bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): a longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection
Authors: O’Laughlin Kelli N. , Thompson Matthew , Hota Bala , Gottlieb Michael , Plumb Ian D. , Chang Anna Marie , Wisk Lauren E. , Hall Aron J. , Wang Ralph C. , Spatz Erica S. , Stephens Kari A. , Huebinger Ryan M. , McDonald Samuel A. , Venkatesh Arjun , Gentile Nikki , Slovis Benjamin H. , Hill Mandy , Saydah Sharon , Idris Ahamed H. , Rodriguez Robert , Krumholz Harlan M. , Elmore Joann G. , Weinstein Robert A. , Nichol Graham ,   INSPIRE Investigators
Published: August 2021

BACKGROUND

Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection.

METHODS

INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses.

RESULTS

Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing.

CONCLUSIONS

This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.
Impact of the World Inflammatory Bowel Disease Day and Crohn’s & Colitis Awareness Week on Population Interest between 2016 and 2020: Google Trends Analysis
Authors: Silangcruz Krixie , Nishimura Yoshito , Czech Torrey , Kimura Nobuhiko , Hagiya Hideharu , Koyama Toshihiro , Otsuka Fumio
Published: August 2021

Background

More than 6 million people are affected by inflammatory bowel disease (IBD) globally. World IBD Day (WID; May 19) and Crohn’s and Colitis Awareness Week (CCAW; December 1–7) occur yearly as national health observances to raise public awareness of IBD, but their effects are unclear.

Methods

This study evaluates the impact of WID and CCAW on the public awareness of IBD in the United States (US) and worldwide from 2016 to 2020 using the relative search volume (RSV) of “IBD,” “Ulcerative colitis,” and “Crohn’s disease” in Google Trends (GT). To identify significant timepoints of trend changes (joinpoints), we performed Joinpoint regression analysis.

Results

No joinpoints were noted around the time of WID or CCAW during the study period in the search results of the US. Worldwide, joinpoints were noted around WID in 2020 with the search for “IBD” and around CAAW in 2017 and 2019 to search for “ulcerative colitis.” However, the extents of trend changes were modest without statistically significant increases.

Conclusions

WID and CCAD may not have worked as expected to raise public awareness of IBD. Additional measures are necessary to help raise awareness of IBD related to the health observances.

World IBD Day and Crohn’s and Colitis Awareness Week are key health observances related to IBD. These observances, however, might not have been effective in raising public awareness of IBD in the US and worldwide, according to Google Trends analysis.
Building knowledge of university campus population dynamics to enhance near-to-source sewage surveillance for SARS-CoV-2 detection
Authors: Sweetapple Chris , Melville-Shreeve Peter , Chen Albert S. , Grimsley Jasmine M. S. , Bunce Joshua T. , Gaze William , Fielding Sean , Wade Matthew J.
Published: August 2021

Wastewater surveillance has been widely implemented for monitoring of SARS-CoV-2 during the global COVID-19 pandemic, and near-to-source monitoring is of particular interest for outbreak management in discrete populations. However, variation in population size poses a challenge to the triggering of public health interventions using wastewater SARS-CoV-2 concentrations. This is especially important for near-to-source sites that are subject to significant daily variability in upstream populations. Focusing on a university campus in England, this study investigates methods to account for variation in upstream populations at a site with highly transient footfall and provides a better understanding of the impact of variable populations on the SARS-CoV-2 trends provided by wastewater-based epidemiology. The potential for complementary data to help direct response activities within the near-to-source population is also explored, and potential concerns arising due to the presence of heavily diluted samples during wet weather are addressed. Using wastewater biomarkers, it is demonstrated that population normalisation can reveal significant differences between days where SARS-CoV-2 concentrations are very similar. Confidence in the trends identified is strongest when samples are collected during dry weather periods; however, wet weather samples can still provide valuable information. It is also shown that building-level occupancy estimates based on complementary data aid identification of potential sources of SARS-CoV-2 and can enable targeted actions to be taken to identify and manage potential sources of pathogen transmission in localised communities.
Pylorus resection versus pylorus preservation in pancreatoduodenectomy (PyloResPes): study protocol and statistical analysis plan for a German multicentre, single-blind, surgical, registry-based randomised controlled trial
Authors: Renz Bernhard W , Adrion Christine , Klinger Carsten , Ilmer Matthias , D'Haese Jan , Buhr Heinz-J , Mansmann Ulrich , Werner Jens ,   PyloResPres study group
Published: August 2021

