bluuebunny/crossref_metadata_2025 huggingface dataset:
3-9SYSTOLIC BLOOD PRESSURE, MEAN ARTERIAL BLOOD PRESSURE RELATED TO CLINICAL OUTCOMES IN HEMORRHAGIC STROKE WITH EMERGENCY HYPERTENSION
Authors: Djohar Yuzar Thesariva , Gamayani Uni , Juli Cep
Published: July 2020

Introduction:

Stroke is a leading cause of mortality and disability in Indonesia. According to classification, 15–20% are hemorrhagic stroke, and 80% are due to hypertension. Many of them with emergency hypertension. Several studies have demonstrated a strong association between an increased level of blood pressure (BP) with poor outcomes. Comprehensive management of emergency hypertension could decrease mortality and disability.

Objective:

To study about the relationship of initial systolic blood pressure (SBP) and initial mean arterial pressure (MAP) with outcome in the patient having a hemorrhagic stroke and emergency hypertension.

Method:

This is an analytic observational study using medical records.The study investigated the association between SBP and MAP with clinical outcome based on The National Institutes of Health Stroke Scale (NIHSS) in living patients and deceased

Result:

We collected 60 subjects. Mean SBP initial 191.22 mmHg, MAP initial 134.26. We found a decrease in BP. Mean SBP at discharge 140.56 mmHg and MAP at discharge 103.0 mmHg. We observed decreasing in NIHSS from 12.89 at initial to 9.5 at discharge. Statistical analysis using Pearson's for delta SBP and MAP with NIHSS initial and discharge was not significant. The average of SBP and MAP of the patient who died is higher than the survived patient; however, it was not statistically significant.

Conclusion:

We could not find the relationship between initial systolic blood pressure, initial mean arterial pressure, and NIHSS in survived and deceased patients.
4-8CENTRAL AORTIC SYSTOLIC PRESSURE MEASUREMENT IN PATIENTS WITH REFRACTORY HYPERTENSION
Authors: Vamsi Varahabhatla , Prkacin Ingrid , Misri Z.K. , Kulkarni Vaman , Kamath Padmanabh , Achappa Basavaprabhu
Published: July 2020

Background:

Aortic systolic pressure is regarded more reliable due to elastic properties of the central arterial walls, than the peripheral blood pressure (BP) brachial arteries being more muscular. The arterial distensibilty is an important factor in determining the vascular age and predicting future acute aortic events. The non-invasive central blood pressure can aid in early detection and harmonising treatment in patients with Refractory hypertension (RH).

Aim:

To assess the Central aortic systolic pressure (CASP) in RH patients.

Methods and materials:

We identified 111 patients with refractory hypertension (uncontrolled BP despite use of 3 or more anti-hypertensives) at the outpatient clinic of Kasturba Medical College Hospital, Mangalore in the period of July-August 2018. The non-invasive CASP, Average systolic, diastolic and pulse (AvgS, AvgD, AvgP) measured with A-PULSE CASPal® Monitoring Device. Statistical analysis using SPSS software and parameters like Independent t-test, descriptive statistics (mean, standard deviation) were calculated.

Results:

The average age of the patients was 58 ± 14.95; 39 (35.1%) were females(F) and 72 (64.9%) were males (M). There was a significant difference in the CASP in F 146.6 ± 29.34 and 139.6 ± 21.8 in M; AvgS in F and M was 157.9 ± 28 and 152.4 ± 21.8 respectively. AvgD and AvgP in F and M were 92.9 ± 17.1, 92.5 ± 13.3 and 83.87 ± 13.9, 79.2 ± 13.6 respectively. Conditions age and CASP p = 0.324; age and AvgS p = 0.338; CASP and AvgS p = 0.919 were significant at p < 0.01.

Conclusions:

In patients with refractory hypertension, chrono-modulation with centrally acting anti-hypertensive drugs and synchronous CASP monitoring non-invasively can predict early target organ damage and helps improve the quality of life.
Where Are We in Bridging the Gender Leadership Gap in Academic Medicine?
Authors: Valantine Hannah A.
Published: July 2020

In nearly all walks of life, leadership sets the tone for what gets done, who does it, and how it is achieved. In 2020, the top ranks of academic medicine have not yet attained gender parity—an aspirational goal set 7 years ago in this journal as “50:50 by 2020,” and a vital aim for the United States’ productivity and innovation as a leader in biomedical research. Parity in academic leadership for women and other groups underrepresented in science and medicine will seed the culture change necessary for inclusive excellence: environments in which individuals from all backgrounds thrive in their pursuit of new knowledge to benefit human health.

