bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondria Participate in Chemoresistance to Cisplatin in Human Ovarian Cancer Cells
Authors: Zampieri Luca X. , Grasso Debora , Bouzin Caroline , Brusa Davide , Rossignol Rodrigue , Sonveaux Pierre 
Published: May 2020

Abstract

Ovarian cancer is an aggressive disease that affects about 300,000 patients worldwide, with a yearly death count of about 185,000. Following surgery, treatment involves adjuvant or neoadjuvant administration of taxane with platinum compounds cisplatin or carboplatin, which alkylate DNA through the same chemical intermediates. However, although platinum-based therapy can cure patients in a number of cases, a majority of them discontinues treatment owing to side effects and to the emergence of resistance. In this study, we focused on resistance to cisplatin and investigated whether metabolic changes could be involved. As models, we used matched pairs of cisplatin-sensitive (SKOV-3 and COV-362) and cisplatin-resistant (SKOV-3-R and COV-362-R) human ovarian carcinoma cells that were selected in vitro following exposure to increasing doses of the chemotherapy. Metabolic comparison revealed that resistant cells undergo a shift toward a more oxidative metabolism. The shift goes along with a reorganization of the mitochondrial network, with a generally increased mitochondrial compartment. More functional mitochondria in cisplatin-resistant compared with cisplatin-sensitive cells were associated to enzymatic changes affecting either the electron transport chain (SKOV-3/SKOV-3-R model) or mitochondrial coupling (COV-362/COV-362-R model). Our findings further indicate that the preservation of functional mitochondria in these cells could be due to an increased mitochondrial turnover rate, suggesting mitophagy inhibition as a potential strategy to tackle cisplatin-resistant human ovarian cancer progression.

Implications:
Besides classical mechanisms related to drug efflux and target modification, we report that preserving functional mitochondria is a strategy used by human ovarian cancer cells to resist to cisplatin chemotherapy.
Corrected QT Interval–Polygenic Risk Score and Its Contribution to Type 1, Type 2, and Type 3 Long-QT Syndrome in Probands and Genotype-Positive Family Members
Authors: Turkowski Kari L. , Dotzler Steven M. , Tester David J. , Giudicessi John R. , Bos J. Martijn , Speziale Ashley D. , Vollenweider Jason M. , Ackerman Michael J. 
Published: May 2020

Background:
Long-QT syndrome (LQTS) is characterized by a prolonged heart rate–corrected QT interval (QTc). Genome-wide association studies identified common genetic variants that collectively explain ≈8% to 10% of QTc variation in the general population.

Methods:
Overall, 423 patients with LQT1, LQT2, or LQT3 were genotyped for 61 QTc-associated genetic variants used in a prototype QTc–polygenic risk score (QTc-PRS). A weighted QTc-PRS (range, 0–154.8 ms) was calculated for each patient, and the FHS (Framingham Heart Study) population-based reference cohort (n=853).

Results:

The average QTc-PRS in LQTS was 88.0±7.2 and explained only ≈2.0% of the QTc variability. The QTc-PRS in LQTS probands (n=137; 89.3±6.8) was significantly greater than both FHS controls (87.2±7.4, difference-in-means±SE: 2.1±0.7,
P
<0.002) and LQTS genotype-positive family members (87.5±7.4, difference-in-mean, 1.8±.7,
P
<0.009). There was no difference in QTc-PRS between symptomatic (n=156, 88.6±7.3) and asymptomatic patients (n=267; 87.7±7.2, difference-in-mean, 0.9±0.7, P=0.15). LQTS patients with a QTc≥480 ms (n=120) had a significantly higher QTc-PRS (89.3±6.7) than patients with a QTc<480 ms (n=303, 87.6±7.4, difference-in-mean, 1.7±0.8,
P
<0.05). There was no difference in QTc-PRS or QTc between genotypes.

Conclusions:
The QTc-PRS explained <2% of the QTc variability in our LQT1, LQT2, and LQT3 cohort, contributing 5× less to their QTc value than in the general population. This prototype QTc-PRS does not distinguish/predict the clinical outcomes of individuals with LQTS.
Spectrum of Cardiac Manifestations in COVID-19
Authors: Szekely Yishay , Lichter Yael , Taieb Philippe , Banai Ariel , Hochstadt Aviram , Merdler Ilan , Gal Oz Amir , Rothschild Ehud , Baruch Guy , Peri Yogev , Arbel Yaron , Topilsky Yan 
Published: May 2020

Background:
Information on the cardiac manifestations of coronavirus disease 2019 (COVID-19) is scarce. We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection.

