bluuebunny/crossref_metadata_2025 huggingface dataset:
Systems-Focused Equity Leadership Learning: Shifting Practice Through Practice
Authors: Honig Meredith I. , Honsa Alyson
Published: June 2020

This article shares our experience using a job-embedded active learning approach to support candidates’ growth as systems-focused equity leaders in the University of Washington’s Leadership for Learning program. We describe how socio-cultural learning theory helped us shift from field-based application projects to job-embedded learning. Our approach involved clarifying systems-focused leadership practices as primary learning targets, centering candidates’ workplaces as the main learning setting, and providing high-quality support consistent with apprenticeships and communities of practice. We conclude with opportunities, challenges, and ways forward for educational leadership programs seeking to design such approaches and develop systems-focused equity leaders.
Geopolitical anxieties of tourism: (Im)mobilities of the COVID-19 pandemic
Authors: Mostafanezhad Mary , Cheer Joseph M , Sin Harng Luh
Published: June 2020

Bringing the political geography of tourism to bear on responses to the COVID-19 pandemic, this commentary reveals how the geopolitical anxieties of tourism are mediated by historical geographies of race as well as contemporary geoeconomic relations and the broader pivot to the Asia-Pacific region.
Geographies of the COVID-19 pandemic
Authors: Rose-Redwood Reuben , Kitchin Rob , Apostolopoulou Elia , Rickards Lauren , Blackman Tyler , Crampton Jeremy , Rossi Ugo , Buckley Michelle
Published: June 2020

The spread of the novel coronavirus (SARS-CoV-2) has resulted in the most devastating global public health crisis in over a century. At present, over 10 million people from around the world have contracted the Coronavirus Disease 2019 (COVID-19), leading to more than 500,000 deaths globally. The global health crisis unleashed by the COVID-19 pandemic has been compounded by political, economic, and social crises that have exacerbated existing inequalities and disproportionately affected the most vulnerable segments of society. The global pandemic has had profoundly geographical consequences, and as the current crisis continues to unfold, there is a pressing need for geographers and other scholars to critically examine its fallout. This introductory article provides an overview of the current special issue on the geographies of the COVID-19 pandemic, which includes 42 commentaries written by contributors from across the globe. Collectively, the contributions in this special issue highlight the diverse theoretical perspectives, methodological approaches, and thematic foci that geographical scholarship can offer to better understand the uneven geographies of the Coronavirus/COVID-19.
Integrated care in atrial fibrillation – Are we truly integrating?
Authors: Hendriks Jeroen M
Published: June 2020

Integrated care is an emerging approach to manage patients with chronic complex conditions, such as atrial fibrillation (AF). The current international practice guidelines recommend an integrated care approach in AF, which consists of four fundamentals being patient involvement, a multidisciplinary team approach, the use of technology, and comprehensive management focussing on the treatment of AF, prevention of thromboembolic complications, and the management of co-morbid conditions, cardiovascular risk factors and lifestyle modification. Despite the guideline recommendations, the term integrated care is being used inconsistently within the current available literature. This publication aims to contribute to the clarification of the integrate AF care concept and the consequent appropriate use in clinical practice and research, whilst awaiting an upcoming update of international practice guidelines.
Interpretative Phenomenological Analysis of the Lived Experiences of Older Adults Regarding Their Functional Activities in Ghana
Authors: Awuviry-Newton Kofi , Tavener Meredith , Wales Kylie , Byles Julie
Published: June 2020

Introduction: Research on disability largely draws on epidemiological data, often conducted in more developed countries. To date, there is little research related to older adults in Ghana, Africa. The purpose of this study was to strengthen understanding of how older adults in Ghana perform functional activities, referenced against the World Health Organization’s International Classification of Functioning, Disability and Health (WHO-ICF) framework. Methods: Interpretative phenomenological analysis (IPA) of semistructured interview data was employed as the methodological approach. Using purposive criterion sampling, 8 older adults admitted to Komfo Anokye Teaching Hospital in Ghana, presenting with any identified health condition and/or frailty were recruited. Results: Analysis of interview data identified 5 interrelated themes: (1) feeling anxious, (2) feeling restricted, (3) understanding and admitting difficulty, (4) striving to be healthy and being productive, and (5) managing functional difficulty. These concerns were classified and related to the WHO-ICF, particularly the contextual factors. Discussion: This study examined in detail experiences of older adults performing functional activities. Our study highlights the relevance of the WHO-ICF framework for understanding the health needs of older adults, emphasizing the functional, social, and environmental factors influencing the functional status of older adults. The findings offer unique insight into the health needs of older adults, drawing attention to the implications for policy and care.
The 100 Most-Cited Publications in Endoscopic Spine Surgery Research
Authors: Zhao Tingxiao , Shen Jianjian , Zheng Biao , Huang Yazeng , Jin Mengran , Morizane Kazuaki , Shao Haiyu , Chen Xinji , Zhang Jun
Published: June 2020

Study Design:

A bibliometric review of the literature.

