bluuebunny/crossref_metadata_2025_split huggingface dataset:
Setanaxib (GKT137831) Ameliorates Doxorubicin-Induced Cardiotoxicity by Inhibiting the NOX1/NOX4/Reactive Oxygen Species/MAPK Pathway
Authors: Zheng Hui , Xu Nannan , Zhang Zihao , Wang Fen , Xiao Jie , Ji Xiaoping 
Published: April 2022

Background: Doxorubicin (DOX)-induced cardiotoxicity is a highly concerning issue, and the mechanism by which DOX induces cardiotoxicity is likely to be multifactorial. NADPH oxidase (NOX) is associated with DOX-induced cardiotoxicity. Setanaxib (GKT137831), a preferential direct inhibitor of NOX1 and NOX4, can delay or prevent the progression of many cardiovascular disorders by inhibiting reactive oxygen species (ROS) generation. In this study, we investigated the role of GKT137831 in ameliorating DOX-induced cardiotoxicity and the potential mechanisms of its action.Methods and Results: The mice model of cardiotoxicity induced by DOX was established, and GKT137831 treatment was performed at the same time. Neonatal rat cardiomyocytes (NRCMs) were treated with DOX or GKT137831 for in vitro experiments. We found that DOX administration impaired cardiac function in vivo, reflected by decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS%). DOX also impaired the viability of NRCMs in vitro. In addition, DOX increased the levels of NOX1 and NOX4 expression and ROS production and the cardiomyocyte apoptosis rate, both in vivo and in vitro. GKT137831 improved cardiac function, as indicated by the increased LVEF and FS%. In vitro, GKT137831 improved NRCM viability. It also decreased ROS production and the cardiomyocyte apoptosis rate. Apoptotic indices, such as cleaved PARP (c-PARP), cleaved caspase 3 (CC3) and BAX expression levels, were decreased, and the antiapoptotic index of Bcl-2 expression was increased. DOX markedly activated phosphorylated JNK, ERK and p38 proteins in NRCMs. Specific inhibitors of JNK (SP600125), ERK (PD98059) or p38 (SB203580) inhibited DOX-induced apoptosis of NRCMs. GKT137831 pretreatment inhibited excessive DOX-induced MAPK pathway activation.Conclusion: This study revealed that GKT137831 can alleviate DOX-induced cardiomyocyte apoptosis by inhibiting NOX1/4-driven ROS production. The upregulation of MAPK pathway induced by NOX1/4-derived ROS production may be the potential mechanism of GKT137831 action. GKT137831 may be a potential drug candidate to ameliorate DOX-induced cardiotoxicity.
Evidence for Bell-Shaped Dose-Response Emetic Effects of Temsirolimus and Analogs: The Broad-Spectrum Antiemetic Efficacy of a Large Dose of Temsirolimus Against Diverse Emetogens in the Least Shrew (Cryptotis parva)
Authors: Belkacemi Louiza , Sun Yina , Darmani Nissar A. 
Published: April 2022

