bluuebunny/crossref_metadata_2025_split huggingface dataset:
Larger perivascular space volume fraction is associated with worse post-stroke sensorimotor outcomes: An ENIGMA analysis
Authors: Chakraborty Stuti , Choupan Jeiran , Marin-Pardo Octavio , Khan Mahir H. , Barisano Giuseppe , Tavenner Bethany P. , Donnelly Miranda R. , Abdullah Aisha , Andrushko Justin W. , Banaj Nerisa , Borich Michael R. , Boyd Lara A. , Buetefisch Cathrin M. , Conforto Adriana B. , Cramer Steven C. , Domin Martin , Adrienne Dula A. , Ferris Jennifer K. , Hordacre Brenton , Kautz Steven A. , Jahanshad Neda , Lotze Martin , Nishimura Kyle , Piras Fabrizio , Revill Kate P. , Schweighofer Nicolas , Soekadar Surjo R. , Srivastava Shraddha , Thomopoulos Sophia I. , Vecchio Daniela , Westlye Lars T. , Winstein Carolee J. , Wittenberg George F. , Wong Kristin A. , Thompson Paul M. , Liew Sook-Lei 
Published: December 2024

ABSTRACTBACKGROUNDPerivascular Spaces (PVS) are a marker of cerebral small vessel disease (CSVD) that are visible on brain imaging. Larger PVS has been associated with poor quality of life and cognitive impairment post-stroke. However, the association between PVS and post-stroke sensorimotor outcomes has not been investigated.METHODS602 individuals with a history of stroke across 24 research cohorts from the ENIGMA Stroke Recovery Working Group were included. PVS volume fractions were obtained using a validated, automated segmentation pipeline from the basal ganglia (BG) and white matter centrum semiovale (CSO), separately. Robust mixed effects regressions were used to a) examine the cross-sectional association between PVS volume fraction and post-stroke sensorimotor outcomes and b) to examine whether PVS volume fraction was associated with other measures of CSVD and overall brain health (e.g., white matter hyperintensities [WMHs], brain age [measured by predicted age difference, brain-PAD]).RESULTSLarger PVS volume fraction in the CSO, but not BG, was associated with worse post-stroke sensorimotor outcomes (b = -0.06, p = 0.047). Higher burden of deep WMH (b = 0.25, p <0.001), periventricular WMH (b = 0.16, p <0.001) and higher brain-PAD (b = 0.09, p <0.001) were associated with larger PVS volume fraction in the CSO.CONCLUSIONSOur data show that PVS volume fraction in the CSO is cross-sectionally associated with sensorimotor outcomes after stroke, above and beyond standard lesion metrics. PVS may provide insight into how the overall vascular health of the brain impacts inter-individual differences in post-stroke sensorimotor outcomes.
Systematic review and individual patient data meta-analysis on glucose- 6 – phosphate dehydrogenase activities measured by a semi-quantitative handheld Biosensor
Authors: Ley Benedikt , Vasquez Laura Rojas , Sitsabasan Avyinaeesh , Adhikari Bipin , Adhikari Nabaraj , Alam Mohammad Shafiul , Das Santasabuj , Ghimire Prakash , Lacerda Marcus V. G. , Price Ric N. , Rijal Komal Raj , von Seidlein Lorenz , Talukdar Arunansu , Thriemer Kamala , Satyagraha Ari Winasti , Sadhewa Arkasha , Rajasekhar Megha , Commons Robert J. 
Published: December 2024