Objective:

Our objective was to identify and analyze the 100 most-cited publications in the field of endoscopic spine surgery (ESS).

Methods:

In order to determine the top cited 100 articles, a 3-step approach was employed. First, the 100 most-cited ESS studies were identified using the key phrase “endoscopic spine surgery.” Then, 8 keywords were identified from the 100 studies of step 1 were used to conduct a second round searching in all databases of the Web of Science. Finally, when the results of the first and second steps were overlapped, duplicated studies were removed. The 100 top-cited articles were used for further analysis.

Results:

The citation number of the top 100 most-cited articles ranged from 44 to 236 with a mean value of 84.4. The most productive periods were from 2001 to 2010. The majority of publications came from Spine and Neurosurgery, where Spine holds the largest number of 35 articles, followed by Neurosurgery with 13 articles. Overall, 10 countries contributed to the 100 articles, with the most productive country being the United States, followed by Germany and Korea.

Conclusion:

This bibliometric study is meant to produce a list of intellectual milestones in the field of ESS. This article’s identification of the most influential articles in the field of ESS gives us a unique and comprehensive insight into the development of ESS in the past several decades.
Multivalvular Endocarditis Involving 3 Valves in a Nonsurgical Candidate
Authors: Boyer Robin , Grandhe Sundeep , Win Theingi , Ragland Alan , Heidari Arash
Published: June 2020

Infective endocarditis is associated with high morbidity and mortality. Hence, early diagnosis and prompt intervention is crucial. Multivalvular endocarditis involving 3 or more valves is rarely reported with little information regarding best management or prognosis, particularly in nonsurgical patients. Conflicting guidelines regarding medical versus surgical treatment in multivalvular endocarditis exist with few studies describing the outcome of medically managed patients. We report the case of a previously healthy male presenting with infective endocarditis involving 3 valves further complicated by multiple septic emboli and deemed a nonsurgical candidate.
Risk of Injuries Associated With Sport Specialization and Intense Training Patterns in Young Athletes: A Longitudinal Clinical Case-Control Study
Authors: Jayanthi Neeru , Kleithermes Stephanie , Dugas Lara , Pasulka Jacqueline , Iqbal Sara , LaBella Cynthia
Published: June 2020

Background:

There are no clinical longitudinal studies exploring the associations between sport specialization and intense training patterns and injuries in young athletes.

Purpose:

To prospectively determine the relationship between young athletes’ degree of sport specialization and their risk of injuries and reinjuries.

Study Design:

Case-control study; Level of evidence, 2.

Methods:

Young athletes aged between 7 and 18 years presenting for sports-related injuries or sports physical examinations were recruited from either sports medicine clinics or pediatric/family medicine offices. Each participant completed a baseline survey at enrollment and an identical follow-up survey every 6 months for 3 years. Surveys assessed training patterns and injuries. Injury type (acute, overuse, or serious overuse) and clinical diagnosis were also recorded from electronic medical records.

Results:

Of the 1208 participants who provided consent, 579 (48%) completed the baseline survey and first follow-up survey at 6 months (mean age, 14.1 ± 2.3 years; 53% female). Of this sample, 27% (158/579) of participants were uninjured, and 73% (421/579) were injured, with 29% (121/421) of injuries classified as reinjuries. Consistent with previous studies, over the 3-year study period, the degree of sport specialization had an effect such that more specialized athletes were significantly more likely to be injured ( P = .03) or have an overuse injury ( P = .02) compared with less specialized athletes after adjusting for potential confounders. Additionally, female athletes were more at risk for all injuries ( P = .01) and overuse injuries ( P = .02) after adjusting for covariates. Finally, young athletes who trained in weekly hours in excess of their age or who trained twice as many hours as their free play were significantly more likely to be injured on univariate analysis (both P < .001).

Conclusion:

Our study confirms that over time, young athletes, and in particular young female athletes, were more likely to be injured and sustain an overuse injury if they had a higher degree of sport specialization. Similarly, those athletes whose training hours exceeded thair age or whose sports hours exceeded their free play by a factor of greater than 2 were also more likely to develop injuries and overuse injuries.
Peak Performance: A Communications-Based Leadership and Teamwork Simulation for Fourth-Year Medical Students
Authors: Smithson Sarah , Beck Dallaghan Gary , Crowner Jason , Derry Laura Trollinger , Vijayakumar Akshitha (Ammu) , Storrie Mindy , Daaleman Timothy P
Published: June 2020

Background:

Medical education has traditionally been rooted in the teaching of health and disease processes, with little attention to the development of teamwork and leadership competencies.