Methods:
One hundred consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared with reference values. Echocardiographic studies included left ventricular (LV) systolic and diastolic function and valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound. A second examination was performed in case of clinical deterioration.

Results:
Thirty-two patients (32%) had a normal echocardiogram at baseline. The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%). Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared with patients with normal troponin or better clinical condition, but they had worse RV function. Clinical deterioration occurred in 20% of patients. In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients). Femoral deep vein thrombosis was diagnosed in 5 of 12 patients with RV failure.

Conclusions:
In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic function and RV function are impaired. Elevated troponin and poorer clinical grade are associated with worse RV function. In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without deep vein thrombosis, is more common, but acute LV systolic dysfunction was noted in ≈20%.
Endothelial Sirtuin 3 Dictates Glucose Transport to Cardiomyocyte and Sensitizes Pressure Overload‐Induced Heart Failure
Authors: Zeng Heng , He Xiaochen , Chen Jian‐Xiong 
Published: May 2020

Background

Alterations of energetic metabolism are suggested to be an important contributor to pressure overload (
PO
)‐induced heart failure. Our previous study reveals that knockout of endothelial Sirtuin 3 (
SIRT
3) alters glycolysis and impairs diastolic function. We hypothesize that endothelial
SIRT
3 regulates glucose utilization of cardiomyocytes and sensitizes
PO
‐induced heart failure.

Methods and Results

SIRT
3 endothelial cell knockout mice and their control
SIRT
3 LoxP mice were subjected to
PO
by transverse aortic constriction for 7 weeks. The ratio of heart weight to tibia length was increased in both strains of mice, in which
SIRT
3 endothelial cell knockout mice+transverse aortic constriction exhibited more severe cardiac hypertrophy. Coronary blood flow and systolic function were significantly decreased in
SIRT
3 endothelial cell knockout mice+transverse aortic constriction compared with
SIRT
3 LoxP mice+transverse aortic constriction, as evidenced by lower systolic/diastolic ratio, ejection fraction, and fractional shortening.
PO
‐induced upregulation of apelin and glucose transporter 4 were significantly reduced in the hearts of
SIRT
3 endothelial cell knockout mice. In vitro
,
levels of hypoxia‐inducible factor‐1α and glucose transporter 1 and glucose uptake were significantly reduced in
SIRT
3 knockout endothelial cells. Furthermore, hypoxia‐induced apelin expression was abolished together with reduced apelin‐mediated glucose uptake in
SIRT
3 knockout endothelial cells. Exposure of cardiomyocyte with apelin increased expression of glucose transporter 1 and glucose transporter 4. This was accompanied by a significant increase in glycolysis. Supplement of apelin in
SIRT
3 knockout hypoxic endothelial cell media increased glycolysis in the cardiomyocytes.

Conclusions

Knockout of
SIRT
3 disrupts glucose transport from endothelial cells to cardiomyocytes, reduces cardiomyocyte glucose utilization via apelin in a paracrine manner, and sensitizes
PO
‐induced heart failure. Endothelial
SIRT
3 may regulate cardiomyocyte glucose availability and govern the function of the heart.
Break in the Stroke Chain of Survival due to COVID-19
Authors: Montaner Joan , Barragán-Prieto Ana , Pérez-Sánchez Soledad , Escudero-Martínez Irene , Moniche Francisco , Sánchez-Miura José Antonio , Ruiz-Bayo Lidia , González Alejandro 
Published: May 2020

Background and Purpose:
Emergency measures to treat patients with coronavirus disease 2019 (COVID-19) and contain the outbreak is the main priority in each of our hospitals; however, these measures are likely to result in collateral damage among patients with other acute diseases. Here, we investigate whether the COVID-19 pandemic affects acute stroke care through interruptions in the stroke chain of survival.

