bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival nomogram and relapse-related factors of clear cell sarcoma of the kidney: A study based on published patients
Authors: Zhang Yuan , Chu Qian , Ma Yue , Miao Chunshu , Diao Juan-juan 
Published: September 2022

BackgroundRarity limits the breadth of study on clear cell sarcoma of the kidney (CCSK). There is currently no predictive model that quantifies the overall survival (OS) of CCSK and a few large sample-based analysis of relapse-related factors.MethodsPatients were collected both from the Surveillance, Epidemiology, and End Results (SEER) database and case report articles extracted from the global online document database to form 2 groups. The first was the OS group, which was used to build and verify the nomogram for predicting the OS of CCSK. Independent predictors of OS were screened by Cox regression analysis to develop the nomogram. Nomogram accuracy was assessed by C-index, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) curves. In addition, the difference in OS between receiving radiotherapy or not in stage I patients was analyzed by the Chi-square test. The second was the relapse group, which was used to analyze the relapse-related factors by Cox regression analysis and the Kaplan–Meier method with the log-rank test.Result256 patients were included in the OS group. The stage, chemotherapy, and radiotherapy were independent OS-related factors of CCSK, and the nomogram for predicting the OS of CCSK was established based on them. The results of the C-index, ROC, calibration, and DCA curves showed that the nomogram has good discrimination, accuracy, and clinical profitability. The Chi-squared test showed no significant difference in OS with receiving radiotherapy or not in stage I patients. The relapse group included 153 patients, of which 60 relapsed. The univariate Cox regression analysis showed no correlation between radiotherapy and relapse. The multivariate Cox regression analysis showed that stage and surgery/chemotherapy sequence were the independent factors for relapse. The log-rank test of seven chemotherapeutic drugs showed that etoposide (E), cyclophosphamide (C), vincristine (V), and doxorubicin (D) (all P &lt; 0.05) had significant differences in preventing relapse, and then drew the relapse-free survival curves of these four drugs.ConclusionOur nomogram accurately quantified the OS of CCSK. There was no significant difference in OS between receiving radiotherapy or not in stage I patients. Stage, surgery/chemotherapy sequence, and the use of ECVD were relapse-related factors. Radiotherapy had no significant contribution to preventing relapse.
WZB117 enhanced the anti-tumor effect of apatinib against melanoma via blocking STAT3/PKM2 axis
Authors: Zhang Ren-Shu , Li Zhi-Ke , Liu Jie , Deng Yao-Tiao , Jiang Yu 
Published: September 2022

Background: Melanoma is the most lethal skin malignant tumor with a short survival once stepping into the metastatic status and poses a therapeutic challenge. Apatinib (a tyrosine kinase inhibitor) is a promising antiangiogenic agent for the treatment of metastatic melanoma. However, antiangiogenic monotherapy is prone to acquired drug resistance and has a limited therapeutic effect. The persistence dependence of glycolytic metabolism in antiangiogenic therapy-resistant cells provides evidence that glycolysis inhibitors may enhance the effect of antiangiogenic therapy. So, this study aimed to investigate whether WZB117 (a specific GLUT1 inhibitor) could enhance the anti-tumor effect of apatinib against melanoma and its potential mechanisms.Methods: We investigated the anti-tumor effects of apatinib alone or in combination with WZB117 on human melanoma cell lines (A375 and SK-MEL-28). The MTT assay determined cell viability and the half-maximal inhibitory concentration (IC50). Multiple drug effect/combination indexes (CI) analysis was conducted to assess interactions between apatinib and WZB117. Signal transducer and activator of transcription 3 (STAT3) pathway measured by western blotting and immunofluorescence staining. RNA expression analyses were performed using the reverse transcription-quantitative PCR method.Results: Apatinib and WZB117 showed dose and time-dependent growth inhibitory effects in both melanoma cells. The IC50 of apatinib at 48 h in A375 and SK-MEL-28 cells was 62.58 and 59.61 μM, respectively, while the IC50 of WZB117 was 116.85 and 113.91 μM, respectively. The CI values of the two drugs were 0.538 and 0.544, respectively, indicating a synergistic effect of apatinib combined with WZB117. We also found that glucose consumption and lactate production were suppressed by apatinib plus WZB117 in a dose-dependent manner, paralleled by reducing glycolytic enzyme pyruvate kinase M2 (PKM2). The potential mechanism of the combination was to suppress the phosphorylation of STAT3. Knockdown of STAT3 by siRNA inhibited the expression of PKM2, while the activation of STAT3 by IL-6 increased the expression of PKM2. The effects of IL-6 were attenuated by apatinib combined with WZB117 treatment.Conclusion: WZB117 enhanced the anti-tumor effect of apatinib against melanoma via modulating glycolysis by blocking the STAT3/PKM2 axis, which suggested the combination of apatinib with WZB117 could be a potential therapeutic candidate for melanoma.
Dose- and time-dependent manners of moxifloxacin induced liver injury by targeted metabolomics study
Authors: Hu Ting , Sun Yuan , An Zhuoling 
Published: September 2022

