bluuebunny/crossref_metadata_2025 huggingface dataset:
Employment and Migration Patterns of Recent Micrographic Surgery and Dermatologic Oncology Fellowship Graduates
Authors: Kodumudi Vijay , Hales Hannah A. , Cohen Jeffrey M. , Feng Hao
Published: April 2021

BACKGROUND

There is currently an uneven distribution of the Mohs surgery workforce, with a dearth in nonurban areas. The relationship between training and employment locations of Mohs surgeons has not been studied.

OBJECTIVE

To analyze the employment location of recent micrographic surgery and dermatologic oncology (MSDO) graduates in reference to residency and fellowship locations.

MATERIALS AND METHODS

Data collection of training and practice locations of 421 MSDO fellowship graduates from 2012 to 2017.

RESULTS

Thirty-two percent (n = 136) and 53% (n = 225) of MSDO fellowship graduates' first employment locations were located within 10 and 100 miles of either their residency or fellowship locations. Ninety-six percent of graduates were employed in a metropolitan location. Female graduates worked closer to training sites than male graduates, with 62% (n = 124) versus 46% (n = 102) working within 100 miles of either training site. Analysis by fellowship census region showed that graduates clustered around training sites in all regions, with 45% to 60% of graduates working within 100 miles of either training site.

CONCLUSION

The majority of graduates chose to work in a metropolitan area. Training location strongly predicts employment location. More than 45% of graduates in any region worked within 100 miles of their residency or fellowship site, and a sizeable portion worked within 10 miles.
Dosimetry in Digital Breast Tomosynthesis Evaluated by Monte Carlo Technique
Authors: Alves Marcos S. , Belinato Walmir , Santos William S. , Galeano Diego C. , Neves Lucio P. , Perini Ana P. , N. Souza Divanizia
Published: April 2021

The influence of the angular deviation of the tube during digital breast tomosynthesis (DBT) acquisition to the dose in the examined breast and in other organs and tissues is not well known. In this work, the Monte Carlo method was used with an adult female virtual anthropomorphic phantom to investigate the impact of this angular variation on the breast dose. The absorbed dose in the examined breast was normalized by the air kerma, which resulted in an absorbed dose coefficient (DT/Kair) for the breast. The absorbed dose in each organ was normalized by the glandular dose in the breast, resulting in the relative organ dose (ROD). An adult female virtual anthropomorphic phantom (FSTA_M50_H50) was incorporated into a scenario containing tomosynthesis equipment with Mo/Mo, Mo/Rh, and W/Rh target/filter combinations and tube voltages of 28 kV. The comparison between the results of the simulations considering digital mammography (DM) and DBT data showed that the DT/Kair values for the examined breast obtained with the DBT parameters were up to 24 times higher than with the DT/Kair obtained with DM parameters. A DT/Kair of 0.97 × 10−1 mGy mGy−1 was obtained in a DBT exam of the right breast. Considering the other organs, the highest ROD values were observed in the thyroid (6.45 × 10−4), eyes (3.87 × 10−4), liver (1.95 × 10−5), and eye lenses (3.21 × 10−3). A variation in the absorbed dose values for the breast and other organs was observed for all projections different from 0°.
The Effect and Effectiveness of Decontaminating a Pond in a Residential Area of Fukushima
Authors: Katengeza Estiner Walusungu , Ochi Kotaro , Sanada Yukihisa , Iimoto Takeshi , Yoshinaga Shinji
Published: April 2021

Special reconstruction and revitalization bases were designated in Fukushima’s difficult-to-return zone by the Japanese government as targets of intensive decontamination to drastically lower air dose rates and enable residents to return. A pond amid residences of one of these bases was targeted for decontamination, and this study aimed at evaluating the effect and effectiveness of the decontamination using decontamination factor, air dose rate reduction factor, and the additional annual effective dose to residents. Air dose rates were measured in situ with the second-generation Kyoto University Radiation Mapping system, while soil core samples were collected and measured for radioactivity in the laboratory by gamma spectrometry. Lower decontamination factors were observed for more deeply distributed radiocesium soil profiles, whereas areas covered with gravel demonstrated the largest reduction in air dose rates. Decontamination effectively lowered the radiocesium inventory and air dose rates by 51–93% and 37–91%, respectively. Moreover, the additional annual effective dose to the public changed from 1.7 ± 0.79 mSv to 1.2 ± 0.57 mSv because of decontamination representing a dose aversion of 29%. These findings demonstrate how decontaminating ponds in residential areas can help to further lower the external exposure.
Biomarkers of Atherosclerotic Vascular Disease in Workers Chronically Exposed to Ionizing Radiation
Authors: Oslina Darya , Rybkina Valentina , Adamova Galina , Zhuntova Galina , Bannikova Maria , Azizova Tamara
Published: April 2021

