bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo variants of IRF2BPL result in developmental epileptic disorder
Authors: Wang Yong , Ke Zhongling , Li Yufen , Qiu Mingqi , Liu Jing , Yang Zuozhen , Wen Shu , Liang Mengmeng , Chen Shan 
Published: March 2024

Abstract
Background
Pathogenic variants of the IRF2BPL gene have been reported to cause neurodevelopmental disorders; however, studies focused on IRF2BPL in zebrafish are limited.

Results
We reported three probands diagnosed with developmental delay and epilepsy and investigated the role of IRF2BPL in neurodevelopmental disorders in zebrafish. The clinical and genetic characteristics of three patients with neurodevelopmental disorder with regression, abnormal movements, loss of speech and seizures (NEDAMSS) were collected. Three de novo variants (NM_024496.4: c.1171 C > T, p.Arg391Cys; c.1157 C > T, p.Thr386Met; and c.273_307del, p.Ala92Thrfs*29) were detected and classified as pathogenic or likely pathogenic according to ACMG guidelines. Zebrafish crispants with disruption of the ortholog gene irf2bpl demonstrated a reduced body length and spontaneous ictal-like and interictal-like discharges in an electrophysiology study. After their spasms were controlled, they gain some development improvements.

Conclusion
We contribute two new pathogenic variants for IRF2BPL related developmental epileptic disorder which provided evidences for genetic counseling. In zebrafish model, we for the first time confirm that disruption of irf2bpl could introduce spontaneous electrographic seizures which mimics key phenotypes in human patients. Our follow-up results suggest that timely cessation of spasmodic seizures can improve the patient’s neurodevelopment.
Development and clinical validation of a seven-gene signature based on tumor stem cell-related genes to predict ovarian cancer prognosis
Authors: Wang Guangwei , Liu Xiaofei , You Yue , Chen Silei , Chang Xiaohan , Yang Qing 
Published: March 2024

Abstract
Objective
Tumors are highly heterogeneous, and within their parenchyma, a small population of tumor-stem cells possessing differentiation potential, high oncogenicity, and self-renewal capabilities exists. These cells are pivotal in mediating tumor development, chemotherapy resistance, and recurrence. Ovarian cancer shares characteristics with tumor stem cells, making it imperative to investigate molecular markers associated with these cells.

Methods
Stem cell-related genes were collected, and molecular subtypes were established based on gene expression profiles from The Cancer Genome Atlas using the R package tool “ConsensusClusterPlus.” Multi-gene prognostic markers were identified using LASSO regression analysis. Gene set enrichment analysis was employed to gain insights into the potential molecular mechanisms of these identified markers. The robustness of these prognostic markers was analyzed across different cohorts, and their clinical independence was determined through multivariate Cox analysis. A nomogram was constructed to assess the model’s clinical applicability. Immunohistochemistry was performed to validate the expression of hub genes.

Results
Utilizing 49 tumor stem cell-related genes associated with prognosis, 362 ovarian cancer samples were divided into two distinct clusters, revealing significant prognostic disparities. A seven-gene signature (GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9), identified through LASSO regression, exhibited stability and robustness across various platforms. Multivariate Cox regression analysis confirmed the signature’s independence in predicting survival in patients with ovarian cancer. Furthermore, a nomogram combining the gene signature demonstrated strong predictive abilities. Immunohistochemistry results indicated significantly elevated GALP, CACNA1C, COL16A1, PENK, C4BPA, PSMA2, and CXCL9 expression in cancer tissues.

Conclusion
The seven-gene signature holds promise as a valuable tool for decision-making and prognosis prediction in patients with ovarian cancer.
Etiological analysis of 167 cases of drug-resistant epilepsy in children
Authors: Zuo Ran-Ran , Jin Mei , Sun Su-Zhen 
Published: March 2024

Abstract
Background
To analyze the etiological distribution characteristics of drug-resistant epilepsy (DRE) in children, with the aim of providing valuable perspectives to enhance clinical practice.

Methods
In this retrospective study, clinical data were collected on 167 children with DRE who were hospitalized between January 2020 and December 2022, including gender, age of onset, seizure types, video electroencephalogram(VEEG) recordings, neuroimaging, and genetic testing results. Based on the etiology of epilepsy, the enrolled children were categorized into different groups. The rank-sum test was conducted to compare the age of onset for different etiologies.

Results
Of the 167 cases, 89 (53.3%) had a clear etiology. Among them, structural factors account for 23.4%, genetic factors for 19.2%, multiple factors for 7.2%, and immunological factors for 3.6%. The age of onset was significantly earlier in children with genetic causes than those with structural (P < 0.001) or immunological (P = 0.001) causes.

