bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac complications in trauma
Authors: Lam Lydia , Kobayashi Leslie , Demetriades Demetrios
Published: March 2021

Post-traumatic cardiac complications may occur after penetrating or blunt injuries to the heart or may follow severe extracardiac injuries. The majority of victims with penetrating injuries to the heart die at the scene and do not reach hospital care. For those patients who reach hospital care, an immediate operation, sometimes in the emergency room, cardiac injury repair, and cardiopulmonary resuscitation provide the only possibility of survival. Many patients develop perioperative cardiac complications such as acute cardiac failure, cardiac arrhythmias, coronary air embolism, and myocardial infarction. Some survivors develop post-operative functional abnormalities or anatomical defects, which may not manifest during the early post-operative period. It is essential that all survivors undergo detailed early and late cardiac evaluations. Blunt cardiac trauma encompasses a wide spectrum of injuries that includes asymptomatic myocardial contusion, arrhythmias, or cardiogenic shock to full-thickness cardiac rupture and death. Clinical examination, electrocardiograms, troponin measurements, and echocardiography are the cornerstone of diagnosis and monitoring of these patients. Lastly, some serious extracardiac traumatic conditions, such as traumatic pneumonectomy and severe traumatic brain injury, may result in cardiac complications. This may include tachyarrhythmias, cardiogenic shock, electrocardiographic changes, troponin elevations, heart failure, and cardiac arrest.
Anaemia and transfusion
Authors: Vranckx Pascal , Cao Davide , Vanderkerckhove Philippe , Mehran Roxana
Published: March 2021

Anaemia is a common condition associated with critically ill patients admitted to an (cardiac) intensive care unit. Anaemia, irrespective of the cause, has an unfavorable impact on mortality. In addition, anaemia is an independent predictor of bleeding. The intensive care physician is faced with the challenge of treating multi-factorial aetiologies of anaemia, mainly overt bleeding and blood loss due to phlebotomy and decreased erythropoiesis. Pharmacotherapy and invasive strategies in acute cardiac patients have to be customized, depending on the balance between ischaemic and bleeding risks, bearing in mind that those patients at the highest risk of further ischaemic events are often also the patients who are at the highest bleeding risk, with around 20% overlap. The risks of anemia are compounded by the risks associated with transfusion of red blood cells, the most common treatment for severe anemia. Moreover, Erythropoiesis-stimulating agents for the treatment of anaemia in acute cardiac care are contraindicated. In this chapter, the etiology and pathogenesis of the anemia in acute cardiac patients are reviewed, and the current opinion on the pros and cons of various management strategies are discussed with emphasize on restrictive transfusion policy.
Development of a Home-Based Telerehabilitation Service Delivery Protocol for Wheelchair Seating and Mobility Within the Veterans Health Administration
Authors: Ott Kaila K , Schein Richard M , Straatmann Joseph , Schmeler Mark R , Dicianno Brad E
Published: March 2021

Introduction

The provision of seating and wheeled mobility devices is a complex process that requires trained professionals and multiple appointments throughout the service delivery process. However, this can be inconvenient and burdensome for individuals with mobility limitations or for individuals who live in rural areas. Rural areas often present unique difficulties regarding the provision of healthcare services including lengthy travel times to medical facilities and lack of specialized providers and medical technology. The purpose of this article is to provide a comprehensive overview of the development and implementation of a service delivery protocol for a home-based telerehabilitation assessment for wheelchair seating and mobility.

Materials and Methods

The telerehabilitation team consists of a trained wheelchair seating and mobility therapist and a telehealth clinical technician (TCT). In order to determine veterans that are appropriate for a home-based telerehabilitation assessment, a three-phase pre-assessment screening process was conducted by the therapist and TCT, including consult, chart, and phone review. Veterans that met all of the predetermined eligibility criteria were recommended for a telerehabilitation wheelchair assessment. The TCT traveled to the veteran’s residence with necessary evaluation and safety equipment and connected with the therapist remotely using the VA Video Connect platform. Assessment and veteran data were collected during the initial evaluation and then during a 21-day follow-up.

Results

Forty-three veterans were successfully seen via telerehabilitation for a seating and wheeled mobility assessment between November, 2017 and July, 2018. The average travel distance between the veteran’s residence and the clinic was 34.1 miles. The total telerehabilitation encounter times ranged from 45 min to 145 min.

Conclusions

The implementation of this service delivery protocol for wheelchair seating and mobility assessments demonstrated the benefits of using telehealth services including reaching rural veterans, reducing distance traveled, maximizing efficiency of provider schedules, and conducting realistic assessments in veterans’ home environments. Success can be attributed to being able to deliver best practice remotely and to the rapport of the TCT with the providers. Cultivating provider buy-in, selecting appropriate outcome measures, and restructuring workflows were additional lessons learned. The VA Video Connect platform is an accessible tool that can be easily learned by both veterans and providers and used beyond initial wheelchair seating evaluations for improved access to follow-up healthcare services.
Lumbar Laminoplasty for Resection of Myxopapillary Ependymoma of the Conus Medullaris: 2-Dimensional Operative Video
Authors: Strong Michael J , Yee Timothy J , Khalsa Siri Sahib S , Saadeh Yamaan S , North Robert , Oppenlander Mark E
Published: March 2021

