bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Oncogene Function of GOLPH3 and Correlated Regulatory Network in Lung Adenocarcinoma
Authors: Zhang Tong , Wang Yue , Chen Yangyang , Jin Shuo , Gao Ying , Zhang Dan , Wu Yonghui 
Published: August 2021

BackgroundGolgi phosphoprotein 3 (GOLPH3) is an oncoprotein localized in the Golgi apparatus. Abnormal GOLPH3 expression is potentially related to carcinogenesis. However, the potential biological regulation network of GOLPH3 in lung adenocarcinoma (LUAD) remains to be determined.MethodsExpression of GOLPH3 was identified in LUAD via TIMER, Oncomine, Lung Cancer Explorer (LCE), Human Protein Atlas (HPA), and UALCAN database. Survival analysis was performed using the Kaplan–Meier plotter. GOLPH3 alterations were analyzed through cBioPortal. LinkedOmics was used to perform functional analysis and predict interacted targets. The protein–protein interaction network was constructed by GeneMANIA. In addition, candidate miRNAs and lncRNAs targeting GOLPH3 were generated to construct competing endogenous RNA (ceRNA) network, and survival analysis of ceRNA was performed using LnCeVar. The mRNA or protein expression of TUG1, miR-142-5p, and GOLPH3 in Beas-2B and LUAD cells was verified using qPCR or Western blotting. CCK-8 assay, wound healing assay, and transwell assay were used to detect the ability of cell proliferation, migration, and invasion.ResultsOverexpression of GOLPH3 was identified in LUAD. UALCAN analysis showed that upregulated GOLPH3 was linked to different pathological features of LUAD patients. Importantly, high GOLPH3 expression indicated a negative correlation with the first progression (FP) in LUAD patients. GOLPH3 alterations were also found. Moreover, co-expressed genes with GOLPH3 were analyzed; and they were involved in ribosome and oxidative phosphorylation pathways. Functional network analysis indicated GOLPH3 regulated T-cell receptor signaling pathway and interferon signaling pathway with kinase and transcription factor targets. Notably, TUG1/miR-142-5p/GOLPH3 affected overall survival of LUAD patients. GOLPH3 expression was decreased in the cells with overexpression of miR-142-5p and TUG1 knockdown. GOLPH3 reduction inhibited cell proliferation, migration, and invasion.ConclusionsUpregulation of GOLPH3 has a positive correlation with clinicopathological subtypes and poor FP in LUAD. GOLPH3 promoted LUAD progression. Moreover, TUG1 may act as ceRNA to regulate GOLPH3 expression by competitive binding miR-142-5p.
Prognostic Biomarkers and Immunotherapeutic Targets Among CXC Chemokines in Pancreatic Adenocarcinoma
Authors: Huang Jiacheng , Chen Zhitao , Ding Chenchen , Lin Shengzhang , Wan Dalong , Ren Kuiwu 
Published: August 2021

