bluuebunny/crossref_metadata_2025 huggingface dataset:
Mandarin multidimensional health literacy questionnaire for patient supporting groups
Authors: Wu Chieh-Liang , Liou Chia-Hua , Liu Shih-An , Sheu Wayne H-H. , Tsai Shang-Feng
Published: November 2020

A patient support group (PSG) can serve the purposes of group therapy and education. However, how to evaluate outcome which can feedback to improve the PSG remains unclear. Health literacy, which is associated with patient outcome, has not been used in the evaluation of PSG.

Since 2017, we had conducted a working group dedicated to the creation and improvement of PSG. We applied a questionnaire (Mandarin Multidimensional Health Literacy Questionnaire, MMHLQ) for PSGs of all kinds of diseases (5 types, 8 diseases). The outcome was evaluated by the MMHLQ (5 dimensions, 20 variables). We determined factors (age, 1st-time/non-1st-time participation, and patient/family participation) that were associated with all 20 health literacy.

We finally obtained 458 questionnaires, with a response rate as high as 91.1% in 8 PSGs. Participants were 55.30 ± 16.39 y/o. The highest score was with the dimension of understanding (12.25 ± 1.85) and the lowest score was with the dimension of appraisal (10.66 ± 2.33). Participating patients (compared to family) were associated with a higher score with “obey the instruction of medical personnel to care disease” but lower score with “find health information from the network”. Moreover, older participants (age ≥65 years) had lower scores for all questions in MMHLQ, within which the dimension of appraisal received the lowest scores (P < .001).

We found that the highest score is with the dimension of understanding, and the lowest score with the dimension of appraisal. The elderly participants showed lower abilities in health literacy, especially with the dimension of the appraisal. Results from MMHLQ can be used to adjust the PSG curriculum to improve the health literacy of participants.
Evaluation of Fecal Incontinence in Pediatric Functional Constipation
Authors: Morera Claudio , Nurko Samuel , Rodriguez Leonel
Published: November 2020

Objectives:

The aim of the study is to evaluate the utility of motility studies in pediatric functional constipation with/without fecal incontinence.

Patients and Methods:

Patients with functional constipation and failure to conventional therapy undergoing colonic manometry (CM) and/or anorectal manometry (ARM) manometry were classified as functional constipation without fecal incontinence (FC) or with fecal incontinence (FCI). Clinical data, motility parameters, and treatment outcomes were compared.

Results:

A total of 280 were included, and all patients underwent CM (229 FC and 51 FCI) and 219 ARM. We found no difference in CM interpretation and presence of normal high amplitude propagating contractions (HAPCs) between groups; however, patients with FCI had higher frequency and presence of HAPCs and normal gastrocolonic meal response (GC). No CM parameter predicted outcomes. In FC, more patients with an abnormal CM responded to therapy compared to those with a normal study (79% vs 65% respectively, P = 0.04). FCI patients had lower median anal resting pressure compared to FC (49 vs 66 mmHg, respectively, P = 0.03); no other ARM parameter differentiated FC from FCI. We found no association between therapy response and ARM interpretation (P = 0.847) or any ARM parameter. A multivariate analysis found only male gender was associated with FCI (P < 0.001).

Conclusions:

FCI patients have higher frequency of normal CM parameters compared to FC, but overall interpretation was no different. CM helped predict response to therapy in FC but not in FCI. ARM demonstrated no added benefit in the evaluation of functional constipation with/without soiling. Patients with both normal ARM and CM had a lower response to therapy than those with abnormal studies.
Behind the Mask
Authors: Duckett Kathy
Published: November 2020

Gaining patient trust has been shown to improve health outcomes. Trust between the patient and the clinician starts with the clinician demonstrating empathy and positive attributes such as kindness and approachability. The advent of COVID-19 and the need for clinicians, patients, and caregivers to wear masks at all times has unintentionally limited nonverbal communication and potentially affected the ability of clinicians to quickly gain patients' and caregivers' trust. With so much time being spent on reeducating clinicians on infection control and donning and doffing personal protective equipment, agencies must not lose sight of the need to ensure that clinicians understand how to improve their communication skills while wearing a mask. This article provides tips on ways to use verbal and nonverbal communication to demonstrate empathy and to build trust in patient interactions to offset the difficulties wearing a mask can impose.
Association of Monocyte Migration Marker CD11b With Pulmonary Function in People Living With HIV
Authors: Kuniholm Mark H. , Bramah-Lawani Mariam , Fitzpatrick Meghan , Nouraie Mehdi , Qin Shulin , Huang Laurence , Vallejo Abbe N. , Landay Alan L. , Morris Alison
Published: November 2020

Background:

Maladaptive immune responses contribute to the pathogenesis of many chronic lung diseases. Here, we tested hypotheses that CD4 and CD8 T-cell and monocyte phenotypes are associated with lung function in people living with HIV and those without HIV.

