bluuebunny/crossref_metadata_2025 huggingface dataset:
Future perspectives of robot psychiatry: can communication robots assist psychiatric evaluation in the COVID-19 pandemic era?
Authors: Yoshikawa Yuichiro , Kumazaki Hirokazu , Kato Takahiro A.
Published: February 2021

Purpose of review

Direct face-to-face interview between a psychiatrist and a patient is crucial in psychiatric evaluation, however, such traditional interviews are becoming difficult to conduct because of the infection risk in the COVID-19 era. As telepsychiatry, video interviews using internet are suggested to be useful to evaluate and assist individuals with mental disorders. However, some patients especially with social phobia, depression, and autism spectrum disorder (ASD) hesitate to use even such face-to-face-like tools. Communication robots have been proposed as future assistant tools for such patients. Herein, we summarize recent advancements in robot psychiatry, and propose the benefits of communication robots in psychiatric evaluation.

Recent findings

Recent studies have suggested that communication robots are effective in assisting people with ASD. As a pilot trial, we herein conducted semi-structured interviews to evaluate depression and hikikomori, a form of pathological social withdrawal, using a communication robot and a psychiatrist, respectively. There was almost identical evaluation between the two. Interestingly, a person with hikikomori answered that the robot was easier to disclose.

Robots can reduce the burden of human resources and the infection risk in the COVID-19 era. Robot interview is expected to be implemented for future evaluation system in psychiatry.
Urbanization and mental health as a research problem in Latin America (with a focus on Brazil)
Authors: Almeida-Filho Naomar
Published: February 2021

Purpose of review

The basic hypothesis of this paper is that, in Latin America, the nature of the set of variables or determinants regarding the relationships of urbanization (and correlated processes of social change, modernization, acculturation, and economic inclusion) and mental health varies with the political context or historical phase considered. To assess the validity of the hypothesis, I propose a periodization of the economic, political, and social changes that occurred in Latin America in the past decades.

Recent findings

A brief review of recent studies on social determinants of mental health (with a focus on Brazil), considering research findings by historical context, shows that urbanization–modernization–migration variables were more present in the literature in the decades of 1980 and 1990, whereas social inequity factors (gender, ethnicity/race, and racism) came to be dominant as a research question after the year 2000.

New approaches of the mental health situation of peripheral societies such as those in the Latin American continent have gone beyond the urban environment as a determinant and start to consider social determination processes and political contexts.
Cancer and schizophrenia
Authors: Nordentoft Merete , Plana-Ripoll Oleguer , Laursen Thomas Munk
Published: February 2021

Purpose of review

On the basis of articles published in 2018, 2019 and 2020, the first aim of this review is to present estimates of incidence rates and excess mortality of overall cancer and organ-specific cancers for patients with schizophrenia compared with the general population.

The second aim is to explore if underdiagnosis and undertreatment can explain – at least partly – the increased mortality of cancer in patients with schizophrenia compared with the general population.

Recent findings

Patients diagnosed with schizophrenia have an approximately 50% increased risk of death by cancer compared to age and sex-matched people in the general population. Studies have confirmed an increased mortality from breast, lung and colon cancer in patients with schizophrenia.

Analyses of incidence of cancer revealed contradicting results, with some studies showing no increase in incidence and others a modestly increased incidence in overall cancer. Studies of incidence of specific types of cancers showed modestly increased risk of pancreas, oesophagus, breast cancer and contradicting results regarding lung cancer.

In studies identified that compared to the general population, patients with schizophrenia were at an increased risk of not being diagnosed or treated for cancer before death of cancer. In addition, patients with schizophrenia had lower chances of getting optimal treatment for colon cancer after diagnosis.

This review indicates that patients with schizophrenia are at increased risk of dying of cancer and of several specific types of cancer. This increased mortality can be reduced if the price of tobacco is increased, if smoking cessation programmes are offered systematically, screening programs better implemented in this highly vulnerable group, and if procedures to facilitate access to early diagnosis and effective treatment are implemented.
Estrogens in schizophrenia: progress, current challenges and opportunities
Authors: Brand Bodyl A. , de Boer Janna N. , Sommer Iris E.C.
Published: February 2021

Purpose of review

Schizophrenia is a heterogeneous psychiatric disorder with a different, but not necessarily milder clinical presentation in women as compared to men. These sex differences have largely been attributed to the protective role of estrogens. This article reviews the current state of estrogen research in schizophrenia.

Recent findings

Estrogens regulate important pathophysiological pathways in schizophrenia, including dopamine activity, mitochondrial function, and the stress system. Estrogen deficiency is common in both sexes and is associated with increases in psychotic symptoms. Hyperprolactinemia causes secondary estrogen deficiency and can be a reaction to stress, or secondary to prolactin-raising antipsychotics. Therefore, prolactin-sparing antipsychotics should be preferred especially in premenopausal women, who are more prone to hyperprolactinemia. Premenopausal women furthermore require lower doses of antipsychotics than men, since estrogens raise the availability and efficacy of antipsychotics.

