bluuebunny/crossref_metadata_2025 huggingface dataset:
Remediation Programs for Regulated Health Care Professionals: A Scoping Review
Authors: Kennedy Geneva , Jacobs Nicole , Freemark Lily , Madan Simran , Chan Natalie , Tran Yvonne , Miller Patricia A.
Published: September 2021

Purpose:

Clinical competence is essential for providing safe, competent care and is regularly assessed to ensure health care practitioners maintain competence. When deficiencies in competence are identified, practitioners may undergo remediation. However, there is limited evidence regarding the effectiveness of remediation programs. The purpose of this review is to examine the purpose, format, and outcomes of remediation programs for regulated health care practitioners.

Methods:

All six stages of the scoping review process as recommended by Levac et al were undertaken. A search was conducted within MEDLINE, Embase, CINAHL, ERIC, gray literature databases, and websites of Canadian provincial regulatory bodies. Emails were sent to Registrars of Canadian regulatory bodies to supplement data gathered from their websites.

Results:

A total of 14 programs were identified, primarily for physicians (n = 8). Reasons for remediation varied widely, with some programs identifying multiple reasons for referral such as deficiencies in recordkeeping (n = 7) and clinical skills (n = 6). Most programs (n = 9) were individualized to address specific deficiencies in competence. The process of remediation followed three stages: (1) assessment, (2) active remediation, and (3) reassessment. Most programs (n = 12) reported that remediation was effective in improving competence.

Conclusions:

Regulatory bodies should consider implementing individualized remediation programs to ensure that clinicians' deficiencies in competence are addressed effectively. Further research is indicated, using reliable and valid outcome measures to assess competence immediately after remediation programs and beyond.
Carotid Arterial Compliance and Aerobic Exercise Training in Chronic Traumatic Brain Injury: A Pilot Study
Authors: Tomoto Tsubasa , Le Tran , Tarumi Takashi , Dieppa Marisara , Bell Kathleen , Madden Christopher , Zhang Rong , Ding Kan
Published: September 2021

Objective:

Decreased carotid arterial compliance (CAC) is associated with cerebral microvascular damage, cerebral blood flow (CBF) dysregulation, and increased risk for stroke and dementia, which are reported to be prevalent after traumatic brain injury (TBI). However, the effect of TBI on CAC has not been reported. The purposes of this pilot study were to (1) compare CAC between participants with chronic traumatic brain injury (cTBI) and age-matched healthy control (HC) subjects and (2) to examine whether CAC changed after 3 months of exercise training in those with cTBI.

Setting:

Community based.

Participants:

Nineteen participants with cTBI (6-72 months postinjury) and 19 HC matched for age and sex were tested at baseline. The same cTBI cohort was enrolled in a proof-of-concept randomized controlled exercise training program to investigate the effects of 3 months of aerobic exercise training (AET) or nonaerobic stretching and toning (SAT) on cerebrovascular parameters.

Design:

Cross-sectional study and randomized controlled trial.

Main Measures:

CAC was measured by tonometry and ultrasonography at the common carotid artery; CBF was measured by ultrasonography at the bilateral internal carotid and vertebral arteries, and pulsatile CBF was measured by transcranial Doppler ultrasonography at the middle cerebral arteries. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by total CBF.

Results:

Relative to HC, the participants with cTBI had lower CAC (0.10 ± 0.03 vs 0.12 ± 0.03 mm2/mm Hg, P = .046) and higher CVR (0.17 ± 0.03 vs 0.15 ± 0.03 mm Hg/mL/min, P = .028). CAC tended to increase after AET compared with SAT (P = .080). Increases in CAC were associated with decreased pulsatile CBF (r = −0.689, P = .003).

Conclusion:

These findings suggest that the individuals with cTBI have decreased CAC, which may potentially be improved by AET.
Thyroid Eye Disease Following COVID-19 Vaccine in a Patient With a History Graves’ Disease: A Case Report
Authors: Rubinstein Tal J.
Published: September 2021

A 50-year-old woman with a history of controlled Graves’ disease without clinical ophthalmopathy presents with 2 months of left more than right periorbital swelling and proptosis. Her eye symptoms and signs began 3 days following her second vaccination against the COVID-19 virus. Orbital imaging, elevated thyroid stimulating immunoglobulin, and negative systemic work up for other diseases were consistent with a diagnosis of active thyroid eye disease. The temporal relationship to her vaccination was likely consistent with autoimmune/inflammatory syndrome associated with adjuvants. Clinicians should remind patients of the symptoms and signs of thyroid eye disease and to seek appropriate medical and ophthalmic advice if they occur after the COVID-19 vaccine.
Cross-Sectional Study of Influences on Maternal Decisions Regarding Feeding Premature and Ill Neonates
Authors: Aquino Laarnie Maria , Newcomb Patricia , True Barbara , Hoff Tammy , Gentile Deborah , Patton Leora , Raquepo Florence , Cash Edelyn
Published: September 2021