Temsirolimus is a prodrug form of sirolimus (rapamycin). With its analogs (everolimus, ridaforolimus, and rapamycin), it forms a group of anticancer agents that block the activity of one of the two mammalian targets of rapamycin (mTOR) complexes, mTORC1. We investigated the emetic potential of varying doses (0, 0.5, 1, 2.5, 5, 10, 20, and 40 mg/kg, i.p.) of temsirolimus in the least shrew. Temsirolimus caused a bell-shaped and dose-dependent increase in both the mean vomit frequency and the number of shrews vomiting with maximal efficacy at 10 mg/kg (p &lt; 0.05 and p &lt; 0.02, respectively). Its larger doses (20 or 40 mg/kg) had no significant emetic effect. We also evaluated the emetic potential of its analogs (5, 10, and 20 mg/kg, i.p.), all of which exhibited a similar emetic profile. Our observational studies indicated that temsirolimus can reduce the shrew motor activity at 40 mg/kg, and subsequently, we examined the motor effects of its lower doses. At 10 and 20 mg/kg, it did not affect the spontaneous locomotor activity (distance moved) but attenuated the mean rearing frequency in a U-shaped manner at 10 mg/kg (p &lt; 0.05). We then determined the broad-spectrum antiemetic potential of a 20 mg/kg (i.p.) dose of temsirolimus against diverse emetogens, including selective and nonselective agonists of 1) dopaminergic D2/3 receptors (apomorphine and quinpirole); 2) serotonergic 5-HT3 receptors [5-HT (serotonin) and 2-methyl-5-HT]; 3) cholinergic M1 receptors (pilocarpine and McN-A-343); 4) substance P neurokinin NK1 receptors (GR73632); 5) the L-type calcium (Ca2+) channel (LTCC) (FPL64176); 6) the sarcoplasmic endoplasmic reticulum Ca2+ ATPase inhibitor, thapsigargin; 7) the CB1 receptor inverse agonist/antagonist, SR141716A; and 8) the chemotherapeutic cisplatin. Temsirolimus prevented vomiting evoked by the aforementioned emetogens with varying degrees. The mechanisms underlying the pro- and antiemetic effects of temsirolimus evaluated by immunochemistry for c-fos expression demonstrated a c-fos induction in the AP and NTS, but not DMNX with the 10 mg/kg emetic dose of temsirolimus, whereas its larger antiemetic dose (20 mg/kg) had no significant effect. Our study is the first to provide preclinical evidence demonstrating the promising antiemetic potential of high doses of temsirolimus and possibly its analogs in least shrews.
Transcranial Electrical Stimulation for Relief of Peripartum Mental Health Disorders in Women Undergoing Cesarean Section With Combined Spinal–Epidural Anesthesia: A Pilot Randomized Clinical Trial
Authors: Zhao Qiu , Han Yuan , Hu Xiao-Yi , Zhang Song , Zhang Long , Wang Jun , Zhang Qian-Qian , Tao Ming-Shu , Fang Jia-xing , Yang Jie , Liu Rong-Guang , Sun Xun , Zhou Jian , Li Xiang , Mannan-Abdul  , Zhang Hongxing , Liu He , Cao Jun-Li 
Published: April 2022

ObjectiveThis study aimed to explore transcranial electrical stimulation (tES) to relieve peripartum anxiety and depressive symptoms in women undergoing cesarean section with combined spinal–epidural anesthesia.MethodsThis double-blind, randomized, sham-controlled trial was conducted in the Affiliated Hospital of Xuzhou Medical University from March 2021 and May 2021. One hundred and forty-eight full-term parturients giving birth by elective cesarean section were selected, and 126 were included in the intent-to-treat analysis. Parturients were provided standardized anesthesia and randomized to the active-tES (a-tES) group and sham-tES group. Parturients and outcome assessors were blinded to treatment allocation. The primary outcome was the changes in peripartum mental health disorders, including anxiety, assessed by the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2). Secondary outcomes included peripartum depressive symptoms, assessed by the Edinburgh Postnatal Depression Scale (EPDS), maternal satisfaction, fatigue level, sleep quality index, and pain score during and after operation. Data were collected before entering the operating room (T0), between post-anesthesia and pre-surgery (T1), before leaving the operating room (T2), and at 24 h post-surgery (T3).ResultsOne hundred and twenty-six eligible parturients were enrolled in the two groups: a-tES group (N = 62) and sham-tES group (N = 64). Treatment with tES resulted in significantly lower scores of anxiety compared with sham-tES (T2: P &lt; 0.001; T3: P = 0.001). Moreover, the a-tES groups showed a significant reduction in depression scores (T2: P = 0.003; T3: P = 0.032).ConclusionIn this randomized pilot study, tES treatment is efficacious in alleviating peripartum anxiety and depressive symptoms in women undergoing cesarean section and has been demonstrated to be a novel strategy for improving peripartum mental health disorders.Clinical Trial Registration[www.chictr.org.cn], identifier [ChiCTR2000040963].
Increased Prefrontal Activation During Verbal Fluency Task After Repetitive Transcranial Magnetic Stimulation Treatment in Depression: A Functional Near-Infrared Spectroscopy Study
Authors: Huang Jiaxi , Zhang Jiaqi , Zhang Tingyu , Wang Pu , Zheng Zhong 
Published: April 2022

