bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicenter double-blind, placebo-controlled randomized trial to evaluate the safety and efficacy of bovine colostrum in the treatment of severe alcoholic hepatitis (SAH)
Authors: Sidhu S. S. , Dusseja A , Shalimar  , Nijhawan S , Kapoor D , Goyal O , Kishore H 
Published: August 2023

Abstract
Background
Severe alcoholic hepatitis (SAH) is associated with high mortality. Numerous studies and meta-analysis have reported that corticosteroids reduce the 28-day mortality in SAH, but not the 6-month mortality. Therefore, newer treatments for SAH need to be studied. A pilot study from our group had recently treated ten patients with SAH with bovine colostrum (BC) [20 g thrice in a day for 8 weeks] and prednisolone. This therapy improved the biological functions and 3-month mortality. However, as more and more data showed the failure of corticosteroids to improve the 3- and 6-month mortality, especially in patients with high mDF and MELD scores, we planned this trial to study the safety and efficacy of BC (without corticosteroids) in the treatment of SAH.

Method
This is a multicenter, parallel, double-blind, randomized (1:1) placebo-controlled trial, which will enroll 174 patients with SAH from 5 academic centers in the India. Patients will receive freeze-dried BC or placebo by random 1:1 allocation for 4 weeks. The primary outcome measure is survival at 3 months. The secondary outcome measures are survival at 1 month, change in mDF and MELD scores, change in endotoxin and cytokines (alpha TNF, IL6, and IL8) levels, number of episodes of sepsis [pneumonia, spontaneous bacterial peritonitis (SBP), cellulitis, urinary tract infection (UTI)] from baseline to 4 weeks.

Discussion
This study will evaluate the safety and efficacy of bovine colostrum in improving the survival of patients with SAH.

Trial registration
ClinicalTrials.gov NCT02473341. Prospectively registered on June 16, 2015.
Potential cognitive and neural benefits of a computerised cognitive training programme based on Structure Learning in healthy adults: study protocol for a randomised controlled trial
Authors: Liu Chia-Lun , Cheng Xiaoqin , Choo Boon Linn , Hong Min , Teo Jia Li , Koo Wei Ler , Tan Jia Yuan Janet , Ubrani Marisha Barth , Suckling John , Gulyás Balázs , Leong Victoria , Kourtzi Zoe , Sahakian Barbara , Robbins Trevor , Chen Annabel Shen-Hsing 
Published: August 2023

Abstract
Background
Cognitive flexibility refers to the capacity to shift between conceptual representations particularly in response to changes in instruction and feedback. It enables individuals to swiftly adapt to changes in their environment and has significant implications for learning. The present study focuses on investigating changes in cognitive flexibility following an intervention programme—Structure Learning training.

Methods
Participants are pseudo-randomised to either the Training or Control group, while matched on age, sex, intelligence and cognitive flexibility performance. In the Training group, participants undergo around 2 weeks of training (at least 13 sessions) on Structure Learning. In the Control group, participants do not have to undergo any training and are never exposed to the Structure Learning task. The effects of Structure Learning training are investigated at both the behavioural and neural level. We measured covariates that can influence an individual’s training performance before the training phase and outcome measures that can potentially show training benefits after the training phase. At the behavioural level, we investigated outcomes in both cognitive and social aspects with a primary focus on executive functions. At the neural level, we employed a multimodality approach and investigated potential changes to functional connectivity patterns, neurometabolite concentration in the frontal brain regions, and brain microstructure and myelination.

Discussion
We reported the development of a novel training programme based on Structure Learning that aims to hone a general learning ability to potentially achieve extensive transfer benefits across various cognitive constructs. Potential transfer benefits can be exhibited through better performance in outcome measures between Training and Control participants, and positive associations between training performance and outcomes after the training in Training participants. Moreover, we attempt to substantiate behavioural findings with evidence of neural changes across different imaging modalities by the Structure Learning training.

