bluuebunny/crossref_metadata_2025 huggingface dataset:
Agent-based modelling of iron cycling bacteria provides a framework for testing alternative environmental conditions and modes of action
Authors: Then Andre , Ewald Jan , Söllner Natalie , Cooper Rebecca E. , Küsel Kirsten , Ibrahim Bashar , Schuster Stefan
Published: May 2022

Iron-reducing and iron-oxidizing bacteria are of interest in a variety of environmental and industrial applications. Such bacteria often co-occur at oxic-anoxic gradients in aquatic and terrestrial habitats. In this paper, we present the first computational agent-based model of microbial iron cycling, between the anaerobic ferric iron (Fe3+)-reducing bacteriaShewanellaspp. and the microaerophilic ferrous iron (Fe2+)-oxidizing bacteriaSideroxydansspp. By including the key processes of reduction/oxidation, movement, adhesion, Fe2+-equilibration and nanoparticle formation, we derive a core model which enables hypothesis testing and prediction for different environmental conditions including temporal cycles of oxic and anoxic conditions. We compared (i) combinations of different Fe3+-reducing/Fe2+-oxidizing modes of action of the bacteria and (ii) system behaviour for different pH values. We predicted that the beneficial effect of a high number of iron-nanoparticles on the total Fe3+reduction rate of the system is not only due to the faster reduction of these iron-nanoparticles, but also to the nanoparticles’ additional capacity to bind Fe2+on their surfaces. Efficient iron-nanoparticle reduction is confined to pH around 6, being twice as high than at pH 7, whereas at pH 5 negligible reduction takes place. Furthermore, in accordance with experimental evidence our model showed that shorter oxic/anoxic periods exhibit a faster increase of total Fe3+reduction rate than longer periods.
Technique-based inoculation against real-world misinformation
Authors: Roozenbeek Jon , Traberg Cecilie S. , van der Linden Sander
Published: May 2022

In recent years, numerous psychological interventions have been developed to reduce susceptibility to misinformation. Inoculation theory has become an increasingly common framework for reducing susceptibility to both individual examples of misinformation (issue-based inoculation) and to the techniques and strategies that are commonly used to mislead or misinform people (technique-based inoculation). In this study, we address two open questions related to technique-based inoculation in two separate experiments (total
n
= 2188; convenience sample recruited via the
Bad News
online game platform): (i) can technique-based inoculation effectively reduce susceptibility to real-world misinformation that went viral on social media? and (ii) can technique-based inoculation confer cross-protection against misinformation that does not make use of any of the techniques against which people were inoculated? We find that playing a 15 min game confers psychological resistance against real-world misinformation that makes use of manipulation techniques against which people were inoculated (Cohen's
d
= 0.37, Cohen's
U
3
= 64.4%,
p
< 0.001), and that cross-protection is achieved but at a reduced effect size (
d
= 0.10,
U
3
= 54.0%,
p
= 0.001).
Ocean nomads or island specialists? Culturally driven habitat partitioning contrasts in scale between geographically isolated sperm whale populations
Authors: Vachon Felicia , Hersh Taylor A. , Rendell Luke , Gero Shane , Whitehead Hal
Published: May 2022

The sperm whale (Physeter macrocephalus) is a deep-diving cetacean with a global distribution and a multi-leveled, culturally segregated, social structure. While sperm whales have previously been described as ‘ocean nomads’, this might not be universal. We conducted surveys of sperm whales along the Lesser Antilles to document the acoustic repertoires, movements and distributions of Eastern Caribbean (EC) sperm whale cultural groups (called vocal clans). In addition to documenting a potential third vocal clan in the EC, we found strong evidence of fine-scale habitat partitioning between vocal clans with scales of horizontal movements an order of magnitude smaller than from comparable studies on Eastern Tropical Pacific sperm whales. These results suggest that sperm whales can display cultural ecological specialization and habitat partitioning on flexible spatial scales according to local conditions and broadens our perception of the ecological flexibility of the species. This study highlights the importance of incorporating multiple temporal and spatial scales to understand the impact of culture on ecological adaptability, as well as the dangers of extrapolating results across geographical areas and cultural groups.
The regulatory landscape of retinoblastoma: a pathway analysis perspective
Authors: Gómez-Romero Laura , Alvarez-Suarez Diana E. , Hernández-Lemus Enrique , Ponce-Castañeda M. Verónica , Tovar Hugo
Published: May 2022