Myxopapillary ependymomas are slow-growing tumors that are located almost exclusively in the region of the conus medullaris, cauda equina, and filum terminale of the spinal cord. Surgical intervention achieving a gross total resection is the main treatment modality. If, however, a gross total resection cannot be achieved, surgery is augmented with radiation therapy. In this video, we present the case of a 27-yr-old male with persistent back pain and radiculopathy who was found to have a myxopapillary ependymoma that was adherent to the conus. Preoperative imaging demonstrated that the tumor was displacing the conus and nerve roots ventrally. A laminoplasty at L1-L2 was performed with near-total resection because of the intimate involvement of neural tissue. The key features of the video include performing laminoplasty and rationale, and performing maximum safe tumor resection with a combination of bipolar cautery, suction, and ultrasonic aspiration augmented with frequent stimulation, gel foam pledgets intradurally, and achieving a watertight closure of the dura and fascia. The patient tolerated the surgery well without any complications. Given his gross residual disease along the conus and young age, he was at a high risk for continued tumor growth without adjuvant therapy, with a recurrence rate of roughly 33% to 45% in patients who underwent subtotal resection. With the addition of adjuvant radiation therapy, the recurrence rate is 20% to 29%.
1,2
He was discharged to home with a plan for conventional fractionated external beam radiation. At the most recent follow-up, he reported decreased back pain and radiculopathy. Appropriate patient consent was obtained.
Deflating the Many Attitudes Problem
Authors: Baker Derek
Published: March 2021

Attitudinal embeddings, such as ‘I hope that murder is wrong’ or ‘she is glad that eating meat is not wrong’ are a less substantial problem for expressivists than is standardly thought. If expressivists are entitled to talk of normative beliefs, they can explain what it is to for an attitude to be semantically related to a normative content in terms of being functionally related to a belief with a normative content.
Glutathione Levels and Glutathione-Glutamate Correlation in Patients With Treatment-Resistant Schizophrenia
Authors: Iwata Yusuke , Nakajima Shinichiro , Plitman Eric , Truong Peter , Bani-Fatemi Ali , Caravaggio Fernando , Kim Julia , Shah Parita , Mar Wanna , Chavez Sofia , Remington Gary , Gerretsen Philip , De Luca Vincenzo , Sailasuta Napapon , Graff-Guerrero Ariel
Published: March 2021

Treatment-resistant schizophrenia (TRS) has been suggested to involve glutamatergic dysfunction. Glutathione (GSH), a dominant antioxidant, is known to be involved in glutamatergic neurotransmission. To date, no study has examined GSH levels in patients with TRS. The aim of this study was to examine GSH levels in the dorsal anterior cingulate cortex (dACC) of patients with TRS. Patients with schizophrenia were categorized into 3 groups with respect to their antipsychotic response: (1) clozapine (CLZ) nonresponders, (2) CLZ responders, and (3) first-line responders (FLR). GSH and glutamine + glutamate (Glx) levels were measured using 3T proton magnetic resonance spectroscopy. Firstly, dACC GSH levels were compared among the patient groups and healthy controls (HCs). Further, relationships between GSH and Glx levels were compared between the groups and GSH levels were explored stratifying the patient groups based on the glutamate-cysteine ligase catalytic (GCLC) subunit polymorphism. There was no difference in GSH levels between the groups. FLR showed a more negative relationship between GSH and Glx levels in the dACC compared to HCs. There were no effects of GCLC genotype on the GSH levels. However, CLZ responders had a higher ratio of high-risk GCLC genotype compared to CLZ nonresponders. This study demonstrated different relationships between GSH and Glx in the dACC between groups. In addition, the results suggest a potential link between CLZ response and GCLC genotype. However, it still remains unclear how these differences are related to the underlying pathophysiology of schizophrenia subtypes or the mechanisms of action of CLZ.
Total evidence phylogenetic analysis reveals polyphyly ofAnostomoidesand uncovers an unexpectedly ancient genus of Anostomidae fishes (Characiformes)
Authors: Sidlauskas Brian L , Assega Fernando M , Melo Bruno F , Oliveira Claudio , Birindelli José L O
Published: March 2021

The nearly 150 species of Anostomidae comprise one of the most diverse and taxonomically dynamic families of Neotropical freshwater fishes. A recent revision of the enigmatic and poorly diagnosed genus Anostomoides demonstrated that it contains two valid species, each with complicated taxonomic histories; however, that study did not address their phylogenetic placement. Herein, we integrate molecular and morphological data to demonstrate their distant evolutionary relationship, and thus the polyphyly of Anostomoides. While we reconstruct one of the species in a previously hypothesized placement within a clade also containing Laemolyta, Rhytiodus and Schizodon, the other represents a morphologically and genetically distinctive lineage that diverged early in the history of the family. We describe and illustrate the osteology of this remarkable species, discuss the evolutionary implications of its unique suite of features, and use those characteristics to diagnose a new genus that evolved independently of all other known members of the family for approximately 37 Myr.
Adherence to High-Intensity Interval Training in Cardiac Rehabilitation
Authors: Taylor Jenna L. , Holland David J. , Keating Shelley E. , Bonikowske Amanda R. , Coombes Jeff S.
Published: March 2021

Purpose:

High-intensity interval training (HIIT) is gaining popularity as a training approach for patients attending cardiac rehabilitation (CR). While the literature has focused on the efficacy of HIIT for improving cardiorespiratory fitness (CRF), particularly when compared with moderate intensity exercise, less emphasis has been placed on adherence to HIIT. The aim of this review was to summarize the current literature regarding adherence to HIIT in CR patients with coronary artery disease.