Introduction
Partial pancreatoduodenectomy (PD) is the treatment of choice for various benign and malignant tumours of the pancreatic head or the periampullary region. For reconstruction of the gastrointestinal passage, two stomach preserving PD variants exist: pylorus preservation (ppPD), or pylorus resection (prPD) with preservation of the stomach. In pancreatic surgery, delayed gastric emptying (DGE) remains a serious complication after PD with an incidence varying between 4.5% and 45%, potentially delaying hospital discharge or further treatment, e.g. adjuvant chemotherapy. Evidence is lacking to assess which variant of PD entails fewer postoperative DGE.
Methods and analysis
The protocol of a large-scale, multicentre, pragmatic, two-arm parallel-group, registry-based randomised controlled trial (rRCT) using a two-stage group-sequential design is presented. This patient-blind rRCT aims to demonstrate the superiority of prPD over ppPD with respect to the overall incidence of DGE within 30 days after index surgery in a German real-world setting. A total of 984 adults undergoing elective PD for any indication will be randomised in a 1:1 ratio. Patients will be recruited at about 30 hospitals being members of the StuDoQ|Pancreas registry established by the German Society of General and Visceral Surgery (DGAV). The postoperative follow-up for each patient will be 30 days. The primary analysis will follow an intention-to-treat approach and applies a binary logistic random intercepts model. Secondary perioperative outcomes include overall severe morbidity (Clavien-Dindo classification), blood loss, 30-day all-cause mortality, postoperative hospital stay, and operation time. Complication rates and adverse events will be closely monitored.
Ethics and dissemination
This protocol was approved by the leading ethics committee of the Medical Faculty of the Ludwig-Maximilians-University, Munich (reference no. 19-221). The results will be published in a peer-reviewed journal and presented at international conferences. Study findings will also be disseminated via the website (http://www.dgav.de/studoq/pylorespres/).
Trial registration number
DRKS-ID: DRKS00018842 (https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018842, prospectively registered on 24-Oct-2019)
Mortality and outcomes after decompressive craniectomy in children with severe traumatic brain injury
Authors: Bruns N. , Kamp O. , Lange K. , Lefering R. , Felderhoff-Müser U. , Dudda M. , Dohna-Schwake C. ,   TraumaRegister DGU
Published: August 2021

Purpose

The effect of decompressive craniectomy (DC) on mortality and outcomes in children with elevated intracranial pressure after severe head trauma is strongly debated and high-quality evidence is lacking. This study was conducted to determine whether DC in children with severe head trauma is associated with a decrease in mortality or poor outcomes at discharge from the intensive care unit.

Methods

Data on patients < 18 years of age treated in Germany, Austria, and Switzerland during a ten-year period were extracted from TraumaRegister DGU®, forming a retrospective multi-centre cohort study. Descriptive and multivariable analyses were performed to compare mortality and outcomes after decompressive craniectomy and medical management.

Results

2507 patients were included, of which 402 underwent decompressive craniectomy. Mortality was 20.6 % in children undergoing DC compared to 13.7 % after medical management. Observed and predicted mortality after DC and medical management matched in all subgroups except in children between six and 17 years of age, where mortality after DC was lower than predicted. Poor outcome was observed in 27.6 % of DC patients vs. 16.1 % receiving medical management. Logistic regression revealed slightly negative effects of DC on mortality (odds ratio 1.20, not significant) and outcomes (odds ratio 1.56 (95% confidence interval 1.01-2.40).

Conclusion

DC did not decrease overall mortality or rates of poor outcome. However, children above six years of age may benefit from DC. High quality prospective studies are urgently needed.
Results dissemination from completed clinical trials conducted at German university medical centers remains delayed and incomplete. The 2014-2017 cohort
Authors: Riedel Nico , Wieschowski Susanne , Bruckner Till , Holst Martin R. , Kahrass Hannes , Nury Edris , Meerpohl Joerg J. , Salholz-Hillel Maia , Strech Daniel
Published: August 2021

Objective

Timely publication of clinical trial results is central for evidence-based medicine. The performance of university medical centers (UMCs) regarding timely results publication informs the local and national decision makers, patients, and the public about the need to improve trial results dissemination.

Study Design and Setting

Following the same search and tracking methods used in our previous study for the years 2009 - 2013, we identified trials led by German UMCs completed between 2014 and 2017 and tracked results dissemination for the identified trials.

Results

We identified 1,658 trials in the 2014-2017 cohort. Of these trials, 43% published results as either journal publication or summary results within 24 months after completion date, which is an improvement of 3.8% percentage points compared to the previous study. At the UMC level, the 24-month publication rates varied from 14% to 71%. Five years after completion, still 30% of the trials remained unpublished.

