bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Demographic Characteristics of COVID-19 Patients Admitted in a Tertiary Care Hospital in the Dominican Republic
Authors: De Luna David , Roque Yori , Batlle Nicolás , Gómez Katherine , Jáquez Miguelina , Cabrera Brinia , de la Cruz Lissa , Tavárez Osvaldo , Belliard Rossy , Sanchez José Javier
Published: December 2020

To present clinical and demographic characteristics of COVID-19 patients admitted to Hospital Metropolitano de Santiago in Dominican Republic, we analyzed electronic medical records of all hospitalized patients clinically admitted as viral pneumonia through March - April, 2020. Of 374 patients, 150 (40.1%) laboratory confirmed, were included in this study. Most of the patients were men (104 / 69.3%) with a median (IQR 44 - 66) age of 54. Hypertension (83 / 55.3%) and diabetes mellitus (49 / 32.7%) were the most common comorbidities, whereas fever (120 / 80%), cough (79 / 52.7%) and fatigue (60 / 40%) were the most common presenting symptoms. 28 (18.7%) patients required admission to the intensive care unit, of them, 26 patients (17.3%) required mechanical ventilation. The overall mortality rate was 10.7% Higher levels of inflammatory markers were associated with longer length of stay (LOS). This findings indulge information that could contribute to stratify patients at higher risk of complications.
Associations of reading skills and properties of cerebral white matter pathways in 8-year-old children born preterm
Authors: Dubner Sarah E , Ben-Shachar Michal , Mezer Aviv , Feldman Heidi M , Travis Katherine E
Published: December 2020

AIM

Children born preterm (PT) experience perinatal white matter injury and later reading deficits at school age. We used two complementary neuroimaging modalities to determine if reading skills would be associated with contemporaneous white matter properties in school-aged PT children.

METHOD

In 8-year-old PT children (N=29), we measured diffusivity (fractional anisotropy, FA), from diffusion MRI, and myelin content (relaxation rate, R1) from quantitative relaxometry. We assessed reading (Gray’s Oral Reading Test, Fifth Edition) in each child. Whole-brain deterministic tractography coupled with automatic segmentation and quantification were applied to extract FA and R1 along four tracts and assess their statistical association with reading scores.

RESULTS

Reading-FA correlations were not significant along the four analyzed tracts. Reading-R1 correlations were significantly positive in portions of the left superior longitudinal fasciculus, right uncinate fasciculus, and left inferior longitudinal fasciculus. FA positively correlated with R1 in limited areas of reading-R1 associations, but did not contribute to the variance in reading scores.

INTERPRETATION

Combining complementary neuroimaging approaches identified relations between reading and white matter properties not found using a single MRI measure. Associations of reading skills and white matter properties may vary across white matter tracts and metrics in PT children.

What this paper adds

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Preterm children’s reading was associated with white matter myelin content.

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Preterm children’s reading was not associated with white matter diffusivity.
Reduction in antibiotic prescribing attainable with a gonococcal vaccine
Authors: Kissler Stephen M. , Mitchell Moriah , Grad Yonatan H.
Published: December 2020

We estimated the fraction of antibiotic prescribing in the US attributable to gonorrhea. Gonorrhea contributes to an outsized proportion of antibiotic prescriptions in young adults, males, and in the southern and western US. A gonococcal vaccine could substantially reduce antibiotic prescribing in these populations.
International Randomized Controlled Trial Evaluating Changes in Oral Health in Smokers after Switching to Combustion-Free Nicotine Delivery Systems: SMILE Study protocol
Authors: Conte Gianluca , Pacino Sebastiano Antonio , Urso Salvatore , Caponnetto Pasquale , Benfatto Francesca , Greiling Doris , Pedullà Eugenio , Generali Luigi , Consolo Ugo , Checchi Vittorio , Kowalski Jan , Nowak Maciej , Górska Renata , Amaliya Amaliya , Chapple Iain , Milward Mike , Maclure Robert , Polosa Riccardo
Published: December 2020

Although the well-known detrimental effects of conventional cigarette smoking on oral health, there are still lack of evidences about the impact of less harmful alternatives (such as electronic cigarettes or heat not burn products), especially in young smokers with clinical absence of signs of periodontitis.

SMILE will be a prospective, multicenter, interventional, open label, randomized, controlled, three parallel-arms study assessing oral health parameters and teeth appearance of 18 months duration.

This study aims to compare short- and long-term impact on oral health between smokers continuing with conventional cigarette smoking, those switching to combustion-free nicotine delivery systems (C-F NDS), and never-smokers by objectively evaluating changes in gingival response, as a proxy for periodontal/gingival.

The total number of participants in the study planned of the trial is 606 (505 regular smokers and 101 never-smokers).

Regular smokers not intending to quit will be randomized in the ratio 1:4 either in continuing to smoke commercially manufactured conventional cigarettes (n = 101; Study Arm A) or switching to C-F NDS (n = 404; Study Arm B), never-smokers will be assigned in Arm C (n= 101).