The past years have established the importance of estrogens in the pathophysiology of schizophrenia and have shown its relevance to clinical practice through its influence on antipsychotic drug efficacy. Future research should focus on the neurobiological and clinical effect of contraceptives in premenopausal women with schizophrenia. Furthermore, the potential of estrogen-like augmentation with raloxifene and phytoestrogens in schizophrenia should be established in the coming years.
Obesity and COVID-19 Mortality A Cross-Country Analysis
Authors: De Giorgi Giacomo , Michalik Felix
Published: February 2021

We highlight a robust correlation between COVID-19 mortality and obesity prevalence using available country level data on COVID-19 mortality as of August 10, 2020. Such association is robust to controlling for other potential comorbidity factors: diabetes, cardio-vascular, and respiratory diseases, further to a set of demographics, urban, and economic, and containment policies controls. We estimate that .6 log point increase in obesity prevalence, or 1 standard deviation, is associated with about an extra .9 log point per 100,000 deaths (or 50% of a standard deviation, .5σ).
Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort
Authors: Pingault Jean-Baptiste , Barkhuizen Wikus , Wang Biyao , Hannigan Laurie J. , Eilertsen Espen Moen , Andreassen Ole A. , Ask Helga , Tesli Martin , Askeland Ragna Bugge , Smith George Davey , Davies Neil , Reichborn-Kjennerud Ted , Ystrom Eivind , Havdahl Alexandra
Published: February 2021

Importance

Knowledge of the mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) symptoms can inform psychosocial interventions.

Objective

To investigate whether parental genetic risk factors associate with their children’s ADHD symptoms due to genetic transmission of risk or due to parental genetic liability that influences offspring ADHD via parenting environments (genetic nurture).

Design and participants

This study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. This prospective cohort study consisted of 5,405 mother-father-offspring trios recruited between 1999 – 2008.

Exposures

We calculated polygenic scores for parental traits previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment and intellectual ability.

Main outcomes and measures

Mothers reported on their 8-year-old children’s ADHD symptoms using the Parent/Teacher Rating Scale for Disruptive Behavior Disorders.

Results

Maternal polygenic scores for ADHD, autism spectrum disorder (ASD), neuroticism and smoking predicted child ADHD symptoms in bivariate analyses. After jointly modelling maternal, paternal and child polygenic scores, ADHD symptoms were predicted by children’s polygenic scores for ADHD (β = 0.10; 95% CI 0.07 to 0.14), smoking (β = 0.07; 95% CI 0.03 to 0.10) and educational attainment (β = −0.09; 95% CI −0.13 to −0.05), indicating direct genetic transmission of risk. Mothers’ polygenic scores for ASD (β = 0.05; 95% CI 0.02 to 0.08) and neuroticism (β = 0.05; 95% CI 0.01 to 0.08) predicted children’s ADHD symptoms conditional on fathers’ and children’s scores, implicating genetic nurture, or effects due to population stratification or assortative mating.

Conclusions

These results suggest that associations between some parental traits and offspring ADHD symptoms likely reflect a nuanced mix of direct genetic transmission (ADHD, smoking and educational attainment) and genetic nurture (ASD and neuroticism). If confirmed, these findings support previous evidence that maternal ASD or neuroticism may be possible targets for intervention to help break the chain of the intergenerational transmission of ADHD risk.
Mortality after surgery with SARS-CoV-2 infection in England: A population-wide epidemiological study
Authors: Abbott T. E. F. , Fowler A. J. , Dobbs T. D. , Gibson J. , Shahid T. , Dias P. , Akbari A. , Whitaker I. S. , Pearse R. M.
Published: February 2021

Objectives

To confirm the incidence of perioperative SARS-CoV-2 infection and associated mortality after surgery.

Design and setting

Analysis of routine electronic health record data from National Health Service (NHS) hospitals in England.

Methods

We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between 1st January 2020 and 31st October 2020. The exposure was SARS-CoV-2 infection defined by ICD-10 codes. The primary outcome measure was 90-day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson co-morbidity index, index of multiple deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals.

Results

We identified 1,972,153 patients undergoing surgery of whom 11,940 (0.6%) had SARS-CoV-2. In total, 19,100 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 2,618/11,940 [21.9%] vs No SARS-CoV-2: 16,482/1,960,213 [0.8%]; OR: 5.8 [5.5 – 6.1]; p<0.001). Amongst patients undergoing elective surgery 1,030/1,374,985 (0.1%) had SARS-CoV-2 of whom 83/1,030 (8.1%) died, compared with 1,092/1,373,955 (0.1%) patients without SARS-CoV-2 (OR: 29.0 [22.5 −37.3]; p<0.001). Amongst patients undergoing emergency surgery 9,742/437,891 (2.2%) patients had SARS-CoV-2, of whom 2,466/9,742 (25.3%) died compared with 14,817/428,149 (3.5%) patients without SARS-CoV-2 (OR: 5.7 [5.4 – 6.0]; p<0.001).