BackgroundPancreatic cancer is one of the principal causes of tumor-related death worldwide. CXC chemokines, a subfamily of functional chemotactic peptides, affect the initiation of tumor cells and clinical outcomes in several human malignant tumors. However, the specific biological functions and clinical significance of CXC chemokines in pancreatic cancer have not been clarified.MethodsBioinformatics analysis tools and databases, including ONCOMINE, GEPIA2, the Human Protein Atlas, DAVID, GeneMANIA, cBioPortal, STRING, DGidb, MethSurv, TRRUST, SurvExpress, SurvivalMeth, and TIMER, were utilized to clarify the clinical significance and biological functions of CXC chemokine in pancreatic cancer.ResultsExcept for CXCL11/12, the transcriptional levels of other CXC chemokines in PAAD tissues were significantly elevated, and the expression level of CXCL16 was the highest among these CXC chemokines. Our findings also suggested that all of the CXC chemokines were linked to tumor-immune dysfunction involving the abundance of immune cell infiltration, and the Cox proportional hazard model confirmed that dendritic and CXCL3/5/7/8/11/17 were significantly associated with the clinical outcome of PAAD patients. Furthermore, increasing expressions of CXCL5/9/10/11/17 were related to unfavorable overall survival (OS), and only CXCL17 was a prognostic factor for disease-free survival (DFS) in PAAD patients. The expression pattern and prognostic power of CXC chemokines were further validated in the independent GSE62452 dataset. For the prognostic value of single CpG of DNA methylation of CXC chemokines in patients with PAAD, we identified 3 CpGs of CXCL1, 2 CpGs of CXCL2, 2 CpGs of CXCL3, 3 CpGs of CXCL4, 10 CpGs of CXCL5, 1 CpG of CXCL6, 1 CpG of CXCL7, 3 CpGs of CXCL12, 3 CpGs of CXCL14, and 5 CpGs of CXCL17 that were significantly associated with prognosis in PAAD patients. Moreover, the prognostic value of CXC chemokine signature in PAAD was explored and tested in two independent cohort, and results indicated that the patients in the low-risk group had a better OS compared with the high-risk group. Survival analysis of the DNA methylation of CXC chemokine signature demonstrated that PAAD patients in the high-risk group had longer survival times.ConclusionsThese findings reveal the novel insights into CXC chemokine expression and their biological functions in the pancreatic cancers, which might serve as accurate prognostic biomarkers and suitable immunotherapeutic targets for patients with pancreatic cancer.
Development of a Nomogram for Moderate-to-Severe Bronchopulmonary Dysplasia or Death: Role of N-Terminal Pro-brain Natriuretic Peptide as a Biomarker
Authors: Song Min , Lei Mengyuan , Luo Chenghan , Shi Zanyang , Cheng Xinru , Ding Wenqian , Cao Wenjun , Zhang Jingdi , Ge Jian , Wang Mengmeng , Xia Peige , Mao Fengxia , Wang Li , Zhang Qian 
Published: August 2021

Objectives: This study aimed to explore the clinical value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting moderate-to-severe bronchopulmonary dysplasia (BPD)/death, and to establish an effective clinical predictive nomogram.Methods: We retrospectively analyzed very low birth weight infants (VLBWs) with gestational age ≤ 32 weeks. The NT-proBNP values were determined on the 1st, 3rd, 7th, 14th, 21st, and 28th days after birth. The correlation between NT-proBNP level and moderate-to-severe BPD/death was evaluated. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction ability. Then, we used multivariable logistic regression to build the prediction model and nomogram, and calibration of the model was assessed by calibration curve.Results: In total, 556 VLBWs were involved, among whom 229 developed BPD (mild: n = 109; moderate: n = 68; severe: n = 52) and 18 died. The NT-proBNP level in the moderate-to-severe BPD/death group was significantly higher than that in the no-to-mild BPD group from the 3rd to 28th day (P &lt; 0.001). When the natural logarithm of the serum NT-ProBNP level increased by 1 unit at day 7 (±2 days) of life, the risk of moderate and severe BPD/death was the highest (OR = 3.753; 95% CI: 2.984~4.720), and ROC analysis identified an optimal cutoff point of 3360 ng/L (sensitivity: 80.0%; specificity: 86.2%; AUC: 0.861). After adjusting for confounding factors, the level of NT-proBNP at day 7 (±2 days) of life still had important predictive value for the development of moderate-to-severe BPD/death, significantly improving the predictive ability of the model.Conclusion: The level of NT-proBNP at day 7 (±2 days) of life can be used as an early promising biomarker for VLBWs to develop moderate-to-severe BPD/death. We constructed an early predictive nomogram to help clinicians identify high-risk populations.
Validation of Point-of-Care Ultrasound to Measure Perioperative Edema in Infants With Congenital Heart Disease
Authors: Persson Jessica N. , Holstein Jacqueline , Silveira Lori , Irons Aimee , Rajab Taufiek Konrad , Jaggers James , Twite Mark D. , Scahill Carly , Kohn Mary , Gold Christine , Davidson Jesse A. 
Published: August 2021