Retinoblastoma (Rb) is a rare intraocular tumour in early childhood, with an approximate incidence of 1 in 18 000 live births. Experimental studies for Rb are complex due to the challenges associated with obtaining a normal retina to contrast with diseased tissue. In this work, we reanalyse a dataset that contains normal retina samples. We identified the individual genes whose expression is different in Rb in contrast with normal tissue, determined the pathways whose global expression pattern is more distant from the global expression observed in normal tissue, and finally, we identified which transcription factors regulate the highest number of differentially expressed genes (DEGs) and proposed as transcriptional master regulators (TMRs). The enrichment of DEGs in the phototransduction and retrograde endocannabinoid signalling pathways could be associated with abnormal behaviour of the processes leading to cellular differentiation and cellular proliferation. On the other hand, the TMRs nuclear receptor subfamily 5 group A member 2 and hepatocyte nuclear factor 4 gamma are involved in hepatocyte differentiation. Therefore, the enrichment of aberrant expression in these transcription factors could suggest an abnormal retina development that could be involved in Rb origin and progression.
Contemporary sea-level changes from global to local scales: a review
Authors: Cazenave Anny , Moreira Lorena
Published: May 2022

Sea-level variations spread over a very broad spectrum of spatial and temporal scales as a result of complex processes occurring in the Earth System in response to natural variability of the climate system, as well as to external forcing due to natural phenomena and anthropogenic factors. Here, we address contemporary sea-level changes, focusing on the satellite altimetry era (since the early 1990s), for which various observing systems from space andin situallow precise monitoring of sea-level variations from global to local scales, as well as improved understanding of the components responsible for the observed variations. This overview presents the most recent results on observed global and regional sea-level changes and on associated causes, focusing on the interannual to decadal time scale. Recent progress in measuring sea level at the coast are presented. Finally, a summary of the most recent sea-level projections from the Intergovernmental Panel on Climate Change is also provided.
Slow improvement to the archiving quality of open datasets shared by researchers in ecology and evolution
Authors: Roche Dominique G. , Berberi Ilias , Dhane Fares , Lauzon Félix , Soeharjono Sandrine , Dakin Roslyn , Binning Sandra A.
Published: May 2022

Many leading journals in ecology and evolution now mandate open data upon publication. Yet, there is very little oversight to ensure the completeness and reusability of archived datasets, and we currently have a poor understanding of the factors associated with high-quality data sharing. We assessed 362 open datasets linked to first- or senior-authored papers published by 100 principal investigators (PIs) in the fields of ecology and evolution over a period of 7 years to identify predictors of data completeness and reusability (data archiving quality). Datasets scored low on these metrics: 56.4% were complete and 45.9% were reusable. Data reusability, but not completeness, was slightly higher for more recently archived datasets and PIs with less seniority. Journal open data policy, PI gender and PI corresponding author status were unrelated to data archiving quality. However, PI identity explained a large proportion of the variance in data completeness (27.8%) and reusability (22.0%), indicating consistent inter-individual differences in data sharing practices by PIs across time and contexts. Several PIs consistently shared data of either high or low archiving quality, but most PIs were inconsistent in how well they shared. One explanation for the high intra-individual variation we observed is that PIs often conduct research through students and postdoctoral researchers, who may be responsible for the data collection, curation and archiving. Levels of data literacy vary among trainees and PIs may not regularly perform quality control over archived files. Our findings suggest that research data management training and culture within a PI's group are likely to be more important determinants of data archiving quality than other factors such as a journal's open data policy. Greater incentives and training for individual researchers at all career stages could improve data sharing practices and enhance data transparency and reusability.
Evolutionary history limits species' ability to match colour sensitivity to available habitat light
Authors: Murphy Matthew J. , Westerman Erica L.
Published: May 2022

The spectrum of light that an animal sees—from ultraviolet to far red light—is governed by the number and wavelength sensitivity of a family of retinal proteins called opsins. It has been hypothesized that the spectrum of light available in an environment influences the range of colours that a species has evolved to see. However, invertebrates and vertebrates use phylogenetically distinct opsins in their retinae, and it remains unclear whether these distinct opsins influence what animals see, or how they adapt to their light environments. Systematically using published visual sensitivity data from across animal phyla, we found that terrestrial animals are more sensitive to shorter and longer wavelengths of light than aquatic animals and that invertebrates are more sensitive to shorter wavelengths of light than vertebrates. Using phylogenetically controlled analyses, we found that closed and open canopy habitat species have different spectral sensitivities when comparing across the Metazoa and excluding habitat generalists, while deepwater animals are no more sensitive to shorter wavelengths of light than shallow-water animals. Our results suggest that animals do adapt to their light environment; however, the invertebrate–vertebrate evolutionary divergence may limit the degree to which animals can perform visual tuning.
Local mechanical stimuli correlate with tissue growth in axolotl salamander joint morphogenesis
Authors: Comellas Ester , Farkas Johanna E. , Kleinberg Giona , Lloyd Katlyn , Mueller Thomas , Duerr Timothy J. , Muñoz Jose J. , Monaghan James R. , Shefelbine Sandra J.
Published: May 2022

Movement-induced forces are critical to correct joint formation, but it is unclear how cells sense and respond to these mechanical cues. To study the role of mechanical stimuli in the shaping of the joint, we combined experiments on regenerating axolotl (
Ambystoma mexicanum
) forelimbs with a poroelastic model of bone rudiment growth. Animals either regrew forelimbs normally (control) or were injected with a transient receptor potential vanilloid 4 (TRPV4) agonist during joint morphogenesis. We quantified growth and shape in regrown humeri from whole-mount light sheet fluorescence images of the regenerated limbs. Results revealed significant differences in morphology and cell proliferation between groups, indicating that TRPV4 desensitization has an effect on joint shape. To link TRPV4 desensitization with impaired mechanosensitivity, we developed a finite element model of a regenerating humerus. Local tissue growth was the sum of a biological contribution proportional to chondrocyte density, which was constant, and a mechanical contribution proportional to fluid pressure. Computational predictions of growth agreed with experimental outcomes of joint shape, suggesting that interstitial pressure driven from cyclic mechanical stimuli promotes local tissue growth. Predictive computational models informed by experimental findings allow us to explore potential physical mechanisms involved in tissue growth to advance our understanding of the mechanobiology of joint morphogenesis.
Vagococcus allomyrinae sp. nov. and Enterococcus larvae sp. nov., isolated from larvae of Allomyrina dichotoma
Authors: Kim Sung-Min , Byeon Yeong-Sik , Yang Hong Lim , Kim In Seop , Lee Soon Dong
Published: May 2022

The taxonomic positions of two novel strains isolated from larvae of an insect (Allomyrina dichotoma) collected in Jeju, Republic of Korea, were determined by a polyphasic approach. Strain BWB3-3T was closely related to the type strain of

Vagococcus salmoninarum

, having 97.2 % 16S rRNA gene sequence similarity, whereas strain BWM-S5T formed an independent cluster within the genus

Enterococcus

in the 16S rRNA gene phylogeny and the closest relative was the type strain of

Enterococcus canis

(98.1 % sequence similarity). The core gene analysis supported the phylogenetic positions of the isolates revealed by 16S rRNA gene phylogeny. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain BWB3-3T and the type strain of

V. salmoninarum

were 73.2 and 20.0 %, respectively, whereas strain BWM-S5 T showed an ANI value of 70.9 % with the type strain of