In this Invited Commentary, the author describes the National Institutes of Health’s (NIH’s) current system-wide framework and tools for creating cultures of inclusive excellence through a set of guiding principles and integrated strategies. Successful efforts will recognize that individually focused solutions are necessary but not sufficient for institutional culture change. In keeping with a systems approach are implementing accountability and transparency; establishing clear metrics of inclusion, diversity, and equity; tracking and evaluating such metrics; as well as tying these metrics to institutional reward systems. These essential steps to institutional culture transformation require strong partnerships between NIH and the academic community. The author argues that with committed vision, focus, and energy, success is attainable, and soon.
Direct Anterior Approach to Total Hip Arthroplasty for Femoral Neck Fractures
Authors: Greenstein Alexander S. , Soles Gillian
Published: July 2020

Femoral neck fractures are a common injury pattern, especially within the elderly. Replacement with either hemiarthroplasty or total hip arthroplasty allows for immediate weight-bearing. This video demonstrates the direct anterior approach to total hip arthroplasty for management of displaced femoral neck fractures.
Total Elbow Arthroplasty for Distal Humerus Fractures
Authors: Page Brian Joseph , Lee Brennan Michael
Published: July 2020

Distal humerus fractures in elderly patients are challenging due to poor bone quality and may threaten the independence of elderly patients due to loss of functional range of motion. Total elbow arthroplasty has gained popularity in the treatment of these injuries. This video demonstrates total elbow arthroplasty in an elderly patient with a comminuted distal humerus fracture.
Distally Based Peroneus Brevis Rotation Flap
Authors: Neiman Rafael , Finkemeier Christopher G. , Swentik Andrew G.
Published: July 2020

Soft tissue defects of the distal leg, ankle, and hindfoot pose challenges for orthopaedic surgeons. The distally based peroneus brevis muscle flap is a viable local muscle rotation flap to cover defects in these challenging circumstances, and can be learned and performed by most orthopaedic surgeons without the need for microvascular techniques. This video demonstrates the technique for a peroneus brevis rotation flap in a patient with a lateral ankle defect and exposed bone.
Dorsal Approach for Dorsal Impaction Distal Radius Fracture—Visualization, Reduction, and Fixation Made Simple
Authors: Via Garrhett G. , Roebke Austin J. , Julka Abhishek
Published: July 2020

Distal radius fractures with dorsal articular surface impaction comprise a difficult fracture pattern to operatively reduce using a standard volar approach. Distal radius open reduction internal fixation using a dorsal approach allows direct visualization and reduction. The surgical technique video presented demonstrates technical pearls for optimal visualization, reduction, and fixation.
Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use
Authors: Papp Zoltán , Agostoni Piergiuseppe , Alvarez Julian , Bettex Dominique , Bouchez Stefan , Brito Dulce , Černý Vladimir , Comin-Colet Josep , Crespo-Leiro Marisa G. , Delgado Juan F. , Édes István , Eremenko Alexander A. , Farmakis Dimitrios , Fedele Francesco , Fonseca Cândida , Fruhwald Sonja , Girardis Massimo , Guarracino Fabio , Harjola Veli-Pekka , Heringlake Matthias , Herpain Antoine , Heunks Leo M. A. , Husebye Tryggve , Ivancan Višnja , Karason Kristjan , Kaul Sundeep , Kivikko Matti , Kubica Janek , Masip Josep , Matskeplishvili Simon , Mebazaa Alexandre , Nieminen Markku S. , Oliva Fabrizio , Papp Julius G. , Parissis John , Parkhomenko Alexander , Põder Pentti , Pölzl Gerhard , Reinecke Alexander , Ricksten Sven-Erik , Riha Hynek , Rudiger Alain , Sarapohja Toni , Schwinger Robert H. G. , Toller Wolfgang , Tritapepe Luigi , Tschöpe Carsten , Wikström Gerhard , Lewinski Dirk von , Vrtovec Bojan , Pollesello Piero
Published: July 2020

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate–dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.
Consensus Recommendations on the Prehospital Care of the Injured Athlete With a Suspected Catastrophic Cervical Spine Injury
Authors: Mills Brianna M. , Conrick Kelsey M. , Anderson Scott , Bailes Julian , Boden Barry P. , Conway Darryl , Ellis James , Feld Francis , Grant Murphy , Hainline Brian , Henry Glenn , Herring Stanley A. , Hsu Wellington K. , Isakov Alex , Lindley Tory , McNamara Lance , Mihalik Jason P. , Neal Timothy L. , Putukian Margot , Rivara Frederick P. , Sills Allen K. , Swartz Erik E. , Vavilala Monica S. , Courson Ron
Published: July 2020

Introduction:

Sports participation is among the leading causes of catastrophic cervical spine injury (CSI) in the United States. Appropriate prehospital care for athletes with suspected CSIs should be available at all levels of sport. The goal of this project was to develop a set of best-practice recommendations appropriate for athletic trainers, emergency responders, sports medicine and emergency physicians, and others engaged in caring for athletes with suspected CSIs.

Methods:

A consensus-driven approach (RAND/UCLA method) in combination with a systematic review of the available literature was used to identify key research questions and develop conclusions and recommendations on the prehospital care of the spine-injured athlete. A diverse panel of experts, including members of the National Athletic Trainers' Association, the National Collegiate Athletic Association, and the Sports Institute at UW Medicine participated in 4 Delphi rounds and a 2-day nominal group technique (NGT) meeting. The systematic review involved 2 independent reviewers and 4 rounds of blinded review.

Results:

The Delphi process identified 8 key questions to be answered by the systematic review. The systematic review comprised 1544 studies, 49 of which were included in the final full-text review. Using the results of the systematic review as a shared evidence base, the NGT meeting created and refined conclusions and recommendations until consensus was achieved.

