bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial focal adhesion kinase contributes to intestinal microvascular leakage during ischemia/reperfusion injury
Authors: Eitnier Rebecca A. , Wang Fang , Yang Clement , Aponte Alexandra M. , Ewing Thomas J. , Wu Mack H.
Published: April 2020

Ischemia/reperfusion (I/R) injury triggers a series of inflammatory responses in the microcirculation characterized by vascular leakage and leukocyte activation leading to organ dysfunction. In this study, we examine whether focal adhesion kinase (FAK) contributes to endothelial barrier dysfunction in response to I/R in splanchnic tissues. Using an in vivo model of intestinal I/R injury, we showed that the increase of microvascular leakage induced by I/R injury was greatly attenuated in endothelial specific, tamoxifen inducible, FAK knockout animals as well as wild type animals given pharmacological inhibition of FAK with PF‐573228. Using murine intestinal endothelial cells, we performed electric cell‐substrate impedance sensing (ECIS) assays with or without FAK inhibitor in the presence of H2O2. Results showed that FAK inhibition significantly attenuated endothelial barrier dysfunction induced by H2O2. Western blot analysis showed that H2O2 promoted FAK phosphorylation in a time course similar to that of endothelial barrier dysfunction. Confocal imaging analysis demonstrated that H2O2 increases the disruption of junctional proteins. The effect was blocked by FAK inhibitor. Taken together, the results suggested that FAK plays an important role in mediating intestinal vascular leakage during I/R injury.

Support or Funding Information

NIH HL120954, VA BX000799
Induction of Labour at 41 Weeks Versus Expectant Management and Induction of Labour at 42 Weeks (SWEdish Post-Term Induction Study, SWEPIS): Multicentre, Open Label, Randomised, Superiority Trial
Authors: Wennerholm Ulla-Britt , Saltvedt Sissel , Wessberg Anna , Alkmark Mårten , Bergh Christina , Brismar Wendel Sophia , Fadl Helena , Jonsson Maria , Ladfors Lars , Sengpiel Verena , Wesstrom Jan , Wennergren Göran , Wikstrom Anna-Karin , Elden Helen , Stephansson Olof , Hagberg Henrik
Published: April 2020

(Abstracted from BMJ 2019;367:l6131)

Adverse perinatal outcomes such as stillbirth and maternal complications have been shown to gradually increase postterm (≥42 weeks [≥294 days]). Despite this, no international agreement exists on how to manage late-term pregnancies (although the World Health Organization does recommend induction of labor at 41 weeks).
American Urogynecologic Society Systematic Review: The Impact of Weight Loss Intervention on Lower Urinary Tract Symptoms and Urinary Incontinence in Overweight and Obese Women
Authors: Yazdany Tajnoos , Jakus-Waldman Sharon , Jeppson Peter C. , Schimpf Megan O. , Yurteri-Kaplan Ladin A. , Ferzandi Tanaz R. , Weber-LeBrun Emily , Knoepp Leise , Mamik Mamta , Viswanathan Meera , Ward Renée M.
Published: April 2020

(Abstracted from Female Pelvic Med Reconstr Surg 2020;26:16–29)

Urinary incontinence (UI) affects many women across the world and can have severe impacts on quality of life. Obesity has been reported to play a role in the development of UI.
How Women Are Treated During Facility-Based Childbirth in Four Countries: A Cross-sectional Study With Labour Observations and Community-Based Surveys
Authors: Bohren Meghan A. , Mehrtash Hedieh , Fawole Bukola , Maung Thae Maung , Balde Mamadou Dioulde , Maya Ernest , Thwin Soe Soe , Aderoba Adeniyi K. , Vogel Joshua P. , Irinyenikan Theresa Azonima , Adeyanju A. Olusoji , Mon Nwe Oo , Adu-Bonsaffoh Kwame , Landoulsi Sihem , Guure Chris , Adanu Richard , Diallo Boubacar Alpha , Gülmezoglu A. Metin , Soumah Anne-Marie , Sall Alpha Oumar , Tunçalp Özge
Published: April 2020

(Abstracted from Lancet 2019;394:1750–1763)

Women around the world experience mistreatment during childbirth. This includes, but is not limited to, physical abuse, verbal abuse, discrimination, and procedures performed without consent.
Adherence of Cell-Free DNA Noninvasive Prenatal Screens to ACMG Recommendations
Authors: Skotko Brian G. , Allyse Megan A. , Bajaj Komal , Best Robert G. , Klugman Susan , Leach Mark , Meredith Stephanie , Michie Marsha , Stoll Katie , Gregg Anthony R.
Published: April 2020

(Abstracted from Genet Med 2019;21:2285–2292)

Noninvasive prenatal screening (NIPS) with analysis of cell-free DNA (cfDNA) is a procedure that tests for fetal aneuploidies. This testing has been available to women in the United States since 2011, and in 2016, the American College of Medical Genetics and Genomics (ACMG) released specific recommendations for laboratories to follow when administering this testing and reporting results.
Dual Antiplatelet Therapy and Surgical Timing in Geriatric Hip Fracture
Authors: Tarrant Seth M. , Kim Raymond G. , McGregor Kassandra L. , Palazzi Kerrin , Attia John , Balogh Zsolt J.
Published: April 2020

Objective:

To determine how timing of surgery affects transfusion, major complications, and mortality in patients who sustain a geriatric hip fracture while taking dual antiplatelet therapy (DAPT; typically aspirin and clopidogrel).