Moxifloxacin is the most widely prescribed antibiotics due to its excellent oral bioavailability and broad-spectrum antibacterial effect. Despite of its popularity, the rare and severe liver injury induced by moxifloxacin is a big concern that cannot be ignored in clinical practice. However, the early warning and related metabolic disturbances of moxifloxacin induced hepatoxicity were rarely reported. In this study, the dose- and time-dependent manners of moxifloxacin induced liver injury were investigated by a targeted metabolomics method. In dose-dependent experiment, three different dosages of moxifloxacin were administered to the rats, including 36 mg kg−1 d−1, 72 mg kg−1 d−1, and 108 mg kg−1 d−1. In time-dependent experiment, moxifloxacin was orally administered to the rats for 3, 7 or 14 consecutive days. Pathological analysis showed that moxifloxacin caused obvious transient hepatotoxicity, with the most serious liver injury occurred in the 7 days continuous administration group. The transient liver injury can be automatically restored over time. Serum levels of liver function related biochemical indicators, including ALT, AST, TBIL, alkaline phosphatase, superoxide dismutase, and malondialdehyde, were also measured for the evaluation of liver injury. However, these indicators can hardly be used for the early warning of hepatotoxicity caused by moxifloxacin due to their limited sensitivity and significant hysteresis. Targeted metabolomics study demonstrated that serum concentrations of fatty acyl carnitines, fatty acids and dehydroepiandrosterone can change dynamically with the severity of moxifloxacin related liver injury. The elevated serum levels of fatty acyl carnitine, fatty acid and dehydroepiandrosterone were promising in predicting the hepatotoxicity induced by moxifloxacin.
Different responses of skeletal muscles to femoral artery ligation-induced ischemia identified in BABL/c and C57BL/6 mice
Authors: Tu Huiyin , Qian Junliang , Zhang Dongze , Barksdale Aaron N. , Wadman Michael C. , Pipinos Iraklis I. , Li Yu-Long 
Published: September 2022

Peripheral arterial disease (PAD) is a common circulatory problem in lower extremities, and the murine ischemic model is used to reproduce human PAD. To compare strain differences of skeletal muscle responses to ischemia, the left femoral artery was blocked by ligation to reduce blood flow to the limb of BALB/c and C57BL/6 mice. After 6 weeks of the femoral artery ligation, the functional and morphological changes of the gastrocnemius muscle were evaluated. BALB/c mice displayed serious muscular dystrophy, including smaller myofibers (524.3 ± 66 µM2), accumulation of adipose-liked tissue (17.8 ± 0.9%), and fibrosis (6.0 ± 0.5%), compared to C57BL/6 mice (1,328.3 ± 76.3 µM2, 0.27 ± 0.09%, and 1.56 ± 0.06%, respectively; p &lt; 0.05). About neuromuscular junctions (NMJs) in the gastrocnemius muscle, 6 weeks of the femoral artery ligation induced more damage in BALB/c mice than that in C57BL/6 mice, demonstrated by the fragment number of nicotinic acetylcholine receptor (nAChR) clusters (8.8 ± 1.3 in BALB/c vs. 2.5 ± 0.7 in C57BL/6 mice, p &lt; 0.05) and amplitude of sciatic nerve stimulated-endplate potentials (EPPs) (9.29 ± 1.34 mV in BALB/c vs. 20.28 ± 1.42 mV in C57BL/6 mice, p &lt; 0.05). More importantly, 6 weeks of the femoral artery ligation significantly weakened sciatic nerve-stimulated skeletal muscle contraction in BALB/c mice, whereas it didn’t alter the skeletal muscle contraction in C57BL/6 mice. These results suggest that the femoral artery ligation in BALB/c mice is a useful animal model to develop new therapeutic approaches to improve limb structure and function in PAD, although the mechanisms about strain differences of skeletal muscle responses to ischemia are unclear.
Cardiovascular and cerebrovascular responses to urodynamics testing after spinal cord injury: The influence of autonomic injury
Authors: Sahota Inderjeet S. , Lucci Vera-Ellen M. , McGrath Maureen S. , Ravensbergen H. J. C. (Rianne) , Claydon Victoria E. 
Published: September 2022

