bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Adherence to Society Guidelines for the Management of Helicobacter Pylori Among Pediatric Gastroenterologists
Authors: Bonilla Silvana , Mitchell Paul D. , Mansuri Ishrat
Published: November 2020

Background:

The revised ESPGHAN/NASPGHAN 2016 guideline on the diagnosis and management of Helicobacter pylori (H pylori) infection discourages a “test and treat” strategy. Instead, upper endoscopy (EGD) is recommended when a valid clinical indication is present. Likewise, new treatment recommendations for first‐line therapies strongly encourage obtaining antimicrobial susceptibility before treatment. We conducted this study to assess the effect of revised guidelines on clinical practice at our center.

Methods:

Retrospective chart review of patients with H pylori infection diagnosis either by serology, stool antigen test, urea breath test, or EGD at Boston Children's Hospital between January 2013 and July 2019. We compared demographic and clinical data between initial guideline and 2016 revision (January 2013 to November 2016) and period after revised guideline (December 2016 to July 2019).

Results:

Two hundred and fifty‐six patients were included. EGD was the initial diagnostic test in 49% (50/103, prerevised guideline) and in 52% (79/153, postrevised guideline). Biopsy culture was sent in 3% of patients for both periods (3/103 and 4/153, respectively). PPI‐clarithromycin‐amoxicillin triple therapy was the most common regimen in both periods. Clarithromycin use was lower in postrevised guideline period (P = 0.003) whereas the opposite was noted for metronidazole and tetracycline (P = 0.009 and P = 0.02, respectively). There was no significant difference in eradication rate between periods (86% vs 81%).

Conclusions:

Low adherence to the updated H pylori guideline recommendations was observed among pediatric gastroenterologists at our center with low use of gastric biopsy culture. The guideline revision was associated with avoidance of clarithromycin use as a second‐line therapy, but no change in eradication rates. Future interventions should address the importance of obtaining gastric biopsy culture for antibiotic susceptibilities to guide therapy.
Antibiotic Prophylaxis for Percutaneous Endoscopic Gastrostomy in Children
Authors: Alessandri Francesco , Strisciuglio Caterina , Borrazzo Cristian , Cozzi Denis , Romano Claudio , Betalli Pietro , Villa Maria Pia , Parisi Pasquale , Ziparo Chiara , Rocco Monica , Evangelisti Melania , Pugliese Francesco , Di Nardo Giovanni
Published: November 2020

Objectives:

Paediatric studies on the role of antibiotic prophylaxis in the prevention of postoperative infections in children undergoing percutaneous endoscopic gastrostomy (PEG) are lacking. The aim of this study was to assess if a single dose of co‐amoxiclav before PEG can decrease the rate of peristomal wound and systemic infection in children.

Methods:

In this prospective, randomised, double‐blind, multicentre trial, children undergoing PEG were randomized to antibiotic prophylaxis with co‐amoxiclav versus placebo and the rate of local and systemic infections were assessed.

Results:

Of the 106 patients considered for inclusion, 49 patients were randomized. In the per‐protocol analysis, the occurrence of wound infection was 5% (1/20) in the antibiotic group and 21% (4/19) in the placebo group (P = 0.13, 16% difference in proportions, odds ratio [OR] 0.19, 95% confidence interval [CI] 0.02–1.9). The occurrence of systemic infection was 9% (2/22) in the antibiotic group and 27.2% (6/25) in the placebo group [P = 0.17, 18% difference in proportions, OR 0.32, 95% CI 0.06%–1.80%]. Similar results were obtained in intention‐to‐treat analysis. Interestingly, the overall infection rate was significantly higher in the placebo group as compared with the antibiotic group (40% vs 13.6%; P = 0.04) and the duration of hospital stay was significantly longer in the placebo group as compared with the antibiotic group (4.4 ± 1.6 vs 3.5 ± 1.05; P = 0.02). The number‐needed‐to‐treat (NTT) to prevent 1 peristomal infection on average are 6.7 patients.

Conclusions:

A preoperative dose of co‐amoxiclav reduces the overall infection rate and the duration of hospital stay. Our data suggest that antibiotic prophylaxis should be recommended in every children undergoing PEG placement.
Team Members' Roles in Home Healthcare
Authors: Adamakidou Theodoula , Triantafyllopoulou Maria-Nikoletta , Feleki Paraskevi , Papadopoulou Lamprini , Kalokairinou Athina
Published: November 2020

Home healthcare has just recently won the interest of policy decision makers in Greece and there is a lack of knowledge regarding the contributions provided by each team member. The aim of this study was to describe the home care interventions carried out by nurses, physicians, and physiotherapists during the AKEΣΩ-1 project. We examined the data from 1,094 patients who received home healthcare (HHC) from an interdisciplinary team from the Hellenic Red Cross HHC services in three major cities in Greece during a 20-month period. The visits and interventions by nurses, physicians, and physiotherapists were grouped and measured. Patients were mostly older adults (80.73%), women (68.37%) with medical problems (46.8%). Nurses conducted 70.76% of the visits, and provided 21,017 interventions. Physiotherapists conducted 22.83% of the visits and 4,627 interventions, and physicians conducted 6.4% of the visits and 2,117 interventions. Nurses provided a wide range of complex skilled nursing interventions that required knowledge of the community and ability to network. Physiotherapy and educating patients and caregivers were the most frequent interventions of physiotherapists. The main role of physicians was to conduct clinical exams. The Greek healthcare system is hospital- and physician-oriented. We documented that in HHC, nurses take a lead role in providing care, organizing services, and collaborating with other community services. From a health and social policy perspective, proper planning and staffing of HHC services are required. From an academic and licensing perspective, it is important to ensure that nurses working in the community have appropriate preparation.
Peripheral Vascular Disease
Authors: Swenty Constance F. , Hall Mellisa
Published: November 2020