This cross-sectional study investigated the influences on feeding decisions made by mothers of infants admitted to neonatal intensive care units. The primary aims were to describe discrete influences on maternal behavior and to test Fishbein and Azjen's Theory of Planned Behavior in the neonatal intensive care unit (NICU) setting. The study included a convenience sample of 445 mothers in North Texas and Wisconsin. An investigator-designed tool was administered to subjects by research team members in the study units. Significant differences between minority and dominant racial groups emerged, which highlight known disparities in perinatal outcomes. Results supported the Theory of Planned Behavior and demonstrated predictors of exclusive breastfeeding at discharge including intention, race/ethnicity, length of stay in the NICU, and beliefs that the following factors influenced feeding decisions: having help with chores or childcare at home, talking with mothers in the NICU, having the NICU nurse help with feeding, and space for breastfeeding in the NICU. Incidental findings included the observation that mothers in the only NICU with private rooms were significantly more likely to report fatigue and to perceive that unit busyness, space, and privacy affected their feeding decisions, although there was no difference in breastfeeding at discharge between this NICU and others.
Changing resuscitation strategies during a pandemic: lessons from the consecutive surges in New York and global challenges
Authors: Jafari Daniel , Cohen Allison L. , Monsieurs Koen , Becker Lance B.
Published: September 2021

Purpose of review

To provide a framework for resuscitation of COVID-19 critical illness for emergency and intensive care clinicians with the most up to date evidence and recommendations in the care of COVID-19 patients in cardiac arrest or in extremis.

Recent findings

Performing cardiopulmonary resuscitation (CPR) on COVID-19 patients requires the clinicians to adopt infection mitigation strategies such as full personal protective equipment, mechanical chest compression devices, and restricting the number of people present during the resuscitation. The time of intubation is a subject of ongoing research and clinicians should use their best judgment for each patient. Clinicians should prepare for CPR in prone position. Particular attention should be given to the psychological well-being of the staff. Point of care ultrasound has proved to be an invaluable diagnostic tool in assessing ventricular dysfunction and parenchymal lung disease. Although novel therapies to supplant the function of diseased lungs have shown promise in select patients the evidence is still being collected. The end-of-life discussions have been negatively impacted by prognostic uncertainty as well as barriers to in person meetings with families.

The resuscitation of critically ill COVID-19 patients poses new challenges, but the principles remain largely unchanged.
Centrality and Decentration
Authors: Phulpin Hugo , Goze Tudi , Faure Karine , Lysaker Paul H.
Published: September 2021

A considerable body of phenomenological research has described different ways in which the relationship of the person to the world in psychosis is affected. This literature, however, has lacked an accepted unifying theoretical model and means of quantitatively measuring these disturbances. To address this, the current article seeks to integrate a novel phenomenological model of psychosis offered by Henri Grivois, which is explicitly concerned with centrality or a person's sense of being the center of all things, with empirical research on the integrative model of metacognition, which allows for measurements of decentration or the degree to which persons can form integrated ideas about their place in their larger community. It is proposed that this literature may allow for a model of how psychotherapy can address centrality through the building of intersubjectivity and enhancing metacognition.
Test-retest Repeatability of the Ohio Contrast Cards
Authors: Osman Mawada , Njeru Stevie M. , Hopkins Gregory R. , Brown Angela M.
Published: September 2021

SIGNIFICANCE

The Ohio Contrast Cards are a repeatable test of contrast sensitivity, and they reveal higher contrast sensitivity for low-vision patients than is shown by the Pelli-Robson chart.

PURPOSE

This study aimed to compare the contrast sensitivity results and test/retest ±limits of agreement for the Ohio Contrast Cards and the Pelli-Robson letter contrast sensitivity chart on two challenging groups of participants, and to compare the Ohio Contrast Card results with grating acuity and the Pelli-Robson results with letter acuity.

METHODS

The Ohio Contrast Card and Pelli-Robson tests were each performed twice by two different examiners within one visit on 40 elder patients in Primary Vision Care (>65 years old) and 23 to 27 low-vision school-aged students. Grating acuity was measured using the Teller Acuity Cards (all participants), and letter acuity was measured using ClearChart (elders) or the Bailey-Lovie chart (students).

RESULTS

The ±95% limits of agreement were similar for the Ohio Contrast Cards and the Pelli-Robson chart. The elders' limits of agreement were ±0.27 (Ohio Contrast Cards) and ±0.28 (Pelli-Robson); the students' limits of agreement were ±0.42 (Ohio Contrast Cards) and ±0.51 (Pelli-Robson). However, Ohio Contrast Card results were 0.41 log10 Michelson units more sensitive than the Pelli-Robson chart (over one line on the Pelli-Robson chart) for the elders and 0.90 log10 Michelson units (three lines on the Pelli-Robson chart) more sensitive for the elders (0.11 and 0.6 log10 Weber units, respectively). The Pelli-Robson results were correlated with letter acuities and Ohio Contrast Card results for both groups, and the Ohio Contrast Card results were correlated with Teller Acuity Card acuities for the elders.