It is well established that cohorts of individuals exposed to ionizing radiation demonstrate increased risks of cardio- and cerebrovascular diseases. However, mechanisms of these radiation-induced diseases developing in individuals exposed to ionizing radiation remain unclear. To identify biomarkers of the atherosclerotic vessel damage in workers chronically exposed to ionizing radiation, this study considered 49 workers of the Russian nuclear production facility—the Mayak Production Association (mean age of 68.73 ± 6.92 years)—and 38 unexposed individuals (mean age of 68.84 ± 6.20 y) who had never been exposed to ionizing radiation (control). All workers were chronically exposed to combined radiation (external gamma rays and internal alpha particles). The mean cumulative liver absorbed dose from external gamma-ray exposure was 0.18 ± 0.12 Gy; the mean cumulative liver absorbed dose from internal alpha-particles was 0.14 ± 0.21 Gy. Levels of biomarkers in blood serum of the study participants were measured using the ELISA method. Elevated levels of apolipoprotein B, superoxide dismutase, monocyte chemoattractant protein 1, vascular cell adhesion protein 1, and a decreased level of endothelin-1 were observed in blood serum of Mayak PA workers chronically exposed to combined radiation compared to control individuals. A significant positive correlation was demonstrated between the vascular cell adhesion protein 1 level and cumulative liver absorbed doses from external gamma radiation and internal alpha radiation. Findings of the study suggest that molecular changes in blood of individuals occupationally exposed to ionizing radiation (combined internal exposure to alpha particles and external exposure to gamma rays) may indicate dyslipidemia, oxidative stress, inflammation, and endothelial dysfunction involved in atherosclerosis development.
Preliminary examination of the relations between disease stage, illness perceptions, coping strategies, and psychological morbidity in chronic hepatitis B and C guided by the Common-Sense Model of Illness
Authors: Ekmen Nergiz , Can Güray , Can Hatice
Published: April 2021

Background and aims

Chronic viral hepatitis (CVH) has a spectrum from asymptomatic disease to cirrhosis and hepatocellular carcinoma. In our study, we aimed to establish the relations between disease stage, illness perception, coping strategies and psychological morbidity in CVH.

Methods

A total of 182 patients with chronic hepatitis B (CHB) (n = 136) and chronic hepatitis C (CHC) (n = 46) were enrolled. Illness perceptions were measured with the Brief Illness Perceptions Questionnaire. Coping strategies were measured with the Carver Brief Coping Questionnaire. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale. Relations were evaluated by structural equation modeling (SEM).

Results

In CHB, combining the questionnaire data using SEM resulted in a final model with an excellent fit [χ
2 (2) = 0.00, P = 1.000, χ
2/N = 0.00, root mean square error of approximation (RMSEA) < 0.001, comparative fit index (CFI) = 1.000, goodness-of-fit index (GFI) = 1.000]. Disease stage had a significant direct influence on illness perceptions (β = 0.23, P = 0.006). Illness perceptions had a significant direct influence on emotional coping strategy, depression and anxiety (β = 0.20, P = 0.019; β = 0.33, P < 0.001; β = 0.59, P < 0.001, respectively). While the use of emotional coping strategies was associated significantly (P = 0.01) with the presence of anxiety, problem-focused coping strategy was associated with depression (P = 0.004). In CHC, SEM resulted in a final model with an excellent fit [χ
2 (2) = 0.078, P = 0.962, χ
2/N = 0.039, RMSEA<0.001, CFI = 1.000, GFI = 0.999]. Disease stage did not have a significant direct influence on illness perceptions (P > 0.05). Illness perceptions had a significant direct influence on depression and anxiety (β = 0.27, P = 0.023; β = 0.44, P < 0.001, respectively).

Conclusion

The psychological consequences of the disease vary depending on the person’s perception of illness and coping strategies.
Prevalence study of different methods for hepatitis B virus diagnosis with blood donor people in Baghdad city
Authors: Saeed Noor AlHuda Ali A.H. , Hamzah Israa Hussein , Al-kadmy Israa M.S.
Published: April 2021

Background:

Globally, infecting with hepatitis B virus (HBV) is a big issue today. The present study was aimed to assess the prevalence and year-wise trend of the HBV surfaces antigens (HBs-Ag), antibodies vs. HBV core antigens (anti-HBcs) while HBV-DNA in serum sample patients and replacement blood donors in Baghdad, Iraq.

Methods:

During the period between 2017 and 2019, a total of 212 blood donors of ages 18–70 years were screened for HBs-Ag, anti-HBs by enzyme-linked immunosorbent assay (ELISA) technique, and anti-HBc antigen–antibody (Ag–Ab) and HBV-DNA using real-time PCR.

Results:

A total of 110 (51.8%) of 212 blood donors were positive to all tests: HBs-Ag, anti-Hbs, anti-HBc and HBV-DNA. Forty-six (41.8%) were positive for HBV-DNA, HBs-Ag and anti-HBc, whereas 14 (12.7%) were positive for HBs-Ag and anti-HBc. Although nine (8.1%) blood donors were positive in real-time PCR (HBV-DNA loaded) with a negative result in ELISA. Forty one (37.2%) markers indicated a high number of inveterate or resolvable contagion. The total diffusion increment significance in 2017–2018, stabilized thereafter and started decreasing from 2018 to 2019 marginally. There is a high significance variance at (P < 0.01) while comparison among examined groups.

