bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Clamp in Electrophysiological Studies on Stem Cell–Derived Cardiomyocytes—Why and How?
Authors: Verkerk Arie O. , Wilders Ronald 
Published: November 2020

Abstract:
Human pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) are supposed to be a good human-based model, with virtually unlimited cell source, for studies on mechanisms underlying cardiac development and cardiac diseases, and for identification of drug targets. However, a major drawback of hPSC-CMs as a model system, especially for electrophysiological studies, is their depolarized state and associated spontaneous electrical activity. Various approaches are used to overcome this drawback, including the injection of “synthetic” inward rectifier potassium current (IK1), which is computed in real time, based on the recorded membrane potential (“dynamic clamp”). Such injection of an IK1-like current results in quiescent hPSC-CMs with a nondepolarized resting potential that show “adult-like” action potentials on stimulation, with functional availability of the most important ion channels involved in cardiac electrophysiology. These days, dynamic clamp has become a widely appreciated electrophysiological tool. However, setting up a dynamic clamp system can still be laborious and difficult, both because of the required hardware and the implementation of the dedicated software. In the present review, we first summarize the potential mechanisms underlying the depolarized state of hPSC-CMs and the functional consequences of this depolarized state. Next, we explain how an existing manual patch clamp setup can be extended with dynamic clamp. Finally, we shortly validate the extended setup with atrial-like and ventricular-like hPSC-CMs. We feel that dynamic clamp is a highly valuable tool in the field of cellular electrophysiological studies on hPSC-CMs and hope that our directions for setting up such dynamic clamp system may prove helpful.
Therapeutic Effects of Medication Use on Intermittent Claudication: A Network Meta-analysis
Authors: Ma Bo , Fan Xueqiang , Liu Peng 
Published: November 2020

Objective:
To systematically evaluate the therapeutic effects of commonly used drugs for the treatment of intermittent claudication in patients with peripheral arterial diseases.

Methods:
We systematically searched bibliographic databases for randomized clinical trials published between 2000 and 2020, through the China National Knowledge Infrastructure, WanFang Data, PubMed, MEDLINE, Embase, and Cochrane library. Included studies focused on therapeutic effects of beraprost, clopidogrel, aspirin, sarpogrelate and cilostazol on treating intermittent claudication. The outcome measures were maximum walking distance, pain-free walking distance, ankle-brachial index, and severe adverse events. The quality of included trials was evaluated by using the bias risk assessment tool recommended by the Cochrane, after extracting data from the literatures. Stata was used to conduct the network meta-analysis.

Results:
There were 27 randomized control trials included in the study, covering in total 9491 patients. The network meta-analysis results showed that for maximum walking distance, better therapeutic effect was noted in using beraprost, sarpogrelate, and cilostazol. Beraprost, beraprost combined with aspirin, and sarpogrelate were better in improving pain-free walking distance than other drugs. For the ankle-brachial index, cilostazol combined with clopidogrel, sarpogrelate, and beraprost had better therapeutic effects than others. The use of sarpogrelate, beraprost, and aspirin was associated with a lower ratio of severe adverse events than the use of cilostazol and placebo.

Conclusions:
Among the commonly used drugs for the treatment of intermittent claudication, beraprost and sarpogrelate may have better efficacy in improving the walking distance and ankle-brachial index, with a beneficial effect on cardiovascular and cerebrovascular comorbidities.
Leonurine Attenuates Myocardial Fibrosis Through Upregulation of miR-29a-3p in Mice Post-myocardial Infarction
Authors: Wang Ruiyu , Peng Linqian , Lv Dingyi , Shang Feifei , Yan Jianghong , Li Guoxing , Li Dan , Ouyang Jing , Yang Jiadan 
Published: November 2020