Design:

Retrospective cohort study.

Setting:

University-affiliated Level 1 Trauma Center.

Patients:

Patients 65 years of age or older on DAPT with a geriatric hip fracture were investigated at a single institution between 2002 and 2017. Demographic and perioperative data were collected from patient records, institutional databases, and national hip fracture registry.

Intervention:

Fixation or arthroplasty.

Main Outcome Measurement:

Transfusion, major complications, and 30-day mortality.

Results:

Of the 6724 patients sustaining a geriatric hip fracture, 122 patients were taking DAPT on admission. Timing of surgery did not influence transfused units (incidence rate ratio 1.00, 95% confidence interval: 0.87–1.15, P = 0.968) but did affect major complications (time modeled as quadratic term; odds ratios ranging from 0.20 to 7.91, ptime = 0.001, ptime*time<0.001) and 30-day mortality (odds ratio 1.32, 95% confidence interval: 1.03–1.68, P = 0.030).

Conclusion:

Surgical delay does not change the need for transfusion of hip fracture patients on DAPT, but it is associated with increased probabilities of major complications and 30-day mortality.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Morbidity and Mortality in Critically Ill Children. II. A Qualitative Patient-Level Analysis of Pathophysiologies and Potential Therapeutic Solutions*
Authors: Meert Kathleen L. , Banks Russell , Holubkov Richard , Pollack Murray M. ,   and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network
Published: April 2020

Objectives:

To describe at the individual patient level the pathophysiologic processes contributing to morbidity and mortality in PICUs and therapeutic additions and advances that could potentially prevent or reduce morbidity and mortality.

Design:

Qualitative content analysis of intensivists’ conclusions on pathophysiologic processes and needed therapeutic advances formulated by structured medical record review.

Setting:

Eight children’s hospitals affiliated with the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.

Patients:

A randomly selected cohort of critically ill children with a new functional morbidity or mortality at hospital discharge. New morbidity was assessed using the Functional Status Scale and defined as worsening by two or more points in a single domain from preillness baseline.

Interventions:

None.

Measurements and Main Results:

Of 292 children, 175 (59.9%) had a new morbidity and 117 (40.1%) died. The most common pathophysiology was impaired substrate delivery (n = 158, 54.1%) manifesting as global or regional hypoxia or ischemia due to low cardiac output or cardiac arrest. Other frequent pathophysiologies were inflammation (n = 104, 35.6%) related to sepsis, respiratory failure, acute respiratory distress syndrome, or multiple organ dysfunction; and direct tissue injury (n = 64, 21.9%) including brain and spinal cord trauma. Chronic conditions were often noted (n = 156, 53.4%) as contributing to adverse outcomes. Drug therapies (n = 149, 51.0%) including chemotherapy, inotropes, vasoactive agents, and sedatives were the most frequently proposed needed therapeutic advances. Other frequently proposed therapies included cell regeneration (n = 115, 39.4%) mainly for treatment of neuronal injury, and improved immune and inflammatory modulation (n = 79, 27.1%).

Conclusions:

Low cardiac output and cardiac arrest, inflammation-related organ failures, and CNS trauma were the most common pathophysiologies leading to morbidity and mortality in PICUs. A research agenda focused on better understanding and treatment of these conditions may have high potential to directly impact patient outcomes.
Expiratory Airflow Limitations on Lung Flute Effectiveness in Secretion Clearance: An Observational Cross-sectional Pilot Study
Authors: da Silva Francisco Carlos Nunes , Stolfi Angela , D'Agati Michael
Published: April 2020

Purpose:

The purpose of this observational study was to assess the validity of the Lung Flute® (LF) manufacturer's criterion for effective use of the device.

Methods:

Peak expiratory flow (PEF) and the ability to activate the oscillatory mechanism in the LF were assessed and compared. The diagnostic accuracy of the manufacturer's PEF threshold value of ≥128.4 L/min was determined, and an optimized threshold was derived.

Results:

The LF manufacturer's PEF threshold value of ≥128.4 L/min had a sensitivity of 100%, a specificity of 55%, and overall diagnostic accuracy of 83%. Nine (45%) of the twenty subjects that were not capable of activating the oscillatory device had a PEF ≥128.4 L/min. The optimal threshold value, with a sensitivity and specificity of 100%, for our sample was 167.5 L/min.