BackgroundPrevious studies have shown the clinical effect of 2 Hz repetitive transcranial magnetic stimulation (rTMS) for depression; however, its underlying neural mechanisms are poorly understood. The aim of this study was to examine the effects of rTMS on the activity of the prefrontal cortex in patients with depression, using functional near-infrared spectroscopy (fNIRS).MethodsForty patients with major depressive disorder (MDD) and 40 healthy controls were enrolled in this study. Patients underwent 4 weeks of 2 Hz TMS delivered to the right dorsolateral prefrontal cortex (DLPFC). fNIRS was used to measure the changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex during a verbal fluency task (VFT) in depressed patients before and after rTMS treatment. The severity of depression was assessed using the Hamilton Rating Scale for Depression-24 item (HAMD-24).ResultsPrior to rTMS, depressed patients exhibited significantly smaller [oxy-Hb] values in the bilateral prefrontal cortex during the VFT compared with the healthy controls. After 4 weeks of 2 Hz right DLPFC rTMS treatment, increased [oxy-Hb] values in the bilateral frontopolar prefrontal cortex (FPPFC), ventrolateral prefrontal cortex (VLPFC) and left DLPFC during the VFT were observed in depressed patients. The increased [oxy-Hb] values from baseline to post-treatment in the right VLPFC in depressed patients were positively related to the reduction of HAMD score following rTMS.ConclusionThese findings suggest that the function of the prefrontal cortex in depressed patients was impaired and could be recovered by 2 Hz rTMS. The fNIRS-measured prefrontal activation during a cognitive task is a potential biomarker for monitoring depressed patients’ treatment response to rTMS.
Health Care Worker Perspectives of HIV Pre-exposure Prophylaxis Service Delivery in Central Uganda
Authors: Muwonge Timothy R. , Nsubuga Rogers , Ware Norma C. , Wyatt Monique A. , Pisarski Emily , Kamusiime Brenda , Kasiita Vicent , Nalukwago Grace Kakoola , Brown Charles , Nakyanzi Agnes , Bagaya Monica , Bambia Felix , Ssebuliba Timothy , Katabira Elly , Kyambadde Peter , Baeten Jared M. , Heffron Renee , Celum Connie , Mujugira Andrew , Haberer Jessica E. 
Published: April 2022

BackgroundScale-up of HIV pre-exposure prophylaxis (PrEP) services in Uganda is ongoing. However, health care workers (HCWs) may not be aware of PrEP nor what offering this service entails. We explored the impact of standardized HCW training on the knowledge and perspectives of PrEP service delivery in Uganda.MethodsWe recruited HCWs from facilities that offered HIV-related services in Central Uganda. Using the Uganda Ministry of Health curriculum, we trained HCWs on PrEP services. We collected data about PrEP knowledge, preparedness, and willingness to deliver PrEP to multiple key populations before the training, immediately after the training, and &gt;6 months later (exit). We additionally conducted 15 qualitative interviews after the exit survey. Quantitative data were analyzed by Fisher exact test, while qualitative interview data were analyzed inductively.ResultsWe recruited 80 HCWs from 35 facilities in urban (N = 24, 30%), peri-urban (N = 30, 37%), and rural (N = 26, 33%) areas. Most HCWs were nurse counselors (N = 52, 65%) or medical/clinical officers (N = 15, 18%). Surveys indicated that awareness of PrEP increased after the training and remained high. Knowledge of PrEP (i.e., as an effective, short-term antiretroviral medication to use before HIV exposure for people at high risk) generally increased with training, but significant gaps remained, and knowledge decreased with time. Most HCWs recommended PrEP for female sex workers and HIV serodifferent couples, as well as other key populations. We observed increases in the number of HCW who felt their facility was prepared to cater for HIV prevention and provide PrEP, but this view was not universal. HCWs believed in PrEP effectiveness and embraced it as an additional HIV prevention method. Concerns included patient adherence and behavioral risk compensation. HCWs noted challenges in PrEP delivery in terms of inadequate clinic preparedness, infrastructure, staff capacity, and poor attitudes toward key populations by untrained health workers. They felt further training was needed to ensure a smooth scale-up of services without stigmatization.ConclusionsStandardized training improved knowledge, willingness, and preparedness to offer PrEP services among most HCWs in Central Uganda. Ongoing training will be needed to optimize PrEP delivery services and expand delivery to levels needed for population-level impact.
Health Care Workers' Perceptions on Factors Affecting Diabetes Self-Management Among Type 2 Diabetes Mellitus Patients in Fiji: A Qualitative Study
Authors: Kumar Lalesh , Mohammadnezhad Masoud 
Published: April 2022

