bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a redox-related gene signature for overall survival prediction and immune infiltration in non-small-cell lung cancer
Authors: Miao Ti-wei , Yang De-qing , Gao Li-juan , Yin Jie , Zhu Qi , Liu Jie , He Yan-qiu , Chen Xin 
Published: August 2022

Background: An imbalance in the redox homeostasis has been reported in multiple cancers and is associated with a poor prognosis of disease. However, the prognostic value of redox-related genes in non-small-cell lung cancer (NSCLC) remains unclear.Methods: RNA sequencing data, DNA methylation data, mutation, and clinical data of NSCLC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Redox-related differentially expressed genes (DEGs) were used to construct the prognostic signature using least absolute shrinkage and selection operator (LASSO) regression analysis. Kaplan–Meier survival curve and receiver operator characteristic (ROC) curve analyses were applied to validate the accuracy of the gene signature. Nomogram and calibration plots of the nomogram were constructed to predict prognosis. Pathway analysis was performed using gene set enrichment analysis. The correlations of risk score with tumor stage, immune infiltration, DNA methylation, tumor mutation burden (TMB), and chemotherapy sensitivity were evaluated. The prognostic signature was validated using GSE31210, GSE26939, and GSE68465 datasets. Real-time polymerase chain reaction (PCR) was used to validate dysregulated genes in NSCLC.Results: A prognostic signature was constructed using the LASSO regression analysis and was represented as a risk score. The high-risk group was significantly correlated with worse overall survival (OS) (p &lt; 0.001). The area under the ROC curve (AUC) at the 5-year stage was 0.657. The risk score was precisely correlated with the tumor stage and was an independent prognostic factor for NSCLC. The constructed nomogram accurately predicted the OS of patients after 1-, 3-, and 5-year periods. DNA replication, cell cycle, and ECM receptor interaction were the main pathways enriched in the high-risk group. In addition, the high-risk score was correlated with higher TMB, lower methylation levels, increased infiltrating macrophages, activated memory CD4+ T cells, and a higher sensitivity to chemotherapy. The signature was validated in GSE31210, GSE26939, and GSE68465 datasets. Real-time PCR validated dysregulated mRNA expression levels in NSCLC.Conclusions: A prognostic redox-related gene signature was successfully established in NSCLC, with potential applications in the clinical setting.
Alterations of brain activity in multiple system atrophy patients with freezing of gait: A resting-state fMRI study
Authors: Cheng Yilin , Yang Huaguang , Liu Weiyin Vivian , Wen Zhi , Chen Jun 
Published: August 2022

BackgroundFreezing of gait (FOG) in multiple system atrophy (MSA) is characterized by a higher risk of falls and a reduced quality of life; however, the mechanisms underlying these effects have yet to be identified by neuroimaging. The aim of this study was to investigate the differences in functional network when compared between MSA patients with and without freezing.MethodsDegree centrality (DC) based on the resting-state functional magnetic resonance imaging was computed in 65 patients with MSA and 36 healthy controls. Brain regions with statistically different DC values between groups were selected as seed points for a second seed-based functional connectivity (FC) analysis. The relationships between brain activity (DC and FC alterations) and the severity of freezing symptoms were then investigated in the two groups of patients with MSA.ResultsCompared to MSA patients without FOG symptoms (MSA-nFOG), patients with MSA-FOG showed an increased DC in the left middle temporal gyrus but a reduced DC in the right superior pole temporal gyrus, left anterior cingulum cortex, left thalamus, and right middle frontal gyrus. Furthermore, in patients with MSA-FOG, the DC in the left thalamus was negatively correlated with FOG scores. Using the left thalamus as a seed, secondary seed-based functional connectivity analysis revealed that patients with MSA-FOG commonly showed the left thalamus-based FC abnormalities in regions related to cognition and emotion. In contrast to the patients with MSA-nFOG, patients with MSA-FOG showed an increased FC between the left thalamus and the left middle temporal gyrus (MTG), right inferior parietal lobule (IPL), bilateral cerebellum_8, and left precuneus.ConclusionFreezing of gait is associated with centrality of the impaired thalamus network. Abnormal FC between the thalamus and left MTG, right IPL, bilateral cerebellum_8, and left precuneus was involved in FOG. These results provide new insight into the pathophysiological mechanism of FOG in MSA.
Analysis of prognosis and treatment decisions for patients with second primary lung cancer following esophageal cancer
Authors: Li Jin-luan , Li Hui , Wu Qian , Zhou Han , Li Yi , Li Yong-heng , Li Jiancheng 
Published: August 2022

