bluuebunny/crossref_metadata_2025 huggingface dataset:
β-hydroxy-β-methylbutyrate supplementation in older persons – an update
Authors: Bear Danielle E. , Cruz-Jentoft Alfonso J. , Stout Jeffrey R.
Published: November 2020

Purpose of review

The interest in the use of beta-hydroxy-beta-methylbutyrate (HMB) as an intervention to prevent and treat sarcopenia has increased over recent years. The purpose of this review is to explore recent evidence pertaining to the mechanism of action of HMB and how this may influence changes in lean mass and strength in older persons who are both hospitalized and living in the community.

Recent findings

No new studies have been published over the last 2 years investigating the effect of HMB in older persons who are hospitalized, aside from one posthoc analysis of a randomized controlled trial exploring the effect of a high protein oral nutrition supplement containing HMB on handgrip strength and nutritional status. Three studies recruiting community-dwelling older adults have been published, but results are influenced by suboptimal methodological quality.

Recent data suggest the need for high-quality studies investigating the effectiveness of HMB to improve outcomes related to sarcopenia in both hospitalized and community-dwelling older persons.
Stem-cell-derived models: tools for studying role of microbiota in intestinal homeostasis and disease
Authors: Dheer Rishu , Young Vincent B.
Published: November 2020

Purpose of review

In this review, we will summarize the recent progress made in generating stem-cell-based organoid and enteroid models of the gastrointestinal tract and their importance in understanding the role of microbes in intestinal epithelial homeostasis and disease.

Recent finding

Intestinal stem-cell-derived culture systems are self-organizing three-dimensional organotypic cultures that recapitulate many cellular, architectural and functional aspects of the human intestine. Progress has been made in the development of methods to incorporate additional cell lineages and physiological cues to better mimic the complexity of the intestine. Current model systems have facilitated both the study of gastrointestinal infections and interactions with normally nonpathogenic microbial residents of the gastrointestinal tract. These studies have illustrated how live microbes, or their metabolites, ligands and virulence factors influence epithelial cell differentiation, maintenance, repair, function and intestine development.

Organotypic models are invaluable tools for studying host–microbe interactions that complement in-vivo experimental model systems. These models have evolved in terms of complexity and fidelity. The stem-cell-based models are already at forefront for studying host–microbe interactions and with continued development, the future looks even more promising.
Applicability of Magnetic Resonance Imaging of the Knee in Forensic Age Estimation
Authors: Uygun Besim , Kaya Kenan , Köse Sevgül , Ekizoğlu Oğuzhan , Hilal Ahmet
Published: November 2020

Age estimation in forensic medicine practice is of particular importance to the legal systems, and it is one of the current research topics in forensic medicine. Age determination is most frequently performed by radiological methods, but recently, nonionized methods are preferred for nonmedical indications. Therefore, we aimed to examine feasibility of MRI imaging, which provides nonionized, noninvasive, and detailed images, in forensic age estimation and to expand the database on this subject. The MRI images of the patients between the ages of 10 and 25 years, who visited Cukurova University Faculty of Medicine between January 2012 and April 2018 for any reason, were retrospectively analyzed according to the staging method described by Dedouit et al. The stage 5 ossification in distal femoral epiphysis indicated an age over 18 years in both sexes (except for 2 cases of 14 and 15 years). The stage 5 ossification in proximal tibial epiphysis indicated an age older than 18 years (except for 1 male case at the age of 15 years and 2 female cases at the age of 14 and 17 years, respectively). It was determined that stage 1 and stage 2 in both distal femur and proximal tibial epiphysis were last seen in younger than 18 years in both sexes. Our study data show that MRI imaging is a nonionized method that can be used in addition to other radiological methods in determining the age limit of 18 years.
BeyondR0: heterogeneity in secondary infections and probabilistic epidemic forecasting
Authors: Hébert-Dufresne Laurent , Althouse Benjamin M. , Scarpino Samuel V. , Allard Antoine
Published: November 2020

The basic reproductive number,R0, is one of the most common and most commonly misapplied numbers in public health. Often used to compare outbreaks and forecast pandemic risk, this single number belies the complexity that different epidemics can exhibit, even when they have the sameR0. Here, we reformulate and extend a classic result from random network theory to forecast the size of an epidemic using estimates of the distribution of secondary infections, leveraging both its averageR0and the underlying heterogeneity. Importantly, epidemics with lowerR0can be larger if they spread more homogeneously (and are therefore more robust to stochastic fluctuations). We illustrate the potential of this approach using different real epidemics with known estimates forR0, heterogeneity and epidemic size in the absence of significant intervention. Further, we discuss the different ways in which this framework can be implemented in the data-scarce reality of emerging pathogens. Lastly, we demonstrate that without data on the heterogeneity in secondary infections for emerging infectious diseases like COVID-19 the uncertainty in outbreak size ranges dramatically. Taken together, our work highlights the critical need for contact tracing during emerging infectious disease outbreaks and the need to look beyondR0.
PBRM1 loss-of-function mutations and response to immune checkpoint blockade in clear cell renal cell carcinoma
Authors: Conway Jake , Taylor-Weiner Amaro , Braun David , Bakouny Ziad , Choueiri Toni K. , Van Allen Eliezer M.
Published: November 2020

