bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring anterior thalamus functional connectivity with cortical regions in prospective memory with ultra-high-field fMRI
Authors: Flanagan Luke , Mansur Bruno de Matos , Reichert Christoph , Richter Anni , Golbabaei Soroosh , Kizilirmak Jasmin M. , Sweeney-Reed Catherine M. 
Published: February 2024

AbstractProspective memory, or memory for future intentions, engages particular cortical regions. Lesion studies also implicate the thalamus, with prospective memory deterioration following thalamic stroke. Neuroimaging, anatomical, and lesion studies suggest the anterior nuclei of the thalamus (ANT) in particular are involved in episodic memory, with electrophysiological studies suggesting an active role in selecting neural assemblies underlying particular memory traces. Here we hypothesized that the ANT are engaged in realizing prospectively-encoded intentions, detectable using ultra-high field strength functional MRI. Using a within-subject design, participants (N = 14; age 20-35 years) performed an ongoing n-back working memory task with two cognitive loads, each with and without a prospective memory component, during 7-Tesla functional MRI. Seed-to-voxel whole brain functional connectivity analyses were performed to establish whether including a prospective memory component in an ongoing task results in greater connectivity between ANT and cortical regions known to be engaged in prospective memory. Repeated measures ANOVAs were applied to behavioral and connectivity measures, with the factorsTask Type(with prospective memory or not) andN-Back(2-back or 3-back). Response accuracy was greater and reaction times faster without the prospective memory component, and accuracy was higher in the 2- than 3-back condition. We observed a main effect ofTask Typeon connectivity with an ANT seed, with greater ANT–DLPFC (dorsolateral prefrontal cortex) and ANT–STG (superior temporal gyrus) connectivity when including a prospective memory component. Post hoc testing based on a significant interaction showed greater ANT–DLPFC connectivity (p-FWE = 0.007) when prospective memory was included with the low and ANT–STG connectivity (p-FWE = 0.019) with the high cognitive load ongoing task. These locations showed no main effect ofN-Back. Connectivity based on a dorsomedial nucleus of the thalamus (DMNT) seed did not differ according toTask Typeat these locations. Enhanced connectivity between the ANT and the DLPFC, a brain region with an established role in strategic monitoring for prospective memory cues, arose with a low cognitive load ongoing task that enabled monitoring. This pattern was absent on directly increasing the cognitive load of the ongoing task without prospective memory, suggesting specificity for prospective memory. Greater ANT–STG connectivity on prospective memory inclusion in the higher cognitive load ongoing task condition fits with reports of STG activation on prospective memory through spontaneous retrieval. Differing connectivity based on a DMNT seed suggests ANT specificity. The findings fit with a coordinating role for the ANT in prospective remembering.
In bacterial membranes lipid II changes the stability of pores formed by the antimicrobial peptide nisin
Authors: Sheridan Miranda S. , Pandey Preeti , Hansmann Ulrich H. E. 
Published: February 2024

ABSTRACTResistance to available antibiotics poses a growing challenge to modern medicine as this often disallows infections to be controlled. This problem can only be alleviated by developing new drugs. Nisin, a natural lantibiotic with broad antimicrobial activity, has shown promise as a potential candidate for combating antibiotic-resistant bacteria. However, nisin is poorly soluble and barely stable at physiological pH, which, despite attempts to address these issues through mutant design, has restricted its use as a antibacterial drug. Therefore, gaining a deeper understanding of the antimicrobial effectiveness, which relies in part on its ability to form pores, is crucial for finding innovative ways to manage infections caused by resistant bacteria. Using large-scale molecular dynamics simulations we find that the bacterial membrane specific lipid II increases the stability of pores formed by nisin, and that the interplay of nisin and lipid II reduces the overall integrity of bacterial membranes by changing local thickness and viscosity.
Establishing Reference Ranges for Vitamin D Levels in a Representative Population of Peshawar, Pakistan
Authors: Usama  , Rehman Zeeshan , Ali Aktar 
Published: February 2024

