bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison between Propofol and Total Inhalational Anaesthesia on Cardiovascular Outcomes Following On-pump Cardiac Surgery in Higher-Risk Patients – A Randomised Controlled Pilot and Feasibility Study
Authors: Milne Benjamin , John Martin , Evans Richard , Robertson Steven , Scanaill Pádraig Ó , Murphy Gavin J , Landoni Giovanni , Marber Mike , Clayton Tim , Kunst Gudrun 
Published: February 2024

AbstractObjectivesMyocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies, however there is uncertainty as whether this translates into clinical benefits.MethodsIn this single blinded parallel group randomised controlled feasibility trial higher-risk patients undergoing elective coronary artery bypass graft surgery with an additive European System for Cardiac Operative Risk Evaluation (EuroScore)>5 were randomised to receive either propofol or total inhalational anaesthesia for maintenance of anaesthesia. The primary outcome was the feasibility to recruit and randomise 50 patients across two cardiac surgical centres and secondary outcomes included the feasibility of collecting the planned perioperative data and clinically relevant outcomes and assessments of effective patient identification, screening and recruitment.ResultsAll 50 patients were recruited within 11 months in two centres allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up.ConclusionsIt is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates.
Prolonged Water-only Fasting is a Safe and Feasible Treatment Option for Managing Stage 1 and 2 Hypertension
Authors: Zeiler Evelyn , Gabriel Sahmla , Ncube Mackson , Thompson Natasha , Scharf Eugene , Goldhamer Alan C. , Myers Toshia R. 
Published: February 2024

AbstractProlonged water-only fasting appears to reduce high blood pressure but randomized controlled trials are needed. This single arm pre-post interventional trial (clinicaltrials.gov,NCT04515095) investigates the safety, feasibility, and effectiveness of prolonged water-only fasting in the treatment of stage 1 and 2 hypertension. Twenty-nine participants with stage 1 and 2 hypertension, who were pre-approved to water-only fast for ≥7 days, were enrolled from a residential fasting center. Participants received 24-hour medical supervision, and adverse events were recorded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Feasibility was assessed based on retention rate, ability to complete minimal fast length, and intervention acceptability. Demographic, anthropometric, medication use, laboratory, and survey data were also collected. Twenty-seven of the 29 enrolled participants attended all study visits through the six-week follow-up visit and completed at least seven consecutive days of water-only fasting. The majority of adverse events were mild and transient and there were no higher-grade or serious adverse events. Overall, the intervention was acceptable. At the six-week follow-up visit, there were sustained reductions in median systolic/diastolic blood pressure (−19.19/-5.13 mmHg), body weight (−6.72 kg), abdominal circumference, −6.55 cm), and anti-hypertensive medication use (−93%), which also persisted at the 12-month follow-up visit. These preliminary data suggest that prolonged water-only fasting is a safe and feasible treatment option for stage 1 and 2 hypertension. The data also suggest that fasting may result in sustainable reductions in high blood pressure and anti-hypertensive medication use.
The risk prediction models of neonatal necrotizing enterocolitis in China: a systematic review
Authors: Wu Jiaming , Du jiajia , Peng Junjie , Guo Xin , Hu Xue , Li Yunchuan , Wu Yuanfang 
Published: February 2024

AbstractObjectiveSystematically evaluate the risk prediction model for neonatal necrotizing enterocolitis (NEC) in China, providing reference for clinical work and future research.MethodsWe searched Chinese and English databases were systematically searched to focus on NEC risk prediction modeling studies.The search time ranged from database establishment to 25 August 2023.Two researchers independently screened the literature and extracted information.Then risk of bias and applicability were assessed by using the Prediction Model Risk of Bias Assessment Tool.ResultsA total of 10 papers involving 12 NEC risk prediction models were included, which is focusing on the populations of preterm infants mostly, building the methods of models diversity, predicting factors discrepancy widely.conclusionThe existing NEC risk prediction models in China have good predictive performance, while they often lack external validation, resulting in an overall high risk of bias. In the future, clinicians and nurses should learn from the evaluation criterions based on the PROBAST, then to test and verify them. Or machine learning algorithms usage is to construct models with operationalization and better predictive efficacy. [REGISTRATION: PROSPERO ID: CRD42024503844]
Functional Analysis of the Zinc Finger Modules of theS. cerevisiaeSplicing Factor Luc7
Authors: Carrocci Tucker J. , DeMario Samuel , He Kevin , Zeps Natalie J. , Harkner Cade T. , Chanfreau Guillaume , Hoskins Aaron A. 
Published: February 2024