The biological role of PBRM1 loss-of-function (LOF) mutations mediating response to immune checkpoint blockade (ICB) in clear cell renal cell carcinoma (ccRCC) remains an area of active investigation. A recent study (hereafter, ‘the MSK study’) evaluated this hypothesis in a clinically heterogeneous single institution retrospective ccRCC cohort using targeted sequencing and did not find a univariable statistically significant association for PBRM1 LOF and time-to-treatment failure (TTF), but did report a significant association between continuous tumor mutational burden (TMB) and ICB TTF. We re-analyzed this cohort to (i) match the methodology from previous studies and (ii) account for differences in cohort development, statistical approaches, mutation classifications, and outcome measurements. Univariable analysis of the PBRM1 LOF mutation hypothesis, when performed analogously to prior studies, demonstrated a modest statistically significant association with TTF on ICB (p = 0.047; HR = 0.7, 95% CI = 0.49 - 0.99). By contrast, when using the different methodology presented in the MSK study, statistical modeling demonstrated that there was insufficient power to detect this association given the altered classification scheme and modest effect size. In addition, after appropriately normalizing TMB to account for anomalous outliers, TMB was not significantly associated with ICB response in ccRCC. Thus, this study provides further support for the biological association between PBRM1 LOF and favorable clinical outcomes on ICB in specific ccRCC clinical contexts. However, we again strongly caution against interpreting that this PBRM1 biological association, likely one of many modest mediators of tumor-immune-stromal interactions, achieves broadly generalizable predictive biomarker status for ICB in diverse clinical contexts. The PBRM1 LOF biological association has only been shown to be modestly predictive in the post-VEGF TKI ICB-monotherapy ccRCC patient population. Given emerging data about the biological role of PBRM1 in contributing to interwoven immune and angiogenesis programs (among many others), and the rapidly shifting therapeutic combination strategies invoking these processes in ccRCC, focused biological and predictive biomarker analyses in specific clinical settings using appropriately annotated clinical trial cohorts are necessary.
Extremely Preterm Children Demonstrate Interhemispheric Hyperconnectivity During Verb Generation: a Multimodal Approach
Authors: Barnes-Davis Maria E. , Merhar Stephanie L. , Holland Scott K. , Parikh Nehal A. , Kadis Darren S.
Published: November 2020

Children born extremely preterm (EPT, <28 weeks gestation) are at risk for delays in development, including language. We use fMRI-constrained magnetoencephalography (MEG) during a verb generation task to assess the extent and functional connectivity (phase locking value, or PLV) of language networks in a large cohort of EPT children and their term comparisons (TC). 73 participants, aged 4 to 6 years, were enrolled (42 TC, 31 EPT). There were no significant group differences in age, sex, race, ethnicity, parental education, or family income. There were significant group differences in expressive language scores (p<0.05). Language representation was not significantly different between groups on fMRI, with task-specific activation involving bilateral temporal and left inferior frontal cortex. There were group differences in functional connectivity seen in MEG. To identify a possible subnetwork contributing to focal spectral differences in connectivity, we ran Network Based Statistics analyses. For both beta (20-25 Hz) and gamma (61-70 Hz) bands, we observed a subnetwork showing hyperconnectivity in the EPT group (p<0.05). Network strength was computed for the beta and gamma subnetworks and assessed for correlation with language performance. For the EPT group, exclusively, strength of the subnetwork identified in the gamma frequency band was positively correlated with expressive language scores (r=0.318, p<0.05). Thus, interhemispheric hyperconnectivity is positively related to language for EPT children and might represent a marker for resiliency in this population.
Rapid classification and prediction of COVID-19 severity by MALDI-TOF mass spectrometry analysis of serum peptidome
Authors: Gomila Rosa M. , Martorell Gabriel , Fraile-Ribot Pablo A. , Doménech-Sánchez Antonio , Oliver Antonio , García-Gasalla Mercedes , Albertí Sebastián
Published: November 2020

Classification and early detection of severe COVID-19 patients is urgently required to establish an effective treatment. Here, we tested the utility of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to classify and predict the severity of COVID-19 in a clinical setting. We used this technology to analyse the mass spectra profiles of the sera from 80 COVID-19 patients, clinically classified as mild (33), severe (26) and critical (21), and 20 healthy controls. We found a clear variability of the serum peptidome profile depending on COVID-19 severity. Seventy-eight peaks were significantly different and 12 at least four fold more intense in the set of critical patients than in the mild ones. Analysis of the resulting matrix of peak intensities by machine learning approaches classified severe (severe and critical) and non-severe (mild) patients with a 90% of accuracy. Furthermore, machine learning predicted correctly the favourable outcome of the severe patients in 85% of the cases and the unfavourable in 38% of the cases. Finally, liquid chromatography mass spectrometry analysis of sera identified five proteins that were significantly upregulated in the critical patients. They included serum amyloid proteins A1 and A2, which probably yielded the most intense peaks with m/z 11,530 and 11,686 detected by MALDI-TOF MS.

