bluuebunny/crossref_metadata_2025_split huggingface dataset:
A qualitative exploration of barriers to efficient and effective Structured Medication Reviews in Primary Care: Findings from the DynAIRx study
Authors: Abuzour Aseel S , Wilson Samantha A , Woodall Alan A , Mair Frances S , Clegg Andrew , Shantsila Eduard , Gabbay Mark , Abaho Michael , Aslam Asra , Bollegala Danushka , Cant Harriet , Griffiths Alan , Hama Layik , Leeming Gary , Lo Emma , Maskell Simon , O’Connell Maurice , Popoola Olusegun , Relton Sam , Ruddle Roy A , Schofield Pieta , Sperrin Matthew , Van Staa Tjeerd , Buchan Iain , Walker Lauren E 
Published: April 2024

AbstractIntroductionStructured medication reviews (SMRs), introduced in the United Kingdom (UK) in 2020, aim to enhance shared decision-making in medication optimisation, particularly for patients with multimorbidity and polypharmacy. Despite its potential, there is limited empirical evidence on the implementation of SMRs, and the challenges faced in the process. This study is part of a larger DynAIRx (Artificial Intelligence for dynamic prescribing optimisation and care integration in multimorbidity) project which aims to introduce Artificial Intelligence (AI) to SMRs and develop machine learning models and visualisation tools for patients with multimorbidity. Here, we explore how SMRs are currently undertaken and what barriers are experienced by those involved in them.MethodsQualitative focus groups and semi-structured interviews took place between 2022-2023. Nine focus groups were conducted with doctors, pharmacists and clinical pharmacologists (n=21), and three patient focus groups with patients at high-risk of rapidly worsening health from multimorbidity (n=13). Five semi-structured interviews were held with 2 pharmacists, 1 trainee doctor, 1 policy-maker and 1 psychiatrist. Transcripts were analysed using a thematic approach.ResultsTwo key themes limiting the effectiveness of SMRs in clinical practice were identified: ‘Medication Reviews in Practice’ and ‘Medication-related Challenges’. Participants noted limitations to the efficient and effectiveness of SMRs in practice including the scarcity of digital tools for identifying and prioritising patients for SMRs; organisational and patient-related challenges in inviting patients for SMRs and ensuring they attend; the time-intensive nature of SMRs, the need for multiple appointments and shared decision-making; the impact of the healthcare context on SMR delivery; poor communication and data sharing issues between primary and secondary care; difficulties in managing mental health medications and specific challenges associated with anticholinergic medication.ConclusionSMRs are complex, time consuming and medication optimisation may require multiple follow-up appointments to enable a comprehensive review. There is a need for a prescribing support system to identify, prioritise and reduce the time needed to understand the patient journey when dealing with large volumes of disparate clinical information in electronic health records. However, monitoring the effects of medication optimisation changes with a feedback loop can be challenging to establish and maintain using current electronic health record systems.
A Meta-analysis of the efficacy of topical antibiotics in spinal surgery for the prevention of surgical site infection
Authors: Wang Yanfei , Song Ke , Cai Songlin , Wu Weifei 
Published: April 2024

AbstractBackgroundDespite significant advancements in clinical aseptic techniques and wound infection control, surgical site infections (SSIs) continue to pose a significant risk and complication following spinal surgery. The use of intrawound antibiotics for the prevention of SSIs after spine surgery is a controversial method.ObjectiveTo conduct a review of the current literature on the use of antibiotics in wound care and evaluate their effectiveness in preventing postoperative SSIs.MethodsKeywords such as “spinal surgery” or “spine”, “antibiotics”, “local” or “topical”, “prevention of infection”, and “infection” were used based on PubMed, Web of Science, Cochrane and Embase database. The literature was screened based on the title, abstract, full text reading, and extraction of relevant research data. Comparisons of the data were performed using RevMan 5.3 software.ResultsA total of 18922 patients from 24 studies were included in the final analysis, 8878 patients received antibiotics (experimental group) to prevent SSIs, and 10044 patients did not receive any additional antibiotics (control group). In the experimental group, 178 patients developed SSIs, compared to 356 patients in the control group. The results of the meta-analysis indicated that the incidence of SSIs in the experimental group was significant lower than that in the control group (95% confidence interval, 0.36-0.75, p=0.0004).ConclusionThe topical application of antibiotics within the wound site is a crucial and efficient method to prevent SSIs after spinal surgery.
Clinical Outcomes Following Optical Coherence Tomographic versus Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Dodoo Sheriff N. , Ibrahim Sammudeen , Osman Abdul-Fatawu , Salih Rayan , Kilaru Vikas , Ampadu Dennis Kwaku , Dodoo Afia S. , Egolum Ugochukwu , Ghasemzadeh Nima , Ramadan Ronnie , Giugliano Gregory , Henry Glen , Ibebuogu Uzoma , Samady Habib 
Published: April 2024