Objective:

In an era of value-based health care provided by high-functioning teams, new approaches are needed to develop communication, leadership, and teamwork skills for medical students.

Design:

We designed and piloted a simulation-based educational activity called Peak Performance that linked a workbook, which focused on self-reflection on communication and leadership skills, with professional coaching. The simulation scenario placed students in the role of an upper-level resident on an inpatient service, followed by a small group debrief with students, a clinical faculty member, and a professional executive coach. After the debriefing session, students were invited to complete a self-reflection workbook within 1 week of the initial simulation. The final element of the curriculum was an individualized session with an executive coach. Peak Performance was offered to all fourth-year medical students enrolled in the Social and Health Systems Science required course at the University of North Carolina School of Medicine.

Results:

Pre-/post-self-assessments of leadership competencies were completed by students. Pre-simulation self-assessment scores ranged from 3.72 to 4.33 on a 5-point scale. The lowest scores were in “Managing Conflict” and “Managing Others.” The highest score was in “Self-Awareness.” The post-simulation scores decreased in every competency, with “Managing Others” dropping significantly from 3.72 pre-simulation to 3.36 post-simulation (0.31, P < .05). Satisfaction with the curriculum was high, as reflected by a Net Promoter Score of 91% (“excellent” > 50%).

Conclusions:

A novel simulation-based educational activity linked to professional coaching is a feasible and impactful strategy to develop leadership, communication, and teamwork skills in medical students. Student insight and self-awareness increased as evidenced by a decrease in competency self-assessment after guided reflection and individualized coaching.
How I treat gastrointestinal bleeding in congenital and acquired von Willebrand disease
Authors: Biguzzi Eugenia , Siboni Simona Maria , Peyvandi Flora
Published: June 2020

Gastrointestinal (GI) bleeding is distinctive of severe von Willebrand disease (VWD), generally arising in older patients; in most cases, blood transfusion and hospitalization are required. The presence of arteriovenous malformations is often described when endoscopic examinations are performed. Patients with congenital type 3, 2A, and 2B are those most frequently affected by this symptom, possibly due to the loss of high-molecular-weight multimers of von Willebrand factor (VWF). GI bleeding can also occur in patients affected by acquired von Willebrand syndrome. Endoscopic examination of the GI tract is necessary to exclude ulcers and polyps or cancer as possible causes of GI bleeding. In congenital VWD, prophylaxis with VWF/factor VIII concentrates is generally started after GI-bleeding events, but this therapy is not always successful. Iron supplementation must be prescribed to avoid chronic iron deficiency. Possible rescue therapies (high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen) were described in a few case reports and series; however, surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding. In this article, we present several clinical cases that highlight the clinical challenges of these patients and possible strategies for their long-term management.
How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies
Authors: Hill Joshua A. , Seo Susan K.
Published: June 2020

Adoptive immunotherapy using B-cell–targeted chimeric antigen receptor (CAR)-modified T cells to treat hematologic malignancies is transforming cancer care for patients with refractory or relapsed diseases. Recent and anticipated regulatory approval for products targeting acute lymphoblastic leukemia, lymphomas, and multiple myeloma have led to global implementation of these novel treatments. The rapidity of commercial utilization of CAR–T-cell therapy has created a largely unexplored gap in patient supportive-care approaches. Such approaches are critical in these complex patients given their high net state of immunosuppression prior to CAR–T-cell infusion coupled with unique acute and persistent insults to their immune function after CAR–T-cell infusion. In this “How I Treat” article, we focus on key questions that arise during 3 phases of management for patients receiving CD19-targeted CAR-T cells: pre CAR–T-cell infusion, immediate post CAR–T-cell infusion, and long-term follow-up. A longitudinal patient case is presented for each phase to highlight fundamental issues including infectious diseases screening, antimicrobial prophylaxis, immunoglobulin supplementation, risk factors for infection, and vaccination. We hope this discussion will provide a framework for institutions and health care providers to formulate their own approach to preventing infections in light of the paucity of data specific to this treatment modality.
MIF as a biomarker and therapeutic target for overcoming resistance to proteasome inhibitors in human myeloma
Authors: Wang Qiang , Zhao Dongyu , Xian Miao , Wang Zhuo , Bi Enguang , Su Pan , Qian Jianfei , Ma Xingzhe , Yang Maojie , Liu Lintao , Zu Youli , Pingali Sai Ravi , Chen Kaifu , Cai Zhen , Yi Qing
Published: June 2020

