bluuebunny/crossref_metadata_2025 huggingface dataset:
Did people’s behavior after receiving negative COVID-19 tests contribute to the spread?
Authors: Robertson Leon S
Published: January 2021

Background

Testing on demand for coronavirus disease (COVID-19) is hypothesized to increase spread of the virus as some persons who test negative falsely assume that they can engage in activities that increase spread.

Methods

Daily new COVID-19 hospitalization counts through 2020 from 25 countries that reported testing and hospitalizations were studied by regression of logarithms of new hospitalizations 14 days out against log(new hospitalizations on a given day), log(negative tests), log(positivity rate) and days since the first hospitalizations were reported. The regression coefficients were examined separately for periods in countries that were following three different testing policies.

Results

Corrected for the other factors, negative test numbers when tested on demand and tested if symptomatic only are associated with an increase in hospitalizations 14 days after the tests. When only the symptomatic and more vulnerable are tested, negative tests are associated with fewer hospitalizations 2 weeks out.

Conclusions

A policy of testing only vulnerable populations, whether symptomatic or not, appears to avoid spreading the virus as a result of testing policy. False confidence of reduced risk among those who test negative may have contributed to the spread in countries that allowed testing on demand or testing only those who claimed to have symptoms.
Roles of the MPFC and insula in impression management under social observation
Authors: Yoon Leehyun , Kim Kwangwook , Jung Daehyun , Kim Hackjin
Published: January 2021

People often engage in impression management by presenting themselves and others as socially desirable. However, specific behavioral manifestations and underlying neural mechanisms of impression management remain unknown. In this study, we investigated the neural mechanism of impression management during self- and friend-evaluation. Only participants assigned to the observation (OBS) group, not the control (CON) group, were informed that their responses would be monitored. They answered how well positive and negative trait adjectives described themselves or their friends. The behavioral results showed that the OBS group was more likely to reject negative traits for self-evaluation and to accept positive traits for friend-evaluation. An independent study revealed that demoting negative traits for oneself and promoting positive traits for a friend helps manage one’s impression. In parallel with the behavioral results, in the OBS vs the CON group, the rostromedial prefrontal cortex (rmPFC) and anterior insula (AI) activity showed a greater increase as the negativity of negatively valenced adjectives increased during self-evaluation and also showed a greater increase as the positivity of positively valenced adjectives increased during friend-evaluation. The present study suggests that rmPFC and AI are critically involved in impression management, promoting socially desirable target evaluations under social observation.
Amphibioplanidae: a new branch and family on the phylogenetic tree of the triclad flatworms (Platyhelminthes: Tricladida), represented by a species from Sardinian caves with a remarkable lifestyle
Authors: Stocchino Giacinta Angela , Dols-Serrate Daniel , Sluys Ronald , Riutort Marta , Onnis Carlo , Manconi Renata
Published: January 2021

In this study we document the phylogenetic position and the anatomical and ecological characteristics of a new taxon of cave-dwelling triclad flatworms. This species from the Mediterranean island of Sardinia (Italy) forms a separate branch on the phylogenetic tree of the planarians for which we proposed a new genus and placed it in a new family. Molecular analysis reveals a sister-group relationship between this new family, Amphibioplanidae, and the family Dimarcusidae of the suborder Cavernicola, together constituting the sister-group of the suborder Maricola. The new species Amphibioplana onnisi Stocchino & Sluys, sp. nov. is slender and furnished with an epidermis that is abundantly and uniformly provided with cilia and rhabdites. The pharynx presents an oesophageal projection pointing into the pharynx lumen. Ovaries are located far behind the brain. A relatively long common oviduct opens into the diverticulum of the bursal canal. The probursal copulatory bursa is lined with a highly vacuolated, syncytial epithelium. The habitat of this species is formed by groundwater in microcrevices of the epikarst and temporary cave pools, but the animals can survive in a basically terrestrial environment, thus exhibiting an amphibious lifestyle. Some tentative scenarios are discussed for the evolution of the new taxon and for the presence of the new species in three separate caves in Sardinia.
Anxiety in Residents in China: Prevalence and Risk Factors in a Multicenter Study
Authors: Bai Song , Chang Qing , Yao Da , Zhang Yixiao , Wu Bin , Zhao Yuhong
Published: January 2021

Purpose

To explore the prevalence of major anxiety and its associated risk factors in residents in China.

Method

This multicenter, cross-sectional study was conducted from December 2019 to February 2020; 1,343 residents from 8 hospitals in Northeast China were included in the final analysis (effective response rate of 86.48%). Demographic characteristics, dietary habits, life-related factors, work-related factors, and psychological characteristics were collected from participants via a self-reported questionnaire. This questionnaire measured sleep quality, physical activity, anxiety, perceived organizational support, psychological capital, and burnout. Adjusted odds ratios (ORs) and 95% confidence intervals were determined using binary logistic regression. Cutoff values and the area under the curve were calculated for risk factors using receiver operating characteristic curve analysis.

