bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pandemic ST131Escherichia colipresenting the UPEC/EAEC and ExPEC/EAEC hybrid pathotypes recovered from extraintestinal infections in a clinical setting of the Brazilian Amazon region
Authors: Bighi Nathália M. S. , Fonseca Érica L. , Freitas Fernanda S. , Morgado Sérgio M. , Vicente Ana Carolina P. 
Published: March 2024

AbstractEscherichia coliis part of the commensal microbiota of human’s and animal’s gut. However, they may become pathogenic due to the acquisition of virulence factors that provide the ability to cause intestinal or extraintestinal infections, which makesE. colithe main cause of diarrheagenic diseases and urinary tract infections (UTIs) worldwide, respectively. Some strains, known as hybrids, may harbour a mix of virulence determinants of both diarrheagenic (DEC) and extraintestinalE. coli(ExPEC) pathotypes. Reports of hybridE. coliin Brazil are rare, and the lineages associated with such pathotypes were poorly explored. This study aimed to characterizeE. colistrains recovered from extraintestinal infections in a clinical setting of the Brazilian Amazon Region by means of lineage determination, antibiotic resistance profile, and investigation of DEC and ExPEC virulence markers. Fifteen ExPEC strains were recovered from distinct extraintestinal sites from inpatients of the General Hospital of Roraima (GHR), placed in the Brazilian Amazon region. Antibiotic susceptibility test revealed that all strains were multidrug-resistant and most of them, including those recovered from urine, were resistant to fluoroquinolones, the main therapeutic option for treating UTIs, probably due to the presence of Ser83Leu and Asp87Asn substitutions in GyrA. The MLST analysis revealed the polyclonal nature of these ExPEC strains since 11 STs were determined, including local and pandemic lineages, such as ST69 and ST131. Among the 15 isolates, 12 were classified as hybrids, due to the presence of theaggRvirulence marker of the EnteroaggregativeE. coli(EAEC) pathotype together with at least one ExPEC (iutA, KPSMTII, sfaDE, papC, afaBC, iucD) or UropathogenicE. coli(UPEC) (vat,fuyA,chuAandyfcV)virulence determinants. These UPEC/EAEC (n=10) and ExPEC/EAEC (n=2) hybrid strains were found among distinct lineages, including new STs, and phylogroups (ST131/B2; ST1196/AxB1; ST9403/A; ST12394/A; NEW1-CC14/B2; NEW2-CC155/B1; NEW3-CC155/B1; NEW4-CC131/B2) and, for the first time, a hybrid phenotype was found in the pandemic ST131 lineage in Brazil. Therefore, this study provides new information on the epidemiological scenario of hybridE. colistrains, contributing to a better understanding of the occurrence and pathogenic potential of these organisms.
Primary health care improvement in Benin: Cocreating an evidence-informed policy framework to guide the practices of primary care physicians
Authors: Bello Kéfilath , Criel Bart , Dossou Jean-Paul , Zannou Djimon Marcel , Lepeleire Jan De 
Published: March 2024

AbstractIntroductionIn Benin, policies for guiding the practices of primary care physicians (PCPs) are sparse and incomplete. This leads to sub-optimal use of these relatively rare human resources and reduces their potential contribution to people’s health and well-being. In this study, a policy framework guiding PCPs’ practice in Benin is developed in cooperation with key stakeholders.MethodsThe cocreation was a long-term process spread over several years, culminating in a two-day workshop in Cotonou (Benin’s capital city) in October 2022. The core principles of a successful cocreation process were respected: a clear definition of goals, the participation of all relevant stakeholders, including community members, and evidence-informed discussions.ResultsThe resulting policy framework includes four overarching dimensions: first, the objectives assigned to PCPs in Benin; second, their roles and related activities; third, their professional identity; and fourth, the governance arrangements guiding their practices. The policy framework provided concrete recommendations for these dimensions based on the Benin context and international evidence.ConclusionThe cocreation process was instrumental in developing an evidence-informed and consensual policy framework guiding PCPs’ practices in Benin. The framework may be relevant for other West African countries but must be customised to each country’s context.
Advanced and more advanced revascularization in STEMI patients: which is better?
Authors: Li Yahui , Zhao Chunxia , Yue Xindi , Zhou Ling , Wang DaoWen , Wang Feng 
Published: March 2024