Purpose: Fluid overload is a common post-operative issue in children following cardiac surgery and is associated with increased morbidity and mortality. There is currently no gold standard for evaluating fluid status. We sought to validate the use of point-of-care ultrasound to measure skin edema in infants and assess the intra- and inter-user variability.Methods: Prospective cohort study of neonates (≤30 d/o) and infants (31 d/o to 12 m/o) undergoing cardiac surgery and neonatal controls. Skin ultrasound was performed on four body sites at baseline and daily post-operatively through post-operative day (POD) 3. Subcutaneous tissue depth was manually measured. Intra- and inter-user variability was assessed using intraclass correlation coefficient (ICC).Results: Fifty control and 22 surgical subjects underwent skin ultrasound. There was no difference between baseline surgical and control neonates. Subcutaneous tissue increased in neonates starting POD 1 with minimal improvement by POD 3. In infants, this pattern was less pronounced with near resolution by POD 3. Intra-user variability was excellent (ICC 0.95). Inter-user variability was very good (ICC 0.82).Conclusion: Point-of-care skin ultrasound is a reproducible and reliable method to measure subcutaneous tissue in infants with and without congenital heart disease. Acute increases in subcutaneous tissue suggests development of skin edema, consistent with extravascular fluid overload. There is evidence of skin edema starting POD 1 in all subjects with no substantial improvement by POD 3 in neonates. Point-of-care ultrasound could be an objective way to measure extravascular fluid overload in infants. Further research is needed to determine how extravascular fluid overload correlates to clinical outcomes.
Dl-3-n-Butylphthalide Ameliorates Diabetic Nephropathy by Ameliorating Excessive Fibrosis and Podocyte Apoptosis
Authors: Xu Jingyu , Tang Zonghao , He Youwu , Cai Shufang , Wang Beini , Zhang Susu , Wu Man , Qian Kai , Zhang Kailun , Chai Bo , Chen Guorong , Xu Ke , Ji Hao , Xiao Jian , Wu Yanqing 
Published: August 2021

Diabetic nephropathy (DN) is a common diabetes associated complication. Thus, it is important to understand the pathological mechanism of DN and find the appropriate therapeutic strategy for it. Dl-3-n-Butylphthalide (DL-NBP) has anti-inflammatory and antioxidant effects, and been widely used for the treatment of stroke and cardiovascular diseases. In this study, we selected three different doses (20, 60, and 120 mg⋅kg−1 d−1) of DL-NBP and attempted to elucidate its role and molecular mechanism underlying DN. We found that DL-NBP, especially at the dose of 60 or 120 mg⋅kg−1 d−1, could significantly ameliorate diabetes-induced elevated blood urea nitrogen (BUN) and creatinine level, and alleviate renal fibrosis. Additionally, the elevated expressions of collagen and α-smooth muscle actin (α-SMA) in the kidney from db/db mice were found to be significantly suppressed after DL-NBP treatment. Furthermore, mechanistic studies revealed that DL-NBP inhibits pro-inflammatory cytokine levels, thereby ameliorating the development of renal fibrosis. Moreover, we found that DL-NBP could not only reduce the endoplasmic reticulum stress (ERS), but also suppress activation of the renin-angiotensin system to inhibit vascular endothelial growth factor (VEGF) level, which subsequently reduces the podocyte apoptosis in kidney of db/db mice. In a word, our findings suggest that DL-NBP may be a potential therapeutic drug in the treatment of DN.
The Effects of Repetitive Use and Pathological Remodeling on Channelrhodopsin Function in Cardiomyocytes
Authors: Ördög Balázs , Teplenin Alexander , De Coster Tim , Bart Cindy I. , Dekker Sven O. , Zhang Juan , Ypey Dirk L. , de Vries Antoine A. F. , Pijnappels Daniël A. 
Published: August 2021

