bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Systemic Lupus Erythematosus on Pregnancy
Authors: Miranda-Hernández Dafhne , Sánchez Antonio , Sánchez-Briones Reyna E. , Rivas-Ruiz Rodolfo , Cruz-Reynoso Leonardo , Cruz-Domínguez Pilar , Jara Luis Javier , Saavedra Miguel Ángel
Published: December 2020

Background

Pregnancy in patients with systemic lupus erythematosus is considered a high risk one since it is associated with a higher rate of maternal-fetal complications compared with the pregnancies in healthy women.

Objectives

The aim of this study was to describe the maternal-fetal outcomes in a cohort of Mexican patients with systemic lupus erythematosus and to identify risk factors associated with adverse maternal and fetal outcomes.

Patients and Methods

A cohort of pregnant lupus patients was analyzed. Maternal-fetal complications were described, and clinical, biochemical, and immunological variables associated with obstetric adverse outcomes were studied. Descriptive statistics, comparison of variables using appropriate tests, and finally logistic regression analysis were performed to identify potential risk factors for adverse maternal and fetal outcomes.

Results

A total of 351 pregnancies were included in a 10-year period. The most frequently observed maternal adverse outcomes were lupus flare (35%) and preeclampsia (14.5%). Active lupus before pregnancy (hazards ratio [HR], 3.7; 95% confidence interval [CI], 1.1–12.5; p = 0.003) was a predictor for these complications, whereas the use of antimalarial drugs (HR, 0.4; 95% CI, 0.2–0.7; p = 0.007) was a protective factor. The most frequent fetal adverse outcomes were preterm birth (38.1%), miscarriages (10%), and low birth weight babies (28%), and very low birth weight newborns (11%). Proteinuria in early pregnancy (HR, 7.1; 95% CI, 1.01–50.3; p = 0.04) and preeclampsia (HR, 9.3; 95% CI, 1.7–49.7; p = 0.009) were risk factors associated with these complications.

Conclusions

Variables related to systemic lupus erythematosus activity predict an adverse maternal outcome, whereas proteinuria in early pregnancy and preeclampsia are associated with an adverse fetal outcome.
Systemic Sclerosis Is Associated With Increased Inpatient Mortality in Patients Admitted for Acute Coronary Syndrome
Authors: Edigin Ehizogie , Ojemolon Pius Ehiremen , Eseaton Precious Obehi , Jamal Shakeel , Shaka Hafeez , Akuna Emmanuel , Asemota Iriagbonse Rotimi , Manadan Augustine
Published: December 2020

Objective

This study aims to compare the outcomes of patients primarily admitted for acute coronary syndrome (ACS) with and without systemic sclerosis (SSc). The primary outcome was odds of inpatient mortality. Hospital length of stay, total hospital charges, rates of cardiovascular procedures, and treatments were secondary outcomes of interest.

Methods

Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 Database. The NIS was searched for hospitalizations for adult patients with ACS (ST-segment elevation myocardial infarction [STEMI], non–ST-segment elevation myocardial infarction [NSTEMI], and unstable angina) as principal diagnosis with and without SSc as secondary diagnosis using International Classification of Diseases, Tenth Revision codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders.

Results

There were more than 71 million discharges included in the combined 2016 and 2017 NIS database. There were 1,319,464 hospitalizations for adult patients with a principal International Classification of Diseases, Tenth Revision code for ACS. There were 1155 (0.09%) of these hospitalizations that had SSc. The adjusted odds ratios for inpatient mortality for ACS, STEMI, and NSTEMI hospitalizations with coexisting SSc compared with those without SSc were 2.02 (95% confidence interval [CI], 1.19–3.43; p = 0.009), 2.47 (95% CI, 1.05–5.79; p = 0.038), and 2.19 (95% CI, 1.14–4.23; p = 0.019), respectively.

Conclusions

Acute coronary syndrome hospitalizations with SSc have increased inpatient mortality compared with those without SSc. ST-segment elevation myocardial infarction and NSTEMI hospitalizations with SSc have increased inpatient mortality compared with STEMI and NSTEMI hospitalizations without SSc, respectively. Acute coronary syndrome hospitalizations with SSc have similar hospital length of stay, total hospital charges, rates of revascularization strategies (percutaneous coronary intervention, coronary artery bypass surgery, and thrombolytics), and other interventions (such as percutaneous external assist device and intra-aortic balloon pump) compared with those without SSc.
Long-term outcomes of psychoactive drug use in trauma patients: A multicenter patient-reported outcomes study
Authors: El Moheb Mohamad , Herrera-Escobar Juan P. , Breen Kerry , Orlas Claudia , Haynes Ashley N. , Levy-Carrick Nomi C. , Nehra Deepika , Sanchez Sabrina E. , Salim Ali , Velmahos George , Kaafarani Haytham M.A.
Published: December 2020

INTRODUCTION

Psychoactive drug use (PDU) is reported in up to 40% of trauma patients and is associated with a higher rate of in-hospital complications. However, little is known about its long-term impact on trauma patients. We aimed to assess the long-term functional, mental, and psychosocial outcomes of PDU in trauma patients 6 to 12 months after injury.