Conclusion

Despite minor improvements compared to the previously investigated cohort, the rate of timely reporting of trials led by German UMCs remains low. German UMCs should take further steps to improve timely reporting rates.
Passive Detection of COVID-19 with Wearable Sensors and Explainable Machine Learning Algorithms
Authors: Gadaleta Matteo , Radin Jennifer M. , Baca-Motes Katie , Ramos Edward , Kheterpal Vik , Topol Eric J. , Steinhubl Steven R. , Quer Giorgio
Published: August 2021

Individual smartwatch or fitness band sensor data in the setting of COVID-19 has shown promise to identify symptomatic and pre-symptomatic infection or the need for hospitalization, correlations between peripheral temperature and self-reported fever, and an association between changes in heart-rate-variability and infection. In our study, a total of 38,911 individuals (61% female, 15% over 65) have been enrolled between March 25, 2020 and April 3, 2021, with 1,118 reported testing positive and 7,032 negative for COVID-19 by nasopharyngeal PCR swab test. We propose an explainable gradient boosting prediction model based on decision trees for the detection of COVID-19 infection that can adapt to the absence of self-reported symptoms and to the available sensor data, and that can explain the importance of each feature and the post-test-behavior for the individuals. We tested it in a cohort of symptomatic individuals who exhibited an AUC of 0.83 [0.81-0.85], or AUC=0.78 [0.75-0.80] when considering only data before the test date, outperforming state-of-the-art algorithm in these conditions. The analysis of all individuals (including asymptomatic and pre-symptomatic) when self-reported symptoms were excluded provided an AUC of 0.78 [0.76-0.79], or AUC of 0.70 [0.69-0.72] when considering only data before the test date. Extending the use of predictive algorithms for detection of COVID-19 infection based only on passively monitored data from any device, we showed that it is possible to scale up this platform and apply the algorithm in other settings where self-reported symptoms can not be collected.
MyPlate, Half-Plate, and No Plate: How Visual Plate-related Dietary Benchmarks Influence Meal Composition
Authors: Wansink Brian , Wansink Audrey
Published: August 2021

Can visual plate-related dietary guidance systems – such as the MyPlate guideline or the Half-Plate Rule – help people eat better when dining at home or in restaurants? To help explore this, 104 young adults completed a food diary study after having been randomly assigned to follow either 1) USDA MyPlate guidelines, 2) the Half-Plate Rule, or 3) no guidelines (control condition). Both of the visual dietary guidance systems were considered easy to understand, to follow, and left people with fewer questions about what to eat (all p<.01). Moreover, people who rated a system “easy to follow” indicated they had consumed less (meat (r = .268), but this was uncorrelated with fruit and vegetable intake (r =.092) and carbohydrate intake (r = .069). There are three key conclusions to these and other findings: First, the simplest guidance system may be more effective than no system. Second, even the most perfect dietary guidance system will not change behavior if the foods are not available or it is not followed. Third, guidance systems could over-increase the consumption of any food they specifically mention.
Long COVID in hospitalized and non-hospitalized patients in a large cohort in Northwest Spain, a prospective cohort study
Authors: Pérez-González Alexandre , Araújo-Ameijeiras Alejandro , Fernández-Villar Alberto , Crespo Manuel , Poveda Eva
Published: August 2021

Background

Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID.

Objective

The aim of this study is to describe persisting symptoms six months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain

Design

This is a prospective cohort study performed in the COVID-19 Cohort of Galicia Sur Health Institute (COHVID-GS).

Participants

This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up.

Main measures and key results

A total of 284 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At six months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs 38.2%) and in women (59.0% vs 40.5%). The multivariate analysis identified Chronic Obstructive Pulmonary Disease (COPD), female gender and tobacco consumption as risk factors for long COVID.

Conclusions

Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and females.
The Impact for implementing Balanced Scorecard in Health Care Organizations: A Systematic Review
Authors: Amer Faten , Hammoud Sahar , Khatatbeh Haitham , Lohner Szimonetta , Boncz Imre , Endrei Dóra
Published: August 2021

Aims

This systematic review aims to assess the impact of Balanced Scorecard (BSC) implementation at Health Care Organizations (HCOs) on Health Care Workers’ (HCWs’) satisfaction, patient satisfaction, and financial performance. Up to now, no previous systematic reviews have performed a comprehensive and rigorous methodological approach to figure out the impact of BSC implementation in HCOs.

Methods

This systematic review was prepared according to PRISMA guidelines. PubMed, Embase, Cochrane, and Google Scholar databases, as well as Google search engine, were inspected to find all BSC implementations at HCOs until 20 September 2020. Then the resulted articles were screened to find the implementations which measured the impact of BSC on HCWs’ satisfaction, patient satisfaction, and financial performance. Quality assessment was performed using the Standards for Reporting Implementation Studies: (StaRI) checklist.

Results

Out of 4031 records, 20 articles were finally included for measuring one or more of the three impact types. 17 measured the impact of BSC on patient satisfaction, 7 on HCWs’ satisfaction, and 12 on financial performance. Studies with higher quality had a higher positive impact.

