bluuebunny/crossref_metadata_2025 huggingface dataset:
Variable freshwater influences on the abundance of Vibrio vulnificus in a tropical urban estuary
Authors: Nigro Olivia D. , James-Davis La’Toya I. , De Carlo Eric Heinen , Li Yuan-Hui , Steward Grieg F.
Published: September 2021

To better understand the controls on the opportunistic human pathogen Vibrio vulnificus in warm tropical waters, we conducted a year-long investigation in the Ala Wai Canal, a channelized estuary in Honolulu, HI. The abundance of V. vulnificus as determined by qPCR of the hemolysin gene (vvhA), varied spatially and temporally nearly four orders of magnitude (≤ 3 to 14,000 mL-1). Unlike in temperate and subtropical systems, temperatures were persistently warm (19–31°C) and explained little of the variability in V. vulnificus abundance. Salinity (1–36 ppt) had a significant, but non-linear, relationship with V. vulnificus abundance with highest vvhA concentrations (> 2,500 mL-1) observed only at salinities from 7 to 22 ppt. V. vulnificus abundances were lower on average in the summer dry season when waters were warmer but more saline. Highest canal-wide average abundances were observed during a time of modest rainfall when moderate salinities and elevated concentrations of reduced nitrogen species and silica suggested a groundwater influence. Distinguishing the abundances of two genotypes of V. vulnificus (C-type and E-type) suggest that C-type strains, which are responsible for most human infections, were usually less abundant (25% on average), but their relative contribution was greater at higher salinities, suggesting a broader salinity tolerance. Generalized regression models suggested up to 67% of sample-to-sample variation in log-transformed V. vulnificus abundance was explained (n = 202) using the measured environmental variables, and up to 97% of the monthly variation in canal-wide average concentrations (n = 13) was explained with the best subset of four variables.

IMPORTANCE

Our data illustrate that, in the absence of strong seasonal variation in water temperature in the tropics, variation in salinity driven by rainfall becomes a primary controlling variable on V. vulnificus abundance. There is thus a tendency for a rainfall-driven seasonal cycle in V. vulnificus abundance that is inverted from the temperature-driven seasonal cycle at higher latitudes. However, stochasticity in rainfall and its non-linear, indirect effects on V. vulnificus concentration means that high abundances can occur at any location in the canal at any time of year, making it challenging to predict concentrations of this pathogen at high temporal or spatial resolution. Much of the variability in canal-wide average concentrations, on the other hand, was explained by a few variables that reflect the magnitude of freshwater input to the system, suggesting that relative risk of exposure to this pathogen could be predicted for the system as a whole.
Social contacts and transmission of COVID-19 in British Columbia, Canada
Authors: Ringa Notice , Otterstatter Michael C. , Iyaniwura Sarafa A. , Irvine Mike A. , Adu Prince , Janjua Naveed Z. , David Samara , Spencer Michelle
Published: September 2021

Purpose

Close-contact rates are thought to be a significant driving force behind the dynamics of transmission for many infectious respiratory diseases. Efforts to control such infections typically focus on the practice of strict contact-avoidance measures. Yet, contact rates and their relation to transmission, and the impact of control measures, are seldom quantified. Here, we quantify the response of contact rates, transmission and new cases of COVID-19 to public health contact-restriction orders, and the associations among these three variables, in the Canadian province of British Columbia (BC) and within its two most densely populated regional health authorities: Fraser Health Authority (FHA) and Vancouver Coastal Health Authority (VCHA).

Methods

We obtained time series for self-reported close-contact rates from the BC Mix COVID-19 Survey, new reported cases of COVID-19 from the BC Center for Disease Control, and transmission rates based on dynamic model fits to reported cases. Our study period was from September 13, 2020 to February 19, 2021, during which three public health contact-restriction orders were introduced (October 26, November 7 and November 19, 2020). We used segmented linear regression to quantify impacts of public health orders, Pearson correlation to assess the instantaneous relation between contact rates and transmission, and vector autoregressive modeling to study the lagged relations among the three variables.

Results

Overall, declines in contact rates and transmission occurred concurrently with the announcement of public health orders, whereas declines in new cases showed a reporting delay of roughly two weeks. The impact of the first public health order (October 26, 2020) on contact rates and transmission was more pronounced than that of the other two health orders. Contact rates and transmission on the same day were strongly correlated (correlation coefficients = 0.64, 0.53 and 0.34 for BC, FHA, and VCHA, respectively). Moreover, contact rates were a significant time-series driver of COVID-19 and explained roughly 30% and 18% of the variation in new cases and transmission, respectively. Interestingly, increases in transmission and new cases were followed by reduced rates of contact: overall, average daily cases explained about 10% of the variation in provincial contact rates.