Methods:

Markers of T cell differentiation, activation, exhaustion and senescence, and markers of monocyte recruitment and migration were quantified in 142 HIV-positive and 73 HIV-negative participants of the Pittsburgh HIV Lung Cohort. All participants underwent lung function testing.

Results:

CD4 or CD8 T-cell phenotypes were not associated with measures of lung function in HIV-positive or HIV-negative participants after adjustment for multiple comparisons. In HIV-positive participants, however, the percentage of classical monocytes that were CD11b+ had positive associations at the Bonferroni-adjusted significance threshold of P = 0.05/63 with prebronchodilator and postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (β = 0.36; P = 0.00003 and β = 0.31; P = 0.0003, respectively). In stratified analyses of n = 87 participants with CD4 ≥ 500 cells/µL, associations of percentage of classical monocytes that were CD11b+ with prebronchodilator and postbronchodilator FEV1/FVC ratio were stronger (β = 0.48 and β = 0.41, for pre- and post-, respectively) than in the entire HIV-positive study population. Significant associations of monocyte phenotypes were not observed in HIV-negative participants after adjustment for multiple comparisons.

Conclusions:

CD11b+ expression on classical monocytes is positively associated with FEV1/FVC ratio in people living with HIV including in those with CD4 T-cell recovery. Given the normal surveillance activity of monocytes, such association suggests this monocyte subset may play a role in preservation of pulmonary function in PLWH.
Integrating HIV Preexposure Prophylaxis With Community-Based Syringe Services for Women Who Inject Drugs: Results From the Project SHE Demonstration Study
Authors: Roth Alexis M. , Tran Nguyen K. , Felsher Marisa , Gadegbeku Annette B. , Piecara Brogan , Fox Rachel , Krakower Douglas S. , Bellamy Scarlett L. , Amico K. Rivet , Benitez Jose A. , Van Der Pol Barbara
Published: November 2020

Introduction:

To guide future preexposure prophylaxis (PrEP) implementation for women who inject drugs (WWID), a population increasingly represented in new HIV cases in the United States, we present results from a demonstration project integrated within a syringe services program (SSP) in Philadelphia, PA.

Methods:

WWID ≥18 years were educated about and offered 24 weeks of daily PrEP. Participants completed surveys and clinical assessments at baseline and at weeks 1, 3, 12, and 24. We used descriptive statistics to estimate feasibility/acceptability, engagement in the care cascade, HIV/sexually transmitted diseases (STI) and pregnancy, issues of safety/tolerability, and preferences/satisfaction with PrEP services. Multivariable logistic regression with generalized estimating equations was used to identify factors associated with PrEP uptake and retention.

Results:

We recruited 136 WWID. Of those, 95 were included in the final sample, and 63 accepted a PrEP prescription at week 1. Uptake was associated with greater baseline frequency of SSP access [adjusted odds ratio (aOR) = 1.85; 95% confidence interval (CI): 1.24 to 2.77], inconsistent condom use (aOR = 3.38; 95% CI: 1.07 to 10.7), and experiencing sexual assault (aOR = 5.89; 95% CI: 1.02, 33.9). Of these 95, 42 (44.2%) were retained at week 24. Retention was higher among women who reported more frequent baseline SSP access (aOR = 1.46; 95% CI: 1.04 to 2.24). Self-reported adherence was high but discordant with urine-based quantification of tenofovir. Baseline STI prevalence was 17.9%; there were 2 HIV seroconversions and 1 pregnancy. Safety/tolerability issues were uncommon, and acceptability/satisfaction was high.

Conclusions:

Integrating PrEP with SSP services is feasible and acceptable for WWID. This suggests that daily PrEP is a viable prevention tool for this vulnerable population.
Efficacy of Serious Games in Healthcare Professions Education
Authors: Maheu-Cadotte Marc-André , Cossette Sylvie , Dubé Véronique , Fontaine Guillaume , Lavallée Andréane , Lavoie Patrick , Mailhot Tanya , Deschênes Marie-France
Published: November 2020

Summary Statement

Serious games (SGs) are interactive and entertaining software designed primarily with an educational purpose. This systematic review synthesizes evidence from experimental studies regarding the efficacy of SGs for supporting engagement and improving learning outcomes in healthcare professions education. Randomized controlled trials (RCTs) published between January 2005 and April 2019 were included. Reference selection and data extraction were performed in duplicate, independently. Thirty-seven RCTs were found and 29 were included in random-effect meta-analyses. Compared with other educational interventions, SGs did not lead to more time spent with the intervention {mean difference 23.21 minutes [95% confidence interval (CI) = −1.25 to 47.66]}, higher knowledge acquisition [standardized mean difference (SMD) = 0.16 (95% CI = −0.20 to 0.52)], cognitive [SMD 0.08 (95% CI = −0.73 to 0.89)], and procedural skills development [SMD 0.05 (95% CI = −0.78 to 0.87)], attitude change [SMD = −0.09 (95% CI = −0.38 to 0.20)], nor behavior change [SMD = 0.2 (95% CI = −0.11 to 0.51)]. Only a small SMD of 0.27 (95% CI = 0.01 to 0.53) was found in favor of SGs for improving confidence in skills.
“I Guess I Didn't Like That Word Unfortunately”
Authors: Koski Kaisu , Ostherr Kirsten
Published: November 2020

