bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modifiable vascular risk factors contribute to stroke in 1080 NOTCH3 R544C carriers in Taiwan Biobank
Authors: Lin Hung-Jen , Chen Chih-Hao , Su Ming-Wei , Lin Chien-Wei , Cheng Yu-Wen , Tang Sung-Chun , Jeng Jiann-Shing 
Published: July 2023

Background and aim: Previous studies have suggested cardiovascular risk factors increase the risk of not only common sporadic stroke but also of stroke in patients with monogenic stroke disorders including CADASIL. We investigated the effects of the NOTCH3 Arg544Cys (R544C) variant and associated vascular risk factors on stroke in the Taiwanese population. Methods: This study was conducted using data from the Taiwan Biobank, consisting of at least 130,000 Han Chinese participants. The genotype was derived from customized genome-wide arrays for 650,000 to 750,000 single-nucleotide polymorphisms (SNPs). Individuals with NOTCH3 R544C were subsequently matched with noncarriers based on the propensity score at a 1:10 ratio by demographic and cardiovascular risk factors. The odds ratio (OR) for stroke or other phenotypes in NOTCH3 R544C carriers and matched noncarriers was then calculated. Univariate and multivariate regression analyses were performed on cardiovascular risk factors in NOTCH3 R544C carriers with and without stroke. The polygenic risk score (PRS) model, adopted from the UK Biobank, was then applied to evaluate the role of NOTCH3 R544C in stroke. Results: From the 114,282 participants with both genotype and questionnaire results, 1080 (0.95%) harbored the pathogenic NOTCH3 R544C variant. When compared to the matched controls ( n = 10,800), the carriers presented with a history of stroke (OR: 2.52, 95% confidence interval (CI) (1.45, 4.37)), dementia (OR: 30.1, 95% CI (3.13, 289.43)), and sibling history of stroke (OR: 2.48, 95% CI (1.85, 3.34)) phenotypes. The risk of stroke increased with every 10-year increase in age ( p = 0.006, Cochran–Mantel–Haenszel test). Among NOTCH3 R544C carriers, 16 (1.3%) of the 1080 carriers with a stroke history were older, male, and more likely to have hypertension, diabetes, dyslipidemia, and a family history of stroke. In the stepwise multivariate analysis, hypertension (OR: 11.28, 95% CI (3.54, 43.3)) and diabetes mellitus (OR: 4.10, 95% CI (1.31, 12.4)) were independently associated with stroke. Harboring the NOTCH3 R544C variant in the Taiwan Biobank is comparable with a 6.74 standard deviations increase in individual’s polygenic risk score for stroke. Conclusion: While the NOTCH3 R544C variant alone increased the risk of stroke, modifiable vascular risk factors also played a role in the occurrence of stroke in Taiwanese community-dwelling individuals carrying the NOTCH3 variant.
Neuroimaging correlates of post-stroke fatigue: A systematic review and meta-analysis
Authors: Jolly Amy A , Zainurin Adriana , Mead Gillian , Markus Hugh S 
Published: July 2023

Background: Fatigue is a common and disabling symptom following stroke, but its underlying mechanisms are unknown. Associations with a number of imaging features have been proposed. Aims: We aimed to assess whether neuroimaging parameters could better inform our understanding of possible causes of post-stroke fatigue (PSF) through systematic review and meta-analysis. Methods: Using a predefined protocol registered with PROSPERO (ID: CRD42022303168), we searched EMBASE, MEDLINE, PubMed, and PsycInfo for studies assessing PSF and computerized tomography (CT), magnetic resonance (MR), positron emission tomography (PET) imaging, or diffusion tensor imaging (DTI). We extracted neuroimaging parameters and narratively analyzed study results to assess any association with PSF. Where there were 3+ similar studies, we carried out a meta-analysis using inverse-variance random-effects model to estimate the total association of each neuroimaging parameter on PSF. The risk of bias was assessed using the Newcastle and Ottawa Scale. Results: We identified 46 studies ( N = 6543); in many studies, associations with fatigue were secondary or subanalyses (28.3%). Imaging parameters were assessed across eight variables: lesion lateralization, lesion location, lesion volume, brain atrophy, infarct number, cerebral microbleeds, white matter hyperintensities (WMHs), and network measures. Most variables showed no conclusive evidence for any association with fatigue. Meta-analysis, where possible, showed no association of the following with PSF; left lesion lateralization (OR: 0.88, 95% CI (0.64, 1. 22) ( p  = 0.45)), infratentorial lesion location (OR: 1.83, 95% CI (0.63, 5.32) ( p  = 0.27)), and WMH (OR: 1.21, 95% CI (0.84, 1.75) ( p  = 0.29)). Many studies assessed lesion location with mixed findings; only one used voxel-symptom lesion-mapping (VSLM). Some small studies suggested an association between altered functional brain networks, namely frontal, fronto-striato-thalamic, and sensory processing networks, with PSF. Conclusion: There was little evidence for the association between any neuroimaging parameters and PSF. Future studies should utilize advanced imaging techniques to fully understand the role of lesion location in PSF, while the role of altered brain networks in mediating PSF merits further research.
Ill-Fitting Dental Appliances and Oral Cancer: A Systematic Review and Case Report
Authors: Yusuf Cynthia T. , Heron Matthew J. , Girard Alisa O. , Zhu Katherine J. , Lopez Christopher D. , Yang Robin 
Published: July 2023