Results

Of participants, 441 (32.80%) reported anxiety symptoms and 133 (9.90%) reported major anxiety symptoms. Four independent risk factors for major anxiety were identified: poor sleep quality (OR = 1.282, P < .001) and 3 dimensions of burnout: higher emotional exhaustion (OR = 1.085, P < .001), higher depersonalization (OR = 1.064, P = .002), and reduced personal accomplishment (OR = 0.951, P < .001). The optimal cutoff values for these risk factors were 7, 10, 9, and 22 scores, respectively.

Conclusions

This study found a considerable prevalence of major anxiety symptoms in residents in China and identified poor sleep quality and higher levels of burnout as having a close association with major anxiety. These findings enrich the existing literature on anxiety and demonstrate a critical need for additional studies that investigate intervention strategies to improve sleep quality and combat burnout, which could improve the mental health of residents.
Distribution and Predictors of Initial Glaucoma Care Among Ophthalmologists and Optometrists: A Population-based Study
Authors: Quinn Matthew P. , Johnson Davin , Whitehead Marlo , Gill Sudeep S. , Campbell Robert J.
Published: January 2021

Purpose:

To evaluate evolution in the distribution of new glaucoma patients between ophthalmologists and optometrists, and to examine factors predicting provider type, in the context of expansion in the scope of optometry practice.

Patients and Methods:

A population-based study was undertaken using validated datasets in Ontario, Canada from 2007 to 2018, encompassing time before and after optometry practice scope expansion in 2011. All patients aged 66 and older receiving a glaucoma suspect diagnosis or first-line therapy for glaucoma from ophthalmologists or optometrists were enrolled. Predictors of provider type were evaluated using logistic regression.

Results:

From 2007 to 2018, 401,560 patients received initial glaucoma care, including 303,440 by ophthalmologists and 98,120 by optometrists. Population rates of glaucoma suspect diagnosis increased for both providers over the study period. The rate of therapy initiation increased annually among optometrists after 2011, while the rate remained stable over that period among ophthalmologists. By 2018, 88% of patients initiating therapy and 59% of patients first diagnosed as a glaucoma suspect received that care from ophthalmologists. In the final study year, therapy initiations per provider were lower among optometrists (median: 2/provider; interquartile range: 1 to 3) than among ophthalmologists (median: 26.5/provider, interquartile range: 10 to 53). Patients were more likely to receive care from an ophthalmologist than an optometrist if they were older, had higher ocular or systemic comorbidity, or lived in urban settings.

Conclusions:

Optometrists have a large and growing role in diagnosing glaucoma suspects; however, despite scope expansion, optometrists play a much smaller role in initiating glaucoma therapy.
Nurse Leaders' Experiences and Learnings Navigating Through the Chaos of a Pandemic
Authors: Cathro Heather , Blackmon Emily
Published: January 2021

This article explores the experiences and learnings of 2 ambulatory care nurse leaders on the front lines of the Covid-19 pandemic using the theory “navigating through chaos” as a framework.
Reinventing the Delivery of Care in a New Women and Children's Center Using an Integrated Lean Model
Authors: Bacon Cynthia Thornton , Pedaline Susan , Henderson Karin , Jenkins Marjorie
Published: January 2021

This article describes one heath system's creation of a new women's health hospital using an innovative model integrating patient care delivery, Lean building design, and Lean integrated project methodology. The article describes a 5-year journey detailing the innovative process that guided the planning and implementation of the new care delivery model, as well as employee and leader roles, employee behavior and engagement, and key insights and lessons learned that will benefit nurse leaders.
Extravasation Volume at Computed Tomography Angiography Correlates With Bleeding Rate and Prognosis in Patients With Overt Gastrointestinal Bleeding
Authors: Tse Justin R. , Shen Jody , Shah Rajesh , Fleischmann Dominik , Kamaya Aya
Published: January 2021

Objective

Despite the identification of active extravasation on computed tomography angiography (CTA) in patients with overt gastrointestinal bleeding (GIB), a large proportion do not have active bleeding or require hemostatic therapy at endoscopy, catheter angiography, or surgery. The objective of our proof-of-concept study was to improve triage of patients with GIB by correlating extravasation volume of first-pass CTA with bleeding rate and clinical outcomes.

Materials and Methods

All patients who presented with overt GIB and active extravasation on CTA from January 2014 to July 2019 were reviewed in this retrospective, institutional review board–approved and Health Insurance Portability and Accountability Act–compliant study. Extravasation volume was assessed using 3-dimensional software and correlated with hemostatic therapy (primary endpoint) and with intraprocedural bleeding, blood transfusions, and mortality as secondary endpoints using logistic regression models (P < 0.0125 indicating statistical significance). Odds ratios were used to determine the effect size of a threshold extravasation volume. Quantitative data (extravasation volume, aorta attenuation, extravasation attenuation and time) were input into a mathematical model to calculate bleeding rate.

