bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical and Ethical Guidelines for the Involvement of Trainees in Global Surgery: Consensus Statement and Recommendations from the Resident and Associate Society of the American College of Surgeons Global Surgery Work Group
Authors: Scott Erin M , Enumah Zachary O , Mehta Kajal , Kontchou Nelly-Ange , Davis Rachel W 
Published: September 2023

BACKGROUND:
The guidelines provided by United States professional surgical organizations for involvement of trainees in global surgery are limited. The aim of this consensus statement is to provide surgical trainees with official recommendations from the Resident and Associate Society of the American College of Surgeons (RAS-ACS) Global Surgery Work Group (GSWG) regarding professional, practical, and ethical guidelines for participation in global surgery endeavors.

STUDY DESIGN:
A task force was created within the GSWG to review and define the scope of involvement of trainees in global surgery, and a consensus process was undertaken for the group at large to approve a set of proposed guidelines.

RESULTS:
The list of practical and ethical guidelines for the engagement of trainees in global surgery, covering the themes of Preparedness, Reciprocity and Collaboration, Ethical Considerations, and Sustainability, was approved with consensus from the GSWG.

CONCLUSION:
This consensus statement from the RAS-ACS GSWG outlines the official recommendations for guidelines for involvement of trainees in global surgery, with an aim to support equitable, sustainable collaborations that center on improving access to safe, timely, and affordable surgical care for the global community at-large. Future processes seek to involve representation and perspectives from a larger body of low-to-middle income country surgical trainees.
Comparing methylation levels assayed in GC-rich regions with current and emerging methods
Authors: Guanzon Dominic , Ross Jason P , Ma Chenkai , Berry Oliver , Liew Yi Jin 
Published: September 2023

AbstractDNA methylation is an epigenetic mechanism that regulates gene expression, and for mammals typically occurs on cytosines within CpG dinucleotides. A significant challenge for methylation detection methods is accurately measuring methylation levels within GC-rich regions such as gene promoters, as inaccuracies compromise downstream biological interpretation of the data. To address this challenge, we compared methylation levels assayed using four different methods: Enzymatic Methyl-seq (EM-seq), whole genome bisulphite sequencing (WGBS), Infinium arrays (Illumina MethylationEPIC, “EPIC”), and Oxford Nanopore Technologies nanopore sequencing (ONT) applied to human DNA. Overall, all methods produced comparable and consistent methylation readouts across the human genome. The flexibility offered by current gold standard WGBS in interrogating genome-wide cytosines is surpassed technically by both EM-seq and ONT, as their coverages and methylation readouts are less prone to GC bias. These advantages are tempered by increased laboratory time (EM-seq) and higher complexity (ONT). We further assess the strengths and weaknesses of each method, and provide recommendations in choosing the most appropriate methylation method for specific scientific questions or translational needs.
Activity-driven emergence of genealogical enclaves in growing bacterial colonies
Authors: Rani Garima , Sengupta Anupam 
Published: September 2023