Review Methods:

A review identified 36 studies investigating HIIT in CR patients with coronary artery disease. Methods and data were extracted for exercise or training adherence (to attendance, intensity, and duration), feasibility of protocols, and CRF. The review summarizes reporting of adherence; adherence to HIIT and comparator/s; the influence of adherence on changes in CRF; and feasibility of HIIT.

Adherence to the attendance of HIIT sessions was high and comparable with moderate-intensity exercise. However, adherence to the intensity and duration of HIIT was variable and underreported, which has implications for determining the treatment effect of the exercise interventions being compared. Furthermore, additional research is needed to investigate the utility of home-based HIIT and long-term adherence to HIIT following supervised programs. This review provides recommendations for researchers in the measurement and reporting of adherence to HIIT and other exercise interventions to facilitate a sufficient and consistent approach for future studies. This article also highlights strategies for clinicians to improve adherence, feasibility, and enjoyment of HIIT for their patients.
Cryoablation as Second-line Therapy for Fibroadipose Vascular Anomaly
Authors: Kaufman Claire , Frodsham Aaron , Arnold Ryan
Published: March 2021

Purpose:

Fibroadipose vascular anomaly (FAVA) is a recently described intramuscular vascular anomaly that replaces normal skeletal muscle with fibrofatty proliferation and phlebectasia causing pain and contractures. Cryoablation has recently emerged as a means of treating FAVA with favorable outcomes. The purpose of our study was to examine our FAVA patients with failed prior interventions who underwent cryoablation as second-line treatment.

Methods:

A retrospective review was performed of all cases of cryoablation for FAVA (diagnosed on imaging or biopsy) who had undergone prior treatment from October 2014 to October 2020 at the adult and children’s hospital. Preprocedure, intraprocedural, and, when available, follow-up imaging was reviewed. Electronic medical record and imaging review was performed to determine demographics, indication, prior treatments both interventional and surgical, symptoms, and clinical response.

Results:

There were 9 patients with 11 ablation procedures; 8/9 patients had decrease in pain. One patient with diffuse FAVA had worsening pain after ablation and was subsequently treated with sirolimus.

Conclusions:

FAVA can be difficult to treat with traditional methods such as sclerotherapy or surgical resection. Cryoablation has recently emerged as a promising treatment. Our experience suggests FAVA with failed prior interventions may respond favorably to cryoablation.
Elevated T cell repertoire diversity is associated with progression of lung squamous cell premalignant lesions
Authors: Maoz Asaf , Merenstein Carter , Koga Yusuke , Potter Austin , Gower Adam C. , Liu Gang , Zhang Sherry , Liu Hanqiao , Stevenson Christopher , Spira Avrum , Reid Mary E. , Campbell Joshua D. , Mazzilli Sarah A. , Lenburg Marc E. , Beane Jennifer E.
Published: March 2021

Objective

The immune response to invasive carcinoma has been the focus of published work, but little is known about the adaptive immune response to bronchial premalignant lesions (PMLs), precursors of lung squamous cell carcinoma. This study was designed to characterize the T cell receptor (TCR) repertoire in PMLs and its association with clinical, pathological, and molecular features.

Methods

Endobronchial biopsies (n=295) and brushings (n=137) from high-risk subjects (n=50), undergoing lung cancer screening at approximately 1-year intervals via autofluorescence bronchoscopy and CT, were profiled by RNA-seq. We applied the TCR Repertoire Utilities for Solid Tissue/Tumor (TRUST) tool to the RNA-seq data to identify TCR CDR3 sequences across all samples. In the biopsies, we measured the correlation of TCR diversity with previously derived immune-associated PML transcriptional signatures and outcome. We also quantified the spatial and temporal distribution of shared and clonally expanded TCRs. Using the biopsies and brushes, the ratio of private (i.e., found in one patient only) and public (i.e., found in two or more patients) TCRs was quantified and the CDR3 sequences were compared to those found in curated databases with known antigen specificities.

Results

We detected 39,303 unique TCR sequences across all samples. In PML biopsies, TCR diversity was negatively associated with a transcriptional signature of T-cell mediated immune activation (Spearman’s rho −0.34, p < 0.001) associated with PML outcome.

Additionally, in lesions of the proliferative molecular subtype, TCR diversity was decreased in regressive versus progressive/persistent PMLs (p=0.045). Within each patient, TCRs were more likely to be shared between biopsies sampled at the same timepoint than biopsies sampled at the same anatomic location at different times. Clonally expanded TCRs, within a biopsied lesion, were more likely to be expanded at future time points than non-expanded clones. The majority of TCR sequences were found in a single sample, with only 3,396 (8.6%) found in more than one sample and 1,057 (2.7%) found in two or more patients (i.e. public), however, when compared to a public database of CDR3 sequences, 4,543 (11.6%) of TCRs were identified as public. TCRs with known antigen specificities were enriched among Public TCRs (p < 0.001).

