bluuebunny/crossref_metadata_2025 huggingface dataset:
Peri-Procedural Intravascular Hemolysis during Atrial Fibrillation Ablation: A Comparison of Pulsed-Field with Radiofrequency Ablation
Authors: Osmancik Pavel , Bacova Barbora , Herman Dalibor , Hozman Marek , Fiserova Ivana , Hassouna Sabri , Melenovsky Vaclav , Vesela Jana , Karch Jakub , Benesova Klara , Reddy Vivek Y. Y.
Published: February 2024

Background Despite the favorable safety profile of pulsed-field (PF) energy during ablation of atrial fibrillation (AF), infrequent cases of renal failure, probably caused by hemolysis, have been recently described. The aim was to analyze hemolysis in patients undergoing pulmonary vein isolation (PVI) with PF ablation (PFA) or radiofrequency ablation (RFA). Methods In consecutive patients, PVI was performed with PFA or RFA. Blood samples were drawn pre-procedure, immediately post-ablation, and one day post-ablation. The concentration of red blood cell microparticles (RBCμ, fragments of damaged erythrocytes) in blood was assessed using flow cytometry (identified as CD235a and annexin V positive events). Lactate-dehydrogenase (LDH), haptoglobin and indirect bilirubin were measured at baseline and at 24 hours. Results Seventy patients (age 64.7±10.2, 47% women, 36 [51.4%] paroxysmal AF) were enrolled, 47 patients in the PFA group (22 PVI only, 36.4±5.5 PF applications vs. 25 PVI plus additional ablations, 67.3±12.4 PF applications). Twenty-three patients underwent RFA. Compared to baseline, the RBCμ concentration increased ~ 12-fold post-PFA, and returned to baseline by 24 h (70.8 Nr/μL, 51.8-102.5 vs. 846.6; 639.2-1,215.5 vs. 59.3; 42.9-86.5 Nr/μL, p<0.001); this increase was greater in PVI-plus compared to PVI-only patients (p=0.007). There was also a significant albeit substantially smaller peri-procedural increase in RBCμ with RFA (77.7; 39.2-92.0 vs. 149.6; 106.6-180.8 vs. 89.0; 61.2-123.4,p<0.001). At 24 h with PFA, the concentration of LDH and indirect bilirubin increased, and of haptoglobin decreased highly-significantly (all p<0.001). Only smaller changes in LDH and haptoglobin concentrations (p=0.03), and no change in bilirubin concentrations were present with RFA. Conclusion PFA was associated with significant peri-procedural hemolysis. The number of PF applications should be minimized.
Impact of Moderate to Severe Mitral and Tricuspid Valves Regurgitation after Transcatheter Aortic Valve Implantation: A Multicenter Retrospective Study
Authors: Abraham Bishoy , Botros Michael , Fath Ayman R. , Kaldas Sara , Megaly Michael S , Chao Chieh-Ju , Arsanjani Reza , Ayoub Chadi , Fortuin F David , Sweeney John P. , Pellikka Patricia A. , Nkomo Vuyisile T , Alkhouli Mohamad , Holmes David R. , Alsidawi Said
Published: February 2024

Tricuspid regurgitation (TR) and mitral regurgitation (MR) are common valvular conditions encountered in patients undergoing transcatheter aortic valve implantation (TAVI). This retrospective study investigates the impact of moderate or severe TR and MR on all-cause mortality in one-year post-TAVI patients. Consecutive patients who underwent TAVI at our institution between 2012 and 2018 were identified. Patients were stratified into 2 groups based on valvular regurgitation severity: moderate/severe MR vs. no/mild MR, and moderate/severe TR vs. no/mild TR. Primary outcome was all-cause mortality at 1-year follow up, and secondary outcome was in-hospital death. Logistic regression analysis was conducted to assess the relationship between moderate/severe MR or TR and all-cause mortality at 1-year follow-up. We included a total of 1,071 patients who underwent TAVI with mean age 80.9 ± 8.6 years, 97% white, and 58.3% males. Moderate or severe MR group included 52 (4.88%) patients while mild or no MR group included 1,015 (95.12%) patients. There was no significant difference between both groups in TAVI procedure success rate (100% vs. 97.83%, p=0.283), in-hospital mortality (0 vs. 1.08%, p=0.450), or mortality at 1-year follow up (15.38% vs. 14.09%, p=0.794). In the logistic regression analysis, moderate or severe MR did not show significant correlation with all-cause mortality at 1-year follow up (OR 0.88, 95% CI [0.38 - 1.99], p=0.761). Moderate or severe TR group included 86 (8.03%) patients while mild or no TR group included 985 (91.97%) patients. There was no difference between both groups in TAVI procedure success (98.8% vs. 97.9%, p=0.54) or in-hospital mortality (0% vs. 1.1%, p=0.33). At 1-year follow up, patients with moderate or severe TR had higher mortality (26.7% vs. 13.2%, p=0.001) compared to patients with mild or no TR. In the logistic regression analysis, moderate or severe TR was correlated with higher all-cause mortality at 1-year (OR 1.89, 95% CI [1.07, 3.34], P=0.027). At 1 year follow up, moderate/severe TR, but not MR, is associated with higher mortality in patients underwent TAVI. Careful assessment of multi-valvular heart disease prior to the procedure is warranted.
Myxomycetes have an allorecognition system that can only discriminate between intraspecies
Authors: Masui Mana , Yamamoto Phillip , Kono Nobuaki
Published: February 2024

