bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genetic molecular markers and immune infiltration characteristics of Alzheimer's disease through weighted gene co-expression network analysis
Authors: Duan KeFei , Ma Yuan , Tan Jin , Miao Yuyang , Zhang Qiang 
Published: August 2022

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disease that leads to cognitive impairment and memory loss. Currently, the pathogenesis and underlying causative genes of AD remain unclear, and there exists no effective treatment for this disease. This study explored AD-related diagnostic and therapeutic biomarkers from the perspective of immune infiltration by analyzing public data from the NCBI Gene Expression Omnibus database.MethodIn this study, weighted gene co-expression network analysis (WGCNA) was conducted to identify modules and hub genes contributing to AD development. A protein–protein interaction network was constructed when the genes in the modules were enriched and examined by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, a gene network was established using topological WGCNA, from which five hub genes were selected. Logistic regression analysis and receiver operating characteristic curve analysis were performed to explore the clinical value of genes in AD diagnosis. The genes in the core module intersected with the hub genes, and four intersection genes (ATP2A2, ATP6V1D, CAP2, and SYNJ1) were selected. These four genes were enriched by gene set enrichment analysis (GSEA). Finally, an immune infiltration analysis was performed.ResultsThe GO/KEGG analysis suggested that genes in the core module played a role in the differentiation and growth of neural cells and in the transmission of neurotransmitters. The GSEA of core genes showed that these four genes were mainly enriched in immune/infection pathways (e.g., cholera infection and Helicobacter pylori infection pathways) and other metabolic pathways. An investigation of immune infiltration characteristics revealed that activated mast cells, regulatory T cells, plasma cells, neutrophils, T follicular helper cells, CD8 T cells, resting memory CD4 T cells, and M1 macrophages were the core immune cells contributing to AD progression. qRT-PCR analysis showed that the ATP6V1D is upregulated in AD.ConclusionThe results of enrichment and immuno-osmotic analyses indicated that immune pathways and immune cells played an important role in the occurrence and development of AD. The selected key genes were used as biomarkers related to the pathogenesis of AD to further explore the pathways and cells, which provided new perspectives on therapeutic targets in AD.
Normative data for rotational chair considering motion susceptibility
Authors: Yu Jiaodan , Wan Yi , Zhao Jieli , Huang Ruonan , Wu Peixia , Li Wenyan 
Published: August 2022

ObjectiveRotational Chair Test (RCT) is considered one of the most critical measures for vestibular functionality, which generally includes the sinusoidal harmonic acceleration test (SHAT), velocity step test (VST), and visual suppression (VS). The purpose of this study was to establish normal values for different age groups on the RCT and investigate whether motion susceptibility, such as with a history of motion sickness or migraine, has any effects on test metrics.MethodsOne hundred and nine subjects aged from 20 to 59 years who were free from neurotological and vestibular disorders were enrolled. According to the history of motion sickness or migraine, participants were divided into four groups: the motion sickness (MS) group (n = 13), the migraine group (n = 8), comorbidity group (n = 11), and the control group (n = 77). The 77 subjects without any history of MS and migraine were then further separated into four age groups: youth group (20–29 years), young and middle-aged group (30–39 years), middle-age group (40–49 years), and middle-age and elderly group (50–59 years). All participants underwent SHAT, VST, and VS, and a comprehensive set of metrics including gain, phase, asymmetry, time constant (TC), and Fixation Index were recorded.ResultsRegarding the VST and VS, no significant differences were observed either across the four groups (MS, migraine, comorbidity, and control group) or four age categories within the control group. For SHAT, VOR gain at the frequency of 0.01 Hz, VOR phase from 0.08 to 0.64 Hz, and asymmetry at 0.01, 0.16, and 0.64 Hz indicated significant differences among various age groups (P &lt; 0.05 for all comparisons). The VOR phase lead was lower in the migraine and comorbidity group than that in the control group at 0.64 Hz (P = 0.027, P = 0.003, respectively).ConclusionsAge slightly affects the result of SHAT, but not for VST and VS. VOR gain is more susceptible to aging at low frequency, while the phase is opposite. Subjects with both migraine and motion sickness show abnormal velocity storage mechanisms. Phase bias should be considered when assessing motion susceptibility with the RCT. SHAT is more sensitive than VST in terms of reflecting motion susceptibility.
Genetic spectrum and characteristics of autosomal optic neuropathy in Korean: Use of next-generation sequencing in suspected hereditary optic atrophy
Authors: Seo Yuri , Kim Tae Young , Won Dongju , Shin Saeam , Choi Jong Rak , Lee Seung-Tae , Lee Byung Joo , Lim Hyun Taek , Han Sueng-Han , Han Jinu 
Published: August 2022