METHODS

Trauma patients with moderate to severe injuries (Injury Severity Score, >9) who had a toxicology screen upon admission to one of three level 1 trauma centers were contacted by phone 6 to 12 months postinjury. Psychoactive drug use was defined as the presence of a psychoactive, nonprescribed substance on toxicology screen including amphetamine, barbiturate, benzodiazepine, cannabinoid, methamphetamine, methadone, opioid, oxycodone, methylenedioxymethamphetamine (ecstasy), phencyclidine, tricyclic antidepressant, and cocaine. The interviews systematically evaluated functional limitations, social functioning, chronic pain, and mental health (posttraumatic stress disorder, depression, anxiety). Patients with a score of ≤47 on the Short-Form Health Survey version 2.0 social functioning subdomain were considered to have social dysfunction. Multivariable regression models were built to determine the independent association between PDU and long-term outcomes.

RESULTS

Of the 1,699 eligible patients, 571 (34%) were included in the analysis, and 173 (30.3%) screened positive for PDU on admission. Patients with PDU were younger (median age [interquartile range], 43 [28–55] years vs. 66 [46–78] years, p < 0.001), had more penetrating injuries (8.7% vs. 4.3%, p = 0.036), and were less likely to have received a college education (41.3% vs. 54.5%, p = 0.004). After adjusting for patients’ characteristics including the presence of a baseline psychiatric comorbidity, patients with PDU on admission were more likely to suffer from daily chronic pain, mental health disorders, and social dysfunction 6 to 12 months after injury. There was no difference in the functional limitations between patients with and without PDU.

CONCLUSION

On the long term, PDU in trauma patients is strongly and independently associated with worse mental health, more chronic pain, and severe impairment in social functioning. A trauma hospitalization presents an opportunity to identify patients at risk and to mitigate the long-term impact of PDU on recovery.

LEVEL OF EVIDENCE

Prognostic/epidemiologic, level III.
Psychiatric Disorders in Alzheimer Disease With the Presenilin-1 L226F Mutation
Authors: Bartesaghi Francesca , Rosci Chiara Emilia , Rassiga Cecilia , Barbieri Valentina , Gambini Orsola , Floro Stefano , D’Arrigo Andrea Maria , Del Sole Angelo , Scarpini Elio Angelo , Galimberti Daniela , Priori Alberto
Published: December 2020

The presenilin-1 (PSEN1) L226F mutation has been linked to very early onset of prominent behavioral and psychiatric disturbances followed by cognitive decline within a few years. We report a novel case of early-onset Alzheimer disease that was originally diagnosed as psychotic depression in a patient with this gene mutation. We also compare our patient’s clinical data to those of other cases of this mutation that have been described in the literature. Because atypical behavioral and psychiatric disturbances in young (<40 years) individuals can herald Alzheimer disease, a tight collaboration between psychiatrists and neurologists is crucial for an early diagnosis.
Frontal Variant of Alzheimer Disease Differentiated From Frontotemporal Dementia Using in Vivo Amyloid and Tau Imaging
Authors: Paquin Vincent , Therriault Joseph , Pascoal Tharick Ali , Rosa-Neto Pedro , Gauthier Serge
Published: December 2020

The frontal variant of Alzheimer disease (fvAD) is characterized by behavioral and/or dysexecutive impairments that can resemble those of behavioral-variant frontotemporal dementia (bvFTD). This overlap, in addition to the lack of consensus clinical criteria for fvAD, complicates its identification. We provide the first case report of fvAD differentiated in vivo from bvFTD using amyloid-beta and tau PET imaging. The patient, a right-handed woman, presented with forgetfulness at age 60. Cognitive testing at that time revealed mild impairments in memory, attention, and executive functions. Three years later, her family reported that she was displaying socially inappropriate behaviors, inertia, diminished social interest, and altered food preferences—the sum of which met the criteria for possible bvFTD. PET using an amyloid-beta tracer (18F-AZD4694) identified diffuse amyloid plaques across the cerebral cortex. PET using a tau tracer specific for neurofibrillary tangles (18F-MK6240) identified substantial tau pathology in the brain’s frontal lobes. Together with the clinical findings, these images supported the diagnosis of fvAD rather than bvFTD. Considering past and emerging evidence that tau topography in Alzheimer disease (AD) matches the clinical features of AD, we discuss the potential utility of in vivo tau imaging using 18F-MK6240 for identifying fvAD.
Do nonlinear vocal phenomena signal negative valence or high emotion intensity?
Authors: Anikin Andrey , Pisanski Katarzyna , Reby David
Published: December 2020

