bluuebunny/crossref_metadata_2025_split huggingface dataset:
Previously defined variants of uncertain significance may play an important role in epilepsy and interactions between certain variants may become pathogenic
Authors: Hussein Yara , Weisblum‐Neuman Hila , Ben Zeev Bruria , Stern Shani 
Published: November 2024

AbstractObjectiveEpilepsy is a chronic neurological disorder related to various etiologies, and the prevalence of active epilepsy is estimated to be between 4 and 10 per 1000 individuals having a significant role in genetic mutations. Next‐Generation Sequencing (NGS) panels are utilized for genetic testing, but a substantial proportion of the results remain uncertain and are not considered directly causative of epilepsy. This study aimed to reevaluate pediatric patients diagnosed with epilepsy who underwent genetic investigation using NGS panels, focusing on inconclusive variant findings or multiple variants of uncertain significance (VUSs).MethodsA subgroup of pediatric patients aged 0–25 years, diagnosed with epilepsy, who underwent genetic investigation with an NGS epilepsy panel at the Child Neurology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, between 2018 and 2022 through Invitae, was reevaluated. Patients with inconclusive variant findings or multiple VUSs in their test results were included. Genetic data were analyzed to identify potentially pathogenic variants and frequent genetic combinations.ResultsTwo unrelated potentially pathogenic variants were identified in the SCN9A and QARS1 genes. A frequent genetic combination, RANBP2&RYR3, was also observed among other combinations. The RANBP2 gene consistently co‐occurred with RYR3 variants in uncertain results, suggesting potential pathogenicity. Analysis of unaffected parents' data revealed certain combinations inherited from different parents, suggesting specific gene combinations as possible risk factors for the disease.SignificanceThis study highlights the importance of reevaluating genetic data from pediatric epilepsy patients with inconclusive variant findings or multiple VUSs. Identification of potentially pathogenic variants and frequent genetic combinations, such as RANBP2&RYR3, could aid in understanding the genetic basis of epilepsy and identifying potential hotspots.Plain Language SummaryWe have performed a retrospective analysis on a subpopulation of pediatric patients diagnosed with epilepsy. We found that specific genetic variants were repeatable, indicating their potential pathogenicity to the disease.
Subcortical Alterations in Newly Diagnosed Epilepsy and Associated Changes in Brain Connectivity and Cognition
Authors: de Bézenac Christophe E. , Leek Nicola , Adan Guleed H. , Mohanraj Rajiv , Biswas Shubhabrata , Marson Anthony G. , Keller Simon S. 
Published: November 2024

ABSTRACTPatients with chronic focal epilepsy commonly exhibit subcortical atrophy, particularly of the thalamus. The timing of these alterations remains uncertain, though preliminary evidence suggests that observable changes may already be present at diagnosis. It is also not yet known how these morphological changes are linked to the coherence of white matter pathways throughout the brain, or to neuropsychological function often compromised before antiseizure medication treatment. This study investigates localized atrophy in subcortical regions using surface shape analysis in individuals with newly diagnosed focal epilepsy (NDfE) and assesses their implications on brain connectivity and cognitive function. We collected structural (T1w) and diffusion‐weighted MRI and neuropsychological data from 104 patients with NDfE and 45 healthy controls (HCs) matched for age, sex, and education. A vertex‐based shape analysis was performed on subcortical structures to compare patients with NDfE and HC, adjusting for age, sex, and intracranial volume. The mean deformation of significance areas (pcor < 0.05) was used to identify white matter pathways associated with overall shape alterations in patients relative to controls using correlational tractography. Additionally, the relationship between significant subcortical shape values and neuropsychological outcomes was evaluated using a generalized canonical correlation approach. Shape analysis revealed bilateral focal inward deformation (a proxy for localized atrophy) in anterior areas of the right and left thalamus and right pallidum in patients with NDfE compared to HC (FWE corrected). No structures showed areas of outward deformation in patients. The connectometry analysis revealed that fractional anisotropy (FA) was positively correlated with thalamic and pallidal shape deformation, that is, reduced FA was associated with inward deformation in tracts proximal to and or connecting with the thalamus including the fornix, frontal, parahippocampal, and corticothalamic pathways. Thalamic and pallidal shape changes were also related to increased depression and anxiety and reduced memory and cognitive function. These findings suggest that atrophy of the thalamus, which has previously been associated with the generation and maintenance of focal seizures, may present at epilepsy diagnosis and relate to alterations in both white matter connectivity and cognitive performance. We suggest that at least some alterations in brain structure and consequent impact on cognitive and affective processes are the result of early epileptogenic processes rather than exclusively due to the chronicity of longstanding epilepsy, recurrent seizures, and treatment with antiseizure medication.
Prevalence, Predictors and Reasons for Discharge Against Medical Advice Among Patients With Chronic Disease During COVID‐19
Authors: Al‐Bataineh Raya T. , Ghaith Ahmad H. 
Published: November 2024