IntroductionAs the long-term prognosis of esophageal cancer (EC) is improving, concerns of a second primary malignancy (SPM) have increased. However, research on lung cancer as the SPM after EC is limited. Therefore, we aimed to explore the prognostic factors and clinical treatment decisions of patients with second primary lung cancer following esophageal cancer (SPLC-EC).Materials and methodsWe identified the data of 715 patients with SPLC-EC from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2016. We established a nomogram through Cox regression modelling to predict the prognosis of patients with SPLC-EC. We determined the association between factors and cancer-specific mortality using the Fine-Gray competing risk model. Then, we performed survival analysis to evaluate the benefits of different treatment methods for overall survival (OS).ResultsThe multivariate analysis indicated that sex, insurance recode, age, surgery and chemotherapy 0for first primary malignancy (FPM), primary site, stage, and surgery for SPM were independent prognostic factors for OS. Using concordance indices for OS, the nomogram of our cohort showed a higher value than the SEER historic-stage nomogram (0.8805 versus 0.7370). The Fine-Gray competing risk model indicated that surgery for FPM and SPM was the independent prognostic factor for EC-specific mortality (P=0.016, hazard ratio [HR] = 0.532) and LC-specific mortality (p=0.016, HR=0.457), respectively (p&lt;0.001). Compared to the patient group having distant metastasis, patients with localized and regional metastasis benefitted from undergoing surgery for SPM (P&lt;0.001, P&lt;0.001, respectively). For patients without surgery for SPM, radiotherapy (P&lt;0.001) and chemotherapy (P&lt;0.001) could improve OS.ConclusionsSurgery remains the mainstay for managing SPLC-EC, especially for localized and regional tumors. However, chemotherapy and radiotherapy are recommended for patients who cannot undergo surgery. These findings can have implications in the treatment decision-making for patients with SPLC-EC.
Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
Authors: Liu Hongyan , Zhang Saichun , Wu Ting , Lv Zhaohui , Ba Jianming , Gu Weijun , Mu Yiming 
Published: August 2022

BackgroundCathepsin K (CTSK) is a protease that degrades type I collagen and extracellular matrix, thereby contributing to bone resorption and tumor invasion. Some pituitary adenomas (PAs) could invade the sphenoid sinus (SS) and cavernous sinus (CS).PurposeThis retrospective cohort study aimed to study the expression of tumoral biomarkers (CTSK, MMP9, MMP2, TIMP2, and PTTG1) and evaluate their clinical significance in non-functioning pituitary adenomas (NFPAs) with different invasion patterns.MethodsWe assessed the expression levels of candidate invasion-specific protein biomarkers CTSK, MMP9, MMP2, TIMP2, and PTTG1 by immunohistochemical staining in paraffin-embedded NFPA tumor tissues. Variations in staining intensity were analyzed in cases with SS and CS invasion and non-invasive NFPAs.ResultsWe found that the levels of CTSK were higher in PA cases with SS invasion than that in PA cases with CS invasion (95.57 ± 31.57 vs. 65.29 ± 29.64, P &lt; 0.001), and the expression of MMP9 and MMP2 was higher in CS-invasive cases than that in SS-invasive cases (145.02 ± 49.25 vs. 111.80 ± 51.37, P = 0.002, and 138.67 ± 52.06 vs. 108.30 ± 41.70, P = 0.002). Multiple Cox regression demonstrated that higher CTSK expression (P=0.011), subtotal resection (P&lt;0.001), invasion (P=0.037), and larger tumor diameter (P=0.001) were independent risk factors for recurrence. A positive correlation was observed between CTSK expression and tumor size (r=0.671, p&lt;0.001). There was no significant difference in TIMP2 and PTTG1 levels between CS-and SS-invasive cases (97.42± 39.80 vs. 102.10± 43.22, P = 0.58 and 13.89 ± 4.59 vs. 12.56 ± 3.96, P = 0.14).ConclusionOur data indicated that CTSK has the potential as a marker for SS invasion of PAs, whereas MMP9 and MMP2 may be markers for CS invasion. And CTSK may play an important role in tumor relapse.
Primary erythromelalgia mainly manifested by hypertensive crisis: A case report and literature review
Authors: Feng Shuo , He Zhanwen , Que Liping , Luo Xiangyang , Liang Liyang , Li Dongfang , Qin Lijun 
Published: August 2022

