bluuebunny/crossref_metadata_2025_split huggingface dataset:
RELAX-Jr: An Automated Pre-Processing Pipeline for Developmental EEG Recordings
Authors: Hill Aron T. , Enticott Peter G. , Fitzgerald Paul B. , Bailey Neil W. 
Published: April 2024

AbstractAutomated EEG pre-processing pipelines provide several key advantages over traditional manual data cleaning approaches; primarily, they are less time-intensive and remove potential experimenter error/bias. Automated pipelines also require fewer technical expertise as they remove the need for manual artifact identification. We recently developed the fully automated Reduction of Electroencephalographic Artifacts (RELAX) pipeline and demonstrated its performance in cleaning EEG data recorded from adult populations. Here, we introduce the RELAX-Jr pipeline, which was adapted from RELAX to be designed specifically for pre- processing of data collected from children. RELAX-Jr implements multi-channel Wiener filtering (MWF) and/or wavelet-enhanced independent component analysis (wICA) combined with the adjusted-ADJUST automated independent component classification algorithm to identify and reduce all artifacts using algorithms adapted to optimally identify artifacts in EEG recordings taken from children. Using a dataset of resting-state EEG recordings (N = 136) from children spanning early-to-middle childhood (4-12 years), we assessed the cleaning performance of RELAX-Jr using a range of metrics including signal-to-error ratio, artifact-to-residue ratio, ability to reduce blink and muscle contamination, and differences in estimates of alpha power between eyes-open and eyes-closed recordings. We also compared the performance of RELAX- Jr against four publicly available automated cleaning pipelines. We demonstrate that RELAX-Jr provides strong cleaning performance across a range of metrics, supporting its use as an effective and fully automated cleaning pipeline for neurodevelopmental EEG data.
Decoding region-level visual functions from invasive EEG data
Authors: Zhang Xin-Ya , Lin Hang , Deng Zeyu , Siegel Markus , Miller Earl K. , Yan Gang 
Published: April 2024

AbstractDecoding vision is an ambitious task as it aims to transform scalar brain activity into dynamic images with refined shapes, colors and movements. In familiar environments, the brain may trigger activity that resembles specific pattern, thereby facilitating decoding. Can an artificial neural network (ANN) decipher such latent patterns? Here, we explore this question using invasive electroencephalography data from monkeys. By decoding multiregion brain activity, ANN effectively captures individual regions’ functional roles as a consequence of minimizing visual errors. For example, ANN recognizes that regions V4 and LIP are involved in visual color and shape processing while MT predominantly handles visual motion, aligning with regional visual functions evident in the brain. ANN likely reconstructs vision by seizing hidden spike patterns, representing stimuli distinctly in a two-dimensional plane. Furthermore, during the encoding process of transforming visual stimuli into neuronal activity, optimal performance is achieved in regions closely associated with vision processing.
DOES QUALITY OF COUNSELING AND EXPOSURE TO FAMILY PLANNING MESSAGES INFLUENCE THE USE OF MODERN CONTRACEPTIVES AMONG WOMEN IN NORTHERN NIGERIA?
Authors: Alabi Matthew , Dougherty Leanne , Etim Eno-Obong , Adedimeji Adebola 
Published: April 2024

ABSTRACTBackgroundFamily Planning Counselling (FPC) involves information exchange on contraceptive methods between a provider and client and providing appropriate support in choosing a method that best suits the client’s needs. Access to sexual and reproductive health information enables women to make informed health decisions. However, the low modern contraceptive prevalence among women in northern Nigeria may be attributed to poor FPC and exposure to FP messages, among other factors. This study examines the impact of quality FPC and exposure to FP messages on modern contraceptive use.MethodsWe conducted a cross-sectional survey of 676 family planning clients aged 15-49 from 163 health facilities in Northern Nigeria. Quantitative data were collected using client exit interviews. The analysis included a binary logistic regression to predict the odds of modern contraceptive use using MII Plus and other explanatory variables.ResultOnly 29% received quality counselling about methods, while 35% were exposed to FP messages. The quality of counselling assessed using MII Plus did not predict modern contraceptive use. However, higher odds of using modern contraceptives were found among clients who reported their provider asked about their previous family planning experience (aOR=3.81; 95% CI: 1.04-13.99) and explained how the selected FP method works (aOR=5.51; 95% CI: 1.11-27.30). Clients who received FP messages from a place of worship (aOR=11.97; 95% CI: 1.76-81.62) and a community ruler (aOR=6.52; 95% CI: 1.02-41.58) had higher odds of using modern contraceptives.ConclusionImproving the quality of FPC and expanding exposure to FP messages through effective community structure can enhance the uptake of modern contraceptives in northern Nigeria.
Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling
Authors: Kentistou Katherine A. , Lim Brandon E. M. , Kaisinger Lena R. , Steinthorsdottir Valgerdur , Sharp Luke N , Patel Kashyap A. , Tragante Vinicius , Hawkes Gareth , Gardner Eugene J. , Olafsdottir Thorhildur , Wood Andrew R. , Zhao Yajie , Thorleifsson Gudmar , Day Felix R. , Ozanne Susan E. , Hattersley Andrew T. , O’Rahilly Stephen , Stefansson Kari , Ong Ken K. , Beaumont Robin N. , Perry John R. B. , Freathy Rachel M. 
Published: April 2024

AbstractInvestigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. Genome-wide association studies of birth weight have highlighted associated variants in more than 200 regions of the genome, but the causal genes are mostly unknown. Rare genetic variants with robust evidence of association are more likely to point to causal genes, but to date, only a few rare variants are known to influence birth weight. We aimed to identify genes that harbour rare variants that impact birth weight when carried by either the fetus or the mother, by analysing whole exome sequence data in UK Biobank participants.We annotated rare (minor allele frequency <0.1%) protein-truncating or high impact missense variants on whole exome sequence data in up to 234,675 participants with data on their own birth weight (fetal variants), and up to 181,883 mothers who reported the birth weight of their first child (maternal variants). Variants within each gene were collapsed to perform gene burden tests and for each associated gene, we compared the observed fetal and maternal effects. We identified 8 genes with evidence of rare fetal variant effects on birth weight, of which 2 also showed maternal effects. One additional gene showed evidence of maternal effects only. We observed 10/11 directionally concordant associations in an independent sample of up to 45,622 individuals (sign testP=0.01).Of the genes identified,IGF1RandPAPPA2(fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling.PPARG, INHBEandACVR1C(all fetal-acting) have known roles in adipose tissue regulation and rare variants in the latter two also showed associations with favourable adiposity patterns in adults. We highlight the dual role ofPPARGin both adipocyte differentiation and placental angiogenesis.NOS3, NRK,andADAMTS8(fetal and maternal-acting) have been implicated in both placental function and hypertension.Analysis of rare coding variants has identified regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, as well as further evidence for the role of insulin-like growth factors.
Effect of pregnancy intention at conception on the continuity of care in maternal healthcare services use in Somalia: Evidence from first national health and demographic survey
Authors: Alam Md Badsha , Khanam Shimlin Jahan , Kabir Md Awal , Khalif Ibrahim Yasin , Khan Md Nuruzzaman 
Published: April 2024

AbstractBackgroundUnintended pregnancies pose a significant challenge to maternal healthcare service utilization and continuity of care (CoC) in low-resource settings. This study investigates the impact of pregnancy intention at conception on CoC in maternal healthcare service use in Somalia.MethodsData comprising 7,079 mothers were extracted from the First National Health and Demographic Survey of Somalia conducted in 2020, with the condition that they had given birth within the three years preceding the survey. Level of Continuity of Care (CoC), categorized as lowest, middle, or highest, in receiving maternal healthcare services, was considered as the explanatory variable and assessed based on the receipt of antenatal healthcare (ANC, <4, ≥4), skilled birth attendance (SBA), and postnatal healthcare (PNC, within 48 hours of birth). Mother’s intention of most recent pregnancy at conception was the primary exposure variable. Unadjusted and adjusted multilevel multinomial logistic regression models were used to assess the effect of unintended pregnancy on the level of CoC completion.ResultsApproximately 38% of live births in Somalia were unintended at conception. Only 2.4% of mothers achieved full CoC, with higher rates observed among those with intended pregnancies (3.0%) compared to those with mistimed (1.6%) or unwanted pregnancies (1.1%). Mothers having mistimed (aOR, 0.59, 95% CI, 0.37-0.95) and unwanted (aOR, 0.28, 95% CI, 0.10-0.79) pregnancies had significantly lower odds of achieving moderate and higher levels of CoC compared to those having intended pregnancies, even after adjusting for socio-demographic factors.ConclusionUnintended pregnancies are associated with lower level of CoC in maternal healthcare service use in Somalia. Strengthening family planning services, promoting contraceptive use, enhancing sexual education, and raising awareness about the importance of maternal healthcare services are essential steps to reduce unintended pregnancies and improve maternal and child health outcomes in the country.
Investigating the relationship between DNA methylation, genetic variation, and suicide attempt in bipolar disorder
Authors: Alrfooh Aysheh , Casten Lucas G. , Richards Jenny Gringer , Wemmie John A. , Magnotta Vincent A. , Fiedorowicz Jess G. , Michaelson Jacob , Williams Aislinn J. , Gaine Marie E. 
Published: April 2024