AbstractBackgroundOptical coherence tomography (OCT) and intravascular ultrasound (IVUS) are adjunctive intracoronary imaging modalities used for optimizing the implantation of coronary stents. However, the impact of the choice of OCT versus IVUS on clinical outcomes and periprocedural complications is unclear.ObjectiveTo perform a meta-analysis of all vetted randomized controlled trials comparing OCT-guided versus IVUS-guided percutaneous coronary intervention.MethodsWe queried MEDLINE, Cochrane Library, Scopus, andclinicalTrials.govdatabases from their commencement to February 2024 for all randomized controlled trials that compared OCT-guided versus IVUS-guided percutaneous coronary interventions. The primary endpoint was major adverse periprocedural events (MAPE), a composite of stent thrombosis (ST), distal embolization (DE), and distal edge dissection (DED). The secondary endpoints included stent thrombosis, distal embolization, distal edge dissection, Major-adverse-cardiac events (MACE)-[a composite of cardiac death, Target vessel myocardial infarction (TVMI), and target vessel revascularization (TVR)], all-cause mortality, cardiac death, TVMI, TVR, and nonfatal stroke. The odds ratio (OR) with a 95% confidence interval (CI) was analyzed using a random-effect model.ResultsSeven randomized controlled trials were included in the analysis, and 4446 patients were enrolled. OCT was associated with lower MAPE (OR: 0.65, CI:0.47-0.91, p= 0.01) compared to IVUS. ST, DE, and DED were similar between OCT and IVUS. There were no significant differences in MACE (OR: 0.86, CI:0.64-1.16, p= 0.32), all-cause mortality (OR: 0.83, CI:0.42-1.66, p= 0.60), Cardiac death (OR: 0.62, CI:0.20-1.89, p= 0.40), TVMI (OR: 0.69, CI:0.33-1.46, p= 0.33), TVR, (OR: 1.09, CI:0.70-1.71, p= 0.70), and non-fatal stroke (OR: 1.82, CI:0.67-4.95, p= 0.24) one year following the index procedure.ConclusionOptical coherence tomographic-guided PCI was associated with lower major adverse peri-procedural events (MAPE), including stent thrombosis, distal embolization, and distal edge dissection, compared to intravascular ultrasound-guided PCI. However, there was no difference in overall major adverse cardiac events, target vessel myocardial infarction, target vessel revascularization, and nonfatal stroke.
Transcriptional Variabilities in Human hiPSC-derived Cardiomyocytes: All Genes Are Not Equal and Their Robustness May Foretell Donor’s Disease Susceptibility
Authors: Charles Gu C. , Matter Andrea , Turner Amy , Aggarwal Praful , Yang Wei , Sun Xiao , Hunt Steven C. , Lewis Cora E. , Arnett Donna K , Anson Blake , Kattman Steve , Broeckel Ulrich 
Published: April 2024

