bluuebunny/crossref_metadata_2025 huggingface dataset:
Agreement of Anterior Segment Parameters Between Schiempflug Topography and Swept-Source Optic Coherence Based Optic Biometry in Keratoconus and Healthy Subjects
Authors: Güçlü Hande , Akaray İrfan , Kaya Sultan , Sattarpanah Samira , Çınar Abdülkadir Can , Sakallıoğlu Kürşad , Korkmaz Selçuk , Gürlü Vuslat
Published: April 2021

Purpose:

The aim of this study is to compare anterior segment parameters, including corneal thickness (CCT), keratometry and anterior chamber depth (ACD), and white to white corneal diameter (WTW), obtained by Pentacam Schiempflug imaging and intraocular lens (IOL) Master 700 swept-source optic coherence tomography biometry in keratoconus patients and healthy subjects.

Methods:

This prospective cross-sectional instrument agreement analysis includes 88 eyes of 50 keratoconus patients and 87 eyes of 50 healthy subjects. Biometry was performed using IOL Master 700, and topography was performed using Pentacam. The keratometry values (Kf, Ks, Km, and Kmax), ACD, WTW, CCT, axial length (AL), anterior chamber angle (ACA), and lens thickness (LT) were evaluated. Levels of agreement between devices were evaluated by Bland–Altman plots with 95% limits of agreement.

Results:

Intraocular lens Master 700 showed higher WTW, ACD, pupil diameter, and CCT values than Pentacam in both the keratoconus and control groups. However, there were no statistically significant differences in flat keratometry (Kf) and steep keratometry (Ks) values between the groups.

Conclusion:

Pentacam and IOL Master 700 may be used interchangeably in normal eyes and keratoconus eyes for the measurement of keratometry values and axis; however, these two devices should not be considered interchangeable for WTW, ACD, pupil diameter, and CCT measurements in both keratoconus patients and healthy subjects.
Effects of Dose, Age, Sex, Body Weight, and Smoking on Plasma Concentrations of Olanzapine and N-desmethyl Olanzapine in Inpatients With Schizophrenia
Authors: An Huimei , Fan Hongzhen , Chen Song , Qi Siyuan , Ma Botao , Shi Jing , Wang Zhiren , Yang Fude
Published: April 2021

Purpose

This study aimed to investigate the combined effects of dose, age, sex, body weight, and smoking on plasma concentrations of olanzapine (OLA) and N-desmethyl olanzapine (DMO) in Chinese inpatients with schizophrenia.

Methods

A retrospective study including 185 inpatients was conducted. The steady-state plasma concentrations of OLA (COLA) and DMO (CDMO) were measured using high-performance liquid chromatography-tandem mass spectrometry. The combined effects of dose, age, sex, body weight, and smoking on COLA and CDMO were evaluated.

Findings

Multiple linear regression analyses revealed that dose, age, body weight, and smoking had significant effects on COLA and CDMO in inpatients with schizophrenia treated with OLA. The dose was the most important determinant of COLA and CDMO and was positively correlated with both. Furthermore, smokers exhibited a significantly lower COLA and COLA + DMO, whereas higher body weight led to the reduction of COLA, CDMO, and COLA + DMO. Advanced age was associated with lower CDMO.

Implications

These results suggest that dose, age, body weight, and smoking have a significant influence on the plasma concentration of OLA and its metabolite DMO. Clinicians should consider the combined effects when prescribing OLA to patients with schizophrenia.
Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome
Authors: Chen Chen X. , Carpenter Janet S. , Gao Xiang , Toh Evelyn , Dong Qunfeng , Nelson David E. , Mitchell Caroline , Fortenberry J. Dennis
Published: April 2021

Background

Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms.

Objectives

The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses.

Methods

We conducted a prospective, longitudinal, pilot study of 20 women (aged 15–24 years) grouped into three dysmenorrhea symptom-based phenotypes: “mild localized pain,” “severe localized pain,” and “severe multiple pain and gastrointestinal symptoms.” Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa.

Results

The vaginal microbiome compositions (n = 40) were different across the three phenotypes. After separating the on-menses (n = 20) and off-menses (n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the “mild localized pain” phenotype, participants in the “multiple severe symptoms” phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses.

Discussion

The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women’s quality of life.
Ocular Point-of-Care Ultrasound
Authors: Shah Rahul , Rychwalski Paul , Kurzweil Ami , Tory Heather , Chicaiza Henry
Published: April 2021

Ocular point-of-care ultrasound has been used to assess for intraocular pathology, including retinal and vitreous detachment. We describe a pediatric patient whose initial point-of-care ultrasound examination appeared to be consistent with bilateral posterior vitreous detachment but who was ultimately diagnosed with intermediate uveitis.
Development of a Parent-Reported Outcome Measure for Febrile Infants ≤60 Days Old
Authors: Aronson Paul L. , Fleischer Eduardo , Schaeffer Paula , Fraenkel Liana , Politi Mary C. , White Marney A.
Published: April 2021

Objective

We aimed to develop a parent-reported outcome measure for febrile infants 60 days or younger evaluated in the emergency department.