Conclusions:

The manufacturer's PEF threshold value of ≥128.4 L/min demonstrated high sensitivity but low specificity for predicting a patient's ability to use the LF device effectively. The optimized threshold value derived from our study was markedly higher. Clinicians should be aware that the LF manufacturer's specifications for the minimum PEF required for effective use of the device may not be evidence-based or accurate and consider this when prescribing this oscillatory positive expiratory pressure device.
Research on the Radiotoxicology of Plutonium Using Animals: Consideration of the 3Rs—Replace, Reduce, Refine
Authors: Griffiths Nina M. , Van der Meeren Anne , Angulo Jaime F. , Vincent-Naulleau Silvia
Published: April 2020

To characterize the health effects of incorporated plutonium, many experiments have been conducted using different animal models. These range from (1) applied (tissue uptake/retention determination, decorporation therapy efficacy), (2) fundamental (gene expression, cancer induction), and (3) dosimetry models. In recent years, the use of animals for scientific purposes has become a public concern. The application of the 3Rs - Replace (use of alternative methods or animals not considered capable of experiencing pain, suffering, and distress), Reduce (reduction in animal numbers), and Refine (better animal welfare and minimization of suffering, pain and distress) - has increased to address ethical concerns and legislative requirements. The introduction of novel non-animal technologies is also an important factor as complementary options to animal experimentation. In radiotoxicology research, it seems there is a natural tendency to Replace given the possibility of data reuse obtained from contamination cases in man and animal studies. The creation of “registries” and “repositories” for nuclear industry workers (civil and military) is now a rich legacy for radiotoxicological measurements. Similarly, Reduction in animal numbers can be achieved by good experimental planning with prior statistical analyses of animal numbers required to obtain robust data. Multiple measurements in the same animal over time (external body counting, excreta collection) with appropriate detection instruments also allow Reduction. In terms of Refinement, this has become “de rigueur” and a necessity given the societal and legal concerns for animal welfare. For research in radiotoxicology, particularly long-term studies, better housing conditions within the constraints of radiation protection issues for research workers are an important concern. These are all pertinent considerations for the 3Rs remit and future research in radiotoxicology.
The Influence of Speed During Stripping in Descemet Membrane Endothelial Keratoplasty Tissue Preparation
Authors: Borroni Davide , Gadhvi Kunal , Wojcik Gabriela , Pennisi Flavia , Vallabh Neeru A. , Galeone Alessandra , Ruzza Alessandro , Arbabi Esmaeil , Menassa Nardine , Kaye Stephen , Ponzin Diego , Ferrari Stefano , Romano Vito
Published: April 2020

Purpose:

To evaluate whether the speed of stripping a Descemet membrane endothelial keratoplasty graft influences the graft scroll width.

Methods:

Human corneas suitable for research were selected for the study. Pairs of corneas were randomly divided into 2 groups: 1 cornea was stripped with a slow speed (group 1) and the contralateral with a fast speed (group 2). Slow speed was defined as the total time greater than 150 seconds or speed <0.057 mm/s. Fast peeling was defined as less than 75 seconds or speed >0.11 mm/s. The grafts acquired were evaluated by microscopy for the graft scroll width and endothelial cell density change pre- and post-preparation.

Results:

Twenty corneas of 10 donors were included in the analysis. The mean donor age was 68.6 ± 7.58 years. The mean total time of the tissue preparation in group 1 was 282.7 ± 28 seconds and in group 2 was 126 ± 50 seconds (P-value = 0.00000047). The mean speed of stripping in group 1 was 0.045 ± 0.006 mm/s and in group 2 was 0.266 ± 0.093 mm/s (P-value = 0.000027). The graft width in group 1 was 6.4 ± 0.92 mm and in group 2 was 2.87 ± 0.32 mm (P-value = 0.00000014). The mean endothelial cell loss in group 1 was 389 ± 149 cells/mm2 and in group 2 was 186 ± 63.44 cells/mm2 (P-value = 0.00134).

Conclusion:

We found a correlation between the speed of stripping, scroll width, and endothelial cell loss. Slow-peeled Descemet membrane endothelial keratoplasty grafts result in a wider scroll width but were associated with a greater reduction in endothelial cell density.
Primary Localized Conjunctival Amyloidosis Presenting Corneal Whorl-like Opacity Patterns
Authors: Sharma Vijay K. , Agarwal Manisha , Tyagi Aman , Sati Alok
Published: April 2020

Purpose:

To report an unusual case of corneal whorl-like opacity patterns in a patient of primary localized conjunctival amyloidosis.

Methods:

Case report and review of literature.

Results:

A 35-year old man with a case of primary localized conjunctival amyloidosis presented with corneal whorl-like opacity patterns and underwent conjunctival and limbal biopsies. Histopathological evaluation showed dense deposition of amorphous, hyaline, eosinophilic material with week periodic acid-Schiff positivity and congophilia on congo red stain. There was birefringence under a polarized microscope. These findings were suggestive of amyloid deposition. tumor-associated calcium signal transducer-2 mutation was negative ruling out gelatinous drop-like corneal dystrophy. Systemic evaluation was negative for primary systemic amyloidosis. A diagnosis of primary localized conjunctival amyloidosis with corneal whorl-like opacity patterns was confirmed.