Results

Fifty consecutive patients including 6 (12%) upper, 18 (36%) small bowel, and 26 (52%) lower GIB met inclusion criteria. Forty-two underwent catheter angiography, endoscopy, or surgery; 16 had intraprocedural active bleeding, and 24 required hemostatic therapy. Higher extravasation volumes correlated with hemostatic therapy (P = 0.007), intraprocedural active bleeding (P = 0.003), and massive transfusion (P = 0.0001), but not mortality (P = 0.936). Using a threshold volume of 0.80 mL or greater, the odds ratio of hemostatic therapy was 8.1 (95% confidence interval, 2.1–26), active bleeding was 11.8 (2.6–45), and massive transfusion was 18 (2.3–65). With mathematical modeling, extravasation volume had a direct and linear relationship with bleeding rate, and the lowest calculated detectable bleeding rate with CTA was less than 0.1 mL/min.

Conclusions

Larger extravasation volumes correlate with higher bleeding rates and may identify patients who require hemostatic therapy, have intraprocedural bleeding, and require blood transfusions. Current CTAs can detect bleeding rates less than 0.1 mL/min.
Planning and Osteotomy Designs in the Correction of Single-Suture Craniosynostosis
Authors: Bertrand Anthony A. , Hu Allison C. , Lee Justine C.
Published: January 2021

Background

Craniosynostosis is among the abnormalities that are more commonly encountered by craniofacial surgeons. Although the overall concepts for cranial vault remodeling are relatively simple, osteotomy designs and methods for calvarial rearrangement are highly varied. In this work, we present a summary of the known designs for correction of single-suture craniosynostosis.

Methods

A review of the literature was performed of the more frequently used osteotomy designs for single-suture craniosynostosis, as well as their reported results and outcomes. Also reviewed are some of the current available approaches for the diagnosis and surgical planning for single-suture craniosynostosis.

Results

There remains a diversity of techniques available for the reconstruction of each fused cranial suture. Certain osteotomy designs are reported in the literature and are used by craniofacial surgeons more frequently. Each has its own benefits and disadvantages, and there is a growing body of outcome data available to guide surgical decision-making. Regarding diagnosis and surgical planning, computed tomography with 3-dimensional reconstruction remains the diagnostic standard of care, and efforts are ongoing to develop and implement new diagnostic modalities like Black Bone MRI to reduce radiation exposure.

Conclusions

There has been ongoing evolution of the surgical techniques available to reconstruct single-suture craniosynostosis, leading to ever-improving patient outcomes.
Feasibility of Customised Polymethyl Methacrylate Implants Fabricated Using 3D Printed Flexible Moulds for Correction of Facial Skeletal Deformities
Authors: Jain Rahul , Mahendru Sanjay , Aggarwal Aditya , Brajesh Vimalendu , Aulakh Hardeep Singh , Singh Sukhdeep , Jain Ankit , Khazanchi Rakesh K.
Published: January 2021

Introduction:

Use of patient specific Polymethyl methacrylate (PMMA) implants for the reconstruction of cranial defects has become a standard practice with excellent long-term results. However, for the reconstruction of midface and mandibular osseous defects other alloplastic materials are preferred but their use is limited due to high cost. This is a report of our experience with the use of low-cost patient specific PMMA implants fabricated using 3D printed moulds in the reconstruction of osseous defects involving different areas of the facial skeleton not limited to cranium.

Methods:

The 25 consecutive patients with craniofacial osseous defects who underwent reconstruction using customized PMMA implants were analyzed. All PMMA implants were fabricated intraoperatively with the use of 3D printed flexible moulds or templates.

Results:

A total of 34 implants were used in 25 consecutive patients. Out of 34 implants 25 were used for midface and mandibular osseous defects. Most common etiology was post-traumatic deformity (n = 19) followed by tumor (n = 3), craniofacial anomalies (n = 2) and post-craniotomy (n = 1). One patient out of 25 (n = 1) had postoperative implant exposure. The follow-up was ranged from 3 to 19 months with an average of 12 months. The aesthetic outcome was found to be good to excellent with mean visual analogue score of 4.08.

Conclusions:

Polymethyl methacrylate implants fabricated intraoperatively using 3D printed moulds provide accurate and precise reconstruction at an exceptionally low cost. PMMA has an excellent moulding property with low infection rates. As shown in our study its application may be easily extended to all areas of the craniofacial skeleton.
Infraorbital Nerve Decompression for Chronic Post Traumatic Neuralgia: A Novel Approach and Review of the Safety and Efficacy of Piezoelectric Surgery on Soft Tissues and Nerves
Authors: Viennas Lambros K. , Wagner Maxwell S.
Published: January 2021