CONCLUSIONS

The Ohio Contrast Cards and Pelli-Robson chart are similarly repeatable. Both contrast sensitivity tests can provide additional clinical information that is not available through visual acuity testing, and Ohio Contrast Card may provide additional information not available from the Pelli-Robson chart.
Case Report: Tubal Atypical Placental Site Nodule
Authors: Yen Ting-Tai , Anderson Jean , Shih Ie-Ming
Published: September 2021

Placental site nodule (PSN) is a benign proliferation of chorionic-type intermediate trophoblastic cells that forms a tumor-like lesion. Most PSNs are intrauterine, but a few have been reported outside the uterus, including in fallopian tubes. PSN is related to epithelioid trophoblastic tumor (ETT) in that both are composed of chorionic-type intermediate trophoblastic cells, while ETT is hypercellular and contains trophoblastic cells with increased nuclear atypia and a higher Ki-67 proliferation index as compared with PSN. Occasionally, an intermediate stage between a PSN and an ETT is observed, and such a lesion is often recognized as an atypical PSN (aPSN) characterized by trophoblastic cells exhibiting morphologic features in transition from a conventional PSN to an ETT. aPSN has been thought to exhibit benign behavior; however, it has also been reported that up to 15% of aPSN lesions either coexist with, or subsequently develop into, ETT. To the best of our knowledge, there has been no case report of an aPSN in an extrauterine site. Here, we reported a highly unusual case of tubal aPSN, which illustrates several key features associated with PSN and its possible pathogenesis.
DNA Damage Response in Glioblastoma
Authors: Bonm Alipi , Kesari Santosh
Published: September 2021

Glioblastoma (GBM) is an intrinsically treatment-resistant tumor and has been shown to upregulate DNA damage response (DDR) components after treatment. DNA damage response signaling mediates treatment resistance by promoting cell cycle arrest in order to allow for DNA damage repair and avoid mitotic catastrophe. Therefore, targeting the DDR pathway is an attractive strategy to combat treatment resistance in GBM. In this review, we discuss the different DDR pathways and then summarize the current preclinical evidence for DDR inhibitors in GBM, as well as completed and ongoing clinical trials.
Advanced Imaging and Computational Techniques for the Diagnostic and Prognostic Assessment of Malignant Gliomas
Authors: Bapuraj Jayapalli Rajiv , Wang Nicholas , Srinivasan Ashok , Rao Arvind
Published: September 2021

Advanced imaging techniques provide a powerful tool to assess the intratumoral and intertumoral heterogeneity of gliomas. Advances in the molecular understanding of glioma subgroups may allow improved diagnostic assessment combining imaging and molecular tumor features, with enhanced prognostic utility and implications for patient treatment. In this article, a comprehensive overview of the physiologic basis for conventional and advanced imaging techniques is presented, and clinical applications before and after treatment are discussed. An introduction to the principles of radiomics and the advanced integration of imaging, clinical outcomes, and genomic data highlights the future potential for this field of research to better stratify and select patients for standard as well as investigational therapies.
Toward the Next Generation of High-Grade Glioma Clinical Trials in the Era of Precision Medicine
Authors: Rahman Rifaquat
Published: September 2021

In the era of precision medicine, there is a desire to harness our improved understanding of genomic and molecular underpinnings of gliomas to develop therapies that can be tailored to individual patients and tumors. With the rapid development of novel therapies, there has been a growing need to develop smart clinical trials that are designed to efficiently test promising agents, identify therapies likely to benefit patients, and discard ineffective therapies. We review clinical trial design in gliomas and developments designed to address the unique challenges of precision medicine. To provide an overview of this topic, we examine considerations for endpoints and response assessment, biomarkers, and novel clinical trial designs such as adaptive platform trials in the testing of new therapies for glioma patients.
Hospital Cultural Competency and Attributes of Patient Safety Culture: A Study of U.S. Hospitals
Authors: Upadhyay Soumya , Stephenson Amber L. , Weech-Maldonado Robert , Cochran Christopher
Published: September 2021

Objective

Given the increasing racial and ethnic diversity in the United States, hospitals face challenges in providing safe and high-quality care to minority patients. Cultural competency fostered through engagement in diversity programs can be used as a resourceful strategy to provide safe care and improve the patient safety culture. This article examined the association of cultural competency and employee’s perceived attributes of safety culture.

Methods

A longitudinal study design was used with 283 unique hospital observations from 2014 to 2016. The dependent variables were percent composite scores for 4 attributes of perceived safety culture: (1) management support for patient safety, (2) teamwork across units, (3) communication openness, and (4) nonpunitive response to an error. The independent variable was an engagement in diversity programs, considered in 3 categories: (1) high, (2) medium, and (3) low. Controls included hospital characteristics, market characteristics, and percent. Ordinal logistic regression was used for imputation, whereas multiple linear regression was used for analyses.

Results

Results indicate that hospitals with high engagement have 4.64% higher perceptions of management support for safety, 3.17% higher perceptions of teamwork across units, and 3.97% higher perceptions of nonpunitive response, as compared with hospitals that have a low engagement in diversity programs (P < 0.05).