The primary outcome will be to assess and compare the percentage mean change in Modified Gingival Index (MGI) score between Baseline and 18 months follow-up between the Study Arms A and B.

Secondary outcomes include the assessment of within- and between-group (Arm A, Arm B and Arm C) variations from baseline to 18 months follow-up of several endpoints, such as MGI, Tooth Stains Assessment, Dental Discolorations, Plaque Score Imaging, Oral Health Quality of Life (OHQOL) assessment and EuroQoL Visual Analog Scale (EQ VAS – QoL) assessment.

Patient recruitment will start in January 2021 and enrolment is expected to be completed by June 2021.

This will be the first study determining overall oral health impact of using CF-NDS in smokers without sign of periodontitis. Data from this study will provide valuable insights into the overall potential of C-F NDS to reduce the risk of periodontal diseases.
Burden of intestinal parasitic infections in children and its association with hand washing practice in Ethiopia: a systematic review and meta-analysis
Authors: Wagnew Fasil , Tadesse Aster , Abajobir Amanuel
Published: December 2020

Background

Intestinal parasitic infections (IPIs) are a major public health challenges in developing countries including Ethiopia, although few studies previously estimated the magnitude of IPIs and associated factors in the country. Reports from these scarce studies were also widely varied and remained inconsistent. This study thus aimed to synthesize the pooled magnitude of IPIs and factors affecting it.

Methods

Internationally broad based medical database including MEDLINE/PubMed, EMBASE, PsychINFO and Web of Science, and Google Scholar for grey literature were exhaustively searched usinga prioriset criteria to identify studies estimating the prevalence of IPIs among children from 2000-2018. PRISMA guideline was used to systematically review and meta-analyze these studies. Details of study characteristics including sample size, magnitude of effect sizes (including odds ratios (ORs)) and standard errors were extracted. Random-effects model was used to calculate pooled estimates in Stata/se version-14. I2and meta-bias statistics assessed heterogeneity and Egger’s test for publication bias. Sub-group analyses were also carried out based on age of children and regions.

Results

Forty-three studies were included in the final analysis (N = 20,008 children). The overall prevalence of IPIs, with one or more species, was 48.2% (95% CI: 40.1, 56.3) in Ethiopian children. Based on sub-group analyses, the highest prevalence of IPIs was observed among school-age children (52.4% (95% CI, 41.3, 63.5)) and in Amhara regional state (52.1% (95% CI, 37.3-66.8)). The odds of having IPIs was nearly six times higher in children who were not practicing hand washing as compared to their counterparts (pooled OR = 5.6 (95% CI: 3.4,9.3). Funnel plot analysis and Egger’s test detected no publication bias.

Conclusion

On aggregate, the pooled prevalence of IPIs among Ethiopian children is significantly high. Not hand washing before eating was a risk factor for IPIs. The establishment of applicable sanitation services and health education will help reduce the magnitude of IPIs and promote a healthier childhood.
Vaccines that prevent SARS-CoV-2 transmission may prevent or dampen a spring wave of COVID-19 cases and deaths in 2021
Authors: Swan David A. , Goyal Ashish , Bracis Chloe , Moore Mia , Krantz Elizabeth , Brown Elizabeth , Cardozo-Ojeda Fabian , Reeves Daniel B , Gao Fei , Gilbert Peter B. , Corey Lawrence , Cohen Myron S. , Janes Holly , Dimitrov Dobromir , Schiffer Joshua T.
Published: December 2020

Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VEDIS), the ability of a vaccine to block symptomatic COVID-19. They will only partially discriminate whether VEDISis mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VESUSC), or by preventing symptoms despite breakthrough infection (vaccine efficacy against symptoms or VESYMP). Vaccine efficacy against infectiousness (VEINF), defined as the decrease in secondary transmissions from infected vaccine recipients versus from infected placebo recipients, is also not being measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna and Pfizer vaccines, which have observed VEDIS>90%, mediate VEDISpredominately by complete protection against infection, then prevention of a fourth epidemic wave in the spring of 2021, and associated reduction of subsequent cases and deaths by 60%, is likely to occur assuming rapid enough vaccine roll out. If high VEDISis explained primarily by reduction in symptoms, then VEINF>50% will be necessary to prevent or limit the extent of this fourth epidemic wave. The potential added benefits of high VEINFwould be evident regardless of vaccine allocation strategy and would be enhanced if vaccine roll out rate is low or if available vaccines demonstrate waning immunity. Finally, we demonstrate that a 1.0 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve VEINF=60% and that human challenge studies with 104 infected participants, or clinical trials in a university student population could estimate VESUSC, VESYMPand VEINFusing viral load metrics.
Using Mobility Data to Understand and Forecast COVID19 Dynamics
Authors: Wang Lijing , Ben Xue , Adiga Aniruddha , Sadilek Adam , Tendulkar Ashish , Venkatramanan Srinivasan , Vullikanti Anil , Aggarwal Gaurav , Talekar Alok , Chen Jiangzhuo , Lewis Bryan Leroy , Swarup Samarth , Kapoor Amol , Tambe Milind , Marathe Madhav
Published: December 2020

