bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Factors Related to Pathological Laughter and Crying in Patients With Amyotrophic Lateral Sclerosis
Authors: Wei Qian-Qian , Ou Ruwei , Lin Junyu , Zhang Lingyu , Hou Yanbing , Cao Bei , Chen Yongping , Yang Tianmi , Shang Huifang 
Published: September 2021

Objective: This study aimed to explore the prevalence and clinical correlates of pathological laughter and crying (PLC) in patients with amyotrophic lateral sclerosis (ALS).Methods: A total of 1,031 ALS patients were enrolled between August 2012 and August 2019. The PLC was recorded by a face-to-face interview. Other characteristics of patients, including depression, anxiety, cognition, and behavior function, were also evaluated. The potential associated factors of PLC were explored using forward binary regression analysis. Survival was analyzed in groups using propensity score matching (PSM) and Cox proportional hazards models.Results: The prevalence of PLC was 11.4% in all patients at baseline. Bulbar-onset and female patients had higher prevalence of PLC. The multivariate regression analysis indicated that PLC in ALS was associated with bulbar onset (p &lt; 0.001), late disease stage (p &lt; 0.001), and higher score in the Hamilton Depression Rating Scale (HDRS) (p = 0.012). The higher score of HDRS was significantly and independently associated with PLC occurrence in bulbar-onset patients (p = 0.032). The late disease stage was related to PLC occurrence in spinal-onset patients (p &lt; 0.001). After comparison with matched pairs by using PSM, PLC at baseline had no impact on survival.Conclusion: PLC was not uncommon in ALS, especially in bulbar-onset and female patients. We highlighted that the emotional state other than cognitive function had possible relationship with PLC in ALS.
A Case Report of Pulsed Radiofrequency Plus Suboccipital Injection of the Greater Occipital Nerve: An Easier Target for Treatment of Cluster Headache
Authors: Belgrado Enrico , Surcinelli Andrea , Gigli Gian Luigi , Pellitteri Gaia , Dalla Torre Chiara , Valente Mariarosaria 
Published: September 2021

Introduction: In cluster headache, the efficacy of suboccipital steroid injection is notable within a few days, although few data are available about the duration of efficacy. A combination treatment, consisting of suboccipital steroid injection plus pulsed radiofrequency, could potentially lead to long-term benefit. Evidence about pulsed radiofrequency of the greater occipital nerve is lacking.Patients and Methods: We retrospectively describe a series of four cluster headache patients treated with suboccipital steroid injection plus pulsed radiofrequency of the greater occipital nerve.Results: All patients achieved a 50% reduction in attack frequency in the 7 days after the first treatment. Moreover, a long pain-free remission period up to 15 months was noted.Conclusion: Suboccipital steroid injection plus pulsed radiofrequency of the greater occipital nerve might have both acute and prophylactic effects in cluster headache. The greater occipital nerve is more accessible to pulsed radiofrequency than other targets.
25(OH)D Levels in Infancy Is Associated With Celiac Disease Autoimmunity in At-Risk Children: A Case–Control Study
Authors: Andrén Aronsson Carin , Liu Xiang , Norris Jill M. , Uusitalo Ulla , Butterworth Martha D. , Koletzko Sibylle , Virtanen Suvi M. , Erlund Iris , Kurppa Kalle , Hagopian William A. , Rewers Marian J. , She Jin-Xiong , Toppari Jorma , Ziegler Anette-G. , Akolkar Beena , Krischer Jeffrey P. , Agardh Daniel 
Published: September 2021

