bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palbociclib Induces Senescence in Melanoma and Breast Cancer Cells and Leads to Additive Growth Arrest in Combination With Irradiation
Authors: Jost Tina , Heinzerling Lucie , Fietkau Rainer , Hecht Markus , Distel Luitpold V. 
Published: October 2021

IntroductionSeveral kinase inhibitors (KI) bear the potential to act as radiosensitizers. Little is known of the radiosensitizing effects of a wide range of other KI like palbociclib, which is approved in ER+/HER2- metastatic breast cancer.MethodIn our study, we used healthy donor fibroblasts and breast cancer and skin cancer cells to investigate the influence of a concomitant KI + radiation therapy. Cell death and cell cycle distribution were studied by flow cytometry after Annexin-V/7-AAD and Hoechst staining. Cellular growth arrest was studied in colony-forming assays. Furthermore, we used C12-FDG staining (senescence) and mRNA expression analysis (qPCR) to clarify cellular mechanisms.ResultsThe CDK4/6 inhibitor palbociclib induced a cell cycle arrest in the G0/G1 phase. Cellular toxicity (cell death) was only slightly increased by palbociclib and not enhanced by additional radiotherapy. As the main outcome of the colony formation assays, we found that cellular growth arrest was induced by palbociclib and improved by radiotherapy in an additive manner. Noticeably, palbociclib treatment clearly induced senescence not only in breast cancer and partly in melanoma cells, but also in healthy fibroblasts. According to these findings, the downregulation of senescence-related FOXM1 might be an involved mechanism of the senescence-induction potential of palbociclib.ConclusionThe effect on cellular growth arrest of palbociclib and radiotherapy is additive. Palbociclib induces permanent G0/G1 cell cycle arrest by inducing senescence in fibroblasts, breast cancer, and melanoma cells. Direct cell death induction is only a minor secondary mechanism of action. Concomitant KI and radiotherapy is a strategy worth studying in clinical trials.
Conbercept for Treatment of Neovascular Age-Related Macular Degeneration and Visual Impairment due to Diabetic Macular Edema or Pathologic Myopia Choroidal Neovascularization: A Systematic Review and Meta-Analysis
Authors: Zhou Pengxiang , Zheng Siqian , Wang Ente , Men Peng , Zhai Suodi 
Published: October 2021

Background: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug. Here, we systematically conducted the efficacy, safety, compliance, and pharmacoeconomic evaluation of intravitreal conbercept (IVC) compared with other treatments in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or pathologic myopia choroidal neovascularization (pmCNV).Methods: Databases of PubMed, Embase, Cochrane Library, ClinicalTrials.gov, SinoMed, China National Knowledge Infrastructure, and WanFang Data were systematically searched from the inception to July 27, 2021. Randomized clinical trials and pharmacoeconomic studies comparing IVC with control groups in adults with nAMD, DME, or pmCNV were reviewed and selected. Meta-analyses were performed using the fixed-effects model when pooled data were homogeneous. Heterogeneous data were analyzed using the random-effects model. Primary outcomes included visual improvement rate, mean change in visual acuity or best corrected visual acuity, and pharmacoeconomic outcomes. Additional outcomes were the mean change in fundus examination values, adverse events (AEs), quality-of-life measures, and number of injections.Results: Among 3,591 screened articles, 22 original studies with 1,910 eyes of patients were finally included. For nAMD and DME, IVC was significantly associated with better visual acuity or best corrected visual acuity improvement and fundus quantitative measures than placebo, laser photocoagulation (LP), or intravitreal triamcinolone acetonide (IVT). However, IVC showed non-inferior efficacy to intravitreal ranibizumab (IVR) according to low quality of evidence, and there was lack of trials comparing the priority of IVC to other anti-VEGF regimens. No definitive increased risk of ocular or non-ocular AEs were observed in the study groups. All patients with AEs recovered after symptomatic treatments, and no severe AEs occurred. Patients treated with IVC might have higher quality-of-life scores than those in IVR in nAMD or LP in DME. Additionally, IVC showed cost–utility advantages in nAMD and cost-effectiveness advantages than IVR in pmCNV in China.Conclusion: IVC is well-tolerated and effective for improving vision acuity and quantitative measures in fundus condition in patients with nAMD and DME compared with LP, IVT, and placebo, but gains comparable efficacy to IVR. However, well-designed, large-sample, and long-term evaluation of IVC shall be conducted in additional studies worldwide.
Predicting the Outcome of Voriconazole Individualized Medication Using Integrated Pharmacokinetic/Pharmacodynamic Model
Authors: Yang Ping , Liu Wei , Zheng Jiajia , Zhang Yuanyuan , Yang Li , He Na , Zhai Suodi 
Published: October 2021