AbstractMeasurement of glucose-6-phosphate dehydrogenase (G6PD) activity guides hypnozoitocidal treatment ofP. vivaxmalaria. The G6PD Standard (SDBiosensor, Republic of Korea) here referred to as “Biosensor” is a quantitative point-of-care diagnostic that measures G6PD activity in U/gHb . The manufacturer recommends cutoffs to define G6PD deficient (≤4.0U/gHb), intermediate (4.1-≤6.0U/gHb) and normal (>6.0U/gHb) individuals. The aim of this individual patient data (IPD) meta- analysis was to evaluate these cutoffs (CRD42023406595).A systematic review identified studies reporting population-level G6PD activity measured by Biosensor, published between January 2017 and May 2023. IPD were collated and standardised. The adjusted male median (AMM) was defined as 100% activity and calculated across all studies (universal AMM) and separately for each setting. The proportion of participants classified as deficient or intermediate were compared using the manufacturer-recommended cutoffs and 30% and 70% of the universal AMM and setting-specific AMM. Associations between G6PD activity and blood sampling method, malaria status, and age were assessed.Eleven studies with 9,724 participants from eight countries were included in this analysis. The universal AMM was 7.7U/gHb and the setting-specific AMMs ranged from 6.2U/gHb to 9.9U/gHb. When using the universal AMM, 4.2% of participants were classified as deficient and 11.9% as intermediate or deficient. The corresponding values were 3.9% and 10.8% for setting-specific cutoffs, and 7.2% and 18.3% for manufacturer-recommended definitions for deficients and intermediates respectively. The manufacturer-recommended cutoff for deficient individuals fitted the distribution of G6PD activities better than definitions based on the percentage of AMM. There was no significant association between malaria status or blood sampling method and G6PD activity. Measured G6PD activity decreased in children 1 to 5 years and plateaued thereafter.The manufacturer’s recommended cutoff is conservative but more reliable at categorising G6PD deficient individuals than those based on calculations of 30% activity using the AMM. The observed decrease in G6PD activity in children between 1 to 5 years of age warrants further investigation.
Causation and prevention in epidemiology: assumptions, derivations, and measures old and new
Authors: Allard Robert 
Published: December 2024

AbstractEpidemiologic measures quantifying the causative or the preventive effect of a particular agent with respect to a given disease are frequently used, but the set of assumptions on which they rest, and the consequences of these assumptions, are not widely understood. We present a rigorous derivation of these measures from the sufficient-causes model of disease occurrence and from the definition of causation as the bringing forward of the occurrence time of an event. This exercise brings out the fact that an understanding of the assumptions underpinning all measures of effect, and of the extent to which they may or may not be met, is necessary to their prudent interpretation. We also introduce a new measure, discarding 1) the sufficient-causes model and 2) the assumption that the agent can only be either causative or preventive, relative to a given disease, but not both. Some may consider this more acceptable than having to decide, on slim or no evidence, that the agent has only one kind of effect on the disease. In any case, I submit that epidemiology should eventually discard the concept of causation, as has been done in some other basic sciences, and replace it with the adequate modeling of disease-producing processes, in individuals and populations.
Antiviral activity of Tecovirimat against Mpox virus clades 1a, 1b, 2a and 2b
Authors: Postal Jeanne , Guivel-Benhassine Florence , Porrot Françoise , Grassin Quentin , Crook Jack M. , Vernuccio Riccardo , Caro Valérie , Vanhomwegen Jessica , Guardado-Calvo Pablo , Simon-Lorière Etienne , Dacheux Laurent , Manuguerra Jean-Claude , Schwartz Olivier 
Published: December 2024

AbstractThe recent Mpox virus (MPXV) outbreak was caused by a novel and more pathogenic clade 1b virus. We compared the antiviral efficacy of Tecovirimat in cell culture, against the two ancestral clades 1a and 2a, the clade 2b that circulated in 2022, and the recent clade 1b virus. We report that Tecovirimat similarly inhibits the replication of all four MPXV clades, at nanomolar concentrations (nM). Our results suggest that Tecovirimat remains a therapeutic option against the latest clade 1b virus.
Genome sequencing reveals the impact of non-canonical exon inclusions in rare genetic disease
Authors: Pitsava Georgia , Hawley Megan , Auriga Light , de Dios Ivan , Ko Arthur , Marmolejos Sofia , Almalvez Miguel , Chen Ingrid , Scozzaro Kaylee , Zhao Jianhua , Barrick Rebekah , Mew Nicholas Ah , Fusaro Vincent A. , LoTempio Jonathan , Taylor Matthew , Mestroni Luisa , Graw Sharon , Milewicz Dianna , Guo Dongchuan , Murdock David R. , Bujakowska Kinga M. ,   UCI-GREGoR Consortium, Xiao Changrui , Délot Emmanuèle C. , Berger Seth I. , Vilain Eric 
Published: December 2024