Conclusions

Decreased TCR diversity may reflect nascent immune responses that contribute to PML elimination. Further studies are needed to explore the potential for immunoprevention of PMLs.
Sequence Analysis of 20,453 SARS-CoV-2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern
Authors: Long S. Wesley , Olsen Randall J. , Christensen Paul A. , Subedi Sishir , Olson Robert , Davis James J. , Saavedra Matthew Ojeda , Yerramilli Prasanti , Pruitt Layne , Reppond Kristina , Shyer Madison N. , Cambric Jessica , Finkelstein Ilya J. , Gollihar Jimmy , Musser James M.
Published: March 2021

[Abstract]

Since the beginning of the SARS-CoV-2 pandemic, there has been international concern about the emergence of virus variants with mutations that increase transmissibility, enhance escape from the human immune response, or otherwise alter biologically important phenotypes. In late 2020, several “variants of concern” emerged globally, including the UK variant (B.1.1.7), South Africa variant (B.1.351), Brazil variants (P.1 and P.2), and two related California “variants of interest” (B.1.429 and B.1.427). These variants are believed to have enhanced transmissibility capacity. For the South Africa and Brazil variants, there is evidence that mutations in spike protein permit it to escape from some vaccines and therapeutic monoclonal antibodies. Based on our extensive genome sequencing program involving 20,453 virus specimens from COVID-19 patients dating from March 2020, we report identification of all important SARS-CoV-2 variants among Houston Methodist Hospital patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency in the population, they are geographically widespread. Houston is the first city in the United States to have all variants documented by genome sequencing. As vaccine deployment accelerates worldwide, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence and frequency of consequential variants and their patterns and trajectory of dissemination. This information is critical for medical and public health efforts to effectively address and mitigate this global crisis.
Introductions and evolutions of SARS-CoV-2 strains in Japan
Authors: Tokumasu Reitaro , Weeraratne Dilhan , Snowdon Jane , Parida Laxmi , Kudo Michiharu , Koyama Takahiko
Published: March 2021

COVID-19 caused by SARS-CoV-2 was first identified in Japan on January 15th, 2020, soon after the pandemic originated in Wuhan, China. Subsequently, Japan experienced three distinct waves of the outbreak in the span of a year and has been attributed to new exogenous strains and evolving existing strains. Japan engaged very early on in tracking different COVID-19 strains and have sequenced approximately 5% of all confirmed cases. While Japan has enforced stringent airport surveillance on cross-border travelers and returnees, some carriers appear to have advanced through the quarantine stations undetected. In this study 30493 genomes sampled in Japan were analyzed to understand the strains, heterogeneity and temporal evolution of different SARS-CoV-2 strains. We identified 12 discrete strains with a substantial number of cases with most strains possessing the spike (S) D614G and nucleocapsid (N) 203_204delinsKR mutations. 155 distinct strains have been introduced into Japan and 39 of them were introduced after strict quarantine policy was implemented. In particular, the B.1.1.7 strain, that emerged in the United Kingdom (UK) in September 2020, has been circulating in Japan since late 2020 after eluding cross-border quarantine stations. Similarly, the B.1.351 strain dubbed the South African variant, P.1 Brazilian strain and R.1 strain with the spike E484K mutation have been detected in Japan. At least 14 exogenous B.1.1.7 sub-strains have been independently introduced in Japan as of late March 2021, and these strains carry mutations that give selective advantage including N501Y, H69_V70del, and E484K that confer increased transmissibility, reduced efficacy to vaccines and possible increased virulence. Furthermore, various strains, which harbor multiple variants in the PCR primers and the probe developed by National Institute of Infectious Disease (NIID), are emerging. It is imperative that the quarantine policy be revised, cross-border surveillance reinforced, and new public health measures implemented to mitigate further transmission of this deadly disease and to identify strains that may engender resistance to vaccines.
Novel polygenic risk score links depression-related cortical transcriptomic changes to brain morphology and symptom severity
Authors: Miles Amy E , Dos Santos Fernanda C , Byrne Enda M , Renteria Miguel E , McIntosh Andrew M , Adams Mark J , Pistis Giorgio , Castelao Enrique , Preisig Martin , Baune Bernhard T , Schubert K Oliver , Lewis Cathryn M , Jones Lisa A , Jones Ian , Uher Rudolf , Smoller Jordan W , Perlis Roy H , Levinson Douglas F , Potash James B , Weissman Myrna M , Shi Jianxin , Lewis Glyn , Penninx Brenda WJH , Boomsma Dorret I , Hamilton Steven P ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sibille Etienne , Hariri Ahmad R , Nikolova Yuliya S
Published: March 2021

