bluuebunny/crossref_metadata_2025 huggingface dataset:
Female Veterans’ Willingness to Seek Veterans Health Administration and Non–Veterans Health Administration Services for Suicidal Thoughts and Mental Health Concerns
Authors: Monteith Lindsey L. , Holliday Ryan , Hoffmire Claire A. , Bahraini Nazanin H.
Published: January 2021

Background:

The extent to which female veterans are willing to seek Veterans Health Administration (VHA) and non-VHA care when they are suicidal or experiencing mental health (MH) concerns is unknown.

Objectives:

The objectives of this study were to: (1) examine whether current, past, and never VHA using female veterans’ willingness to seek VHA care differs from their willingness to seek non-VHA care if suicidal or experiencing MH symptoms; (2) examine if VHA use, military sexual trauma, and suicidal ideation and attempt are associated with female veterans’ willingness to use VHA and non-VHA care when experiencing suicidal thoughts or MH symptoms.

Research Design:

A cross-sectional anonymous survey.

Subjects:

Four hundred thirty nine female veterans, including current, past, and never VHA users were included.

Measures:

General Help-Seeking Questionnaire, Self-Injurious Thoughts and Behaviors Interview, and the VA Military Sexual Trauma Screening Questions.

Results:

Current VHA users reported more willingness to use VHA than non-VHA care; conversely, past and never VHA users reported less willingness to use VHA care relative to non-VHA care. Military sexual assault and none or past VHA use were associated with lower willingness to use VHA care if suicidal or experiencing MH symptoms. In contrast, those with none or past VHA use reported greater willingness to use non-VHA care if suicidal or experiencing MH symptoms, while prior suicide attempt was associated with lower willingness.

Conclusions:

Ensuring that acceptable and effective suicide prevention services are available to female veterans in both VHA and community settings is critical. Increasing help-seeking intentions among female veterans who have attempted suicide or experienced military sexual assault is also essential.
Embryonal Tumor With Multilayered Rosettes of the Parietooccipital Region: A Case Report
Authors: Horwitz Jennifer , Huang Annie , McAuley David , Jansen Gerard H. , Johnston Donna
Published: January 2021

Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient’s sustained remission at 2.5-years follow-up.
Two Clonally Distinct B-Cell Lymphomas Reveal the Diagnosis of XLP1 in a Male Child and His Asymptomatic Male Relatives: Case Report and Review of the Literature
Authors: Iglesias Cardenas Fiorella , Agarwal Archana M. , Vagher Jennie , Maese Luke , Fluchel Mark , Afify Zeinab
Published: January 2021

X-linked lymphoproliferative disease type 1 (XLP1) is a primary immunodeficiency disorder caused by pathogenic variants in the SH2D1A gene (SH2 domain containing protein 1A). Patients with XLP1 may present acutely with fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis, and/or B-cell non–Hodgkin lymphoma (B-NHL). We report a boy who developed 2 clonally distinct B-NHL 4 years apart and was found to have previously unrecognized XLP1. The report highlights the importance of clonal analysis and XLP1 testing in males with presumed late recurrences of B-NHL, and the role of allogeneic stem cell transplant (allo-SCT) in XLP1 patients and their affected male relatives.
Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases
Authors: Shibayama Takahiro , Makise Naohiro , Motoi Toru , Mori Taisuke , Hiraoka Nobuyoshi , Yonemori Kan , Watanabe Shun-ichi , Esaki Minoru , Morizane Chigusa , Okuma Tomotake , Kawai Akira , Ushiku Tetsuo , Yatabe Yasushi , Yoshida Akihiko
Published: January 2021

Epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial neoplasm with characteristic histology and distinctive fusion genes. Its clinical presentation and outcome are heterogeneous, and the determinants of survival are controversial. In this study, we aimed to identify clinicopathologic prognostic factors of EHE in a retrospective cohort of 62 cases with CAMTA1/TFE3/WWTR1 alterations. The tumors were of the CAMTA1 subtype for 59 cases, TFE3 subtype for 2 cases, and variant WWTR1 subtype (WWTR1-ACTL6A) for 1 case. Twenty-two tumors (35.5%) demonstrated atypical histology, defined by having at least 2 of the following 3 findings: high mitotic activity (>1/2 mm2), high nuclear grade, and coagulative necrosis. During a median follow-up of 34 months, 11 patients (18%) died, and the 5-year overall survival rate was 78.8%. Survival did not correlate with such clinical parameters as age, sex, tumor sites, multifocality, and multiorgan involvement. Conversely, based on both univariate and multivariate analyses, large tumor size (>30 mm) and histologic atypia were significantly associated with a shorter survival. A proposed 3-tiered risk assessment system using these 2 parameters significantly stratified the patients into low-risk, intermediate-risk, and high-risk groups with 5-year overall survival rates of 100%, 81.8%, and 16.9%, respectively (P<0.001). Four tumors (6.4%) expressed synaptophysin, which all belonged to the high-risk group and pursued an aggressive course. The present study demonstrated the independent prognostic significance of large tumor size and atypical histology in EHE, as well as the value of risk stratification using these 2 factors. Moreover, we revealed a small EHE subset with aberrant synaptophysin expression, which may have potential prognostic and diagnostic implications.
A Framework for Pediatric Intensivists Providing Compassionate Extubation at Home*
Authors: Woodruff Alan G. , Bingham Sarah B. , Jarrah Rima J. , Bass Andora L. , Nageswaran Savithri
Published: January 2021