Multiple myeloma (MM) remains largely incurable despite significant advances in biotherapy and chemotherapy. The development of drug resistance is a major problem in MM management. Macrophage migration inhibitory factor (MIF) expression was significantly higher in purified MM cells from relapsed patients than those with sustained response, and MM patients with high MIF had significantly shorter progression-free survival (PFS) and overall survival (OS). MM cell lines also express high levels of MIF, and knocking out MIF made them more sensitive to proteasome inhibitor (PI)-induced apoptosis not observed with other chemotherapy drugs. Mechanistic studies showed that MIF protects MM cells from PI-induced apoptosis by maintaining mitochondrial function via suppression of superoxide production in response to PIs. Specifically, MIF, in the form of a homotrimer, acts as a chaperone for superoxide dismutase 1 (SOD1) to suppress PI-induced SOD1 misfolding and to maintain SOD1 activity. MIF inhibitor 4-iodo-6-phenylpyrimidine and homotrimer disrupter ebselen, which do not kill MM cells, enhanced PI-induced SOD1 misfolding and loss of function, resulting in significantly more cell death in both cell lines and primary MM cells. More importantly, inhibiting MIF activity in vivo displayed synergistic antitumor activity with PIs and resensitized PI-resistant MM cells to treatment. In support of these findings, gene-profiling data showed a significantly negative correlation between MIF and SOD1 expression and response to PI treatment in patients with MM. This study shows that MIF plays a crucial role in MM sensitivity to PIs and suggests that targeting MIF may be a promising strategy to (re)sensitize MM to the treatment.
Circadian asthma airway responses are gated by REV-ERBα
Authors: Durrington Hannah J. , Krakowiak Karolina , Meijer Peter , Begley Nicola , Maidstone Robert , Goosey Laurence , Gibbs Julie E. , Blaikley John F. , Gregory Lisa G. , Lloyd Clare M. , Loudon Andrew S. I. , Ray D. W.
Published: June 2020

Background

Asthma is an inflammatory disease of the airway showing a strong time of day rhythm. Airway hyperresponsiveness is a dominant feature of asthma, but it is not known if this is under clock control. The circadian clock powerfully regulates inflammation. The clock protein REV-ERBα is known to play a key role as a repressor of the inflammatory response.

Objectives

To determine if allergy mediated airway hyperresponsiveness is gated by the clock protein, REV-ERBα.

Methods

After exposure to the intra-nasal house dust mite allergen challenge model at either dawn or dusk, airway hyper-responsiveness to methacholine was measured invasively in mice.

Main Results

Wild-type mice showed marked time-of-day differential responses of airway hyper-responsiveness (maximal at dusk, start of the active phase), both in vivo and ex vivo in precision cut lung slices. Hyper-responsive time of day effects were abolished in mice lacking the clock gene Rev-erbα, indicating that time-of-day effects on asthma responses are likely mediated via the circadian clock. We suggest that muscarinic receptors 1 and 3 (Chrm 1, 3) may play a role in this pathway.

Conclusions

We identify a novel circuit regulating a core process in asthma, potentially involving circadian control of muscarinic receptor expression, in a REV-ERBα dependent fashion.

Clinical Implication

These insights suggest the importance of considering timing of drug administration in clinic trials, and in clinical practice; chronotherapy.
Open-loop analysis on sympathetically mediated arterial pressure and urine output responses in rats: effect of renal denervation
Authors: Kawada Toru , Hayama Yohsuke , Nishikawa Takuya , Suehara Satoru , Sawada Satoshi , Tanaka Tetsuo , Uenohara Minako , Sugimachi Masaru
Published: June 2020

Primary acute sympathetic activation (PASA) can increase arterial pressure (AP). Under this situation, the kidneys may receive mutually opposing influences from sympathetic activation: a direct anti-diuretic effect via the renal innervation and pressure diuresis. We examined whether PASA would reduce urine output regardless of the AP elevation. We also examined the impact of renal denervation (RDN) on urine output during PASA. The experiment was performed on rats 3 to 9 days after unilateral RDN (n = 10). Under anesthesia, systemic sympathetic nerve activity (SNA) was varied over a wide range via the carotid sinus baroreflex. The slope of urine flow versus SNA was positive (0.252 ± 0.052 μL·min−1·kg−1· %−1) on the intact side, and it was greater on the denervated side (0.331 ± 0.069 μL·min−1·kg−1· %−1, P < 0.05). In conclusion, urine output change was an effect of elevated AP during PASA. Nevertheless, RDN was able to augment pressure diuresis during PASA.
Correction to: Comparison of minimally invasive Ivor Lewis esophagectomy and left transthoracic esophagectomy in esophageal squamous cell carcinoma patients: a propensity score-matched analysis
Authors: Wang Qi , Wu Zixiang , Zhan Tianwei , Fang Shuai , Zhang Sai , Shen Gang , Wu Ming
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
A blended intervention to promote physical activity, health and work productivity among office employees using intervention mapping: a study protocol for a cluster-randomized controlled trial
Authors: Sun Yan , Wang Aiwei , Yu Siyue , Hagger Martin S. , Chen Xiangyan , Fong Shirley Siu Ming , Zhang Chunqing , Huang Wendy Yajun , Baker Julien S. , Dutheil Frédéric , Gao Yang
Published: June 2020

