bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between C-Reactive Protein and Risk of Amyotrophic Lateral Sclerosis: A Mendelian Randomization Study
Authors: Zhu Yahui , Li Mao , Zhang Jinghong , Huang Xusheng 
Published: May 2022

Background: Until now, the relationship between C-reactive protein (CRP) levels and amyotrophic lateral sclerosis (ALS) risk has not been fully established. It is necessary to assess whether there is a causal relationship between C-reactive protein levels and ALS risk.Objective and Methods: We aimed to determine whether CRP has causal effects on risk of ALS. In this present study, summary-level data for ALS (20,806 cases and 59,804 controls) was obtained from large analyses of genome-wide association studies. For instrumental variables, 37 single nucleotide polymorphisms that had been previously identified to be related to CRP levels were used, including 4 SNPs of conservative CRP genetic variants and 33 SNPs of liberal CRP genetic variants. MR estimates were calculated using the inverse-variance weighted method, supplemented by MR-Egger, weighted median, and MR-PRESSO methods.Results: There was no significant causal relationship between genetically predicted CRP levels and ALS risk (OR = 1.123, 95% CI = 0.963–1.309, p = 0.139) and results for the conservative CRP instruments were consistent (OR = 0.964, 95% CI = 0.830–1.119, p = 0.628). Pleiotropic bias was not observed in this study.Conclusions: This study suggests that genetically predicted CRP levels may not be a causal risk factor for ALS.
PD-L1 Protein Expression Is Associated With Good Clinical Outcomes and Nomogram for Prediction of Disease Free Survival and Overall Survival in Breast Cancer Patients Received Neoadjuvant Chemotherapy
Authors: Chen Li , Huang Shaolong , Liu Qiang , Kong Xiangyi , Su Zhaohui , Zhu Mengliu , Fang Yi , Zhang Lin , Li Xingrui , Wang Jing 
Published: May 2022

ObjectiveThis study aims to investigate the potential prognostic significance of programmed death ligand-1 (PD-L1) protein expression in tumor cells of breast cancer patients received neoadjuvant chemotherapy (NACT).MethodsUsing semiquantitative immunohistochemistry, the PD-L1 protein expression in breast cancer tissues was analyzed. The correlations between PD-L1 protein expression and clinicopathologic characteristics were analyzed using Chi-square test or Fisher’s exact test. The survival curve was stemmed from Kaplan-Meier assay, and the log-rank test was used to compare survival distributions against individual index levels. Univariate and multivariate Cox proportional hazards regression models were accessed to analyze the associations between PD-L1 protein expression and survival outcomes. A predictive nomogram model was constructed in accordance with the results of multivariate Cox model. Calibration analyses and decision curve analyses (DCA) were performed for the calibration of the nomogram model, and subsequently adopted to assess the accuracy and benefits of the nomogram model.ResultsA total of 104 breast cancer patients received NACT were enrolled into this study. According to semiquantitative scoring for IHC, patients were divided into: low PD-L1 group (61 cases) and high PD-L1 group (43 cases). Patients with high PD-L1 protein expression were associated with longer disease free survival (DFS) (mean: 48.21 months vs. 31.16 months; P=0.011) and overall survival (OS) (mean: 83.18 months vs. 63.31 months; P=0.019) than those with low PD-L1 protein expression. Univariate and multivariate analyses indicated that PD-L1, duration of neoadjuvant therapy, E-Cadherin, targeted therapy were the independent prognostic factors for patients’ DFS and OS. Nomogram based on these independent prognostic factors was used to evaluate the DFS and OS time. The calibration plots shown PD-L1 based nomogram predictions were basically consistent with actual observations for assessments of 1-, 3-, and 5-year DFS and OS time. The DCA curves indicated the PD-L1 based nomogram had better predictive clinical applications regarding prognostic assessments of 3- and 5-year DFS and OS, respectively.ConclusionHigh PD-L1 protein expression was associated with significantly better prognoses and longer DFS and OS in breast cancer patients. Furthermore, PD-L1 protein expression was found to be a significant prognostic factor for patients who received NACT.
Factors Associated With Neurosyphilis in Patients With Syphilis Treatment Failure: A Retrospective Study of 165 HIV-Negative Patients
Authors: Cui Wenying , Yan Junling , Weng Wenjia , Gao Yanqing , Zhu Wei 
Published: May 2022