AbstractBackgroundVitamin D deficiency is prevalent in Pakistan, yet there is no consensus on the optimal range for 25-hydroxyvitamin D (25(OH)D) levels. Establishing reference ranges specific to the population is essential due to variations in age, sex, race, and diet. Parathyroid hormone (PTH) serves as a surrogate marker for vitamin D deficiency. This study aims to determine the reference range for plasma vitamin D in a healthy population in Peshawar, considering various demographic and biochemical factors.MethodsA population-based cross-sectional study was conducted in four union councils of District Peshawar. Participants (n=200) aged 18-54 years underwent serum vitamin D and PTH analysis using ELISA kits. Data on sun exposure, anthropometric measurements, and dietary habits were collected.ResultsThe majority of participants (92%) reported daily sun exposure of 15-30 minutes and had a mean BMI of 23.598±3.988 kg/m2. Only 28% of participants were vitamin D sufficient, while 72% were deficient. test results obtained for the reference values were 6.43–45.0 ng/mL for the percentile range of 2.5–97.5.ConclusionThe high prevalence of vitamin D deficiency underscores the need for governmental and educational interventions to promote awareness and address this issue. Additionally, tailored nutrition plans are crucial to mitigate vitamin D deficiency in the local population.
Rare Diseases Clinical Trials Toolbox - Public resources and main considerations to set up a clinical trial on medicinal products for humans in Europe
Authors: del Álamo Marta , Zafirova Biljana , Esdaile Martina , Karam Sarah , Klager Sabine , Kubiak Christine 
Published: February 2024

AbstractBackgroundDrug development programmes in rare diseases have many challenges, some of which differ from those facing researchers working on common diseases, like the scarcity of patients.Over the past years, research and regulatory initiatives, as well as resources have been implemented to expedite drug development for rare diseases. Nevertheless, these tools have been developed in the context of different projects and with diverse aims. Therefore, they have not yet been structured to encompass the conduct of clinical trials as a whole. To address this issue, the EJP RD (European Joint Program for Rare Diseases) has developed the Rare Diseases Clinical Trial Toolbox.PurposeThis toolbox collates the accumulated knowledge, experience, and resources (collectively termed ‘tools’) generated by projects, research infrastructures and/or other organizations into a structured, practical and guided instrument to help clinical trialists and trial managers understand the regulations and requirements for conducting trials, with a special focus on investigator-initiated trials for rare diseases.MethodsThe toolbox is organized into five domains: research question, plan, execution, analysis, and end of trial. Each domain describes one or several activities to be considered in this step and indicate at what stage of the trial pathway these activities should take place, regardless of the therapeutic area. Each activity is further linked to specific resources (the tools) that are relevant for those activities. Associated resources are in the public domain developed in the context of research projects or by relevant clinical research stakeholders. Selected tools must be of fundamental importance to clinical trials and be applicable torare diseases clinical research. Rare-diseases specific resources are highlighted as such and include those specially relevant to paediatric clinical research, considering than one half of rare disorders affect children and some 60% of designated orphan medicines are intended for paediatric use.ResultsThe current version of the Toolbox includes 111 resources tagged as relevant for any of the 18 activities within the clinical trial outline. Overall, 75 % of all resources are relevant to any clinical trial while 25 % are tagged as “rare disease specific”.ConclusionAccess to public resources relevant to the development of clinical trials for rare diseases is sometimes challenged by limited awareness and/or the absence of an adequate framework that enables their findability. This Toolbox aims at building a framework supporting the optimal use of existing tools.
Screening Accuracy and Age-based Scoring Procedures of the Polish Version of Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist
Authors: Sobieski Mateusz , Kopszak Anna , Wrona Sylwia , Bujnowska-Fedak Maria Magdalena 
Published: February 2024