AimsTo evaluate the clinical characteristics and causative genetic variants in autosomal optic atrophy diagnosed using next-generation sequencing (NGS).MethodsA cohort of 57 unrelated families affected with bilateral optic atrophy were recruited from two university-based tertiary referral hospitals from May 2016 to April 2022. Genetic variants were detected using a target enrichment panel consisting of 429 or 595 genes and known deep intronic variants associated with inherited eye diseases, exome sequencing, or genome sequencing. The results of detailed clinical examinations, disease-causing variants, and clinical diagnoses were analyzed.ResultsAmong the 57 probands, 33 (57.9%) were men, and the median age at genetic testing was 19.1 years (interquartile range, 7.6–42.5 years). We identified 22 likely causative variants in 18 families and corresponding diagnostic yields of 31.6% (95% confidence interval, 21.0–44.5%). The diagnostic rate of NGS was higher in patients with infantile or early childhood onset optic atrophy than in those with late-onset or unknown optic atrophy (18/39, 46.2% vs. 0/18, 0%, P &lt; 0.001). Among the 22 variants, 15 were novel in our cohort. The OPA1 variants (n = 7) were found to be the major genetic causes, followed by the NR2F1 variant (n = 4). The causative variants in PTPN23, TMEM126A, NBAS, and WFS1 genes were identified in 4 probands with a recessive form of optic atrophy.ConclusionsBased on the results of diagnostic NGS for optic atrophy, the causative variant could be detected in 31.6% of patients. Our study also demonstrated that NGS is unlikely to help identify molecular causes in late-onset unexplained optic atrophy.
Coffee and caffeine consumption and risk of renal cell carcinoma: A Mendelian randomization study
Authors: Li Bing-Hui , Yan Si-Yu , Li Xu-Hui , Huang Qiao , Luo Li-Sha , Wang Yun-Yun , Huang Jiao , Jin Ying-Hui , Wang Yong-Bo 
Published: August 2022

BackgroundThe association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.Materials and methodsIn this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of p &lt; 5 × 10–8 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.ResultsThe genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio (OR) per 50% increase of coffee consumption was 0.752 [95% confidence interval (CI), 0.512–1.105; p = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance (p &lt; 5 × 10–8). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled OR = 0.872, 95% CI: 0.676–1.125, p = 0.292).ConclusionOur MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
Sustained effect of habitual feeding time on daily rhythm of core body temperature in mice
Authors: Ando Hitoshi , Nagata Naoto , Hosono Takashi , Hasan Nazmul , Morishige Jun-ichi , Daikoku Takiko , Maida Yoshiko , Ono Masanori , Fujiwara Tomoko , Fujiwara Hiroshi 
Published: August 2022

Background and aimCircadian clocks in most peripheral tissues are entrained mainly by feeding. Therefore, this study aimed to investigate whether the daily rhythm of core body temperature (CBT), including the effect of diet-induced thermogenesis, varies according to habitual feeding time.MethodsWild-type and uncoupling protein 1 (UCP1) knockout mice were fed only during the first 4 h (Breakfast group) or the last 4 h of the dark period (Dinner group) for 17 days. On day 18, both groups were fed twice for 2 h, at the same starting times. Locomotor activity and CBT were measured continuously during the experiment.ResultsOn day 18, CBT increased at the beginning of each feeding period, regardless of the group and strain. However, the CBT increase induced by the first meal decreased sharply in the Breakfast group and mildly in the Dinner group; the opposite was observed after the second meal. In UCP1 knockout, but not wild-type, mice, the total amount of CBT was significantly lower in the Dinner group than in the Breakfast group. These effects were mostly independent of the locomotor activity and food intake.ConclusionThese results reveal that the effect of habitual feeding time on the daily rhythm of CBT is sustained at least until the following day. These effects may be mediated by both UCP1-dependent and -independent mechanisms.
Clinical independent prognostic factors and overall survival prognostic nomogram for intracranial subependymoma: A SEER population-based analysis 2004–2016
Authors: Zhang Zibin , Pang Xiaojun , Wei Yuyu , Lv Qingping , Jin Xuhong , Chen Huai 
Published: August 2022