Myxomycetes are multinucleate unicellular organisms. They form a plasmodium that moves by protoplasmic flow and prey on microorganisms. When encountering intraspecifics, the plasmodium has the capacity for "fusion", actively approaching and fusing its cells, or "avoidance", altering its direction to avoid the other individual. This is an allorecognition ability. However, it remains unclear whether the range of allorecognition extends to other species, and its ecological significance is also obscure. Here, we conduct a quantitative evaluation of contact responses from closely related species of plasmodium to clarify the recognition range of the allorecognition system in Myxomycetes. Behavioral assays demonstrate that the allorecognition system recognizes individuals within the same species while failing to recognize those of different species. The allorecognition is an extremely narrow and inward-focused mechanism, arguing for a highly specialized system of self-other recognition.
K2R: Tinted de Bruijn Graphs implementation for efficient read extraction from sequencing datasets
Authors: Vandamme Léa , Cazaux Bastien , Limasset Antoine
Published: February 2024

The analysis of biological sequences often depends on reference genomes; however, achieving accurate assemblies remains a significant challenge. As a result, de novo analysis directly from raw sequencing reads, without pre-processing, is frequently a more practical approach. A common need across various applications is the ability to identify reads containing a specifick-mer within a dataset. Thisk-mer-to-read association is critical in multiple contexts, such as genotyping, bacterial strain resolution, profiling, data compression, error correction, and assembly. While this challenge appears similar to the extensively researched colored de Bruijn graph problem, resolving it at the read level is prohibitively resource-intensive for practical applications. In this work, we demonstrate its tractable resolution by leveraging reasonnable assumptions for genome sequencing dataset indexing. To tackle this challenge, we introduce the Tinted de Bruijn Graph concept, an altered version of the colored de Bruijn graph where each read in a sequencing dataset acts as a distinct source. We developed K2R, a highly scalable index that implements this framework efficiently. K2R’s performance, in terms of index size, memory footprint, throughput, and construction time, is benchmarked against leading methods, including hashing techniques (e.g., Short Read Connector and Fulgor), full-text indexing (e.g., Movi and Themisto) across various datasets. To demonstrate K2R’s scalability, we indexed two human datasets from the T2T consortium. The 126X coverage ONT dataset was indexed in 9 hours using 61GB of RAM, resulting in a 30GB index. Similarly, the 56X coverage HiFi dataset was indexed in less than 5 hours using 39GB of RAM, producing a 20.5GB index. Developed in C++, the K2R index is open-source and available on GitHub athttp://github.com/LeaVandamme/K2R.
Integrating environmental and ecological monitoring with seaweed farming
Authors: Berger Christian , Marshall Beth , Papazova Polina , Evans Fergus , Williams Craig
Published: February 2024

We explore the biodiversity impacts of seaweed and shellfish farms in Pembrokeshire, UK, with a focus on using monitoring methods that are affordable and can be integrated into existing seaweed farming operations. Monitoring methods used include Baited Remote Underwater Video Systems (BRUVs), Passive Acoustic Monitoring (PAM) and visual surveys of cultivation lines and natural settlement on farm infrastructure. BRUVs detected 13 motile fauna taxa, influenced mainly by site conditions, while PAM observed distinct patterns in dolphin and porpoise activity that changes between seasons. Visual surveys revealed colonisation of algal, hydroid, and bryozoan species on both the surface and seabed infrastructure, indicating that the farming structures serve as stable substrates for biodiversity accumulation. Apart from the natural settlement on infrastructure, our data does not show a conclusive link between biodiversity and farming due to the highly dynamic environment, small scale of operations, and relatively short monitoring timeframe. Despite these limitations, the data sets a crucial baseline for future studies and showed no negative impacts even as farming activities intensified over the monitoring period. The study aligns with what's feasible for time-constrained farm operators and forms a foundation for routine, integrated environmental and biodiversity monitoring.
AlphaFind: Discover structure similarity across the entire known proteome
Authors: Prochazka David , Slaninakova Terezia , Olha Jaroslav , Rosinec Adrian , Gresova Katarina , Janosova Miriama , Cillik Jakub , Porubska Jana , Svobodova Radka , Dohnal Vlastislav , Antol Matej
Published: February 2024

AlphaFind is a web-based search engine that provides fast structure-based retrieval in the entire set of AlphaFold DB structures. Unlike other protein processing tools, AlphaFind is focused entirely on tertiary structure, automatically extracting the main 3D features of each protein chain and using a machine learning model to find the most similar structures. This indexing approach and the 3D feature extraction method used by AlphaFind have both demonstrated remarkable scalability to large datasets as well as to large protein structures. The web application itself has been designed with a focus on clarity and ease of use. The searcher accepts any valid Uniprot ID, PDB ID or gene symbol as input, and returns a set of similar protein chains from AlphaFold DB, including various similarity metrics between the query and each of the retrieved results. In addition to the main search functionality, the application provides 3D visualizations of protein structure superpositions in order to allow researchers to instantly analyze the structural similarity of the retrieved results. The AlphaFind web application is available online for free and without any registration at https://alphafind.fi.muni.cz.
Genome announcement and analysis of five new mycobacteriophages belonging to the F, G, K, and P clusters
Authors: Arora Ritu , Das Ritam , Nadar Kanika , Bajpai Urmi
Published: February 2024

