bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Spironolactone the Preferred Renin–Angiotensin–Aldosterone Inhibitor for Protection Against COVID-19?
Authors: Wilcox Christopher S. , Pitt Bertram 
Published: December 2020

Abstract:
The high mortality of specific groups from COVID-19 highlights the importance of host–viral interactions and the potential benefits from enhancing host defenses. SARS-CoV-2 requires angiotensin-converting enzyme (ACE) 2 as a receptor for cell entry and infection. Although both ACE inhibitors and spironolactone can upregulate tissue ACE2, there are important points of discrimination between these approaches. The virus requires proteolytic processing of its spike protein by transmembrane protease receptor serine type 2 (TMPRSS2) to enable binding to cellular ACE2. Because TMPRSS2 contains an androgen promoter, it may be downregulated by the antiandrogenic actions of spironolactone. Furin and plasmin also process the spike protein. They are inhibited by protease nexin 1 or serpin E2 (PN1) that is upregulated by angiotensin II but downregulated by aldosterone. Therefore, spironolactone should selectively downregulate furin and plasmin. Furin also promotes pulmonary edema, whereas plasmin promotes hemovascular dysfunction. Thus, a downregulation of furin and plasmin by PN1 could be a further benefit of MRAs beyond their well-established organ protection. We review the evidence that spironolactone may be the preferred RASSi to increase PN1 and decrease TMPRSS2, furin, and plasmin activities and thereby reduce viral cell binding, entry, infectivity, and bad outcomes. This hypothesis requires direct investigation.
Do Vancomycin Pharmacokinetics Differ Between Obese and Non-obese Patients? Comparison of a General-Purpose and Four Obesity-Specific Pharmacokinetic Models
Authors: Colin Pieter J. , Eleveld Douglas J. , Hart Andrew , Thomson Alison H. 
Published: December 2020

Background:
Over the past decade, numerous obesity-specific pharmacokinetic (PK) models and dosage regimens have been developed. However, it is unclear whether vancomycin PKs differ between obese and other patients after accounting for weight, age, and kidney function. In this study, the authors investigated whether using obesity-specific population PK models for vancomycin offers any advantage in accuracy and precision over using a recently developed general-purpose model.

Methods:
Vancomycin plasma concentrations in a cohort of 49 obese patients (body mass index [BMI] >30 kg/m2), not previously used in the development of any of the evaluated models, were used to validate the performance of 4 obesity-specific models and a general model. Bias and imprecision were calculated for the a priori and a posteriori predictive performance.

Results:
The bias of the a priori prediction was lowest for one of the obesity-specific models (−1.40%) and that of the general model was a close second (−7.0%). The imprecision was lowest for the general model (4.34 mg/L). The predictive performance for the a posteriori predictions was best for the general model, both for bias (1.96%) and imprecision (2.75 mg/L).

Conclusions:
The results of the external validation of vancomycin PK in obese patients showed that currently available obesity-specific models do not necessarily outperform a broadly supported general-purpose model. Based on these results, the authors conclude that there is no advantage in using vancomycin PK models specifically tailored to obese patients over the general-purpose model reported by Colin et al.
High Intrapatient Variability in Tacrolimus Exposure Calculated Over a Long Period Is Associated With De Novo Donor-Specific Antibody Development and/or Late Rejection in Thai Kidney Transplant Patients Receiving Concomitant CYP3A4/5 Inhibitors
Authors: Larpparisuth Nuttasith , Pongnatcha Tanapon , Panprom Pera , Promraj Ratchawat , Premasathian Nalinee , Vongwiwatana Attapong 
Published: December 2020

Background:
High intrapatient variability in tacrolimus trough levels (Tac IPV) is associated with poor allograft outcomes. Tac IPV was previously calculated using trough levels 6–12 months after kidney transplantation (KT). Data on the accuracy of Tac IPV calculation over a longer period, the association between high Tac IPV and donor-specific antibody (DSA) development after KT in Asian patients, and the role of IPV in patients receiving concomitant cytochrome P450 (CYP)3A4/5 inhibitors (CYPinh) are limited.

Methods:
A retrospective review of patients who underwent KT at our center in 2005–2015, and who received Tac with mycophenolate during the first 2 years after KT was performed. IPV was calculated using Tac levels adjusted by dosage. DSA was monitored annually after KT using a Luminex microbead assay.