Disease dynamics, human mobility, and public policies co-evolve during a pandemic such as COVID-19. Understanding dynamic human mobility changes and spatial interaction patterns are crucial for understanding and forecasting COVID-19 dynamics. We introduce a novel graph-based neural network(GNN) to incorporate global aggregated mobility flows for a better understanding of the impact of human mobility on COVID-19 dynamics as well as better forecasting of disease dynamics.
We propose a recurrent message passing graph neural network that embeds spatio-temporal disease dynamics and human mobility dynamics for daily state-level new confirmed cases forecasting. This work represents one of the early papers on the use of GNNs to forecast COVID-19 incidence dynamics and our methods are competitive to existing methods. We show that the spatial and temporal dynamic mobility graph leveraged by the graph neural network enables better long-term forecasting performance compared to baselines.
Diarrhea, Helminth Infection, Dehydration, and Malnutrition Associated with Water, Sanitation, and Hygiene Facilities and Poor Handwashing in Schools in Metro Manila, Philippines: A Cross-Sectional Study
Authors: Sangalang Stephanie O. , Prado Nelissa O. , Lemence Allen Lemuel G. , Cayetano Mylene G. , Lu Jinky Leilanie DP. , Valencia John Cedrick , Kistemann Thomas , Borgemeister Christian
Published: December 2020

Diarrhea, soil-transmitted helminth (STH) infection, and malnutrition threaten the lives of millions of children globally but particularly in the Global South, where inadequate water, sanitation, and hygiene (WaSH) drive disease risk. The aim of our study was to identify environmental and behavioral risk factors of these diseases among schoolchildren in Metro Manila, Philippines. We analyzed data from a multistage cluster sample of grade 5-10 students to investigate WaSH facilities and hygiene practices. Outcomes were self-reported diarrhea and STH infection and observed malnutrition (stunting, undernutrition, over-nutrition); we used logistic regression models to explore correlates. We included 1,558 students from 15 schools in 3 cities. Over 14% (212) of students experienced diarrhea only, 29.7% (438) experienced STH infection only, and 14% (207) experienced both diarrhea and STH infection. Over 15% (227) of students were stunted, ∼6% (87) were undernourished, and 21% (306) were over-nourished. While diarrhea was associated with poor handwashing, avoiding school restrooms, and lack of a restroom cleaning policy, STH infection was associated with students’ dissatisfaction with school restrooms. Risk of having both diarrhea and STH infection increased when school restrooms lacked water or were unclean. Being only stunted was associated with diarrhea, while being both stunted and undernourished was associated with STH infection. These findings demonstrate that adequate water supply and cleanliness of school WaSH facilities must be achieved and maintained to prevent disease. Future school-based WaSH interventions are recommended to provide clean WaSH facilities that have water, promote handwashing, and discourage avoidance of school toilets.
Association of Mortality and Aspirin Prescription for COVID-19 Patients at the Veterans Health Administration
Authors: Osborne Thomas F , Veigulis Zachary P , Arreola David M , Mahajan Satish , Röösli Eliane , Curtin Catherine M
Published: December 2020

There is growing evidence that thrombotic and inflammatory pathways contribute to the severity of COVID-19. Common medications such as aspirin, that mitigate these pathways, may decrease COVID-19 mortality. This assessment was designed to quantify the correlation between aspirin and mortality for COVID-19 positive patients in our care. Data from the Veterans Health Administration national electronic health record database was utilized for the evaluation. Veterans from across the country with a first positive COVID-19 polymerase chain reaction lab result were included in the evaluation which comprised 28,350 patients from March 2, 2020 to September 13, 2020 for the 14-day mortality cohort and 26,346 patients from March 2, 2020 to August 28, 2020 for the 30-day mortality cohort. Patients were matched via propensity scores and the odds of mortality were then compared. Among COVID-19 positive Veterans, preexisting aspirin prescription was associated with a statistically and clinically significant decrease in overall mortality at 14-days (OR 0.38, 95% CI 0.32-0.46) and at 30-days (OR 0.38, 95% CI 0.33-0.45), cutting the odds of mortality by more than half. Findings demonstrated that pre-diagnosis aspirin prescription was strongly associated with decreased mortality rates for Veterans diagnosed with COVID-19. Prospective evaluation is required to more completely assess this correlation and its implications for patient care.
Association Between Sampling Method and Covid-19 Test Positivity Among Undergraduate Students: Testing Friendship Paradox in Covid-19 Network of Transmission
Authors: Kianersi Sina , Ahn Yong-Yeol , Rosenberg Molly
Published: December 2020

In November 2020, we conducted a cross sectional study to implement and test the method of acquaintance sampling (randomly sampling friends of randomly sampled individuals) in detecting students with higher probability of COVID-19 positivity. Overall, 879 students were randomly sampled and participated in this study. In an online survey, the randomly sampled participants nominated a friend, and reported their own and their nominated friend's COVID-19 status. Nominated friends were about 1.64 (95% CI: 1.33, 2.00) times more likely to have ever been infected with COVID-19, compared to randomly sampled students. Our study corroborates the effectiveness of acquaintance sampling for identifying members of networks with higher COVID-19 risk. These findings could be useful for university policy makers when developing mitigation testing programs and intervention strategies against COVID-19 spread.
Investigating mental and physical disorders associated with COVID-19 in online health forums
Authors: Patel Rashmi , Smeraldi Fabrizio , Abdollahyan Maryam , Irving Jessica , Bessant Conrad
Published: December 2020

Objectives: Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users.

