bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autosomal recessive variants c.953A>C and c.97-1G>C in NSUN2 causing intellectual disability: a molecular dynamics simulation study of loss-of-function mechanisms
Authors: Muhammad Nazif , Hussain Syeda Iqra , Rehman Zia Ur , Khan Sher Alam , Jan Samin , Khan Niamatullah , Muzammal Muhammad , Abbasi Sumra Wajid , Kakar Naseebullah , Rehman Zia Ur , Khan Muzammil Ahmad , Mirza Muhammad Usman , Muhammad Noor , Khan Saadullah , Wasif Naveed 
Published: May 2023

IntroductionIntellectual disability (ID) is a clinically and genetically heterogeneous disorder. It drastically affects the learning capabilities of patients and eventually reduces their IQ level below 70.MethodsThe current genetic study ascertained two consanguineous Pakistani families suffering from autosomal recessive intellectual developmental disorder-5 (MRT5). We have used exome sequencing followed by Sanger sequencing to identify the disease-causing variants.Results and discussionGenetic analysis using whole exome sequencing in these families identified two novel mutations in the NSUN2 (NM_017755.5). Family-A segregated a novel missense variant c.953A&gt;C; p.Tyr318Ser in exon-9 of the NSUN2. The variant substituted an amino acid Tyr318, highly conserved among different animal species and located in the functional domain of NSUN2 known as “SAM-dependent methyltransferase RsmB/NOP2-type”. Whereas in family B, we identified a novel splice site variant c.97-1G&gt;C that affects the splice acceptor site of NSUN2. The identified splice variant (c.97-1G&gt;C) was predicted to result in the skipping of exon-2, which would lead to a frameshift followed by a premature stop codon (p. His86Profs*16). Furthermore, it could result in the termination of translation and synthesis of dysfunctional protein, most likely leading to nonsense-mediated decay. The dynamic consequences of NSUN2 missense variant was further explored together with wildtype through molecular dynamic simulations, which uncovered the disruption of NSUN2 function due to a gain in structural flexibility. The present molecular genetic study further extends the mutational spectrum of NSUN2 to be involved in ID and its genetic heterogeneity in the Pakistani population.
Can we trust computers to assess the cognition of stroke patients? A systematic review
Authors: Zhang Qi , Wei Jia-Hang , Fu Xue , Liu Xin , Li Xin-Yi , Liu Wei , Liu Zhong-Liang , Duan Xiao-Qin , Zheng Bin 
Published: May 2023

PurposeTo summarize the classification of computerized cognitive assessment (CCA) tools for assessing stroke patients, to clarify their benefits and limitations, and to reveal strategies for future studies on CCA tools.MethodsA literature review was performed using PubMed, Embase, Scopus, JAMA Network, Cochrane Library and PsycINFO databases from January 1st, 2010, to August 1st, 2022. Two authors independently screened the literature following the same criteria, evaluated the study quality, and collected data from the articles.ResultsA total of 8,697 papers were acquired from the six databases. A total of 74 potentially eligible articles were selected for review. Of these, 29 articles were not relevant to this research, 3 were reviews, 2 were not written in English, and 1 was on an ongoing trial. By screening the references of the reviews, 3 additional articles were included in this study. Thus, a total of 42 articles met the criteria for the review. In terms of the CCA tools analyzed in these studies, they included five types: virtual reality (VR)-based, robot-based, telephone-based, smartphone-based, and computer-based cognitive assessments. Patients' stages of the disease ranged from the subacute phase and rehabilitation phase to the community phase. A total of 27 studies supported the effectiveness of CCA tools, while 22 out of 42 articles mentioned their benefits and 32 revealed areas for future improvement of CCA tools.ConclusionsAlthough the use of CCA tools for assessing the cognition of post-stroke patients is becoming popular, there are still some limitations and challenges of using such tools in stroke survivors. More evidence is thus needed to verify the value and specific role of these tools in assessing the cognitive impairment of stroke patients.
The role of brain-localized gamma and alpha oscillations in inattentional deafness: implications for understanding human attention
Authors: Callan Daniel E. , Fukada Takashi , Dehais Frédéric , Ishii Shin 
Published: May 2023