For families facing end-of-life decisions for their critically ill children, compassionate extubation at home is a valuable service that pediatric intensivists can provide. Compassionate extubation at home is resource intensive and can be logistically challenging. Discouragingly, guidance on compassionate extubation at home in the literature is limited. We developed an evidence- and experience-based framework for compassionate extubation at home addressing common planning challenges and resource management. Our objective is to share this framework and an accompanying checklist, so that pediatric intensivists in other institutions can adapt these tools for their use, reducing barriers to providing compassionate extubation at home for critically ill children at the end of life.
How to One Up a Pandemic
Authors: Topor Lauren , Balser David , Bruhnding Paul , Dvorak James , Anderson Carly , Tanguay Bethany , Seidel Erica , Tonkin Brionn , Senk Alexander
Published: January 2021

Drastic and rapid changes to medical education are uncommon because of regulations and restrictions designed to ensure consistency among medical school curriculums and to safeguard student well-being. As a consequence of the COVID-19 pandemic, medical education had to break away from its conventions and transition from time-honored teaching methods to innovative solutions. This article explores the anticipated and actual efficacy of the swift conversion of a specialty elective from a traditional in-person format to a fully virtual clerkship. In addition, it includes a noninferiority study to determine where a virtual classroom may excel or fall short in comparison with conventional clinical rotations.
Rehabilitation Nursing Challenges for Patients With Lower Limb Amputation
Authors: Parnell Brittany , Urton Michael
Published: January 2021

There are over 185,000 amputations annually in the United States, and most of these patients will receive a short inpatient rehabilitation hospital stay as part of their recovery. Complications in care after amputation can negatively impact rehabilitation and subsequent disposition and community reintegration after discharge. The purpose of this article is to discuss the literature, significance, and practice recommendations for three specific challenges—skin integrity, postamputation pain, and falls. The focus population is rehabilitation patients who have undergone nontraumatic, lower limb amputation. Information about the incidence and risks of these complications give nurses necessary knowledge to improve care delivery, reduce suffering, and improve patient safety for postamputation patients during inpatient rehabilitation.
The Road to Family Resiliency: A Case Report of a Family’s Experiences Following Adolescent Stroke
Authors: Szigeti Zara , Nalder Emily , King Gillian , Farthing Julie , Gauvin-Lepage Jérôme
Published: January 2021

Purpose

This study generated an understanding of familial resiliency following an adolescent’s stroke and what resiliency-related outcomes were important to this family.

Design and Methods

A qualitative case study design was used to collect data during an in-person interview. The interview was transcribed verbatim and analyzed using thematic analysis.

Findings

Participants’ narratives revealed that reengaging and establishing new activities, reconstructing identities, and changing perceptions regarding health and life itself were important resiliency-related outcomes.

Conclusions

The findings from this case study highlight innovative strategies that can be used to facilitate resiliency during strenuous times in a family’s life, such as following an adolescent’s stroke.

Clinical Relevance

Clinicians and service providers have the opportunity to help facilitate resiliency by identifying which protective factors and positive outcomes are most important to a family following an adolescent’s stroke, allowing clinicians to assist in achieving these outcomes. This research illustrates ways for families to convert resources into personally meaningful resiliency-related outcomes. Further research is needed to study familial resiliency as a part of an intervention to promote occupational engagement.
Reliability and Validity of the Function-Focused Care Checklist for Caregivers
Authors: Resnick Barbara , Boltz Marie , Galik Elizabeth
Published: January 2021

Purpose

The purpose of this study was to test the reliability and validity of the Function-Focused Care Checklist for Caregivers using Rasch analysis.

Design

This was a descriptive study using data from the study “Testing the Dissemination and Implementation of Function-Focused Care for Assisted Living Using the Evidence Integration Triangle.” The study was approved by a university institutional review board.

Methods

A Rasch analysis was completed, which included 691 staff–resident observations from 85 assisted living facilities.

Findings

There was evidence of internal consistency (alpha coefficient of .93), construct validity except for a high OUTFIT statistic for wheelchair mobility, and hypothesis testing based on an increase in performance of function-focused care by caregivers over 12 months.

Conclusions

The findings provided psychometric support for the measure and guidance for revisions.

Clinical Relevance

This measure can be used clinically to teach caregivers to provide function-focused care to residents in assisted living.
Breast Implant–Associated Anaplastic Large Cell Lymphoma Online Education Tools
Authors: Yesantharao Pooja S. , Hunt Megan F. , Bekheet Faraah , Manahan Michele A.
Published: January 2021

Purpose

In light of highly publicized media coverage on breast implant recalls and Food and Drug Administration hearings on breast implant safety, online searches of these topics have surged. It is thus critical to determine whether such searches are providing meaningful information for those who use them. Patient/laywomen-directed online education materials on breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) must not only be comprehensible but also accurate, actionable, and culturally concordant, especially as more diverse populations turn to the internet for breast implant–related information. This study assessed the overall suitability of BIA-ALCL patient–directed educational text and video-based materials online.

