bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open Abdominal Management for Damage Control in Liver Transplantation: A Single-center Experience
Authors: Hara Takanobu , Soyama Akihiko , Matsushima Hajime , Imamura Hajime , Yamashita Mampei , Ishizaki Hironori , Yano Rintaro , Matsumoto Sojiro , Ichinomiya Taiga , Higashijima Ushio , Sekino Motohiro , Fukumoto Masayuki , Migita Kazushige , Kawaguchi Yuta , Adachi Tomohiko , Hara Tetsuya , Eguchi Susumu 
Published: August 2024

Background.
Patients undergoing liver transplantation are in a state of coagulopathy before surgery because of liver failure. Intraoperative hemorrhage, massive transfusions, and post–reperfusion syndrome further contribute to coagulopathy, acidosis, and hypothermia. In such situations, temporary cessation of surgery with open abdominal management and resuscitation in the intensive care unit (ICU), which is commonly used as a damage control strategy in trauma care, may be effective. We assessed the outcomes of open abdominal management in liver transplantation and the corresponding complication rates.

Methods.
We retrospectively reviewed the outcomes of patients undergoing open abdominal management among 250 consecutive liver transplantation cases performed at our institution from 2009 to 2022.

Results.
Open abdominal management was indicated in 16 patients. The open abdomen management group had higher Model for End-stage Liver Disease scores (24 versus 16, P < 0.01), a higher incidence of previous upper abdominal surgery (50% versus 18%, P < 0.01), more pretransplant ICU treatment (31% versus 10%, P = 0.03), and more renal replacement therapy (38% versus 12%, P = 0.01). At the time of the damage control decision, coagulopathy (81%), acidosis (38%), hypothermia (31%), and a high-dose noradrenaline requirement (75%) were observed. The abdominal wall was closed in the second operation in 75% of patients, in the third operation in 19%, and in the fourth operation in 6%. Postoperatively, the frequency of early allograft dysfunction was predominantly higher in the open abdominal management group (69%), whereas the frequency of vascular complications and intra-abdominal infection was the same as in other patients.

Conclusions.
Open abdominal management can be a crucial option in cases of complex liver transplant complicated by conditions such as hypothermia, acidosis, coagulopathy, and hemodynamic instability. Damage control management minimizes deterioration of the patient’s condition during surgery, allowing completion of the planned procedure after stabilizing the patient’s overall condition in the ICU.
An instantaneous voice synthesis neuroprosthesis
Authors: Wairagkar Maitreyee , Card Nicholas S. , Singer-Clark Tyler , Hou Xianda , Iacobacci Carrina , Hochberg Leigh R. , Brandman David M. , Stavisky Sergey D. 
Published: August 2024

AbstractBrain computer interfaces (BCIs) have the potential to restore communication to people who have lost the ability to speak due to neurological disease or injury. BCIs have been used to translate the neural correlates of attempted speech into text1–3. However, text communication fails to capture the nuances of human speech such as prosody, intonation and immediately hearing one’s own voice. Here, we demonstrate a “brain-to-voice” neuroprosthesis that instantaneously synthesizes voice with closed-loop audio feedback by decoding neural activity from 256 microelectrodes implanted into the ventral precentral gyrus of a man with amyotrophic lateral sclerosis and severe dysarthria. We overcame the challenge of lacking ground-truth speech for training the neural decoder and were able to accurately synthesize his voice. Along with phonemic content, we were also able to decode paralinguistic features from intracortical activity, enabling the participant to modulate his BCI-synthesized voice in real-time to change intonation, emphasize words, and sing short melodies. These results demonstrate the feasibility of enabling people with paralysis to speak intelligibly and expressively through a BCI.
Disentangling the drivers of heterogeneity in SARS-CoV-2 transmission from data on viral load and daily contact rates
Authors: Quilty Billy J , Chapman Lloyd AC , Munday James D , Wong Kerry LM , Gimma Amy , Pickering Suzanne , Neil Stuart JD , Galão Rui Pedro , Edmunds W John , Jarvis Christopher I , Kucharski Adam J 
Published: August 2024