Therapeutic drug monitoring is considered to be an effective tool for the individualized use of voriconazole. However, drug concentration measurement alone doesn’t take into account the susceptibility of the infecting microorganisms to the drug. Linking pharmacodynamic data with the pharmacokinetic profile of individuals is expected to be an effective method to predict the probability of a certain therapeutic outcome. The objective of this study was to individualize voriconazole regimens by integrating individual pharmacokinetic parameters and pathogen susceptibility data through Monte Carlo simulations The individual pharmacokinetic parameters of 35 hospitalized patients who received voriconazole were calculated based on a validated population pharmacokinetic model. The area under the concentration-time curve for free drug/minimal inhibitory concentration (fAUCss/MIC) &gt; 25 was selected as the pharmacokinetic/pharmacodynamic (PK/PD) parameter predicting the efficacy of voriconazole. The cumulative fraction of response (CFR) of the target value was assessed. To verify this conclusion, a logistic regression analysis was used to explore the relationship between actual clinical efficiency and the CFR value. For the 35 patients, the area under the free drug concentration-time curve (fAUCss) was calculated to be 34.90 ± 21.67 mgh/L. According to the dualistic logistic regression analysis, the minimal inhibitory concentration (MIC) value of different kinds of fungi had a great influence on the effectiveness of clinical treatment. It also showed that the actual clinical efficacy and the CFR value of fAUCss/MIC had a high degree of consistency. The results suggest that it is feasible to individualize voriconazole dosing and predict clinical outcomes through the integration of data on pharmacokinetics and antifungal susceptibility.
Estimating Precipitating Energy Flux, Average Energy, and Hall Auroral Conductance From THEMIS All-Sky-Imagers With Focus on Mesoscales
Authors: Gabrielse Christine , Nishimura Toshi , Chen Margaret , Hecht James H. , Kaeppler Stephen R. , Gillies D. Megan , Reimer Ashton S. , Lyons Larry R. , Deng Yue , Donovan Eric , Evans J. Scott 
Published: October 2021

Recent attention has been given to mesoscale phenomena across geospace (∼10 s km to 500 km in the ionosphere or ∼0.5 RE to several RE in the magnetosphere), as their contributions to the system global response are important yet remain uncharacterized mostly due to limitations in data resolution and coverage as well as in computational power. As data and models improve, it becomes increasingly valuable to advance understanding of the role of mesoscale phenomena contributions—specifically, in magnetosphere-ionosphere coupling. This paper describes a new method that utilizes the 2D array of Time History of Events and Macroscale Interactions during Substorms (THEMIS) white-light all-sky-imagers (ASI), in conjunction with meridian scanning photometers, to estimate the auroral scale sizes of intense precipitating energy fluxes and the associated Hall conductances. As an example of the technique, we investigated the role of precipitated energy flux and average energy on mesoscales as contrasted to large-scales for two back-to-back substorms, finding that mesoscale aurora contributes up to ∼80% (∼60%) of the total energy flux immediately after onset during the early expansion phase of the first (second) substorm, and continues to contribute ∼30–55% throughout the remainder of the substorm. The average energy estimated from the ASI mosaic field of view also peaked during the initial expansion phase. Using the measured energy flux and tables produced from the Boltzmann Three Constituent (B3C) auroral transport code (Strickland et al., 1976; 1993), we also estimated the 2D Hall conductance and compared it to Poker Flat Incoherent Scatter Radar conductance values, finding good agreement for both discrete and diffuse aurora.
Reduced Plasma Levels of α-Klotho and Their Correlation With Klotho Polymorphisms in Elderly Patients With Major Depressive Disorders
Authors: Gao Xiang , Sun Zuoli , Ma Guangwei , Li Yuhong , Liu Min , Zhang Guofu , Xu Hong , Gao Yane , Zhou Jixuan , Deng Qi , Li Rena 
Published: October 2021