ABSTRACTBackgroundDischarge against medical advice (DAMA) is used in healthcare facilities in a situation where patients refuse care or decide to leave the hospital before the treating physician recommends discharge. Previous studies have found DAMA to be prevalent among patients with various chronic conditions. The study had four objectives. The study aimed to investigate: (1) the prevalence of DAMA during COVID‐19 (2020–2021) among Jordanian patients with chronic diseases, (2) the association between DAMA and sociodemographic and clinical characteristics of patients with chronic diseases, (3) the predictors of DAMA and (4) the reasons behind DAMA at the patient, hospital and environmental levels.MethodsA descriptive cross‐sectional correlational design was used in the study. A convenience sampling approach was used to collect data from 1576 patients with chronic diseases from 3 private hospitals.ResultsThe study found that the prevalence rate of DAMA was 33.3%. There was a significant association between the sociodemographic and clinical characteristics of patients with chronic diseases and DAMA. Health insurance found to be the strongest predictor of DAMA. Finally, the study found that patient, hospital and environmental‐related factors had a low impact on DAMA.ConclusionsDAMA is prevalent among patients with chronic diseases in Jordan during COVID‐19 pandemic. The current study's findings can serve as an empirical basis for planning and implementing DAMA prevention programs and/or establishing or revising policies for the target population.
The Role of Artificial Intelligence in Accelerating Vaccine Development: Challenges and Opportunities in Pandemic Preparedness
Authors: Barreto Marina dos Santos , Correa Adriana Kelly Santana , Santos Ronaldy Santana , Silva Eloia Emanuelly Dias , Silva Deise Maria Rego Rodrigues , Moura Pedro Henrique Macedo , Jesus Pamela Chaves de , Souza Jessiane Bispo de , Santana Lucas Alves da Mota , Gopalsamy Rajiv Gandhi , Hariharan Govindasamy , Guimarães Adriana Gibara , Borges Lysandro Pinto 
Published: November 2024

ABSTRACTArtificial intelligence (AI) has been studied and applied to medicines and vaccine development. However, there is still a need to understand the processes used and improve them. With this letter, we draw attention to AI use as a tool in vaccine production, supporting scientists and enabling optimization in this process. In this way, it can be applied to contain pandemics and epidemics.
Clinical and Epidemiological Features of Pediatric COVID‐19: A Retrospective Study
Authors: Mirkarimi Mohammadreza , Heidari Solmaz , Shamsizadeh Ahmad , Tahouri Kia , Alisamir Mohsen , Fathi Mohammadreza , Mohammadi Shooka 
Published: November 2024