Setting and design: We obtained data from 739,434 posts by 53,134 unique users of three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1st January 2020 to 31st May 2020. Using NLP, we analysed the content of posts related to COVID-19.

Primary outcome measures:
(i) Proportion of forum posts containing COVID-19 keywords
(ii) Proportion of forum users making their very first post about COVID-19
(iii) Number of COVID-19 related posts containing content related to physical and mental health comorbidities

Results: Posts discussing COVID-19 and related comorbid disorders spiked in early- to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health.

Conclusions: We demonstrate it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.
Interpreting Mendelian randomization estimates of the effects of categorical exposures such as disease status and educational attainment
Authors: Howe Laurence J , Tudball Matthew , Smith George Davey , Davies Neil M
Published: December 2020

Mendelian randomization has been previously used to estimate the effects of binary and ordinal categorical exposures - e.g. type 2 diabetes or educational attainment defined by qualification - on outcomes. Binary and categorical phenotypes can be modelled in terms of liability, an underlying latent continuous variable with liability thresholds separating individuals into categories. Genetic variants typically influence an individual’s categorical exposure via their effects on liability, thus Mendelian randomization analyses with categorical exposures will capture effects of liability which act independent of exposure category.

We discuss how groups where the categorical exposure is invariant can be used to detect liability effects acting independently of exposure category. For example, associations between an adult educational attainment polygenic score (PGS) and BMI measured before the minimum school leaving age (e.g. age 10), cannot indicate the effects of years in full-time education on this outcome. Using UK Biobank data, we show that a higher education PGS is strongly associated with lower smoking initiation and higher glasses use at age 15. These associations were replicated in sibling models. An orthogonal approach using the raising of the school leaving age (ROSLA) policy change found that individuals who chose to remain in education to age 16 before the reform likely had higher liability to educational attainment than those who were compelled to remain in education to 16 after the reform, and had higher income, decreased cigarette smoking, higher glasses use and lower deprivation in adulthood. These results suggest that liability to educational attainment associates with health and social outcomes independent of years in full-time education.

Mendelian randomization studies with non-continuous exposures should be interpreted in terms of liability, which may affect the outcome via changes in exposure category and/or independently.
Intuitive Graphical Visualization of Transcriptomes by Nonlinear Dimensionality Reduction Exposes Relatedness between Human Placenta Tissues
Authors: Yajun Liu , Yi Zhang , Cui Jinquan
Published: December 2020

The establishment of a complex multi-scale model of biological tissue is of great significance for the study of related diseases, and the integration of relevant quantitative data is the premise to achieve this goal. Whereas, the systematic collation of data sets related to placental tissue is relatively lacking. In this study, 18 published transcriptomes (a total of 425 samples) datasets of human pregnancy-related tissues (including chorionic villus and decidua, term placenta, endometrium, in vitro cell lines, etc.) from public databases were collected and analyzed. We compared the most widely used dimensionality reduction (DR) methods to generate a 2D-map for visualization of these data. We also compared the effects of different parameter settings and commonly used manifold learning methods on the results. The result indicates that the nonlinear method can better preserve the small differences between different subtypes of placental tissue than linear method. It led the foundation for the study on accurate computational modeling of placental tissue development in the future. The datasets and analysis provide a useful source for the researchers in the field of the maternal-fetal interface and the establishment of pregnancy.
A gene regulatory network critical for axillary bud dormancy directly controlled by Arabidopsis BRANCHED1
Authors: van Es Sam W. , Muñoz-Gasca Aitor , Romero-Campero Francisco J. , González-Grandío Eduardo , de los Reyes Pedro , Tarancón Carlos , van Dijk Aalt D.J. , van Esse Wilma , Angenent Gerco C. , Immink Richard , Cubas Pilar
Published: December 2020

The control of branch outgrowth is critical for plant fitness, stress resilience and crop yield. The Arabidopsis thaliana transcription factor BRANCHED1 (BRC1) plays a pivotal role in this process as it integrates signals that inhibit axillary bud growth to control shoot branching. Despite the remarkable activity of BRC1 as a potent growth inhibitor, the mechanisms by which it promotes and maintains bud dormancy are still largely unknown.