IntroductionThe processes involved in how the attention system selectively focuses on perceptual and motor aspects related to a specific task, while suppressing features of other tasks and/or objects in the environment, are of considerable interest for cognitive neuroscience. The goal of this experiment was to investigate neural processes involved in selective attention and performance under multi-task situations. Several studies have suggested that attention-related gamma-band activity facilitates processing in task-specific modalities, while alpha-band activity inhibits processing in non-task-related modalities. However, investigations into the phenomenon of inattentional deafness/blindness (inability to observe stimuli in non-dominant task when primary task is demanding) have yet to observe gamma-band activity.MethodsThis EEG experiment utilizes an engaging whole-body perceptual motor task while carrying out a secondary auditory detection task to investigate neural correlates of inattentional deafness in natural immersive high workload conditions. Differences between hits and misses on the auditory detection task in the gamma (30–50 Hz) and alpha frequency (8–12 Hz) range were carried out at the cortical source level using LORETA.ResultsParticipant auditory task performance correlated with an increase in gamma-band activity for hits over misses pre- and post-stimulus in left auditory processing regions. Alpha-band activity was greater for misses relative to hits in right auditory processing regions pre- and post-stimulus onset. These results are consistent with the facilitatory/inhibitory role of gamma/alpha-band activity for neural processing. Additional gamma- and alpha-band activity was found in frontal and parietal brain regions which are thought to reflect various attentional monitoring, selection, and switching processes.DiscussionThe results of this study help to elucidate the role of gamma and alpha frequency bands in frontal and modality-specific regions involved with selective attention in multi-task immersive situations.
The association between recreational physical activity and depression in the short sleep population: a cross-sectional study
Authors: You Yanwei , Wei Mengxian , Chen Yuquan , Fu Yingyao , Ablitip Alimjan , Liu Jianxiu , Ma Xindong 
Published: May 2023

BackgroundShort sleep is more common in the modern society. Recreational physical activity (RPA) like exercise brings both mental and physiological benefits to depression; paradoxically, lack of sleep is harmful. Evidence on the association between RPA and depression in the short sleep population is limited.MethodsParticipants with short sleep condition from the National health and Nutrition Examination Surveys (NHANES 2007–2018) were included in the present study. Short sleep condition was defined as ≤ 7 h per night. Sleep duration and RPA status were self-reported in NHANES by the Physical Activity Questionnaire using a 7-day recall method. Multivariable logistic regression was applied to evaluate the association between RPA and depression. Additionally, the non-linear relationship between RPA and depression was evaluated using the threshold effect analysis and restricted cubic spline.ResultsThis cross-sectional study comprised 6,846 adults' data, and the weighted participants were 52,501,159. The weighted prevalence of depression was higher in females, which took up 65.85% of all depression patients. In fully adjusted models, sufficient volume of RPA was associated with lower depression risks, with OR (95% CI) =0.678 (0.520, 0.883). Further analysis revealed a U-shaped association between RPA and incident depression, and the inflection point was 640 MET-minutes/week. When RPA &lt;640 MET-minutes/week, increased RPA was associated with lower risk of incident depression, with OR (95% CI) = 0.891 (0.834, 0.953). When RPA ≥ 640 MET-minutes/week, the benefits of RPA seemed to be not significant, with OR (95% CI) = 0.999 (0.990, 1.009).ConclusionOur findings observed associations between RPA condition and incident depression in the short sleep population. Moderate RPA was beneficial to maintain mental health and associated with lower incidence of depression for short sleepers, but excessive RPA might increase the risk of depression. For general short sleepers, keeping the RPA volume approximately 640 MET-minutes/week was beneficial to lower risks of depression. Gender difference should be considered as an important factor for further studies to examine these relationships and explore mechanisms.
Association and mediating mechanism between remnant cholesterol and first-ever stroke among the Chinese general population
Authors: Li Heng , Miao Shuai , Chen Lu , Liu Bin , Li Yan-Bin , Duan Rui-Sheng 
Published: May 2023