SUMMARYHuman induced pluripotent stem cells (hiPSCs) are frequently used to study disease-associated variations. We characterized transcriptional variability from a hiPSC-derived cardiomyocyte (hiPSC-CM) study of left ventricular hypertrophy (LVH) using donor samples from the HyperGEN study. Multiple hiPSC-CM differentiations over reprogramming events (iPSC generation) across 7 donors were used to assess variabilities from reprogramming, differentiation, and donor LVH status. Variability arising from pathological alterations was assessed using a cardiac stimulant applied to the hiPSC-CMs to trigger hypertrophic responses. We found that for most genes (73.3%∼85.5%), technical variability was smaller than biological variability. Further, we identified and characterized lists of“noise” genesshowing greater technical variability and“signal” genesshowing greater biological variability. Together, they support a “genetic robustness” hypothesis of disease-modeling whereby cellular response torelevantstimuli in hiPSC-derived somatic cells fromdiseased donorstends to showmoretranscriptional variability. Our findings suggest that hiPSC-CMs can provide a valid model for cardiac hypertrophy and distinguish between technical and disease-relevant transcriptional changes.
Exploring the Influence of Pore Shape on Conductance and Permeation
Authors: Seiferth David , Biggin Philip C. 
Published: April 2024

AbstractThere are increasing numbers of ion channel structures featuring heteromeric subunit assembly, exemplified by synaptic α1βBGlycine and α4β2 Nicotinic receptors. These structures exhibit inherent pore asymmetry, but the relevance of this to function is unknown. Furthermore, molecular dynamics simulations performed on symmetrical homomeric channels often leads to thermal distortion whereby conformations of the resulting ensemble are also asymmetrical. When functionally annotating ion channels, researchers often rely on minimal constrictions determined via radius-profile calculations performed with computer programs, such as HOLE or CHAP, coupled with an assessment of pore hydrophobicity. However, such tools typically employ spherical probe particles, limiting their ability to accurately capture pore asymmetry. Here, we introduce an algorithm that employs ellipsoidal probe particles, enabling a more comprehensive representation of the pore geometry. Our analysis reveals that the use of non-spherical ellipsoids for pore characterization, provides a more accurate and easily interpretable depiction of conductance. To quantify the implications of pore asymmetry on conductance, we systematically investigated carbon nanotubes (CNTs) with varying degrees of pore asymmetry as model systems. The conductance through these channels shows surprising effects that would otherwise not be predicted with spherical probes. The results have broad implications not only for the functional annotation of biological ion channels, but also for the design of synthetic channel systems for use in areas such as water filtration. Furthermore, we make use of the more accurate characterization of channel pores to refine a physical conductance model to obtain a heuristic estimate for single channel conductance. The code is freely available, obtainable as pip-installable python package and provided as a webservice.
Functional traits and phylogeny predict vertical foraging in terrestrial mammals and birds
Authors: Jantz Patrick , Abraham Andrew , Scheffers Brett , Gaillard Camille , Harfoot Mike , Goetz Scott , Doughty Christopher E. 
Published: April 2024

AbstractEarth’s ecosystems are characterized by numerous gradients related to the distribution of environmental conditions and resources. Niche theory predicts that animals will evolve traits to exploit changing resource availability and environmental conditions across these gradients. Much work has been done examining how animal traits like body mass and diet change across gradients from regional to global scales. Environmental and resource gradients in the vertical dimension tend to exhibit strong changes over relatively short distances due to the influence of elevation and vegetation. Vegetation structure may be an especially important vertical axis as it contributes to strong gradients in micro- climate, food resources, and predation risk. To investigate interrelationships between the vertical niche and its presumed drivers, we use functional traits, phylogenies, and predation risk to predict the vertical foraging niche for 4,828 mammals and 9,437 birds globally. To provide biogeographic context to the predictive analysis, we use species ranges to map geographic distributions of the vertical foraging niche and relationships between the niche and its presumed drivers. Linking trait databases with species range maps revealed distinct global distributions of vertical foraging niches for mammals and birds. The most important predictors of these niches varied by taxon but there were several systematic relationships. Diet, body mass, and phylogeny were strong predictors of vertical foraging niche across mammal and bird species. Percent fruit in diet exhibited progressively more positive relationships with higher canopy foraging positions. Predation pressure was relatively unimportant in predicting most vertical foraging niches for birds and mammals but displayed a positive trend with arboreal foraging. Geographic hotspots for the importance of fruit in both mammal and bird diets included the Andes-Amazon transition zone, the Amazon Basin, and New Guinea. Our results provide support for the theory of resource driven vertical niche partitioning but also reveal that vertical niches are strongly associated with phylogeny, suggesting niche conservatism in numerous mammal and bird families. Geographic patterns in variable importance values suggest multiple mechanisms behind spatial structure in eco- evolutionary relationships, including latitudinal gradients in vegetation structure and composition, historical patterns of island isolation (in Southeast Asia), and the influence of habitat heterogeneity driven by tectonic processes (in South America).
Smpd1regulates chitin-clearance for tracheal gas-filling in theDrosophilaembryo in a ceramide-specific manner
Authors: Hull Alexander J , Atilano Magda L , Hallqvist Jenny , Heywood Wendy , Kinghorn Kerri J 
Published: April 2024