Conclusions:

Significance and impact of study: the prevalence of HBV infection in 3 years is lower in Baghdad blood donors (51.8%) compared to other regions of Iraq. A high number of infections with no signs of HBs-Ag or viral DNA were recorded. Therefore, the inclusion of anti-HBc seromarker and DNA in the routine screening could isolate potential infectious blood units.
The Impact of Coping Strategies on Suicide Attempts and Suicidal Ideation in Bipolar Disorder
Authors: Aksoy Poyraz Cana , Özdemir Armağan , Çakir Şen Cansu , Usta Sağlam Nazife Gamze , Enginkaya Semra , Tomruk Nesrin
Published: April 2021

The stress coping strategies of patients with bipolar disorder (BD) may affect their suicide risk. We examined coping behaviors and impact of coping strategies and clinical characteristics on suicide attempts and lifetime suicidal ideation in patients with BD I, compared with a healthy control group. We recruited 185 euthymic patients with BD and 94 healthy controls. Participants completed the Coping Orientation to Problems Experienced Inventory. Suicide attempt prevalence in patients with BD was around 34%, and frequency of lifetime suicide ideation was around 60%. Binary logistic regression analysis revealed greater use of behavioral disengagement and religious coping strategies among patients with BD, compared with controls. Patients with previous suicide attempts presented a more severe illness course, notably early onset, with more depressive and mixed episodes and a more dysfunctional coping style than nonsuicidal patients. Behavioral interventions can target avoidant coping behavior, such as denial, especially in patients with suicide attempts.
Children develop robust and sustained cross-reactive spike-specific immune responses following SARS-CoV-2 infection
Authors: Dowell Alexander C. , Butler Megan S. , Jinks Elizabeth , Tut Gokhan , Lancaster Tara , Sylla Panagiota , Begum Jusnara , Bruton Rachel , Pearce Hayden , Verma Kriti , Logan Nicola , Tyson Grace , Spalkova Eliska , Margielewska-Davies Sandra , Taylor Graham S. , Syrimi Eleni , Baawuah Frances , Beckmann Joanne , Okike Ifeanyichukwu , Ahmad Shazaad , Garstang Joanna , Brent Andrew J , Brent Bernadette , Ireland Georgina , Aiano Felicity , Amin-Chowdhury Zahin , Jones Samuel , Borrow Ray , Linley Ezra , Wright John , Azad Rafaq , Waiblinger Dagmar , Davis Chris , Thomson Emma , Palmarini Massimo , Willett Brian J. , Barclay Wendy S. , Poh John , Saliba Vanessa , Amirthalingam Gayatri , Brown Kevin E , Ramsay Mary E , Zuo Jianmin , Moss Paul , Ladhani Shamez
Published: April 2021

SARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody responses against spike and receptor binding domain (RBD) were high in children and seroconversion boosted antibody responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Seroneutralisation assays against alpha, beta and delta SARS-CoV-2 variants demonstrated comparable neutralising activity between children and adults. T cell responses against spike were >2-fold higher in children compared to adults and displayed a TH1 cytokine profile. SARS-CoV-2 spike-specific T cells were also detected in many seronegative children, revealing pre-existing responses that were cross-reactive with seasonal Alpha and Beta-coronaviruses. Importantly, all children retained high antibody titres and cellular responses at 6 months after infection whilst relative antibody waning was seen in adults. Spike-specific responses in children also remained broadly stable beyond 12 months. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection with focussed specificity against spike protein. These observations demonstrate novel features of SARS-CoV-2-specific immune responses in children and may provide insight into their relative clinical protection. Furthermore, this information will help to guide the introduction of vaccination regimens in the paediatric population.
Differential Performance of CoronaCHEK SARS-CoV-2 Lateral Flow Antibody Assay by Geographic Origin of Samples
Authors: Baker Owen R. , Grabowski M. Kate , Galiwango Ronald M. , Nalumansi Aminah , Serwanga Jennifer , Clarke William , Hsieh Yu-Hsiang , Rothman Richard E. , Fernandez Reinaldo E. , Serwadda David , Kagaayi Joseph , Lutalo Tom , Reynolds Steven J. , Kaleebu Pontiano , Quinn Thomas C. , Laeyendecker Oliver
Published: April 2021

Background

We assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance.

Methods

Serum samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic individuals (Uganda 1077 and Baltimore 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test.

Results

After first positive PCR in Ugandan samples the sensitivity was: 45% (95% CI 24,68) at 0-7 days; 79% (95%CI 64,91) 8-14 days; and 76% (95%CI 50,93) >15 days. In samples from Baltimore, sensitivity was: 39% (95% CI 30, 49) 0-7 days; 86% (95% CI 79,92) 8-14 days; and 100% (95% CI 89,100) 15 days post positive PCR. The specificity of 96.5% (95% CI 97.5,95.2) in Ugandan samples was significantly lower than samples from Baltimore 99.3% (95% CI 98.1,99.8), p<0.01. In Ugandan samples, individuals with a false positive result were more likely to be male (PR 2.04, 95% CI 1.03,3.69) or individuals who had a fever more than a month prior to sample acquisition (PR 2.87, 95% CI 1.12,7.35).