ABSTRACTIdentification of splice sites is a critical step in pre-mRNA splicing since definition of the exon/intron boundaries controls what nucleotides are incorporated into mature mRNAs. The intron boundary with the upstream exon is initially identified through interactions with the U1 snRNP. This involves both base pairing between the U1 snRNA and the pre-mRNA as well as snRNP proteins interacting with the 5’ splice site/snRNA duplex. In yeast, this duplex is buttressed by two conserved protein factors, Yhc1 and Luc7. Luc7 has three human paralogs (LUC7L, LUC7L2, and LUC7L3) which play roles in alternative splicing. What domains of these paralogs promote splicing at particular sites is not yet clear. Here, we humanized the zinc finger domains of the yeast Luc7 protein in order to understand their roles in splice site selection using reporter assays, transcriptome analysis, and genetic interactions. While we were unable to determine a function for the first zinc finger domain, humanization of the second zinc finger domain to mirror that found in LUC7L or LUC7L2 resulted in altered usage of nonconsensus 5’ splice sites. In contrast, the corresponding zinc finger domain of LUC7L3 could not support yeast viability. Further, humanization of Luc7 can suppress mutation of the ATPase Prp28, which is involved in U1 release and exchange for U6 at the 5’ splice site. Our work reveals a role for the second zinc finger of Luc7 in splice site selection and suggests that different zinc finger domains may have different ATPase requirements for release by Prp28.
Variant Surface Protein GP60 Contributes to Host Infectivity ofCryptosporidium parvum
Authors: Li Muxiao , Yang Fuxian , Hou Tianyi , Gong Xiaoqing , Li Na , Sibley L. David , Feng Yaoyu , Xiao Lihua , Guo Yaqiong 
Published: February 2024

AbstractBiological studies of the determinants ofCryptosporidiuminfectivity and virulence are lacking despite the fact that cryptosporidiosis is a major public health problem. Here, we used advanced genetic tools to investigate the processing, fate, and function of the 60-kDa glycoprotein (GP60), an immunodominant variable antigen associated with protection against reinfection. Endogenous gene tagging revealed that GP60 is highly expressed in sporozoites, merozoites and male gametes, suggesting that it may be involved in both invasion and sexual replication. GP60 is translocated to the parasite membrane and cleaved at the furin cleavage site into GP40 and GP15. During invasion, GP40 translocates to the apical end of the zoites and remains detectable at the parasite-host interface. Although GP60 is dispensable, both gene deletion and replacement reduce parasite growth and severity of infection. Depletion of its structural domains, GP40, or GP15 individually affects GP60 translocation but has less effect on its function. These findings suggest that the GP60 protein contributes to host infectivity likely through its multiple functions inC. parvum-host interactions. They further our understanding of the pathogenesis of cryptosporidiosis.
Profiling multi-body interactions of BCL2 with single-molecule co-immunoprecipitation reveals the molecular mechanism of ABT-199 resistance
Authors: Chun Changju , Yoon Tae-Young 
Published: February 2024