Methods

We conducted a 3-part study: (1) individual, semistructured interviews with parents of febrile infants 60 days or younger to generate potential items for the measure; (2) expert review with pediatric emergency medicine physicians and member checking with parents, who rated each item's clarity and relevance using 4-point scales; and (3) cognitive interviews with a new sample of parents, who gave feedback and rated the measure's ease of use on a 4-point scale. The measure was iteratively revised during each part of the development process.

Results

In part 1, we interviewed 24 parents of 21 infants. Interviews revealed several themes: parents' experiences with medical care, communication, and decision making; parents' emotions, particularly worry, fear, and stress; the infant's outcomes valued by parents; and the impact of the infant's illness on the family. From these themes, we identified 22 potential items for inclusion in the measure. In part 2, 10 items were revised for clarity based on feedback from physicians and parents, primarily under the domains of parents' emotions and the infant's outcomes. In part 3, we further revised the measure for clarity and added an item. The final measure included 23 items and was rated as excellent in its ease of use.

Conclusions

The 23-item parent-reported outcome measure includes the experiences and outcomes important to parents. Further studies are needed to evaluate the measure's psychometric properties.
Agitation and Restraint in a Pediatric Psychiatric Emergency Program
Authors: Agraharkar Shilpa , Horwitz Sarah , Lewis Kristen , Goldstein Gabriella , Havens Jennifer , Gerson Ruth
Published: April 2021

Objectives

Agitation and restraint among pediatric psychiatric patients are a frequent, yet little studied, source of morbidity and, rarely, mortality in the emergency department (ED). This study examined agitation and restraint among youth patients in a specialized pediatric psychiatric ED, considering clinical and sociodemographic characteristics of those who required restraint to determine the clinical correlates of agitation and restraint in this population.

Methods

This descriptive study was a 6-year retrospective chart review of all patients restrained for acute agitation. Demographics, clinical characteristics, diagnoses, and reasons for restraint were collected. Relationships between sociodemographic and clinical variables to types of restraints used were examined, along with change over the study period in rate of and mean time in restraint.

Results

The average restraint rate was 1.94%, which remained fairly consistent throughout study period, although average time in restraint decreased significantly. Restraints were more common in males. Adolescents were overrepresented in the ED population, and after controlling for this, restraint rates were similar in adolescents and younger children. Physical aggression was the most frequent precipitant, although among adolescents verbal aggression was also a precipitant (more so than in younger children). Disruptive behavior disorder diagnoses were most frequently associated with restraint.

Conclusions

A lower rate of restraint is reported here than has been seen in programs where youths are treated in medical or adult psychiatric EDs. Hospitals without specialized pediatric psychiatric emergency programs should invest in staff training in deescalation techniques and in access to pediatric psychiatric treatment. The finding that, of youth restrained, a significant proportion were under 12 years old and/or carried diagnoses not typically associated with aggressive behavior, indicates that crisis prevention, management, and treatment should include younger populations and diverse diagnostic groups, rather than focusing narrowly on older patients with psychotic or substance use disorders.
Physician Risk Perception and Testing Behaviors for Children With Fever
Authors: Marchese Ashley L. , Fine Andrew M. , Levy Jason A. , Monuteaux Michael C. , Michelson Kenneth A.
Published: April 2021

Objectives

Risk tolerance and risk perceptions may impact clinicians' decisions to obtain diagnostic tests. We sought to determine whether physician risk perception was associated with the decision to obtain blood or imaging tests among children who present to the emergency department with fever.

Methods

We conducted a retrospective, cross-sectional study in the Boston Children's Hospital emergency department. We included children aged 6 months to 18 years from May 1, 2014 to April 30, 2019, with fever. Our primary outcome was diagnostic testing: obtaining a blood and/or imaging test. We assessed risk perception using 3 scales: the Risk Tolerance Scale (RTS), Stress From Uncertainty Scale (SUS), and Malpractice Fear Scale (MFS). A z score was assigned to each physician for each scale. Mixed-effects logistic regression assessed the association between physician risk perception and blood or imaging testing. We also examined the relationship between each risk perception scale and several secondary outcomes: blood testing, urine testing, diagnostic imaging, specialist consultation, hospitalization, and revisit within 72 hours.

Results

The response rate was 55/56 (98%). We analyzed 12,527 encounters. Blood/imaging testing varied between physicians (median, 48%; interquartile range, 41%–53%; range, 30%–71%). Risk Tolerance Scale responses were not associated with blood/imaging testing (odds ratio [OR], 1.03 per SD of increased risk perception; 95% confidence interval [CI], 0.95–1.13). Stress From Uncertainty Scale responses were not associated with blood/imaging testing (OR, 1.04 per SD; 95% CI, 0.95–1.14). Malpractice Fear Scale responses were not associated with blood/imaging testing (OR, 1.00 per SD; 95% CI, 0.91–1.09). There was no significant association between RTS, MFS, or SUS and any secondary outcome, except that there was a weak association between SUS and specialist consultation (OR, 1.12; 95% CI, 1.00–1.24).