Conclusions:

These conclusions and recommendations represent a pragmatic approach, balancing expert experiences and the available scientific evidence.
Congenital Benign Metastasizing Teratoma? A Case Report and Literature Review
Authors: Russell Daniel H.
Published: July 2020

A case is presented of a patient with completely resected congenital immature gastric teratoma containing yolk sac tumor, with locoregional recurrence and peritoneal seeding 25 months later as pure mature teratoma. To the knowledge of the author, this is the first case of its type to progress purely as mature teratoma.
Rectal Perivascular Epithelioid Cell Tumor With Partial CD117 Expression and Giant Cells
Authors: Maskoliūnaitė Vygantė , Jakubauskas Matas , Garnelytė Aušra , Jotautas Valdemaras , Stankevičienė Jolanta , Strupas Kestutis , Mickys Ugnius
Published: July 2020

Perivascular epithelioid cell tumor (PEComa) is a rare entity, characterized as a mesenchymal tumor with coexpression of melanocytic and smooth muscle markers. The involvement of the gastrointestinal tract is described in up to 100 cases in the English literature. Rectal PEComas are even more uncommon, with only 10 previously described cases. We present the case of a 62-year-old man with rectal PEComa with some unusual features, such as gastrointestinal stromal tumor–like CD117 positivity and HMB45 (human melanoma black-45)–positive multinucleated giant tumor cells. After 12 months' follow-up, the patient is alive with no radiologic, endoscopic, or histologic evidence of disease recurrence.
The Head and Neck Oncology Specimen: The Gross Examination as an Essential Component to Diagnosis and Optimal Patient Outcomes
Authors: Laklouk Israa , Sadow Peter M.
Published: July 2020

Achieving complete resection in head and neck oncologic cancer surgeries without leaving behind residual disease is the most significant factor to minimize the risk of locoregional recurrence and overall survival. Approaches regarding how to handle en bloc specimens for margin assessment also impact patients' long-term outcomes. Although sampling the tumor bed to evaluate for residual tumor at surgical margins (excision edges) is the most commonly practiced technique, some studies have shown that separately submitted tumor bed margins have lower sensitivity for tumor assessment compared with detection of those positive margins from direct sampling of the en bloc specimen. Close collaboration between the surgeon and pathologist is fundamental to optimize surgical margin assessment and reporting. Current American Joint Committee on Cancer (eighth edition) and National Comprehensive Cancer Network guidelines recommend the en bloc specimen sampling for intraoperative assessment of surgical margins. Cutoffs less than 5 mm between tumor and the surgical margin had been considered adequate in specific subsites in head and neck region. Emerging in situ imaging modalities and molecular testing may help to reduce inadequate surgical margins during tumor resections; however, further studies and validation are needed. This article presents a review of recent publications and guidelines of general grossing principles and recent updates to optimize cancer-free surgical margins and to emphasize the limitation issues encountered in routine practice.
Galectin-3 and Risk of Late Graft Failure in Kidney Transplant Recipients: A 10-year Prospective Cohort Study
Authors: Sotomayor Camilo G. , te Velde-Keyzer Charlotte A. , Diepstra Arjan , van Londen Marco , Pol Robert A. , Post Adrian , Gans Rijk O.B. , Nolte Ilja M. , Slart Riemer H.J.A. , de Borst Martin H. , Berger Stefan P. , Rodrigo Ramón , Navis Gerjan J. , de Boer Rudolf A. , Bakker Stephan J.L.
Published: July 2020

Background.

Galectin-3 may play a causal role in kidney inflammation and fibrosis, which may also be involved in the development of kidney graft failure. With novel galectin-3-targeted pharmacological therapies increasingly coming available, we aimed to investigate whether galectin-3 is associated with risk of late graft failure in kidney transplant recipients (KTR).

Methods.

We studied adult KTR who participated in TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study, recruited in a university setting (2001–2003). Follow-up was performed for a median of 9.5 (interquartile range, 6.2–10.2) years. Overall and stratified (P
interaction < 0.05) multivariable-adjusted Cox proportional-hazards regression analyses were performed to study the association of galectin-3 with risk of graft failure (restart of dialysis or retransplantation).

Results.

Among 561 KTR (age 52 ± 12 y; 54% males), baseline median galectin-3 was 21.1 (interquartile range, 17.0–27.2) ng/mL. During follow-up, 72 KTR developed graft failure (13, 18, and 44 events over increasing tertiles of galectin-3). Independent of adjustment for donor, recipient, and transplant characteristics, galectin-3-associated with increased risk of graft failure (hazard ratios [HR] per 1 SD change, 2.12; 95% confidence interval [CI], 1.63-2.75; P < 0.001), particularly among KTR with systolic blood pressure ≥140 mmHg (HR, 2.29; 95% CI, 1.80-2.92; P < 0.001; P
interaction = 0.01) or smoking history (HR, 2.56; 95% CI, 1.95-3.37; P < 0.001; P
interaction = 0.03). Similarly, patients in the highest tertile of galectin-3 were consistently at increased risk of graft failure.

Conclusions.

Serum galectin-3 levels are elevated in KTR, and independently associated with increased risk of late graft failure. Whether galectin-3-targeted therapies may represent novel opportunities to decrease the long-standing high burden of late graft failure in stable KTR warrants further studies.
Clinicopathologic Characteristics of JC Virus Nephropathy in Kidney Transplant Recipients
Authors: Wiegley Nasim , Walavalkar Vighnesh , Aujla Harleen , Chen Ling-Xin , Huang Yihung , Lee Brian K. , Jen Kuang-Yu
Published: July 2020

Background.

