bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carvedilol alleviates the detrimental effects of azathioprine on hepatic tissues in experimental rats: Focusing on redox system, inflammatory and apoptosis pathways
Authors: Shalkami Abdel-Gawad S. , El-Shoura Ehab A. M. , Hassan Mohammed I. A. 
Published: July 2024

Purpose Drug-induced liver injury is becoming an increasingly important topic in drug research and clinical practice. Due to a lack of experimental animal models, predicting drug-induced liver injury in humans is challenging. Azathioprine (AZA) is a classical immunosuppressant with hepatotoxic adverse effects. The present study aimed to address the hepatoprotective effect of carvedilol (CAR) against AZA-induced hepatocellular injury via assessing redox-sensitive signals. Method To achieve this purpose, rats were allocated into four groups: control, CAR only, AZA only, and CAR plus AZA groups. The induction of hepatic injury was induced by a single intraperitoneal injection of AZA at a dose of 50 mg/kg on the 6th day of the experiment. Each experimental protocol was approved and supervised by the Ethics Committee for Animal Experiments. Results The results of the present study revealed that CAR administration significantly diminished AZA-induced hepatic dysfunction, as evidenced by relief of hepatic function biomarkers and histopathological aberration induced by AZA injection. Besides, CAR restored oxidant/antioxidant balance as well as NRF2 expression. In addition, CAR suppressed inflammatory response induced by AZA challenge as evidenced by downregulation of TLR4, TNF-α, MPO, and eNOS/iNOS levels in hepatic tissue. Moreover, CAR recovered apoptotic/anti-apoptotic status by modulation of caspase-3/Bcl2 expression. Conclusion Taken together, CAR protects against AZA-induced hepatic injury via antioxidant, anti-inflammatory, and anti-apoptotic activities. These findings revealed that CAR could be a good candidate for hepatic injury protection and can be added to AZA therapeutic regimen to reduce their adverse effect.
The first global landscape analysis of multiple sclerosis research funding
Authors: Bebo Bruce , Coetzee Tim , Gray Emma , Helme Anne , Kanellis Pamela , Landsman Douglas , Mai Michaela , Martinez de la Cruz Beatriz , Morahan Julia , Plassart Emmanuelle , Pickrell Baylee , Rawlings Sarah , Skovgaard Lasse , Zaratin Paola , Rechtman Lindsay 
Published: July 2024

Introduction: Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis. Methods: This study identified MS research projects funded between 2021 and 2023 by government and non-profit organization sources. Projects were described by type of scientific approach, Pathways to Cure research category (i.e. Stop, Restore, End), and other key characteristics. Results: Over 2,300 MS research projects were identified through 16 non-profit MS organizations and 18 government databases. The overall global portfolio of these projects is valued at nearly one and a half billion Euros. The majority of projects were classified in the Stop category (60%). Research collaboration occurs in many forms among the research community; around 272 projects were reported to be co-funded. Conclusion: Global MS research collaboration will accelerate progress toward increased knowledge, effective treatments, improved health outcomes, and ultimately cures for MS. This landscape analysis highlights the current distribution of MS research investment between topics and begins to suggest where the MS community should focus to increase potential impact for current and future endeavors.
Emotion dysregulation in autism: A meta-analysis
Authors: McDonald Rachel G. , Cargill Mary Isaac , Khawar Sadaf , Kang Erin 
Published: July 2024

Autism is associated with significantly higher rates of internalizing and externalizing disorders compared to neurotypical (NT) individuals. Emotion dysregulation (ED) is prevalent in autistic individuals and has been proposed to underlie both internalizing disorders and behavioral challenges in autism. This study sought to use a meta-analytic approach to examine the magnitude of ED severity in autistic samples compared to NT and other clinical (OC) samples. Following a review of the literature, a total of 35 studies were included in the analyses. In general, when comparing autistic to non-autistic individuals, findings suggest a medium magnitude of difference in ED severity between autistic and comparison groups overall. Subgroup analyses indicate that autistic individuals experience significantly higher ED severity when compared to NT peers. However, when compared to OC peers, the effect is small, suggesting the severity of ED may be more similar between OC and autistic groups. Moderators were also explored, including autistic traits, age, and sex composition. These findings provide integral information about the severity of ED in autistic populations compared to other non-autistic populations, assisting in further clarifying the presence of mental health challenges in autistic youth. Lay Abstract Autistic people often experience other mental health challenges, which makes it particularly important to understand factors that may contribute to the development of these conditions. Emotion dysregulation, or difficulties in effectively regulating one’s own emotions in response to a changing environment, is one factor that is experienced frequently by autistic and non-autistic people and is commonly related to a wide range of mental health conditions. This article represents a quantitative synthesis of the current state of the literature on emotion dysregulation, with a specific focus on how the severity of emotion dysregulation differs across autistic and non-autistic people across the lifespan. The findings suggest elevated emotion dysregulation in autistic individuals compared to both neurotypical and other clinical populations and provide insights into the experiences of emotion dysregulation in autistic people. Overall, this article underscores the importance of more research into emotion dysregulation in autistic people to inform areas of challenges related to emotion dysregulation that can be used to better inform treatment targets.
Switching within versus out of class following first-line TNFi failure in ulcerative colitis: real-world outcomes from a German claims data analysis
Authors: Zhuleku Evi , Wirth Daniel , Nissinen Riikka , Bravatà Ivana , Ziavra Despina , Duva Andreas , Lee Jennifer , Fuchs Andreas , Mueller Sabrina , Wilke Thomas , Bokemeyer Bernd 
Published: July 2024