BackgroundPrimary erythrocytic (PEM) is a rare autosomal dominant single gene disease. Most of the changes of gene loci can be found by whole exon gene sequencing, and the clinical symptoms and patient survival can be improved by specific site-to-site drug treatment. The other manifestations of this patient population are not remarkable. After the application of common drugs, the toxicity and side effects can be limiting. In addition to other common clinical manifestations, we found that the only unique manifestation of this patient was hypertensive crisis. Following multidisciplinary diagnosis and treatment (MDT), we decided to first control hypertension to alleviate the acute and critical patients. However, after controlling the hypertensive crisis, we unexpectedly found that the clinical symptoms of the patients had been significantly improved. Therefore, we concluded that the use of antihypertensive drugs can treat erythematous limb pain with the clinical manifestation of hypertensive crisis. Here, we describe a typical PEM disease, primary clinical features, diagnosis and treatment.MethodsMedical records of an 8-year-old boy with PEM were analyzed retrospectively, which included clinical characteristics, follow-up information, and SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9) gene analysis.ResultsThe 8-year-old boy had complained of abnormal paresthesia in his feet and ankles with burning sensation and pain for 2 years. The skin of both lower legs was red and underwent ichthyosis and lichenification. Genetic analysis confirmed the existence of a SCN9A gene mutation. The symptoms were gradually improved by treating with intravenous drip and oral administration of nitroglycerin to slow his heart rhythm.ConclusionPrimary erythrocytic is characterized by skin ulceration, redness, elevated temperature, and severe burning pain primarily in both lower extremities. PEM can be diagnosed by genetic analysis. As this case demonstrates, treating with nitroglycerin as the drug of choice to control the hypertensive crisis significantly improved the symptoms of PEM and hypertension in this patient.
Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, a Potential Oral Drug Candidate for COVID-19 Treatment
Authors: Wang Amy Q. , Hagen Natalie R. , Padilha Elias C. , Yang Mengbi , Shah Pranav , Chen Catherine Z. , Huang Wenwei , Terse Pramod , Sanderson Philip , Zheng Wei , Xu Xin 
Published: August 2022

Preclinical pharmacokinetics (PK) andIn VitroADME properties of GS-441524, a potential oral agent for the treatment of Covid-19, were studied. GS-441524 was stablein vitroin liver microsomes, cytosols, and hepatocytes of mice, rats, monkeys, dogs, and humans. The plasma free fractions of GS-441524 were 62–78% across all studied species. Thein vitrotransporter study results showed that GS-441524 was a substrate of MDR1, BCRP, CNT3, ENT1, and ENT2; but not a substrate of CNT1, CNT2, and ENT4. GS-441524 had a low to moderate plasma clearance (CLp), ranging from 4.1 mL/min/kg in dogs to 26 mL/min/kg in mice; the steady state volume distribution (Vdss) ranged from 0.9 L/kg in dogs to 2.4 L/kg in mice after IV administration. Urinary excretion appeared to be the major elimination process for GS-441524. Following oral administration, the oral bioavailability was 8.3% in monkeys, 33% in rats, 39% in mice, and 85% in dogs. The PK and ADME properties of GS-441524 support its further development as an oral drug candidate.
Sappanone a prevents diabetic kidney disease by inhibiting kidney inflammation and fibrosis via the NF-κB signaling pathway
Authors: Wang Zhe , Chen Zhida , Wang Xinyi , Hu Yepeng , Kong Jing , Lai Jiabin , Li Tiekun , Hu Bibi , Zhang Yikai , Zheng Xianan , Liu Xiaoxian , Wang Shengyao , Ye Shu , Zhou Qiao , Zheng Chao 
Published: August 2022

