bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood Hepatitis B Immunization Coverage and Barriers in Sierra Leone, Liberia, and Guinea: Analysis of National Surveys (2018-2020)
Authors: Yendewa George A. , James Peter B. , Mohareb Amir M. , Barrie Umaru , Massaquoi Samuel P.E. , Yendewa Sahr A. , Ghazzawi Manal , Bockarie Tahir , Cumming Peterlyn E. , Diallo Ibrahima S. , Johnson Ambulai , Vohnm Benjamin , Babawo Lawrence S. , Deen Gibrilla F. , Kabba Mustapha , Sahr Foday , Lakoh Sulaiman , Salata Robert A. 
Published: March 2023

ABSTRACTVaccination against hepatitis B virus (HBV) is effective at preventing mother-to-child transmission. Sierra Leone, Liberia and Guinea are hyperendemic West African countries; yet childhood immunization coverage is suboptimal and barriers to immunization are poorly understood. We analyzed national survey data (2018-2020) of children aged 4-35 months to assess full HBV immunization (receiving 3 doses of the pentavalent vaccine) and incomplete immunization (receiving < 3 doses). Statistical analysis was conducted using the complex sample command in SPSS (version 28). Multivariate logistic regression was used to identify determinants of incomplete immunization. Overall, 11181 mothers were analyzed (4846 from Sierra Leone, 2788 from Liberia and 3547 from Guinea). Sierra Leone had the highest HBV childhood immunization coverage (70.3%), followed by Liberia (64.5%) and Guinea (40.0%). Within countries, immunization coverage varied by sociodemographic characteristics (education, religion, household wealth index, access to mass media) and healthcare access (antenatal visits, place of delivery and health facility proximity). In multivariate regression analysis, Muslim mothers, lower household wealth index, < 4 antenatal visits, home delivery and distance to health facility were predictors of incomplete immunization (all p < 0.05). Addressing these socioeconomic and healthcare access barriers will be essential to help achieve the 2030 viral hepatitis elimination goals.
Understanding the Lived Experience of Chronic Pain: A Systematic Review and Synthesis of Qualitative Evidence Syntheses
Authors: van Rysewyk S , Blomkvist R , Crighton R , Hodson F , Roomes D , Shea E , Smith BH , Toye F 
Published: March 2023

AbstractBackgroundAlthough multiple measures of the causes and consequences of chronic non-cancer pain (CNCP) are available and can inform pain management, no quantitative summary of these measures can describe the meaning of pain for a patient. The lived experience of pain tends to be a blind spot in pain management. This study aimed to: (1) integrate qualitative research investigating the lived experience of a range of CNCP conditions; (2) establish common qualitative themes in CNCP experience; and (3) evaluate the relevance of our results through a survey questionnaire based on these themes, administered across the United Kingdom.MethodsSix bibliographic databases were searched from inception to February 2021 to identify Qualitative Evidence Syntheses (QES) that investigated the lived experience of CNCP and its impact on everyday life and activities. Themes and trends were derived by thematic qualitative analysis in collaboration with two patient and public involvement representatives through two workshops. The output from these workshops helped inform the creation of twenty survey statements.ResultsThe research team identified and screened 1,323 titles, and considered 86 abstracts, including 20 in the final review. Eight themes were developed from the study findings: (1) my pain gives rise to negative emotions; (2) changes to my life and to my self; (3) adapting to my new normal; (4) effects of my pain management strategies; (5) hiding and showing my pain; (6) medically explaining my pain; (7) relationships to those around me; and (8) working while in pain. Each theme gave rise to one or two survey questions. The survey was shared with members of the UK pain community over a two-week period in November 2021, and was completed by 1,219 people, largely confirming the above themes.Conclusion/implicationsThis study provides a validated summary of the lived experience of CNCP. It highlights the adverse nature, complications, and consequences of living with CNCP in the UK, and the multiple shortcomings in the ways in which pain is addressed by others in the UK. Our findings are consistent with published meta-ethnographies on chronic non-malignant musculoskeletal pain, and chronic low-back pain. Despite the underrepresentation of qualitative research in the pain literature compared to quantitative approaches, for understanding the complexity of the lived experience of pain, qualitative research is an essential tool.
Childhood trauma is prevalent and associated with co-occurring depression, anxiety, mania and psychosis in young people attending Australian youth mental health services
Authors: Bendall Sarah , Eastwood Oliver , Spelman Tim , McGorry Patrick , Hickie Ian , Yung Alison R. , Amminger Paul , Wood Stephen J. , Pantelis Christos , Purcell Rosemary , Phillips Lisa 
Published: March 2023

ObjectivesChildhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorder groups, there is evidence that trauma is associated with an admixture of affective, anxiety, and psychotic symptoms in adults. Given that both early onset of mental disorder and trauma exposure herald poor outcomes, it is important to examine trauma prevalence rates in youth mental health services and to determine whether this trauma-related clustering is present in help-seeking young people.MethodsWe used data from the Transitions Study, a longitudinal investigation of young people attending one of four headspace youth mental health services in Melbourne and Sydney, Australia between January 2011 and August 2012. Participants were 775 young people aged 12 to 25 (65.9% female; mean age = 18.3, SD = 3.2). Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Multinomial regression was used to assess whether reported childhood trauma was more strongly associated with the co-occurrence of depression, anxiety, mania, and psychosis symptoms than with any one in isolation.ResultsApproximately 84% of participants reported some form of abuse (emotional: 68%; physical: 32%; sexual: 22%) or neglect (emotional: 65%; physical: 46%) during childhood or adolescence. Exposure to multiple trauma types was common. Childhood trauma was significantly associated with each symptom domain (depression, mania, anxiety and psychosis). Childhood trauma was more strongly associated with the co-occurrence of these symptoms than with any one of these domains in isolation, such that trauma-exposed young people were more likely to experience increased symptom clustering than their non-exposed counterparts.ConclusionsChildhood trauma is pervasive in youth mental health services and associated with a heterogeneous symptom profile that cuts across traditional diagnostic boundaries.
Peripheral and Cerebral Vascular Reactivity in Black and White Women: Examining the Impact of Psychosocial Stress Exposure Versus Internalization and Coping
Authors: Martin Zachary T. , Al-daas Iman O. , Cardenas Natalia , Kolade John O. , Merlau Emily R. , Vu Joshua K. , Brown Kyrah K. , Brothers R. Matthew 
Published: March 2023

AbstractBlack women have the highest rates of cardiovascular and cerebrovascular disease prevalence and mortality in part due to blunted vascular function. Psychosocial stress likely also contributes but its relationship to vascular function remains incompletely understood. Recent studies suggest that internalization and coping strategies are more important than stress exposure alone. We hypothesized that Black women have blunted peripheral and cerebral vascular function and that, among Black women, this would be inversely related with psychosocial stress internalization/coping but not stress exposures. Healthy Black (n= 21; 20 ± 2 yr) and White (n= 16; 25 ± 7 yr) women underwent testing for forearm reactive hyperemia (RH), brachial artery flow-mediated dilation (FMD), and cerebrovascular reactivity (CVR). Psychosocial stress exposure (adverse childhood experiences, ACEs; past week discrimination, PWD) and internalization/coping techniques (John Henryism Active Coping Scale, JHAC12; Giscombe Superwoman Schema Questionnaire, G-SWS-Q) were assessed. RH and CVR (p> 0.05) were not different between groups whereas FMD was lower in Black women (p= 0.007). Neither ACEs nor PWD were associated with FMD in either group (p> 0.05 for all). JHAC12 scores were negatively associated with FMD in Black women (p= 0.014) but positively associated with FMD in White women (p= 0.042). SWS-Succeed was negatively associated (p= 0.044) and SWS-Vulnerable tended to be negatively associated (p= 0.057) with FMD in Black women. These findings indicate that blunted FMD in Black women may be due more to internalization and maladaptive coping than stress exposure alone.
How attaining the goals of a stroke care pathway is related to functional outcome after stroke. A nationwide study
Authors: Bergh Elin , Askim Torunn , Rønning Ole Morten , Fjærtoft Hild , Thommessen Bente 
Published: March 2023

