bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering 3’ UTR mediated gene regulation using interpretable deep representation learning
Authors: Yang Yuning , Li Gen , Pang Kuan , Cao Wuxinhao , Li Xiangtao , Zhang Zhaolei 
Published: September 2023

AbstractThe 3’untranslated regions (3’UTRs) of messenger RNAs contain many important cis-regulatory elements that are under functional and evolutionary constraints. We hypothesize that these constraints are similar to grammars and syntaxes in human languages and can be modeled by advanced natural language models such as Transformers, which has been very effective in modeling protein sequence and structures. Here we describe 3UTRBERT, which implements an attention-based language model, i.e., Bidirectional Encoder Representations from Transformers (BERT). 3UTRBERT was pre-trained on aggregated 3’UTR sequences of human mRNAs in a task-agnostic manner; the pre-trained model was then fine-tuned for specific downstream tasks such as predicting RBP binding sites, m6A RNA modification sites, and predicting RNA sub-cellular localizations. Benchmark results showed that 3UTRBERT generally outperformed other contemporary methods in each of these tasks. We also showed that the self-attention mechanism within 3UTRBERT allows direct visualization of the semantic relationship between sequence elements.
Bayesian phylogenetics on globally emerging SARS-CoV-2 variant BA.2.86 suggest global distribution and rapid evolution
Authors: Rothstein Andrew P. , Qiu Xueting , Robison Keith , Collins Susan , Muir Gabi , Lu Bernadette , Plocik Alex M. , Simen Birgitte B. , Philipson Casandra W. 
Published: September 2023

AbstractUsing bioinformatic pipelines and Bayseian phylogenetic analyses, we characterized a SARS-CoV-2 variant designated by the World Health Organization as a variant under monitoring in August 2023. Here we analyze the genomes of this SARS-CoV-2 variant, BA.2.86, deposited into GISAID within the two weeks of its emergence (2023-08-14 first submission to 2023-08-31), including the first BA.2.86 genome reported from a traveler originating from Japan. We present bioinformatics methods using publicly available tools to help analysts identify the lineage-defining 12 nucleotide insertion (S:Ins16MPLF), which is often masked by most bioinformatics pipelines. We also applied maximum-likelihood and Bayesian phylogenetics to demonstrate the high mutational rate of the tree branch leading to the emergence of BA.2.86, hinting at possible origins, and predict that BA.2.86 emerged around May 2023 and spread globally rapidly. Taken together, these results provide a framework for more rigorous bioinformatics approaches for teams performing genomic surveillance on viral respiratory pathogens.
Derivation, Validation, and Prediction of Loading-Induced Mineral Apposition Rates at Endocortical and Periosteal Bone Surfaces Based on Fluid Velocity and Pore Pressure
Authors: Singh Sanjay , Singh Satwinder Jit , Prasad Jitendra 
Published: September 2023

AbstractBones adapt to mechanical forces driven by osteocytes in the lacunae canalicular network (LCN). Osteocytes sense signals such as strain, interstitial fluid flow, and pore pressure. Physiological tissue strain is insufficient to induce bone formation, and fluid flow-based models struggle to predict bone formation at both the periosteal and endocortical surfaces, simultaneously. This prompted the exploration of pore pressure’s role.The study introduces dissipation energy density as a more significant stimulus, combining various LCN parameters, including the waveforms of both fluid velocity and pore pressure and the number of loading cycles. A pivotal achievement is the mathematical derivation of the Mineral Apposition Rate (MAR), linked proportionally to the square root of the dissipation energy density minus its reference value. This hypothesis is subjected to testing/ validation for both endocortical and periosteal surfaces for an in-vivo study on mouse tibia available in the literature.Computational implementation of this mathematical model adopts a poroelastic finite element analysis approach, treating bone as a porous fluid-filled entity. Crucially, assumptions underpinning the model, such as the impermeability of the periosteum to fluid and the maintenance of a reference zero pressure at the endosteal surface, are corroborated by relevant experimental studies.As a bottom line, the resulting model is the first of its kind, as it has been able to predict MAR at both endocortical and periosteal surfaces, significantly advancing our understanding of cortical bone adaptation to exogenous mechanical loading.
Recruitment and Retention in mhealth Interventions for Addiction and Problematic Substance Use: A Systematic Review
Authors: Kidd Bruce , McCormack Jessica C , Newcombe David , Garner Katie , O’Shea Azim , Humphrey Gayl 
Published: September 2023