The vast majority of polyomavirus nephropathy (PVN) is due to BK virus, but rare cases result from JC virus reactivation. To date, only a handful of biopsy-proven JC-PVN cases have been reported. Here, we describe the clinical and pathologic findings in 7 patients with biopsy-proven JC-PVN.

Methods.

Search of the pathology archives at 2 institutions found 7 cases of JC-PVN. Clinical data were extracted from the electronic medical records, and the biopsies were reviewed.

Results.

Four cases were diagnosed at 6 y posttransplant or later. The remaining 3 cases presented within approximately 2 y posttransplant, of which 2 showed subclinical JC-PVN on surveillance biopsy. Two early presenting patients were treated for acute rejection just before acquiring JC-PVN. Late presenting patients had higher chronicity, which correlated to worse outcome. All but 1 biopsy showed nonspecific inflammation within areas of interstitial fibrosis without significant inflammation in unscarred cortex. The earliest presenting patient was the exception and showed active inflammation with tubulitis. Viral cytopathic changes were detected in all cases with moderate or high-histologic viral load (pvl), showing preference for the distal tubules and medulla. The 2 cases with low pvl did not demonstrate cytopathic changes but were SV40 positive.

Conclusions.

JC-PVN can be insidious in presentation, which may cause delayed or missed diagnosis. Unlike BK-PVN, which typically occurs early in the posttransplant period, JC-PVN can occur both early and late following transplant. Overreliance on negative plasma and urine BK viral loads to exclude PVN can be a pitfall.
Comparing Donor Heart Assessment Strategies During Ex Situ Heart Perfusion to Better Estimate Posttransplant Cardiac Function
Authors: Ribeiro Roberto Vanin Pinto , Alvarez Juglans Souto , Yu Frank , Adamson Mitchell Brady , Paradiso Emanuela , Hondjeu Arnaud Romeo Mbadjeu , Xin Liming , Gellner Bryan , Degen Maja , Bissoondath Ved , Meineri Massimiliano , Rao Vivek , Badiwala Mitesh Vallabh
Published: July 2020

Background.

Ex situ heart perfusion (ESHP) limits ischemic periods and enables continuous monitoring of donated hearts; however, a validated assessment method to predict cardiac performance has yet to be established. We compare biventricular contractile and metabolic parameters measured during ESHP to determine the best evaluation strategy to estimate cardiac function following transplantation.

Methods.

Donor pigs were assigned to undergo beating-heart donation (n = 9) or donation after circulatory death (n = 8) induced by hypoxia. Hearts were preserved for 4 hours with ESHP while invasive and noninvasive (NI) biventricular contractile, and metabolic assessments were performed. Following transplantation, hearts were evaluated at 3 hours of reperfusion. Spearman correlation was used to determine the relationship between ESHP parameters and posttransplant function.

Results.

We performed 17 transplants; 14 successfully weaned from bypass (beating-heart donation versus donation after circulatory death; P = 0.580). Left ventricular invasive preload recruitable stroke work (PRSW) (r = 0.770; P = 0.009), NI PRSW (r = 0.730; P = 0.001), and NI maximum elastance (r = 0.706; P = 0.002) strongly correlated with cardiac index (CI) following transplantation. Right ventricular NI PRSW moderately correlated to CI following transplantation (r = 0.688; P = 0.003). Lactate levels were weakly correlated with CI following transplantation (r = −0.495; P = 0.043). None of the echocardiography measurements correlated with cardiac function following transplantation.

Conclusions.

Left ventricular functional parameters, especially ventricular work and reserve, provided the best estimation of myocardial performance following transplantation. Furthermore, simple NI estimates of ventricular function proved useful in this setting. Right ventricular and metabolic measurements were limited in their ability to correlate with myocardial recovery. This emphasizes the need for an ESHP platform capable of assessing myocardial contractility and suggests that metabolic parameters alone do not provide a reliable evaluation.
Attitudes Toward Organ, Tissue, and Vascularized Composite Allograft (VCA) Donation and Transplantation: A Survey of United States Military Veterans
Authors: Ward Stephanie , Boger Matthew , Fleishman Aaron , Shenkel Jessica , Calvo Amanda , Pomahac Bohdan , Zwolak Robert , Krishnan Namrata , Rodrigue James R.
Published: July 2020

Background.

There are 20 million living US armed forces veterans; however, the organ donation attitudes of veterans have not been examined.

Methods.

Over a 17-month period, a convenience sample of 1517 veterans in New England completed a survey to assess attitudes about organ, tissue, and vascularized composite allograft (VCA) donation.

Results.

Most veterans (96%) supported the donation of organs and tissue for transplantation, and 59% were registered as an organ and tissue donor. Being younger (adjusted odds ratio [aOR]: 0.960.970.98; P = 0.01), female (aOR: 1.061.462.03; P = 0.02), non-Hispanic white (aOR: 1.302.073.30; P = 0.01), Hispanic (aOR: 1.282.434.61; P = 0.01), and having more trust that the transplant process is fair and equal (aOR: 1.191.401.65; P = 0.01) were predictive of donor registration. Also, most veterans were willing to donate their face (57%), hands/arms (81%), legs (81%), penis (men: 61%), and uterus (women: 76%) at time of death; donation willingness was higher for upper and lower limbs than for face or genitourinary organs (P < 0.001). Those unwilling to donate VCA organs expressed concerns about identity loss, psychological discomfort of self and others, body integrity, funeral presentation, and religious beliefs. Most (54%) felt that VCA donation should require permission of legal next-of-kin at the time of one’s death, even if the decedent was a registered donor.