Background

Regular participation in moderate-to-vigorous physical activity (MVPA) is related to decreased risk of morbidity and mortality. Among working populations, lack of MVPA may also be a risk factor for absenteeism and presenteeism. Both traditional workplace-based and web-based interventions have been suggested as being effective in promoting participation MVPA, health-related outcomes, and work-related productivity. However, several challenges limit their application in real world contexts. A ‘blended’ intervention approach combining the two intervention strategies is proposed to overcome these limitations. The proposed intervention aims to utilize the blended approach to increase participation in MVPA, health-related outcomes, and work productivity among inactive workers.

Methods

The study will comprise of a three-group cluster randomized controlled trial (cluster-RCT), comprising a three-month actual intervention and a nine-month behavioral follow-up period. The three groups will be: a web-based intervention group, a blended intervention group combining the web-based components with face-to-face workshops and posters, and a control group. Physically inactive office employees (N = 495) from 33 companies (i.e., clusters) will be recruited and randomly assigned to the three groups by cluster randomization. The intervention mapping (IM) framework will be used for selecting and applying effective health behavioral theories and behavioral change techniques (BCTs) to the development, implementation and assessment of the intervention, which will be personally tailored. The primary outcome variable will be objectively-measured MVPA using an accelerometer. Secondary outcomes will consist of indices of health including adiposity, blood pressure, blood sugar, blood lipids, self-reported depression, anxiety, stress, health-related quality of life and work-related variables including absenteeism and presenteeism.

Discussion

The proposed study adopts a robust blended intervention approach that is expected to overcome challenges in applying workplace-based and web-based interventions separately and yield larger effects in promoting MVPA participation, health-related outcomes and work productivity. Improvements in work productivity outcomes will be of particular interest to employers. If more effective, the new blended intervention has the potential to be implemented on a larger scale to benefit workplace populations.

Trial registration

The trial is prospectively registered at the ClinicalTrials.gov PRS (Trial ID: NCT04391270; Date of First Posted: May 18, 2020).
Treating periodontitis-a systematic review and meta-analysis comparing ultrasonic and manual subgingival scaling at different probing pocket depths
Authors: Zhang Xin , Hu Zixuan , Zhu Xuesong , Li Wenjie , Chen Jun
Published: June 2020

Background

Mechanical plaque removal has been commonly accepted to be the basis for periodontal treatment. This study aims to compare the effectiveness of ultrasonic and manual subgingival scaling at different initial probing pocket depths (PPD) in periodontal treatment.

Methods

English-language databases (PubMed, Cochrane Central Register of Controlled Trials, EMBASE, Medline, and ClinicalTrials.gov, by January, 2019) were searched. Weighted mean differences in primary outcomes, PPD and clinical attachment loss (CAL) reduction, were estimated by random effects model. Secondary outcomes, bleeding on probing (BOP), gingival recession (GR), and post-scaling residual dental calculus, were analyzed by comparing the results of each study. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The GRADE approach was used to assess quality of evidence.

Results

Ten randomized controlled trials were included out of 1434 identified. Initial PPD and follow-up periods formed subgroups. For 3-months follow-up: (1) too few shallow initial pocket studies available to draw a conclusion; (2) the heterogeneity of medium depth studies was so high that could not be merged to draw a conclusion; (3) deep pocket studies showed no statistical differences in PPD and CAL reduction between ultrasonic and manual groups. For 6-months follow-up: (1) too few shallow initial PPD studies to draw a conclusion; (2) at medium pocket depth, PPD reduction showed manual subgingival scaling better than ultrasound. No statistical differences were observed in CAL reduction between the two approaches; (3) for deep initial PPD studies, both PPD and CAL reduction showed manual subgingival scaling better. GR results indicated no statistical differences at medium and deep initial pocket studies between the two methods. BOP results showed more reduction at deep pocket depths with manual subgingival scaling. No conclusion could be drawn about residual dental calculus.

Conclusion

When initial PPD was 4-6 mm, PPD reduction proved manual subgingival scaling was superior, but CAL results showed no statistical differences between the two means. When initial PPD was ≥6 mm, PPD and CAL reductions suggested that manual subgingival scaling was superior.
Correction to: Exam performance of different admission quotas in the first part of the state examination in medicine: a cross-sectional study
Authors: Mommert Alex , Wagner Josefin , Jünger Jana , Westermann Jürgen
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
A prospect on the use of antiviral drugs to control local outbreaks of COVID-19
Authors: Torneri Andrea , Libin Pieter , Vanderlocht Joris , Vandamme Anne-Mieke , Neyts Johan , Hens Niel
Published: June 2020

Background

Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic.

