bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-centre, non-randomised clinical trial at a tertiary care centre to investigate 1-year changes in social experiences and biomarkers of well-being after bariatric surgery in individuals with severe obesity: protocol for the Bariatric Surgery and Social Experiences (BaSES) study
Authors: Pfabigan Daniela M. , Hertel Jens K. , Svanevik Marius , Lindberg Morten , Sailer Uta , Hjelmesæth Jøran 
Published: December 2022

AbstractIntroductionObesity is linked to increased loneliness and less enjoyment of social interactions. While bariatric surgery is the most effective treatment targeting severe obesity, there is limited understanding as to whether patients experience social interactions differently after surgery. The Bariatric Surgery and Social Experiences Study (BaSES) is designed to assess potential changes in how much patients enjoy and engage in daily social interactions 1 year after Roux- en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG).Methods and analysisSingle-centre, non-randomised clinical trial carried out at the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust, Norway. Eligible patients (N=113) will undergo either RYGB, SG or single anastomosis sleeve ileal bypass (SASI). The primary outcome measure is change in the social experience score (assessed with a questionnaire) from a pre-surgery to a follow-up assessment 1 year after RYGB and SG. The respective changes after SASI will be assessed and considered exploratory.Ethics and disseminationThe most recent protocol version of this study was reviewed and approved by the Regional Committee for Medical Research Ethics South East Norway (REK sør-øst A) on the 29thof August 2022 (ref: 238406). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences.Trial registration numberNCT05207917 (ClinicalTrials.gov)Article SummaryStrengths and limitations of this studyThe primary outcome (frequency and quality of social interactions) is assessed over a 14-days period per measurement timepoint to comprehensibly capture daily variation.Multiple clinically relevant secondary outcomes including hair cortisol, endocannabinoid, and fasting ghrelin concentrations, cardiovascular risk factors and health-related and psychological patient-reported-outcomes are assessed.The sample size is limited and thus may not provide sufficient statistical power to compare the effects of RYGB and SG on secondary outcomes.
Out of Pocket Spending on Insulin under $35 Copayment Caps
Authors: Bakkila Baylee F. , Basu Sanjay , Lipska Kasia J. 
Published: December 2022

AbstractThe high cost of insulin has made it inaccessible to many patients who need it. The Inflation Reduction Act (IRA), which was recently signed into law, limits out of pocket (OOP) spending on insulin to $35 for a 30-day supply for individuals covered by Medicare. In this study, we estimate substantial OOP savings for individuals who require insulin, finding that Medicare-insured persons are projected to save nearly one-fifth of their expenditures on insulin.
It’s complicated…: Exploring the missed opportunities and reasons for non-performance of assisted vaginal births in Kenya
Authors: Dickinson Fiona M , Allott Helen , Nyongesa Paul , Eyinde Martin , Muchemi Onesmus M , Karangau Stephen W , Ogoti Evans , Shaban Nassir A , Godia Pamela , Nyaga Lucy , Ameh Charles A 
Published: December 2022

AbstractUnnecessary Caesarean Section (CS) can have adverse effects on women and their newborn. Assisted vaginal birth/delivery (AVB/AVD) using a suction device or obstetric forceps is a potential alternative when delays or complications occur in the second stage of labour. Unlike CS, AVB using a suction device does not require regional or general anaesthesia, can often be performed by midwives, and does not scar the uterus, lowering the risk of maternal mortality and morbidity, in this and subsequent pregnancies. This study examined the justification for, and outcomes of second stage CS (SSCS) and reasons for low levels of use of AVB, in Kenya.Using a mixed methods study design, we reviewed case-notes from women having AVB and second-stage CS births, and conducted key informant interviews with healthcare providers, from 8 purposively selected hospitals in Kenya. Randomly selected SSCS and all AVB case-notes were reviewed by a panel of four experienced obstetricians, and appropriateness of the procedure assessed. Semi-structured interviews were conducted and analysed using a thematic approach.Review of 67 SSCS case-notes showed 10% might have been conducted as AVBs, with a further 58% unable to be classified due to inadequate/inconsistent record keeping or excessive delay following initial CS decision. Outcomes following SSCS showed perinatal mortality rate of 89.6/1,000 births, with 11% of infants and 9% of mothers experiencing complications. Non-referred cases of AVB showed good outcomes. Twenty interviews were conducted with obstetricians, medical officers and midwives. The findings explored the experience and confidence of healthcare providers in performing AVBs, and adequacy of the training they received. Key reasons for non-performance included lack of functioning equipment, lack of trained staff or their rotation to other departments.Reasons for non-performance of AVB were complex and often multiple. Any solutions to these problems will need to address various local, regional and national issues.
CHC22 clathrin functions in the early secretory pathway by two-site interaction with SNX5 and p115
Authors: Greig Joshua , Bates George T. , Yin Daowen I. , Briant Kit , Simonetti Boris , Cullen Peter J. , Brodsky Frances M. 
Published: December 2022