Conclusions

The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

Summary boxes

What is already known on this topic

High mortality rates have been reported amongst surgical patients who develop COVID-19 but we don’t know how this compares to the concurrent surgical population unaffected by COVID-19.

Strict infection prevention and control procedures have substantially reduced the capacity of surgical treatment pathways in many hospitals.

The very large backlog in delayed and cancelled surgical procedures is a growing public health concern.

What this study adds

Fewer than 1 in 100 surgical patients are affected by COVID-19 in the English National Health Service.

Elective surgical patients who do develop COVID-19 are 30 times more likely to die while in hospital.

Infection prevention and control procedures in NHS surgical pathways are highly effective but cannot be safely relaxed.
Neuropsychiatric and cognitive symptoms across the Alzheimer’s disease clinical spectrum: Cross-sectional and longitudinal associations
Authors: Eikelboom Willem S. , van den Berg Esther , Singleton Ellen , Baart Sara J. , Coesmans Michiel , Leeuwis Annebet E. , Teunissen Charlotte E. , van Berckel Bart N.M. , Pijnenburg Yolande A.L. , Scheltens Philip , van der Flier Wiesje M. , Ossenkoppele Rik , Papma Janne M.
Published: February 2021

Objective

To investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of amyloid-β positive individuals across the Alzheimer’s disease (AD) clinical spectrum.

Methods

We included 1,524 amyloid-β positive individuals from the Amsterdam Dementia Cohort with subjective cognitive decline (SCD, n=113), mild cognitive impairment (MCI, n=321), or dementia (n=1,090). We measured NPS with the neuropsychiatric inventory (NPI), examining total scores and the presence of specific NPI-items. Cognition was assessed across five cognitive domains and with the MMSE. We examined trajectories including model based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time-points (subsample n=520, Mean=1.8 [SD=0.7] years follow-up).

Results

NPS were prevalent across all clinical AD stages (NPI total score ≥1 81.4% in SCD, 81.2% in MCI, 88.7% in dementia). Cognitive functioning showed an uniform gradual decline; while in contrast, large intra-individual heterogeneity of NPS was observed over time across all groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range β:-0.18–0.11, FDR-adjusted p<0.05), while there were no cross-sectional relationships in SCD and MCI (β:-0.32– 0.36, FDR-adjusted p>0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage (β:-0.13–0.44, FDR-adjusted p>0.05).

Conclusion

NPS and cognitive symptoms are both prevalent across the AD continuum, but show a different evolution during the course of the disease.
Early Identification of SARS-CoV-2 Emergence in the DoD via Retrospective Analysis of 2019-2020 Upper Respiratory Illness Samples
Authors: Chapleau Richard R. , Christian Monica , Connors Benjamin , Premo Christa , Chao Tim C. , Rodriguez Juan , Huntsberger Shana , Meyer Jennifer , Javorina Amanda , Reynolds Kenney , Riddle David , Lisanby Mark , Starr Clarise
Published: February 2021

The first case of non-travel related SARS-COV-2 was detected late February 2020 in California, however the delay of diagnostic testing and initial stringent testing criteria made it difficult to identify those who could have acquired it through community spread. There was speculation by many that the virus may have been circulating at least a month earlier [1], and environmental sampling has suggested that versions of this virus were found many months before the first human samples were identified [2]. Here we performed a retrospective study from residual samples collected from a global DoD Respiratory Surveillance Program to establish a tentative timeline by which this virus was circulating in our DoD population. We performed RT-PCR for SARS-COV-2 and compared to the dates of these cases to the first cases identified in respective states and counties using the Johns Hopkins COVID tracker website. Twenty-four positive samples were identified out of approximately 7,000 tested. Although we found some early cases in certain regions, we did not see circulation before late February in samples collected both in the US and outside the USA.

What is already known about this topic?

We know that the first reported case of SARS-COV-2 was mid-January; however, there has been conjecture that the virus was found in the community before this date.

What is added by this report?

Here we took samples collection from a global respiratory surveillance program and evaluated for the presence of SARS-COV-2 RNA. The first case we found in the surveillance program was approximately 30-60 days before the first case was identified on military installations via diagnostic testing, however was not earlier than the mid-January reported case in California.

What are the implications for public health practice?