In summary, we demonstrated the potential of the MALDI-TOF MS as a bench to bedside technology to aid clinicians in their decisions to classify COVID-19 patients and predict their evolution.
High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report
Authors: Riley Steven , Ainslie Kylie E. C. , Eales Oliver , Walters Caroline E. , Wang Haowei , Atchison Christina , Fronterre Claudio , Diggle Peter J. , Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul
Published: November 2020

Background

REACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive.

Methods

REACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive.

Results

Overall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0.96%) up 2-fold from 0.35% (0.28%, 0.43%). Prevalence remained highest in 18 to 24-year olds at 2.25% (1.47%, 3.42%).

Conclusion

The co-occurrence of high prevalence and rapid growth means that the second wave of the epidemic in England has now reached a critical stage. Whether via regional or national measures, it is now time-critical to control the virus and turn R below one if further hospital admissions and deaths from COVID-19 are to be avoided.
Robot-based assessment of HIV-related motor and cognitive impairment for neurorehabilitation
Authors: Bui Kevin D. , Wamsley Carol A. , Shofer Frances S. , Kolson Dennis L. , Johnson Michelle J.
Published: November 2020

There is a pressing need for strategies to slow or treat the progression of functional decline in people living with HIV. This paper explores a novel rehabilitation robotics approach to measuring cognitive and motor impairment in adults living with HIV, including a subset with stroke. We conducted a cross-sectional study with 21 subjects exhibiting varying levels of cognitive and motor impairment. We developed three robot-based tasks trajectory tracking, N-back, and spatial span – to assess if metrics derived from these tasks were sensitive to differences in subjects with varying levels of executive function and upper limb motor impairments. We also examined if these metrics could estimate clinical cognitive and motor scores. The results showed that the average sequence length on the robot-based spatial span task was the most sensitive to differences between subjects’ cognitive and motor impairment levels. We observed strong correlations between robot-based measures and clinical cognitive and motor assessments relevant to the HIV population, such as the Color Trails 1 (rho = 0.83), Color Trails 2 (rho = 0.71), Digit Symbol – Coding (rho = 0.81), Montreal Cognitive Assessment – Executive Function subscore (rho = 0.70), and Box and Block Test (rho = 0.74). Importantly, our results highlight that gross motor impairment may be overlooked in the assessment of HIV-related disability. This study shows that rehabilitation robotics can be expanded to new populations beyond stroke, namely to people living with HIV and those with cognitive impairments.
A Natural Language Processing Tool to Extract Quantitative Smoking Status from Clinical Narratives
Authors: Yang Xi , Yang Hanyuan , Lyu Tianchen , Yang Shuang , Guo Yi , Bian Jiang , Xu Hua , Wu Yonghui
Published: November 2020

This study presents a natural language processing (NLP) tool to extract quantitative smoking information (e.g., Pack-Year, Quit Year, Smoking Year, and Pack per Day) from clinical notes and standardized them into Pack-Year unit. We annotated a corpus of 200 clinical notes from patients who had low-dose CT imaging procedures for lung cancer screening and developed an NLP system using a two-layer rule-engine structure. We divided the 200 notes into a training set and a test set and developed the NLP system only using the training set. The experimental results on the test set showed that our NLP system achieved the best F1 scores of 0.963 and 0.946 for lenient and strict evaluation, respectively.

Note

Accepted as a presentation at the 2020 IEEE International Conference on Healthcare Informatics (ICHI) Workshop on Health Natural Language Processing (HealthNLP 2020).

https://ohnlp.github.io/HealthNLP2020/healthnlp2020#.
Optimizing training programs for athletic performance: a Monte-Carlo Tree Search variant method
Authors: Houy Nicolas
Published: November 2020

Purpose

Using a variant of the Monte-Carlo Tree Search (MCTS) algorithm, we compute optimal personalized and generic training programs for athletic performance.

Methods

We use a non-linear performance model with population variability for athletes and non-athletes previously used in the literature. Then, we simulate an in-silico test population. For each individual of this population, we compute the performance obtained after implementing several widely used training programs as well as the one obtained by our variant of the MCTS algorithm. Two cases are considered depending on individual parameters being observed and personalized programs being possible or only parameter distributions being available and only generic training programs being implementable.