Introduction

This article explores tacit techniques embedded in standardized patients' (SPs) unscripted dialog in a context of breaking bad news (BBN) education. It identifies a technique in which the SP explicitly repeats 1 or more of the medical student's words and analyzes the function and impact of this technique.

Methods

This film-based ethnographic inquiry used conversation analysis to examine so-called echo utterances, through which the SP repeats all or part of what the student has said. The data set includes 9 student encounters with 2 female SPs who specialize in the BBN simulation.

Results

The authors identified a technique of “repair request” used by the SPs to provide an opportunity for the student to reformulate their utterance in character. Repair requests emerged from 4 main types of student speech: speculative language, inappropriate utterances, awkward timing, and medical jargon.

Conclusions

The technique of repair request is used to heighten the student's language sensitivity and foster the ability to respond to criticism or misunderstanding in character. Discovery of the tacit, unscripted technique of repair request in this study provides an opportunity to disseminate this technique in SP training for BBN and other simulation scenarios. These findings suggest the need for further research to identify additional tacit techniques used by SPs to improve medical education.
COVID-19 in Hospitalized Ethiopian Children: Characteristics and Outcome Profile
Authors: Leulseged Tigist Workneh , Hassen Ishmael Shemsedin , Maru Endalkachew Hailu , Zewde Wuletaw Chane , Chamiso Negat Woldehawariat , Edo Mesay Gemechu , Abebe Daniel Simeneh , Aliy Muktar Awol
Published: November 2020

Background

Considering the number of people affected and the burden to the health care system due to the Coronavirus pandemic, there is still a gap in understanding the disease better leaving a space for new evidence to be filled by researchers. This scarcity of evidence is observed especially among children with the virus. Therefore, this study aimed to assess the characteristics and outcome profile of children with COVID-19 admitted to Millennium COVID-19 Care Center in Ethiopia.

Methods

A prospective cohort study was conducted among 90 children with COVID-19 who were admitted from June 23 to September 17, 2020. Data was summarized using frequency tables, mean ± standard deviation or median with Inter Quartile range values. A chi-square test/ Fischer’s exact test was used to compare disease severity between groups.

Results

The median age of the participants was 15 years and 57 were females. The most common reported route of disease transmission was through close contact with a diagnosed person (41/90). Only three had a history of pre-existing comorbid illness. One-third (31/90) had one or more symptoms at diagnosis, the most common being cough (20/90). Among the 90 patients, 59 were asymptomatic, 14 had mild disease and the rest 17 had moderate disease. Based on the chi-square/ Fischer’s exact test result, no statistically significant difference was observed between the age groups and sex.

Conclusions

Pediatric patients seemed to have a milder disease presentation and a favorable outcome compared to other countries report and also the adult pattern observed in our country.
Estimating latent positions in social and biological networks using Graph Neural Networks in R with GCN4R
Authors: Levy Joshua , Bobak Carly , Christensen Brock , Vaickus Louis , O’Malley James
Published: November 2020

Network analysis methods are useful to better understand and contextualize relationships between entities. While statistical and machine learning prediction models generally assume independence between actors, network-based statistical methods for social network data allow for dyadic dependence between actors. While numerous methods have been developed for the R statistical software to analyze such data, deep learning methods have not been implemented in this language. Here, we introduce GCN4R, an R library for fitting graph neural networks on independent networks to aggregate actor covariate information to yield meaningful embeddings for a variety of network-based tasks (e.g. community detection, peer effects models, social influence). We provide an extensive overview of insights and methods utilized by the deep learning community on learning on social and biological networks, followed by a tutorial that demonstrates some of the capabilities of the GCN4R framework to make these methods more accessible to the R research community.
Strong and localized recurrence controls dimensionality of neural activity across brain areas
Authors: Dahmen David , Recanatesi Stefano , Jia Xiaoxuan , Ocker Gabriel K. , Campagnola Luke , Seeman Stephanie , Jarsky Tim , Helias Moritz , Shea-Brown Eric
Published: November 2020