The implementation of new and emerging pathogen detection assays into already established surveillance programs could detect early community spread and possibly reduce spread of pathogen among vulnerable populations.
Visuospatial processing impairment following mild COVID-19
Authors: de Paula Jonas Jardim , Paiva Rachel Elisa Rodrigues Pereira , Costa Danielle de Souza , Souza e Silva Nathália Gualberto , Rosa Daniela Valadão , Januário José Nélio , Silva Luciana Costa , de Miranda Débora Marques , Romano-Silva Marco Aurélio
Published: February 2021

Severe Acute Respiratory Syndrome Coronavirus 2 infection causes coronavirus disease 2019. COVID-19 was an unknown infection that reached pandemic proportions in 2020 and has shown to bring long-term negative consequences. Here, we used a case-control design to investigate the performance of relatively young people recovered from COVID 19 in objective neuropsychological tests. We found significant differences between groups for all measures of the ROCFT with a large difference in the copy, a moderate difference in immediate recall, and a large difference in delayed recall. No significant differences were found for the measures from all the other five neuropsychological tests used.About one quarter of COVID 19 patients were below the 10th percentile according to normative data.
Low somatosensory cortex excitability in the acute stage of low back pain causes chronic pain
Authors: Jenkins Luke C , Chang Wei-Ju , Buscemi Valentina , Liston Matthew , Skippen Patrick , Cashin Aidan G , McAuley James H , Schabrun Siobhan M
Published: February 2021

BACKGROUND

Determining the mechanistic causes of complex biopsychosocial health conditions such as low back pain (LBP) is challenging, and research is scarce. Cross-sectional studies demonstrate altered excitability and organisation of the primary somatosensory and primary motor cortex in people with acute and chronic LBP, however, no study has explored these mechanisms longitudinally or attempted to draw causal inferences.

METHODS

Prospective, longitudinal, cohort study including 120 people with an acute episode of LBP. Sensory evoked potential area measurements were used to assess primary and secondary somatosensory cortex excitability. Transcranial magnetic stimulation derived map volume was used to assess corticomotor excitability. Directed acyclic graphs identified variables potentially confounding the exposure-outcome relationship. The effect of acute-stage sensorimotor cortex excitability on six-month LBP outcome was estimated using multivariable regression modelling, with adjusted and unadjusted estimates reported. Sensitivity analyses were performed to explore the effect of unmeasured confounding and missing data.

RESULTS

Lower primary (OR = 2.08, 95% CI = 1.22 to 3.57) and secondary (OR = 2.56, 95% CI = 1.37 to 4.76) somatosensory cortex excitability in the acute stage of LBP increased the odds of developing chronic pain at six-month follow-up. This finding was robust to confounder adjustment and unmeasured confounding (E-Value = 2.24 & 2.58, respectively). Corticomotor excitability in the acute stage of LBP was associated with higher pain intensity at 6-month follow-up (B = −0.15, 95% CI: −0.28 to −0.02) but this association did not remain after confounder adjustment.

CONCLUSION

These data provide the first evidence that low somatosensory cortex excitability in the acute stage of LBP is a cause of chronic pain. Interventions designed to increase somatosensory cortex excitability in acute LBP may be relevant to the prevention of chronic pain.
Rapid increase of SARS-CoV-2 seroprevalence during the 2020 pandemic year in the population of the city of Tirana, Albania
Authors: Sulcebe Genc , Ylli Alban , Cenko Fabian , Kurti-Prifti Margarita
Published: February 2021

Introduction

While the identification of anti SARS-CoV-2 antibodies has been used to measure the hidden circulation of the COVID-19 in communities, there are few publications on the dynamics of SARS-CoV-2 seroprevalence during both waves of 2020. This study provides original data about the change in proportion of individuals showing immune response to COVID-19 between beginning of July and end of December 2020.

Methods

The study was conducted in two rounds, 27 June −3 July, and 21-28 December 2020, using two independently selected samples of individuals 20-70 years old. Study participants were randomly selected from lists of the inhabitants of the catchment communities of four primary health care centers in Tirana City. Serological testing was performed by an ELISA method which determines IgG class antibodies anti S1 protein of SARS-CoV-2 virus. The validity of the method was tested in a sample of blood donor’s sera of 2018.

Results

The proportion of individuals classified as seropositive during the first round, in early July was 7.5% (95% CI: 4.3% −10.7%). The proportion rose sharply in the second round, by late December 2020, reaching 48.2% (95% CI: 44.8% −51.7%). The same increasing pattern was observed in all studied categories. No statistical significance was found between men and women and between age categories. The prevalence of seropositive individuals was always significantly higher among those who reported symptoms and those who had done the molecular test.

Conclusion

The ratio of total infected cases over confirmed cases was estimated to be higher than 10 to 1 in Albania. The rapid increase in SARS-CoV-2 seroprevalence observed in Tirana City may have been facilitated by a number of factors, including the very low infection exposure during the period March -May 2020, and the consecutive high susceptibility in population. Despite the observed high seroprevalence, one month after the study, COVID-19 incidence continued to increase in Tirana.
Gut microbiota link dietary fiber intake and short-chain fatty acid metabolism with eating behaviour
Authors: Medawar Evelyn , Haange Sven-Bastiaan , Rolle-Kampczyk Ulrike , Engelmann Beatrice , Dietrich Arne , Thieleking Ronja , Wiegank Charlotte , Fries Charlotte , Horstmann Annette , Villringer Arno , von Bergen Martin , Fenske Wiebke , Witte A. Veronica
Published: February 2021

Background

The gut microbiome modulates human brain function and eating behavior through multiple factors, including short-chain fatty acid (SCFA) signaling. We aimed to explore which bacterial genera relate to eating behavior, diet and SCFA metabolites in overweight adults. In addition, we tested whether eating-related microbiota relate to treatment success in patients after Roux-en-Y gastric bypass (RYGB).