Aim: Channelrhodopsins (ChRs) are a large family of light-gated ion channels with distinct properties, which is of great importance in the selection of a ChR variant for a given application. However, data to guide such selection for cardiac optogenetic applications are lacking. Therefore, we investigated the functioning of different ChR variants in normal and pathological hypertrophic cardiomyocytes subjected to various illumination protocols.Methods and Results: Isolated neonatal rat ventricular cardiomyocytes (NRVMs) were transduced with lentiviral vectors to express one of the following ChR variants: H134R, CatCh, ReaChR, or GtACR1. NRVMs were treated with phenylephrine (PE) to induce pathological hypertrophy (PE group) or left untreated [control (CTL) group]. In these groups, ChR currents displayed unique and significantly different properties for each ChR variant on activation by a single 1-s light pulse (1 mW/mm2: 470, 565, or 617 nm). The concomitant membrane potential (Vm) responses also showed a ChR variant-specific profile, with GtACR1 causing a slight increase in average Vm during illumination (Vplateau: −38 mV) as compared with a Vplateau &gt; −20 mV for the other ChR variants. On repetitive activation at increasing frequencies (10-ms pulses at 1–10 Hz for 30 s), peak currents, which are important for cardiac pacing, decreased with increasing activation frequencies by 17–78% (p &lt; 0.05), while plateau currents, which are critical for arrhythmia termination, decreased by 10–75% (p &lt; 0.05), both in a variant-specific manner. In contrast, the corresponding Vplateau remained largely stable. Importantly, current properties and Vm responses were not statistically different between the PE and CTL groups, irrespective of the variant used (p &gt; 0.05).Conclusion: Our data show that ChR variants function equally well in cell culture models of healthy and pathologically hypertrophic myocardium but show strong, variant-specific use-dependence. This use-dependent nature of ChR function should be taken into account during the design of cardiac optogenetic studies and the interpretation of the experimental findings thereof.
A Global Survey on Changes in the Supply, Price, and Use of Illicit Drugs and Alcohol, and Related Complications During the 2020 COVID-19 Pandemic
Authors: Farhoudian Ali , Radfar Seyed Ramin , Mohaddes Ardabili Hossein , Rafei Parnian , Ebrahimi Mohsen , Khojasteh Zonoozi Arash , De Jong Cornelis A. J. , Vahidi Mehrnoosh , Yunesian Masud , Kouimtsidis Christos , Arunogiri Shalini , Hansen Helena , Brady Kathleen T. 
Published: August 2021

Background and Aims: COVID-19 has infected more than 77 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders (SUDs). Quarantines, travel bans, regulatory changes, social distancing, and “lockdown” measures have affected drug and alcohol supply chains and subsequently their availability, price, and use patterns, with possible downstream effects on presentations of SUDs and demand for treatment. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine (ISAM) network in order to understand the status of substance-use patterns during the current pandemic.Design: Cross-sectional survey.Setting: Worldwide.Participants: Starting on April 4, 2020 during a 5-week period, the survey received 185 responses from 77 countries.Measurements: To assess addiction medicine professionals' perceived changes in drug and alcohol supply, price, use pattern, and related complications during the COVID-19 pandemic.Findings: Participants reported (among who answered “decreased” or “increased”) a decrease in drug supply (69.0%) and at the same time an increase in price (95.3%) globally. With respect to changes in use patterns, an increase in alcohol (71.7%), cannabis (63.0%), prescription opioids (70.9%), and sedative/hypnotics (84.6%) use was reported, while the use of amphetamines (59.7%), cocaine (67.5%), and opiates (58.2%) was reported to decrease overall.Conclusions: The global report on changes in the availability, use patterns, and complications of alcohol and drugs during the COVID-19 pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic (and probable future ones) in order to minimize risks to people with SUD.
Common Mental Disorders Among Informal Primary Caregivers of Adults With Mental Illness During the Coronavirus Disease 2019 Epidemic in Eastern Ethiopia: A Cross-Sectional Study
Authors: Abdeta Tilahun , Desalegn Defaru 
Published: August 2021