AbstractA capability to characterize protein-protein interactions (PPIs) in a quantitative manner with an increased speed would form a technical basis for accelerating drug discovery targeting the PPI network. We here used the single-molecule pull-down and co-IP platform to examine PPI between BCL2 and BH3-only proteins in crude extract environments. We focused on how the PPI strengths changed with single-point BCL2 mutations found in relapsed chronic lymphocytic leukemia showing ABT-199 resistance, where we took a mix-and-match approach to examine various pairs of baits and preys while titrating their concentrations. This allowed us to examine total 21 PPI reactions and 420 data points, forming a high-resolution large data set of the dissociation constants (Kd) and the drug inhibitory constants (Ki). Our data suggest that the different BCL2 mutants take different routes to acquire resistance to ABT-199, demonstrating how large-scale, quantitative PPI data sets reveal insights into the evolving dynamics of PPI networks.
Functional Modification of Cyanobacterial Phycobiliprotein and Phycobilisomes through Bilin Metabolism Control
Authors: Sato Mizuho , Kawaguchi Takeshi , Maeda Kaisei , Watanabe Mai , Ikeuchi Masahiko , Narikawa Rei , Watanabe Satoru 
Published: February 2024

ABSTRACTThe light-harvesting antenna complexes in cyanobacteria are known as phycobilisomes (PBSs), and they can adapt to a diverse range of light environments owing to the deployment of different phycobiliproteins within the PBS structures. Freshwater cyanobacteria such asSynechococcus elongatusPCC 7942 thrive under red light due to phycocyanin (PC), along with phycocyanobilin (PCB), in PBS. Conversely, cyanobacteria in shorter-wavelength light environments, such as green light, employ phycoerythrin paired with phycoerythrobilin (PEB) alongside PC in PBS. Synthetic biology studies have shown that PEB production can be enhanced by additional expression of the heterologous PEB synthases, namely 15,16-dihydrobiliverdin:ferredoxin oxidoreductase and PEB:ferredoxin oxidoreductase (PebAB), leading to cellular browning due to PEB accumulation. This approach is genetically unstable, and the properties of the resulting PEB-bound PBS complexes remain uncharacterized. Herein, we engineered a novel strain ofSynechococcus7942 PEB1, with finely tuned control of PEB metabolism. PEB1 exhibited a remarkable and reversible color shift from green to brown and pink, based on the PebAB induction levels. High induction led to a complete PCB-to-PEB substitution, causing the disassembly of the PBS rod complex. In contrast, low PebAB levels resulted in the formation of a stable chimeric PBS complex with partial PCB-to-PEB substitution. This adaptation enabled efficient light harvesting in the green spectrum and energy transfer to the photosynthetic reaction center. These findings, which improve our understanding of PBS and highlight the structural importance of the bilin composition, lay the foundation for future PBS adaptation studies in bioengineering, synthetic biology, and renewable energy.
Changes in Gait Asymmetry May Be Caused by Adaptation of Spinal Reflexes
Authors: Refy Omar , Mo Owen , Hsu Jacob , Weber Douglas J. , Geyer Hartmut 
Published: February 2024

AbstractIn a recent human study, we found that adaptive changes in step length asymmetry (SLA) are correlated with similar changes in the H-reflex gains of the leg muscles during split-belt treadmill locomotion. While this observation indicated a closer link between gait asymmetry and spinal reflex adaptation, it did not reveal their causal relationship. To better understand this relationship, here we use a neuromuscular model of human walking whose control relies primarily on spinal reflexes. Subjecting the model to split-belt treadmill locomotion with different combinations of belt speed and reflex gain adaptation patterns, we find that belt speed changes increase the variability in SLA but do not result in consistent SLA patterns as observed in human experiments, whereas reflex gain adaptations do. Furthermore, we find that the model produces SLA patterns similar to healthy adults when its reflex gains are adapted in a way similar to the H-reflex changes we observed in our previous human study. The model also predicts SLA patterns similar to the ones observed for cerebellar degeneration patients when the reflexes do not adapt beyond a sudden dip at the time the ipsilateral belt speed is lowered. Our results suggest that SLA does not arise from imposing belt speed changes but requires the adaptation of the reflex gains, and that the dynamic adaptation of these gains may be an essential part of human gait control when encountering unexpected environment changes such as the uneven speed changes in split-belt treadmill locomotion.
Acquiring social safety engages oxytocin neurons in the supraoptic nucleus – role of Magel2 deficiency
Authors: Chakraborty Prabahan , Lamat Hugo , André Emilie M. , Fontanaud Pierre , Jeanneteau Freddy 
Published: February 2024