ABSTRACTBackground and AimsThere is a demand for additional data regarding the impact of coronavirus disease 2019 (COVID‐19) on the pediatric population. This study sought to determine the clinical and epidemiological features of pediatric COVID‐19 in Iran.MethodsA retrospective study was performed to assess medical records of children with COVID‐19 admitted to Abuzar Hospital in Ahvaz (Iran). Their clinical and demographic data were recorded.ResultsIn this study, 600 medical records of pediatric COVID‐19 patients were evaluated. Over 50% of them were boys. Mild, moderate, and severe manifestations of COVID‐19 were identified in 250, 200, and 150 children, respectively. Patients with severe or moderate COVID‐19 had substantially higher levels of various inflammatory markers (C‐reactive protein (CRP), fibrinogen, and d‐dimer), alanine transaminase (ALT), creatine kinase (CPK), blood urea nitrogen (BUN), neutrophils, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatinine (Cr), bilirubin, and gamma‐glutamyl transferase (GGT) compared to children with mild COVID‐19 (p < 0.001); they also had lower levels of lymphocytes, hemoglobin (Hb), and vitamin D than patients with mild COVID‐19 (p < 0.001). In addition, children with severe or moderate COVID‐19 had a notably higher incidence of fever or dry cough and longer hospital stays than those with mild COVID‐19 (p < 0.001). The prevalence of malnutrition and anemia in patients was 50.6% and 31.5%, respectively. A significant proportion of children who were underweight and stunted experienced moderate to severe COVID‐19. Furthermore, there was a considerably higher prevalence of malnutrition, anemia, and vitamin D insufficiency, or deficiency in children with moderate‐to‐severe COVID‐19 compared to patients with mild COVID‐19 (p < 0.001).ConclusionThe outcomes of this study revealed a significantly higher prevalence of malnutrition, anemia, vitamin D insufficiency or deficiency, elevated liver and kidney function test results, and increased inflammatory markers in children with moderate to severe COVID‐19 compared to those with mild COVID‐19.
Association between inflammation‐related indicators and vertebral fracture in older adults in the United States: A cross‐sectional study based on National Health and Nutrition Examination Survey 2013–2014
Authors: Gou Yuwei , Xie Xiansong , Yin Heng , Wu Yucheng , Wen Yongjie , Zhang Yingbo 
Published: November 2024

AbstractObjectiveThis study was to examine the association between inflammation‐related indexes SII (systemic immune‐inflammation index), NLR (neutrophil‐to‐lymphocyte ratio), PPN (product of platelet count and neutrophil count), and PLR (platelet‐to‐lymphocyte ratio), and the occurrence of vertebral fractures in older Americans.MethodsPatients ⩾60 years of age from the 2013–2014 NHANES database were selected for this study. Restricted cubic spline models and weighted logistic regression models were used to assess the association between inflammation‐related indexes and the occurrence of vertebral fractures in older Americans. The predictive value of the inflammation‐related indexes on the occurrence of vertebral fractures was assessed using receiver operating characteristic curves (ROC). To examine the robustness of the main findings, a sensitivity analysis was conducted.ResultsA total of 1281 patients were included in the analysis, of whole 120 suffered vertebral fractures. Fully adjusted logistic regression showed a significant linear relationship between NLR and the occurrence of vertebral fracture in older Americans (p < .05), but no relationship was found between SII, PLR, and the occurrence of vertebral fracture in older Americans. Meanwhile, NLR was slightly better than other indicators in predicting vertebral fracture.ConclusionsThis study found that NLR, as a novel inflammatory marker, can predict the risk of vertebral fracture in older Americans, which is of clinical significance for the prevention and treatment of vertebral fracture in older adults.
Hypoxia and TNF‐alpha modulate extracellular vesicle release from human induced pluripotent stem cell‐derived cardiomyocytes
Authors: Viola Margarida , Bebelman Maarten P. , Maas Renee G. C. , de Voogt Willemijn S. , Verweij Frederik J. , Seinen Cor S. , de Jager Saskia C. A. , Vader Pieter , Pegtel Dirk Michiel , Petrus Gerardus Sluijter Joost 
Published: November 2024

AbstractExtracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte‐derived EV (CM‐EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) that express NanoLuc‐tetraspanin reporters. These modified hiPSC‐CMs allow for quantification of tetraspanin‐positive CM‐EV secretion from small numbers of cells without the need for time‐consuming EV isolation techniques. We subjected these cells to a panel of small molecules to study their effect on CM‐EV biogenesis and secretion under basal and stress‐associated conditions. We observed that EV biogenesis is context‐dependent in hiPSC‐CMs. Nutrient starvation decreases CM‐EV secretion while hypoxia increases the production of CM‐EVs in a nSmase2‐dependent manner. Moreover, the inflammatory cytokine TNF‐α increased CM‐EV secretion through a process involving NLRP3 inflammasome activation and mTOR signalling. Here, we detailed for the first time the regulatory mechanisms of EV biogenesis in hiPSC‐CMs upon MI‐associated stressors.
Real‐time demands, restaurant density, and delivery reliability: An empirical analysis of on‐demand meal delivery
Authors: Li Xiaohan , Wang Xuequn , Liu Zilong , Zhang Jie , Tang Jiafu 
Published: November 2024

AbstractA surge in technological advancements and innovations has spurred the rise of on‐demand meal delivery platforms. Despite their widespread appeal, these platforms face two critical challenges (i.e., order batching and demand allocation) in effectively managing the delivery process while maintaining reliability. In response, this study aims to address these two challenges by examining the effects of real‐time demands and restaurant density on delivery reliability, as well as how the type of driver (i.e., in‐house versus crowdsourced drivers) moderates these effects. We evaluated our model with a unique dataset obtained from one of the top three on‐demand meal delivery platforms in China, and our research sheds light on several key findings. Specifically, our study finds inverted U‐shaped relationships between real‐time demands and delivery reliability and a positive relationship between restaurant density and delivery reliability. In addition, it reveals that crowdsourced drivers perform better than in‐house drivers under high real‐time demands. This study contributes to the literature by clarifying how delivery reliability can be influenced by real‐time demands and restaurant density. The results offer important implications for on‐demand meal delivery platforms to improve delivery performance and allocate demands amid complicated market conditions.
Imaging of Peritoneal Surface Malignancies
Authors: Caruso Damiano , Sammartino Paolo , Polici Michela , Masci Giorgio , Biacchi Daniele , Zerunian Marta , Scuto Daniele , Gallotti Maria Gloria , Iafrate Franco , Laghi Andrea 
Published: November 2024

ABSTRACTManagement of peritoneal surface malignancies is currently entrusted to a multimodality approach. Computed tomography (CT) scan remains the first imaging method despite the limitations in identifying small implants in critical regions. Magnetic resonance imaging is usually recommended for its performance in small implants, mesentery, and small bowel assessment. Positron emission tomography/CT plays an important role only in pseudomyxoma peritonei. Thus, becoming aware of the imaging strengths and drawbacks and having a multimodality imaging approach might be the best option for the patients.
The Impact of Chondrosarcoma with Positive Margins and Extraosseous Extension on Patient Outcomes
Authors: Yu Austin , Poulson Trevor , Butler Zachary , Demetrious Matthew , Colman Matthew , Gitelis Steven , Blank Alan T. 
Published: November 2024

ABSTRACTBackgroundChondrosarcoma accounts for 20% of all bony sarcomas and may present with extraosseous extension (EOE). The presence of an extraosseous component, along with positive surgical margins, has been separately associated with increased risk of local recurrence and decreased survival. This study compared the outcomes between patients with EOE, EOE and positive margins, and a control chondrosarcoma cohort with neither feature.MethodsThis was a retrospective review of 91 patients over a consecutive 13‐year period. Data including treatment details and outcomes were included. Thirty‐two patients had EOE of their chondrosarcoma, 7 patients had positive margins and EOE, and 52 chondrosarcoma patients had neither characteristic. Tumor characteristics, patient demographics, and overall survival, recurrence rates, and metastatic rates were compared among the three groups.ResultsPatients with positive surgical margins and EOE were noted to have significantly higher resection grade, dedifferentiation on presentation, and use of adjuvant chemotherapy compared to control. Patients with EOE alone were noted to have significantly higher grade and use of adjuvant chemotherapy compared to control. Patients with positive surgical margins and EOE additionally had significantly higher rates of mortality, recurrence, and metastasis on survival analysis compared to control. However, patients with EOE alone did not have significantly different survival rates compared to control.ConclusionThis study is one of the first to analyze the survival impact of EOE with positive surgical margins in chondrosarcoma. The significance found in mortality, recurrence, and metastatic rates in this unique subgroup may warrant further longitudinal observation and dictate future treatment options.
TERT Gene Mutation in Gliomas Cross‐Linked With (NTRK, PDL1, ALK, IDH, P53, EGFR, HER2): A Integrative Review TERT Gene Mutation in Gliomas
Authors: Santos Gunter Gerson , Nogueira Guilherme Nobre , Saldanha Iasmin Maria Rodrigues , Farias Ana Gabriela Ponte , Mateus Cauan Miranda , Neto Osvaldo Mariano Viana , Teixeira Maria Jânia 
Published: November 2024