Nonlinear vocal phenomena (NLPs) are commonly reported in animal calls and, increasingly, in human vocalizations. These perceptually harsh and chaotic voice features function to attract attention and convey urgency, but they may also signal aversive states. To test whether NLPs enhance the perception of negative affect or only signal high arousal, we added subharmonics, sidebands or deterministic chaos to 48 synthetic human nonverbal vocalizations of ambiguous valence: gasps of fright/surprise, moans of pain/pleasure, roars of frustration/achievement and screams of fear/delight. In playback experiments (
N
= 900 listeners), we compared their perceived valence and emotion intensity in positive or negative contexts or in the absence of any contextual cues. Primarily, NLPs increased the perceived aversiveness of vocalizations regardless of context. To a smaller extent, they also increased the perceived emotion intensity, particularly when the context was negative or absent. However, NLPs also enhanced the perceived intensity of roars of achievement, indicating that their effects can generalize to positive emotions. In sum, a harsh voice with NLPs strongly tips the balance towards negative emotions when a vocalization is ambiguous, but with sufficiently informative contextual cues, NLPs may be re-evaluated as expressions of intense positive affect, underlining the importance of context in nonverbal communication.
The genetic basis for the evolution of soma: mechanistic evidence for the co-option of a stress-induced gene into a developmental master regulator
Authors: König Stephan G. , Nedelcu Aurora M.
Published: December 2020

In multicellular organisms with specialized cells, the most significant distinction among cell types is between reproductive (germ) cells and non-reproductive/somatic cells (soma). Although soma contributed to the marked increase in complexity of many multicellular lineages, little is known about its evolutionary origins. We have previously suggested that the evolution of genes responsible for the differentiation of somatic cells involved the co-option of life history trade-off genes that in unicellular organisms enhanced survival at a cost to immediate reproduction. In the multicellular green alga,Volvox carteri, cell fate is established early in development by the differential expression of a master regulatory gene known asregA. A closely relatedRegA-Like Sequence (RLS1) is present in its single-celled relative,Chlamydomonas reinhardtii.RLS1is expressed in response to stress, and we proposed that an environmentally inducedRLS1-like gene was co-opted into a developmental pathway in the lineage leading toV. carteri. However, the exact evolutionary scenario responsible for the postulated co-option event remains to be determined. Here, we show that in addition to being developmentally regulated,regAcan also be induced by environmental cues, indicating thatregAhas maintained its ancestral regulation. We also found that the absence of a functional RegA protein confers increased sensitivity to stress, consistent with RegA having a direct or indirect role in stress responses. Overall, this study (i) provides mechanistic evidence for the co-option of an environmentally induced gene into a major developmental regulator, (ii) supports the view that major morphological innovations can evolve via regulatory changes and (iii) argues for the role of stress in the evolution of multicellular complexity.
Archaeological mitogenomes illuminate the historical ecology of sea otters (
Enhydra lutris
) and the viability of reintroduction
Authors: Wellman Hannah P. , Austin Rita M. , Dagtas Nihan D. , Moss Madonna L. , Rick Torben C. , Hofman Courtney A.
Published: December 2020

Genetic analyses are an important contribution to wildlife reintroductions, particularly in the modern context of extirpations and ecological destruction. To address the complex historical ecology of the sea otter (
Enhydra lutris
) and its failed 1970s reintroduction to coastal Oregon, we compared mitochondrial genomes of pre-extirpation Oregon sea otters to extant and historical populations across the range. We sequenced, to our knowledge, the first complete ancient mitogenomes from archaeological Oregon sea otter dentine and historical sea otter dental calculus. Archaeological Oregon sea otters (
n
= 20) represent 10 haplotypes, which cluster with haplotypes from Alaska, Washington and British Columbia, and exhibit a clear division from California haplotypes. Our results suggest that extant northern populations are appropriate for future reintroduction efforts. This project demonstrates the feasibility of mitogenome capture and sequencing from non-human dental calculus and the diverse applications of ancient DNA analyses to pressing ecological and conservation topics and the management of at-risk/extirpated species.
Smart Investment of Virus RNA Testing Resources to Enhance Covid-19 Mitigation
Authors: Gorji Hossein , Arnoldini Markus , Jenny David F. , Hardt Wolf-Dietrich , Jenny Patrick
Published: December 2020

Covid-19 mitigation commonly involves contact tracing (CT) and social distancing. Due to its high economic toll and its impact on personal freedom, we need to ease social distancing and deploy alternative measures, while preventing further waves of infections. While reliable mass testing (for virus RNA) would require too many resources to be effective, CT, which focuses on isolating symptomatic cases and their contacts, has been implemented in many countries. However, the latter approach has reduced efficiency when high numbers of positive patients are burdening the tracing centers. Moreover, CT misses transmissions by asymptomatic cases. Therefore, its effect in reducing the reproduction number has a theoretical limit.

To improve effectiveness of contact tracing, we propose to complement it with a strategy relying on identifying and testing symptom free subgroups with a significantly higher than average virus prevalence. We call this smart testing (ST). By testing everybody in these subgroups, in addition to symptomatic cases, also large fractions of pre- and asymptomatic persons can be identified, which enhances the effectiveness of contact tracing. High prevalence subgroups can be found in different ways, which are discussed in this paper. A particularly efficient way is via preselection using cheap and fast virus antigen tests, as proposed recently. Mathematical modeling quantifies the potential reduction of the reproduction number by such a two-stage ST strategy. In addition to global scenarios, also more realistic local applications of two-stage ST have been investigated, that is, within counties, institutions, schools, companies, etc., where members have internal as well as external contacts. All involved model parameters have been varied within realistic ranges and results are presented with probabilities. Even with the most pessimistic parameter set, these results suggest that the effect of two-stage ST on the reproduction number would clearly outweigh its economic cost. Two-stage ST is technically and logistically feasible. Further, it is locally effective also when only applied within small local subpopulations. Thereby, two-stage ST efficiently complements the portfolio of mitigation strategies, which allow easing social distancing without compromising public health.

