bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico studies of benzothiazole derivatives as potential inhibitors of Anopheles funestus and Anopheles gambiae trehalase
Authors: Ogunnupebi Temitope A. , Oduselu Gbolahan O. , Elebiju Oluwadunni F. , Ajani Olayinka O. , Adebiyi Ezekiel 
Published: August 2024

IntroductionIn malaria management, insecticides play a crucial role in targeting disease vectors. Benzothiazole derivatives have also been reported to possess insecticidal properties, among several other properties they exhibit. The female Anopheles mosquito is responsible for transmitting the malaria parasite when infected. Anopheles gambiae (Ag) and Anopheles funestus (Af) are two of the most notable Anopheles species known to spread malaria in Nigeria. Trehalase is an enzyme that breaks down trehalose. Recent research has proposed it as a viable target for inhibition since it aids in flight and stress adaptation.MethodsThis study aimed to investigate benzothiazole derivatives as potential inhibitors of trehalase of Anopheles funestus (AfTre) and Anopheles gambiae (AgTre) using toxicity profiling, molecular docking, and dynamic simulation for future insecticidal intervention. A total of 4,214 benzothiazole-based compounds were obtained from the PubChem database and subjected to screening against the 3D modelled structure of AfTre and AgTre. Compounds with some toxicity levels were optimised, and the obtained lead compounds were further investigated through molecular docking studies. Furthermore, the best hit was subjected to parameters such as RMSD, RMSF, SASA, Rg, and hydrogen bond to confirm its stability when in a complex with AfTre, and these parameters were compared to that of validamycin A (control ligand).Results and discussionThe post-screening analysis showed binding affinities of −8.7 and −8.2 kcal/mol (compound 1), −8.2 and −7.4 kcal/mol (compound 2), compared to −6.3 and −5.1 kcal/mol (Validamycin A, a known inhibitor) against AfTre and AgTre, respectively. The molecular dynamics simulation showed that compound 1 (the best hit) had good stability when in complex with AfTre. These findings suggest that these best hits can serve as potential inhibitors for the development of novel insecticides in the control of malaria vectors.
Case Report: Electroanatomic mapping as an early diagnostic tool in arrhythmogenic cardiomyopathy
Authors: de Melo Jose F. , Shabtaie Samuel A. , van Zyl Martin , Collins Jeremy D. , Siontis Konstantinos C. 
Published: August 2024

BackgroundAbnormal substrate on invasive electroanatomic mapping (EAM) correlates with areas of myocardial thinning and fibrofatty replacement in Arrhythmogenic Cardiomyopathy (ACM). However, EAM parameters are absent from all sets of diagnostic criteria for ACM.Case summaryA 41-year-old female with no significant family history was referred for evaluation of frequent premature ventricular complexes (PVCs). Twelve-lead ECG showed diffuse low-voltage QRS complexes. Holter monitor showed 28% burden of PVCs with various morphologies consistent with right ventricular (RV) inflow and outflow tract exits. Transthoracic echocardiogram revealed normal biventricular function and dimension. Cardiac magnetic resonance revealed a mildly increased indexed RV end-diastolic volume with normal RV systolic function and no dyssynchrony, akinesia, dyskinesia, or late gadolinium enhancement. Electrophysiologic study demonstrated 2 predominant PVC morphologies that were targeted with ablation, in addition to extensive abnormality with low-voltage and fractionated electrograms in the peri-tricuspid and right ventricular outflow tract free wall regions with septal sparing, suggestive of RV cardiomyopathy. Subsequent genetic testing revealed two pathogenic variants in the desmoplakin and plakophilin-2 genes, confirming the diagnosis of ACM.ConclusionAdvanced RV electropathy can precede RV structural changes in ACM. Invasive evaluation of the electroanatomic substrate should be considered in select cases even when imaging findings are not diagnostic. Future iterations of ACM guidelines may need to consider EAM substrate as one of the diagnostic criteria. A high index of diagnostic suspicion for ACM should be maintained in patients with multifocal RV ectopy.
PhD-supervisors experiences during and after the COVID-19 pandemic: a case study
Authors: Krumsvik Rune J. , Røkenes Fredrik Mørk , Skaar Øystein O. , Jones Lise , Solstad Stein H. , Salhus Øystein , Høydal Kjetil L. 
Published: August 2024