Conclusions

Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.
Development and validation of a productive liquid chromatography-tandem mass spectrometry method for the analysis of androgens, estrogens, glucocorticoids and progestagens in human serum
Authors: Iannone Michele , Dima Anna Pia , Sciarra Francesca , Botrè Francesco , Isidori Andrea M.
Published: April 2021

Adrenal and gonadal disorders are very often coupled, due to common etiology or pathophysiology. We present the development, validation and application of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of androgens (androstenedione (A4), testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate (DHEA-S)), estrogens (estrone (E1), estradiol (E2), estriol (E3)), glucocorticoids (cortisol (F), cortisone (E), corticosterone (B), 11-deoxycortisol (S), 21-deoxycortisol (21DF), 11-deoxycorticosterone (11DB)), and progestagens (progesterone (P4), 17α-hydroxyprogesterone (17OHP4) and 17α-hydroxypregnenolone (17OHP5)) in human serum for clinical use. Samples (250 &[mu]L of matrix) spiked with isotopic labelled internal standards were extracted with tert-butylmethyl ether (TBME) prior to LC-MS/MS analysis. The chromatographic separation of the underivatized endogenous steroids was achieved on a reversed-phase column (C18 Zorbax Eclipse Plus) using a methanol-water gradient. The LC column was coupled to a triple quadrupole mass spectrometer equipped with an electrospray (ESI) source operating both in positive and in negative mode, with acquisition in multiple reaction mode. The method was validated using surrogated matrices and human serum samples. The proposed method was proven to be specific for all the considered steroids; and linearity was also assessed (R2 > 0.99) in the ranges of quantification investigated. The lower limits of quantification (LLOQs) were in the range of 10 - 400 pg/mL depending on the target steroid. Accuracy was in the range 80 - 120% for all the target compounds, the extraction recovery was higher than 65% for all the steroids considered and no remarkable matrix effect, expressed in terms of ion enhancement and ion suppression, was observed. To test the reliability of the developed and validated method, the analysis of serum samples collected from ten healthy subjects (5M/5F) was performed. In the clinical settings there is a growing need to develop accessible methods for full steroid hormone profiling. The dynamic link between steroidogenic glands and liver enzymatic processing (activation and clearance) attributes to the profile a much greater clinical meaning than a set of individually measured hormones. The presented method can be used to identify trajectories of deviation from the concentration normality ranges applied to disorders of the gonadal and adrenal axes.
Identification of natural SARS-CoV-2 infection in seroprevalence studies among vaccinated populations
Authors: Demmer Ryan T. , Baumgartner Brett , Wiggen Talia D. , Ulrich Angela K. , Strickland Ali J. , Naumchik Brianna M. , Bohn Bruno , Walsh Sara , Smith Stephen , Kline Susan , Stovitz Steve D. , Yendell Stephanie , Beebe Tim , Hedberg Craig
Published: April 2021

Importance

Identification of SARS-CoV-2 infection via antibody assays is important for monitoring natural infection rates. Most antibody assays cannot distinguish natural infection from vaccination.

Objective

To assess the accuracy of a nucleocapsid-containing assay in identifying natural infection among vaccinated individuals.

Design

A longitudinal cohort comprised of healthcare workers (HCW) in the Minneapolis/St. Paul metropolitan area was enrolled. Two rounds of seroprevalence studies separated by one month were conducted from 11/2020–1/2021. Capillary blood from round 1 and 2 was tested for IgG antibodies against SARS-CoV-2 spike proteins with a qualitative chemiluminescent ELISA (spike-only assay). In a subsample of participants (n=82) at round 2, a second assay was performed that measured IgGs reactive to SARS-CoV-2 nucleocapsid protein (nucleocapsid-containing assay). Round 1 biospecimen collections occurred prior to vaccination in all participants. Vaccination status at round 2 was determined via self-report.

Setting

The Minneapolis/St. Paul, Minnesota metropolitan area.

Participants

HCW age 18-80 years.

Exposures

Round 1 recent SARS-CoV-2 infection assessed via a spike-only assay and participant self-report.

Outcomes

Round 2 SARS-CoV-2 infection assessed via the nucleocapsid-containing assay. Area under the curve (AUC) was computed to determine the discriminatory ability of round 2 IgG reactivity to nucleocapsid for identification of recent infection determined during round 1

Results

Participants had a mean age of 40 (range=23-66) years, 83% were female, 46% reported vaccination prior to the round 2 testing. Round 1 seroprevalence was 9.5%. Among those not recently infected, when comparing vaccinated vs. unvaccinated individuals, elevated levels of spike 1 (p<0.001) and spike 2 (p=0.01) were observed while nucleocapsid levels were not statistically significantly different (p=0.90). Among all participants, nucleocapsid response predicted recent infection with an AUC(95%CI) of 0.93(0.88,0.99). Among individuals vaccinated >10 days prior to antibody testing, the specificity of the nucleocapsid-containing assay was 92% and while the specificity of the spike-only assay was 0%.