AbstractBackgroundThe first stage of diagnosing autism spectrum disorders usually involves population screening to detect children at risk. The aim of this study was to develop cut-off points and assess diagnostic properties for the Polish version of the Communication and Symbolic Behavior Scales-Developmental Profile – Infant-Toddler Checklist for the possibility of using this questionnaire in population screening.MethodThe study was conducted among 602 children from the general population who had previously participated in the earlier phase of validation of the questionnaire for Polish conditions. The collected data were statistically processed to calculate the accuracy (i.e. sensitivity, specificity) of the questionnaire.ResultsIn individual age groups, the sensitivity of the questionnaire varies from 0.667 to 0.750, specificity from 0.854 to 0.939, positive predictive value from 0.261 to 0.4 and negative predictive value - from 0.979 to 0.981.ConclusionsThese results indicate that the Polish version of the Communication and Symbolic Behavior Scales-Developmental Profile – Infant-Toddler Checklist can be used as an effective tool for ASD universal screening.
Enhancing Semantic Segmentation in Chest X-Ray Images through Image Preprocessing: ps-KDE for Pixel-wise Substitution by Kernel Density Estimation
Authors: Wang Yuanchen , Guo Yujie , Wang Ziqi , Yu Linzi , Yan Yujie , Gu Zifan 
Published: February 2024

BackgroundDeep-learning-based semantic segmentation algorithms, in combination with image preprocessing techniques, can reduce the need for human annotation and advance disease classification. Among established preprocessing techniques, CLAHE has demonstrated efficacy in enhancing the segmentations algorithms across various modalities.MethodThis study proposes a novel preprocessing technique, ps-KDE, to investigate its impact on deep learning algorithms to segment major organs in posterior-anterior chest X-rays. Ps-KDE augments image contrast by substituting pixel values based on their normalized frequency across all images. Our approach employs a U-Net architecture with ResNet34 (pre-trained on ImageNet) serving as the decoder. Five separate models are trained to segment the heart, left lung, right lung, left clavicle, and right clavicle.ResultsThe model trained to segment the left lung using ps-KDE achieved a Dice score of 0.780 (SD=0.13), while that trained on CLAHE achieved a Dice score of 0.717 (SD=0.19),p<0.01. ps-KDE also appears to be more robust as CLAHE-based models misclassified right lungs in select test images for the left lung model.DiscussionOur results suggest that ps-KDE offers advantages over current preprocessing techniques when segmenting certain lung regions. This could be beneficial in subsequent analysis such as disease classification and risk stratification.
Effectiveness of Omicron XBB.1.5 vaccine against SARS-CoV-2 Omicron XBB and JN.1 infection in a prospective cohort study in the Netherlands, October 2023 to January 2024
Authors: Huiberts Anne J. , Hoeve Christina E. , de Gier Brechje , Cremer Jeroen , van der Veer Bas , de Melker Hester E. , van de Wijgert Janneke H.H.M. , van den Hof Susan , Eggink Dirk , Knol Mirjam J. 
Published: February 2024

AbstractWe estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. VE was 41% (95%CI:23-55) in 18-59-year-olds and 50% (95%CI:44-56) in 60-85-year-olds. Sequencing data in a subset of infections suggests immune escape of the emerging BA.2.86 (JN.1) variant from recent prior infection (OR:2.6; 95%CI:1.1-6.3) and, although not statistically significant, from XBB.1.5 vaccination (OR:1.6; 95%CI:0.9-2.9).A monovalent mRNA vaccine targeting the SARS-CoV-2 Omicron XBB.1.5 subvariant (Comirnaty) was used in the 2023 Dutch COVID-19 vaccination campaign that started on October 2, 2023. Individuals aged ≥60 years, medical risk groups, pregnant women and healthcare workers were eligible for vaccination. Since September 2023, a new Omicron BA.2.86 sub-variant named JN.1 has emerged and quickly became dominant in the Netherlands and globally [1, 2]. BA.2.86 is genetically divergent from the previously circulating XBB variants, indicating potential for immune escape [3].We estimated vaccine effectiveness (VE) of XBB.1.5 vaccination against self-reported SARS-CoV-2 infection between 9 October 2023 and 9 January 2024 among adults aged 18-85 years who had previously received primary vaccination and at least one booster vaccination before 2 October 2023 and were eligible for XBB.1.5 vaccination. To assess potential immune escape by JN.1, we analyzed whether there was an association between XBB.1.5 vaccination or prior infection and the Omicron variant causing the infection (XBB vs. BA.2.86, including JN.1). The variant was determined by sequencing of viral genetic material present in positive lateral flow antigen self-tests.
Prevalence of Microvascular Complications and Associated Risk Factors among Diabetes Mellitus Patients attending Nyeri County Referral Hospital, Kenya: a cross-sectional Study
Authors: Ireri Rachael , Kikuvi Gideon , Mambo susan , cheriro besty 
Published: February 2024