The brain contains an astronomical number of neurons, but it is their collective activity that underlies brain function. The number of degrees of freedom that this collective activity explores – its dimensionality – is therefore a fundamental signature of neural dynamics and computation (1–7). However, it is not known what controls this dimensionality in the biological brain – and in particular whether and how recurrent synaptic networks play a role (8–10). Through analysis of high-density Neuropixels recordings (11), we argue that areas across the mouse cortex operate in asensitive regimethat gives these synaptic networks a very strong role in controlling dimensionality. We show that this control is expressed across time, as cortical activity transitions among states with different dimensionalities. Moreover, we show that the control is mediated through highly tractable features of synaptic networks. We then analyze these key features via a massive synaptic physiology dataset (12). Quantifying these features in terms of cell-type specific network motifs, we find that the synaptic patterns that impact dimensionality are prevalent in both mouse and human brains. Thus local circuitry scales up systematically to help control the degrees of freedom that brain networks may explore and exploit.
Information-theory-based benchmarking and feature selection algorithm improve cell type annotation and reproducibility of single cell RNA-seq data analysis pipelines
Authors: Ren Ziyou , Gerlach Martin , Shi Hanyu , Budinger GR Scott , Nunes Amaral Luís A.
Published: November 2020

Single cell RNA sequencing (scRNA-seq) data are now routinely generated in experimental practice because of their promise to enable the quantitative study of biological processes at the single cell level. However, cell type and cell state annotations remain an important computational challenge in analyzing scRNA-seq data. Here, we report on the development of a benchmark dataset where reference annotations are generated independently from transcriptomic measurements. We used this benchmark to systematically investigate the impact on labelling accuracy of different approaches to feature selection, of different clustering algorithms, and of different sets of parameter values. We show that an approach grounded on information theory can provide a general, reliable, and accurate process for discarding uninformative features and to optimize cluster resolution in single cell RNA-seq data analysis.
ntHits:de novorepeat identification of genomics data using a streaming approach
Authors: Mohamadi Hamid , Chu Justin , Coombe Lauren , Warren Rene , Birol Inanc
Published: November 2020

Motivation

Repeat elements such as satellites, transposons, high number of gene copies, and segmental duplications are abundant in eukaryotic genomes. They often induce many local alignments, complicating sequence assembly and comparisons between genomes and analysis of large-scale duplications and rearrangements. Hence, identification and classification of repeats is a fundamental step in many genomics applications and their downstream analysis tools.

Results

In this work, we present an efficient streaming algorithm and software tool, ntHits, forde novorepeat identification based on the statistical analysis of thek-mer content profile of large-scale DNA sequencing data. In the proposed algorithm, we first obtain thek-mer coverage histograms of input datasets using the ntCard algorithm, an efficient streaming algorithm for estimating thek-mer coverage histograms. From the obtainedk-mer coverage histogram, the repetitivek-mers would present a long tail to the distribution ofk-mer coverage profile. Experimental results show that ntHits can efficiently and accurately identify the repeat content in large-scale DNA sequencing data. For example, ntHits accurately identifies the repeatk-mers in the white spruce sequencing data set with 96× sequencing coverage in about 12 hours and using less than 150GB of memory, while using the exact methods for reporting the repeatedk-mers takes several days and terabytes of memory and disk space.

Availability

ntHits is written in C++ and is released under the MIT License. It is freely available athttps://github.com/bcgsc/ntHits.

Contact

hmohamadi@bcgsc.ca
Estimating direct and indirect genetic effects on offspring phenotypes using genome-wide summary results data: a comparison of multivariate methods
Authors: Warrington Nicole M. , Hwang Liang-Dar , Nivard Michel , Evans David M.
Published: November 2020

Estimation of the direct genetic effect of an individuals’ own genotype on their phenotype, independent of any contaminating indirect parental genetic effects is becoming increasingly important. These conditional estimates are of interest in their own right, but are also useful for downstream analyses such as intergenerational Mendelian randomization. We compare several available multivariate methods that utilize summary results statistics from genome-wide association studies to determine how well they estimate conditional direct and indirect genetic effects, while accounting for sample overlap. Using robustly associated birth weight variants and data from the UK Biobank, we contrasted the point estimates and their standard errors at each of the individual loci compared to those obtained using individual level genotype data, in addition to comparing the computational time, inflation of the test statistics and number of genome-wide significant SNPs identified by each of the methods. We show that Genomic SEM outperforms the other methods in accurately estimating conditional genetic effects and their standard errors. We subsequently applied Genomic SEM to fertility data in the UK Biobank and partitioned the genetic effect into female and male fertility in addition to a sibling specific effect. This analysis identified one novel locus for fertility and replicated seven previously identified loci. We also identified genetic correlations between fertility and educational attainment, risk taking behaviour, autism and subjective well-being. We therefore recommend Genomic SEM to be used to partition genetic effects across the genome into direct and indirect components.
Demarcation line determination for diagnosis of gastric cancer disease range using unsupervised machine learning in magnifying narrow-band imaging
Authors: Okumura Shunsuke , Goudo Misa , Hiwa Satoru , Yasuda Takeshi , Kitae Hiroaki , Yasuda Yuriko , Tomie Akira , Omatsu Tatsushi , Ichikawa Hiroshi , Yagi Nobuaki , Hiroyasu Tomoyuki
Published: November 2020

Objectives

It is important to determine an accurate demarcation line (DL) between the cancerous lesions and background mucosa in magnifying narrow-band imaging (M-NBI)-based diagnosis. However, it is difficult for novice endoscopists. Our aim was to automatically determine the accurate DL using a machine learning method.