AbstractBackground and purposeIn 2018 a stroke care pathway (SCP) was introduced in Norway. The goal of the pathway was to improve acute stroke care by reducing time-delay. We aimed to evaluate if achieving the target times of the SCP was associated with a better functional outcome at 3 months post-stroke and to identify characteristics of patients attaining the goals.MethodsWe performed a register-based study with data from the Norwegian stroke register (NSR). Patients registered with acute stroke in 2019 were included. Functional outcome at 3 months in the patients with “achievement” was compared to patients with “non-achievement”. Achievement was defined as attaining three important goals in the SCP; 1) time from symptom onset to contact with the emergency medical service, 2) time from symptom onset to arrival in hospital, 3) time from arrival in hospital to admission to a stroke unit. Additionally, we evaluated time from arrival in hospital to treatment with intravenous thrombolysis. Modified Rankin Scale (mRS) was used to measure functional outcome at 3 months post-stroke and functional independence was defined as mRS 0-2. Characteristics of the “achievers” were analysed by univariate and multivariate logistic regression analyses.ResultsIn total 2818 patients were included, 460 (16%) were in the achievement group. The mean (SD) age was 72.5 (12.6) years and 1201 (43%) were women. The probability of being independent at 3 months post-stroke was significantly higher in the achievement group versus the non-achievement group (OR 1.36, 95% CI 1.04-1.79, p=0.026). The “achievers” were significantly younger, less likely to be living alone, less likely to have diabetes, more often had an ischemic stroke and were admitted with more severe strokes than the “non-achievers”.ConclusionGoal achievement in the SCP was significantly associated with independence 3 months post-stroke.
AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors
Authors: Danneskiold-Samsøe Niels Banhos , Kavi Deniz , Jude Kevin M. , Nissen Silas Boye , Wat Lianna W. , Coassolo Laetitia , Zhao Meng , Santana-Oikawa Galia Asae , Broido Beatrice Blythe , Garcia K. Christopher , Svensson Katrin J. 
Published: March 2023

AbstractSecreted proteins play crucial roles in paracrine and endocrine signaling; however, identifying novel ligand-receptor interactions remains challenging. Here, we benchmarked AlphaFold as a screening approach to identify extracellular ligand-binding pairs using a structural library of single-pass transmembrane receptors. Key to the approach is the optimization of AlphaFold input and output for screening ligands against receptors to predict the most probable ligand-receptor interactions. Importantly, the predictions were performed on ligand-receptor pairs not used for AlphaFold training. We demonstrate high discriminatory power and a success rate of close to 90 % for known ligand-receptor pairs and 50 % for a diverse set of experimentally validated interactions. These results demonstrate proof-of-concept of a rapid and accurate screening platform to predict high-confidence cell-surface receptors for a diverse set of ligands by structural binding prediction, with potentially wide applicability for the understanding of cell-cell communication.
A Weakly Supervised U-Net Model for Precise Whole Brain Immunolabeled Cell Detection
Authors: Wang Li-Wen , Wu Ya-Lun , Lee Chih-Lin , Cheng Ching-Chuan , Lu Kuan-Yi , Tsai Jyun-Huei , Lin Ya-Hui , Hsu Ching-Han , Kuo Tsung-Han , Chu Li-An 
Published: March 2023

AbstractCell segmentation’s low precision due to the intensity differences hinders widespread use of whole brain microscopy imaging. Previous studies used ResNet or CNN to account for this problem, but are unapplicable to immunolabeled signals across samples. Here we present a semiauto ground truth generation and weakly-supervised U-Net-based Deep-learning precise segmentation pipeline for whole brain immunopositive c-FOS signals, which reveals the distinct neural activity maps with different social motivations.
Keypoint-MoSeq: parsing behavior by linking point tracking to pose dynamics
Authors: Weinreb Caleb , Pearl Jonah , Lin Sherry , Osman Mohammed Abdal Monium , Zhang Libby , Annapragada Sidharth , Conlin Eli , Hoffman Red , Makowska Sofia , Gillis Winthrop F. , Jay Maya , Ye Shaokai , Mathis Alexander , Mathis Mackenzie Weygandt , Pereira Talmo , Linderman Scott W. , Datta Sandeep Robert 
Published: March 2023