AbstractThe two clathrin isoforms, CHC17 and CHC22, mediate separate intracellular transport routes. CHC17 performs endocytosis and housekeeping membrane traffic in all cells. CHC22, expressed most highly in skeletal muscle, transports the glucose transporter GLUT4 from the endoplasmic-reticulum-to-Golgi intermediate compartment (ERGIC) directly to an intracellular GLUT4 storage compartment (GSC) from where GLUT4 can be mobilized to the plasma membrane by insulin. Here, the molecular determinants distinguishing CHC22 from CHC17 trafficking are defined. The C-terminal trimerization domain of CHC22 binds SNX5, which also binds the ERGIC tether p115. SNX5, and the functionally redundant SNX6, are required for CHC22 localization independently of their participation in the endosomal ESCPE-1 complex. In tandem, an isoform-specific patch in the CHC22 N-terminal domain separately mediates binding to p115. This dual mode of clathrin recruitment, involving interactions at both heavy chain termini, is required for CHC22 targeting to ERGIC membranes to mediate the Golgi bypass route for GLUT4 traffic. Interference with either interaction inhibits GLUT4 targeting to the GSC, defining a bipartite mechanism regulating a key pathway in human glucose metabolism.
Evolutionary stability of social interaction rules in collective decision-making
Authors: Sigalou Anna , Mann Richard P. 
Published: December 2022

AbstractSocial animals can use the choices made by other members of their groups as cues in decision making. Individuals must balance the private information they receive from their own sensory cues with the social information provided by observing what others have chosen. These two cues can be integrated using decision making rules, which specify the probability to select one or other options based on the quality and quantity of social and non-social information. Previous empirical work has investigated which decision making rules can replicate the observable features of collective decision making, while other theoretical research has derived forms for decision making rules based on normative assumptions about how rational agents should respond to the available information. Here we explore the performance of one commonly used decision making rule in terms of the expected decision accuracy of individuals employing it. We show that parameters of this model which have typically been treated as independent variables in empirical model-fitting studies obey necessary relationships under the assumption that animals are evolutionarily optimised to their environment. We further investigate whether this decision making model is appropriate to all animal groups by testing its evolutionary stability to invasion by alternative strategies that use social information differently, and show that the likely evolutionary equilibrium of these strategies depends sensitively on the precise nature of group identity among the wider population of animals it is embedded within.
Establishment of Bovine Trophoblast Stem Cells
Authors: Wang Yinjuan , Yu Leqian , Li Jie , Zhu Linkai , Ming Hao , Arteaga Carlos Pinzon , Sun Hai-Xi , Wu Jun , Jiang Zongliang 
Published: December 2022

AbstractHere we report that a chemical cocktail (LCDM: hLIF,CHIR99021,DiM andMiH) previously used for extended potential pluripotent stem cells enables the de novo derivation and long-term culture of bovine trophoblast stem cells (TSCs). Bovine TSCs exhibit transcriptomic and epigenetic features characteristic of trophectoderm cells from bovine embryos and retain developmental potency to differentiate into mature trophoblast cells.
PeptideForest: Semisupervised machine learning integrating multiple search engines for peptide identification
Authors: Ranff T. , Dennison M. , Bédorf J. , Schulze S. , Zinn N , Bantscheff M. , van Heugten J.J.R.M. , Fufezan C. 
Published: December 2022