Conclusions and Relevance

An IgG assay identifying reactivity to nucleocapsid protein is an accurate predictor of natural infection among vaccinated individuals while a spike-only assay performed poorly. In the era of SARS-CoV-2 vaccination, seroprevalence studies monitoring natural infection will require assays that do not rely on spike-protein response alone.
Rapid, inexpensive methods for exploring SARS CoV-2 D614G mutation
Authors: Al-Jaf Sirwan M.A. , Niranji Sherko Subhan , Mahmood Zana Hameed
Published: April 2021

A common mutation has occurred in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), known as D614G (A23403G). There are discrepancies in impacting of this mutation on the virus’s infectivity, and the whole genome sequencings are expensive and time-consuming. This study aims to develop three fast economical assays for prompt identifications of the D614G mutation including Taqman probe-based real-time reverse transcriptase polymerase chain reaction (rRT PCR), an amplification refractory mutation system (ARMS) RT and restriction fragment length polymorphism (RFLP), in nasopharyngeal swab samples. Both rRT and ARMS data showed G614 mutant indicated by presence of HEX probe and 176bp, respectively. Additionally, the results of the RFLP data and DNA sequencings confirmed the prevalence of G614 mutant. These methods will be important, in epidemiological, reinfections and zoonotic aspects, through detecting the G614 mutant in retro-perspective samples to track its origins and future re-emergence of D614 wild type.
Primary care and point-of-care testing during a pandemic: Clinician’s perspectives on integrating rapid testing for COVID-19 into the primary care pathway
Authors: Kierkegaard Patrick , Hicks Timothy , Yang Yaling , Lee Joseph , Hayward Gail , Turner Philip J. , Allen A. Joy , Nicholson Brian D.
Published: April 2021

Background

Real-world evidence to support the adoption of SARS-CoV-2 point-of-care (POC) tests in primary care is limited. As the first point of contact of the health system for most patients, POC testing can potentially support general practitioners (GPs) quickly identify infectious and non-infectious individuals to rapidly inform patient triaging, clinical management, and safely restore more in-person services.

Objectives

To explore the potential role of SARS-CoV-2 point-of-care testing in primary care services.

Design

A qualitative study using an inductive thematic analysis.

Setting

21 general practices located across three regions in England.

Results

Three major themes were identified related to POC test implementation in primary care: (1) Insights into SARS-CoV-2 POC tests; (2) System and organisational factors; and (3) Practice-level service delivery strategies. Thematic subcategories included involvement in rapid testing, knowledge and perception of the current POC testing landscape, capacity for testing, economic concerns, resource necessities, perception of personal risk and safety, responsibility for administering the test, and targeted testing strategies.

Conclusion

GPs knowledge of POC tests influences their degree of trust, uncertainty, and their perception of risk of POC test use. Concerns around funding, occupational exposure, and workload play a crucial role in GPs hesitation to provide POC testing services. These concerns could potentially be addressed with government funding, the use of targeted testing, and improved triaging strategies to limit testing to essential patient cohorts.
Outcomes of COVID-19 infection in patients treated with Clozapine
Authors: Govind Risha , de Freitas Daniela Fonseca , Pritchard Megan , Khondoker Mizanur , Teo James T , Stewart Robert , Hayes Richard D. , MacCabe James H.
Published: April 2021

Background

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics.

Aims

To investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation and intensive care treatment, and death, among patients taking antipsychotics with schizophrenia-spectrum disorders.

Method

Using data from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics at the time of the COVID-19 pandemic in the UK, and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores.

Results

In the 157 individuals who developed COVID while on antipsychotics, there were 44 COVID-related hospitalisations, 13 COVID-related intensive care treatments and 13 deaths of any cause during the follow-up period. In the unadjusted analysis, there was no significant association between clozapine and any of the outcomes and there remained no associations following adjusting for the confounding variables.

Conclusions

In our sample of patients with COVID-19 and schizophrenia-spectrum disorders, we found no evidence that clozapine treatment puts patients at increased risk of hospitalisation, intensive care treatment or death, compared to any other antipsychotic treatment. However, further research should be considered in larger samples to confirm this.

Conflict of interest

RDH has received research funding from Roche, Pfizer, Janssen, and Lundbeck. DFF has received research funding from Janssen and Lundbeck. JHM has received research funding from Lundbeck. JTT has received research funding from Bristol-Meyers-Squibb. RS declares research support in the last 36 months from Janssen, GSK and Takeda.

Ethics statement

The research was conducted under ethical approval reference 18/SC/0372 from Oxfordshire Research Ethics Committee C.
Distinct SARS-CoV-2 Antibody Responses Elicited by Natural Infection and mRNA Vaccination
Authors: Assis Rafael , Jain Aarti , Nakajima Rie , Jasinskas Al , Kahn Saahir , Palma Anton , Parker Daniel M. , Chau Anthony , Leung Amanda , Grabar Christina , Muqolli Fjolla , Khalil Ghali , Escobar Jessica Colin , Ventura Jenny , Davies D. Huw , Albala Bruce , Boden-Albala Bernadette , Schubl Sebastian , Felgner Philip L.
Published: April 2021