Microvascular complications are one of the major causes of morbidity and mortality worldwide among patients with diabetes mellitus (DM). In Kenya, Nyeri County has the highest prevalence of diabetes mellitus compared to other counties. More than 50% of Nyeri County Referral Hospital (NCRH) admissions result from non-communicable diseases (NCDs) and over 55% of hospital deaths are attributable to NCDs. This study therefore sought to assess the prevalence of microvascular complications and the associated risk factors among patients attending Nyeri County Referral Hospital in Kenya. A hospital-based cross-sectional study was conducted on 314 DM patients on follow-up at NCRH from August 2022 to October 2022. The socio-demographic, anthropometric, biochemical, and clinical data were recorded using a structured survey. All the recruited patients underwent an extensive examination for the presence of Microvascular complications like neuropathy, retinopathy, and nephropathy. Data were analyzed using STATA version 17. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with Microvascular complications of DM. Among the 314 patients with DM, 58% were women. The overall prevalence of Microvascular complications (MVCs) is 36.62%. Diabetic peripheral neuropathy was the most frequent complication (27.4%), followed by retinopathy (10.8%) and nephropathy (8%). Inadequate physical exercise was a risk factor for all MVCs. Age, marital status, and level of education were risk factors for neuropathy while smoking and alcohol intake were risk factors for nephropathy. Additionally marital status was a risk factor for retinopathy. Further, the analysis revealed the risk of non-smokers getting neuropathy reduced by 98% compared to smokers (P-0.0001; CI 0.003058-0.191502). lack of regular physical exercise was significantly associated with retinopathy (P 0.012; CI 0.046816-0.690638). One in ten patients with DM had a microvascular complication. The benefits of microvascular complications prevention should thus be factored into the management of patients with diabetes mellitus.
Multivariate genome-wide association analysis of quantitative reading skill and dyslexia improves gene discovery
Authors: Mountford Hayley S. , Eising Else , Fontanillas Pierre , Auton Adam ,   23andMe Research Team, Irving-Pease Evan K. , Doust Catherine , Bates Timothy C. , Martin Nicholas G. , Fisher Simon E. , Luciano Michelle 
Published: February 2024

AbstractThe ability to read is an important life skill and a major route to education. Individual differences in reading ability are influenced by genetic variation, with a heritability of 0.66 for word reading, estimated by twin studies. Until recently, genomic investigations were limited by modest sample size. Here we use a multivariate genome-wide association study (GWAS) method, MTAG, to leverage summary statistics from two independent GWAS efforts, boosting power for analyses of reading ability; GenLang meta-analysis of word reading (N = 27 180) and the 23andMe, Inc., study of dyslexia (Ncases= 51 800, Ncontrols= 1 087 070). We increase effective sample size to N = 102 082, representing the largest genetic study of reading ability, to date. We identified 35 independent genome-wide significant loci, including 7 regions not previously reported. Single-nucleotide polymorphism (SNP) based heritability was estimated at 24%. We observed clear positive genetic correlations with cognitive and educational measures. Gene-set analyses implicated neuronal synapses and proneural glioblastoma pathways, further supported by enrichment of neuronally expressed genes in the developing embryonic brain. Polygenic scores of our multivariate results predicted between 2.29-3.50% of variance in reading ability in an independent sample, the National Child Development Study cohort (N = 6 410). Polygenic adaptation was examined using a large panel of ancient genomes spanning the last ∼15k years. We did not find evidence of selection, suggesting that reading ability may not have been subject to recent selection pressure in Europeans. By combining existing datasets to improve statistical power, these results provide novel insights into the biology of reading.
Artificial intelligence to facilitate clinical trial recruitment in age-related macular degeneration
Authors: Williamson Dominic J. , Struyven Robbert R. , Antaki Fares , Chia Mark A. , Wagner Siegfried K. , Jhingan Mahima , Wu Zhichao , Guymer Robyn , Skene Simon S. , Tammuz Naaman , Thomson Blaise , Chopra Reena , Keane Pearse A. 
Published: February 2024