Abstract:
Myocardial fibrosis (MF) is a pathological process that accelerates cardiac remodeling in myocardial infarction (MI), and miR-29 has become one of the foci of research into MF. As an alkaloid extracted from Herba leonuri, leonurine (LE) has been found to be an effective natural active ingredient for inhibiting fibrosis in many preclinical experiments. However, whether LE protects against MF after MI through modifying miR-29 remains unclear. The present study aimed to investigate the therapeutic effects of LE on MF, and to elucidate the underlying mechanisms involved. A mouse model of MI was established, followed by administration of LE for 4 weeks. We found that LE effectively improved cardiac function, and attenuated fibrosis and cardiac remodeling in mice post-MI. In vitro, LE simultaneously inhibited proliferation and migration of neonatal mouse cardiac fibroblasts (CFs) exposed to angiotensin II (Ang II), and the activation of collagen synthesis and myofibroblast generation was markedly suppressed by LE. Notably, we found that all mature miR-29 family members were downregulated in the myocardial tissues of mice post-MI, whereas LE significantly upregulated miR-29a-3p expression, and such upregulation was also detected in LE-treated CFs under Ang II stimulation. Knockdown of miR-29a-3p by a specific miRNA inhibitor upregulated the protein levels of TGF-β, collagen III, and collagen I in CFs, and completely reversed the antifibrotic effects of LE on CFs. Our study suggests that LE exerts cardioprotective effects against MF, possibly through the upregulation of miR-29a-3p.
Comparative Study of Metabolite Changes After Antihypertensive Therapy With Calcium Channel Blockers or Angiotensin Type 1 Receptor Blockers
Authors: Lu Jieyu , Tian Yunfan , Gu Jia , Qiu Ming , Lu Yan , Sun Wei , Kong Xiangqing 
Published: November 2020

Abstract:
The high prevalence of hypertension contributes to an increased global burden of cardiovascular diseases. Calcium channel blockers (CCBs) and angiotensin type 1 receptor blockers (ARBs) are the most widely used antihypertensive drugs, and the effects of these drugs on serum metabolites remain unknown. Untargeted metabolomics has been proved to be a powerful approach for the detection of biomarkers and new compounds. In this study, we aimed to determine the changes in metabolites after single-drug therapy with a CCB or ARB in patients newly diagnosed with mild to moderate primary hypertension. We enrolled 33 patients and used an untargeted metabolomics approach to measure 625 metabolites associated with the response to a 4-week treatment of antihypertensive drugs. After screening based on P < 0.05, fold change > 1.2 or fold change < 0.83, and variable importance in projection > 1, 63 differential metabolites were collected. Four metabolic pathways—cysteine and methionine metabolism, phenylalanine metabolism, taurine and hypotaurine metabolism, and tyrosine metabolism—were identified in participants treated with ARBs. Only taurine and hypotaurine metabolism were identified in participants treated with CCBs. Furthermore, homocitrulline and glucosamine-6-phosphate were relevant to whether the blood pressure reduction achieved the target blood pressure (P < 0.05). Our study provides some evidence that changes in certain metabolites may be a potential marker for the dynamic monitoring of the protective effects and side effects of antihypertensive drugs.
Knockdown of H19 Attenuates Ox-LDL-induced Vascular Smooth Muscle Cell Proliferation, Migration, and Invasion by Regulating miR-599/PAPPA Axis
Authors: Lu Guoyong , Chu Yongxin , Tian Peng 
Published: November 2020

Abstract:
Long noncoding RNAs could participate in the development of atherosclerosis (AS). However, the underlying mechanism by which long noncoding RNA H19 is implicated in AS remains largely unknown. In this study, we investigated the function of H19 on cell proliferation, migration, and invasion in oxidized low-density lipoprotein (ox-LDL)-treated human aortic vascular smooth muscle cells (HA-VSMCs), and on hyperlipidemia response in high-fat diet (HFD)-treated ApoE−/− mice. Moreover, we explored the target interaction among H19, microRNA (miR)-599, and pappalysin 1 (PAPPA). Our results showed that H19 expression was elevated in serum samples of patients with AS and ox-LDL-treated HA-VSMC. H19 silence mitigated ox-LDL-induced proliferation, migration, and invasion of HA-VSMCs. H19 acted as a sponge for miR-599, and miR-599 knockdown reversed the suppressive effect of H19 silence on proliferation, migration, and invasion of HA-VSMCs. PAPPA was a target of miR-599 and attenuated the inhibitive role of miR-599 in HA-VSMC processes. H19 knockdown repressed PAPPA expression by increasing miR-599. Moreover, H19 interference alleviated hyperlipidemia response in HFD-treated ApoE−/− mice. Collectively, knockdown of H19 inhibited proliferation, migration, and invasion of ox-LDL-treated HA-VSMCs and hyperlipidemia response in HFD-treated ApoE−/− mice by regulating miR-599/PAPPA axis, indicating H19 might act as a potential target for the treatment of AS.
A Systematic Review of Randomized Controlled Trials Comparing Renal Sympathetic Denervation Versus Sham Procedure for the Management of Uncontrolled Hypertension
Authors: Maqsood Muhammad H. , Rubab Kinza , Anwar Fazeel , Afzal Khan Muhammad T. , Maqsood Muhammad A. , Farooq Minaam , Tabaza Luai , Rangaswami Janani , Virk Hafeez ul H. 
Published: November 2020