Bacterial dispersal, the movement of cells spanning diverse physical scales and environments, has been long investigated owing to its far-reaching ramifications in the ecology and evolution of bacterial species and their consortia. A major proportion of bacterial species are surface associated, yet if and how they disperse, specifically during the early stages of biofilm formation, remains to be understood. While physical vectors like fluid flow drive dispersal across large scales, surface-associated cells may benefit from the active biomechanical forces to navigate locally within a colony. Here, by analyzing sessile bacterial colonies, we study how cells disperse over generations due to the growth-induced forces under different conditions. A custom-built labelfree algorithm, developed to track the progeny cells as they grow and divide, reveals the emergence of distinct self-similar genealogical enclaves which intermix over time. Biological activity, indicated by the division times, is a key determinant of the intermixing dynamics; while topological defects appearing at the interface of the enclaves mediate the morphology of finger-like interfacial domains. By quantifying the Shannon entropy, we show that dividing bacterial cells have spatial affinity to close relatives, at the cost of the entropically favourable option of intermixing, wherein faster growing colonies show higher drop in the Shannon entropy over time. A coarse-grained lattice modelling of such colonies, combined with insights from the thermodynamics of phase separation, suggest that the emergence of genealogical enclaves results from an interplay of growth-induced cell dispersal within the colony (which promotes intermixing) and stochasticity of cell division, alongwith the cell-cell interactions at a given growth condition. Our study uncovers the evolution of so-far hidden emergent self-organising features within growing bacterial colonies, which while displaying a high degree of self-similarity on a range of phenotypic traits, point at competing roles of growth-induced forces and entropic landscapes which ultimately shape the genealogical distance of cells to their kith and kin within growing colonies.One Sentence SummaryLabel-free tracking of cells reveals spatio-temporal evolution of genealogical enclaves in growing bacterial colonies resulting from activity-controlled emergent demixing of cell lineages.
Ganglioside Lipids Inhibit the Aggregation of the Alzheimer’s Related Peptide Amyloid-β
Authors: Toprakcioglu Zenon , Jayaram Akhila K. , Knowles Tuomas P. J. 
Published: September 2023

AbstractThe aggregation of the amyloid-β(Aβ) peptides (Aβ42/Aβ40) into toxic amyloid fibrils and plaques is one of the molecular hallmarks in dementia and Alzheimers disease (AD). While the molecular mechanisms behind this aggregation process are not fully known, it has been shown that some biomolecules can accelerate this process while others can inhibit amyloid formation. Lipids, which are ubiquitously found in cell membranes, play a pivotal role in protein aggregation. Here, we investigate how ganglioside lipids, which are abundant in the brain and in neurons, can influence the aggregation kinetics of both Aβ42 and Aβ40. We find that ganglioside lipids can drastically inhibit the aggregation of Aβ42, while in the case of the smaller peptide (Aβ40), gangliosides can completely inhibit the aggregation process. Moreover, through kinetic analysis we show that the primary nucleation rate is greatly affected by the addition of gangliosides, and that the presence of these lipids can inhibit the primary nucleation rate of Aβ42 by 3 orders of magnitude. By means of viability assays of neuroblastoma cells (SH-SY5Y), we further demonstrate that amyloid fibrils formed in the absence of gangliosides are more toxic to these cells than amyloid fibrils formed in the presence of gangliosides, elucidating the inhibitory and potentially protective role that these lipids can play. Additionally, we show that monomeric Aβ40/Aβ42 form complexes with gangliosides, but not with other lipids such as POPS, suggesting that formation of ganglioside-Aβcomplexes can act as a potential pathway towards inhibiting amyloid-βaggregation. Taken together, our results provide a quantitative description of how lipid molecules such as gangliosides can inhibit the aggregation of Aβand shed light on the key factors that control these processes, especially in view of the fact that declining levels of gangliosides in neurons have been associated with ageing.
Majority of human circulating plasmablasts stop blasting: A probable misnomer
Authors: Nguyen Doan C. , Saney Celia , Hentenaar Ian T. , Cabrera-Mora Monica , Woodruff Matthew C. , Andrews Joel , Lonial Sagar , Sanz Ignacio , Lee F. Eun-Hyung 
Published: September 2023