Our group developed a transcriptome-based polygenic risk score (T-PRS) that uses common genetic variants to capture ‘depression-like’ shifts in cortical gene expression. Here, we mapped T-PRS onto diagnosis and symptom severity in major depressive disorder (MDD) cases and controls from the Psychiatric Genomics Consortium (PGC). To evaluate potential mechanisms, we further mapped T-PRS onto discrete measures of brain morphology and broad depression risk in healthy young adults. Genetic, self-report, and/or neuroimaging data were available in 29,340 PGC participants (59% women; 12,923 MDD cases, 16,417 controls) and 482 participants in the Duke Neurogenetics Study (DNS: 53% women; aged 19.8±1.2 years). T-PRS was computed from SNP data using PrediXcan to impute cortical expression levels of MDD-related genes from a previous post-mortem transcriptome meta-analysis. Sex-specific regressions were used to test effects of T-PRS on depression diagnosis, symptom severity, and Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index in the PGC and DNS samples, respectively. T-PRS did not predict depression diagnosis (OR=1.007, 95%CI=[0.997-1.018]); however, it correlated with symptom severity in men (rho=0.175, p=7.957×10−4) in one large PGC cohort (N=762, 48% men). In DNS, T-PRS was associated with smaller amygdala volume in women (β=-0.186, t=-3.478, p=.001) and less prefrontal gyrification (max≤-2.970, p≤.006) in both sexes. In men, prefrontal gyrification mediated an indirect effect of T-PRS on broad depression risk (b=.005, p=.029), indexed using self-reported family history of depression. Depression-like shifts in cortical gene expression predict symptom severity in men and may contribute to disease vulnerability through their effect on cortical gyrification.
Evaluating a first fully automated interview grounded in Multiple Mini Interview (MMI) methodology: results from a feasibility study
Authors: Callwood Alison , Gillam Lee , Christidis Angelos , Doulton Jia , Harris Jenny , Coleman Marianne , Kubacki Angela , Tiffin Paul , Roberts Karen , Tarmey Drew , Dalton Doris , Valentin Virginia
Published: March 2021

Objectives

Global, Covid-driven restrictions around face-to-face interviews for healthcare student selection have forced admissions staff to rapidly adopt adapted online systems before supporting evidence is available. We have developed, what we believe is, the first fully automated interview grounded in Multiple Mini-Interview (MMI) methodology. This study aimed to explore test re-test reliability, acceptability and usability of the system.

Design, setting and participants

mixed-methods feasibility study in Physician Associate (PA) programmes from two UK and one US university during 2019 - 2020.

Primary, secondary outcomes

Feasibility measures (test retest reliability acceptability and usability) were assessed using intra-class correlation (ICC), descriptive statistics, thematic and content analysis.

Methods

Volunteers took (T1), then repeated (T2), the automated MMI, with a seven-day interval (+/− 2) then completed an evaluation questionnaire. Admissions staff participated in focus group discussions.

Results

Sixty-two students and seven admission staff participated; 34 students and four staff from UK and 28 students and three staff from US universities.

Good-excellent test-retest reliability was observed with T1 and T2 ICC between 0.62-0.81 (p<0.001) when assessed by individual total scores (range 80.6-119), station total scores 0.6-0.91, p<0.005, individual site (all ICC≥ 0.76 p<0.001) and mean test retest across sites 0.82 p<0.001 (95% CI 0.7-0.9).

Admissions staff reported potential to reduce resource costs and bias through a more objective screening tool for pre-selection or to replace some MMI stations in a ‘hybrid model’. Maintaining human interaction through ‘touch points’ was considered essential.

Users positively evaluated the system, stating it was intuitive with an accessible interface. Concepts chosen for dynamic probing needed to be appropriately tailored.

Conclusion

These preliminary findings suggest that the system is reliable, generating consistent scores for candidates and is acceptable to end-users provided human touchpoints are maintained. Thus, there is evidence for the potential of such an automated system to augment healthcare student selection processes.
Revisiting Bias in Odds Ratios
Authors: Foppa Ivo M , Dahlgren Fredrick S
Published: March 2021

Ratio measures of effect, such as the odds ratio (OR), are consistent, but the presumption of their unbiasedness is founded on a false premise: The equality of the expected value of a ratio and the ratio of expected values. We show that the invalidity of this assumptions is an important source of empirical bias in ratio measures of effect, which is due to properties of the expectation of ratios of count random variables. We investigate ORs (unconfounded, no effect modification), proposing a correction that leads to “almost unbiased” estimates. We also explore ORs with covariates. We find substantial bias in OR estimates for smaller sample sizes, which can be corrected by the proposed method. Bias correction is more elusive for adjusted analyses. The notion of unbiasedness of OR for the effect of interest for smaller sample sizes is challenged.
Vaccine hesitancy and reasons for refusing the COVID-19 vaccination among the U.S. public: A cross-sectional survey
Authors: Raja Ali S. , Niforatos Joshua D. , Anaya Nancy , Graterol Joseph , Rodriguez Robert M.
Published: March 2021

Importance

Although widespread vaccination will be the most important cornerstone of the public health response to the COVID-19 pandemic, a critical question remains as to how much of the United States population will accept it.

Objective

Determine: 1) rate of COVID-19 vaccine hesitancy in the United States public, 2) patient characteristics associated with hesitancy, 3) reasons for hesitancy, 4) healthcare sites where vaccine acceptors would prefer to be vaccinated.

Design

43-question cross-sectional survey conducted November 17-18, 2020, distributed on Amazon Mechanical Turk, an online labor marketplace where individuals receive a nominal fee (here, $1.80) for anonymously completing tasks.

Eligible Participants

United States residents 18-88 years of age, excluding healthcare workers. A total 1,756 volunteer respondents completed the survey (median age 38 years, 53% female).

Main Outcome Measure

Multivariable logistic regression modeled the primary outcome of COVID-19 vaccine hesitancy (defined as non-acceptance or being unsure about acceptance of the COVID-19 vaccine) with respondent characteristics.

