bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing Epilepsy with Normal Interictal EEG Using Dynamic Network Models
Authors: Myers Patrick , Gunnarsdottir Kristin , Li Adam , Razskazovskiy Vlad , Wyeth Dale , Wyeth Edmund , Tillery Alana , Zaghloul Kareem , Inati Sara , Hopp Jennifer , Haridas Babitha , Gonzalez-Martinez Jorge , Bagíc Anto , Kang Joon-yi , Sperling Michael , Barot Niravkumar , Sarma Sridevi V. , Husari Khalil S. 
Published: August 2023

AbstractObjectiveWhile scalp EEG is important for diagnosing epilepsy, a single routine EEG is limited in its diagnostic value. Only a small percentage of routine EEGs show interictal epileptiform discharges (IEDs) and overall misdiagnosis rates of epilepsy are 20-30%. We aim to demonstrate how analyzing network properties in EEG recordings can be used to improve the speed and accuracy of epilepsy diagnosis - even in the absence of IEDs.MethodsIn this multicenter study, we analyzed routine scalp EEGs from 198 patients with suspected epilepsy and normal initial EEGs. The patients’ diagnoses were later confirmed based on an epilepsy monitoring unit (EMU) admission. About 46% ultimately being diagnosed with epilepsy and 54% with non-epileptic conditions. A logistic regression model was trained using spectral and network-derived EEG features to differentiate between epilepsy and non-epilepsy. The model was trained using 10-fold cross-validation on 70% of the data, which was stratified to include equal numbers of epilepsy and non-epilepsy patients in both training and testing groups. The resulting tool was named EpiScalp.ResultsEpiScalp achieved an area under the curve (AUC) of 0.940. The model had an accuracy of 0.904, a sensitivity of 0.835, and a specificity of 0.963 in classifying patients as having epilepsy or not.InterpretationEpiScalp provides accurate diagnostic aid from a single initial EEG recording, even in more challenging epilepsy cases with normal initial EEGs. This may represent a paradigm shift in epilepsy diagnosis by deriving an objective measure of epilepsy likelihood from previously uninformative EEGs.
Investigating the role of the relaxin-3/RXFP3 system in neuropsychiatric disorders and metabolic phenotypes: a candidate gene approach
Authors: Wong Win Lee Edwin , Arathimos Ryan , Lewis Cathryn M. , Young Allan H. , Dawe Gavin Stewart 
Published: August 2023

AbstractThe relaxin-3/RXFP3 system has been implicated in the modulation of depressive- and anxiety-like behaviour in the animal literature; however, there is a lack of human studies investigating this signalling system. We seek to bridge this gap by leveraging the large UK Biobank study to retrospectively assess genetic risk variants linked with this neuropeptidergic system. Specifically, we conducted a candidate gene study in the UK Biobank to test for potential associations between a set of functional, candidate single nucleotide polymorphisms (SNPs) pertinent to relaxin-3 signalling, determined usingin silicotools, and several outcomes, including depression, atypical depression, anxiety and metabolic syndrome. For each outcome, we used several rigorously defined phenotypes, culminating in subsample sizes ranging from 85,881 to 386,769 participants. Across all outcomes, there were no associations between any candidate SNP and any outcome phenotype, following corrections for multiple testing burden. Regression models comprising several SNPs per relevant candidate gene as exploratory variables further exhibited no prediction of outcome. Our findings corroborate conclusions from previous literature about the limitations of candidate gene approaches, even when based on firm biological hypotheses, in the domain of genetic research for neuropsychiatric disorders.
Temporal trends of dengue seroprevalence among children in coastal Kenya, 1998–2018: a longitudinal cohort study
Authors: Karanja Henry K. , Orindi Benedict , Gitonga John N. , Mugo Daisy , Mwai Kennedy , Nyamwaya Doris K. , Omuoyo Donwilliams , Kitsao Barnes S. , Musyoki Jennifer N. , Wambua Julianna , Otieno Edward , Ochola-Oyier Lynette Isabella , Bejon Philip , Warimwe George M. 
Published: August 2023