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8,476 finger stick blood specimens were collected before and after an aggressive mRNA vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing 10 SARS-CoV-2 antigens, 4 SARS, 3 MERS, 12 Common CoV, and 8 Influenza antigens. Twenty-six percent of 3,347 specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive. The Ab response was predominantly against nucleocapsid (NP), full length spike and the spike S2 domain. Anti-receptor binding domain (RBD) reactivity was low and there was no cross-reactivity against SARS S1 or SARS RBD. An aggressive mRNA vaccination campaign at the UCI Medical Center started on December 16, 2020 and 6,724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% in December to 79% in January, 93% in February and 99% in March. mRNA vaccination induced much higher Ab levels especially against the RBD domain and significant cross-reactivity against SARS RBD and S1 was also observed. Nucleocapsid protein Abs can be used to distinguish individuals in a population of vaccinees to classify those who have been previously infected and those who have not, because nucleocapsid is not in the vaccine. Previously infected individuals developed higher Ab titers to the vaccine than those who have not been previously exposed. These results indicate that mRNA vaccination rapidly induces a much stronger and broader Ab response than SARS-CoV-2 infection.
Will the Large-scale Vaccination Succeed in Containing the COVID-19 Epidemic and How Soon?
Authors: Zhao Shilei , Sha Tong , Xue Yongbiao , Wu Chung-I , Chen Hua
Published: April 2021

The availability of vaccines provides a promising solution to containing the COVID-19 pandemic. Here, we develop an epidemiological model to quantitatively analyze and predict the epidemic dynamics of COVID-19 under vaccination. The model is applied to the daily released numbers of confirmed cases of Israel and United States of America to explore and predict the trend under vaccination based on their current epidemic status and intervention measures.

For Israel, of which 53.83% of the population was fully vaccinated, under the current intensity of NPIs and vaccination scheme, the pandemic is predicted to end between May 14, 2021 to May 16, 2021 depending on an immunity duration between 180 days and 365 days; Assuming no NPIs after March 24, 2021, the pandemic will ends later, between July 4, 2021 to August 26, 2021. For USA, if we assume the current vaccination rate (0.268% per day) and intensity of NPIs, the pandemic will end between February 3, 2022 and August 17, 2029 depending on an immunity duration between 180 days and 365 days. However, assuming an immunity duration of 180 days and with no NPIs, the pandemic will not end, and instead reach an equilibrium state with a proportion of the population remaining actively infected.

Overall the daily vaccination rate should be chosen according to the vaccine efficacy and the immunity duration to achieve herd immunity. In some situations, vaccination alone cannot stop the pandemic, and NPIs are necessary both to supplement vaccination and accelerate the end of the pandemic. Considering that vaccine efficacy and duration of immunity may be reduced for new mutant strains, it is necessary to remain cautiously optimistic about the prospect of the pandemic under vaccination.
Role of hyper-reflective spots in predicting outcomes of intravitreal therapy in diabetic macular edema: A systematic review and meta-analysis
Authors: Ganne Pratyusha , Krishnappa Nagesha C , Chaitanya Ganne , Karthikeyan Siddharth K
Published: April 2021

Purpose

Predicting response to intravitreal therapy in DME has become a challenging task. Individual studies have shown that HRS could be a reliable biomarker. This systematic review aimed to determine if there was a quantitative reduction in hyperreflective spots (HRS) following intravitreal therapy in diabetic macular edema (DME), if the type of intravitreal therapy (anti-VEGF versus steroid) had differential effects on quantitative HRS change and finally, if HRS at the start of therapy was associated with improvement in visual acuity (VA) or reduction in central macular thickness (CMT). We also aimed at bringing out the lacunae in the existing literature on HRS in DME and propose goals for future studies.

Methods

PubMed/MEDLINE, Scopus, ProQuest, CINAHL, Wiley online and Web of Science were searched based on MOOSE guidelines for non-randomized studies evaluating HRS as a biomarker in DME (between 1st January 2011 and 1st July 2020). Publication bias was analyzed using Begg and Mazumdar rank correlation test and funnel plots. Heterogeneity was assessed using the I2 statistic. Meta-analysis was done using a random-effects model.

Results

A total of 1168 eyes from 19 studies were eligible for inclusion. Pooled standardized mean differences showed that intravitreal therapy was associated with a reduction in quantitative HRS (z=-6.3, CI95%=-1.09 to −0.55, p<0.0001). Extreme between-study heterogeneity was observed (I2=93.2%) with significant publication bias. There was no difference in outcomes between anti-VEGF and steroid therapies (p=0.23). No definite conclusions could be drawn regarding the predictive value of HRS in determining the final VA and CMT.

Conclusion

This review could conclude that there is a definite reduction in quantitative HRS following either form of intravitreal therapy. Our conclusion about the role of HRS in predicting visual outcome and CMT change was limited by the number of analyzable studies owing to the wide variation in the study designs, methods and reporting.
Healthy longevity from incidence-based models: More kinds of health than stars in the sky
Authors: Caswell Hal , van Daalen Silke F.
Published: April 2021

Background

Healthy longevity (HL) is an important measure of the prospects for quality of life in ageing societies. Incidence-based (cf. prevalence-based) models describe transitions among age classes and health stages. Despite the probabilistic nature of those transitions, analyses of healthy longevity have focused persistently on means (“health expectancy”), neglecting variances and higher moments.

Objectives

Our goal is a comprehensive methodology to analyse HL in terms of any combination of health stages and age classes, or of transitions among health stages, or of values (e.g., quality of life) associated with health stages or transitions.

Methods

We construct multistate Markov chains for individuals classified by age and health stage and use Markov chains with rewards to compute all moments of HL.

