bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empagliflozin improves chronic hypercortisolism-induced abnormal myocardial structure and cardiac function in mice
Authors: Zhang Qing-Qing , Li Guo-Qing , Zhong Yi , Wang Jie , Wang An-Ning , Zhou Xiao , Mao Xiao-Ming 
Published: November 2020

Background: Chronic exposure to excess glucocorticoids is frequently associated with a specific cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has beneficial effects as it aids in the reduction of heart failure and cardiovascular mortality in hospitalized patients. The aim of this study was to investigate the effects of empagliflozin on chronic hypercortisolism-induced myocardial fibrosis and myocardial dysfunction in mice. Methods: Male C57BL/6J mice (6 weeks old) were randomized to control, corticosterone (CORT), and empagliflozin + CORT groups. After 4 weeks of administration, heart structure and function were evaluated by echocardiography, and peripheral blood and tissue samples were collected. Expressions of Ccl2, Itgax, Mrc1, and Adgre1 mRNA in heart tissue were evaluated by RT-PCR, and signal transducer and activator of transcription 3 (STAT3) and Toll-like receptor 4 (TLR4) protein expression were analyzed by Western blotting. Results: Empagliflozin effectively reduced body weight, liver triglyceride, visceral adipose volume, and uric acid in CORT-treated mice. Left ventricular hypertrophy and cardiac dysfunction were improved significantly, phosphorylated STAT3 and TLR4 were alleviated, and macrophage infiltration in the myocardium was inhibited after administration of empagliflozin in CORT-treated mice. Conclusion: Empagliflozin has beneficial effects on specific cardiomyopathy associated with CORT, and the results provide new evidence that empagliflozin might be a potential drug for the prevention of this disease.
Management of Patients With Glomerulonephritis During the COVID-19 Pandemic: Recommendations From the Canadian Society of Nephrology COVID-19 Rapid Response Team
Authors: Moran Sarah M. , Barbour Sean , Dipchand Christine , Garland Jocelyn S. , Hladunewich Michelle , Jauhal Arenn , Kappel Joanne E. , Levin Adeera , Pandeya Sanjay , Reich Heather N. , Thanabalasingam Susan , Thomas Dorothy , Ma Jeffrey C. , White Christine ,   On Behalf of the CSN COVID-19 Rapid Response Team, Antonsen John , Banks Cheryl , Clark David , Clark Edward , Copland Michael , Davison Sara N. , Goldberg Aviva , Hemmett Juliya , Hiremath Swapnil , Kappel Joanne , MacRae Jennifer M. , Mac-Way Fabrice , Mathew Anna , McCormick Brendan , Moist Louise , Moran Sarah , Pandeya Sanjay , Qirjazi Elena , Ryz Krista , Singh Suneet , Soroka Steven , Suri Rita , Tennankore Karthik , Thanabalasingam Susan , Wald Ron , Weir Mathew , White Christine , Zimmerman Deborah , Levin Adeera , Mustafa Reem A. , Nesrallah Gihad , Soroka Steven , Zimmerman Deborah 
Published: November 2020