AbstractIntroductionExposure to social trauma may alter engagement with both fear-related and unrelated social stimuli long after. Intriguingly, how simultaneous discrimination of social fear and safety is affected in neurodevelopmental conditions like autism remains underexplored. The role of the neuropeptide oxytocin is established in social behaviors, and yet unexplored during such a challenge post-social trauma.MethodsUsingMagel2knockout mice, an animal model of Prader Willi Syndrome (PWS) and autism spectrum disorders, we tested memory of social fear and safety after a modified social fear conditioning task. Additionally, we tracked the activity of oxytocin neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus by fibre photometry, as animals were simultaneously presented with a choice between a fear and safe social cue during recall.ResultsMaleMagel2KO mice trained to fear females with electrical footshocks avoided both unfamiliar females and males during recalls, lasting even a week post-conditioning. On the contrary, trainedMagel2WT avoided only females during recalls, lasting days rather than a week post-conditioning. Inability to overcome social fear and avoidance of social safety inMagel2KO mice were associated with reduced engagement of oxytocin neurons in the SON, but not the PVN.ConclusionIn a preclinical model of PWS, we demonstrated region-specific deficit in oxytocin activity associated with behavioral generalization of social fear to social safety. Insights from this study add to our understanding of oxytocin action in the brain at the intersection of social trauma, PWS and related autism spectrum disorders.
Visual stimulation drives retinotopic acetylcholine release in the mouse visual cortex
Authors: Knudstrup Scott G. , Martinez Catalina , Rauscher Bradley C. , Doran Patrick R. , Fomin-Thunemann Natalie , Kilic Kivilcim , Jiang John , Devor Anna , Thunemann Martin , Gavornik Jeffrey P. 
Published: February 2024

AbstractCholinergic signaling is involved with a variety of brain functions including learning and memory, attention, and behavioral state modulation. The spatiotemporal characteristics of neocortical acetylcholine (ACh) release in response to sensory inputs are poorly understood, but a lack of intra-region topographic organization of cholinergic projections from the basal forebrain has suggested diffuse release patterns and volume transmission. Here, we use mesoscopic imaging of fluorescent ACh sensors to show that visual stimulation results in ACh release patterns that conform to a retinotopic map of visual space in the mouse primary visual cortex, suggesting new modes of functional cholinergic signaling in cortical circuits.x
Functional variation in human Carbohydrate-Active enZYmes (hCAZymes) in relation to the efficacy of a FODMAP-reducing diet in IBS patients
Authors: Zamfir-Taranu Andreea , Löscher Britt-Sabina , Carbone Florencia , Hoter Abdullah , Blanco Cristina Esteban , Bozzarelli Isotta , Torices Leire , Routhiaux Karen , Van den Houte Karen , Bonfiglio Ferdinando , Mayr Gabriele , Corsetti Maura , Naim Hassan Y , Franke Andre , Tack Jan , D’Amato Mauro 
Published: February 2024