IntroductionThe COVID-19 pandemic has significantly impacted the education sector, and this case study examined nearly three hundred PhD supervisors in Norway. The study was driven by the urgent need to better understand the professional, social, and existential conditions faced by doctoral supervisors during extended societal shutdowns. This explorative case study builds on a former study among PhD candidates and investigates the experiences of doctoral supervisors when remote work, digital teaching, and digital supervision suddenly replaced physical presence in the workplace, largely between March 12, 2020, and autumn 2022, due to the COVID-19 pandemic.MethodsA mixed-methods research approach, incorporating formative dialog research and case study design, was employed to bridge the conceptual and contextual understanding of this phenomenon. The primary data sources were a survey (N = 298, 53.7% women, 46.3% men, response rate 80.54%) and semi-structured interviews (with nine PhD supervisors). Supplementary data collection was based on formative dialog research. It included field dialog (four PhD supervision seminars), open survey responses (n = 1,438), one focus group (n = 5), an additional survey (n = 85), and document analysis of PhD policy documents and doctoral supervision seminar evaluations (n = 7). The survey data, interview data, focus group data, and supplementary data focus also retrospectively on the first year of the pandemic and were collected from August 2022 until October 2023.ResultsThe findings from the explorative case study revealed that the PhD supervisors faced numerous challenges during the pandemic, both professionally and personally. For PhD supervisors who extensively worked from home over a long period, the situation created new conditions that affected their job performance. These altered conditions hindered their research capacity, their ability to follow up with their PhD candidates, and their capacity to fulfill other job responsibilities. Although the PhD supervisors received some support during the pandemic, it seems that the incremental measures provided were insufficient.DiscussionThe case study results indicate that it is more important than ever to understand the gap between the formulation, transformation, and realization arenas when distinguishing between incremental, semi-structural changes and fundamental changes in PhD regulations and guidelines brought on by societal crises. This highlights the need for better crisis preparedness at the doctoral level in the years to come.
Adjunctive benefits of low-frequency transcutaneous electrical nerve stimulation for obesity frequent chronic conditions: a systematic review
Authors: Yu An , Li Xiang , Zhang Wei , Zhang Yazhou , Chen Xi , Wang Liuyan , Xie Mei , Yang Lei 
Published: August 2024

BackgroundObesity is widely recognized for its role in predisposing individuals to a spectrum of chronic health conditions. Emerging preliminary evidence points to the potential benefits of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in enhancing various health outcomes among those with obesity and associated disorders.ObjectiveThis systematic review was designed to assess the effectiveness of Lo-TENS for managing obesity and its related chronic diseases.MethodsFor this systematic review, we included randomized controlled trials that evaluated the impact of Lo-TENS on individuals with obesity and its associated chronic diseases.ResultsEight trials encompassing 671 participants and spanning three unique populations: essential hypertension (EH), type 2 diabetes mellitus (T2DM), and obesity were deemed eligible for inclusion in this review. Compared to baseline measurements, Lo-TENS demonstrated a tendency to positively affect blood pressure in individuals with EH and metabolic parameters in those with T2DM. Nonetheless, the efficacy of Lo-TENS in treating obesity is not yet clear when contrasted with a no-intervention control group. When compared with other intervention modalities, three of the trials reported less favorable results.ConclusionsAlthough Lo-TENS did not consistently surpass other treatments or yield substantial improvements, it generally provided greater benefits than the majority of placebo controls. This suggests that Lo-TENS could potentially serve as a beneficial adjunctive therapy in the management of obesity and its associated conditions. However, given the limited number of trials assessed, the elevated risk of bias within these studies, and the scarce evidence currently available, it is too early to reach definitive conclusions. Caution should be exercised when interpreting the current findings. There is an imperative for further high-quality research to thoroughly investigate and substantiate the efficacy of Lo-TENS in relation to obesity and its related disorders.
A loss of function mutation in SOCS2 results in increased inflammatory response of macrophages to TLR ligands and Staphylococcus aureus
Authors: Guzylack-Piriou Laurence , Gausseres Blandine , Tasca Christian , Hassel Chervin , Tabouret Guillaume , Foucras Gilles 
Published: August 2024