Conclusion

This paper offers evidence to HCOs and policymakers on the benefits of implementing BSC. BSC implementations showed a positive impact on patient satisfaction and financial performance in HCOs. However, less impact was found on HCWs’ satisfaction, which should be given better consideration in future BSC implementations. High and medium-quality BSC studies were associated with higher positive impacts than low ones. BSC can be utilized as an effective tool to improve HCOs’ performance during the COVID-19 pandemic.
OtoXNet - Automated Identification of Eardrum Diseases from Otoscope Videos: A Deep Learning Study for Video-representing Images
Authors: Binol Hamidullah , Niazi M. Khalid Khan , Elmaraghy Charles , Moberly Aaron C. , Gurcan Metin N.
Published: August 2021

Background

The lack of an objective method to evaluate the eardrum is a critical barrier to an accurate diagnosis. Eardrum images are classified into normal or abnormal categories with machine learning techniques. If the input is an otoscopy video, a traditional approach requires great effort and expertise to manually determine the representative frame(s).

Methods

In this paper, we propose a novel deep learning-based method, called OtoXNet, which automatically learns features for eardrum classification from otoscope video clips. We utilized multiple composite image generation methods to construct a highly representative version of otoscopy videos to diagnose three major eardrum diseases, i.e., otitis media with effusion, eardrum perforation, and tympanosclerosis versus normal (healthy). We compared the performance of OtoXNet against methods with that either use a single composite image or a keyframe selected by an experienced human. Our dataset consists of 394 otoscopy videos from 312 patients and 765 composite images before augmentation.

Results

OtoXNet with multiple composite images achieved 84.8% class-weighted accuracy with 3.8% standard deviation, whereas with the human-selected keyframes and single composite images, the accuracies were respectively, 81.8% ± 5.0% and 80.1% ± 4.8% on multi-class eardrum video classification task using an 8-fold cross-validation scheme. A paired t-test shows that there is a statistically significant difference (p-value of 1.3 × 10−2) between the performance values of OtoXNet (multiple composite images) and the human-selected keyframes. Contrarily, the difference in means of keyframe and single composites was not significant (p = 5.49 × 10−1). OtoXNet surpasses the baseline approaches in qualitative results.

Conclusion

The use of multiple composite images in analyzing eardrum abnormalities is advantageous compared to using single composite images or manual keyframe selection.
Determinants of the COVID-19 Vaccine Hesitancy Spectrum
Authors: Piltch-Loeb Rachael , Silver Diana , Kim Yeerae , Norris Hope , McNeill Elizabeth , Abramson David
Published: August 2021

Polls report nearly one-third of the United States population is skeptical or opposed to getting the COVID-19 vaccine. Most of these polls, as well as the scientific research that has been conducted on vaccine hesitancy, was done prior to vaccine eligibility opening to all adults. Now that COVID-19 vaccines are widely available, further research is needed to understand the factors contributing to vaccine intentions across the vaccine hesitancy spectrum. This study conducted an online survey using the Social Science Research Solution (SSRS) Opinion Panel web panelists, representative of U.S. adults age 18 and older who use the internet, with an oversample of rural-dwelling and minority populations between April 8 and April 22, 2021- as vaccine eligibility opened to the country. We examined the relationship between COVID-19 exposure and socio-demographics with vaccine intentions [eager-to-take, wait-and-see, undecided, refuse] among the unvaccinated using multinomial logistic regressions [ref: fully/partially vaccinated]. Results showed vaccine intentions varied by demographic characteristics and risk exposures during the period that eligibility for the vaccine was extended to all adults.

Funding statement

Funding for this research was provided by a grant from the National Science Foundation (Grant #2049886). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Phenotyping of acute and persistent COVID-19 features in the outpatient setting: exploratory analysis of an international cross-sectional online survey
Authors: Sahanic Sabina , Tymoszuk Piotr , Ausserhofer Dietmar , Rass Verena , Pizzini Alex , Nordmeyer Goetz , Hüfner Katharina , Kurz Katharina , Weber Paulina Maria , Sonnweber Thomas , Boehm Anna , Aichner Magdalena , Cima Katharina , Boeckle Barbara , Holzner Bernhard , Rumpold Gerhard , Puelacher Christoph , Kiechl Stefan , Huber Andreas , Wiedermann Christian J. , Sperner-Unterweger Barbara , Tancevski Ivan , Bellmann-Weiler Rosa , Bachler Herbert , Piccoliori Giuliano , Helbok Raimund , Weiss Guenter , Loeffler-Ragg Judith
Published: August 2021

BACKGROUND

Long COVID, defined as presence of COVID-19 related symptoms 28 days or more after the onset of acute SARS-CoV-2 infection, is an emerging challenge to healthcare systems. The objective of this study was to phenotype recovery trajectories of non-hospitalized COVID-19 individuals.

METHODS

We performed an international, multi-center, exploratory online survey study on demographics, comorbidities, COVID-19 symptoms and recovery status of non-hospitalized SARS-CoV-2 infected adults (Austria: n=1157), and Italy: n= 893).