Abstract:
The efficacy of renal sympathetic denervation (RSD) in the treatment of uncontrolled hypertension (HTN) remains uncertain. A systematic review of randomized controlled trials was performed to evaluate the efficacy and safety of RSD for resistant HTN. PubMed, EMBASE, MEDLINE, Cochrane, Directory of Open Access Journals, CINAHL, and Google Scholar were searched from January 01, 2001, through July 30, 2020. Randomized controlled trials comparing RSD with the sham procedure for uncontrolled HTN were selected. The primary efficacy outcome was the reduction in ambulatory systolic blood pressure. We used random-effects models. Nine prospective clinical trials met the inclusion criteria. The ReSet and Symplicity HTN-3 Trial showed no significant changes because of discrepancies in complete circumferential ablation during RSD. The Relief study, The Radiance HTN solo, and the SPYRAL HTN OFF medical trials showed a significant reduction in systolic blood pressure in the group that had undergone the intervention compared with the sham group attributed to rigorous trial design. In conclusion, our systematic review suggests that efficacy of RSD seems to be superior to sham-controlled interventions provided circumferential denervation is performed. However, difference in efficacy is marginal.
Plasma Concentrations and Safety of Lopinavir/Ritonavir in COVID-19 Patients
Authors: Chouchana Laurent , Boujaafar Sana , Gana Ines , Preta Laure-Hélène , Regard Lucile , Legendre Paul , Azoulay Celia , Canouï Etienne , Zerbit Jeremie , Carlier Nicolas , Terrier Benjamin , Kernéis Solen , Batista Rui , Treluyer Jean-Marc , Zheng Yi , Benaboud Sihem 
Published: November 2020

Background:
Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential.

Methods:
Real-world COVID-19 data based on a retrospective study.

Results:
Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6–6.2), compared with the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders.

Conclusions:
Lopinavir plasma concentrations in patients with moderate-to-severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Caution is essential because off-label use can be associated with a new drug safety profile.
Developing and evaluating a patient decision aid for hormone therapy to manage symptoms of surgical menopause: the story behind the “SheEmpowers” patient decision aid
Authors: Siyam Tasneem , Shivji Alisha , Ross Sue , Eurich Dean T. , Lavasanifar Afsaneh , Yuksel Nesé 
Published: November 2020

Abstract

Objectives:
To develop and evaluate an evidence-based patient decision aid (PDA) that can support women making decisions on hormone therapy (HT) for the management of early surgical menopause.

Methods:
The PDA development was guided by the Ottawa Decision Support Framework and the International Patient Decision Aid Standards and involved three phases: an exploratory phase to identify women's decisional needs; a development phase to identify evidence related to treatment options and draft initial prototype; and an evaluation phase to evaluate the prototype and elicit views on acceptability in women (N = 12). All phases were driven by a multidisciplinary group of researchers, clinicians, and patient stakeholders to ensure women's priorities were met.

Results:
A prototype PDA was drafted based on needs identified from the exploratory phase. The PDA has five domains: information on surgical menopause and HT; HT outcome probabilities; patient stories; values clarification; and guidance in deliberation. Participants in the evaluation phase perceived the tool as acceptable and offered suggestions for modifications.