Results:
In total, 236 patients were enrolled. CYPinh were prescribed to 189 patients (80.1%): 145 (61.4%), 31 (13.1%), and 13 (5.5%) received diltiazem, fluconazole, and ketoconazole, respectively. Mean IPV calculated from adjusted Tac levels for 6–12 months (IPV6–12) and 6–24 months (IPV6–24) after KT were 20.64% ± 11.68% and 23.53% ± 10.39%, respectively. Twenty-six patients (11%) showed late rejection and/or DSA occurrence, and had significantly higher IPV6–24 (29.42% ± 13.78%) than others (22.77% ± 9.64%; P = 0.02). There was no difference in IPV6–12 (24.31% ± 14.98% versus 20.17% ± 10.90%; P = 0.18). IPV6–12 and IPV6–24 were comparable in patients who did and did not receive CYPinh. When using mean IPV6–24 as a cutoff, patients with higher IPV6–24 had a higher probability of developing DSA and/or late rejection (P = 0.048).

Conclusions:
Tac IPV6–24 was higher and more significantly associated with DSA development and/or late rejection than Tac IPV6–12, independent of Tac trough level. This is the first study to demonstrate the impact of high IPV on DSA development in Asian patients, and that Tac IPV is comparable between patients with and without CYPinh.
Rheological behavior of commercial artificial tear solutions
Authors: Arshinoff Steve , Hofmann Ilan , Nae Hemi 
Published: December 2020

Purpose:
To measure the rheological behavior of artificial tears to gain insight into the potential role of rheology in predicting the efficacy of artificial tear solutions for the treatment of dry-eye disease (DED).

Setting:
Research laboratories of I-MED Pharma, Canada, Rohn and Associates, Inc., New Jersey, and Hydan Technologies, New Jersey.

Design:
Laboratory investigation.

Methods:
Twenty commercially available artificial tear drops were purchased in Canada and the United Kingdom. Rheological measurements of viscosity and normal stress as a function of shear rate were performed at 25°C.

Results:
For comparison of the rheological behavior, the various artificial tears were sorted into 3 groups: group A, which exhibit significant non-Newtonian shear-thinning behavior; group B, which exhibit moderate non-Newtonian shear-thinning behavior; and group C, which exhibit Newtonian behavior throughout the shear rate range. Results of normal stress difference, N1, as a function of shear rate were concordant with the rheological testing, indicated the viscoelastic nature of the samples in groups A and B, whereas members of group C did not exhibit any elasticity.

Conclusions:
The various artificial tear solutions were sorted into groups based on their Newtonian or non-Newtonian behaviors. The results suggest that non-Newtonian solutions should provide better comfort and longer-lasting symptomatic relief for DED. It remains to be confirmed clinically if there is a direct correlation between the rheological behavior of artificial tears and their ability to provide prolonged relief in DED, or if other factors are more important.
Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study
Authors: Fan Song , Zhen Qi , Chen Cheng , Wang Wenjun , Wu Qibing , Ma Huihui , Zhang Chengyuan , Zhang Li , Lu Baojing , Ge Huiyao , Yong Liang , Li Bao , Yu Yafen , Chen Weiwei , Mao Yiwen , Qu Guangbo , Su Li , Wang Aoli , Ding Zhen , Li Haiwen , Zhang Jin , Wang Yonglian , Gao Yufeng , Xu Xihai , Zhu Zhongming , Chen Jun , Zhang Long , Liang Hongqiang , Wu Song , Huang Meng , Xia Quan , Li Ping , Sun Yehuan , Liang Chaozhao , Wei Wei , Liu Qingsong , Sun Liangdan 
Published: December 2020

Objective:
Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19).

Methods:
In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022).

Results:
The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.

Conclusion:
Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.
Mendelian randomization as a tool for causal inference in human nutrition and metabolism
Authors: Larsson Susanna C. 
Published: December 2020

Purpose of review
The current review describes the fundamentals of the Mendelian randomization framework and its current application for causal inference in human nutrition and metabolism.

Recent findings
In the Mendelian randomization framework, genetic variants that are strongly associated with the potential risk factor are used as instrumental variables to determine whether the risk factor is a cause of the disease. Mendelian randomization studies are less susceptible to confounding and reverse causality compared with traditional observational studies. The Mendelian randomization study design has been increasingly used in recent years to appraise the causal associations of various nutritional factors, such as milk and alcohol intake, circulating levels of micronutrients and metabolites, and obesity with risk of different health outcomes. Mendelian randomization studies have confirmed some but challenged other nutrition-disease associations recognized by traditional observational studies. Yet, the causal role of many nutritional factors and intermediate metabolic changes for health and disease remains unresolved.