Conclusions.

There is a high level of support for organ, tissue, and VCA transplantation and donation among veterans, despite limited educational campaigns targeting this population. There is high potential among veterans to further increase donor registry enrollment and raise awareness about VCA benefits for severely injured service members.
Evaluation of Longitudinal Exposure to Tacrolimus as a Risk Factor of Chronic Kidney Disease Occurrence Within the First-year Post-Liver Transplantation
Authors: Maurel Pauline , Prémaud Aurélie , Carrier Paul , Essig Marie , Barbier Louise , Rousseau Annick , Silvain Christine , Causse Xavier , Debette-Gratien Marilyne , Jacques Jérémie , Marquet Pierre , Salamé Ephrem , Loustaud-Ratti Véronique
Published: July 2020

Background.

Renal failure is predictive of mortality in the early postliver-transplantation period and calcineurin inhibitors toxicity is a main challenge. Our aim is to assess the impact of longitudinal tacrolimus exposure (TLE) and other variables on chronic kidney disease (CKD)-free 1-year-survival.

Methods.

Retrospective data of consecutive patients transplanted between 2011 and 2016 and treated with tacrolimus were collected. TLE and all relevant pre- and post-liver transplantation (LT) predictive factors of CKD were tested and included in a time-to-event model. CKD was defined by repeated estimated glomerular filtration rate (eGFR) values below 60 mL/min/1.73m2 at least for the last 3 months before M12 post-LT.

Results.

Data from 180 patients were analyzed. CKD-free survival was 74.5% and was not associated with TLE. Pre-LT acute kidney injury (AKI) and eGFR at 1-month post-LT (eGFRM1) <60 mL/min/1.73m2 were significant predictors of CKD. By distinguishing 2 situations within AKI (ie, with or without hepatorenal syndrome [HRS]), only HRS-AKI remained associated to CKD. HRS-AKI and eGFRM1 <60 mL/min/1.73m2 increased the risk of CKD (hazard ratio, 2.5; 95% confidence interval, 1.2-4.9; hazard ratio, 4.8; 95% confidence interval, 2.6-8.8, respectively).

Conclusions.

In our study, TLE, unlike HRS-AKI and eGFRM1, was not predictive of CKD-free survival at 1-year post-LT. Our results once again question the reversibility of HRS-AKI.
COVID-19 and Abdominal Transplant: A Stepwise Approach to Practice During Pandemic Conditions
Authors: Syed Shareef M. , Gardner James , Roll Garrett , Webber Allison , Mehta Neil , Shoji Jun , Adelmann Dieter , Niemann Claus , Braun Hillary J. , Mello Anna , Yao Francis , Posselt Andrew , Kang Sang-Mo , Hirose Ryutaro , Roberts John , Feng Sandy , Ascher Nancy , Stock Peter , Freise Chris
Published: July 2020

Background.

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease has transformed innumerable aspects of medical practice, particularly in the field of transplantation.

Main Body.

Here we describe a single-center approach to creating a generalizable, comprehensive, and graduated set of recommendations to respond in stepwise fashion to the challenges posed by these conditions, and the underlying principles guiding such decisions.

Conclusions.

Creation of a stepwise plan will allow transplant centers to respond in a dynamic fashion to the ongoing challenges posed by the COVID-19 pandemic.
Minutes of the International Committee on Systematics of Prokaryotes online discussion on the proposed use of gene sequences as type for naming of prokaryotes, and outcome of vote
Authors: Sutcliffe Iain C. , Dijkshoorn Lenie , Whitman William B. , Executive Board on behalf of the ICSP
Published: July 2020

The International Committee on Systematics of Prokaryotes has held an electronic discussion on proposals to amend the International Code of Nomenclature of Prokaryotes in order to allow the use of gene sequence data as type. The scientific discussion is reported. Subsequently members of the International Committee on Systematics of Prokaryotes voted on these proposals, which were rejected.
Dual-Histamine Receptor Blockade with Cetirizine - Famotidine Reduces Pulmonary Symptoms in COVID-19 Patients
Authors: Hogan Reed B. , Hogan Reed B. , Cannon Tim , Rappai Maria , Studdard John , Paul Doug , Dooley Thomas P.
Published: July 2020

Background

The COVID-19 pandemic due to SARS-CoV-2 infection can produce Acute Respiratory Distress Syndrome as a result of a pulmonary cytokine storm. Antihistamines are safe and effective treatments for reducing inflammation and cytokine release. Combinations of Histamine-1 and Histamine-2 receptor antagonists have been effective in urticaria, and might reduce the histamine-mediated pulmonary cytokine storm in COVID-19. Can a combination of Histamine-1 and Histamine-2 receptor blockers improve COVID-19 inpatient outcomes?

Methods

A physician-sponsored cohort study of cetirizine and famotidine was performed in hospitalized patients with severe to critical pulmonary symptoms. Pulmonologists led the inpatient care in a single medical center of 110 high-acuity patients that were treated with cetirizine 10 mgb.i.d. and famotidine 20 mgb.i.d. plus standard-of-care.