AbstractSerosurveys suggest widespread dengue virus (DENV) transmission in Africa but there is limited information on the temporal patterns of exposure. Here, we estimated the prevalence and incidence of DENV infections in coastal Kenya over a 20-year period (1998–2018). Sera (n=8038) obtained annually from a longitudinal cohort of 1847 children aged 15 years and below were screened for anti-DENV IgG antibodies. Anti-DENV IgG seroprevalence increased with age and peaked during outbreak years. Among 1354 children who were seronegative at recruitment, we observed an overall incidence (seroconversion) rate of 129.5 (95% CI 118.7–141.4) DENV infections per 1000 person-years. The highest incidence was observed in 2013 at 520 infections per 1000 person-years (95% CI 443.6–610.2) coinciding with a large DENV outbreak in coastal Kenya. Our data suggest long-term DENV exposure among children in coastal Kenya highlighting an urgent need for clinical surveillance to determine the associated health burden in this setting.
Does screening forNeisseria gonorrhoeaeandChlamydia trachomatisaffect the incidence of these infections in men who have sex with men taking HIV pre-exposure prophylaxis (PrEP)Results from a randomized, multicentre controlled trial (the Gonoscreen study)
Authors: Vanbaelen Thibaut , Tsoumanis Achilleas , Florence Eric , Van Dijck Christophe , Huis in ‘t Veld Diana , Sauvage Anne-Sophie , Herssens Natacha , De Baetselier Irith , Rotsaert Anke , Verhoeven Veronique , Henrard Sophie , Van Herrewege Yven , Van den Bossche Dorien , Goffard Jean-Christophe , Padalko Elizaveta , Reyniers Thijs , Vuylsteke Bea , Hayette Marie-Pierre , Libois Agnes , Kenyon Chris 
Published: August 2023

SummaryBackgroundGuidelines recommend three-site (urine, anal, pharynx) three-monthly (3X3 screening) screening for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in men who have sex with men (MSM) taking HIV pre-exposure prophylaxis (PrEP). We present the first randomized controlled trial to compare the effect of screening versus non-screening for NG/CT on the incidence of these infections in MSM taking PrEP.MethodsA multicenter, randomized, controlled trial of 3X3 screening for NG/CT versus non-screening was conducted among MSM taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. NG/CT was tested at each visit in both arms, but results were not provided to the non-screening arm. The primary outcome was the incidence rate (IR) of NG/CT infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% confidence interval of the IR ratio (IRR) was lower than 1.25. The trial protocol was registered atclinicaltrials.gov(NCT04269434).FindingsBetween September 2020 and June 2021, 508 subjects were randomized to the 3X3 screening arm and 506 to the non-screening arm. The overall IR of NG/CT was 0.155 cases/100 person-days (95%CI 0.128-0.186) in the 3×3 screening arm and 0.205 (95%CI 0.171-0.246) in the non-screening arm. The IR was significantly higher in the non-screening arm (IRR 1.318, 95%CI 1.068-1.627). Participants in the non-screening arm had a higher incidence of CT infections and symptomatic CT infections. There were no significant differences in NG infections. Participants in the non-screening arm consumed significantly less antimicrobials. No serious adverse events were reported.InterpretationWe failed to show that non-screening for NG/CT is non-inferior to 3-site 3-monthly screening in MSM taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of NG. Therefore, our findings do not provide strong support for screening for NG/CT in this population.FundingBelgian Healthcare Knowledge Center (KCE - INV18-1133)
Effect of Daytime Nap on Attention, Working Memory, and Recognition Memory
Authors: Zare Shahab , Dortaj Fariborz , Setareh Javad 
Published: August 2023