Peripheral vascular disease (PVD) is a leading health concern in the United States, with an estimated prevalence of 8.5 million. The incidence of PVD is growing due to increasing rates of obesity and diabetes, as well as an aging population. Peripheral vascular disease is categorized as either venous, arterial, or mixed. A differential assessment is essential to identify the type of PVD and to plan management strategies to prevent further vascular dysfunction. This article describes assessment of patients with PVD, risk factors, treatments, and patient education.
Proposal to reclassify the proteobacterial classes Deltaproteobacteria and Oligoflexia, and the phylum Thermodesulfobacteria into four phyla reflecting major functional capabilities
Authors: Waite David W , Chuvochina Maria , Pelikan Claus , Parks Donovan H , Yilmaz Pelin , Wagner Michael , Loy Alexander , Naganuma Takeshi , Nakai Ryosuke , Whitman William B , Hahn Martin W , Kuever Jan , Hugenholtz Philip
Published: November 2020

The classDeltaproteobacteriacomprises an ecologically and metabolically diverse group of bacteria best known for dissimilatory sulphate reduction and predatory behaviour. Although this lineage is the fourth described class of the phylumProteobacteria, it rarely affiliates with other proteobacterial classes and is frequently not recovered as a monophyletic unit in phylogenetic analyses. Indeed, one branch of the classDeltaproteobacteriaencompassingBdellovibrio-like predators was recently reclassified into a separate proteobacterial class, theOligoflexia. Here we systematically explore the phylogeny of taxa currently assigned to these classes using 120 conserved single-copy marker genes as well as rRNA genes. The overwhelming majority of markers reject the inclusion of the classesDeltaproteobacteriaandOligoflexiain the phylumProteobacteria. Instead, the great majority of currently recognized members of the classDeltaproteobacteriaare better classified into four novel phylum-level lineages. We propose the namesDesulfobacterotaphyl. nov. andMyxococcotaphyl. nov. for two of these phyla, based on the oldest validly published names in each lineage, and retain the placeholder name SAR324 for the third phylum pending formal description of type material. Members of the classOligoflexiarepresent a separate phylum for which we propose the nameBdellovibrionotaphyl. nov. based on priority in the literature and general recognition of the genusBdellovibrio. Desulfobacterotaphyl. nov. includes the taxa previously classified in the phylumThermodesulfobacteria, and these reclassifications imply that the ability of sulphate reduction was vertically inherited in theThermodesulfobacteriarather than laterally acquired as previously inferred. Our analysis also indicates the independent acquisition of predatory behaviour in the phylaMyxococcotaandBdellovibrionota, which is consistent with their distinct modes of action. This work represents a stable reclassification of one of the most taxonomically challenging areas of the bacterial tree and provides a robust framework for future ecological and systematic studies.
Disentangling cause and consequence: Genetic dissection of theDANGEROUS MIX2risk locus, and activation of the DM2h NLR in autoimmunity
Authors: Ordon Jana , Martin Patrick , Erickson Jessica Lee , Ferik Filiz , Balcke Gerd , Bonas Ulla , Stuttmann Johannes
Published: November 2020

Nucleotide-binding domain–leucine-rich repeat-type immune receptors (NLRs) protect plants against pathogenic microbes through intracellular detection of effector proteins. However, this comes at a cost, as NLRs can also induce detrimental autoimmunity in genetic interactions with foreign alleles. This may occur when independently evolved genomes are combined in inter- or intraspecific crosses, or when foreign alleles are introduced by mutagenesis or transgenesis. Most autoimmunity-inducing NLRs are encoded within highly variableNLRgene clusters with no known immune functions, which were termed autoimmune risk loci. Whether risk NLRs differ from sensor NLRs operating in natural pathogen resistance and how risk NLRs are activated in autoimmunity is unknown. Here, we analyzed theDANGEROUS MIX2risk locus, a major autoimmunity hotspot inArabidopsis thaliana. By gene editing and heterologous expression, we show that a single gene,DM2h, is necessary and sufficient for autoimmune induction in three independent cases of autoimmunity in accession Landsbergerecta. We focus on autoimmunity provoked by an EDS1-YFPNLSfusion protein to functionally characterize DM2h and determine features of EDS1-YFPNLSactivating the immune receptor. Our data suggest that risk NLRs function reminiscent of sensor NLRs, while autoimmunity-inducing properties of EDS1-YFPNLSare in this context unrelated to the protein’s functions as immune regulator. We propose that autoimmunity may, at least in some cases, be caused by spurious, stochastic interactions of foreign alleles with co-incidentally matching risk NLRs.
Benefits and risks of zinc for adults during covid-19: rapid systematic review and meta-analysis of randomised controlled trials
Authors: Hunter Jennifer , Arentz Susan , Goldenberg Joshua , Yang Guoyan , Beardsley Jennifer , Myers Stephen P , Mertz Dominik , Leeder Stephen
Published: November 2020

Objective

To evaluate the benefits and risks of any type of zinc intervention to prevent or treat SARS-CoV-2.