RESULTS

Working age subjects (Austria median: 43 yrs (IQR: 31 – 53), Italy: 45 yrs (IQR: 35 – 55)) and females (65.1% and 68.3%) predominated the study cohorts. Course of acute COVID-19 was characterized by a high symptom burden (median 13 (IQR: 9 – 18) and 13 (7 – 18) out of 44 features queried), a 47.6 – 49.3% rate of symptom persistence beyond 28 days and 20.9 – 31.9% relapse rate. By cluster analysis, two acute symptom phenotypes could be discerned: the non-specific infection phenotype and the multi-organ phenotype (MOP), the latter encompassing multiple neurological, cardiopulmonary, gastrointestinal and dermatological features. Clustering of long COVID subjects yielded three distinct subgroups, with a subset of 48.7 – 55 % long COVID individuals particularly affected by post-acute MOP symptoms. The number and presence of specific acute MOP symptoms and pre-existing multi-morbidity was linked to elevated risk of long COVID.

CONCLUSION

The consistent findings of two independent cohorts further delineate patterns of acute and post-acute COVID-19 and emphasize the importance of symptom phenotyping of home-isolated COVID-19 patients to predict protracted convalescence and to allocate medical resources.

Key Points

Question

Which acute symptom patterns of acute COVID-19 are associated with prolonged symptom persistence, symptom relapse or physical performance impairment?

Findings

In this multicenter international comparative survey study on non-hospitalized SARS- CoV-2 infected adults (Austria: n = 1157, Italy: n = 893) we identified distinct and reproducible phenotypes of acute and persistent features. Acute multi-organ symptoms including neurological and cardiopulmonary manifestations are linked to elevated risk of long COVID.

Meaning

These findings suggest to employ symptom phenotyping of home-isolated COVID-19 patients to predict protracted convalescence and to allocate medical resources.
Methods used to select results to include in meta-analyses of nutrition research: a meta-research study
Authors: Kanukula Raju , McKenzie Joanne E , Bero Lisa , Dai Zhaoli , McDonald Sally , Kroeger Cynthia M , Korevaar Elizabeth , Page Matthew J
Published: August 2021

Objectives: To investigate the extent of multiplicity of results in study reports of nutrition research, and the methods specified in systematic reviews to select results for inclusion in meta-analyses.
Methods: MEDLINE and Epistemonikos were searched (January 2018 - June 2019) to identify systematic reviews with meta-analysis of the association between food/diet and health-related outcomes. A random sample of these reviews was selected, and for the first presented ('index') meta-analysis, rules used to select effect estimates to include in this meta-analysis were extracted from the reviews and their protocols. All effect estimates from the primary studies that were eligible for inclusion in the index meta-analyses were extracted.
Results: Forty-two systematic reviews were included, 14 of which had a protocol. In 29% of review protocols and 69% of reviews, at least one decision rule to select effect estimates when multiple were available was specified. In 69% (204/325) of studies included in the index meta-analyses, there was at least one type of multiplicity of results.
Conclusions: Authors of systematic reviews of nutrition research should anticipate encountering multiplicity of results in the included primary studies. Specification of methods to handle multiplicity when designing reviews is therefore recommended.
An introgression breakthrough left by an anthropogenic contact between two ascidians
Authors: Moan Alan Le , Roby Charlotte , Fraisse Christelle , Daguin-Thiébaut Claire , Bierne Nicolas , Viard Frédérique
Published: August 2021

Human-driven translocations of species have diverse evolutionary consequences such as promoting hybridization between previously geographically isolated taxa. This is well-illustrated by the solitary tunicate, Ciona robusta, native to the North East Pacific and introduced in the North East Atlantic. It is now co-occurring with its congener C. intestinalis in the English Channel, and C. roulei in the Mediterranean Sea. Despite their long allopatric divergence, first and second generation crosses showed a high hybridization success between the introduced and native taxa in the laboratory. However, previous genetic studies failed to provide evidence of recent hybridization between C. robusta and C. intestinalis in the wild. Using SNPs obtained from ddRAD-sequencing of 397 individuals from 26 populations, we further explored the genome-wide population structure of the native Ciona taxa. We first confirmed results documented in previous studies, notably i) a chaotic genetic structure at regional scale, and ii) a high genetic similarity between C. roulei and C. intestinalis, which is calling for further taxonomic investigation. More importantly, and unexpectedly, we also observed a genomic hotspot of long introgressed C. robusta tracts into C. intestinalis genomes at several locations of their contact zone. Both the genomic architecture of introgression, restricted to a 1.5 Mb region of chromosome 5, and its absence in allopatric populations suggest introgression is recent and occurred after the introduction of the non-indigenous species. Overall, our study shows that anthropogenic hybridization can be effective in promoting introgression breakthroughs between species at a late stage of the speciation continuum.
MorphData: Automating the data extraction process of morphological features of microglial cells in ImageJ
Authors: Campos Ana Bela , Duarte-Silva Sara , Ambrósio António Francisco , Maciel Patrícia , Fernandes Bruno
Published: August 2021