Enterococcus canis

. The dDDH values between strain BWM-S5T and all the type strains of

Enterococcus

species were ≤25.1 %. On the basis of the results obtained here, the two isolates are considered to constitute two novel species of the family

Enterococcaceae

, for which the names Vagococcus allomyrineae sp. nov. and Enterococcus larvae sp. nov. are proposed, with the type strains BWB3-3T (=KCTC 43277T=CCM 9080T) and BWM-S5T (=KACC 22156T=CCM 9075T), respectively.
Methanococcoides orientis sp. nov., a methylotrophic methanogen isolated from sediment of the East China Sea
Authors: Liang Lewen , Sun Yu , Dong Yijing , Ahmad Tariq , Chen Yifan , Wang Jing , Wang Fengping
Published: May 2022

A novel methylotrophic methanogen Methanococcoides orientis sp. nov. was isolated from East China Sea sediment. Type strain LMO-1T of Methanococcoides orientis sp. nov. was irregular 1–2 µm cocci without flagella. Strain LMO-1T could utilize a variety of methylated compounds including methanol, methylamine, dimethylamine and trimethylamine for growth and methanogenesis, while H2/CO2 or acetate could not be used for growth or methanogenesis. Optimum growth temperature was 30–35 °C, optimum pH range for growth was 7.0–7.5, while the optimum salinity spectrum for growth was 1.0%–5.0% NaCl. Based on 16S rRNA gene similarity, strain LMO-1T belongs to

Methanococcoides

, with the highest sequence similarity to

Methanococcoides methylutens

DSM 2657T (99.8 %),

Methanococcoides vulcani

SLH33T(99.4 %), followed by

Methanococcoides alaskense

AK-5T(98.1 %),

Methanococcoides burtonii

DSM 6242T (98.0 %). Digital DNA–DNA hybridization also showed highest similarity with

Methanococcoides methylutens

DSM 2657T, with the value of 58.4 %. The average nucleotide identity between strain LMO-1T and

Methanococcoides methylutens

DSM 2657T was 94.06 %. In summary, LMO-1T represents a novel species of the genus Methaococcoides, for which the name Methanococcoides orientis sp. nov. is proposed. The type strain is LMO-1T (=MCCC 4K00106T=JCM 39195T).
Disruption of the cGAS/STING axis does not impair sensing of MVA in BHK21 cells
Authors: Hood Alasdair J. M. , Sumner Rebecca P. , Maluquer de Motes Carlos
Published: May 2022

Modified vaccinia Ankara (MVA) is an attenuated strain of vaccinia virus (VACV), a dsDNA virus that replicates its genome in the cytoplasm and as a result is canonically sensed by the cyclic GMP-AMP synthase (cGAS) and its downstream stimulator of interferon genes (STING). MVA has a highly restricted host range due to major deletions in its genome including inactivation of immunomodulatory genes, only being able to grow in avian cells and the hamster cell line BHK21. Here we studied the interplay between MVA and the cGAS/STING DNA in this permissive cell line and determined whether manipulation of this axis could impact MVA replication and cell responses. We demonstrate that BHK21 cells retain a functional cGAS/STING axis that responds to canonical DNA sensing agonists, upregulating interferon stimulated genes (ISGs). BHK21 cells also respond to MVA, but with a distinct ISG profile. This profile remains unaltered after CRISPR/Cas9 knock-out editing of STING and ablation of cytosolic DNA responses, indicating that MVA responses are independent of the cGAS/STING axis. Furthermore, infection by MVA diminishes the ability of BHK21 cells to respond to exogenous DNA suggesting that MVA still encodes uncharacterised inhibitors of DNA sensing. This suggests that using attenuated strains in permissive cell lines may assist in identification of novel host-virus interactions that may be of relevance to disease or the therapeutic applications of poxviruses.
Enabling genomic island prediction and comparison in multiple genomes to investigate bacterial evolution and outbreaks
Authors: Bertelli Claire , Gray Kristen L. , Woods Nolan , Lim Adrian C. , Tilley Keith E. , Winsor Geoffrey L. , Hoad Gemma R. , Roudgar Ata , Spencer Adam , Peltier James , Warren Derek , Raphenya Amogelang R. , McArthur Andrew G. , Brinkman Fiona S. L.
Published: May 2022