Methods

We used an unsupervised machine learning approach to determine the DLs because it can reduce the burden of training machine learning models and labeling large datasets. Our method consists of the following four steps: 1) An M-NBI image is segmented into superpixels (a group of neighboring pixels) using simple linear iterative clustering. 2) The image features are extracted for each superpixel. 3) The superpixels are grouped into several clusters using the k-means method. 4) The boundaries of the clusters are extracted as DL candidates. To validate the proposed method, 23 M-NBI images of 11 cases were used for performance evaluation. The evaluation investigated the similarity of the DLs identified by endoscopists and our method, and the Euclidean distance between the two DLs was calculated. For the single case of 11 cases, the histopathological examination was also conducted and was used to evaluate the proposed system.

Results

The average Euclidean distances for the 11 cases were10.65, 11.97, 7.82, 8.46, 8.59, 9.72, 12.20, 9.06, 22.86, 8.45, and 25.36. The results indicated that the specific selection of the number of clusters enabled the proposed method to detect DLs that were similar to those of the endoscopists. The DLs identified by our method represented the complex shapes of the DLs, similarly to those identified by experienced doctors. Also, it was confirmed that the proposed system could generate the pathologically valid DLs by increasing the number of clusters.

Conclusions

Our proposed system can support the training of inexperienced doctors, as well as enrich the knowledge of experienced doctors in endoscopy.
Retrospective survey from Vascular Access Team Lombardy Net in COVID-19 era
Authors: Antonio Gidaro , Davide Vailati , Marco Gemma , Francesca Lugli , Francesco Casella , Chiara Cogliati , Antonio Canelli , Cremonesi Nadia , Davide Monolo , Giuseppe Cordio , Chiara Frosi , Riccardo Destefanis , Anna Rossi , Chiara Alemanno Maria , Franco Valenza , Stefano Elli , Andrea Caldarini , Alberto Lucchini , Stefano Paglia , Monica Baroni , Davide Giustivi
Published: November 2020

Background

Venous Access Devices (VADs) are the most used device in COVID-19 patients.

Objective

Identify VADs implanted, catheter related thrombosis (CRT), catheter-related bloodstream infection (CRBSI), and accidental remove of VADs in both COVID-19 positive and COVID-19 free patients. Successive analysis was conducted comparing COVID-19 positive patients with COVID-19 free with inverse probability propensity score weights using simple regression to account for these two confounders (peripheral tip as central/peripheral and hospitalization as no/yes).

Methods

This multicenter, retrospective cohort study was conducted using data from 7 hospitals in Lombardy during the pandemic period from February 21st to May 31st 2020.

Results

2206 VADs were evaluated, of which 1107 (50.2%) were inserted in COVID-19 patients. In COVID-19 cohort the first choice was Long Peripheral Cannula in 388 patients (35.1%) followed by Midline Catheter in 385 (34.8%). The number of “central tip” VADs inserted in COVID-free inpatients and COVID-19 positive were similar (307vs334). We recorded 42 (1.9%) CRT; 32 (79.2%) were observed in COVID-19 patients. 19 CRBSI were diagnosed; 15 (78.95%) were observed in COVID-19. Accidental removals were the more represented complication with 123 cases, 85 (69.1%) of them were in COVID-19. COVID-19 significantly predicted occurrence of CRT (OR = 2.00(1.85-5.03); P<0.001), CRSB (OR = 3.82(1.82-8.97); P<0.001), and Accidental Removal (OR = 2.39(1.80-3.20); P<0.001) in our propensity score weighted models.

Conclusions

CRT, CRBSI, and accidental removal are significantly more frequent in COVID-19 patients. Accidental removals are the principal complication, for this reason use of subcutaneously anchored securement is recommended for shorter period than usual.
Connection “Stripes” in the Primate Insula
Authors: Krockenberger M. , Saleh T.O. , Logothetis N.K. , Evrard H.C.
Published: November 2020