Chronic post traumatic infraorbital nerve (ION) hyperesthesia is a rare complication of orbital floor fractures. Surgical decompression of the ION has been reported to relieve chronic post traumatic infraorbital neuralgia. This case report describes a novel approach for ION decompression in a patient who suffered from chronic infraorbital neuralgia associated with a healed displaced orbital floor fracture. We used an intraoperative 3D image-guided navigation system to accurately localize the fracture site and employed piezoelectric surgery for nerve decompression. We further review the literature on the safety and efficacy of piezoelectric surgery on soft tissue and nerves.
Time Reduction by Prebending Osteosynthesis Plates Using 3D-Printed Anatomical Models, In Patients Treated With Open Reduction and Internal Fixation
Authors: Rendón-Medina Marco Aurelio , Hanson-Viana Erik , Montoya-García Silvia Claudia , Vázquez-Morales Hecly Lya , Pacheco-López Ricardo César
Published: January 2021

Introduction:

The incidence of facial bones fractures is 18 to 32 for each 100,000 inhabitants. The most affected population are young working people. Fractures are most commonly caused by assaults and motor vehicle accidents. Its cost of care reaches 1.06 billion dollars. Premodeling osteosynthesis plates with anatomical models can decrease surgical time, bleeding, and increase patient satisfaction. This study aims to evaluate the impact of premodeled osteosynthesis plates, using anatomical models in patients with facial fractures.

Material and Methods:

Patients with facial fractures treated by open reduction and internal fixation were included—Group A without premolding plates and Group B with premolding. The variables studied were: age, sex, etiology of the fractures, number of fractures, among other variables that reflect the quality of the results.

Results:

A total of 17 osteosynthesis plates were included in 6 patients. The age was 22 to 47 years; all patients were male. The maximum surgery time was 129 to 300 minutes. The average time to start work was 4.8 weeks. When comparing the variables between the groups, we found no difference between the groups for bleeding P = 0.24, the start of work P = 0.19, the time of surgery P = 0.082, or for osteosynthesis time P = 0.15. There was only a significant difference in patient satisfaction, P = 0.04.

Conclusions:

The evidence collected shows that premodeling the plates only improves patients’ satisfaction among facial fractures treated by open reduction and internal fixation.
In vitro synergy of 5-nitrofurans, vancomycin and sodium deoxycholate against Gram-negative pathogens
Authors: Olivera Catrina , Le Vuong Van Hung , Davenport Catherine , Rakonjac Jasna
Published: January 2021

Introduction. There is an urgent need for effective therapies against bacterial infections, especially those caused by antibiotic-resistant Gram-negative pathogens.

Hypothesis. Synergistic combinations of existing antimicrobials show promise due to their enhanced efficacies and reduced dosages which can mitigate adverse effects, and therefore can be used as potential antibacterial therapy.

Aim. In this study, we sought to characterize the in vitro interaction of 5-nitrofurans, vancomycin and sodium deoxycholate (NVD) against pathogenic bacteria.

Methodology. The synergy of the NVD combination was investigated in terms of growth inhibition and bacterial killing using checkerboard and time-kill assays, respectively.

Results. Using a three-dimensional checkerboard assay, we showed that 5-nitrofurans, sodium deoxycholate and vancomycin interact synergistically in the growth inhibition of 15 out of 20 Gram-negative strains tested, including clinically significant pathogens such as carbapenemase-producing

Escherichia coli

,

Klebsiella pneumoniae

and

Acinetobacter baumannii

, and interact indifferently against the Gram-positive strains tested. The time-kill assay further confirmed that the triple combination was bactericidal in a synergistic manner.

Conclusion. This study demonstrates the synergistic effect of 5-nitrofurans, sodium deoxycholate and vancomycin against Gram-negative pathogens and highlights the potential of the combination as a treatment for Gram-negative and Gram-positive infections.
Motor Protein MYO1C is Critical for Photoreceptor Opsin Trafficking and Visual Function
Authors: Solanki Ashish K. , Walterhouse Stephen , Martin René , Obert Elisabeth , Arif Ehtesham , Rahman Bushra , Rohrer Barbel , Lipschutz Joshua , Mukherjee Rupak D. , Norris Russell A. , Sundstrom Jeffery , Knölker Hans-Joachim , Husain Shahid , Biswal Manas R. , Nihalani Deepak , Lobo Glenn P.
Published: January 2021

Unconventional myosins linked to deafness are also proposed to play a role in retinal cell physiology. However, their direct role in photoreceptor function remains unclear. We demonstrate that systemic loss of the unconventional myosin MYO1C in mice specifically affected opsin trafficking, leading to loss of visual function. Electroretinogram analysis ofMyo1cknockout (Myo1c-KO) mice showed a progressive loss of photoreceptor function. Immunohistochemistry and binding assays demonstrated MYO1C localization to photoreceptor inner and outer segments (OS) and identified a direct interaction of rhodopsin with the MYO1C cargo domain. InMyo1c-KO retinas, rhodopsin mislocalized to rod inner segments (IS) and cell bodies, while cone opsins in OS showed punctate staining. In aged mice, the histological and ultrastructural examination of the phenotype ofMyo1c-KO retinas showed progressively shorter photoreceptor OS. These results demonstrate that MYO1C is critical for opsin trafficking to the photoreceptor OS and for normal visual function.
Dynamic Prediction of SARS-CoV-2 RT-PCR status on Chest Radiographs using Deep Learning Enabled Radiogenomics
Authors: Chiu Wan Hang Keith , Poplavskiy Dmytro , Zhang Sailong , Ho Yu Philip Leong , Kuo Michael D.
Published: January 2021