Trial registration
National Institutes of Health U.S. National Library of Medicine ClinicalTrials.gov NCT05611788. Registered on 7 November 2022. Protocol version: 11 May 2023.
Rotational ThromboElastometry-guided blood component administration versus standard of care in patients with Cirrhosis and coagulopathy undergoing Invasive ProcEdures (RECIPE): study protocol for a randomised controlled trial
Authors: Janko Natasha , Majeed Ammar , Kemp William , Hogan Chris , Nandurkar Harshal , Roberts Stuart K. 
Published: August 2023

Abstract
Background
Patients with cirrhosis often undergo invasive procedures both for management of complications of their advanced liver disease, including treatment for hepatocellular carcinoma, as well as underlying comorbidities. Despite a current understanding that most patients with cirrhosis are in a rebalanced haemostatic state (despite abnormalities in conventional coagulation tests, namely INR and platelet count), patients with cirrhosis are still often given prophylactic blood components based on these conventional parameters, in an effort to reduce procedure-related bleeding. Viscoelastic tests such as Rotational Thromboelastometry (ROTEM) provide a global measurement of haemostasis and have been shown to predict bleeding risk more accurately than conventional coagulation tests, and better guide blood product transfusion in a number of surgical and trauma-related settings. The aim of this study is to assess the utility of a ROTEM-based algorithm to guide prophylactic blood component delivery in patients with cirrhosis undergoing invasive procedures. We hypothesise that ROTEM-based decision-making will lead to a reduction in pre-procedural blood component usage, particularly fresh frozen plasma (FFP), compared with standard of care, whilst maintaining optimal clinical outcomes.

Methods
This is a multi-centre randomised controlled trial comparing ROTEM-guided prophylactic blood component administration to standard of care in patients with cirrhosis and coagulopathy undergoing invasive procedures. The primary efficacy outcome of the trial is the proportion of procedures requiring prophylactic transfusion, with the primary safety outcome being procedure-related bleeding complications. Secondary outcomes include the amount of blood products (FFP, platelets, cryoprecipitate) transfused, transfusion-related side effects, procedure-related complications other than bleeding, hospital length of stay and survival.

Discussion
We anticipate that this project will lead to improved prognostication of patients with cirrhosis, in terms of their peri-procedural bleeding risk. We hope to show that a significant proportion of cirrhotic patients, deemed coagulopathic on the basis of standard coagulation tests such as INR and platelet count, are actually in a haemostatic balance and thus do not require prophylactic blood product, leading to decreased and more efficient blood component use.

Trial registration
RECIPE has been prospectively registered with the Australia and New Zealand Clinical Trials Registry on the 30th April 2019 (ACTRN12619000644167).
Co-effects of m6A and chromatin accessibility dynamics in the regulation of cardiomyocyte differentiation
Authors: Liu Xue-Hong , Liu Zhun , Ren Ze-Hui , Chen Hong-Xuan , Zhang Ying , Zhang Zhang , Cao Nan , Luo Guan-Zheng 
Published: August 2023

Abstract
Background
Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood.

Results
We investigated the relationship between m6A modification and cardiomyocyte differentiation by conducting a comprehensive profiling of m6A dynamics during the transition from pluripotent stem cells to cardiomyocytes. Our findings reveal that while the overall m6A modification level remains relatively stable, the m6A levels of individual genes undergo significant changes throughout cardiomyocyte differentiation. We discovered the correlation between alterations in chromatin accessibility and the binding capabilities of m6A writers, erasers, and readers. The changes in chromatin accessibility influence the recruitment and activity of m6A regulatory proteins, thereby impacting the levels of m6A modification on specific mRNA transcripts.

