bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROS scavengers decrease γH2ax spots in motor neuronal nuclei of ALS model mice in vitro
Authors: Junghans Maya , John Felix , Cihankaya Hilal , Schliebs Daniel , Winklhofer Konstanze F. , Bader Verian , Matschke Johann , Theiss Carsten , Matschke Veronika 
Published: August 2022

Background: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the loss of motor neurons in cerebral cortex, brainstem and spinal cord. Numerous studies have demonstrated signs of oxidative stress in postmortem neuronal tissue, cerebrospinal fluid, plasma and urine of ALS patients, without focusing on the specific processes within motor neurons. Thus, we aimed to investigate the relevance of reactive oxygen species (ROS) detoxification mechanisms and its consequences on the formation of toxic/lethal DNA double strand breaks (DSBs) in the ALS model of the Wobbler mouse.Methods: Live cell imaging in dissociated motor neuronal cultures was used to investigate the production of ROS using Dihydroethidium (DHE). The expression levels of ROS detoxifying molecules were investigated by qPCR as well as Western blots. Furthermore, the expression levels of DNA damage response proteins p53bp1 and H2ax were investigated using qPCR and immunofluorescence staining. Proof-of-principle experiments using ROS scavengers were performed in vitro to decipher the influence of ROS on the formation of DNA double strand breaks quantifying the γH2ax spots formation.Results: Here, we verified an elevated ROS-level in spinal motor neurons of symptomatic Wobbler mice in vitro. As a result, an increased number of DNA damage response proteins p53bp1 and γH2ax in dissociated motor neurons of the spinal cord of Wobbler mice was observed. Furthermore, we found a significantly altered expression of several antioxidant molecules in the spinal cord of Wobbler mice, suggesting a deficit in ROS detoxification mechanisms. This hypothesis could be verified by using ROS scavenger molecules in vitro to reduce the number of γH2ax foci in dissociated motor neurons and thus counteract the harmful effects of ROS.Conclusion: Our data indicate that maintenance of redox homeostasis may play a key role in the therapy of the neurodegenerative disease ALS. Our results underline a necessity for multimodal treatment approaches to prolong the average lifespan of motor neurons and thus slow down the progression of the disease, since a focused intervention in one pathomechanism seems to be insufficient in ALS therapy.
More than just statics: Static and temporal dynamic changes in intrinsic brain activity in unilateral temporal lobe epilepsy
Authors: Song Chengru , Zhang Xiaonan , Han Shaoqiang , Ma Keran , Wang Kefan , Mao Xinyue , Lian Yajun , Zhang Xianchang , Zhu Jinxia , Zhang Yong , Cheng Jingliang 
Published: August 2022

BackgroundTemporal lobe epilepsy (TLE) is the most prevalent refractory focal epilepsy and is more likely accompanied by cognitive impairment. The fully understanding of the neuronal activity underlying TLE is of great significance.ObjectiveThis study aimed to comprehensively explore the potential brain activity abnormalities affected by TLE and detect whether the changes were associated with cognition.MethodsSix static intrinsic brain activity (IBA) indicators [amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC), global signal correlation (GSCorr), and voxel-mirrored homotopic connectivity (VMHC)] and their corresponding dynamic indicators, such as dynamic ALFF (dALFF), dynamic fALFF (dfALFF), dynamic ReHo (dReHo), dynamic DC (dDC), dynamic VMHC (dVMHC), and dynamic GSCorr (dGSCorr), in 57 patients with unilateral TLE and 42 healthy volunteers were compared. Correlation analyses were also performed between these indicators in areas displaying group differences and cognitive function, epilepsy duration, and severity.ResultsMarked overlap was present among the abnormal brain regions detected using various static and dynamic indicators, primarily including increased ALFF/dALFF/fALFF in the bilateral medial temporal lobe and thalamus, decreased ALFF/dALFF/fALFF in the frontal lobe contralateral to the epileptogenic side, decreased fALFF, ReHo, dReHo, DC, dDC, GSCorr, dGSCorr, and VMHC in the temporal neocortex ipsilateral to the epileptogenic foci, decreased dReHo, dDC, dGSCorr, and dVMHC in the occipital lobe, and increased ALFF, fALFF, dfALFF, ReHo, and DC in the supplementary motor area ipsilateral to the epileptogenic foci. Furthermore, most IBA indicators in the abnormal brain region significantly correlated with the duration of epilepsy and several cognitive scale scores (P &lt; 0.05).ConclusionThe combined application of static and dynamic IBA indicators could comprehensively reveal more real abnormal neuronal activity and the impairment and compensatory mechanisms of cognitive function in TLE. Moreover, it might help in the lateralization of epileptogenic foci and exploration of the transmission and inhibition pathways of epileptic activity.
m6A-related lncRNAs are potential biomarkers for the prognosis of COAD patients
Authors: Xu Chenyang , He Tingting , Shao Xinxin , Gao Ling , Cao Lei 
Published: August 2022