AbstractThe first step in bottom-up proteomics is the assignment of measured fragmentation mass spectra to peptide sequences, also known as peptide spectrum matches. In recent years novel algorithms have pushed the assignment to new heights, unfortunately, different algorithms come with different strengths and weaknesses and choosing the appropriate algorithm poses a challenge for the user. Here we introduce PeptideForest, a semi-supervised machine learning approach that integrates the assignments of multiple algorithms to train a random forest classifier to elevate that issue. Additionally, PeptideForest increases the number of peptide-to-spectrum matches that exhibit a q-value lower than 1% by 25.2 ± 1.6% compared to MS-GF+ data on samples containing mixed HEK andE. coliproteomes. However, an increase in quantity does not necessarily reflect an increase in quality and this is why we devised a novel approach to determine the quality of the assigned spectra through TMT quantification of samples with known ground truths. Thereby, we could show that the increase in PSMs below 1% q-value does not come with a decrease in quantification quality and as such PeptideForest offers a possibility to gain deeper insights into bottom-up proteomics. PeptideForest has been integrated into our pipeline framework Ursgal and can therefore be combined with a wide array of algorithms.
A method for differential expression analysis and pseudo-temporal locating and ordering of genes in single-cell transcriptomic data
Authors: Zhang Bao , Zhang Hongbo 
Published: December 2022

AbstractIdentification of differentially expressed genes (DEGs) is a pivotal step in single-cell RNA sequencing (scRNA-seq) data analysis. The sparsity and multi-model distribution of scRNA-seq data decides that the traditional tools designed for bulk RNA-seq have several limitations when applied to single-cell data. On the other hand, tools specifically for DEGs analysis of scRNA-seq data normally does not consider the high dimensionality of the data. To this end, we present DEAPLOG, a method for differential expression analysis and pseudo-temporal locating and ordering of genes in single-cell transcriptomic data. We show that DEAPLOG has higher accurate and efficient in DEGs identification when compared with existing methods in both artificial and real datasets. Additionally, DEAPLOG can infer pseudo-time and embedding coordinates of genes, therefore is useful in identifying regulators in trajectory of cell fate decision.
The Mba1 homologue ofTrypanosoma bruceiis involved in the biogenesis of oxidative phosphorylation complexes
Authors: Wenger Christoph , Harsman Anke , Niemann Moritz , Oeljeklaus Silke , von Känel Corinne , Calderaro Salvatore , Warscheid Bettina , Schneider André 
Published: December 2022

AbstractConsistent with other eukaryotes, theTrypanosoma bruceimitochondrial genome encodes mainly hydrophobic core subunits of the oxidative phosphorylation system. These proteins must be co-translationally inserted into the inner mitochondrial membrane and are synthesized by the highly divergent trypanosomal mitoribosomes, which have a much higher protein to RNA ratio than any other ribosome. Here, we show that the trypanosomal ortholog of the mitoribosome receptor Mba1 (TbMba1) is essential for normal growth of procyclic trypanosomes but redundant in the bloodstream form, which lacks an oxidative phosphorylation system. Proteomic analyses of TbMba1-depleted mitochondria from procyclic cells revealed reduced levels of many components of the oxidative phosphorylation system, most of which belong to the cytochrome c oxidase (Cox) complex, three subunits of which are mitochondrially encoded. However, the integrity of the mitoribosome and its interaction with the inner membrane were not affected. Pulldown experiments showed that TbMba1 forms a dynamic interaction network that includes the trypanosomal Mdm38/Letm1 ortholog and a trypanosome-specific factor that stabilizes the CoxI and CoxII mRNAs. In summary, our study suggests that the function of Mba1 in the biogenesis of membrane subunits of OXPHOS complexes is conserved among yeast, mammalian, and trypanosomes, which belong to two eukaryotic supergroups.
Prediction error drives associative olfactory learning and conditioned behavior in a spiking model ofDrosophila larva
Authors: Jürgensen Anna-Maria , Sakagiannis Panagiotis , Schleyer Michael , Gerber Bertram , Nawrot Martin Paul 
Published: December 2022