Conclusions
More than half of children with DRE have a distinct underlying cause, predominantly attributed to structural factors, followed by genetic factors. Genetic etiology primarily manifests at an early age, especially among children aged less than one year. This underscores the need for proactive enhancements in genetic testing to unveil the underlying causes and subsequently guide treatment protocols.
Thermodynamic investigation on the aqueous mixtures of choline chloride/propylene glycol deep eutectic solvent at T = (293.15 to 313.15) K
Authors: Zarghampour Aynaz , Jafari Parisa , Rahimpour Elaheh , Jouyban Abolghasem 
Published: March 2024

AbstractThis work focuses on physicochemical features of the choline chloride/propylene glycol deep eutectic solvent (DES) + water mixtures by determining their density values in mono- and mixed- states over various temperatures in the range of 293.15–318.15 K. The density data obtained from measurements were utilized for the computation of various quantities such as excess molar volumes, molar volume, apparent molar volume, limiting apparent molar expansibility, and isobaric thermal expansion coefficient. Furthermore, the experimental densities were fitted to some mathematical equations such as Jouyban-Acree, Jouyban-Acreevan’t Hoff, modified Jouyban-Acree-van’t Hoff, Redlich–Kister and Emmerling. Studies of this nature can provide useful insights into solute–solvent interactions in aqueous solutions of DES, especially about to their novel application in drug solubilization.
Compliance with infection prevention and control standard precautions and factors associated with noncompliance among healthcare workers working in public hospitals in Addis Ababa, Ethiopia
Authors: Senbato Feyissa Regassa , Wolde Deneke , Belina Merga , Kotiso Kehabtimer Shiferaw , Medhin Girmay , Amogne Wondwossen , Eguale Tadesse 
Published: March 2024

AbstractBackgroundStandard Precautions (SPs) are the minimal infection prevention and control (IPC) measures that apply to all patient care activities at all times, regardless of whether the patient has a suspected or proven disease, in any place where healthcare service is provided. These evidence-based practices protect healthcare workers (HCWs) from infection while preventing the spread of infectious agents among patients, visitors, and the environment.ObjectivesAssessed compliance of HCWs working in public hospitals in Addis Ababa to infection prevention and control SPs, and factors associated with noncompliance.MethodsIn a hospital-based cross-sectional study, 422 HCWs were recruited from nine public hospitals in Addis Ababa using a stratified random sampling technique. Data were collected using self-administered questionnaires, entered into a computer using Epi data, and analyzed using SPSS version 25. The association between the independent and the outcome variables was investigated using logistic regression. Odd ratios with corresponding 95% confidence intervals (CI) were used as measures of the strength of the association between the outcome and the explanatory variables. Ap-value below 5% was considered an indicator of statistical significance.ResultsThe level of knowledge of HCWs about IPC and SPs was 51.9% and 36.49% of the respondents were compliant with SPs. Receiving IPC Training [Adjusted Odds Ratio (AOR) = 1.81, 95% CI 1.06, 3.09], knowing SPs [AOR = 3.46, 95% CI = 1.83, 6.54], presence of a mechanism in the hospital to enforce the IPC practices [AOR = 1.71 95% CI = 1.01, 2.89], and availability of cleaning and disinfection chemicals in the hospital [AOR = 2.18, 95%CI = 1.15, 4.13] were significantly associated with the HCWs’ compliance with SPs.ConclusionCompliance with IPC standard precautions of HCWs in public hospitals of Addis Ababa is suboptimal. Working in medical units, less work experience, lack of training, poor knowledge, absence of a mechanism to enforce adherence, and inadequate resources are independent predictors for non-compliance of the HCWs.
Effects of a 14-day social media abstinence on mental health and well-being: results from an experimental study
Authors: de Hesselle Lea C. , Montag Christian 
Published: March 2024

Abstract
Background and aim
The study investigated the effects of a 14-day social media abstinence on various mental health factors using an experimental design with follow-up assessment. Hypotheses included positive associations between problematic smartphone use (PSU) and depression, anxiety, fear of missing out (FoMO), and screentime. Decreases in screentime, PSU, depression and anxiety, and increases in body image were assumed for the abstinence group. Additionally, daily changes in FoMO and loneliness were explored.

Methods
Participants completed different questionnaires assessing PSU, FoMO, depression and anxiety, loneliness and body image and were randomized into control and social media abstinence groups. Daily questionnaires over 14 days assessed FoMO, loneliness, screentime, and depression and anxiety. 14 days after the abstinence, a follow-up questionnaire was administered. Multilevel models were used to assess changes over time.