BackgroundIn recent years, the incidence of syphilis has increased year by year. Our study is to explore the risk factors for the development of neurosyphilis in patients who failed syphilis treatment.MethodsA total number of 165 patients with complete medical records and who agreed to undergo lumbar puncture were divided into 47 neurosyphilis cases and 118 non-neurosyphilis cases according to the diagnostic criteria of neurosyphilis, and the differences in clinical characteristics and laboratory features between the two groups were analyzed. Significant variables were entered into multivariable logistic regression models.Results(1) There were statistical differences (p &lt; 0.05) between the neurosyphilis (NS) group and the non-neurosyphilis (NNS) group in terms of the higher proportion of male and serum rapid plasma reagin (RPR) &gt; 1:32 and the elevated cerebrospinal fluid white blood cell (CSF WBC) and CSF protein in the neurosyphilis group compared with the non-neurosyphilis group. (2) Male gender, serum RPR titers &gt;1:32 at lumbar puncture, CSF WBC &gt;8 × 106/L were significantly associated with neurosyphilis.ConclusionFor patients who have failed syphilis treatment, lumbar puncture should be performed to exclude neurosyphilis, to enable early diagnosis and treatment, and to prevent irreversible damage of neurosyphilis, especially if the patient is male and has a serum RPR&gt;1:32 and elevated CSF WBC at lumbar puncture, which are risk factors for neurosyphilis.
Inhaled CO2 vs. Hypercapnia Obtained by Low Tidal Volume or Instrumental Dead Space in Unilateral Pulmonary Artery Ligation: Any Difference for Lung Protection?
Authors: Spinelli Elena , Pesenti Antonio , Lopez Gianluca , Damia Anna , Damarco Francesco , Garbelli Erica , Dal Santo Gaia , Caccioppola Alessio , Giudici Giorgio , Figgiaconi Virginia , Biancolilli Osvaldo , Battistin Michele , Lonati Caterina , Vaira Valentina , Rosso Lorenzo , Ferrero Stefano , Gatti Stefano , Mauri Tommaso 
Published: May 2022

BackgroundUnilateral ligation of the pulmonary artery (UPAL) induces bilateral lung injury in pigs undergoing controlled mechanical ventilation. Possible mechanisms include redistribution of ventilation toward the non-ligated lung and hypoperfusion of the ligated lung. The addition of 5% CO2 to the inspiratory gas (FiCO2) prevents the injury, but it is not clear whether lung protection is a direct effect of CO2 inhalation or it is mediated by plasmatic hypercapnia. This study aims to compare the effects and mechanisms of FiCO2vs. hypercapnia induced by low tidal volume ventilation or instrumental dead space.MethodsHealthy pigs underwent left UPAL and were allocated for 48 h to the following: Volume-controlled ventilation (VCV) with VT 10 ml/kg (injury, n = 6); VCV plus 5% FiCO2 (FiCO2, n = 7); VCV with VT 6 ml/kg (low VT, n = 6); VCV plus additional circuit dead space (instrumental VD, n = 6). Histological score, regional compliance, wet-to-dry ratio, and inflammatory infiltrate were assessed to evaluate lung injury at the end of the study. To investigate the mechanisms of protection, we quantified the redistribution of ventilation to the non-ligated lung, as the ratio between the percentage of tidal volume to the right and to the left lung (VTRIGHT/LEFT), and the hypoperfusion of the ligated lung as the percentage of blood flow reaching the left lung (PerfusionLEFT).ResultsIn the left ligated lung, injury was prevented only in the FiCO2 group, as indicated by lower histological score, higher regional compliance, lower wet-to-dry ratio and lower density of inflammatory cells compared to other groups. For the right lung, the histological score was lower both in the FiCO2 and in the low VT groups, but the other measures of injury showed lower intensity only in the FiCO2 group. VTRIGHT/LEFT was lower and PerfusionLEFT was higher in the FiCO2 group compared to other groups.ConclusionIn a model of UPAL, inhaled CO2 but not hypercapnia grants bilateral lung protection. Mechanisms of protection include reduced overdistension of the non-ligated and increased perfusion of the ligated lung.
Identification of a Diagnostic Signature and Immune Cell Infiltration Characteristics in Keloids
Authors: Xia Yijun , Wang Youbin , Xiao Yingjie , Shan Mengjie , Hao Yan , Zhang Lingyun 
Published: May 2022