Conclusions:

This is an unusual case report of primary localized conjunctival amyloidosis, presenting as corneal whorl-like opacity patterns. Primary localized conjunctival amyloidosis usually involves the fornix and then spreads to lids causing lid thickening, blepharoptosis, subconjunctival, or orbital mass. In our case, it probably started around limbus, involving palisades of Vogt and caused corneal whorl-like opacity patterns which were the presenting feature.
The Effect of Commonly Performed Exercises on the Levator Hiatus Area and the Length and Strength of Pelvic Floor Muscles in Postpartum Women
Authors: Siff Lauren N. , Hill Audra J. , Walters Samantha J. , Walters Ginny , Walters Mark D.
Published: April 2020

(Abstracted from Female Pelvic Med Reconstr Surg 2020;26:61–66)

Previous research has demonstrated that postpartum pelvic floor exercises can lead to an increase in strength of the pelvic floor muscles (PFMs) and a reduction in pelvic floor disorders. However, as many as 23% of patients perform these exercises incorrectly, which may be due to barriers from patient awareness, education, disagreement about techniques, and compliance.
Ethical Problems in Decision Making in the Neonatal ICU
Authors: Lantos John D.
Published: April 2020

(Abstracted from N Engl J Med 2018;379(19):1851–1860)

In the neonatal intensive care unit (NICU), disagreements about whether life-sustaining treatment can ethically be withheld or withdrawn are not uncommon. At times, doctors recommend treatments and parents refuse, and sometimes, parents request continued treatment that doctors think inappropriate.
Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants
Authors: Katheria Anup , Reister Frank , Essers Jochen , Mendler Marc , Hummler Helmut , Subramaniam Akila , Carlo Waldemar , Tita Alan , Truong Giang , Davis-Nelson Shareece , Schmölzer Georg , Chari Radha , Kaempf Joseph , Tomlinson Mark , Yanowitz Toby , Beck Stacy , Simhan Hyagriv , Dempsey Eugene , O'Donoghue Keelin , Bhat Shazia , Hoffman Matthew , Faksh Arij , Arnell Kathy , Rich Wade , Finer Neil , Vaucher Yvonne , Khanna Paritosh , Meyers Mariana , Varner Michael , Allman Phillip , Szychowski Jeff , Cutter Gary
Published: April 2020

(Abstracted from JAMA 2019;322(19):1877–1886)

Delayed umbilical cord clamping is the current standard of care for newborn management at delivery. The extended time between delivery and umbilical cord clamping allows for a higher quantity of placental blood to reach the newborn.
Low MicroRNA-126 Levels in Right Ventricular Endomyocardial Biopsies Coincide With Cardiac Allograft Vasculopathy in Heart Transplant Patients
Authors: Heggermont Ward A. , Delrue Leen , Dierickx Karen , Dierckx Riet , Verstreken Sofie , Goethals Marc , Bartunek Jozef , Vanderheyden Marc
Published: April 2020

Background.

Endothelium-enriched microRNAs (miRs) are involved in the development of cardiac allograft vasculopathy (CAV). Recently, serum-derived miR-126-3p and -5p, known endothelial microRNAs with a crucial function in angiogenesis and re-endothelialization, provided additional predictive power for cardiac allograft vasculopathy in addition to clinical predictors. However, their myocardial expression in and relationship with CAV are still unknown. Our study aim was to investigate the expression of endomyocardial microRNA-126-3p and microRNA-126-5p levels in heart transplant recipients and their relationship with allograft vasculopathy.

Methods.

We studied 39 heart transplant recipients, 21 with proven allograft vasculopathy (CAV+) and 18 without allograft vasculopathy (CAV−) with serial coronary angiograms. Additionally, 8 patients with end-stage native coronary artery disease (CAD) were added to the study to investigate disease specificity of the microRNA signature. The mRNA levels of miR-126-3p and miR-126-5p were determined by qRT-PCR in the right ventricular endomyocardial biopsies obtained at baseline and during routine follow-up.

Results.

MiR-126-3p levels were significantly lower in the CAV+ group compared to the CAV− group at follow-up, while miR-126-5p levels were unaltered. This was in stark contrast to native CAD patients in whom miR-126-3p and -5p levels were significantly higher. qPCR levels of miR-126 targets are differentially regulated in CAV versus ischemic cardiomyopathy and are influenced by the administration of immunosuppressive agents in endothelial cells.

Conclusions.

Our data provide evidence for a distinct microRNA signature in heart transplantation patients with allograft vasculopathy. In contrast to CAD patients, lower miR-126-3p levels coincide with the development of cardiac allograft vasculopathy. Further studies in a larger patient population are warranted to determine if the serial measurement of myocardial microRNA-126 products could help in risk assessment and early detection of CAV.
The poly-ADP ribose polymerase-1/apoptosis-inducing factor pathway may help mediate the protective effect of electroacupuncture on early brain injury after subarachnoid hemorrhage
Authors: Lang Shuhui , Yan Xiaogang , Wang Chunsheng , Wu Yan , Liu Xing , Ma Chunxiang , Li Yongju , Xia Hechun
Published: April 2020