Reverse Transcription-Polymerase Chain Reaction (RT-PCR) is the gold standard for diagnosis of SARS-CoV-2 infection, but requires specialized equipment and reagents and suffers from long turnaround times. While valuable, chest imaging currently only detects COVID-19 pneumonia, but if it can predict actual RT-PCR SARS-CoV-2 status is unknown. Radiogenomics may provide an effective and accurate RT-PCR-based surrogate. We describe a deep learning radiogenomics (DLR) model (RadGen) that predicts a patient's RT-PCR SARS-CoV-2 status solely from their frontal chest radiograph (CXR).
Vaccination in a two-group epidemic model
Authors: Aniţa Sebastian , Banerjee Malay , Ghosh Samiran , Volpert Vitaly
Published: January 2021

Epidemic progression depends on the structure of the population. We study a two-group epidemic model with the difference between the groups determined by the rate of disease transmission. The basic reproduction number, the maximal and the total number of infected individuals are characterized by the proportion between the groups. We consider different vaccination strategies and determine the outcome of the vaccination campaign depending on the distribution of vaccinated individuals between the groups.
Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease
Authors: Levin Michael G. , Zuber Verena , Walker Venexia M. , Klarin Derek , Lynch Julie , Malik Rainer , Aday Aaron W. , Bottolo Leonardo , Pradhan Aruna D. , Dichgans Martin , Chang Kyong-Mi , Rader Daniel J. , Tsao Philip S. , Voight Benjamin F. , Gill Dipender , Burgess Stephen , Damrauer Scott M.
Published: January 2021

Background

Circulating lipid and lipoprotein levels have consistently been identified as risk factors for atherosclerotic cardiovascular disease (ASCVD), largely on the basis of studies focused on coronary artery disease (CAD). The relative contributions of specific lipoproteins to risk of peripheral artery disease (PAD) have not been well-defined. Here, we leveraged large scale genetic association data to identify genetic proxies for circulating lipoprotein-related traits, and employed Mendelian randomization analyses to investigate their effects on PAD risk.

Methods

Genome-wide association study summary statistics for PAD (Veterans Affairs Million Veteran Program, 31,307 cases) and CAD (CARDIoGRAMplusC4D, 60,801 cases) were used in the Mendelian Randomization Bayesian model averaging (MR-BMA) framework to prioritize the most likely causal major lipoprotein and subfraction risk factors for PAD and CAD. Mendelian randomization was used to estimate the effect of apolipoprotein B lowering on PAD risk using gene regions that proxy potential lipid-lowering drug targets. Transcriptome-wide association studies were performed to identify genes relevant to circulating levels of prioritized lipoprotein subfractions.

Results

ApoB was identified as the most likely causal lipoprotein-related risk factor for both PAD (marginal inclusion probability 0.86, p = 0.003) and CAD (marginal inclusion probability 0.92, p = 0.005). Genetic proxies for ApoB-lowering medications were associated with reduced risk of both PAD (OR 0.87 per 1 standard deviation decrease in ApoB, 95% CI 0.84 to 0.91, p = 9 × 10−10) and CAD (OR 0.66, 95% CI 0.63 to 0.69, p = 4 × 10−73), with a stronger predicted effect of ApoB-lowering on CAD (ratio of ORs 1.33, 95% CI 1.25 to 1.42, p = 9 × 10−19). Among ApoB-containing subfractions, extra-small VLDL particle concentration (XS.VLDL.P) was identified as the most likely subfraction associated with PAD risk (marginal inclusion probability 0.91, p = 2.3 × 10−4), while large LDL particle concentration (L.LDL.P) was the most likely subfraction associated with CAD risk (marginal inclusion probability 0.95, p = 0.011). Genes associated with XS.VLDL.P and L.LDL.P included canonical ApoB-pathway components, although gene-specific effects varied across the lipoprotein subfractions.

Conclusion

ApoB was prioritized as the major lipoprotein fraction causally responsible for both PAD and CAD risk. However, diverse effects of ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions on ASCVD, and distinct subfraction-associated genes suggest possible biologic differences in the role of lipoproteins in the pathogenesis of PAD and CAD.
A national survey of potential acceptance of COVID-19 vaccines in healthcare workers in Egypt
Authors: Hussein Aliae AR Mohamed , Galal Islam , Makhlouf Nahed A , Makhlouf Hoda A , Abd-Elaal Howaida K , Kholief Karima MS , Saad Mahmoud M , Abdellah Doaa A
Published: January 2021

Background

Since the start of COVID-19 outbreak investigators are competing to develop and exam vaccines against COVID-19. It would be valuable to protect the population especially health care employees from COVID-19 infection. The success of COVID-19 vaccination programs will rely heavily on public willingness to accept the vaccine.