Purpose of program: This article will provide guidance on how to best manage patients with glomerulonephritis (GN) during the COVID-19 pandemic. Sources of information: We reviewed relevant published literature, program-specific documents, and guidance documents from international societies. An informal survey of Canadian nephrologists was conducted to identify practice patterns and expert opinions. We hosted a national webinar with invited input and feedback after webinar. Methods: The Canadian Society of Nephrology (CSN) Board of Directors invited physicians with expertise in GN to contribute. Specific COVID-19-related themes in GN were identified, and consensus-based recommendations were made by this group of nephrologists. The recommendations received further peer input and review by Canadian nephrologists via a CSN-sponsored webinar. This was attended by 150 kidney health care professionals. The final consensus recommendations also incorporated review by Editors of the Canadian Journal of Kidney Health and Disease. Key findings: We identified 9 areas of GN management that may be affected by the COVID-19 pandemic: (1) clinic visit scheduling, (2) clinic visit type, (3) provision of multidisciplinary care, (4) blood and urine testing, (5) home-based monitoring essentials, (6) immunosuppression, (7) other medications, (8) patient education and support, and (9) employment. Limitations: These recommendations are expert opinion, and are subject to the biases associated with this level of evidence. To expedite the publication of this work, a parallel review process was created that may not be as robust as standard arm’s length peer review processes. Implications: These recommendations are intended to provide optimal care during the COVID-19 pandemic. Our recommendations may change based on the evolving evidence.
The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) Trial: A Protocol for a Randomized, Crossover, Placebo-Controlled Blinded Trial
Authors: Collister David , Pohl Kayla , Herrington Gwen , Lee Shun Fu , Rabbat Christian , Tennankore Karthik , Zimmermann Deborah , Tangri Navdeep , Wald Ron , Manns Braden , Suri Rita S. , Nadeau-Fredette Annie-Claire , Goupil Remi , Silver Samuel A. , Walsh Michael 
Published: November 2020

Background: Restless legs syndrome (RLS) affects approximately 30% of patients with end-stage kidney disease and is associated with impaired sleep and health-related quality of life. Medications used to treat RLS in patients receiving dialysis may have an increased risk of adverse events with dose titration, and residual RLS symptoms are common despite the use of effective treatments. Randomized controlled trials of monotherapy and combination pharmacologic therapy for RLS in hemodialysis are needed. Objective: To perform a randomized, crossover, placebo-controlled blinded trial of pharmacologic therapy for RLS in hemodialysis. Design/setting: The DIalysis Symptom COntrol-Restless Legs Syndrome (DISCO-RLS) trial is a randomized, crossover, placebo-controlled blinded trial of fixed low-dose pharmacologic therapy in patients receiving hemodialysis in 10 centers across Canada. It uses patient partners in its design, conduct, and reporting. Participants: Adults receiving thrice-weekly hemodialysis for at least 3 months with RLS of at least mild symptoms defined International Restless Legs Syndrome Study Group Rating Scale (IRLS) of 10 or more will enter a double placebo run-in period to exclude nonadherent participants and those unable to tolerate double placebo. Seventy-two participants who completed the run-in period will be randomized to 1 of 8 treatment sequences based on modeling with 4 treatment periods. Methods: Each treatment period lasts 4 weeks and consists of ropinirole 0.5 mg daily and gabapentin 100 mg daily, both together or neither with a double dummy placebo control for each treatment. The primary outcome is the difference in change scores of the IRLS between study treatments. Secondary outcomes are the differences in change scores of the Restless Legs Syndrome-6 Scale, patient global impression, 5-level EQ-5D version, and safety outcomes. Results: This randomized, crossover, placebo-controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination of ropinirole and gabapentin in patients receiving hemodialysis with RLS. Limitations: Patients with chronic kidney disease not on dialysis, kidney transplant recipients and those receiving peritoneal dialysis or home hemodialysis are not included. The intervention’s long term safety and efficacy including the risk of augmentation is not captured. Conclusion: This randomized crossover placebo controlled blinded trial will evaluate the efficacy and safety of fixed low-dose combination ropinirole and gabapentin in patients receiving hemodialysis with RLS. Trial Registration: ClinicalTrials.gov (NCT03806530)
A Framework to Ensure Patient Partners Have Equal and Contributing Voices Throughout the Research Program Evaluation Process
Authors: Hillier David R. , Tang Mila , Clark William , MacDonald Cynthia , Connolly Carol , Large Chantel , King Malcolm , Singer Joel , Levin Adeera , Manns Braden , Konvalinka Ana , Scholey James , Rosenblum Norman D. 
Published: November 2020