Mycobacterial infections are accountable for some of the most challenging to treat diseases in humans and animals. With the rise in drug-resistant clinical isolates of Mycobacterium spp., phage therapy is emerging as a promising alternative to antibiotic therapy. Isolation of genetically diverse phages that can infect pathogenic mycobacterium species is an important exercise. Here, we present the complete genome sequences of five mycobacteriophages isolated from environmental samples using Mycobacterium smegmatis Mc2 155 as the bacterial host. These phages belong to different clusters, including F, G, K and P and contribute to the diversity of sequenced mycobacteriophages.
Positioning Genomic Features in Biomedical Knowledge Graphs using the Homo sapiens Chromosomal Location Ontology for GRCh38 (HSCLO38)
Authors: Mohseni Ahooyi Taha , Stear Benjamin J , Taylor Deanne M.
Published: February 2024

The Homo sapiens Chromosomal Location Ontology for GRCh38 (HSCLO38) represents a knowledge-graph-ready framework for connecting genomic features at multiple resolutions. We present the methodology behind the development of HSCLO38 and its integration with current genomic standards for application in biomedical research. We explore the performance and scalability of HSCLO38 in specific use cases in handling large-scale genomic data in a biomedical knowledge graph.
A Comprehensive Analysis of 3-UTRs in Caenorhabditis elegans
Authors: Murari Emma , Meadows Dalton , Cuda Nicholas , Mangone Marco
Published: February 2024

3Untranslated Regions (3UTRs) are essential portions of genes containing elements necessary for pre-mRNA 3end processing and are involved in post-transcriptional gene regulation. Despite their importance, they remain poorly characterized in eukaryotes. Here, we have used a multi-pronged approach to extract and curate 3UTR data from 11,533 publicly available datasets, corresponding to the entire collection of C. elegans transcriptomes stored in the NCBI repository from 2009 to 2023, and present its complete 3UTRome dataset sequenced at single-base resolution. This updated C. elegans 3UTRome is the most comprehensive resource in any metazoan, covering 97.4% of the 20,362 experimentally validated protein-coding genes with refined and updated 3UTR boundaries for 23,489 3UTR isoforms. We also used this novel dataset to identify and characterize sequence elements involved in pre-mRNA 3end processing and update miRNA target predictions. This resource provides important insights into the 3UTR formation, function, and regulation in eukaryotes.
The interplay between electron transport chain function and iron regulatory factors influences melanin formation inCryptococcus neoformans
Authors: Xue Peng , Sánchez-León Eddy , Hu Guanggan , Lee Christopher , Black Braydon , Brisland Anna , Li Haohua , Jung Won Hee , Kronstad James W.
Published: February 2024

Mitochondrial functions are critical for the ability of the fungal pathogenCryptococcus neoformansto cause disease. However, mechanistic connections between key functions such as the mitochondrial electron transport chain (ETC) and virulence factor elaboration have yet to be thoroughly characterized. Here, we observed that inhibition of ETC complex III suppressed melanin formation, a major virulence factor. This inhibition was partially blocked upon loss of Cir1 or HapX, two transcription factors that regulate iron acquisition and use. In this regard, loss of Cir1 derepresses the expression of laccase genes as a potential mechanism to restore melanin, while HapX may condition melanin formation by controlling oxidative stress. We hypothesize that ETC dysfunction alters redox homeostasis to influence melanin formation. Consistent with this idea, inhibition of growth by hydrogen peroxide was exacerbated in the presence of the melanin substrate L-DOPA. Additionally, loss of the mitochondrial chaperone Mrj1, which influences the activity of ETC complex III and reduces ROS accumulation, also partially blocked antimycin A inhibition of melanin. The phenotypic impact of mitochondrial dysfunction was consistent with RNA-Seq analyses of WT cells treated with antimycin A or L-DOPA, or cells lacking Cir1 that revealed influences on transcripts encoding mitochondrial functions (e.g., ETC components and proteins for Fe-S cluster assembly). Overall, these findings reveal mitochondria-nuclear communication via ROS and iron regulators to control virulence factor production inC. neoformans.
TANK binding kinase 1 promotes BACH1 degradation through both phosphorylation-dependent and -independent mechanisms without relying on heme and FBXO22
Authors: Liu Liang , Matsumoto Mitsuyo , Matsui-Watanabe Miki , Nakagawa Tadashi , Nagasawa Yuko , Pang Jingyao , Callens Bert K.K. , Muto Akihiko , Ochiai Kyoko , Takekawa Hirotaka , Alam Mahabub , Nishizawa Hironari , Shirouzu Mikako , Shima Hiroki , Nakayama Keiko , Igarashi Kazuhiko
Published: February 2024

