bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use: a single arm trial
Authors: Hahn Judith A. , Ngabirano Christine , Fatch Robin , Emenyonu Nneka I. , Cheng Debbie M. , Adong Julian , Tumwegamire Adah , Terrault Norah A. , Linas Benjamin P. , Jacobson Karen R. , Muyindike Winnie R. 
Published: June 2023

Objective:
Isoniazid (INH) preventive therapy is recommended to prevent tuberculosis (TB) disease for persons with HIV (PWH), except for those with regular and heavy alcohol consumption, due to hepatotoxicity concerns. We aimed to quantify the incidence of severe INH-related toxicity among PWH with and without recent alcohol consumption.

Design:
Prospective study of PWH receiving INH.

Methods:
We included PWH in southwest Uganda with recent (prior three months) (n = 200) or no (prior year) self-reported alcohol consumption (n = 101), on antiretroviral therapy, TB infected (≥5 mm on tuberculin skin test), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2x the upper limit of normal (ULN). Grade 3+ INH-related toxicity was ALT or AST ≥5x the ULN or severe symptoms; we stopped IPT upon detection. Grade 2 INH-related toxicity was ALT or AST 2-5x the ULN or moderate symptoms.

Results:
The cumulative incidence of Grade 3+ INH-related toxicity was 8.3% (95% CI: 5.7–12.0); all resolved after INH cessation. Incidence was 6.0% (95% CI: 3.1–10.2) among those reporting recent alcohol use and 12.9% (95% CI: 7.0–21.0) of those reporting no prior year alcohol use. We found no differences by baseline phosphatidylethanol-confirmed alcohol severity. The cumulative incidence of Grade 2 toxicities (without Grade 3+) was 21.7% (95% CI: 17.2–27.0); 25.0% (95% CI: 19.0–31.8) among those with recent alcohol use and 14.8% (95% CI: 8.1–23.9) among those with no prior year alcohol use.

Conclusions:
Alcohol use does not appear to increase risk for serious INH-related toxicity among PWH without significant liver enzyme elevations at baseline (≤2x ULN).
Respiratory protection: what SARS-CoV-2 has taught us
Authors: Loeb Mark 
Published: June 2023

Purpose of review
This review summarizes the epidemiological evidence for respiratory personal protective equipment for SARA-CoV-2, a topic of considerable controversy.

Recent findings
The main findings are that the observational studies and non-coronavirus disease 2019 (COVID-19) randomized trials do not provide clear evidence that the N95 respirators offer superior protection over surgical masks. A randomized controlled trial on COVID-19 provides evidence that the absolute risk to healthcare workers over time using surgical masks is similar to N95 respirators.

Summary
The implications of the findings are that surgical masks and N95 respirators can be considered for respiratory protection in healthcare workers.
BactoBattle: A game-based learning companion for medical bacteriology
Authors: Imwattana Korakrit , Methawirune Areeya , Voralakkulchai Isara , Ngamskulrungroj Popchai 
Published: June 2023

A card game called “BactoBattle” was developed to help medical students who have just started learning medical bacteriology improve their learning efficacy and learning satisfaction, especially on the topic of antimicrobial resistance. Copies of the game were placed in the students’ study room (approximately 1 set per 12 students) and made available to the students throughout the study period so that students could choose to play the game during their free time if desired. After the study period had ended, the students were asked to complete a questionnaire and a post-test. In total, 33 students completed the questionnaire, and were split into two groups: the player group, comprising 12 (36.4%) students who had played the game, and the non-player group. The player group perceived that they could memorize more knowledge compared to the non-player group and indeed recorded higher post-test scores than the non-player group (10.4 vs. 8.3 [out of 15 points], p = 0.031). However, there was no difference in the learning motivation (p = 0.441) nor enjoyment (p = 0.562) between the two groups. A majority of the players said they would continue playing the game after the study period and would recommend the game to other students. In short, the BactoBattle game can be a useful tool to improve the learning efficacy of students, but its effect on learning satisfaction remains unclear.
Brain Tuberculoma: CSF CBNAAT for Mycobacterium tuberculosis negative but Biopsy Culture positive - OLD is still GOLD: a case report
Authors: Shankar Gokul S , Nair Sreeja , Jacob Teena , Idikula Mercy John 
Published: June 2023

