bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of reference design on estimating SARS-CoV-2 lineage abundances from wastewater sequencing data
Authors: Aßmann Eva , Agrawal Shelesh , Orschler Laura , Böttcher Sindy , Lackner Susanne , Hölzer Martin 
Published: June 2023

AbstractBackgroundSequencing of SARS-CoV-2 RNA from wastewater samples has emerged as a valuable tool for detecting the presence and relative abundances of SARS-CoV-2 variants in a community. By analyzing the viral genetic material present in wastewater, public health officials can gain early insights into the spread of the virus and inform timely intervention measures. The construction of reference datasets from known SARS-CoV-2 lineages and their mutation profies has become state-of-the-art for assigning viral lineages and their relative abundances from wastewater sequencing data. However, the selection of reference sequences or mutations directly affects the predictive power.ResultsHere, we show the impact of amutation-andsequence-basedreference reconstruction for SARS-CoV-2 abundance estimation. We benchmark three data sets: 1) synthetic “spike-in” mixtures, 2) German samples from early 2021, mainly comprising Alpha, and 3) samples obtained from wastewater at an international airport in Germany from the end of 2021, including 1rst signals of Omicron. The two approaches differ in sub-lineage detection, with the marker-mutation-basedmethod, in particular, being challenged by the increasing number of mutations and lineages. However, the estimations of both approaches depend on selecting representative references and optimized parameter settings. By performing parameter escalation experiments, we demonstrate the effects of reference size and alternative allele frequency cutoffs for abundance estimation. We show how different parameter settings can lead to different results for our test data sets, and illustrate the effects of virus lineage composition of wastewater samples and references.ConclusionsHere, we compare amutation-andsequence-basedreference construction and assignment for SARS-CoV-2 abundance estimation from wastewater samples. Our study highlights current computational challenges, focusing on the general reference design, which significantly and directly impacts abundance allocations. We illustrate advantages and disadvantages that may be relevant for further developments in the wastewater community and in the context of higher standardization.
The ORP9-ORP11 dimer promotes sphingomyelin synthesis
Authors: Cabukusta Birol , Pauwels Shalom Borst , Akkermans Jimmy J.L.L. , Blomberg Niek , Mulder Aat A. , Koning Roman I. , Giera Martin , Neefjes Jacques 
Published: June 2023

AbstractNumerous lipids are heterogeneously distributed among organelles. Most lipid trafficking between organelles is achieved by a group of lipid transfer proteins (LTPs) that carry lipids using their hydrophobic cavities. The human genome encodes many intracellular LTPs responsible for lipid trafficking and the function of many LTPs in defining cellular lipid levels and distributions is unclear. Here, we created a gene knockout library targeting 90 intracellular LTPs and performed whole-cell lipidomics analysis. This analysis confirmed known lipid disturbances and identified new ones caused by loss of LTPs. Among these, we found major sphingolipid imbalances in ORP9 and ORP11 knockout cells, two proteins of previously unknown function in sphingolipid metabolism. ORP9 and ORP11 form a heterodimer to localize at the ER-transGolgi membrane contact sites, where the dimer exchanges phosphatidylserine (PS) for phosphatidylinositol-4-phosphate (PI(4)P) between the two organelles. Consequently, loss of either protein causes phospholipid imbalances in the Golgi apparatus that result in lowered sphingomyelin synthesis at this organelle. Overall, our LTP knockout library toolbox identifies various proteins in control of cellular lipid levels, including the ORP9-ORP11 heterodimer, which exchanges PS and PI(4)P at the ER-Golgi membrane contact site as a critical step in sphingomyelin synthesis in the Golgi apparatus.
Genetic diversity, determinants, and dissemination ofBurkholderia pseudomalleilineages implicated in melioidosis in northeast Thailand
Authors: Seng Rathanin , Chomkatekaew Chalita , Tandhavanant Sarunporn , Saiprom Natnaree , Phunpang Rungnapa , Thaipadungpanit Janjira , Batty Elizabeth M , Day Nicholas PJ , Chantratita Wasun , West T. Eoin , Thomson Nicholas R , Parkhill Julian , Chewapreecha Claire , Chantratita Narisara 
Published: June 2023