Conclusion
Our data demonstrate that the coordinated dynamics of m6A modification and chromatin accessibility are prominent during the cardiomyocyte differentiation.
The association of serum C-peptide with the risk of cardiovascular events: a meta-analysis and systematic review
Authors: Jahromi Mitra Kazemi , Ahmadirad Hamid , Jamshidi Sanaz , Farhadnejad Hossein , Mokhtari Ebrahim , Shahrokhtabar Tahere , Tavakkoli Saeed , Teymoori Farshad , Mirmiran Parvin 
Published: August 2023

Abstract
Background
C-peptide is considered a peptide with active function in the body, which can affect people’s health. However, the results of previous studies on the possible association of C-peptide with the risk of cardiometabolic disorders have not been fully understood. This systematic review and meta-analysis aimed to investigate the association between serum C-peptide level and the risk of cardiovascular disease (CVD) events.

Methods
The various important databases, including PubMed, Scopus, and Web of Science, were searched comprehensively to November 2022 to identify the relevant studies. The HR(95% CI) or OR(95% CI) for observational studies were extracted and converted into log HR or log OR and their standard deviation(SD) was computed. A random-effects model with an inverse variance weighting method was conducted, to calculate the pooled effect size.

Results
Sixteen observational studies, including one case-control study, eight cohort studies, and seven cross-sectional studies were included in the current meta-analysis. The sample size ranged from 90 to 7030, with an age range from 12 to 85 years. During the follow-up time (ranging from 5 to 17 years), 4852 CVD events occurred. Based on cohort and case-control studies, the pooled results showed no significant association between serum C-peptide with CVD events risk (RR = 1.02;95%CI:0.91–1.15, I2 = 34.7%; P-heterogeneity = 0.140). For cross-sectional studies, the pooled results indicated a positive association between serum C-peptide and the odds of CVD outcomes (OR = 1.35;95%CI:1.04–1.76, I2 = 83.6%; P-heterogeneity < 0.001).

Conclusions
The pooled results of the current study suggested that C-peptide level was not related to the risk of CVD events in cohort studies, however, the meta-analysis of cross-sectional studies showed a significant association between C-peptide and an increased risk of CVD events.
Network analysis of neuropsychiatric symptoms in Alzheimer’s disease
Authors: Goodwin Grace J. , Moeller Stacey , Nguyen Amy , Cummings Jeffrey L. , John Samantha E. 
Published: August 2023

AbstractBackgroundNeuropsychiatric symptoms due to Alzheimer’s disease (AD) and mild cognitive impairment (MCI) can decrease quality of life for patients and increase caregiver burden. Better characterization of neuropsychiatric symptoms and methods of analysis are needed to identify effective treatment targets. The current investigation leveraged the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) to examine the network structure of neuropsychiatric symptoms among symptomatic older adults with cognitive impairment.MethodsThe network relationships of behavioral symptoms were estimated from Neuropsychiatric Inventory Questionnaire (NPI-Q) data acquired from 12,494 older adults with MCI and AD during their initial visit. Network analysis provides insight into the relationships among sets of symptoms and allows calculation of the strengths of the relationships. Nodes represented individual NPI-Q symptoms and edges represented the pairwise dependency between symptoms. Node centrality was calculated to determine the relative importance of each symptom in the network.ResultsThe analysis showed patterns of connectivity among the symptoms of the NPI-Q. The network (M = .28) consisted of mostly positive edges. The strongest edges connected nodes within symptom domain. Disinhibition and agitation/aggression were the most central symptoms in the network. Depression/dysphoria was the most frequently endorsed symptom, but it was not central in the network.ConclusionsNeuropsychiatric symptoms in MCI and AD are highly comorbid and mutually reinforcing. The presence of disinhibition and agitation/aggression yielded a higher probability of additional neuropsychiatric symptoms. Interventions targeting these symptoms may lead to greater neuropsychiatric symptom improvement overall. Future work will compare neuropsychiatric symptom networks across dementia etiologies, informant relationships, and ethnic/racial groups, and will explore the utility of network analysis as a means of interrogating treatment effects.
Fetal Muse-based therapy prevents lethal radio-induced gastrointestinal syndrome by intestinal regeneration
Authors: Dushime Honorine , Moreno Stéphanie G. , Linard Christine , Adrait Annie , Couté Yohann , Peltzer Juliette , Messiaen Sébastien , Torres Claire , Bensemmane Lydia , Lewandowski Daniel , Romeo Paul-Henri , Petit Vanessa , Gault Nathalie 
Published: August 2023