The insula has been classically divided into vast granular, dysgranular and agranular sectors. Over the years, several distinct studies proposed subdivisions of these sectors, with however no consensus. We recently proposed a cyto- and myelo-architectonic partition in which each sector contained sharply delimited areas (Evrardet al.2014 J Comp Neurol 522: 64-97). Some of these areas were further divided into distinct subareas with obvious functional implications. Here, we examined the spatial relationship between architectonic boundaries and tract-tracing labeling in the insula in the macaque monkey. Injections of neuronal tracers in distinct areas of the prefrontal or anterior cingulate cortices produced heterogeneous and discontinuous patterns of anterograde and retrograde labeling in the insula. These patterns were made of sharply delimited patches forming anteroposterior stripes across consecutive coronal sections. While the overall pattern of labeling varied with the injection site, the patches systematically coincided with specific architectonic subareas, particularly in the dysgranular insula. This unequivocally validates our prior architectonic partition and strongly supports the idea of a refined modularBauplanof the primate insula. This modular organization may underlie a serial stream of integration of interoception with ‘self-agency’ and ‘social’ activities across distinct insulo-prefrontal processing units that need to be explored.
Deep Learning Enables Individual Xenograft Cell Classification in Histological Images by Analysis of Contextual Features
Authors: Juppet Quentin , De Martino Fabio , Weigert Martin , Burri Olivier , Unser Michaël , Brisken Cathrin , Sage Daniel
Published: November 2020

Patient-Derived Xenografts (PDXs) are the preclinical models which best recapitulate inter- and intra-patient complexity of human breast malignancies, and are also emerging as useful tools to study the normal breast epithelium. However, data analysis generated with such models is often confounded by the presence of host cells and can give rise to data misinterpretation. For instance, it is important to discriminate between xenografted and host cells in histological sections prior to performing immunostainings. We developed Single Cell Classifier (SCC), a data-driven deep learning-based computational tool that provides an innovative approach for automated cell species discrimination based on a multi-step process entailing nuclei segmentation and single cell classification. We show that human and murine cells contextual features, more than cell-intrinsic ones, can be exploited to discriminate between cell species in both normal and malignant tissues, yielding up to 96% classification accuracy. SCC will facilitate the interpretation of H&E stained histological sections of xenografted human-in-mouse tissues and it is open to new in-house built models for further applications. SCC is released as an open-source plugin in ImageJ/Fiji available at the following link:https://github.com/Biomedical-Imaging-Group/SingleCellClassifier.

Author summary

Breast cancer is the most commonly diagnosed tumor in women worldwide and its incidence in the population is increasing over time. Because our understanding of such disease has been hampered by the lack of adequate human preclinical model, efforts have been made in order to develop better approaches to model the human complexity. Recent advances in this regard were achieved with Patient-Derived Xenografts (PDXs), which entail the implantation of human-derived specimens to recipient immunosuppressed mice and are, thus far, the preclinical system best recapitulating the heterogeneity of both normal and malignant human tissues. However, histological analyses of the resulting tissues are usually confounded by the presence of cells of different species. To circumvent this hurdle and to facilitate the discrimination of human and murine cells in xenografted samples, we developed Single Cell Classifier (SCC), a deep learning-based open-source software, available as a plugin in ImageJ/Fiji, performing automated species classification of individual cells in H&E stained sections. We show that SCC can reach up to 96% classification accuracy to classify cells of different species mainly leveraging on their contextual features in both normal and tumor PDXs. SCC will improve and automate histological analyses of human-in-mouse xenografts and is open to new in-house built models for further classification tasks and applications in image analysis.
Proximate and Genetic Analysis of Blackfin Tuna (T. atlanticus)
Authors: Núñez-Mata Yuridia M. , Ríos Rodríguez Jesse R. , Perales-Torres Adriana L. , De la Rosa-Reyna Xochitl F. , Vázquez-Rodríguez Jesús A. , Fernández-Santos Nadia A. , Montoya Humberto Martínez
Published: November 2020

The tuna meat is a nutritious food that possesses high content of protein, its low content of saturated fatty acids makes it a high demand food in the world. TheThunnusgenus is composed of eight species, albacore (T. alalunga), bigeye (T. obesus), long tail tuna (T. tonggol), yellowfin tuna (T. albacares), pacific bluefin tuna (T. orientalis), bluefin tuna (T. maccoyii), Atlantic bluefin tuna (T. thynnus) and blackfin tuna (T. atlanticus). The blackfin tuna (BFT) (Thunnus atlanticus) represent the smallest species within theThunnusgenus. This species inhabits the warm waters of the West Atlantic Ocean, from the shore of Massachusetts in the north, to Rio De Janeiro in Brazil. The first objective of this study was to evaluate the nutritional composition of BFT captured in the Gulf of Mexico, we determined ash, moisture, fat, protein and carbohydrates in BFT muscle and compared the obtained data with the nutritional reports from commercial tuna species including yellowfin tuna, Atlantic bluefin tuna and salmon (Salmo salar).