Results

Compared to widely used training programs, our optimization leads to an increase in performance between 1.1 (95% CI: 0.9 – 1.4) percentage point of the performance obtained with stationary optimal training dose (pp POTD) for athletes and unknown individual characteristics to 10.0 (95% CI: 9.6 – 10.3) pp POTD for nonathletes and known individual characteristics. The value of information when using MCTS optimized training strategies, i.e. the difference between the performance that can be reached with knowledge of individual characteristics and the performance that can be reached without it is 14.7 (95% CI: 12.8 – 16.7) pp POTD for athletes and 3.0 (95% CI: 2.6 – 3.4) pp POTD for non-athletes.
Cell phone mobility data and manifold learning: Insights into population behavior during the COVID-19 pandemic
Authors: Levin Roman , Chao Dennis L. , Wenger Edward A. , Proctor Joshua L.
Published: November 2020

As COVID-19 cases resurge in the United States, understanding the complex interplay between human behavior, disease transmission, and non-pharmaceutical interventions during the pandemic could provide valuable insights to focus future public health efforts. Cell-phone mobility data offers a modern measurement instrument to investigate human mobility and behavior at an unprecedented scale. We investigate mobility data collected, aggregated, and anonymized by SafeGraph Inc. which measures how populations at the census-block-group geographic scale stayed at home in California, Georgia, Texas, and Washington since the beginning of the pandemic. Using manifold learning techniques, we find patterns of mobility behavior that align with stay-at-home orders, correlate with socioeconomic factors, cluster geographically, and reveal sub-populations that likely migrated out of urban areas. The analysis and approach provides policy makers a framework for interpreting mobility data and behavior to inform actions aimed at curbing the spread of COVID-19.
Low dose hydroxychloroquine is associated with lower mortality in COVID-19: a meta-analysis of 26 studies and 44,521 patients
Authors: Di Castelnuovo Augusto , Costanzo Simona , Cassone Antonio , Cauda Roberto , de Gaetano Giovanni , Iacoviello Licia
Published: November 2020

Background

Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is not well characterized. We conducted two meta-analyses to evaluate the association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.

Methods

Articles were retrieved until October 20th, 2020 by searching in seven databases. Data were combined using the general variance-based method on relative risk estimates.

Results

A total of 26 articles were found (N=44,521 COVID-19 patients, including N=7,324 from 4 randomized clinical trials (RCTs)); 10 studies were valuable for analysing the association of HCQ+AZM. Overall, the use of HCQ was associated with 21% lower mortality risk (pooled risk ratio: 0.79, 95%CI: 0.67 to 0.93; high level of heterogeneity: I2=82%, random effects). This association vanished (1.10, 95%CI: 0.99 to 1.23 and 1.10, 95%CI: 0.99 to 1.23) when daily dose >400 mg or total dose >4,400 mg were used, respectively). HCQ+AZM was also associated with 25% lower mortality risk, but uncertainty was large (95%CI: 0.50 to 1.13; P=0.17). No association was apparent when only pooling the 4 RCTs (13.8% of the overall weight; pooled risk ratio: 1.11, 95%CI: 0.99 to 1.24).

Conclusions

HCQ use was not associated with either increased or decreased mortality in COVID-19 patients when 4 RCTs only were evaluated, while a 7% to 33% reduced mortality was observed when observational studies were also included. The association was mainly apparent when pooling studies using lower doses of HCQ. These findings can help disentangling the debate on HCQ use in COVID-19.

Key-points

Low dose hydroxychloroquine was associated with reduced mortality in COVID-19 patients, as seen in observational studies but not in randomised clinical trials, which used high doses of hydroxychloroquine. These findings can help disentangling the debate on hydroxychloroquine use in COVID-19.
The impact of keeping a religious beard in the COVID-19 pandemic: an online cross sectional survey study exploring experiences of male medical healthcare professionals
Authors: Hamed Amer , Latif Asam , Haris Mohammad , Patel Sufyan , Patel Muhammad I , Rahman Mustafa Syed Abdur , Khan Omeair , Shoaib Ahmad , Waqar Salman
Published: November 2020

There has been a disproportionate effect on individuals from black Asian & Minority Ehnic (BAME) in the UK in Coronavirus disease (COVID-19) pandemic, especially in the NHS staff. Many of them have been asked to remove their beard to be eligible to do the fit test which can have negative implications on their spiritual, psychological & emotional wellbeing. This paper surveyed the responses of 469 healthcare professionals (HCPs) with beards regarding the challenges they face in regard to personal protective equipment (PPE), mask fit testing and attitude of employers & colleagues.

Professional discrimination through fit testing rejection, unavailability or inadequate PPE and the pressure to shave their beard are unpleasant outcomes of this pandemic for some of the NHS staff. NHS trusts & hospitals need to adjust their practices to include staff with beard in their COVID-19 arrangements.
Factors Associated with Coronavirus (COVID-19) Deaths and Infections: A Cross Country Evidence
Authors: Shimul Shafiun Nahin , Kadir Fariha , Ihsan- Ul- Kabir Muhammad
Published: November 2020