Background: Associations between the use of dental appliances and oral cancer remain controversial. No studies have reported a relationship between dental appliances in the setting of cleft palate management and oral cancer. This study characterizes the correlation between dental appliances and oral cancer and includes a case report of a patient with a history of cleft palate repair who later developed oral squamous cell carcinoma (OSCC). Methods: We performed a systematic review for studies from 1980 to 2022 of patients who had dental prostheses and who were subsequently diagnosed with OSCC. Variables included the percentage of OSCC cases wearing dental appliances, intraoral cancer location, and noted associations between reported risk factors and OSCC. Results: Of the 6323 patients from the 31 articles analyzed, the most common specified locations for the neoplastic lesion were at the gingiva and lateral border of the tongue. Seventeen studies found an association between OSCC and denture use (54.8%), while 9 studies (29.0%) specifically found a positive association between oral sores and OSCC. Our case patient had complete dental extraction at the age of 12 with subsequent life-long dentures. At age 69, he presented with invasive OSCC. Conclusions: Chronic irritation from ill-fitted dental appliances are associated with oral sores and cancer. This study reports a cleft palate repair patient with lifelong use of dentures who presented with OSCC despite having no known risk factors for oral cancer.
A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials
Authors: Silbert Sara K. , Madan Sanna , Holland Elizabeth M. , Steinberg Seth M. , Little Lauren , Foley Toni , Epstein Monica , Sarkisian Angela , Lee Daniel W. , Nikitina Ekaterina , Kakumanu Showri , Ruppin Eytan , Shalabi Haneen , Yates Bonnie , Shah Nirali N. 
Published: July 2023

Abstract
The tremendous success of chimeric antigen receptor (CAR) T cells in children and young adults (CAYAs) with relapsed/refractory B-cell acute lymphoblastic leukemia is tempered by toxicities such as cytokine release syndrome (CRS). Despite expansive information about CRS, profiling of specific end-organ toxicities secondary to CAR T-cell therapy in CAYAs is limited. This retrospective, single-center study sought to characterize end-organ specific adverse events (AEs) experienced by CAYAs during the first 30 days after CAR T-cell infusion. AEs graded using Common Terminology Criteria for Adverse Events were retrospectively analyzed for 134 patients enrolled in 1 of 3 phase 1 CAR T-cell trials (NCT01593696, NCT02315612, and NCT03448393), targeting CD19 and/or CD22. A total of 133 patients (99.3%) experienced at least 1 grade ≥3 (≥Gr3) AE across 17 organ systems, of which 75 (4.4%) were considered dose- or treatment-limiting toxicities. Excluding cytopenias, 109 patients (81.3%) experienced a median of 3 ≥Gr3 noncytopenia (NC) AEs. The incidence of ≥Gr3 NC AEs was associated with the development and severity of CRS as well as preinfusion disease burden (≥ 25% marrow blasts). Although those with complete remission trended toward experiencing more ≥Gr3 NC AEs than nonresponders (median, 4 vs 3), nonresponders experiencing CRS (n = 17; 37.8%) had the highest degree of NC AEs across all patients (median, 7 vs 4 in responders experiencing CRS). Greater understanding of these toxicities and the ability to predict which patients may experience more toxicities is critical as the array of CAR T-cell therapies expand. This retrospective study was registered at www.clinicaltrials.gov as NCT03827343.
Respiratory infections predominate after day 100 following B-cell maturation antigen–directed CAR T-cell therapy
Authors: Little Jessica S. , Tandon Megha , Hong Joseph Seungpyo , Nadeem Omar , Sperling Adam S. , Raje Noopur , Munshi Nikhil , Frigault Matthew , Barmettler Sara , Hammond Sarah P. 
Published: July 2023