Background: Keloid disorder is a recurrent fibroproliferative cutaneous tumor. Due to the lack of early identification of keloid patients before the formation of keloids, it is impossible to carry out pre-traumatic intervention and prevention for these patients. This led us to identify and determine signatures with diagnostic significance for keloids.Methods: Public series of matrix files were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were calculated from expression profiling data, and the diagnostic signature was identified by constructing a protein-protein interaction (PPI) network. The diagnostic efficacy of the screened signature was assessed by employing receiver operating characteristic (ROC) curves. Furthermore, we calculated the proportion of different immune cells in the gene expression matrix microenvironment by the “ssGSEA” algorithm, and assessed the difference in immune cell abundance between keloids and control groups and the relationship between the signature and immune cell infiltration. Clinical keloid and normal skin tissues were collected, and the expression of the screened diagnostic signature was validated by RT-qPCR and immunohistochemical assay.Results: By screening the key genes in PPI, TGM2 was recognized and validated as a diagnostic signature and the infiltrating abundance of 10 immune cells was significantly correlated with TGM2 expression. Gene ontology enrichment analysis demonstrated that TGM2 and molecules interacting with it were mainly enriched in processes involving wound healing and collagen fiber organization. TGM2 correlated positively with HIF-1A (R = 0.82, p-value = 1.4e-05), IL6 (R = 0.62, p-value = 0.0053), and FN1 (R = 0.66, p-value = 0.0019). Besides, TGM2 was significantly upregulated in clinical keloid samples compared to normal skin tissues.Conclusion: TGM2 may serve as an auxiliary diagnostic indicator for keloids. However, the role of TGM2 in keloids has not been adequately reported in the current literature, which may provide a new direction for molecular studies of keloids.
Tap Test Can Predict Cognitive Improvement in Patients With iNPH—Results From the Multicenter Prospective Studies SINPHONI-1 and –2
Authors: Nakajima Madoka , Yamada Shigeki , Miyajima Masakazu , Kawamura Kaito , Akiba Chihiro , Kazui Hiroaki , Mori Etsuro , Ishikawa Masatsune ,   The SINPHONI-2 Investigators
Published: May 2022

Background: We analyzed the predictive value of the tap test (TT) on the outcome of cerebrospinal fluid (CSF) shunting in patients with idiopathic normal pressure hydrocephalus (iNPH) and cognitive impairment up to 12 months postoperatively.Methods: We analyzed the data of two prospective multicenter studies on ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) use in iNPH patients. We selected patients with Mini-Mental State Examination (MMSE) scores ≤ 26 points as study subjects. We used a multivariate logistic regression model to obtain the optimal threshold of MMSE scores after TT to predict the score improvement at 12 months following shunting and that helped to control for confounding factors such as age and MMSE scores before TT. We used logistic regression models to identify variables with age-adjusted odds ratio (A-OR) and multivariate-adjusted OR (M-OR).Results: For an improvement of ≥3 points in the MMSE score cutoff 7 days following TT in VPS and LPS cohort studies, the MMSE scores improved by 6 points after 12 months. The VPS cohort had sensitivity, specificity, and area under the curve (AUC) of 69.2, 73.7, and 0.771%, respectively; however, for the LPS cohort, they were 86.2, 90.9, and 0.906%, respectively. For MMSE scores that improved by ≥3 points in patients after the TT, the possibility of an improvement by 6 points at 12 months following CSF shunt had A-OR 7.77 and M-OR 6.3 times for the VPS, and A-OR 62.3 and M-OR 59.6 times for the LPS cohort.Conclusion: CSF shunting contributes to improved cognitive function in iNPH patients. Furthermore, MMSE score evaluation at the TT can sensitively predict improvement in postoperative MMSE scores following LPS intervention.Clinical Trial Registration: SINPHONI-1 (ClinicalTrials.gov, no. NCT00221091), first posted: September 22, 2005.SINPHONI-2 [University Hospital Medical Information Network (UMIN) Clinical Trials no. UMIN000002730], the posted: February 1, 2010.
Neutrophil-to-Lymphocyte Ratio Is Associated With Circumferential Wall Enhancement of Unruptured Intracranial Aneurysm
Authors: Wu Xiao-Bing , Zhong Jing-Lian , Wang Sheng-Wen , Su Yun , Chen Pei-Sheng , Li Zhong-Jun , Xiang Chun , Cai Wang-Qing , Shi Zhong-Song 
Published: May 2022