Here we combine ChIP-seq, transcriptomic and systems biology approaches to characterise the BRC1-regulated gene network. We identify a group of BRC1 direct target genes encoding transcription factors (BTFs) that orchestrate, together with BRC1, an intricate transcriptional network enriched in abscisic acid signalling components. The BRC1 network is enriched in feed-forward loops and feed-back loops, robust against noise and mutation, reversible in response to stimuli, and stable once established. This knowledge is fundamental to adapt plant architecture and crop production to ever-changing environmental conditions.
Genomic surveillance framework and global population structure forKlebsiella pneumoniae
Authors: Lam Margaret M. C. , Wick Ryan R. , Watts Stephen C. , Cerdeira Louise T. , Wyres Kelly L. , Holt Kathryn E.
Published: December 2020

K. pneumoniaeis a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation ofK. pneumoniaegenome data. Here we introduce Kleborate, a tool for analysing genomes ofK. pneumoniaeand its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly availableKlebsiellagenomes, including clinical isolates from a pan-European study of carbapenemase-producingKlebsiella, highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and typeK. pneumoniaefrom gut metagenomes.
Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain
Authors: Playfoot Christopher J. , Duc Julien , Sheppard Shaoline , Dind Sagane , Coudray Alexandre , Planet Evarist , Trono Didier
Published: December 2020

Transposable elements (TEs) constitute 50% of the human genome and many have been co-opted throughout human evolution due to gain of advantageous regulatory functions controlling gene expression networks. Several lines of evidence suggest these networks can be fine-tuned by the largest family of TE controllers, the KRAB-containing zinc finger proteins (KZFPs). One tissue permissive for TE transcriptional activation (termed ‘transposcription’) is the adult human brain, however comprehensive studies on the extent of this process and its potential contribution to human brain development are lacking.

In order to elucidate the spatiotemporal transposcriptome of the developing human brain, we have analysed two independent RNA-seq datasets encompassing 16 distinct brain regions from eight weeks post-conception into adulthood. We reveal an anti-correlated, KZFP:TE transcriptional profile defining the late prenatal to early postnatal transition, and the spatiotemporal and cell type specific activation of TE-derived alternative promoters driving the expression of neurogenesis-associated genes. We also demonstrate experimentally that a co-opted antisense L2 element drives temporal protein re-localisation away from the endoplasmic reticulum, suggestive of novel TE dependent protein function in primate evolution. This work highlights the widespread dynamic nature of the spatiotemporal KZFP:TE transcriptome and its potential importance throughout neurotypical human brain development.
Deep learning classification of canine behavior using a single collar-mounted accelerometer: Real-world validation
Authors: Chambers Robert D. , Yoder Nathanael C. , Carson Aletha B. , Junge Christian , Allen David E. , Prescott Laura M. , Bradley Sophie , Wymore Garrett , Lloyd Kevin , Lyle Scott
Published: December 2020

Collar-mounted canine activity monitors can use accelerometer data to estimate dog activity levels, step counts, and distance traveled. With recent advances in machine learning and embedded computing, much more nuanced and accurate behavior classification has become possible, giving these affordable consumer devices the potential to improve the efficiency and effectiveness of pet healthcare. Here we describe a novel deep learning algorithm that classifies dog behavior at sub-second resolution using commercial pet activity monitors. We built machine learning training databases from over 5,000 videos of over 2,500 dogs and ran the algorithms in production on over 11 million days of device data. We then surveyed project participants representing 10,550 dogs, they provided us 163,110 event responses to validate real-world detection of eating and drinking behavior. The resultant algorithm displayed a sensitivity and specificity for detecting drinking behavior (0.949 and 0.999, respectively) and eating behavior (0.988, 0.983). We also demonstrated detection of licking, petting, rubbing, scratching, and sniffing. We show that the devices’ position on the collar has no measurable impact on performance. In production, users reported a true positive rate of 95.3% for eating (among 1,514 users), and of 94.9% (among 1,491 users) for drinking. The study demonstrates the accurate detection of important health-related canine behaviors using a collar-mounted accelerometer. We trained and validated our algorithms on a large and realistic training dataset, and we assessed and confirmed accuracy in production via user validation.
A high-throughput metabolic microarray assay reveals antibacterial effects of black and red raspberries and blackberries againstHelicobacter pyloriinfection
Authors: Goodman Candace , Lyon Katrina , Scotto Aitana , Roe Mandi M. , Moghimpour Farimah , Sebrell T. Andrew , Gentry Andrew B. , Bala Ganesh , Stoner Gary , Bimczok Diane
Published: December 2020

