bluuebunny/crossref_metadata_2025_split huggingface dataset:
CONORM: Context-Aware Entity Normalization for Adverse Drug Event Detection
Authors: Yazdani Anthony , Rouhizadeh Hossein , Bornet Alban , Teodoro Douglas 
Published: September 2023

AbstractAdverse drug events (ADEs) are a critical aspect of patient safety and pharmacovigilance, with significant implications for patient outcomes and public health monitoring. The increasing availability of electronic health records, social media, and online patient forums provides valuable yet challenging unstructured data sources for ADE surveillance. To address these challenges, we introduce CONORM, a novel framework that integrates named entity recognition (NER) and entity normalization (EN) for ADE extraction across diverse textual domains. CONORM comprises two components: CONORM-NER, a subword-aware, transformer-based model for ADE detection, and CONORM-EN, an entity normalization module using dual-encoder embeddings and dynamic context refining. CONORM was evaluated on SMM4H 2023 (tweets), CADEC (forum posts), and TAC (product labels), where it consistently outperformed existing methods. It achieved end-to-end F1-scores of 63.86% on SMM4H, 72.45% on CADEC, and 84.99% on TAC, surpassing existing solutions by an average margin of 35%. The results demonstrate CONORM’s adaptability across informal, semi-formal, and formal text sources. Stratified analyses showed stronger results for well-represented system organ classes (SOCs) and moderate-to-long contexts. CONORM offers a scalable and reproducible solution for real-world pharmacovigilance, with pre-computed target embeddings enhancing inference efficiency for large medical ontologies. Its generalization capabilities across diverse text domains establish it as a robust tool for ADE surveillance. To support reproducibility, all source code is publicly available athttps://github.com/ds4dh/CONORM. Future work will explore multilingual capabilities, rare SOC data augmentation, and optimizations for long-form narratives.
Protocol for Systematic Review of Interventions to Improve Sleep Health in Adolescents Living in Low-and-Middle-Income Countries
Authors: Olorunmoteni Oluwatosin Eunice , Daniel Jeremiah Oluwatomi Itodo , Ayantayo Temitayo , Guvoeke Virginia , Akano Lordstrong 
Published: September 2023

AbstractIntroductionAdolescence is a transitory phase marked by significant changes. While adolescents are not exempted from the increasing prevalence of sleep-related issues, an urgent need for understanding the factors responsible for sleep problems in this age group and evaluating the possible interventions to mitigate this scourge has risen globally. However, despite facing substantial sleep-related issues, there has been no focus on adolescents in low-middle-income countries (LMICs). This study seeks to serve as a much-needed tool to evaluate and compare the different interventions for adolescents with sleep-related problems in LMICs and provide valuable insights to stakeholders involved with adolescents to improve overall adolescent health.Methods and AnalysisThe study will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA] guideline 2020. Eligible studies for this review will be identified following an exhaustive literature search on the following databases: PubMed, Embase, Scopus, PsychInfo, and AJOL. Our outcomes will include quantitative measures of sleep health and other health indicators.Data will be presented qualitatively using tables and diagrams, with narrative synthesis. Two independent reviewers will screen, review, and extract data from studies, with a third reviewer resolving discrepancies. Additionally, we will assess study details, the risk of bias, and the strength of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework.Ethics and disseminationThis review will be conducted using existing studies; hence, ethical approval will not be required. We aim to present our findings at conferences and publish our manuscript in a peer- reviewed journal for widespread dissemination.
Inhibition ofNeisseria gonorrhoeaecomplement-mediated killing during acute gonorrhoea is dependent upon the IgG2:IgG3 antibody ratio
Authors: McKeand Samantha A. , Faustini Sian E. , Cook Alex , Kennett Nikki , Drayson Mark T. , Cunningham Adam F. , Henderson Ian R. , Ross Jonathan D. C. , Cole Jeffrey A. , Rossiter-Pearson Amanda E. 
Published: September 2023