Objectives: An observed variation in the risk of celiac disease, according to the season of birth, suggests that vitamin D may affect the development of the disease. The aim of this study was to investigate if vitamin D concentration is associated with the risk of celiac disease autoimmunity (CDA) in genetically at-risk children.Study Design: Children prospectively followed in the multinational The Environmental Determinants of Diabetes in the Young study, conducted at six centers in Europe and the US, were selected for a 1-to-3 nested case–control study. In total, 281 case–control sets were identified. CDA was defined as positivity for tissue transglutaminase autoantibodies (tTGA) on two or more consecutive visits. Vitamin D was measured as 25-hydroxyvitamin D [25(OH)D] concentrations in all plasma samples prior to, and including, the first tTGA positive visit. Conditional logistic regression was used to examine the association between 25(OH)D and risk of CDA.Results: No significant association was seen between 25(OH)D concentrations (per 5 nmol/L increase) and risk for CDA development during early infancy (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.95–1.04) or childhood (OR 1.02, 95% CI 0.97–1.07). When categorizing 25(OH)D concentrations, there was an increased risk of CDA with 25(OH)D concentrations &lt;30 nmol/L (OR 2.23, 95% CI 1.29, 3.84) and &gt;75 nmol/L (OR 2.10, 95% CI 1.28–3.44) in early infancy, as compared with 50–75 nmol/L.Conclusion: This study indicates that 25(OH)D concentrations &lt;30 nmol/L and &gt;75 nmol/L during early infancy were associated with an increased risk of developing CDA in genetically at-risk children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the relation to celiac disease onset.
Identification of Key Genes Related to CD8+ T-Cell Infiltration as Prognostic Biomarkers for Lung Adenocarcinoma
Authors: Du Minjun , Liang Yicheng , Liu Zixu , Li Xingkai , Liang Mei , Zhou Boxuan , Gao Yushun 
Published: September 2021

BackgroundCD8+ T cells are one of the central effector cells in the immune microenvironment. CD8+ T cells play a vital role in the development and progression of lung adenocarcinoma (LUAD). This study aimed to explore the key genes related to CD8+ T-cell infiltration in LUAD and to develop a novel prognosis model based on these genes.MethodsWith the use of the LUAD dataset from The Cancer Genome Atlas (TCGA), the differentially expressed genes (DEGs) were analyzed, and a co-expression network was constructed by weighted gene co-expression network analysis (WGCNA). Combined with the CIBERSORT algorithm, the gene module in WGCNA, which was the most significantly correlated with CD8+ T cells, was selected for the subsequent analyses. Key genes were then identified by co-expression network analysis, protein–protein interactions network analysis, and least absolute shrinkage and selection operator (Lasso)-penalized Cox regression analysis. A risk assessment model was built based on these key genes and then validated by the dataset from the Gene Expression Omnibus (GEO) database and multiple fluorescence in situ hybridization experiments of a tissue microarray.ResultsFive key genes (MZT2A, ALG3, ATIC, GPI, and GAPDH) related to prognosis and CD8+ T-cell infiltration were identified, and a risk assessment model was established based on them. We found that the risk score could well predict the prognosis of LUAD, and the risk score was negatively related to CD8+ T-cell infiltration and correlated with the advanced tumor stage. The results of the GEO database and tissue microarray were consistent with those of TCGA. Furthermore, the risk score was higher significantly in tumor tissues than in adjacent lung tissues and was correlated with the advanced tumor stage.ConclusionsThis study may provide a novel risk assessment model for prognosis prediction and a new perspective to explore the mechanism of tumor immune microenvironment related to CD8+ T-cell infiltration in LUAD.
The Landscape of Immune Cells Indicates Prognosis and Applicability of Checkpoint Therapy in Hepatocellular Carcinoma
Authors: Huang Jiacheng , Zhang Lele , Chen Jianxiang , Wan Dalong , Zhou Lin , Zheng Shusen , Qiao Yiting 
Published: September 2021

BackgroundTumor-infiltrating immune cells are important components of tumor microenvironment (TME), and their composition reflects the confrontation between host immune system and tumor cells. However, the relationship between the composition of infiltrating immune cells, prognosis, and the applicability of anti-PD-1/PD-L1 therapy in hepatocellular carcinoma (HCC) needs systematic examination.MethodsCell-Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) was applied to evaluate the infiltration of immune cells based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) cohort. Diagnostic and prognostic models were constructed based on immune cells, and the models were validated by two external cohorts. The relationship between immune cells and PD-L1 was evaluated by Spearman correlation, and the finding was validated in our in-house HCC sample.ResultPatients in TCGA LIHC cohort were classified into six subtypes with different prognosis based on the proportion of tumor-infiltrating immune cells simulated via CIBERSORT. Among 22 types of immune cells, intratumoral PD-L1 mRNA level exhibited linear relationship with the fraction of five types of immune cells (M1 macrophages, plasma cells, CD8+ T cells, resting mast cells, and regulatory T cells), and M1 macrophages showed the strongest relevance (R = 0.26, p &lt; 0.001). Immunohistochemistry of our in-house HCC specimens verified this conclusion. Moreover, intratumoral mRNA levels of M1 macrophage-associated cytokines were positively correlated with PD-L1 level.ConclusionsOur study demonstrated that the prognosis of HCC patients was associated with the pattern of infiltrating immune cells in TME, and macrophage-associated cytokines might be a potential non-invasive marker for predicting the PD-L1 level for HCC patients.
Addition of Plasma Myeloperoxidase and Trimethylamine N-Oxide to the GRACE Score Improves Prediction of Near-Term Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Tan Yu , Zhou Jinying , Yang Shujun , Li Jiannan , Zhao Hanjun , Song Li , Yan Hongbing 
Published: September 2021

