the necessary features of the time-frequency complex tensor that can be used to address the problem of recognizing different human subjects. Real data is collected relating to eight human subjects using a continuous wave radar operating at K-band. The experimental results illustrate that by using the human gait micro-Doppler features, the DCNN can achieve an accuracy rate of 96.9% on personnel recognition.
A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR-Dependent Mechanism for Stomatal Development1

The hypomorphic mutant speechless-5 reveals a brassinosteroid-dependent mechanism for stomata formation and the involvement of the bHLH domain of SPEECHLESS in proper expression of some target genes. The asymmetric cell divisions necessary for stomatal lineage initiation and progression in Arabidopsis (Arabidopsis thaliana) require the function of the basic helix-loop-helix (bHLH) transcription factor SPEECHLESS (SPCH). Mutants lacking SPCH do not produce stomata or lineages. Here, we isolated a new spch-5 allele carrying a point mutation in the bHLH domain that displayed normal growth, but had an extremely low number of sometimes clustered stomata in the leaves, whereas the hypocotyls did not have any stomata. In vivo tracking of leaf epidermal cell divisions, combined with marker lines and genetic analysis, showed that the spch-5 leaf phenotype is dosage dependent and results from the decreased ability to initiate and amplify lineages, defects in asymmetric cell fate allocation, and misorientation of asymmetric division planes. Notably, application of brassinosteroids (BRs) partly rescued the stomatal leaf phenotype of spch-5. Transcriptomic analysis combining spch-5 with BR treatments revealed that the expression of a set of SPCH target genes was restored by BRs. Our results also show that BR-dependent stomata formation and expression of some, but not all, SPCH target genes require the integrity of the bHLH domain of SPCH.
Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis

Background Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out. Methods A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches. Results Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: −90.44 IU/L; 95% confidence interval [CI]: −119.95 to −60.92; P<0.00001), gamma-glutamyl transferase (MD: −61.58 IU/L; 95% CI: −122.80 to −0.35; P=0.05), immunoglobulin M (MD: −38.45 mg/dL; 95% CI: −64.38 to −12.51; P=0.004), and triglycerides (MD: −0.41 mg/dL; 95% CI: −0.82 to −0.01; P=0.05). However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09–1.78; P=0.23), total bilirubin (MD: −0.05 mg/dL; 95% CI: −0.21 to 0.12; P=0.58), and alanine aminotransferase (MD: −3.31 IU/L; 95% CI: −14.60 to 7.97; P=0.56) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03–1.25; P=0.09) between patients treated with combination therapy and those treated with monotherapy. Conclusion In this meta-analysis, combination therapy with UDCA and fenofibrate was more effective in reducing alkaline phosphatase than UDCA monotherapy, but it did not improve clinical symptoms. There did not appear to be an increase in adverse events with combination therapy.
Synthesis, Molecular Docking, and Antimycotic Evaluation of Some 3-Acyl Imidazo[1,2-a]pyrimidines

A series of 3-benzoyl imidazo[1,2-a]pyrimidines, obtained from N-heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven Candida species (Candida albicans (ATCC 10231), Candida dubliniensis (CD36), Candida glabrata (CBS138), Candida guilliermondii (ATCC 6260), Candida kefyr, Candida krusei (ATCC 6358) and Candida tropicalis (MYA-3404)). To predict binding mode and energy, each compound was docked in the active site of the lanosterol 14α-demethylase enzyme (CYP51), essential for fungal growth of Candida species. Antimycotic activity was evaluated as the 50% minimum inhibitory concentration (MIC50) for the test compounds and two reference drugs, ketoconazole and fluconazole. All test compounds had a better binding energy (range: −6.11 to −9.43 kcal/mol) than that found for the reference drugs (range: 48.93 to −6.16 kcal/mol). In general, the test compounds showed greater inhibitory activity of yeast growth than the reference drugs. Compounds 4j and 4f were the most active, indicating an important role in biological activity for the benzene ring with electron-withdrawing substituents. These compounds show the best MIC50 against C. guilliermondii and C. glabrata, respectively. The current findings suggest that the 3-benzoyl imidazo[1,2-a]pyrimidine derivatives, herein synthesized by an accessible methodology, are potential antifungal drugs.
Remote memory in the age of fast networks

As the latency of the network approaches that of memory, it becomes increasingly attractive for applications to use remote memory---random-access memory at another computer that is accessed using the virtual memory subsystem. This is an old idea whose time has come, in the age of fast networks. To work effectively, remote memory must address many technical challenges. In this paper, we enumerate these challenges, discuss their feasibility, explain how some of them are addressed by recent work, and indicate other promising ways to tackle them. Some challenges remain as open problems, while others deserve more study. In this paper, we hope to provide a broad research agenda around this topic, by proposing more problems than solutions.
Delayed Absorption of Subretinal Fluid after Retinal Reattachment Surgery and Associated Choroidal Features