Results

Of all patients, including those with Do Not Resuscitate directives, receiving the dual-histamine receptor blockade for at least 48 hours, the combination drug treatment resulted in a 16.4% rate of intubation, a 7.3% rate of intubation after a minimum of 48 hours of treatment, a 15.5% rate of inpatient mortality, and 11.0 days duration of hospitalization. The drug combination exhibited beneficial reductions in inpatient mortality and symptom progression when compared to published reports of COVID-19 inpatients. Concomitant medications were assessed and hydroxychloroquine was correlated with worse outcomes.

Conclusions

This physician-sponsored cohort study of cetirizine and famotidine provides proof-of-concept of a safe and effective method to reduce the progression in symptom severity, presumably by minimizing the histamine-mediated cytokine storm. Further clinical studies in COVID-19 are warranted of the repurposed off-label combination of two historically-safe histamine receptor blockers.
State-dependent mapping of GlyR-cholesterol interactions by coupling crosslinking with mass spectrometry
Authors: Ferraro Nicholas A. , Cascio Michael
Published: July 2020

Pentameric ligand-gated ion channel (pLGIC) allostery is dependent on dynamic associations with its diverse environment. The cellular membrane’s lipid composition influences channel function with cholesterol being a key regulator of channel activity. Humanα1 glycine receptor (GlyR) was purified from baculovirus infected insect cells and reconstituted in unilamellar vesicles at physiological cholesterol:lipid ratios with aliquots of azi-cholesterol, a photoactivatable non-specific crosslinker. The receptor in vesicles was then enriched in either a resting, open, or desensitized state prior to photocrosslinking. Following photoactivation, crosslinked cholesterol-GlyR was trypsinized and sites of direct covalent attachment to peptides were identified by targeted MS/MS. Dozens of state-dependent crosslinks were identified and differential patterns of cholesterol-GlyR crosslinks were observed in the extracellular region nearing the lipid bilayer, in the M4 transmembrane helix, and in the large intracellular M3-M4 loop. Unique crosslinks in comparative studies identify changes in lipid accessibility or modulation of hydrophobic cavities in GlyR as a function of receptor allostery. Most notably, the outward twisting of M4 and differential crosslinking within the M3-M4 loop provide new insight into allosteric repositioning of GlyR. More generally, this study provides an accurate and sensitive approach to mapping the protein-lipid interactions to discern state-dependent structural movements of membrane proteins embedded in lipid-bilayers.

Significance

Ion channels are highly allosteric molecular machines whose structure and function are sensitive to lipids and ligands. While the structures of many pLGICs are known, these are often truncated forms of the receptor in a membrane-mimetic environment locked in ligand-bound conformational states that may not accurately reflect the conformation and dynamics of the receptor in a native lipid environment. Crosslinking coupled with mass spectrometry (CX-MS) has the capability of interrogating the structure of full-length receptors in a lipid environment. In this study, CX-MS was used to identify state-dependent cholesterol-GlyR interactions to identify differential cholesterol accessibility as a function of channel dynamics upon gating and desensitization.
Modelling the impact of climate change on the distribution and abundance of tsetse in Northern Zimbabwe
Authors: Longbottom Joshua , Caminade Cyril , Gibson Harry S. , Weiss Daniel J. , Torr Steve , Lord Jennifer S.
Published: July 2020

Background

Climate change is predicted to impact the transmission dynamics of vector-borne diseases. Tsetse flies (Glossina) transmit species ofTrypanosomathat cause human and animal African trypanosomiasis. A previous modelling study showed that temperature increases between 1990 and 2017 can explain the observed decline in abundance of tsetse at a single site in the Mana Pools National Park of Zimbabwe. Here, we apply a mechanistic model of tsetse population dynamics to predict how increases in temperature may have changed the distribution and relative abundance ofGlossina pallidipesacross northern Zimbabwe.

Methods

Local weather station temperature measurements were previously used to fit the mechanistic model to longitudinalG. pallidipescatch data. To extend the use of the model, we converted MODIS land surface temperature to air temperature, compared the converted temperatures with available weather station data to confirm they aligned, and then re-fitted the mechanistic model usingG. pallidipescatch data and air temperature estimates. We projected this fitted model across northern Zimbabwe, using simulations at a 1 km × 1 km spatial resolution, between 2000 to 2016.

Results

We produce estimates of relative changes inG. pallidipesmortality, larviposition, emergence rates and abundance, for northern Zimbabwe. Our model predicts decreasing tsetse populations within low elevation areas in response to increasing temperature trends during 2000-2016. Conversely, we show that high elevation areas (>1000 M.A.S.L), previously considered too cold to sustain tsetse, may now be climatically suitable.