AbstractType A and B Niemann Pick (NPD) is an inherited multisystem lysosomal storage disorder caused by mutations in theSMPD1gene. Respiratory dysfunction is a key hallmark of NPD, although the precise mechanisms underlying these pathologies is underexplored. Here we present aDrosophilamodel ofSmpd1loss-of-function that displays significant respiratory defects.Smpd1is expressed in the late-embryonic fly respiratory network, the trachea, and is secreted into the tracheal lumen. Loss ofSmpd1results in embryonic lethality, and although tracheal morphology appears normal, trachea fail to fill with gas prior to eclosion. We demonstrate that clearance of luminal constituents through endocytosis prior to gas-filling is defective inSmpd1mutants. This is coincident with autophagic, but not lysosomal defects. Finally, we show that although bulk sphingolipids are unchanged, dietary loss of lipids in combination with genetic and pharmacological block of ceramide synthesis is sufficient to rescue gas-filling defects. In summary, we present a novel NPD model amenable to genetic and pharmacological screens, and highlight myriocin, an inhibitor of ceramide synthesis, as a potential therapeutic drug for the treatment of NPD.
New role for cardiomyocyteBmal1in the regulation of sex-specific heart transcriptomes
Authors: Zhang Xiping , Procopio Spencer B. , Ding Haocheng , Semel Maya G. , Schroder Elizabeth A. , Seward Tanya S. , Du Ping , Wu Kevin , Johnson Sidney R. , Prabhat Abhilash , Schneider David J. , Stumpf Isabel G , Rozmus Ezekiel R , Huo Zhiguang , Delisle Brian P. , Esser Karyn A. 
Published: April 2024

AbstractIt has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the the core clock genes are expressed in common in both sexes but the circadian transcriptome of the mouse heart is very sex-specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts and the temporal pattern of REGs was distinctly different between sexes. We next used a cardiomyocyte-specific knock out of the core clock gene,Bmal1, to investigate its role in sex-specific gene expression in the heart. All sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss ofBmal1. Surprisingly, loss of cardiomyocyteBmal1also resulted in a roughly 8-fold reduction in the number of all the differentially expressed genes between male and female hearts. We conclude that cardiomyocyte-specificBmal1, and potentially the core clock mechanism, is vital in conferring sex-specific gene expression in the adult mouse heart.
Machine learning methods for predicting guide RNA effects in CRISPR epigenome editing experiments
Authors: Mu Wancen , Luo Tianyou , Barrera Alejandro , Bounds Lexi R. , Klann Tyler S. , Weele Maria ter , Bryois Julien , Crawford Gregory E. , Sullivan Patrick F. , Gersbach Charles A. , Love Michael I. , Li Yun 
Published: April 2024