Conclusions

Across 55 pediatric emergency physicians with variable testing practices, there was no association between risk perception and blood/imaging testing in febrile children.
Point-of-Care Ultrasound on Management of Cellulitis Versus Local Angioedema in the Pediatric Emergency Department
Authors: Tay Ee Tein , Ngai Ka Ming , Tsung James W. , Sanders Jennifer E.
Published: April 2021

Objectives

To evaluate whether ultrasound can differentiate between cellulitis and angioedema from insect bites in pediatric patients.

Methods

A prospective, pre-post study in an urban pediatric emergency department of patients younger than 21 years with soft tissue swelling from insect bites without abscesses were enrolled. Treating physician's pretest opinions regarding the diagnosis and need for antibiotics were determined. Ultrasound of the affected areas was performed, and effects on management were recorded. Further imaging, medications, and disposition were at the discretion of the enrolling physician. Phone call follow-ups were made within a week of presentation.

Results

Among 103 patients enrolled with soft tissue swelling secondary to insect bites, ultrasound changed the management in 27 (26%) patients (95% confidence interval [CI], 18–35%). Of the patients who were indeterminate or believed to require antibiotics, ultrasound changed management in 6 (23%) of 26 patients (95% CI, 6%–40%). In those patients who were believed not to require antibiotics, ultrasound changed management in 12 (16%) 77 patients (95% CI, 7%–24%). Patients with diagnosis of local angioedema achieved symptom resolution 1.4 days sooner than patients diagnosed with cellulitis (mean, −1.389; 95% CI, −2.087 to −0.690; P < 0.001). No patient who was initially diagnosed as local angioedema received antibiotics upon patient follow-up.

Conclusions

Point-of-care ultrasound changed physician management in 1 of 4 patients in the pediatric emergency department with soft tissue swelling secondary to insect bites. Ultrasound may guide the management in these patients and lead to improved antibiotic stewardship in conjunction with history and physical examination.
Maternal Confidence and Emergency Department Utilization Among Infants
Authors: Giusto Jina , Anton Megan , Gaiazov Sabrina , Huddleston Kathi , Levy Shira , Fuller Alma , Hourigan Suchitra , Niederhuber John , Hwang Vivian
Published: April 2021

Objectives

To determine if maternal confidence affects emergency department (ED) utilization in the first year of life.

Methods

This retrospective cohort study examined the Maternal Confidence Questionnaire responses from a longitudinal birth cohort study and ED visits for these subjects across all Inova hospitals from January 2012 to July 2017 for full-term children 12 months or younger at the time of visit. Using logistic regression, maternal confidence, maternal race/ethnicity, age, education, parity, and insurance were evaluated against Emergency Severity Index acuity levels and ED visit frequency.

Results

Of 2429 participants in the longitudinal study, 316 subjects visited the ED and met inclusion criteria. Medicaid status was the main factor associated with any ED visit. Low maternal confidence did not correlate with more frequent or nonurgent ED visits. Higher maternal confidence scores were seen in Hispanic or Latino mothers and mothers with parity greater than 1. Hispanic or Latino mothers were more likely to have Medicaid and more likely to bring their child to the ED. Mothers with college education had lower maternal confidence scores, were less likely to visit the ED, but had higher acuity level visits.

Conclusions

Low maternal confidence did not correlate with frequent ED visits or nonurgent visits. Medicaid status was the main factor associated with any ED visit. Hispanic or Latino mothers had higher maternal confidence scores, were more likely to have Medicaid and more likely to bring their child to the ED.
Growth Faltering and Developmental Delay in HIV-Exposed Uninfected Ugandan Infants: A Prospective Cohort Study
Authors: Sirajee Reshma , Conroy Andrea L. , Namasopo Sophie , Opoka Robert O. , Lavoie Stephanie , Forgie Sarah , Salami Bukola O. , Hawkes Michael T.
Published: April 2021

Background:

HIV-exposed but uninfected (HEU) infants are at increased risk of impaired early linear growth and cognitive development. We examined associations between prenatal and postnatal growth and subsequent neurodevelopment in Ugandan HEU infants, hypothesizing that early insults may explain alterations in both somatic growth and brain development.

Methods:

We prospectively followed a cohort of HEU infants from birth to 18 months of age, and measured length/height, weight, head, and arm circumference longitudinally. The Malawi Development Assessment Tool (MDAT, 12 and 18 months) and the Color Object Association Test (18 months) were used for developmental assessments.