AbstractMelioidosis is an often-fatal neglected tropical disease caused by an environmental bacteriumBurkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conducted a comprehensive genomic analysis of 1,391B. pseudomalleiisolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identified three dominant lineages with unique gene sets enhancing bacterial fitness, indicating lineage-specific adaptation strategies. Crucially, recombination was found to drive lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage revealed heightened expression of lineage-specific genes in environmental versus infection conditions, notably under nutrient depletion, highlighting environmental persistence as a key factor in the success of dominant lineages. The study also revealed the role of environmental factors – slope of terrain, altitude, direction of rivers, and the northeast monsoons – in shapingB. pseudomalleigeographical dispersal. Collectively, our findings highlight persistence in the environment as a pivotal element facilitatingB. pseudomalleispread, and as a prelude to exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies.
Elucidating the mechanism of microbial thermogenesis
Authors: Dhatt Puneet Singh , Moon Tae Seok 
Published: June 2023

AbstractOrganisms necessarily release heat energy in their pursuit of survival. This process is known as cellular thermogenesis and is implicated in many processes from cancer metabolism to spontaneous farm fires1,2. However, the molecular basis for this fundamental phenomenon is yet to be elucidated. Here, we show that the major players involved in cellular thermogenesis are the protein kinases ArcB, GlnL, and YccC inEscherichia coli. We also reveal the substrate-level control of ATP-driven autophosphorylation that governs cellular thermogenesis. Through live-cell microcalorimetric experimentation, we find that only three of the 231 regulatory proteins, when knocked out in a modelEscherichia colistrain, dysregulate cellular thermogenesis. This dysregulation can be seen in an average 25% or greater increase in heat output by these cells. We also discover that both heat output and intracellular ATP levels are maximal during the late log phase of growth. Our results demonstrate a correlation between ATP concentrations in the cell and a cell’s ability to generate excess heat. We expect this work to be the foundation for engineering a new generation of thermogenically-tuned organisms for a variety of applications.
Morphological brain networks of white matter: mapping, evaluation, characterization and application
Authors: Li Junle , Li Zhen , Yang Yuping , Luo Zhenzhen , Liu Yaou , Wang Jinhui 
Published: June 2023

AbstractNeuroimaging-based connectomics studies have long focused on the wiring patterns between gray matter regions. In recent years, increasing evidence emerges that neural activity in specific sets of white matter (WM) tracts dynamically fluctuates in a coordinated manner. However, the structural basis underlying the coordination is poorly understood largely due to the lack of approaches for estimating structural relations between WM regions. Here, we developed an approach to construct morphological WM networks based on structural magnetic resonance imaging. We found that the morphological WM networks exhibited nontrivial organizational principles, presented good to excellent short- and long-term reliability, accounted for phenotypic interindividual differences (Motor and Cognition), and were under genetic control. Interestingly, highly heritable edges contributed largely to interindividual differences in phenotype. Through integration with other multimodal and multiscale data, we further showed that the morphological WM networks were able to predict regional profiles of hamodynamic coherence, metabolic synchronization, gene co-expression and chemoarchitectonic covariance. Moreover, the prediction followed functional connectomic hierarchy of WM for hamodynamic coherence, was driven by genes enriched in the forebrain neuron development and differentiation for gene co-expression, and was attributed to serotonergic system-related receptors and transporters for chemoarchitectonic covariance. Finally, applying our approach to multiple sclerosis and neuromyelitis optica spectrum disorders, we found that both diseases were associated with morphological WM dysconnectivity, which was correlated with clinical variables and able to diagnose and differentiate the diseases. Altogether, our findings indicate that morphological WM networks provide a reliable and meaningful means to explore WM architecture in health and disease.
Defining Vaginal Community Dynamics: daily microbiome transitions, the role of menstruation, bacteriophages and bacterial genes
Authors: Hugerth Luisa W. , Krog Maria Christine , Vomstein Kilian , Du Juan , Bashir Zahra , Kaldhusdal Vilde , Fransson Emma , Engstrand Lars , Nielsen Henriette Svarre , Schuppe-Koistinen Ina 
Published: June 2023