Helicobacter pyloriis an important bacterial pathogen that causes chronic infection of the human stomach, leading to gastritis, peptic ulcer disease and gastric cancer. Treatment with appropriate antibiotics can eliminateH. pyloriinfection and reduce the risk for severe disease outcomes. However, sinceH. pyloriis becoming increasingly resistant to standard antibiotic regimens, novel treatment strategies are needed. Previous studies have demonstrated that black and red berries may have antibacterial properties. Therefore, we analyzed organic extracts and powders from black and red raspberries and blackberries and determined their antibacterial effects on multipleH. pyloristrains. We used high-performance liquid chromatography to measure berry anthocyanins, which are considered the major active ingredients. To monitor antibiotic effects of the berry preparations onH. pylori, we developed a high-throughput metabolic growth assay based on the OmniLog™ system. All berry preparations tested had significant bactericidal effectsin vitro, with MIC90values ranging from 0.49 to 4.17%. We next used human gastric epithelial organoids to evaluate biocompatibility of the berry preparations and showed that black raspberry extract, which had the strongest antimicrobial activity, was non-toxic at the concentration required for complete bacterial growth inhibition. To determine whether dietary black raspberry application could eliminateH. pyloriinfectionin vivo, mice were infected withH. pyloriand then were placed on a diet containing 10% black raspberry powder. However, this treatment did not significantly impact bacterial infection rates or gastric pathology. In summary, our data indicate that black and red raspberry and blackberry products have potential applications in the treatment and prevention ofH. pyloriinfection, because of their antibacterial effects and good biocompatibility. However, delivery and formulation of berry compounds needs to be optimized to achieve significant antibacterial effectsin vivo.
Exposure to Renin-Angiotensin System Inhibitors Is Associated with Reduced Mortality of Older Hypertensive Covid-19 Patients
Authors: Gori Mauro , Berzuini Carlo , D’Elia Emilia , Ghirardi Arianna , Bernardinelli Luisa , Gavazzi Antonello , Balestrieri Giulio , Giammarresi Andrea , Trevisan Roberto , Di Marco Fabiano , Bellasi Antonio , Amoroso Mariangela , Raimondi Federico , Novelli Luca , Magro Bianca , Mangia Gianpaolo , Lorini Ferdinando L. , Guagliumi Giulio , Fagiuoli Stefano , Parati Gianfranco , Senni Michele
Published: December 2020

From a cohort of 1352 consecutive patients admitted with coronavirus disease (Covid-19) to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied 688 patients with arterial hypertension (254 deaths) to assess whether use of renin-angiotensin system inhibitors (RASIs) prior to hospital admission affects mortality from Covid-19. Prior use of RASIs was associated with a lower mortality in the over-68 group of patients, whereas no evidence of a similar effect (whether protective or adverse) was found in the younger group. There was positive relative excess due to a statistically significant (p =0.001) interaction between prior RASI exposure and an age greater than 68 years, corresponding to a positive relative excess risk. Next we used the subgroup of 411 hypertensive patients older than 68 yrs to separately assess the effects prior use of two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs) and angiogiotensin receptor blockers (ARBs), by comparing these two exposures with no exposure to RASIs. We found both prior use of ACEIs and prior use of ARBs to be associated with a lower Covid-19 mortality, after adjusting for 32 medical history variables via propensity score matching. (ORACEI = 0.57, 95%CI 0.36 to 0.91, p =0.018) (ORARB = 0.49, 95%CI 0.29 to 0.82, p =0.006).
A deep convolutional neural network-based algorithm for muscle biopsy diagnosis outperforms human specialists
Authors: Kabeya Yoshinori , Okubo Mariko , Yonezawa Sho , Nakano Hiroki , Inoue Michio , Ogasawara Masashi , Saito Yoshihiko , Tanboon Jantima , Indrawati Luh Ari , Kumutpongpanich Theerawat , Chen Yen-Lin , Yoshioka Wakako , Hayashi Shinichiro , Iwamori Toshiya , Takeuchi Yusuke , Tokumasu Reitaro , Takano Atsushi , Matsuda Fumihiko , Nishino Ichizo
Published: December 2020

Histopathologic evaluation is essential for categorizing and studying neuromuscular disorders. However, experienced specialists and pathologists are limited, especially in underserved areas. Although new technologies, such as artificial intelligence, are expected to improve medical reach, their use in rare diseases is challenging because of the limited availability of training datasets. To address this knowledge gap, we developed an algorithm based on deep convolutional neural networks that used data from microscopic images of hematoxylin-and-eosin-stained pathology slides. Our algorithm differentiated idiopathic inflammatory myopathies (mostly treatable) from hereditary muscle diseases (mostly non-treatable) and achieved better sensitivity and specificity than real physicians' diagnoses. Furthermore, it successfully and accurately classified four subtypes of the abovementioned muscular conditions. These results suggest that our algorithm can be safely used in a clinical setting. We established the similarity between the algorithm's and physicians' predictions using visualization technology, and clarified the validity of the predictions.
Quantifying the importance and location of SARS-CoV-2 transmission events in large metropolitan areas
Authors: Aleta Alberto , Martín-Corral David , Bakker Michiel A. , y Piontti Ana Pastore , Ajelli Marco , Litvinova Maria , Chinazzi Matteo , Dean Natalie E. , Halloran M. Elizabeth , Longini Ira M. , Pentland Alex , Vespignani Alessandro , Moreno Yamir , Moro Esteban
Published: December 2020