Single Sentence Summary

Identification of high prevalence groups within subpopulations to enhance detection rate of Covid-19 infections by virus RNA tests combined with subsequent isolation.
Sex-specific associations of adiposity with cardiometabolic traits: multi-life-stage cohort study with repeat metabolomics
Authors: O’Keeffe Linda M. , Bell Joshua A. , O’Neill Kate N. , Lee Matthew , Woodward Mark , Peters Sanne , Smith George Davey , Kearney Patricia M.
Published: December 2020

Background

Sex differences in cardiometabolic disease risk are commonly observed across the life course but are poorly understood and may be due to different cardiometabolic consequences of adiposity in females and males. We examined whether adiposity influences cardiometabolic trait levels differently in females and males at four different life stages.

Methods

Data were from two generations (offspring, Generation 1 [G1] and their parents, Generation 0 [G0]) of the Avon Longitudinal Study of Parents and Children birth cohort study. Body mass index (BMI) and total fat mass from dual-energy x-ray absorptiometry were measured at mean age 9y, 15y and 18y in G1. Waist circumference was measured at 9y and 15y in G1. Concentrations of 148 cardiometabolic traits quantified using nuclear magnetic resonance spectroscopy were measured at 15y, 18y and 25y in G1. In G0, all three adiposity measures and the same 148 traits were available at 50y.Using linear regression models, sex-specific associations of adiposity measures at each time point (9y, 15y and 18y) with cardiometabolic traits 3 to 6 years later were examined in G1. In G0, sex-specific associations of adiposity measures and cardiometabolic traits were examined cross- sectionally at 50y.

Results

3081 G1 and 4887 G0 participants contributed to analyses. BMI was more strongly associated with key atherogenic traits in males at younger ages (15y-25y) and associations were more similar between the sexes or stronger in females at 50y, particularly for apolipoprotein-B-containing lipoprotein particles and lipid concentrations. For example, a 1- SD (3.8 kg/m2) higher BMI at 18y was associated with 0.36 SD (95% Confidence Interval (CI) = 0.20, 0.52) higher concentrations of extremely large very-low-density lipoprotein (VLDL) particles at 25y in males compared with 0.15 SD (95% CI = 0.09, 0.21) in females. In contrast, at 50y, a 1-SD (4.8 kg/m2) higher BMI was associated with 0.33 SD (95% CI = 0.25, 0.42) and 0.30 SD (95% CI = 0.26, 0.33) higher concentrations of extremely large VLDL particles in males and females respectively. Sex-specific associations of DXA-measured fat mass and waist circumference were similar to findings for BMI in both generations and at all ages.

Conclusion

The results of this study suggest that the adverse cardiometabolic effects of adiposity are stronger and begin earlier in the life course among males compared with females until mid life, particularly for key atherogenic lipids. Adolescent and young adult males may therefore be high priority targets for obesity prevention efforts.
Risk assessment for airborne disease transmission by poly-pathogen aerosols
Authors: Nordsiek Freja , Bodenschatz Eberhard , Bagheri Gholamhossein
Published: December 2020

In the case of airborne diseases, pathogen copies are transmitted by droplets of respiratory tract fluid that are exhaled by the infectious that stay suspended in the air for some time and, after partial or full drying, inhaled as aerosols by the susceptible. The risk of infection in indoor environments is typically modelled using the Wells-Riley model or a Wells-Riley-like formulation, usually assuming the pathogen dose follows a Poisson distribution (mono-pathogen assumption). Aerosols that hold more than one pathogen copy, i.e. poly-pathogen aerosols, break this assumption even if the aerosol dose itself follows a Poisson distribution. For the largest aerosols where the number of pathogen in each aerosol can sometimes be several hundred or several thousand, the effect is non-negligible, especially in diseases where the risk of infection per pathogen is high. Here we report on a generalization of the Wells-Riley model and dose-response models for poly-pathogen aerosols by separately modeling each number of pathogen copies per aerosol, while the aerosol dose itself follows a Poisson distribution. This results in a model for computational risk assessment suitable for mono-/poly-pathogen aerosols. We show that the mono-pathogen assumption significantly overestimates the risk of infection for high pathogen concentrations in the respiratory tract fluid. The model also includes the aerosol removal due to filtering by the individuals which becomes significant for poorly ventilated environments with a high density of individuals, and systematically includes the effects of facemasks in the infectious aerosol source and sink terms and dose calculations.
Social network-based strategies for classroom size reduction can help limit outbreaks of SARS-CoV-2 in high schools. A simulation study in classrooms of four European countries
Authors: Kaiser Anna , Kretschmer David , Leszczensky Lars
Published: December 2020