IntroductionThe role of suppressor of cytokine signaling (SOCS)2 in anti-infective bacterial immunity has been poorly investigated compared to other members of the SOCS family.MethodsWe characterized the previously identified loss of function R96C point mutation of SOCS2 using a genome-edited mouse model that resumes the phenotype of Socs2 knockout mice. The response of macrophages to TLR-ligands and Staphylococcus aureus was examined.Results and discussionConversely to previously published data using human monocyte-derived macrophages, the stimulation of bone-marrow-derived macrophages with various TLR ligands did not show any difference according to the SOCS2 variant. Upregulation of IL-6 and TNF-α pro-inflammatory cytokines production was only seen when the SOCS2 expression was promoted by the culture of macrophages in the presence of GM-CSF. Furthermore, we showed that the SOCS2 point mutation is associated with heightened STAT5 phosphorylation in a short time frame upon GM-CSF incubation. In mice, recruitment of neutrophil and F4/80int Ly6C+ inflammatory macrophage, as well as IFN-γ and IL-10 concentrations, are significantly increased upon S. aureus peritoneal infection. Altogether, these data support the idea that by lowering the pro-inflammatory environment, SOCS2 favors better control of bacterial burden during a systemic infection caused by S. aureus.
Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer: a systematic review and meta-analysis
Authors: Yan Guangwei , Du Yanmin , Zhang Huanhuan , Yan Jinxiang , Liu Yixuan , Ban Zhenying , Guo Yong-Zhen , Zeng Xianxu 
Published: August 2024

BackgroundVarious trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer.MethodsWe utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR).ResultsFour trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9–36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1–70.2) for dMMR group and 33.1% (95% CI: 25.7–40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3–78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5–97.6) for the dMMR group and 76.3% (95% CI: 66.3–86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5–100.0) and 80.2% (95% CI: 59.9–100.0), respectively.ConclusionLenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.
The role of methylprednisolone in severe COVID-19 patients: a meta-analysis
Authors: Xu Wanru , Zeng Yujun , Han Hedong , Lv Tangfeng , Lin Dang 
Published: August 2024

BackgroundThe purpose of this study is to assess the effectiveness of methylprednisolone in severe COVID-19.MethodsPubMed, the Cochrane Library and Web of Science were searched for literatures comparing methylprednisolone and control treatment in severe COVID-19 patients. Statistical pooling was reported as risk ratio (RR) with corresponding 95% confidence interval (CI). The outcomes of interest in the literature survey were mortality and adverse events.ResultsA total of 13 studies were included, including 3,138 patients with severe COVID-19, of which 1,634 patients were treated with methylprednisolone and 1,504 patients were treated with control treatment. Five of the 13 studies reported severe adverse events. Our meta-analysis indicates that methylprednisolone treatment in COVID-19 patients is associated with a significant reduction in mortality (RR 0.62, 95% CI 0.46–0.85, p = 0.003) compared to control treatment, without an increased risk of adverse events (RR 1.20, 95% CI 0.92–1.56, p = 0.17). Moreover, high-dose methylprednisolone treatment (RR 0.57; 95% CI 0.40–0.82, p = 0.003) and short-course methylprednisolone treatment (RR 0.54; 95% CI 0.38–0.89, p = 0.01) found to significantly reduce mortality. Additionally, it was found that younger severe COVID-19 patients (RR 0.40; 95% CI 0.20–0.80, p = 0.01) had better outcomes to methylprednisolone than older patients.ConclusionMethylprednisolone was correlated with lower mortality compared with control treatment in severe COVID-19 patients without increasing serious adverse reactions. Furthermore, high-doses and short-term of methylprednisolone treatment were linked with better younger COVID-19 reported higher benefit from methylprednisolone than older COVID-19 patients.
Efficacy of percutaneous microwave ablation guided by contrast-enhanced and two-dimensional ultrasound for in hepatic alveolar echinococcosis in difficult/dangerous locations
Authors: Huang Wangxing , Hu Zhipeng , Qi Lina , Zhang Xiaoyan , Li Min , Yu Mingan , Hua Guoyong 
Published: August 2024

BackgroundUltrasound-guided microwave ablation (MWA) has become a popular method for treating malignant liver tumors. However, few studies have investigated its use in the treatment of hepatoalveolar echinococcosis (HAE). This study aimed to explore the effectiveness and safety of contrast-enhanced ultrasound combined with two-dimensional ultrasound-guided MWA for the treatment of HAE in difficult/dangerous locations.MethodsData from 81 patients, who were diagnosed with hepatic alveolar hydatid disease in difficult/dangerous locations between January 2018 and January 2023, and underwent contrast-enhanced ultrasonography combined with two-dimensional ultrasound-guided MWA, were analyzed. After undergoing MWA, patients were followed up to determine whether the lesions recurred and to evaluate the therapeutic effect of MWA. Preoperatively, individualized strategies were designed for lesions in different locations, and different auxiliary ablation technologies were used for contrast-enhanced ultrasound combined with two-dimensional ultrasound-guided MWA to achieve complete inactivation of lesions in difficult/dangerous locations.ResultsMWA was performed on 89 HAE lesions in 81 patients. The median diameter of the lesions was 2.86 cm (interquartile range [IQR] 2.36–3.49 cm). The complete ablation rate after surgery was 100%, with a recurrence rate of 11.11%, and median follow-up of 24 months (IQR 12–48 months). The incidence of minor complications was 14.81%; no serious complications or deaths occurred. Compared with before surgery, TB, DB, alanine aminotransferase, and aspartate aminotransferase levels increased (p &lt; 0.001), albumin platelets and activated partial thromboplastin time decreased (p &lt; 0.05), with no statistical difference in prothrombin time (p &gt; 0.05).ConclusionMWA may be a safe and effective method for treating HAE in difficult/dangerous locations, and may represent a new and alternative option for this patient population.
Association between serum vitamin D and the risk of diabetic kidney disease in patients with type 2 diabetes
Authors: Wang Yujie , Hu Chenggang , Li Ying , Liu Qi , Gao Lichao , Zhang Dongmei , Cao Ling 
Published: August 2024