AbstractObjectiveTo compare the long-term prognosis of patients who experienced acute ST-segment elevation myocardial infarction and underwent either late percutaneous coronary intervention (PCI) within a period of 2 days to less than 1 week or more advanced PCI within 1 week to less than 1 month.MethodsWe enrolled 198 patients from Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, between June 2019 and August 2022. These patients had experienced acute ST-segment elevation myocardial infarction and underwent either late PCI or more advanced PCI. Long-term follow-up was conducted through outpatient clinic visits or telephone interviews. The study endpoints included all-cause death, nonfatal myocardial infarction, and New York Heart Association class IV heart failure. We utilized the Kaplan-Meier method to illustrate the cumulative incidence of endpoint events in both patient groups. Statistical significance in survival differences was assessed using the log-rank test. Additionally, the Cox proportional risk model was employed to analyze whether the timing of late revascularization procedures had an impact on the long-term prognosis of the patients.ResultsAmong the 198 patients included in the study, 108 underwent late PCI, while 90 underwent more advanced PCI. The majority were male (73.74%), with an average age of 62 ± 13 years. The follow-up period averaged 20 (15, 28) months, and all patients successfully completed the follow-up process. Analysis based on the Kaplan-Meier method revealed that the incidence of all-cause death [11.1% vs. 5.6%, P=0.165], nonfatal myocardial infarction [7.4% vs. 7.8%, P=0.922], New York Heart Association class IV heart failure [2.8% vs. 3.3%, P>0.999], and the composite endpoint [18.5% vs. 14.4%, P=0.444] were not statistically significant between the late PCI and more advanced PCI groups. After adjusting for factors like left ventricular ejection fraction, renin-angiotensin system inhibitors, β-blockers, and statins, the results still indicated no statistically significant differences between the two groups in terms of rates for all-cause death, recurrent myocardial infarction, New York Heart Association class IV heart failure, and composite endpoints (P=0.05).ConclusionThis study’s 20 (15, 28) months follow-up suggests that patients experiencing acute ST-segment elevation myocardial infarction have a comparable prognosis regardless of whether they underwent late or more advanced PCI.
Evolutionary double-bind treatment using radiotherapy and NK cell-based immunotherapy in prostate cancer
Authors: Luddy Kimberly A , West Jeffrey , Robertson-Tessi Mark , Desai Bina , Bursell Taylor M. , Barrett Sarah , O’Sullivan Jacintha , Marignol Laure , Gatenby Robert A , Brown Joel S , Anderson Alexander RA , O’Farrelly Cliona 
Published: March 2024

AbstractEvolution-informed therapies exploit ecological and evolutionary consequences of drug resistance to inhibit the expansion of treatment-resistant populations and prolong time to progression. One strategy, termed an evolutionary double-bind, uses an initial therapy to elicit a specific adaptive response by the cancer cells, which is then selectively targeted by a follow-on therapy. Here we examine the combination of radiation therapy and immunotherapy as a quantifiable double-bind strategy. Radiotherapy (RT) induces lethal double-strand DNA breaks, but cancer cells can adapt by upregulating DNA damage response pathways. While this evolutionary strategy increases resistance to DNA damaging agents, it also results in enhanced expression of natural killer (NK) cell ligands potentially increasing vulnerability to an immune response.Using a radiation-resistant human prostate carcinoma cell line (22Rv1), we demonstrate that RT-resistant cells upregulate NK cell ligands, including major histocompatibility complex class I chain-related protein A/B (MICA/B), and poliovirus receptors (PVR1, PVRL2) with a 2-fold increase in sensitivity to NK cell mediated killing.We investigated this potential evolutionary double bind throughin vitrostudies and evolution-based mathematical models. Radiotherapy alone slowed overall growth but strongly selected for RT-resistant cells. NK cell therapy alone suppressed the RT-resistant population but with a surviving population of radiation-sensitive cells. These dynamics were framed mathematically, and model simulation predicted optimal tumour control would be achieved through initial RT rapidly followed by NK-based immunotherapy. Subsequent experiments confirmed the model prediction. We conclude that radiotherapy and NK cell-based immunotherapy produces an evolutionary double bind that can be exploited in heterogenous tumours to limit RT resistance.
Improving protein function prediction by learning and integrating representations of protein sequences and function labels
Authors: Boadu Frimpong , Cheng Jianlin 
Published: March 2024