Dividing classrooms may reduce the risk of SARS-CoV-2 outbreaks in schools. We investigate how classroom cohorting strategies, which downsize and isolate groups, may curb the spread of SARS-CoV-2. Using agent-based modelling based on a rich multi-country network dataset comprising 507 classrooms and 12,291 students, we assess random cohorting and three network-based strategies that consider students’ out-of-school contacts with classmates. Investigating effects on the number of cross-cohort transmissions, overall infections, and quarantines, our findings suggest that all cohorting strategies help to contain outbreaks, but that minimizing out-of-school contact between cohorts is most effective. Since this strategy may be hard to implement in practice, we show that a network chain nomination procedure and splitting classes by gender, both of which are easier to realize, also outperform random cohorting considerably. For all cohorting strategies, we find that rota-systems with instruction in alternating weeks contain outbreaks more effectively than same-day in-person instruction.
Predictive accuracy of computer-aided versions of the on-admission National Early Warning Score in estimating the risk of COVID-19 for unplanned admission to hospital: a retrospective development and validation study
Authors: Faisal Muhammad , Mohammed Mohammed A , Richardson Donald , Steyerberg Ewout W. , Fiori Massimo , Beatson Kevin
Published: December 2020

Objectives

To consider the potential of the National Early Warning Score (NEWS2) for COVID-19 risk prediction on unplanned admission to hospital.

Design

Logistic regression model development and validation study using a cohort of unplanned emergency medical admission to hospital.

Setting

York Hospital (YH) as model development dataset and Scarborough Hospital (SH) as model validation dataset.

Participants

Unplanned adult medical admissions discharged over 3 months (11 March 2020 to 13 June 2020) from two hospitals (YH for model development; SH for external model validation) based on admission NEWS2 electronically recorded within ±24 hours of admission. We used logistic regression modelling to predict the risk of COVID-19 using NEWS2 (Model M0’) versus enhanced cNEWS models which included age + sex (model M1’) + subcomponents (including diastolic blood pressure + oxygen flow rate + oxygen scale) of NEWS2 (model M2’). The ICD-10 code ‘U071’ was used to identify COVID-19 admissions. Model performance was evaluated according to discrimination (c statistic), calibration (graphically), and clinical usefulness at NEWS2 ≥5.

Results

The prevalence of COVID-19 was higher in SH (11.0%=277/2520) than YH (8.7%=343/3924) with higher index NEWS2 (3.2 vs 2.8) but similar in-hospital mortality (8.4% vs 8.2%). The c-statistics for predicting COVID-19 for cNEWS models (M1’,M2’) was substantially better than NEWS2 alone (M0’) in development (M2’: 0.78 (95%CI 0.75-0.80) vs M0’ 0.71 (95%CI 0.68-0.74)) and validation datasets (M2’: 0.72 (95%CI 0.69-0.75) vs M0’ 0.65 (95%CI 0.61-0.68)). Model M2’ had better calibration than Model M0’ with improved sensitivity (M2’: 57% (95%CI 51%-63%) vs M0’ 44% (95%CI 38%-50%)) and similar specificity (M2’: 76% (95%CI 74%-78%) vs M0’ 75% (95%CI 73%-77%)) for validation dataset at NEWS2≥5.

Conclusions

Model M2’ is reasonably accurate for predicting the on-admission risk of COVID-19. It may be clinically useful for an early warning system at the time of admission especially to triage large numbers of unplanned hospital admissions.
NEC-Associated DNA Methylation Signatures in Colon are Evident in Stool Samples of Affected Individuals
Authors: Good Misty , Chu Tianjiao , Shaw Patricia , Nolan Lila S. , McClain Lora , Chamberlain Austin , Castro Carlos , Gong Qingqing , Cooksey Krista , Linneman Laura , Finegold David N. , Peters David
Published: December 2020

Neonatal necrotizing enterocolitis (NEC) is a devastating and unpredictable gastrointestinal disease with a high mortality rate in premature infants. Currently, no predictive or diagnostic biomarkers exist for NEC. Clinical intervention is reactive to the overt manifestations of disease resulting in high levels of morbidity and mortality. To better understand the molecular mechanisms that underpin NEC, we have undertaken a high resolution genome wide epigenomic analysis using solution phase hybridization and next generation DNA sequencing of bisulfite converted DNA. Our data reveal a broad and significant genomic hypermethylation in surgical NEC tissues compared to non-NEC controls. These changes were found to be far more pronounced in regions outside CpG islands and gene regulatory elements, which suggests that NEC-specific hypermethylation is not a non-specific global phenomenon. We identified a number of important biological pathways that are dysregulated in NEC and observed a clear association between NEC methylation changes and gene expression. Significantly, we found that the same patterns of global methylation identified in surgical NEC tissue are also detectable in stool samples from affected infants. To our knowledge, this is the first evidence of a methylomic signature that is both associated with NEC and detectable non-invasively. These findings point towards a new opportunity for the development of novel screening, diagnostic and phenotyping methods for NEC that could be deployed in the NICU for improved detection of this devastating disease.
Serological prevalence of SARS-CoV-2 infection and associated factors in healthcare workers in a “non-COVID” hospital in Mexico City
Authors: Cruz-Arenas Esteban , Cabrera-Ruiz Elizabeth , Laguna-Barcenas Sara , Colin-Castro Claudia A. , Chavez Tatiana , Franco-Cendejas Rafael , Ibarra Clemente , Perez-Orive Javier
Published: December 2020

