bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Hydrogen Sulfide in Myocardial Ischemia–Reperfusion Injury
Authors: Zhang Peng , Yu Yue , Wang Pei , Shen Hua , Ling Xinyu , Xue Xiaofei , Yang Qian , Zhang Yufeng , Xiao Jian , Wang Zhinong 
Published: November 2020

Abstract:
Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide and carbon monoxide, has been found as an important endogenous gasotransmitter in the last few decades, and it plays a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia–reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of I/R injury, such as S-sulfhydrated modification, antiapoptosis, effects on microRNA, bidirectional effect on autophagy, antioxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development, and the pharmacological characterization of H2S donor drugs have made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.
Quantitative Method for the Analysis of Ivacaftor, Hydroxymethyl Ivacaftor, Ivacaftor Carboxylate, Lumacaftor, and Tezacaftor in Plasma and Sputum Using Liquid Chromatography With Tandem Mass Spectrometry and Its Clinical Applicability
Authors: Vonk Steffie E. M. , van der Meer-Vos Marloes , Bos Lieuwe D. J. , Neerincx Anne H. , Majoor Christof J. , Maitland-van der Zee Anke-Hilse , Mathôt Ron A. A. , Kemper E. Marleen ,   on behalf of the Amsterdam Mucociliary Clearance Disease (AMCD) research group
Published: November 2020

Background:
The novel cystic fibrosis transmembrane conductance regulator (CFTR) modulators, ivacaftor, lumacaftor, and tezacaftor, are the first drugs directly targeting the underlying pathophysiological mechanism in cystic fibrosis (CF); however, independent studies describing their pharmacokinetics are lacking. The aim of this study was to develop a quantification method for ivacaftor and its 2 main metabolites, lumacaftor and tezacaftor, in plasma and sputum using liquid chromatography with tandem mass spectrometry.

Methods:
The developed method used a small sample volume (20 µL) and simple pretreatment method; protein precipitation solution and internal standard were added in one step to each sample. Liquid chromatography with tandem mass spectrometry was performed for a total run time of 6 minutes. The method was validated by assessing selectivity, carryover, linearity, accuracy and precision, dilution, matrix effects, and stability.

Results:
The selectivity was good as no interference from matrices was observed. In the concentration range from 0.01 to 10.0 mg/L, calibration curves were linear with a correlation coefficient >0.9997 for all compounds. The within-run and between-run accuracy were between 99.7% and 116% at the lower limit of quantitation (LLOQ) and between 95.8% and 112.9% for all concentrations above LLOQ for all analytes in plasma and sputum. Within-run and between-run precisions were <12.7% for LLOQ and <6.7% for the higher limit of quantitation. Samples were stable, with no significant degradation at examined temperatures and time points. Clinical applicability was revealed by analyzing samples from 2 patients with CF.

Conclusions:
The presented method enables simultaneous quantification of ivacaftor, lumacaftor, and tezacaftor in plasma and sputum and is an improvement over previous methods because it uses smaller sample volumes, a simple pretreatment protocol, and includes tezacaftor. In future studies, it can be applied for examining pharmacokinetics characteristics of new CF transmembrane conductance regulator modulators.
Prospective Evaluation of Childhood Encephalitis
Authors: Fowler Åsa , Ygberg Sofia , Svensson Eva , Bergman Kristian , Cooray Gerald , Wickström Ronny 
Published: November 2020

Background:
Acute encephalitis in childhood is a serious condition. The severity varies between studies, partly reflecting differences in study design where only severe cases from referral centers often are reported. The aim of this study was to prospectively study the clinical picture and etiology of acute encephalitis in childhood at a primary and tertiary pediatric hospital in Sweden.

Methods:
All children with acute encephalitis were prospectively included from 2011 to 2016. Laboratory tests, investigations and follow-up were performed according to standardized study protocols.

Results:
Eighty-nine children were included (46 female and 43 male) with a median age of 53 months. An etiology was established in 61/89. Tick-borne encephalitis virus, enterovirus and rotavirus dominated and 34% were caused by a virus preventable by vaccination. Immune-mediated encephalitis was seen in 7 children. An abnormal electroencephalography picture was seen in 77/86, pathologic findings on neuroimaging in 13/49, and 38/89 children had seizures. Sequelae were reported by 49%. A high prevalence of previous contact with child and adolescent psychiatry was seen and, although not statistically significant, the need for extra support at school before encephalitis and the presence of central nervous system disease in the family seemed to predispose for a longer hospital stay.