Design

A living, systematic review and meta-analysis, incorporating rapid review methods.

Data sources

17 English and Chinese databases and clinical trial registries were searched in April/May 2020, with additional covid-19 focused searches in June and August 2020.

Eligibilitycriteria and analysis

Randomized control trials (RCTs) published in any language comparing zinc to a control to prevent or treat SARS-CoV-2. Other viral respiratory tract infections (RTIs) were included, but the certainty of evidence downgraded twice for indirectness. Screening, data extraction, risk of bias appraisal (RoB-2 tool) and verification was performed by calibrated, single reviewers. RCTs with adult populations were prioritised for analysis.

Results

123 RCTs were identified. None were specific to SARS-CoV-2 nor other coronaviruses. 28 RCTs evaluated oral (15-45mg daily), sublingual (45-300mg daily), or topical nasal (0.09-2.6 mg daily) zinc to prevent or treat nonspecific viral RTIs in 3,597 adults without zinc deficiency. Compared to placebo, zinc prevented 5 mild to moderate RTIs per 100 person-months, including in older adults (95% confidence interval 1 to 9) (number needed to treat (NTT)=20). There was no significant difference in the rates of non-serious adverse events (AE). For RTI treatment, a clinically important reduction in peak symptom severity scores was found for zinc compared to placebo (mean difference 1.2 points, 0.7 to 1.7), but not average daily symptom severity (standardised mean difference 0.2, 0.1 to 0.4). 19 fewer per 100 adults were at risk of remaining symptomatic over the first 7 days (2 to 38, NNT=5) and the mean duration of symptoms was 2 days shorter (0.2 to 3.5), however, there was substantial heterogeneity (I2 = 82% and 97%). 14 more per 100 experienced a non-serious AE (4 to 16, NNT=7) such as nausea, or mouth or nasal irritation. No differences in illness duration nor AE were found when zinc was compared to active controls. No serious AE, including copper deficiency, were reported by any RCT. Quality of life outcomes were not assessed. Confidence in these findings for SARS-CoV-2 is very low due to serious indirectness and some concerns about bias for most outcomes.

Conclusions

Zinc is a potential therapeutic candidate for preventing and treating SARS-CoV-2, including older adults and adults without zinc deficiency (very low certainty). Zinc may also help to prevent other viral RTIs during the pandemic (moderate certainty) and reduce the severity and duration of symptoms (very low certainty). The pending results from seven RCTs evaluating zinc for SARS-CoV-2 will be tracked.

Systematic review registration

PROSPERO CRD42020182044
Data driven mathematical model of colon cancer progression
Authors: Kirshtein Arkadz , Akbarinejad Shaya , Hao Wenrui , Le Trang , Aronow Rachel A. , Shahriyari Leili
Published: November 2020

Every colon cancer has its own unique characteristics, and therefore may respond differently to identical treatments. Here, we develop a data driven mathematical model for the interaction network of key components of immune microenvironment in colon cancer. We estimate the relative abundance of each immune cell from gene expression profiles of tumors, and group patients based on their immune patterns. Then we compare the tumor sensitivity and progression in each of these groups of patients, and observe differences in the patterns of tumor growth between the groups. For instance, in tumors with a smaller density of naive macrophages than activated macrophages, a higher activation rate of macrophages leads to an increase in cancer cell density, demonstrating a negative effect of macrophages. Other tumors however, exhibit an opposite trend, showing a positive effect of macrophages in controlling tumor size. Although the results indicate that for all patients, the size of the tumor is sensitive to the parameters related to macrophages such as their activation and death rate, this research demonstrates that no single biomarker could predict the dynamics of tumors.
Spirometric classifications of COPD severity as predictive markers for clinical outcomes: the HUNT Study
Authors: Bhatta Laxmi , Leivseth Linda , Mai Xiao-Mei , Henriksen Anne Hildur , Carslake David , Chen Yue , Martinez-Camblor Pablo , Langhammer Arnulf , Brumpton Ben Michael
Published: November 2020

Rationale

GOLD grades based on percent-predicted FEV1 poorly predicts mortality. Studies have recommended alternative expressions of FEV1 for the classification of COPD severity and they warrant investigation.

Objective

To compare the predictive abilities of ppFEV1 (ppFEV1 quartiles, GOLD grades, ATS/ERS grades), FEV1 z-score (FEV1 z-score quartiles, FEV1 z-score grades), FEV1.Ht-2 (FEV1.Ht-2 quartiles, FEV1.Ht-2 grades), FEV1.Ht-3 (FEV1.Ht-3 quartiles), and FEV1Q (FEV1Q quartiles) to predict clinical outcomes.

Methods

People aged ≥40 years with COPD (n=890) who participated in the HUNT Study (1995-1997) were followed for 5 years (short-term) and up to 20.4 years (long-term). Survival analysis and time-dependent area under curve (AUC) were used to compare the predictive abilities. A regression tree approach was applied to obtain optimal cut-offs of different expressions of FEV1. The UK Biobank (n=6495) was used as a replication cohort with a 5-year follow-up.