AbstractIndividuals with bipolar disorder are at increased risk for suicide, and this can be influenced by a range of biological, clinical, and environmental risk factors. Biological components associated with suicide include DNA modifications that lead to changes in gene expression. Common genetic variation and DNA methylation changes are some of the most frequent types of DNA findings associated with an increased risk for suicidal behavior. Importantly, the interplay between genetic predisposition and DNA methylation patterns is becoming more prevalent in genetic studies. We hypothesized that DNA methylation patterns in specific loci already genetically associated with suicide would be altered in individuals with bipolar disorder and a history of suicide attempt. To test this hypothesis, we searched the literature to identify common genetic variants (N=34) previously associated with suicidal thoughts and behaviors in individuals with bipolar disorder. We then created a customized sequencing panel that covered our chosen genomic loci. We profiled DNA methylation patterns from blood samples collected from bipolar disorder participants with suicidal behavior (N=55) and without suicidal behavior (N=51). We identified seven differentially methylated CpG sites and five differentially methylated regions between the two groups. Additionally, we found that DNA methylation changes inMIFandCACNA1Cwere associated with lethality or number of suicide attempts. Finally, we identified three meQTLs inSIRT1,IMPA2, andINPP1. This study illustrates that DNA methylation is altered in individuals with bipolar disorder and a history of suicide attempts in regions known to harbor suicide-related variants.
Ventral frontostriatal circuitry mediates the computation of reinforcement from symbolic gains and losses
Authors: Tang Hua , Bartolo Ramon , Averbeck Bruno B. 
Published: April 2024

SUMMARYReinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens. We then recorded simultaneously from the orbitofrontal cortex (OFC), ventral striatum (VS), amygdala (AMY), and the mediodorsal thalamus (MDt). We found that the OFC played a dominant role in coding token outcomes and token prediction errors. The other areas contributed complementary functions with the VS coding appetitive outcomes and the AMY coding the salience of outcomes. The MDt coded actions and relayed information about tokens between the OFC and VS. Thus, OFC leads the process of symbolic reinforcement learning in the ventral frontostriatal circuitry.
Identification of markers for the isolation of neuron-specific extracellular vesicles
Authors: Ter-Ovanesyan Dmitry , Whiteman Sara , Gilboa Tal , Kowal Emma JK , Trieu Wendy , Iyer Siddharth , Budnik Bogdan , Babila Clarissa May , Heimberg Graham , Burgess Michael W , Keshishian Hasmik , Carr Steven A , Regev Aviv , Church George M , Walt David R 
Published: April 2024

AbstractExtracellular vesicles (EVs) are released by all cells and contain RNA and protein from their cell of origin. EVs in biofluids could be used as diagnostic biomarkers to non-invasively report the state of inaccessible cells, such as neurons in the brain. As biofluids such as cerebrospinal fluid (CSF) and plasma contain EVs originating from many different cells, isolating cell type-specific EVs and measuring their cargo could help determine the state of specific cell types. Here, we demonstrate an approach aiming to immuno-isolate EVs from neurons based on neuron-derived protein surface markers. We first developed a framework to select transmembrane proteins suitable as neuron-specific EV markers based on gene expression and EV proteomics data. Leveraging a novel, high-purity EV isolation method we developed, we further cataloged the proteins present on EVs in human CSF and plasma. Using ultrasensitive immunoassays against several of the predicted neuron-specific proteins, we confirmed one marker, NRXN3 as present on EVs in CSF and plasma by size exclusion chromatography (SEC) and density gradient centrifugation (DGC). Finally, we developed efficient EV immuno-isolation methods and applied them to isolate NRXN3+EVs. Our study provides a general methodology for the isolation of cell-type specific EVs and paves the way for the use of neuron-derived EVs to study and diagnose neurological disease.
A genomic duplication spanning multiple P450s contributes to insecticide resistance in the dengue mosquitoAedes aegypti
Authors: Bacot Tiphaine , Haberkorn Chloé , Guilliet Joseph , Cattel Julien , Kefi Mary , Nadalin Louis , Filee Jonathan , Boyer Frederic , Gaude Thierry , Laporte Frederic , Tutagata Jordan , Vontas John , Dusfour Isabelle , Bonneville Jean-Marc , David Jean-Philippe 
Published: April 2024