Tuberculoma of the brain is one of the most severe extrapulmonary forms that affect patients less than 40 years of age. They are space-occupying masses of granulomatous tissue that result from haematogenous spread from a distant focus of tuberculous infection by Mycobacterium tuberculosis. Symptoms and radiologic features being nonspecific usually leads to misdiagnosis and mimics a variety of other infectious diseases. Anti- Tubercular drugs are essential for the successful treatment of cerebral tuberculomas. A 52-year-old woman with known co-morbidities and chronic kidney disease presented with complaints of disoriented talk, vomiting, fever, and decreased response since 1 day. The initial radiological imaging showed ring-enhancing lesions and a differential diagnosis of septic emboli, vasculitis, and tuberculosis was considered. A repeat MRI suggested Tuberculoma. CSF studies showed predominant lymphocytes with elevated protein. CBNAAT & AFB smears of CSF were negative. The patient was started on anti-tuberculous drugs and steroids. But did not respond to the treatment and twelve days later, a brain biopsy was taken and sent for cultures. She deteriorated progressively and died 14 days after admission. Twelve days after her demise, the Mycobacterial culture of the brain biopsy specimen grew Mycobacterium tuberculosis.
Metagenomic sequencing detects human respiratory and enteric viruses in air samples collected from congregate settings
Authors: Minor Nicholas R. , Ramuta Mitchell D. , Stauss Miranda R. , Harwood Olivia E. , Brakefield Savannah F. , Alberts Alexandra , Vuyk William C. , Bobholz Max J. , Rosinski Jenna R. , Wolf Sydney , Lund Madelyn , Mussa Madison , Beversdorf Lucas J. , Aliota Matthew T. , O’Connor Shelby L. , O’Connor David H. 
Published: June 2023

AbstractInnovative methods for evaluating virus risk and spread, independent of test-seeking behavior, are needed to improve routine public health surveillance, outbreak response, and pandemic preparedness. Throughout the COVID-19 pandemic, environmental surveillance strategies, including wastewater and air sampling, have been used alongside widespread individual-based SARS-CoV-2 testing programs to provide population-level data. These environmental surveillance strategies have predominantly relied on pathogen-specific detection methods to monitor viruses through space and time. However, this provides a limited picture of the virome present in an environmental sample, leaving us blind to most circulating viruses. In this study, we explore whether pathogen-agnostic deep sequencing can expand the utility of air sampling to detect many human viruses. We show that sequence-independent single-primer amplification sequencing of nucleic acids from air samples can detect common and unexpected human respiratory and enteric viruses, including influenza virus type A and C, respiratory syncytial virus, human coronaviruses, rhinovirus, SARS-CoV-2, rotavirus, mamastrovirus, and astrovirus.
Identification of Key Biomarkers for Early Warning of Diabetic Retinopathy Using BP Neural Network Algorithm and Hierarchical Clustering Analysis
Authors: Li Peiyu , Wang Hui , Fan Zhihui , Tian Guo 
Published: June 2023

AbstractBackgroundDiabetic retinopathy is one of the most common microangiopathy in diabetes, essentially caused by abnormal blood glucose metabolism resulting from insufficient insulin secretion or reduced insulin activity. Epidemiological survey results show that about one third of diabetes patients have signs of diabetic retinopathy, and another third may suffer from serious retinopathy that threatens vision. However, the pathogenesis of diabetic retinopathy is still unclear, and there is no systematic method to detect the onset of the disease and effectively predict its occurrence.MethodsIn this study, we used medical detection data from diabetic retinopathy patients to determine key biomarkers that induce disease onset through BP neural network algorithm and hierarchical clustering analysis, ultimately obtaining early warning signals of the disease.ResultsThe key markers that induce diabetic retinopathy have been detected, which can also be used to explore the induction mechanism of disease occurrence and deliver strong warning signal before disease occurrence. We found that multiple clinical indicators that form key markers, such as glycated hemoglobin, serum uric acid, alanine aminotransferase are closely related to the occurrence of the disease. They respectively induced disease from the aspects of the individual lipid metabolism, cell oxidation reduction, bone metabolism and bone resorption and cell function of blood coagulation.ConclusionsThe key markers that induce diabetic retinopathy complications do not act independently, but form a complete module to coordinate and work together before the onset of the disease, and transmit a strong warning signal. The key markers detected by this algorithm are more sensitive and effective in the early warning of disease. Hence, a new method related to key markers is proposed for the study of diabetic microvascular lesions. In clinical prediction and diagnosis, doctors can use key markers to give early warning of individual diseases and make early intervention.
The effect of a video intervention on knowledge, awareness and perception of Natural Procreative Technology (NaProTechnology) among pharmacy undergraduate students in Nigeria
Authors: Mosanya Adaobi Uchenna , Ezenkwele Eziamaka Pauline , Jacinta Emegoakor Fausta Chioma , Okeh Mmaduabuchi , Isah Abdulmuminu 
Published: June 2023