BackgroundType 2 Diabetes Mellitus (T2DM) is known as a major cause of mortality globally. Diabetes self-management refers to daily activities undertaken to control or reduce the impact of diabetes on health and well-being to avoid further illness. Health Care Workers' (HCWs) can assist patients to be aware of self-care and solve the challenges diabetes presents. The management of diabetes can improve once HCWs promote measures that facilitate self-care activities by providing necessary information and supporting patients' initiatives to make lifestyle changes. This study aimed to explore HCWs perceptions on factors affecting diabetes self-management among T2DM patients of Fiji.MethodsA qualitative study design was conducted to explore HCWs perceptions on factors affecting diabetes self-management using two Focus Group Discussions (FGDs) in Labasa, Fiji in 2021. The study settings were the Diabetic Hub Center, special outpatient department Labasa hospital and Nasea health Center Labasa. The study settings are located in an urban area. These health facilities provide special outpatient clinics to T2DM patients including clinics for other medical conditions. Nasea Health Center had 1,300 patients, the special outpatient's department Labasa hospital had 560 patients and the diabetic hub center Labasa had 295 patients at the time of the study. These patients either had T2DM or T2DM with other medical conditions. Purposive sampling was employed to recruit HCWs. The data were collected using an interview guide in semi-structured interviews and the interviews were audio recorded. The recorded data was transcribed verbatim and analyzed using thematic analysis process.ResultsThe participants were 9 HCWs with age range of 25-49 years. A counselor, a medical officer, physiotherapist, nurses and dieticians were among the HCWs. Three major themes and seven sub themes were identified. These included Theme 1- “availability of services” with the sub themes of clinical services for T2DM and other support services available for T2DM patients. Theme 2- “barriers and challenges to diabetes self-management” with the sub themes of health system factors, socioeconomic factors and health system factors. Theme 3- “Needs for diabetes management” with the sub themes resources and skilled personnel.ConclusionThe findings of this study demonstrate health system challenges such as lack of material resources and human resources compounded the factors affecting diabetes self-management. HCWs training as diabetes educators and developing policy on diabetes self-management are highly recommended to facilitate diabetes self-management.
Spatial Effect Analysis of Health Expenditure and Health Output in China From 2011 to 2018
Authors: Xu Penghui , Zhao Xicang , Li Haili , Guo Shi 
Published: April 2022

ObjectiveThe objective of this study is to study the spatial effects of health expenditure and health output in China.MethodsUsing the spatial panel data of 31 provinces in China from 2011 to 2018, the spatial weight matrix was introduced to analyze the spatial correlation, and the spatial Durbin model (SDM) was used to investigate the health output effect of health expenditure.ResultsExcluding the number of doctors per thousand, the provincial health expenditure, the number of beds per thousand population, and per capita education level had a positive impact on the regional health output. The health effect of China's health inputs showed a spatial spillover effect.ConclusionDue to the significant spatial effect, the health output of 31 provinces in China benefits not only from the local health inputs, but also from the health inputs of neighboring provinces.SuggestionsThis article puts forward some suggestions based on the conclusion: China should strengthen the health cooperation among neighboring provinces, promote the free flow of various health factors among provinces, make full use of the spillover and interdependence of health investment among provinces, and improve the medical policy environment in China.
The Influence of a School Social Network Intervention on Adolescent's Health Behaviors: A Gender-Specific Agent-Based Model
Authors: Zhang Shu , Xiao Tianyi , He Jie 
Published: April 2022

IntroductionAdolescence is a crucial stage for health behavior development, which is associated with health in adulthood. School closures caused by the coronavirus disease 2019 (COVID-19) pandemic have exposed adolescents to an increased risk of obesity due to a lack of physical activity. Although social network interventions provide an effective approach for promoting health-related behavior, current practices neglect gender differences in adolescent behavioral patterns and emotional preferences. The aim of this study was to examine the effectiveness of centrality-based methods integrated with of gender contexts in a social network intervention to improve adolescent's health behavior.MethodsWe developed an agent-based model (ABM) that supports the small-world characteristics of adolescent social networks. Health-related data for junior middle school students (n = 234, 48% girls) were collected in November 2018, 2019 and 2020 in Tianjin, China. We simulated multiple network-based interventions with different criteria for influential agents (i.e., betweenness centrality, closeness centrality, eigenvector centrality, and PageRank) and a random condition. The rules for generating peer influence and accelerating behavioral changes were based on the diffusion of innovations theory, with gender specifications.ResultsAfter the school closures, there was a significant increase in the prevalence of overweight and obesity among adolescents, with a greater increase in girls than in boys (+8.85% vs. +1.65%, p &lt; 0.001). Simulations showed that centrality-based network interventions were more effective than the random condition (average 6.17% per tick vs. 5.22% per tick, p &lt; 0.05), with a higher efficiency in girls than boys (average 3.68% vs. 2.99% per tick, p &lt; 0.05). PageRank outperformed other centrality conditions at the population level (6.37% per tick, p &lt; 0.05). In girls, betweenness centrality was the best method (3.85% per tick, p &lt; 0.05), while in boys, PageRank still had the greatest efficiency (3.21% per tick, p &lt; 0.05).ConclusionsWe found evidence for gender differences in the negative impact of COVID-19-related school closures and the potential for centrality-based social network interventions to affect adolescent health behavior. Therefore, we emphasize the importance of gender-specific targeting strategies to further promote health-related school programs in the post-pandemic era.
Development and Validation of a Nomogram to Predict Cancer-Specific Survival in Elderly Patients With Papillary Renal Cell Carcinoma
Authors: Zhanghuang Chenghao , Wang Jinkui , Yao Zhigang , Li Li , Xie Yucheng , Tang Haoyu , Zhang Kun , Wu Chengchuang , Yang Zhen , Yan Bing 
Published: April 2022