Conclusions

Culturally competent hospitals have better safety culture than their counterparts. Cultural competency is an important resource to build a safety culture so that safe care for patients from minority and diverse backgrounds can be delivered.
Factors Associated With Children Diagnosed With Attention-Deficit/Hyperactivity Disorder and 30-Day Follow-up Care With Practitioners Among Medicaid Recipients in Georgia
Authors: Yin Henry , Ibe Brendan , Parr Tiffany L. , Csukas Seema , Jones Bobby L. , Thompson Sandra
Published: September 2021

Background and Objectives:

It is important that children prescribed attention-deficit/hyperactivity disorder (ADHD) medication get timely follow-up care. In 2018, only 44% of US Medicaid recipients attended a follow-up visit within 30 days of their first ADHD prescription. The objective of this study was to identify the member and practitioner-related predictors that were associated with children who were diagnosed with ADHD and had a follow-up visit within 30 days (initiation phase) of their first prescription of ADHD medication (Index Prescription Start Date, or IPSD).

Methods:

A cross-sectional study was conducted to identify the independent predictors of a follow-up visit within 30 days and 2 follow-up visits within 270 days after the initiation phase (continuation and maintenance phase, or C&M phase) for Medicaid recipients. Predictive factors examined included race, school age group, gender, geography of residence, Medicaid service region, newly diagnosed ADHD, hospital admission, emergency department (ED) visit, types of ADHD medication, other psychosocial or behavioral diagnoses, psychosocial or behavioral therapy, prescriber specialty, and school season.

Results:

There were 2369 members eligible for the initiation phase measure, of whom 330 members were eligible for the C&M phase measure. Multiple regression analysis found that unmet 30-day follow-up was significantly associated with African American children with an existing diagnosis of ADHD (adjusted odds ratio [AOR] = 2.13; 95% confidence interval [CI], 1.64-2.76), middle school-aged children (AOR = 1.49; 95% CI, 1.23-1.80), rural residence (AOR = 1.27; 95% CI, 1.05-1.55), no ED visit (AOR = 1.57; 95% CI, 1.16-2.12), no psychosocial or behavioral therapy prior to the IPSD (AOR = 2.30; 95% CI, 1.65-3.21), and primary care practitioners (AOR = 1.88; 95% CI, 1.45-2.44).

Conclusion:

Pediatrics was the most common specialty prescribing ADHD medications. Managed care organizations can focus intervention efforts to improve compliance with 30-day follow-up among Medicaid children by targeting the high-risk categories identified above. They can also focus on facilitating communication between behavioral health practitioners and pediatricians about several key points: (1) the importance of using behavioral health therapy prior to prescribing medication; (2) the importance of timely follow-up care; and (3) the importance of medication management in combination with behavioral health therapy.
Six-Month Outcomes of Reimplantation of a Coin-Sized Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome With Urgency Urinary Incontinence
Authors: Kaaki Bilal , English Sharon , Gilling Peter , Meffan Patrick , Lucente Vincent , MacDiarmid Scott , Clark Matthew , Sen Subhro K.
Published: September 2021

Objective

The eCoin (Valencia Technologies Corporation, Valencia, CA) is a battery-powered, nickel-sized and shaped neuromodulation device for the treatment of overactive bladder, and it is implanted in the lower leg in a short office or outpatient procedure under local anesthesia. A follow-on trial was conducted to evaluate the feasibility, safety, and efficacy of eCoin reimplantation.

Methods

This was a prospective, single-arm, open-label study, including 23 participants with refractory urgency urinary incontinence (UUI) who were previously participants in the eCoin clinical feasibility trial. This follow-on study was conducted at 7 sites in the United States and New Zealand. Participants were reimplanted with a new eCoin device and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 12 weeks and 24 weeks postactivation, were compared with baseline.

Results

Participants of the study were considered responders if they reported a ≥ 50% reduction from baseline in episodes of UUI on a 3-day voiding diary. At 12 weeks of treatment, 74% (95% confidence interval [CI], 52%–90%) of participants were considered responders. At 24 weeks of treatment, 82% (95% CI, 60%–95%) of participants were considered responders with 36% (95% CI, 20%–57%) of participants achieving complete continence. There were no device-related serious adverse events reported during the study.

Conclusions

The reimplantation of eCoin was both safe and effective in treating UUI associated with overactive bladder syndrome. The demonstrated significant reduction or resolution of symptoms with no serious safety concern suggests that eCoin is a convenient and maintainable therapeutic device.
Racial and Ethnic Disparities in Obliterative Procedures for the Treatment of Vaginal Prolapse
Authors: Winkelman William D. , Hacker Michele R. , Anand Malika , Lefevre Roger , Richardson Monica L.
Published: September 2021

Objectives

Although racial disparities are well documented for common gynecologic surgical procedures, few studies have assessed racial disparities in the surgical treatment of vaginal prolapse. This study aimed to compare the use of obliterative procedures for the treatment of vaginal prolapse across racial and ethnic groups.

Study Design

This is a retrospective cohort study of surgical cases from 2010 to 2018 from the American College of Surgeons National Surgical Quality Improvement Program, a nationally validated database. Cases were identified by Current Procedural Terminology codes. Modified Poisson regression was used to calculate risk ratios and 95% confidence intervals, adjusting for potential confounders selected a priori.