AbstractExcessive binding of antibodies to the bacterial cell surface can paradoxically increase resistance of some Gram-negative pathogens to complement-mediated killing (CMK). We examined CMK of 336Neisseria gonorrhoeaeclinical isolates sampled from participants recruited to a clinical trial. Serum bactericidal assays revealed 3% (9/336) of the autologous participant sera that were tested inhibited CMK. Gonococci isolated from these participants were resistant to the autologous host serum, sensitive to a pool of healthy control sera (HCS) and protected by the host serum in a 1:1 mixture with HCS. Analysis of the clinical metadata showed that there were a significantly higher proportion of inhibitory sera found in participants with urethral infections and from men within the transmission network of men who have sex with women (MSW), when compared to the whole cohort. Following antibody purification from selected participants with inhibitory sera (5/9), IgG and IgM protected the autologous isolates from HCS-mediated killing. Only three of these isolates were protected by purified IgA. A closer examination of IgG subclasses using whole gonococcal cell ELISAs revealed a strong correlation between increased IgG2 binding and decreased IgG3 binding to the bacterial cell surface of isolates that were resistant to CMK. This suggests that IgG2 prevents bactericidal IgG3 from initiating CMK and that the IgG2:IgG3 ratio is important for determining either inhibition or killing of isolates. We therefore reveal a previously unreported mechanism by which inhibitory antibodies prevent CMK ofN. gonorrhoeae.
High plasticity of ribosomal DNA organization in budding yeast
Authors: Jiang Shuangying , Cai Zelin , Wang Yun , Zeng Cheng , Zhang Jiaying , Yu Wenfei , Su Chenghao , Zhao Shijun , Chen Ying , Shen Yue , Ma Yingxin , Cai Yizhi , Dai Junbiao 
Published: September 2023

SummaryIn eukaryotic genomes, ribosomal DNA (rDNA) generally resides as a highly repetitive and dynamic structure, making it difficult to study. Here, a synthetic rDNA array on chromosome III in budding yeast was constructed to serve as the sole source of rRNA. Utilizing the loxPsym site within each rDNA repeat and the Cre recombinase, we were able to reduce the copy number to as few as eight copies. Additionally, we constructed strains with two or three rDNA arrays, and found that the presence of multiple arrays did not affect the formation of a single nucleolus. Although alteration on the position and number of rDNA arrays did impact three-dimensional genome structure, the additional rDNA arrays had no deleterious influence on cell growth or transcriptomes. Together, this study sheds light on the high plasticity of rDNA organization and opens up opportunities for future rDNA engineering.HighlightsA method was established for efficient construction of synthetic rDNA arrays in budding yeastThe rDNA repeats in a haploid yeast can be reduced to as few as eight copies to support cell viabilityYeast cells with two or three DNA arrays on distinct chromosomes form a single nucleolus.Dispersed rDNA arrays result in no deleterious influence on cell growth or transcriptomes.
In silicoanalyses identifies sequence contamination thresholds for Nanopore-generated SARS-CoV2 sequences
Authors: Bolaji Ayooluwa J. , Duggan Ana T. 
Published: September 2023