AbstractDaytime napping has gained attention for its potential to enhance cognitive functions. While the positive impact of nocturnal sleep on cognitive functions is widely acknowledged, limited research has focused on the effects of daytime naps. In this study, we investigated the influence of a 30-minute afternoon nap on cognitive functions in healthy adults.Ten participants (4 females) were involved in both nap and non-nap (control) conditions. Participants were randomly selected from the sleep department of Zare Hospital. During the nap condition, participants engaged in a 30-minute nap at approximately 14:00. Cognitive assessments were performed 30 minutes after the nap to reduce the effects of sleep inertia. Three days after nap condition, cognitive evaluations were conducted again at approximately 15:00, in the non-nap condition.Working memory, evaluated using the Backward Digit Span Task using a paired sample t-test, exhibited significant improvement during napping (p = 0.0164, d = 0.459), highlighting its practical significance. Attention, assessed with the Stroop test, and the Wilcoxon signed-rank test showed significant differences between nap and non-nap conditions, emphasizing napping’s role in sustaining attention and alertness. Recognition memory, gauged through the Auditory Verbal Learning Test, revealed superior performance in the nap condition, particularly in False Alarm scores.Despite limitations such as sample size and nap monitoring, our study contributes valuable insights into the cognitive benefits of daytime napping. By refining our understanding of napping’s effects, tailored interventions can be developed, promoting cognitive health and performance enhancement across various contexts.Iranian Registry of Clinical Trials (IRCT) registration number 66862. Date of registration: 12/31/2022The study was approved by the Research Ethics Committee of Allameh Tabataba’i University (IR.ATU.REC.1401.030).Statements and DeclarationsThe writers confirm that they have no affiliations or engagements with any organization or institution that holds any financial or non-financial interest in the subject matter or materials addressed in this publication.
Designer small molecule control system based on Minocycline induced disruption of protein-protein interaction
Authors: Jha Ram , Kinna Alexander , Hotblack Alastair , Bughda Reyisa , Bulek Anna , Gannon Isaac , Ilca Tudor , Allen Christopher , Lamb Katarina , Dolor Abigail , Parekh Farhaan , Sillibourne James , Cordoba Shaun , Onuoha Shimobi , Thomas Simon , Ferrari Mathieu , Pule Martin 
Published: August 2023

ABSTRACTA versatile, safe, and effective small-molecule control system is highly desirable for clinical cell therapy applications. Therefore, we developed a two-component small-molecule control system based on the disruption of protein-protein interactions using minocycline, an FDA-approved antibiotic with wide availability, excellent bio-distribution, and low toxicity. The system comprises an anti-minocycline single-domain antibody (sdAb) and a minocycline-displaceable cyclic peptide.Here we show how this versatile system can be applied to OFF-switch split CAR systems (MinoCAR) and universal CAR adaptors (MinoUniCAR) with reversible, transient, and dose-dependent suppression; to a tunable T cell activation module based on MyD88/CD40 signaling; to a controllable cellular payload secretion system based on IL-12 KDEL retention and as a cell/cell inducible junction.This work represents an important step forward in the development of a remote-controlled system to precisely control the timing, intensity, and safety of therapeutic interventions.
A framework for decolonising and diversifying biomedical sciences curricula: rediscovery, representation and readiness
Authors: Lu Tianqi , Bashir Zafar I. , Dalceggio Alessia , McKinnon Caroline M. , Miles Lydia , Mosley Amy , Burton Bronwen R. , Robson Alice 
Published: August 2023

AbstractTo date, most efforts to decolonise curricula have focussed on the arts and humanities, with many believing that science subjects are objective, unbiased, and unaffected by colonial legacies. However, research is shaped by cultural and historical context, and inequities exist in funding, publishing and acknowledging scientific achievements. Our curricula reflect these inequities, perpetuating bias to future generations of scientists. We examined attitudes and understanding towards decolonising and diversifying the curriculum among students and teaching staff in the biomedical sciences at the University of Bristol, to discover whether our current teaching practice is perceived as inclusive. We used a mixed methods study including surveys of staff (N=71) and students (N=121) and focus groups. Quantitative data showed that staff and students think decolonising the curriculum is important, but this is more important to female respondents (p<0.001). Students are less aware than staff of current efforts to decolonise the curriculum, while students from minority ethnic groups feel less represented by the curriculum than white students. Thematic analysis of qualitative data revealed three themes that are important for a decolonised curriculum: rediscovery, representation and readiness. We propose that this ‘3Rs framework’ could guide future efforts to decolonise and diversify the curriculum in the biomedical sciences and beyond.
Medulloblastoma-associated DDX3X mutants are oncogenic having a defect in translation-promoting activity but functional in stress granule formation and interferon signaling
Authors: Singh Satishkumar Vishram , Bharambe Harish Shrikrishna , Masurkar Shalaka Arun , Bapat Purna , Gadewal Nikhil , Shirsat Neelam Vishwanath 
Published: August 2023