Results

We identified 45,865 surgical cases, of which 10% involved an obliterative procedure. In the unadjusted model, non-Hispanic Asian and non-Hispanic Black patients were more likely to undergo an obliterative procedure compared with non-Hispanic White patients (risk ratio [95% confidence interval], 2.4 [2.1–2.7] and 1.2 [1.03–1.3], respectively). These relative risks were largely unchanged when controlling for age, body mass index, diabetes, American Society of Anesthesiologists classification, and concurrent hysterectomy.

Conclusions

Although both obliterative and reconstructive procedures have their respective risks and benefits, the proportion of patients undergoing each procedure differs by race and ethnicity. It is unclear whether such disparities may be attributable to differences in preference or inequity in care.
T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies
Authors: Jansen Josephina A. , Omuro Antonio , Lucca Liliana E.
Published: September 2021

Purpose of review

Immunotherapies such as immune checkpoint blockade have revolutionized cancer treatment, but current approaches have failed to improve outcomes in glioblastoma and other brain tumours. T cell dysfunction has emerged as one of the major barriers for the development of central nervous system (CNS)-directed immunotherapy. Here, we explore the unique requirements that T cells must fulfil to ensure immune surveillance in the CNS, and we analyse T cell dysfunction in glioblastoma (GBM) through the prism of CNS-resident immune responses.

Recent findings

Using comprehensive and unbiased techniques such as single-cell RNA sequencing, multiple studies have dissected the transcriptional state of CNS-resident T cells that patrol the homeostatic brain. A similar approach has revealed that in GBM, tumour-infiltrating T cells lack the hallmarks of antigen-driven exhaustion typical of melanoma and other solid tumours, suggesting the need for better presentation of tumour-derived antigens. Consistently, in a mouse model of GBM, increasing lymphatic drainage to the cervical lymph node was sufficient to promote tumour rejection.

For the success of future immunotherapy strategies, further work needs to explore the natural history of dysfunction in GBM tumour-infiltrating T cells, establish whether these originate from CNS-resident T cells and how they can be manipulated therapeutically.
Contact surveys reveal heterogeneities in age-group contributions to SARS-CoV-2 dynamics in the United States
Authors: Chin Taylor , Feehan Dennis M. , Buckee Caroline O. , Mahmud Ayesha S.
Published: September 2021

SARS-CoV-2 is spread primarily through person-to-person contacts. Quantifying population contact rates is important for understanding the impact of physical distancing policies and for modeling COVID-19, but contact patterns have changed substantially over time due to shifting policies and behaviors. There are surprisingly few empirical estimates of age-structured contact rates in the United States both before and throughout the COVID-19 pandemic that capture these changes. Here, we use data from six waves of the Berkeley Interpersonal Contact Survey (BICS), which collected detailed contact data between March 22, 2020 and February 15, 2021 across six metropolitan designated market areas (DMA) in the United States. Contact rates were low across all six DMAs at the start of the pandemic. We find steady increases in the mean and median number of contacts across these localities over time, as well as a greater proportion of respondents reporting a high number of contacts. We also find that young adults between ages 18 and 34 reported more contacts on average compared to other age groups. The 65 and older age group consistently reported low levels of contact throughout the study period. To understand the impact of these changing contact patterns, we simulate COVID-19 dynamics in each DMA using an age-structured mechanistic model. We compare results from models that use BICS contact rate estimates versus commonly used alternative contact rate sources. We find that simulations parameterized with BICS estimates give insight into time-varying changes in relative incidence by age group that are not captured in the absence of these frequently updated estimates. We also find that simulation results based on BICS estimates closely match observed data on the age distribution of cases, and changes in these distributions over time. Together these findings highlight the role of different age groups in driving and sustaining SARS-CoV-2 transmission in the U.S. We also show the utility of repeated contact surveys in revealing heterogeneities in the epidemiology of COVID-19 across localities in the United States.
Epidemiology, Clinico-Pathological Characteristics, and Comorbidities of SARS-CoV-2 infected Pakistani Patients
Authors: Omer Saadia , Sarwar Muhammad Bilal , Roman Muhammad , Usman Muhammad , Alam Muhammad , Afzal Nadeem , Qaiser Tanveer Ahmed , Yasir Muhammad , Shahzad Faheem , Tahir Romeeza , Ayub Saima , Akram Javid , Jahan Shah
Published: September 2021