Abstract
Infections are an important complication after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy and risks may differ between the early and late periods. We evaluated infections in 99 adults who received a first BCMA–directed CAR T-cell therapy (commercial and investigational autologous BCMA CAR T-cell products at the recommended phase 2 dose) for relapsed/refractory multiple myeloma between November 2016 and May 2022. Infections were recorded until day 365, if patients experienced symptoms with a microbiologic diagnosis, or for symptomatic site-specific infections treated with antimicrobials. One-year cumulative incidence functions were calculated based on time to first respiratory infection using dates of infection-free death and receipt of additional antineoplastic therapies as competing risks. Secondary analysis evaluated risk factors for late respiratory infections using univariate and multivariable Cox regression models. Thirty-seven patients (37%) experienced 64 infectious events over the first year after BCMA–directed CAR T-cell therapy, with 42 early infectious events (days, 0-100), and 22 late infectious events (days, 101-365). Respiratory infections were the most common site-specific infection and the relative proportion of respiratory infections increased in the late period (31% of early events vs 77% of late events). On multivariable analysis, hypogammaglobulinemia (hazard ratio [HR], 6.06; P = .044) and diagnosis of an early respiratory viral infection (HR, 2.95; P = .048) were independent risk factors for late respiratory infection. Respiratory infections predominate after BCMA CAR T-cell therapy, particularly after day 100. Hypogammaglobulinemia and diagnosis of an early respiratory infection are risk factors for late respiratory infections that may be used to guide targeted preventive strategies.
Linking information on unemployment benefit sanctions from different datasets about welfare receipt: proceedings and research potential
Authors: Schmidtke Julia 
Published: July 2023

AbstractMost studies on benefit sanctions within the German welfare system rely on established datasets about welfare receipt. This paper analyzes how using a dataset from the operational system of the German Federal Employment Agency for processing welfare claims can contribute to further research on benefit sanctions. For this purpose, I use a random sample of welfare recipients with at least one sanction between 2016 and 2018. First, this allows the detailed analysis of time lags between different steps in the sanction process. Second, linking this dataset with established datasets allows the identification of imposed sanctions for which sanction periods could not be (fully) implemented. This is largely explained by individuals leaving the welfare system between sanction events and sanction periods, e.g., by taking up employment. Third, the paper shows differences in benefit cuts across subgroups. This opens up paths for future research.
Identification of key modules and driving genes in nonalcoholic fatty liver disease by weighted gene co-expression network analysis
Authors: Song Zhengmao , Wang Yun , Lin Pingli , Yang Kaichun , Jiang Xilin , Dong Junchen , Xie Shangjin , Rao Rong , Cui Lishan , Liu Feng , Huang Xuefeng 
Published: July 2023

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive liver fat deposition, and progresses to liver cirrhosis, and even hepatocellular carcinoma. However, the invasive diagnosis of NAFLD with histopathological evaluation remains risky. This study investigated potential genes correlated with NAFLD, which may serve as diagnostic biomarkers and even potential treatment targets.

Methods
The weighted gene co-expression network analysis (WGCNA) was constructed based on dataset E-MEXP-3291. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to evaluate the function of genes.

Results
Blue module was positively correlated, and turquoise module negatively correlated with the severity of NAFLD. Furthermore, 8 driving genes (ANXA9, FBXO2, ORAI3, NAGS, C/EBPα, CRYAA, GOLM1, TRIM14) were identified from the overlap of genes in blue module and GSE89632. And another 8 driving genes were identified from the overlap of turquoise module and GSE89632. Among these driving genes, C/EBPα (CCAAT/enhancer binding protein α) was the most notable. By validating the expression of C/EBPα in the liver of NAFLD mice using immunohistochemistry, we discovered a significant upregulation of C/EBPα protein in NAFLD.