ABSTRACTBackgroundDisordered and problematic addictions are significant public health issues. It has been proposed that mHealth interventions can provide new models and intervention delivery modalities. However, research shows that studies that evaluate mHealth interventions for addiction disorders have low recruitment and high attrition. This study aims to identify published peer-reviewed literature on the recruitment and retention of participants in studies of mHealth interventions for people with addiction or problematic use and to identify successful recruitment and retention strategies.MethodsRelevant studies were identified through Medline, Embase, PsychINFO, and Cochrane Central Register of Controlled Trials (CENTRAL) after January 1998. Studies were limited to peer-reviewed literature and English language published up to 2023. The revised Cochrane Risk of Bias RoB 2 tool was used to assess the risk of bias.ResultsOf the 2135 articles found, 60 met the inclusion criteria and were included. The majority of studies were for smoking cessation. Only three studies retained 95% of participants at the longest follow-up, with ten studies retaining less than 80% at the longest follow-up, indicating a high risk of retention bias. Those studies with high retention rates used a variety of recruitment modalities; however, they also recruited from populations already partially engaged with health support services rather than those not accessing services.ConclusionsThis review of recruitment and retention outcomes with mHealth interventions highlights the need for multimodal recruitment methods. However, significant gaps in effective engagement and retention strategies limit the positive outcomes expected from mHealth interventions.
Reference frames for encoding of translation and tilt in the caudal cerebellar vermis
Authors: Buron Félix , Martin Christophe Z. , Brooks Jessica X. , Green Andrea M. 
Published: September 2023

AbstractMany daily behaviors rely critically on estimates of our body’s motion and orientation in space. Vestibular signals are essential for such estimates but to contribute appropriately two key sets of computations are required. First, ambiguous motion information from the otolith organs must be combined with spatially transformed rotational signals (e.g., from the canals) to distinguish head translation from tilt. Second, tilt and translation estimates must be transformed from a head- to a body-centered reference frame to correctly interpret the body’s motion. Studies have shown that cells in the caudal cerebellar vermis (nodulus and ventral uvula, NU) reflect the output of the first set of computations to estimate translation and tilt. However, it remains unknown whether these estimates are encoded exclusively in head-centered coordinates or whether they reflect a further transformation towards body-centered coordinates. Here we addressed this question by examining how the 3D spatial tuning of otolith and canal signals on translation- and tilt-selective NU neurons varies with changes in head-re-body and body-re-gravity orientation. We show that NU cell tuning properties are consistent with head-centered coding of otolith signals during translation. Furthermore, while canals signals in the NU have been transformed into world-referenced estimates of reorientation relative to gravity (i.e., tilt), as needed to resolve the tilt-translation ambiguity, the resulting tilt estimates are encoded in head-centered coordinates. Our results thus suggest that body-centered motion and orientation estimates required for postural control, navigation and reaching are computed elsewhere either by further transforming NU outputs or via computations in other parallel pathways.
The McMaster Racialized Resident Mentorship Program Evaluation Protocol: Evaluating a racialized resident to racialized staff physician mentorship network on resident sense of belonging and medical training outcomes
Authors: Menezes Anjali , Arora Neha , Sobchak Curtis , Mercado Marck , McDonald Madeline , Monteiro Sandra , Semalulu Teresa , Agarwal Gina , Archie Suzanne ,   the DARe Group Collaborative
Published: September 2023