Conclusion:
Encephalitis is a condition with long-term consequences. Most children need admission to hospital, and many need surveillance in the intensive care unit. The etiology can be determined in a majority of cases, and 1/3 could have been prevented by vaccination. This study corroborates electroencephalography as a cornerstone in diagnosis.
Hypersensitivity Myocarditis Due to Antitubercular Drugs in Children
Authors: Dhochak Nitin , Ram Jat Kana , Sankar Jhuma , Kabra Sushil K. , Lodha Rakesh 
Published: November 2020

Background:
Drug-related hypersensitivity myocarditis is a rare acute hypersensitivity reaction to therapeutic agents. Reports of antitubercular drugs causing hypersensitivity myocarditis are not described in literature.

Methods:
Retrospective chart review of children admitted between January 1, 2016, and March 31, 2019, was conducted to identify children receiving antitubercular drugs who were diagnosed with hypersensitivity myocarditis.

Results:
Three children (2 girls), who had hypersensitivity myocarditis due to antitubercular therapy, were identified. Cases 1 and 2 developed hypersensitivity myocarditis due to rifampicin, and isoniazid-rifampicin combination, respectively, on reintroduction of drugs, while case 3 developed hypersensitivity to streptomycin on first exposure. All children developed symptoms within minutes to hours of starting the offending drugs. Severe myocardial dysfunction leading to shock and pulmonary edema was seen in cases 1 and 3, while case 2 presented with wide QRS complex ventricular rhythm with bradycardia and hypotensive shock. Cases 1 and 2 were treated with steroids. Cases 1 and 3 received intravenous immunoglobulin therapy. First 2 children survived while third died of refractory shock. Total serum IgE levels were elevated in all children (range: 161–3053 kU/L).

Conclusion:
Hypersensitivity myocarditis is a rare but life-threatening adverse effect of antitubercular drugs. Prompt diagnosis of hypersensitivity myocarditis and timely steroid therapy can be lifesaving.
Missed Opportunity Encounters for Early Diagnosis of HIV Infection in Adolescents
Authors: Most Zachary M. , Warraich Gohar J. , James Lorraine , Costello Kathleen , Dietz Stephen , Lamb Gabriella S. , Evans Amanda S. 
Published: November 2020

Background:
Early diagnosis of HIV infection improves patient outcomes and reduces transmission. Adolescents make up one-fifth of new HIV diagnoses in the United States. We sought to quantify the number of missed opportunity encounters (MOEs) before HIV diagnosis for adolescents at a pediatric hospital (PediHosp) and a proximate adult hospital which employs universal HIV screening in its emergency department (ED) (CountyHosp).

Methods:
An observational study at 2 academic tertiary care hospitals in the United States that included all adolescents 13–20 years old with a new diagnosis of behaviorally-acquired HIV infection from 2006 to 2017. MOE were defined as any encounter at PediHosp or CountyHosp after the latter of the individual’s 13th birthday or the date 3 months after the individual’s most recent negative HIV screen, and before the encounter of HIV diagnosis. Comparisons were made by site of diagnosis and location of MOE.

Results:
Two-hundred five subjects met inclusion criteria: 68% male, 76% Black and 81% men who have sex with men. There were 264 MOE, the proportion of adolescent ED encounters that were MOE at the PediHosp ED was 8.3 MOE per 10,000 encounters and the proportion at the CountyHosp ED was 1.2 (relative risk = 6.7; 95% CI: 4.1–11.0; P < 0.001).

Conclusions:
MOE for HIV diagnosis in adolescents occur frequently and are greater in number at a PediHosp as compared with a similar adult setting with universal screening. Universal HIV screening protocols at PediHosp may identify HIV-positive adolescents earlier.
Radiomics-Based Prediction of Long-Term Treatment Response of Vestibular Schwannomas Following Stereotactic Radiosurgery
Authors: Langenhuizen Patrick P. J. H. , Zinger Svetlana , Leenstra Sieger , Kunst Henricus P. M. , Mulder Jef J. S. , Hanssens Patrick E. J. , de With Peter H. N. , Verheul Jeroen B. 
Published: November 2020

Objective:
Stereotactic radiosurgery (SRS) is one of the treatment modalities for vestibular schwannomas (VSs). However, tumor progression can still occur after treatment. Currently, it remains unknown how to predict long-term SRS treatment outcome. This study investigates possible magnetic resonance imaging (MRI)-based predictors of long-term tumor control following SRS.