SARS-CoV-2 is a causative agent for COVI-19 disease, initially reported from Wuhan, China. Infected Patients experienced mild to severe symptoms, resulting in several fatalities due to a weak understanding of its pathogenesis, which is the same even to date. This cross-sectional study has been designed on four hundred and fifty-two symptomatic, mild-to-moderate, and severe/critical patients to understand the epidemiology and clinical characteristics of COVID-19 patients with their comorbidities and response to treatment. The mean age of studied patients was (58±14.42) years, and the overall male to female ratio was 61.7 to 38.2%, respectively. 27.3% of the patients had a history of exposure, 11.9% travel history, while for 60% of patients, the source of infection was unknown. The most prevalent signs and symptoms in ICU patients were dry coughs, myalgias, shortness of breath, gastrointestinal discomfort, and abnormal Chest X-ray (p<0.001), along with the high percentage of hypertension (p=0.007) and COPD (p=0.029) as leading comorbidities. Complete Blood Counts indicators were significantly increased in severe patients, while the Coagulation Profile and D-dimer values were significantly higher in mild-to-moderate (non-ICU) patients (p < 0.001). Serum Creatinine (1.22 umole L-1; p = 0.016) and LDH (619 umol L-1; p < 0.001) indicators were significantly high in non-ICU patients while, raised values of Total Bilirubin (0.91 umol L-1; p = 0.054), CRP (84.68 mg L-1; p = 0.001) and Ferritin (996.81 mg L-1; p < 0.001) were found in ICU patients. Drug Dexamethasone was the leading prescribed and administrated medicine to the COVID-19 patients, followed by Remdesivir, Meropenem, Heparin, and Tocilizumab, respectively. A characteristic pattern of Ground glass opacities (GGO), consolidation, and interlobular septal thickening were prominent in severely infected patients. These findings could be used for future research, control, and prevention of SARS-CoV-2 infected patients.
Deactivation of SARS-CoV-2 surrogate porcine epidemic diarrhea virus with electron beam irradiation under the cold chain transportation condition
Authors: Liu Yan , Shao Yang , Wang Lu , Lu Weilai , Li Shihua , Xu Diandou , Fu Yu Vincent
Published: September 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prevailed all over the world and emerged as a significant public health emergency. The rapid outbreak of SARS-CoV-2 is largely due to its high transmission capacity. Studies implied that the cold chain logistics would be a potential route for the spread of SARS-CoV-2. The low temperature condition of the cold chain is conducive to survival and transmission of virus. Thus, the virus disinfection in cold chain should not be neglected for controlling COVID-19. However, due to the low temperature feature of the cold-chain, the virus disinfecting methods suitable in cold chain are limited. Here the high-energy electron beam irradiation is proposed to disinfect the SARS-CoV-2 in cold chain logistics. We evaluated the impact of high-energy electron beam irradiation on porcine epidemic diarrhea virus (PEDV), an enveloped virus surrogate for SARS-CoV-2, and explored the possible mechanism of the action of high-energy electron beam irradiation on PEDV. The irradiation dose of 10 kGy inactivated 98.1 % PEDV on the both top and bottom surfaces of various packaging materials under cold chain frozen condition. High-energy electron beam inactivated PEDV by inducing damages on viral genome or even capsid.
Flygenvectors: The spatial and temporal structure of neural activity across the fly brain
Authors: Schaffer Evan S. , Mishra Neeli , Whiteway Matthew R. , Li Wenze , Vancura Michelle B. , Freedman Jason , Patel Kripa B. , Voleti Venkatakaushik , Paninski Liam , Hillman Elizabeth M.C. , Abbott L.F. , Axel Richard
Published: September 2021

What are the spatial and temporal scales of brainwide neuronal activity, and how do activities at different scales interact? We used SCAPE microscopy to image a large fraction of the central brain of adultDrosophila melanogasterwith high spatiotemporal resolution while flies engaged in a variety of behaviors, including running, grooming and flailing. This revealed neural representations of behavior on multiple spatial and temporal scales. The activity of most neurons across the brain correlated (or, in some cases, anticorrelated) with running and flailing over timescales that ranged from seconds to almost a minute. Grooming elicited a much weaker global response. Although these behaviors accounted for a large fraction of neural activity, residual activity not directly correlated with behavior was high dimensional. Many dimensions of the residual activity reflect the activity of small clusters of spatially organized neurons that may correspond to genetically defined cell types. These clusters participate in the global dynamics, indicating that neural activity reflects a combination of local and broadly distributed components. This suggests that microcircuits with highly specified functions are provided with knowledge of the larger context in which they operate, conferring a useful balance of specificity and flexibility.
Comparative genomics reveals electron transfer and syntrophic mechanisms differentiating methanotrophic and methanogenic archaea
Authors: Chadwick Grayson L , Skennerton Connor T , Laso-Pérez Rafael , Leu Andy O , Speth Daan R , Yu Hang , Morgan-Lang Connor , Hatzenpichler Roland , Goudeau Danielle , Malmstrom Rex , Brazelton William J , Woyke Tanja , Hallam Steven J , Tyson Gene W , Wegener Gunter , Boetius Antje , Orphan Victoria J
Published: September 2021

The anaerobic oxidation of methane coupled to sulfate reduction is a microbially mediated process requiring a syntrophic partnership between anaerobic methanotrophic (ANME) archaea and sulfate reducing bacteria (SRB). Based on genome taxonomy, ANME lineages are polyphyletic within the phylumHalobacterota, none of which have been isolated in pure culture. Here we reconstruct 28 ANME genomes from environmental metagenomes and flow sorted syntrophic consortia. Together with a reanalysis of previously published datasets, these genomes enable a comparative analysis of all marine ANME clades. We review the genomic features which separate ANME from their methanogenic relatives and identify what differentiates ANME clades. Large multiheme cytochromes and bioenergetic complexes predicted to be involved in novel electron bifurcation reactions are well-distributed and conserved in the ANME archaea, while significant variations in the anabolic C1 pathways exists between clades. Our analysis raises the possibility that methylotrophic methanogenesis may have evolved from a methanotrophic ancestor.
Clinician and patient experience of neurology telephone consultations during the COVID-19 pandemic
Authors: Nakornchai Tagore , Conci Elena , Hensiek Anke , Brown J William L
Published: September 2021

Background

Telephone consultations are already employed in specific neurological settings. At Cambridge University Hospitals, the COVID-19 pandemic initially prompted almost all face-to-face appointments to be delivered by telephone, providing a uniquely unselected population to assess.