Autonomic dysfunction is a prominent concern following spinal cord injury (SCI). In particular, autonomic dysreflexia (AD; paroxysmal hypertension and concurrent bradycardia in response to sensory stimuli below the level of injury) is common in autonomically-complete injuries at or above T6. AD is currently defined as a &gt;20 mmHg increase in systolic arterial pressure (SAP) from baseline, without heart rate (HR) criteria. Urodynamics testing (UDS) is performed routinely after SCI to monitor urological sequelae, often provoking AD. We, therefore, aimed to assess the cardiovascular and cerebrovascular responses to UDS and their association with autonomic injury in individuals with chronic (&gt;1 year) SCI. Following blood draw (plasma norepinephrine [NE]), continuous SAP, HR, and middle cerebral artery blood flow velocity (MCAv) were recorded at baseline (10-minute supine), during standard clinical UDS, and recovery (10-minute supine) (n = 22, age 41.1 ± 2 years, 15 male). Low frequency variability in systolic arterial pressure (LF SAP; a marker of sympathetic modulation of blood pressure) and cerebral resistance were determined. High-level injury (≥T6) with blunted/absent LF SAP (&lt;1.0 mmHg2) and/or low plasma NE (&lt;0.56 nmol•L−1) indicated autonomically-complete injury. Known electrocardiographic markers of atrial (p-wave duration variability) and ventricular arrhythmia (T-peak–T-end variability) were evaluated at baseline and during UDS. Nine participants were determined as autonomically-complete, yet 20 participants had increased SAP &gt;20 mmHg during UDS. Qualitative autonomic assessment did not discriminate autonomic injury. Maximum SAP was higher in autonomically-complete injuries (207.1 ± 2.3 mmHg) than autonomically-incomplete injuries (165.9 ± 5.3 mmHg) during UDS (p &lt; 0.001). HR during UDS was reduced compared to baseline (p = 0.056) and recovery (p = 0.048) only in autonomically-complete lesions. MCAv was not different between groups or phases (all p &gt; 0.05). Cerebrovascular resistance index was increased during UDS in autonomically-complete injuries compared to baseline (p &lt; 0.001) and recovery (p &lt; 0.001) reflecting intact cerebral autoregulation. Risk for both atrial and ventricular arrhythmia increased during UDS compared to baseline (p &lt; 0.05), particularly in autonomically-complete injuries (p &lt; 0.05). UDS is recommended yearly in chronic SCI but is associated with profound AD and an increased risk of arrhythmia, highlighting the need for continued monitoring during UDS. Our data also highlight the need for HR criteria in the definition of AD and the need for quantitative consideration of autonomic function after SCI.
Prevalence of depression, anxiety and post-traumatic stress in war- and conflict-afflicted areas: A meta-analysis
Authors: Lim Isis Claire Z. Y. , Tam Wilson W. S. , Chudzicka-Czupała Agata , McIntyre Roger S. , Teopiz Kayla M. , Ho Roger C. , Ho Cyrus S. H. 
Published: September 2022