Results

As a continuous variable, FEV1Q had the highest AUCs for all-cause mortality (short-term 70.2, long-term 68.3), respiratory mortality (short-term 68.4, long-term 67.7), cardiovascular mortality (short-term 63.1, long-term 62.3), COPD hospitalization (short-term 71.3, long-term 70.9), and pneumonia hospitalization (short-term 67.8, long-term 66.6), followed by FEV1.Ht-2 or FEV1.Ht-3. Generally, similar results were observed for FEV1Q quartiles. The optimal cut-offs of FEV1Q had higher AUCs compared to GOLD grades for predicting short-term and long-term clinical outcomes. Similar results were found in UK Biobank.

Conclusions

FEV1Q best predicted the clinical outcomes and could improve the classification of COPD severity.
An international survey on the impact of COVID-19 in individuals with Down syndrome
Authors: Hüls Anke , Costa Alberto C. S. , Dierssen Mara , Baksh R. Asaad , Bargagna Stefania , Baumer Nicole T. , Brandão Ana Claudia , Carfi Angelo , Carmona-Iragui Maria , Chicoine Brain Allen , Ghosh Sujay , Lakhanpaul Monica , Manso Coral , Mayer Miguel-Angel , del Carmen Ortega Maria , de Asua Diego Real , Rebillat Anne-Sophie , Russell Lauren Ashley , Sgandurra Giuseppina , Valentini Diletta , Sherman Stephanie L , Strydom Andre
Published: November 2020

Background

Health conditions and immune dysfunction associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19 once infected by SARS-CoV-2.

Methods

The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers/family members on patients with COVID-19 and DS (N=1046). De-identified survey data collected between April and October 2020 were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. COVID-19 patients with DS from the ISARIC4C survey (ISARIC4C DS cases=100) were matched to a random set of patients without DS (ISARIC4C controls=400) and hospitalized DS cases in the T21RS survey (T21RS DS cases=100) based on age, gender, and ethnicity.

Finding

The mean age in the T21RS survey was 29 years (SD=18), 73% lived with their family. Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Pain and nausea were reported less frequently (p<0.01), whereas altered consciousness/confusion were reported more frequently (p<0.01). Risk factors for hospitalization and mortality were similar to the general population (age, male gender, diabetes, obesity, dementia) with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher than for controls (T21RS DS versus controls: risk ratio (RR)=3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus controls: RR=2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality.

Interpretation

Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of mortality, especially from age 40.

Funding

Down Syndrome Affiliates in Action, Down Syndrome Medical Interest Group-USA, GiGi’s Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, Matthews Foundation, National Down Syndrome Society, National Task Group on Intellectual Disabilities and Dementia Practices.
Using Capture-Recapture Methods to Estimate Influenza Hospitalization Incidence Rates
Authors: Balasubramani GK , Nowalk Mary Patricia , Clarke Lloyd G. , Dauer Klancie , Silveira Fernanda , Middleton Donald B. , Yassin Mohamed , Zimmerman Richard K.
Published: November 2020

Background

Accurate population estimates of disease incidence and burden are needed to set appropriate public health policy. The capture-recapture (C-R) method combines data from multiple sources to provide better estimates than is possible using single sources.

Methods

Data were derived from clinical virology test results and from an influenza vaccine effectiveness study from seasons 2016-2017 to 2018-2019. The Petersen C-R method was used to estimate the population size of influenza cases; these estimates were then used to calculate adult influenza hospitalization burden using a Centers for Disease Control and Prevention (CDC) multiplier method.

Results

Over all seasons, 343 influenza cases were reported in the clinical database and 313 in the research database. Fifty-nine cases (17%) reported in the clinical database were not captured in the research database, and 29 (9%) cases in the research database were not captured in the clinical database. Influenza hospitalizations were higher among vaccinated (58%) than the unvaccinated (35%) in the current season and were similar among unvaccinated (51%) and vaccinated (49%) in the previous year. Completeness of the influenza hospitalization capture was estimated to be 76%. The incidence rates for influenza hospitalizations varied by age and season and averaged 307-309 cases/100,000 adult population annually.

Conclusion

Using Capture-Recapture methods with more than one database, along with a multiplier method with adjustments improves the population estimates of influenza disease burden compared with relying on a single data source.
Data Veracity of Patients and Health Consumers Reported Adverse Drug Reactions on Twitter: Key Linguistic Features, Twitter Variables, and Association Rules
Authors: Lyu Tianchu , Eidson Andrew , Jun Jungmi , Zhou Xiajie , Cui Xiang , Liang Chen
Published: November 2020

Adverse drug reactions (ADRs) lead to high disease burden and health expenditure. Aside from traditional data sources used for pharmacovigilance, social media have emerged as an important supplemental data source for monitoring patients and consumers reported ADRs. Recently, there have been increasing concerns about the data veracity of ADRs extracted from social media. Our objective is to categorize different levels of data veracity and explore influential linguistic features and Twitter variables as they may be used for screening ADRs for high data veracity. We annotated a corpus of ADRs with linguistic features validated by clinical experts. Multinomial logistic regression was applied to investigate the associations between the linguistic features and levels of data veracity. We found that using first-person pronouns, expressing negative sentiment, ADR and drug name being in the same sentence were significantly associated with higher levels of data veracity (all p < 0.05), using medical terminology and less indications were associated with good data veracity (p < 0.05), less drug numbers were marginally associated with good data veracity (p = 0.053). These findings suggest an opportunity of developing machine learning models for automatic screening of ADRs from Twitter using identified key linguistic features, Twitter variables, and association rules.
COVID-19 surveillance - a descriptive study on data quality issues
Authors: Costa-Santos Cristina , Luísa Neves Ana , Correia Ricardo , Santos Paulo , Monteiro-Soares Matilde , Freitas Alberto , Ribeiro-Vaz Inês , Henriques Teresa , Rodrigues Pedro Pereira , Costa-Pereira Altamiro , Pereira Ana Margarida , Fonseca João
Published: November 2020

Background

High-quality data is crucial for guiding decision making and practicing evidence-based healthcare, especially if previous knowledge is lacking. Nevertheless, data quality frailties have been exposed worldwide during the current COVID-19 pandemic. Focusing on a major Portuguese surveillance dataset, our study aims to assess data quality issues and suggest possible solutions.