ABSTRACTObjectiveLimiting the dietary intake of carbohydrates poorly absorbed in the small intestine (FODMAPs) has therapeutic effects in some but not all irritable bowel syndrome (IBS) patients. We investigated genetic variation in human Carbohydrate-Active enZYmes (hCAZymes) genes in relation to the response to a FODMAP-lowering diet in the DOMINO study.DesignhCAZy polymorphism was studied in IBS patients from the dietary (FODMAP-lowering; N=196) and medication (otilonium bromide; N=54) arms of the DOMINO trial via targeted sequencing of 6 genes of interest (AMY2B,LCT,MGAM,MGAM2,SIandTREH). hCAZyme defective (hypomorphic) variants were identified via computational annotation using clinical pathogenicity classifiers. Age-and sex-adjusted logistic regression was used to test hCAZyme polymorphisms in cumulative analyses where IBS patients were stratified into carrier and non-carrier groups (collapsing all hCAZyme hypomorphic variants into a single bin). Quantitative analysis of hCAZyme variation was also performed, in which the number of hCAZyme genes affected by a hypomorphic variant was taken into account.ResultsIn the dietary arm, the number of hypomorphic hCAZyme genes positively correlated with treatment response rate (P=0.03, OR=1.51 [CI=0.99-2.32]). In the IBS-D group (N=55), hCAZyme carriers were six times more likely to respond to the diet than non-carriers (P=0.002, OR=6.33 [CI=1.83-24.77]). These trends were not observed in the medication arm.ConclusionshCAZYme genetic variation may be relevant to the efficacy of a carbohydrate-lowering diet. This warrants additional testing and replication of findings, including mechanistic investigations of this phenomenon.WHAT IS KNOWNCarbohydrates are known triggers of IBS symptoms, and limiting their dietary consumption appears to have therapeutic effectsThe lowFODMAP diet improves symptoms in some but not all IBS patientsWHAT IS NEW HERECarrying hypomorphic hCAZyme gene variants associates with increased efficacy of a FODMAP-lowering diet in IBS, especially in patients with diarrhoea (IBS-D)hCAZyme genotype information may be relevant to increase therapeutic precision in IBS, contributing to personalising carbohydrate-focused dietary interventions
The natural recovery of visuospatial neglect: a systematic review and meta-analysis
Authors: Overman Margot Juliëtte , Binns Elena , Milosevich Elise T , Demeyere Nele 
Published: February 2024

ABSTRACTBackgroundVisuospatial neglect is a common consequence of stroke and is characterised by impaired attention to contralesional space. Currently, the extent and time course of recovery from neglect are not clearly established. This systematic review and meta-analysis aimed to determine the natural recovery trajectory of post-stroke neglect.MethodsPsycInfo, Embase, and MEDLINE were searched for articles reporting recovery rates of neglect after stroke. Time since stroke was categorised into early (0-3 months), mid (3-6 months), or late (>6 months) recovery phases. Random-effects models for pooled prevalence were generated for each phase, and potential sources of heterogeneity were explored with meta-regressions. Methodological quality of each study was assessed using the Joanna Briggs Institute checklist, with low-quality studies excluded in sensitivity analyses.ResultsA total of 27 studies reporting data from 839 stroke survivors with neglect were included. Meta-analyses indicated a recovery rate of 42% in the early phase, which increased to 53% in the mid-recovery phase. Additional recovery in the late phase was minimal, with an estimated 56% recovery rate. Estimates were robust to sensitivity analyses. Meta-regressions showed significantly greater recovery in studies which included patients with left-hemisphere lesions (ß=0.275,p<0.05).ConclusionsMost natural recovery from neglect occurs in the first three months, although additional gains can be expected up to 6 months post-stroke. Whilst a large proportion of patients recover from neglect, over 40% show persistent symptoms. Further research is needed on effective rehabilitation interventions, particularly focusing on patients most at risk of chronic visuospatial neglect.
Evolutionary Lags in the Primate Brain Size/Body Size Relationship
Authors: Dunbar Robin 
Published: February 2024

AbstractINTRODUCTIONThe original brain lag hypothesis proposed that primate brain evolution depended on spare energy derivative of savings of scale enabled by increasing body size. Deaner & Nunn [1] concluded that, in fact, there was no evidence for a brain lag. However, their result may have been due to a number of possible confounds in their analysis.METHODSI revisit their analysis to test for potential confounds using updated datasets. I also ask how primates paid for the energy costs incurred by changes in brain and body mass, and whether the impetus for these changes was predation risk. Finally, I ask whether the observed patterns explain the brain/body size ratio trajectory observed in fossil hominins.RESULTSI show that using statistically more appropriate statistics and updated data yields a significant brain lag effect. However, contrary to the original brain lag hypothesis, the brain/body ratio does not converge back on the allometric regression line, but continues to evolve beyond it. Increases in brain size are correlated with exploiting large group size rather than body size as the principal defence against predation risk, with significant growth in brain size (but not body size) only being possible if species adopted a more frugivorous diet. Finally, I show that hominins followed a similar trajectory from an australopithecine baseline that fell on the relevant allometric regression.CONCLUSIONThe brain lag effect is much more complicated than the original hypothesis proposed, with a distinctive switch from body to brain over evolutionary time.