PurposeThis study was launched to ascertain the independent prognostic factors influencing the overall survival (OS) prognosis of intracranial subependymoma and construct a prognostic model to predict OS time.Materials and methodsWe collected data from patients with intracranial subependymoma, including treatment data, follow-up data, and clinical and pathological characteristics from the SEER database within 2004 to 2016, and patients were randomly classified into training and validation cohorts. Univariate and multivariate analyses were applied to the training group through building a Cox proportional hazards model. According to the results of multivariate analysis, we established a nomogram to forecast the OS rate of the per-case patient graphically, then calculated the accuracy of verification in both training and validation cohorts by concordance index (C-index). Univariate and multivariate analyses were used for different subgroups of unoperated versus operated, gross total resection (GTR), subtotal resection (STR), and biopsy after using the propensity score matching (PSM) analyses.ResultsA total of 667 patients were enrolled, and we randomly assigned 535 patients (80.21%) into the training cohort and 132 patients (19.79%) into the validation cohort. Age [hazard ratio (HR) = 6.355; 95% confidence interval (CI), 2.240–18.029; p = 0.001] and sex (HR = 0.475; 95% CI, 0.232–0.974; p = 0.042) were the independent prognostic factors in the training cohort. On the basis of age and sex, the nomogram was established to predict the OS for every patient (C-index = 0.733 ± 0.065 in the training cohort and 0.850 ± 0.065 in the validation cohort), and calibration plots reflected the reliability of the nomogram. Age, gender, or laterality was the independent prognostic factor for OS in the different matched subgroups of unoperated versus operated, GTR, STR, and biopsy. Surgical treatment, race, year of diagnosis, insurance, tumor location, tumor size, pathology, tumor grade, and radiation were not statistically significantly different in OS for subependymoma in our research.ConclusionAge and sex were the independent prognostic variables for OS in intracranial subependymoma. According to our research, we should not be more inclined to choose conservative or surgical treatment. Nonetheless, the information that we present might be useful to suggest potential hypotheses to be tested in the clinical research setting.
Expression, correlation, and prognostic significance of different nicotinic acetylcholine receptors, programed death ligand 1, and dopamine receptor D2 in lung adenocarcinoma
Authors: Pal Krishnendu , Hussain Tabish , Xie Hao , Li Shenduo , Yang Ping , Mansfield Aaron , Lou Yanyan , Chowdhury Shantanu , Mukhopadhyay Debabrata 
Published: August 2022

ObjectiveThe objective of this study is to evaluate the expression of different nicotinic acetylcholine receptors (nAChRs), programmed death ligand-1 (PD-L1), and dopamine receptor D2 (DRD2) as prognostic factors in lung cancer and any correlation among them. Since all of the above genes are typically upregulated in response to smoking, we hypothesized that a correlation might exist between DRD2, PD-L1, and nAChR expression in NSCLC patients with a smoking history and a prediction model may be developed to assess the clinical outcome.MethodsWe retrospectively analyzed samples from 46 patients with primary lung adenocarcinoma who underwent surgical resection at Mayo Clinic Rochester from June 2000 to October 2008. The expression of PD-L1, DRD2, CHRNA5, CHRNA7, and CHRNA9 were analyzed by quantitative PCR and correlated amongst themselves and with age, stage and grade, smoking status, overall survival (OS), and relapse-free survival (RFS).ResultsOnly PD-L1 showed a statistically significant increase in expression in patients older than 65. All the above genes showed higher expression in stage IIIB than IIIA, but none reached statistical significance. Interestingly, we did not observe significant differences among never, former, and current smokers, but patients with pack years greater than 30 showed significantly higher expression of CHRNA9. We observed a strong positive correlation between PD-L1/DRD2, PD-L1/CHRNA5, and CHRNA5/CHRNA7 and a weak positive correlation between DRD2/CHRNA5 and DRD2/CHRNA7. Older age was independently associated with poor OS, whereas lower CHRNA7 expression was independently associated with better OS.ConclusionsWe observed strong positive correlations among PD-L1, DRD2, and some of the nAChRs. We investigated their prognostic significance in lung cancer patients and found CHRNA7 to be an independent prognostic factor. Overall, the results obtained from this preliminary study warrant a large cohort-based analysis that may ultimately lead to potential patient-specific stratification biomarkers predicting cancer-treatment outcomes.
Local ablation of pulmonary malignancies abutting pleura: Evaluation of midterm local efficacy and safety
Authors: Hu Hong-Tao , Zhao Xiao-Hui , Guo Chen-Yang , Yao Quan-Jun , Geng Xiang , Zhu Wen-Bo , Li Hong-Le , Fan Wei-Jun , Li Hai-Liang 
Published: August 2022

ObjectiveTo retrospectively evaluate the efficacy and safety of local ablation treatment for adjacent pleural lung tumors.Materials and methodsSixty-two patients who underwent pulmonary nodule ablation at the Affiliated Cancer Hospital of Zhengzhou University were enrolled between January 2016 and December 2020. All patients were followed up with enhanced computed tomography or magnetic resonance imaging within 48 h after treatment and 2, 4, 6, 9, and 12 months after treatment. All patients were followed for at least 12 months.ResultsA total of 84 targeted tumors (62 patients) underwent 94 ablations. In the 12-month follow-up images, 69 of the 84 targeted tumors were completely ablated, 15 had incomplete ablation, and the 12-month incomplete ablation rate was 17.8% (15/84). Of the 15 incompletely ablated tumors, six had partial responses, five had stable disease, and four had progressive disease. The most common adverse event was pneumothorax, with an incidence of 54.8% (34/62). The second most common complication was pleural effusion, with an incidence rate of 41.9% (26/62). The incidence of needle-tract bleeding was 21% (13/62) and all patients were cured using hemostatic drugs. Serious complications were bronchopleural fistula in four patients (6.5%, 4/62) and needle tract metastasis in one patient. Four cases of bronchopleural fistula were found in the early stages and were cured after symptomatic treatment.ConclusionLocal ablation is effective for the treatment of adjacent pleural lung tumors, and its operation is safe and controllable.
Designing and validating the Dubai Tool for Developmental Screening (DTDS)
Authors: Alolama Fatma Mohammad , Mohammad Haitham Mahmoud , Alhmid Idris Helal , Alhammadi Hanan Mohammed 
Published: August 2022