AbstractMotivationAs fewer than 1% of proteins have protein function information determined experimentally, computationally predicting the function of proteins is critical for obtaining functional information for most proteins and has been a major challenge in protein bioinformatics. Despite the significant progress made in protein function prediction by the community in the last decade, the general accuracy of protein function prediction is still not high, particularly for rare function terms associated with few proteins in the protein function annotation database such as the UniProt.ResultsWe introduce TransFew, a new transformer model, to learn the representations of both protein sequences and function labels (Gene Ontology (GO) terms) to predict the function of proteins. TransFew leverages a large pre-trained protein language model (ESM2-t48) to learn function-relevant representations of proteins from raw protein sequences and uses a biological natural language model (BioBert) and a graph convolutional neural network-based autoencoder to generate semantic representations of GO terms from their textual definition and hierarchical relationships, which are combined together to predict protein function via the cross-attention. Integrating the protein sequence and label representations not only enhances overall function prediction accuracy over the existing methods, but substantially improves the accuracy of predicting rare function terms with limited annotations by facilitating annotation transfer between GO terms.Availabilityhttps://github.com/BioinfoMachineLearning/TransFewContactchengji@missouri.eduSupplementary informationSupplementary data are available .
Cohort profile: the Viral load Cohort North-East Lesotho (VICONEL) from 2016 to 2022 – cohort description, test volumes, predictors of viraemia, and the road ahead
Authors: Brown Jennifer A. , Motaboli Lipontso , Lerotholi Malebanye , Kohler Maurus , Hänggi Kathrin , Mokete Moliehi , Chakela Makobefo G. , Kao Mpho , Kopo Mathebe , Mokebe Moleboheng , Nsakala Bienvenu L. , Lukau Blaise , Ayakaka Irene , Amstutz Alain , Ehmer Jochen , Klimkait Thomas , Glass Tracy R. , Muhairwe Josephine , Chammartin Frédérique , Tschumi Nadine , Labhardt Niklaus D. 
Published: March 2024

AbstractPurposeThe prospective Viral load Cohort North-East Lesotho (VICONEL) aims to support clinical management and generate scientific evidence to inform HIV care. Specifically, VICONEL allows for monitoring of HIV treatment outcomes and health system performance, encompasses a biobank for further research with routinely collected blood plasma samples of consenting participants, and provides a valuable framework for nested observational and interventional studies.ParticipantsVICONEL captures routine viral load test results alongside associated demographic and treatment information among people in care for HIV in Lesotho, southern Africa. As of December 2022, it encompasses all viral load testing from 23 healthcare facilities in two districts of Lesotho.Findings to dateFrom January 2016 to December 2022, 114’838 viral load test results were available for 27,472 participants. At the time of the last viral load test, median age was 42 years (interquartile range [IQR]: 33-53); 17,324 (63%) were adult women, 9,273 (34%) adult men, and 870 (3%) children <15 years (age/sex missing for 5); and median time taking antiretroviral therapy (ART) was 6.0 years (IQR 3.0-9.2). Overall, the proportion of cohort participants with viral suppression to <1,000 copies/mL has continually exceeded 90% and has been above 95% since 2020; however, this proportion has consistently been lower among children. Sex, age category / ART regimen core agent (combined variable), time since ART initiation, and district were independently associated with viraemia.Future plansVICONEL offers potential for i) further digitalisation and automation of results sharing at the client, facility, and district/national level, ii) integration of additional clinical and diagnostic data, including HIV comorbidities, and iii) embedding randomised trials.Strengths and limitations-VICONEL covers all HIV viral load testing from 23 clinics in two districts in Lesotho and is thus highly representative.-Data capture occurs at the time point of viral load testing; thus, treatment or clinical data are not updated between viral load tests, and reasons for exiting the cohort are not followed up.-Participant data beyond viral load results are limited to key demographic, clinical, and treatment information.-The cohort and associated biobank have proven to be a valuable platform for nested observational and interventional research, including randomised trials.-Core functions can be maintained at low cost, constituting a model for near-real-time monitoring of treatment outcomes with limited resources.
Intra- and interindividual variability in fasted gastric content volume
Authors: Roelofs Julia J.M. , Camps Guido , Leenders Louise M. , Marciani Luca , Spiller Robin C. , van Eijnatten Elise J.M. , Alyami Jaber , Deng Ruoxuan , Freitas Daniela , Grimm Michael , Karhunen Leila J. , Krishnasamy Shanthi , Le Feunteun Steven , Lobo Dileep N. , Mackie Alan R. , Mayar Morwarid , Weitschies Werner , Smeets Paul A.M. 
Published: March 2024