Purpose of program: Traditionally, peer review was a closed process conducted only by individuals working in the research field. To establish a more integrated and patient-centered approach, one of Canada’s largest kidney research networks (Can-SOLVE CKD) has created a Research Operations Committee (ROC) that includes patients as key members. The ROC represents one way for achieving meaningful patient-oriented research (POR). Source of information: Can-SOLVE CKD, a network created as part of the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR). Methods: The ROC consists of patients, physicians, scientists, Indigenous partners, experts in research methodology, and a member of Can-SOLVE CKD’s operational team. On an annual basis, Can-SOLVE CKD’s research teams provide the ROC with a review package, which incorporates information from patient engagement check-in calls and surveys, the project’s knowledge translation plan and products, and a progress report written by the project team. The ROC evaluates the review package and provides feedback and recommendations accordingly. Key findings: The transparent nature of the process, regular feedback and review, along with an overt accountability and scoring system, has been embraced by both patients and researchers. As a result of the ROC process, the number of patient leads for each project has grown over a 3-year period and more researchers have received POR and cultural sensitivity training. Limitations: While anecdotal evidence suggests this approach is beneficial for achieving POR, formal mechanisms of evaluation are currently lacking. Implications: This ROC framework ensures patients are active contributors throughout the research process and could be adopted by other organizations to achieve a more patient-centered approach to research.
Effect of Endodontic Treatment on Serum Glutathione (GSH) Levels in Patients with Chronic Apical Periodontitis: A Clinical Pilot Study
Authors: Bains Rhythm , Tikku Aseem P. , Chandra Anil , Ali Wahid , Verma Promila 
Published: November 2020

Aim: To assess the before- and after-treatment levels of glutathione (GSH) in the serum of patients with chronic apical periodontitis. Materials and Methods: The study involved 20 systemically healthy patients with radiographic evidence of chronic apical periodontitis in at least one tooth, of which 11 were finally assessed. 10 mL of the patient’s venous blood was obtained before commencing the endodontic treatment to assess the pre-operative serum GSH levels (T0). The canals cleaned and shaped, and irrigated with 2.5% sodium hypochlorite, and filled with a calcium hydroxide based intracanal medicament. At the subsequent appointment after one week, teeth were obturated. The patients were recalled 30 days after the completion of endodontic therapy, and blood samples were assessed again at time frame T1 for serum GSH. The difference in pre- and post-treatment values for T0 and T1 was statistically analyzed. Results: The mean age of the subjects ( N = 11) was 21.09±3.24 years, with 19.50±0.71 years in female group and 21.44±3.50 years in the male group. The mean GSH at T0 was 11.73±8.30 units, which was increased to 14.04±13.96 units at T1. However, no significant change was observed in the GSH level from T0 to T1 (change = –2.30, t-value = –0.49, P = .635). Conclusion: The results of this study suggest that endodontic therapy may play a role in restoring the systemic oxidative balance, as seen by the increase in post-treatment serum GSH levels.
Survivin Expression in Metastatic and Nonmetastatic Oral Squamous Cell Carcinoma: A Comparative Study
Authors: Sekar B. , Indrapriyadharshini K. , Ambika M. , Saranyan R. , Nirmal Madhavan , Manzoor Sathick 
Published: November 2020

Aim: Survivin is a multifunctional protein chiefly involved in apoptosis and cell cycle regulation. Increased expression of survivin in tumors and fetal tissue determines its antiapoptotic activity. The aim of the study is to identify the immunoexpression of survivin in metastatic and nonmetastatic oral squamous cell carcinoma (OSCC) and also to evaluate and compare the expression of survivin in metastatic and nonmetastatic OSCC of buccal mucosa. Materials and Methods: In total, 40 histopathologically proven cases of OSCC, including 20 metastatic and 20 nonmetastatic cases, are selected. Among the 20 metastatic and nonmetastatic cases, 10 well-differentiated and 10 moderately differentiated squamous cell carcinoma cases were included and were subjected to immunohistochemical staining for survivin expression. The results were analyzed by SPSS version 11.5 using chi-square test. Results: The expression of survivin in metastatic and nonmetastatic tumors is 15%–70% and 15%–60%, respectively. When comparing the cases of moderately differentiated squamous cell carcinoma in metastatic and nonmetastatic tumors, 70% cases show moderate staining intensity. Conclusion: The survivin expression was comparatively high in metastatic OSCC. Also based on the aforementioned results, survivin expression was high in increasing grades of OSCC.
A Randomized, Crossover Pilot Study of a Novel Web-Based/Mobile Platform for Collaborative Small Group Practice in Therapeutic Reasoning
Authors: Gruenberg Katherine , Brock Tina , Garcia Joshua , MacDougall Conan 
Published: November 2020