AbstractBackgroundNatural Procreative Technology (NaProTechnology) is a system of management of infertility and other reproductive health issues which requires the application of a woman’s observation and record of key events throughout her menstrual cycle.ObjectivesThe study assessed the knowledge, awareness, and perception of NaProTechnology as well as the effect of an educational intervention among pharmacy undergraduate students at University of Nigeria, Nsukka.MethodsIt was a cross-sectional, questionnaire-based study. The ethical approval was obtained from the research ethics committee of the Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka. At baseline, the knowledge, awareness and perception of the students were assessed. Followed by the administration of an educational video on NaProTechnology. Then a post intervention survey was done to assess the effect of the educational intervention.Key findingsThere were 410 and 350 students in the pre- and post-intervention surveys respectively with relatively equal number of males and females. Majority were between 18 and 29 years old. Less than 5% were married while the highest proportion of the respondents were from 300 level The knowledge, awareness, and positive perception of NaProTechnology among the pharmacy students prior to intervention were poor but improved markedly post intervention (P < 0.001).ConclusionA video intervention was effective in improving the short-term knowledge, awareness and positive perception of NaProTechnology among pharmacy students.Key messagesWhat is already known on this topic?Natural Procreative Technology (NaProTechnology) is a system of management of infertility based on the observation and record of fertility biomarkers by a woman.What this study adds?The level of knowledge, awareness, and positive perception of NaProTechnology among the pharmacy undergraduates students were poor prior to a video intervention but improved markedly afterwardsHow this study might affect research, practice or policy?This study would lead to the public health system approach of informing, educating and communicating NaProTechnology to pharmacy students to achieve long-term effects by using well-designed courses and curriculum implementation.
Low-usage splice junctions underpin immune-mediated disease risk
Authors: El Garwany Omar , Panousis Nikolaos I , Knights Andrew , Kumasaka Natsuhiko , Imaz Maria , Vilarino Lorena Boquete , Tsingene Anthi , Barnett Alice , Gomez Celine , Gaffney Daniel J , Anderson Carl A. 
Published: June 2023

AbstractThe majority of immune-mediated disease (IMD) risk loci are located in non-coding regions of the genome, making it difficult to decipher their functional effects. To assess the extent to which alternative splicing contributes to IMD risk, we mapped genetic variants associated with alternative splicing (splicing quantitative trait loci or sQTL) in macrophages exposed to 24 cellular conditions. We found that genes involved in innate immune response pathways undergo extensive differential splicing in response to stimulation and detected significant sQTL effects for 5,734 genes across all conditions. We colocalised sQTL signals for over 700 genes with IMD-associated risk loci from 21 IMDs with high confidence (PP4 ≥ 0.75). Approximately half of the colocalisations implicate lowly-used splice junctions (mean usage ratio < 0.1). Finally, we demonstrate how an inflammatory bowel disease (IBD) risk allele increases the usage of a lowly-used isoform of PTPN2, a negative regulator of inflammation. Together, our findings highlight the role alternative splicing plays in IMD risk, and suggest that lowly-used splicing events significantly contribute to complex disease risk.
Biomechanical Strain Responses in the Optic Nerve Head Region in Glaucoma Patients After Intraocular Pressure Lowering
Authors: Yuan Zhuochen , Czerpak Cameron A. , Kashaf Michael Saheb , Quigley Harry A. , Nguyen Thao D. 
Published: June 2023

AbstractObjectiveTo measure strain values and their association with intraocular pressure (IOP) change across five posterior eye regions in glaucoma patients.DesignCohort study.ParticipantsGlaucoma patients who were imaged with optical coherence tomography (OCT) prior to and after laser suturelysis following trabeculectomy surgery (29 image pairs, 26 persons)InterventionNoninvasive imaging of the eye.Main OutcomesStrain values in eye regions.ResultsMean strains were lowest in the retina and highest in the prelaminar neural tissue (PLNT) forEmax,Γmax, andEzz. The values ofEmaxin the anterior lamina cribrosa (ALC) and sclera were significantly related (P=0.0094, linear regression). Higher axial strain (Ezz) was significantly associated with greater IOP decrease in the ALC, PLNT, and retina (P<0.05). HigherΓmaxandEmaxstrains were significantly associated with greater IOP decreases across all 5 eye regions. ALC and PLNT had negative median radial (Err) compliance, while sclera had positiveErrcompliance (P=0.017).EmaxandΓmaxstrains of the ALC were significantly and positively associated with these strains in the other 4 regions (P<0.005). Likewise, theEzzof ALC had a significant positive relationship with the other 4 regions (P<0.05).ConclusionsRegional strains in the optic nerve head zone can be effectively measured using OCT and are related to the magnitude of IOP change. Strains were largest in PLNT and ALC and were smallest in retina. The sclera and choroid on average expand radially and circumferentially indicating a volume increase with IOP lowering.
sPreserved recognition of basic visual features despite lack of awareness of shape: evidence from a case of neglect
Authors: Karakose-Akbiyik Seda , Schubert Teresa , Caramazza Alfonso 
Published: June 2023