Methods:
A descriptive analysis of acute stroke care activity before and after the COVID-19 outbreak is given for a stroke network in southern Europe. To quantify the impact of the pandemic, the number of stroke code activations, ambulance transfers, consultations through telestroke, stroke unit admissions, and reperfusion therapy times and rates are described in temporal relationship with the rising number of COVID-19 cases in the region.

Results:

Following confinement of the population, our stroke unit activity decreased sharply, with a 25% reduction in admitted cases (mean number of 58 cases every 15 days in previous months to 44 cases in the 15 days after the outbreak,
P
<0.001). Consultations to the telestroke network declined from 25 every 15 days before the outbreak to 7 after the outbreak (
P
<0.001). The increasing trend in the prehospital diagnosis of stroke activated by 911 calls stopped abruptly in the region, regressing to 2019 levels. The mean number of stroke codes dispatched to hospitals decreased (78% versus 57%,
P
<0.001). Time of arrival from symptoms onset to stroke units was delayed >30 minutes, reperfusion therapy cases fell, and door-to-needle time started 16 minutes later than usual.

Conclusions:
The COVID-19 pandemic is disruptive for acute stroke pathways. Bottlenecks in the access and delivery of patients to our secured stroke centers are among the main challenges. It is critical to encourage patients to continue seeking emergency care if experiencing acute stroke symptoms and to ensure that emergency professionals continue to use stroke code activation and telestroke networks.
A Response to Stephen L. Young, “Let’s Take the Text Seriously”: the Protectionist Doxa in Mainstream New Testament Studies
Authors: Dye Guillaume 
Published: May 2020

Abstract
This response to Stephen Young’s excellent paper vindicates his general argument against protectionism, connects his analyses to some aspects of contemporary Qurʾanic and Early Islamic studies, and highlights some of the problems with the distinction between dominant protectionism and dominated protectionism.
Challenges to Understanding Extreme Weather Changes in Lower Income Countries
Authors: Otto Friederike E. L. , Harrington Luke , Schmitt Katharina , Philip Sjoukje , Kew Sarah , van Oldenborgh Geert Jan , Singh Roop , Kimutai Joyce , Wolski Piotr 
Published: May 2020

AbstractThe science of event attribution has emerged to routinely answer the question whether and to what extent human-induced climate change altered the likelihood and intensity of recently observed extreme weather events. In Europe a pilot program to operationalize the method started in November 2019, highlighting the demand for timely information on the role of climate change when it is needed most: in the direct aftermath of an extreme event. Independent of whether studies are provided operationally or as academic studies, the necessity of good observational data and well-verified climate models imply most attributions are currently made for highly developed countries only. Current attribution assessments therefore provide very little information about those events and regions where the largest damages and socio-economic losses are incurred. Arguably, these larger damages signify a much greater need for information on how the likelihood and intensity of such high-impact events have been changing and are likely to change in a warmer world. In short, why do we not focus event attribution research efforts on the whole world, and particularly events in the developing world? The reasons are not just societal and political but also scientific. We simply cannot attribute these events in the same probabilistic framework employed in most studies today. We outline six focus areas to lessen these barriers, but we will not overcome them in the near future.
Effects of Cognitive and Physical Loads on Dynamic and Static Balance Performance of Healthy Older Adults Under Single-, Dual-, and Multi-task Conditions
Authors: Allahverdipour Hamid , Dianat Iman , Mameh Galavizh , Asghari Jafarabadi Mohammad 
Published: May 2020

Objective The aim of this study is to examine the effects of cognitive and physical loads on dynamic and static balance performance of healthy older adults under single-, dual-, and multi-task conditions. Background Previous studies on postural control in older adults have generally used dual-task methodology, whereas less attention has been paid to multi-task performance, despite its importance in many daily and occupational activities. Method The effects of single versus combined (dual-task and multi-task) cognitive (to speak out the name of the weekdays in a reverse order) and physical (with three levels including handling weights of 1, 2, and 3 kg in each hand) loads on dynamic and static balance performance of 42 older adults (21 males and 21 females) aged ≥60 years were examined. Dynamic and static balance measures were evaluated using the Timed Up and Go (TUG) and stabilometer (sway index) tests, respectively. Results The TUG speed of female participants was generally slower than that of male participants. Age had no effect on balance performance measures. Under dual-task conditions, cognitive load decreased the dynamic balance performance, while the physical task levels had no effect. The dual-task conditions had no impact on the static balance performance. The effects of cognitive and physical loads on dynamic balance performance varied under dual- and multi-task conditions. Conclusion The findings highlight differences between dual- and multi-task protocols and add to the understanding of balance performance in older adults under cognitive and physical loads. Application The present study highlights differences between dual- and multi-task methodologies that need to be considered in future studies of balance and control in older adults.
From folk therapy to evidence-based psychiatry practice: The benefit of evidence-based psychiatry in treatment-naive psychotic patients
Authors: Wang Hung-Yu , Huang Joh-Jong , Su Shu-Fang , Hsu Sheng-Hao , Chou Li-Shiu , Chou Frank Huang-Chih 
Published: May 2020