Results

A total 663 respondents (37.8%) were COVID-19 vaccine hesitant (374 [21.3%] non-acceptors and 289 [16.5%] unsure about accepting). Vaccine hesitancy was associated with not receiving influenza vaccination in the past 5 years (odds ratio [OR] 4.07, 95% confidence interval [CI] 3.26-5.07, p<0.01), female gender (OR 2.12, 95%CI 1.70-2.65, p<0.01), Black race (OR 1.54, 95%CI 1.05-2.26, p=0.03), having a high school education or less (OR 1.46, 95%CI 1.03-2.07, p=0.03), and Republican party affiliation (OR 2.41, 95%CI 1.88-3.10, p<0.01). Primary reasons for hesitancy were concerns about side effects, need for more information, and doubts about vaccine efficacy. Preferred sites for vaccination for acceptors were primary doctors’ offices/clinics, pharmacies, and dedicated vaccination locations.

Conclusions

In this recent national survey, over one-third of respondents were COVID-19 vaccine hesitant. To increase vaccine acceptance, public health interventions should target vaccine hesitant populations with messaging that addresses their concerns about safety and efficacy.
Development of a Metastatic Uveal Melanoma Prognostic risk Score (MUMPS) for use in patients receiving immune checkpoint inhibitors
Authors: Kelly Deirdre , Rose April A. N. , Muniz Thiago Pimentel , Hogg David , Butler Marcus O. , Saibil Samuel D. , King Ian , Kamil Zaid Saeed , Ghazarian Danny , Ross Kendra , Iafolla Marco , Araujo Daniel V. , Waldron John , Laperriere Normand , Krema Hatem , Spreafico Anna
Published: March 2021

Background

Metastatic uveal melanoma (mUM) is a rare disease for which no systemic therapy has demonstrated overall survival (OS) benefit. There are no robust data on prognostic factors for OS in patients with mUM treated with immune checkpoint inhibitors (ICI).

Retrospective and non-randomized prospective studies have reported response rates of 0-37% for anti-PD1/L1 +/-anti-CTLA4 ICI in mUM, indicating a potential benefit only in a subset of patients. This study evaluates the characteristics associated with ICI benefit in patients with mUM.

Methods

We performed a single-center retrospective cohort study of patients with mUM who received anti-PD1/L1 +/-anti-CTLA4 ICI between 2014–2019. Clinical and genomic characteristics were collected from chart review. Treatment response and clinical progression were determined by physician assessment. Multivariable Cox regression models and Kaplan-Meier log-rank tests were used to assess differences in clinical progression-free survival (cPFS) and OS between groups and to identify clinical variables associated with ICI outcomes.

Results

We identified 71 mUM patients who received 75 lines of ICI therapy. Of these, 54 received anti-PD1/L1 alone, and 21 received anti-PD1/L1 + anti-CTLA4. Patient characteristics were: 53% female, 48% were 65 or older, 72% received one or fewer lines of prior therapy. Within our cohort, 53% of patients had developed stage IV disease < 2 years after their initial diagnosis. Bone metastases were present in 12% of patients. For the entire cohort, the median cPFS was 2.7 months and median OS was 10.0 months. In multivariable analyses for both cPFS and OS, the following variables were associated with good prognosis: ≥ 2yrs from initial diagnosis to stage IV (n=25), LDH <1.5xULN (n=45), and absence of bone metastases (n=66). We developed a Metastatic Uveal Melanoma Prognostic risk Score (MUMPS). Patients were divided into 3 MUMPS risk groups based on the number of the above-mentioned prognostic variables: Poor risk (0-1), Intermediate risk (2) and Good risk (3). Good risk patients experienced longer cPFS (6.0 months) and OS (34.5 months) than patients with intermediate (2.3 months cPFS, 9.4 months OS) and poor risk disease (1.8 months cPFS, 3.9 months OS); P<0.0001.

Conclusion

We developed a MUMPS risk score, based on retrospective data, that is comprised of 3 readily available clinical variables (time to stage IV diagnosis, presence of bone metastases, and LDH). This MUMPS risk score has potential prognostic value. Further validation in independent datasets is warranted to determine the role of this MUMPS risk score in selecting ICI treatment management for mUM.
Shifting research priorities in maternal and child health in the COVID-19 pandemic era in India: a renewed focus on systems strengthening
Authors: Mehta Kayur , Zodpey Sanjay , Banerjee Preetika , Pocius Stephanie L. , Dhaliwal Baldeep K. , DeLuca Andrea , Bhattacharya Sangeeta Das , Hedge Shailendra , Sengupta Paramita , Gupta Madhu , Shet Anita
Published: March 2021

Background

The remarkable progress seen in maternal and child health (MCH) in India over the past two decades has been impacted by setbacks from the COVID-19 pandemic. We aimed to undertake a rapid assessment to identify key priorities for public health research in MCH in India within the context and aftermath of the COVID-19 pandemic.

Methods

A web-based survey was developed to identify top research priorities in MCH. It consisted of 26 questions on six broad domains: vaccine preventable diseases, outbreak preparedness, primary healthcare integration, maternal health, neonatal health, and infectious diseases. Key stakeholders were invited to participate between September and November 2020. Participants assigned importance on a 5-point Likert scale, and assigned overall ranks to each sub-domain research priority. Descriptive statistics were used to examine Likert scale responses, and a ranking analysis was done to obtain an “average ranking score” and identify the top research priority under each domain.