Methods

Anthropometrics, dietary fibre intake, eating behaviour, 16S-rRNA-derived microbiota and SCFA measured in feces and blood were correlated in young overweight adults (n=27 (9F), 21-36 years, BMI 25-31 kg/m2). Correlated genera were compared in RYGB (n=23 (16F), 41-70 years, BMI 25-62 kg/m2) and in control patients (n=17 (11F), 26-69 years, BMI 25-48 kg/m2).

Results

In young adults, 7 bacteria genera, i.e. Alistipes, Blautia, Clostridiales cluster XVIII, Gemmiger, Roseburia, Ruminococcus and Streptococcus, correlated with healthier eating behavior, while 5 genera, i.e. Clostridiales cluster IV and XIVb, Collinsella, Fusicatenibacter and Parabacteroides, correlated with unhealthier eating (all |r| > 0.4, FDR-corrected p < 0.05). Some of these genera including Parabacteroides related to fiber intake and SCFA metabolites, and to weight status and treatment response in overweight/obese patients.

Conclusions

Specific bacterial genera, particularly Parabacteroides, were associated with weight status and eating behavior in two independent well-characterized cross-sectional samples. These exploratory findings indicate two groups of presumably beneficial and unfavourable genera that relate to eating behaviour and weight status, and indicate that dietary fiber and SCFA metabolism may modify these relationships.
The source of individual heterogeneity shapes infectious disease outbreaks
Authors: Elie Baptiste , Selinger Christian , Alizon Samuel
Published: February 2021

There is known heterogeneity between individuals in infectious disease transmission patterns. The source of this heterogeneity is thought to affect epidemiological dynamics but studies tend not to control for the overall heterogeneity in the number of secondary cases caused by an infection. To explore the role of individual variation in infection duration and transmission rate on parasite emergence and spread, while controlling for this potential bias, we simulate stochastic outbreaks with and without parasite evolution. As expected, heterogeneity in the number of secondary cases decreases the probability of outbreak emergence. Furthermore, for epidemics that do emerge, assuming more realistic infection duration distributions leads to faster outbreaks and higher epidemic peaks. When parasites require adaptive mutations to cause large epidemics, the impact of heterogeneity depends on the underlying evolutionary model. If emergence relies on within-host evolution, decreasing the infection duration variance decreases the probability of emergence. These results underline the importance of accounting for realistic distributions of infection rates to anticipate the effect of individual heterogeneity on epidemiological dynamics.
openEHR is FAIR-Enabling by Design
Authors: Frexia Francesca , Mascia Cecilia , Lianas Luca , Delussu Giovanni , Sulis Alessandro , Meloni Vittorio , Del Rio Mauro , Zanetti Gianluigi
Published: February 2021

The FAIR Principles are a set of recommendations that aim to underpin knowledge discovery and integration by making the research outcomes Findable, Accessible, Interoperable and Reusable. These guidelines encourage the accurate recording and exchange of structured data, coupled with contextual information about their creation, expressed in domain-specific standards and machine readable formats. This paper analyses the potential support to FAIRness of the openEHR e-health standard, by theoretically assessing the compliance with each of the 15 FAIR principles of a hypothetical Clinical Data Repository (CDR) developed according to the openEHR specifications. Our study highlights how the openEHR approach, thanks to its computable semantics-oriented design, is inherently FAIR-enabling and is a promising implementation strategy for creating FAIR-compliant CDRs.
Association between benzodiazepine receptor agonist use and increased mortality among patients hospitalized for COVID-19: results from an observational study
Authors: Hoertel N. , Sánchez-Rico M. , Gulbins E. , Kornhuber J. , Vernet R. , Beeker N. , Neuraz A. , Blanco C. , Olfson M. , Airagnes G. , Lemogne C. , Alvarado J. M. , Arnaout M. , Meneton P. , Limosin F.
Published: February 2021

Objective

To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalized for COVID-19.

Methods

We conducted an observational multicenter retrospective cohort study at AP-HP Greater Paris University hospitals. The sample involved 14,381 adult patients hospitalized for COVID-19. 686 (4.8%) inpatients received a BZRA within at the time of hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (SD=25.4). The study baseline was the date of hospital admission and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for patient characteristics (such as age, sex, obesity and comorbidity) and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW).

