bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neural network model that generates salt concentration memory-dependent chemotaxis inCaenorhabditis elegans
Authors: Hironaka Masakatsu , Sumi Tomonari 
Published: November 2024

AbstractA neuroanatomical minimal network model was revisited to elucidate the mechanism of salt concentration memory-dependent chemotaxis observed inCaenorhabditis elegans. C. elegansmemorizes the salt concentration during cultivation, manifesting a pronounced taste preference for this concentration. The right-side head sensory neuron, designated ASER, exhibits a response to a decrease in salt concentration. The basal level of glutamate transmission from ASER has been demonstrated to transiently increase and decrease when the current environmental salt concentrations are lower and higher, respectively, than that during previous cultivation. Given the sensitivity of excitatory/inhibitory glutamate receptors expressed on the postsynaptic AIY interneurons, it can be anticipated that the ASER-AIY synaptic transmission will undergo a reversal due to alterations in the basal glutamate release. The neural network model, derived with the hypothesis, reproduced the salt concentration memory-dependent preference behavior and revealed the modular neural circuit function downstream of ASE that is responsible for salt klinotaxis.
Time course of Quadriceps thickness changes over six months post-anterior cruciate ligament reconstruction: unveiling critical impairments in vastii muscles
Authors: De la Fuente Carlos , Silvestre Rony , Martinez-Valdes Eduardo , Yañez Roberto , Abat Ferran , Neira Alejandro , de Andrade André Gustavo , Carpes Felipe P 
Published: November 2024

AbstractThe mechanisms behind the persistent Quadriceps weakness observed after an Anterior Cruciate Ligament reconstruction (ACLr) remain debatable. We described the time course of changes in Quadriceps thickness, strength, and thigh circumference over six months following an ACLr. We also studied the causal relation between Quadriceps thickness, total thickness and strength. Quadriceps thicknesses, Quadriceps strength, and thigh circumference were measured preoperative, 3, and 6 months post-ACLr surgery in 103 patients (77 men and 26 women). Limbs and time were compared with repeated-measures ANOVA and causal relations through mediation analysis (α = 5%). From 0 to 3 months post-surgery, Quadriceps strength (p<0.05), and VI (p<0.05) and VL (p<0.001) thicknesses was reduced. From 3 to 6 months, Quadriceps strength (p<0.05), total Quadriceps thickness (p<0.001), and VI (p<0.001) and VL (p<0.05) thicknesses increased. VM and RF thicknesses increase to 3 months after ACLr (p<0.05). Quadriceps strength, circumference at 5 cm, VI, VL, VM, and total Quadriceps thickness remain lower than the contralateral limb 6 months following an ACLr (p<0.05). The VI thickness determine indirectly (p<0.001) through the total Quadriceps thickness the Quadriceps strength pattern, while the VL thickness directly determined it (p=0.034). Quadriceps thickness adapts heterogeneously, with VI and VL atrophying for up to three months, explaining the post-ACLr quadriceps weakness. By 6 months, VI does not recover its thickness proportion, and VI and VL do not return to pre-surgery conditions. Both vastii muscles primarily determine Quadriceps strength changes, eliciting the VI thickness as a key biomarker for Quadriceps weakness following ACLr.
Recommended Interventions for Enhanced Recovery After Cesarean Delivery in the United States
Authors: Sultan Pervez , Zakowski M , Joudi Kareem , Singh DJ , Gregory Kimberly D. , Lyell D , Carvalho Brendan ,   Study investigators
Published: November 2024