Aims

This study aimed to describe the existing COVID-19 vaccine approval landscape among the health care providers and to identify the most probable cause of agreement or disagreement of COVID-19 vaccine.

Methods

A cross-sectional online survey was done.

Results

The present study included 496 health care employees, 55% were at age group from 18-45 years old. History of chronic diseases was recorded in 40.4%, and definite history of drug/food allergy in 10.1%. Only 13.5% totally agree to receive the vaccine, 32.4% somewhat agree and 40.9% disagreed to take the vaccine. Causes of disagreement were none safety, fear of genetic mutation and recent techniques and believe that the vaccine is not effective (57%, 20.2%, 17.7% and 16.6% respectively). The most trusted vaccine was the mRNA based vaccine. The age of health care employees and the presence of comorbidities or chronic diseases were the main factors related to COVID-19 acceptance (P<0.001 and 0.02 respectively).

Conclusion

Vaccine hesitancy is not uncommon in healthcare employees in Egypt and this may be an alarming barrier of vaccine acceptance in the rest of population. There is an urgent need to start campaigns to increase the awareness of the vaccine importance.
Maternal prenatal stress during the first trimester and infant birthweight in Soweto, South Africa
Authors: Kim Andrew Wooyoung , Mohamed Rihlat Said , Kuzawa Christopher W. , Norris Shane A.
Published: January 2021

Background

Approximately 14.2% of newborns are estimated to be born low birth weight (LBW) in South Africa. Past work has implicated maternal prenatal stress as a potent predictor of poor birth outcomes, including preterm birth, intrauterine growth restriction, and LBW. However, less is presently known about the impacts of prenatal stress during early gestation in low- and middle-income contexts, where public health burdens due to LBW are much higher.

Objective

We assess the effects of psychosocial stress during the first trimester on birthweight in a large sample of women (n = 657) in Soweto, South Africa, a peri-urban township located in the Greater Johannesburg area.

Methods

Data come from the Soweto First 1000 Days Cohort, a study of maternal and fetal predictors of infant birth outcomes. Multiple regression models were used to examine the impact of prenatal stress on infant birthweight.

Results

The prevalence of LBW was 16.6%. Adjusting for maternal age, gestational age, fetal gender, body mass index, and parity, maternal prenatal stress during the first trimester was a borderline predictor of lower birthweight in this sample (β = 12.7, p = 0.071, 95% CI [-26.4, 1.10]). Women who reported greater levels of stress appeared to have non-significantly longer gestations, and the negative impact of maternal stress on birthweight only appeared after adjusting for this pattern.

Conclusions

These results suggest that fetal growth restriction associated with first trimester maternal stress may contribute to lower birthweights in this sample. Our findings report modest relationships between maternal stress specific to early gestation as likely important to birth outcomes in this urban South African sample.
High Throughput Screening for Expanded CTG repeats in Myotonic Dystrophy Type 1 Using Melt Curve Analysis
Authors: Butterfield Russell J , Imburgia Carina , Mayne Katie , Newcomb Tara , Dunn Diane M , Duval Brett , Feldkamp Marcia L , Johnson Nicholas E , Weiss Robert B
Published: January 2021

Background

Myotonic dystrophy type 1 (DM1) is caused by CTG repeat expansions in the DMPK gene and is the most common form of muscular dystrophy. Patients can have long delays from onset to diagnosis, since clinical signs and symptoms are often non-specific and overlapping with other disorders. Clinical genetic testing by Southern blot or triplet-primed PCR (TP-PCR) is technically challenging and cost prohibitive for population surveys.

Methods

Here, we present a high throughput, low-cost screening tool for CTG repeat expansions using TP-PCR followed by high resolution melt curve analysis with saturating concentrations of SYBR GreenER dye.

Results

We determined that multimodal melt profiles from the TP-PCR assay are a proxy for amplicon length stoichiometry. In a screen of 10,097 newborn blood spots, melt profile analysis accurately reflected the tri-modal distribution of common alleles from 5 to 35 CTG repeats, and identified the premutation and full expansion alleles.

Conclusion

We demonstrate that robust detection of expanded CTG repeats in a single tube can be achieved from samples derived from specimens with minimal template DNA such as dried blood spots (DBS). This technique is readily adaptable to large-scale testing programs such as population studies and newborn screening programs.
Acquired olfactory loss alters functional connectivity and morphology
Authors: Iravani Behzad , Peter Moa G. , Arshamian Artin , Olsson Mats J. , Hummel Thomas , Kitzler Hagen H. , Lundström Johan N.
Published: January 2021