BackgroundColon adenocarcinoma (COAD) is the most common subtype of colon cancer. However, the 5-year survival rate of COAD patients remains unsatisfactory. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of COAD. Herein, we are committed to establish and validate a prognostic m6A-related lncRNA signature.MethodsWe obtained m6A-related lncRNAs by coexpression. The m6A-related lncRNA risk signature (m6ALncSig) was developed via univariate, LASSO, and multivariate Cox regression analyses. Kaplan-Meier (KM) survival curves, gene set enrichment analysis (GSEA), and nomogram generation were conducted to assess m6ALncSig. In addition, the potential immunotherapeutic signatures were also discussed. Real-time PCR and CCK8 analysis were performed to evaluate the expression and functions of lncRNA UBA6-AS1, which was selected.ResultsThe risk signature comprising 14 m6A-related lncRNAs (m6ALncSig) was established, which possessed a superior predictive ability of prognosis. Meanwhile, m6ALncSig was linked to immune cell infiltration. The level of UBA6-AS1 expression was validated in 17 pairs of COAD samples. In cell function experiments, UBA6-AS1 knockdown attenuated cell proliferation capacity.ConclusionsCollectively, m6ALncSig could serve as an independent predictive factor for COAD and accurately estimate the outcome for COAD patients. Importantly, UBA6-AS1 was first identified as an oncogene in COAD.
Efficacy, safety and predictors of combined fruquintinib with programmed death-1 inhibitors for advanced microsatellite-stable colorectal cancer: A retrospective study
Authors: Zhang Weijie , Zhang Zhongyue , Lou Shitong , Li Donghui , Ma Zhijun , Xue Lei 
Published: August 2022

BackgroundResearch findings have revealed that combining anti-angiogenesis inhibitors with programmed death-1(PD-1) inhibitors can reverse the immunosuppressive tumor microenvironment and enhance the antitumor immune response. To explore the therapeutic options for breaking immune tolerance in microsatellite stability (MSS) or mismatch repair-proficiency (pMMR) advanced colorectal cancer (CRC), we assessed the efficacy, safety and predictors of the fruquintinib and PD-1 inhibitors combination in patients with MSS/pMMR advanced CRC in a real-world environment.MethodsWe conducted a single-center retrospective study by collecting relevant data on patients with MSS/pMMR advanced CRC who received fruquintinib coupled with PD-1 inhibitors in the First Affiliated Hospital of Zhengzhou University between August 2019 and November 2021, focusing on progression-free survival.ResultsWe enrolled 110 eligible patients in this study between August 2019 and November 2021. At the deadline (January 20, 2022), 13 patients had objective responses. The objective response rate was 11.8% (13/110, 95% confidence interval [CI]: 6.4-18.2), the disease control rate was 70.0% (82/110, 95% CI: 60.9-78.2), and the progression-free survival was 5.4 months (95% CI: 4.0-6.8). Liver metastases (hazard ratio [HR]: 0.594, 95% CI: 0.363-0.973, P&lt;0.05), alkaline phosphatase elevation (ALP&gt;160U/L) (HR: 0.478, 95%CI: 0.241-0.948, P&lt;0.05), fibrinogen elevation (FIB&gt;4g/L) (HR: 0.517, 95% CI: 0.313-0.855, P&lt;0.05), and an increase in the ALP level from the baseline after treatment (HR: 1.673, 95% CI: 1.040-2.690, P&lt;0.05) were negative predictors of the progression-free survival. A total of 101 of 110 patients experienced treatment-related adverse events, including 14 who experienced grade 3 or above treatment-related adverse events, and no treatment-related deaths occurred. Hypertension was the most frequently encountered grade 3 treatment-related adverse event.ConclusionFruquintinib combined with PD-1 inhibitors has antitumor activity and manageable safety in treating patients with MSS/pMMR advanced CRC. Liver metastases, ALP level and FIB level might be a prediction of the patient response to this therapy.
Incidence of pelvic high-grade serous carcinoma after isolated STIC diagnosis: A systematic review of the literature
Authors: Linz Valerie Catherine , Löwe Amelie , van der Ven Josche , Hasenburg Annette , Battista Marco Johannes 
Published: August 2022