Subarachnoid hemorrhage (SAH) is a clinically common, acute, critical cerebrovascular disease associated with high mortality. Here, we investigated the effects of electroacupuncture on early brain injury after SAH. We successfully established a Sprague–Dawley rat model of the SAH model, and randomly divided the rats into four groups: sham-operated group, SAH group, positive control group, and electroacupuncture group. Electroacupuncture effectively decreased the number of transferase UTP nick end labeling-positive cells and extent of DNA fragmentation compared with the control, indicating a decrease in apoptosis. Moreover, electroacupuncture decreased the expression of proteins involved in the poly-ADP ribose polymerase-1/apoptosis-inducing factor (PARP-1/AIF) pathway in vivo, and the difference was statistically significant (P < 0.05). Treatment with electroacupuncture resulted in a significant improvement in neurological function. It inhibited the increase in blood–brain barrier permeability by regulating the protein expression of matrix metalloproteinase-9, occludin, and claudin-5. Additionally, electroacupuncture limited the development of cerebral edema and microglial activation in early brain injury after SAH. In conclusion, electroacupuncture can ameliorate early brain injury after SAH, and this may occur via inhibition of the PARP-1/AIF pathway.
Vapor H2O2 sterilization as a decontamination method for the reuse of N95 respirators in the COVID-19 emergency
Authors: Oral Ebru , Wannomae Keith K. , Connolly Rachel , Gardecki Joseph , Leung Hui Min , Muratoglu Orhun , Griffiths Anthony , Honko Anna N. , Avena Laura E. , McKay Lindsay G. A. , Flynn Nick , Storm Nadia , Downs Sierra N. , Jones Ralph , Emmal Brandon
Published: April 2020

There are a variety of methods routinely used in the sterilization of medical devices using hydrogen peroxide (H2O2) including vaporization, plasma generation and ionization. Many of these systems are used for sterilization and are validated for bioburden reduction using bacterial spores.

Here, we explored the benefits of using vaporized H2O2 (VHP) treatment of N95 respirators for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency. The factors that are considered for the effective reuse of these respirators are the fit, the filter efficiency and the decontamination/disinfection level for SARS-CoV-2, which is the causative virus for COVID-19 and other organisms of concern in the hospital environment such as methicillin-resistant Staphylococcus aureus or Clostridium difficile. WE showed that the method did not affect fit or filter efficiency at least for one cycle and resulted in a >6 log reduction in bacterial spores and >3.8 log reduction in the infectious SARS-CoV2 load on N95 respirators.
Cardiovascular Diseases Burden in COVID-19: Systematic Review and Meta-analysis
Authors: Hessami Amirhossein , Shamshirian Amir , Heydari Keyvan , Pourali Fatemeh , Alizadeh-Navaei Reza , Moosazadeh Mahmood , Abrotan Saeed , Shojaei Layla , Sedighi Sogol , Shamshirian Danial , Rezaei Nima
Published: April 2020

Background

High rate of cardiovascular disease (CVD) have been reported among patients with novel coronavirus disease (COVID-19). Meanwhile there were controversies among different studies about CVD burden in COVID-19 patients. Hence, we aimed to study CVD burden among COVID-19 patients, using a systematic review and meta-analysis.

Methods

We have systematically searched databases including PubMed, Embase, Cochrane Library, Scopus, Web of Science as well as medRxiv pre-print database. Hand searched was also conducted in journal websites and Google Scholar. Meta-analyses were carried out for Odds Ratio (OR) of mortality and Intensive Care Unit (ICU) admission for different CVDs. We have also performed a descriptive meta-analysis on different CVDs.

Results

Fifty-six studies entered into meta-analysis for ICU admission and mortality outcome and 198 papers for descriptive outcomes, including 159,698 COVID-19 patients. Results of meta-analysis indicated that acute cardiac injury, (OR: 13.29, 95% CI 7.35-24.03), hypertension (OR: 2.60, 95% CI 2.11-3.19), heart Failure (OR: 6.72, 95% CI 3.34-13.52), arrhythmia (OR: 2.75, 95% CI 1.43-5.25), coronary artery disease (OR: 3.78, 95% CI 2.42-5.90), and cardiovascular disease (OR: 2.61, 95% CI 1.89-3.62) were significantly associated with mortality. Arrhythmia (OR: 7.03, 95% CI 2.79-17.69), acute cardiac injury (OR: 15.58, 95% CI 5.15-47.12), coronary heart disease (OR: 2.61, 95% CI 1.09-6.26), cardiovascular disease (OR: 3.11, 95% CI 1.59-6.09), and hypertension (OR: 1.95, 95% CI 1.41-2.68) were also significantly associated with ICU admission in COVID-19 patients.

Conclusion

Findings of this study revealed a high burden of CVDs among COVID-19 patients, which was significantly associated with mortality and ICU admission. Proper management of CVD patients with COVID-19 and monitoring COVID-19 patients for acute cardiac conditions is highly recommended to prevent mortality and critical situations.

Graphical abstract
How does external lateral stabilization constrain normal gait, apart from improving medio-lateral gait stability?
Authors: Mahaki Mohammadreza , IJmker Trienke , Houdijk Han , Bruijn Sjoerd Matthijs
Published: April 2020

Background

The effect of external lateral stabilization on medio-lateral gait stability has been investigated previously. However, existing lateral stabilization devices not only constrains lateral motions, but also transverse and frontal pelvis rotations. This study aimed to investigate the effect of external lateral stabilization with and without constrained transverse pelvis rotation on mechanical and metabolic gait features.