Methods

This was a cross-sectional, multimetric investigation of online text– and video-based patient-directed educational materials for BIA-ALCL using multiple validated measures. Two reviewers assessed each resource. Kruskal-Wallis and Fisher exact analyses were used as appropriate to compare text- and video-based online resources.

Results

In total, 30 websites and 15 videos were evaluated, more than half (56%) of which were from academic/physician or governmental/nonprofit sources. Overall, website and video content, as well as quality, varied by source. Academic/physician or governmental/nonprofit sources tended to be more comprehensive and have higher-quality information than commercial/media outlet sources. Median actionability of websites was 38%, well below the threshold of 70% used in the literature to identify actionable resources. The median suitability score for BIA-ALCL websites was 57%, which is considered “adequate” based on published thresholds. The mean overall Cultural Sensitivity Assessment Tool score for websites was 2.4; Cultural Sensitivity Assessment Tool scores higher than 2.5 are generally regarded as culturally sensitive. In general, videos were more understandable than websites. Substantial interrater reliability across the validated tools used in this study was noted using Pearson correlation coefficients.

Conclusions

Online resources varied in content and quality by source. As BIA-ALCL becomes an increasingly salient topic among both providers and patients, it is important to empower women with accurate information about this implant-associated cancer. Of available resources, providers should refer patients or those seeking more information to websites from governmental/academic organizations (“.gov” or “.org” domains) and videos from academic/physician or governmental sources, given that among high-quality resources, these were most clear/comprehensible. Overall, there is a need for improved online content on this topic.
Application of Autologous Cartilage Transplantation in the Reconstruction of Congenital Nasal Soft Triangle Deformities in Asians
Authors: Ma Zhibing , Wang Yawen , Chen Gang , Wang Jinming , Zhang Jun , Huang Jinlong
Published: January 2021

Background

Nasal soft triangle is one of the areas usually left unattended in most rhinoplasties, whereas its unique anatomy puts it at great risk of deformities. Its appearance is critical to the natural contour of the nasal tip lobule. The purpose of this study was to evaluate the outcome of autologous cartilage transplantation in treating congenital nasal soft triangle deformities in Asians.

Methods

From January 2016 to January 2018, 32 patients underwent the procedure, in which costal cartilage, septal cartilage, or conchal cartilage was taken. All cases were operated upon using the external rhinoplasty approach. The cartilage was carved into battens as the lateral and intermediate crura grafts to reconstruct the dome of alar cartilage and treat the soft triangle deformities. The costal cartilage or septal cartilage was used as a columella strut. At the same time, a prosthesis or costal cartilage scaffold was placed onto the nasal dorsum, and finally the fascia was placed on the tip of the nose to relieve tension. The changes of the angle between the intermediate and lateral crura of the alar cartilage before and after cartilage graft and the difference between the greatest distance from the long axis of the nostrils to the alar rim before and after surgery were statistically analyzed. In addition, we compared the preoperative and postoperative nasal contour and evaluated the outcome of soft tissue triangle deformities and asymmetry correction and the whole procedure.

Results

The angle between the lateral and medial crura of the 32 patients decreased from 51.5 ± 10.9 degrees preoperatively to 37.2 ± 5.9 degrees at completion of the nasal dome reconstruction (P < 0.05). The maximum distance from the long axis of the nostrils to the alar rim was 3.3 ± 0.6 mm preoperatively and 1.9 ± 0.7 mm postoperatively (P < 0.05). The patients were followed up for 6 to 18 months, and the noses were with natural contour and tactile impression and without any serious complications. The degree of satisfaction was 87.5%.

Conclusions

The application of autologous cartilage is an ideal choice to treat soft triangle deformities, which can result in significant improvement of the nasal contour and high degree of satisfaction postoperatively.
Le Fort Fractures With Maxillary Immobility
Authors: Liao Han-Tsung , Mittal Rashu , Kang Gavin , Chen Chien-Tzung
Published: January 2021

Background

Le Fort fractures with maxillary immobility are an uncommon presentation of facial trauma often associated with the disturbance of occlusion. Historically, cases involving high Le Fort fractures require a coronal extensive approach to mobilize the maxilla for occlusion restoration. Here, we review our institutional series of immobile Le Fort fractures and present their treatment approach, outcomes, classification, and then rationalize our treatment with a concept philosophy.

Materials and Methods

We treated 12 consecutive patients with unilateral and bilateral immobile Le Fort fractures from 2010 to 2017. The mean age was 27.1 years. Ten patients had a unilateral greenstick Le Fort III fracture. Five patients also had associated mandible fractures. Intraoperative occlusions could only be restored after Le Fort I osteotomy was performed on the side of the immobile Le Fort fracture. The mean follow-up period was 1.6 years.

Results

All patients presented good long-term occlusion restoration. There were no cases of nonunion or significant complications. None of the patients complained of any malar or periorbital cosmetic issues during follow-up sessions.