ObjectiveSerous tubal intraepithelial carcinoma (STIC) is a precursor lesion of pelvic high-grade serous carcinoma (HGSC). Information on treatment and outcome of isolated STIC is rare. Therefore, we reviewed systematically the published literature to determine the incidence of subsequent HGSC in the high- and low-risk population and to summarize the current diagnostic and therapeutic options.MethodsA systematic review of the literature was conducted in MEDLINE-Ovid, Cochrane Library and Web of Science of articles published from February 2006 to July 2021. Patients with an isolated STIC diagnosis and clinical follow-up were included. Study exclusion criteria for review were the presence of synchronous gynaecological cancer and/or concurrent non-gynaecological malignancies.Results3031 abstracts were screened. 112 isolated STIC patients out of 21 publications were included in our analysis with a pooled median follow-up of 36 (interquartile range (IQR): 25.3-84) months. 71.4% of the patients had peritoneal washings (negative: 62.5%, positive: 8%, atypic cells: 0.9%). Surgical staging was performed in 28.6% of all STICs and did not show any malignancies. 14 out of 112 (12.5%) patients received adjuvant chemotherapy with Carboplatin and Paclitaxel. Eight (7.1%) patients developed a recurrence 42.5 (IQR: 33-72) months after isolated STIC diagnosis. Cumulative incidence of HGSC after five (ten) years was 10.5% (21.6%). Recurrence occurred only in BRCA1 carriers (seven out of eight patients, one patient with unknown BRCA status).ConclusionThe rate of HGSC after an isolated STIC diagnosis was 7.1% with a cumulative incidence of 10.5% (21.6%) after five (ten) years. HGSC was only observed in BRCA1 carriers. The role of adjuvant therapy and routine surveillance remains unclear, however, intense surveillance up to ten years is necessary.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021278340.
Flavonoids-Rich Plant Extracts Against Helicobacter pylori Infection as Prevention to Gastric Cancer
Authors: Ivyna de Araújo Rêgo Renaly , Guedes Silvestre Geovana Ferreira , Ferreira de Melo Demis , Albino Sonaly Lima , Pimentel Marcela Monteiro , Silva Costa Cruz Sara Brito , Silva Wurzba Sabrina Daniela , Rodrigues Wellington Francisco , Goulart de Lima Damasceno Bolívar Ponciano , Cançado Castellano Lúcio Roberto 
Published: August 2022