Results

We present a new and straightforward algorithm to create the multistate reward matrices for occupancy, transitions, or values associated with occupancy or transitions. As an example, we analyse a published model for colorectal cancer. The possible definitions of HL in this simple model outnumber the stars in the visible universe. Our method can analyse any of them; we show four examples: longevity without abnormal cells, cancer-free longevity, and longevity with cancer before or after a critical age.

Contribution

Our methods make it possible to analyse any incidence-based model, with any number of health stages, any pattern of transitions, and any kind of values assigned to stages. It is easily computable, requires no simulations, provides all the moments of healthy longevity, and solves the inhomogeneity problem.
Prospective predictive performance comparison between Clinical Gestalt and validated COVID-19 mortality scores
Authors: Soto-Mota Adrian , Marfil-Garza Braulio A. , de Obeso Santiago Castiello , Martínez Erick , Carrillo-Vázquez Daniel Alberto , Tadeo-Espinoza Hiram , Guerrero-Cabrera Jessica Paola , Dardón-Fierro Francisco Eduardo , Escobar Valderrama Juan Manuel , Alanis-Mendizabal Jorge , Gutiérrez Juan
Published: April 2021

Background

Most COVID-19 mortality scores were developed in the early months of the pandemic and now available evidence-based interventions have helped reduce its lethality. It has not been evaluated if the original predictive performance of these scores holds true nor compared it against Clinical Gestalt predictions. We tested the current predictive accuracy of six COVID-19 scores and compared it with Clinical Gestalt predictions.

Methods

200 COVID-19 patients were enrolled in a tertiary hospital in Mexico City between September and December 2020. Clinical Gestalt predictions of death (as a percentage) and LOW-HARM, qSOFA, MSL-COVID-19, NUTRI-CoV and NEWS2 were obtained at admission. We calculated the AUC of each score and compared it against Clinical Gestalt predictions and against their respective originally reported value.

Results

106 men and 60 women aged 56+/-9 and with confirmed COVID-19 were included in the analysis. The observed AUC of all scores was significantly lower than originally reported; LOW-HARM 0.96 (0.94-0.98) vs 0.76 (0.69-0.84), qSOFA 0.74 (0.65-0.81) vs 0.61 (0.53-0.69), MSL-COVID-19 0.72 (0.69-0.75) vs 0.64 (0.55-0.73) NUTRI-CoV 0.79 (0.76-0.82) vs 0.60 (0.51-0.69), NEWS2 0.84 (0.79-0.90) vs 0.65 (0.56-0.75), Neutrophil-Lymphocyte ratio 0.74 (0.62-0.85) vs 0.65 (0.57-0.73). Clinical Gestalt predictions were non-inferior to mortality scores (AUC=0.68 (0.59-0.77)). Adjusting the LOW-HARM score with locally derived likelihood ratios did not improve its performance. However, some scores performed better than Clinical Gestalt predictions when clinician’s confidence of prediction was <80%.

Conclusion

No score was significantly better than Clinical Gestalt predictions. Despite its subjective nature, Clinical Gestalt has relevant advantages for predicting COVID-19 clinical outcomes.
CCL2/CCR2 inhibition in atherosclerosis: a meta-analysis of preclinical studies
Authors: Živković Luka , Asare Yaw , Bernhagen Jürgen , Dichgans Martin , Georgakis Marios K.
Published: April 2021

Rationale

The CC-chemokine ligand-2 (CCL2)/ CC-chemokine receptor-2 (CCR2) axis governs monocyte recruitment to atherosclerotic lesions. Coherent evidence from experimental studies employing genetic deletion of CCL2 or CCR2 and human epidemiological studies support a causal involvement of the CCL2/CCR2 axis in atherosclerosis. Still, preclinical studies testing pharmacological inhibition of CCL2 or CCR2 in atheroprone mice apply widely different approaches and report inconsistent results, thus halting clinical translation.

Objective

To systematically review and meta-analyze preclinical studies pharmacologically targeting the CCL2/CCR2 axis in atherosclerosis in an effort to inform the design of future trials.

Methods and Results

We identified 14 studies testing CCL2/CCR2 inhibition using 11 different pharmacological agents in mouse models of atherosclerosis. In meta-analyses, blockade of CCL2 or CCR2 attenuated atherosclerotic lesion size in the aortic root or arch (g=-0.75 [-1.17 to -0.32], p=6×10−4; N=171/171 mice in experimental/control group), the carotid (g=-2.39 [-4.23 to -0.55], p=0.01; N=24/25) and the femoral artery (g=-2.38 [-3.50 to -1.26], p=3×10−5; N=10/10). Furthermore, CCL2/CCR2 inhibition reduced intralesional macrophage accumulation and increased smooth muscle cell content and collagen deposition, consistent with a plaque-stabilizing effect. While there was heterogeneity across studies, the effects of CCL2/CCR2 inhibition on lesion size correlated with reductions in plaque macrophage accumulation, in accord with a prominent role of CCL2/CCR2 signaling in monocyte recruitment. Subgroup analyses revealed similar efficacy of both CCL2- and CCR2-inhibiting approaches across different atherosclerosis models in reducing lesion size and intralesional macrophage accumulation, but stronger atheroprotective effects in carotid and femoral arteries, as compared to the aorta.