Objectives

We explored patient and clinician experience of telephone consultations; and whether telephone consultations might be preferable for pre-identifiable subgroups of patients after the pandemic.

Methods

Clinicians delivering neurological consultations converted to telephone between April-July 2020 were invited to complete a questionnaire following each consult (430 respondents) and the corresponding patients were subsequently surveyed (290 respondents). The questionnaires assessed clinician and patient goal achievement (and the reasons for any dissatisfaction). Clinicians also described consultation duration (in comparison to face-to-face) while patients detailed comparative convenience and preference.

Results

The majority of clinicians (335/430, 78%) and patients (227/290, 78%) achieved their consultation goals by telephone, particularly during follow-up consultations (clinicians 272/329, 83%, patients 176/216, 81%) and in some disease subgroups (e.g. seizures/epilepsy (clinicians 114/122 (93%), patients 71/81 (88%)). 95% of telephone consultations were estimated to take the same or less time than an equivalent face-to-face consultation. Most patients found telephone consultations convenient (69%) with 149/211 (71%) indicating they would like telephone or video consultations to play some role in their future follow-up.

Conclusion

Telephone consultations appear effective, convenient and popular in prespecified subgroups of neurological outpatients. Further work comparing telephone, video and face-to-face consultations across multiple centres is now needed.
Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke
Authors: Irie Takashi , Matsuda Taito , Hayashi Yoshinori , Kamiya Akihide , Kira Jun-ichi , Nakashima Kinichi
Published: September 2021

Ischaemic brain injury causes permanent neuronal loss, which often results in persistent severe neurological dysfunctions. Although generating new neurons in the injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability. Here, we show that direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischaemic brain injury. After transient middle cerebral artery occlusion in adult mice, microglia/macrophages converge at the lesion core of the striatum, where neuronal loss is prominent. Targeted expression of a neurogenic transcription factor, NeuroD1, in microglia/macrophages in the injured striatum enables their conversion into induced neuronal cells that functionally integrate into the existing neuronal circuits. Furthermore, NeuroD1-mediated induced neuronal cell generation significantly improves neurological function in the mouse stroke model, and ablation of these cells abolishes the gained functional recovery. Our findings thus demonstrate that neuronal conversion contributes directly to functional recovery after stroke and shed further light on the development of therapies for ischaemic brain injury by in situ neuronal conversion technology.
Broadscale evolutionary analysis of eukaryotic DDE transposons
Authors: Dupeyron Mathilde , Baril Tobias , Hayward Alexander
Published: September 2021

DDE transposons are widespread selfish genetic elements, often comprising a large proportion of eukaryotic genomic content. DDE transposons have also made important contributions to varied host functions during eukaryotic evolution, and their transposases may be the most abundant and ubiquitous genes in nature. Yet much remains unknown about their basic biology. We employ a broadscale screen of DDE transposase diversity to characterise major evolutionary patterns for all 19 DDE transposon superfamilies. We identify considerable variation in DDE transposon superfamily size, and find a dominant association with animal hosts. While few DDE transposon superfamilies specialise in plants or fungi, the four largest superfamilies contain major plant-associated clades, at least partially underlying their relative success. We recover a pattern of host conservation among DDE transposon lineages, punctuated by occasional horizontal transfer to distantly related hosts. Host range and horizontal transfer are strongly positively correlated with DDE transposon superfamily size, arguing against variation in the capacity for generalism. We find that rates of horizontal transfer decrease sharply with increasing levels of host taxonomy, supporting the existence of host-associated barriers to DDE transposon spread. Overall, despite their relatively simple genetic structure, our results imply that trade-offs in host adaptation are important in defining DDE transposon-host relationships and evolution. In addition, our study provides a phylogenetic framework to facilitate the identification and further analysis of DDE transposons.
Rapid evolution and strain turnover in the infant gut microbiome
Authors: Chen Daisy W. , Garud Nandita R.
Published: September 2021