BTB and CNC homology 1 (BACH1) represses the expression of genes involved in the metabolism of iron, heme and reactive oxygen species. While BACH1 is rapidly degraded when it is bound to heme, it remains unclear how BACH1 degradation is regulated under other conditions. We found that FBXO22, a ubiquitin ligase previously reported to promote BACH1 degradation, polyubiquitinated BACH1 only in the presence of heme in a highly purified reconstitution assay. In parallel to this regulatory mechanism, TANK binding kinase 1 (TBK1), a protein kinase that activates innate immune response and regulates iron metabolism via ferritinophagy, was found to promote BACH1 degradation when overexpressed in 293T cells. While TBK1 phosphorylated BACH1 at multiple serine and threonine residues, BACH1 degradation was observed with not only the wild-type TBK1 but also catalytically impaired TBK1. The BACH1 degradation in response to catalytically impaired TBK1 was not dependent on FBXO22 but involved both autophagy-lysosome and ubiquitin-proteasome pathways judging from its suppression by using inhibitors of lysosome and proteasome. Chemical inhibition of TBK1 in hepatoma Hepa1 cells showed that TBK1 was not required for the heme-induced BACH1 degradation. Its inhibition in Namalwa B lymphoma cells increased endogenous BACH1 protein. These results suggest that TBK1 promotes BACH1 degradation in parallel to the FBXO22- and heme-dependent pathway, placing BACH1 as a downstream effector of TBK1 in iron metabolism or innate immune response.
A comprehensive evaluation of taxonomic classifiers in marine vertebrate eDNA studies
Authors: Bayer Philipp E. , Bennett Adam , Nester Georgia , Corrigan Shannon , Raes Eric J. , McInnes Allison S. , Cooper Madalyn , Ayad Marcelle E. , McVey Philip , Kardailsky Anya , Pearce Jessica , Fraser Matthew W. , Goncalves Priscila , Burnell Stephen , Rauschert Sebastian
Published: February 2024

Environmental DNA (eDNA) metabarcoding is a widely used tool for surveying marine vertebrate biodiversity. To this end, many computational tools have been released and a plethora of bioinformatic approaches are used for eDNA-based community composition analysis. Simulation studies and careful evaluation of taxonomic classifiers are essential to establish reliable benchmarks to improve accuracy and reproducibility of eDNA-based findings. Here we present a comprehensive evaluation of nine taxonomic classifiers exploring three widely used mitochondrial markers (12S rDNA, 16S rDNA, and COI) in Australian marine vertebrates. Curated reference databases and exclusion database tests were used to simulate diverse species compositions, including three positive control and two negative control datasets. Using these simulated datasets, we were able to identify between 19% to 85% of marine vertebrate species using mitochondrial markers. We show that MMSeqs2 and Metabuli generally outperform BLAST with 10% and 11% higher F1 scores for 12S and 16S rDNA markers, respectively, and that Naive Bayes Classifiers such as Mothur outperform sequence-based classifiers except MMSeqs2 for COI markers by 11%. Database exclusion tests reveal that MMSeqs2 and BLAST are less susceptible to false positives compared to Kraken2 with default parameters. Based on these findings, we recommend that MMSeqs2 is used for taxonomic classification of marine vertebrates given its ability to improve species-level assignments while reducing the number of false positives. Our work contributes to the establishment of best practices in eDNA-based biodiversity analysis to ultimately increase the reliability of this monitoring tool in the context of marine vertebrate conservation.
Quantifying the impact of cascade inequalities: a modelling study on the prevention impacts of antiretroviral therapy scale-up in Eswatini
Authors: Knight Jesse , Ma Huiting , Sithole Bheki , Khumalo Lungile , Wang Linwei , Schwartz Sheree , Muzart Laura , Matse Sindy , Mnisi Zandile , Kaul Rupert , Escobar Michael , Baral Stefan , Mishra Sharmistha
Published: February 2024

Background

Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95-95-95 targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate additional HIV infections expected in Eswatini if cascade scale-up had not been equal, and under which epidemic conditions these inequalities could have the largest influence.

Methods

Drawing on population-level and FSW-specific surveys in Eswatini, we developed a compartmental model of heterosexual HIV transmission which included eight subpopulations and four sexual partnership types. We calibrated the model to stratified HIV prevalence, incidence, and ART cascade data. Taking observed cascade scale-up in Eswatini as the basecase — reaching 95-95-95 in the overall population by 2020 — we defined four counterfactual scenarios in which the population overall reached 80-80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60-40-80. We quantified relative additional cumulative HIV infections by 2030 in counterfactualvsbase-case scenarios. We further estimated linear effects of viral suppression gap among FSW and clients on additional infections by 2030, plus effect modification by FSW/client population sizes, rates of turnover, and HIV prevalence ratios.

Results

Compared with the base-case scenario, leaving behind neither FSW nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 14.9 (10.4, 18.4) %vs26.3 (19.7, 33.0) % if both were left behind — a 73 (40, 149) % increase. The effect of lower cascade on additional infections was larger for clientsvsFSW, and both effects increased with population size and relative HIV incidence.

Conclusions

Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade, particularly those that intersect with high transmission risk, could maximize incidence reductions from cascade scale-up.
STUDY ABOUT THE EFFECTS OF SMOKING ON SLEEP APNEA IN A SAMPLE OF SYRIAN SOCIETY
Authors: Al Chaar Deena Osama , Al Chaar mudar , Al bardan hussam , Al Chaar Adele
Published: February 2024

Background To explore whether the use of cigarettes affects the prevalence of obstructive sleep apnea (OSA) in adults. Methods A questionnaire-based cross- sectional study was conducted among 233 participants. The questionnaire link was published on November 13, 2023 on social media sites and the Internet.The adults were divided into four groups: noncurrent smokers, current electronic cigarettes (e-cigarette) users only, current conventional cigarettes (c-cigarette) users only, and dual users. OSA was assessed by three main signs and symptoms from the questionnaire. Multivariable logistic regression after adjusting for covariates was conducted to investigate the association of OSA with different smoking patterns. The sample size was calculated as 233 to a population of 12,900000 with a margin error of 5% and a confidence interval of 95% using a sample size calculator. Conclusion Our study found that 68% of sleep apnea patients were smokers, with 24% passive smoking, 36% smoking regular cigarettes, 24% smoking hookah, and 8% smoking electronic cigarettes, which confirmed that sleep apnea is more related to smoking regular cigarettes than Electronic cigarettes
Virtual Reality for Pediatric Trauma Education - A Face and Content Validation Study
Authors: Botelho Fabio , Ashkar Said , Kundu Shreenik , Mathews TJ , Guadagno Elena , Harley Jason , Poenaru Dan D
Published: February 2024