BackgroundEarly detection of developmental problems is vital for facilitating early access to targeted intervention and augmenting its beneficial outcomes. Standardized developmental screening tools are known to enhance detection rates of developmental problems compared to clinical judgment alone and are widely recommended to be used in infants and young children. Most of the available developmental screening tools have been developed in Western countries. Many of their items may not be suitable for other cultures while others are expensive. Currently, none of the developmental screening tools have been validated in the United Arab Emirates (UAE), with only a few available in the Arabic language.ObjectiveTo create and validate a developmental screening tool, in both English and Arabic, that is simple, quick to use, and culturally relevant to the United Arab Emirates (UAE) child population aged 9–48 months.MethodsThe available literature was used to create a list of developmental milestones in five domains for children aged 9–48 months, divided into seven age groups. The selected milestones were used to create questionnaires in both English and Arabic, which were pilot tested twice. Each time, the results were analyzed and used to select, modify, and rephrase questions. Validation of the Dubai Tool for Developmental Screening (DTDS) was done against Parents' Evaluation of Developmental Status (PEDS) as a gold standard instrument. The DTDS and PEDS were administered cross-sectionally to parents of 1,400 children in seven age groups. Sensitivity, specificity, and kappa agreement of the DTDS compared with PEDS were calculated.ResultsThe DTDS had a sensitivity of 100% in four age groups and 75–78% in the other three age groups. Specificity ranged from 96 to 99% across all age groups. The kappa measure showed substantial agreement in five age groups, a moderate agreement in one age group, and a fair agreement in one age group.ConclusionsThe DTDS is a valid screening tool for early identification of developmental delays and disabilities in early childhood.
Adverse drug reactions and correlations with drug–drug interactions: A retrospective study of reports from 2011 to 2020
Authors: Jiang Huaqiao , Lin Yanhua , Ren Weifang , Fang Zhonghong , Liu Yujuan , Tan Xiaofang , Lv Xiaoqun , Zhang Ning 
Published: August 2022

Introduction: Adverse drug reactions (ADRs) represent a public health problem worldwide that deserves attention due to the impact on mortality, morbidity, and healthcare costs. Drug–drug interactions (DDIs) are an important contributor to ADRs. Most of the studies focused only on potential DDIs (pDDIs), while the detailed data are limited regarding the ADRs associated with actual DDIs.Methods: This retrospective study evaluated ADRs reported between 2011 and 2020 in a tertiary hospital. The causality and severity of ADRs were evaluated through the Naranjo Algorithm and Hartwig’s scale, respectively. Preventability classification was based on the modified Schoumock and Thornton scale. For ADRs with at least two suspected drugs, pDDIs were identified according to the Lexi-Interact. We further checked whether the ADR description in the reports corresponded to the clinical consequences of the pDDIs.Results: A total of 1,803 ADRs were reported, of which 36.77% ADRs were classified as mild, 43.26% as moderate, and 19.97% as severe. The assessment of causality showed that the distributions of definite, probable, and possible categories were 0.33%, 58.68%, and 40.99%, respectively. A total of 53.97% of ADRs were identified as preventable ADRs, while 46.03% were recognized as unpreventable. The severity of ADRs was significantly correlated with age, the number of suspected drugs and preventability. Antimicrobial agents were the most common implicated pharmacological group, and the most frequently affected system was the gastrointestinal system. Considering individual drugs, aspirin was the most frequently reported drug. Among 573 ADRs with at least two suspected drugs, 105 ADRs were caused by actual DDIs, of which only 59 and 6 ADRs were caused by actual DDIs in category D and X, respectively. The most frequent drugs involved in actual DDIs of category D were aspirin and heparin, with the majority of ADRs being gastrointestinal bleeding.Conclusion: This study analyzed the pattern of ADRs in detail and obtained clinical evidence about ADRs associated with actual DDIs. These findings may be useful to compare patterns between different centers and to design preventive strategies for ADRs. Continuous education and training should be provided for physicians regarding the knowledge and recognition of ADRs associated with DDIs.