AbstractPredicting reinforcement from the presence of environmental clues is an essential component of guiding goal-directed behavior. In insect brains, the mushroom body is central to learning the necessary associations between sensory signals and reinforcement. We propose a biologically realistic spiking network model of the Drosophila larva olfactory pathway for the association of odors and reinforcement to bias behavior towards approach or avoidance. We demonstrate that prediction error coding through the integration of currently present and expected reinforcement in dopaminergic neurons can serve as a driving force in learning that can, combined with a synaptic homeostasis mechanism, account for experimentally observed features of acquisition and loss of associations in the larva that depend on the intensity of odor and reinforcement and temporal features of their pairing. To allow direct comparisons of our simulations with behavioral data [1], we model learning-induced plasticity over the complete time course of behavioral experiments and simulate the locomotion of individual larvae towards or away from odor sources in a virtual environment.
BioNumPy: Fast and easy analysis of biological data with Python
Authors: Rand Knut , Grytten Ivar , Pavlovic Milena , Kanduri Chakravarthi , Sandve Geir Kjetil 
Published: December 2022

AbstractPython is a popular and widespread programming language for scientific computing, in large part due to the powerfularray programminglibrary NumPy, which makes it easy to write clean, vectorized and efficient code for handling large datasets. A challenge with using array programming for biological data is that the data is often non-numeric and variable-length (such as DNA sequences), inhibiting out-of-the-box use of standard array programming techniques. Thus, a tradition in bioinformatics has been to use low-level languages like C and C++ to write efficient code. This makes the tools less transparent to the average computational biologist - making them harder to understand, modify and contribute to.We here present a new Python package BioNumPy, which adds a layer on top of NumPy in order to enable intuitive array programming on biological datasets. BioNumPy is able to efficiently load biological datasets (e.g. FASTQ-files, BED-files and BAM-files) into NumPy-like data structures, so that NumPy operations like indexing, vectorized functions and reductions can be applied to the data. We show that BioNumPy is considerably faster than vanilla Python and other Python packages for common bioinformatics tasks, and in many cases as fast as tools written in C/C++. BioNumPy thus bridges a long-lasting gap in bioinformatics, allowing the same programming language (Python) to be used across the full spectrum from quick and simple scripts to computationally efficient processing of large-scale data.
THE REACTION TIME COSTS OF TRAJECTORY PLANNING
Authors: Feinstein Gil , Shkedy-Rabani Anat , Shmuelof Lior 
Published: December 2022

AbstractIssuing a goal-directed action requires specifying the goal of the action as well as planning the hand trajectory to obtain it. Accumulating results suggest that planning a straight point-to-point trajectory is more efficient and likely to involve simpler optimization process compared to the planning of trajectories with more complex shapes (e.g., curved trajectories). We sought to find evidence for the qualitative difference between the two planning modes through the investigation of reaction times (RT) in a pointing task performed with the wrist. In experiment 1, 18 subjects performed delayed straight and curved via-point reaching movements to arrays of 2 or 8 targets. Both trajectory type and number of possible targets affected RT. In experiment 2 (N=14), we demonstrate a switching cost between the issuing of the two types of trajectories, irrespective of changes in target position. Unexpectedly, trajectory type did not affect RT in experiment 2, likely due to the lack of target pre-cuing in experiment 2. Our results suggest that the planning of curved and straight trajectories differ in their memory load during pre-planning and requires a time-consuming update of the motor commands when switching between straight and curved plans.
Dysregulated cysteine metabolism leads to worsened liver pathology in diabetes-tuberculosis comorbid mice
Authors: Chaudhary Shweta , Pahwa Falak , Nanda Ranjan K. 
Published: December 2022

AbstractDiabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Interestingly, DM is growing to pandemic proportions in TB endemic South-East Asian countries. DM-TB comorbidity induced pathophysiological changes warrants a better understanding to develop effective therapeutics. Tissue metabolomic profiling of streptozotocin (STZ) induced diabetic animals, infected withMycobacterium tuberculosisH37Rv, showed metabolic dysregulation in the lungs, liver, brain, kidney and thigh muscle. At 3 w.p.i., the tissue (lungs, spleen, liver) bacterial loads were similar between DM-TB and TB with worsened lung pathology. Enrichment analysis of the deregulated liver metabolites (n=20; log2DM-TB/TB>±1.0) showed major perturbation in the cysteine-methionine, glycine-serine, branched chain amino acid (BCAA) and fatty acid metabolism. Parallel relative quantification of liver proteome of DM-TB and control mice groups (TB, DM and healthy) identified 1833 proteins which showed group specific variations. Enrichment analysis of significantly altered proteins (n=60; log2DM-TB/TB>±1.0) showed major perturbations in cysteine-methionine metabolism corroborating the metabolomics data. In addition, amino acid biosynthesis, retinol metabolism and polyol biosynthetic process were also differentially enriched in DM-TB groups compared to controls. Furthermore, a global correlation analysis of liver metabolome and proteome data showed strong association between aspartic acid, pyruvic acid, leucine and isoleucine with Cyp450 enzymes (Cyp2a5, Cyp3a11, Cyp4a10, Cyp4a14) involved in retinol metabolism. Whereas iminodiacetic acid, isoleucine and γ-aminobutyric acid strongly correlated to enzymes (Cth, Ahcy, Kyat3, Mat1a) involved in the cysteine metabolism. So, targeting the perturbed liver cysteine and retinol metabolism in DM-TB comorbid condition might improve therapeutic outcomes and prevent organ damage.
Ion mobility mass spectrometry unveils global protein conformations in response to conditions that promote and reverse liquid-liquid phase separation
Authors: Robb Christina Glen , Dao Thuy P. , Ujma Jakub , Castañeda Carlos A. , Beveridge Rebecca 
Published: December 2022