Conclusion

We show that close-contact rates were a significant driver of transmission of COVID-19 in British Columbia, Canada and that they varied in response to public health orders. Our results also suggest a possible feedback, by which contact rates respond to recent changes in reported cases. Our findings help to explain and validate the commonly assumed, but rarely measured, response of close contact rates to public health guidelines and their impact on the dynamics of infectious diseases.
Behavioral Markers for Deficits in Speed of Processing in Cerebrovascular Disease
Authors: Chen Ying , Sunderland Kelly M , Khoo Yuelee , McLaughlin Paula M. , Kwan Donna , Fraser Julia , Ramirez Joel , Binns Malcolm A. , Arnott Stephen R. , Beaton Derek , Brien Donald C. , Casaubon Leanne K. , Coe Brian C. , Cornish Benjamin , Dowlatshahi Dariush , Hassan Ayman , Levine Brian , Lou Wendy , Mandzia Jennifer , McIlroy William , Montero-Odasso Manuel , Van Ooteghem Karen , Orange Joseph B. , Peltsch Alicia J. , Pieruccini-Faria Frederico , Raamana Pradeep Reddy , Roberts Angela C. , Sahlas Demetrios , Saposnik Gustavo , Strother Stephen C. , Swartz Richard H. , Troyer Angela K. ,   the ONDRI Investigators, Munoz Douglas P.
Published: September 2021

Objective

To assess overlap and uniqueness of established behavioral markers of speed of processing for different aspects of visual information within a cerebrovascular disease cohort, and to examine the link between these speed of processing markers and functional behavior, specifically walking.

Methods

A cohort of 161 participants with cerebrovascular disease recruited to the Ontario Neurodegenerative Disease Research Initiative (ONDRI) were examined with three types of assessments: neuropsychology, saccadic eye movement and gait. Principal component analysis (PCA) and canonical correlation analysis (CCA) were performed on select variables from these assessments to reveal commonalities and discrepancies among the measures.

Results

PCA analysis revealed different variable patterns between neuropsychology and saccade assessments, with the first component characterized primarily by neuropsychology, and the second and third components more influenced by the saccade assessments. CCA analysis did not reveal association between different types of assessments with the exception of a modest, but significant, positive association between speed of processing measures from the neuropsychological assessments and gait speed.

Discussion

Neuropsychological tests and the pro-saccade task can be used for assessment of speed of processing for two major features of visual information, visual perception vs. spatial location. Despite a general lack of association between different types of assessments, combining gait speed as an important contributor to the models reinforces the idea of the link between speed of processing and complex function such as walking, and provides support for the importance of attending to the potential consequences of changes in speed of processing after neurologic injury.
COVID-19 Vaccine Breakthrough Infections in Veterans Health Administration
Authors: Sharma Aditya , Oda Gina , Holodniy Mark
Published: September 2021

Background

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by rising concern of vaccine breakthrough due to SARS-CoV-2 variants, waning protection over time, differential vaccine effectiveness, and regional resurgence of Coronavirus 2019 (COVID-19). Characterizing the frequency and drivers of vaccine breakthrough is necessary to inform COVID-19 control efforts.

Methods

We performed a retrospective cohort study of vaccine breakthrough infections in fully vaccinated persons in Veterans Health Administration. We applied Cox proportional hazard models to estimate cumulative incidence, assess differences in outcomes by vaccine, and identify associations with individual characteristics as well as time-dependent geographic variation in COVID-19 incidence, proportion of delta variant, and vaccine coverage.

Results

Among 3,032,561 fully vaccinated persons, documented SARS-CoV-2 infection occurred in 11,197 (0.37%) and COVID-19 hospitalization occurred in 2,080 (0.07%). Compared to Ad26.COV2.S, BNT162b2 and mRNA-1273 had lower occurrence of documented SARS-CoV-2 infection (aHR 0.54, 95% confidence interval (CI) 0.51-0.58; aHR 0.36; 95% CI 0.33-0.38; respectively) and COVID-19 hospitalization (aHR 0.56, 95% CI 0.47-0.66; aHR 0.30; 0.25-0.35; respectively). Documented SARS-CoV-2 infection and COVID-19 hospitalization were associated with younger age, Hispanic or Latino ethnicity, number of comorbidities, and previous SARS-CoV-2 infection. Regional proportion of delta variant and county-level COVID-19 incidence were predictors of vaccine breakthrough events; county-level vaccine coverage was inversely associated.

Conclusions

Vaccine breakthrough was rare among fully vaccinated persons. mRNA-1273 and BNT162b2 were more protective against documented SARS-CoV-2 infection and COVID-19 hospitalization compared to Ad26.COV2.S. Efforts to limit COVID-19 transmission and bolster vaccine coverage would also curtail vaccine breakthrough.
Relationship between support for workers with illness and work functioning impairment in Japan during the COVID-19 pandemic
Authors: Igarashi Yu , Tateishi Seiichiro , Harada Arisa , Hino Ayako , Tsuji Mayumi , Ogami Akira , Mori Koji , Matsugaki Ryutaro , Fujino Yoshihisa ,   for the CORoNaWork project
Published: September 2021

Objective

This study examined the relationship between job accommodations for workers with poor health and work functioning impairment during the COVID-19 pandemic.

Methods

An internet survey was conducted in December 2020. We included 24,429 subjects for analysis. One question was used to determine whether subjects needed job accommodations from their company to continue working in their current health condition. The odds ratios (ORs) of the necessity of job accommodations for sick workers associated with work functioning impairment were estimated using multilevel logistic regression analysis.