AbstractResistance of mosquitoes to insecticides is one example of rapid adaptation to anthropogenic selection pressures having a strong impact on human health and activities. Target-site modification and increased insecticide detoxification are the two main mechanisms underlying insecticide resistance in mosquitoes. While target-sites mutations are well characterised and often used to track resistance in the field, the genomic events associated with insecticide detoxification remain partially characterised. Recent studies evidenced the key role of gene duplications in the over-expression of detoxification enzymes and their potential use to track metabolic resistance alleles in the field. However, such genomic events remain difficult to characterise due to their complex genomic architecture and their co-occurrence with other resistance alleles. In this concern, the present work investigated the role of a large genomic duplication affecting a cluster of detoxification enzymes in conferring resistance to the pyrethroid insecticide deltamethrin in the mosquitoAedes aegypti.Two isofemale lines originating from French Guiana and being deprived from major target-site mutations showed distinct insecticide resistance levels. Combining RNA-seq and whole genome pool-seq identified a 220 Kb genomic duplication enhancing the expression of multiple contiguous cytochrome P450s in the resistant line. The genomic architecture of the duplicated loci was elucidated through long read sequencing, evidencing its transposon-mediated evolutionary origin. The involvement of this P450 duplication in deltamethrin survival was supported by a significant phenotypic response to the P450 inhibitor piperonyl butoxide together with genotype-phenotype association and RNA interference. Experimental evolution suggested that this P450 duplication is associated with a significant fitness cost, potentially affecting its adaptive value in presence of other resistance alleles.Overall, this study supports the importance of genomic duplications affecting detoxification enzymes in the rapid adaptation of mosquitoes to insecticides. Deciphering their genomic architecture provides new insights into the evolutionary processes underlying such rapid adaptation. Such findings provide new tools for the surveillance and management of resistance in the field.
Functional reorganization of brain regions supporting non-adjacent dependency learning across the first half year of life
Authors: Cai Lin , Hakuno Yoko , Hata Masahiro , Hoshino Ei-ichi , Arimitsu Takeshi , Shinohara Naomi , Takahashi Takao , Watson Stuart , Townsend Simon , Mueller Jutta L. , Minagawa Yasuyo 
Published: April 2024

AbstractPre-babbling infants can track nonadjacent dependencies (NADs) in the auditory domain. While this forms a crucial prerequisite for language acquisition, the neurodevelopmental origins of this ability remain unknown. We applied functional near- infrared spectroscopy in neonates and 6-7-month-old infants to investigate the neural substrate supporting NAD learning using tone sequences in an artificial grammar learning paradigm. Detection of NADs was indicated by left prefrontal activation in neonates while by left supramarginal gyrus (SMG), superior temporal gyrus (STG), and inferior frontal gyrus activation in 6-7-month-olds. Functional connectivity analyses further indicated that the neonate activation pattern during the test phase benefited from a brain network consisting of prefrontal regions, left SMG and STG during the rest and learning phases. These findings suggest a left-hemispheric learning-related functional brain network may emerge at birth and be strengthened by complex auditory input across the first half year of life, providing a neural basis for language acquisition.
WITHDRAWN: Discovery of a potent inhibitor that suppresses glioblastoma by dual targeting of both syntenin PDZ domains
Authors: Heo Yunseok , Moon Jihoon , Lee Jisoo , Kim Minsup , Ko Yoon-Joo , Kim Kyung Hwan , Yoon Ki-Jun , Koo Bon-Kyoung , Shariff Fairolniza Mohd , Yun Ji-Hye , Lee Weontae 
Published: April 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to correct and validate the errors before resubmitting. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Onco-Circuit Addiction and Onco-Nutrient mTORC1 Signaling Vulnerability in a Model of Aggressive T Cell Malignancy
Authors: Wang Xinxin , Cornish Andrew E. , Do Mytrang H. , Brunner Julia S. , Hsu Ting-Wei , Xu Zijian , Malik Isha , Edwards Chaucie , Capistrano Kristelle J. , Zhang Xian , Ginsberg Mark H. , Finley Lydia W.S. , Lim Megan S. , Horwitz Steven M. , Li Ming O. 
Published: April 2024