In spite of high mortality from COVID-19, in Mexico the number of confirmed cases and diagnostic tests per million population are lower than for other comparable countries, which leads to uncertainty about the actual extent of the pandemic. In Mexico City, healthcare workers represent an important fraction of individuals with SARS-CoV-2 infection. This work aims to estimate the frequency of antibodies to SARS-CoV-2 and identify associated factors in healthcare workers at a large hospital in Mexico City. We conducted a serological survey in a non-COVID national referral teaching hospital. We selected a representative sample of 300 individuals. Blood samples were collected and questionnaires were applied between August 10th and September 9th, 2020. ELISA results indicate a serological prevalence of SARS-CoV-2 infection of 13.0%. Working in the janitorial and security groups, having an educational level below a university degree, and living with a larger number of people, were also identified as sociodemographic factors that increase the risk of having SARS-CoV-2 infection. Thus, less favored socioeconomic groups are at significantly higher risk of experiencing SARS-CoV-2 infection. Even in healthcare workers there is still a majority of individuals that are seronegative, and thus the risk of continued epidemic waves and mortality remains high.
A Healthy Buildings Guideline for the COVID-19 Pandemic and Beyond
Authors: Federspiel Clifford
Published: December 2020

Public health experts have confirmed that airborne transmission of SARS-CoV-2 (COVID-19) is one of the primary mechanisms of infection (CDC, 2020). In addition to social distancing, mask wearing and hand washing, experts now recommend increasing the ventilation and filtration of indoor air. While there is widespread consensus on this general approach, to date there are no published guidelines for the levels of ventilation, filtration, etc. that are required to control the pandemic. This is an urgent concern because colder weather in the Northern Hemisphere has moved social activity indoors where the risk of infection is higher.
Predicting patients with false negative SARS-CoV-2 testing at hospital admission: A retrospective multi-center study
Authors: Ghazi Lama , Simonov Michael , Mansour Sherry , Moledina Dennis , Greenberg Jason , Yamamoto Yu , Biswas Aditya , Wilson F. Perry
Published: December 2020

Importance

False negative SARS-CoV-2 tests can lead to spread of infection in the inpatient setting to other patients and healthcare workers. However, the population of patients with COVID who are admitted with false negative testing is unstudied.

Objective

To characterize and develop a model to predict true SARS-CoV-2 infection among patients who initially test negative for COVID by PCR.

Design

Retrospective cohort study.

Setting

Five hospitals within the Yale New Haven Health System between 3/10/2020 and 9/1/2020. Participants: Adult patients who received diagnostic testing for SARS-CoV-2 virus within the first 96 hours of hospitalization.

Exposure

We developed a logistic regression model from readily available electronic health record data to predict SARS-CoV-2 positivity in patients who were positive for COVID and those who were negative and never retested.

Main Outcomes and Measures

This model was applied to patients testing negative for SARS-CoV-2 who were retested within the first 96 hours of hospitalization. We evaluated the ability of the model to discriminate between patients who would subsequently retest negative and those who would subsequently retest positive.

Results

We included 31,459 hospitalized adult patients; 2,666 of these patients tested positive for COVID and 3,511 initially tested negative for COVID and were retested. Of the patients who were retested, 61 (1.7%) had a subsequent positive COVID test. The model showed that higher age, vital sign abnormalities, and lower white blood cell count served as strong predictors for COVID positivity in these patients. The model had moderate performance to predict which patients would retest positive with a test set area under the receiver-operator characteristic (ROC) of 0.76 (95% CI 0.70 - 0.83). Using a cutpoint for our risk prediction model at the 90th percentile for probability, we were able to capture 35/61 (57%) of the patients who would retest positive. This cutpoint amounts to a number-needed-to-retest range between 15 and 77 patients.

Conclusion and Relevance

We show that a pragmatic model can predict which patients should be retested for COVID. Further research is required to determine if this risk model can be applied prospectively in hospitalized patients to prevent the spread of SARS-CoV-2 infections.
InsectBrainDatabase - A unified platform to manage, share, and archive morphological and functional data
Authors: Heinze Stanley , el Jundi Basil , Berg Bente G. , Homberg Uwe , Menzel Randolf , Pfeiffer Keram , Dacke Marie , Warrant Eric , Pfuhl Gerit , Rybak Jürgen , Tedore Kevin
Published: December 2020

Insect neuroscience generates vast amounts of highly diverse data, of which only a small fraction are findable, accessible and reusable, despite open data mandates by funding bodies. We have therefore developed the InsectBrainDatabase (IBdb), an open platform for depositing, sharing and managing a wide range of insect neuroanatomical and functional data. It facilities biological insight by enabling effective cross-species comparisons, by intimately linking data on structure and function, and by serving as hub for information on insect neuroethology. TheIBdbprovides novel visualization and search tools, which are also available in a unique private mode of the database, before data is made public. This allows users to manage and visualize unpublished data, creating a strong incentive for data contribution and eliminating additional effort when publicly depositing the data at a later stage. These design principles could also serve as a blueprint for similar databases in other fields.
MR-based camera-less eye tracking using deep neural networks
Authors: Frey Markus , Nau Matthias , Doeller Christian F.
Published: December 2020