Results:

Among 170 HEU infants, the prevalence of low-birth weight and failure to thrive was 7.6% and 37%, respectively. HEU infants had MDAT scores that were similar to the reference population. The mean (SD) score on the Color Object Association Test was 5.5 (3.1) compared with 6.9 (5.3) in developmentally normal children. Developmental ability at age 18 months showed strong cross-sectional correlation with weight-for-age (ρ = 0.36,P< 0.0001), length/height-for-age (ρ = 0.41,P< 0.0001), head circumference-for-age (ρ = 0.26,P= 0.0011), and mid-upper arm circumference-for-age (ρ = 0.34,P= 0.0014). There was a statistically significant correlation between birth weight and MDAT z-score at 18 months (ρ = 0.20,P= 0.010). Failure to thrive was associated with lower MDAT z-score [median −0.13 (IQR −0.75 to +0.14) versus +0.14 (IQR −0.44 to +0.63),P= 0.042].

Conclusion:

Growth faltering in HEU infants was associated with lower attainment of developmental milestones at age 18 months. Our findings point to a simple screening method for identifying HEU infants at risk for developmental intervention.
Composite grafts for fingertip amputations: a systematic review
Authors: Landin Madeleine L. , Borrelli Mimi R. , Sinha Vikram , Agha Riaz , Greig Aina V.H.
Published: April 2021

There is debate in the literature surrounding the management of fingertip amputations. The role of composite grafts lacks clarity in terms of outcomes and complications. Hence, there is a need for an evidence synthesis to guide practice. A search of the databases OVID MEDLINE, PubMed, EMBASE, SCOPUS, The Cochrane Library, and clinical trial registries was conducted, from 1946 to January 2020, using the key terms “fingertip,” “digital tip,” “digit,” “finger,” “thumb,” “amputation,” “replantation,” “reattachment,” “reimplantation,” and “composite graft.” Studies reporting primary data on the outcomes of composite grafts of 5 or more digits were included. The studies included in this systematic review ranged in year of publication from 1959 to 2019. Data extraction included demographic details, functional, esthetic and adverse outcomes. Twenty-three articles were included. Outcome data on composite grafts are heterogeneous and little standardization of measurements exists, making interpretation challenging. Identified factors associated with improved outcomes include lower age, distal amputation levels by cut mechanism and decreased time to operation. Smoking is associated with poorer composite graft outcomes. Although survival rates vary greatly, composite grafting may be useful in certain cases and provide good functional and sensation outcomes with good patient satisfaction.
The female protective effect against autism spectrum disorder
Authors: Wigdor Emilie M. , Weiner Daniel J. , Grove Jakob , Fu Jack M. , Thompson Wesley K. , Carey Caitlin E. , Baya Nikolas , van der Merwe Celia , Walters Raymond K. , Satterstrom F. Kyle , Palmer Duncan S. , Rosengren Anders , Bybjerg-Grauholm Jonas ,   iPSYCH Consortium, Hougaard David M. , Mortensen Preben Bo , Daly Mark J. , Talkowski Michael E. , Sanders Stephan J. , Bishop Somer L. , Børglum Anders D. , Robinson Elise B.
Published: April 2021

Autism spectrum disorder (ASD) is diagnosed 3-4 times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common, inherited genetic risk for ASD are less studied. Leveraging the nationally representative Danish iPSYCH resource, we found siblings of female ASD cases had higher rates of ASD than siblings of male ASD cases (P < 0.01). In the Simons Simplex and SPARK collections, mothers of ASD cases carried more polygenic risk for ASD than fathers of ASD cases (P = 7.0 × 10−7). Male unaffected siblings under-inherited polygenic risk (P = 0.03); female unaffected siblings did not. Further, female ASD cases without a high-impact de novo variant over-inherited nearly three-fold the polygenic risk of male cases with a high-impact de novo (P = 0.02). Our findings support a FPE against ASD that includes common, inherited genetic variation.
Predictive modelling of COVID-19 New Confirmed Cases in Algeria using Artificial Neural Network
Authors: Djeddou Messaoud , Hameed Ibrahim A. , Hellal Aouatef , Nejatian Abolfazel
Published: April 2021

This study investigates the potential of a simple artificial neural network for the prediction of COVID-19 New Confirmed Cases in Algeria (CNCC).

Four different ANN models were built (GRNN, RBFNN, ELM, and MLP). The performance of the predictive models is evaluated based on four numerical parameters, namely root mean squared error (RMSE), mean absolute error (MAE), Nash-Sutcliffe efficiency (NSE), and Pearson correlation coefficient (R). Taylor diagram was also used to examine the similarities and differences between the observed and predicted values obtained from the proposed models.

The results showed the potential of the multi-layer perceptron neural network (MLPNN) which exhibited a high level of accuracy in comparison to the other models.
RELATIONSHIP OF LIVER ENZYME LEVELS WITH THE CLINICAL COURSE OF COVID-19
Authors: İnce Ulku , Duran Harun Tolga
Published: April 2021

Introduction

Covid 19 infection, which can affect many systems in the human body, can cause organ dysfunction. High liver serum enzymes can be found in covid-19 patients, and many factors cause this stop. Patients with high levels of liver enzymes that require invasive mechanical ventilation during their follow-up were examined, and it was aimed to determine whether it was among the predictive indicators of mortality.