AbstractSARS-CoV-2 spreads predominantly through superspreading, with a minority of individuals responsible for the majority of transmission, though the drivers of this heterogeneity are unclear. Here, we assess the contribution of variation in viral load and daily contact rates to this heterogeneity by combining viral load and contact survey data in a mathematical model to estimate the secondary infection distribution. Using data from the BBC Pandemic and CoMix contact surveys, we estimate the basic reproduction number (R0= 2.2, 95% CI 2.1-2.2) from first principles and the secondary infection distribution throughout the pandemic in the UK in 2020, and the effectiveness of frequent and pre-event rapid testing for reducing superspreading events. We find that individual heterogeneity in contacts – rather than individual heterogeneity in shedding – drives observed heterogeneity in the secondary infection distribution. Our results suggest that regular testing every 3 days, or pre-event testing with a minimum event size of 10, could reduce the mean reproduction number below 1 with moderate to high levels of uptake (60-80%) for pre-pandemic contact levels. This work demonstrates the potential for using viral load and contact data to predict heterogeneity in transmission and the effectiveness of rapid testing strategies for curbing transmission in future pandemics.
Exploring ancestry inference of the Middle East
Authors: Herrick Noah , Ghemrawi Mirna , Singh Sylvia , Mahfouz Rami , Walsh Susan 
Published: August 2024

AbstractThe capability to infer biogeographic ancestry with curated panels of ancestry informative markers (AIMs) is a critical component to DNA intelligence. There are many AIM panels that resolve population differentiation at a continental level. Of late, several studies have directed marker discovery to the Middle East because of the difficulties for AIM panels to resolve this region amongst populations in Eurasia. The AIM discovery process has remained largely unchanged, except for the most recent additions of whole-genome sequence (WGS) data repositories which now include Middle Eastern individuals. Here, the latest WGS data from 1000 Genomes Project and Human Genome Diversity Project was paired with novel Middle Eastern population data from Lebanon for AIMs discovery. An unbiased genetic clustering approach was employed for selecting population clusters for allelic frequency comparisons. Two candidate AIMs were reported, compared, and evaluated together with the autosomal AIMs from the VISAGE Enhanced Tool. These comparisons involved a validation dataset from Middle Eastern WGS data published by the Wellcome Sanger Institute and resulted in slight gains of Middle Eastern ancestry proportions for several Middle Eastern samples with varying levels of co-ancestries. The validation samples also underwent an unsupervised worldwide ADMIXTURE analysis alongside previously mentioned WGS datasets using nearly two million markers (r2 < 0.1) to establish a ‘ground truth’ population membership. Lastly, a novel application of the deep learning dimensional reduction algorithm ‘popVAE’ is provided as an open-source web tool to illustrate the AIM panels variance among these population clusters within two dimensions for easy global ancestry visualization in addition to providing a closest population membership metric.
Investigating Polyreactivity of CD4+ T Cells to the Intestinal Microbiota
Authors: Saadawi Ahmed , Mair Florian , Rosenwald Esther , Hoces Daniel , Slack Emma , Kopf Manfred 
Published: August 2024

AbstractThe symbiotic relationship between host and microbiota plays a pivotal role in training and development of the host’s innate and adaptive immune systems. Antigen-specific recognition of microbiota by T cells enforces tolerance at homeostasis. Conversely, dysbiosis—characterized by alterations in microbiota diversity and abundance—leads to imbalanced T cell responses and triggering of inflammatory and autoimmune diseases. Despite their significance, the identities of immunogenic microbial antigens are still largely enigmatic. Here, we leveraged an in-house developed antigen screening platform, the MCR system1, to delineate CD4+ T cell reactivity againstAkkermansia muciniphila(AKK) andBacteroides thetaiotaomicron(BT), —two prominent members of the gut microbiota. T-cell hybridomas reactive to AKK and BT bacteria showed polyreactivity to select microbiota-derived peptides in MCR co-cultures. We discovered 13 novel antigenic epitopes from AKK and 14 from BT. Steady-state T cells recognized these epitopes in an MHC-restricted fashion. Ex vivo stimulation of peptide-specific T cells revealed induction of type 1 and type 17 immune responses, albeit with non-overlapping specificities, contrary to MCR system results. Our findings further demonstrated that most identified epitopes are broadly conserved within the given phylum and originate from both membrane and intracellular proteins. Our work showcases the potential of the MCR system for identifying immunogenic microbial epitopes, providing a valuable resource. Additionally, it indicates the existence of mucosal T cells with a tropism toward broadly conserved bacterial epitopes. Overall, our study forms the basis for decoding antigen specificity in immune system-bacterial interactions, with applications in understanding both microbiome and pathogenic bacterial immunity.
Personalized whole-brain activity patterns predict human corticospinal tract activation in real-time
Authors: Khatri Uttara U , Pulliam Kristen , Manesiya Muskan , Cortez Melanie Vieyra , Millán José del R. , Hussain Sara J 
Published: August 2024