Background: Biologic agents have demonstrated efficacy in treating ulcerative colitis (UC); however, treatment failure to tumor necrosis factor inhibitors (TNFi) is common in the real world. Data on preferential sequencing in clinical practice after failure remain limited. Objectives: This study aimed to evaluate real-world outcomes of patients cycling to TNFis or switching to non-TNFi biologics following first-line failure with TNFis. Design: Retrospective cohort study in Germany. Methods: Adult patients with UC were identified using administrative claims data from 1 May 2014 to 30 June 2022 provided by a statutory sickness fund. Patients newly initiating first-line therapy with TNFis and then switching to another agent were identified. Patients were defined as within-class switched (WCS), if they cycled to another TNFi, or outside-class switchers (OCS), if they switched to a non-TNFi biologic [ustekinumab (UST) or vedolizumab (VDZ)] and followed from index (switch date) to death, insurance end, or study end on 30 June 2022. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline characteristics between groups, and weighted Cox regression models were used to compare primary (time to discontinuation and second treatment switch) and secondary outcomes (corticosteroid-free drug survival). Results: We identified 166 patients initiating TNFis and switching to a subsequent treatment (mean age: 42.9 years, 49.4% female). Following IPTW, there were 71 and 76 patients in the WCS and OCS groups, respectively. Compared to OCS, WCS were more likely to discontinue the new therapy [hazard ratio (HR), 1.82, 95% confidence interval (CI), 1.14–2.89, p = 0.012], and switch a second time (HR, 3.46, 95% CI, 1.89–6.36, p < 0.001). Moreover, WCS showed an increased likelihood of initiating prolonged corticosteroid therapy (HR, 1.42, 95% CI, 0.77–2.59, p = 0.260); however, the results were not significant. Conclusion: Following first-line TNFi failure, this study suggests that real-world outcomes among patients with UC are less favorable when cycling to another TNFi, compared to switching to a non-TNFi such as UST or VDZ.
Network meta-analysis of novel targeted therapies for relapsed/refractory chronic lymphocytic leukemia
Authors: Monica Magdalena , Reczek Monika , Kawalec Paweł 
Published: July 2024

Background:The recent development of new antileukemic therapies (anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhbitors, phosphoinositide 3-kinase inhibitors, and B-cell lymyphoma-2 antagonists) improved the progression-free survival (PFS) compared with selected standard regimens in clinical trials for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Unfortunately, the relative efficacy of all possible therapeutic options remains unknown because there is no direct evidence for all possible comparisons.Objectives:We aimed to compare the efficacy and safety of novel agents, chemotherapy, and immunotherapy using a Bayesian network meta-analysis (NMA).Design:Systematic literature review with Bayesian NMA.Methods:An extensive systematic literature review of randomized clinical trials for relapsed/refractory CLL was performed. We searched for articles indexed in medical databases (MEDLINE, Embase, The Cochrane Library) and gray literature that could be further implemented into the Bayesian NMA.Results:The systematic search identified 15 randomized trials that formed networks comparing PFS, overall survival (OS), overall response rates, and serious adverse events. Our study showed that all regimens containing novel agents significantly prolonged PFS compared with standard chemoimmunotherapy and immunotherapy. Among targeted drugs, venetoclax (VEN) + rituximab (RTX) had comparable efficacy in terms of PFS to zanubrutinib (ZAN) [hazard ratio (95% credible interval), 1.10 (0.59–2.08)], acalabrutinib (ACA) [0.78 (0.47–1.30)], ibrutinib (IBR) monotherapy [0.72 (0.41–1.27)], and other IBR-based regimens. ZAN was superior to IBR monotherapy [0.65 (0.49–0.86)] but not to ACA [0.71 (0.49–1.02)]. There were no significant differences in OS in any of the above comparisons.Conclusion:All novel therapies have better efficacy than chemoimmunotherapy and immunotherapy regimens. Among novel agents, the relative efficacy of VEN + RTX was similar to all BTKi, while ZAN was superior to IBR and comparable to ACA.Trial registration:PROSPERO CRD42022304330.
Empagliflozin’s role in early tubular protection for type 2 diabetes patients
Authors: Zhang Chuangbiao , Ren Weiwei , Lu Xiaohua , Feng Lie , Li Jiaying , Zhu Beibei 
Published: July 2024

Abstract
Background
Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria.