AbstractDDX3X, a DEAD box-containing RNA helicase, is known to play diverse roles in RNA metabolism, stress response, innate immunity, and cancer. Medulloblastoma is the single most common malignant brain tumor in children. DDX3X is recurrently mutated in the WNT and SHH subgroups of medulloblastoma. CRISPR-Cas9 mediated DDX3X knockout was successful in the HEK293FT cells but generated only non-truncating indels in the medulloblastoma cells suggesting DDX3X is necessary for the viability of the cells. Downregulation of DDX3X expression using shRNA also brought about a considerable reduction in proliferation, clonogenic potential, and anchorage-independent growth of the medulloblastoma cells. Thus, DDX3X expression was found to be essential for the survival, growth, and malignant potential of the medulloblastoma cells consistent with the non-truncating nature of medulloblastoma-associated DDX3X mutations. The medulloblastoma-associated DDX3X mutants were found to be defective in their ability to drive the translation of mRNAs with complex 5’-UTR that is dependent on the ATP-dependent helicase activity of DDX3X. These helicase defective DDX3X mutants could restore the expression of interferon signaling genes and malignant potential lost upon DDX3X knockdown in medulloblastoma cells. Their N-terminal domain is intact and was found to be functional in stress granule formation. DDX3X mutants upregulated expression of malignancy-related genes suggesting tumor suppressive role for the helicase activity in the medulloblastoma pathogenesis. Inhibitors of the N-terminal domain of DDX3X which is essential for the viability of medulloblastoma cells could have therapeutic potential in the treatment of WNT and SHH subgroup medulloblastomas.
Wiskott-Aldrich Syndrome Protein Regulates Nucleolar Organization and Function in Innate Immune Response
Authors: Zhou Xuan , Yuan Baolei , Tian Yeteng , Zhou Juexiao , Wang Mengge , Shakir Ismail , Zhang Yingzi , Bi Chongwei , Aljamal Bayan Mohammed , Hashem Mais O. , Abuyousef Omar Imad , Abdulwahab Firdous Mohammed , Ali Afshan , Dunn Sarah , Moresco James J. , Yates John R. , Frassoni Francesco , Gao Xin , Alkuraya Fowzan S. , Belmonte Juan Carlos Izpisua , Li Mo 
Published: August 2023

ABSTRACTWiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by the dysfunction of the WAS protein (WASP). Using an isogenic macrophage model derived from genome edited induced pluripotent stem cells we demonstrated that WASP functions in the nucleolus, which plays important roles in immune regulation. The absence of WASP resulted in smaller and misshapen nucleoli, decreased fibrillar center territory, and impaired ribosomal RNA (rRNA) transcription. The nucleolar and rRNA phenotypes were confirmed in WAS patient samples. Furthermore, WASP interacts with nucleolar proteins, including nucleophosmin 1 (NPM1) and fibrillarin (FBL). NPM1 deficiency is known to cause elevated cytokine expression following lipopolysaccharide (LPS) stimulation. Consistently, WASP deficient cells displayed lower levels of NPM1 and a heightened inflammatory cytokine response to LPS, which was rescued by overexpressing NPM1. Together, our research provides novel insights into the critical role of WASP in nucleolar function and the modulation of inflammatory cytokine production.
An atypical basement membrane forms a midline barrier during left-right asymmetric gut development in the chicken embryo
Authors: Demler Cora , Lawlor John Coates , Yelin Ronit , Llivichuzcha-Loja Dhana , Shaulov Lihi , Kim David , Stewart Megan , Lee Frank , Shylo Natalia A. , Trainor Paul A. , Schultheiss Thomas , Kurpios Natasza A. 
Published: August 2023