Conclusions

We presented an institutional series and classification of unusual Le Fort fractures with maxillary immobility, including a previously unreported fracture configuration of greenstick unilateral Le Fort III fractures combined with complete contralateral Le Fort I fracture. Based on our moment concept to rationalize treatment, as well as a systematic review of published literature, we advocate the judicious use of Le Fort I osteotomy to efficiently and safely treat these unusual fractures.
Using Various Skin Graft Techniques in Major Burn Reconstruction
Authors: Wu Chang-Ju , Li Jung-Jie , Liao Wen-Chieh , Wang Tien-Hsiang , Perng Cherng-Kang , Ma Hsu , Shih Yu-Chung , Chen Mei-Chun , Lin Chih-Hsun
Published: January 2021

Purpose

Four hundred and ninety-nine patients had burn injuries in an explosion in Taiwan on June 27, 2015, 24 were admitted to the intensive care units of Taipei Veterans General Hospital. This study details our experience with surgical management of these patients, focusing primarily on various skin graft techniques.

Materials and Methods

This single-center retrospective study included patients who underwent at least one of the previously mentioned skin graft techniques because of extensive skin defects. The demography, burn diagram, treatment modalities, postoperative outcome, and costs were all analyzed, and a comparison with traditional mesh skin grafts was performed. The literature was also reviewed.

Results

Fourteen patients underwent the Meek skin graft technique. Only 3 received ReCell and 1 cultured epithelial autograft (CEA) at separate time point. Overall, the autologous skin grafts, including Meek/ReCell/CEA were completed within 6 months. The average skin graft success rate was approximately 72.9%, 79.2%, and 38% in Meek, ReCell, and CEA, respectively. The infection rate was approximately 35.7%, 25%, and 100% in Meek, ReCell, and CEA, respectively. The average surgical cost and total medical cost were significantly higher in patients who underwent Meek/ReCell/CEA treatments.

Conclusions

In our experience, Meek and ReCell treatments had acceptable success rates, but CEA treatment not. ReCell and CEA treatments are useful in the event of extremely limited donor sites, and they are fragile, easily infected, and technically challenging. These techniques also require longer hospitalization and tend to be more expensive, all factors that should be considered when assessing treatment options.
Molecular Dynamics Analysis of a Flexible Loop at the Binding Interface of the SARS-CoV-2 Spike Protein Receptor-Binding Domain
Authors: Williams Jonathan K. , Wang Baifan , Sam Andrew , Hoop Cody L. , Case David A. , Baum Jean
Published: January 2021

Since the identification of the SARS-CoV-2 virus as the causative agent of the current COVID-19 pandemic, considerable effort has been spent characterizing the interaction between the Spike protein receptor-binding domain (RBD) and the human angiotensin converting enzyme 2 (ACE2) receptor. This has provided a detailed picture of the end point structure of the RBD-ACE2 binding event, but what remains to be elucidated is the conformation and dynamics of the RBD prior to its interaction with ACE2. In this work we utilize molecular dynamics simulations to probe the flexibility and conformational ensemble of the unbound state of the receptor-binding domain from SARS-CoV-2 and SARS-CoV. We have found that the unbound RBD has a localized region of dynamic flexibility in Loop 3 and that mutations identified during the COVID-19 pandemic in Loop 3 do not affect this flexibility. We use a loop-modeling protocol to generate and simulate novel conformations of the CoV2-RBD Loop 3 region that sample conformational space beyond the ACE2 bound crystal structure. This has allowed for the identification of interesting substates of the unbound RBD that are lower energy than the ACE2-bound conformation, and that block key residues along the ACE2 binding interface. These novel unbound substates may represent new targets for therapeutic design.
Impact of COVID-19 pandemic on use of Pediatric Emergency Health Services in a Tertiary Care Pediatric Hospital in North India
Authors: Sodani Ravitanaya , Gupta Shalu , Kumar Virendra
Published: January 2021

Objective

To compare Pediatric Emergency attendance pre-COVID 19 to that during COVID 19 pandemic and to study changes in patient profiles attending Pediatric Emergency Department during COVID 19 pandemic.

Methods

We conducted a retrospective cross-sectional observational study and collected data from Medical Record Section during the COVID-19 pandemic from January to June 2020 and compared it with data from 2019 in similar months. Data collected was analyzed to find out the impact of COVID – 19 on use of pediatric emergency health services with respect to patient attendance, age and clinical profile before and during COVID-19 in a tertiary care hospital in New Delhi.

Results

We observed a 43% decline in PED visits which increased to 75% during the period of lock-down (p value = 0.005). There was a significant decrease in children of age group 1-5 years attending PED. Mortality rate during lockdown had gone up by nearly 3times than the average monthly mortality.

Conclusions

While children might not have been directly affected by the COVID-19 pandemic, but the fear of COVID 19 and measures taken to control the pandemic has affected the health seeking behavior of patients to an extent that indirectly caused more damage than anticipated.
Risk factors for bacterial infections in patients with moderate to severe COVID-19: A case control study
Authors: Nasir N. , Rehman F. , Omair S.F.
Published: January 2021

Objective

Bacterial infections are known to complicate respiratory viral infections and are associated with adverse outcomes in COVID-19 patients. A case control study was conducted to determine risk factors for bacterial infections where cases were defined as moderate to severe/critical COVID-19 patients with bacterial infection and those without were included as controls. Logistic regression analysis was performed.