BackgroundWith the rise of fragility, conflict and violence (FCV), understanding the prevalence and risk factors associated with mental disorders is beneficial to direct aid to vulnerable groups. To better understand mental disorders depending on the population and the timeframe, we performed a systematic review to investigate the aggregate prevalence of depression, anxiety and post-traumatic stress symptoms among both civilian and military population exposed to war.MethodsWe used MEDLINE (PubMed), Web of Science, PsycINFO, and Embase to identify studies published from inception or 1–Jan, 1945 (whichever earlier), to 31–May, 2022, to reporting on the prevalence of depression, anxiety and post-traumatic stress symptoms using structured clinical interviews and validated questionnaires as well as variables known to be associated with prevalence to perform meta-regression. We then used random-effects bivariate meta-analysis models to estimate the aggregate prevalence rate.ResultsThe aggregate prevalence of depression, anxiety and post-traumatic stress during times of conflict or war were 28.9, 30.7, and 23.5%, respectively. Our results indicate a significant difference in the levels of depression and anxiety, but not post-traumatic stress, between the civilian group and the military group respectively (depression 34.7 vs 21.1%, p &lt; 0.001; anxiety 38.6 vs 16.2%, p &lt; 0.001; post-traumatic stress: 25.7 vs 21.3%, p = 0.256). The aggregate prevalence of depression during the wars was 38.7% (95% CI: 30.0–48.3, I2 = 98.1%), while the aggregate prevalence of depression post-wars was 29.1% (95% CI: 24.7–33.9, I2 = 99.2%). The aggregate prevalence of anxiety during the wars was 43.4% (95% CI: 27.5–60.7, I2 = 98.6%), while the aggregate prevalence of anxiety post-wars was 30.3% (95% CI: 24.5–36.9, I2 = 99.2%). The subgroup analysis showed significant difference in prevalence of depression, and anxiety between the civilians and military group (p &lt; 0.001).ConclusionThe aggregate prevalence of depression, anxiety and post-traumatic stress in populations experiencing FCV are 28.9, 30.7, and 23.5%, respectively. There is a significant difference in prevalence of depression and anxiety between civilians and the military personnels. Our results show that there is a significant difference in the prevalence of depression and anxiety among individuals in areas affected by FCV during the wars compared to after the wars. Overall, these results highlight that mental health in times of conflict is a public health issue that cannot be ignored, and that appropriate aid made available to at risk populations can reduce the prevalence of psychiatric symptoms during time of FCV.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337486, Identifier 337486.
Acceptance of coronavirus disease 2019 (COVID-19) vaccines among healthcare workers: A meta-analysis
Authors: Wang Linlin , Wang Ye , Cheng Xianbin , Li Xingzhao , Yang Yanyan , Li Jun 
Published: September 2022

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has posed increasing challenges to global health systems. Vaccination against COVID-19 can effectively prevent the public, particularly healthcare workers (HCWs), from being infected by this disease.ObjectivesWe aim to understand the factors influencing HCWs' acceptance of COVID-19 vaccines.MethodsWe searched PubMed, Embase and Web of Science to collect literature published before May 15, 2022, about HCWs' acceptance of COVID-19 vaccines. The Newcastle–Ottawa quality assessment scale was used to assess the risk of bias and the quality of the included studies. We utilized Stata 14.0 software for this meta-analysis with a random-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were reported. This meta-analysis was conducted in alignment with the preferred reporting items for systematic review and meta-analysis (PRISMA) guideline.ResultsOur meta-analysis included 71 articles with 93,508 HCWs involved. The research showed that the acceptance of vaccines had significantly increased among HCWs compared to non-HCWs (OR = 1.91, 95% CI: 1.16–3.12). A willingness to undergo COVID-19 vaccination was observed in 66% (95% CI: 0.61–0.67) of HCWs. Among the HCWs involved, doctors showed a generally increased intention to be vaccinated compared with nurses (OR = 2.22, 95% CI: 1.71–2.89). Additionally, males were found to hold more positive attitudes toward vaccination than females (OR = 1.81, 95% CI: 1.55–2.12). When the effectiveness of COVID-19 vaccines was improved, the vaccination acceptance of HCWs was greatly increased accordingly (OR = 5.03, 95% CI: 2.77–9.11). The HCWs who were willing to vaccinate against seasonal influenza showed an increased acceptance of COVID-19 vaccines (OR = 3.52, 95% CI: 2.34–5.28). Our study also showed that HCWs who were willing to be vaccinated against COVID-19 experienced a reduced rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (OR = 0.78, 95% CI: 0.66–0.92).ConclusionsOur analysis revealed that the five factors of occupation, gender, vaccine effectiveness, seasonal influenza vaccines, and SARS-CoV-2 infection presumably affected the acceptance of COVID-19 vaccines among HCWs. It is essential to boost the confidence of HCWs in COVID-19 vaccines for the containment of the epidemic.
Cost of health inequality to the NHS in Wales
Authors: Kadel Rajendra , Allen James , Darlington Oliver , Masters Rebecca , Collins Brendan , Charles Joanna M. , Asaria Miqdad , Dyakova Mariana , Bellis Mark , Cookson Richard 
Published: September 2022