Conclusions

Pharmacological targeting of CCL2 or CCR2 lowers atherosclerotic lesion burden and confers plaque stability in mice across different vascular territories, drug candidates, and models of atherosclerosis. Our findings in conjunction with recent human data highlight the translational potential of targeting the CCL2/CCR2 axis in atherosclerosis and can inform future clinical trials.

Subject codes

atherosclerosis, inflammation, vascular biology, translational studies
Hybridisation boosts dispersal of two contrasted ecotypes in a grass species
Authors: Curran Emma V. , Scott Matilda S. , Olofsson Jill K. , Nyirenda Florence , Sotelo Graciela , Bianconi Matheus E. , Manzi Sophie , Besnard Guillaume , Christin Pascal-Antoine
Published: April 2021

In the absence of strong reproductive barriers, genetic exchanges between closely related groups of organisms with different adaptations have well-documented beneficial and detrimental consequences. In plants, pollen-mediated exchanges affect the sorting of alleles across physical landscapes, and influence rates of hybridisation. How these dynamics affect the emergence and spread of novel ecological strategies remains only partially understood.

We use phylogenomics and population genomics to retrace the origin of two geographically overlapping ecotypes of the African grassAlloteropsis angusta.

We report the existence of a previously undescribed ecotype inhabiting miombo woodlands and grasslands. The two ecotypes have divergent nuclear genomes. However, the seed-transported chloroplast genomes are consistently shared by distinct ecotypes inhabiting the same region. These patterns suggest that the nuclear genome of one ecotype can reach the seeds of the other via pollen movements, with strong selection subsequently sorting nuclear alleles by habitat.

The contrasting ecotypes ofA. angustacan use each other as a gateway to new locations across a large part of Africa. Coupled with newly discovered hybridisation with the sister speciesA. semialata, our results show that hybridisation can facilitate the geographical dispersal of distinct ecotypes of the same grass species.
Genome of the estuarine oyster provides insights into climate impact and adaptive plasticity
Authors: Li Ao , Dai He , Guo Ximing , Zhang Ziyan , Zhang Kexin , Wang Chaogang , Wang Wei , Chen Hongju , Li Xumin , Zheng Hongkun , Zhang Guofan , Li Li
Published: April 2021

Understanding the roles of genetic divergence and phenotypic plasticity in adaptation is central to evolutionary biology and important for assessing adaptive potential of species under climate change. Analysis of a chromosome-level assembly and resequencing of individuals across wide latitude distribution in the estuarine oyster (Crassostrea ariakensis) revealed unexpectedly low genomic diversity and population structures shaped by historical glaciation, geological events and oceanographic forces. Strong selection signals were detected in genes responding to temperature and salinity stress, especially of the expandedsolute carrierfamilies, highlighting the significance of gene expansion in environmental adaptation. Genes exhibiting high plasticity showed strong selection in upstream regulatory regions that modulate transcription, indicating selection favoring plasticity. Our findings suggest that genomic variation and population structure in marine bivalves are heavily influenced by climate history and physical forces, and gene expansion and selection may enhance phenotypic plasticity that is critical for the adaptation to rapidly changing environments.
Sonicated fibrils of huntingtin exon-1 preferentially seed neurons and produce toxic assemblies
Authors: Chongtham Anjalika , Isas J Mario , Pandey Nitin K , Rawat Anoop , Yoo Jung Hyun , Mastro Tara , Kennedy Marry , Langen Ralf , Khoshnan Ali
Published: April 2021

Huntington’s disease (HD) is a genetically inherited neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) repeats in the exon-1 of huntingtin protein (HTT). The expanded polyQ enhances the amyloidogenic propensity of HTT exon 1 (HTTex1), which forms a heterogeneous mixture of assemblies with some being neurotoxic. While predominantly intracellular, monomeric and aggregated mutant HTT species are also present in the cerebrospinal fluids of HD patients, however, their biological properties are not well understood. To explore the role of extracellular mutant HTT in aggregation and toxicity, we investigated the possible uptake and amplification of recombinant HTTex1 assemblies in cell culture models. We found seeding-competent species in the sonicated HTTex1 fibrils, which preferentially entered human neurons and triggered the amplification of neurotoxic assemblies; astrocytes or epithelial cells were not permissive to the HTTex1 seeding. The aggregation of HTTex1 seeds in neurons depleted endogenous HTT protein with non-pathogenic polyQ repeat, activated apoptotic caspase-3 pathway and induced nuclear fragmentation. Using a panel of novel monoclonal antibodies and genetic mutation, we identified epitopes within the N-terminal 17 amino acids and proline-rich domain of HTTex1 mediating neural seeding. Synaptosome preparations from the brains of HD mice also contained similar neurotoxic seeding-competent mutant HTT species. Our findings suggest that amyloidogenic extracellular mutant HTT assemblies may selectively enter neurons, propagate and produce neurotoxic assemblies.
Thalamocortical mechanisms regulating the relationship between transient beta events and human tactile perception
Authors: Law Robert G. , Pugliese Sarah , Shin Hyeyoung , Sliva Danielle D. , Lee Shane , Neymotin Samuel , Moore Christopher , Jones Stephanie R.
Published: April 2021

Transient neocortical events with high spectral power in the 15–29Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100–300ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, non-lemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300ms time scale to suppress sensory information. Further analysis showed that the same beta generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event faciliatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.