AbstractIntroductionAdvancements in sequencing technologies have significantly improved clinical genetic testing, yet the diagnostic yield remains around 30-40%. Emerging sequencing technologies are now being deployed in the clinical setting to address the remaining diagnostic gap.MethodsWe tested whether short-read genome sequencing could increase diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive clinical genetic testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing.ResultsWe sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) of them. Of these diagnoses, 55.5% were previously missed because the causative variants were in regions not interrogated by the original testing. In 9 cases, they were deep intronic variants, 5 of which led to abnormal splicing and cryptic exon inclusion, as directly shown by RNA sequencing. All 5 of these variants had inconclusive spliceAI scores. In 26% of newly diagnosed cases, the causal variant could have been detected by exome sequencing reanalysis.ConclusionGenome sequencing overcomes multiple limitations of clinical genetic testing, such as inability to call intronic variants and technical limitations. Our findings highlight cryptic exon inclusion as a common mechanism via which deep intronic variants cause Mendelian disease. However, they also reinforce that reanalysis of exome datasets can be a fruitful approach.
Functional network dynamics in photosensitive epilepsy depend on stimulation frequency and photosensitivity type
Authors: Timar Lili , Deplazes Sina , Bothmann Julia , Renzel Roland , Ledergerber Debora , Dubcek Tena , Imbach Lukas 
Published: December 2024

AbstractObjectiveTo describe the underlying dynamical mechanisms of photosensitive epilepsy (PSE) and different photosensitivity types.MethodsThis retrospective study included healthy controls (HC), non-PSE patients with epilepsy (PWE), and PSE patients. All participants were stimulated with flickering white light (1-60Hz) under 10-20 EEG monitoring.ResultsWe observed significantly higher occipital Photoparoxysmal response (PPR) power in PSE patients compared to HC for stimulation frequencies 10Hz-20Hz. This activity was highest in Type 4, which shows a type-specific variation of the PPR. However, the excitability of the visual cortex, investigated by the occipital transient (P100) and steady-state visual evoked potentials (ssVEP), remained unchanged in most PSE types compared to HC and to PWE. The ssVEP power only increased significantly in Type 4 compared to HC. Instead, PSE patients showed apparent differences in functional connectivity in the PPR band (3-4Hz) with hypoconnected centro-parietal regions and hyperconnected anterior and anterio-posterior areas compared to HC and PWE for stimulation frequencies 10Hz-20Hz.ConclusionPSE is a network effect modulated by hyperconnected anterior and anterio-posterior regions, accompanied by a hyperexcitable visual cortex.SignificanceWe provide novel evidence that altered network dynamics in PSE patients are likely a prerequisite for the propagation of the PPR and type-specific responses.
Mouse brain organoids modelin vivoneurodevelopment and function and capture differences to human
Authors: Lloyd-Davies Sánchez Daniel J , Lindhout Feline W , Anderson Alexander J , Pellegrini Laura , Lancaster Madeline A 
Published: December 2024