Background: The Global Registry of Acute Coronary Events (GRACE) risk score (GRS) is an established powerful model in predicting prognosis of patients with acute coronary syndrome. However, it does not contain pathophysiological biomarkers. Myeloperoxidase (MPO) and trimethylamine N-oxide (TMAO) are novel biomarkers of different pathophysiological processes of acute myocardial infarction, and each of them predicts risk of adverse clinical outcomes. We aimed to investigate whether the addition of MPO and TMAO could improve a GRS-based prediction model in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A prospective cohort of 444 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were enrolled in this study. Plasma levels of MPO and TMAO were measured using samples collected before the interventional procedure. GRS at admission was calculated. Death and nonfatal myocardial infarction were recorded as major adverse cardiac events (MACEs). Kaplan–Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of MPO and TMAO. Area under the receiver-operator characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to evaluate the increment of predictive value for the combination of MPO and TMAO with GRS in predicting adverse clinical outcomes.Results: During 6 months follow-up, 27 patients suffered MACEs. Both MPO (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.11–5.87; p &lt; 0.05) and TMAO (HR: 4.50, 95% CI: 1.78–11.40, p &lt; 0.01) predicted MACEs at 6 months. The AUC for MPO, TMAO, GRS, and their combination in predicting risk of MACEs at 6 months is 0.642, 0.692, 0.736, and 0.760, respectively. The addition of MPO and TMAO significantly improved the net reclassification of GRS for predicting MACEs at 6 months (NRI: 0.42, p = 0.032).Conclusion: Plasma MPO and TMAO each predict near-term risk of adverse outcomes in patients with STEMI. Furthermore, the combination of MPO and TMAO with GRS enables more accurate prediction of cardiovascular events compared with GRS alone.
Risk of Cardiovascular Events and Medical Cost of Dapagliflozin and Dipeptidyl Peptidase-4 Inhibitors
Authors: Seong Jong-Mi , Kim Jong Joo , Kim Hae Jin , Sohn Hyun Soon 
Published: September 2021

This study compared dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, and dipeptidyl peptidase-4 inhibitors (DPP-4i) with regard to cardiovascular (CV) event incidence and direct medical costs during type 2 diabetes treatment. A retrospective cohort study was conducted using national health insurance claims data from September 1, 2014, to June 30, 2018, of patients in Korea. Patients who were prescribed dapagliflozin and DPP-4i for the first time were included. The primary outcome was the incidence of a composite of major adverse CV events (MACEs)—nonfatal myocardial infarction, nonfatal stroke, or in-hospital CV death. Proportional hazard models after propensity score weighting were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE in the dapagliflozin and DPP-4i groups. A decision analytic model was used to compare direct medical costs between the two treatment groups from a healthcare provider’s perspective. Of the 260,336 patients in the cohort, 23,147 and 237,189 received dapagliflozin and DPP-4i, respectively. During the follow-up, 184 patients receiving dapagliflozin and 3,674 receiving DPP-4i (incidence, 6.47 and 11.33 events/1,000 person-years, respectively) had MACE. The adjusted HR of MACE for dapagliflozin compared with that for DPP-4i was 0.69 (95% CI 0.57–0.83). The corresponding HRs were consistent among patients with and without underlying CV disease. The estimated direct medical cost appeared to be lower by $68,452 in the dapagliflozin group than that in the DPP-4i group for 3 years, in 1,000 hypothetical patients. In this population-based cohort study, the use of dapagliflozin instead of DPP-4i was associated with a reduced risk of MACE, which subsequently reduced direct medical costs. These data provide valuable information to patients, practitioners, and authorities regarding the risk of CV events associated with dapagliflozin versus DPP-4i use in clinical practice.
Understanding Fatal and Non-Fatal Drug Overdose Risk Factors: Overdose Risk Questionnaire Pilot Study—Validation
Authors: Doggui Radhouene , Adib Keyrellous , Baldacchino Alex 
Published: September 2021