Results

The OR of work functioning impairment among sick workers not receiving job accommodations was 5.75 (95% confidence interval (CI) 5.34-6.20, p<0.001) and those receiving job accommodations was 1.88 (95% CI 1.69-2.08, p<0.001) compared to healthy workers.

Conclusions

This study suggests that providing job accommodations to workers with poor health may improve their work functioning impairment.
Antibody titers against the Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 induced by BNT162b2 vaccination measured using automated chemiluminescent enzyme immunoassay
Authors: Kato Hideaki , Miyakawa Kei , Ohtake Norihisa , Go Hirofumi , Yamaoka Yutaro , Yajima Satoshi , Shimada Tomoko , Goto Atsushi , Nakajima Hideaki , Ryo Akihide
Published: September 2021

Background

Levels of 50% neutralizing titer (NT50) reflect a vaccine-induced humoral immunity after the vaccination against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Measurements of NT50 are difficult to implement in large quantities. A high-throughput laboratory test is expected for determining the level of herd immunity against SARS-CoV-2.

Methods

We analyzed samples from 168 Japanese healthcare workers who had completed two doses of the BNT162b2 vaccine. We analyzed immunoglobulin G (IgG) index values against spike protein (SP) using automated chemiluminescent enzyme immunoassay system AIA-CL and analyzed the background factors affecting antibody titer. SP IgG index was compared with 50% neutralization titers.

Results

The median SP IgG index values of the subjects (mean age = 43 years; 75% female) were 0.1, 1.35, 60.80, and 97.35 before and at 2, 4, and 6 weeks after the first dose, respectively. At 4 and 6 weeks after the first dose, SP IgG titers were found to have positive correlation with NT50 titer (r=0.7535 in 4 weeks; r=0.4376 in 6 weeks). Proportions of the SP IgG index values against the Alpha, Beta, Gamma, and Delta variants compared with the original strain were 2.029, 0.544, 1.017, and 0.6096 respectively. Older age was associated with lower SP IgG titer index 6 weeks after the first dose.

Conclusions

SP IgG index values were raised at 3 weeks after two doses of BNT162b2 vaccination and have positive correlation with NT50. SP IgG index values were lower in the older individuals and against Beta and Delta strain.
Decrease of heart rate variability during exercise: an index of cardiorespiratory fitness
Authors: Mongin Denis , Chabert Clovis , Extremera Manuel Gomez , Hue Olivier , Courvoisier Delphine Sophie , Carpena Pedro , Bernaola Galvan Pedro Angel
Published: September 2021

The present study proposes to measure and quantify the heart rate variability (HRV) changes during effort and to test the capacity of the produced indices to predict cardiorespiratory fitness measures. Therefore, the beat-to-beat cardiac time interval series of 18 adolescent athletes (15.2 ± 2.0 years) measured during maximal graded effort test were detrended using a dynamical first-order differential equation model. Heart rate variability was then calculated as the standard deviation of the detrended RR intervals within successive windows of one minute. The variation of this measure of HRV during exercise is properly adjusted by an exponential decrease of the heart rate. The amplitude and the decay rate of this exponential trend are strongly associated with maximum oxygen consumption, maximal aerobic power, and ventilatory thresholds. It indicates that among athletes with better fitness, HRV has higher values at low heart rate and decreases faster when the heart rate increases during exercise. This analysis, based only on cardiac measurements, provides a promising tool for the study of cardiac measurements generated by portable devices.
Self-modulation of motor cortex activity after stroke alters behavior and corticospinal tract structure: a randomized controlled trial
Authors: Sanders Zeena-Britt , Fleming Melanie K. , Smejka Tom , Marzolla Marilien C. , Zich Catharina , Rieger Sebastian W. , Lührs Michael , Goebel Rainer , Sampaio-Baptista Cassandra , Johansen-Berg Heidi
Published: September 2021

Real-time functional magnetic resonance imaging (fMRI) neurofeedback allows individuals to self-modulate their ongoing brain activity. This may be a useful tool in clinical disorders which are associated with altered brain activity patterns. Motor impairment after stroke has previously been associated with decreased laterality of motor cortex activity. Here we examined whether chronic stroke survivors were able to use real-time fMRI neurofeedback to increase laterality of motor cortex activity and assessed effects on motor performance and on brain structure and function. We carried out a randomized, double-blind, sham-controlled trial in which 24 chronic stroke survivors with mild to moderate upper limb impairment experienced three training days of either Real (n=12) or Sham (n=12) neurofeedback. Stroke survivors were able to use Real neurofeedback to increase laterality of motor cortex activity within, but not across, training days. Improvement in gross hand motor performance assessed by the Jebsen Taylor Test (JTT) was observed in the Real neurofeedback group compared to Sham. However, there were no improvements on the Action Research Arm Test (ARAT) or the Upper Extremity Fugl-Meyer (UE-FM) score. Additionally, decreased white-matter asymmetry of the corticospinal tracts was detected 1-week after neurofeedback training, indicating that the tracts become more similar with Real neurofeedback. Changes in the affected corticospinal tract was positively correlated with neurofeedback performance. Therefore, here we demonstrate that chronic stroke survivors are able to use fMRI neurofeedback to self-modulate motor cortex activity, and that training is associated with improvements in hand motor performance and with white matter structural changes.
Status Quo and Influencing Factors of Family Doctors Performance in Dongguan City
Authors: Wang Jiao , Xiao Junhui , Li Xiali , Zhang Lin , Wang Na
Published: September 2021

Background

The low-performance rate of family doctors is the most important problem in the implementation of the contract service system of family doctors in China, and improving the performance rate of family doctors has become a topic of common concern. We investigated the performance behavior of family doctors in Dongguan, Guangdong Province, to understand the current situation of family doctors performance in Dongguan, and to explore the influencing factors of their performance.