AimsThis investigation explored the potential correlation between serum vitamin D concentration and diabetic kidney disease (DKD) among patients with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study assessed 4,570 patients with T2DM drawn from the National Health and Nutrition Examination Survey (NHANES) dataset. Restricted cubic splines were utilized to examine the dose–response relationship between serum vitamin D levels and the risk of DKD in patients with T2DM. Serum vitamin D concentrations were divided into quartiles for multivariable logistic regression analysis to evaluate the association between varying serum vitamin D levels and DKD risk in patients with T2DM. Additionally, sex-stratified analyses were conducted to determine consistency of the results. The influence of vitamin D concentrations on mortality risk was assessed using a Cox regression model.ResultsOf the patients with T2DM, 33% were diagnosed with DKD. Restricted cubic spline plots revealed a U-shaped relationship between vitamin D levels and DKD risk, with a protective effect noted in the mid-range, indicating optimal serum vitamin D concentrations between 59.6 nmol/L and 84.3 nmol/L. The multivariate Cox regression analysis suggested that higher VID levels were associated with a reduced mortality risk, particularly in male patients.ConclusionThe regulation and monitoring of serum vitamin D levels within an optimal range may play a pivotal role in the prevention of DKD in patients with T2DM. Public health strategies should emphasize the regular monitoring of vitamin D levels, especially among populations at elevated risk, to mitigate the progression of DKD and decrease the associated mortality rates.
Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system
Authors: Shera Simer , Katzka William , Yang Julianne C. , Chang Candace , Arias-Jayo Nerea , Lagishetty Venu , Balioukova Anna , Chen Yijun , Dutson Erik , Li Zhaoping , Mayer Emeran A. , Pisegna Joseph R. , Sanmiguel Claudia , Pawar Shrey , Zhang David , Leitman Madelaine , Hernandez Laura , Jacobs Jonathan P. , Dong Tien S. 
Published: August 2024

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research. Previous studies have identified the microbiome’s role in bariatric surgery and in inflammatory immune cell populations. The host innate immune system modulates hepatic inflammation and fibrosis, and thus the progression of MASLD. The precise role of immune cell types in the pathogenesis of MASLD remains an active area of investigation. The aim of this study was to understand the interplay between microbiota composition post-bariatric surgery and the immune system in MASLD.MethodsEighteen morbidly obese females undergoing sleeve gastrectomy were followed pre-and post-surgery. Stool from four patients, showing resolved MASLD post-surgery with sustained weight loss, was transplanted into antibiotic treated mice. Mice received pre-or post-surgery stool and were fed a standard or high-fat diet. Bodyweight, food intake, and physiological parameters were tracked weekly. Metabolic parameters were measured post-study termination.ResultsThe human study revealed that bariatric surgery led to significant weight loss (p &gt; 0.05), decreased inflammatory markers, and improved glucose levels six months post-surgery. Patients with weight loss of 20% or more showed distinct changes in blood metabolites and gut microbiome composition, notably an increase in Bacteroides. The mouse model confirmed surgery-induced microbiome changes to be a major factor in the reduction of markers and attenuation of MASLD progression. Mice receiving post-surgery fecal transplants had significantly less weight gain and liver steatosis compared to pre-surgery recipients. There was also a significant decrease in inflammatory cytokines interferon gamma, interleukin 2, interleukin 15, and mig. This was accompanied by alterations in liver immunophenotype, including an increase in natural killer T cells and reduction of Kupfer cells in the post-surgery transplant group.DiscussionOur findings suggest surgery induced microbial changes significantly reduce inflammatory markers and fatty liver progression. The results indicate a potential causal link between the microbiome and the host immune system, possibly mediated through modulation of liver NKT and Kupffer cells.