Background and PurposeNeutrophil-lymphocyte ratio (NLR) predicts clinical outcomes in patients with stroke. Aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) is an inflammation marker for intracranial aneurysm (IA). This study aims to evaluate the association of NLR as a peripheral blood inflammatory marker with circumferential AWE in patients with IA.MethodsWe analyzed data of consecutive patients harboring IAs between September 2017 and December 2021 at our institution. The peripheral blood inflammatory indicators were compared between patients with ruptured and unruptured IAs. The presence of circumferential AWE in unruptured IA was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) on HR-VWI. We used the optimal cutoff value of 0.5 for CRstalk to differentiate circumferential AWE in unruptured IAs. We assessed the relationship of clinical, laboratory, and radiological characteristics with circumferential AWE and CRstalk ≥0.5 in unruptured IAs.ResultsThe study group was composed of one hundred and twenty-five patients with 142 IAs. NLR level at admission was significantly higher in patients with ruptured IAs than those with unruptured IAs (7.55 vs. 1.81; P &lt; 0.001). AWE on HR-VWI was present in 30 patients with unruptured IAs (38.5%), including 12 with focal AWE and 18 with circumferential AWE. NLR (odds ratio (OR), 2.168; 95% CI, 1.149–4.088) and size (odds ratio, 1.370; 95% CI, 1.126–1.667) were independently associated with circumferential AWE in unruptured IA. NLR was also independently associated with circumferential AWE in small unruptured IA (&lt;7 mm). Furthermore, NLR level at admission was associated with CRstalk ≥.5 in patients with unruptured IA. The optimal cutoff value of NLR for circumferential AWE was 1.86.ConclusionNLR is a valuable peripheral blood inflammatory marker is more often in the rupture status of IA and was associated with circumferential AWE on HR-VWI in unruptured IA.
Multiomics Data Analysis and Identification of Immune-Related Prognostic Signatures With Potential Implications in Prognosis and Immune Checkpoint Blockade Therapy of Glioblastoma
Authors: Ma Shuai , Wang Fang , Wang Nan , Jin Jiaqi , Ba Yixu , Ji Hang , Du Jianyang , Hu Shaoshan 
Published: May 2022

BackgroundIn recent years, glioblastoma multiforme (GBM) has been a concern of many researchers, as it is one of the main drivers of cancer-related deaths worldwide. GBM in general usually does not responding well to immunotherapy due to its unique microenvironment.MethodsTo uncover any further informative immune-related prognostic signatures, we explored the immune-related distinction in the genetic or epigenetic features of the three types (expression profile, somatic mutation, and DNA methylation). Twenty eight immune-related hub genes were identified by Weighted Gene Co-Expression Network Analysis (WGCNA). The findings showed that three genes (IL1R1, TNFSF12, and VDR) were identified to construct an immune-related prognostic model (IRPM) by lasso regression. Then, we used three hub genes to construct an IRPM for GBM and clarify the immunity, mutation, and methylation characteristics.ResultsSurvival analysis of patients undergoing anti-program cell death protein 1 (anti-PD-1) therapy showed that overall survival was superior in the low-risk group than in the high-risk group. The high-risk group had an association with epithelial-mesenchymal transition (EMT), high immune cell infiltration, immune activation, a low mutation number, and high methylation, while the low-risk group was adverse status.ConclusionsIn conclusion, IRPM is a promising tool to distinguish the prognosis of patients and molecular and immune characteristics in GBM, and the IRPM risk score can be used to predict patient sensitivity to checkpoint inhibitor blockade therapy. Thus, three immune-related signatures will guide us in improving treatment strategies and developing objective diagnostic tools.
Models of Care in Multiple Sclerosis: A Survey of Canadian Health Providers
Authors: Marrie Ruth Ann , Donkers Sarah J. , Jichici Draga , Hrebicek Olinka , Metz Luanne , Morrow Sarah A. , Oh Jiwon , Pétrin Julie , Smyth Penelope , Devonshire Virginia 
Published: May 2022