Abstract
Background
Human multilineage-differentiating stress enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be easily obtained from various adult or fetal tissues. Regenerative effects of Muse cells have been shown in some disease models. Muse cells specifically home in damaged tissues where they exert pleiotropic effects. Exposition of the small intestine to high doses of irradiation (IR) delivered after radiotherapy or nuclear accident results in a lethal gastrointestinal syndrome (GIS) characterized by acute loss of intestinal stem cells, impaired epithelial regeneration and subsequent loss of the mucosal barrier resulting in sepsis and death. To date, there is no effective medical treatment for GIS. Here, we investigate whether Muse cells can prevent lethal GIS and study how they act on intestinal stem cell microenvironment to promote intestinal regeneration.

Methods
Human Muse cells from Wharton’s jelly matrix of umbilical cord (WJ-Muse) were sorted by flow cytometry using the SSEA-3 marker, characterized and compared to bone-marrow derived Muse cells (BM-Muse). Under gas anesthesia, GIS mice were treated or not through an intravenous retro-orbital injection of 50,000 WJ-Muse, freshly isolated or cryopreserved, shortly after an 18 Gy-abdominal IR. No immunosuppressant was delivered to the mice. Mice were euthanized either 24 h post-IR to assess early small intestine tissue response, or 7 days post-IR to assess any regenerative response. Mouse survival, histological stainings, apoptosis and cell proliferation were studied and measurement of cytokines, recruitment of immune cells and barrier functional assay were performed.

Results
Injection of WJ-Muse shortly after abdominal IR highly improved mouse survival as a result of a rapid regeneration of intestinal epithelium with the rescue of the impaired epithelial barrier. In small intestine of Muse-treated mice, an early enhanced secretion of IL-6 and MCP-1 cytokines was observed associated with (1) recruitment of monocytes/M2-like macrophages and (2) proliferation of Paneth cells through activation of the IL-6/Stat3 pathway.

Conclusion
Our findings indicate that a single injection of a small quantity of WJ-Muse may be a new and easy therapeutic strategy for treating lethal GIS.
A deep learning framework for accurate reaction prediction and its application on high-throughput experimentation data
Authors: Li Baiqing , Su Shimin , Zhu Chan , Lin Jie , Hu Xinyue , Su Lebin , Yu Zhunzhun , Liao Kuangbiao , Chen Hongming 
Published: August 2023

AbstractIn recent years, it has been seen that artificial intelligence (AI) starts to bring revolutionary changes to chemical synthesis. However, the lack of suitable ways of representing chemical reactions and the scarceness of reaction data has limited the wider application of AI to reaction prediction. Here, we introduce a novel reaction representation, GraphRXN, for reaction prediction. It utilizes a universal graph-based neural network framework to encode chemical reactions by directly taking two-dimension reaction structures as inputs. The GraphRXN model was evaluated by three publically available chemical reaction datasets and gave on-par or superior results compared with other baseline models. To further evaluate the effectiveness of GraphRXN, wet-lab experiments were carried out for the purpose of generating reaction data. GraphRXN model was then built on high-throughput experimentation data and a decent accuracy (R2 of 0.712) was obtained on our in-house data. This highlights that the GraphRXN model can be deployed in an integrated workflow which combines robotics and AI technologies for forward reaction prediction.
Dynamic of the nonclassical diffusion equation with memory
Authors: Wang Jing , Ma Qiaozhen , Zhou Wenxue , Yao Xiaobin 
Published: August 2023