Though most of the countries across the world are crippled with COVID-19, there has been substantial variations in death and infection rates. While some countries are overwhelmed, a few are spared. Little is known what explains this variation. This study attempts to understand the covariates of death and infection rates of COVID-19 across countries using multivariate regression analysis and least absolute shrinkage and selection operator (LASSO) regression. The OLS estimates show that the aging population and hospital bed per capita are significantly associated with the fatality rate of COVID-19, while urbanization has a positive correlation with the inflection rate. The study suggests that an increase in health systems capacity can significantly reduce the fatality rates due to COVID-19.
Reproducibility and sensitivity of 36 methods to quantify the SARS-CoV-2 genetic signal in raw wastewater: findings from an interlaboratory methods evaluation in the U.S.
Authors: Pecson Brian M. , Darby Emily , Haas Charles N. , Amha Yamrot , Bartolo Mitchel , Danielson Richard , Dearborn Yeggie , Di Giovanni George , Ferguson Christobel , Fevig Stephanie , Gaddis Erica , Gray Don , Lukasik George , Mull Bonnie , Olivas Liana , Olivieri Adam , Qu Yan ,   SARS-CoV-2 Interlaboratory Consortium
Published: November 2020

1

In response to COVID-19, the international water community rapidly developed methods to quantify the SARS-CoV-2 genetic signal in untreated wastewater. Wastewater surveillance using such methods has the potential to complement clinical testing in assessing community health. This interlaboratory assessment evaluated the reproducibility and sensitivity of 36 standard operating procedures (SOPs), divided into eight method groups based on sample concentration approach and whether solids were removed. Two raw wastewater samples were collected in August 2020, amended with a matrix spike (betacoronavirus OC43), and distributed to 32 laboratories across the U.S. Replicate samples analyzed in accordance with the project’s quality assurance plan showed high reproducibility across the 36 SOPs: 80% of the recovery-corrected results fell within a band of +/- 1.15-log10 genome copies/L with higher reproducibility observed within a single SOP (standard deviation of 0.13-log10). The inclusion of a solids removal step and the selection of a concentration method did not show a clear, systematic impact on the recovery-corrected results. Other methodological variations (e.g., pasteurization, primer set selection, and use of RT-qPCR or RT-dPCR platforms) generally resulted in small differences compared to other sources of variability. These findings suggest that a variety of methods are capable of producing reproducible results, though the same SOP or laboratory should be selected to track SARS-CoV-2 trends at a given facility. The methods showed a 7-log10 range of recovery efficiency and limit of detection highlighting the importance of recovery correction and the need to consider method sensitivity when selecting methods for wastewater surveillance.
Brain-derived neurotrophic factor in cerebrospinal fluid and plasma is not a biomarker for Huntington’s disease
Authors: Andy Ou Zhen-Yi , Byrne Lauren M. , Rodrigues Filipe B. , Tortelli Rosanna , Johnson Eileanoir B. , Foiani Martha S. , Arridge Marzena , De Vita Enrico , Scahill Rachael I. , Heslegrave Amanda , Zetterberg Henrik , Wild Edward J.
Published: November 2020

Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function is reduced in Huntington’s disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to striatal neurodegeneration. The BDNF trophic pathway is a therapeutic target, and blood BDNF has been suggested as a potential biomarker for HD, but BDNF has not been quantified in cerebrospinal fluid (CSF) in HD.

BDNF in CSF and plasma in the HD-CSF cohort (20 pre-manifest and 40 manifest HD mutation carriers and 20 age and gender-matched controls) were quantified using conventional ELISAs and an ultra-sensitive immunoassay.

BDNF concentration was below the limit of detection of the conventional ELISAs, raising doubt about previous CSF reports in neurodegeneration. Using the ultra-sensitive method, BDNF concentration was quantifiable in all samples but did not differ between controls and HD mutation carriers in CSF or plasma, was not associated with clinical scores or MRI brain volumetric measures, and had poor ability to discriminate controls from HD mutation carriers, and premanifest from manifest HD.

BDNF in CSF and plasma is unlikely to be a biomarker of HD progression, and urge caution in interpreting studies where conventional ELISA was used to quantify CSF BDNF.
Outbreak investigation of Visceral Leishmaniasis in Borena Zone, Oromia Region, Ethiopia, November 2019: Case Control study
Authors: Regassa Belay , Deyessa Negussie , Addissie Adamu , Abagero Abdulnasir , Shumi Gemechu , Gudina Gemechu
Published: November 2020

Background

Visceral Leishmaniasis (VL) caused by Leishmania parasites, infects mammals transmitted by Phlebotomine sand-flies and mostly affects the poorest. VL distributed worldwide and prevalent in Ethiopia. Knowing occurrence of disease and risk factor is a remedy for controlling. The aim of study was to identify factors associated with VL.

Methods

Case control study was carried out during October-November 2019 in Borena. A 1:2 Cases and controls were identified by case definition and 33 cases were included in the study. Participants >18years interviewed and caregivers of <18 were questioned for legal issue. Epi-info and SPSS were used for data entry and analysis. Primarily predictors were identified using chi-square at significant level P<0.05 with 95%CI, then candidate predictors were analysed using bivariate and multivariate analysis to identify associated factors.