Purpose: Pediatric trauma is a leading cause of death and disability among children. While trauma education can improve these outcomes, it remains expensive and available only to a few providers worldwide. Innovative educational technologies like virtual reality (VR) can be key to democratizing trauma education. This study, therefore, evaluates the face and content validity of a VR platform designed to enhance pediatric trauma skills. Specifically, we seek to determine whether the platform effectively presents an injured child and comprehensively covers the essential tasks to successfully treat them within a trauma team. Methods: Physicians were invited to test a VR platform simulating a child with blunt head and truncal trauma. After the simulation, they filled out surveys assessing the face and content validity of the scenario, including their opinions on the realism, interaction, ease of use, and the educational content of the platform. Additionally, they completed a cybersickness questionnaire. Demographic data were also collected, including age, gender, country of medical education, and previous experience with VR. A descriptive analysis was performed. Results: Eleven physicians graduated from eight different countries tested the VR platform. Most (87%) found it valuable, and 81% preferred using it over high-fidelity mannequins for training purposes. The platform received more favorable evaluations for non-technical skills training (median: 5, IQR: 5.0 to 5.0) than for technical skills (median: 4, IQR: 3.0 to 5.0). Regarding cybersickness, 73% of the participants reported experiencing any or minimal discomfort during the simulation, and none needed to stop the test due to discomfort. Conclusion: Our initial validation of a VR platform designed for pediatric trauma education was positive. Participants endorsed VR and its potential to enhance performance, particularly in non-technical skills. Encouraged by these results, we will proceed with feasibility and implementation studies, comparing VR to high-fidelity mannequins.
Performance evaluation of the Xpert MTB/XDR test for the detection of drug resistance toMycobacterium tuberculosisamong people diagnosed with tuberculosis in South Africa
Authors: Omar Shaheed Vally , Louw Gail , Ismail Farzana , Liu Xiaohong , Ngcamu Dumsani , Gwala Thabisile , van der Meulen Minty , Joseph Lavania
Published: February 2024

Background: Tuberculosis (TB) remains a significant public health concern in South Africa, with high incidence rates and a growing burden of drug-resistant TB. This study aimed to assess the diagnostic performance of the Xpert MTB/XDR test, a novel molecular assay, for detecting drug resistance in TB patients using archived sputum sediments. Methods: The study involved a comprehensive analysis of 322 samples collected from presumptive TB patients between 2016 - 2019 across South Africa, previously characterized by phenotypic and genotypic methods. The Xpert MTB/XDR test was evaluated for its ability to detect resistance to isoniazid (INH), ethionamide (ETH), fluoroquinolones (FLQ), and second-line injectable drugs (SLID) compared to phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS). The Xpert MTB/RIF Ultra and G4 tests were performed to determine agreement with this test for TB detection. Findings: The Xpert MTB/XDR test performance showed excellent sensitivity and specificity for detecting Mycobacterium tuberculosis (M. tuberculosis), with a sensitivity of 98.3% and specificity of 100% compared to culture. The sensitivities using a composite reference standard, pDST and sequencing, were over 90% for INH, FLQ, AMK, KAN, and CAP resistance, meeting the WHO target product profile criteria for this class. A lower sensitivity of 65.9% for ETH resistance was observed, driven by the limited targets covered by the assay. Interpretation: The Xpert MTB/XDR test offers a promising solution for the rapid detection of drug-resistant TB in South Africa. It could significantly enhance TB control efforts in this setting and contribute to improved patient care and management.
Vaporized Cannabis versus Placebo for Acute Migraine: A Randomized Controlled Trial
Authors: Schuster Nathaniel M , Wallace Mark S , Marcotte Thomas D , Buse Dawn C , Lee Euyhyun , Liu Lin , Sexton Michelle
Published: February 2024

Background Preclinical and retrospective studies suggest cannabinoids may be effective in migraine treatment. However, there have been no randomized clinical trials examining the efficacy of cannabinoids for acute migraine. Methods In this randomized, double-blind, placebo-controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with vaporized 1) 6% tetrahydrocannabinol (THC-dominant); 2) 11% cannabidiol (CBD-dominant); 3) 6% THC+11% CBD; and 4) placebo cannabis flower in a randomized order. Washout period between treated attack was 1 week. The primary endpoint was pain relief and secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom, all assessed at 2 hours post-vaporization. Results Ninety-two participants were enrolled and randomized, and 247 migraine attacks were treated. THC+CBD was superior to placebo at achieving pain relief (67.2% vs 46.6%, Odds Ratio [95% Confidence Interval] 2.85 [1.22, 6.65], p=0.016), pain freedom (34.5% vs. 15.5%, 3.30 [1.24, 8.80], p=0.017) and MBS freedom (60.3% vs. 34.5%, 3.32 [1.45, 7.64], p=0.005) at 2 hours, as well as sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. THC-dominant was superior to placebo for pain relief (68.9% vs. 46.6%, 3.14 [1.35, 7.30], p=0.008) but not pain freedom or MBS freedom at 2 hours. CBD-dominant was not superior to placebo for pain relief, pain freedom or MBS freedom at 2 hours. There were no serious adverse events. Conclusions Acute migraine treatment with 6% THC+11% CBD was superior to placebo at 2 hours post-treatment with sustained benefits at 24 and 48 hours.
Pathway-based polygenic score analysis identifies the NRF2-KEAP1 and mRNA splicing - minor pathways as enriched in shared genetic variation between chronotype and bipolar disorder.
Authors: Fahey Laura , Lopez Lorna M.
Published: February 2024

