bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically Engineered Mouse Models Unveil Mechanisms and Therapeutic Strategies for GMPPB-Associated Dystroglycanopathy
Authors: Wang Yuxiang , fu Ziwei , Wang Wangtong , Chen Yanyan , Zhang Chenyang , Yang Ju , Yang Hua , Yan Bing , Gong Baoming , Lu Weiqiao , Liu Ying , Sun Lei , Jiang Hao , Zhang Zhao , Chen Bo , Liu Xiuping 
Published: August 2024

Abstract

The pathogenesis and therapeutic avenues for GDP-mannose pyrophosphorylase
B (GMPPB)-associated dystroglycanopathy (DPG) have not been comprehensively
characterized. Recent studies have highlighted a significant association between
mutations in GMPPB with DGP, a rare disease characterized by neuromuscular
phenotypes. To interrogate the molecular mechanisms driving the onset and progression
and to identify potential therapeutic approaches for GMPPB-associated DGP, we here
constructed genetically engineered mice models of Gmppb. We show that Gmppb
knockout and P32L mutant mice are lethal in the homozygous form, whereas
homologous R287Q mutants are viable. Heterozygous Gmppb-P32L mutant mice
exhibit reduced muscle strength, decreased locomotor ability, elevated creatine kinase
levels and increased centrally nucleated myofibers. Furthermore, loss of GMPPB
results in defective differentiation of muscle stem cells, leading to failure to develop
into mature myotubes and diminished muscle regeneration capability. Biochemical and
transcriptomic analyses indicate that loss of GMPPB is associated with significant
alterations in protein glycosylation, intracellular Ca2+ storage and release, and the
Wnt/β-catenin signaling pathway. Pharmacological activation of the Wnt pathway
alleviated disruption of muscle differentiation and regeneration post muscle injury in
Gmppb-deficient models. Additionally, adeno-associated virus (AAV)-mediated gene
replacement therapy successfully ameliorated the muscular phenotypes. Collectively,
our findings provide direct evidence that impaired muscle stem cell differentiation
contributes to GMPPB-associated dystroglycanopathy. Wnt pathway agonists and AAV
gene therapy represent potential effective intervention strategies for treating DGP
disease.
Von Hippel-Lindau Disease Presenting with Renal Cell Carcinoma and Multiple Organ Involvement: A Case Report
Authors: Hashemi Peyman , Aalinezhad Marzieh , Shahsavan Mahdi , Naderi Yosra 
Published: August 2024

Abstract

Introduction:
Von Hippel-Lindau (VHL) disease is a rare autosomal dominant disorder characterized by the development of both neoplastic and cystic lesions in multiple organs, including the central nervous system (CNS), retina, kidneys, pancreas, and adrenal glands. Early detection and careful management are critical due to the potential for significant morbidity and mortality associated with this condition.
Case Presentation:
A 37-year-old man with a history of VHL presented with abdominal discomfort and hematuria. His medical history included surgical resection of a cerebellar hemangioblastoma 20 years ago and a retinal capillary hemangioma diagnosed 5 years ago. Genetic testing confirmed the presence of a pathogenic VHL variant. Abdominopelvic multidetector computed tomography revealed multiple pancreatic cysts, renal cysts, two enhancing renal lesions suggestive of renal cell carcinoma (RCC), and a retroperitoneal mass indicative of extra-adrenal paraganglioma. Biopsy confirmed the presence of clear cell RCC. The patient exhibited classic manifestations of VHL, including central nervous system hemangioblastomas, retinal hemangiomas, pancreatic cysts, RCC, and extra-adrenal paragangliomas.
Conclusions
This case highlights the diverse manifestations of VHL disease, including CNS hemangioblastomas, retinal hemangiomas, pancreatic cysts, RCC, and paragangliomas. The patient's comprehensive clinical, imaging, and histopathological evaluations met the diagnostic criteria for VHL. Regular screening and close follow-up are crucial to detect complications early, allowing for timely intervention and improved outcomes.
Ongoing intensification of El Niño impacts on East Asia's summer climate with achieved carbon neutrality
Authors: Tao Weichen , Zhang Wen , Huang Gang , Hu Kaiming , Qu Xia , Wang Ya , Tang Haosu , Zhang Suqin 
Published: August 2024