Detailed characterization of SARS-CoV-2 transmission across different settings can help design less disruptive interventions. We used real-time, privacy-enhanced mobility data in the New York City and Seattle metropolitan areas to build a detailed agent-based model of SARS-CoV-2 infection to estimate the where, when, and magnitude of transmission events during the pandemic’s first wave. We estimate that only 18% of individuals produce most infections (80%), with about 10% of events that can be considered super-spreading events (SSEs). Although mass-gatherings present an important risk for SSEs, we estimate that the bulk of transmission occurred in smaller events in settings like workplaces, grocery stores, or food venues. The places most important for transmission change during the pandemic and are different across cities, signaling the large underlying behavioral component underneath them. Our modeling complements case studies and epidemiological data and indicates that real-time tracking of transmission events could help evaluate and define targeted mitigation policies.
Cyclic gallium-68 labeled peptides for specific detection of human angiotensin-converting enzyme 2
Authors: Parker Matthew F. L. , Blecha Joseph , Rosenberg Oren , Ohliger Michael , Flavell Robert R. , Wilson David M.
Published: December 2020

In this study, we developed ACE2-specific, peptide-derived68Ga-labeled radiotracers, motivated by the hypotheses that (1) ACE2 is an important determinant of SARS-CoV-2 susceptibility, and (2) that modulation of ACE2 in COVID-19 drives severe organ injury.

Methods

A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears two cystine residues, both linear and cyclic peptides were studied. An ACE2 inhibition assay was used to identify lead compounds, which were labeled with68Ga to generate peptide radiotracers ([68Ga]NOTA-PEP). The aminocaproate-derived radiotracer [68Ga]NOTA-PEP4 was subsequently studied in a humanized ACE2 (hACE2) transgenic model.

Results

Cyclic DX-600 derived peptides had markedly lower IC50’s than their linear counterparts. The three cyclic peptides with triglycine, aminocaproate, and polyethylene glycol linkers had calculated IC50’s similar to, or lower than the parent DX600 molecule. Peptides were readily labeled with68Ga, and the biodistribution of [68Ga]NOTA-PEP4 was determined in a hACE2 transgenic murine cohort. Pharmacologic concentrations of co-administered NOTA-PEP (“blocking”) showed significant reduction of [68Ga]NOTA-PEP4 signals in the in the heart, liver, lungs, and small intestine.Ex vivohACE2 activity in these organs was confirmed as a correlate toin vivoresults.

Conclusions

NOTA-conjugated, cyclic peptides derived from the known ACE2 inhibitor DX600 retain their activity when N-conjugated for68Ga chelation.In vivostudies in a transgenic hACE2 murine model using the lead tracer [68Ga]NOTA-PEP4 showed specific binding in the heart, liver, lungs and intestine - organs known to be affected in SARS-CoV-2 infection. These results suggest that [68Ga]NOTA-PEP4 could be used to detect organ-specific suppression of ACE2 in SARS-CoV-2 infected murine models and COVID-19 patients.

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For Table of Contents use only
Do Motoneurons’ Discharge Rate Slow With Aging? A Systematic Review And Meta-Analysis
Authors: Orssatto Lucas B. R. , Borg David N. , Pendrith Linda , Blazevich Anthony J. , Shield Anthony J. , Trajano Gabriel S.
Published: December 2020

Nervous system maladaptation is linked to the loss of maximal strength production and motor control with aging. Motor unit discharge rates are a critical determinant of force production; thus, lower discharge rates could be a mechanism underpinning maximal strength and motor control losses during aging. This meta-analysis summarized the findings of studies comparing motor unit discharge rates between young and older adults, and examined the effect of distinct muscles and contraction intensities on the magnitude of discharge rates difference between these two groups. Eligible studies were combined in a meta-analysis, including tested contraction intensities and muscles in different levels, to investigate whether there were differences in discharge rates between younger and older adults. Motor unit discharge rates were higher in younger adults compared to older adults, with a pooled standardized mean difference (SMD) for all studies of 0.63 (95%CI= 0.27 to 0.99). Contraction intensity had a significant effect on the pooled SMD, with a 1% increase in intensity associated with a 0.009 (95%CI= 0.003 to 0.015) change in the pooled SMD. These findings suggest that the reductions in motor unit discharge rates, especially at higher contraction intensities, may be an important mechanism underpinning age-related losses in maximal strength production.
Varia: Prediction, analysis and visualisation of variable genes
Authors: Mackenzie Gavin , Jensen Rasmus W. , Lavstsen Thomas , Otto Thomas D.
Published: December 2020

Assessing the diversity or expression of variable gene families in pathogens can inform about immune escape mechanisms or host interaction phenotypes of clinical relevance. However, obtaining the sequences and quantifying their expression is a challenge. Here, we present a tool, which based on unique sequence tag similarity between members of a gene family, predicts the domains encoded by the queried gene. As an example, we are using thevargene family, encoding the major virulence proteins (PfEMP1) of the human malaria parasite,Plasmodium falciparum. We developed Varia, which predicts the likelyvargene sequence and encoded protein domain composition of a gene from short sequence tags. We provide a new extended annotatedvargenome database, in which Varia identifies genes with identical tag sequences and compares these to return the most probable domain composition of the query gene. Varia’s ability to predict correct PfEMP1 domain compositions from shortvarsequence tags was tested in two complementary pipelines to (a) return the putative gene sequences and domain compositions of the query gene from any partial sequence provided, thereby enabling detailed assessment of specific genes’ putative function and experimental validation of these (b) to accommodate rapid profiling ofvargene expression in complex patient samples, by compiling the overall domain prevalence amongvartranscripts predicted identified and quantified by next generation sequencing of so-calledvarDBLα-sequence tags.