MATERIAL AND METHODS

Patients infected with covid 19 who were hospitalized in the intensive care unit between March 30 and December 1, 2020 according to the criteria of hospitalization in the intensive care unit, clinical trials such as age, gender, length of stay, additional diseases, liver enzyme levels and whether invasive mechanical ventilation is required their characteristics were recorded and analyzed retrospectively and compared.

RESULTS

Data were collected from 111 patients whose liver enzyme levels were measured from 131 patients included in the study. It was found that aspartate transaminase, alanine aminotransferase, and gamma-glutamyl transferase levels were statistically higher in the invasive mechanical ventilation group compared to the patients who did not undergo invasive mechanical ventilation.

CONCLUSION

Alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were statistically higher in COVID19-infected patients who were treated in intensive care and undergoing invasive mechanical ventilation. These enzymes are easily accessible and are shown among predictive values in mortality.
Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
Authors: Xu Ke , Shi Xingyi , Husted Chris , Hong Rui , Wang Yichen , Ning Boting , Sullivan Travis , Rieger-Christ Kimberly M , Duan Fenghai , Marques Helga , Gower Adam C. , Xiao Xiaohui , Liu Hanqiao , Liu Gang , Duclos Grant , Spira Avrum , Mazzilli Sarah A. , Billatos Ehab , Lenburg Marc E. , Campbell Joshua D. , Beane Jennifer
Published: April 2021

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 SARS-CoV-2), which infects host cells with help from the Viral Entry (VE) proteins ACE2, TMPRSS2, and CTSL1–4. Proposed risk factors for viral infection, as well as the rate of disease progression, include age5,6, sex7, chronic obstructive pulmonary disease7,8, cancer9, and cigarette smoking10–13. To investigate whether the proposed risk factors increase viral infection by modulation of the VE genes, we examined gene expression profiles of 796 nasal and 1,673 bronchial samples across four lung cancer screening cohorts containing individuals without COVID-19. Smoking was the only clinical factor reproducibly associated with the expression of any VE gene across cohorts. ACE2 expression was significantly up-regulated with smoking in the bronchus but significantly down-regulated with smoking in the nose. Furthermore, expression of individual VE genes were not correlated between paired nasal and bronchial samples from the same patients. Single-cell RNA-seq of nasal brushings revealed that an ACE2 gene module was detected in a variety of nasal secretory cells with the highest expression in the C15orf48+ secretory cells, while a TMPRSS2 gene module was most highly expressed in nasal keratinizing epithelial cells. In contrast, single-cell RNA-seq of bronchial brushings revealed that ACE2 and

TMPRSS2 gene modules were most enriched in MUC5AC+ bronchial goblet cells. The CTSL gene module was highly expressed in immune populations of both nasal and bronchial brushings. Deconvolution of bulk RNA-seq showed that the proportion of MUC5AC+ goblet cells was increased in current smokers in both the nose and bronchus but proportions of nasal keratinizing epithelial cells, C15orf48+ secretory cells, and immune cells were not associated with smoking status. The complex association between VE gene expression and smoking in the nasal and bronchial epithelium revealed by our results may partially explain conflicting reports on the association between smoking and SARS-CoV-2 infection.
Differences in risk for SARS-CoV-2 infection among healthcare workers
Authors: Elfström K. Miriam , Blomqvist Jonas , Nilsson Peter , Hober Sophia , Pin Elisa , Månberg Anna , Pimenoff Ville N. , Arroyo Mühr Laila Sara , Lundgren Kalle Conneryd , Dillner Joakim
Published: April 2021

Healthcare workers (HCWs) are a risk group for SARS-CoV-2 infection, but which healthcare work that conveys risk and to what extent such risk can be prevented is not clear. Starting on April 24th, 2020, all employees at work (n=15,300) at the Karolinska University Hospital, Stockholm, Sweden were invited and 92% consented to participate in a SARS-CoV-2 cohort study. Complete SARS-CoV-2 serology was available for n=12,928 employees and seroprevalences were analyzed by age, sex, profession, patient contact, and hospital department. Relative risks were estimated to examine the association between type of hospital department as a proxy for different working environment exposure and risk for seropositivity, adjusting for age, sex, sampling week, and profession. Wards that were primarily responsible for COVID-19 patients were at increased risk (adjusted OR 1.95 (95% CI 1.65-2.32) with the notable exception of the infectious diseases and intensive care units (adjusted OR 0.86 (95% CI 0.66-1.13)), that were not at increased risk despite being highly exposed. Several units with similar types of work varied greatly in seroprevalences. Among the professions examined, nurse assistants had the highest risk (adjusted OR 1.62 (95% CI 1.38-1.90)). Although healthcare workers, in particular nurse assistants, who attend to COVID-19 patients are a risk group for SARS-CoV-2 infection, several units caring for COVID-19 patients had no excess risk. Large variations in seroprevalences among similar units suggest that healthcare work-related risk of SARS-CoV-2 infection may be preventable.
Impact of COVID-19 in Individuals with Autism Spectrum Disorders: Analysis of a National Private Claims Insurance Database
Authors: Karpur Arun , Vasudevan Vijay , Shih Andy , Frazier Thomas
Published: April 2021