Background: As Taiwan’s Mental Health Act (MHA) clearly states that the human rights and legal rights of psychotic patients should be respected and guaranteed; however, a temple asylum violates the law in the 21st century. Hundreds of patients were constrained in the asylum for years without consent. Because of outbreak of infectious diseases, patients were evacuated from the asylum by the official intervention. Aims: To evaluate the outcomes of these patients from folk therapy to conventional treatment. Method: The study recruited the drug-naive psychotic patients constrained in an asylum for decades. Before and after the formal treatment, 253 patients were diagnosed with schizophrenia and other psychotic disorders with assessment of using the Mini Positive and Negative Syndrome Scale (Mini-PANSS) and Comprehensive Occupational Therapy Evaluation (COTE) scale. In addition, family function, self-care ability and nutritional status were also evaluated. Results: The initial data show the improvement in psychotic symptoms and occupational function in these patients. Furthermore, the ratio of patients who were classified as being at risk for malnutrition was decreased by 21.7% after treatment. There was no statistically significant difference in self-care ability before and after treatment. Conclusion: The psychotic symptoms and occupational function of these patients were improved after the formal treatment compared to the folk therapy. The care model for the psychotic patients in the temple asylum should be more thoroughly discussed in consideration of the medical ethics principles.
Barriers to access to mental health services among Colombia outpatients
Authors: Campo-Arias Adalberto , Ceballos-Ospino Guillermo A , Herazo Edwin 
Published: May 2020

Background: Access barriers are all situations or conditions that limit seeking, receiving or enjoying benefits offered by the health system. This set of situations translates into underutilization of the services offered. In Colombia, there is little information about barriers to accessing medical care in general, and even less in the specific field of mental health. Aim: To determine the barriers to accessing psychiatric care in outpatients in Santa Marta, Colombia. Methods: The authors designed a cross-sectional study with a non-probability sample of adult patients who consulted between August and December 2018. The barriers to access were measured with a 20-item version of the Barriers to Access to Care Evaluation (BACE) scale. Results: A total of 247 patients participated; they were between 18 and 82 years (mean ( M) = 47.5, standard deviation ( SD) = 13.9). A total of 69 (27.9%) patients classified as having major attitudinal barriers; 62 (25.1%) patients, major barriers related to stigma-discrimination; and 41 (16.6%) patients, major instrumental barriers. Concerning the associated variables, age less than 45 years was related to major attitudinal barriers (odds ratio (OR) = 2.9, 95% confidence interval (CI) 1.6-5.5), major barriers related to stigma-discrimination (OR = 3.8, 95% CI 2.0-7.2) and major instrumental barriers (OR = 2.7, 95% CI 1.3-5.3). Men reported major instrumental barriers more frequently than women (OR = 2.8, 95% CI 1.3-5.8). Conclusion: The major attitudinal, related to stigma-discrimination and instrumental barriers to access frequently delay a consultation with mental health services. Actions are necessary to reduce barriers to accessing mental health care.
The Incorporation of Social Organizations under the MAS in Bolivia
Authors: McNelly Angus 
Published: May 2020