Viewing behavior provides a window into many central aspects of human cognition and health, and it is an important variable of interest or confound in many fMRI studies. To make eye tracking freely and widely available for MRI research, we developed DeepMReye: a convolutional neural network that decodes gaze position from the MR-signal of the eyeballs. It performs camera-less eye tracking at sub-imaging temporal resolution in held-out participants with little training data and across a broad range of scanning protocols. Critically, it works even in existing datasets and when the eyes are closed. Decoded eye movements explain network-wide brain activity also in regions not associated with oculomotor function. This work emphasizes the importance of eye tracking for the interpretation of fMRI results and provides an open-source software solution that is widely applicable in research and clinical settings.
An experimental assessment of the distribution of environmental DNA along the water column
Authors: Agostinis André O. , Dal Pont Giorgi , Borio Alexandre , Horodesky Aline , da Silva Bertão Ana Paula , Mäder Netto Otto Samuel , Zanin Thiago Luis , Ostrensky Antonio , Pie Marcio R.
Published: December 2020

The study of environmental DNA (eDNA) is increasingly becoming a valuable tool to survey and monitor aquatic communities. However, there are important gaps in our understanding of the dynamics governing the distribution of eDNA under natural conditions. In this report we carry out controlled experiments to assess the extent and timing of eDNA distribution along the water column. A sample of known eDNA concentration was placed at the bottom of a 5-m high tube (20 cm in diameter and total volume of 160 L), and water samples were obtained at different depths over an 8 h-period. The presence of the target eDNA was assessed by qPCR analysis. This sampling protocol allowed for assessing the timescale for the diffusion of eDNA while minimizing the influence of turbulence. We demonstrate that, after a time-period of as little as 30 min, the eDNA had spread across the entire container. The implications of these results for eDNA sampling protocols in the field are discussed.
β-cell SENP1 facilitates responsiveness to incretins and limits oral glucose intolerance in high fat fed mice
Authors: Lin Haopeng , Smith Nancy , Spigelman Aliya F , Suzuki Kunimasa , Ferdaoussi Mourad , Jin Yaxing , Bautista Austin , Wang Ying Wayne , Fox Jocelyn E. Manning , Buteau Jean , MacDonald Patrick E
Published: December 2020

SUMOylation reduces oxidative stress and preserves islet mass; but this happens at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzymesentrin-specificprotease1(SENP1) in glycemia following metabolic stress, we put pancreas/gut-specific SENP1 knockout mice (pSENP1-KO) on an 8-10-week high fat diet (HFD). Male pSENP1-KO mice were more glucose intolerant following HFD than littermate controls, but this was only obvious in response to oral glucose, and a similar but milder phenotype was observed in females. Plasma incretin responses were identical, and glucose-dependent insulinotropic polypeptide (GIP) was equally upregulated after HFD, in pSENP1-KO and - WT littermates. Islet mass was not different, but insulin secretion and β-cell exocytotic responses to Exendin4 (Ex4) and GIP were impaired in islets lacking SENP1. Glucagon secretion from pSENP1-KO islets was also reduced, consistent with the expected SENP1 knockout in all islet cells, so we generated β-cell–specific SENP1 knockout mice (βSENP1-KO). These phenocopied the pSENP1-KO mice with selective impairment in oral glucose tolerance following HFD, preserved islet mass expansion, and impaired β-cell exocytosis and insulin secretion to Ex4 and GIP. Thus, β-cell SENP1 limits glucose intolerance following HFD by ensuring a robust facilitation of insulin secretion by incretins such as GIP.
wQFM: Statistically Consistent Genome-scale Species Tree Estimation from Weighted Quartets
Authors: Mahbub Mahim , Wahab Zahin , Reaz Rezwana , Rahman M. Saifur , Bayzid Md. Shamsuzzoha
Published: December 2020

Motivation

Species tree estimation from genes sampled from throughout the whole genome is complicated due to thegene tree-species tree discordance. Incomplete lineage sorting (ILS) is one of the most frequent causes for this discordance, where alleles can coexist in populations for periods that may span several speciation events. Quartet-based summary methods for estimating species trees from a collection of gene trees are becoming popular due to their high accuracy and statistical guarantee under ILS. Generating quartets with appropriate weights, where weights correspond to the relative importance of quartets, and subsequently amalgamating the weighted quartets to infer a single coherent species tree allows for a statistically consistent way of estimating species trees. However, handling weighted quartets is challenging.

Results

We propose wQFM, a highly accurate method for species tree estimation from multi-locus data, by extending the quartet FM (QFM) algorithm to a weighted setting. wQFM was assessed on a collection of simulated and real biological datasets, including the avian phylogenomic dataset which is one of the largest phylogenomic datasets to date. We compared wQFM with wQMC, which is the best alternate method for weighted quartet amalgamation, and with ASTRAL, which is one of the most accurate and widely used coalescent-based species tree estimation methods. Our results suggest that wQFM matches or improves upon the accuracy of wQMC and ASTRAL.