Removing function from a developed and functional sensory system is known to alter both cerebral morphology and functional connections. To date, a majority of studies assessing sensory-dependent plasticity have focused on effects from either early onset or long-term sensory loss and little is known how the recent sensory loss affects the human brain. With the aim of determining how recent sensory loss affects cerebral morphology and functional connectivity, we assessed differences between individuals with acquired olfactory loss (duration 7-36 months, n=20) and matched healthy controls (n=23) in their grey matter volume, using multivariate pattern analyses, and functional connectivity, using dynamic connectivity analyses, within and from the olfactory cortex. Our results demonstrate that acquired olfactory loss alters grey matter volume in, among others, posterior piriform cortex, a core olfactory processing area, as well as the inferior frontal gyrus and angular gyrus. In addition, compared to controls, individuals with acquired anosmia displayed significantly stronger dynamic functional connectivity from the posterior piriform cortex to, among others, the angular gyrus, a known multisensory integration area. No significantly stronger connectivity in healthy control participants were demonstrated. When assessing differences in dynamic functional connectivity from the angular gyrus, individuals with acquired anosmia had stronger connectivity from the angular gyrus to areas primary responsible for basic visual and taste processing. These results demonstrate that recently acquired sensory loss alters both cerebral morphology within core olfactory areas and increase dynamic functional connectivity from olfactory cortex to cerebral areas processing multisensory integration.
The visual cortex produces gamma band echo in response to broadband visual flicker
Authors: Zhigalov Alexander , Duecker Katharina , Jensen Ole
Published: January 2021

The aim of this study is to uncover the network dynamics of the human visual cortex by driving it with a broadband random visual flicker. We here applied a broadband flicker (1–720 Hz) while measuring the MEG and then estimated the temporal response function (TRF) between the visual input and the MEG response. This TRF revealed an early response in the 40–60 Hz gamma range as well as in the 8–12 Hz alpha band. While the gamma band response is novel, the latter has been termed the alpha band perceptual echo. The gamma echo preceded the alpha perceptual echo. The dominant frequency of the gamma echo was subject-specific thereby reflecting the individual dynamical properties of the early visual cortex. To understand the neuronal mechanisms generating the gamma echo, we implemented a pyramidal-interneuron gamma (PING) model that produces gamma oscillations in the presence of constant input currents. Applying a broadband input current mimicking the visual stimulation allowed us to estimate TRF between the input current and the population response (akin to the local field potentials). The TRF revealed a gamma echo that was similar to the one we observed in the MEG data. Our results suggest that the visual gamma echo can be explained by the dynamics of the PING model even in the absence of sustained gamma oscillations.

Author Summary

The properties of the neuronal dynamics governing the visual system are highly debated. While some emphasize the neuronal firing rate and evoked activity in response to visual stimuli, others emphasize the oscillatory neuronal dynamics. To investigate the dynamical properties of the visual system, we recorded the magnetoencephalography while stimulating the visual system using a broadband (1–720 Hz) visual flicker. By estimating the temporal response function (similar to cross-correlation) between the visual input and neuronal activity, we demonstrated a clear response in the gamma band that we term the gamma echo. We then constructed a physiologically realistic network model that could generate gamma-band oscillations by a pyramidal-interneuron gamma (PING) mechanism. This model allowed us to account for empirically observed response in the gamma band, and to provide novel insight on the neuronal dynamics governing the early visual system. The stage is now set for further investigating how the gamma echo is modulated by tasks such as spatial attention as well as uncovering how the echo might propagate in the visual hierarchy.
Lymphotoxin β receptor: A crucial role in innate and adaptive immune responses againstToxoplasmagondii
Authors: Tersteegen Anne , Sorg Ursula R. , Virgen-Slane Richard , Helle Marcel , Petzsch Patrick , Dunay Ildiko R. , Köhrer Karl , Degrandi Daniel , Ware Carl F. , Pfeffer Klaus
Published: January 2021

The LTβR plays an essential role in the initiation of immune responses to intracellular pathogens. In mice, the LTβR is crucial for surviving acute toxoplasmosis, however, up to now a functional analysis is largely incomplete. Here, we demonstrate that the LTβR is a key regulator required for the intricate balance of adaptive immune responses.T. gondiiinfected LTβR−/−mice show globally altered IFNγ regulation, reduced IFNγ-controlled host effector molecule expression, impaired T cell functionality and an absent anti-parasite specific IgG response resulting in a severe loss of immune control of the parasites. Reconstitution of LTβR−/−mice with toxoplasma immune serum significantly prolongs the survival followingT. gondiiinfection. Notably, analysis of RNAseq data clearly indicates a specific effect ofT. gondiiinfection on the B cell response and isotype switching. This study unfolds the decisive role of the LTβR in cytokine regulation and adaptive immune responses to controlT. gondii.
Bacterial superinfection pneumonia in SARS-CoV-2 respiratory failure
Authors: Pickens Chiagozie O. , Gao Catherine A. , Cuttica Michael , Smith Sean B. , Pesce Lorenzo , Grant Rogan , Kang Mengjia , Morales-Nebreda Luisa , Bavishi Avni A. , Arnold Jason , Pawlowski Anna , Qi Chao , Budinger GR Scott , Singer Benjamin D. , Wunderink Richard G. ,   for the NU COVID Investigators
Published: January 2021

Background

Severe community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations.

Methods

We obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care.