SUMMARYHow genetic lesions drive cell transformation and whether they can be circumvented without compromising function of non-transformed cells are enduring questions in oncology. Here we show that in mature T cells—in which physiologic clonal proliferation is a cardinal feature— constitutiveMYCtranscription andTsc1loss in mice modeled aggressive human malignancy by reinforcing each other’s oncogenic programs. This cooperation was supported by MYC-induced large neutral amino acid transporter chaperone SLC3A2 and dietary leucine, which in synergy withTsc1deletion overstimulated mTORC1 to promote mitochondrial fitness and MYC protein overexpression in a positive feedback circuit. A low leucine diet was therapeutic even in late-stage disease but did not hinder T cell immunity to infectious challenge, nor impede T cell transformation driven by constitutive nutrient mTORC1 signaling viaDepdc5loss. Thus, mTORC1 signaling hypersensitivity to leucine as an onco-nutrient enables an onco-circuit, decoupling pathologic from physiologic utilization of nutrient acquisition pathways.
Zebrafish Foxl2l suppresses stemness of germline progenitors and directs feminization
Authors: Hsu Chen-wei , Ho Hao , Yang Ching-Hsin , Wang Yan-wei , Li Ker-Chau , Chung Bon-chu 
Published: April 2024

AbstractZebrafish is an important organism for genetic studies, but its germ cell types and the mechanism of sex differentiation remain elusive. Here, we conducted a single-cell transcriptomic profiling and charted a developmental trajectory going from germline stem cells, through early, committed, and late progenitors, to pre-meiotic and meiotic cells. A transcription factor, Foxl2l, is expressed in the progenitors committed to the ovary fate. CRISPR-Cas9-mediated mutation offoxl2lproduced 100% male fish with normal fertility. Another single-cell profiling offoxl2l-/-germ cells reveals the arrest of early progenitors. Concomitantly the expression ofnanos2(stem cell marker) andid1(transcription repressor in stem cells) was elevated together with an increase ofnanos2+germ cell infoxl2lmutants, indicating the reversion to the stem cell state. Thus, we have identified developmental stages of germ cells in juvenile zebrafish and demonstrated that Foxl2l drives zebrafish germ cell progenitors toward feminization and prevents them from reverting back to the stem cell state.
Redox Conduction Through Cytochrome ‘Nanowires’ Can Sustain Cellular Respiration
Authors: Guberman-Pfeffer Matthew J. 
Published: April 2024

AbstractMicron-scale electron transfer through polymeric cytochrome ‘nanowires’ powers prokaryotic life from hydrothermal vents to terrestrial soils in ways not fully understood. Herein, six reduction potentials from recently reported spectroelectrochemistry are each assigned with <0.04 eV to the cryogenic electron microscopy structure of the hexa-heme homopolymeric outer-membrane cytochrome type S (OmcS) fromGeobacter sulfurreducensusing hybrid quantum/classical computations. The unambiguous assignments define a reversible free energy ‘roller-coaster’ that is dynamically modulated by <0.1 V under the flow of electrons due to redox cooperativities between adjacent hemes. A physiologically relevant tens to hundreds of filaments are predicted to suffice for cellular respiration by pairing, in the context of non-adiabatic Marcus theory, the free energy landscape with reorganization energies that account for active site or protein-water electronic polarizability, and electronic couplings characteristic of the highly conserved heme packing motifs. General considerations on protein electron transfer and comparison to all known cytochrome ‘nanowires’ suggest the mechanistic insights are broadly applicable to multi-heme cytochromes in all kingdoms of life.