Background: Recent literature suggests that α-Klotho, a widely recognized anti-aging protein, is involved in longevity as well as in many diseases, including Alzheimer's disease, and depression. Although the Klotho gene encodes α-Klotho, a single transmembrane protein with intracellular and extracellular domains, the relationship between Klotho gene polymorphism and circulating α-Klotho levels in patients with major depressive disorder (MDD) is not clear.Methods: A total of 144 MDD patients and 112 age-matched healthy controls were included in this study. The Klotho genetic polymorphisms (rs9536314, rs9527025, and rs9315202) and plasma α-Klotho levels were measured by PCR and ELISA, respectively. The severity of depressive symptoms was estimated using the Hamilton Depression Scale (HAMD).Results: We found a significantly lower level of plasma α-Klotho in the MDD patients than in controls. Among them, only elderly MDD patients (first episode) showed significantly lower α-Klotho levels than the age-matched controls, while elderly recurrent and young MDD patients showed no difference in plasma α-Klotho levels from age-matched controls. The young MDD group showed a significantly earlier onset age, higher plasma α-Klotho levels, and lower HAMD scores than those in the elderly MDD group. While the plasma α-Klotho levels were higher in rs9315202 T alleles carrier regardless age or sex, the rs9315202 T allele was negatively correlated with disease severity only in the elderly MDD patients.Conclusion: The results of our study showed that only elderly MDD patients showed a decrease in plasma α-Klotho levels along with an increase in disease severity as well as an association with the number of rs9315202 T alleles, and not young MDD patients compared to age-matched controls. Our data suggest that circulating α-Klotho levels combined with Klotho genetic polymorphisms are important in elderly MDD patients, particularly carriers of the Klotho gene rs9315202 T allele.
Which Social, Economic, and Health Sector Strategies Will Deliver the Greatest Impacts for Youth Mental Health and Suicide Prevention? Protocol for an Advanced, Systems Modelling Approach
Authors: Occhipinti Jo-An , Skinner Adam , Freebairn Louise , Song Yun Ju Christine , Ho Nicholas , Lawson Kenny , Lee Grace Yeeun , Hickie Ian B. 
Published: October 2021

Background:Current global challenges are generating extensive social disruption and uncertainty that have the potential to undermine the mental health, wellbeing, and futures of young people. The scale and complexity of challenges call for engagement with systems science-based decision analytic tools that can capture the dynamics and interrelationships between physical, social, economic, and health systems, and support effective national and regional responses. At the outset of the pandemic mental health-related systems models were developed for the Australian context, however, the extent to which findings are generalisable across diverse regions remains unknown. This study aims to explore the context dependency of systems modelling insights.Methods:This study will employ a comparative case study design, applying participatory system dynamics modelling across eight diverse regions of Australia to answer three primary research questions: (i) Will current regional differences in key youth mental health outcomes be exacerbated in forward projections due to the social and economic impacts of COVID-19?; (ii) What combination of social policies and health system strengthening initiatives will deliver the greatest impacts within each region?; (iii) To what extent are optimal strategic responses consistent across the diverse regions? We provide a detailed technical blueprint as a potential springboard for more timely construction and deployment of systems models in international contexts to facilitate a broader examination of the question of generalisability and inform investments in the mental health and wellbeing of young people in the post COVID-19 recovery.Discussion:Computer simulation is known as the third pillar of science (after theory and experiment). Simulation allows researchers and decision makers to move beyond what can be manipulated within the scale, time, and ethical limits of the experimental approach. Such learning when achieved collectively, has the potential to enhance regional self-determination, help move beyond incremental adjustments to the status quo, and catalyze transformational change. This research seeks to advance efforts to establish regional decision support infrastructure and empower communities to effectively respond. In addition, this research seeks to move towards an understanding of the extent to which systems modelling insights may be relevant to the global mental health response by encouraging researchers to use, challenge, and advance the existing work for scientific and societal progress.
Characterizing the Heterogeneity of Aging: A Vision for a Staging System for Aging
Authors: Jaul Efraim , Barron Jeremy 
Published: October 2021