ABSTRACTThe McMaster Racialized Resident Mentorship Program Evaluation will formally evaluate the effectiveness of a racialized resident mentorship network at increasing racialized residents’ sense of belonging to the medical training environment and reducing the racial attainment gap in medical careers. The program is composed of three phases. Phase 1 is an acceptability study of the collection of race0based data from all matriculating residents at McMaster University. Phases 2 and 3 will focus on family medicine residents. Phase 2 is a formal program evaluation of a mentorship network connecting matriculating racialized residents with racialized physician mentors, intended to run for 24 months and using repeat focus groups to explore the impacts of the program on residents’ sense of belonging. Phase 3 is a cross sectional study of graduating family medicine residents, examining associations between residents’ identities and attainment within residency training.The program evaluation will involve formal mentor training, a mentor Community of Practice, and mentor and resident focus groups examining experiences within the program and sense of belonging to the Department of Family Medicine and their training sites. The program process inputs will include: the number of faculty who attend mentor training, and the number of racialized faculty mentors and racialized residents who register for the program; attendance at the Community of Practice; and attendance at focus groups of mentors and residents. An exit survey will assess the number of residents who participated in the program, the duration of participation, expected graduation time, number of mentor meetings. Short term outcomes will be measured at the phase 1 survey and at program enrollment and include: resident awareness of racialized mentors, and sense of support and sense of belonging. Long-term outcomes for the program will be assessed in phase 3, examining associations between resident social identities (including race) and family medicine residency training outcomes.The project results will represent the first investigation of racial attainment in postgraduate medical training in Canada, with changes in residents’ sense of belonging and attainment during residency as indicators of Mentorship program effectiveness.
Detection of carbapenem resistance genes inCampylobacter coliandCampylobacter jejuniisolated from chickens, and diarrheic children aged less than five years in Kampala city, Uganda
Authors: Okello Walter , Nanteza Ann , Opiyo Felix , Okello Justin , Ninsiima Lesley Rose , Marin Peter , Onafruo David , Pithua Patrick , Kankya Clovice , Odoch Terence 
Published: September 2023

AbstractCampylobacterspecies are recognized as one of the significant causative agents of global foodborne illnesses and potential reservoirs for dissemination of antimicrobial resistance due to their zoonotic nature. Unlike other bacteria such asKlebsiella pneumoniae, E. coli, Enterobacter, etc.,Campylobacterhas shown limited or absent resistance to Carbapenems, critically important “last resort” antibiotics. This distinct resistance profile prompted this investigation into the prevalence of Carbapenem resistance genes inCampylobacterspecies, specificallyCampylobacter coli(C. coli) andCampylobacter jejuni(C. jejuni).Analyses were conducted on 292 archivedC. coliandC. jejuniisolates obtained from chickens and diarrheic children under five years of age in Kampala city, Uganda. The primary objectives included assessment of phenotypic susceptibility of the isolates to Meropenem and Imipenem using the Kirby Bauer disk diffusion method, as well as determination of the occurrence of four selected Carbapenem resistance genes (blaVIM, blaNDM-1, blaIMP, and blaOXA-48) using multiplex polymerase chain reaction (PCR).Interestingly, despite the observed phenotypic susceptibility to Meropenem and Imipenem in all theCampylobacterisolates, 29.8% harbored at least one of the four selected Carbapenem resistance genes, including blaVIM, blaNDM-1, blaIMP, and blaOXA-48. The prevalence of the resistance genes was 55(28.1%) in chickens and 15(38.5%) in children. Notably, blaVIM was the predominant gene, detected in 57.1% of the isolates, followed by blaNDM-1 (11.4%), blaIMP (8.6%), and blaOXA-48 (5.7%). Coexistence of multiple resistance genes was also observed, with blaVIM and blaIMP present in 10.0% of the isolates, and blaVIM and blaNDM-1 in 5.7%. One isolate displayed simultaneous presence of blaNDM-1, blaVIM, and blaIMP.This study uncovered a previously unexplored realm inCampylobacterresearch, identifying Carbapenem resistance genes inCampylobacterin Uganda. The identification of these resistance genes, despite the apparent phenotypic susceptibility to Carbapenems, signifies the presence of a substantial reservoir of carbapenem resistance genes inCampylobacter.
Navigating the Neurological Aftermath of COVID-19: An In-Depth Exploration
Authors: Butt Maliha , Nagpal Shavy , Phillips Ellex , Shah Shazia Q. , Dogar Zeryab , Loh Hanyou , Mishra Sakshi , Vijayan Rupalakshmi , Jeyakumar Rishan , Makkar Sarabjot Singh , Jahan Samia , Díaz Gabriela Marie , Franca Hudson , Javed Schaza , Belizaire Marie-Pierre , Somagutta Manoj Reddy 
Published: September 2023