AbstractFollowing infection or vaccination, early-minted antibody secreting cells (ASC) or plasmablasts appear in circulation transiently, and a small fraction migrates to the spleen or bone marrow (BM) to mature into long-lived plasma cells (LLPC). While LLPC, by definition, are quiescent or non-dividing, the majority of blood ASC are thought to be “blasting” or proliferative. In this study, we find >95% nascent blood ASC in culture express Ki-67 but only 6-12% incorporate BrdU after 4h or 24h labeling. In contrast, <5% BM LLPC in culture are Ki-67+with no BrdU uptake. Due to limitations of traditional flow cytometry, we utilized a novel optofluidic technology to evaluate cell division with simultaneous functional Ig secretion. We find 11% early-minted blood ASC undergo division, and none of the terminally differentiated BM LLPC (CD19-CD38hiCD138+) divide during the 7-21 days in culture. While BM LLPC undergo complete cell cycle arrest, the process of differentiation into an ASC of plasmablasts discourages entry into S phase. Since the majority of Ki-67+nascent blood ASC have exited cell cycle and are no longer actively “blasting”, the term “plasmablast”, which traditionally refers to an ASC that still has the capacity to divide, may probably be a misnomer.
Cell4D: A general purpose spatial stochastic simulator for cellular pathways
Authors: Chan Donny , Cromar Graham L. , Taj Billy , Parkinson John 
Published: September 2023

STRUCTURED ABSTRACTMotivationWith the generation of vast compendia of ‘omics datasets, the challenge is how best to interpret these datasets to gain meaningful biological insights. Key to this challenge are computational methods that enable domain-users to generate novel hypotheses that can be used to guide future experiments. Of particular interest are flexible modeling platforms, capable of simulating a diverse range of biological systems with low barriers of adoption to those with limited computational expertise.ResultsWe introduce Cell4D, a spatial-temporal modeling platform combining a robust simulation engine with integrated graphics visualization, a model design editor, and an underlying XML data model capable of capturing a variety of cellular functions. Cell4D provides an interactive visualization mode, allowing intuitive feedback on model behaviour and exploration of novel hypotheses, together with a non-graphics mode, compatible with high performance cloud compute solutions, to facilitate generation of statistical data. To demonstrate the flexibility and effectiveness of Cell4D, we investigate the dynamics of CEACAM1 localization in T-cell activation. We confirm the importance of Ca++microdomains in activating calmodulin and highlight a key role of activated calmodulin on the surface expression of CEACAM1. We further show how lymphocyte-specific protein tyrosine kinase can help regulate this cell surface expression and exploit spatial modeling features of Cell4D to test the hypothesis that lipid rafts regulate clustering of CEACAM1 to promote trans-binding to neighbouring cells. Through demonstrating its ability to test and generate hypotheses, Cell4D represents an effective tool to help interpret complex ‘omics datasets.Availability and Implementationhttps://github.com/ParkinsonLab/cell4dContactjparkin@sickkids.ca
Duoculture diminishes social interaction costs and improves growth rates of two fish species at different temperatures
Authors: Yao Hong , O’Bryant Paul. , Rapp Dean. , Gao Zhe-Xia. , Wang Han-Ping 
Published: September 2023

AbstractDuoculture has been reported to increase growth rates of some fishes when reared in combination, due to “shading” effects between the species. Two experiments, one involving outdoor cage-rearing in a reservoir, and the other, indoor tank-rearing, were conducted within each of three temperatures ranges (means of ∼18.0°C, ∼22.0°C and ∼26.5°C), to determine whether duoculture of bluegill (BG)Lepomis macrochirusand yellow perch (YP)Perca flavescenswould lead to improved growth relative to when the two species were reared separately. Juvenile bluegill and yellow perch were reared in triplicated groups each involving monoculture sets of 100% BG and 100% YP, and a duoculture set of 50% BG + 50% YP. Experiments in cages (Exp. 1) ran for 150 days while those in tanks ran for 126 days (Exp. 2). In Experiment 1, bluegill exhibited significantly greater (P<0.05) mean weight (P<0.05) in duoculture than in monoculture, under the high summer-like range of temperature (∼26.5°C) over most of the experiment, whereas yellow perch showed no significant difference in mean weight in duoculture versus monoculture. By the end of a 150-d experiment, bluegill in duoculture outweighed those in monoculture by 62.5%. In Experiment 2, yellow perch in duoculture grew significantly larger than in monoculture (P<0.05) under the warm thermal regime (mean of ∼22°C), while no significant differences were detected in mean weight of bluegill in monoculture versus duoculture. Yellow perch in duoculture outweighed those in monoculture by 33.1% at the end of the experiment. Yellow perch performed better in duoculture than in monoculture under the low thermal regime (mean of ∼18°C) in both experiments. A significantly greater reduction of CVwtwas observed for both bluegill and yellow perch in duoculture than in monoculture in Experiment 1, while no differences in CVwtreduction were detected for bluegill in Experiment 2. Feed conversion ratios (FCR) of bluegill and yellow perch reared in duoculture were significantly lower than for both fishes reared in monoculture in Experiment 1, while there were no significant differences in FCR among the three groups throughout most of Experiment 2. Findings indicate that duoculture of yellow perch and bluegill holds good potential to improve growth and FCR, and to reduce size variation by diminishing social interaction costs.
Assessing the potential of eDNA analysis for spawning surveys in marine environments: A case study on Japanese jack mackerel
Authors: Tsuji Satsuki , Murakami Hiroaki , Masuda Reiji 
Published: September 2023