Microglial cells are the first line of defense within the central nervous system, with morphological characterization being widely used to define their activation status. Most methods to evaluate microglia status are manual, and, therefore, often biased, inaccurate, and time consuming. In fact, the process to collect morphological data starts with the acquisition of photomicrographs from where images of single cells are extracted. Then, the researcher collects the morphological features that characterize each cell. However, a manual data collection process from single cells can take weeks to complete. This work describes an open-source ImageJ plugin, MorphData, which automatizes the data extraction process of morphological features of single microglial cells. The plugin collects, processes, and organizes features associated with cell complexity and ramification. In a computer with limited computing power, MorphData was able to handle 699 single cells in less than 14 minutes. The same process, if performed manually, would take almost 19 working days. Overall, MorphData significantly reduces the time taken to collect morphological data from microglial cells, which can then be used to study, understand, and characterize microglia behavior in the brain of human patients or of animal models of neurological and psychiatric diseases.
Establishment of a prognosis prediction model based on pyroptosis-related signatures associated with the immune microenvironment and molecular heterogeneity in clear cell renal carcinoma
Authors: Jiang Aimin , Meng Jialin , Bao Yewei , Wang Anbang , Gong Wenliang , Gan Xinxin , Wang Jie , Bao Yi , Wu Zhenjie , Lu Juan , Liu Bing , Wang Linhui
Published: August 2021

Background

Pytoptosis is essential for tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the heterogeneity of pyroposis and its relationship with the tumor microenvironment (TME) remain unclear. The aim of the present study was to identify proptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures.

Methods

First, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model establsihed by LASSO regression was verified by ICGC database. Then, the clinical significance, functional status, immune infiltration, cell-cell communication, genomic alteration and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model.

Results

Two heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype, and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in C2 subgroup was lower than that in C1 subgroup. Pyroptosis related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters via Pyroptosis related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while C2 was characterized by more significant alterations in SPEN and ROS1 mutation. Finally, we constructed and validated a robust and promising signature based on the pyroptosis-related risk score for assessing the prognosis in ccRCC.

Conclusion

We identified two heterogeneous pyroptosis subtypes and 5 reliable risk signatures to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.
Pupil correlates of decision variables in mice playing a competitive mixed-strategy game
Authors: Wang Hongli , Ortega Heather K. , Atilgan Huriye , Murphy Cayla E. , Kwan Alex C.
Published: August 2021

In a competitive game involving an animal and an opponent, the outcome is contingent on the choices of both players. To succeed, the animal must continually adapt to competitive pressure, or else risk being exploited and lose out on rewards. In this study, we demonstrate that head-fixed mice can be trained to play the iterative competitive game ‘matching pennies’ against a virtual computer opponent. We find that the animals’ performance is well described by a hybrid computational model that includes Q-learning and choice kernels. Comparing between matching pennies and a non-competitive two-armed bandit task, we show that the tasks encourage animals to operate at different regimes of reinforcement learning. To understand the involvement of neuromodulatory mechanisms, we measure fluctuations in pupil size and use multiple linear regression to relate the trial-by-trial transient pupil responses to decision-related variables. The analysis reveals that pupil responses are modulated by observable variables, including choice and outcome, as well as latent variables for value updating, but not action selection. Collectively, these results establish a paradigm for studying competitive decision-making in head-fixed mice and provide insights into the role of arousal-linked neuromodulation in the decision process.
Division of Labor between SOS and PafBC in mycobacterial DNA Repair and Mutagenesis
Authors: Adefisayo Oyindamola O. , Dupuy Pierre , Bean James M. , Glickman Michael S.
Published: August 2021

DNA repair systems allow microbes to survive in diverse environments that compromise chromosomal integrity. Pathogens such as M. tuberculosis must contend with the genotoxic host environment, which generates the mutations that underlie antibiotic resistance. Mycobacteria encode the widely distributed SOS pathway, governed by the LexA repressor, but also encode PafBC, a positive regulator of the transcriptional DNA damage response (DDR). Although the transcriptional outputs of these systems have been characterized, their full functional division of labor in survival and mutagenesis is unknown. Here we specifically ablate the PafBC or SOS pathways, alone and in combination, and test their relative contributions to repair. We find that SOS and PafBC have both distinct and overlapping roles that depend on the type of DNA damage. Most notably, we find that quinolone antibiotics and replication fork perturbation are inducers of the PafBC pathway, and that chromosomal mutagenesis is codependent on PafBC and SOS, through shared regulation of the DnaE2/ImuA/B mutasome. These studies define the complex transcriptional regulatory network of the DDR in mycobacteria and provide new insight into the regulatory mechanisms controlling the genesis of antibiotic resistance in M. tuberculosis.
Functionalized Biomimetic Hydrogels Enhance Salivary Stem/Progenitor Cell Organization
Authors: Martinez Mariane , Witt Robert L. , Farach-Carson Mary C. , Harrington Daniel A.
Published: August 2021