Background: Coronaviruses (CoVs) are emerging respiratory viruses and cause illnesses ranging from the common cold to severe acute respiratory syndrome (SARS). Informal primary caregivers of individuals with mental illness were special populations suffering from both the burden of caring for mentally ill individuals and the danger of the Coronavirus disease 2019 (Covid-19) epidemic.Objective: The objective of the study was to assess the prevalence and associated factors of common mental disorders (CMDs) among the informal primary caregivers of adults with mental illness during the Covid-19 epidemic.Methods: A hospital-based cross-sectional study design was conducted from July 1 to 30, 2020. A systematic random sampling technique was used to get samples of informal primary caregivers. Data were analyzed by bivariable and multivariable logistic regression analysis. In the final model, variables having a p-value &lt; 0.05 were declared as associated with CMDs.Result: Out of a total of 218 informal primary caregivers, 215 responded to this study. The prevalence of CMDs was 40.5% [95% confidence interval (CI) = 36.66, 44.3%] among informal primary caregivers. Being female informal primary caregivers [adjusted odds ratios (AOR) 1.98, 95% CI = 1.05, 3.76], being student informal primary caregivers (AOR 5.8, 95% CI: 1.2, 28.4), caring patients with psychosis (AOR 3.33, 95% CI: 1.12, 9.92) and caring patients with bipolar disorder (AOR 3.12, 95% CI: 1.35, 7.23) were significantly associated with CMDs.Conclusion: Our study cannot show the causal relationship due to its cross-sectional study design nature. However, this study showed relatively higher prevalence of CMDs among informal primary caregivers of adults with any mental illness during the Covid-19 epidemics relative to pre-Covid-19 times. Being a female caregiver, being a student caregiver, and caring for adults with psychosis and bipolar disorder were factors associated with CMDs. Attention should be given, and essential psychosocial care should be provided, to maintain the mental health of informal primary caregivers of individuals with mental illness especially during the Covid-19 pandemic.
Factors Associated With HIV-Related Stigma Toward People Living With HIV Among Nurses in Liangshan Yi Autonomous Prefecture, China: A Cross-Sectional Study
Authors: Yin Yao , Chen Angela Chia-Chen , Wan Shaoping , Chen Hong 
Published: August 2021

Background: The Liangshan Yi Autonomous Prefecture has one of the most serious human immunodeficiency virus (HIV) epidemics in China. Evidence shows HIV-related stigma toward people living with HIV (PLWH) among nurses impedes HIV prevention and treatment. However, only limited research about HIV-related stigma toward PLWH from the perspective of nurses in Liangshan has been conducted.Objective: This study aimed to assess HIV-related stigma toward PLWH among nurses and determine factors associated with it in Liangshan, China.Design: We conducted a cross-sectional survey using a stratified, random cluster sampling method.Participants: Registered nurses (N = 1,248; primary hospitals = 102, secondary hospitals = 592, tertiary hospitals = 554) who were aged 18 or older, worked in the selected hospitals for at least 6 months, and consented to participate were recruited.Methods: All participants completed an anonymous online survey measuring sociodemographic characteristics, HIV-related stigma and HIV knowledge. We used multiple stepwise regression analysis to examine factors associated with HIV-related stigma toward PLWH among these nurses.Results: The mean score of HIV-related stigma among nurses was 50.7 (SD = 8.3; range 25–78). Nurses who were more experienced, had higher levels of education, and were working in tertiary hospitals reported higher level of HIV-related stigma. Those who had better HIV knowledge, reported a willingness to receive HIV-related training, were working in areas that had a high prevalence of HIV, had prior experience working in AIDS specialized hospitals, and worked in hospitals that had policies to protect PLWH showed a lower level of HIV-related stigma toward PLWH.Conclusions: Our findings suggested that providing culturally congruent education and training about HIV and care, and having hospitals that promoted policies protecting PLWH, may reduce HIV-related stigma toward PLWH among nurses in China.
The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia
Authors: Li Xue , Fan Xiaoduo , Yuan Xiuxia , Pang Lijuan , Hu Shaohua , Wang Yunpeng , Huang Xufeng , Song Xueqin 
Published: August 2021

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's &lt; 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's &lt; 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.