Methods

Using a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process.

Results

For an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out.

Conclusion

In all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19.
Ab locks for improving the selectivity and safety of antibody drugs
Authors: Lin Wen-Wei , Lu Yun-Chi , Chuang Chih-Hung , Cheng Tian-Lu
Published: June 2020

Monoclonal antibodies (mAbs) are a major targeted therapy for malignancies, infectious diseases, autoimmune diseases, transplant rejection and chronic inflammatory diseases due to their antigen specificity and longer half-life than conventional drugs. However, long-term systemic antigen neutralization by mAbs may cause severe adverse events. Improving the selectivity of mAbs to distinguish target antigens at the disease site from normal healthy tissue and reducing severe adverse events caused by the mechanisms-of-action of mAbs is still a pressing need. Development of pro-antibodies (pro-Abs) by installing a protease-cleavable Ab lock is a novel and advanced recombinant Ab-based strategy that efficiently masks the antigen binding ability of mAbs in the normal state and selectively “turns on” the mAb activity when the pro-Ab reaches the proteolytic protease-overexpressed diseased tissue. In this review, we discuss the design and advantages/disadvantages of different Ab lock strategies, focusing particularly on spatial-hindrance-based and affinity peptide-based approaches. We expect that the development of different masking strategies for mAbs will benefit the local reactivity of mAbs at the disease site, increase the therapeutic efficacy and safety of long-term treatment with mAbs in chronic diseases and even permit scientists to develop Ab drugs for formerly undruggable targets and satisfy the unmet medical needs of mAb therapy.
Dietary inflammatory index, risk of incident hypertension, and effect modification from BMI
Authors: MacDonald Conor-James , Laouali Nasser , Madika Anne-Laure , Mancini Francesca Romana , Boutron-Ruault Marie-Christine
Published: June 2020

Introduction

Previous studies have identified a positive association between the inflammatory potential of the diet and hypertension. It is not known if BMI is an effect modifier for this association, nor if the association is dose-respondent. This study aimed to assess the association between the dietary inflammatory index (DII) and the risk of hypertension, and assess any effect modification from BMI.

Methods

Data from the E3N cohort study, a French prospective population-based study initiated in 1990 was used. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,652 women. The adapted DII was assessed with data from the dietary questionnaire. Hypertension cases were self-reported and verified through a drug-reimbursement database. Cox proportional hazard models were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship.

Results

During 884,267 person-years, 13,183 cases of incident hypertension were identified. The median DII in the population was slightly pro-inflammatory (DII = + 0.44). A highly pro-inflammatory diet (DII >  3.0) was associated with a slight increase in hypertension risk (HRQ1-Q5 = 1.07 [1.02, 1.13]). Evidence was observed for effect modification from BMI, with associations strongest amongst women in the 18.5–21.0 BMI range (HRQ1-Q5 = 1.17 [1.06, 1.29]). A weak dose-respondent relationship was observed.

Conclusion

Evidence for a weak association between DII and hypertension was observed. Associations were stronger amongst healthy-lean women.
ERNICA guidelines for the management of rectosigmoid Hirschsprung’s disease
Authors: Kyrklund Kristiina , Sloots Cornelius E. J. , de Blaauw Ivo , Bjørnland Kristin , Rolle Udo , Cavalieri Duccio , Francalanci Paola , Fusaro Fabio , Lemli Annette , Schwarzer Nicole , Fascetti-Leon Francesco , Thapar Nikhil , Johansen Lars Søndergaard , Berrebi Dominique , Hugot Jean-Pierre , Crétolle Célia , Brooks Alice S. , Hofstra Robert M. , Wester Tomas , Pakarinen Mikko P.
Published: June 2020

Background

Hirschsprung’s disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management.

Aims

This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders.

Methods

Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted.

Results

Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion.

Conclusion

In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.
Correction to: The role of high load herpes simplex virus in patients with mechanical ventilation: a real hospital acquired viral lung infection needs antiviral therapy?
Authors: Wang Heyan , He Hangyong
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Core outcome sets through the healthcare ecosystem: the case of type 2 diabetes mellitus
Authors: Dodd Susanna , Harman Nicola , Taske Nichole , Minchin Mark , Tan Toni , Williamson Paula R.
Published: June 2020

Background

It is increasingly accepted that insufficient attention has been given to the patient health outcomes that are important to measure in comparative effectiveness research that will inform decision-making. The relationship between outcomes chosen for comparative effectiveness research, outcomes used in decision-making in routine care, and outcome data recorded in electronic health records (EHR) is also poorly understood. The COMET Initiative (http://www.comet-initiative.org/. Accessed 3 Apr 2020) supports and encourages the development and use of ‘core outcome sets’ (COS), which represent the minimum set of patient health outcomes that should be measured and reported for a specific condition. There is growing interest in identifying how COS might fit into the different stages of the healthcare research and delivery ecosystem, and whether inclusion in the EHR might facilitate this.