AbstractCorrect intestinal morphogenesis depends on the early embryonic process of gut rotation, an evolutionarily conserved program in which a straight gut tube elongates and forms into its first loops. However, the gut tube requires guidance to loop in a reproducible manner. The dorsal mesentery (DM) connects the gut tube to the body and directs the lengthening gut into stereotypical loops via left-right (LR) asymmetric cellular and extracellular behavior. The LR asymmetry of the DM also governs blood and lymphatic vessel formation for the digestive tract, which is essential for prenatal organ development and postnatal vital functions including nutrient absorption. Although the genetic LR asymmetry of the DM has been extensively studied, a divider between the left and right DM has yet to be identified. Setting up LR asymmetry for the entire body requires aLefty1+ midline barrier to separate the two sides of the embryo, without it, embryos have lethal or congenital LR patterning defects. Individual organs including the brain, heart, and gut also have LR asymmetry, and while the consequences of left and right signals mixing are severe or even lethal, organ-specific mechanisms for separating these signals are poorly understood. Here, we uncover a midline structure composed of a transient double basement membrane, which separates the left and right halves of the embryonic chick DM during the establishment of intestinal and vascular asymmetries. Unlike other basement membranes of the DM, the midline is resistant to disruption by intercalation of Netrin4 (Ntn4). We propose that this atypical midline forms the boundary between left and right sides and functions as a barrier necessary to establish and protect organ asymmetry.
EWSR1’s visual modalities are defined by its association with nucleic acids and RNA polymerase II
Authors: Rajan Soumya Sundara , Ebegboni Vernon J. , Pichling Patricio , Ludwig Katelyn R. , Jones Tamara L. , Chari Raj , Tran Andy , Kruhlak Michael J. , Loncarek Jadranka , Caplen Natasha J. 
Published: August 2023

ABSTRACTWe report systematic analysis of endogenous EWSR1’s cellular organization. We demonstrate that EWSR1, which contains low complexity and nucleic acid binding domains, is present in cells in faster and slower-recovering fractions, indicative of a protein undergoing both rapid exchange and longer-term interactions. The employment of complementary high-resolution imaging approaches shows EWSR1 exists in in two visual modalities, a distributed state which is present throughout the nucleoplasm, and a concentrated state consistent with the formation of foci. Both EWSR1 visual modalities localize with nascent RNA. EWSR1 foci concentrate in regions of euchromatin, adjacent to protein markers of transcriptional activation, and significantly colocalize with phosphorylated RNA polymerase II. Interestingly, EWSR1 and FUS, another FET protein, exhibit distinct spatial organizations. Our results contribute to bridging the gap between our understanding of the biophysical and biochemical properties of FET proteins, including EWSR1, their functions as transcriptional regulators, and the participation of these proteins in tumorigenesis and neurodegenerative disease.SUMMARYRajan et al. report the visualization of endogenous EWSR1. EWSR1 exists in two visual modalities in the nucleoplasm, one distributed and one as foci. Both EWSR1 modalities localize with nascent RNA. EWSR1 foci concentrate in regions of euchromatin and colocalize with phosphorylated RNA polymerase II.
Angpt1 binding to Tie1 regulates the signaling required for lymphatic vessel development in zebrafish
Authors: Morooka Nanami , Gui Ning , Ando Koji , Sako Keisuke , Fukumoto Moe , Hußmann Melina , Schulte-Merker Stefan , Mochizuki Naoki , Nakajima Hiroyuki 
Published: August 2023

ABSTRACTDevelopment of the vascular system is regulated by multiple signaling pathways mediated by receptor tyrosine kinases (RTKs). Among them, Angiopoietin (Ang)/Tie signaling regulates lymphatic and blood vessel development in mammals. Of the two Tie receptors, Tie2 is well known as a key mediator of Ang/Tie signaling, but unexpectedly, recent studies reveal that theTie2locus has been lost in many vertebrate species, while theTie1gene is more commonly present. However, Tie1-driven signaling pathways, including ligands and cellular functions, are not well understood. Here, we performed comprehensive mutant analyses of Angiopoietins and Tie receptors in zebrafish and found that onlyangpt1andtie1mutants show defects in trunk lymphatic vessel development. Among zebrafish Angiopoietins, only Angpt1 binds to Tie1 as a ligand. We indirectly monitored Ang1/Tie1 signaling and detected Tie1 activation in sprouting endothelial cells (ECs), where Tie1 inhibits nuclear import of EGFP-Foxo1a. Angpt1/Tie1 signaling functions in EC migration, proliferation, and lymphatic specification during early lymphangiogenesis, at least in part by modulating Vegfc/Vegfr3 signaling. Thus, we show Angpt1/Tie1 signaling to constitute an essential signaling pathway for lymphatic development in zebrafish.Brief Summary StatementZebrafish Angpt1/Tie1 signaling is characterized as an essential signaling pathway for trunk lymphatic development, with Tie1 regulating Foxo1 localization and modulating Vegfc/Vegfr3 signaling.