ObjectivePapillary renal cell carcinoma (pRCC) is the second most common type of renal cell carcinoma and an important disease affecting older patients. We aimed to establish a nomogram to predict cancer-specific survival (CSS) in elderly patients with pRCC.MethodsPatient information was downloaded from the Surveillance, Epidemiology, and End Results (SEER) project, and we included all elderly patients with pRCC from 2004 to 2018. All patients were randomly divided into a training cohort and a validation cohort. Univariate and multivariate Cox proportional risk regression models were used to identify patient independent risk factors. We constructed a nomogram based on a multivariate Cox regression model to predict CSS for 1-, 3-, and 5- years in elderly patients with pRCC. A series of validation methods were used to validate the accuracy and reliability of the model, including consistency index (C-index), calibration curve, and area under the Subject operating curve (AUC).ResultsA total of 13,105 elderly patients with pRCC were enrolled. Univariate and multivariate Cox regression analysis suggested that age, tumor size, histological grade, TNM stage, surgery, radiotherapy and chemotherapy were independent risk factors for survival. We constructed a nomogram to predict patients' CSS. The training and validation cohort's C-index were 0.853 (95%CI: 0.859–0.847) and 0.855 (95%CI: 0.865–0.845), respectively, suggesting that the model had good discrimination ability. The AUC showed the same results. The calibration curve also indicates that the model has good accuracy.ConclusionsIn this study, we constructed a nomogram to predict the CSS of elderly pRCC patients, which has good accuracy and reliability and can help doctors and patients make clinical decisions.
Front-Face Fluorescence Spectroscopy and Feature Selection for Fruit Classification Based on N-CovSel Method
Authors: Latchoumane Lorraine , Alary Karine , Minier Jérôme , Davrieux Fabrice , Lugan Raphaël , Chillet Marc , Roger Jean-Michel 
Published: April 2022

Internal disorder is a major problem in fruit production and is responsible for considerable economical losses. Symptoms are not externally visible, making it difficult to assess the problem. In recent years, 3D fluorescence spectroscopy has been used to reveal features of interest in agronomical field, such as plant stress and plant infection. Such technique could provide useful information regarding changes that occur at the tissue level, in order to distinguish spectral differences between healthy and disordered fruits. This paper introduces the use of the new three-way feature extraction N-CovSel method, compared to the commonly used N-PLS-DA method. These approaches were used upon front-face fluorescence spectra of 27 fruit pulp and skin samples, by analysing excitation wavelengths ranging from 250 to 650 nm, and emission wavelengths varying from 290 to 800 nm. N-CovSel method was applied to identify the most relevant features on: 1) excitation-emission wavelength couples, 2) excitation wavelengths whatever the emission wavelengths and 3) emission wavelengths whatever the excitation wavelengths. Discriminant analysis of the selected features were performed across classes. The constructed models provided key features to differentiate healthy fruits from disordered ones. These results highlighted the capability of N-CovSel method to extract the most fitted features for enhanced fruit classification using front-face fluorescence spectroscopy. They revealed characteristic fluorophores involved in the structural modifications generated by the physiological disorder studied. This paper provides preliminary results concerning the suitability of N-CovSel method for the desired application. Further investigations could be performed on intact fresh fruits in a non-destructive way, allowing an earlier and faster detection of the internal disorder for in-field or industrial applications.