AbstractIn the last decade since their emergence, brain organoids have offered an increasingly popular and powerful model for the study of early development and disease in humans. These 3D stem cell-derived models exist in a newer space at the intersection ofin vivoand 2Din vitromodels. Functional benchmarking has so far remained largely uncharacterised however, leaving the extent to which these models may accurately portrayin vivoprocesses still yet to be fully realised. Here we present a standardised unguided protocol to generate brain organoids from mice, the most commonly-usedin vivomammalian model; and in parallel establish a guided protocol for generating region-specific choroid plexus mouse organoids. Both unguided and guided mouse organoids progress through neurodevelopmental stages with anin vivo-like tempo and recapitulate species-specific characteristics of neural and choroid plexus development, respectively. Neuroepithelial cells generate neural progenitors that give rise to different neural subtypes including deep-layer neurons, upper-layer neurons, and glial cells. We further adapted protocols to prolong mouse cerebral organoid (CO) cultures as slices at the air-liquid interface (ALI), enhancing accessibility for long-term studies and functional investigations. In mature mouse ALI-COs, we observed mature glia, as well as synaptic structures and long-range axon tracts projecting to distant regions, suggesting an establishment and maturation of neural circuitry. Indeed, functional analyses with high-density multi-electrode arrays (HD-MEAs) indicate comparable activity toex vivoorganotypic mouse brain slices. Having established protocols for both region-specific and unpatterned mouse brain organoids, we demonstrate that their neurodevelopmental trajectories, and resultant mature features, closely mimic thein vivomodels to which they are benchmarked across multiple biochemical, morphological, and functional read-outs. We propose that mouse brain organoids are a valuable model for functional studies, and provide insight into how closely brain organoids of other species, such as human, may recapitulate their own respectivein vivodevelopment.
Induction of an early IFN-γ cellular response and high plasma levels of SDF-1α are inversely associated with COVID-19 severity and residence in rural areas in Kenyan patients
Authors: Wanjiku perpetual Njeri , Orindi Benedict , Kimotho John , Sayed Shahin , Shah Reena , Saleh Mansoor , Mwacharo Jedidah , Maronga Christopher , Olouch Vivianne , Karanu Ann , Shah Jasmit , Nneka Zaitun , Ochola-Oyier Lynette Isabella , Abdi Abdirahman I. , Dunachie Susanna , Bejon Philip , Nduati Eunice , Ndungu Francis M. 
Published: December 2024

Introduction COVID-19 was less severe in Sub-Saharan Africa (SSA) compared with Europe and North America. It is unclear whether these differences could be explained immunologically. Here we determined the levels of ex vivo SARS-CoV-2 peptide-specific IFN-γ producing cells, and levels of plasma cytokines and chemokines over the first month of COVID-19 diagnosis among Kenyan COVID-19 patients from urban and rural areas. Methods Between June 2020 and August 2022, we recruited and longitudinally monitored 188 COVID-19 patients from two regions in Kenya, Nairobi (urban, n = 152) and Kilifi (rural, n = 36), with varying levels of disease severity ­– severe, mild/moderate, and asymptomatic. IFN-γ secreting cells were enumerated at 0-, 7-, 14- and 28-days post diagnosis by an ex vivo enzyme-linked immunospot (ELISpot) assay following in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with overlapping peptides from several SARS-CoV-2 proteins. A multiplexed binding assay was used to measure the levels of 22 plasma cytokines and chemokines. Results Higher frequencies of IFN-γ-secreting cells against the SARS-CoV-2 spike peptides were observed on the day of diagnosis among the asymptomatic compared to the patients with severe COVID-19. Higher concentrations of 17 of the 22 cytokines and chemokines measured were positively associated with severe disease, and in particular interleukin (IL)-8, IL-18 and IL-1ra (p<0.0001), while a lower concentration of SDF-1α was associated with severe disease (p<0.0001). Concentrations of 8 and 16 cytokines and chemokines including IL-18 were higher among Nairobi asymptomatic and mild patients compared to their respective Kilifi counterparts. Conversely, the concentrations for SDF-1α were higher in rural Kilifi compared to Nairobi (p=0.012). Conclusion In Kenya, as seen elsewhere, pro-inflammatory cytokines and chemokines were associated with severe COVID-19, while an early IFN-γ cellular response to overlapping SARS-CoV-2 spike peptides was associated with reduced risk of disease. Living in urban Nairobi (compared with rural Kilifi) was associated with increased levels of pro-inflammatory cytokines/chemokines.
Development and Feasibility Evaluation of a Telehealth System (Impak Sihat) to Empower Rural Population in Malaysia on the Quality Use of Medicines
Authors: Nazar Nor Ilyani Mohamed , Rahman Norny Syafinaz Ab , Alias Nor Elina , Zaini Syahrir , Kamil Tg Karmila Tg Mohd , Jamani Nurjasmine Aida , Elnaem Mohamed Hassan 
Published: December 2024