AbstractKeypoint tracking algorithms have revolutionized the analysis of animal behavior, enabling investigators to flexibly quantify behavioral dynamics from conventional video recordings obtained in a wide variety of settings. However, it remains unclear how to parse continuous keypoint data into the modules out of which behavior is organized. This challenge is particularly acute because keypoint data is susceptible to high frequency jitter that clustering algorithms can mistake for transitions between behavioral modules. Here we present keypoint-MoSeq, a machine learning-based platform for identifying behavioral modules (“syllables”) from keypoint data without human supervision. Keypoint-MoSeq uses a generative model to distinguish keypoint noise from behavior, enabling it to effectively identify syllables whose boundaries correspond to natural sub-second discontinuities inherent to mouse behavior. Keypoint-MoSeq outperforms commonly used alternative clustering methods at identifying these transitions, at capturing correlations between neural activity and behavior, and at classifying either solitary or social behaviors in accordance with human annotations. Keypoint-MoSeq therefore renders behavioral syllables and grammar accessible to the many researchers who use standard video to capture animal behavior.
Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation
Authors: Raso Fiona , Liu Shuozhi , Willett Mikala JoAnn , Barton Gregory , Mayer Christian Thomas , Bannard Oliver , Acharya Mridu , Muppidi Jagan R. , Marshak-Rothstein Ann , Reboldi Andrea 
Published: March 2023

AbstractImmunoglobulin A (IgA), the main antibody isotype found in the intestine, has evolved to maintain the stability of commensal communities, and prevent dysbiosis. In stark contrast to systemic antibody response against pathogens, the generation of IgA against intestinal resident microbes assures the simultaneous binding to multiple and diverse commensal-derived antigens. However, the exact mechanisms by which B cells mount such broadly reactive IgA response to the gut microbiome at the mucosal barrier remain elusive. Here we show surface IgA B cell receptor (BCR) is required to confer enhanced B cell fitness during the germinal center reaction in Peyer’s patches and to mediate selection of gut-homing plasma cells with higher efficiency. We demonstrate that, upon antigen stimulation, IgA+ BCR drives greater intracellular signaling in mouse and human B cells and as consequence, IgA+ B cells received higher positive selection cues in the germinal center. Mechanistically,in vivoIgA BCR signaling offsets Fas-mediated cell death to rescue low affinity B cell clones and redirects the humoral response to an increased variety of commensal strains at the intestinal interface. Our findings revealed a new mechanism linking tissue-specific antigen receptor signaling with B cell fate and localization of antibody production; and have implications for understanding how intestinal antigen recognition shapes humoral immunity in health and disease.
Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14
Authors: Zhang Chi , Tunes Luiza , Hsieh Meng-Hsiung , Wang Ping , Kumar Ashwani , Khadgi Brijesh B. , Yang YenYu , Doxtader Katelyn A. , Herrell Emily , Koczy Oliwia , Setlem Rohit , Zhang Xunzhi , Evers Bret , Wang Yinsheng , Xing Chao , Zhu Hao , Nam Yunsun 
Published: March 2023

AbstractChemical modification of RNAs is important for post-transcriptional gene regulation. The METTL3-METTL14 complex generates mostN6-methyladenosine (m6A) modifications in mRNAs, and dysregulated methyltransferase expression has been linked to numerous cancers. Here we show that changes in m6A modification location can impact oncogenesis. A gain-of-function missense mutation found in cancer patients, METTL14R298P, promotes malignant cell growth in culture and in transgenic mice. The mutant methyltransferase preferentially modifies noncanonical sites containing a GGAU motif and transforms gene expression without increasing global m6A levels in mRNAs. The altered substrate specificity is intrinsic to METTL3-METTL14, helping us to propose a structural model for how the METTL3-METTL14 complex selects the cognate RNA sequences for modification. Together, our work highlights that sequence-specific m6A deposition is important for proper function of the modification and that noncanonical methylation events can impact aberrant gene expression and oncogenesis.
Draft Genome Assembly of the Ancient Tetraploid Orphan Legume Marama Bean (Tylosema esculentum) with PacBio HiFi data
Authors: Li Jin , Cullis Christopher 
Published: March 2023