Complex branched salivary structures remain challenging to replicate within implant ready hydrogels. We showed previously that hyaluronic acid (HA)-based hydrogels enable growth and organization of primary salivary-derived human stem/progenitor cells (hS/PCs) into multicellular spheroids. Here, we systematically functionalized three components of migration-permissive hydrogels to foster salivary tissue morphogenesis. We separately analyzed contributions of an enzymatically degradable crosslinker, a pendant integrin-binding site, and hydrogel porosity to best support high viability, integrin-dependent cell adhesion and migration. Structure size, frequency, and morphology were all affected by hydrogel crosslink density and integration of biofunctional peptides. Viability and proliferation data suggested that integration of integrin binding sites had the greatest effect on hS/PCs behavior. A larger internal matrix space, created by increasing both crosslinker length and PEG content, was needed to form large multicellular hS/PC structures. Peptide-modified hydrogels with more internal space shifted hS/PC organization from spheroidal, surrounded by thick basement membrane, to an asymmetric arrangement with punctate matrix proteins defining a “wrinkled” perimeter. Integrin-binding peptides activated integrin β1, with highest activation observed in hydrogels having both cleavable peptide and integrin ligand. The design parameters we prescribe allowed us to encapsulate hS/PCs in a humanized biomimetic hydrogel matrix able to support morphogenesis needed for salivary restoration.
Neural manifolds for odor-driven innate and acquired appetitive preferences
Authors: Chandak Rishabh , Raman Barani
Published: August 2021

Sensory stimuli evoke spiking neural responses that innately or after learning drive suitable behavioral outputs. How are these spiking activities intrinsically patterned to encode for innate preferences, and could the neural response organization impose constraints on learning? We examined this issue in the locust olfactory system. Using a diverse odor panel, we found that ensemble activities both during (‘ON response’) and after stimulus presentations (‘OFF response’) could be linearly mapped onto overall appetitive preference indices. Although diverse, ON and OFF response patterns generated by innately appetitive odorants were still limited to a low-dimensional subspace (a ‘neural manifold’). Similarly, innately non-appetitive odorants evoked responses that were separable yet confined to another neural manifold. Notably, only odorants that evoked neural response excursions in the appetitive manifold were conducive for learning. In sum, these results provide insights on how encoding for innate preferences can also set limits on associative learning.
Global change affects differently at local scales animal populations: why Starlings still expands to the south while other temperate species go to the north?
Authors: Rodriguez Alexandra , La Gioia Giuseppe , Le Quilliec Patricia , Fourcy Damien , Clergeau Philippe
Published: August 2021

Global change, which regroups global warming, landscape transformations and other anthropic modifications of ecosystems, has effects on populations and communities and produces modifications in the expansion area of species. While some species disappear, other ones are beneficiated by the new conditions and some of them evolve in new adapted forms or leave their ancient distribution area.

As climate change tends to increase the temperature in several regions of the world, some species have been seen to leave areas in equatorial regions in order to join colder areas either towards the north of the northern hemisphere or towards the south of the southern one.

Many birds as have moved geographically in direction to the poles and in many cases they have anticipated their laying dates. Actually, two tit species that use to lay their eggs in a period that their fledging dates synchronize with the emerging dates of caterpillars are now evolving to reproductive in periods earlier than before the climate change. Several species are reacting like that and other ones are moving to the north in Europe for example. Nevertheless, and very curiously, European starling, Sturnus vulgaris, populations are behaving on the contrary: their laying dates are moving towards later spring and their distribution area is moving towards the south. In this study we explore and discuss about different factors that may explain this difference from other birds.
Age and smoking predict antibody titres at 3 months after the second dose of the BNT162b2 COVID-19 vaccine
Authors: Nomura Yushi , Sawahata Michiru , Nakamura Yosikazu , Kurihara Momoko , Koike Ryousuke , Katsube Otohiro , Hagiwara Koichi , Niho Seiji , Masuda Norihiro , Tanaka Takaaki , Sugiyama Kumiya
Published: August 2021

Objective

We aimed to determine antibody (Ab) titres 3 months after the second dose of the BNT162b2 coronavirus disease-2019 (COVID-19) vaccine and to explore clinical variables predicting these titres in Japan.

Methods

We enrolled 378 healthcare workers (255 women, 123 men) whose blood samples were collected 91±15 days after the second of two inoculations of the BNT162b2 COVID-19 mRNA vaccine (Pfizer/BioNTech) given 3 weeks apart. Medical histories and demographic characteristics were recorded using a structured self-reported questionnaire. The relationships between Ab titres and these factors were analysed.