AbstractBACKGROUNDTranscranial magnetic stimulation (TMS) interventions could feasibly treat stroke-related motor impairments, but their effects are highly variable. Brain state-dependent TMS approaches are a promising solution to this problem, but inter-individual variation in lesion location and oscillatory dynamics can make translating them to the poststroke brain challenging. Personalized brain state-dependent approaches specifically designed to address these challenges are therefore needed.METHODSAs a first step towards this goal, we tested a novel machine learning-based EEG-TMS system that identifies personalized brain activity patterns reflecting strong and weak corticospinal tract (CST) output (strong and weak CST states) in healthy adults in real-time. Participants completed a single-session study that included the acquisition of a TMS-EEG-EMG training dataset, personalized classifier training, and real-time EEG-informed single pulse TMS during classifier-predicted personalized CST states.RESULTSMEP amplitudes elicited in real-time during personalized strong CST states were significantly larger than those elicited during personalized weak and random CST states. MEP amplitudes elicited in real-time during personalized strong CST states were also significantly less variable than those elicited during personalized weak CST states. Personalized CST states lasted for ∼1-2 seconds at a time and ∼1 second elapsed between consecutive similar states. Individual participants exhibited unique differences in spectro-spatial EEG patterns between personalized strong and weak CST states.CONCLUSIONOur results show for the first time that personalized whole-brain EEG activity patterns predict CST activation in real-time in healthy humans. These findings represent a pivotal step towards using personalized brain state-dependent TMS interventions to promote poststroke CST function.
Headwinds to Understanding Stress Response Physiology: A Systematic Review Reveals Mismatch between Real and Simulated Marine Heatwaves
Authors: Martell Harmony A. , Donner Simon D. 
Published: August 2024

ABSTRACTLaboratory experiments have long been used to guide predictions of organismal stress in response to our rapidly changing climate. However, the ability to simulate real world conditions in the laboratory can be a major barrier to prediction accuracy, creating obstacles to efforts informing ecosystem conservation and management. Capitalizing on an extensive experimental literature of coral bleaching physiology, we performed a systematic review of the literature and assembled a database to identify the methods being used to measure coral bleaching in heating experiments and assess how closely heating experiments resembled marine heatwaves (MHWs) on coral reefs. Observations of the maximum photochemical yield of Photosystem II (FV/FM), though not a direct measure of bleaching, vastly outnumbered Symbiodiniaceae density and chlorophyll (μg cm-2, pg cell-1) observations in the available literature, indicating the widespread misuse ofFV/FMas a proxy for coral bleaching. Laboratory studies in our database used significantly higher maximum temperatures, degree heating times (∼ 1.7 ×) and heating rates (∼ 7.3 ×), and significantly shorter durations (∼ 1.5 ×), than MHWs on coral reefs. We then asked whether exposure differences between lab and reef altered the relationship between coral bleaching and heating metrics using the example of hormesis, the biphasic dose response wherein low to moderate doses elicit some benefit, while high doses are deleterious. We fit curves on the data both with and without ecologically relevant heating metrics and found hormetic curves in some response variables were altered with the exclusion of exposures that fell outside of the bounds of MHWs on coral reefs. Differences between lab exposures and real-world MHWs were large enough to alter the relationships, indicating a high likelihood of prediction error. We recommend laboratory-based studies of coral bleaching use ecologically relevant exposures to improve our predictions of the coral physiological response to our rapidly warming oceans.
Robustness and variability inCaenorhabditis elegansdauer gene expression
Authors: Corchado Johnny Cruz , Godthi Abhishiktha , Selvarasu Kavinila , Prahlad Veena 
Published: August 2024