Conclusion
we identified two modules and 16 driving genes associated with the progression of NAFLD, and confirmed the protein expression of C/EBPα, which had been paid little attention to in the context of NAFLD, in the present study. Our study will advance the understanding of NAFLD. Moreover, these driving genes may serve as biomarkers and therapeutic targets of NAFLD.
Rare case of exostosin 1/exostosin 2-related membranous lupus nephritis concomitant with dual ANCA- and anti-GBM antibody-associated crescentic glomerulonephritis effectively diagnosed by mass spectrometry: a case report
Authors: Yamazaki Takuya , Takahashi Haruka , Takeuchi Kazuhiro , Sakamoto Emi , Tominaga Kenta , Sakurabayashi Syun , Abe Tetsuya , Sano Takashi , Wada Yukihiro , Kuwahara Naomi , Shimizu Akira , Takeuchi Yasuo 
Published: July 2023

Abstract
Background
Recent developments in mass spectrometry (MS) have revealed target antigens for membranous nephropathy (MN), including phospholipase A2 receptor and exostosin 1/exostosin 2 (EXT1/2). EXT1/2 are known antigens of autoimmune disease-related MN, especially membranous lupus nephritis. We describe the case of an elderly man who developed nephrotic syndrome followed by progressive renal dysfunction.

Case presentation
A 78-year-old man presented with rapidly progressive renal dysfunction with proteinuria and hematuria. Three years previously, he had developed leg edema but did not receive any treatment. Laboratory tests showed elevated anti-nuclear antibody (Ab), anti-dsDNA Ab titer, and hypocomplementemia, indicating systemic lupus erythematous. Myeloperoxidase anti-neutrophil cytoplasmic Ab (ANCA) and anti-glomerular basement membrane (GBM) Ab were also detected. The renal pathologic findings were compatible with crescentic glomerulonephritis (GN), whereas non-crescentic glomeruli exhibited MN without remarkable endocapillary or mesangial proliferative change. Immunofluorescence microscopy revealed glomerular IgG, C3, and C1q deposition. All IgG subclasses were positive in glomeruli. Anti-PLA2R Ab in serum was negative. MS analysis was performed to detect the antigens of MN, and EXT1/2 was detected in glomeruli. Therefore, we reached a diagnosis of membranous lupus nephritis concurrent with both ANCA-associated vasculitis and anti-GBM-GN. The simultaneous occurrence of these three diseases is extremely rare.

Conclusions
This is the first report of EXT1/2-related membranous lupus nephritis concurrent with ANCA-associated vasculitis and anti-GBM-GN. This case demonstrates the usefulness of MS in diagnosing complicated cases of MN.
Antiretroviral therapy non-adherence and its relationship with cognitive impairment, alcohol use disorder, and depression in adolescents living with HIV
Authors: Olashore Anthony A. , Chiliza Bonginkosi , Paruk Saeeda 
Published: July 2023

Abstract
Objective
We aimed to compare antiretroviral non-adherence in the behaviourally infected (BIAs) and congenitally infected adolescents (CIAs) and explore its associations with depression, cognitive impairment, and alcohol use disorder (AUD) in adolescents living with HIV(ALWHIV) in Botswana.

Methods
This study was a cross-sectional, comparative, multi-center research that involved collecting samples from different HIV clinics in Botswana. Of the 622 ALWHIV, 223 were identified as BIAs and 399 as CIAs. They were evaluated using various tools such as MINI-KID for psychiatric disorders, DSM-5 for AUD, CAT-rapid for cognitive assessment, and Visual Analogue Scale (VAS) for non-adherence (the outcome). The data were analysed using both bivariate and multivariate regression analyses.

Results
The participants’ mean age (SD) was 17.7(1.60). The CIAs were more likely to have cognitive impairment (t -7.25; p < 0.01), while the BIAs had more depression (χ2 = 5.86; p = 0.016) and AUD (χ2 = 4.39; p = 0.036) and were more likely to be non-adherent (t = 3.14; p = 0.002). In the CIA group, cognitive impairment (AOR = 2.86; 95% CI:1.77–4.64) (AOR = 2.79; 95%CI:1.73–4.48) and depression (AOR = 2.69; 95%CI:1.48–4.90 were associated with ART non-adherence. In the BIA group, depression (AOR = 2.55; 95%CI:1.27–5.16), AUD (AOR = 2.58; 95%CI:1.21–5.49) and struggling to accept status (AOR = 2.54; 95%CI:1.41–4.56) predicted non-adherence to treatment.