Abstract

A notable anomalous lower-tropospheric anticyclone appears over the western North Pacific (WNP) during post-El Niño summer, exerting a profound influence on the East Asia summertime climate. Here, we employ a suite of global climate model projections under symmetric CO2 ramp-up (RU) and ramp-down (RD) scenarios to reveal the asymmetric response of the WNP anticyclone (WNPAC). Our results demonstrate a progressive strengthening of the WNPAC with rising CO2 concentrations, a trend that persists as CO2 declines, followed by gradual recovery, and the anomalous anticyclone fails to return to its initial state when CO2 concentrations return to pre-industrial levels, attributed to Indo-Pacific zonal SST gradient variations. In contrast to the CO2 RU phase, the increased zonal SST gradient is witnessed in the CO2 RD phase, favoring anomalous moisture convergence over the Maritime Continent (MC). This strengthens the WNPAC through Kelvin wave-induced Ekman divergence or local Hadley circulation adjustment. The increased zonal SST gradient is associated with strengthened SST warming in the MC and accelerated decay of El Niño-related positive SST anomalies in the equatorial Central Pacific, ultimately attributed to a climatological equatorial Pacific El Niño-like warming pattern driving intricate air-sea interactions and processes. Our findings indicate that the overshoot of the WNPAC during the CO2 RD phase may exacerbate the flood and high temperature risks in densely populated East Asia.
Design and Analysis of Electrical characteristic of Non-contact Capacitive Electrode for ECG Application
Authors: S Ramya Lakshmi V , Raajan N R 
Published: August 2024

Abstract

Purpose: Capacitive-based sensors have become prominent in physiological sig- nal measurement over the past decade. The electrical characteristics of the capacitive electrode depend on various parameters.
Methods: In this work, we proposed a Capacitive Electrode (CE) with optimal Shielding and Guarding design (SGD). The gold was coated over the copper on the base material FR4 is used for electrode material. Three different designs were proposed. The performance of each design was evaluated using the Finite Element Method (FEM).
Results: On comparing all the electrophysical parameters of the three designs, the design: ”The shielding was designed in such a way that it conversed with the electrode, and the guarding was formed as a concentric around the sensing plate” shows optimal SGD, which enables higher performance. The proposed electrode was applied for the ECG application. The optimal electrodes (OE) were placed in the lead I and V1 V2 lead positions. The experimental results conducted by Finite Element Method (FEM) show that the lead I position is the optimal lead position for ECG measurement. The developed Capacitive electrodes were tested to fetch the ECG signal. When comparing the proposed electrode with the traditional 12-lead ECG system and the AD8232 sensor, the SNR value shows better signal quality for the proposed electrode.
Conclusion: This research mainly concentrates on the electrical characteristics of the capacitive electrodes with optimal shielding and guarding design. The proposed capacitive electrode can also used to fetch other bio-signals.
Identifying factors that determine functional status of stroke patients using partial proportional odds model at Felege Hiwot Referral Hospital, Ethiopia
Authors: Berehan Haymanot B. , Berehan Yebelay B. , Kassie Maru Z. , Motbayhon Habitamu W. , Arega Gezachew G. , Awoke Shegaw M. 
Published: August 2024

Abstract

In many clinical trials, patients who are followed up over time may typically measure repeatedly multiple outcomes. Ignoring such repeatedly measured outcome or biomarker and considering cross-sectional analyses can leads to biased estimates. In this context, we presented partial proportional odds model for longitudinal functional status measures among stroke patients at FHRH Bahir Dar, Ethiopia. We considered 400 patients who had stroke under the medical ward outpatient stroke who started treatment from September 2018 to August 2021 by a retrospective cohort study design. Among 400 stroke patients taken from the repository of FHRH, 188(47%) were females. The patients mean age and corresponding 95%CI was (58; 95%CI=55-58) at baseline. Among different candidates of demographic and clinical variables, age, diabetes, blood urea nitrogen, Glasgow coma scale, white blood cell count, and stroke complication were statistically significant predictors. the ordinal longitudinal modeling approach, provides wide-ranging information about the longitudinal pattern of the functional status. Furthermore, the results of the study can be used as a motivation for future scholars. since stroke is one of the most frequent diseases in Ethiopia as well as in the world, it needs more attention and study in a wider study area.
Bioinformatics analysis and population sample validation of ferroptosis related genes in coronary heart disease
Authors: Li LiHeng , Chen CuiHua , Dong QingHua , Xie YuBo 
Published: August 2024