BackgroundRemnant cholesterol (RC) has been suggested to be implicated in atherosclerosis. The objective of the study was to evaluate the association between RC and first-ever stroke in the Chinese general population and to investigate whether the association is mediated via hypertension or diabetes.MethodsThis study is a retrospective cohort analysis of participants from the China Health and Nutrition Survey. Participants without previous stroke and myocardial infarction in 2009 were enrolled and followed up in 2011 and 2015. Logistic regression analyses were adopted to explore the association of RC with stroke risk. Propensity score methods and doubly robust estimation method were used to ensure the robustness of our findings. Potential mediators were identified by mediation analyses.ResultsA total of 7,035 participants were involved, and during 6 years of follow-up, 78 (1.1%) participants experienced a first-ever stroke. Participants with high RC had a significantly higher incidence of stroke (1.4% versus 0.8%; p = 0.007). High RC was associated with 74% higher stroke risk after adjusting for multiple relevant variables (odds ratio [OR], 1.74; 95% CI, 1.06–2.85). The association was consistent in analyses using propensity score methods and doubly robust estimation method. Hypertension showed a significant mediating effect on the association between RC and stroke, while the mediating effect of diabetes was not significant.ConclusionHigh RC increased the risk of first-ever stroke in the Chinese general population without previous stroke and myocardial infarction, partially through the pathway of hypertension. RC might be a potential target for the primary prevention of stroke.
Characteristics of large vestibular aqueduct syndrome in wideband acoustic immittance
Authors: Li Ao , Du Haoliang , Gao Junyan , Xu Yuqin , Zhao Ning , Gao Song , Xing Yuxuan , Qian Xiaoyun , Gao Xia , Yang Ye 
Published: May 2023

ObjectiveTo describe the characteristics of large vestibular aqueduct syndrome (LVAS) in wideband acoustic immittance (WAI) and to explore whether inner ear deformity has an impact on WAI results.MethodsSubjects with typical LVAS (LVAS group) and control subjects with a normal anatomical structure of the inner ear (control group) were screened from pediatric patients with cochlear implants using thin-slice computed tomography (CT) images of the temporal bone. With inflammation of the auditory canal and middle ear excluded by routine ear examination and 226 Hz acoustic immittance, WAI data were acquired. Then, the maximum absorbance as the major observation indicator on the mean tympanogram was compared between the LVAS group and control group, and a descriptive comparison of the mean tympanogram and frequency-absorbance curve at peak pressure was performed between the two groups.ResultsThe LVAS group included 21 cases (38 ears), and the control group included 27 cases (45 ears). All LVAS subjects met the Valvassori criteria, and the VA at the horizontal semicircular canal displayed flared expansion. On the mean tympanogram, the maximum absorbance in the LVAS group (0.542 ± 0.087) was significantly higher than that in the control group (0.455 ± 0.087) (p &lt; 0.001). The tympanogram in the LVAS group showed an overall elevation, and the absorbance at all pressure sampling points was significantly higher than that in the control group (p &lt; 0.001). The frequency-absorbance curve at peak pressure first increased and then decreased in both groups, and the LVAS group showed higher absorbance than the control group in the frequency range below 2,828 Hz. The absorbance at 343–1,124 Hz was significantly different between the two groups (p &lt; 0.001), and 343–1,124 Hz was the major frequency range at which the maximum absorbance on the mean tympanogram increased in the LVAS group.ConclusionLarge vestibular aqueduct syndrome (LVAS) shows increased absorbance in low and medium frequency ranges in WAI. The maximum absorbance on the mean tympanogram can serve as a reliable evaluation indicator. Inner ear factors must be considered when middle ear lesions are analyzed by WAI.
Mitochondrial DNA methylation in metabolic associated fatty liver disease
Authors: Mposhi Archibold , Cortés-Mancera Fabian , Heegsma Janette , de Meijer Vincent E. , van de Sluis Bart , Sydor Svenja , Bechmann Lars P. , Theys Claudia , de Rijk Peter , De Pooter Tim , Vanden Berghe Wim , İnce İkbal Agah , Faber Klaas Nico , Rots Marianne G. 
Published: May 2023