By drawing on the theoretical framework of the second incorporation of heterogeneous social organizations by progressive governments through informal contestation and/or technocratic implementation of their demands in Latin America, this article argues that the first presidential term of Evo Morales in Bolivia (2006–2009) was marked by the incorporation of combative social movements through both a multidimensional co-optation of movements and the technocratic competition of the central movement demands for the nationalization of gas and the rewriting of the constitution through a constituent assembly. However, by 2010, this incorporation had stripped social movements of their ability to mobilize for change and the political conjuncture had shifted, making the government less dependent on its social bases to maintain political stability. This simultaneously transformed movements into defensive movements protecting the gains from the previous period and state–social-movement relations into informal contestatory regimes in which movements could only struggle against proposed political agendas. En base a un marco teórico que abarca la segunda incorporación de organizaciones sociales heterogéneas por parte de gobiernos progresistas a través de la contestación informal y/o la implementación tecnocrática de sus demandas en América Latina, un análisis del proyecto político de Evo Morales en Bolivia sostiene que su primer mandato presidencial se vio caracterizado por la incorporación de movimientos sociales combativos a través de una cooptación multidimensional de dichos movimientos y la competencia tecnocrática de las demandas del movimiento central en torno a la nacionalización del gas y la modificación de la constitución por una asamblea constituyente. Sin embargo, para 2010, esta incorporación había despojado a los movimientos sociales de su capacidad de movilizarse a favor del cambio y la coyuntura política había cambiado, haciendo que el gobierno dependiera menos de sus bases sociales para mantener la estabilidad política. Esto transformó a los movimientos en entidades defensivas dedicadas a proteger las ganancias del período anterior y las relaciones entre el estado y los movimientos sociales en regímenes informales de impugnación dentro de los cuales los movimientos mismos sólo podían luchar contra las agendas políticas propuestas.
Factors associated with loss to follow-up of outpatients with depression in general hospitals
Authors: Zhang Jingjing , Ye Chenyu 
Published: May 2020

Objective We aimed to understand the reasons behind outpatient loss to follow-up and the views of Chinese patients with depression regarding disease diagnosis and antidepressant therapy. Methods Consecutive outpatients with newly diagnosed depressive disorder between September 2012 and August 2013 at the Shanghai First People’s Hospital (a tertiary hospital) were categorized into follow-up and lost-to-follow-up groups. We collected information on demographics, the Hamilton depression (HAMD) scale, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale, and Symptom Checklist-90. Patients were routinely followed at 2, 4, 8, and 12 weeks. Any missed appointment was considered lost to follow-up. Results After 12 weeks of treatment, only 42.2% (70/166) of patients were continuing follow-up. Patients lost to follow-up were significantly younger (median, 42.5 vs. 56.5 years), had different marital status, higher education level, higher SDS score (43.8 ± 10.8 vs. 40.2 ± 10.9), and higher HAMD score (median, 21 vs. 19). Age (odds ratio (OR) = 0.97, 95% confidence interval (CI): 0.95–0.997), and HAMD score (OR = 1.14, 95% CI: 1.01–1.29) were independently associated with loss to follow-up. Conclusion Young age, higher HAMD score, and poor knowledge of depression and treatment were the main factors associated with loss to follow-up during depression management among our Chinese patients.
BI6727, a polo-like kinase 1 inhibitor with promising efficacy on Burkitt lymphoma cells
Authors: Chen Er , Pei Renzhi 
Published: May 2020

Objective BI6727, an ATP-competitive PLK1 inhibitor, has been shown to cause cell death in multi-tumors. This study aimed to investigate the anti-tumor effect and potential molecular mechanism of BI6727 in human Burkitt lymphoma (BL) cell lines. Methods We assessed polo-like kinase 1 (PLK1) expression in BL patient tissues and cells, also investigated the cytotoxic effect using CCK8 assay and flow cytometry. In addition, western blotting and real-time polymerase chain reaction (RT-PCR) assays were used to explore the molecular mechanisms of BI6727 in human BL cell lines. Results PLK1 was overexpressed in BL cells compared with normal cells. The PLK1 inhibitor BI6727 reduced activated PLK1 expression and caused mitotic arrest in BL cells. Additionally, BI6727 suppressed cellular proliferation and induced apoptosis in BL cell lines. BI6727 treatment also decreased C-MYC protein and mRNA expression, blocked the PI3K/AKT/mTOR signaling pathway, and stabilized the FBXW7 protein. Conclusions Our findings explained a potential molecular mechanism of BI6727 in BL cells and suggested that BI6727 might be a new therapeutic agent for BL in the future.