Results

Over a mean follow-up of 14.5 days (SD=18.1), the primary endpoint occurred in 186 patients (27.1%) who received a BZRA and in 1,134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (HR=3.20; 95% CI=2.74-3.74; p<0.01) and in the primary IPW analysis (HR=1.61; 95% CI=1.31-1.98, p<0.01), with a significant dose-dependent relationship (HR=1.55; 95% CI=1.08-2.22; p=0.02). This association remained significant in multiple sensitivity analyses.

Conclusions

BZRA use was associated with increased mortality among patients hospitalized for COVID-19 with a dose-dependent relationship, suggesting a potential benefit of decreasing dose or tapering off these medications when possible in these patients.
A computationally efficient approach to segmentation of the aorta and coronary arteries using deep learning
Authors: Cheung Wing Keung , Bell Robert , Nair Arjun , Menezies Leon , Patel Riyaz , Wan Simon , Chou Kacy , Chen Jiahang , Torii Ryo , Davies Rhodri H. , Moon James C. , Alexander Daniel C. , Jacob Joseph
Published: February 2021

A fully automatic two-dimensional Unet model is proposed to segment aorta and coronary arteries in computed tomography images. Two models are trained to segment two regions of interest, (1) the aorta and the coronary arteries or (2) the coronary arteries alone. Our method achieves 91.20% and 88.80% dice similarity coefficient accuracy on regions of interest 1 and 2 respectively. Compared with a semi-automatic segmentation method, our model performs better when segmenting the coronary arteries alone. The performance of the proposed method is comparable to existing published two-dimensional or three-dimensional deep learning models. Furthermore, the algorithmic and graphical processing unit memory efficiencies are maintained such that the model can be deployed within hospital computer networks where graphical processing units are typically not available.
Statewide Impact of COVID-19 on Social Determinants of Health - A First Look: Findings from the Survey of the Health of Wisconsin
Authors: Malecki Kristen M.C. , Schultz Amy A. , Nikodemova Maria , Walsh Matt C. , Bersch Andrew J. , Cronin Jacquie , Cadmus-Bertram Lisa , Engelman Corinne D. , Lubsen Julia R. , Peppard Paul E. , Sethi Ajay K.
Published: February 2021

There is an urgent need to track the early and ongoing impact of the COVID-19 pandemic on population health from local to global scales. At the same time, there is an overall lack of U.S. state-specific surveillance data tracking social determinants of health (SDOH) and associations with population well-being, individual mitigation and coping strategies, family dynamics and other economic shocks of the pandemic in populations. Statewide data can offer important insights into how SDOH shape the long-term effects of COVID-19 in the population since implementation of many policies and programs varied widely early on in the pandemic. In May of 2020, the Survey of the Health of Wisconsin (SHOW) program launched a statewide online/phone survey of early and ongoing impacts of COVID-19 on health and well-being across diverse communities and families. The goal of this study is to provide descriptive data including perceived COVID-19 risks, access to and results of COVID-19 antigen testing, individual mitigation and coping strategies, family dynamics and other economic shocks of the pandemic on health and mental health in populations. Key findings include higher rates of testing and perceived past infection from COVID-19 among non-white respondents. Higher economic shifts and job changes in female vs male respondents. Families with children reported overall higher levels of stress, and stress from the pandemic. There were urban and rural differences in changes to access to care. Rural regions, which had a lower prevalence of infections early in the pandemic as compared to urban areas, also reported fewer delays or missed appointments due to COVID-19. Key findings show that SDOH are shaping impacts of health and well-being early on in the pandemic and future longitudinal follow-up will be important to shape policies and programs well into the future.
quincunx: an R package to query, download and wrangle PGS Catalog data
Authors: Magno Ramiro , Duarte Isabel , Maia Ana -Teresa
Published: February 2021

Motivation

The Polygenic Score (PGS) Catalog is a recently established open database of published polygenic scores that, to date, has collected, curated, and made available 721 polygenic scores from over 133 publications. The PGS Catalog REST API is the only method allowing programmatic access to this resource.

Results

Here, we describequincunx, an R package that provides the first client interface to the PGS Catalog REST API.quincunxenables users to query and quickly retrieve, filter and integrate metadata associated with polygenic scores, as well as polygenic scoring files in tidy table format.

Availability

quincunxis freely available under an MIT License, and can be accessed fromhttps://github.com/maialab/quincunx.
High Light and High Temperature Reduce Photosynthesis via Different Mechanisms in the C4ModelSetaria viridis
Authors: Anderson Cheyenne M. , Mattoon Erin M. , Zhang Ningning , Becker Eric , McHargue William , Yang Jiani , Patel Dhruv , Dautermann Oliver , McAdam Scott A. M. , Tarin Tonantzin , Pathak Sunita , Avenson Tom J. , Berry Jeffrey , Braud Maxwell , Niyogi Krishna K. , Wilson Margaret , Nusinow Dmitri A. , Vargas Rodrigo , Czymmek Kirk J. , Eveland Andrea L. , Zhang Ru
Published: February 2021