Results

The 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days.

Conclusions

With use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.
A rare missense variant in theATP2C2gene is associated with language impairment and related measures
Authors: Martinelli Angela , Rice Mabel , Talcott Joel B. , Diaz Rebeca , Smith Shelley , Raza Muhammad Hashim , Snowling Margaret J. , Hulme Charles , Stein John , Hayiou-Thomas Marianna E. , Hawi Ziarih , Kent Lindsey , Pitt Samantha J. , Newbury Dianne F. , Paracchini Silvia
Published: January 2021

At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in theATP2C2gene.ATP2C2was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N=360) compared to cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24,046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N=42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N=1825) (minimum p = 0.002 for nonword reading).ATP2C2encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role ofATP2C2locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.
Estimating the long-term health impact of nicotine exposure by dissecting the effects of nicotine versus non-nicotine constituents of tobacco smoke: A multivariable Mendelian randomisation study
Authors: Khouja J. N. , Sanderson E. , Wootton R.E. , Taylor A. E. , Church B. A. , Richmond R. C. , Munafo M. R.
Published: January 2021

The detrimental health effects of smoking are well-known, but the impact of long-term nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing long-term use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of long-term nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]). The results suggest that these smoking-related outcomes are not due to nicotine exposure but are caused by the other components of tobacco smoke; however, there are multiple potential sources of bias, and the results should be triangulated using evidence from a range of methodologies.
Variation in waiting times by diagnostic category: an observational study of 1951 referrals to a neurology outpatient clinic
Authors: Biggin Fran , Howcroft Timothy , Davies Quinta , Knight Jo , Emsley Hedley
Published: January 2021

Objective

To investigate the frequency of diagnoses seen among new referrals to neurology outpatient services; to understand how these services are used through exploratory analysis of diagnostic tests and follow-up appointments; and to examine the waiting times between referral and appointment.

Methods

Routine data from new NHS appointments at a single consultant-delivered clinic between Sept 2016 and January 2019 were collected. These clinical data were then linked to hospital administrative data. The combined data were assigned diagnostic categories based on working diagnoses to allow further analysis using descriptive statistics.

Results

Five diagnostic categories accounted for 62% of all patients seen within the study period, the most common of which was headache disorders. Following a first appointment, 50% of all patients were offered at least one diagnostic test, and 35% were offered a follow-up appointment, with variation in both measures by diagnostic category. Waiting times from referral to appointment also varied by diagnostic category. 65% of patients with a seizure/epilepsy disorder were seen within the 18 week referral to treatment target, compared to 38% of patients with a movement disorder.

Conclusions

A small number of diagnostic categories account for a large proportion of new patients. This information could be used in policy decision making to describe a minimum subset of categories for diagnostic coding. We found significant differences in waiting times by diagnostic category, as well as tests ordered, and follow-up offered; further investigation could address causes of variation.
Understanding non-adherence to tuberculosis medications in India using urine drug metabolite testing: a cohort study
Authors: Subbaraman Ramnath , Thomas Beena E. , Kumar J. Vignesh , Thiruvengadam Kannan , Khandewale Amit , Kokila S. , Lubeck-Schricker Maya , Kumar M. Ranjith , Gaurkhede Gunjan Rahul , Walgude Apurva Shashikant , Mercy J. Hephzibah , Kumbhar Jagannath Dattatraya , Eliasziw Misha , Mayer Kenneth H. , Haberer Jessica E.
Published: January 2021

Background

Suboptimal adherence to tuberculosis (TB) treatment is associated with increased disease recurrence and death. Little research has been conducted in India to understand TB medication non-adherence.

Methods

We enrolled adult drug-susceptible TB patients, about half of whom were people living with HIV (PLHIV), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for non-adherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for non-adherence and identified factors associated with non-adherence (negative urine test) using multivariable logistic regression. We also assessed the association between non-adherence and unfavorable treatment outcomes.

Results

Of 650 patients in the cohort, 77 (11.8%) had a negative urine test result. Non-adherence was independently associated with daily wage labor (aOR 3.1, CI: 1.3—7.7), smear-positive pulmonary disease (aOR 2.1, CI: 1.1—4.1), alcohol use (aOR 2.3, CI: 1.1—4.8), and spending 60 minutes or more picking up medication refills (aOR 9.1, CI: 1.8—45.4). PLHIV reported greater barriers to picking up medications than non-PLHIV. Among 167 patients who reported missing doses, common reasons reported included traveling away from home, forgetting, feeling depressed, and running out of pills. The odds of non-adherence was 3.8 (CI: 2.1—6.9) times higher among patients with unfavorable treatment outcomes compared to those with favorable outcomes.

Conclusion

Addressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify non-adherent patients to facilitate early intervention during treatment.

Key points

We evaluated adherence to tuberculosis medications in 650 Indian patients by conducting urine isoniazid tests collected during unannounced home visits. Structural barriers to collecting medication refills and psychosocial barriers emerged as the most important factors contributing to medication non-adherence.