Summary
Mendelian randomization can be used as a tool to improve causal inference in observational studies assessing the role of nutritional factors and metabolites in health and disease. There is a need for more large-scale genome-wide association studies to identify more genetic variants for nutritional factors that can be utilized for Mendelian randomization analyses.
The use of grafts in frontal sinus drill-outs
Authors: Yin Tary , Douglas Richard 
Published: December 2020

Purpose of review
A significant complication of the frontal sinus drill-out procedure is restenosis of the frontal neo-ostium. To improve postoperative healing in this region, various mucosal grafts and pedicled flaps have been designed to reconstruct the mucosal lining of the frontal neo-ostium. We provide an overview of the types of grafts described for reconstruction and discuss the latest evidence on their efficacy.

Recent findings
Frontal neo-ostium mucosal reconstruction may be performed using free, pedicled, or a combination of grafts. There are several case series that report good outcomes and low revision rates following the use of grafts in frontal sinus drill-outs, and one randomized controlled study demonstrating increased ostial patency. However, the use of grafts did not alter the rate of revision surgery and only one study reported an improvement in Sino-Nasal Outcome Test-22 scores after one year.

Summary
Studies have suggested that frontal sinus drill-out grafts result in favorable restenosis and graft success rates. However, larger randomized control trials will be required to determine whether frontal sinus drill-out grafts contribute to a tangible clinical benefit for patients.
Multisystem inflammatory syndrome in children
Authors: Soma Vijaya L. , Shust Gail F. , Ratner Adam J. 
Published: December 2020

Purpose of review
Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases.

Recent findings
Clinical presentation of MIS-C is dominated by significant inflammation. Fever, gastrointestinal symptoms, cardiac dysfunction, and hypotension are common features. Kawasaki disease-like findings are common, but epidemiologic data and recent mechanistic studies suggest that distinct inflammatory pathways mediate Kawasaki disease and MIS-C. A broad diagnostic approach is recommended, given overlapping presentations between MIS-C and many other disease processes. Current management of MIS-C is highly variable, depending on illness severity, and can range from supportive care to aggressive immune modulation. A multidisciplinary approach with early involvement of multiple pediatric subspecialists is recommended for complicated cases.

Summary
Several studies have described the clinical manifestations of MIS-C, but definitive diagnosis remains challenging. Robust information about long-term outcomes awaits further study, as do immunologic data to refine diagnostic and therapeutic strategies.
Heart transplantation candidacy
Authors: Vieira Jefferson L. , Mehra Mandeep R. 
Published: December 2020

Purpose of review
Timely referral of eligible candidates for consideration of advanced therapies, such as a heart transplantation or mechanical circulatory support is essential. The characteristics of heart transplantation candidates have changed significantly over the years, leading to a more complex evaluation process. The present review summarizes recent advances in the evaluation process for heart transplantation eligibility.

Recent findings
The heart transplantation allocation policy was recently reviewed in the USA in an effort to reduce waitlist mortality and to ensure fair geographic allocation of organs to the sickest patients. Moreover, patients with chronic infectious diseases, as well as malignancies, are being currently considered acceptable candidates for transplantation. Listing practices for heart transplantation vary between programmes, with a greater willingness to consider high-risk candidates at higher-volume centres.

Summary
The ultimate decision to place high-risk candidates on the heart transplantation waitlist should be based on a combination of quantitative and qualitative data analysis informed by clinical judgement, and the chronic shortage of organ donors makes this process an important ethical concern for any society. Future guidelines should discuss approaches to achieve fair organ allocation while preserving improved outcomes after transplantation.
MicroRNAs: small molecules, big effects
Authors: Tinel Claire , Lamarthée Baptiste , Anglicheau Dany 
Published: December 2020

Purpose of review
In kidney transplantation, microRNAs (miRNAs) have been extensively studied over the past decade, and panels of differentially expressed miRNAs have been identified from various body fluids/tissues, including blood, plasma, urine, or allograft biopsies, and in various conditions, such as acute T-cell-mediated and antibody-mediated rejections, chronic allograft rejection, interstitial fibrosis and tubular atrophy, acute tubular necrosis or BKV nephropathy.

Recent findings
This review outlines our current knowledge regarding the complexity of miRNA regulation in fine-tuning expression of two-thirds of the human genome and the potential of miRNAs as biomarkers, based on an increasing number of case--control studies with, however, no evidence of short-term clinical development. Instead, a progressive change in study objectives is reported, with the most recent literature using miRNA-targeted genes as entry points for studying disease pathways.