C4plants frequently experience damaging high light (HL) and high temperature (HT) conditions in native environments, which reduce growth and yield. However, the mechanisms underlying these stress responses in C4plants have been under-explored, especially the coordination between mesophyll (M) and bundle sheath (BS) cells. We investigated how the C4model plantSetaria viridisresponded to a four-hour HL or HT treatment at the photosynthetic, transcriptomic, and ultrastructural levels. Although we observed a comparable reduction of photosynthetic efficiency in HL- or HT-treated leaves, detailed analysis of multi-level responses revealed important differences in key pathways and M/BS specificity responding to HL and HT. We provide a systematic analysis of HL and HT responses inS. viridis, reveal different acclimation strategies to these two stresses in C4plants, discover unique light/temperature responses in C4plants in comparison to C3plants, and identify potential targets to improve abiotic stress tolerance in C4crops.
Cohesin-independent STAG proteins interact with RNA and localise to R-loops to promote complex loading
Authors: Porter Hayley , Li Yang , Neguembor Maria Victoria , Beltran Manuel , Varsally Wazeer , Martin Laura , Cornejo Manuel Tavares , Pezic Dubravka , Bhamra Amandeep , Surinova Silvia , Jenner Richard G. , Cosma Maria Pia , Hadjur Suzana
Published: February 2021

Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in the localization of cohesin to diverse biological processes and promotes loading of the complex at these sites. We show that in cells acutely depleted for RAD21, SA proteins remain bound to chromatin, cluster in 3D and interact with CTCF, as well as with a wide range of RNA binding proteins involved in multiple RNA processing mechanisms. Accordingly, SA proteins interact with RNA and are localised to R-loops where they contribute to R-loop regulation. Our results place SA1 within R-loop domains upstream of the cohesin complex and reveal a role for SA1 in cohesin loading which is independent of NIPBL, the canonical cohesin loader. We propose that SA1 takes advantage of structural R-loop platforms to link cohesin loading and chromatin structure with diverse functions. Since SA proteins are pan-cancer targets, and R-loops play an increasingly prevalent role in cancer biology, our results have important implications for the mechanistic understanding of SA proteins in cancer and disease.
Waves of sumoylation support transcription dynamics during adipocyte differentiation
Authors: Zhao Xu , Hendriks Ivo A. , Gras Stéphanie Le , Ye Tao , Nguéa P Aurélie , Ramos-Alonso Lucia , Lien Guro Flor , Klungland Arne , Jost Bernard , Enserink Jorrit M. , Nielsen Michael L. , Chymkowitch Pierre
Published: February 2021

Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, little is known about the mechanisms that orchestrate the dramatic transcriptional changes leading to adipocyte differentiation. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like Pparγ/RXR and their co-factors is associated with the transcription of adipogenic genes. Our data demonstrate that the sumoylation pathway coordinates the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides an in-depth resource of gene transcription dynamics, SUMO-regulated genes and sumoylation sites during adipogenesis.
KLF2 is a therapeutic target for COVID-19 induced endothelial dysfunction
Authors: Xu Suowen , Luo Sihui , Zheng Xueying , Weng Jianping
Published: February 2021

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its mechanism being incompletely understood. Emerging evidence has demonstrated that the endothelium represents the Achilles' heel in COVID-19 patients and that endothelial dysfunction precipitates COVID-19 and accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. Primary human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) were treated with serum from control subjects or COVID-19 patients. Downstream monocyte adhesion and associated gene/protein expression was evaluated in endothelial cells exposed to COVID-19 patient serum in the presence of KLF2 activator (Atorvastatin) or KLF2 overexpression by an adenoviral vector. Here, we demonstrate that the expression of KLF2 was significantly reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1β and TNF-α, two cytokines observed in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis and reduced angiogenesis). Treatment of HPMECs with atorvastatin or KLF2 adenovirus ameliorate COVID-19 serum-induced increase in endothelial inflammation and monocyte adhesion by increasing KLF2 expression. Altogether, the present study demonstrates that genetic and pharmacological activation of KLF2 represses COVID-19 associated endothelial dysfunction, heralding a potentially new direction to treat endothelialitis accompanying COVID-19.
CheSPI: Chemical shift Secondary structure Population Inference
Authors: Nielsen Jakob Toudahl , Mulder Frans A.A.
Published: February 2021