ABSTRACTBackgroundThe COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people and can result in both immediate and prolonged neurological effects, including severe complications. While numerous studies have explored the occurrence and consequences of neurological issues in COVID-19, they have often involved limited sample sizes.PurposeThis paper aims to determine the overall occurrence of neurological complications in COVID-19, examine their links with patient demographics, and assess their impact on patient outcomes. Additionally, it seeks to provide an overview of the current understanding of the underlying mechanisms.MethodologyTwo systematic reviews were conducted to investigate acute and chronic neurological complications associated with COVID-19. A comprehensive search of medical databases was performed, and relevant studies were evaluated following PRISMA guidelines. Meta-analysis was carried out using the Mantel-Haenszel method, with subgroup analysis and meta-regression used to assess heterogeneity.ResultsThe analysis of acute complications included 20,011 patients with an average age of 58.1 years and a slight male predominance (55.2%). Common neurological symptoms included loss of taste and smell, headaches, acute encephalopathy, and stroke. For the analysis of long-term complications, 2,094 patients were included. Survivors of COVID-19 experienced ongoing neurological issues ranging from sensory impairments to fatigue, headaches, strokes, and even cognitive and psychiatric problems.ConclusionBy examining various neurological symptoms, this study found a significant association between these manifestations and worse overall outcomes, especially in patients over 60 years old. Identifying high-risk individuals and maintaining a high level of suspicion are crucial for enhancing our understanding of the underlying mechanisms, validating biomarkers, and improving the management of these neurological issues.
Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1
Authors: Hu Yanping , Zou Jing , Kurhade Chaitanya , Deng Xiangxue , Chang Hope C. , Kim Debora K. , Shi Pei-Yong , Ren Ping , Xie Xuping 
Published: September 2023

AbstractThe highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential to evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live SARS-CoV-2 neutralization assay to compare the neutralization evasion ability of BA.2.86 with other emerged SARS-CoV-2 subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, and XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and FL.1.5.1. Our results show that BA.2.86 is less neutralization evasive than XBB sublineages. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In comparison to XBB.1.5, the more recent XBB descendants, particularly EG.5.1 and FL.1.5.1, display increased resistance to neutralization induced by parental COVID-19 mRNA vaccine and a BA.5-Bivalent-booster. In contrast, XBC.1.6 shows a slight reduction but remains comparable sensitivity to neutralization when compared to BA.5. Furthermore, a recent XBB.1.5-breakthrough infection significantly enhances the breadth and potency of cross-neutralization. These findings reinforce the expectation that the upcoming XBB.1.5 mRNA vaccine would likely boost the neutralization of currently circulating variants, while also underscoring the critical importance of ongoing surveillance to monitor the evolution and immune evasion potential of SARS-CoV-2 variants.
Is the distribution of plasmid lengths bimodal?
Authors: Dewan Ian , Uecker Hildegard 
Published: September 2023

AbstractThe length of a plasmid is a key property which is linked to many aspects of plas-mid biology. When distributions of plasmid lengths are shown in the literature, they are usually plotted with length on a logarithmic scale. However, a quantity and its logarithm have distinct distributions which may differ considerably in shape. Mistaking the distribution of log-lengths for the distribution of lengths can therefore lead to distorted conclusions about the distribution; in particular, the distribution of log-lengths may be bimodal when the distribution of lengths is only unimodal. This particular confusion has arisen in the literature where the length distribution is often claimed to be bimodal based on examination of what is in fact the log-length distribution. While the length distribution is indeed bimodal within many bacterial families, it is not across the ensemble of all plasmids. We suggest that authors should be careful to show the plasmid length distribution, or to distinguish the two distributions, to avoid misleading inferences.HighlightsThe distributions of lengths and log-lengths of plasmids are different, and have considerably different shapes.The typical practice of using a logarithmic scale for plasmid lengths leads to confusion between the two distributions.In particular, the distribution of log-lengths can be bimodal when the distribution of lengths is not.The length distribution within bacterial families is often bimodal, but across all plasmids, it is unimodal.Clearly distinguishing between the distributions will ensure that biological conclusions drawn from them are robust.
Human Pannexin 1 Channel is NOT Phosphorylated by Src Tyrosine Kinase at Tyr199 and Tyr309
Authors: Ruan Zheng , Lee Junuk , Li Yangyang , Du Juan , Lü Wei 
Published: September 2023