AbstractThe SARS-CoV-2 pandemic has brought molecular biology and genomic sequencing into the public consciousness and lexicon. With an emphasis on rapid turnaround, genomic data has been used to inform both diagnostic and surveillance decisions for the current pa ndemic at a previously unheard-of scale. The surge in the submission of genomic data to publicly-available databases has proved essential as comparing different genome sequences offers a wealth of knowledge, including phylogenetic links, modes of transmission, rates of evolution, and the impact of mutations on infection and disease severity. However, the scale of the pandemic has meant that once sequencing runs are performed, they are rarely repeated due to limited sample material and/or the availability of sequencing resources, resulting in some imperfect runs being uploaded to public repositories. As a result, it is crucial to investigate the data obtained from these imperfect runs to determine whether the results are reliable. Numerous studies have identified a variety of sources of contamination in public next-generation sequencing (NGS) data as the number of NGS studies increases along with the diversity of sequencing technologies and procedures [1–3]. For this study, we conducted anin silicoexperiment with known SARS-CoV-2 sequences produced from Oxford Nanopore Technologies sequencing to investigate the effect of contamination on lineage calls and single nucleotide variations (SNVs). Through a series of analyses, we identified a contamination threshold below which runs are expected to generate accurate lineage calls and maintain genomic sequence integrity. Together, these findings provide a benchmark below which imperfect runs may be considered robust for reporting results to both stakeholders and public repositories and reduce the need for repeat or wasted runs.Author SummaryLarge-scale genomic comparisons provide a wealth of knowledge, including modes of transmission, rates of evolution, and the impact of mutations on infection, disease severity, and treatment effectiveness. As a result, the public release of genomic data has proven to be crucial. However, studies continue to show that some of the genomic data in public repositories are contaminated due to a variety of reasons. For instance, in the case of SARS-CoV-2 sequences, the pandemic prevented many sequencing runs from being repeated, resulting in some imperfect runs being uploaded to public repositories. It is of note that when genomic data is contaminated, both scientific decisions/studies and public health measures may be compromised. To identify genome contamination threshold(s) for SARS-CoV-2 sequences generated by Nanopore sequencing, computational biology techniques were utilized to generate artificially subsampled contaminated genomes. This is the first study of its kind and so our hope is that the results obtained provide a starting point for the investigation of reporting contamination of NGS data.
Cdc42 activation is necessary for heterosynaptic cooperation and competition
Authors: Nunes Mariana , Madeira Natália , Fonseca Rosalina 
Published: September 2023

AbstractSynapses change their weights in response to neuronal activity and in turn, neuronal networks alter their response properties and ultimately allow the brain to store information as memories. As for memories, not all events are maintained over time. Maintenance of synaptic plasticity depends on the interplay between functional changes at synapses and the synthesis of plasticity-related proteins that are involved in stabilizing the initial functional changes. Different forms of synaptic plasticity coexist in time and across the neuronal dendritic area. Thus, homosynaptic plasticity refers to activity-dependent synaptic modifications that are input-specific, whereas heterosynaptic plasticity relates to changes in non-activated synapses. Heterosynaptic forms of plasticity, such as synaptic cooperation and competition allow neurons to integrate events that occur separated by relatively large time windows, up to one hour. Here, we show that activation of Cdc42, a Rho GTPase that regulates actin cytoskeleton dynamics, is necessary for the maintenance of long-term potentiation (LTP) in a time-dependent manner. Inhibiting Cdc42 activation does not alter the time-course of LTP induction and its initial expression but blocks its late maintenance. We show that Cdc42 activation is involved in the phosphorylation of cofilin, a protein involved in modulating actin filaments and that weak and strong synaptic activation leads to similar levels on cofilin phosphorylation, despite different levels of LTP expression. We show that Cdc42 activation is required for synapses to interact by cooperation or competition, supporting the hypothesis that modulation of the actin cytoskeleton provides an activity-dependent and time-restricted permissive state of synapses allowing synaptic plasticity to occur. We found that under competition, the sequence in which synapses are activated determines the degree of LTP destabilization, demonstrating that competition is an active destabilization process. Taken together, we show that a dynamic actin cytoskeleton is necessary for the expression of homosynaptic and heterosynaptic forms of plasticity. Determining the temporal and spatial rules that determine whether synapses cooperate or compete will allow us to understand how memories are associated.Graphical AbstractHighlightsCdc42 is required for the maintenance of homosynaptic synaptic plasticityWeak and strong stimulation modulate actin by cofilin phosphorylationCdc42 activation is necessary for heterosynaptic cooperation and competitionSynaptic competition is an active destabilization processThe time-window of synaptic cooperation and competition is activity dependent
Regulation of Chromatin Architecture by Transcription Factor Binding
Authors: Portillo-Ledesma Stephanie , Chung Suckwoo , Hoffman Jill , Schlick Tamar 
Published: September 2023