Methods

We undertook 2 experiments with eleven and ten young adult subjects, respectively. Experiment 2 supplemented experiment 1, as it considered several potential confounding factors in the design and set-up of experiment 1. Kinematic, kinetic, and breath-by-breath oxygen consumption data were recorded during 3 walking conditions (normal walking (Normal), lateral stabilization with (Free) and without transverse pelvis rotation (Restricted)) and at 3 speeds (0.83, 1.25, and 1.66 m/s) for each condition.

Results

External lateral stabilization significantly reduced the amplitudes of the transverse and frontal pelvis rotations, medio-lateral pelvis displacement, transverse thorax rotation, arm swing, and step width. The amplitudes of free vertical moment, anterior-posterior and vertical pelvis displacements, step length, and energy cost were not significantly influenced by external lateral stabilization. The removal of transverse pelvis rotation restriction by our experimental set-up resulted in significantly higher transverse pelvis rotation, although it remained significantly less than Normal condition. In concert, concomitant gait features such as transverse thorax rotation and arm swing were not significantly influenced by our new set-up.

Conclusion

Existing lateral stabilization set-ups not only constrain medio-lateral motions (i.e. medio-lateral pelvis displacement), but also constrains other movements such as transverse and frontal pelvis rotations, which leads to several other gait changes such as reduced transverse thorax rotation, and arm swing. Our new setup allowed for more transverse pelvis rotation, however, this did not result in more normal pelvis rotation, arm swing, etc. Hence, to provide medio-lateral support without constraining other gait variables, more elaborate set-ups are needed. Unless such a set-up is realized the observed side effects need to be taken into account when interpreting the effects of lateral stabilization as reported in previous studies.
Cryo-electron tomography of cardiac myofibrils reveals a contraction-induced lattice twist in the Z-discs
Authors: Oda Toshiyuki , Yanagisawa Haruaki
Published: April 2020

The Z-disc forms a boundary between sarcomeres, which constitute structural and functional units of striated muscle tissue. Actin filaments from adjacent sarcomeres are cross-bridged by α-actinin in the Z-disc, allowing transmission of tension across the myofibril. Despite decades of studies, the 3D structure of Z-disc has been elusive due to the limited resolution of conventional electron microscopy. Here, we observed porcine cardiac myofibrils using cryo-electron tomography and reconstructed the 3D structures of the actinactinin cross-bridging complexes within the Z-discs in relaxed and activated states. We found that the α-actinin showed a contraction-induced swing motion along with a global twist in the actin lattice. Our observation suggests that the elasticity and the integrity of the Z-disc during the muscle contraction cycle are maintained by the structural flexibility within the actin-actinin complex.
Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain
Authors: Chi Xiaojing , Liu Xiuying , Wang Conghui , Zhang Xinhui , Ren Lili , Jin Qi , Wang Jianwei , Yang Wei
Published: April 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across more than 200 countries and regions, leading to an unprecedented medical burden and live lost. SARS-CoV-2 specific antivirals or prophylactic vaccines are not available. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Using SARS-CoV-2 spike RBD as a bait, we have discovered a panel of humanized single domain antibodies (sdAbs). These sdAbs revealed binding kinetics with the equilibrium dissociation constant (KD) of 0.7~33 nM. The monomeric sdAbs showed half maximal inhibitory concentration (IC50) of 0.003~0.3 μg/mL in pseudotyped particle neutralization assay, and 0.23~0.50 μg/mL in authentic SARS-CoV-2 neutralization assay. Competitive ligand-binding data suggested that the sdAbs either completely blocked or significantly inhibited the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Finally, we showed that fusion of the human IgG1 Fc to sdAbs improved their neutralization activity by tens of times. These results reveal the novel SARS-CoV-2 RBD targeting sdAbs and pave a road for antibody drug development.
Further analysis of the impact of distancing upon the COVID-19 pandemic
Authors: Bernstein Daniel J.
Published: April 2020

This paper questions various claims from the paper “Social distancing strategies for curbing the COVID-19 epidemic” by Kissler, Tedijanto, Lipsitch, and Grad: most importantly, the claim that China’s “intense” distancing measures achieved only a 60% reduction in R0.
Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.
Authors: Ma Henry , Lundy Jeneveve D. , Cottle Emily L. , O'Malley Katherine J. , Trichel Anita M. , Klimstra William B. , Hartman Amy L. , Reed Douglas S. , Teichert Tobias
Published: April 2020

Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naïve macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 – 4Hz); theta: [4 – 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.
PickPocket : Pocket binding prediction for specific ligands family using neural networks.
Authors: VIART Benjamin Thomas , Lorenzi Claudio , Moriel-Carretero María , Kossida Sofia
Published: April 2020