Methods

We sought to determine the degree of overlap between outcomes within COS for research and routine care, EMA, FDA and NICE guidelines, NICE quality statements/indicators, EHR and a point-of-care randomised clinical trial, using type 2 diabetes (T2D) as a case study.

Results

There is substantial agreement about important patient outcomes for T2D for research and healthcare, with associated coverage within the UK general practice EHR.

Conclusions

This case study has demonstrated the potential for efficient research and value-based healthcare when the EHR can include COS for both research and care, where the COS comprises outcomes of importance to all relevant stakeholders. However, this concordance may not hold more generally, as the focus on patient-centred outcomes may well be greater in T2D than in other conditions. Work is ongoing to examine other clinical areas, in order to highlight any current inefficiencies when health outcomes in research and healthcare do not agree with core outcomes identified by patients, clinicians and other key stakeholders.
FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial
Authors: Poinas Alexandra , Lemoigne Marie , Le Naour Sarah , Nguyen Jean-Michel , Schirr-Bonnans Solène , Riche Valery-Pierre , Vrignaud Florence , Machet Laurent , Claudel Jean-Paul , Leccia Marie-Thérèse , Hainaut Ewa , Beneton Nathalie , Dert Cécile , Boisrobert Aurélie , Flet Laurent , Chiffoleau Anne , Corvec Stéphane , Khammari Amir , Dréno Brigitte
Published: June 2020

Background

Acne vulgaris has increased in women over the past 10 years; it currently affects 20–30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone’s efficacy in order to establish it as an alternative to cyclines.

Methods

Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months.

Discussion

The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage.

Trial registration

ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.
Multiplex PCR for simultaneous genotyping of kdr mutations V410L, V1016I and F1534C in Aedes aegypti (L.)
Authors: Villanueva-Segura Karina , Ponce-Garcia Gustavo , Lopez-Monroy Beatriz , Mora-Jasso Esteban , Perales Lucia , Gonzalez-Santillan Francisco J. , Ontiveros-Zapata Kevin , Davila-Barboza Jesus A. , Flores Adriana E.
Published: June 2020

Background

Knockdown resistance (kdr) is the main mechanism that confers resistance to pyrethroids and DDT. This is a product of non-synonymous mutations in the voltage-gated sodium channel (vgsc) gene, and these mutations produce a change of a single amino acid which reduces the affinity of the target site for the insecticide molecule. In Mexico, V410L, V1016I and F1534C mutations are common in pyrethroid-resistant Aedes aegypti (L.) populations.

Methods

A multiplex PCR was developed to detect the V410L, V1016I and F1534C mutations in Ae. aegypti. The validation of the technique was carried out by DNA sequencing using field populations previously characterized for the three mutations through allele-specific PCR (AS-PCR) and with different levels of genotypic frequencies.

Results

The standardized protocol for multiplex end-point PCR was highly effective in detecting 15 genotypes considering the three mutations V410L, V1106I and F1534C, in 12 field populations of Ae. aegypti from Mexico. A complete concordance with AS-PCR and DNA sequencing was found for the simultaneous detection of the three kdr mutations.

Conclusions

Our diagnostic method is highly effective for the simultaneous detection of V410L, V1016I and F1534C, when they co-occur. This technique represents a viable alternative to complement and strengthen current monitoring and resistance management strategies against Ae. aegypti.
Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets
Authors: Krushkal Julia , Silvers Thomas , Reinhold William C. , Sonkin Dmitriy , Vural Suleyman , Connelly John , Varma Sudhir , Meltzer Paul S. , Kunkel Mark , Rapisarda Annamaria , Evans David , Pommier Yves , Teicher Beverly A.
Published: June 2020

Background

Small cell lung cancer (SCLC) is an aggressive neuroendocrine lung cancer. SCLC progression and treatment resistance involve epigenetic processes. However, links between SCLC DNA methylation and drug response remain unclear. We performed an epigenome-wide study of 66 human SCLC cell lines using the Illumina Infinium MethylationEPIC BeadChip array. Correlations of SCLC DNA methylation and gene expression with in vitro response to 526 antitumor agents were examined.