AbstractHuman visual experience of objects comprises a combination of different visual features, such as their color, position, and shape. Spatial attention is thought to play a role in creating a coherent perceptual experience, integrating visual information coming from a given location, but the mechanisms underlying this process are not entirely understood. Deficits of spatial attention in which this integration process does not occur normally, such as neglect, can provide insights regarding the mechanisms of spatial attention in visual object recognition. In this study, we describe a series of experiments conducted with an individual with neglect, XX. XX presents characteristic lack of awareness of the left side of individual objects, evidenced by poor object and face recognition, and impaired word reading. However, he exhibits intact recognition of color within the boundaries of the same objects he fails to recognize. Furthermore, he can also report the orientation and location of a colored region on the neglected left side despite lack of awareness of the shape of the region. To our knowledge, selective lack of awareness of shape despite intact processing of basic visual features in the same spatial location has not been reported previously. XX’s performance raises intriguing questions and challenges about the role of spatial attention in the formation of coherent object percepts and visual awareness.
Tuning methylation-dependent silencing dynamics by synthetic modulation of CpG density
Authors: Ma Yitong , Budde Mark W. , Zhu Junqin , Elowitz Michael B. 
Published: June 2023

ABSTRACTMethylation of cytosines in CG dinucleotides (CpGs) within promoters has been shown to lead to gene silencing in mammals in natural contexts. Recently, engineered recruitment of methyltransferases (DNMTs) at specific loci was shown to be sufficient to silence synthetic and endogenous gene expression through this mechanism. A critical parameter for DNA methylation-based silencing is the distribution of CpGs within the target promoter. However, how the number or density of CpGs in the target promoter affects the dynamics of silencing by DNMT recruitment has remained unclear. Here we constructed a library of promoters with systematically varying CpG content, and analyzed the rate of silencing in response to recruitment of DNMT. We observed a tight correlation between silencing rate and CpG content. Further, methylation-specific analysis revealed a constant accumulation rate of methylation at the promoter after DNMT recruitment. We identified a single CpG site between TATA box and transcription start site (TSS) that accounted for a substantial part of the difference in silencing rates between promoters with differing CpG content, indicating that certain residues play disproportionate roles in controlling silencing. Together, these results provide a library of promoters for synthetic epigenetic and gene regulation applications, as well as insights into the regulatory link between CpG content and silencing rate.
COBRA improves the quality of viral genomes assembled from metagenomes
Authors: Chen LinXing , Banfield Jillian F. 
Published: June 2023

AbstractMicrobial and viral diversity, distribution, and ecological impacts are often studied using metagenome-assembled sequences, but genome incompleteness hampers comprehensive and accurate analyses. Here we introduce COBRA (ContigOverlapBasedRe-Assembly), a tool that resolvesde Bruijngraph based assembly breakpoints and joins contigs. While applicable to any short-read assembled DNA sequences, we benchmarked COBRA by using a dataset of published complete viral genomes from the ocean. COBRA accurately joined contigs assembled by metaSPAdes, IDBA_UD, and MEGAHIT, outcompeting several existing binning tools and achieving significantly higher genome accuracy (96.6% vs 19.8-59.6%). We applied COBRA to viral contigs that we assembled from 231 published freshwater metagenomes and obtained 7,334 high-quality or complete species-level genomes (clusters with 95% average nucleotide identity) for viruses of bacteria (phages), ∼83% of which represent new phage species. Notably, ∼70% of the 7,334 species genomes were circular, compared to 34% before COBRA analyses. We expanded genomic sampling of ≥ 200 kbp phages (i.e., huge phages), the largest of which was curated to completion (717 kbp in length). The improved phage genomes from Rotsee Lake provided context for metatranscriptomic data and indicatedin situactivity of huge phages, WhiB andcysC/cysHencoding phages from this site. In conclusion, COBRA improves the assembly contiguity and completeness of microbial and viral genomes and thus, the accuracy and reliability of analyses of gene content, diversity, and evolution.
Invasion of spontaneous germinal centers by naive B cells is rapid and persistent
Authors: van den Broek T. , Oleinika K. , Rahmayanti S. , Castrillon C. , van der Poel C.E. , Carroll M.C. 
Published: June 2023

AbstractIn autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a novel tool for identifying early events in the breaking of B cell tolerance in autoimmunity.One Sentence SummaryThe autoreactive germinal center is an open structure that is susceptible to rapid and persistent naive B cell invasion, with clonal expansion and auto-antibody induction and diversification.