Result

Among 153 suspected cases, 9 suspected deaths reported; 33 (22%) cases and 3 deaths were verified for VL. Among 33 verified cases 15(45.5%) were in July 2019, in comparison of 4years data, there is surge cases in July-August 2019, 26(79%) of cases were from Dire, Attack Rate (AR) = 15/100,000, CFR=9.1%. Among all, 15-64year were highly affected with AR=19.3. A case control engaged 99(100%) respondents and among all 93(93.9%) were male, 68(68.8%) were 15-64years. Adult education Adjusted Odds Ratio (AOR) = 30.438(2.378, 389.602), bed-net AOR=9.024 (1.763, 46.205) and walling AOR=0.052(0.004, 0.739) were associated factors with VL at 95%CI with p-value<0.05.

Conclusion

Male 15-64years were highly susceptible. Level of education, ITNs and walling were associated factors with VL. Formulating policies and guidelines for male 15-64 years related vector control and awareness creation regarding feeding habit of sand fly, prevention and control were recommended. Awareness of community on prevention method; using repellents, ITNs utilization, and safe sleeping mechanisms are mandatory. Further investigation on the issue is best remedy to overcome future VL outbreak occurrence.
Rapid SARS-CoV-2 Detection by Carbon Nanotube-Based Near-Infrared Nanosensors
Authors: Pinals Rebecca L. , Ledesma Francis , Yang Darwin , Navarro Nicole , Jeong Sanghwa , Pak John E. , Kuo Lili , Chuang Yung-Chun , Cheng Yu-Wei , Sun Hung-Yu , Landry Markita P.
Published: November 2020

To effectively track and eliminate COVID-19, it is critical to develop tools for rapid and accessible diagnosis of actively infected individuals. Here, we introduce a single-walled carbon nanotube (SWCNT)-based optical sensing approach towards these ends. We construct a nanosensor based on SWCNTs noncovalently functionalized with ACE2, a host protein with high binding affinity for the SARS-CoV-2 spike protein. Presence of the SARS-CoV-2 spike protein elicits a robust, two-fold nanosensor fluorescence increase within 90 min of spike protein exposure. We characterize the nanosensor stability and sensing mechanism, and passivate the nanosensor to preserve sensing response in saliva and viral transport medium. We further demonstrate that these ACE2-SWCNT nanosensors retain sensing capacity in a surface-immobilized format, exhibiting a 73% fluorescence turn-on response within 5 s of exposure to 35 mg/L SARS-CoV-2 virus-like particles. Our data demonstrate that ACE2-SWCNT nanosensors can be developed into an optical tool for rapid SARS-CoV-2 detection.

Abstract Figure
Covid-19 fatality prediction in people with diabetes and prediabetes using a simple score at hospital admission
Authors: Sourij H. , Aziz F. , Bräuer A. , Ciardi C. , Clodi M. , Fasching P. , Karolyi M. , Kautzky-Willer A. , Klammer C. , Malle O. , Oulhaj A. , Pawelka E. , Peric S. , Ress C. , Sourij C. , Stechemesser L. , Stingl H. , Stulnig TM. , Tripolt N. , Wagner M. , Wolf P. , Zitterl A. , Kaser S. ,   for the COVID-19 in Diabetes in Austria - study group
Published: November 2020

AIM

We assessed predictors of in-hospital mortality in people with prediabetes and diabetes hospitalized for COVID-19 infection and developed a risk score for identifying those at the highest risk of a fatal outcome.

MATERIALS AND METHODS

A combined prospective and retrospective multicenter cohort study was conducted in 10 sites in Austria on 247 people with diabetes or newly diagnosed prediabetes, who were hospitalised for COVID-19. The primary outcome was in-hospital mortality and predictor variables at the time of admission included clinical data, comorbidities of diabetes or laboratory data. Logistic regression analyses were performed to identify significant predictors and develop a risk score for in-hospital mortality.

RESULTS

The mean age of people hospitalized (n=238) for COVID-19 was 71.1 ± 12.9 years, 63.6% were males, 75.6% had type 2 diabetes, 4.6% had type 1 diabetes, and 19.8% had prediabetes. The mean duration of hospital stay was 18 ± 16 days, 23.9% required ventilation therapy, and 24.4% died in the hospital. Mortality rate in people with diabetes was numerically higher (26.7%) as compared to those with prediabetes (14.9%) but without statistical significance (p=0.128). A score including age, arterial occlusive disease, CRP, eGFR and AST levels at admission predicted in-hospital mortality with a C-statistics of 0.889 (95%CI: 0.837 – 0.941) and calibration of 1.000 (p=0.909).

CONCLUSIONS

The in-hospital mortality for COVID-19 was high in people with diabetes and not significantly different to the risk in people with prediabetes. A risk score using five routinely available patient parameters demonstrated excellent predictive performance for assessing in-hospital mortality.
Prevalence Of COVID-19 In Rural Versus Urban Areas in a Low-Income Country: Findings from a State-Wide Study in Karnataka, India
Authors: Mohanan Manoj , Malani Anup , Krishnan Kaushik , Acharya Anu
Published: November 2020