Gastric cancer is the fifth most common and fourth type to cause the highest mortality rates worldwide. The leading cause is related to Helicobacter pylori (H. pylori) infection. Unfortunately, current treatments have low success rates, highlighting the need for alternative treatments against carcinogenic agents, specifically H. pylori. Noteworthy, natural origin products contain pharmacologically active metabolites such as flavonoids, with potential antimicrobial applications.Objective: This article overviews flavonoid-rich extracts’ biological and pharmacological activities. It focuses on using these substances against Helicobacter pylori infection to prevent gastric cancer. For this, PubMed and Science Direct databases were searched for studies that reported the activity of flavonoids against H. pylori, published within a 10-year time frame (2010 to August 2020). It resulted in 1,773 publications, of which 44 were selected according to the search criteria. The plant family primarily found in publications was Fabaceae (9.61%). Among the flavonoids identified after extraction, the most prevalent were quercetin (19.61%), catechin (13.72), epicatechin (11.76), and rutin (11.76). The potential mechanisms associated with anti-H. pylori activity to the extracts were: inhibition of urease, damage to genetic material, inhibition of protein synthesis, and adhesion of the microorganism to host cells.Conclusion: Plant extracts rich in flavonoids with anti-H. pylori potential proved to be a promising alternative therapy source, reinforcing the relevance of studies with natural products.
Concordance of the treatment patterns for major depressive disorders between the Canadian Network for Mood and Anxiety Treatments (CANMAT) algorithm and real-world practice in China
Authors: Yang Lu , Su Yousong , Dong Sijia , Wu Tao , Zhang Yongjing , Qiu Hong , Gu Wenjie , Qiu Hong , Xu Yifeng , Wang JianLi , Chen Jun , Fang Yiru 
Published: August 2022

Background: Antidepressant (AD) algorithm is an important tool to support treatment decision-making and improve management of major depressive disorder (MDD). However, little is known about its concordance with real-world practice. This study aimed to assess the concordance between the longitudinal treatment patterns and AD algorithm recommended by a clinical practice guideline in China.Methods: Data were obtained from the electronic medical records of Shanghai Mental Health Center (SMHC), one of the largest mental health institutions in China. We examined the concordance between clinical practice and the Canadian Network for Mood and Anxiety Treatments (CANMAT) algorithm among a cohort composed of 19,955 MDD patients. The longitudinal characteristics of treatment regimen and duration were described to identify the specific inconsistencies. Demographics and health utilizations of the algorithm-concordant and -discordant subgroups with optimized treatment were measured separately.Results: The overall proportion of algorithm-concordant treatment significantly increased from 84.45% to 86.03% during the year of 2015–2017. Among the patients who received recommended first-line drugs with subsequent optimized treatment (n = 2977), the concordance proportion was 27.24%. Mirtazapine and trazodone were the most used drugs for adjunctive strategy. Inadequate or extended duration before optimized treatment are common inconsistency. The median length of follow-up for algorithm-concordant (n = 811) and algorithm-discordant patients (n = 2166) were 153 days (Q1-Q3 = 79–328) and 368 days (Q1-Q3 = 181–577) respectively, and the average number of clinical visits per person-year was 13.07 and 13.08 respectively.Conclusion: Gap existed between clinical practice and AD algorithm. Improved access to evidence-based treatment is required, especially for optimized strategies during outpatient follow-up.
Identification and validation of roles of lysyl oxidases in the predictions of prognosis, chemotherapy and immunotherapy in glioma
Authors: Xia Qin-Xuan , Yu Jing , Wang Zhao-Jun , Guan Qi-Wen , Mao Xiao-Yuan 
Published: August 2022