Introduction: Older adulthood encompasses several decades of change and heterogeneity. Primary care providers need a geriatric comprehensive vision for defining older adult subpopulations.Methods: Using PubMed and Google searches, we reviewed the literature on epidemiology of age-related physiological changes, age-related diseases and geriatric syndromes, functional state, and emotional and social changes. We divided old age into strata based on chronological age and strata based on functional state, disease burden, and geriatric syndromes.Results: We describe 4 chronological-age strata beginning at age 60, and 4 functional-age strata based on frailty according to a modified clinical frailty scale. We provide clinical considerations and anticipatory guidance topics for each of the age strata and functional strata.Conclusion: Chronological age, functional status, chronic disease burden and geriatric syndromes, and life expectancy are all important domains that impact clinical care and appropriate anticipatory guidance for individual older adults. Better knowledge for differentiating subpopulations of older adults may improve clinical care, reduce medical overuse, improve personalized anticipatory guidance, and focus on the impact of functional state on the quality of life.
Effect of Anxiety About COVID-19 Infection in the Workplace on the Association Between Job Demands and Psychological Distress
Authors: Eguchi Hisashi , Hino Ayako , Inoue Akiomi , Tsuji Mayumi , Tateishi Seiichiro , Ando Hajime , Nagata Tomohisa , Matsuda Shinya , Fujino Yoshihisa 
Published: October 2021

Purpose: There is limited information about the association between workplace psychosocial factors and general worker mental health status during the COVID-19 pandemic. In the present study, we examined how anxiety about being infected by COVID-19 in the workplace affected the association between job demands and psychological distress (PD).Method: A cross-sectional online survey was conducted in December 2020. The final analyzed sample was 27,036. The dependent variable of PD was assessed using the Kessler Psychological Distress Scale (K6). Job demands were assessed using the Job Content Questionnaire. Feelings of anxiety were assessed by participants' responses to the following question: “Do you feel anxiety about being infected by COVID-19 in the workplace?” We used a two-level regression adjusting for prefectural level: each individual-level variable at level 1 was nested into each prefecture at level 2, stratified by presence of anxiety.Results: A total of 50.5% of participants felt anxious about being infected by COVID-19 in the workplace. The interaction between anxiety and job demands was significant. Job demands were positively associated with PD. In the stratified analysis, the associations were stronger among employees who experienced anxiety about COVID-19 infection in the workplace than among those who did not.Conclusion: The association between job demands and PD may be strengthened by anxiety about COVID-19 infection in the workplace.
Uneven Use of Remote Work to Prevent the Spread of COVID-19 in South Korea's Stratified Labor Market
Authors: Park Saejung , Lee Sanghee , Cho Joonmo 
Published: October 2021

Background: This research analyzed whether South Korean companies adopted remote work during the COVID-19 pandemic by focusing on the dual labor market structure comprising of primary sector (large corporations) and secondary sector [small and medium enterprises (SMEs)]. Companies in the dual labor market were classified based on firm size.Methods: We used August supplementary data from the Economically Active Population Survey covering 2017–2020 provided by Statistics Korea. In this empirical study, a Linear Probability Model was used to analyze the probability that employees would work for companies that introduced remote work since COVID-19 depending on the size of the company.Results: This study showed three main results. First, unlike other flexible work systems, the use of remote work has increased rapidly since COVID-19. Second, the larger the size of the company, the higher the probability that employees would work for companies that introduced remote work after COVID-19. Third, according to the analysis by industry, the difference in remote work utilization between large corporations and SMEs was relatively small because of a similar working method in manufacturing.Conclusion: Results of this study suggested that polarization within the dual labor market structure also spilled over to adoption of remote work, which was initially introduced to prevent the spread of the pandemic. This study examined the system and factors of labor-management relations contributing to such polarization and presented policy directions for the current labor market structure.
Effects of Tranexamic Acid on Bleeding in Pediatric Surgeries: A Systematic Review and Meta-Analysis
Authors: Wei Yiyong , Zhang Yajun , Jin Tao , Wang Haiying , Li Jia , Zhang Donghang 
Published: October 2021