BackgroundForty years from the seminal work of Welsh GP Julian Tudor Hart on the Inverse Care Law, inequalities in health and healthcare remain deeply embedded in Wales. There is a wider gap (over 17 years) in healthy life expectancy between people living in the most and least deprived neighborhoods in Wales. This health inequality is reflected in additional healthcare use. In this study we estimate the cost of inequality associated with this additional healthcare use to the publicly funded National Health Service (NHS) in Wales.MethodsWe retrieved administrative data on all NHS inpatient admissions, outpatient and accident and emergency attendances in Wales between April 2018 and March 2019 from Digital Health and Care Wales (DHCW). Hospital service use data were translated to costs using Healthcare Resource Group (HRG) and health service specific unit cost data and linked with area level mid-year population and deprivation indices in order to calculate the healthcare costs associated with socioeconomics deprivation.ResultsInequality in healthcare use between people from more and less deprived neighborhoods was associated with an additional cost of £322 million per year to the NHS in Wales, accounting for 8.7% of total NHS hospital expenditure in the country. Emergency inpatient admissions made up by far the largest component of this additional cost contributing £247.4 million, 77% of the total. There are also substantial costs of inequality for A&amp;E attendances and outpatient visits, though not maternity services. Elective admissions overall have a negative cost of inequality, since among men aged 50–75 and women aged 60–70, elective utilization is actually negatively associated with deprivation.ConclusionThere are wide inequalities in health and healthcare use between people living in more deprived neighborhoods and those living in less deprived neighborhoods in Wales. Tackling health inequality through a combination of health promotion and early intervention policies targeted toward deprived communities could yield substantial improvement in health and wellbeing, as well as savings for the Welsh NHS through reduced use of emergency hospital care.
Production of microalgae-derived exo-polygalacturonase for fruit juice clarification
Authors: Uzuner Sibel , Evrendilek Gulsun Akdemir , Kurhan Sebnem 
Published: September 2022

Due to the growing demand for commercial enzymes derived from renewable and sustainable resources with higher efficacy, algal biomass has gained more attention. Thus, the production of exo-polygalacturonase (PGase) from Bacillus subtilis under submerged fermentation (SmF) using algal feedstocks as a carbon source in fermentation medium and its potential use for the clarification of apple and carrot juices with the optimization of the enzyme loading, pH, and time using Box–Behnken response surface methodology (RSM) were prompted. The maximum PGase activity of 510.61 ± 7.86 U/L was achieved at pH 5.0 after 48 h at 40°C using 0.5% (w/v) pectin, 0.1% (w/v) yeast extract, 0.02% (w/v) MgSO47H2O, 0.02% (w/v) K2HPO4, 0.3% (w/v) glucose, and 0.583% (w/v) microalgae hydrolysate as a fermentation medium. PGase production without glucose was favored by SmF with a shake flask working volume of 100 ml (248.90 ± 4.58 U/L) as compared to a bioreactor with a working volume of 1 L (192.99 ± 0.84) for 48 h. Both carrot and apple juices were treated with the crude PGase (248.9 U/L) at different concentrations (0.1–0.5%), temperature (30–50°C), and time (30–120 min), and the maximal clarification conditions were obtained as 0.3% (w/v) enzyme concentration at 50°C for 30 min exposure time. This study revealed that microalgae-derived PGase in crude form could be effectively used for clarification of the juices.