AbstractLiquid-liquid phase separation (LLPS) is a process by which biomacromolecules, particularly proteins, condense into a dense phase that resembles liquid droplets. Dysregulation of LLPS is implicated in disease, yet the relationship between protein conformational changes and LLPS remain difficult to discern. This is due to the high flexibility and disordered nature of many proteins that phase separate under physiological conditions, and their tendency to oligomerise. Here we demonstrate that ion mobility mass spectrometry (IM-MS) overcomes these limitations. We used IM-MS to investigate the conformational states of full-length ubiquilin-2 (UBQLN2) protein, LLPS of which is driven by high salt concentration and reversed by noncovalent interactions with ubiquitin (Ub). IM-MS revealed that UBQLN2 exists as a mixture of monomers and dimers, and that increasing salt concentration causes the UBQLN2 dimers to undergo a subtle shift towards extended conformations. UBQLN2 binds to Ub in 2:1 and 2:2 UBQLN2:Ub complexes which have compact geometries compared to free UBQLN2 dimers. Together, these results suggest that extended conformations of UBQLN2 are correlated with UBQLN2’s ability to phase separate. Overall, delineating protein conformations that are implicit in LLPS will greatly increase understanding of the phase separation process, both in normal cell physiology and disease states.
Molecular anatomy of eosinophil activation by IL5 and IL33
Authors: Mitchell Joshua M. , Mabin Justin W. , Muehlbauer Laura K. , Annis Douglas S. , Mathur Sameer K. , Johansson Mats W. , Hebert Alex S. , Fogerty Frances J. , Coon Joshua J. , Mosher Deane F. 
Published: December 2022

ABSTRACTIL5 and IL33 are major activating cytokines that cause circulating eosinophils to polarize, adhere, and release their granule contents. We correlated microscopic features of purified human blood eosinophils stimulated for 10 min with IL5 or IL33 with phosphoproteomic changes determined by multiplexed isobaric labeling. IL5 caused phosphorylation of sites implicated in JAK/STAT signaling and localization of pYSTAT3 to nuclear speckles whereas IL33 caused phosphorylation of sites implicated in NFκB signaling and localization of RELA to nuclear speckles. Phosphosites commonly impacted by IL5 and IL33 were involved in networks associated with cytoskeletal organization and eosinophil adhesion and migration. Many differentially regulated phosphosites were in a diverse set of large proteins—RAB44, a “large RAB” associated with crystalloid granules; NHSL2 and VIM that change localization along with the nucleus during polarization; TNFAIP3 vital for control of NFκB signaling, and SRRM2 and PML that localize, respectively, to nuclear speckles and PML bodies. Gene expression analysis demonstrated differential effects of IL5 and IL33 on IL18, CCL5, CSF1, and TNFSF14. Thus, common effects of IL5 and IL33 on the eosinophil phosphoproteome are important for positioning in tissues, degranulation, and initiation of new protein synthesis whereas specific effects on protein synthesis contribute to phenotypic heterogeneity.KEY POINTSIL33 and IL5 impact common pathways of eosinophil cytoskeletal reorganization, adhesion and migration.Each lobe of the human eosinophil nucleus has a specific anatomy poised for new onset of cytokine-specific transcription and splicing.