Availability

wQFM is available in open source form athttps://github.com/Mahim1997/wQFM-2020.
Landmark-Based Turn-by-Turn Instructions Enhance Incidental Spatial Knowledge Acquisition
Authors: Wunderlich Anna , Grieger Sabine , Gramann Klaus
Published: December 2020

The augmentation of landmarks in auditory navigation instructions had been shown to improve incidental spatial knowledge acquisition during assisted navigation. Here, two driving simulator experiments are reported that replicated this effect even when adding a three-week delay between navigation and spatial tasks and varying the degree of detail in the provided landmark information. Performance in free- and cued-recall of landmarks and driving the route again without assistance demonstrated increased landmark and route knowledge when navigating with landmark-based compared to standard instructions. The results emphasize that small changes to existing navigation systems can foster spatial knowledge acquisition during every-day navigation.
A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation
Authors: Milosevic Luka , Kalia Suneil K , Hodaie Mojgan , Lozano Andres M , Popovic Milos R , Hutchison William D , Lankarany Milad
Published: December 2020

With the growing interest in the expansion of deep brain stimulation indications, we aimed to provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on human neuronal activity. Experimentally, we demonstrated microstimulation-evoked excitatory neuronal responses in the ventral intermediate nucleus and reticular thalamus, and inhibitory responses in the subthalamic nucleus and substantia nigra pars reticulata; hypothesized to be the result of simultaneous activations of convergent afferent inputs. Higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression; hypothesized to be mediated by synaptic depression. These experimental findings were reproduced by a computational framework in which relative distributions of convergent excitatory/inhibitory afferents were embedded within a model of short-term synaptic plasticity for the prediction of site-specific and frequency-dependent responses to extracellular stimulation. This theoretical framework may aid in the design of physiologically-informed stimulation paradigms in existing or prospective deep brain stimulation indications.
Strain- and age-dependent features of the nigro-striatal circuit in three common laboratory mouse strains, C57BL/6J, A/J, and DBA/2J -Implications for Parkinson’s disease modeling
Authors: Thomas Mélanie H. , Karout Mona , Rodriguez Beatriz Pardo , Gui Yujuan , Jaeger Christian , Michelucci Alessandro , Kollmus Heike , Schughart Klaus , Coowar Djalil , Balling Rudi , Mittelbronn Michel , Sinkkonen Lasse , Garcia Pierre , Buttini Manuel
Published: December 2020

Mouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.

Highlights

Study of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different ages

Age related evolution of essential features of nigral dopaminergic neurons differ between strains

Consider background strain and age is crutial to study the nigrostriatal circuit in health and disease
Freely behaving mice can brake and turn during optogenetic stimulation of the Mesencephalic Locomotor Region
Authors: van der Zouwen Cornelis Immanuel , Boutin Joël , Fougère Maxime , Flaive Aurélie , Vivancos Mélanie , Santuz Alessandro , Akay Turgay , Sarret Philippe , Ryczko Dimitri
Published: December 2020

Abstract

Background

Stimulation of the Mesencephalic Locomotor Region (MLR) is increasingly considered as a target to improve locomotor function in Parkinson’s disease, spinal cord injury and stroke. A key function of the MLR is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented.

Objective/hypothesis

We investigated whether freely behaving mice could brake or turn based on environmental cues during MLR stimulation.

Methods

We stimulated the cuneiform nucleus in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites.

Results

Optogenetic stimulation of the MLR evoked locomotion and increasing laser power increased locomotor speed. Gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. Mice could brake and make sharp turns (∼90⁰) when approaching a corner during MLR stimulation in an open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. In a reporter mouse, many Vglut2-ZsGreen neurons were immunopositive for glutamate in the MLR. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short latency spiking in MLR neurons.

Conclusion

MLR glutamatergic neurons are a relevant target to improve locomotor activity without impeding the ability to brake and turn when approaching an obstacle, thus ensuring smooth and adaptable navigation.

Highlights

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Mice brake and turn when approaching the arena’s corner during MLR-evoked locomotion

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Speed decrease is scaled to speed before the turn during MLR-evoked locomotion

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Turn angle is scaled to turn speed during MLR-evoked locomotion

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Gait and limb kinematics are similar during spontaneous and MLR-evoked locomotion
The transcriptional landscape ofArabidopsis thalianapattern-triggered immunity
Authors: Bjornson Marta , Pimprikar Priya , Nürnberger Thorsten , Zipfel Cyril
Published: December 2020

Plants initiate immunity upon recognition of a wide array of self and non-self molecular patterns. Whether plants tune their immune outputs to patterns of different biological origins or of different biochemical nature remains mostly unclear. Here, we performed a detailed early time-series transcriptomics analysis inArabidopsis thaliana, revealing that the response to diverse patterns is remarkably congruent. Early transcriptional reprogramming is dominated by a plant general stress response (GSR), which is essential for pattern-induced immunity. The definition of ‘core immunity response’ genes common and specific to pattern response in addition revealed the function of previously uncharacterized GLUTAMATE RECEPTOR-LIKE calcium-permeable channels in immunity. This study thus illustrates general and unique properties of early immune transcriptional reprogramming and uncovered important components of plant immunity.

One Sentence Summary

Time-resolved transcriptomics reveals new properties of pattern-triggered immunity and function of calcium-permeable channels.