AbstractUnderstanding spawning ecology is important for species/population management and conservation. However, conventional surveys are often time- and labour-consuming and invasive. To address these challenges, environmental DNA (eDNA) analysis has emerged as a promising method for spawning surveys. This study investigated the spawning season and diurnal changes in eDNA concentrations targeted Japanese jack mackerel in Maizuru Bay, Japan, to assess the potential of eDNA-based spawning surveys in the marine environment. First, to estimate the spawning season, eDNA concentrations at sunset and sunrise were compared monthly for one year at three sites. As Japanese jack mackerel are nocturnal spawners, eDNA concentration will increase at night during the spawning season. A significant increase in eDNA concentration was observed between sunset and sunrise in July, suggesting that this period corresponded to the spawning season. This was confirmed by egg collection surveys using a plankton net. Second, to investigate diurnal changes in eDNA concentrations during the spawning season, time-series sampling was conducted every three hours for 24 hours in July. The results indicated that eDNA concentration showed a significant diurnal change with a peak between 9 PM and midnight, which is suggested to be their spawning time window. This study successfully estimated the spawning season of Japanese jack mackerel and demonstrated the potential of eDNA-based spawning surveys for the first time in marine environments. These surveys are expected to contribute to the advancement of this field as a new approach to overcoming traditional challenges in marine spawning surveys.HighlightsThe potential of eDNA for spawning surveys was assessed in jack mackerel.Monthly morning and evening eDNA sampling identified spawning activity in July.Egg surveys using a plankton net confirmed the spawning event.Time-series sampling showed a diurnal change in eDNA concentrations in July.eDNA analysis is thus applicable for detecting spawning in marine species.
Predictive Modeling of Clinical Trial Outcomes for Novel Drugs using Digital Twin Patient Cohorts and GenerativeAI
Authors: Chebanov Dmitrii K , Misyurin Vsevolod A 
Published: September 2023

ABSTRACTThere is a problem of clinical trial failure, as each new drug should surpass the effectiveness of existing treatment regimens, which becomes increasingly challenging over time. Another significant issue is treating patients who have developed resistance to the current therapies.Essentially, the use of drug combinations or off-label drug use, where the indication does not match the diagnosis, is akin to an experiment, as there is insufficient data on which drug or combination to use.This work proposes an approach utilizing computer modeling of patients using gene expression and clinical data. Deep learning and generative adversarial networks are employed as modeling tools. The training data for the algorithms were sourced from publicly available databases such as TCGA and Drugbank.The modeling is based on the hypothesis of similarity between patients, similarity between drugs, as well as the similarity between individual organs and patient tissues with cell lines, with similarity being computed mathematically. As a result, a patient model is created, where the input consists of drugs and their combinations, and the output provides survival probability values. These model data can be generated in any required quantity with generative adversarial networks (GAN) technology to create observation and control groups. Consequently, it becomes possible to simulate clinical trials, forecasting their outcomes, and, most importantly, optimizing the trial parameters to maximize the likelihood of success.
IMPALA: A Comprehensive Pipeline for Detecting and Elucidating Mechanisms of Allele Specific Expression in Cancer
Authors: Chang Glenn , Porter Vanessa L. , O’Neill Kieran , Culibrk Luka , Akbari Vahid , Marra Marco A. , Jones Steven J. M. 
Published: September 2023