It has been postulated that circadian dysfunction may contribute to the sleep problems prevalent in neurodevelopmental and neuropsychiatric conditions. Genetic correlations between numerous pairs of neurodevelopmental or neuropsychiatric and sleep phenotypes have been identified. We hypothesize that this overlapping genetic variation is enriched in certain biological pathways. We used genome-wide polygenic score analysis to confirm previously reported genetic correlations and pathway-based polygenic score analysis to identify enriched pathways. We created polygenic scores using summary statistics from the largest genome-wide association studies (GWAS) of autism (AUT), attention-deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ) and bipolar disorder (BP). We tested the performance of these polygenic scores in predicting chronotype and insomnia status of UK Biobank participants. For the pathway-based polygenic scores, we restricted genetic variation to SNPs that mapped to genes within 451 pathways from the Reactome database. Genome-wide polygenic scores for AUT, SCZ and BP were found to be associated with an evening chronotype, and polygenic scores for ADHD, AUT, SCZ and BP were found to be associated with insomnia status. Pathway-based polygenic score analysis identified the NRF2 KEAP1 and mRNA splicing minor pathways as being enriched for genetic variation overlapping between chronotype and BP. For the NRF2 KEAP1 pathway, the signal is enriched in the subset of genes that function with KEAP1 to regulate NRF2 expression. Examination of eQTL data pointed to BP associated SNPs within these gene-sets being associated with expression changes of many genes to which they map. A number of these eQTL SNPs were reported to be genome-wide significant for SCZ in previous studies. These results demonstrate that the overlapping genetic variation between chronotype and BP is enriched in genes involved in the NRF2-KEAP1 and mRNA splicing minor pathways. Animal model and human cell line studies have previously linked the NRF2 pathway to the pathology of BP and SCZ. Additionally, NRF2 and splicing components have been reported to be rhythmically regulated by circadian clock genes. Our results suggest that these pathways could be involved in mediating the disrupted circadian rhythm phenotype of BP.
Causal mediation for uncausally related mediators in the context of survival analysis
Authors: Domingo-Relloso Arce , Jerolon Allan , Tellez-Plaza Maria , Bermudez Jose D
Published: February 2024

Objective: The study of the potential intermediate effect of several variables on the association between an exposure and a time-to-event outcome is a question of interest in epidemiologic research. However, to our knowledge, no tools have been developed for the evaluation of multiple correlated mediators in a survival setting. Methods: In this work, we extended the multimediate algorithm, which conducts mediation analysis in the context of multiple uncausally correlated mediators, to a time-to-event setting using the semiparametric additive hazards model. We theoretically demonstrated that, under certain assumptions, indirect, direct and total effects can be calculated using the counterfactual framework with collapsible survival models. We also adapted the algorithm to accommodate exposure-mediator interactions. Results and conclusions: Using simulations, we demonstrated that our algorithm performs better than the product of coefficients method, even for uncorrelated mediators. The additive hazards model quantifies the effects as rate differences, which constitute a measure of impact, with applications that can be highly informative for public health. Our algorithm can be found in the R package multimediate, which is available in Github.
High prevalence of anxiety and depression among patients hospitalized with acute febrile illness in Sri Lanka
Authors: Bodinayake Champica K. , Nagahawatta Ajith De Silva , Ranaweera Arachchige Wasana Sevwandi , Sahabandu Senuri C , Pushpakumara Aruna , Wijayarathna Piyumi , Jayasekhara Bhagya , Thilakarathna Gayani
Published: February 2024

Introduction: Acute febrile illnesses (AFI) such as dengue, leptospirosis, and influenza result in large numbers of hospitalization in the tropics. These illnesses may negatively impact patients’ mental health. We evaluated the prevalence of anxiety and depression and risk factors associated with these conditions in patients hospitalized with AFI. Methodology: From July- October 2017, we conducted a cross-sectional study of consecutive patients ≥12 years admitted with AFI to a tertiary care hospital in Sri Lanka. We administered the Hospital Anxiety and Depression Scale (HADS) validated in the local language of Sinhala to identify the presence and severity of anxiety and depression. We identified the prevalence of anxiety and depression and determined the association with sociodemographic and clinical characteristics using Chi square and t-tests and multivariabele logistic regression. Results: Of 193 enrolled, 44.6% were male. AFI included dengue (62.7%), viral fever (10.4%), urinary tract infection (6.2%), leptospirosis (4.7%), pneumonia (3.1%) and typhus (0.5%). Overall, 41.4% patients had anxiety and 42.5% had depression. On multivariable analysis, anxiety was associated with awareness of diagnosis (OR=4.3, CI 1.3-13.76, p=.03), lower satisfaction score (OR=0.73, CI 0.58-0.92, p=.008) and lower income (OR=1.92, CI 1.03-3.57, p=.03). Depression was associated with anorexia (OR=2.8, CI 1.33-5.87, p=.006) and diarrhea (OR=2.29, CI 1.17-4.47, p=.01). Conclusions: Patients hospitalized with AFI had a high prevalence of anxiety and depression. Gastrointestinal symptoms, lower socioeconomic status, and awareness of illness diagnosis were all associated with anxiety. Our findings may be helpful in developing interventions to counteract anxiety and depression among patients hospitalized with AFI.
Cost-effectiveness of romosozumab for severe postmenopausal osteoporosis at very high risk of fracture in Mexico.
Authors: Diaz Martinez Juan Pablo , Aubry de Maraumont Therese , Natty Sánchez Elly , Camacho Cordero Luis Miguel , Yeh Eric
Published: February 2024