IntroductionHepatic lipid accumulation and mitochondrial dysfunction are hallmarks of metabolic associated fatty liver disease (MAFLD), yet molecular parameters underlying MAFLD progression are not well understood. Differential methylation within the mitochondrial DNA (mtDNA) has been suggested to be associated with dysfunctional mitochondria, also during progression to Metabolic Steatohepatitis (MeSH). This study further investigates whether mtDNA methylation is associated with hepatic lipid accumulation and MAFLD.MethodsHepG2 cells were constructed to stably express mitochondria-targeted viral and prokaryotic cytosine DNA methyltransferases (mtM.CviPI or mtM.SssI for GpC or CpG methylation, respectively). A catalytically inactive variant (mtM.CviPI-Mut) was constructed as a control. Mouse and human patients’ samples were also investigated. mtDNA methylation was assessed by pyro- or nanopore sequencing.Results and discussionDifferentially induced mtDNA hypermethylation impaired mitochondrial gene expression and metabolic activity in HepG2-mtM.CviPI and HepG2-mtM.SssI cells and was associated with increased lipid accumulation, when compared to the controls. To test whether lipid accumulation causes mtDNA methylation, HepG2 cells were subjected to 1 or 2 weeks of fatty acid treatment, but no clear differences in mtDNA methylation were detected. In contrast, hepatic Nd6 mitochondrial gene body cytosine methylation and Nd6 gene expression were increased in mice fed a high-fat high cholesterol diet (HFC for 6 or 20 weeks), when compared to controls, while mtDNA content was unchanged. For patients with simple steatosis, a higher ND6 methylation was confirmed using Methylation Specific PCR, but no additional distinctive cytosines could be identified using pyrosequencing. This study warrants further investigation into a role for mtDNA methylation in promoting mitochondrial dysfunction and impaired lipid metabolism in MAFLD.
Preoperative prediction of VETC in hepatocellular carcinoma using non-Gaussian diffusion-weighted imaging at high b values: a pilot study
Authors: Li Chenhui , Wen Yan , Xie Jinhuan , Chen Qianjuan , Dang Yiwu , Zhang Huiting , Guo Hu , Long Liling 
Published: May 2023

BackgroundVessels encapsulating tumor clusters (VETC) have been considered an important cause of hepatocellular carcinoma (HCC) metastasis.PurposeTo compare the potential of various diffusion parameters derived from the monoexponential model and four non-Gaussian models (DKI, SEM, FROC, and CTRW) in preoperatively predicting the VETC of HCC.Methods86 HCC patients (40 VETC-positive and 46 VETC-negative) were prospectively enrolled. Diffusion-weighted images were acquired using six b-values (range from 0 to 3000 s/mm2). Various diffusion parameters derived from diffusion kurtosis (DK), stretched-exponential (SE), fractional-order calculus (FROC), and continuous-time random walk (CTRW) models, together with the conventional apparent diffusion coefficient (ADC) derived from the monoexponential model were calculated. All parameters were compared between VETC-positive and VETC-negative groups using an independent sample t-test or Mann-Whitney U test, and then the parameters with significant differences between the two groups were combined to establish a predictive model by binary logistic regression. Receiver operating characteristic (ROC) analyses were used to assess diagnostic performance.ResultsAmong all studied diffusion parameters, only DKI_K and CTRW_α significantly differed between groups (P=0.002 and 0.004, respectively). For predicting the presence of VETC in HCC patients, the combination of DKI_K and CTRW_α had the larger area under the ROC curve (AUC) than the two parameters individually (AUC=0.747 vs. 0.678 and 0.672, respectively).ConclusionDKI_K and CTRW_α outperformed traditional ADC for predicting the VETC of HCC.
Indolyl-chalcone derivatives trigger apoptosis in cisplatin-resistant mesothelioma cells through aberrant tubulin polymerization and deregulation of microtubule-associated proteins
Authors: Steinlein Sophia , Essmann Frank , Ghilardi Amanda Franceschini , Horn Heike , Schüler Julia , Hausser Angelika , Sun Lijun , Ott German , Kalla Claudia 
Published: May 2023

IntroductionMalignant pleural mesothelioma (MPM) is a neoplasm with dismal prognosis and notorious resistance to the standard therapeutics cisplatin and pemetrexed. Chalcone derivatives are efficacious anti-cancer agents with minimal toxicity and have, therefore, gained pharmaceutical interest. Here, we investigated the efficacy of CIT-026 and CIT-223, two indolyl-chalcones (CITs), to inhibit growth and viability of MPM cells and defined the mechanism by which the compounds induce cell death.MethodsThe effects of CIT-026 and CIT-223 were analyzed in five MPM cell lines, using viability, immunofluorescence, real-time cell death monitoring, and tubulin polymerization assays, along with siRNA knockdown. Phospho-kinase arrays and immunoblotting were used to identify signaling molecules that contribute to cell death.ResultsCIT-026 and CIT-223 were toxic in all cell lines at sub-micromolar concentrations, in particular in MPM cells resistant to cisplatin and pemetrexed, while normal fibroblasts were only modestly affected. Both CITs targeted tubulin polymerization via (1) direct interaction with tubulin and (2) phosphorylation of microtubule regulators STMN1, CRMP2 and WNK1. Formation of aberrant tubulin fibers caused abnormal spindle morphology, mitotic arrest and apoptosis. CIT activity was not reduced in CRMP2-negative and STMN1-silenced MPM cells, indicating that direct tubulin targeting is sufficient for toxic effects of CITs.DiscussionCIT-026 and CIT-223 are highly effective inducers of tumor cell apoptosis by disrupting microtubule assembly, with only modest effects on non-malignant cells. CITs are potent anti-tumor agents against MPM cells, in particular cells resistant to standard therapeutics, and thus warrant further evaluation as potential small-molecule therapeutics in MPM.
The relationship between women’s body mass index and breast cancer outcomes was U-shaped
Authors: Wei Wensong , Wei Suosu , Huang Zhen , Zhang Qiuhuan , Liu Fei , Xie Yujie , Wei Jing , Mo Chongde , Zhou Ying , Qin Shengpeng , Zou Quanqing , Yang Jianrong 
Published: May 2023