Secondly, we report the genetic diversity and genetic differentiation of BFT within its geographical distribution range using the Cytochrome Oxidase I (COI) and control region sequenced data and from specimens collected in the Gulf of Mexico. We observed a nucleotide diversity π=0.001, 24 segregating sites and 10 parsimony informative. Within the CR we found nine different haplotypes π=0.044, 39 segregating sites, 16 parsimony informative sites. We concluded that according with the haplotype distribution there are differences among the BFT from the Gulf of Mexico and the North Atlantic compared to the South Atlantic. The Caribbean Sea is a migration point of the BFT, where all except the South Atlantic haplotypes were found.
Transcriptome atlas ofPhalaenopsis equestris
Authors: Klepikova Anna V. , Kasianov Artem S. , Ezhova Margarita A. , Penin Aleksey A. , Logacheva Maria D.
Published: November 2020

The vast diversity of Orchidaceae together with sophisticated adaptations to pollinators and other unique features make this family an attractive model for evolutionary and functional studies. The sequenced genome ofPhalaenopsis equestrisfacilitates Orchidaceae research. Here we present an RNA-seq based transcriptome map ofP. equestriswhich covers 19 organs of the plant including leaves, roots, floral organs and shoot apical meristem. We demonstrated the high quality of the data and showed the similarity ofP. equestristranscriptome map with gene expression atlases of other plants. The transcriptome map can be easily accessed through our database Transcriptome Variation Analysis (TraVA) visualizing gene expression profiles. As an example of the application we analyzed the expression ofPhalaenopsis“orphan” genes – the ones that do not have recognizable similarity with genes of other plants. We found that about a half of them are not expressed; the ones that are expressed have a predominant expression pattern in reproductive structures.
No leading-edge effect in North Atlantic harbor porpoises: Evolutionary and conservation implications
Authors: Chehida Yacine Ben , Loughnane Roisin , Thumloup Julie , Kaschner Kristin , Garilao Cristina , Rosel Patricia E. , Fontaine Michael C.
Published: November 2020

Understanding a species response to past environmental changes can help forecast how they will cope with ongoing climate changes. Harbor porpoises are widely distributed in the North Atlantic and were deeply impacted by the Pleistocene changes with the split of three sub-species. Despite major impacts of fisheries on natural populations, little is known about population connectivity and dispersal, how they reacted to the Pleistocene changes and how they will evolve in the future. Here, we used phylogenetics, population genetics, and predictive habitat modelling to investigate population structure and phylogeographic history of the North Atlantic porpoises. A total of 925 porpoises were characterized at 10 microsatellite loci and one-quarter of the mitogenome (mtDNA). A highly divergent mtDNA lineage was uncovered in one porpoise off Western Greenland, suggesting that a cryptic group may occur and could belong to a recently discovered mesopelagic ecotype off Greenland. Aside from it and the southern sub-species, spatial genetic variation showed that porpoises from both sides of the North Atlantic form a continuous system belonging to the same subspecies (Phocoena phocoena phoceona). Yet, we identified important departures from random mating and restricted intergenerational dispersal forming a highly significant isolation-by-distance (IBD) at both mtDNA and nuclear markers. A ten times stronger IBD at mtDNA compared to nuclear loci supported previous evidence of female philopatry. Together with the lack of spatial trends in genetic diversity, this IBD suggests that migration-drift equilibrium has been reached, erasing any genetic signal of a leading-edge effect that accompanied the predicted recolonization of the northern habitats freed from Pleistocene ice. These results illuminate the processes shaping porpoise population structure and provide a framework for designing conservation strategies and forecasting future population evolution.
How simple cell to cell communication rules can generate and maintain scale invariant gradients of signalling activity across a multicellular population
Authors: Oldham Jack
Published: November 2020

This paper shows computationally and conceptually how gradients of signalling activity can be generated and dynamically maintained across a population of cells using very simple cell to cell communication rules. The rules work on the basis of cells regulating their production rate of a signalling molecule according to the production rates of their immediate neighbours. Highly stable, scale invariant signalling gradients can be formed across the population, with highest rates at the centre and lowest at the periphery.

The cell to cell communication behaviour that causes gradient formation is first explained in a descriptive, thought experiment type manner. It is then defined more formally using a conceptual, mathematically discrete computational model, which provides a network or graph type framework in which it is easy to analyse and control discrete signals that are sent between neighbouring cells. This provides an intuitive method of explaining how the signalling gradient emerges as a result of local cell to cell communication. Finally, examples of gradient formation are shown using software implementations of the model.
Highly conserved andcis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage
Authors: Degani Neta , Ainbinder Elena , Ulitsky Igor
Published: November 2020

Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterizeHOXA-AS3andHOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar homologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon, and their co-regulation by the CDX1/2 transcription factors. Functionally, the RNA products ofHOXA-AS3andHOXB-AS3regulate the expression of their overlapping HOX5–7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.
Environmental factors drive release ofPerkinsus marinusfrom infected oysters
Authors: Gignoux-Wolfsohn Sarah A. , Newcomb Matilda S. R. , Ruiz Gregory M. , Pagenkopp Lohan Katrina M.
Published: November 2020