AbstractBackgroundThe composition of the vaginal microbiota during the menstrual cycle is dynamic, with some women remaining eu- or dysbiotic and others transitioning between these states. What defines these dynamics, and whether these differences are microbiome-intrinsic or mostly driven by the host is unknown. To address this, we characterized 49 healthy, young women by metagenomic sequencing of daily vaginal swabs during a menstrual cycle. We classified the dynamics of the vaginal microbiome and assessed the impact of host behavior as well as microbiome differences at the species, strain, gene and phage levels.ResultsBased on the daily shifts in community state types (CSTs) during a menstrual cycle the vaginal microbiome was classified into four Vaginal Community Dynamics (VCDs) and reported in a classification tool, named VALODY: constant eubiotic, constant dysbiotic, menses-related and unstable dysbiotic. The abundance of bacteria, phages, and bacterial gene content was compared between the four VCDs. Women with different VCDs showed significant differences in relative phage abundance and bacterial composition even when assigned to the same CST. Women with unstable VCDs had higher phage counts and were more likely dominated byL. iners. TheirGardnerella spp.strains were also more likely to harbour bacteriocin-coding genes.ConclusionsThe VCDs present a novel time series classification which highlights the complexity of varying degrees of vaginal dysbiosis. Knowing the differences in phage levels and the genomic strains present allows a deeper understanding of the initiation and maintenance of permanent dysbiosis. Applying the VCD’s to further characterize the different types of microbiome dynamics qualifies the investigation of disease and enables comparisons at individual and population levels. Based on our data, to be able to classify a dysbiotic sample into the accurate VCD, clinicians would need two-three mid-cyclical samples and two samples during menses. In the future, it will be important to address whether transient VCDs pose a similar risk profile to persistent dysbiosis with similar clinical outcomes. This framework may aid interdisciplinary translational teams in deciphering the role of the vaginal microbiome in women’s health and reproduction.
Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis
Authors: Wang Fangyan , Liu Xiujie , Huang Furong , Zhou Yan , Wang Xinyu , Song Zhengyang , Wang Sisi , Wang Xiaoting , Shi Dibang , Ruan Gaoyi , Ji Xiawei , Zhang Eryao , Tan Zenglin , Ye Yuqing , Wang Chuang , Zhu Jesse , Wang Wantie 
Published: June 2023

AbstractHepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation (FMT) treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase (GAD) and putrescine aminotransferase (PAT), in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.
Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting
Authors: Wu Yangyu , Yan Yangyang , Yang Youshan , Bian Shumin , Rivetta Alberto , Allen Ken , Sigworth Fred J. 
Published: June 2023

SummaryWe present near-atomic-resolution cryo-EM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 Å, 2.5 Å, 3.2 Å, and 2.9Å. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2-2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin α-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.
Learning to quantify uncertainty in off-target activity for CRISPR guide RNAs
Authors: Özden Furkan , Minary Peter 
Published: June 2023

AbstractCRISPR-based genome editing technologies have revolutionised the field of molecular biology, offering unprecedented opportunities for precise genetic manipulation. However, off-target effects remain a significant challenge, potentially leading to unintended consequences and limiting the applicability of CRISPR-based genome editing technologies in clinical settings. Current literature predominantly focuses on point predictions for off-target activity, which may not fully capture the range of possible outcomes and associated risks. Here, we present crispAI, a neural network architecture-based approach for predicting uncertainty estimates for off-target cleavage activity, providing a more comprehensive risk assessment and facilitating improved decision-making in single guide RNA (sgRNA) design. Our approach makes use of the count noise model Zero Inflated Negative Binomial (ZINB) to model the uncertainty in the off-target cleavage activity data. In addition, we present the first-of-its-kind genome-wide sgRNA efficiency score, crispAI-aggregate, enabling prioritization among sgRNAs with similar point aggregate predictions by providing richer information compared to existing aggregate scores. We show that uncertainty estimates of our approach are calibrated and its predictive performance is superior to state-of-the-artin silicooff-target cleavage activity prediction methods.
Utilizing Large Language Models to Simplify Radiology Reports: a comparative analysis of ChatGPT3.5, ChatGPT4.0, Google Bard, and Microsoft Bing
Authors: Doshi Rushabh , Amin Kanhai , Khosla Pavan , Bajaj Simar , Chheang Sophie , Forman Howard P. 
Published: June 2023