Although the vast majority of confirmed cases of COVID-19 are in low- and middle-income countries, there are relatively few published studies on the epidemiology of SARS-CoV-2 in these countries. The few there are focus on disease prevalence in urban areas. We conducted state-wide surveillance for COVID-19, in both rural and urban areas of Karnataka between June 15-August 29, 2020. We tested for both viral RNA and antibodies targeting the receptor binding domain (RBD). Adjusted seroprevalence across Karnataka was 46.7% (95% CI: 43.3-50.0), including 44.1% (95% CI: 40.0-48.2) in rural and 53.8% (95% CI: 48.4-59.2) in urban areas. The proportion of those testing positive on RT-PCR, ranged from 1.5 to 7.7% in rural areas and 4.0 to 10.5% in urban areas, suggesting a rapidly growing epidemic. The relatively high prevalence in rural areas is consistent with the higher level of mobility measured in rural areas, perhaps because of agricultural activity. Overall seroprevalence in the state implies that by August at least 31.5 million residents had been infected by August, nearly an order of magnitude larger than confirmed cases.
Amplification of frog calls by leaf substrates: implications for terrestrial and arboreal species
Authors: Muñoz Matías I. , Halfwerk Wouter
Published: November 2020

Signal detection is a minimum requirement for any communicative interaction. Acoustic signals, however, often experience amplitude losses during their transmission through the environment, reducing their detection range. Displaying from sites that increase the amplitude of the sound produced, such as cavities or some reflective surfaces, can improve the detectability of signals by distant receivers. Understanding how display sites influence sound production is, however, far from understood. We measured the effect of leaf calling sites on the calls of an arboreal (Hyalinobatrachium fleischmanni) and a leaf-litter specialist (Silverstoneia flotator) frog species. We collected the leaves where males of both species were observed calling, and conducted playback experiments to measure their effect on the amplitude of frog calls. Overall, the leaves used byH. fleischmanniandS. flotatorwere of similar dimensions, and amplified the calls of each species by about 5.0 and 2.5 dB, respectively. The degree of call amplification was unrelated to leaf dimensions or the position of the frogs on the leaves, but explained by the different frequency content of the calls of each species. Depending on the spatial location of intended and unintended receivers, we suggest that amplification of frog calls by leaves could represent either a benefit or impose costs for arboreal and terrestrial species. We argue that the microhabitat of the substrate from which animals display needs to be considered when addressing signal evolution.

Lay summary

Animals produce signals from specific locations in the environment, yet we know surprisingly little about the effects of the small-scale habitat on animal communication. Here we show that the calls of a terrestrial and an arboreal frog species are amplified by the leaves they use as calling sites. We argue that the consequences of this enhancement need to be considered in relation to the spatial location of intended (males and females) and unintended receivers (predators and parasites).
A feedback-loop between telomerase activity and stemness factors regulates PDAC stem cells
Authors: Walter Karolin , Rodriguez-Aznar Eva , Ventura Ferreira Monica S. , Frappart Pierre-Olivier , Dittrich Tabea , Tiwary Kanishka , Meessen Sabine , Lerma Laura , Daiss Nora , Schulte Lucas-Alexander , Arnold Frank , Usachov Valentyn , Azoitei Ninel , Erkan Mert , Lechel Andre , Brümmendorf Tim H. , Seufferlein Thomas , Kleger Alexander , Tabarés Enrique , Günes Cagatay , Beier Fabian , Sainz Bruno , Hermann Patrick C.
Published: November 2020

To date, it is still unclear how cancer stem cells (CSCs) regulate their stemness properties, and to what extent they share common features with normal stem cells. Telomerase regulation is a key factor in stem cell maintenance. In this study, we investigate how telomerase regulation affects cancer stem cell biology in pancreatic ductal adenocarcinoma (PDAC), and delineate the mechanisms by which telomerase activity and CSC properties are linked. Using primary patient-derived pancreatic cancer cells, we show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using geneticTERT-knockdown or pharmacological inhibitor (BIBR1532) resulted in CSC marker depletionin vitro, and reduced tumorigenicityin vivo. Furthermore, we identify a positive feedback loop between stemness factors (KLF4, SOX2, OCT3/4, NANOG) and telomerase, which is essential for the self-renewal of pancreatic CSCs. Disruption the balance between telomerase activity and stemness factors, eliminates CSCs via induction of DNA damage and apoptosis, opening future perspectives to avoid CSC driven therapy resistance and tumor relapse in PDAC patients.
Identification of Cross-Reactive CD8+T Cell Receptors with High Functional Avidity to a SARS-CoV-2 Immunodominant Epitope and Its Natural Mutant Variants
Authors: Hu Chao , Shen Meiying , Han Xiaojian , Chen Qian , Li Luo , Chen Siyin , Zhang Jing , Gao Fengxia , Wang Wang , Wang Yingming , Li Tingting , Li Shenglong , Huang Jingjing , Wang Jianwei , Zhu Ju , Chen Dan , Wu Qingchen , Tao Kun , Pang Da , Jin Aishun
Published: November 2020