Abstract

The aim of this study was to investigate the association between coronary heart disease (CHD) and ferroptosis, furthermore, to identify the relevant genes and potential diagnostic biomarkers by bioinformatics analysis. CHD was the main cause of cardiovascular diseases, its pathogenesis was complex. As an iron-dependent form of cell death, ferroptosis was believed to play a significant role in various diseases. Studies have shown that genes associated with ferroptosis include PRKAA2, NOX4, GLS2, and G6PD. Further data analysis and meta-analysis revealed that NOX4 gene expression was significantly upregulated in patients with CHD (P<0.05), which may be related to coronary atherosclerosis and myocardial injury. Additionally, the upregulation of NOX4 expression was validated through RT-PCR. In summary, this study revealed the association between CHD and ferroptosis, providing insights into the pathogenesis of CHD. Genes such as NOX4 may serve as diagnostic biomarkers for CHD, offering new perspectives and approaches for its early diagnosis and treatment.
Influence of MMP12 Single Nucleotide Polymorphism rs586701 on the Prognosis of Primary Lung Cancer in Chinese Han Chinese
Authors: Xu Chang , Du Wei , Sun Zhenyu , Gao Zhunyi , Xiao Man , Guo Shicheng , Wang Yi , Wang Haijian , Li Qiang , Wu Junjie , Shen Bo , Shang Yan , Jiang Gengxi , Bao Yang 
Published: August 2024

Abstract

Purpose
Lung cancer is now one of the most common cancers in the world, with a high mortality rate and poor prognosis. Predicting the prognosis of lung cancer patients and using this information to develop treatment strategies and interventions is important for prolonging patient survival. A stratified analysis was conducted on Han Chinese primary lung cancer patients in the Chinese population, with the objective of investigating the relationship between matrix metalloproteinase 12(MMP12) gene polymorphism rs586701 and the prognosis of lung cancer patients.
Methods
A total of 888 Han Chinese primary lung cancer patients (exclusive of minors) were recruited between January and November 2009 (10 months) and provided written informed consent. The study included subjects from Changhai Hospital of the Naval Medical University (Second Military Medical University) and Taizhou Institute of Health Sciences of Fudan University. A total of 49 subjects were excluded due to incomplete data collection for various reasons. Blood samples were collected from 839 patients diagnosed with lung cancer, and genomic DNA was extracted for genotyping using SNPscan technology. In order to adjust for multiple factors, the data was stratified by age, sex, smoking status, family history of malignancy, TNM stage, and lung cancer tissue type. The association between lung cancer prognosis and genotype was then analyzed using a multivariate Cox proportional risk model.
Results
A polymorphism in the MMP12 gene, specifically the T > G variant at position 586701, has been associated with a reduction in survival time in lung cancer patients. In the overall sample, patients with the TG genotype (TG vs TT, adjusted HR = 1.21, 95% CI: 1.01–1.44, P = 0.035) exhibited a shorter survival time and a worse prognosis. Stratified analyses showed that among male lung cancer patients, lung cancer patients younger than 60 years old, and smoking lung cancer patients, patients with the TG genotype had a lower survival time than patients with the TT genotype (adjusted risk ratio HR = 1.24, 95% CI: 1.01–1.52, P = 0.04; HR = 1.58, 95% CI: 1.18–2.12, P = 0.002; HR= (1.30, 95% CI: 1.06–1.61, P = 0.013). In patients with SCC and NSCLC, survival time was shorter in patients with the TG genotype (TG vs TT, adjusted risk ratio HR = 1.48, 95% CI: 1.10–2.01, P = 0.010; HR = 1.21, 95% CI: 1.01–1.46, P = 0.038). In the designed genetic model, the dominant genotype TG + GG was associated with a shorter survival time and worse prognosis among lung cancer patients aged less than 60 years (TG + GG vs TT, adjusted risk ratio HR = 1.43, 95% CI: 1.07–1.90, P = 0.014).
Conclusion
The MMP12 polymorphism rs586701 may be associated with the prognosis of lung cancer. Specifically, the MMP12 polymorphism rs586701 T > G has been found to lead to a worse prognosis.
Florida man exonerated: an amphipod case study on the implications of cryptic species complexes and global invasions.
Authors: Sawicki Thomas R , Cannizzaro A. G. 
Published: August 2024