ABSTRACTIntroductionRecent advancements in glioma treatment are largely driven by the identification of genetic alterations, which enhance diagnostic precision and prognostic assessments, and unveil potential therapeutic targets. TERT promoter mutations, in particular, are associated with a poorer prognosis and aggressive clinical behavior.MethodologyThis study explores the genetic interplay between TERT and other genes (ntrk, pdl1, alk, idh, p53, egfr, her2) in brain tumors through an integrative literature review. This method synthesizes evidence from selected articles spanning 2014 to 2023.ResultsThe review identified 65 articles based on defined inclusion criteria, out of which 14 were analyzed in depth. Findings reveal that TERT, TP53, and IDH1 are the most frequently mutated genes in gliomas. The prognosis of glioma patients can be refined through the combined analysis of IDH and TERT mutations. Additionally, PD‐L1 expression levels are associated with prognosis and may influence treatment responses, particularly, in immunotherapy.DiscussionThe study underscores the importance of molecular diagnostics, such as Next‐Generation Sequencing (NGS), in detecting key genetic mutations. These advancements have paved the way for new therapeutic strategies and better patient outcomes. The findings highlight the crucial role of genetic markers in glioma treatment and prognosis, advocating for continued research to enhance clinical applications and patient care.ConclusionThe use of NGS is indispensable in identifying biomarkers associated with mutations in the TERT gene.
Three‐Dimensional Volume Ultrasound Assessment of Cesarean Scar Niche and Cervix in Pregnant Women
Authors: Ivan Maria , Mahdy Heba , Banerjee Amrita , Tetteh Amos , Greenwold Natalie , Casagrandi Davide , Jurkovic Davor , Napolitano Raffaele , David Anna L. 
Published: November 2024

ObjectiveTo assess the reproducibility of standardized 3‐dimensional (3D) ultrasound volume analysis of the dimensions and the position of cesarean birth (CB) scar niche relative to the cervix in pregnant women.MethodsThis prospective single‐center study in women with 1 previous CB ≥8 cm cervical dilatation acquired ultrasound volumes between 11 and 24 weeks' gestation in a mid‐sagittal plane. Two experienced operators processed the volumes using virtual organ computer‐aided analysis. A CB scar niche was defined as an indentation at the scar site of ≥2 mm in depth. Niche and cervix volumes were calculated using manual contouring. Agreement for categorical variables was expressed using intraclass correlation coefficient (ICC). The Bland–Altman method was used to assess numerical variable reproducibility.ResultsTo achieve the desired statistical power, 52 participants were included. The intraobserver agreement on niche classification relative to the internal os was 100%, with an interobserver kappa coefficient of 0.98 (95% confidence interval [CI] 0.97–0.99, P < .05).The intraobserver ICC for niche volume was 0.94 (95% CI 0.90–0.96; P < .001), with a mean difference of −15.32 mm3 (±109.32). The interobserver ICC was 0.78 (95% CI 0.62–0.87; P < .001), with a mean difference of −21.57 mm3 (±202.01). The ICC for niche/cervix volume ratio were 0.94 (95% CI 0.90–0.96; P < .001) and 0.79 (95% CI 0.63–0.87; P < .001) for intra‐ and interobserver reproducibility, respectively.ConclusionsThis study demonstrates that 3D CB scar sonographic features are highly reproducible in pregnant women with a history of advanced labor CB. The validated protocol can guide future research on the association with subsequent adverse pregnancy outcomes.