Most of the protein biological functions occur through contacts with other proteins or ligands. The residues that constitute the contact surface of a ligand-binding pocket are usually located far away within its sequence. Therefore, the identification of such motifs is more challenging than the linear protein domains. To discover new binding sites, we developed a tool called PickPocket that focuses on a small set of user-defined ligands and uses neural networks to train a ligand-binding prediction model. We tested PickPocket on fatty acid-like ligands due to their structural similarities and their under-representation in the ligand-pocket binding literature. Our results show that for fatty acid-like molecules, pocket descriptors and secondary structures are enough to obtain predictions with accuracy >90% using a dataset of 1740 manually curated ligand-binding pockets. The trained model could also successfully predict the ligand-binding pockets using unseen structural data of two recently reported fatty acid-binding proteins. We think that the PickPocket tool can help to discover new protein functions by investigating the binding sites of specific ligand families. The source code and all datasets contained in this work are freely available at https://github.com/benjaminviart/PickPocket .
Investigating the origin and consequences of endogenous default options in repeated economic choices
Authors: Couto Joaquina , van Maanen Leendert , Lebreton Maël
Published: April 2020

Classical value-based decision theories state that economic choices are solely based on the value of available options. Experimental evidence suggests, however, that individuals’ choices are biased towards default options, prompted by the framing of decisions. Although the effects of default options created by exogenous framing – such as how choice options are displayed – are well-documented, little is known about the potential effects and properties of endogenous framing, that is, originating from an individual’s internal state. In this study, we investigated the existence and properties of endogenous default options in a task involving choices between risky lotteries. By manipulating and examining the effects of three experimental features – time pressure, time spent on task and relative choice proportion towards a specific option –, we reveal and dissociate two features of endogenous default options which bias individuals’ choices: a natural tendency to prefer certain types of options (natural default), and the tendency to implicitly learn a default option from past choices (learned default). Additional analyses suggest that while the natural default may bias the standard choice process towards an option category, the learned default effects may be attributable to a second independent choice process. Overall, these investigations provide a first experimental evidence of how individuals build and apply diverse endogenous default options in economic decision-making and how this biases their choices.
Analyzing engineered point spread functions using phasor-based single-molecule localization microscopy
Authors: Martens Koen J.A. , Jabermoradi Abbas , Yang Suyeon , Hohlbein Johannes
Published: April 2020

The point spread function (PSF) of single molecule emitters can be engineered in the Fourier plane to encode three-dimensional localization information, creating double-helix, saddle-point or tetra-pod PSFs. Here, we describe and assess adaptations of the phasor-based single-molecule localization microscopy (pSMLM) algorithm to localize single molecules using these PSFs with sub-pixel accuracy. For double-helix, pSMLM identifies the two individual lobes and uses their relative rotation for obtainingz-resolved localizations, while for saddle-point or tetra-pod, a novel phasor-based deconvolution approach is used. The pSMLM software package delivers similar precision and recall rates to the best-in-class software package (SMAP) at signal-to-noise ratios typical for organic fluorophores. pSMLM substantially improves the localization rate by a factor of 2 - 4x on a standard CPU, with 1-1.5·104(double-helix) or 2.5·105(saddle-point/tetra-pod) localizations/second.
COVID-19 is an emergent disease of aging
Authors: Santesmasses Didac , Castro José Pedro , Zenin Aleksandr A. , Shindyapina Anastasia V. , Gerashchenko Maxim V. , Zhang Bohan , Kerepesi Csaba , Yim Sun Hee , Fedichev Peter O. , Gladyshev Vadim N.
Published: April 2020

COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that poses one of the greatest challenges to public health in recent years. SARS-CoV-2 is highly contagious and often leads to severe viral pneumonia with respiratory failure and death in the elderly and subjects with pre-existing conditions, but the reason for this age dependence is unclear. Here, we found that the case fatality rate for COVID-19 grows exponentially with age in Italy, Spain, South Korea, and China, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to therapeutic approaches that affect specific pathways, by approaches that target the aging process.
Revisiting the interaction of heme with hemopexin: Recommendations for the responsible use of an emerging drug
Authors: Detzel Milena S. , Syllwasschy Benjamin F. , Steinbock Francèl , Ramoji Anuradha , Hopp Marie-Thérèse , George Ajay A. Paul , Neugebauer Ute , Imhof Diana
Published: April 2020

In hemolytic disorders, erythrocyte lysis results in massive release of hemoglobin and, subsequently, toxic heme. Hemopexin is the major protective factor against heme toxicity in human blood and currently considered for therapeutic use. It has been widely accepted that hemopexin binds heme with extraordinarily high affinity in a 1:1 ratio. Here we show that hemopexin binds heme with lower affinity than previously assumed and that the interaction ratio tends to 2:1 (heme:hemopexin) or above. The heme-binding sites of hemopexin were characterized using hemopexin-derived peptide models and competitive displacement assays. In addition,in silicomolecular modelling with a newly created homology model of human hemopexin allowed us to propose a recruiting mechanism by which heme consecutively binds to several histidine residues and is finally funnelled into the high-affinity binding pocket. Our findings have direct implications for the biomedical application of hemopexin and its potential administration in hemolytic disorders.
Space vector modulation with reduced common mode voltage for six-phase drives
Authors: Zandzadeh Mohammad Jafar , Saniei Mohsen , Kianinezhad Reza
Published: April 2020

Purpose

This paper aims to present a modified space vector pulse width modulation (SVPWM) technique for six-phase induction motor drive based on common-mode voltage (CMV) and current losses which are two important issues affecting drive system behavior and quality.