Methods
A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment.

Results
Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group.

Conclusion
Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.
DGCPPISP: a PPI site prediction model based on dynamic graph convolutional network and two-stage transfer learning
Authors: Feng Zijian , Huang Weihong , Li Haohao , Zhu Hancan , Kang Yanlei , Li Zhong 
Published: July 2024

Abstract
Background
Proteins play a pivotal role in the diverse array of biological processes, making the precise prediction of protein–protein interaction (PPI) sites critical to numerous disciplines including biology, medicine and pharmacy. While deep learning methods have progressively been implemented for the prediction of PPI sites within proteins, the task of enhancing their predictive performance remains an arduous challenge.

Results
In this paper, we propose a novel PPI site prediction model (DGCPPISP) based on a dynamic graph convolutional neural network and a two-stage transfer learning strategy. Initially, we implement the transfer learning from dual perspectives, namely feature input and model training that serve to supply efficacious prior knowledge for our model. Subsequently, we construct a network designed for the second stage of training, which is built on the foundation of dynamic graph convolution.

Conclusions
To evaluate its effectiveness, the performance of the DGCPPISP model is scrutinized using two benchmark datasets. The ensuing results demonstrate that DGCPPISP outshines competing methods in terms of performance. Specifically, DGCPPISP surpasses the second-best method, EGRET, by margins of 5.9%, 10.1%, and 13.3% for F1-measure, AUPRC, and MCC metrics respectively on Dset_186_72_PDB164. Similarly, on Dset_331, it eclipses the performance of the runner-up method, HN-PPISP, by 14.5%, 19.8%, and 29.9% respectively.
AMF inhibit the production of phenolic acid autotoxins at the seed-filling stage in soybeans with continuous monocropping
Authors: Shi Hao , Lu Chengcheng , Wu Yunshu , Wang Lei , Cai Baiyan 
Published: July 2024

Abstract
Background
Soybean is the main oil crop in Northeast China. Continuous monocropping is more commonly used for soybean production due to rising market demand and arable land constraints. However, autotoxic substances, such as phenolic acids, produced by continuously cropped soybean can reduce yield and quality. The mycorrhiza formed of Arbuscular mycorrhizal fungi (AMF) and plant roots regulate the metabolic activities of the host plant and increase its disease resistance. The main purpose of this study was to inhibit the production of phenolic acids and determine the adverse effects on the growth of continuous monocropping soybean by inoculating Funneliformis mosseae (F. mosseae).

Results
Transcriptomics results showed that the production of phenolic acids in continuous monocropping soybean roots was mainly regulated by the expression of the CHS6, PCL1, SAMT, SRG1, and ACO1 genes, and the expression of these genes was significantly downregulated after inoculation with F. mosseae. Metabolomics results showed that continuous monocropping soybean roots inoculated with F. mosseae inhibited phenolic acid production through the phenylpropane biosynthetic, α-linoleic acid, linoleic acid, and other metabolic pathways. Phenolic acids in the phenylpropane metabolic pathway, such as 4-hydroxybenzoic acid, phthalic acid, and vanillic acid, decreased significantly after inoculation with F. mosseae. The combined analysis of the two showed that genes such as YLS9 and ARF3 were positively correlated with 4-hydroxybenzoic acid and so on, while genes such as CHS6 and SRG1 were negatively correlated with butyric acid and so on.

Conclusion
F. mosseae regulated the expression of functional genes and related phenolic acid metabolic pathways produced by continuous monocropping soybean roots, inhibiting the production of phenolic acid autotoxic substances in continuous cropped soybean, and slowing down the disturbance of continuous monocropping. This study provides a new solution for continuous monocropping of plants to overcome the autotoxicity barrier and provides a new basis for the development and utilization of AMF as a biological agent.
Branched-chain amino acids and the risk of hypertension; a persian cohort-based study
Authors: Salimi Zahra , Aminnezhad Kavkani Bahareh , Allahyari Pooneh , Askarpour Seyed Ali , Mahmoudi Zahra , Torkaman Mahdie , Hoseini Mohadeseh Sadat Mousavi , Mousavi Zahra , Tajadod Shirin , Valisoltani Neda , Khoshdooz Sara , Doaei Saeid , Kooshki Akram , Gholamalizadeh Maryam 
Published: July 2024

Abstract
Background
The association of hypertension (HTN) and different types of dietary amino acids is not yet clear. The aim of the present study was to investigate the association of branch chain amino acids (BCAAs) and the prevention of HTN.