While the ecological dynamics of the infant gut microbiome have been intensely studied, relatively little is known about the evolutionary dynamics in the infant gut microbiome. Here we analyze longitudinal fecal metagenomic data from >700 infants and their mothers over the first year of life and find that the evolutionary dynamics in infant gut microbiomes are distinct from that of adults. We find evidence for almost 100-fold increase in the rate of evolution and strain turnover in the infant gut compared to healthy adults, with the mother-infant transition at delivery being a particularly dynamic period in which gene loss dominates. Within a few months after birth, these dynamics stabilize, and gene gains become increasingly frequent as the microbiome matures. We furthermore find that evolutionary changes in infants show signatures of being seeded by a mixture ofde novomutations and transmissions of pre-evolved lineages from the broader family. Several of these evolutionary changes occur in parallel in multiple infants, highlighting candidate genes that may play important roles in the development of the infant gut microbiome. Our results point to a picture of a volatile infant gut microbiome characterized by rapid evolutionary and ecological change in the early days of life.
Injectable Liposome-based Supramolecular Hydrogels for the Programmable Release of Multiple Protein Drugs
Authors: Correa Santiago , Grosskopf Abigail K. , Klich John H. , Hernandez Hector Lopez , Appel Eric A.
Published: September 2021

Directing and manipulating biological functions is at the heart of next-generation biomedical initiatives such as tissue and immuno-engineering. Yet, the ambitious goal of engineering complex biological networks requires the ability to precisely perturb specific signaling pathways at distinct times and places. Using lipid nanotechnology and the principles of supramolecular self-assembly, we have developed an injectable liposomal nanocomposite hydrogel platform to precisely control drug presentation through programing of the co-release of multiple protein drugs. These liposomal hydrogels exhibited robust shear-thinning and self-healing behaviors enabling facile injectability for local drug delivery applications. By integrating modular lipid nanotechnology into this hydrogel platform, we introduced multiple mechanisms of protein release based on liposome surface chemistry. When injected into immuno-competent mice, these liposomal hydrogels exhibited formulation-dependent rates of dissolution and excellent biocompatibility. To fully validate the utility of this system for multi-protein delivery, we demonstrated the synchronized, sustained, and localized release of IgG antibody and IL-12 cytokine in vivo, despite the significant size differences between these two proteins. Overall, these liposomal nanocomposite hydrogels are a highly modular platform technology with the ability the mediate orthogonal modes of protein release and the potential to precisely coordinate biological cues both in vitro and in vivo.
SARS- CoV-2 viroporins: A multi-omics insight from nucleotides to amino acids
Authors: Sarkar Manish , Etheimer Paul , Hannothiaux Victor , Saha Soham
Published: September 2021

COVID-19 is caused by SARS-CoV-2 which has so far affected more than 500 million people worldwide and killed over 6 million as of 1st May, 2022. The approved emergency-use vaccines were lifesaving to such a devastating pandemic. Viroporins are important players of the life cycle of SARS-CoV-2 and are primary to its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a sequential and structural point of view. Orf3a is a cation selective viral ion channel which has been shown to disrupt the endosomal pathways. E protein is one of the most conserved proteins among the SARS-CoV proteome which affects the ERGIC related pathways. The aqueous medium through the viroporins mediates the non-selective translocation of cations, affecting ionic homeostasis in the host cellular compartments. This ionic imbalance could potentially lead to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be potentially leveraged for the development of antiviral therapeutics. Our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated.
Human neutrophils are not activated by Zika virus but reduce the infection of susceptible cells
Authors: Aggio Juliana Bernardi , Porto Bárbara Nery , dos Santos Claudia Nunes Duarte , Mosimann Ana Luiza Pamplona , Wowk Pryscilla Fanini
Published: September 2021

Zika virus (ZIKV) emergence highlighted the need for a deeper understanding on virus-host interaction to pave the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are an important effector cell in innate immunity involved in the host response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strains replication. Indeed, after stimulation with ZIKV, neutrophils were not primed against the virus as evaluated by the absence of CD11b modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, ZIKV infection of primary innate immune cells in vitro did not trigger neutrophil migration. However, neutrophil co-cultured with ZIKV susceptible cells (A549) resulted in lower frequencies of infection on A549 cells by cell-to-cell contact. In vivo, neutrophil depletion from immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest human neutrophils do not play a per se antiviral role against ZIKV, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.
G4-Selective Ligand Induced Autophagy
Authors: Majumder Piyali , Shukla Chinmayee , Datta Bhaskar
Published: September 2021

G-quadruplex (G4) structures have emerged as singular therapeutic targets for cancer and neurodegeneration. Autophagy is a housekeeping cellular homeostatic mechanism and deregulation of autophagy is common in cancer and in neurodegenerative diseases. In this study, we identified the presence of 46 putative G4 sequences in the MTOR gene by use of QGRS mapper tool. We sought to connect these putative G4 sequences to a functional context by leveraging G4-targeting ligands. A G4-selective dimeric carbocyanine dye Bis-4,3 and the porphyrin TMPyP4 were used to affect the replication, transcription and translation of the MTOR gene. The ligand-induced induction of autophagic pathway via MTOR gene regulation was monitored upon treatment of HeLa and SHSY-5Y cells with G4-targeting ligands. The use of Bis-4,3 was compared with the known G4-stabilizing activity of TMPyP4. Our results show that treatment with G4-selective ligands downregulates mTOR activity and leads to the induction of excessive autophagy. This is first report on effect of G4-selective ligands on MTOR regulation and mTOR expression. mTOR being the key negative regulator of autophagy, the current work suggests potential of G4 stabilizing ligands towards induction of autophagy through the downregulation of mTOR.