Conclusions

The results of this research represent the first regional-scale assessment of temperature related tsetse population dynamics, and the first high spatial-resolution estimates of this metric for northern Zimbabwe. Our results suggest that tsetse abundance may have declined across much of the Zambezi valley in response to changing climatic conditions during the study period. Future research including empirical studies is planned to improve model accuracy and validate predictions for other field sites in Zimbabwe.
Noncanonical WNT activation in human right ventricular heart failure
Authors: Edwards Jonathan J. , Brandimarto Jeffrey , Hu Dong-Qing , Jeong Sunhye , Yucel Nora , Li Li , Bedi Kenneth C. , Wada Shogo , Murashige Danielle , Hwang Hyun Tae , Zhao Mingming , Margulies Kenneth B. , Bernstein Daniel , Reddy Sushma , Arany Zoltan P.
Published: July 2020

A significant barrier to developing therapies to treat right ventricular (RV) remodeling and RV failure (RVF) has been a lack of understanding for the molecular pathways that are specifically activated in pathologic human RV remodeling. Since murine models have suggested involvement of Wnt signaling in pathologic RV remodeling, we used a candidate gene approach to study differential WNT expression in human RV remodeling using RVs from three groups: nonfailing donors, explanted dilated and ischemic cardiomyopathy with either preserved RV function or with RVF. We identified the noncanonical WNT receptor ROR2 as transcriptionally strongly upregulated in RVF. ROR2 protein expression correlated linearly to mRNA expression and to worse RV performance using pretransplant hemodynamic assessments. High ROR2 expression in RVF also correlated to expression of the WNT5A/ROR2/Ca2+ responsive protease calpain as well as cleavage of its downstream target FLNA, and FLNA phosphorylation, another marker of activation downstream of ROR2. Here we demonstrate robust reactivation of a fetal WNT gene program, specifically its noncanonical arm, in human RVF characterized by activation of ROR2/calpain mediated cytoskeleton protein cleavage.
Dengue antibodies can cross-react with SARS-CoV-2 and vice versa-Antibody detection kits can give false-positive results for both viruses in regions where both COVID-19 and Dengue co-exist
Authors: Nath Himadri , Mallick Abinash , Roy Subrata , Sukla Soumi , Basu Keya , De Abhishek , Biswas Subhajit
Published: July 2020

Five of thirteen Dengue antibody-positive serum samples, dated 2017 (pre-dating the COVID-19 outbreak) produced false-positive results in SARS-CoV-2 IgG/IgM rapid strip tests. Our results emphasize the importance of NAT and/or virus antigen tests to complement sero-surveillance for definitive diagnosis of COVID-19/Dengue in regions where both viruses are co-endemic.
The Study of Acute Myocardial Infarctions Triggers in North-Western Iran
Authors: Khademvatani Kamal , Sedokani Amin , Masudi Sima , Nejati Parisa , Mohammadzad Mir Hosein Seyyed , Rahmani Alireza
Published: July 2020

Background

Myocardial infarction (MI) is one of the important cardiovascular diseases. A trigger is an external stimulus, potential to create a pathological change leading to a clinical event. In addition to the risk factors of myocardial infarction, MI triggers play critical roles in the incidence of acute MI.

Methods and Results

This is a cross-sectional study of patients with the first acute myocardial infarction in Seyedoshohada heart center of Urmia, Iran. 254 patients were enrolled in the study within one year of study. After 48h of hospitalization, the patients were provided with the questionnaire to collecting the history of the disease ad triggers. Out of 220 (86.4%) patients with STEMI and 34 (13.6%) patients with NSTEMI, there were significant differences (p <0.05) in AMI triggers with LVEF (0.03), gender (0.027), residency and living area (0.039), occupation (0.002), smoking (0.008), abnormal serum TG levels (0.018) and the season of AMI occurrence (0.013). The mean age for AMI patients was 60.4±12.97 years old with a mean BMI of 26.65±4.35 kg/m2.

Conclusion

In addition to classic risk factors of myocardial infarction, health care systems must pay more attention to triggers that may induce an acute myocardial infarction in people with predisposing factors especially in the male sex, stressful and hand working jobs, and psychological and mental tension patients.
Somatic variant analysis of linked-reads sequencing data with Lancet
Authors: Musunuri Rajeeva , Arora Kanika , Corvelo André , Shah Minita , Shelton Jennifer , Zody Michael C. , Narzisi Giuseppe
Published: July 2020

We present a new version of the popular somatic variant caller, Lancet, that supports the analysis oflinked-readssequencing data. By seamlessly integrating barcodes and haplotype read assignments within the colored De Bruijn graph local-assembly framework, Lancet computes a barcode-aware coverage and identifies variants that disagree with the local haplotype structure.

Availability and Implementation

Lancet is implemented in C++ and is available for academic and non-commercial research purposes as an open-source package athttps://github.com/nygenome/lancet.

Contact

gnarzisi@nygenome.org
BERTMeSH: Deep Contextual Representation Learning for Large-scale High-performance MeSH Indexing with Full Text
Authors: You Ronghui , Liu Yuxuan , Mamitsuka Hiroshi , Zhu Shanfeng
Published: July 2020

Motivation

With the rapid increase of biomedical articles, large-scale automatic Medical Subject Headings (MeSH) indexing has become increasingly important. FullMeSH, the only method for large-scale MeSH indexing with full text, suffers from three major drawbacks: FullMeSH 1) uses Learning To Rank (LTR), which is time-consuming, 2) can capture some pre-defined sections only in full text, and 3) ignores the whole MEDLINE database.