AbstractBackgroundExisting enhanced recovery after cesarean delivery (ERAC) professional society recommendations lack intersociety collaboration, multidisciplinary expert input and involvement of patient stakeholders. This initiative aimed to develop a multidisciplinary set of ERAC interventions endorsed by relevant US professional societies and patient representatives.MethodsThis American Society of Anesthesiologists (ASA) and American College of Obstetricians and Gynecologists (ACOG) led initiative received IRB approval from Stanford University. In total 19 stakeholders were invited to participate in this Delphi study, including 13 representatives from 8 US professional societies (American Society of Anesthesiologists (ASA - 1 representative), Society for Obstetric Anesthesia and Perinatology (SOAP - 2), American College of Obstetricians and Gynecologists (ACOG - 4), Society for Maternal Fetal Medicine (SMFM - 1), Society of OBGYN Hospitalists (SOGH - 1), Enhanced Recovery After Surgery Society (ERAS Society - 1), Association of Women’s Health Obstetric and Neonatal Nurses ((AWHONN -2), American Association of Nurse Anesthesiology (AANA - 1), a physical therapist, a lactation expert and 4 patient representatives from diverse backgrounds. A three-round modified Delphi approach was conducted (2 rounds of electronic questionnaires and a 3rdround of e-discussion), to produce the final set of ERAC recommendations. An initial list of 70 interventions was compiled based on a previously published systematic review of ERAC studies and professional society guidelines/recommendations (ERAS Society, SOAP, and Healthcare Canada). Consensus was obtained for the final list of interventions, with strong consensus defined as ≥70% agreement and weak consensus as 50–69% agreement.ResultsAll professional societies that were approached provided content-expert stakeholders to participate, and all stakeholders completed all rounds of the Delphi process. A final set of 32 interventions (6 preoperative, 13 intraoperative and 13 postoperative) achieved strong consensus.ConclusionsThis US intersociety and multidisciplinary Delphi study resulted in a list of ERAC interventions, which should be considered when implementing ERAC within US labor and delivery units.
A Randomized Clinical Trial Comparing Visual Inspection with Acetic Acid (VIA) to Pocket Colposcopy for the Triage of HPV+ women living with HIV in Kisumu, Kenya
Authors: Dotson Mary E. , Steinberg Eliza , Santos Maria Olivia , Ambaka Jeniffer , Huchko Megan , Ramanujam Nimmi 
Published: November 2024

AbstractObjectiveThe World Health Organization recommends a “screen, triage, treat” approach for cervical cancer screening for Women Living with HIV (WLWH) in resource-limited settings, with Human Papillomavirus (HPV) testing preferred for screening. We assessed the use of the Pocket colposcope as an adjunct tool to Visual Assessment with Acetic Acid (VIA) for the triage of HPV+ WLWH.MethodsWe carried out a randomized clinical trial across six clinics in Kisumu, Kenya between November 2022 and April 2023 (NCT04998318). WLWH who screened positive with self-collected HPV were randomized to either the VIA or Pocket arm. Exam positivity was determined by presence or absence of aceto-white epithelium (AWE). Directed biopsies were performed on AWE; if negative, two random biopsies were taken. Pathology was used to determine diagnostic accuracy. Providers and participants took brief surveys after each exam.FindingsThe rate of a positive exams was 17.3% for VIA compared to 14.3% for the Pocket. The overall rate of CIN2/3 was 15.4%, with 12.2% in the VIA Arm and is 18.8% in the Pocket Arm. Pocket and VIA performed comparably on all sensitivity, specificity and negative predictive value (NPV). For Pocket compared to VIA, Sensitivity was 26.3% vs 25.0%; specificity was 88.9% vs 84.0%; and NPV was 82.9% vs 87.1%. However, the positive predictive value (PPV) of the Pocket colposcope arm was almost a factor of two higher than that of the VIA arm (Pocket arm PPV was 375 is and that of the VIA arm was 20.6%). The Pocket Colposcope was acceptable to providers and patients for clinic-based triage of HPV positivity.ConclusionProvider assessment with the Pocket colposcope detected significantly more treatable disease, thereby reducing the need for overtreatment. This study indicates that the Pocket colposcope is a feasible, lower cost colposcopic device, which could facilitate biopsy-confirmation of disease, increase provider training, patient education and facilitate remote diagnosis.
Potential causal links between genetic variants inSAMM50,SUGP1,MAU2, andGATAD2Aand liver fat in individuals with normal weight
Authors: Piras Ignazio S. , Don Janith , Schork Nicholas J. , DiStefano Johanna K. 
Published: November 2024