Objectives

To understand the status quo of family doctors performance in Dongguan City, Guangdong Province, and to explore the influencing factors of family doctors agreement fulfillment rate.

Methods

The multi-stage sampling method was used to randomly select family doctors in Dongguan City, Guangdong Province, to investigate the status quo of family doctors performance in community health service institutions in Dongguan City. Logistic regression analysis was used to investigate the influencing factors of family doctors performance, and decision trees and associations were used to further identify the influencing factors of family doctors performance.

Results

100 family doctors participated in the survey, and 75% of them were generally able to perform their duties. Logistic regression analysis shows that whether a family doctor signs a contract with a resident is the influencing factor of family doctor performance behavior, and the higher the family doctor signing rate, the higher the family doctor performance rate. The results of decision tree analysis showed that the biggest influence factor of family doctors performance behavior is whether the family doctors are contracted residents or not. ROC curve was 0.860, and pAUC was 0.073 respectively. The most influential factor in decreasing the average Gini index of random forest is whether the family doctor signed a contract or not. The results of association rules showed that there was a correlation between whether the family doctor signed a contract or not and the performance of the family doctor.

Conclusions

The performance rate of family doctors in Dongguan City, Guangdong Province is relatively high. Whether family doctors sign contracts with residents is the influencing factor of family doctors performance. Improving the contract rate of family doctors is the key to improve the performance rate of family doctors.
The COMBAT-TB Workbench: Making powerful TB bioinformatics accessible
Authors: van Heusden Peter , Mashologu Ziphozakhe , Lose Thoba , Warren Robin , Christoffels Alan
Published: September 2021

Whole Genome Sequencing (WGS) is a powerful method for detecting drug resistance, genetic diversity and transmission dynamics of Mycobacterium tuberculosis. Implementation of WGS in public health microbiology laboratories is impeded by a lack of user-friendly, automated and semi-automated pipelines. We present the COMBAT-TB workbench, a modular, easy to install application that provides a web based environment for Mycobacterium tuberculosis bioinformatics. The COMBAT-TB Workbench is built using two main software components: the IRIDA Platform for its web-based user interface and data management capabilities and the Galaxy bioinformatics workflow platform for workflow execution. These components are combined into a single easy to install application using Docker container technology. We implemented two workflows, for M. tuberculosis sample analysis and phylogeny, in Galaxy. Building our workflows involved updating some Galaxy tools (Trimmomatic, snippy and snp-sites) and writing new Galaxy tools (snp-dists, TB-Profiler, tb_variant_filter and TB Variant Report). The irida-wf-ga2xml tool was updated to be able to work with recent versions of Galaxy and was further developed into IRIDA plugins for both workflows. In the case of the M. tuberculosis sample analysis an interface was added to update the metadata stored for each sequence sample with results gleaned from the Galaxy workflow output. Data can be loaded into the COMBAT-TB Workbench via the web interface or via the command line IRIDA uploader tool. The COMBAT-TB Workbench application deploys IRIDA, the COMBAT-TB IRIDA plugins, the MariaDB database and Galaxy using Docker containers (https://github.com/COMBAT-TB/irida-galaxy-deploy).

Importance

While the reduction in cost of WGS is making sequencing more affordable in Lower and Middle Income Countries, public health laboratories in these countries seldom have access to bioinformaticians and system support engineers adept at using the Linux command line and complex bioinformatics software. The COMBAT-TB Workbench provides an open source, modular, easy to deploy and use environment for managing and analysing M. tuberculosis WGS data and thereby makes WGS usable in practice in the LMIC context.
Structural and diffusion weighted brain imaging biomarkers for ADHD and its symptomology in very young (4–7-year-old) children
Authors: Öztekin Ilke , Garic Dea , Finlayson Mark A. , Graziano Paulo A. , Dick Anthony Steven
Published: September 2021