Results

Amongst the 84 respondents, 37% were public-health researchers, 25% healthcare providers, 20% academic faculty and 13% were policy makers. Across the six domains, most respondents considered conducting research on systems strengthening as extremely important. The highest ranked research priorities were strengthening the public sector workforce (vaccine preventable diseases), enhancing public-health surveillance networks (outbreak preparedness), nutrition support through community workers (primary care integration), encouraging at least 4-8 antenatal visits (maternal health), neonatal resuscitation to reduce birth asphyxia (neonatal health) and pediatric and maternal screening and treatment of tuberculosis (infectious diseases). Common themes identified through open-ended questions were also systems strengthening priorities across domains.

Conclusions

The overall focus for research priorities in MCH in India during the COVID-19 pandemic is on strengthening existing services and service delivery, rather than novel research. Our results highlight pivotal steps within the roadmap for advancing and sustaining maternal and child health gains during the ongoing COVID-19 pandemic and beyond.
Phosphate transporter genes: genome-wide identification and characterization in Camelina sativa
Authors: Hasanzadeh Soosan , Faraji Sahar ,   Abdullah, Heidari Parviz
Published: March 2021

Phosphorus is known as a key element associated with growth, energy, and cell signaling. In plants, phosphate transporters (PHTs) are responsible for moving and distributing phosphorus in cells and organs. PHT genes have been genome-wide identified and characterized in various plant species, however, these genes have not been widely identified based on available genomic data in Camellia sativa, which is an important oil seed plant. In the present study, we found 66 PHT genes involved in phosphate transporter/translocate in C. sativa. The recognized genes belonged to PHTs1, PHTs2, PHTs4, PHOs1, PHO1 homologs, glycerol-3-PHTs, sodium dependent PHTs, inorganic PHTs, xylulose 5-PHTs, glucose-6-phosphate translocators, and phosphoenolpyruvate translocators. Our finding revealed that PHT proteins are divers based on their physicochemical properties such as Isoelectric point (pI), molecular weight, GRAVY value, and exon-intron number(s). Besides, the expression profile of PHT genes in C. sativa based on RNA-seq data indicate that PHTs are involved in response to abiotic stresses such as cold, drought, salt, and cadmium. The tissue specific expression high expression of PHO1 genes in root tissues of C. sativa. In additions, four PHTs, including a PHT4;5 gene, a sodium dependent PHT gene, and two PHO1 homolog 3 genes were found with an upregulation in response to aforementioned studied stresses. In the current study, we found that PHO1 proteins and their homologs have high potential to post-translation modifications such as N-glycosylation and phosphorylation. Besides, different cis-acting elements associated with response to stress and phytohormone were found in the promoter region of PHT genes. Overall, our results show that PHT genes play various functions in C. Sativa and regulate Camellia responses to external and intracellular stimuli. The results can be used in future studies related to the functional genomics of C. sativa.
A breast cancer patient-derived xenograft and organoid platform for drug discovery and precision oncology
Authors: Guillen Katrin P. , Fujita Maihi , Butterfield Andrew J. , Scherer Sandra D. , Bailey Matthew H. , Chu Zhengtao , DeRose Yoko S. , Zhao Ling , Cortes-Sanchez Emilio , Yang Chieh-Hsiang , Toner Jennifer , Wang Guoying , Qiao Yi , Huang Xiaomeng , Greenland Jeffery A. , Vahrenkamp Jeffery M. , Lum David H. , Factor Rachel E. , Nelson Edward W. , Matsen Cindy B. , Poretta Jane M. , Rosenthal Regina , Beck Anna C. , Buys Saundra S. , Vaklavas Christos , Ward John H. , Jensen Randy L. , Jones Kevin B. , Li Zheqi , Oesterreich Steffi , Dobrolecki Lacey E. , Pathi Satya S. , Woo Xing Yi , Berrett Kristofer C. , Wadsworth Mark E. , Chuang Jeffrey H. , Lewis Michael T. , Marth Gabor T. , Gertz Jason , Varley Katherine E. , Welm Bryan E. , Welm Alana L.
Published: March 2021

Model systems that recapitulate the complexity of human tumors and the reality of variable treatment responses are urgently needed to better understand cancer biology and to develop more effective cancer therapies. Here we report development and characterization of a large bank of patient-derived xenografts (PDX) and matched organoid cultures from tumors that represent some of the greatest unmet needs in breast cancer research and treatment. These include endocrine-resistant, treatment-refractory, and metastatic breast cancers and, in some cases, multiple tumor collections from the same patients. The models can be grown long-term with high fidelity to the original tumors. We show that development of matched PDX and PDX-derived organoid (PDxO) models facilitates high-throughput drug screening that is feasible and cost-effective, while also allowingin vivovalidation of results. Our data reveal consistency between drug screening results in organoids and drug responses in breast cancer PDX. Moreover, we demonstrate the feasibility of using these patient-derived models for precision oncology in real time with patient care, using a case of a triple negative breast cancer with early metastatic recurrence as an example. Our results uncovered an FDA-approved drug with high efficacy against the models. Treatment with the PDxO-directed therapy resulted in a complete response for the patient and a progression-free survival period more than three times longer than her previous therapies. This work provides valuable new methods and resources for functional precision medicine and drug development for human breast cancer.