AbstractBackground & AimsMetabolic-associated steatotic liver disease (MASLD) affects individuals across a range of body weights, but little is known about the genetic determinants of this condition in individuals with normal BMI. This study aimed to identify genetic variants contributing to hepatic fat levels in normal-weight individuals.MethodsWe conducted a genome-wide association study (GWAS) using magnetic resonance imaging-proton density fat fraction (MRI-PDFF) data from 10,918 normal-weight participants (BMI < 25 kg/m²) of European ancestry from the UK Biobank. We employed a case-control (CC) design to assess hepatic steatosis and a quantitative trait (QT) design for liver fat content. Fine mapping was conducted to identify potential causal variants, while Multi-marker Analysis of GenoMic Annotation (MAGMA) and transcriptome-wide association studies (TWAS) were performed to assess gene-level associations and impute liver-specific gene expression.ResultsWe identified 241 (CC-GWAS) and 418 (QT-GWAS) significant variants located predominantly in genes on chromosomes 19 and 22, includingPNPLA3,TM6SF2, andSAMM50. Fine mapping revealed three potential causal variants inSUGP1,GATAD2A, andMAU2. MAGMA analysis identified eight genes in CC-GWAS and 19 in QT-GWAS, including the novel association withRFXANK. TWAS detectedMBOAT7andSAMM50, withSAMM50being further implicated as a potential causal gene through TWAS fine mapping.ConclusionsThis study, only the second to identify associations at the genome-wide level, represents a significant step forward in understanding the genetic basis of hepatic steatosis in normal-weight individuals, identifying both novel and established genetic variants. These findings provide insights into the pathophysiology of MASLD in this understudied population, emphasizing the importance of genetic predisposition beyond obesity-related mechanisms, and provide potential targets for personalized treatment and prevention strategies.Impact and implicationsThis study provides relevant insights into the genetic risk factors of MASLD in normal-weight individuals, a population often overlooked in liver disease research. By identifying both novel and established genetic variants, this work highlights the genetic predisposition to hepatic steatosis independent of obesity-related factors. The findings offer potential targets for early detection and therapeutic intervention in normal-weight individuals, which could be applied by physicians, patients, and policymakers to inform precision medicine approaches and preventive strategies. The study provides valuable insights based on a population of European ancestry, and future research can build upon these findings to explore their applicability to patients from diverse ethnic groups.
Perceived barriers and facilitators to implementing preventive therapy for tuberculosis in Malaysian prisons: Perspectives from prison personnel
Authors: Chen Phoebe , Altice Frederick , Ghoshal Divya , Ahmad Ahsan , Long Jiang , Saifi Rumana , Koh Hui Moon , Nagadevi Naga , Baharudin Mohd Norbayusri , Min Fui Esther Wong , Kamarulzaman Adeeba , Shenoi Sheela 
Published: November 2024

AbstractTuberculosis (TB) is a major health threat worldwide. TB is concentrated in prisons, where TB preventive therapy (TPT) implementation has been limited. Prisons generally, and especially in Malaysia, are overcrowded, minimally resourced, and have high prevalence of latent TB.As prison personnel are largely responsible for TPT implementation, their perspectives were sought to identify barriers and potential solutions for implementing TPT in Malaysia’s largest prison. A focus group using nominal group technique (NGT) was conducted with 9 prison officers with experience related to TPT to generate a list and rank-order the top TPT barriers. The process was repeated to assess facilitators.The top three barriers to implementing TPT were: 1) disruptions involved in prison activities (e.g., intra- and extra-prison transfers; 8 votes); 2) insufficient workforce (5 votes), and unanticipated inter-prison transfers (4 votes). Potential solutions included implementing care coordination protocols between officers and medical staff (8 votes), placing a medical hold until TPT completion (5 votes), and improving medication delivery logistics (4 votes). All prison officers supported a short-course TPT regimen administered once-weekly for 12 weeks (i.e. rifapentine and isoniazid (3HP)), over a daily TPT regimen for 6 months (i.e. isoniazid (26H)), due to less logistics and staff time required.From the perspective of prison officer stakeholders, logistical constraints commonly observed in prisons were perceived to impact the implementation of TPT, yet they prioritized pragmatic solutions that align with known implementation strategies to employ to optimize TPT delivery, including developing stakeholder relationships between medical and prison personnel and changing infrastructure to address frequent transfers within and between prisons and the community.
Impact of implementation of rapid syndromic molecular diagnostics on self-reported clinical and public health practice: a qualitative study in small island health services
Authors: Pae Riinu , Millest Adam , Tirion Anna , Dryden Matthew , Lee John E. , Wight Natalie , Fraser Graham , Toplass Janice , Weston Dale 
Published: November 2024