Results

Out of a total of 50 cases and 50 controls, greater proportion of cases had severe or critical disease at presentation as compared to control i.e 80% vs 30% (p<0.001). Hospital acquired pneumonia (72%) and Gram negative organisms (82%) were predominant. Overall antibiotic utilization was 82% and was 64% in patients who had no evidence of bacterial infection. The median length of stay was significantly longer among cases compared to controls (12.5 versus 7.5 days) (p=0.001). The overall mortality was 30%, with comparatively higher proportion of deaths among cases (42% versus 18%) (p=0.009). Severe or critical COVID-19 at presentation (AOR: 4.42 times; 95% CI; 1.63-11.9) and use of steroids (AOR: 4.60; 95% CI 1.24-17.05) were independently associated with risk of bacterial infections. These findings have implications for antibiotic stewardship as antibiotics can be reserved for those at higher risk for bacterial superinfections.
Impact of Residential Neighborhood and Race/Ethnicity on Outcomes of Hospitalized Patients with COVID-19 in the Bronx
Authors: Miller Dwayvania , Sarwal Amara , Yu Bo , Gomez Edgar , Perez-Gutierrez Victor , Gossai Marcia , Valdez Elisenda , Mendez Astrid , Chaudry Sarah , Venugopal Usha , Dimitrov Vihren , Kasubhai Moiz , Menon Vidya
Published: January 2021

The socially vulnerable have been most affected due to the COVID-19 pandemic, similar to the aftermath of any major disaster. Racial and social minorities are experiencing a disproportionate burden of morbidity and mortality.

The aim of this study was to evaluate the impact of residential location/community and race/ethnicity on outcomes of COVID-19 infection among hospitalized patients within the Bronx. This was a single center retrospective observational cohort study that included SARS-CoV2 positive adult residents of the Bronx (stratified as residents of South Bronx vs Rest of Bronx) hospitalized between March-May 2020. Data extracted from hospital electronic medical records included residential addresses, race, comorbidities, and insurance details. Comorbidity burden other clinical and laboratory details were also assessed to determine their correlation to COVID-19 severity of illness and outcomes of mortality and length of stay.

As expected, the COVID-19 pandemic differentially affected outcomes in those in the more socially disadvantaged area of the South Bronx versus the rest of the Bronx borough. Residents of the South Bronx had a significantly higher comorbidity burden and had public insurance to access medical care in comparison to the remainder of the Bronx. Interestingly, for the patient population studied there was no observed difference in 30-day mortality by race/ethnicity among those infected with COVID- 19 in spite of the increased disease burden observed.

This adds an interesting perspective to the current literature, and highlights the need to address the social/economic factors contributing to health access disparity to reduce the adverse impact of COVID-19 in these communities.
Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA SARS 2 S in preclinical vaccination
Authors: Tscherne Alina , Schwarz Jan Hendrik , Rohde Cornelius , Kupke Alexandra , Kalodimou Georgia , Limpinsel Leonard , Okba Nisreen M.A. , Bošnjak Berislav , Sandrock Inga , Halwe Sandro , Sauerhering Lucie , Brosinski Katrin , Liangliang Nan , Duell Elke , Jany Sylvia , Freudenstein Astrid , Schmidt Jörg , Werner Anke , Sera Michelle Gellhorn , Klüver Michael , Guggemos Wolfgang , Seilmaier Michael , Wendtner Clemens-Martin , Förster Reinhold , Haagmans Bart L. , Becker Stephan , Sutter Gerd , Volz Asisa
Published: January 2021

The severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on vaccinia virus MVA against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust synthesis of S antigen, make it a suitable candidate vaccine for industrial scale production. Vaccinated mice produced S antigen-specific CD8+ T cells and serum antibodies binding to S glycoprotein that neutralized SARS-CoV-2. Prime-boost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19.

Significance Statement

The highly attenuated vaccinia virus MVA is licensed as smallpox vaccine, and as vector it is a component of the approved Adenovirus-MVA-based prime-boost vaccine against Ebola virus disease. Here we provide results from testing the COVID-19 candidate vaccine MVA-SARS-2-S, a poxvirus-based vector vaccine that proceeded to clinical evaluation. When administered by intramuscular inoculation, MVA-SARS-2-S expresses and safely delivers the full-length SARS-CoV-2 spike (S) protein, inducing balanced SARS-CoV-2-specific cellular and humoral immunity, and protective efficacy in vaccinated mice. Substantial clinical experience has already been gained with MVA vectors using homologous and heterologous prime-boost applications, including the immunization of children and immunocompromised individuals. Thus, MVA-SARS-2-S represents an important resource for developing further optimized COVID-19 vaccines.
Serologic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Infection in Hospital Health Care Workers
Authors: Sikkens Jonne J. , Buis David T.P. , Peters Edgar J.G. , Dekker Mireille , Schinkel Michiel , Reijnders Tom. D.Y. , Schuurman Alex. R. , Brabander Justin de , Lavell Ayesha H.A. , Maas Jaap. J. , Koopsen Jelle , Han Alvin X. , Russell Colin A. , Schinkel Janke , Jonges Marcel , Matamoros Sebastien P.F. , Jurriaans Suzanne , van Mansfeld Rosa , Wiersinga W. Joost , Smulders Yvo M. , de Jong Menno D. , Bomers Marije K.
Published: January 2021

BACKGROUND

It is unclear how, when and where health care workers (HCW) working in hospitals are infected with SARS-CoV-2.