Background: Major pediatric surgeries can cause severe intraoperative blood loss. This meta-analysis aims to evaluate the efficacy of tranexamic acid (TXA) in pediatric surgeries.Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library from the conception to March 31, 2021 to identify eligible randomized controlled trials (RCTs) that evaluated the efficacy of TXA in pediatric surgeries. Two reviewers choosed studies, evaluated quality, extracted data, and assessed the risk of bias independently. Mean difference (MD) was calculated as the summary statistic for continuous data. We used a random-effects model to measure mean effects. Data were generated from the corresponding 95% confidence interval (CI) using RevMan 5.3 software. Primary outcomes included intraoperative and postoperative blood loss, red blood cell (RBC) transfusion as well as fresh frozen plasma (FFP) transfusion.Results: Fifteen studies enrolling 1,332 patients were included in this study. The pooled outcomes demonstrated that TXA was associated with a decreased intraoperative (MD = −1.57 mL/kg, 95% CI, −2.54 to −0.60, P = 0.002) and postoperative (MD = −7.85 mL/kg, 95% CI, −10.52 to −5.19, P &lt; 0.001) blood loss, a decreased intraoperative (MD = −7.08 mL/kg, 95% CI, −8.01 to −6.16, P &lt; 0.001) and postoperative (MD = −5.30 mL/kg, 95% CI, −6.89 to −3.70, P &lt; 0.001) RBC transfusion, as well as a decreased intraoperative (MD = −2.74 mL/kg, 95% CI, −4.54 to −0.94, P = 0.003) and postoperative (MD = −6.09 mL/kg, 95% CI, −8.26 to −3.91, P &lt; 0.001) FFP transfusion in pediatric surgeries. However, no significant difference was noted between two groups in duration of surgery (MD = −12.51 min, 95% CI −36.65 to 11.63, P = 0.31). Outcomes of intraoperative and postoperative blood loss and the duration of surgery in included studies were not pooled due to the high heterogeneity.Conclusion: This meta-analysis demonstrated that TXA was beneficial for bleeding in pediatric surgeries.
In Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy Systemic Inflammation Response Index is a Useful Prognostic Indicator
Authors: Chen Li , Chen Yong , Zhang Lele , Xue Yingwei , Zhang Shiwei , Li Xingrui , Song Hongjiang 
Published: October 2021

Background: The preoperative systemic inflammation response index (SIRI), based on peripheral neutrophil (N), monocyte (M), and lymphocyte (L) counts, has shown mounting evidence as an effective prognostic indicator in some malignant tumors. The aim of the present study was to evaluate the prognostic significance of pre-treatment SIRI in gastric cancer patients who received neoadjuvant chemotherapy (NACT).Methods: This retrospective study comprised 107 patients with advanced gastric cancer treated with NACT between July 2007 and September 2015 in our hospital. SIRI was calculated from peripheral venous blood samples obtained prior to treatment. The best cutoff value for SIRI by receiver operating characteristic (ROC) curve was 1.2 (low SIRI &lt;1.21, high SIRI ≥1.21). The clinical outcomes of disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier survival analysis and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox proportional hazards regression model.Results: The results demonstrated that the low SIRI group was statistically associated with gender, primary tumor site, white blood cell, neutrophil, and monocyte counts, NLR (neutrophil to lymphocyte ratio), MLR (monocyte to lymphocyte ratio), and PLR (platelet to lymphocyte ratio). The SIRI was predictive for DFS and OS by univariate and multivariate analysis; the low SIRI group had better median DFS and OS than the high SIRI group (median DFS 27.03 vs. 22.33 months, median OS 29.73 vs. 24.43 months). The DFS and OS in the low SIRI group were longer than the high SIRI group.Conclusions: SIRI may qualify as a useful, reliable, and convenient prognostic indicator in patients with advanced gastric cancer to help physicians to provide personalized prognostication for gastric cancer patients treated with NACT.