BackgroundSeveral studies have analyzed the relationship between body mass index (BMI) and the prognosis of breast cancer (BC). However, whether their relationship is linear or curvilinear remains unclear. This cohort study examined the specific relationship between BMI and BC outcomes.MethodsThis retrospective cohort study included 1049 BC patients from March 7, 2013 through December 31, 2019 in a hospital. Kaplan-Meier curves, multivariate Cox proportional models, and restricted cubic spline (RCS) was used to analysis the relationship between BMI and overall survival (OS) and breast cancer-specific survival (BCSS) was analyzed.ResultsDuring a median of 4.87 (IQR:3.26-6.84) years of follow-up period, 71 patients (6.77%) died, of which 50 (70.42%) were attributed to BC. RCS analysis revealed a U- shaped relationship between BMI levels and OS and BCSS after adjusting for other variables. The turning points of the U-shaped curves were 23 kg/m2. On the left side of the turning point, the risk of OS (HR, 0.83; 95% CI, 0.70, 0.98) and BCSS (HR, 0.80; 95% CI, 0.65, 0.98) were adversely correlated with BMI. In contrast, to the right of the turning point, the risk of OS (HR, 1.22; 95% CI, 1.10, 1.37) and BCSS (HR, 1.28; 95% CI, 1.13, 1.46) was positively related to BMI. Kaplan-Meier curves and multivariate Cox regression analyses shown consistent results with RCS analyses.ConclusionBMI was an independent prognostic factor for BC, and had a U-shaped relationship with OS and BCSS. Interventions should be designed to improve patient outcomes based on BMI.
A systematic review of in utero cannabis exposure and risk for structural birth defects
Authors: Sujan Ayesha C. , Pal Anish , Avalos Lyndsay A. , Young-Wolff Kelly C. 
Published: May 2023

IntroductionCannabis use among pregnant women has increased over time. Therefore, there is a great public health need to understand the consequences of in utero cannabis exposure. While several meta-analyses and reviews have summarized the evidence of in utero cannabis exposure on adverse obstetric outcomes (e.g., low birth weight and preterm birth) and long-term offspring development, there has not been a focus on in utero cannabis exposure and risk for structural birth defects.MethodsWe conducted a systematic review using PRISMA guidelines to evaluate the association between in utero cannabis exposure and structural birth defects.ResultsWe identified 20 articles to include in our review and focused on interpreting findings from the 12 that adjusted for potential confounders. We report findings by seven organ systems. Within the 12 articles, four reported on cardiac malformations, three reported on central nervous system malformations, one reported on eye malformations, three reported on gastrointestinal malformations, one reported on genitourinary malformations, one reported on musculoskeletal malformations, and two reported on orofacial malformations.DiscussionFindings on associations between in utero cannabis exposure and birth defects reported in more than two articles were mixed (i.e., findings for cardiac, gastrointestinal, central nervous system malformations). Findings for associations between in utero cannabis exposure and birth defects reported in two articles (i.e., orofacial malformations) or in a single article (eye, genitourinary, and musculoskeletal) suggested that cannabis exposure was not associated with these types of malformations, but strong conclusions cannot be drawn from such sparce research. We review the limitations and gaps in the existing literature and call for more research to rigorously evaluate associations between in utero cannabis exposure and structural birth defects.Systematic Review Registrationidentifier CRD42022308130.