METHODS

Prospective cohort study comprising 4-weekly measurement of SARS-CoV-2 specific antibodies and questionnaires from March to June 2020. We compared SARS-CoV-2 incidence between HCW working in Covid-19 patient care, HCW working in non-Covid-19 patient care and HCW not in patient care. Phylogenetic analyses of SARS-CoV-2 samples from patients and HCW were performed to identify potential transmission clusters.

RESULTS

We included 801 HCW: 439 in the Covid-19 patient care group, 164 in the non-Covid-19 patient care group and 198 in the no patient care group. SARS-CoV-2 incidence was highest in HCW working in Covid-19 patient care (13.2%), as compared with HCW in non-Covid-19 patient care (6.7%, hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.2 to 4.3) and in HCW not working in patient care (3.6%, HR 3.9, 95% CI 1.8 to 8.6). Within the group of HCW caring for Covid-19 patients, SARS-CoV-2 cumulative incidence was highest in HCW working on Covid-19 wards (25.7%), as compared with HCW working on intensive care units (7.1%, HR 3.6, 95% CI 1.9 to 6.9), and HCW working in the emergency room (8.0%, HR 3.3, 95% CI 1.5 to 7.1). Phylogenetic analyses on Covid-19 wards identified multiple potential HCW-to-HCW transmission clusters while no patient-to-HCW transmission clusters were identified.

CONCLUSIONS

HCW working on Covid-19 wards are at increased risk for nosocomial SARS-CoV-2 infection, with an important role for HCW-to-HCW transmission.

(Funded by the Netherlands Organization for Health Research and Development ZonMw & the Corona Research Fund Amsterdam UMC; Netherlands Trial Register number NL8645)
Effects of surgical masks on droplet and aerosol dispersion under various oxygen delivery modalities
Authors: Takazono Takahiro , Yamamoto Kazuko , Okamoto Ryuta , Tashiro Masato , Morimoto Shimpei , Hosogaya Naoki , Miyazaki Taiga , Yanagihara Katsunori , Izumikawa Koichi , Mukae Hiroshi
Published: January 2021

Rationale

Aerosol dispersion under various oxygen delivery modalities, including high flow nasal cannula, is a critical concern for healthcare workers who treat acute hypoxemic respiratory failure during the coronavirus disease 2019 pandemic. Effects of surgical masks on droplet and aerosol dispersion under oxygen delivery modalities are not yet clarified.

Objectives

To visualize and quantify dispersion particles under various oxygen delivery modalities and examine the protective effect of surgical masks on particle dispersion.

Methods

Three and five healthy men were enrolled for video recording and quantification of particles, respectively. Various oxygen delivery modalities including high flow nasal cannula were used in this study. Particle dispersions during rest breathing, speaking, and coughing were recorded and automatically counted in each condition and were evaluated with or without surgical masks.

Measurements and Main Results

Coughing led to the maximum amount and distance of particle dispersion, regardless of modalities. Droplet dispersion was not visually increased by oxygen delivery modalities compared to breathing at room air. With surgical masks over the nasal cannula or high-flow nasal cannula, droplet dispersion was barely visible. Oxygen modalities did not increase the particle dispersion counts regardless of breathing pattens. Wearing surgical masks significantly decreased particle dispersion in all modalities while speaking and coughing, regardless of particle sizes, and reduction rates were approximately 95 and 80-90 % for larger (> 5 μm) and smaller (> 0.5 μm) particles, respectively.

Conclusions

Surgical mask over high flow nasal canula may be safely used for acute hypoxemic respiratory failure including coronavirus disease 2019 patients.

Subject Category List

4.13 Ventilation: Non-Invasive/Long-Term/Weaning

*This article has an online data supplement, which is accessible from this issue’s table of content online at www.atsjournals.org.
Reverse causal effect of atrial fibrillation on 17 site-specific cancer risk: A Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Cho Semin , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki
Published: January 2021

Background

Bidirectional association between atrial fibrillation (AF) and cancer was reported by observational investigations. Additional study is warranted to investigate the causal effects of AF on risk of cancer.

Methods

This study was a summary-level Mendelian randomization (MR) analysis. Genetic instrument for AF was developed from a genome-wide association study (GWAS) meta-analysis for AF including 537,409 European ancestry individuals including 55,144 AF cases. The outcome data for risk of 17 site-specific cancer from a previous GWAS meta-analysis of the UK Biobank (48,961/359,825 case/controls) and Genetic Epidemiology Research on Adult Health and Aging (16,001/50,525 case/controls) cohorts including European ancestry individuals was investigated. Inverse variance weighted method was the main MR method, supported by pleiotropy-robust sensitivity analysis including MR-Egger regression and penalized weighted median method.