2AbstractBackgroundGastric fluid plays a key role in food digestion and drug dissolution, therefore, the amount of gastric fluid present in a fasted state may influence subsequent digestion and drug delivery. We aimed to describe intra- and interindividual variation in fasted gastric content volume (FGCV) and to determine the association with age, sex, and body size characteristics.MethodsData from 24 MRI studies measuring FGCV in healthy, mostly young individuals after an overnight fast were pooled. Analysis included 366 participants with a total of 870 measurements. Linear mixed model analysis was performed to calculate intra- and interindividual variability and to assess the effects of age, sex, weight, height, weight*height as a proxy for body size, and body mass index (BMI).ResultsFGCV ranged from 0 to 156 mL, with a mean (± SD) value of 33 ± 25 mL. The overall coefficient of variation within the study population was 75.6%, interindividual SD was 15 mL, and the intraindividual SD was 19 mL. Age, weight, height, weight*height, and BMI had no effect on FGCV. Women had lower volumes compared to men (MD: -6 mL), when corrected for the aforementioned factors.ConclusionFGCV is highly variable, with higher intraindividual compared to interindividual variability, indicating that FGCV is subject to day-to-day and within-day variation and is not a stable personal characteristic. This highlights the importance of considering FGCV when studying digestion and drug dissolution. Exact implications remain to be studied.GRAPHICAL ABSTRACTKEY POINTSFasted gastric content volume is highly variable, both within an individual and between individuals, and should range between 0 and 138 mL in healthy young individuals.Women have lower fasted gastric content volume compared to men; age, body weight and body size were not associated with differences in fasted gastric content volume.Fasted gastric content volume can impact both digestion and drug dissolution, although exact implications of the observed variations remain to be studied.
Gene Sequence to 2D Vector Transformation for Virus Classification
Authors: Sanchez-Gendriz Ignacio , Azevedo Karolayne S. , de Souza Luísa C. , Dalmolin Matheus G. S. , Fernandes Marcelo A. C. 
Published: March 2024

ABSTRACTBackgroundDNA sequences harbor vital information regarding various organisms and viruses. The ability to analyze extensive DNA sequences using methods amenable to conventional computer hardware has proven invaluable, especially in timely response to global pandemics such as COVID-19.ObjectivesThis study introduces a new representation that encodes DNA sequences in unit vector transitions in a 2D space, extracted from the 2019 repository Novel Coronavirus Resource (2019nCoVR). The main objective is to elucidate the potential of this method to facilitate virus classification using minimal hardware resources. It also aims to demonstrate the feasibility of the technique through dimensionality reduction and the application of machine learning models.MethodsDNA sequences were transformed into two-nucleotide base transitions (referred to as ‘transitions’). Each transition was represented as a corresponding unit vector in 2D space. This coding scheme allowed DNA sequences to be efficiently represented as dynamic transitions. After applying a moving average and resampling, these transitions underwent dimensionality reduction processes such as Principal Component Analysis (PCA). After subsequent processing and dimensionality reduction, conventional machine learning approaches were applied, obtaining as output a multiple classification among six species of viruses belonging to the coronaviridae family, including SARS-CoV-2.Results and DiscussionsThe implemented method effectively facilitated a careful representation of the sequences, allowing visual differentiation between six types of viruses from the Coronaviridae family through direct plotting. The results obtained by this technique reveal values accuracy, sensitivity, specificity and F1-score equal to or greater than 99%, applied in a stratified cross-validation, used to evaluate the model. The results found produced performance comparable, if not superior, to the computationally intensive methods discussed in the state of the art.ConclusionsThe proposed coding method appears as a computationally efficient and promising addition to contemporary DNA sequence coding techniques. Its merits lie in its simplicity, visual interpretability and ease of implementation, making it a potential resource in complementing existing strategies in the field.
Measuring what matters: context-specific indicators for assessing immunisation performance in Pacific Island Countries and Areas
Authors: Patel Cyra , Sargent Ginny M , Tinessia Adeline , Mayfield Helen , Chateau Dan , Ali Akeem , Tuibeqa Ilisapeci , Sheel Meru 
Published: March 2024