Methods

On April 27th 2020, the Portuguese Directorate-General of Health (DGS) made available a dataset (DGSApril) for researchers, upon request. On August 4th, an updated dataset (DGSAugust) was also obtained. The quality of data was assessed through analysis of data completeness and consistency between both datasets.

Results

DGSAugust has not followed the data format and variables as DGSApril and a significant number of missing data and inconsistencies were found (e.g. 4,075 cases from the DGSApril were apparently not included in DGSAugust). Several variables also showed a low degree of completeness and/or changed their values from one dataset to another (e.g. the variable ‘underlying conditions’ had more than half of cases showing different information between datasets). There were also significant inconsistencies between the number of cases and deaths due to COVID-19 shown in DGSAugust and by the DGS reports publicly provided daily.

Conclusions

The low quality of COVID-19 surveillance datasets limits its usability to inform good decisions and perform useful research. Major improvements in surveillance datasets are therefore urgently needed - e.g. simplification of data entry processes, constant monitoring of data, and increased training and awareness of health care providers - as low data quality may lead to a deficient pandemic control.
Extensive and accurate benchmarking of DIA acquisition methods and software tools using a complex proteomic standard
Authors: Gotti Clarisse , Roux-Dalvai Florence , Joly-Beauparlant Charles , Mangnier Loïc , Leclercq Mickaël , Droit Arnaud
Published: November 2020

Over the past decade, the data-independent acquisition mode has gained popularity for broad coverage of complex proteomes by LC-MS/MS and quantification of low-abundance proteins. However, there is no consensus in the literature on the best data acquisition parameters and processing tools to use for this specific application. Here, we present the most comprehensive comparison of DIA workflows on Orbitrap instruments published so far in the field of proteomics. Using a standard human 48 proteins mixture (UPS1 – Sigma) at 8 different concentrations in anE. coliproteome background, we tested 36 workflows including 4 different DIA window acquisition schemes and 6 different software tools (DIA-NN, DIA-Umpire, OpenSWATH, ScaffoldDIA, Skyline and Spectronaut) with or without the use of a DDA spectral library. Based on the number of proteins identified, quantification linearity and reproducibility, as well as sensitivity and specificity in 28 pairwise comparisons of different UPS1 concentrations, we summarize the major considerations and propose guidelines for choosing the DIA workflow best suited for LC-MS/MS proteomic analyses. Our 96 DIA raw files and software outputs have been deposited on ProteomeXchange for testing or developing new DIA processing tools.
Exploring the relationship between functional structure and ecosystem multifunctionality requires intraspecific trait variability
Authors: Zhang Li , Shipley Bill , Zhou Shurong
Published: November 2020

The authors have withdrawn their manuscript whilst they conduct additional data analysis to confirm if some of their conclusions are affected by data analysis artefact or not. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
New water and air pollution sensors added to the Sonic Kayak citizen science system for low cost environmental mapping
Authors: Griffiths Amber GF , Garrett Joanne K , Duffy James P , Matthews Kaffe , Visi Federico G , Eatock Claire , Robinson Mike , Griffiths David J
Published: November 2020

Sonic Kayaks are low-cost open-source systems for gathering fine-scale environmental data. The system is designed to be simple to fit on to standard kayaks or canoes, and full instructions have been made available for anyone wishing to build their own. The first version included temperature sensors and a hydrophone for recording underwater sound. Here we outline the design and integration of two new sensors, for underwater turbidity and above water air particulate pollution. All sensors record continually, and the GPS location, time and date are also stored for every data point, allowing fine-scale environmental data mapping. The data being collected by the sensors is sonified (turned into sound) in real-time, allowing the paddler to hear the data as they are collecting it, making it possible to locate and follow interesting occurrences. We present proof-of principle data for the first time for all the sensors, demonstrating how the system can be used for environmental mapping, and discuss potential future applications and adaptations. We believe the Sonic Kayak system offers particular promise for citizen science and environmental activism, as well as allowing professional researchers to gather data that was previously difficult or impossible to obtain.
Variant Calling Parallelization on Processor-in-Memory Architecture
Authors: Lavenier Dominique , Cimadomo Remy , Jodin Romaric
Published: November 2020

In this paper, we introduce a new combination of software and hardware PIM (Process-in-Memory) architecture to accelerate the variant calling genomic process. PIM translates into bringing data intensive calculations directly where the data is: within the DRAM, enhanced with thousands of processing units. The energy consumption, in large part due to data movement, is significantly lowered at a marginal additional hardware cost. Such design allows an unprecedented level of parallelism to process billions of short reads. Experiments on real PIM devices developed by the UPMEM company show significant speed-up compared to pure software implementation. The PIM solution also compared nicely to FPGA or GPU based acceleration bringing similar to twice the processing speed but most importantly being 5 to 8 times cheaper to deploy with up to 6 times less power consumption.
Geographic microevolution ofMycobacterium ulceranssustains Buruli ulcer extension, Australia
Authors: Saad Jamal , Hammoudi Nassim , Zgheib Rita , Anani Hussein , Drancourt Michel
Published: November 2020