Results

The causal estimates indicated that AF was causally linked to higher risk of cancers of lung, breast, cervix, endometrium, and melanoma. MR-Egger test for directional pleiotropy indicated absence of a pleiotropy in the identified causal estimates and MR-Egger regression and median-based methods provided similarly significant findings. On the other hand, the genetic predisposition of AF was significantly associated with lower risk of esophagus/gastric cancer, but possibility of a directional pleiotropy remained in the association.

Conclusions

AF is a causal factor for certain types of cancer. Appropriate cancer screening should be suggested in clinical guidelines for AF patients. Future trial is necessary to confirm whether appropriate management of AF may reduce the risk of cancer which is a major cause of deaths in AF patients.
Identification of Fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration
Authors: Ambati Meenakshi , Apicella Ivana , Narendran Siddharth , Wang Shao-bin , Leung Hannah , Pereira Felipe , Varshney Akhil , Baker Kirstie L. , Marion Kenneth M. , Shadmehr Mehrdad , Stains Cliff I. , Sadda Srinivas R. , Taylor Ethan W. , Sutton S. Scott , Werner Brian C. , Magagnoli Joseph , Gelfand Bradley D.
Published: January 2021

The atrophic form of age-related macular degeneration (dry AMD) affects nearly 200 million people worldwide. There is no FDA-approved therapy for this disease, which is the leading cause of irreversible blindness among people over 50 years of age. Vision loss in dry AMD results from degeneration of the retinal pigmented epithelium (RPE). RPE cell death is driven in part by accumulation ofAluRNAs, which are noncoding transcripts of a human retrotransposon.AluRNA induces RPE degeneration by activating the NLRP3-ASC inflammasome. We report that fluoxetine, an FDA-approved drug for treating clinical depression, binds NLRP3 in silico, in vitro, and in vivo, and that it inhibits activation of the NLRP3-ASC inflammasome in RPE cells and macrophages, two critical cell types in dry AMD. We also demonstrate that fluoxetine, unlike several other anti-depressant drugs, reducesAluRNA-induced RPE degeneration in mice. Finally, by analyzing two health insurance databases comprising more than 100 million Americans, we report a reduced hazard of developing dry AMD among patients with depression who were treated with fluoxetine. Collectively, these studies triangulate to link fluoxetine as a potential drug repurposing candidate for a major unmet medical need that causes blindness in millions of people in the United States and across the world.

Significance Statement

Dry age-related macular degeneration (AMD) affects the vision of millions of people worldwide. There is currently no FDA-approved treatment for dry AMD. The inflammasome components NLRP3 and ASC have been implicated in the pathogenesis of dry AMD. We report that fluoxetine, which is approved for the treatment of clinical depression, directly binds the NLRP3 protein and prevents the assembly and activation of the NLRP3-ASC inflammasome. As a result, it also blocks the degeneration of retinal pigmented epithelium (RPE) cells in an animal model of dry AMD. Furthermore, we demonstrate through an analysis of health insurance databases that use of this FDA-approved anti-depressant drug is associated with reduced incidence of dry AMD. These studies identify that fluoxetine is a potential repurposing candidate for AMD, a prevalent cause of blindness.
Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit
Authors: Yong Xuan Ling Hilary , Zhang Lingrui , Yang Liming , Chen Xiumin , Yu Xiaojun , Chandra Mintu , Livingstone Emma , Tan Jing Zhi Anson , Widagdo Jocelyn , Vieira Marta M. , Roche Katherine W. , Lynch Joseph W. , Keramidas Angelo , Collins Brett M. , Anggono Victor
Published: January 2021

NMDAR-dependent Ca2+influx underpins multiple forms of synaptic plasticity. In the adult forebrain, the majority of synaptic NMDAR currents are mediated by GluN2A-containing NMDARs. These receptors are rapidly inserted into synapses during LTP; however, the underlying molecular mechanisms remain poorly understood. Here we show that GluN2A is phosphorylated at Ser-1459 by CaMKIIα in response to glycine stimulation that mimics LTP in primary neurons. Phosphorylation of Ser-1459 promotes GluN2A interaction with the SNX27-retromer complex, therefore enhancing the endosomal recycling of NMDARs. Loss of SNX27 or CaMKIIα function blocks the glycine-induced increase in GluN2A-NMDARs on the neuronal membrane. Interestingly, mutations of Ser-1459, including the rare S1459G human epilepsy variant, prolong decay times of NMDAR-mediated synaptic currents in heterosynapses by increasing the active duration of channel openings. Taken together, these findings not only identify a critical role of Ser-1459 phosphorylation in regulating the function of NMDARs, but also explain how the S1459G epilepsy variant dysregulates NMDAR function.
Experimental corticosterone manipulation increases mature feather corticosterone content: implications for inferring avian stress history from feather analyses
Authors: Aharon-Rotman Yaara , Buttemer William A. , Koren Lee , Wynne-Edwards Katherine
Published: January 2021