Results

We found multiple significant correlations between DNA methylation and chemosensitivity. A potentially important association was observed for TREX1, which encodes the 3′ exonuclease I that serves as a STING antagonist in the regulation of a cytosolic DNA-sensing pathway. Increased methylation and low expression of TREX1 were associated with the sensitivity to Aurora kinase inhibitors AZD-1152, SCH-1473759, SNS-314, and TAK-901; the CDK inhibitor R-547; the Vertex ATR inhibitor Cpd 45; and the mitotic spindle disruptor vinorelbine. Compared with cell lines of other cancer types, TREX1 had low mRNA expression and increased upstream region methylation in SCLC, suggesting a possible relationship with SCLC sensitivity to Aurora kinase inhibitors.

We also identified multiple additional correlations indicative of potential mechanisms of chemosensitivity. Methylation of the 3′UTR of CEP350 and MLPH, involved in centrosome machinery and microtubule tracking, respectively, was associated with response to Aurora kinase inhibitors and other agents. EPAS1 methylation was associated with response to Aurora kinase inhibitors, a PLK-1 inhibitor and a Bcl-2 inhibitor. KDM1A methylation was associated with PLK-1 inhibitors and a KSP inhibitor. Increased promoter methylation of SLFN11 was correlated with resistance to DNA damaging agents, as a result of low or no SLFN11 expression. The 5′ UTR of the epigenetic modifier EZH2 was associated with response to Aurora kinase inhibitors and a FGFR inhibitor. Methylation and expression of YAP1 were correlated with response to an mTOR inhibitor. Among non-neuroendocrine markers, EPHA2 was associated with response to Aurora kinase inhibitors and a PLK-1 inhibitor and CD151 with Bcl-2 inhibitors.

Conclusions

Multiple associations indicate potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggest targets for combination therapies. While many correlations were not specific to SCLC lineages, several lineage markers were associated with specific agents.
Anaerobic methane-oxidizing bacterial communities in sediments of a drinking reservoir, Beijing, China
Authors: Liu Yang , Wang Xiaoyan , Chen Yongjuan , Zhang Lingrong , Xu Kangli , Du Yi
Published: June 2020

Purpose

Nitrate/nitrite-dependent anaerobic methane oxidation (N-DAMO) connects the global cycle of carbon and nitrogen in aquatic ecosystems. The aims of this study were to investigate the spatiotemporal variation of N-DAMO bacteria and its driving factors in a drinking reservoir which are strongly affected by human consumption.

Methods

Cloning analyses were used to study the pmoA and 16S rRNA genes of N-DAMO bacteria. Sequencing and phylogenetic analyses were used to investigate the bacterial composition and structure. Redundancy analyses (RDA) and spearman’s correlations analyses were applied to analyze the relationships between bacterial distribution and environmental factors.

Result

There were remarkable spatial variations of N-DAMO bacteria in winter. Shannon biodiversity of 16S rRNA genes was higher in winter than that in summer. Compared with other freshwater ecosystems, there was higher diversity of N-DAMO bacteria in Miyun Reservoir. The N-DAMO bacterial communities (16S rRNA and pmoA genes) in sampling sites near to dam were different from the bacterial communities in other sampling sites. The N-DAMO bacterial community structure in dam areas may be associated with the water column depth in front of the dam. Moreover, Spearman’s correlations revealed that DO, NO3− -N, NO2−-N, and NH4+-N in interstitial water and sediment were potential determinant factors influencing the diversity of N-DAMO bacteria (16S rRNA and pmoA genes).

Conclusion

There were distinct seasonal variations in 16S rRNA and spatial variations in pmoA genes. N-DAMO bacterial communities contained novel Methylomirabilis oxyfera-like pmoA genes in Miyun Reservoir. Nitrogen (NO2−-N, NO3−-N, and NH4+-N) were the dominant factor influencing the N-DAMO bacterial community structure in the drinking reservoir. N-DAMO bacterial community structure in dam areas indicates that water depth and DO might be the dominant factor influencing the N-DAMO bacterial communities in the reservoir.
A depthwise separable convolutional neural network for keyword spotting on an embedded system
Authors: Sørensen Peter Mølgaard , Epp Bastian , May Tobias
Published: June 2020

A keyword spotting algorithm implemented on an embedded system using a depthwise separable convolutional neural network classifier is reported. The proposed system was derived from a high-complexity system with the goal to reduce complexity and to increase efficiency. In order to meet the requirements set by hardware resource constraints, a limited hyper-parameter grid search was performed, which showed that network complexity could be drastically reduced with little effect on classification accuracy. It was furthermore found that quantization of pre-trained networks using mixed and dynamic fixed point principles could reduce the memory footprint and computational requirements without lowering classification accuracy. Data augmentation techniques were used to increase network robustness in unseen acoustic conditions by mixing training data with realistic noise recordings. Finally, the system’s ability to detect keywords in a continuous audio stream was successfully demonstrated.