The reason why severe cases of Buruli ulcers caused byMycobacterium ulceransare emerging in some South Australia counties has not been determined. In this study, we measured the diversity ofM. ulceranscomplex whole genome sequences (WGS) and reported a marker of this diversity. Using this marker as a probe, we compared WGS diversity in Buruli ulcer-epidemic South Australia counties versus non-epidemic Australian counties and further refined comparisons at the level of counties where severe Buruli ulcer cases have been reported. Analyzing 218 WGS (35 complete and 183 reconstructed WGS, including 174 Australian WGS) yielded 15M. ulceranscomplex genotypes, including three genotypes specific to Australia and one genotype specific to South Australia. A 1,068-bp PPE family protein gene exhibiting genotype-specific sequence variations was employed to further probe 13 minority clones hidden in sequence reads. The repartition of these clones significantly differed between South Australia and the rest of Australia. In addition, a significantly higher prevalence of 3/13 clones was observed in South Australia counties of the Mornington Peninsula, Melbourne and Bellarine Peninsula than in other South Australia counties. The data presented in this report suggest that the microevolution of threeM. ulceranscomplex clones drove the emergence of severe Buruli ulcer cases in some South Australia counties. Sequencing one specificPPEgene served to efficiently probeM. ulceranscomplex clones. Further functional studies may balance the environmental adaptation and virulence of these clones.
Immediate impact of transcranial magnetic stimulation on brain structure: short-term neuroplasticity following one session of cTBS
Authors: Jung JeYoung , Lambon Ralph Matthew A.
Published: November 2020

Recent evidence demonstrates that activation-dependent neuroplasticity on a structural level can occur in a short time (2 hour or less) in humans. However, the exact time scale of structural plasticity in adult human brain remains unclear. Using voxel-based morphometry (VBM), we investigated changes in gray matter (GM) after one session of continuous theta-burst stimulation (cTBS) delivered to the anterior temporal lobe (ATL). Twenty-five participants were received cTBS over the left ATL or occipital pole as a control site outside of the scanner and had structural and functional imaging. During functional imaging, participants performed a semantic association task. VBM result revealed decreased GM in the left ATL and right cerebellum after ATL stimulation compared to the control stimulation. In addition, cTBS over the left ATL induced slower reaction time in sematic task performance, reduced regional activity at the target site, and altered functional connectivity between the left and right ATL during semantic processing. Furthermore, the ATL GM changes were associated with the functional connectivity changes in the ATL-connectivity during semantic processing. These structural alterations are mirrored by functional changes in cortical excitability attributed to the GM changes and demonstrate the rapid dynamics of cortical plasticity. Our findings support fast adjusting neuronal systems, such as postsynaptic morphology changes and neuronal turnover. Our results suggest that TBS is able to produce powerful changes in regional synaptic activity in human adult brain.
Spatial management can significantly reduce dFAD beachings in Indian and Atlantic Ocean tropical tuna purse seine fisheries
Authors: Imzilen Taha , Lett Christophe , Chassot Emmanuel , Kaplan David M.
Published: November 2020

Debris from fisheries pose significant threats to coastal marine ecosystems worldwide. Tropical tuna purse seine fisheries contribute to this problem via the construction and deployment of thousands of man-made drifting fish aggregating devices (dFADs) annually, many of which end up beaching in coastal areas. Here, we analyzed approximately 40 000 dFAD trajectories in the Indian Ocean (IO) and 12 000 dFAD trajectories in the Atlantic Ocean (AO) deployed over the decade 2008-2017 to identify where and when beachings occur. We find that there is tremendous promise for reducing beaching events by prohibiting deployments in areas most likely to lead to a beaching. For example, our results indicate that around 40% of beachings can be prevented if deployments are prohibited in areas in the south of 8°S latitude, the Somali zone in winter, and the western Maldives in summer for the IO, and in an elongated strip of areas adjacent to the western African coast for the AO. In both oceans, the riskiest areas for beaching are not coincident with areas of high dFAD deployment activity, suggesting that these closures could be implemented with relatively minimal impact to fisheries. Furthermore, the existence of clear hotspots for beaching likelihood and the high rates of putative recovery of dFAD buoys by small-scale fishers in some areas suggests that early warning systems and dFAD recovery programs may be effective in areas that cannot be protected via closures if appropriate incentives can be provided to local partners for participating in these programs.
Variations in photoreceptor throughput to mouse visual cortex and the unique effects on tuning
Authors: Rhim I. , Coello-Reyes G. , Nauhaus I.
Published: November 2020