Availability and implementation

Varia is available on GitHub (https://github.com/GCJMacken-zie/Varia) under the MIT license.

Contact

thomasl@sund.ku.dk,thomasdan.otto@glasgow.ac.uk
The 3'tsRNAs are aminoacylated: Implications for their biogenesis
Authors: Liu Ziwei , Kim Hak kyun , Xu Jianpeng , Kay Mark A.
Published: December 2020

Emerging evidence indicates that tRNA-derived small RNAs (tsRNAs) are involved in fine-tuning gene expression and become dysregulated in various cancers. We recently showed that the 22nt LeuCAG tsRNA from 3’ end of tRNALeuis required for efficient translation of a ribosomal protein mRNA and ribosome biogenesis. Inactivation of this tsRNA induced apoptosis in rapidly dividing cells and suppressed the growth of a patient derived orthotopic hepatocellular carcinoma in mice. The mechanism involved in the generation of the 3’-tsRNAs remains elusive and it is unclear if the 3’-ends of 3’-tsRNAs are aminoacylated. Here we report an enzymatic method utilizing exonuclease T to determine the 3’charging status of tRNAs and tsRNAs. Our results showed that the LeuCAG 3’-tsRNA is fully charged and originated solely from charged mature tRNA. When the leucyl-tRNA synthetase was knocked down, less tsRNA was generated while the mature tRNA was not reduced further supporting that tsRNA generation is regulated. The fact that the 3’-tsRNA is aminoacylated has implications for their biogenesis and provides additional insights into their biological role in post-transcriptional gene regulation.
Endothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys
Authors: Srivastava Swayam Prakash , Li Jinpeng , Takagaki Yuta , Kitada Munehiro , Goodwin Julie , Kanasaki Keizo , Koya Daisuke
Published: December 2020

Defects in endothelial cells cause deterioration in kidney function and structure. Here, we found that endothelial SIRT3 regulates metabolic reprogramming and fibrogenesis in the kidneys of diabetic mice. By analyzing, gain-of-function of the SIRT3 gene by overexpression in a fibrotic mouse strain conferred disease resistance against diabetic kidney fibrosis; while its loss-of-function in endothelial cells exacerbated the levels of diabetic kidney fibrosis. Regulation of endothelial cell SIRT3 on fibrogenic processes was due to tight control over the defective central metabolism and linked-activation of endothelial-to-mesenchymal transition (EndMT). SIRT3 deficiency in endothelial cells stimulated the TGFβ/Smad3-depandent mesenchymal transformations in renal tubular epithelial cells. These data demonstrate that SIRT3 regulates defective metabolism and EndMT-mediated activation of the fibrogenic pathways in the diabetic kidneys. Together, our findings show that endothelial cell SIRT3 is a fundamental regulator of defective metabolism regulating health and disease processes in the kidney.

Context and significance

The present study describes that endothelial cell SIRT3 protects against renal fibrosis by mitigating the metabolic reprogramming and associated mesenchymal transformations in diabetes. Accordingly, amelioration of endothelial cell SIRT3 and targeting the defective metabolism offer a potential therapeutic approach to treat or prevent the progression of diabetic kidney disease. Further investigation would delineate the mechanisms of SIRT3 up-regulation in diabetic kidney disease and discover small molecules to increase the expression of the SIRT3. In addition, this study describes the biology of SIRT3 in the health and disease processes of kidney endothelial cells.
Co-option of a seed-like proteome by oil-rich tubers
Authors: Niemeyer Philipp William , Schmitt Kerstin , Valerius Oliver , Braus Gerhard H. , deVries Jan , Carlsson Anders Sven , Hofvander Per , Ischebeck Till
Published: December 2020

Co-option is an important aspect of evolution that can occur on several levels. Genes, whose function was molded by selection in the evolutionary past, are readily observed to serve a new function when acting in a different context in an extant system. Whole organs can be co-opted for new roles as well. For example, roots that evolved from shoot-like axes. Finally a framework of genes and its coded proteins can be co-opted to serve a similar molecular function but in a completely different organ, drastically changing its properties. Here, we describe such an example, where a set of proteins important for desiccation tolerance and oil accumulation in seeds of most angiosperms was co-opted in the tubers of yellow nutsedge (Cyperus esculentus). These tubers are not only desiccation tolerant but also store a large amount of lipids—especially TAG, similar to seeds. We generated nanoLC-MS/MS-based proteomes in five replicates of four stages of tuber development and compared them to the proteomes of roots and leaves, yielding 2257 distinct protein groups. Our data reveal a striking upregulation of hallmark proteins of seeds in the tubers. A deeper comparison to a previously published proteome of Arabidopsis seeds and seedlings indicate that indeed a seed-like proteome was co-opted. This was further supported by an analysis of the proteome of a lipid-droplet enriched fraction of yellow nutsedge, which also displayed seed-like characteristics.