AbstractBackgroundRecent developments in artificial intelligence (AI) have positioned it to transform several stages of the clinical trial process. In this study, we explore the role of AI in clinical trial recruitment of individuals with geographic atrophy (GA), an advanced stage of age-related macular degeneration, amidst numerous ongoing clinical trials for this condition.MethodsUsing a diverse retrospective dataset from Moorfields Eye Hospital (London, United Kingdom) between 2008 and 2023 (602,826 eyes from 306,651 patients), we deployed a deep learning system trained on optical coherence tomography (OCT) scans to generate segmentations of the retinal tissue. AI outputs were used to identify a shortlist of patients with the highest likelihood of being eligible for GA clinical trials, and were compared to patients identified using a keyword-based electronic health record (EHR) search. A clinical validation with fundus autofluorescence (FAF) images was performed to calculate the positive predictive value (PPV) of this approach, by comparing AI predictions to expert assessments.ResultsThe AI system shortlisted a larger number of eligible patients with greater precision (1,139, PPV: 63%; 95% CI: 54–71%) compared to the EHR search (693, PPV: 40%; 95% CI: 39– 42%). A combined AI-EHR approach identified 604 eligible patients with a PPV of 86% (95% CI: 79–92%). Intraclass correlation of GA area segmented on FAF versus AI-segmented area on OCT was 0.77 (95% CI: 0.68–0.84) for cases meeting trial criteria. The AI also adjusts to the distinct imaging criteria from several clinical trials, generating tailored shortlists ranging from 438 to 1,817 patients.ConclusionsWe demonstrate the potential for AI in facilitating automated pre-screening for clinical trials in GA, enabling site feasibility assessments, data-driven protocol design, and cost reduction. Once treatments are available, similar AI systems could also be used to identify individuals who may benefit from treatment.
Value sets and the problem of redundancy in value set repositories
Authors: Gold Sigfried , Lehmann Harold P. , Schilling Lisa M. , Lutters Wayne G. 
Published: February 2024

AbstractObjectiveCrafting high-quality value sets is time-consuming and requires a range of clinical, terminological, and informatics expertise. Despite widespread agreement on the importance of reusing value sets, value set repositories suffer from clutter and redundancy, greatly complicating efforts at reuse. When users encounter multiple value sets with the same name or ostensibly representing the same clinical condition, it can be difficult to choose amongst them or determine if any differences among them are due to error or intentional decision.MethodsThis paper offers a view of value set development and reuse based on a field study of researchers and informaticists. The results emerge from an analysis of relevant literature, reflective practice, and the field research data.ResultsQualitative analysis of our study data, the relevant literature, and our own professional experience led us to three dichotomous concepts that frame an understanding of diverse practices and perspectives surrounding value set development:Permissible values versus analytic value sets;Prescriptive versus descriptive approaches to controlled medical vocabulary use; andSemantic and empirical types of value set development and evaluation practices and the data they rely on.This three-fold framework opens up the redundancy problem, explaining why multiple value sets may or may not be needed and advancing academic understanding of value set development.ConclusionThe paper catalogues the methods and practices used and provides practical aid in managing the value set development process. It offers recommendations for improving that process and for software innovation in to support. In order for value set repositories to become more rather than less useful over time, software must channel user efforts into either improving existing value sets or making new ones only when absolutely necessary.