Results
PSU was positively associated with symptoms of depression, anxiety and FoMO, but not with screentime. Spline models identified decreased screentime and body image dissatisfaction for the intervention group. Depression and anxiety symptoms, PSU, trait and state FoMO, and loneliness, showed a decrease during the overall intervention time but no difference between the investigated groups could be observed (hence this was an overall trend). For appearance evaluation and body area satisfaction, an increase in both groups was seen. Daily changes in both loneliness and FoMO were best modelled using cubic trends, but no group differences were significant.

Discussion
Results provide insights into effects of not using social media for 14 days and show that screentime and body image dissatisfaction decrease. The study also suggests areas for future studies to better understand how and why interventions show better results for some individuals.
Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers
Authors: Palard-Novello Xavier , Visser Denise , Tolboom Nelleke , Smith Charlotte L. C. , Zwezerijnen Gerben , van de Giessen Elsmarieke , den Hollander Marijke E. , Barkhof Frederik , Windhorst Albert D. , van Berckel Bart NM , Boellaard Ronald , Yaqub Maqsood 
Published: March 2024

Abstract
Background
Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings.

Methods
Eight [18F]FDG and 10 [18F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system. PET images were reconstructed using various reconstruction settings. IDIFs were taken from ascending aorta (AA), descending aorta (DA), and left ventricular cavity (LV). The calibration factor (CF) extracted from the comparison between the IDIFs and the manual blood samples as reference was used for IDIFs accuracy and precision assessment. To illustrate the effect of various calibrated-IDIFs on Patlak linearization for [18F]FDG and Logan linearization for [18F]DPA-714, the same target time-activity curves were applied for each calibrated-IDIF.

Results
For [18F]FDG, the accuracy and precision of the IDIFs were high (mean CF ≥ 0.82, SD ≤ 0.06). Compared to the striatum influx (Ki) extracted using calibrated AA IDIF with the updated European Association of Nuclear Medicine Research Ltd. standard reconstruction (EARL2), Ki mean differences were < 2% using the other calibrated IDIFs. For [18F]DPA714, high accuracy of the IDIFs was observed (mean CF ≥ 0.86) except using absolute scatter correction, DA and LV (respectively mean CF = 0.68, 0.47 and 0.44). However, the precision of the AA IDIFs was low (SD ≥ 0.10). Compared to the distribution volume (VT) in a frontal region obtained using calibrated continuous arterial sampler input function as reference, VT mean differences were small using calibrated AA IDIFs (for example VT mean difference = -5.3% using EARL2), but higher using calibrated DA and LV IDIFs (respectively + 12.5% and + 19.1%).

Conclusions
For [18F]FDG, IDIF do not need calibration against manual blood samples. For [18F]DPA-714, AA IDIF can replace continuous arterial sampling for simplified kinetic quantification but only with calibration against arterial blood samples. The accuracy and precision of IDIF from LAFOV PET/CT system depend on tracer, reconstruction settings and IDIF VOI locations, warranting careful optimization.
Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis: initial results from the randomized, double-blind, sham-controlled RESET-RA study
Authors: Peterson Daniel , Van Poppel Mark , Boling Warren , Santos Perry , Schwalb Jason , Eisenberg Howard , Mehta Ashesh , Spader Heather , Botros James , Vrionis Frank D. , Ko Andrew , Adelson P. David , Lega Bradley , Konrad Peter , Calle Guillermo , Vale Fernando L. , Bucholz Richard , Richardson R. Mark 
Published: March 2024

Abstract
Background
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes persistent synovitis, bone damage, and progressive joint destruction. Neuroimmune modulation through electrical stimulation of the vagus nerve activates the inflammatory reflex and has been shown to inhibit the production and release of inflammatory cytokines and decrease clinical signs and symptoms in RA. The RESET-RA study was designed to determine the safety and efficacy of an active implantable device for treating RA.

Methods
The RESET-RA study is a randomized, double-blind, sham-controlled, multi-center, two-stage pivotal trial that enrolled patients with moderate-to-severe RA who were incomplete responders or intolerant to at least one biologic or targeted synthetic disease-modifying anti-rheumatic drug. A neuroimmune modulation device (SetPoint Medical, Valencia, CA) was implanted on the left cervical vagus nerve within the carotid sheath in all patients. Following post-surgical clearance, patients were randomly assigned (1:1) to active stimulation or non-active (control) stimulation for 1 min once per day. A predefined blinded interim analysis was performed in patients enrolled in the study’s initial stage (Stage 1) that included demographics, enrollment rates, device implantation rates, and safety of the surgical procedure, device, and stimulation over 12 weeks of treatment.