Visual input to primary visual cortex (V1) depends on highly adaptive filtering in the retina. In turn, isolation of V1 computations to study cortical circuits requires control over retinal adaption and its corresponding spatio-temporal-chromatic output. Here, we first measure the balance of input to V1 from the three main photoreceptor opsins – M-opsin, S-opsin, and rhodopsin – as a function of light adaption and retinotopy. Results show that V1 is rod-mediated in common laboratory settings, yet cone-mediated in natural daylight, as evidenced by exclusive sensitivity to UV wavelengths via cone S-opsin in the upper visual field. Next, we show that cone-mediated V1 responds to 2.5-fold higher temporal frequencies than rod-mediated V1. Furthermore, cone-mediated V1 has smaller RFs, yet similar spatial frequency tuning. V1 responses in rod-deficient (Gnat1−/−) mice confirm that the effects are due to differences in photoreceptor contribution. This study provides foundation for using mouse V1 to study cortical circuits.
Conjunctive spatial and idiothetic codes are topographically organized in the GABAergic cells of the lateral septum
Authors: van der Veldt Suzanne , Etter Guillaume , Mosser Coralie-Anne , Manseau Frédéric , Williams Sylvain
Published: November 2020

The hippocampal spatial code’s relevance for downstream neuronal populations – particularly its major subcortical output the lateral septum (LS) - is still poorly understood. Here, using calcium imaging combined with unbiased analytical methods, we functionally characterized and compared the spatial tuning of LS GABAergic cells to those of dorsal CA3 and CA1 cells. We identified a significant number of LS cells that are modulated by place, speed, acceleration, and direction, as well as conjunctions of these properties, directly comparable to hippocampal CA1 and CA3 spatially modulated cells. Interestingly, Bayesian decoding of position based on LS spatial cells reflected the animal’s location as accurately as decoding using the activity of hippocampal pyramidal cells. A portion of LS cells showed stable spatial codes over the course of multiple days, potentially reflecting long-term episodic memory. The distributions of cells exhibiting these properties formed gradients along the anterior-posterior and dorsal-ventral axes of the LS, directly reflecting the topographical organization of hippocampal inputs to the LS. Finally, we show using trans-synaptic tracing that LS neurons receiving CA3 and CA1 excitatory input send projections to the hypothalamus and medial septum, regions that are not targeted directly by principal cells of the dorsal hippocampus. Together, our findings demonstrate that the LS accurately and robustly represents spatial, directional as well as self-motion information and is uniquely positioned to relay this information from the hippocampus to its downstream regions, thus occupying a key position within a distributed spatial memory network.
Photoperiod Sensitive Energy Sorghum Responses to Environmental and Nitrogen Variabilities
Authors: Schetter August , Lin Cheng-Hsien , Zumpf Colleen , Jang Chunhwa , Hoffmann Leo , Rooney William , Lee D.K.
Published: November 2020

Recently introduced photoperiod-sensitive (PS) biomass sorghum (Sorghum bicolorL. Moench) needs to be investigated for their yield potentials under different cultivation environments with reasonable nitrogen (N) inputs. The objectives of this study were to 1) evaluate the biomass yield and feedstock quality of four sorghum hybrids with different levels of PS ranging from very PS (VPS) hybrids and to moderate PS (MPS) hybrids, and 2) determine the optimal N inputs (0~168 kg N ha−1) under four environments: combinations of both temperate (Urbana, IL) and subtropical (College Station, TX) regions during 2018 and 2019. Compared to TX, the PS sorghums in central IL showed higher yield potential and steady feedstock production with an extended daylength and with less precipitation variability, especially for the VPS hybrids. The mean dry matter (DM) yields of VPS hybrids were 20.5 Mg DM ha−1and 17.7 Mg DM ha−1in IL and TX, respectively. The highest N use efficiency occurred at a low N rate of 56 kg N ha−1by improving approximately 33 kg DM ha−1per 1.0 kg N ha−1input. Approximately 70% of the PS sorghum biomass can be utilized for biofuel production, consisting of 58-65% of the cell wall components and 4-11% of the soluble sugar. This study demonstrated that the rainfed temperate area (e.g., IL) has a great potential for the sustainable cultivation of PS energy sorghum due their observed high yield potential, stable production, and low N requirements.
Muscle Atrophy: Different Strains of Mice Respond Differently to Single Limb Immobilization
Authors: Maroni Camilla Reina , Friedman Michael A , Zhang Yue , McClure Michael J , Fulle Stefania , Farber Charles R. , Donahue Henry J.
Published: November 2020

To examine whether genetic variability plays a role in muscle adaption to its mechanical environment, we examined hind limb immobilization in five different strains of mice: CAST/EiJ, NOD/ShiLtJ, NZO/HILtJ, 129S1/SvImJ and A/J. Mice had one limb immobilized by a cast for three weeks. The response to immobilization was dependent on the strain of mice examined. A/J mice lost the most body weight following immobilization and displayed a significant decrease in physical activity. None of the other strains displayed a significant decrease in activity. Food consumption was significantly increased in NOD/ShiLtJ mice. All other strains had non-significant changes in food consumption. Muscle mass/body weight was decreased by immobilization, to varying degrees, in all strains except 1291/SvImJ. Casting decreased absolute muscle mass in both quadriceps and gastrocnemius in NOD/ShiltJ and NZO/HILtJ mice, two strains that can develop diabetes, but not in the other strains. Three weeks of immobilization caused a significant increase in quadriceps levels of atrogenes in CAST/EiJ mice but not in other strains. Immobilization caused a significant increase in quadriceps and gastrocnemius levels ofMyh4in CAST/EiJ mice but not in any other strain. A similar trend was observed forMyh7in gastrocnemius muscle. Immobilization resulted in a decrease the p-p70S6K1/total p706SK1 ratio in quadriceps of NOD/ShiLtJ mice and the gastrocnemius of A/J mice, but not in other strains. Immobilization did not affect the p-4EBP1/total 4EBP1 ratio in quadriceps of any of the strains examined. However, the p-4EBP1/total 4EBP1 ratio in gastrocnemius was greater in immobilized, relative to control, limbs in CAST/EiJ mice. Muscle mass normalized to body weight in both gastrocnemius and quadriceps displayed the greatest degree of heritability. These results reveal remarkable variability in responsiveness to immobilization across five different genetic strains of mice.
Geographic variation in the seed mycobiome ofPseudotsuga menziesiivar.menziesiiacross the Pacific Northwest, USA
Authors: Bergmann Gillian E. , Busby Posy E.
Published: November 2020