The current study aimed to identify the key neurobiology of Attention-Deficit/Hyperactivity Disorder (ADHD), as it relates to ADHD diagnostic category and symptoms of hyperactive/impulsive behavior and inattention. To do so, we adapted a predictive modeling approach to identify the key structural and diffusion weighted brain imaging measures, and their relative standing with respect to teacher ratings of executive function – EF (measured by the Metacognition Index of the Behavior Rating Inventory of Executive Function– BRIEF), negativity and emotion regulation – ER (measured by the Emotion Regulation Checklist, ERC), in a critical young age range (ages 4 to 7, mean age 5.52 years, 82.2% Hispanic/Latino), where initial contact with educators and clinicians typically take place. Teacher ratings of EF and ER were predictive of both ADHD diagnostic category and symptoms of hyperactive/impulsive behavior and inattention. Among the neural measures evaluated, the current study identified the critical importance of the largely understudied diffusion weighted imaging measures for the underlying neurobiology of ADHD and its associated symptomology. Specifically, our analyses implicated the inferior frontal gyrus, the pericallosal sulcus, and the caudate as critical predictors of ADHD diagnostic category and its associated symptomology, above and beyond teacher ratings of EF and ER. Collectively, the current set of findings have implications for theories of ADHD, the relative utility of neurobiological measures with respect to teacher ratings of EF and ER, and the developmental trajectory of its underlying neurobiology.
Prediction of radiation-induced hypothyroidism using radiomic data analysis does not show superiority over standard normal tissue complication models
Authors: Smyczynska Urszula , Grabia Szymon , Nowicka Zuzanna , Papis-Ubych Anna , Bibik Robert , Latusek Tomasz , Rutkowski Tomasz , Fijuth Jacek , Fendler Wojciech , Tomasik Bartłomiej
Published: September 2021

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33–35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). Our models reach accuracy comparable with or better than previously presented non-radiomic NTCP models. The benefit of our approach is obtaining the RIHT predictions before treatment planning to adjust IMRT plan to avoid the thyroid region in most susceptible patients.
Cross-sectional assessment of predictors for COVID-19 vaccine uptake: an online survey in Greece
Authors: Galanis Petros , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsiroumpa Aglaia , Moisoglou Ioannis , Kaitelidou Daphne
Published: September 2021

Background

A high level of COVID-19 vaccine uptake in the general population is essential to control the pandemic.

Objective

To estimate the percentage of the general population vaccinated against the COVID-19 and to investigate the factors associated with COVID-19 vaccine uptake.

Methods

We conducted an online cross-sectional study in Greece during August 2021. We included individuals over 18 years of age. Independent variables included socio-demographic data of the participants and attitudes towards COVID-19 vaccination and pandemic. Our outcome variable was COVID-19 vaccination status, measured through “yes/no” answers.

Results

Most participants had been vaccinated against the COVID-19 (87.8%), while about half had been vaccinated against the influenza (52.5%). Multivariate analysis identified that increased age and higher level of education were associated with an increased likelihood of COVID-19 vaccination. Also, participants working in health services, participants without a previous COVID-19 diagnosis and those with previous seasonal influenza vaccination history had a greater probability to take a COVID-19 vaccine. Additionally, increased self-perceived severity of COVID-19, knowledge regarding COVID-19, and trust in COVID-19 vaccines and scientists were associated with COVID-19 vaccine uptake. On the other hand, the likelihood of vaccination was lower for participants who were more concerned about the side effects of COVID-19 vaccination.

Conclusions

Understanding the factors affecting individuals’ decision to take a COVID-19 vaccine is essential to improve the COVID-19 vaccination coverage rate. Policymakers and scientists should scale up their efforts to increase the COVID-19 vaccination rate among specific population groups such as young people, people with low level of education, people with negative attitudes towards vaccination, etc.
Neutralizing efficacy of vaccines against the SARS-CoV-2 Mu variant
Authors: Miyakawa Kei , Jeremiah Sundararaj Stanleyraj , Kato Hideaki , Ryo Akihide
Published: September 2021

The rise of mutant strains of SARS-CoV-2 poses an additional problem to the existing pandemic of COVID-19. There are rising concerns about the Mu variant which can escape humoral immunity acquired from infections from previous strains or vaccines. We examined the neutralizing efficacy of the BNT162b2 mRNA vaccine against the Mu variant and report that the vaccine has 76% neutralizing effectiveness against the Mu compared to 96% with the original strain. We also show that Mu, similar to the Delta variant, causes cell-to-cell fusion which can be an additional factor for the variant to escape vaccine-mediated humoral immunity. Despite the rise in vaccine escape strains, the vaccine still possesses adequate ability to neutralize majority of the mutants.
Assessing the impact of temperature and humidity exposures during early infection stages on case-fatality of COVID-19: a modelling study in Europe
Authors: Liang Jingbo , Yuan Hsiang-Yu
Published: September 2021

Background

Although associations between key weather indicators (i.e. temperature and humidity) and COVID-19 mortality has been reported, the relationship between these exposures among different timing in early infection stages (from virus exposure up to a few days after symptom onset) and the probability of death after infection (also called case fatality rate, CFR) has yet to be determined.

Methods

We estimated the instantaneous CFR of eight European countries using Bayesian inference in conjunction with stochastic transmission models, taking account of delays in reporting the number of newly confirmed cases and deaths. The exposure-lag–response associations between fatality rate and weather conditions to which patients were exposed at different timing were obtained using distributed lag nonlinear models coupled with mixed-effect models.