Abstract

The crangonyctid amphipod Crangonyx floridanus is considered to have a natural distribution across much of the eastern United States and is thought to be invasive in parts of the western United States, Japan, and the British Isles. Recent investigations have revealed highly endemic cryptic species among populations of Crangonyx floridanus sensu lato occurring at approximately 30 oN latitude in the Panhandle of Florida, USA. To date, none of the published cryptic lineages of C. floridanus sensu lato phylogenetically align with the invasive populations. Despite years of collecting efforts, C. floridanus sensu stricto has not been identified from its type locality in Highlands Hammock State Park, in Highlands County, Florida, since its initial collection in 1962. To assess the status of C. floridanus sensu stricto, environmental DNA was used to analyze the V4/V5 hypervariable regions of the nuclear 18S rRNA gene from the type locality. These data revealed that the species has not been extirpated from the type locality, and that it is not the source of the invasive populations. In addition, populations of C. floridanus sensu lato collected for this study from Alabama, Ohio, and Pennsylvania, USA, displayed 100% identity to invasive populations in the western United States, Japan, and the British Isles, at both the 18S rRNA and mitochondrial cytochrome c oxidase subunit I genes. This study demonstrates that traditional diagnostic characteristics may lead to incorrect assumptions about the taxonomic status of invasive species.
Implementation of a Novel TRIZ-Based Model to Increase the Reporting of Adverse Events in the Healthcare Center
Authors: Lee Jiun-Yih , Lee Pei-Shan , Chiang Cheng-Hsien , Chen Yi-Ping , Chen Chiung-Ju , Huang Yuan-Ming , Chiu Jlan-Ren , Yang Pei-Ching , Chang Jui-Ting , Yeh Chen-An 
Published: August 2024

Abstract

Objectives
Underreporting of adverse events in healthcare systems is a global concern. This study aims to address the underreporting of adverse events by implementing a TRIZ-based model to identify and overcome barriers to reporting, thus filling gaps in current reporting practices and improving incident recognition.
Methods
A TRIZ (Theory of Inventive Problem Solving) approach was adopted, integrating with SERVQUAL methodologies to design interventions. Preintervention and postintervention surveys were conducted to evaluate changes in barriers to reporting and the recognition of adverse events. Statistical analyses were performed to assess the effectiveness of the interventions.
Findings:
Barriers to reporting AEs significantly decreased, and recognition improved. Monthly reported cases rose from 33.7 to 50.3 (p = 0.000), demonstrating the effectiveness of the TRIZ-based interventions.
Conclusions
Implementing a TRIZ-based model significantly improved adverse event reporting by overcoming identified barriers and enhancing the recognition of reportable events. Future research should explore the long-term sustainability of these interventions and their broader applicability in diverse healthcare settings.
High concentrations of L-lysine cause mitochondrial damage and necrosis in isolated pancreatic acinar cells
Authors: Végh Eszter T. , Balla Zsolt , Tóth Brigitta , Elperin Jason , Speakman Steven , Pallagi Petra , Rázga Zsolt , Kiss Lóránd , Gukovskaya Anna , Rakonczay Zoltán 
Published: August 2024