Background: Drug overdoses (fatal and non-fatal) are among the leading causes of death in population with substance use disorders. The aim of the current study was to identify risk factors for fatal and non-fatal drug overdose for predominantly opioid-dependent treatment–seeking population.Methods: Data were collected from 640 adult patients using a self-reported 25-item Overdose Risk (OdRi) questionnaire pertaining to drug use and identified related domains. The exploratory factor analysis (EFA) was primarily used to improve the interpretability of this questionnaire. Two sets of EFA were conducted; in the first set of analysis, all items were included, while in the second set, items related to the experience of overdose were removed. Logistic regression was used for the assessment of latent factors’ association with both fatal and non-fatal overdoses.Results: EFA suggested a three-factor solution accounting for 75 and 97% of the variance for items treated in the first and second sets of analysis, respectively. Factor 1 was common for both sets of EFA analysis, containing six items (Cronbach’s α = 0.70) focusing around “illicit drug use and lack of treatment.” In the first set of analysis, Factors 2 (Cronbach’s α = 0.60) and 3 (Cronbach’s α = 0.34) were focusing around “mental health and emotional trauma” and “chronic drug use and frequent overdose” domains, respectively. The increase of Factor 2 was found to be a risk factor for fatal drug overdose (adjusted coefficient = 1.94, p = 0.038). In the second set of analysis, Factors 2 (Cronbach’s α = 0.65) and 3 (Cronbach’s α = 0.59) as well as Factor 1 were found to be risk factors for non-fatal drug overdose ever occurring. Only Factors 1 and 3 were positively associated with non-fatal overdose (one in a past year).Conclusion: The OdRi tool developed here could be helpful for clinical studies for the overdose risk assessment. However, integrating validated tools for mental health can probably help refining the accuracy of latent variables and the questionnaire’s consistency. Mental health and life stress appear as important predictors of both fatal and non-fatal overdoses.
Effects of Radix Scrophulariae on Hyperthyroidism Assessed by Metabonomics and Network Pharmacology
Authors: Zhang Ning , Lu Fang , Li Zihui , Zhao Hongwei , Pang Mu , Ye Tao , Wang Xijun , Liu Shumin 
Published: September 2021

Radix Scrophulariae (Chinese name: Xuanshen), a traditional Chinese herb, is used for the treatment of hyperthyroidism, and in this study, its mechanisms were evaluated by metabonomics and system pharmacology. To study the anti-hyperthyroidism effects of R. Scrophulariae, a male SD rat (180–220 g) model of hyperthyroidism induced by Euthyrox was used. Thirty rats were randomly distributed into three groups: the Model group, the R. Scrophulariae treatment group (RS group) and the healthy Control group. Using the UHPLC/Q-TOF-MS metabolomics approach, 44 metabolites were found to be profoundly altered in the model group, and the levels of these biomarkers were significantly decreased after treatment with R. Scrophulariae. Forty-four metabolites and 13 signaling pathways related to R. Scrophulariae, including the biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis and sphingolipid metabolism, were explored, and linoleic acid metabolism and sphingolipid metabolism were identified as the most relevant metabolic pathways. In addition, the system pharmacology paradigm revealed that R. Scrophulariae contains 83 active ingredients and is related to 795 genes, and 804 disease genes are related to hyperthyroidism. The construction of the R. Scrophulariaceae-chemical composition-target-hyperthyroidism network identified a total of 112 intersection genes. The enriched gene targets were analyzed, and five pathways were found to be enriched. Among them pathways, the HIF signaling pathway had the highest enrichment score, which indicated that this pathway might be the main signaling pathway related to the treatment of hyperthyroidism by R. Scrophulariae.The integrated approach involving metabolomics and network pharmacology revealed that R. Scrophulariae might play a role in the treatment of hyperthyroidism by regulating the “IL6-APOA1-cholesterol” pathway and disturbing the HIF signaling pathway. The results demonstrate that the combination of metabolomics and network pharmacology could be used to reflect the effects of R. Scrophulariae on the biological network and metabolic state of hyperthyroidism and to evaluate the drug efficacy of R. Scrophulariaceae and its related mechanisms.
Leading Innovative Work-Behavior in Times of COVID-19: Relationship Between Leadership Style, Innovative Work-Behavior, Work-Related Flow, and IT-Enabled Presence Awareness During the First and Second Wave of the COVID-19 Pandemic
Authors: Coun Martine J. H. , Edelbroek Robin , Peters Pascale , Blomme Robert J. 
Published: September 2021