Conclusion:
Through our adopted, systematic approach the SheEmpowers PDA was developed to help women overcome deterrents to decision-making related to lack of knowledge, decision-making skills, and involvement in therapy decisions. The decisional effectiveness of the tool is to be assessed in future studies.
Estimation of Heights and Body Masses of Tuberculosis Patients in the Canadian Fluoroscopy Cohort Study for Use in Individual Dosimetry
Authors: Thiessen Kathleen M. , Apostoaei A. Iulian , Zablotska Lydia B. 
Published: November 2020

Abstract
This paper documents the estimation of mean heights and body masses, by age and sex, used in development of organ-specific dose conversion coefficients for external radiation for a historical cohort of about 64,000 patients from the Canadian Fluoroscopy Cohort Study. Patients were exposed to repeated fluoroscopy and chest radiography examinations in the course of treatment for tuberculosis in residential medical facilities throughout Canada between 1930 and 1969. Using Canadian national survey data and extensive literature review, mean heights and masses were obtained for the White population of Canada during the time period of interest, and the differences in mean body mass between tuberculosis patients and the general population were estimated. Results in terms of mean height and body mass of Canadian tuberculosis patients, with uncertainties, are reported for selected age groups (children of ages 1, 5, 10, and 15 y and adults age 20+) and for both sexes. Use of estimated average heights and body masses by age and sex permits the adjustment of computerized phantoms for body mass for a given age, thereby increasing the relevance of the organ-specific dose conversion coefficients for the cohort and improving the accuracy of the resulting estimated organ doses.
Identification of Volume of Distribution for 239Pu in Rats
Authors: Cook Madeline C. , Brey Richard R. 
Published: November 2020

Abstract
The work within identifies the volume of distribution (VD) of plutonium using data from studies in which rats were administered an intravenous bolus injection of 239Pu4+-citrate. The research investigated two separate datasets. Data published by Durbin and colleagues in “Plutonium Deposition Kinetics in Rats” and studies conducted by Lovelace Respiratory Research Institute (LRRI) were examined. The goal of this research was to identify a value of VD consistent with the known biological behavior of plutonium. The identified VD is necessary to develop a physiologically-based pharmacokinetic (PBPK) model. The creation of a PBPK model describing the behavior of plutonium in the body enables the comparison of transfer rates to validate the biokinetic models currently in use for internal dosimetry purposes. The VD of a substance describes the distribution between intracellular and extracellular fluid compartments, providing information such as cellular uptake and protein binding. The VD time profiles and values found using the Durbin data were consistent with known behavior of plutonium. The VD values found using data provided by LRRI were not consistent with known behavior of plutonium; however, the VD time profiles generated may still be of use for PBPK modeling.
Invasive Bacterial and Fungal Infections After Pediatric Cardiac Surgery: A Single-center Experience
Authors: Tönz Gian Maria , Kadner Alexander , Pfammatter Jean-Pierre , Agyeman Philipp Kwame Abayie 
Published: November 2020

Background:
Discrimination of infectious and noninfectious complications in children with inflammatory signs after cardiac surgery is challenging. Given the low prevalence of infectious complications after heart surgery, there might be a risk of excessive antibiotic usage. We performed this study to determine the rate of invasive bacterial or fungal infections in children after cardiac surgery at our institution and to evaluate our postoperative management.

Methods:
This single-center retrospective observational cohort study included children 16 years of age or younger who underwent cardiac surgery at our institution between January 2012 and December 2015.

Results:
We analyzed 395 surgical procedures. Thirty-five postoperative invasive bacterial or fungal infections were detected in 29 episodes (7%, 0.42 per 100 admission days). Among bacterial infections, the most common infection sites were bacteremia and pneumonia, accounting for 37% (13/35) and 23% (8/35) of infections respectively. The rate of postoperative infections was associated with surgical complexity score and length of postoperative pediatric intensive care unit (PICU) stay. In 154 (43%) of 357 episodes without microbiologically documented infection, uninterrupted postoperative antibiotic administration was continued for more than 3 days and in 80 (22%) for more than 5 days.