ABSTRACTTranscription factors (TF) bind to chromatin and regulate the expression of genes. The pair Myc:Max binds to E-box regulatory DNA elements throughout the genome, controlling transcription of a large group of specific genes. We introduce an implicit modeling protocol for Myc:Max binding to mesoscale chromatin fibers to determine TF effect on chromatin architecture and shed light on its mechanism of gene regulation. We first bind Myc:Max to different chromatin locations and show how it can direct fiber folding and formation of microdomains, and how this depends on the linker DNA length. Second, by simulating increasing concentrations of Myc:Max binding to fibers that differ in the DNA linker length, linker histone density, and acetylation levels, we assess the interplay between Myc:Max and other chromatin internal parameters. Third, we study the mechanism of gene silencing by Myc:Max binding to the Eed gene loci. Overall, our results show how chromatin architecture can be regulated by TF binding. The position of TF binding dictates the formation of microdomains that appear visible only at the ensemble level. On the other hand, the presence of linker histone, acetylations, or different linker DNA lengths regulates the concentration-dependent effect of TF binding. Furthermore, we show how TF binding can repress gene expression by increasing fiber folding motifs that help compact and occlude the promoter region. Importantly, this effect can be reversed by increasing linker histone density. Overall, these results shed light on the epigenetic control of the genome dictated by TF binding.
Identification of potent and orally efficacious phosphodiesterase inhibitors in sCryptosporidium parvum-infected immunocompromised mice
Authors: Teixeira Jose E. , Gasonoo Makafui , Miller Peter , Ajiboye Jubilee , Cameron Alexandra C. , Stebbins Erin , Campbell Scott D. , Griggs David W. , Spangenberg Thomas , Meyers Marvin J. , Huston Christopher D. 
Published: September 2023

AbstractCryptosporidiumspecies, mostlyC. parvumandC. hominisin humans, are intestinal apicomplexan parasites that cause life-threatening diarrhea in young children and people with cell-mediated immune defects, such as due to AIDS. There is only one approved treatment for cryptosporidiosis, but it is ineffective for immunocompromised people and only modestly effective for children. In this study, screening 278 compounds from the Merck KGaA, Darmstadt, Germany collection and accelerated follow-up work enabled by prior investigation of the compounds resulted in identification of a series of pyrazolopyrimidine human phosphodiesterase (PDE)-V inhibitors with potent anticryptosporidial activity and efficacy following oral administration inC. parvum-infected immunocompromised mice. The novel PDE inhibitor leads (compounds PDEi2andPDEi5) affect parasite egress from infected host cells.They have comparable activity againstC. parvumandC. hominis, rapidly eliminateC. parvumin tissue culture, and have minimal off-target effects in a panel of safety screening assays. In comparison, the potent human PDE-V inhibitors sildenafil and the 4-aminoquinoline compound 7a have no useful activity againstC. parvum.Based on homology modeling andin silicocompound docking,PDEi5interacts directly with an active-site metal ion and docks well to twoC. parvumPDEs. In contrast, larger amino acid side groups (Val900/Tyr11128 and His884/Asn1112) in bothC. parvumPDEs replace alanine in human PDE-V and block sildenafil binding, explaining its lack of efficacy. These results identify a promising new drug target and lead series for anticryptosporidial drug development and validates a route to target-based optimization.
Healthcare practitioners’ attitudes toward patient safety in hospital settings in Jeddah, Kingdom of Saudi Arabia
Authors: Atwa Hani , Alfadani Anas , Damanhori Joud , Seifalyazal Mohamed , Shehata Mohamed , Abdel Nasser Asmaa 
Published: September 2023

PurposePatient safety focuses on minimizing risks that might occur to patients during provision of healthcare. The purpose of this study was to explore healthcare practitioners’ attitudes towards patient safety inside different hospital settings in Jeddah, Kingdom of Saudi Arabia.Design/methodology/approachA descriptive, cross-sectional study was conducted on a sample of healthcare practitioners in main hospitals in Jeddah. Two main hospitals (one governmental and one private) were selected from each region of Jeddah (east, west, north and south), with a total number of eight out of thirty hospitals. Data were collected through the Attitudes to Patient Safety Questionnaire III that was distributed online. The questionnaire used a 5-point scale. Descriptive statistics were used. Comparisons were made by independent t-test and ANOVA. The statistical significance level was set at p < 0.05.FindingsThe study included 341 healthcare practitioners of different sexes and specialties in eight major governmental and private hospitals in Jeddah. “Working hours as error cause” subscale had the highest mean score (4.03 ± 0.89), while “Professional incompetence as error cause” had the lowest mean score (3.49 ± 0.97). The total questionnaire had a moderate average score (3.74 ± 0.63). Weak correlations between the average score of the questionnaire and sex, occupation and workplace were found (−0.119, −0.018 and −0.088, respectively).Practical implicationsHospitals need to develop targeted interventions, including continuing professional development programs, to enhance patient safety culture and practices. Moreover, patient safety training is required at the undergraduate education level, which necessitates health professions education institutions to give more attention to patient safety education in their curricula.Originality/valueThe study contributed to the existing literature on patient safety culture in hospital settings in Jeddah, Saudi Arabia. The insights generated by the study can inform targeted interventions to enhance patient safety culture in hospitals and improve patient outcomes.
State-business relations for entrepreneurial takeoff in Africa: institutional analysis
Authors: Hossain Farhad , Mamman Aminu , Yeboah-Assiamah Emmanuel , Rees Christopher J. 
Published: September 2023