Background: Previous investigations have illustrated that lysyl oxidase family enzymes (LOXs) are contributing factors for tumor progression and remodeling immunomicroenvironment. However, it is scarce regarding comprehensive analysis of LOXs in the predictions of prognosis, chemotherapy and immunotherapy in glioma, the highly invasive brain tumor. Our present work aimed to explore the prognostic value, chemotherapeutic drug sensitivity and immunotherapy according to distinct LOXs expressions in glioma through bioinformatics analysis and experimental verification.Methods: We collected gene expression data and clinical characteristics from the public databases including Chinese Glioma Genome Atlas (CGGA)-325, CGGA-693, the Cancer Genome Atlas (TCGA), IMvigor210 and Van Allen 2015 cohorts. The correlations between the clinicopathological factors and differential LOXs expressions were analyzed. The ROC curve and Kaplan-Meier analysis were conducted to evaluate the prediction ability of prognosis. Chemotherapeutic drug sensitivity via distinct LOXs expression levels was predicted using the pRRophetic package. Immune score, immune cell infiltration and immune checkpoint expression levels were also analyzed through diverse algorithms in R software. Finally, mRNA and protein expressions of LOXs were validated in glioma cells (T98G and A172) by real-time quantitative PCR and Western blot, respectively.Results: Our results demonstrated that high levels of LOXs expressions were positively associated with glioma grades, older age and MGMT unmethylated status while elevations of LOXs were negatively correlated with IDH mutation or 1p/19q co-deletion. Furthermore, the glioma patients with low levels of LOXs also exhibited better prognosis. Also, differential LOXs expressions were associated with at least 12 chemotherapeutic drug sensitivity. Besides, it was also found that glioma patients with high LOXs expressions showed higher enrichment scores for immune cell infiltration and increased levels of immune checkpoints, suggesting the critical role of distinct LOXs expression levels for glioma immunotherapy. The predictive roles of LOXs expression in tumor immunotherapy were also validated in two immunotherapy cohorts including IMvigor 210 and Van Allen 2015. Experimental results revealed that expressions of LOX, LOXL1, LOXL2, and LOXL3 were higher in glioma cell lines at mRNA and protein levels.Conclusion: Our findings altogether indicate that LOXs have potent predictive value for prognosis, chemotherapy and immunotherapy in glioma patients.
Association between Serum Cystatin C levels and long‐term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea
Authors: Li Jian-Hua , Gao Ying-Hui , Xue Xin , Su Xiao-Feng , Wang Huan-Huan , Lin Jun-Ling , Zhao Li-Bo , Zou Xiao , Gao Yan , Guo Jing-Jing , Shi Min , Xu Wei-Hao , Wang Ya-Bin , Qian Xiao-Shun , Chen Kai-Bing , Fan Li , Liu Lin 
Published: August 2022

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA.Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality.Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60–96) years. At baseline, apnea–hypopnea index (AHI) (r = 0.128, p &lt; 0.05), oxygen desaturation index (ODI) (r = 0.116, p &lt; 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = −0.097, p &lt; 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28–12.30, p &lt; 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09–44.72, p &lt; 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality).Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.
Relationship of neurocognitive ability, perspective taking, and psychoticism with hostile attribution bias in non-clinical participants: Theory of mind as a mediator
Authors: Koo Se Jun , Kim Ye Jin , Seo Eunchong , Park Hye Yoon , Min Jee Eun , Bang Minji , Park Jin Young , Lee Eun , An Suk Kyoon 
Published: August 2022

ObjectivesHostile attribution bias is reportedly common from non-clinical population to those with serious mental illness, such as schizophrenia, and is known to be closely related to theory of mind (ToM). This study aimed to investigate whether ToM skills mediate the relationship among neurocognitive ability, personality traits, and attribution bias.MethodsA total of 198 (101 females) non-clinical youths were recruited. To assess their neurocognitive ability and ToM skills, the participants were asked to complete Raven’s Standard Progressive Matrices (SPM) and the Korean version of the Reading the Mind in Eyes Test (K-RMET). To determine their personality traits, the Eysenck Personality Questionnaire (psychoticism) and interpersonal reactivity index (perspective taking) were used. To evaluate hostile attribution bias, the Ambiguous Intentions Hostility Questionnaire was administered. Path analysis and bias-corrected percentile bootstrap methods were used to estimate model fit and the parameters of the mediating effects.ResultsBased on model comparison, the best model characterized (1) two direct pathways from psychoticism and the K-RMET to hostility attribution bias and (2) three indirect pathways, wherein SPM, perspective taking, and psychoticism influenced hostile attribution bias through K-RMET. The final model fit indices were good [x2/df = 1.126; comparative fit index = 0.996; root mean square error of approximation = 0.026; standard root mean square residual = 0.026 and Akaike information criterion = 28.251] and the K-RMET fully mediated the association between SPM, perspective taking, psychoticism, and hostile attribution bias.ConclusionThe main findings suggested that ToM skills, such as the RMET, play an important role in explaining the relationship among neurocognitive ability, personality traits, and hostile attribution bias. ToM skills and a remediation strategy may need to be developed to balance the enhanced hostility bias that underlies the paranoia.