Study Design:
Retrospective cohort study.

Setting:
Tertiary referral center.

Patients:
Analysis was performed on a database containing 735 patients with unilateral VS, treated with SRS between June 2002 and December 2014. Using strict volumetric criteria for long-term tumor control and tumor progression, a total of 85 patients were included for tumor texture analysis.

Intervention(s):
All patients underwent SRS and had at least 2 years of follow-up.

Main Outcome Measure(s):
Quantitative tumor texture features were extracted from conventional MRI scans. These features were supplied to a machine learning stage to train prediction models. Prediction accuracy, sensitivity, specificity, and area under the receiver operating curve (AUC) are evaluated.

Results:
Gray-level co-occurrence matrices, which capture statistics from specific MRI tumor texture features, obtained the best prediction scores: 0.77 accuracy, 0.71 sensitivity, 0.83 specificity, and 0.93 AUC. These prediction scores further improved to 0.83, 0.83, 0.82, and 0.99, respectively, for tumors larger than 5 cm3.

Conclusions:
Results of this study show the feasibility of predicting the long-term SRS treatment response of VS tumors on an individual basis, using MRI-based tumor texture features. These results can be exploited for further research into creating a clinical decision support system, facilitating physicians, and patients to select a personalized optimal treatment strategy.
Vestibular Schwannoma Practice Patterns: An International Cross-specialty Survey
Authors: Macielak Robert J. , Driscoll Colin L.W. , Link Michael J. , Haynes David S. , Lohse Christine M. , Carlson Matthew L. 
Published: November 2020

Objective:
To assess vestibular schwannoma (VS) practice patterns among providers.

Study Design:
Cross-sectional survey.

Setting:
8th Quadrennial International Conference on Vestibular Schwannoma and Other CPA Tumors.

Subjects:
Clinicians who specialize in the management of VS.

Main Outcome Measures:
Responses to questions on the management and anticipated outcomes of VS for a series of common clinical scenarios were compared by specialty (otolaryngology versus neurosurgery), level of experience, scope of practice (surgery versus radiation and surgery), and geographic location of practice (United States versus international).

Results:
Responses from 110 participants were analyzed. Overall, 53% of respondents were otolaryngologists, 60% had greater than 10 years of experience, and 57% practiced within the United States. In total, 86% of respondents would pursue initial observation for themselves if diagnosed with a 4 mm distal intracanalicular VS; however, practicing radiosurgeons were more likely to select stereotactic radiosurgery for this scenario compared with providers who solely practice surgery (14 versus 0%; p = 0.032). Otolaryngologists and neurosurgeons alike report that radiosurgery should not be considered a long-term hearing preservation strategy.
Otolaryngologists were more optimistic regarding microsurgical hearing preservation outcomes for small distal intracanalicular tumors compared with neurosurgeons (11 versus 3% selected a high likelihood of maintaining class A/B hearing; p = 0.007). Ninety-five percent of respondents prioritized facial nerve outcome over complete disease removal in the context of microsurgical resection of large tumors.

Conclusions:
Management decision-making and expected outcomes for various clinical scenarios were largely similar among providers; however, variances in several key clinical areas exist. This study points to the feasibility of developing a widely accepted consensus statement among VS experts across specialties.
Working Toward Consensus on Sporadic Vestibular Schwannoma Care: A Modified Delphi Study
Authors: Carlson Matthew L. , Link Michael J. , Driscoll Colin L.W. , Haynes David S. , Billings Heather A. , Lohse Christine M. , Hall Elissa R. , Agazzi Siviero , Barker Frederick G. , Brackmann Derald E. , Cueva Roberto A. , Golfinos John G. , Gurgel Richard K. , Kondziolka Douglas , Kutz J. Walter , Neff Brian A. , Sheehan Jason P. , Van Gompel Jamie J. , Yu Chung Ping 
Published: November 2020

Objective:To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma.Study Design:Modified Delphi method.Methods:The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at ≥67% agreement, and strong consensus, at ≥80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round.Results:Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus.Conclusion:This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.
Identifying Relative Changes in Social Risk Factors
Authors: Xu Stanley , Goodrich Glenn K. , Moore Kelly R. , Manson Spero M. , Gottlieb Laura M. , Hessler Danielle , Schroeder Emily B. , Steiner John F. 
Published: November 2020

Background:
Individuals often report concurrent social risk factors such as food insecurity, unstable housing, and transportation barriers. Comparing relative changes between pairs of social risk factors may identify those that are more resistant to change.