Feathers incorporate plasma corticosterone (CORT) during their development and, because feathers lack blood supply at maturity, the CORT content of feathers (CORTf) is presumed to represent an integrated average of plasma CORT levels during feather growth. We tested this assumption by quantifying CORTf in feathers of house sparrows (Passer domesticus) that were plucked before and after being implanted with either a corticosterone-filled, metyrapone-filled, or empty (sham) silastic capsule. Two of the seven flight feathers collected from each bird were fully grown when birds received implants. We found that CORTf of all seven feathers corresponded with treatment type, and with plasma CORT levels of non-moulting reference sparrows also given these implants. We also found that CORTf of the two mature feathers of each bird were 4 to 10-fold higher than values measured in new feathers. Given the avascular nature of mature feathers, and the fact that we did not wash the feathers prior to analysis, the most plausible explanation for our results is that CORT was externally deposited on feathers after implant. This outcome emphasises the need for follow-up studies to identify the external sources of CORT that may affect the CORTf of feathers. We hope this study will stimulate discussions and further much needed studies on the mechanism of CORT deposition in feathers and open exciting opportunities for application of such methods in ecological research, such as measuring multiple time scales in such a non-invasive manner.
Characterizing scaling laws in gut microbial dynamics from time series data: caution is warranted
Authors: Wang Xu-Wen , Liu Yang-Yu
Published: January 2021

Many studies have revealed that both host and environmental factors can impact the gut microbial compositions, implying that the gut microbiota is considerably dynamic1–5. In their Article, Ji et al.6performed comprehensive analysis of multiple high-resolution time series data of human and mouse gut microbiota. They found that both human and mouse gut microbiota dynamics can be characterized by several robust scaling laws describing short- and long-term changes in gut microbiota abundances, distributions of species residence and return times, and the correlation between the mean and the temporal variance of species abundances. They claimed that those scaling laws characterize both short- and long-term dynamics of gut microbiota. However, we are concerned that their interpretation is quite misleading, because all the scaling laws can be reproduced by the shuffled time series with completely randomized time stamps of the microbiome samples.
YHP: Y-chromosome Haplogroup Predictor for predicting male lineages based on Y-STRs
Authors: Song Mengyuan , Song Feng , Zhao Chenxi , Hou Yiping
Published: January 2021

Human Y chromosome reflects the evolutionary process of males. Male lineage tracing by Y chromosome is of great use in evolutionary, forensic, and anthropological studies when male samples exist or especially when the biological sample is a mixture of male and female individuals. Identifying the male lineage based on the specific distribution of Y haplogroups narrows down the investigation scope. Integrating previously published datasets with genotypes of Y chromosome short tandem repeats (Y-STRs) and high-resolution haplogroups (122 haplogroups in total), we developed YHP (Y Haplogroup Predictor), an open-access and userfriendly software package to predict haplogroups, compare the similarity, and conduct mismatch analysis of samples with Y-STR profiles. The software is available at Github (https://github.com/cissy123/YHP-Y-Haplogroup-Predictor-).

Author Summary

Familial searching has been used in forensic, anthropologic, and personalized scenarios. Software packages have been developed to assist in male familial searching, such as predicting Y-SNP haplogroups by Y-STRs. However, these software packages, in general, achieve this goal with a rough resolution. In this study, we developed a software package to conduct high-resolution haplogroup inference to help familial searching and at the same time reduce the cost, since it does not require tiresome Y-SNP sequencing.
Spatial Congruence Analysis (SCAN): An objective method for detecting biogeographical patterns based on species’ range congruences
Authors: Gatto Cassiano A F R , Cohn-Haft Mario
Published: January 2021

Similar species ranges may represent outcomes of common biological processes and so form the basis for biogeographical concepts such as areas of endemism and ecoregions. Nevertheless, spatial range congruence is rarely quantified, much less incorporated in bioregionalization methods as an explicit parameter. Furthermore, most available methods suffer from limitations related to the loss, or the excess of range information, or scale bias associated with the use of grids, and the incapacity to recognize independent overlapped patterns or gradients of range distributions. Here, we propose an analytical method, Spatial Congruence Analysis (SCAN), to identify biogeographically meaningful groups of species, called biogeographic elements. Such elements are based on direct and indirect spatial relationships among species’ ranges and vary depending on an explicit measure of range congruence controlled as a numerical parameter in the analysis. A one-layered network connects species (vertices) using pairwise spatial congruence estimates (edges). This network is then analyzed for each species, separately, by an algorithm that accesses the entire web of spatial relationships to the reference species. The method was applied to two datasets: a simulated gradient of ranges and real distributions of birds. The gradient results showed that SCAN can describe gradients of distribution with a high level of detail, without confounding transition zones with true biogeographical units, a frequent pitfall of other methods. The bird dataset showed that only a small portion of range overlaps is biogeographically meaningful, and that there is a large variation in types of patterns that can be found with real distributions. Distinct reference species may converge on similar or identical groups of spatially related species, may lead to recognition of nested species groups, or may even generate similar spatial patterns with no species in common. The biological significance or causal processes of these patterns should be investigated a posteriori. Patterns can vary from simple ones, composed by few highly congruent species, to complex, with numerous alternative component species and spatial configurations, depending on particular parameter settings as determined by the investigator. This approach eliminates or reduces limitations of other methods and permits pattern description without hidden assumptions about processes, and so should make a valuable contribution to the biogeographer’s toolbox.

“If there is any basic unit of biogeography, it is the geographic range of a species.” - Brown, Stevens & Kaufman [1].

“[spatial] congruence […] should be optimized, while realizing that this criterion will most likely never be fully met” - HP Linder [2].