Background and Purpose: Therapeutic reasoning—the mental process of making judgments and decisions about treatment—is developed through acquisition of knowledge and application in actual or simulated experiences. Health professions education frequently uses collaborative small group work to practice therapeutic reasoning. This pilot study compared the impact of a web-based/mobile tool for collaborative case work and discussion to usual practice on student perceptions and performance on questions designed to test therapeutic knowledge and reasoning. Methods: In a therapeutics course that includes case-based workshops, student teams of 3 to 4 were randomly assigned to usual workshop preparation (group SOAP sheet) or preparation using the Practice Improvement using Virtual Online Training (PIVOT) platform. PIVOT was also used in the workshop to review the case and student responses. The next week, groups crossed over to the other condition. Students rated favorability with the preparatory and in-workshop experiences and provided comments about the PIVOT platform via a survey. Student performance on examination items related to the 2 workshop topics was compared. Results: One hundred and eleven students (94%) completed post-workshop surveys after both workshops. The majority of students (57%) preferred using the PIVOT platform for workshop collaboration. Favorability ratings for the in-workshop experience did not change significantly from first to second study week, regardless of sequence of exposure. There was no relationship between examination item scores and the workshop platform the students were exposed to for that content ( P = .29). Student responses highlighted the efficiency of working independently before collaborating as a group and the ability to see other students’ thought processes as valuable aspects of PIVOT. Students expressed frustration with the PIVOT user interface and the lack of anonymity when discussing their answers in the workshop. Conclusion: A web-based/mobile platform for student team collaboration on therapeutic reasoning cases discussed in small group settings yielded favorable ratings, examination performance comparable to standard approaches, and was preferred by a majority of students. During the rapid shift to substantial online learning for the COVID-19 pandemic, virtual collaboration tools like PIVOT may help health professions teachers to better support groups working virtually on scaffolded therapeutic reasoning tasks.
Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody
Authors: Quijada Hector , Bermudez Tadeo , Kempf Carrie L. , Valera Daniel G. , Garcia Alexander N. , Camp Sara M. , Song Jin H. , Franco Evelyn , Burt Jessica K. , Sun Belinda , Mascarenhas Joseph B. , Burns Kimberlie , Gaber Amir , Oita Radu C. , Reyes Hernon Vivian , Barber Christy , Moreno-Vinasco Liliana , Sun Xiaoguang , Cress Anne E. , Martin Diego , Liu Zhonglin , Desai Ankit A. , Natarajan Viswanathan , Jacobson Jeffrey R. , Dudek Steven M. , Bime Christian , Sammani Saad , Garcia Joe G.N. 
Published: November 2020