Objective:
The objective of this study was to develop a method to describe relative changes in pairs of social risk factors.

Research Design:
This was a prospective cohort study.

Subjects:
Participants in a randomized controlled trial of hypertension care in an Urban Indian Health Organization.

Measures:
We measured 7 social risk factors (housing, transportation, food, clothing, health care, utilities, and debts) at enrollment, 6, and 12 months among 295 participants in the trial. We hypothesized that pairwise comparisons could identify social risk factors that were less likely to change over time. We used conditional odds ratios (ORs) with 95% confidence intervals (CIs) to rank each pair.

Results:
Food, clothing, health care, utilities, and debts had more changes between 0 and 6 months relative to housing (OR=2.3, 3.4, 4.7, 3.5, and 3.4, respectively; all 95% CI excluded 1.0). These same social risk factors also had more changes between baseline and 6 months relative to transportation (OR=2.8, 3.4, 4.9, 4.7, and 4.1, respectively; all 95% CI excluded 1.0). Changes in housing and transportation risk factors were comparable (OR=0.7, 95% CI: 0.4–1.4). Relative changes between 6 and 12 months were similar.

Conclusions:
Housing and transportation exhibited fewer relative changes than other social risk factors and might be more resistant to change. Awareness of the relationships between social risk factors can help define priorities for intervention.
Using an Agent-based Model to Examine Deimplementation of Breast Cancer Screening
Authors: Nowak Sarah A. , Parker Andrew M. , Radhakrishnan Archana , Schoenborn Nancy , Pollack Craig E. 
Published: November 2020

Objective:
The objective of this study was to examine the potential impact of provider social networks and experiences with patients on deimplementation of breast cancer screening.

Research Design:
We constructed the Breast Cancer-Social network Agent-based Model (BC-SAM), which depicts breast cancer screening decisions, incidence, and progression among 10,000 women ages 40 and over and the screening recommendations of their providers over a 30-year period. The model has patient and provider modules that each incorporate social network influences. Patients and providers were connected in a network, which represented patient-patient peer connections, provider-provider peer connections, connections between providers and patients they treat, and friend/family relationships between patients and providers. We calibrated provider decisions in the model using data from the CanSNET national survey of primary care physicians in the United States, which we fielded in 2016.

Results:
First, assuming that providers’ screening recommendations for women ages 50–74 remain unchanged but their recommendations for screening among younger (below 50 y old) and older (75+ y old) women decrease, we observed a decline in predicted screening rates for women ages 50–74 due to spillover effects. Second, screening rates for younger and older women were slow to respond to changes in provider recommendations; a 78% decline in provider recommendations to older women over 30 years resulted in an estimated 23% decline in patient screening in that group. Third, providers’ experiences with unscreened patients, friends, and family members modestly increased screening recommendations over time (7 percentage points). Finally, we found that provider peer effects can have a substantial impact on population screening rates and can entrench existing practices.

Conclusion:
Modeling cancer screening as a complex social system demonstrates a range of potential effects and may help target future interventions designed to reduce overscreening.
TaleNeprilysin and Neprilysin inhibition in chronic kidney disease
Authors: Judge Parminder K. , Haynes Richard 
Published: November 2020

Purpose of review
Chronic kidney disease (CKD) is associated with increased risk of progression to end-stage kidney disease and cardiovascular events. There is limited evidence that available treatments have beneficial effects on cardiorenal outcomes in all people with nondiabetic CKD. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD.

Recent findings
NEPi enhances the activity of the natriuretic peptide system producing natriuresis, diuresis and inhibition of the renin–angiotensin system and sympathetic nervous system. Sacubitril/valsartan is the first Angiotensin receptor-neprilysin inhibitor (ARNI) to be produced and has been shown to substantially improve cardiovascular outcomes in heart failure and delay progression of kidney disease in this population. Although ARNIs have not shown similar effects on kidney function in the short-to-medium term in people with CKD, they are associated with substantial reductions in cardiac biomarkers and blood pressure in CKD.

Summary
These data suggest that NEPi with an ARNI could benefit patients with CKD by reducing the risk of cardiovascular disease and have the possibility of retarding the progression of CKD (hence delaying the need for renal replacement therapy).