AbstractTylosema esculentum(marama bean), an underutilized orphan legume, has long been considered to have the potential to be domesticated as a crop to improve local food security due to the nutrient-rich seeds. As a plant species that grows naturally in the deserts of southern Africa, marama also serves as a good model for studying plant adaptation to extreme environments. In this study, HMW leaf DNA samples were prepared to generate 21.6 Gb PacBio HiFi data, which was assembled into to a raw tetraploid genome assembly of 1.24 Gb using Canu and into a partially phased assembly of 564.8 Mb by Hifiasm. The N50 values were 1.28 Mb and 2.75 Mb, respectively, and the BUSCO completeness were all above 99%. Repeats were found to account for 27.35% of the genome. The k-mer analysis indicated that marama was likely to be an autotetraploid plant with an estimated haplotype genome size of only 277 Mb. The current assembly was aligned with the genome ofBauhinia variegata, the closest species to marama whose genome has been sequenced, with an overall alignment rate of only 20.36% indicating a significant divergence between the two. This is the first high-quality genome assembly of marama bean, albeit unphased and still fragmented. However, some of the long contigs, which can be close to half the chromosome length, can serve as good references for studying the genes underlying the traits of interest. This will greatly facilitate the molecular breeding of the bean.
Hardwired to attack: Transcriptionally defined amygdala subpopulations play distinct roles in innate social behaviors
Authors: Lischinsky Julieta E. , Yin Luping , Shi Chenxi , Prakash Nandkishore , Burke Jared , Shekaran Govind , Grba Maria , Corbin Joshua G. , Lin Dayu 
Published: March 2023

AbstractSocial behaviors are innate and supported by dedicated neural circuits, but it remains unclear whether these circuits are developmentally hardwired or established through social experience. Here, we revealed distinct response patterns and functions in social behavior of medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages. MeA cells in male mice that express the transcription factor Foxp2 (MeAFoxp2) are specialized for processing male conspecific cues even before puberty and are essential for adult inter-male aggression. In contrast, MeA cells derived from theDbx1-lineage (MeADbx1) respond broadly to social cues and are non-essential for male aggression. Furthermore, MeAFoxp2and MeADbx1cells show differential anatomical and functional connectivity. Altogether, our results support a developmentally hardwired aggression circuit at the level of the MeA and we propose a lineage-based circuit organization by which a cell’s embryonic transcription factor profile determines its social information representation and behavior relevance during adulthood.HighlightsMeAFoxp2cells in male mice show highly specific responses to male conspecific cues and during attack while MeADbx1cells are broadly tuned to social cues.The male-specific response of MeAFoxp2cells is present in naïve adult males and adult social experience refines the response by increasing its trial-to-trial reliability and temporal precision.MeAFoxp2cells show biased response to males even before puberty.Activation of MeAFoxp2, but not MeADbx1, cells promote inter-male aggression in naïve male mice.Inactivation of MeAFoxp2, but not MeADbx1, cells suppresses inter-male aggression.MeAFoxp2and MeADbx1cells show differential connectivity at both the input and output levels.
Ultra-high throughput mapping of genetic design space
Authors: O’Connell Ronan W. , Rai Kshitij , Piepergerdes Trenton C. , Wang Yiduo , Samra Kian D. , Wilson Jack A. , Lin Shujian , Zhang Thomas H. , Ramos Eduardo M. , Sun Andrew , Kille Bryce , Curry Kristen D. , Rocks Jason W. , Treangen Todd J. , Mehta Pankaj , Bashor Caleb J. 
Published: March 2023

ABSTRACTMassively parallel genetic screens have been used to map sequence-to-function relationships for a variety of genetic elements. However, because these approaches only interrogate short sequences, it remains challenging to perform high throughput (HT) assays on constructs containing combinations of multiple sequence elements arranged across multikb length scales. Overcoming this barrier could accelerate synthetic biology; by screening diverse gene circuit designs, “composition-to-function” mappings could be created that reveal genetic part composability rules and enable rapid identification of behavior-optimized variants. Here, we introduce CLASSIC, a genetic screening platform that combines long– and short-read next-generation sequencing (NGS) modalities to quantitatively assess pools of constructs of arbitrary length containing diverse part compositions. We show that CLASSIC can measure expression profiles of >105 drug-inducible gene circuit designs (from 6-9 kb) in a single experiment in human cells. Using statistical inference and machine learning (ML) approaches, we demonstrate that data obtained with CLASSIC enables accurate predictive modeling of an entire circuit design landscape, offering critical insight into underlying design principles. Our work shows that by expanding the throughput and understanding gained with each design-build-test-learn (DBTL) cycle, CLASSIC dramatically augments the pace and scale of synthetic biology and establishes an experimental basis for data-driven design of complex genetic systems.