Results

Our results showed that the Odds Ratio (OR) of death is negatively associated with the temperature, with two maxima (OR=1.29 (95% CI: 1.23, 1.35) at -0.1°C; OR=1.12 (95% CI: 1.08, 1.16) at 0.1°C) occurred at the time of virus exposure and after symptom onset. Two minima (OR=0.81 (95% CI: 0.71, 0.92) at 23.2°C; OR=0.71 (95% CI: 0.63, 0.80) at 21.7°C) also occurred at these two distinct periods correspondingly. Low humidity (below 50%) during the early stages and high humidity (approximately 89%) after symptom onset were related to the lower fatality.

Conclusion

Environmental conditions may affect not only the initial viral load when exposure to viruses but also individuals’ immunity response around symptom onset. Warmer temperatures and higher humidity after symptom onset were related to the lower fatality.

Highlights

Temperature and humidity conditions that patients were exposed to during their early infection stages were associated with COVID-19 case fatality rate.

Warmer temperatures (> 20°C) at infection time or after symptom onset, but not during the incubation period, were associated with lower death risk. Low relative humidity (< 50%) during the early stages and high relative humidity (> 85%) after symptom onset were related to higher death risk.

Creating optimal indoor conditions for cases who are under quarantine/isolation may reduce their risk of death.
Development and validation of an electronic health records-based opioid use disorder algorithm by expert clinical adjudication
Authors: Ranapurwala Shabbar I. , Alam Ishrat Z. , Pence Brian W. , Carey Timothy S. , Christensen Sean , Clark Marshall , Chelminski Paul R. , Wu Li-Tzy , Greenblatt Lawrence H. , Korte Jeffrey E. , Wolfson Mark , Douglas Heather E. , Bowlby Lynn A. , Capata Michael , Marshall Stephen W.
Published: September 2021

Background

In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may contribute substantially to prevention of overdose deaths. However, OUD research is limited, the specificity and sensitivity of OUD ICD codes are unknown, and the ICD codes are known to underestimate OUD prevalence. We developed and validated algorithms to identify OUD from EHR data and examine validity of ICD-based definitions for OUD.

Methods

Through multiple iterations, we developed EHR-based algorithms to identify OUD. These algorithms and ICD-based OUD definition were validated against a total of 169 independent gold standard EHR chart reviews conducted by an expert adjudication panel of eight pain and addiction medicine clinical experts across four large healthcare systems. The experts relied on clinical judgement and current Diagnostic and Statistical Manual of Mental Disorders-5 criteria for making OUD diagnoses.

Results

Of the 169 EHR charts, 81 (48%) were reviewed by more than one expert and exhibited 85% agreement between the reviewing experts. The OUD ICD codes alone had 10% sensitivity and 99% specificity, underscoring the strong potential for OUD underestimation in studies depending on ICD codes alone. In comparison, after four iterations, the algorithms identified OUD with a 23% sensitivity and 98% specificity.

Conclusions and Relevance

This is the first study to evaluate the validity of OUD ICD codes and develop validated EHR-based algorithms to address OUD underestimation. This work has the potential to inform future research on early intervention and prevention of OUD.
The unmutated common ancestor of Gp41 conformational epitope targeting variable heavy chain 1-02 utilizing antibodies maintains antibody dependent cell cytotoxicity
Authors: Wrotniak Brian H. , Garrett Meghan , Baron Sarah , Sojar Hakimuddin , Shon Alyssa , Asiago-Reddy Elizabeth , Yager Jessica , Kalams Spyros , Croix Michael , Hicar Mark D
Published: September 2021

In studies on monoclonal Abs (mAbs) from long-term non-progressors (LTNPs), our laboratory has previously described highly mutated Abs against a complex conformational epitope with contributions from both gp41 heptad repeat regions. Despite using the VH1-02 gene segment, known to contribute to some of the broadest neutralizing Abs against HIV, members of these Abs, termed group 76C Abs, did not exhibit broad neutralization.

Because of the excessive mutations and use of VH1-02, our goal was to characterize the non-neutralizing functions of Abs of group 76C, to assess targeting of the epitope in various clinical presentations, and to assess the development of these Abs by comparison to their predicted common ancestor. Serum competition assays showed group 76C Abs were enriched in LTNPs, in comparison to VRC-01. Specific group 76C clones 6F5 and 6F11, expressed as recombinant Abs, both have robust ADCC activity, despite their sequence disparity. Sequence analysis predicted the common ancestor of this clonal group would utilize the germline non-mutated variable gene. We produced a recombinant ancestor Ab (76Canc) with a heavy chain utilizing the germline variable gene sequence paired to the 6F5 light chain. Competition with group 76C recombinant Ab 6F5 confirms 76Canc binds HIV envelope constructs near the original group C epitope. 76Canc demonstrates comparable ADCC to 6F5 and 6F11 when targeting both clade B and C HIV constructs. The functional capability of Abs utilizing germline VH1-02 has implications for disease control and vaccine development.
Modeling the transmission of the SARS-CoV-2 delta variant in a partially vaccinated population
Authors: de León Ugo Avila-Ponce , Avila-Vales Eric , Huang Kuan-lin
Published: September 2021

In a population with ongoing vaccination, the trajectory of a pandemic is determined by how the virus spreads in unvaccinated and vaccinated individuals that exhibit distinct transmission dynamics based on different levels of natural and vaccine-induced immunity. We developed a mathematical model that considers both subpopulations and immunity parameters including vaccination rates, vaccine effectiveness, and a gradual loss of protection. The model forecasted the spread of the SARS-CoV-2 delta variant in the US under varied transmission and vaccination rates. We further obtained the control reproduction number and conducted sensitivity analyses to determine how each parameter may affect virus transmission. Our results show that a combination of strengthening vaccine-induced immunity and preventative behavioral measures will likely be required to deaccelerate the rise of infectious SARS-CoV-2 variants.