Conclusion
The two groups of adolescents differ regarding ART non-adherence and associated psychosocial issues, indicating the need for differentiated care to address non-adherence in the ALWHIV, especially in high-burden, resource-constrained settings, such as Botswana.
A multi-country survey of the socio-demographic factors associated with adherence to COVID-19 preventive measures during the first wave of the COVID-19 pandemic
Authors: Folayan Morenike Oluwatoyin , Abeldaño Zuñiga Roberto Ariel , Virtanen Jorma I. , Ezechi Oliver C. , Yousaf Muhammad Abrar , Jafer Mohammed , Al-Tammemi Ala’a B. , Ellakany Passent , Ara Eshrat , Ayanore Martin Amogre , Gaffar Balgis , Aly Nourhan M. , Idigbe Ifeoma , Lusher Joanne , El Tantawi Maha , Nguyen Annie L. 
Published: July 2023

Abstract
Background
Health behaviours are influenced by individual characteristics including age, gender, education and economic level. This study aimed to assess the associations between individual-level determinants and adherence to COVID-19 preventive measures.

Methods
We performed secondary analyses of international data collected using an online survey during the first wave of the COVID-19 pandemic between June and December 2020. The dependent variables were self-reported adherence to COVID-19 preventive measures (wearing of face masks, frequent washing/sanitizing of hands, physical distancing, working remotely). The independent variables were age, sex at birth (female vs male), having a chronic disease related elevated risk for severe COVID-19 (none/little, might be at increased risk, at increased risk), educational level completed (no formal education, primary, secondary vs college/university) and employment status (retiree, students, not employed vs employed). Four multivariate logistic regression analyses were conducted to determine the associations between the dependent variables and independent variables. Interaction terms with country-income level were tested in regressions to explore its moderating effect.

Results
Out of 16,866 respondents, 12,634 (74.9%) wore masks or face coverings, 12,336 (73.1%) washed or sanitized their hands frequently, 11,464 (68.0%) reported adherence to physical distancing and 5,646 (33.5%) worked remotely. In adjusted analyses, increased age, college/university education, employment, and having risks for severe COVID-19 were associated with significantly higher odds of adhering to COVID-19 preventive measures. Retirees and students had lower odds of adhering to COVID-19 prevention measures than employed individuals. Males had significantly lower odds of wearing face masks (AOR: 0.901), frequent washing/sanitizing hands (AOR: 0.774) and working remotely (AOR: 0.875) compared to females. Country-income level generally moderated the above relationships such that the associations disappeared in lower income countries.

Conclusion
The study findings suggest that the individual socio-demographic factors—age, sex, employment status, education status and having a chronic disease – influence adherence to COVID-19 preventive measures. Findings further reiterate the need for health education and health promotion campaigns on preventive health measures to focus on subpopulations, such as younger males, students and retirees, that require targeted or unique messaging.
Can locally applied risedronate be an effective agent when combined with xenografts? An animal study
Authors: Özer Taha , Guliyeva Vusala , Aktaş Alper , Barış Emre , Ocak Mert 
Published: July 2023

Abstract
Background
To examine the effects of local risedronate application with xenografts on healing of rabbit skull defects using histological, histomorphometric, immunohistochemical, and three-dimensional radiological methods.

Methods
Two critical-sized defects with a diameter of 10 mm were created in 16 rabbits and filled with xenogenic bone graft and xenogenic bone graft + 5 mg risedronate in the control I and risedronate (RIS) groups, respectively. Residual graft, new bone, soft tissue areas, and bone volume were evaluated in the 4- and 8-week study groups.

Results
In both the 4- and 8-week samples, the RIS group samples had significantly higher mean new bone area values than the C group (p < 0.05). In both groups, the values for the new bone area were significantly higher in the 8-week-old samples than in the 4-week-old samples (p < 0.05). The h scores obtained for sialoprotein and osteopontin did not differ significantly between the groups at either time point (p > 0.05). The results of radiological evaluation showed that the bone density value was significantly higher in the C group than in the RIS group at either time point (p < 0.05).

Conclusions
Although this study aimed to demonstrate the effect of risedronate on the osteoconductive properties of xenografts when applied locally, targeted results could not be achieved.