Introduction: This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to denosumab, for the treatment of severe postmenopausal osteoporosis at very high risk of fractures in Mexican women. Methods: A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to denosumab for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 74 years, a T-score -2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Mexican healthcare system and used a discount rate of 5% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2023 Mexican pesos), quality-adjusted life years (QALYs) and life-years gained (LYs). Results: Base case results showed that, compared with teriparatide/ denosumab, romosozumab/ denosumab reduced costs by $51,363 MXN per patient and yielded 0.03 additional QALYs and 0.01 LYs. Scenario analyses and probabilistic sensitivity analyses confirmed that results are robust to uncertainty in model assumptions and inputs. Conclusions: Results show that romosozumab/ denosumab produces greater health benefits at a lower total cost than teriparatide/ denosumab.
External validation of Finnish Diabetes Risk Score (FINDRISC) and Latin American FINDRISC for screening of undiagnosed dysglycemia: analysis in a Peruvian hospital health care workers sample.
Authors: Yovera-Aldana Marlon , Mezones-Holguín Edward , Agüero-Zamora Rosa , Damas-Casani Lucy , Uriol-Llanos Becky , Espinoza-Morales Frank , Soto-Becerra Percy , Ticse-Aguirre Ray
Published: February 2024

Aims To evaluate the external validity of Finnish diabetes risk score (FINDRISC) and Latin American FINDRISC (LAFINDRISC) for undiagnosed dysglycemia in hospital health care workers. Methods We carried out a cross-sectional study on health workers without a prior history of diabetes mellitus (DM). Undiagnosed dysglycemia (prediabetes or diabetes mellitus) was defined using fasting glucose and two-hour oral glucose tolerance test. LAFINDRISC is an adapted version of FINDRISC with different waist circumference cut-off points. We calculated the area under the receptor operational characteristic curve (AUROC) and explored the best cut-off point. Results We included 549 participants in the analysis. The frequency of undiagnosed dysglycemia was 17.8%. The AUROC of LAFINDRISC and FINDRISC were 71.5% and 69.2%; p=0.007, respectively. The optimal cut-off for undiagnosed dysglycemiaaccording to Index Youden was ≥ 11 in LAFINDRISC (Sensitivity: 78.6%; Specificity: 51.7%) and ≥12 in FINDRISC (Sensitivity: 70.4%; Specificity: 53.9%) Conclusion The discriminative capacity of both questionnaires is good for the diagnosis of dysglycemia in the healthcare personnel of the María Auxiliadora hospital. The LAFINDRISC presented a small statistical difference, nontheless clinically similar, since there was no difference by age or sex. Further studies in the general population are required to validate these results.
A retrospective study of the effects of COVID-19 Non-pharmaceutical interventions on Influenza in Canada.
Authors: Betti Matthew , MacTavish Heather , MacIntyre Kenzie Grace Audrey , Moradi Zadeh Paniz
Published: February 2024

The COVID-19 pandemic had a significant impact on endemic respiratory illnesses. Through behavioural changes in populations and government policy, mainly through non-pharmaceutical interventions (NPIs), Canada saw historic lows in the number of Influenza A cases from 2020 through 2022. In this study, we use historical influenza A data for Canada and three provincial jurisdictions within Canada: Ontario, Quebec and Alberta to quantify the effects of these NPIs on influenza A. We aim to see which base parameters and derived parameters of an SIR model are most affected by NPIs. We find that the effective population size is the main driver of change, and discuss how these retrospective estimates can be used for future forecasting.
Associations between Diabetes Self-Management and Microvascular Complications Among Patients Living in Rural Areas, in Kenya
Authors: Ireri Rachael , Kikuvi gideon , mambo susan , cheriro besty
Published: February 2024

Introduction Diabetes is a major public health concern worldwide. Low and middle-income countries are the most affected. Diabetes self-management can significantly reduce the burden of diabetes complications and mortality. Methods This cross-sectional study was conducted at the outpatient department of a county referral hospital in Kenya, from 1st August 2022 to 30th October 2022. Patients with known type II diabetes of age ≥20 years visiting the hospital for routine follow-up visits were included. A 7-tem Summary of Diabetes Self-care Activities (SDSAC) Questionnaire was used to assess Diabetes self-care activities. For data entry and statistical analysis, SPSS for Windows version 27.0 was used. Results There were 96 (39.2%) males and 149 (60.8%) females. Most of the participants were more than 61 years 148 (60.4%). Prevalence of Diabetes microvascular complications among the study participants was 56.78%, 25.3%, and 14.7% for neuropathy, retinopathy, and nephropathy respectively. significant association was found between the sum scale scores of dietary activities, blood glucose testing, physical activity, foot care, and neuropathy at 95% CI and (P< 0.001). Scores on the Blood glucose testing and foot care activities subscale were significantly associated with Retinopathy (p<0.001). Additionally, significant associations were found between the presence of nephropathy and dietary activities, f00t care, and physical activity subscale (p=<0.oo1). Conclusions Diabetes self-management activities have an impact on microvascular complications in patients with diabetes.
Innovative Approaches in Pericardiocentesis Training: A Comparative Study of 3D-Printed Mannequins and Virtual Reality Simulations
Authors: Rubio-López Alberto , García-Carmona Rodrigo , Zarandieta-Román Laura , Rubio-Navas Alejandro , González-Pinto Ángel , Cardinal-Fernández Pablo
Published: February 2024