NMR chemical shifts (CSs) are delicate reporters of local protein structure, and recent advances in random coil CS (RCCS) prediction and interpretation now offer the compelling prospect of inferring small populations of structure from small deviations from RCCSs. Here, we present CheSPI, a simple and efficient method that provides unbiased and sensitive aggregate measures of local structure and disorder. It is demonstrated that CheSPI can predict even very small amounts of residual structure and robustly delineate subtle differences into four structural classes for intrinsically disordered proteins. For structured regions and proteins, CheSPI can assign up to eight structural classes, which coincide with the well-known DSSP classification. The program is freely available, and can either be invoked from URLwww.protein-nmr.orgas a web implementation, or run locally from command line as a python program. CheSPI generates comprehensive numeric and graphical output for intuitive annotation and visualization of protein structures. A number of examples are provided.
Target enrichment and extensive population sampling help untangle the recent, rapid radiation of Oenothera sect. Calylophus
Authors: Cooper Benjamin J. , Moore Michael J. , Douglas Norman A. , Wagner Warren L. , Johnson Matthew G. , Overson Rick P. , McDonnell Angela J. , Levin Rachel A. , Raguso Robert A. , Olvera Hilda Flores , Ochoterena Helga , Fant Jeremie B. , Skogen Krissa A. , Wickett Norman J.
Published: February 2021

Oenothera sect. Calylophus is a North American group of 13 recognized taxa in the evening primrose family (Onagraceae) with an evolutionary history that may include independent origins of bee pollination, edaphic endemism, and permanent translocation heterozygosity. Like other groups that radiated relatively recently and rapidly, taxon boundaries within Oenothera sect. Calylophus have remained challenging to circumscribe. In this study, we used target enrichment, flanking non-coding regions, summary coalescent methods, tests for gene flow modified for target-enrichment data, and morphometric analysis to reconstruct phylogenetic hypotheses, evaluate current taxon circumscriptions, and examine character evolution in Oenothera sect. Calylophus. Because sect. Calylophus comprises a clade with a relatively restricted geographic range, we were able to extensively sample across the range of geographic and morphological diversity in the group. We found that the combination of exons and flanking non-coding regions led to improved support for species relationships. We reconstructed potential hybrid origins of some accessions and note that if processes such as hybridization are not taken into account, the number of inferred evolutionary transitions may be artificially inflated. We recovered strong evidence for multiple origins of the evolution of bee pollination from ancestral hawkmoth pollination, the evolution of edaphic specialization on gypsum, and permanent translocation heterozygosity. This study applies newly emerging techniques alongside dense infraspecific sampling and morphological analyses to effectively address a relatively common but recalcitrant problem in evolutionary biology.
Widespread cryptic variation in genetic architecture between the sexes
Authors: van der Bijl Wouter , Mank Judith E.
Published: February 2021

The majority of the genome is shared between the sexes, and it is expected that the genetic architecture of most traits is shared as well. This common architecture has been viewed as a major source of constraint on the evolution of sexual dimorphism (SD). SD is nonetheless common in nature, leading to assumptions that it results from differential regulation of shared genetic architecture. Here, we study the effect of thousands of gene knock-out mutations on 202 mouse phenotypes to explore how regulatory variation affects SD. We show that many traits are dimorphic to some extent, and that a surprising proportion of knock-outs have sex-specific phenotypic effects. Many traits, regardless whether they are monomorphic or dimorphic, harbor cryptic differences in genetic architecture between the sexes, resulting in sexually discordant phenotypic effects from sexually concordant regulatory changes. This provides an alternative route to dimorphism through sex-specific genetic architecture, rather than differential regulation of shared architecture.
Modulating the properties of DNA-SWCNT sensors using chemically modified DNA
Authors: Gillen Alice J. , Lambert Benjamin P. , Antonucci Alessandra , Molina-Romero Daniel , Boghossian Ardemis A.
Published: February 2021

Properties of SWCNT-based sensors such as brightness and detection capabilities strongly depend on the characteristics of the wrapping used to suspend the nanotubes. In this study, we explore ways to modify the properties of DNA-SWCNT sensors by using chemically modified DNA sequences, with the aim of creating sensors more suitable for use in in vivo and in vitro applications. We show that both the fluorescence intensity and sensor reactivity are strongly impacted not only by the chemical modification of the DNA but also by the method of preparation. In the absence of modifications, the sensors prepared using MeOH-assisted surfactant exchange exhibited higher overall fluorescence compared to those prepared by direct sonication. However, we demonstrate that the incorporation of chemical modifications in the DNA sequence could be used to enhance the fluorescence intensity of sonicated samples. We attribute these improvements to both a change in dispersion efficiency as well as to a change in SWCNT chirality distribution.

Furthermore, despite their higher intensities, the response capabilities of sensors prepared by MeOH-assisted surfactant exchange were shown to be significantly reduced compared to their sonicated counterparts. Sonicated sensors exhibited a globally higher turn-on response towards dopamine compared to the exchanged samples, with modified samples retaining their relative intensity enhancement. As the increases in fluorescence intensity were achieved without needing to alter the base sequence of the DNA wrapping or to add any exogenous compounds, these modifications can - in theory - be applied to nearly any DNA sequence to increase the brightness and penetration depths of a variety of DNA-SWCNT sensors without affecting biocompatibility or reducing the near-limitless sequence space available. This makes these sensors an attractive alternative for dopamine sensing in vitro and in vivo by enabling significantly higher penetration depths and shorter laser exposure times.