Summary
Our nascent understanding of their presumed roles in alloimmunity suggests that miRNAs are key regulators in many allograft injuries. Future directions should investigate how the integration of miRNAs with other layers of molecular data, such as genomic, transcriptomic, or proteomic data, could help to characterize the cellular interactions involved in allograft rejection and whether miRNA-based therapy could be of relevance for transplant medicine.
Congenital Symmastia
Authors: Kraft Casey T. , Chandawarkar Rajiv , Chetta Matthew D. , Poteet Stephen J. 
Published: December 2020

Abstract
Congenital symmastia is a relatively uncommon condition and poorly described in the literature. Although numerous studies have evaluated iatrogenic symmastia including its prevention and treatment, considerably less has been studied with regard to congenital symmastia. In this review, the authors seek to consolidate the literature published thus far and provide techniques and principles of management that may guide surgeons treating patients with this condition.
Abdominoplasty
Authors: Ramirez Alejandro E. , Hsieh Tung-Ying , Cardenas Juan P. , Lao William W. 
Published: December 2020

Background
Abdominoplasty has been evolving since the 1960s with many technical innovations throughout the years. It has become one of the most frequent and common procedures done in aesthetic plastic surgery, with the ultimate goal of not only to remove the excess tissue in the abdominal area but also to achieve an aesthetic trunk silhouette.

Objective
The prime objective of this article was to describe our preferred approach for a full cosmetic abdominoplasty.

Methods
We summarized all the key technical aspects from our shared surgical approach for abdominoplasty. The article describes collective experiences from authors performing the surgery in South America, North America, and Asia.

Results
The key technical aspects identified were conservative muscle plication, customized excess tissue resection, and ultrasound-assisted liposuction to improve definition in the abdominal lines and body curves, combined with lipofilling. The aesthetic results are presented.

Conclusions
Abdominoplasty should be customized to every patient's anatomy and desired cosmetic outcome, taking into consideration all the anatomical areas surrounding the abdominal wall.
Stroke epidemiology and COVID-19 pandemic
Authors: Logroscino Giancarlo , Beghi Ettore 
Published: December 2020

Purpose of review
The aim of this study was to describe the impact of the COVID-19 outbreak on the epidemiology, cause and clinical characteristics of incident stroke in different settings and populations.

Recent findings
Several studies have shown that there are three main themes in the epidemiology of stroke during the COVID-19 pandemic: COVID-19 seems to be associated with stroke in a significant number of patients. This association has been reported in several clinical series, mainly from China. There is a consistent trend towards a decreased number of hospital admissions of stroke patients during the pandemic. There are no population-based data available on incident stroke in individuals with COVID-19.

Summary
In this review, we report on increased rates and severe prognosis of ischemic stroke among individuals with COVID-19, probably explained by hypercoagulability and inflammation, documented since the early phase of disease.
We confirm the presence of falling rates of new ischemic stroke admissions in hospitals, probably due to social consequences of the pandemic: fear to be infected or not adequately treated in the hospital. This phenomenon is restricted to mild stroke and transient ischemic attacks.
Short and long-term consequences of this trend of new strokes in the pandemic need to be evaluated.
Facial and vocal markers of schizophrenia measured using remote smartphone assessments
Authors: Galatzer-Levy Isaac R. , Abbas Anzar , Koesmahargyo Vidya , Yadav Vijay , Perez-Rodriguez M. Mercedes , Rosenfield Paul , Patil Omkar , Dockendorf Marissa F. , Moyer Matthew , Shipley Lisa A. , Hansen Bryan J. 
Published: December 2020

AbstractBackgroundMachine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis and severity. Here, we determine their accuracy of when acquired through automated assessments conducted remotely through smartphones. Demonstrating utility and validity of remote and automated assessments conducted outside of controlled experimental settings can facilitate scaling such measurement tools to aid in risk assessment and tracking of treatment response in difficult to engage populations.MethodsMeasurements of facial and vocal characteristics including facial expressivity, vocal acoustics, and speech prevalence were assessed in 20 schizophrenia patients over the course of 2 weeks in response to two classes of prompts previously utilized in experimental laboratory assessments: evoked prompts, where subjects are guided to produce specific facial expressions and phonations, and spontaneous prompts, where subjects are presented stimuli in the form of emotionally evocative imagery and asked to freely respond. Facial and vocal measurements were assessed in relation to schizophrenia symptom severity using the Positive and Negative Syndrome Scale.ResultsVocal markers including speech prevalence, vocal jitter, fundamental frequency, and vocal intensity demonstrated specificity as markers of negative symptom severity while measurement of facial expressivity demonstrated itself as a robust marker of overall schizophrenia severity.ConclusionEstablished facial and vocal measurements, collected remotely in schizophrenia patients via smartphones in response to automated task prompts, demonstrated accuracy as markers of schizophrenia severity. Clinical implications are discussed.