Background

The CoBaTrICE initiative standardized intensive care training throughout Europe. Pericardiocentesis, an important yet infrequent operation, poses unique training challenges often unmet by conventional methods. This study evaluates the efficacy of virtual reality (VR) simulations and 3D-printed mannequins in this procedure training, both crafted from scratch using highly affordable materials and free software.

Methods

Thirty-five final-year medical students participated in this prospective, quasi-experimental study. Initially, students underwent VR simulation training, followed by training using 3D-printed self-made mannequins. Learning outcomes were assessed using the Objective and Structured Clinical Examination (OSCE) questionnaire. Heart rate variability (HRV) analysis was employed to monitor stress responses, while the NASA Task Load Index (NASA-TLX) was used to gauge self-perceived difficulty.

Results

Although the mannequin model induced more stress reactions, it excelled in tasks requiring fine motor skills, such as correct placement and asepsis maintenance. In contrast, lower NASA-TLX scores indicated that the VR model imposed less mental demand and effort, reflecting a reduced cognitive load.

Conclusion

Both VR simulations and 3D-printed mannequins effectively taught pericardiocentesis skills, each offering distinct advantages. Mannequins enhanced fine motor skills, whereas VR reduced cognitive load and increased engagement. The combination of both approaches could maximize training outcomes, particularly in resource-constrained environments, thus broadening access to advanced simulation education.
Similar and different: systematic investigation of proteogenomic variation between sexes and its relevance for human diseases
Authors: Koprulu Mine , Wheeler Eleanor , Kerrison Nicola D. , Denaxas Spiros , Carrasco-Zanini Julia , Orkin Chloe M. , Hemingway Harry , Wareham Nicolas J. , Pietzner Maik , Langenberg Claudia
Published: February 2024

To better understand sex differences in human health and disease, we conducted a systematic, large-scale investigation of sex differences in the genetic regulation of the plasma proteome (>5,000 targets), including their disease relevance.

Plasma levels of two-thirds of protein targets differed significantly by sex. In contrast, genetic effects on protein targets were remarkably similar, with very few protein quantitative loci (pQTLs, n=74) showing significant sex-differential effects (for 3.9% and 0.3% of protein targets from antibody- and aptamer-based platforms, respectively). Most of these 74 pQTLs represented directionally concordant effects significant in both sexes, with only 21 pQTLs showing evidence of sexual dimorphism, i.e. effects restricted to one sex (n=20) or with opposite directions between sexes (n=1 for CDH15). None of the sex-differential pQTLs translated into sex-differential disease risk.

Our results demonstrate strong similarity in the genetic regulation of the plasma proteome between sexes with important implications for genetically guided drug target discovery and validation.
Parkinson's disease psychosis associated with accelerated multi-domain cognitive decline
Authors: Pisani Sara , Gosse Luca , Aarsland Dag , Chaudhuri K Ray , Ballard Clive , ffytche Dominic , Velayudhan Latha , Bhattacharyya Sagnik
Published: February 2024

Cognitive deficits are associated with poor quality of life and increased risk of development of dementia in people with Parkinson's Disease (PD) with psychosis. However, the pattern of progression of cognitive decline within PD psychosis remains unclear. Here, we examined this using data from the Parkinson's Progression Markers Initiative study. We obtained data on drug-naïve PD patients (n=676) and healthy controls (HC, n=187) who underwent baseline and follow-up (year 1 to 5) assessments. We classified PD patients into PD without psychosis (PDnP) and PD with psychosis (PDP) using the MDS-UPDRS part I hallucinations/psychosis item. We examined all cognitive measures assessed at each time point. We used linear mixed-effect models with restricted maximum likelihood. We examined the role of age, sex, ethnicity, education, and neuropsychiatric and PD-specific symptoms as covariates of interest. There were no baseline differences on any cognitive measures between PD patient groups. There were differences in cognitive performance between PD and HC across the majority of the assessments. PDP patients showed a more prominent cognitive decline from baseline to year 5 compared with PDnP across most domains even after controlling for socio-demographics, depression, sleepiness, REM behaviour sleep disorder, and motor symptom severity (immediate recall, b=-0.288, P=0.003; delayed recall, b=-0.146, P=0.003; global cognition, MoCA, b=-0.206, P <0.001; visuo-spatial, b=-0.178, P=0.012; semantic fluency, b=-0.704, P=0.002; processing speed, b=-0.337, P=0.029). Over five years, PD psychosis patients showed worsening of performance in semantic aspects of language, processing speed, global cognition, visuo-spatial abilities, and memory sub-components, regardless of socio-demographic characteristics, neuropsychiatric and motor symptoms. Collectively, these cognitive domains, particularly semantic aspects of language may therefore play an important role in PD psychosis and warrant further investigation.