ABSTRACTObjectiveThis evaluation aimed to assess the impact of implementing Biofire© filmarray rapid syndromic molecular diagnostics systems in UK Overseas Territories, which are small jurisdictions with historically limited microbiological diagnostic capacity. The diagnostic systems were installed to improve patient management and public health response.MethodsWe conducted a qualitative evaluation. Data were gathered through semi-structured interviews and a focus group with clinicians, laboratory staff, and Chief Medical Officers.ResultsThe interviewees’ reported substantial improvements in diagnostic capabilities. Interviewees shared that implementation reduced test turnaround times to 1-24 hours compared to several days to weeks pre-implementation, enabling faster and more accurate clinical management and improving clinician and patient satisfaction. Reduced reliance on off-island reference laboratories and patient medical evacuations was reported, contributing to potential cost savings and increased health system resilience. Respondents found rapid diagnostics to be useful in the context of communicable disease outbreaks. However, high test cartridge costs, supply and logistics issues, and lack of or low utilisation of protocols were noted challenges.ConclusionThe implementation of this rapid automated syndromic molecular diagnostics technology markedly enhanced diagnostic capacity in territories included in this evaluation, particularly for respiratory, bloodstream, and gastrointestinal infections. This advancement accelerated diagnosis, was seen to improve patient management and antimicrobial stewardship. Despite these benefits, challenges remain. Further research is needed to assess the long-term impact on clinical practice, health outcomes, and cost-effectiveness, particularly in the unique contexts of small islands.
How to minimize mechanical power during controlled mechanical ventilation
Authors: Fabry Ben 
Published: November 2024

AbstractHigh intrapulmonary pressures, large tidal volumes, and elevated respiratory rates during controlled mechanical ventilation can lead to barotrauma, volutrauma, and atelectrauma. Mechanical power - defined as the product of the pressure-volume integral and respiratory rate - consolidates these three risk factors into a single, intuitive parameter. Several studies have demonstrated that higher mechanical power correlates with an increased risk of lung injury and mortality, prompting the suggestion that mechanical power should be minimized. However, under the constraint of maintaining a fixed alveolar minute ventilation and positive end-expiratory pressure (PEEP), it remains unclear how to adjust respiratory rate and tidal volume to minimize mechanical power. This study provides an analytical solution to this optimization problem. Accordingly, only the elastic component of mechanical power should be targeted for minimization. Regardless of lung elastance or resistance, or the mode and settings of the ventilator, the elastic power is minimized at a tidal volume equal to twice the anatomic dead space, or approximately 4.4 ml/kg of body weight.
Early transcriptional changes in neutrophil-mediated processes following recanalization after ischemic stroke
Authors: Bui Truong An , Ma Yonglie , Jickling Glen C , Winship Ian R 
Published: November 2024