PurposeReports and experiences suggest that several developing African economies are faced with entrepreneurial-impeding forces such as lengthy bureaucratic processes and poor regulatory space. The study examines a general trend in “doing business performance” among selected African countries and uses the case of Ghana to explore how particular indicators or forces affect the development and deployment of small and medium-sized enterprise (SME) policies.Design/methodology/approachComparative analysis of six African economies on their ease of doing business score. This is followed by a critical review of the literature to develop a six-point explanatory framework to explore the relative position of the six countries on the ease of doing business scores. Using Ghana as a critical case study, the authors deploy an in-depth case study analysis via in-depth interviews of relevant stakeholders to validate the information from secondary sources.FindingsThe study observes that the nature of leadership, socio-cultural imperatives, economic structure and policy and the role of domestic institutional players and international players have implications for the extent to which the state creates an enabling environment for SMEs and entrepreneurial activities. The role of supportive cultural software that will help drive SME and entrepreneurial growth has been established. The study contends that different aspects of national culture do have implications for the tendency for people to be business-minded or to have the ability to take risks. The demand and supply sides are crucial in promoting SME growth.Originality/valueThe study develops a framework that helps explore elements to help explain ease of doing business scores and the viability of SMEs in Africa. These elements were validated through qualitative interviews as well.
Detailed investigation on thermal enhancement and mass transport in 3D flow of Carreau–Yasuda ternary and hybrid nanofluids using the finite element method
Authors: Rana Shafia , Nawaz M. , Alharbi Sayer Obaid 
Published: September 2023

Purpose
The purpose of this study is to analyze the transportation of heat and mass in three-dimensional (3D) shear rate-dependent viscous fluid. Thermal enhancement plays a significant role in industrial and engineering applications. For this, the authors dispersed trihybrid nanoparticles into the fluid to enhance the working fluid’s thermal enhancement.

Design/methodology/approach
The finite element method is a numerical scheme and is powerful in achieving convergent and grid-independent solutions compared with other numerical techniques. This method was initially assigned to structural problems. However, it is equally successful for computational fluid dynamics problems.

Findings
Wall shear stress has shown an increasing behavior as the intensity of the magnetic field is increased. Simulations have predicted that Ohmic heat in the case of trihybrid nanofluid (MoS2–Al2O3–Cu/C2H6O2) has the greatest value in comparison with mono and hybrid nanofluids. The most significant influence of chemical reaction on the concentration in tri-nanofluid is noted. This observation is pointed out for both types of chemical reaction (destructive or generative) parameters.

Originality/value
Through a literature survey, the authors analyzed that no one has yet to work on a 3D magnetohydrodynamics Carreau–Yasuda trihybrid nanofluid over a stretched sheet for improving heat and mass transfer over hybrid nanofluids. Herein, molybdenum disulfide (MoS2), aluminum oxide (Al2O3) and copper (Cu) nanoparticles are mixed in ethylene glycol (C2H6O2) to study the thermal enhancement and mass transport of their corresponding resultant mono (Cu/C2H6O2), hybrid (Al2O3–Cu/C2H6O2) and trihybrid (MoS2–Al2O3–Cu/C2H6O2) nanofluids.