Design/methodology/approach

It is shown that the presence of z-component currents and the presence of CMV in six-phase drive system are two major limiting factors in space vector selection. The behavior of several space vector selections in a two-level inverter considering minimum CMV and z-components is investigated. Then, the space vectors in a three-level inverter is analyzed and tried to explore an SVM technique with better behavior.

Findings

The analyses show that all the problems cannot be solved in a six-phase drive system with two-level inverter despite having 64 space vectors; this study tried to overcome the limitations by exploring space vectors in a three-level inverter.

Originality/value

The proposed pulse width modulation (PWM) strategy leads to minimum current distortion and undesired current components with zero CMV and modest torque ripple.
ECLECTIC 4.0: the new learning model for business schools
Authors: Sathya Sowmya
Published: April 2020

Purpose

Current learning models need to change to facilitate learners acquiring and assimilating the competencies required for the future work scenario. The purpose of this paper is to propose a new learning model, ECLECTIC 4.0, comprising elements drawn from various sources, theories, styles, authors, technology and ideas to gain maximum insight.

Design/methodology/approach

The ECLECTIC 4.0 learning model is based on Robert J Sternberg's triarchic theory of intelligence, which proposes that varied contexts and tasks require different kinds of analytical, creative and practical intelligence. This paper discusses the interplay between the triarchic theory of intelligence and the ECLECTIC 4.0 learning model, highlighting the model's expected modifications for teaching toolkits, business schools and industry. Examples of current practices in business schools and industry that are paving the way for what is proposed in the model are provided and discussed.

Findings

To compete and succeed in the future work scenario, the competencies required (e.g. agility, mindfulness, collaboration, co-creation and design thinking) are different from those prevalent today. To acquire and assimilate these competencies, current business school learning and teaching models needs to change. The proposed model incorporates eight learning characteristics: embedding in business; collaborative learning; linking humanities to management; encouraging non-linear thinking; complementary insight enabling co-creation; technology to solve problems; innovating in response to demands and creating an experience centre.

Originality/value

The new ECLECTIC 4.0 learning model addresses the need for educationalists, especially in management education, to adopt the most appropriate teaching toolkits.
Corporate carbon risk, voluntary disclosure and debt maturity
Authors: Lemma Tesfaye Taddese , Azmi Shabestari Mehrzad , Freedman Martin , Lulseged Ayalew , Mlilo Mthokozisi
Published: April 2020

Purpose

This study aims to investigate the association between corporate carbon risk and debt maturity and the moderating role of voluntary disclosure, within the context of South Africa, an emerging player in the climate policy debate.

Design/methodology/approach

Based on the insights drawn from agency as well as information asymmetry theories, the authors develop models that link debt maturity with corporate carbon risk and voluntary disclosure and examine data obtained from companies listed on the Johannesburg Securities Exchange (JSE), for the period 2011-2015.

Findings

The findings document that, other things being equal, debt maturity is significantly higher, both statistically and economically, for companies with lower carbon intensity (risk). In addition, high-quality carbon disclosure accentuates the positive association between debt maturity and the inverse of carbon intensity. The results are robust to alternative measures of corporate carbon risk and issues of endogeneity. The findings are consistent with the view that lenders in South Africa use debt maturity as a non-price mechanism to address borrower risk and grant lower carbon risk companies that voluntarily provide higher quality carbon disclosures an even higher access to longer maturity debts; JSE-listed companies could use voluntary carbon disclosure to ease their access to debt with longer maturity.

Practical implications

The findings of this study have important implications to borrowers, pressure groups, policymakers and other stakeholders.

Originality/value

To the best of the authors’ knowledge, this study is the first to document evidence suggesting that lenders in South Africa use debt maturity as a non-price mechanism to address borrower risk.
Building harmony in diverse society: insights from practical wisdom
Authors: Huda Miftachul , Nor Muhamad Nasrul Hisyam , Isyanto Puji , Muhamat Razaleigh , Marni Nurazmallail , Ahmad Kilani Mohamed , Safar Jimaain
Published: April 2020

Purpose

Increasing diversity leads to local, national and transnational challenges requiring a novel and explicit problem-solving approach. Practical wisdom, which emerges from an integration knowledge and ability through religious awareness, can promote peaceful coexistence in diverse societies with adequate theological and educational infrastructures. This paper aims to critically examine practical wisdom as the religious awareness to underlying building harmony in the diverse society.

Design/methodology/approach

Literature from refereed and peer-reviewed journals and articles was reviewed using thematic topic analysis to propose a model of the practical wisdom as a foundation for building harmony in a diverse society.

Findings

This result shows that there are several discussions with specific objectives of practical wisdom as the result of core understanding of religious awareness underlying the potential solutions in the diverse society; the significant essence of practical wisdom as the core element for building harmony; exploring how practical wisdom should be a wide particular element in building integrity and harmony in the diverse society.

Originality/value

Practical wisdom can establish peaceful and respectful relations amongst diverse segments of the population. It is, therefore, crucial for scholars and practitioners to explore practical wisdom in depth and devise ways of promoting this important characteristic at a social level through the exchange of common ideas and goals.