RationaleThe severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 pandemic has highlighted the serious unmet need for effective therapies that reduce acute respiratory distress syndrome (ARDS) mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor (TLR)4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target.MethodsWild-type C57BL/6J or endothelial cell (EC)-cNAMPT−/−knockout mice (targeted ECNAMPTdeletion) were exposed to either a lipopolysaccharide (LPS)-induced (“one-hit”) or a combined LPS/ventilator (“two-hit”)-induced acute inflammatory lung injury model. A NAMPT-specific monoclonal antibody (mAb) imaging probe (99mTc-ProNamptor) was used to detect NAMPT expression in lung tissues. Either an eNAMPT-neutralising goat polyclonal antibody (pAb) or a humanised monoclonal antibody (ALT-100 mAb) were usedin vitroandin vivo.ResultsImmunohistochemical, biochemical and imaging studies validated time-dependent increases in NAMPT lung tissue expression in both pre-clinical ARDS models. Intravenous delivery of either eNAMPT-neutralising pAb or mAb significantly attenuated inflammatory lung injury (haematoxylin and eosin staining, bronchoalveolar lavage (BAL) protein, BAL polymorphonuclear cells, plasma interleukin-6) in both pre-clinical models.In vitrohuman lung EC studies demonstrated eNAMPT-neutralising antibodies (pAb, mAb) to strongly abrogate eNAMPT-induced TLR4 pathway activation and EC barrier disruption.In vivostudies in wild-type and EC-cNAMPT−/−mice confirmed a highly significant contribution of EC-derived NAMPT to the severity of inflammatory lung injury in both pre-clinical ARDS models.ConclusionsThese findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker andNAMPTgenotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine.
Development and validation of a deep learning algorithm detecting 10 common abnormalities on chest radiographs
Authors: Nam Ju Gang , Kim Minchul , Park Jongchan , Hwang Eui Jin , Lee Jong Hyuk , Hong Jung Hee , Goo Jin Mo , Park Chang Min 
Published: November 2020

We aimed to develop a deep learning algorithm detecting 10 common abnormalities (DLAD-10) on chest radiographs, and to evaluate its impact in diagnostic accuracy, timeliness of reporting and workflow efficacy.DLAD-10 was trained with 146 717 radiographs from 108 053 patients using a ResNet34-based neural network with lesion-specific channels for 10 common radiological abnormalities (pneumothorax, mediastinal widening, pneumoperitoneum, nodule/mass, consolidation, pleural effusion, linear atelectasis, fibrosis, calcification and cardiomegaly). For external validation, the performance of DLAD-10 on a same-day computed tomography (CT)-confirmed dataset (normal:abnormal 53:147) and an open-source dataset (PadChest; normal:abnormal 339:334) was compared with that of three radiologists. Separate simulated reading tests were conducted on another dataset adjusted to real-world disease prevalence in the emergency department, consisting of four critical, 52 urgent and 146 nonurgent cases. Six radiologists participated in the simulated reading sessions with and without DLAD-10.DLAD-10 exhibited area under the receiver operating characteristic curve values of 0.895–1.00 in the CT-confirmed dataset and 0.913–0.997 in the PadChest dataset. DLAD-10 correctly classified significantly more critical abnormalities (95.0% (57/60)) than pooled radiologists (84.4% (152/180); p=0.01). In simulated reading tests for emergency department patients, pooled readers detected significantly more critical (70.8% (17/24)versus29.2% (7/24); p=0.006) and urgent (82.7% (258/312)versus78.2% (244/312); p=0.04) abnormalities when aided by DLAD-10. DLAD-10 assistance shortened the mean±sdtime-to-report critical and urgent radiographs (640.5±466.3versus3371.0±1352.5 s and 1840.3±1141.1versus2127.1±1468.2 s, respectively; all p<0.01) and reduced the mean±sdinterpretation time (20.5±22.8versus23.5±23.7 s; p<0.001).DLAD-10 showed excellent performance, improving radiologists' performance and shortening the reporting time for critical and urgent cases.
Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan
Authors: du Cros Philipp , Khamraev Atadjan , Tigay Zinaida , Abdrasuliev Tleubergen , Greig Jane , Cooke Graham , Herboczek Krzysztof , Pylypenko Tanya , Berry Catherine , Ronnachit Amrita , Lister David , Dietrich Sebastian , Ariti Cono , Safaev Khasan , Nyang'wa Bern-Thomas , Parpieva Nargiza , Tillashaikhov Mirzagalib , Achar Jay 
Published: November 2020

BackgroundIn 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.MethodsConsecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.ResultsOf 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression.ConclusionsOverall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.