ABSTRACTBoth plasticity and robustness are pervasive features of developmental programs. The dauer inCaenorhabditis elegansis an arrested, hypometabolic alternative to the third larval stage of the nematode. Dauers undergo dramatic tissue remodeling and extensive physiological, metabolic, behavioral, and gene expression changes compared to conspecifics that continue development and can be induced by several adverse environments or genetic mutations that act as independent and parallel inputs into the larval developmental program. Therefore, dauer induction is an example of phenotypic plasticity. However, whether gene expression in dauer larvae induced to arrest development by different genetic or environmental triggers is invariant or varies depending on their route into dauer has not been examined. By using RNA-sequencing to characterize gene expression in different types of dauer larvae and computing the variance and concordance within Gene Ontologies (GO) and gene expression networks, we find that the expression patterns within most pathways are strongly correlated between dauer larvae, suggestive of transcriptional robustness. However, gene expression within specific defense pathways, pathways regulating some morphological traits, and several metabolic pathways differ between the dauer larvae. We speculate that the transcriptional robustness of core dauer pathways allows for the buffering of variation in the expression of genes involved in adaptation, allowing the dauers induced by different stimuli to survive in and exploit different niches.
A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer
Authors: Walke Prachi , Price Jared D.W. , Vizeacoumar Frederick S. , Joseph Nickson , Maranda Vincent , Chowdhury Bari , Patel Jay , Zhang Yue , Dong He , New Lara , Ganapathysamy Ashtalakshmi , Gong Li Hui , Elhasasna Hussain , Bhanumathy Kalpana K. , Wu Yuliang , Freywald Andrew , Krishnan Anand , Vizeacoumar Franco J. 
Published: August 2024

SummaryNeuroendocrine prostate cancer (NEPC) presents a formidable clinical challenge owing to its aggressive progression and resistance to conventional therapies. A key driver of NEPC is the overexpression ofMYCN, a well-established oncogene associated with neuroendocrine tumors. However, efforts to directly inhibit the N-Myc protein encoded by this gene have resulted in limited success, thereby hindering therapeutic advancements. To overcome this obstacle, we conducted unbiased genome-wide screening using isogenic prostate cancer cell lines to identify the synthetic vulnerabilities ofMYCN. Among the identified candidates,NEUROG2emerged as a significant candidate. Neurog2 is a proneural transcription factor (PTF) known for its role in developmental processes and trans-differentiation of adult cells. Our findings demonstrate that Neurog2 depletion does not affect non-malignant cells, but significantly suppresses the growth ofMYCN-overexpressing cells and tumors in orthotopic NEPC models. Furthermore, our observations indicate that the Neurog2-mediated regulation of PTFs can facilitate NEPC development. Thus, targeting Neurog2 holds promise as an effective therapeutic strategy forMYCN-overexpressing NEPC.
14-3-3 promotes sarcolemmal expression of cardiac CaV1.2 and nucleates isoproterenol-triggered channel super-clustering
Authors: Spooner Heather C. , Costa Alexandre D. , González Adriana Hernández , Ibrahimkhail Husna , Yarov-Yarovoy Vladimir , Horne Mary , Dickson Eamonn J. , Dixon Rose E. 
Published: August 2024