Conclusions:
The rate of postoperative bacterial or fungal infection at our institution is comparable to current literature. High surgical complexity score and prolonged length of PICU stay were risk factors for bacterial or fungal infections in this patient population.
Translation and validation of the traditional Chinese version of the Constipation Severity Instrument
Authors: Tsai Yi-Jian , Yang Yi-Wen , Lan Yuan-Tzu 
Published: November 2020

Background:
The Constipation Severity Instrument (CSI) is a well-validated measure for assessing constipation severity. At present, no translated traditional Chinese version of the scale is available. We aimed to develop a traditional Chinese version of the CSI and to validate the translated version.

Methods:
The CSI questionnaire was translated into traditional Chinese language, followed by linguistic validation. It was tested on 45 constipated patients and 55 controls from colorectal outpatient clinics and volunteers. A retest was performed in a subgroup of 39 patients 2 weeks later. Convergent validation was assessed using the Cleveland constipation scoring system (CSS) and quality of life was assessed with the 12-item short-form health survey (SF-12). The reliability and validity were assessed using Cronbach’s α coefficient, intraclass correlation coefficient (ICC), and the Spearman correlation test.

Results:
Cronbach’s α coefficient for the CSI total score and its three subscale scores were all above 0.93. Test–retest reliability was good for the CSI total score (ICC = 0.865) and its three subscale scores (ICC = 0.709–0.882). The constipated participants could be effectively differentiated from the controls based on the CSI total score and its three subscales. The convergent validation was good between the CSI and CSS (Spearman’s ρ = 0.711, p < 0.001). The CSI score correlated negatively with the physical composite score and mental composite score of the SF-12 quality of life scale, indicating poorer quality of life in constipated patients.

Conclusion:
We demonstrated the reliability and validity of the traditional Chinese version of the CSI, which could be a standardized tool for future studies on constipation.
Omeprazole vs famotidine for the prevention of gastroduodenal injury in high-risk users of low-dose aspirin: A randomized controlled trial
Authors: Tseng Zhi-Fu , Hsu Ping-I , Peng Nan-Jing , Kao Sung-Shuo , Tsay Feng-Woei , Cheng Jin-Shiung , Chen Wen-Chi , Tsai Kun-Feng , Tang Sheng-Yeh , Chuah Seng-Kee , Shie Chang-Bih 
Published: November 2020

Background:
Low-dose aspirin is widely used in the prevention of cardiovascular diseases. However, the use of aspirin is associated with an increased risk of gastrointestinal injury.

Methods:
Low-dose aspirin users with a history of peptic ulcers who did not have gastroduodenal mucosal breaks at initial endoscopy were randomly assigned to receive famotidine (20 mg bid) or omeprazole (20 mg qd) for 6 months. Follow-up endoscopy was performed at the end of the sixth month and whenever epigastric discomfort, hematemesis, or melena occurred. The primary end point was the occurrence of gastroduodenal mucosal breaks. The secondary end points were (1) the occurrence of gastroduodenal ulcers and (2) the occurrence of gastroduodenal bleeding.

Result:
Between November 2013 and June 2018, 170 patients were randomly assigned to receive either famotidine (n = 84) or omeprazole (n = 86). The incidence of gastroduodenal mucosal breaks was 33.8% among the patients receiving famotidine, and 19.8% among those receiving omeprazole (95% CI: 0.4%-27.5%; p = 0.045). The two patient groups had comparable incidence rates of gastroduodenal ulcers (20.0% vs 9.8%; p = 0.071), and gastroduodenal bleeding (2.5% vs 0%; p = 0.243). Multivariate analysis showed that use of the proton pump inhibitor was an independent protective factor (odds ratio: 0.47; 95% CI: 0.23-0.99; p = 0.047), and that smoking was a risk factor for mucosal breaks (odds ratio: 3.84; 95% CI: 1.52-9.71; p = 0.004).

Conclusion:
Proton pump inhibitor was superior to histamine-2 receptor antagonist in the prevention of gastroduodenal mucosal breaks in high-risk users of low-dose aspirin, and smoking was an independent risk factor for developing gastroduodenal mucosal breaks.