Results

We propose a computationally lighter, full-text and deep learning based MeSH indexing method, BERTMeSH, which is flexible for section organization in full text. BERTMeSH has two technologies: 1) the state-of-the-art pre-trained deep contextual representation, BERT (Bidirectional Encoder Representations from Transformers), which makes BERTMeSH capture deep semantics of full text. 2) a transfer learning strategy for using both full text in PubMed Central (PMC) and title and abstract (only and no full text) in MEDLINE, to take advantages of both. In our experiments, BERTMeSH was pre-trained with 3 million MEDLINE citations and trained on approximately 1.5 million full text in PMC. BERTMeSH outperformed various cutting edge baselines. For example, for 20K test articles of PMC, BERTMeSH achieved a Micro F-measure of 69.2%, which was 6.3% higher than FullMeSH with the difference being statistically significant. Also prediction of 20K test articles needed 5 minutes by BERTMeSH, while it took more than 10 hours by FullMeSH, proving the computational efficiency of BERTMeSH.

Contact

zhusf@fudan.edu.cn
Reinforcement Learning and Bayesian Inference Provide Complementary Models for the Unique Advantage of Adolescents in Stochastic Reversal
Authors: Eckstein Maria K. , Master Sarah L. , Dahl Ronald E. , Wilbrecht Linda , Collins Anne G.E.
Published: July 2020

During adolescence, youth venture out, explore the wider world, and are challenged to learn how to navigate novel and uncertain environments. We investigated whether adolescents are uniquely adapted to this transition, compared to younger children and adults. In a stochastic, volatile reversal-learning task with a sample of 291 participants aged 8-30, we found that adolescents outperformed both younger and older participants. We developed two independent cognitive models, based on Reinforcement learning (RL) and Bayesian inference (BI). The RL parameter for learning from negative outcomes and the BI parameters specifying participants’ mental models peaked closest to optimal in adolescents, suggesting a central role in adolescent cognitive processing. By contrast, persistence and noise parameters improved monotonously with age. We distilled the insights of RL and BI using principal component analysis and found that three shared components interacted to form the adolescent performance peak: adult-like behavioral quality, child-like time scales, and developmentally-unique processing of positive feedback. This research highlights adolescence as a neurodevelopmental window that may be specifically adapted for volatile and uncertain environments. It also shows how detailed insights can be gleaned by using cognitive models in new ways.
Tau conformers in FTLD-MAPT undergo liquid-liquid phase separation and perturb the nuclear envelope
Authors: Kang Sang-Gyun , Han Zhuang Zhuang , Daude Nathalie , McNamara Emily , Wohlgemuth Serene , Safar Jiri G. , Mok Sue-Ann , Westaway David
Published: July 2020

Recent studies show that a singleMAPTgene mutation can promote alternative tau misfolding pathways engendering divergent forms of frontotemporal dementia and that under conditions of molecular crowding, the repertoire of tau forms can include liquid-liquid phase separation (LLPS). We show here that following pathogenic seeding, tau condenses on the nuclear envelope (NE) and disrupts nuclear-cytoplasmic transport (NCT). Interestingly, NE fluorescent tau signals and small fluorescent inclusions behaved as demixed liquid droplets in living cells. Thioflavin S-positive intracellular aggregates were prevalent in tau-derived inclusions with a size bigger than 3 μm2, indicating that a threshold of critical mass in the liquid state condensation may drive liquid-solid phase transitions. Our findings indicate that tau undergoing LLPS is more toxic amongst a spectrum of alternative conformers; LLPS droplets on the NE that disrupt NCT serve to trigger cell death and can act as nurseries for fibrillar structures abundantly detected in end-stage disease.
Individual differences show that only some bats can cope with noise-induced masking and distraction
Authors: Gomes Dylan G.E. , Goerlitz Holger R.
Published: July 2020

Anthropogenic noise is a widespread pollutant that has received considerable recent attention. While alarming effects on wildlife have been documented, we have limited understanding of the perceptual mechanisms of noise disturbance, which are required to understand potential mitigation measures. Likewise, individual differences in response to noise (especially via perceptual mechanisms) are likely widespread, but lacking in empirical data. Here we use echolocating bats, a trained discrimination task, and experimental noise playback to explicitly test perceptual mechanisms of noise disturbance. We demonstrate high individual variability in response to noise treatments and evidence for multiple perceptual mechanisms. Additionally, we highlight that only some individuals are able to cope with noise, while others are not. We tested for changes in echolocation call duration, amplitude, and peak frequency as possible ways of coping with noise. Although all bats strongly increased call amplitude and showed additional minor changes in call duration and frequency, these changes cannot explain the differences in coping and non-coping individuals. Our understanding of noise disturbance needs to become more mechanistic and individualistic as research knowledge is transformed into policy changes and conservation action.
Telomere lengths in plants are correlated with flowering time variation
Authors: Choi Jae Young , Purugganan Michael D.
Published: July 2020

Telomeres are highly repetitive tandemly repeating DNA sequences found at chromosomal ends that protect chromosomes from deterioration during cell division. Using whole genome re-sequencing data, we found substantial natural intraspecific variation in telomere lengths in Arabidopsis thaliana, Oryza sativa (rice) and Zea mays (maize). Genome-wide association mapping in A. thaliana identifies a region that includes the telomerase reverse transcriptase (TERT) gene as underlying telomere length variation. TERT appears to exist in two haplotype groups (L and S), of which the L haplogroup allele shows evidence of a selective sweep in Arabidopsis. We find that telomere length is negatively correlated with flowering time variation not only in A. thaliana, but also in maize and rice, indicating a link between life history traits and chromosome integrity. We suggest that longer telomeres may be more adaptive in plants that have faster developmental rates (and therefore flower earlier), and that chromosomal structure itself is an adaptive trait associated with plant life history strategies.