Abstract

Intraperitoneal administration of high doses of basic amino acids, such as L-lysine (L-Lys), L-arginine (L-Arg) or L-ornithine (L-Orn) induces acute pancreatitis in rodents. Although the exact mechanism of their action is not fully understood, the role of mitochondria has been implicated. We aimed to investigate the effects of basic amino acids, particularly L-Lys, on isolated pancreatic acinar cells. Isolated mouse or rat pancreatic acinar cells were treated with high concentrations (10–60 mM) of L-Lys, L-Arg or L-Orn. The morphology of acinar mitochondria was observed by electron microscopy. The function of mitochondria was assessed by mitochondrial membrane potential (∆Ψm) and cellular ATP level measurements. Changes in intracellular Ca2+ concentration ([Ca2+]i), trypsin activity and cellular viabilities were also determined. Treatment of acinar cells with L-Lys caused mitochondrial swelling. L-Lys and L-Orn dramatically decreased ∆Ψm after 6 h of treatment, whereas L-Arg reduced ∆Ψm after 3 h of treatment. Intracellular ATP levels were also reduced by basic amino acids. L-Lys did not alter [Ca2+]i and did not induce early trypsinogen activation. Furthermore, L-Lys administration primarily caused acinar necrosis. Overall, L-Lys primarily damaged pancreatic acinar mitochondria and caused necrotic cell death without affecting [Ca2+]i.
Technology for obtaining linseed protein concentrate minimized in antinutritional factors
Authors: Cargnin Gregorio , Adorian Taida Juliana , Falcone Diuly Bortoluzzi , de Freitas Ana Maria Liberalesso , Robalo Silvino Sasso , Silva Stéfane Sauzem , Silva Leila Picolli da 
Published: August 2024

Abstract

The linseed processing was carried out on a laboratory scale to obtain the linseed protein concentrate (LPC), using the physical method. The analyzes were carried out on whole grains (WG), demucilated grains (GD) and LPC. In the fractions obtained, the chemical composition (dry matter, ash, lipids, crude protein, total dietary fiber, soluble fiber and insoluble fiber), total phenolic compounds and physicochemical properties were evaluated in the obtained fractions. The amino acid profile was determined for WG, GD and LPC. Protein molecular weight electrophoresis was determined for WG, GD and LPC. The results indicated that, in the physical process for protein concentration, LPC presented a protein content 96% higher than that of linseed grains and obtained less than 8% of lipids in its composition. Furthermore, LPC improved the amino acid profile and at the phenolic compounds of the different fractions of flaxseed, we see that their contents were concentrated in the LPC, which was 83.75% higher than the WG. The electrophoresis results demonstrate that physical processing caused a reduction in the molecular weight of the reducing and non-reducing flaxseed proteins. The present study allows us to conclude that it is possible to separate flaxseed into different fractions, using physical processes, obtaining a protective concentrate. The inclusion of these products in animal feed needs to be evaluated to determine levels of acceptance.
The effect of brolucizumab on diabetic macular edema and ischemia; a real world analysis
Authors: Chronopoulos Argyrios , Sas Lea Karla , Holzwarth Jakob Wilhelm , Hattenbach Lars-Olof 
Published: August 2024

Abstract

Objective The response to intravitreal brolucizumab on diabetic macular edema and macular ischemia was studied in treatment-refractory and treatment-naïve patients.Methods Patients with either treatment resistant or treatment naive diabetic macular edema were studied retrospectively before and after intravitreal brolucizumab. All patients underwent a comprehensive ophthalmological examination including optical coherence tomography (OCT) and OCT-angiography (OCT-A) to compare their macular edema and macular ischemia before initiation of intravitreal brolucizumab treatment and at the end of the upload phase.Results A total of 31 eyes of 27 diabetic patients were examined. 19 eyes were switched to brolucizumab after long prior anti-VEGF treatment history; 12 eyes were treatment naive with respect to macular edema. All eyes responded positively to brolucizumab with complete resolution of diabetic macular edema: group 1: 369 vs 302 µm (p = 0.007), group 2: 415 vs 259 µm (p = 0.01). All eyes also manifested improvement in vision: group 1: 0.3 vs 0 .6 (0.5 ± 0.5 logMAR vs. 0.22 ± 0.5 logMAR) (p = 0.01), group 2: 0.3 vs 0.5 (0.5 ± 0.7 logMAR vs. 0.2 ± 0.7 logMAR) (p = 0.00002). Interestingly, in group 2 there was also significant improvement in vessel and perfusion density, especially in the central and inner diameter: central vessel density of 6.55 vs 9.03 mm/mm2 (p = 0.008), inner of 11.2 vs 13, 9 mm/mm2 (p = 0.02), and central perfusion density of 15.5% vs 20.7% (p = 0.02). Although not statistically significant, there was also a tendency to improved foveal circularity.Conclusion Intravitreal brolucizumab leads to significant functional and anatomical improvement in diabetic macular edema and has also a beneficial effect on macular ischemia reflected by foveal capillary anatomy and perfusion density.