AbstractSummaryAllele-specific expression (ASE), where transcripts from one allele are more abundant than transcripts from the other, can arise from various genetic mechanisms and has implications for gene regulation and disease. We present IMPALA (Integrated Mapping and Profiling of Allelically-expressed Loci with Annotations), a versioned and containerized pipeline for detecting ASE in samples including cancer genomes. IMPALA leverages RNA sequencing data and, optionally, phased variant, copy number variant (CNV), allelic methylation, and mutation data to identify ASE genes and uncover underlying regulatory mechanisms. IMPALA incorporates the MBASED framework for ASE detection, and outputs a comprehensive summary table and informative figures to visualize the genomic distribution of ASE genes and their correlation with potential regulatory causes. We applied IMPALA to a cancer sample and identified thousands of genes with ASE and highlighted potential somatic events that may have influenced ASE of these genes. ASE data can be used to detect the downstream consequences of genomic alterations, which facilitates the identification of dysregulated cancer-related genes. IMPALA thus provides researchers with a powerful tool for both ASE analysis and for investigating genetic factors correlated with ASE.Availability and implementationIMPALA is licensed under GNU General Public License v3.0 and freely available athttps://github.com/bcgsc/IMPALAandhttps://doi.org/10.5281/zenodo.8019168with documentation and tutorial.Contactsjones@bcgsc.caSupplemental informationSupplemental materials are available at Bioinformatics online. Issue section: Gene expression
Winners and losers under past and future climate change
Authors: Thomas Anne E. , Larcombe Matthew J. , Higgins Steven I. , Trabucco Antonio , Tanentzap Andrew J. 
Published: September 2023

ABSTRACTUnderstanding the historical and physiological context of species’ vulnerabilities to climate change is a crucial step in predicting “winners” and “losers” under climate change. However, few studies have compared the magnitude and mechanisms of extant species’ responses to climate change in both the past and the future. By combining temporally contrasting range and niche projections, we show that range shifts in the next 50 years will need to be more extreme than in the past 6000 years to track climate niches in a large plant radiation. A new subset of physiological niche traits, particularly temperature and radiation tolerance, will be strong filters of range occupancy under anthropogenic compared with Holocene climate change. In the absence of migration, temperature niche shifts tracking the magnitude of climate change will also be required for many species to maintain their present ranges. Where range shifts occur, our results suggest that communities will be restructured differently in different habitats, with widespread range contraction in the mountains and potential latitudinal range expansion in the lowlands. Our study adds to a growing body of evidence that despite the threats posed by climate change to many species, not all species will experience unmitigated loss, and that it may be possible to predict which species are most at risk based on physiological and geographical traits.
Disease related changes in ATAC-Seq of more than 450 iPSC-derived motor neuron lines from ALS patients and controls
Authors: Tsitkov Stanislav , Valentine Kelsey , Kozareva Velina , Donde Aneesh , Frank Aaron , Lei Susan ,   the Answer ALS Consortium, Eyk Jennifer Van , Finkbeiner Steve , Rothstein Jeffrey , Thompson Leslie , Sareen Dhruv , Svendsen Clive N. , Fraenkel Ernest 
Published: September 2023

AbstractAmyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing. Once these covariates are corrected for, we are able to identify robust ALS-specific signals in the data. Additionally, we find that the ATAC-seq data is able to predict ALS disease progression rates with similar accuracy to methods based on biomarkers and clinical status. These results suggest that iPSC-derived motor neurons recapitulate important disease-relevant epigenomic changes.