Fungal symbionts occur in all plant tissues, and many aid their host plants with critical functions, including nutrient acquisition, defense against pathogens, and tolerance of abiotic stress. “Core” taxa in the plant mycobiome, defined as fungi present across individuals, populations, or time, may be particularly crucial to plant survival during the challenging seedling stage. However, studies on core seed fungi are limited to individual sampling sites, raising the question of whether core taxa exist across large geographic scales. We addressed this question using both culture-based and culture-free techniques to identify the fungi found in individual seeds collected from nine provenances across the range of Coastal Douglas-fir (Pseudotsuga menziesiivar.menziesii), a foundation tree species in the Pacific Northwest and a globally important timber crop that is propagated commercially by seed. Two key findings emerged: 1) Seed mycobiome composition differed among seed provenances. 2) Despite spatial variation in the seed mycobiome, we detected four core members, none of which is a known pathogen of Douglas-fir:Trichodermaspp.,Hormonema macrosporum,Mucor plumbeusandTalaromyces rugulosus. Our results support the concept of a core seed microbiome, yet additional work is needed to determine the functional consequences of core taxa for seedling germination, growth, survival and competition.
Genome-wide characterization of human minisatellite VNTRs: population-specific alleles and gene expression differences
Authors: Rasekh Marzieh Eslami , Hernandez Yozen , Drinan Samantha D. , Bass Juan I. Fuxman , Benson Gary
Published: November 2020

Variable Number Tandem Repeats (VNTRs) are tandem repeat (TR) loci that vary in copy number across a population. Using our program, VNTRseek, we analyzed human whole genome sequencing datasets from 2,770 individuals in order to detect minisatellite VNTRs, i.e., those with pattern sizes ≥7 bp. We detected 35,638 VNTR loci and classified 5,676 as commonly polymorphic (i.e., with non-reference alleles occurring in >5% of the population). Commonly polymorphic VNTR loci were found to be enriched in genomic regions with regulatory function, i.e., transcription start sites and enhancers. Investigation of the commonly polymorphic VNTRs in the context of population ancestry revealed that 1,096 loci contained population-specific alleles and that those could be used to classify individuals into super-populations with near-perfect accuracy. Search for quantitative trait loci (eQTLs), among the VNTRs proximal to genes, indicated that in 187 genes expression differences correlated with VNTR genotype. We validated our predictions in several ways, including experimentally, through the identification of predicted alleles in long reads, and by comparisons showing consistency between sequencing platforms. This study is the most comprehensive analysis of minisatellite VNTRs in the human population to date.
9p21 Loss Defines the Evolutionary Patterns of Aggressive Renal Cell Carcinomas
Authors: Carbone Federica , Huang Justin K. , Perelli Luigi , Poggetto Edoardo Del , Gutschner Tony , Tomihara Hideo , Soeung Melinda , Lam Truong Nguyen Anh , Xia Ruohan , Zhu Cihui , Song Xingzhi , Zhang Jianhua , Sircar Kanishka , Malouf Gabriel G. , Sgambato Alessandro , Karam Jose A. , Gao JianJun , Jonasch Eric , Viale Andrea , Draetta Giulio F. , Futreal Andrew , Bakouny Ziad , Van Allen Eliezer M. , Choueiri Toni , Msaouel Pavlos , Litchfield Kevin , Turajlic Samra , Heffernan Timothy P. , Chen Ying Bei , DiNatale Renzo G. , Hakimi A. Ari , Bristow Christopher A. , Tannir Nizar M. , Carugo Alessandro , Genovese Giannicola
Published: November 2020

Dedifferentiation and acquisition of chromosomal instability in renal cell carcinoma portends dismal prognosis and aggressive clinical behavior. However, the absence of reliable experimental models dramatically impacts the understanding of mechanisms underlying malignant progression. Here we established anin vivogenetic platform to rapidly generate somatic mosaic genetically engineerd immune-competent mouse models of renal tumors, recapitulating the genomic and phenotypic features of these malignancies. Leveraging somatic chromosomal engineering, we demonstrated that ablation of the murine locus syntenic to human 9p21 drives the rapid expansion of aggressive mesenchymal clones with prominent metastatic behavior, characterized by early emergence of chromosomal instability, whole-genome duplication, and conserved patterns of aneuploidy. This model of punctuated equilibrium provides a remarkable example of cross-species convergent evolution.

Significance

To better understand the role of 9p21 in malignant progression, we generated a somatic mosaic GEMM of renal cancer, capturing the histological, genomic and evolutionary features of human disease. With this technology we demonstrated a critica role of 9p21 loss in metastatic evolution of RCC and provide a unique tool for testing new therapeutic treatments.