Results
Sixty patients were implanted during Stage 1 of the study. All device implant procedures were completed without intraoperative complications, infections, or surgical revisions. No unanticipated adverse events were reported during the perioperative period and at the end of 12 weeks of follow-up. No study discontinuations were due to adverse events, and no serious adverse events were related to the device or stimulation. Two serious adverse events were related to the implantation procedure: vocal cord paresis and prolonged hoarseness. These were reported in two patients and are known complications of surgical implantation procedures with vagus nerve stimulation devices. The adverse event of vocal cord paresis resolved after vocal cord augmentation injections with filler and speech therapy. The prolonged hoarseness had improved with speech therapy, but mild hoarseness persists.

Conclusions
The surgical procedures for implantation of the novel neuroimmune modulation device for the treatment of RA were safe, and the device and its use were well tolerated.

Trial registration
NCT04539964; August 31, 2020.
To evaluate the relationship of obstructive sleep apnea with chronic periodontitis and its association with coronary artery disease by assessing serum tumor necrosis factor-α
Authors: Gupta Shilpi , Lal Nand , Ali Wahid , Pradhan Akshyaya , Verma Ajay Kumar , Gupta Prashant , Kumar Neeraj , Singh Balendra Pratap , Sinha Neeraj 
Published: March 2024

AbstractThe periodontal tissue initiates an immune-inflammatory response against bacteria and their products at the site of periodontal infection, and systemic attack by these pathogens triggers an acute phase response that contributes to the systemic inflammatory burden. Obstructive sleep apnea (OSA) and periodontal diseases share many common risk factors and are therefore disorders associated with, and possibly related to, systemic inflammation.Objectives 1.) To evaluate the severity of infection-causing chronic periodontitis subjects leading to Coronary Artery Disease (CAD) risk.2.) To evaluate specific Inflammatory marker TNF-α in coronary artery disease (CAD) subjects with chronic periodontitis and obstructive sleep apnea.Methods A total of 5 ml of the venous blood was collected from each participant which was separated out by centrifugation at 3000 rpm for 5–10 min at room temperature for the estimation of inflammatory markers. Collected samples were labeled and stored at − 20 °C in a deep freezer. The estimation of human TNF-α (tumor necrosis factor-alpha) levels was determined using an ELISA kit based on the Sandwich-ELISA principle.Conclusion TNF-α may serve as important markers for the diagnosis of chronic periodontitis and obstructive sleep apnea and the prediction of the severity of cardiovascular diseases. Cardiovascular disease can be efficiently circumvented with a biomarker-based approach to treatment, which also benefits patients' quality of life.Results The result of our study showed that TNF-α is involved in the onset and progression of obstructive sleep apnea leading to coronary artery disease since the expression levels of TNF in the case group were considerably higher than those in the control group.
Biodistribution of Drug/ADA Complexes: The Impact of Immune Complex Formation on Antibody Distribution
Authors: Opolka-Hoffmann Eugenia , Edelmann Martin R. , Otteneder Michael B. , Hauri Simon , Jordan Gregor , Schrag Peter , Lechmann Martin , Winter Gerhard , Staack Roland F. 
Published: March 2024

AbstractThe clinical use of therapeutic monoclonal antibodies (mAbs) for the treatment of cancer, inflammation, and other indications has been successfully established. A critical aspect of drug-antibody pharmacokinetics is immunogenicity, which triggers an immune response via an anti-drug antibody (ADA) and forms drug/ADA immune complexes (ICs). As a consequence, there may be a reduced efficacy upon neutralization by ADA or an accelerated drug clearance. It is therefore important to understand immunogenicity in biological therapies. A drug-like immunoglobulin G (IgG) was radiolabeled with tritium, and ICs were formed using polyclonal ADA, directed against the complementary-determining region of the drug-IgG, to investigate in vivo biodistribution in rodents. It was demonstrated that 65% of the radioactive IC dose was excreted within the first 24 h, compared with only 6% in the control group who received non-complexed 3H-drug. Autoradiographic imaging at the early time point indicated a deposition of immune complexes in the liver, lung, and spleen indicated by an increased radioactivity signal. A biodistribution study confirmed the results and revealed further insights regarding excretion and plasma profiles. It is assumed that the immune complexes are readily taken up by the reticuloendothelial system. The ICs are degraded proteolytically, and the released radioactively labeled amino acids are redistributed throughout the body. These are mainly renally excreted as indicated by urine measurements or incorporated into protein synthesis. These biodistribution studies using tritium-labeled immune complexes described in this article underline the importance of understanding the immunogenicity induced by therapeutic proteins and the resulting influence on biological behavior.
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Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle
Authors: Jin Chaofan , Yan Kai , Wang Mengya , Song Weihao , Wang Bo , Men Yu , Niu Jingjing , He Yan , Zhang Quanqi , Qi Jie 
Published: March 2024

ABSTRACT
Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages – regressed, regenerating and differentiating – were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.