Methods
This cross-sectional study was conducted on 4184 people aged 35 to 70 using data from the Sabzevar Persian cohort study in Sabzevar, Iran. Data on dietary intake of BCAAs including leucine, isoleucine, and valine were obtained using a validated Food Frequency Questionnaire (FFQ). Multivariable logistic regression analysis assessed the link between HTN and BCAAs.

Results
The results showed that participants with HTN had a higher total protein and BCAAs intake than participants with normal BP (P < 0.01). A marginally significant association was found between the risk of HTN with the total intake of BCAAs (OR = 1.018, CI95%: 1.001–1.035, P = 0.04), leucine (OR = 1.040, CI95%:1.002–1.080, P = 0.03), isoleucine (OR = 1.068, CI95%:1.001–1.140, P = 0.04), and valine (OR = 1.060, CI95%:1.003–1.121, P = 0.04). However, the association disappeared after adjusting the total protein and calorie intake.

Conclusions
The results indicated that the dietary intake of BCAAs may be associated with the risk of HTN. Future longitudinal research is warranted.
Characteristics of blunt and penetrating trauma among victims of physical violence: A retrospective study
Authors: Zohrevandi Behzad , Shahrestani Mahsa Farzaneh , Mohammadnia Hamideh , asadi Kamran , Khodadadi-Hassankiadeh Naema 
Published: July 2024

Abstract
Background
A significant number of referrals to the emergency departments is due to violence and conflict leading to serious injuries and death. The increasing number of such cases highlights the urgent need for investigating victimization of physical violence.

Aim
The purpose of this study was to determine the frequency of demographic and clinical characteristics in victims of violence and classify them based on penetrating or blunt trauma.

Methods
The data of the patients who had been the victims of violence in 2020 were extracted from the Trauma Registry System(TRS) of the Guilan Road Trauma Research Center(GTRC). All analyses were performed using SPSS software version 24. The significance level was considered less than 0.05.

Results
There was a significant difference in the type of violence-related trauma in different age groups (P < 0.001), based on sex (P = 0.002), and marital status (P = 0.012). A significant difference also existed between the trauma type and clinical variables including smoking (P = 0.032), history of alcohol drinking (P = 0.005), and other substance use (P = 0.002), the anatomical location of injury (P < 0.001) and therapeutic interventions (p < 0.001(.

Conclusion
Most of the clients of the violence suffered from blunt trauma, the severity of which was mild, and they were treated supportively without the need for surgery. Blunt trauma was seen more in women, divorcees, over 40 years and non-smokers. Penetrating trauma was observed more in lower limb injuries and alcohol and amphetamine users. Prevention programs and educational interventions should be programmed for the society long before men alcohol and amphetamine abusers reach their fourth decade of life. Accurately recording the type of physical violence, and the weapon used, and determining the injury severity score in TRS can lead to more reliable results in researching the field of violence issues.
Social support resources in adolescents and young adults with advanced cancer: a qualitative analysis
Authors: Lau Nancy , Steineck Angela , Walsh Casey , Fladeboe Kaitlyn M. , Yi-Frazier Joyce P. , Rosenberg Abby R. , Barton Krysta 
Published: July 2024

Abstract
Purpose
Adolescents and Young Adults (AYAs) with cancer are an at-risk group with unique palliative and supportive care needs. Social support in AYAs with cancer is associated with better coping, quality of life, and psychosocial well-being. Here, we extend existing research to examine the sources and types of support received by AYAs with advanced cancer.

Methods
AYAs participated in a semi-structured, 1:1 interview on communication and psychosocial support needs. The present analysis focused on social support experiences for AYAs with advanced cancer. Directed content analysis was used to develop the codebook. Established social support constructs provided a coding framework. We presented our qualitative findings as a code frequency report with quantified frequency counts of all “source of support” and “type of support” codes. We assigned a global “sufficiency of support code” to each AYA.

Results
We interviewed 32 AYAs with advanced cancer (Mage = 18, SDage = 3.2, 41% female). Most AYAs identified family (namely, caregivers) as their primary source of support and stated that family universally provided all types of support: emotional, informational, instrumental, and social companionship. They received informational and emotional support from clinicians, and received emotional support and social companionship from healthy peers, cancer peers, and their existing community. One-third of participants were coded as having “mixed support” and described a lack of support in some domains.

Conclusion
AYAs with advanced cancer described caregivers as their universal source of support, and that other support sources provided support for specific needs. Future research should continue to evaluate social support needs and family-based palliative and supportive care interventions to bolster social support resources in this high-risk group.