Purpose The aim of this study was to investigate the incidence and associated clinical factors of delayed absorption of subretinal fluid (SRF) after surgery for rhegmatogenous retinal detachment. Methods This study involved 36 eyes of 36 consecutive patients who underwent successful surgery for rhegmatogenous retinal detachment. A complete ophthalmologic evaluation, including clinical fundus examination, optical coherence tomography, and indocyanine green angiography, was conducted before and after surgery. Delayed absorption was defined as the presence of residual concave SRF or an SRF bleb at 6 months after surgery. Clinical factors and choroidal features on indocyanine green angiography were compared according to the presence and absence of delayed absorption. Results Eighteen of 36 eyes (50%) showed delayed absorption. Macular involvement and worse preoperative visual acuity were significantly related to the presence of delayed absorption (p = 0.001 and p = 0.034, respectively). On indocyanine green angiography, preoperative choroidal vascular hyperpermeability was noted in 70% of eyes with delayed absorption and in 14% of eyes without it (p = 0.010). Conclusions Delayed absorption of SRF after retinal reattachment surgery was not rare, with a 50% of incidence in this study. Macula-off status was significantly related to the incidence of delayed SRF absorption, and choroidal features such as choroidal vascular hyperpermeability might be responsible in part, possibly through the resultant exudative property of choroid.
Narrative skills in two languages of Mandarin–English bilingual children

Abstract Purpose: Narrative skills between Mandarin and English in Mandarin–English (ME) bilingual children were compared, exploring cross-linguistic interactions of these skills, and influences of age and current language experience (input and output) on narrative performance. Method: Macrostructure and microstructure in elicited narratives from 21 ME bilingual children were analysed. Language experience was collected by parent report and entered as a covariate. Repeated measures analysis of covariance (ANCOVA) was conducted to compare the two languages. Result: Children demonstrated better narrative performance in English than Mandarin, with a larger cross-linguistic difference in microstructure than macrostructure. Significant cross-linguistic correlations were only found in children with high Mandarin vocabulary. Age, associated with length of English exposure, only significantly correlated with narrative performance in English. Output had stronger correlations with narrative skills than input. Conclusion: Macrostructure may be less variable across languages than microstructure. Children may need to reach a threshold of vocabulary for cross-linguistic interactions of narrative skills to occur. The effect of age in English may be related to increased cumulative English experience. Children may experience a plateau in Mandarin due to insufficient Mandarin exposure. Stronger correlations between output and narrative skills may be attributed to the expressive nature of both.
Mesenchymal stem cells enhance NOX2-dependent reactive oxygen species production and bacterial killing in macrophages during sepsis

Human mesenchymal stem/stromal cells (MSCs) have been reported to produce an M2-like, alternatively activated phenotype in macrophages. In addition, MSCs mediate effective bacterial clearance in pre-clinical sepsis models. Thus, MSCs have a paradoxical antimicrobial and anti-inflammatory response that is not understood. Here, we studied the phenotypic and functional response of monocyte-derived human macrophages to MSC exposure in vitro. MSCs induced two distinct, coexistent phenotypes: M2-like macrophages (generally elongated morphology, CD163+, acute phagosomal acidification, low NOX2 expression and limited phagosomal superoxide production) and M1-like macrophages characterised by high levels of phagosomal superoxide production. Enhanced phagosomal reactive oxygen species production was also observed in alveolar macrophages from a rodent model of pneumonia-induced sepsis. The production of M1-like macrophages was dependent on prostaglandin E2 and phosphatidylinositol 3-kinase. MSCs enhanced human macrophage phagocytosis of unopsonised bacteria and enhanced bacterial killing compared with untreated macrophages. Bacterial killing was significantly reduced by blockade of NOX2 using diphenyleneiodonium, suggesting that M1-like cells are primarily responsible for this effect. MSCs also enhanced phagocytosis and polarisation of M1-like macrophages derived from patients with severe sepsis. The enhanced antimicrobial capacity (M1-like) and inflammation resolving phenotype (M2-like) may account for the paradoxical effect of these cells in sepsis in vivo. Mesenchymal stem cells enhance bacterial killing via production of phagosomal reactive oxygen species in macrophages http://ow.ly/tigl30iGFPG
Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration

Head injury survivors can develop neurodegeneration associated with persistent neuroinflammation, but whether the latter is harmful or beneficial is unclear. Scott et al. report that minocycline reduces neuroinflammation months and years after injury but increases a blood marker of neurodegeneration, suggesting that persistent neuroinflammation has reparative effects long after injury.
Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial

Background. Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm3 on small arterial elasticity (SAE) and large artery elasticity (LAE). Methods. Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. Results. Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm3 and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. Conclusions. Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity.
Analysis of experience-regulated transcriptome and imprintome during critical periods of mouse visual system development reveals spatiotemporal dynamics

Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.
PML protein organizes heterochromatin domains where it regulates histone H3.3 deposition by ATRX/DAXX

Maintenance of chromatin homeostasis involves proper delivery of histone variants to the genome. The interplay between different chaperones regulating the supply of histone variants to distinct chromatin domains remains largely undeciphered. We report a role of promyelocytic leukemia (PML) protein in the routing of histone variant H3.3 to chromatin and in the organization of megabase-size heterochromatic PML-associated domains that we call PADs. Loss of PML alters the heterochromatic state of PADs by shifting the histone H3 methylation balance from K9me3 to K27me3. Loss of PML impairs deposition of H3.3 by ATRX and DAXX in PADs but preserves the H3.3 loading function of HIRA in these regions. Our results unveil an unappreciated role of PML in the large-scale organization of chromatin and demonstrate a PML-dependent role of ATRX/DAXX in the deposition of H3.3 in PADs. Our data suggest that H3.3 loading by HIRA and ATRX-dependent H3K27 trimethylation constitute mechanisms ensuring maintenance of heterochromatin when the integrity of these domains is compromised.