Results

Median age (interquartile range [IQR]) of the participants was 44 (32-54) years. Median Ab titre (IQR) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen was 764 (423-1140) U/mL. Older participants had significantly lower Ab titres; median (IQR) Ab titres were 942 (675-1390) and 1095 (741-1613) U/mL in men and women in their 20s, respectively, but 490 (297-571) and 519 (285-761) U/mL in men and women in their 60s-70s, respectively. In the age-adjusted analysis, the only risk factors for lower Ab titres were male sex and smoking. However, the sex difference may have arisen from the sex difference in smoking rate. Moreover, Ab titres were significantly lower in current smokers than in ex-smokers.

Conclusion

The most important factors associated with low Ab titres were age and smoking habit. In particular, current smoking status caused lower Ab titres, and smoking cessation before vaccination may improve the individual efficacy of the BNT162b2 vaccine.
Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow
Authors: Liu Zixian , Wang Jinhong , Xie Miner , Wu Peng , Ma Yao , Zhang Sen , Wang Xiaofang , Dong Fang , Cheng Hui , Zhu Ping , Han Mingzhe , Ema Hideo
Published: August 2021

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in C57BL/6 mice. Single-cell transplantation and single-cell colony assay showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average eight megakaryocytes per colony) than did previously reported megakaryocyte progenitors (MkPs). Single-cell RNA-sequencing supported that these MgPs lie between HSCs and MkPs along the megakaryocyte differentiation pathway. Single-cell colony assay and single-cell RT-PCR analysis suggested the coexpression of CD41 and Pf4 is associated with megakaryocyte colony-forming activity. Single-cell colony assay of a small number of cells generated from single HSCs in culture suggested that MgPs are not direct progeny of HSCs. In this study, we propose a differentiation model in which HSCs give rise to MkPs through MgPs.
Assessment of native cadmium-resistant bacteria in cacao (Theobroma cacao L.) - cultivated soils
Authors: Cordoba-Novoa Henry A. , Cáceres-Zambrano Jeimmy , Torres-Rojas Esperanza
Published: August 2021

Traces of cadmium (Cd) have been reported in some chocolate products due to soils with Cd and the high ability of cacao plants to extract, transport, and accumulate it in their tissues. An agronomic strategy to minimize the uptake of Cd by plants is the use of cadmium-resistant bacteria (Cd-RB). However, knowledge about Cd-RB associated with cacao soils is scarce. This study was aimed to isolate and characterize Cd-RB associated with cacao-cultivated soils in Colombia that may be used in the bioremediation of Cd-polluted soils. Diversity of culturable Cd-RB, qualitative functional analysis related to nitrogen, phosphorous, carbon, and Cd were performed. Thirty different Cd-RB morphotypes were isolated from soils with medium (NC, Y1, Y2) and high (Y3) Cd concentrations using culture media with 6 mg Kg-1 Cd. Cd-RB were identified based on morphological and molecular analyses. The most abundant morphotypes (90%) were gram-negative belong to Phylum Proteobacteria and almost half of them showed the capacity to fix nitrogen, solubilize phosphates and degrade cellulose. Unique morphotypes were isolated from Y3 soils where Burkholderia and Pseudomonas were the dominant genera indicating their capacity to resist high Cd concentrations. P. putida GB78, P. aeruginosa NB2, and Burkholderia sp. NB10 were the only morphotypes that grew on 18 up to 90 (GB78) and 140 mg Kg-1 Cd (NB2-NB10); however, GB78 showed the highest Cd bioaccumulation (5.92 mg g-1). This study provides novel information about culturable Cd-RB soil diversity with the potential to develop biotechnology-based strategies.
Rotavirus pre-symptomatically downregulates ileum-innervating sympathetic nerves concomitant with increased intestinal transit and altered brain activity
Authors: Hellysaz Arash , Svensson Lennart , Hagbom Marie
Published: August 2021

While diarrhea, the hallmark symptom of rotavirus infection, has been considered to occur only due to intrinsic intestinal effects, we show evidence for central control underlying the symptomology. With large-scale 3D volumetric tissue imaging a mouse model, we show that rotavirus infection disrupts the autonomic balance by downregulating the noradrenergic sympathetic nervous system in ileum, concomitant with increased intestinal transit. A most interesting observation was that nervous response from CNS occurs pre-symptomatically, an observation that bring new understanding to how virus give raise to clinical symptoms. In the CNS of infected animals, we found increased pS6 immunoreactivity in the area postrema and decreased phosphorylated STAT5-immunoreactive neurons in the bed nucleus of the stria terminalis, which are associated with autonomic control including stress response. Our observations bring new and important knowledge of how rotavirus virus infection induce gut-nerve-brain crosstalk giving raise to sickness symptoms.