AbstractThe L-type Ca2+channel (CaV1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca2+flux that drives Ca2+-induced-Ca2+-release, CaV1.2 channels must be expressed on the sarcolemma; thus the regulatory mechanisms that tune CaV1.2 expression to meet contractile demand are an emerging area of research. A ubiquitously expressed protein called 14-3-3 has been proposed to affect Ca2+channel trafficking in non-myocytes, however whether 14-3-3 has similar effects on CaV1.2 in cardiomyocytes is unknown. 14-3-3 preferentially binds phospho-serine/threonine residues to affect many cellular processes and is known to regulate cardiac ion channels including NaV1.5 and hERG. Altered 14-3-3 expression and function have been implicated in cardiac pathologies including hypertrophy. Accordingly, we tested the hypothesis that 14-3-3 interacts with CaV1.2 in a phosphorylation-dependent manner and regulates cardiac CaV1.2 trafficking and recycling. Confocal imaging, proximity ligation assays, super-resolution imaging, and co-immunoprecipitation revealed a population of 14-3-3 colocalized and closely associated with CaV1.2. The degree of 14-3-3/CaV1.2 colocalization increased upon stimulation ofβ-adrenergic receptors with isoproterenol. Notably, only the 14-3-3-associated CaV1.2 population displayed increased cluster size with isoproterenol, revealing a role for 14-3-3 as a nucleation factor that directs CaV1.2 super-clustering. 14-3-3 overexpression increased basal CaV1.2 cluster size and Ca2+currents in ventricular myocytes, with maintained channel responsivity to isoproterenol. In contrast, isoproterenol-stimulated augmentation of sarcolemmal CaV1.2 expression and currents in ventricular myocytes were abrogated by 14-3-3 inhibition. These data support a model where 14-3-3 interacts with CaV1.2 in a phosphorylation-dependent manner to promote enhanced trafficking/recycling, clustering, and activity duringβ-adrenergic stimulation.Significance StatementThe L-type Ca2+channel, CaV1.2, plays an essential role in excitation-contraction coupling in the heart and in part regulates the overall strength of contraction during basal and fight- or-flightβ-adrenergic signaling conditions. Proteins that modulate the trafficking and/or activity of CaV1.2 are interesting both from a physiological and pathological perspective, since alterations in CaV1.2 can impact action potential duration and cause arrythmias. A small protein called 14-3-3 regulates other ion channels in the heart and other Ca2+channels, but how it may interact with CaV1.2 in the heart has never been studied. Examining factors that affect CaV1.2 at rest and duringβ-adrenergic stimulation is crucial for our ability to understand and treat disease and aging conditions where these pathways are altered.
Trade-offs beget trade-offs: Causal analysis of mammalian population dynamics
Authors: Bergman Juraj , Pedersen Rasmus Ø. , Lundgren Erick J. , Trepel Jonas , Pearce Elena A. , Czyżewski Szymon , Tietje Melanie , Lemoine Rhys T. , Macià Moisès Coll , Schierup Mikkel H. , Svenning Jens-Christian 
Published: August 2024

AbstractSurvival and reproduction strategies in mammals are determined by trade-offs between life history traits. In turn, the unique configuration of traits that characterizes mammalian species gives rise to species-specific population dynamics. The dependence of population dynamics on life history has been primarily studied as the relationship between population density and size-related traits. With the recent accumulation of genomic data, the effective population size (number of breeding individuals;Ne) over the last 100-800 kya has become quantifiable for a large proportion of mammals. Using phylogenetic path analysis, we compared the dependence of population density andNeon eleven traits that characterize mammalian allometry, diet and reproduction. We found variable trait impacts on these two metrics of population dynamics across different phylogenetic, ecological and conservation classifications of mammals. Brain size had a negative effect on density but a positive effect onNe, especially in primates and carnivores. Diet specialization had a negative effect on both density andNe. The relationship betweenNe(but not density) and several traits showed biome-related gradients. We found that critically endangered species have life history strategies that impede population recovery, as reflected by the strong positive dependence of both density andNeon generation length. Our findings demonstrate that trade-offs characterizing life history evolution are not only trait-specific, but are also present between different metrics of population dynamics. This challenges the static nature of the “energetic equivalence” rule and has major implications for selecting the appropriate population metric in species conservation and restoration strategies.Significance statementTrade-offs are an essential component of trait evolution, underlying various strategies used by species to mitigate environmental pressures and ensure their survival. We investigated how traits affect mammalian population-level parameters, including population density and effective population size (number of breeding individuals;Ne). We found that the impact of traits on these two measures of population dynamics was variable. For example, both density andNedecreased in species with larger body size, while brain size was negatively related to population density but positively related toNe. We therefore show that evolutionary trade-offs are not limited to traits, but are also present between population-level parameters, which can have important implications for future conservation and restoration efforts.