Background: Low grade of sterile inflammation plays detrimental roles in the progression of diabetic kidney disease (DKD). Sappanone A (SA), a kind of homoisoflavanone isolated from the heartwood of Caesalpinia sappan, exerts anti-inflammatory effects in acute kidney injury. However, whether SA has beneficial effects on diabetic kidney disease remains further exploration.Methods and Results: In the present study, uninephrectomized male mice were treated with Streptozotocin (STZ, 50 mg/kg) for five consecutive days to induce diabetes. Next, the diabetic mice were administered orally with SA (10, 20, or 30 mg/kg) or vehicle once per day. Our results showed that STZ treatment significantly enhanced damage in the kidney, as indicated by an increased ratio of kidney weight/body weight, elevated serum creatinine and blood urea nitrogen (BUN), as well as increased 24-h urinary protein excretion, whereas SA-treated mice exhibited a markedly amelioration in these kidney damages. Furthermore, SA attenuated the pathological changes, alleviated fibrotic molecules transforming growth factor-β1 (TGF-β1) and Collagen-IV (Col-IV) production, decreased inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) expression in STZ-treated mice. Similarly, in glomerular mesangial cells, SA pretreatment decreased high glucose (HG)-induced proliferation, inflammatory cytokines excretion, and fibrotic molecules expression. Mechanistically, SA decreased the expression of nuclear factor kappa B (NF-κB) and restored the expression of total NF-κB inhibitor alpha (IκBα) both in vivo and in vitro.Conclusion: Our data suggest that SA may prevent diabetes-induced kidney inflammation and fibrosis by inhibiting the NF-κB pathway. Hence, SA can be potential and specific therapeutic value in DKD.
The influence of blue light on sleep, performance and wellbeing in young adults: A systematic review
Authors: Silvani Marcia Ines , Werder Robert , Perret Claudio 
Published: August 2022

Introduction: Blue light from electronic devices has a bad reputation. It has a wavelength which may influence our circadian rhythm and cause bad sleep. But there are other aspects of blue light exposure which are often overlooked, for example, it may influence performance and wellbeing. However, few resources summarize its effects systematically. Therefore, the goal of this systematic review was to distil the present evidence on blue light exposure and its influence on sleep, performance and wellbeing and discuss its significance for athletes.Methods: The databases that were searched were Cochrane, Embase, Pubmed, Scopus, and Virtual Health Library. The studies included investigated the influence of blue light exposure on either sleep, performance, wellbeing or a combination of those parameters on healthy humans. Quality assessment was done based on the quantitative assessment tool “QualSyst.”Results: Summarizing the influence of blue light exposure, the following results were found (expressed as proportion to the number of studies investigating the particular parameter): Fifty percent of studies found tiredness to be decreased. One fifth of studies found sleep quality to be decreased and one third found sleep duration to be decreased. Half of the studies found sleep efficacy to be decreased and slightly less than half found sleep latency to be increased. More than one half of the studies found cognitive performance to be increased. Slightly more than two thirds found alertness to be increased and reaction time to be decreased. Slightly less than half of the studies found wellbeing to be increased.Conclusion: Blue light exposure can positively affect cognitive performance, alertness, and reaction time. This might benefit sports reliant on team-work and decision-making and may help prevent injury. Blue light might also have negative effects such as the decrease in sleep quality and sleep duration, which might worsen an athlete’s physical and cognitive performance and recovery. Further research should explore if blue light can improve sleep, performance and wellbeing to significantly benefit athletic performance.
Differences in fear response strategy and stress susceptibility amongst four different commercial layer strains reared cage free
Authors: Brown Austin A. , Sobotik Eric B. , House Gabrielle M. , Nelson Jill R. , Archer Gregory S. 
Published: August 2022

Different commercial lines of laying hens may show varying levels of fearfulness in response to stressful events or situations. It is important to understand the differences in fear response and stress susceptibility. In this study, four commercial laying hen lines reared from hatch to 32 weeks of age in a cage free system Strains consisted of a brown egg laying line (Hyline Brown; HB) and three white egg laying lines (W36, W80, and LSL). Sixty hens from each strain were used. Each hen was assessed for fearfulness using the following tests: isolation (ISO), emergence (EMG), inversion (INV), and tonic immobility (TI). Stress was assessed based on physical asymmetry (ASYM), corticosterone (CORT) concentrations, and heterophil:lymphocyte ratio (HL). At 3 weeks of age, the W80 birds exhibited more vocalizations during ISO and a shorter duration to emerge than other lines except the HB birds during EMG. Conversely the W36 birds had fewer vocalizations during ISO and emerged quicker than other birds except the LSL during EMG. At 16 weeks of age, the LSL and the W36 bird demonstrated greater fear in TI than the HB. At 30 weeks of age, the observed fear response strategies of each strain changed from previous age and differences were observed between lines (p&lt; 0.05). At both 16 and 30 weeks of age the HB birds had the highest (p&lt; 0.05) stress indicators (CORT, HL, and ASYM). Furthermore, they had a higher CORT after acute stressor (p&lt; 0.05). Commercial lines of laying hens show clear variation in their stress response strategy and stress susceptibility. Brown egg laying hens tend to actively avoid perceived threats whereas white egg laying hens use passive avoidance. Brown egg laying hens also have higher levels in the measures of stress susceptibility than white egg laying hens. Understanding of individual strain response to fearful stimuli and other stressors is important knowledge to appropriately determine welfare differences between strains of layers as the baseline measures are often different.
Childhood adversity and cognitive impairment in later life
Authors: Xiang Xiaoling , Cho Joonyoung , Sun Yihang , Wang Xiafei 
Published: August 2022