AbstractThe global rise of chronic diseases necessitates quality use of medicines (QUM) and adherence for effective management. Insufficient QUM understanding among patients adversely affects healthcare outcomes in Malaysia. High rates of irrational medication use, particularly in rural areas, are influenced by various factors. Continuous engagement from healthcare providers is essential, potentially facilitated by a tailored telehealth system. This study aimed to design a customized telehealth system for Malaysia’s rural population and assess patient experiences and acceptance. The study comprised three phases: i) a qualitative pre-development phase exploring internet access and health information-seeking behaviours; ii)development of the telehealth system (Impak Sihat-healthy impact) based on identified needs; and iii) a post-development feasibility evaluation of the Impak Sihat system through community demonstration and validated questionnaires. Fifteen respondents were interviewed during the pre-development phase, achieving saturation and revealing insights on health issues, internet usage, social media preferences, and technology literacy. A customized telehealth system was developed, addressing the identified needs with relevant content and resources. Following system development, a feasibility study with 77 participants indicated acceptable scores of 73 to 87% across six domains. However, older age was significantly linked to lower scores in the ‘User-friendly features and ease of learning and understanding’ domain (p<0.01). The telehealth system effectively meets Malaysia’s rural population’s needs and has been successfully developed. To optimize this system’s effectiveness, considerations regarding older age, socioeconomic status, internet reliability, and information confidentiality must be addressed.
Different Methods of Ankle-Brachial Index Calculation on the Prevalence of Peripheral Arterial Disease and Arterial Calcification in Subjects with Type 2 Diabetes Mellitus from a Public Hospital in Peru
Authors: Espinoza-Enciso Luis Fernando , Hernández-Gozar Iván Gonzalo , Zuñiga-Baldarrago Kevin Clared , Lozano-Purizaca Robert , Briceño-Alvarado Manolo , Yovera-Aldana Marlon 
Published: December 2024

AbstractObjectiveTo determine the frequency of peripheral arterial disease (PAD) and arterial calcification (AC) using three methods of ankle-brachial index (ABI) in patients with type 2 diabetes mellitus.MethodologyA descriptive cross-sectional study using data from the Foot at Risk Program of the Endocrinology Department at Hospital María Auxiliadora from 2015 to 2020. We calculated the ABI for each lower limb using the lowest, highest, or average systolic pressure from the dorsalis pedis or posterior tibial artery in the ipsilateral leg. We defined PAD if any ABI from either leg was <0.9; AC if ABI was >1.3; and the rest were classified as normal. We calculated the prevalence of PAD and AC for each ABI method and assessed differences between ABI categories based on clinical variables using the chi-square or Fisher’s exact test.ResultsWe included 643 subjects with a mean age of 61.4 years, 69.8% female. The prevalence of PAD was 7.8%, 15.4%, and 28.2% using the highest, average, or lowest systolic pressure as the numerator in the ABI, respectively. The highest prevalence of PAD occurred with the lowest pressure and the lowest with the highest pressure. AC was observed in 18.2%, 11%, and 16.2%, and normal values were 74%, 73.6%, and 55.7%. In all three methods, PAD was associated with older age and AC was associated with longer duration of diabetes.ConclusionsUsing different ABI methods, we observed a prevalence of PAD ranging from 7.8% to 28%, and a prevalence of CA between 11% and 18% among patients with type 2 diabetes mellitus at a public hospital in Peru. Further research is necessary to verify if the new ABI calculation methods provide improved accuracy in predicting complications.
The significance of molecular heterogeneity in breast cancer batch correction and dataset integration
Authors: Moir Nicholas , Pearce Dominic A. , Langdon Simon P. , Simpson T. Ian 
Published: December 2024

AbstractBreast cancer research benefits from a substantial collection of gene expression datasets that are commonly integrated to increase analytical power. Gene expression batch effects arising between experimental batches, where signal differences confound true biological variation, must be addressed when integrating datasets and several approaches exist to address these technical differences. This brief communication study clearly demonstrates that popular batch correction techniques can significantly distort key biomarker expression signals. Through the implementation of ComBat batch correction and evaluation of integrated expression values, we profile the extent of these distortions and consider an additional mitigatory batch correction step. We demonstrate that leveraginga prioriknowledge of sample molecular subtype classification can optimally remove batch effect distortion while preserving key biomarker expression variation and transcriptional legitimacy. To the best of our knowledge, this study presents the first analysis of the interplay between dataset molecular composition and the concomitant robustness of integrated, batch-corrected biological expression signal.