Graphical Abstract
CADA: Phenotype-driven gene prioritization based on a case-enriched knowledge graph
Authors: Peng Chengyao , Dieck Simon , Schmid Alexander , Ahmad Ashar , Knaus Alexej , Wenzel Maren , Mehnert Laura , Zirn Birgit , Haack Tobias , Ossowski Stephan , Wagner Matias , Brunet Teresa , Ehmke Nadja , Danyel Magdalena , Rosnev Stanislav , Kamphans Tom , Nadav Guy , Fleischer Nicole , Fröhlich Holger , Krawitz Peter
Published: March 2021

Many rare syndromes can be well described and delineated from other disorders by a combination of characteristic symptoms. These phenotypic features are best documented with terms of the human phenotype ontology (HPO), which is increasingly used in electronic health records (EHRs), too. Many algorithms that perform HPO-based gene prioritization have also been developed, however, the performance of many such tools suffers from an overrepresentation of atypical cases in the medical literature. This is certainly the case if the algorithm cannot handle features that occur with reduced frequency in a disorder. With CADA we built a knowledge-graph that is based on case annotations and disorder annotations and show that CADA exhibits superior performance particularly for patients that present with the pathognomonic findings of a disease. Crucial in the design of our approach is the use of the growing amount of phenotypic information that diagnostic labs deposit in databases such as ClinVar. By this means CADA is an ideal reference tool for differential diagnostics in rare disorders that can also be updated regularly.
The impact of COVID-19 on primary health care and antibiotic prescribing in rural China: qualitative study
Authors: Zhang Tingting , Shen Xingrong , Liu Rong , Zhao Linhai , Wang Debin , Lambert Helen , Cabral Christie
Published: March 2021

Introduction

Primary health care (PHC) system is designated to be responsible for epidemic control and prevention during the outbreak of COVID-19 in China, while COVID-19 suspected cases in PHC are required to be transferred to specialist fever clinics at higher level hospitals. This study aims to understand to impact of COVID-19 on PHC delivery and antibiotic prescribing at community level in the rural areas of central China.

Methods

Qualitative semi-structured interviews were conducted with 18 PHC practitioners and seven patients recruited from two township health centres (THCs) and nine village clinics (VCs) in two rural residential areas of Anhui province. Interviews were transcribed verbatim and thematically analysed.

Results

Practitioners’ and patients’ views and perspectives on COVID-19 impacts on PHC services and antibiotic prescribing are organised into four broad themes: switch from PHC to epidemic prevention and control, concerns and challenges faced by those delivering PHC, diminished PHC, and COVID-19 as a different class of illness.

Conclusion

The COVID-19 epidemic has had a considerable impact on the roles of rural PHC clinics in China that shifted to public health from principal medical, and highlighted the difficulties in rural PHC including inadequately trained practitioners, additional work and financial pressure, particularly in VCs. Antibiotic prescribing practices for non-COVID-19 respiratory tract infections remained unchanged since the knowledge of COVID-19 was not seen as relevant to practitioners’ antibiotic treatment practices, although overall rates were reduced because fewer patients were attending rural PHC clinics. Since COVID-19 epidemic control work has been designated as a long-term task in China, rural PHC clinics now face the challenge of how to balance their principal clinical and public health roles and, in the case of the VCs, remain financially viable.
Determinants of adolescent lung function in Indians: race, nutrition and systemic inflammation
Authors: Aggarwal Mohit , Bansal Anubhuti , Desiraju Bapu Koundinya , Singh Shailendra , Agrawal Anurag
Published: March 2021

Rationale

While determining normal variation of spirometric volumes, the geo-political construct of ‘Indian’ inadequately captures the diverse racial structure and varied lifestyles that exist for 1 in 5 people globally. It is necessary to determine the degree of racial heterogeneity and other underlying factors to know whether lower spirometric volumes of ‘Indians’ is normal or abnormal.

Objectives

To investigate the differences in spirometric volumes and their associations with overall health parameters, for adolescent children and young adults, across geo-ethnic regions within India.

Methods

Data was analyzed for 2338 healthy subjects aged 9-19 years with acceptable spirometry from SOLID cohort. Associations between lung function and potential determinants (Race, anthropometry, nutrition, family/life history, airway oscillometric parameters and systemic inflammation) were examined by using multiple regression. Latent profile analysis (LPA) was performed for 903 subjects to uncover hidden sub-phenotypes.

Results

FEV1 and FVC varied significantly between Indian genetic ancestries, being highest in Tibeto-Burmans and lowest in Dravidians. After statistical adjustments, FEV1 and FVC were positively correlated with waist-height-ratio, shoulder-height-ratio, normalized BMI, and blood hemoglobin. Lower FVC was associated with lower expiratory flows (PEF and FEF25-75), higher lung reactance (X5), higher airway resistance (R10 and R15), gastro-intestinal symptoms, and higher inflammation (IL-8 and IL-17). A sub-phenotype of thinness, higher inflammation (IFN-gamma, IL-17, TNF-alpha, IL-8) and lower FVC was identified on LPA for 35% of the sample.

Conclusions

Spirometric volumes in Indians are different between major racial subgroups but may also be abnormally low due to prevalent nutritional or environmental adversity. Care must be taken while establishing normative standards.