ObjectivesThis study examined the association between childhood adversity and cognitive impairment in later life and explored the potential moderation effect of gender and race.MethodsThe study sample included 15,133 participants of the Health and Retirement Study (1998–2016 surveys) who had complete data on key study measures and were more than 50. The outcome variable is a dichotomous indicator of cognitive impairment as assessed by the Telephone Interview for Cognitive Status for self-respondents and the 16-item Informant Questionnaire on Cognitive Decline in the Elderly for proxies. A total of six childhood adversity indicators included grade retention, parental substance abuse, physical abuse, trouble with the police, moving due to financial hardship, and receipt of help due to financial hardship in early life. The estimation of the association between childhood adversity and cognitive impairment involved Cox proportional hazards regression. Results: Grade retention had the largest effect on incident cognitive impairment (HR = 1.3, 95% CI = 1.23–1.38, p &lt; 0.001), followed by physical abuse by a parent (HR = 1.10, 95% CI = 1.00–1.20, p = 0.001). The impact of grade retention was more detrimental to women than men (interaction term HR = 0.89, 95% CI = 0.80–1.00, p = 0.048, female as the reference). Parental substance abuse was associated with a lower risk of incident cognitive impairment for most racial groups (HR = 0.89, 95% CI = 0.83–0.95, p = 0.001), but this association was reversed in “non-Hispanic other” race, consisting mainly of Asians (HR = 1.54, 95% CI = 1.05–2.26, p = 0.025).DiscussionSome aspects of childhood adversity continue to harm cognitive functioning in later life, while some events may have the opposite effect, with evidence of heterogeneity across gender and race.
The efficacy and safety of exercise and physical activity on psychosis: A systematic review and meta-analysis
Authors: Ziebart Christina , Bobos Pavlos , MacDermid Joy C. , Furtado Rochelle , Sobczak Daniel J. , Doering Michele 
Published: August 2022

BackgroundTreatment of psychosis typically focuses on medication, but some of these medications can have unintended side effects, exercise has global health benefits, with minimal side effects. The purpose of this systematic review and meta-analysis is to investigate the effectiveness and safety of exercise and physical activity on psychotic symptoms, in people with psychosis when compared to usual care, in a hospital setting.MethodsA systematic electronic search of the literature was performed in June 2022, in PubMed, Scopus, and PsychINFO with no date restrictions. We included randomized trials (RCTs) with patients with psychosis that received an exercise intervention within a hospital setting. The primary outcome of interest was Positive and Negative Symptom Severity Scale (PANSS) overall score. Secondary outcomes were adverse or serious adverse events.ResultsA total of 24 trials were included in this systematic review, with 9 included in the meta-analysis, including 1,426 participants. Aerobic had more pronounced effects when compared to usual care in PANSS positive (−0.23, 95% CI −0.53 to 0.07), negative (−0.38, 95% CI −0.65 to −0.10), general (−0.42, 95% CI −0.71 to −0.13) and overall scores (−0.25, 95% CI −0.52 to 0.03). Yoga when compared to usual care had no difference in PANSS subscale and overall scores. We found no difference on relapsing of psychiatric symptoms or somatic hospitalization when we compared aerobic or yoga to usual care (Risk Ratio, 1.12 95% CI 0.44–2.81).ConclusionAerobic activity as an exercise modality in a hospital setting can be effective in decreasing negative and general psychosis symptom severity scores compared to usual care, however, it was uncertain if the effects were clinically important. More trials are needed to confirm the clinically benefit of aerobic exercise.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021224997].