Aim: The present study contributes to the conversation on remote (home) working, leadership, and innovation in times of COVID-19 by examining the mediating role of work-related flow in the relationship between empowering and directive leadership, on the one hand, and innovative work-behavior, on the other, and the moderating role of IT-enabled presence awareness in two lockdown periods during the pandemic.Method: We employed PLS-SEM analysis to analyze the perceptions, experiences, and behaviors of a group of employees (N = 257) regarding the study’s core variables during two phases of the COVID-19 pandemic (summer 2020 and autumn 2020).Results: In line with expectations, in the earlier phase of the pandemic, empowering leadership had both a positive direct and indirect relationship with innovative work-behavior via work-related flow, whereas directive leadership only had a negative direct relationship with innovative work-behavior. In the second phase, however, empowering leadership only had a positive indirect relationship with innovative work-behavior, running via work-related flow. Moreover, directive leadership was both directly and indirectly negatively related to innovative work-behavior, via work-related flow. In contrast to our expectations, IT-enabled presence awareness did not play a moderating role in these relationships in any phase.Discussion: Our findings underline the importance of empowerment in sustaining innovative work-behavior, particularly in intense and enduring remote work contexts, as this can amplify employees’ ability, motivation and opportunity to generate, share and implement novel ideas. In remote work contexts, empowering leadership can particularly foster innovation indirectly via work-related flow, which was also shown to be an increasingly important underlying mechanism across time periods. Directive leadership, in contrast, can reduce work-related flow and, therefore, hinder innovation. Our study did not find evidence for the moderating role of employees’ perceptions of IT-enabled presence awareness.Conclusion: We conclude that regardless of the IT-quality, the leadership style chosen plays an important role in innovative work-behavior in remote work-contexts, particularly in view of the divergent effects of empowering and directive leadership on work-related flow in enduring and intense remote work contexts.
The Methylation of Clock Genes in Perinatal Depression: Which Role for Oxytocin?
Authors: Iodice Simona , Di Paolo Martina , Barkin Jennifer Lynn , Tarantini Letizia , Grassi Silvia , Redaelli Marta , Serati Marta , Favalli Virginia , Cirella Luisa , Bollati Valentina , Buoli Massimiliano 
Published: September 2021

Background: Perinatal Depression (PD) is a widespread disabling condition that is hypothesized to be associated with abnormalities in circadian rhythms and neuropeptide release including oxytocin (OXT).Methods: Fourty-four pregnant women (28 with PD, and 16 controls) were evaluated through the Edinburgh Postnatal Depression Scale (EPDS), the State/Trait Anxiety Inventory Form Y (STAI-Y), and the Prenatal Attachment Inventory (PAI). A blood sample was collected from all participants, and OXT plasma levels, DNA methylation of clock genes, as well as of FOXp3 and HERV-W were measured. Linear regression analyses were performed to assess the effect of oxytocin on the methylation of selected genes. Continuous ordinal regression models was further applied to see if the score of rating scales was associated to gene methylation, adjusting for oxytocin-methylation interaction.Results: OXT plasma levels were positively associated with CRY1 methylation. Women with higher OXT plasma levels showed an association between higher degree of CRY2 methylation (thus, reduced expression) and lower EPDS (OR = 0.21; P = 0.043) and STAI-S scores (OR = 6.96; P = 0.019). Finally, with high OXT levels, hypermethylation of CRY1 was associated to higher scores on the PAI (OR = 2.74; P = 0.029) while higher methylation of HERV-W related to lower PAI scores (OR = 0.273; P = 0.019).Conclusion: Our results suggest a possible protective role played by oxytocin in the development of PD by promoting a favorable methylation profile characterized by reduced expression of CRY1 and CRY2. Moreover, oxytocin strengthens the association between maternal prenatal attachment with a favorable pattern of methylation of clock genes and HERV-W, which is essential for pregnancy outcomes.