One-Sentence Summary

Mathematical models considering vaccinated and unvaccinated individuals help forecast and manage the spread of new SARS-CoV-2 variants.
Sleep in the Intensive Care Unit through the Lens of Breathing and Heart Rate Variability: A Cross-Sectional Study
Authors: Ganglberger Wolfgang , Krishnamurthy Parimala Velpula , Quadri Syed A. , Tesh Ryan A. , Bucklin Abigail A. , Adra Noor , Da Silva Cardoso Madalena , Leone Michael J. , Hemmige Aashritha , Rajan Subapriya , Panneerselvam Ezhil , Paixao Luis , Higgins Jasmine , Ayub Muhammad Abubakar , Shao Yu-Ping , Coughlin Brian , Sun Haoqi , Ye Elissa M. , Cash Sydney S. , Thompson B. Taylor , Akeju Oluwaseun , Kuller David , Thomas Robert J. , Westover M. Brandon
Published: September 2021

Background

Full polysomnography, the gold standard of sleep measurement, is impractical for widespread use in the intensive care unit (ICU). Wrist-worn actigraphy and subjective sleep assessments do not measure sleep physiology adequately. Here, we explore the feasibility of estimating conventional sleep indices in the ICU with heart rate variability (HRV) and respiration signals using artificial intelligence methods.

Methods

We used deep learning models to stage sleep with HRV (through electrocardiogram) and respiratory effort (through a wearable belt) signals in critically ill adult patients admitted to surgical and medical ICUs, and in covariate-matched sleep laboratory patients. We analyzed the agreement of the determined sleep stages between the HRV- and breathing-based models, computed sleep indices, and quantified breathing variables during sleep.

Results

We studied 102 adult patients in the ICU across multiple days and nights, and 220 patients in a clinical sleep laboratory. We found that sleep stages predicted by HRV- and breathing-based models showed agreement in 60% of the ICU data and in 81% of the sleep laboratory data. In the ICU, deep NREM (N2 + N3) proportion of total sleep duration was reduced (ICU 39%, sleep laboratory 57%, p<0.01), REM proportion showed heavy-tailed distribution, and the number of wake transitions per hour of sleep (median = 3.6) was comparable to sleep laboratory patients with sleep-disordered breathing (median = 3.9). Sleep in the ICU was also fragmented, with 38% of sleep occurring during daytime hours. Finally, patients in the ICU showed faster and less variable breathing patterns compared to sleep laboratory patients.

Conclusions

Cardiovascular and respiratory signals encode sleep state information, which can be utilized to measure sleep state in the ICU. Using these easily measurable variables can provide automated information about sleep in the ICU.
Social and emotional characteristics of girls and young women withDDX3X-linked intellectual disability: A descriptive and comparative study
Authors: Ng-Cordell Elise , Kolesnik-Taylor Anna , O’Brien Sinéad , Astle Duncan , Scerif Gaia , Baker Kate
Published: September 2021

Background

DDX3Xvariants are a common cause of intellectual disability (ID) in females. Previous studies have reported high rates of autism spectrum disorder and emotional-behavioural difficulties within this group. However, no study has compared social and emotional characteristics in individuals withDDX3Xvariants to individuals with other monogenic causes of ID.

Methods

Twenty-three females with pathogenic or likely pathogenicDDX3Xvariants were recruited via UK regional genetics centres, genetic research cohorts, and family support groups. Twenty-three females with ID and variants in other genes were recruited via the same routes. Phenotypic data were collected through semi-structured interviews and standardised questionnaires.

Results

In line with previous research, we found a wide range of adaptive, social and emotional function within theDDX3Xgroup. Autism characteristics assessed via the Social Responsiveness Scale (SRS) did not differ betweenDDX3Xand comparison groups, while levels of anxiety and self-injurious behaviour (SIB) scores assessed via the Developmental Behaviour Checklist (DBC) were significantly higher in theDDX3Xgroup. Autistic characteristics, anxiety and SIB scores were positively correlated within theDDX3Xgroup. Individuals withDDX3Xmissense variants had poorer adaptive abilities than those with protein truncating variants as previously reported, butDDX3Xvariant type did not significantly predict emotional and behavioural characteristics.