ABSTRACTProtein phosphorylation is one of the major molecular mechanisms regulating protein activity and function throughout the cell. Pannexin 1 (PANX1) is a large-pore channel permeable to ATP and other cellular metabolites. Its tyrosine phosphorylation and subsequent activation have been found to play critical roles in diverse cellular conditions, including neuronal cell death, acute inflammation, and smooth muscle contraction. Specifically, the non-receptor kinase Src has been reported to phosphorylate Tyr198 and Tyr308 of mouse PANX1 (equivalent to Tyr199 and Tyr309 of human PANX1), resulting in channel opening and ATP release. Although the Src-dependent PANX1 activation mechanism has been widely discussed in the literature, independent validation of the tyrosine phosphorylation of PANX1 has been lacking. Here, we show that commercially available antibodies against the two phosphorylation sites mentioned above—which were used to identify endogenous PANX1 phosphorylation at these two sites— are nonspecific and should not be used to interpret results related to PANX1 phosphorylation. We further provide evidence that neither tyrosine residue is a major phosphorylation site for Src kinase in heterologous expression systems. We call on the field to re-examine the existing paradigm of tyrosine phosphorylation-dependent activation of the PANX1 channel.
Association between Haloperidol use and Risk of Rheumatoid Arthritis
Authors: Ambati Vidya L. , Cummings Tammy H. , Yerramothu Praveen , Nguyen Joseph , Sutton S. Scott , Werner Brian C. , Magagnoli Joseph 
Published: September 2023

ABSTRACTHaloperidol is an anti-psychotic used for the treatment of schizophrenia or Tourette disorder. Here we report, by studying three large administrative health insurance databases, that haloperidol use is associated with a reduced risk of developing rheumatoid arthritis. A meta-analysis revealed a 31% reduced hazard of incident rheumatoid arthritis among individuals with schizophrenia or Tourette disorder treated with haloperidol compared to those treated with other anti-psychotic drugs. These findings suggest a potential benefit of haloperidol in rheumatoid arthritis and provide a rationale for randomized controlled trials to provide causal insights.
Building National Patient Registries in Mexico: Insights from the MexOMICS Consortium
Authors: Reyes-Perez Paula , Hernández-Ledesma Ana Laura , Román-López Talía V. , García-Vilchis Brisa , Ramírez-González Diego , Lázaro-Figueroa Alejandra , Martínez Domingo , Flores-Ocampo Victor , Espinosa-Méndez Ian M. , Rentería Miguel E. , Ruíz-Contreras Alejandra E. , Alcauter Sarael , Medina-Rivera Alejandra 
Published: September 2023

ABSTRACTOBJECTIVETo introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population.METHODSThe Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX) and the Mexican Parkinson’s Research Network (Mex-PD) were designed and implemented using Research Electronic Data Capture web-based application. Registries were compiled through voluntary participation and on-site engagement with medical specialists. In some instances, DNA samples and Magnetic Resonance Imaging images were also acquired.RESULTSSince 2019, the MexOMICS Consortium has successfully established three electronic-based registries: TwinsMX (n=2915), LupusRGMX (n=1761) and Mex-PD (n=750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected samples for genetic determinations across the three registries. Cognitive function assessments, conducted using the Montreal Cognitive Assessment, have been administered to a subsample of 376 Mex-PD participants. Furthermore, a subset of 267 twins underwent measurements of structural, functional, and spectroscopy brain images; comparable evaluations are projected for LupusRGMX and Mex-PD.CONCLUSIONSThe MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.