AbstractIn this paper, we consider the nonclassical diffusion equation with memory and the nonlinearity of the polynomial growth condition of arbitrary order in the time-dependent space. First, the well-posedness of the solution for the equation is obtained in the time-dependent space $\mathscr{U}_{t}$

U
t

. Then, we establish the existence and regularity of the time-dependent global attractor. Finally, we also conclude that the fractal dimension of the time-dependent attractor is finite.
Blockchain enabled task offloading based on edge cooperation in the digital twin vehicular edge network
Authors: Li Chunhai , Chen Qiyong , Chen Mingfeng , Su Zhaoyu , Ding Yong , Lan Dapeng , Taherkordi Amir 
Published: August 2023

AbstractThe rapid development of the Internet of Vehicles (IoV) along with the emergence of intelligent applications have put forward higher requirements for massive task offloading. Even though Mobile Edge Computing (MEC) can diminish network transmission delay and ease network congestion, the constrained heterogeneous resources of a single edge server and the highly dynamic topology of vehicular edge networks may compromise the efficiency of task offloading, including latency and energy consumption. Vehicular edge networks are also vulnerable to malicious outside attacks. In this paper, we propose a new blockchain-enabled digital twin vehicular edge network (DTVEN) where digital twin (DT) is exploited to monitor network communication, computation, and caching (3C) resources management in real time to provide rich data for offloading decision-making, and blockchain is utilized to secure fair and decentralized offloading transactions among DTs. To ensure 3C resources sharing across edge servers, we design a DT-assisted edge cooperation scheme, which makes full use of edge resources in vehicular networks. Furthermore, a DT-based smart contract is built to achieve a quick and effective consensus process. Then, we apply a task offloading algorithm based on an improved cuckoo algorithm (ICA) and a resource allocation scheme based on greedy strategy to minimize network cost by comprehensively taking into account latency and energy consumption. Numerical results demonstrate that our proposed scheme outperforms the existing schemes in terms of network cost.
Association between usage of household cooking fuel and congenital birth defects-18 months multi-centric cohort study in Nepal
Authors: KC Ashish , Halme Sanni , Gurung Rejina , Basnet Omkar , Olsson Erik , Malmqvist Ebba 
Published: August 2023

Abstract
Background
- An estimated 240,000 newborns die worldwide within 28 days of birth every year due to congenital birth defect. Exposure to poor indoor environment contributes to poor health outcomes. In this research, we aim to evaluate the association between the usage of different type household cooking fuel and congenital birth defects in Nepal, as well as investigate whether air ventilation usage had a modifying effect on the possible association.

Methods
- This is a secondary analysis of multi-centric prospective cohort study evaluating Quality Improvement Project in 12 public referral hospitals of Nepal from 2017 to 2018. The study sample was 66,713 women with a newborn, whose information was available in hospital records and exit interviews. The association between cooking fuel type usage and congenital birth defects was investigated with adjusted multivariable logistic regression. To investigate the air ventilation usage, a stratified multivariable logistic regression analysis was performed.

Results
-In the study population (N = 66,713), 60.0% used polluting fuels for cooking and 89.6% did not have proper air ventilation. The prevalence rate of congenital birth defect was higher among the families who used polluting fuels for cooking than those who used cleaner fuels (5.5/1000 vs. 3.5/1000, p < 0.001). Families using polluting fuels had higher odds (aOR 1.49; 95% CI; 1.16, 1.91) of having a child with a congenital birth defect compared to mothers using cleaner fuels adjusted with all available co-variates. Families not using ventilation while cooking had even higher but statistically insignificant odds of having a child with congenital birth defects (aOR 1.34; 95% CI; 0.86, 2.07) adjusted with all other variates.

Conclusion
- The usage of polluted fuels for cooking has an increased odds of congenital birth defects with no significant association with ventilation. This study adds to the increasing knowledge on the adverse effect of polluting fuels for cooking and the need for action to reduce this exposure.