Conclusions

We provide quantitative evidence that overall incidence of autistic characteristics is not higher amongst girls and women withDDX3Xvariants than expected for ID. However, theDDX3Xgroup demonstrates more SIBs and anxiety symptoms than expected, with close relationships between SIBs and anxiety, and between anxiety and autistic characteristics. Future work is warranted to explore the multilevel mechanisms contributing to social and emotional development in individuals withDDX3Xvariants, and consider whether these mechanisms are specific to this genetic diagnosis or shared with a subset of people with ID due to other causes.
Real-Time Semi-Automated and Automated Voxel Placement for Repeated Acquisition Magnetic Resonance Spectroscopy
Authors: Bishop James H. , Geoly Andrew , Khan Naushaba , Tischler Claudia , Krueger Ruben , Amin Heer , Baltusis Laima , Wu Hua , Spiegel David , Williams Nolan , Sacchet Matthew D.
Published: September 2021

Magnetic resonance spectroscopy (MRS) is heavily dependent on the investigative team to prescribe, or demarcate, the desired tissue volume-of-interest. Manual prescription, the current standard in the field, requires expertise in neuroanatomy to ensure spatial consistency within and across subjects. Spatial precision of MRS voxel placement thus presents challenges for cross-sectional studies, and even more so for repeated-measure and multi-acquisition designs. Furthermore, voxel prescriptions based-solely on anatomical landmarks may not be ideal in regions with substantial functional and cytoarchitectural variability or to examine individualized/targeted interventions. Here we propose and validate robust and real-time methods to automate MRS voxel placement using functionally defined coordinates within the left dorsolateral prefrontal cortex in clinical cohorts of chronic pain and depression. We hypothesized that increased automation would produce more consistent voxel placement across repeated acquisitions particularly in reference to standard manual prescription. Data were collected and analyzed using two independent prospective transcranial magnetic stimulation studies: 1) a single-day multi-session sandwich design and 2) a longitudinal design. Participants with fibromyalgia syndrome (N=50) and major depressive disorder (N=35) underwent MRI as part of ongoing clinical studies. MEGA-PRESS and Optimized-PRESS MRS acquisitions were acquired at 3-tesla. Evaluation of the reproducibility of spatial location and tissue segmentation was assessed for: 1) manual, 2) semi-automated, and 3) automated voxel prescription approaches. Variability of grey and white matter voxel tissue composition was reduced using automated placement protocols as confirmed by common MRS software processing pipelines (Gannet; SPM-based segmentation) and via Freesurfer-based segmentation. Spatially, post-to pre-voxel center-of-gravity distance was reduced and voxel overlap increased significantly across datasets using automated compared to manual procedures. These results demonstrate the within subject reliability and reproducibility of a method for reducing variability introduced by spatial inconsistencies during MRS acquisitions. The proposed method is a meaningful advance toward improved consistency of MRS data in neuroscience and can be leveraged for multi-session and longitudinal studies that target precisely defined regions-of-interest via a coordinate-based approach.
Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis
Authors: Zeng Baoqi , Gao Le , Zhou Qingxin , Yu Kai , Sun Feng
Published: September 2021

Background

It was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC.

Methods

Published and preprinted randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, or Delta) were searched until 31 August 2021. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1− estimate).

Results

Seven RCTs (51,169 participants), 10 cohort studies (14,385,909 participants) and 16 case-control studies (734,607 cases) were included. Eight COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, and BBIBP-CorV) were included in this analysis. Full vaccination was effective against Alpha, Beta/Gamma, and Delta variants, with VE of 88.3% (95% CI, 82.4–92.2), 70.7% (95% CI, 59.9–78.5), and 71.6% (95% CI, 64.1–77.4), respectively. But partial vaccination was less effective, with VE of 59.0% (95% CI, 51.3–65.5), 49.3% (95% CI, 33.0–61.6), and 52.6% (95% CI, 43.3–60.4), respectively. mRNA vaccines seemed to have higher VE against VOC over others, significant interactions (pinteraction< 0.10) were observed between VE and vaccine type (mRNA vaccines vs. non-mRNA vaccines).

Conclusions

Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta/Gamma and Delta variants. Partial vaccination has less VE against VOC. mRNA vaccines seem to have higher VE against Alpha, Beta/Gamma, and Delta variants over others.
Mechanical characterisation of the developing cell wall layers of tension wood fibres by Atomic Force Microscopy
Authors: Arnould Olivier , Capron Marie , Ramonda Michel , Laurans Françoise , Alméras Tancrède , Pilate Gilles , Clair Bruno
Published: September 2021

Abstract

Trees generate mechanical stresses at periphery of stem and branches to improve their strength and to control the orientation of their axes. This key factor in the biomechanical design of trees, named “maturation stress”, occurs in wood fibres during cellular maturation when their secondary cell wall thickens. In this study, the spatial and temporal stiffening kinetics of the different cell wall layers were recorded during fibre maturation on a sample of poplar tension wood using atomic force microscopy. The thickening of the different layers was also recorded. The stiffening of the CML, S1 and S2-layers was initially synchronous with the thickening of the S2-layer and continued a little after the S2-layer reached its final thickness as the G-layer began to develop. In contrast, the global stiffness of the G-layer, which initially increased with its thickening, was close to stable long before it reached its final maximum thickness. A limited radial gradient of stiffness was observed in the G-layer, but it decreased sharply on the lumen side, where the new sub-layers are deposited during cell wall thickening. Although very similar at the ultrastructural and biochemical levels, the stiffening kinetics of the poplar G-layer appears to be very different from that described in maturing bast fibres.