AbstractBackgroundIschemic stroke is a leading cause of mortality and long-term disability globally. Current recanalization therapies, including mechanical thrombectomy and thrombolysis, aim to restore blood flow in acute ischemic stroke patients. However, many patients with successful recanalization still experience poor clinical outcomes. This phenomenon, where the restoration of blood flow does not translate into functional recovery, is known as futile recanalization.MethodsUsing a murine middle cerebral occlusion (MCAO) model that mimics a large vessel occlusion with recanalization, a comprehensive microarray analysis of gene expression from blood samples collected during MCAO and after recanalization (N=44) was performed.ResultsIl1r2, Cd55, Mmp8, Cd14,andCd69were key regulatory genes expressed early after MCAO and recanalization. A comparison with gene expression data from human stroke patients and rat MCAO model (GSE16561 and GSE21136) revealedVcanas a differentially expressed gene conserved across species, marking it as a novel indicator of recanalization that was detected as early as 3 hours post-recanalization (4 hours post-MCAO) in mice and 24 hours after recanalization rats (MCAO-thrombectomy) and humans (rtPA-thrombolysis). Leukocyte and neutrophil activation pathways were significantly enriched in the mouse data and human samples from GSE16561, with greater upregulation in female subjects. The analysis identified key miRNAs regulating gene expression in response to recanalization, and NFE4 and MTF1 as crucial transcription factors regulating these processes. Based on these data, a coregulatory network underlying neutrophil activity was constructed, highlighting its central role in early recanalization responses, especially in females.ConclusionsThis study identified new genomic markers in blood associated with recanalization, and identified critical age- and sex-specific factors. By mapping a coregulatory network of interacting genes and neutrophil-related pathways, the data provides insights to inform future research and develop targeted therapies. Such therapies can improve recanalization efficacy or modulate leukocytes to reduce futile recanalization, ultimately enhancing clinical outcomes for ischemic stroke patients.Graphical Abstract
Distant Ribose 2’-O-Methylation of 23S rRNA Helix 69 Pre-Orders the Capreomycin Drug Binding Pocket at the Ribosome Subunit Interface
Authors: Nandi Suparno , Dey Debayan , Srinivas Pooja , Dunham Christine M. , Conn Graeme L. 
Published: November 2024

ABSTRACTLoss of ribosomal RNA (rRNA) modifications incorporated by the intrinsic methyltransferase TlyA results in reduced sensitivity to tuberactinomycin antibiotics such as capreomycin. However, the mechanism by which rRNA methylation alters drug binding, particularly at the distant but functionally more important site in 23S rRNA Helix 69 (H69), is currently unknown. We determined high-resolution cryo-electron microscopy structures of theMycolicibacterium smegmatis70S ribosome with or without the two ribose 2’-O-methyl modifications incorporated by TlyA. In the unmodified ribosome, the tip of H69 adopts a more compact conformation, positioning two key nucleotides (A2137 and C2138) such that interactions with capreomycin would be lost and the binding pocket partially occluded. In contrast, methylation of 23S rRNA nucleotide C2144 results in conformational changes that propagate from the site of modification to the H69 tip, resulting in its movement away from h44, a more favorable positioning of C2138 and adoption of a more open conformation to enable capreomycin binding. Methylation of h44 also results in structural rearrangements at the H69-h44 interface that further support antibiotic binding. These structures thus reveal the effect and regulation of distant rRNA methylation on ribosome-targeting antibiotic binding.
A Proximity MAP of RAB GTPases
Authors: St-Laurent Véronique Gaudeault , Marchand Benoit , Larcher Raphaëlle , Nassari Sonya , Bourassa Francis , Moreau Mathilde , Jean Dominique , Boisvert François-Michel , Brunet Marie A. , Jean Steve 
Published: November 2024

ABSTRACTRAB GTPases are the most abundant family of small GTPases and regulate multiple aspects of membrane trafficking events, from cargo sorting to vesicle budding, transport, docking, and fusion. To regulate these processes, RABs are tightly regulated by guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs). Activated RABs recruit effector proteins that regulate trafficking. Identifying RAB-associated proteins has proven to be difficult because their association with interacting proteins is often transient. Recent advances in proximity labeling approaches that allow for the covalent labeling of neighbors of proteins of interest now permit the cataloging of proteins in the vicinity of RAB GTPases. Here, we report APEX2 proximity labeling of 23 human RABs and their neighboring proteomes. We have used bioinformatic analyses to map specific proximal proteins for an extensive array of RAB GTPases, and RAB localization can be inferred from their adjacent proteins. Focusing on specific examples, we identified a physical interaction between RAB25 and DENND6A, which affects cell migration. We also show functional relationships between RAB14 and the EARP complex, or between RAB14 and SHIP164 and its close ortholog UHRF1BP1. Our dataset provides an extensive resource to the community and helps define novel functional connections between RAB GTPases and their neighboring proteins.