Since the discovery ofPerkinsus marinusas the cause of dermo disease inCrassostrea virginica, salinity and temperature have been identified as the main environmental drivers of parasite prevalence. However, little is known about how these variables affect the movement of parasites from host to water column. In order to elucidate how environmental factors can influence the abundance of this parasite in the water column, we conducted a series of experiments testing the effects of time of day, temperature, and salinity on release ofP. marinuscells from infected oysters. We found thatP. marinuscells were released on a diurnal cycle, with most cells released during the hottest and brightest period of the day (12:00-18:00). Temperature also had a strong and immediate effect on number of cells released, but salinity did not, only influencing the intensity of infection over the course of several months. Taken together, our results demonstrate that 1) the number of parasites in the water column fluctuates according to a diurnal cycle, 2) temperature and salinity act on different timescales to influence parasite abundance, and 3) live infected oysters may substantially contribute to the abundance of transmissive parasites in the water column under particular environmental conditions.
Galectin-9 Regulates The Threshold of B Cell Activation and Autoimmunity
Authors: Smith Logan K. , Fawaz Kareem , Treanor Bebhinn
Published: November 2020

Despite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low affinity endogenous antigens are not fully understood. Here, we demonstrate a critical role for the glycan-binding protein galectin-9 in setting the threshold of B cell activation and that loss of this regulatory network is sufficient to drive spontaneous autoimmunity. We further demonstrate a critical role for galectin-9 in restraining not only conventional B-2 B cells, but also innate-like B-1a cells. We show that galectin-9 deficient mice have an expanded population of B1a cells and increased titers of B-1a derived autoantibodies. Mechanistically, we demonstrate that galectin-9 regulates BCR and distinct TLR responses in B-1a, but not B-1b cells, by regulating the interaction between BCR and TLRs with the regulatory molecules CD5 and CD180, respectively. In the absence of galectin-9, B-1a cells are more readily activated and secrete increased titers of autoantibodies that facilitate auto-antigen delivery to the spleen, driving autoimmune responses.
Analysing the Yeast Complexome - The Complex Portal rising to the challenge
Authors: Meldal Birgit H M , Pons Carles , Perfetto Livia , Del-Toro Noemi , Wong Edith , Aloy Patrick , Hermjakob Henning , Orchard Sandra , Porras Pablo
Published: November 2020

The EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data is freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration withSaccharomycesGenome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organismSaccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members.
Intracellular sterol sensing controls intestinal B cell differentiation
Authors: Trindade Bruno C. , Ceglia Simona , Berthelette Alyssa , Raso Fiona , Howley Kelsey , Muppidi Jagan R. , Reboldi Andrea
Published: November 2020

Intestinal B cell responses are critical for the maintenance of gut homeostasis, yet environmental signals that control B cell metabolism and effector function remain poorly characterized. Here, we show that Peyer’s patches germinal center (GC) B cells are sensitive to 25-hydroxycholesterol (25-HC), an oxidized metabolite of cholesterol produced by the enzyme cholesterol 25-hydroxylase (CH25H). In mice lacking CH25H, antigen-specific GC B cells show an increased cholesterol metabolic signature and preferentially differentiate in plasma cells (PCs), thereby inducing a stronger intestinal IgA response upon immunization or infection. GC B cells express the sterol sensor SREBP2 and use it to sense 25-HC. Deletion of SREBP2 from GC B cells prevents PC differentiation and forces the maintenance of GC identity. GC localized oxysterol production by follicular dendritic cells is central in dictating GC metabolism and imposing B cell fate. Our findings show that the 25-HC-SREBP2 axis shapes B cell effector function in intestinal lymphoid organs and indicate that dietary cholesterol can instruct local B cell response.
The Correlation of Substitution Effects Across Populations and Generations in the Presence of Non-Additive Functional Gene Action
Authors: Legarra A. , Garcia-Baccino C.A. , Wientjes Y.C.J. , Vitezica Z.G.
Published: November 2020

Allele substitution effects at quantitative trait loci (QTL) are part of the basis of quantitative genetics theory and applications such as association analysis and genomic prediction. In the presence of non-additive functional gene action, substitution effects are not constant across populations. We develop an original approach to model the difference in substitution effects across populations as a first order Taylor series expansion from a “focal” population. This expansion involves the difference in allele frequencies and second-order statistical effects (additive by additive and dominance). The change in allele frequencies is a function of relationships (or genetic distances) across populations. As a result, it is possible to estimate the correlation of substitution effects across two populations using three elements: magnitudes of additive, dominance and additive by additive variances; relationships (Nei’s minimum distances or Fst indexes); and assumed heterozygosities. Similarly, the theory applies as well to distinct generations in a population, in which case the distance across generations is a function of increase of inbreeding. Simulation results confirmed our derivations. Slight biases were observed, depending on the non-additive mechanism and the reference allele. Our derivations are useful to understand and forecast the possibility of prediction across populations and the similarity of GWAS effects.