AbstractCRISPR epigenomic editing technologies enable functional interrogation of non-coding elements. However, current computational methods for guide RNA (gRNA) design do not effectively predict the power potential, molecular and cellular impact to optimize for efficient gRNAs, which are crucial for successful applications of these technologies.We present “launch-dCas9” (machine LeArning based UNified CompreHensive framework for CRISPR-dCas9) to predict gRNA impact from multiple perspectives, including cell fitness, wild-type abundance (gauging power potential), and gene expression in single cells. Our launch-dCas9, built and evaluated using experiments involving >1 million gRNAs targeted across the human genome, demonstrates relatively high prediction accuracy (AUC up to 0.81) and generalizes across cell lines. Method-prioritized top gRNA(s) are 4.6-fold more likely to exert effects, compared to other gRNAs in the same cis-regulatory region. Furthermore, launch-dCas9 identifies the most critical sequence-related features and functional annotations from >40 features considered. Our results establish launch-dCas9 as a promising approach to design gRNAs for CRISPR epigenomic experiments.
Dynamic reconfiguration of aperiodic brain activity supports cognitive functioning in epilepsy: a neural fingerprint identification
Authors: Lopez Emahnuel Troisi , Corsi Marie-Constance , Danieli Alberto , Antoniazzi Lisa , Angiolelli Marianna , Bonanni Paolo , Sorrentino Pierpaolo , Duma Gian Marco 
Published: April 2024

AbstractBackgroundTemporal lobe epilepsy (TLE) is characterized by alterations of brain dynamic at large scale associated with altered cognitive functioning. Interindividual variability of brain activity is a source of heterogeneity in this disorder. Here, we aimed at analyzing dynamical reconfiguration of brain activity, using the neural fingerprint approach, to delineate subject-specific characteristics and their cognitive correlates in TLE.MethodsWe collected 10 minutes of resting state electroencephalography (128 channels), free from epileptiform activity, from 68 TLE patients and 34 healthy controls. The functional network was defined by the spatio-temporal spreading, across cortical regions, of aperiodic bursts of activations (neuronal avalanches). This metric allowed encapsulating brain reconfiguration patterns into the avalanche transition matrix (ATM). We used a neural fingerprint approach to differentiate across controls and patients diagnosis, linking altered brain dynamic with cognitive outcome.FindingsPatients’ brain dynamics were more stereotyped as compared to controls. The neural fingerprint using ATMs differentiated, in a data-driven fashion, patients with respect to healthy controls, being sensitive not only to the pathology but also to the subtype (unilateral vs. bilateral TLE). Notably, in unilateral TLE patients, a better memory performance was associated with a larger similarity of the brain dynamic configuration with controls.InterpretationTLE is characterized by reduced variability and more stereotyped brain dynamics, implicating widespread alterations across the brain. These alterations correlate with cognitive function in patients with unilateral TLE. This study underscores the utility of brain fingerprinting in elucidating disease-specific brain dynamics, offering novel metrics for personalized patient care.
A novel food frequency questionnaire for Brazilian adults based on the Nova classification system: development, reproducibility and validation
Authors: Frade Evelyn Oliveira da Silva , Gabe Kamila Tiemann , Costa Caroline dos Santos , Neri Daniela , Steele Euridice Martinez , Rauber Fernanda , Steluti Josiane , Levy Renata Bertazzi , Louzada Maria Laura da Costa 
Published: April 2024

AbstractThe Nova system categorizes foods according to processing levels, and dietary intake instruments not developed to assess this criteria may introduce bias in epidemiological studies. To address this gap, we developed and validated the Nova Food Frequency Questionnaire (NovaFFQ) for Brazilian adults. The NovaFFQ includes commonly consumed foods and drinks based on 2017-2018 National Food Survey data. Reproducibility was assessed by comparing NovaFFQ estimates on two occasions. Criterion validity was assessed by comparing the mean dietary contribution of Nova groups obtained from the first NovaFFQ against two Nova24h. Strong reproducibility was observed with an intraclass correlation coefficient (ICC) of 0.91 for all Nova groups. Criterion validity showed a moderate ICC, ranging from 0.61 to 0.65, and substantial agreement in ranking individuals, as indicated by prevalence and bias-adjusted kappa, ranging from 0.70 to 0.74. The NovaFFQ is a valid instrument for assessing food consumption according to food processing.