ObjectiveLittle work has evaluated integrated models of care in multiple sclerosis (MS) and the composition of MS care teams across Canada is largely unknown. We aimed to gather information regarding existing models of MS care across Canada, and to assess the perceptions of health care providers (HCPs) regarding the models of care required to fully meet the needs of the person with MS.MethodsWe conducted an anonymous online survey targeting Canadian HCPs working in MS Clinics, and neurologists delivering MS care whether or not they were based in an MS Clinic. We queried the types of HCPs delivering care within formal MS Clinics, wait times for HCPs, the perceived importance of different types of HCPs for good quality care, assessments conducted, and whether clinic databases were used. We summarized survey responses using descriptive statistics.ResultsOf the 716 HCPs to whom the survey was distributed, 100 (13.9%) people responded. Of the 100 respondents, 85 (85%) indicated that their clinical practice included people with MS and responded to specific questions about clinical care. The most common types of providers within MS Clinics with integrated models of care were neurologists and MS nurses. Of 23 responding MS Clinics, 10 (43.5%) indicated that there were not enough neurologists, and 16 (69.6%) indicated that there were not enough non-neurologist HCPs to provide adequate care. More than 50% of clinics reported wait times exceeding 3 months for physiatrists, physiotherapists, psychiatrists, psychologists, neuropsychologists and urologists; in some clinics wait times for these providers exceeded 1 year. Multiple disciplines were identified as important or very important for delivering good quality MS care. Over 90% of respondents thought it was important for neurologists, nurse practitioners, MS nurses and psychiatrists to be co-located within MS Clinics.ConclusionCanadian HCPs viewed the ideal MS service as being multidisciplinary in nature and ideally integrated. Efforts are needed to improve timely access to specialized MS care in Canada, and to evaluate how outcomes are influenced by access to care.
Associations Between Vitamin D Levels and Risk of Heart Failure: A Bidirectional Mendelian Randomization Study
Authors: Gao Ning , Li Xuebiao , Kong Minjian , Ni Ming , Wei Dongdong , Zhu Xian , Wang Yifan , Hong Ze , Dong Aiqiang 
Published: May 2022

BackgroundAlthough studies suggest that concentrations of serum 25-hydroxyvitamin D (25(OH)D) are lower in individuals with Heart Failure (HF), the beneficial effects of vitamin D supplementation are controversial. Therefore, in this study, we aimed to determine whether there is a causal relationship between serum Vitamin D (VD) levels and HF.MethodsWe obtained genetic instruments from the largest available genome-wide association study (GWAS) of European descent for 25(OH)D (443, 734 individuals) to investigate the association with HF (47,309 cases, 930,014 controls), and vice versa. Two-sample bidirectional Mendelian Randomization (MR) analysis was performed to infer the causality. In addition to the primary analysis using inverse variance-weighted (IVW) MR, we applied five additional methods to control for pleiotropy [MR-Egger, weighted median, Maximum-likelihood, MR-robust adjusted profile score (MR-RAPS) and MR-pleiotropy residual sum and outlier (MR-PRESSO)] and compared their respective MR estimates. We also performed a sensitivity analysis to ensure that our results were robust.ResultsMendelian randomized analysis showed that increased serum 25(OH)D was associated with a lower risk of HF in the IVW method (odds ratio [OR] = 0. 81;95%CI, 0.70–0.94, P = 0.006). In the reverse MR analyses, the genetic predisposition to HF was negatively correlated with serum 25(OH)D level (OR = 0. 89;95%CI, (0.82–0.97), P = 0.009).ConclusionOur study revealed the possible causal role of 25(OH)D on decreasing the risk for HF. Meanwhile, reverse MR analysis suggested that HF may be associated with lower vitamin D levels, it could be the potential implications for dietary recommendations.