Despite the growing knowledge of T cell responses and their epitopes in COVID-19 patients, there is a lack of detailed characterizations for T cell-antigen interactions and T cell functions. Using a peptide library predicted with HLA class I-restriction, specific CD8+T cell responses were identified in over 75% of COVID-19 convalescent patients. Among the 15 SARS-CoV-2 epitopes identified from the S and N proteins, N361-369(KTFPPTEPK) was the most dominant epitope. Importantly, we discovered 2 N361-369-specific T cell receptors (TCRs) with high functional avidity, and they exhibited complementary cross-reactivity to reported N361-369mutant variants. In dendritic cells (DCs) and the lung organoid model, we found that the N361-369epitope could be processed and endogenously presented to elicit the activation and cytotoxicity of CD8+T cellsex vivo. Our study evidenced potential mechanisms of cellular immunity to SARS-CoV-2, illuminating natural ways of viral clearance with high relevancy in the vaccine development.
Proprioception Has Limited Influence on Tactile Reference Frame Selection
Authors: Yizhar Or , Buchs Galit , Heimler Benedetta , Friedman Doron , Amedi Amir
Published: November 2020

Perceiving the spatial location and physical dimensions of objects that we touch is crucial for goal-directed actions. To achieve this, our brain transforms skin-based coordinates into a reference frame by integrating visual and proprioceptive cues, a process known as tactile remapping. In the current study, we examine the role of proprioception in the remapping process when information from the more dominant visual modality is withheld. We developed a new visual-to-touch sensory substitution device and asked participants to perform a spatial localization task in three different arm postures that included posture switches between blocks of trials. We observed that in the absence of visual information novel proprioceptive inputs can be overridden after switching postures. This behavior demonstrates effective top-down modulations of proprioception and points to the unequal contribution of different sensory modalities to tactile remapping.
Statistical Physics of DNA melting: Unveiling the artificial corrections for self-complementary sequences
Authors: Plata C. A. , Marni S. , Maritan A. , Bellini T. , Suweis S.
Published: November 2020

DNA hybridization is at the heart of countless biological and biotechnological processes. Its theoretical modeling played a crucial role, since it has enabled extracting the relevant thermodynamic parameters from systematic measurements of DNA melting curves. However, in its current state, hybridization modelling requires introducing an extra entropic contribution in self-complementary sequences that lacks any biophysical meaning. In this article, we propose a framework based on statistical physics to describe DNA hybridization and melting in an arbitrary mixture of DNA strands. In particular, we are able to analytically derive closed expressions of the system partition functions for any numberNof strings, and explicitly calculate them in two paradigmatic situations: (i) a system made of self-complementary sequences and (ii) a system comprising two mutually complementary sequences. We derive the melting curve in the thermodynamic limit (N→ ∞) of our description, which differs from the expression commonly used to evaluate the melting of self-complementary systems in that it does not require correcting terms. We provide a thorough study comprising limit cases and alternative approaches showing how our framework can give a comprehensive view of hybridization and melting phenomena.

SIGNIFICANCE

In this study, we provide a transparent derivation of the melting curves of DNA duplexes using basic tools of statistical mechanics. We find that in the case of self-complementary sequences, our expression differs from the one used in literature, which is generally amended by the introduction of a phenomenological correction which in our approach becomes unnecessary. By offering a clean formal description of DNA hybridization, our approach sharpens our understanding of DNA interactions and opens the way to study the pairing of DNA oligomers away from any thermodynamic limit.
Machine learning enabled phenotyping for GWAS and TWAS of WUE traits in 869 field-grown sorghum accessions
Authors: Ferguson John N. , Fernandes Samuel B. , Monier Brandon , Miller Nathan D. , Allan Dylan , Dmitrieva Anna , Schmuker Peter , Lozano Roberto , Valluru Ravi , Buckler Edward S. , Gore Michael A. , Brown Patrick J. , Spalding Edgar P. , Leakey Andrew D.B.
Published: November 2020

Sorghum is a model C4 crop made experimentally tractable by extensive genomic and genetic resources. Biomass sorghum is also studied as a feedstock for biofuel and forage. Mechanistic modelling suggests that reducing stomatal conductance (gs) could improve sorghum intrinsic water use efficiency (iWUE) and biomass production. Phenotyping for discovery of genotype to phenotype associations remain bottlenecks in efforts to understand the mechanistic basis for natural variation ingsandiWUE. This study addressed multiple methodological limitations. Optical tomography and a novel machine learning tool were combined to measure stomatal density (SD). This was combined with rapid measurements of leaf photosynthetic gas exchange and specific leaf area (SLA). These traits were then the subject of genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) across 869 field-grown biomass sorghum accessions. SD was correlated with plant height and biomass production. Plasticity in SD and SLA were interrelated with each other, and productivity, across wet versus dry growing seasons. Moderate-to-high heritability of traits studied across the large mapping population supported identification of associations between DNA sequence variation, or RNA transcript abundance, and trait variation. 394 unique genes underpinning variation in WUE-related traits are described with higher confidence because they were identified in multiple independent tests. This list was enriched in genes whose orthologs in Arabidopsis have functions related to stomatal or leaf development and leaf gas exchange. These advances in methodology and knowledge will aid efforts to improve the WUE of C4 crops.