AbstractThis paper investigates the application of Large Language Models (LLMs), specifically OpenAI’s ChatGPT3.5, ChatGPT4.0, Google Bard, and Microsoft Bing, in simplifying radiology reports, thus potentially enhancing patient understanding. We examined 254 anonymized radiology reports from diverse examination types and used three different prompts to guide the LLMs’ simplification processes. The resulting simplified reports were evaluated using four established readability indices. All LLMs significantly simplified the reports, but performance varied based on the prompt used and the specific model. The ChatGPT models performed best when additional context was provided (i.e., specifying user as a patient or requesting simplification at the 7th grade level). Our findings suggest that LLMs can effectively simplify radiology reports, although improvements are needed to ensure accurate clinical representation and optimal readability. These models have the potential to improve patient health literacy, patient-provider communication, and ultimately, health outcomes.
Mental health issues among medical students: Exploring predictors of mental health in Dhaka during COVID-19 pandemic
Authors: Lama Subigya Man , Ahad Md. Toufiq Elahi 
Published: June 2023

ABSTRACTBackgroundMental health has always been under the shadow of everyone’s belief about their health. Concerns about mental health have already risen in the whole world. The COVID-19 pandemic has caused havoc worldwide, notably in the educational system. It has been difficult to quantify the influence of COVID-19 on the mental health of medical students in Bangladesh.AimsThis study was conducted to assess medical students’ mental health status in Dhaka during COVID-19 pandemic.MethodsThis study was undertaken at Dhaka Medical College, Dhaka, Bangladesh and 359 medical students were the primary respondents for this study.ResultsDepression, anxiety and stress were found in around half of the study participants. Overall, three-fourth of the medical students had poor mental health status. The research study showed that depression, anxiety and stress were dependent on various socio-demographic and behavioral characteristics of medical students.ConclusionPoor mental health is still highly prevalent in the medical students. Different factors like age, gender, academic year, and physical exercise behavior have affected medical students’ mental health. This calls for attention towards the needs of the more vulnerable demographics and creating a welcoming environment for medical students.
Prevalence and Recurrence of Pica Behaviors in Early Childhood: Findings from the ALSPAC Birth Cohort
Authors: Papini Natalie M. , Bulik Cynthia M. , Chawner Samuel JRA , Micali Nadia 
Published: June 2023

AbstractObjectivePica has been largely understudied in general population samples. Pica occurs most often in childhood and appears more prevalent in individuals with autism and developmental delays (DD). Pica occurrence in the general population is poorly understood due to few epidemiological studies.MethodData on 10,109 caregivers from the Avon Longitudinal Study of Parents and Children (ALSPAC) study who reported pica behavior at 36, 54, 66, 77, and 115 months on their child were included. Autism was obtained through clinical and education records, while DD was derived from the Denver Developmental Screening Test.ResultsA total of 312 parents reported pica behaviors in their child. Of these, 19.55% reported pica at least at two waves (n=61). Pica was most common at 36 months (N=226; 2.29%) and decreased as children aged. A significant association was found between pica and autism at all five waves (p < .001). There was a significant relationship between pica and DD, with individuals with DD more likely to experience pica than those without DD at 36 (p = .01), and 54 (p < .001), 65 (p=.04), 77 (p <.001), and 115 months (p=.006). Exploratory analyses examined pica behaviors with broader eating difficulties and child body mass index.DiscussionPica is an uncommon behavior in childhood; however, children with DD or autism may benefit from pica screening and diagnosis between ages 36-115 months. Children who exhibit undereating, overeating, and food fussiness may also engage in pica behaviors.
Residual Radiation Risk Disparities Across Sex and Race or Ethnic Groups for Lifetime Never-Smokers on Lunar Missions
Authors: Cucinotta Francis A. , Saganti Premkumar B. 
Published: June 2023

AbstractIn the current decade missions to the Earth’s moon are of scientific and societal interest, however pose the problem of risks of late effects for returning crew persons, most importantly cancer and circulatory diseases. In this paper, we discuss NSCR-2022 model risk estimates for lunar missions for US racial and ethnic groups comparing never-smokers to US averages for each group and sex. We show that differences within groups between men and women are largely reduced for NS compared to the average population. Race and ethnic group dependent cancer and circulatory disease risks are reduced by 10% to 40% for NS with the largest decrease for Whites. Circulatory disease risks are changed by less than 10% for NS and in several cases modestly increased due to increased lifespan for NS. Asian-Pacific Islander (API) and Hispanics NS are at lower risk compared to Whites and Blacks. Differences between groups is narrowed for NS compared to predictions for average populations, however disparities remain especially for Blacks and to a lesser extent Whites compared to API or Hispanic NS groups.