The COVID-19 pandemic continues to have a detrimental impact on individuals with disabilities. Data from FAIR Health’s FH® NPIC (National Private Insurance Claims) database,1 one of the nation’s largest databases of private insurance claim records, were analyzed to understand the experiences of individuals with ASD in COVID-19 pandemic. Multivariate logistic regression models revealed that individuals with ASD + ID were nine times more likely to be hospitalized (OR = 9.3; 95% CI: 6.9 – 12.5) and were nearly six times more likely have an elevated length of hospital stay(OR = 5.9; 95% CI: 3.5 – 10.1) compared those without ASD + ID. These findings point to their need for prioritization in access to vaccines for preventing COVID-19 infection and morbidities.
Commercialized kit to assess T-cell responses against SARS-CoV-2 S peptides. A pilot study in Health Care Workers
Authors: Martínez-Gallo Mónica , Esperalba-Esquerra Juliana , Pujol-Borrell Ricardo , Sandá Víctor , Arrese-Muñoz Iria , Fernández-Naval Candela , Antón-Pagarolas Andrés , Cardona Victoria , Labrador-Horrillo Moisés , Pumarola-Suñé Tomás , Hernandéz-González Manuel
Published: April 2021

Background

It is crucial to assess the levels of protection generated by natural infection or SARS-CoV-2 vaccines, mainly in individuals professionally exposed and in vulnerable groups. Measuring T-cell responses may complement antibody tests currently in use as correlates of protection. Our aim was to assess the feasibility of a validated assay of T-cell responses.

Methods

Twenty health-care-workers (HCW) were included. Antibody test to SARS-CoV-2 N and S-proteins in parallel with a commercially available whole-blood-interferon-gamma-release-assay (IGRA) to S-peptides and two detection methods, CLIA and ELISA were determined.

Results

IGRA test detected T-cell responses in naturally exposed and vaccinated HCW already after first vaccination dose. The correlation by the two detection methods was very high (R>0.8) and sensitivity and specificity ranged between 100 and 86% and 100-73% respectively. Even though there was a very high concordance between specific antibody levels and the IGRA assay in the ability to detect immune response to SARS-CoV-2, there was a relatively low quantitative correlation. In the small group primed by natural infection, one vaccine dose was sufficient to reach immune response plateau. IGRA was positive in one, with Ig(S) antibody negative vaccinated immunosuppressed HCW illustrating another advantage of the IGRA-test.

Conclusion

Whole-blood-IGRA-tests amenable to automation and constitutes a promising additional tool for measuring the state of the immune response to SARS-CoV-2; they are applicable to large number of samples and may become a valuable correlate of protection to COVID-19, particularly for vulnerable groups at risk of being re-exposed to infection, as are health-care-workers.
Autoantibodies stabilize neutrophil extracellular traps in COVID-19
Authors: Zuo Yu , Yalavarthi Srilakshmi , Navaz Sherwin , Hoy Claire , Harbaugh Alyssa , Gockman Kelsey , Zuo Melanie , Madison Jacqueline A. , Shi Hui , Kanthi Yogendra , Knight Jason S.
Published: April 2021

The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19 where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured anti-NET antibodies in 328 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of 27% and 60% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM (r=0.4, p<0.0001). Both anti-NET IgG and IgM tracked with high levels of circulating NETs, impaired oxygenation efficiency, and high circulating D-dimer. Furthermore, patients who required mechanical ventilation had a greater burden of anti-NET antibodies than did those not requiring oxygen supplementation. Levels of anti-NET IgG (and to a lesser extent anti-NET IgM) demonstrated an inverse correlation with the efficiency of NET degradation by COVID sera. Furthermore, purified IgG from COVID sera with high levels of anti-NET antibodies impaired the ability of healthy control serum to degrade NETs. In summary, many individuals hospitalized with COVID-19 have anti-NET antibodies, which likely impair NET clearance and may potentiate SARS-CoV-2-mediated thromboinflammation.
Growth Functions as a tool to model SARS-CoV-2 pandemic trajectory and related-deaths worldwide
Authors: Fonseca Vagner , Mascarenhas Edson , Ramos Paulo , Coelho Leandro , Frias Diego
Published: April 2021