AbstractIncreasing countries’ access to data can improve immunisation coverage through evidence-based decision-making. However, data collection and reporting is resource-intensive, so needs to be pragmatic, especially in low-and-middle-income countries. We aimed to identify which indicators are most important for measuring, and improving, national immunisation performance in Pacific Island Countries (PICs). We conducted an expert elicitation study, asking 13 experts involved in delivering immunisation programs, decision-makers, health information specialists, and global development partners across PICs to rate 41 indicators based on their knowledge of the feasibility and relevance of each indicator. We also asked experts their preferences for indicators to be retained or removed from a list of indicators for PICs. Experts participated in two rating rounds, with a discussion on the reasons for ratings before the second round. We calculated mean scores for feasibility and relevance, and ranked indicators based on experts’ preferences and mean scores. We used framework analysis to identify reasons for selecting indicators. Experts agreed that certain indicators were essential to measure (e.g. data use in program planning and measles vaccination coverage), but preferences varied for most indicators. Preferences to include indicators in a set of indicators for PICs moderately correlated with scores for relevance (r=0.68) and feasibility (r=0.56). In discussions, experts highlighted usefulness for decision-making and ease of data collection, reporting and interpretation as the main reasons driving indicator selection. Country-specific factors such as health system factors, roles and influence of various immunisation actors, and macro-level factors (namely population size, distribution and mobility) affected relevance and feasibility, leading us to conclude that a single set of indicators for all PICs is inappropriate. Rather than having a strict set of indicators that all countries must measure and report against, performance indicators should be flexible, country-specific, and selected in consultation with stakeholders who collect and use the data.
Effects of Systemic Lupus Erythematosus on the Brain: A Systematic Review of Structural MRI Findings and their Relationships with Cognitive Dysfunction
Authors: Valdés Cabrera Diana , El Tal Tala , Mohamed Ibrahim , Arciniegas Santiago Eduardo , Fevrier Stephanie , Ledochowski Justine , Knight Andrea 
Published: March 2024

AbstractBackgroundCognitive dysfunction (CD) is highly prevalent in systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Neuroimaging utilizing advanced magnetic resonance imaging (MRI) metrics may yield mechanistic insights. We conducted a systematic review of neuroimaging studies to investigate the relationship between structural and diffusion MRI metrics and CD in SLE.MethodsWe systematically searched several databases between January 2000 and October 2023 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Retrospective, and prospective studies were screened for search criteria keywords (including structural or diffusion MRI, cognitive function, and SLE) to identify peer-reviewed articles reporting advanced structural MRI metrics and evaluating CD in human patients with SLE.ResultsEighteen studies (8 structural MRI, 9 diffusion MRI, and 1 with both modalities) were included; sample sizes ranged from 11 to 120 participants with SLE. Neurocognitive assessments and neuroimaging techniques, parameters, and processing differed across articles. The most frequently affected cognitive domains were memory, psychomotor speed, and attention; while abnormal structural and/or diffusion MRI metrics were found more consistently in the hippocampus, corpus callosum, and frontal cortex of patients with SLE, with and without clinically diagnosed CNS involvement.ConclusionAdvanced structural MRI analysis can identify total and regional brain abnormalities associated with CD in patients with SLE, with potential to enhance clinical assessment. Future collaborative, longitudinal studies of neuroimaging in SLE are needed to better characterize CD, with focus on harmonized neurocognitive assessments, neuroimaging acquisitions and post-processing analyses, and improved clinical characterization of SLE cohorts.