The international scientific community from different areas of knowledge has made efforts to provide information and methods that contribute to the adoption of the most appropriate measures to curb the spread of the COVID-19 disease. In particular, the data analysis community has been very active in publishing a large number of papers. A good part of them is related to the prediction of epidemic variables (number of cases and deaths) in different time horizons. To solve the problem of the prediction of COVID-19, an important place is occupied by the sigmoidal growth functions, as they have often been used successfully in previous epidemic outbreaks. The objective of this work was to investigate, on a statistical basis, the ability of classical growth functions to model the data from the COVID-19 pandemic. But for that, it was necessary to establish a clear classification of the 5 types of problems that can be faced with data analysis techniques in this specific context and to define a methodology based on quantitative metrics to measure the performance in solving these different types of problems. The basic concept used was that of an epidemic wave consisting of an initial-increasing and a final-decreasing phase. A classification of the COVID-19 waves in 4 types was done based on mining data from all available countries. Thus, it was possible to determine the resolvability of each type of problem depending on the stage of the epidemic wave. The biggest conclusion was the impossibility of solving the long-term forecasting problems (problem 5 – to estimate the total value of an epidemic wave) with data from the first phase only. Using this theoretical-methodological framework, we evaluated, using metrics specifically designed for these types of problems, the performance of 3 classic growth functions: Logistics, Gompertz and Richards (a generalization of the previous two) in 2 types of problems: (1) Description of the trajectory of the epidemic and (2) Prediction of the total numbers of cases and deaths. We used data from 10 countries, 7 of them with more than 100 daily deaths on the peak day. The results show a generalized underperformance of the logistic function in all aspects and place the Gompertz function as the best cost-benefit alternative, as it has performance comparable to the Richards function, but it has one less parameter to be adjusted, in the process of regression of the model to the observed data.
Is convalescent plasma futile in COVID-19? A Bayesian re-analysis of the RECOVERY randomised controlled trial
Authors: Hamilton FW , Lee TC , Arnold DT , Lilford R , Hemming K
Published: April 2021

Introduction

Randomised trials are generally performed from a frequentist perspective reporting point estimates and 95% confidence intervals. This approach can confuse “evidence of no effect” with “no evidence of an effect” and does not allow for contextual knowledge. The RECOVERY trial evaluated convalescent plasma for patients hospitalised with COVID-19, the interaction test for the primary outcome was not statistically significant, and the trial concluded no evidence of an effect. From the clinical immunology perspective, there is strong justification to expect differential responses to convalescent plasma in patients who already have their own antibodies to SARS-CoV2 (seropositive) versus those who do not (seronegative).

Methods

Outcome data was extracted from the RECOVERY trial both overall and for seronegative participants. A Bayesian re-analysis with a wide variety of priors (vague, optimistic, skeptical and pessimistic) was performed calculating the posterior probability for both any benefit or a modest benefit (number needed to treat of 100).

Results

Across all patients, when analysed with a vague prior the likelihood of any benefit or a modest benefit was estimated to be 64% and 18% respectively. In contrast, in the seronegative subgroup, the likelihood of any benefit or a modest benefit was estimated to be 90% and 74%. Results were broadly consistent across all prior distributions.

Conclusion

Performing clinical trials during a pandemic is challenging, and RECOVERY has provided high quality evidence for numerous therapies. However, the use of frequentist hypothesis testing in this trial has led to the trialists and governing bodies to conclude a strong evidence of no effect. Based on this trial, and other prior knowledge there remains a strong probability that convalescent plasma provides at least a modest benefit in seronegative patients.
Mechanisms and fluid dynamics of foraging in heterotrophic nanoflagellates
Authors: Suzuki Sei , Andersen Anders , Kiørboe Thomas
Published: April 2021

Heterotrophic nanoflagellates are the main consumers of bacteria and picophytoplankton in the ocean. In their micro-scale world, viscosity impedes predator-prey contact, and the mechanisms that allow flagellates to daily clear a volume of water for prey corresponding to 106times their own volume is unclear. It is also unclear what limits observed maximum ingestion rates of about 104bacterial prey per day. We used high-speed video-microscopy to describe feeding flows, flagellum kinematics, and prey searching, capture, and handling in four species with different foraging strategies. In three species, prey-handling times limit ingestion rates and account well for their reported maximum values. Similarly, observed feeding flows match reported clearance rates. Simple point-force models allowed us to estimate the forces required to generate the feeding flows, between 4-13 pN, and consistent with the force produced by the hairy (hispid) flagellum, as estimated using resistive force theory. Hispid flagella can produce a force that is much higher than the force produced by a naked flagellum with similar kinematics, and the hairy flagellum is therefore key to foraging in most nanoflagellates. Our findings provide a mechanistic underpinning of observed functional responses of prey ingestion rates in nanoflagellates.
Equity Impacts of Dollar Store Vaccine Distribution
Authors: Chevalier Judith A. , Schwartz Jason L. , Su Yihua , Williams Kevin R.
Published: April 2021

We use geospatial data to examine the unprecedented national program currently underway in the United States to distribute and administer vaccines against COVID-19. We quantify the impact of the proposed federal partnership with the company Dollar General to serve as vaccination sites and compare vaccine access with Dollar General to the current Federal Retail Pharmacy Partnership Program. Although dollar stores have been viewed with skepticism and controversy in the policy sector, we show that, relative to the locations of the current federal program, Dollar General stores are disproportionately likely to be located in Census tracts with high social vulnerability; using these stores as vaccination sites would greatly decrease the distance to vaccines for both low-income and minority households. We consider a hypothetical alternative partnership with Dollar Tree and show that adding these stores to the vaccination program would be similarly valuable, but impact different geographic areas than the Dollar General partnership. Adding Dollar General to the current pharmacy partners greatly surpasses the goal set by the Biden administration of having 90% of the population within 5 miles of a vaccine site. We discuss the potential benefits of leveraging these partnerships for other vaccinations, including against influenza.
Asymmetric learning facilitates human inference of transitive relations
Authors: Ciranka Simon , Linde-Domingo Juan , Padezhki Ivan , Wicharz Clara , Wu Charley M. , Spitzer Bernhard
Published: April 2021

Humans and other animals are capable of inferring never-experienced relations (e.g., A>C) from other relational observations (e.g., A>B and B>C). The processes behind such transitive inference are subject to intense research. Here, we demonstrate a new aspect of relational learning, building on previous evidence that transitive inference can be accomplished through simple reinforcement learning mechanisms. We show in simulations that inference of novel relations benefits from an asymmetric learning policy, where observers update only their belief about the winner (or loser) in a pair. Across 4 experiments (n=145), we find substantial empirical support for such asymmetries in inferential learning. The learning policy favoured by our simulations and experiments gives rise to a compression of values which is routinely observed in psychophysics and behavioural economics. In other words, a seemingly biased learning strategy that yields well-known cognitive distortions can be beneficial for transitive inferential judgments.
Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding
Authors: Ranjan Prashant , Neha  , Devi Chandra , Das Parimal
Published: April 2021

Prevailing COVID-19 vaccines are based on the spike protein of earlier SARS-CoV-2 strain that emerged in Wuhan, China. The continuously evolving nature of SARS-CoV-2 resulting emergence of new variants raises the risk of immune absconds. During the last few months, several RBD (receptor-binding domain) variants have been reported to affect the vaccine efficacy considerably. Soon after reporting of a new double mutant variant (L452R & E484Q) in India, the country facing a deadlier second wave of infections which prompts researchers to suspects this variant to be accountable. To address the relevant concerns about this new variant affecting vaccine efficacy, we performed molecular simulation dynamics based structural analysis of spike protein of double mutant (L452R & E484Q) along with K417G variants and earlier reported RBD variants and found structural changes in RBD region after comparing with the wild type. Comparison of the binding affinity of the double mutant and earlier reported RBD variant for ACE2 (angiotensin 2 altered enzymes) receptor and CR3022 antibody with the wild-type strain revealed the lowest binding affinity of the double mutant for CR3022 among all other variants. These findings suggest that the newly emerged double mutant could significantly reduce the impact of the current vaccine which threatens the protective efficacy of current vaccine therapy.
Expression-based species deconvolution and realignment removes misalignment error in multispecies single-cell data
Authors: Choi Jaeyong , Lee Woochan , Yoon Jung-Ki , Choi Sun Mi , Lee Chang-Hoon , Moon Hyeong-Gon , Cho Sukki , Chung Jin-Haeng , Yang Han-Kwang , Kim Jong-Il
Published: April 2021

Although single-cell RNA sequencing of xenograft samples has been widely used, no comprehensive bioinformatics pipeline is available for human and mouse mixed single-cell analyses. Considering the numerous homologous genes across the human and mouse genomes, misalignment errors should be evaluated, and a new algorithm is required. We assessed the extents and effects of misalignment errors when using human and mouse combined reference data and developed a new bioinformatics pipeline with expression-based species deconvolution to minimize errors. We also evaluated false-positive signals for a species presumed to originate from ambient RNA of the other species and applied a computational method to remove them. Misaligned reads account for an average of 0.5% of total reads, but such reads were concentrated to few genes that were greatly affected. Human and mouse mixed single-cell data, analyzed using our pipeline, clustered well with unmixed data and showed higher k-nearest-neighbor batch effect test and Local Inverse Simpson’s Index scores than those derived from Cell Ranger. We also applied our pipeline to multispecies multisample single-cell library containing breast cancer xenograft tissue and successfully identified all samples using genomic array and expression. Moreover, diverse cell types in the tumor microenvironment were well captured. We present our bioinformatics pipeline for mixed human and mouse single-cell data, which can also be applied to pooled libraries to obtain cost-effective single-cell data. We also address major consideration points when analyzing multispecies single-cell data for other applications.