Outbreaks of virulent and/or drug-resistant bacteria have a significant impact on human health and major economic consequences. Genomic islands (GIs; defined as clusters of genes of probable horizontal origin) are of high interest because they disproportionately encode virulence factors, some antimicrobial-resistance (AMR) genes, and other adaptations of medical or environmental interest. While microbial genome sequencing has become rapid and inexpensive, current computational methods for GI analysis are not amenable for rapid, accurate, user-friendly and scalable comparative analysis of sets of related genomes. To help fill this gap, we have developed IslandCompare, an open-source computational pipeline for GI prediction and comparison across several to hundreds of bacterial genomes. A dynamic and interactive visualization strategy displays a bacterial core-genome phylogeny, with bacterial genomes linearly displayed at the phylogenetic tree leaves. Genomes are overlaid with GI predictions and AMR determinants from the Comprehensive Antibiotic Resistance Database (CARD), and regions of similarity between the genomes are also displayed. GI predictions are performed using Sigi-HMM and IslandPath-DIMOB, the two most precise GI prediction tools based on nucleotide composition biases, as well as a novel blast-based consistency step to improve cross-genome prediction consistency. GIs across genomes sharing sequence similarity are grouped into clusters, further aiding comparative analysis and visualization of acquisition and loss of mobile GIs in specific sub-clades. IslandCompare is an open-source software that is containerized for local use, plus available via a user-friendly, web-based interface to allow direct use by bioinformaticians, biologists and clinicians (at https://islandcompare.ca).
Variation in the Incidence of ventriculostomy related infection in critically ill patients
Authors: Bassin Sara N. , Tian David H. , Chadwick Simon , Mahendran Sajeev , Flower Oliver , Fitzgerald Emily , Parkinson Jonathon , Darbar Archie , Janin Pierre , Delaney Anthony
Published: May 2022

Introduction

Ventriculostomy related infection (VRI) or ventriculitis is a common and serious complication related to the placement of an external ventricular drain. Numerous sets of diagnostic criteria for VRI have been reported. We sought to estimate the variation in the incidence of VRI in a cohort of patients according to published diagnostic criteria.

Materials and Methods

We conducted a retrospective cohort study. We included adult patients admitted to the Neuroscience intensive care unit with traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) who required an EVD. We estimated the incidence of VRI according to published diagnostic criteria. We compared the incidence to clinicians’ diagnoses of VRI. The primary outcome was the estimated incidence of VRI.

Results

There were 190 study participants, median age (interquartile range) of 58 (48 - 72), 106 (55.8%) were female. Admitting diagnoses was ICH in 30 (15.8%), TBI in 49 (25.8%) and SAH in 111 (58.4%) of cases respectively. There were 158 (83.2%) who required mechanical ventilation for a median of 6 (2-13) days. There were 29 (15.3%) who were treated for VRI by clinicians, with 6 (3.2%) having a positive culture. Variation in the diagnostic criteria led to an estimated incidence of VRI that ranged from 1 (0.5%) to 178 (93.7%).

Conclusion

In this critically ill cohort, the estimated incidence of VRI varied widely depending on which diagnostic criteria for VRI were applied. A comprehensive, consistent, objective and universal set of diagnostic criteria for ventriculostomy related infection is needed.
School Feeding Programmes and Physical Nutrition Outcomes of Primary School Children in Developing Countries
Authors: Yussif Mustapha Titi , Adocta Vincent Awuah , Apprey Charles , Annan Reginald Adjetey , Galseku Prosper
Published: May 2022

Context

School feeding programmes have been widely implemented and particularly in developing countries with the aim to improve school enrolment and attendance especially of girls and to reduce short term hunger to improve children’s performance in school.

Beyond the first 1000 days of the lives of children, school feeding programmes remain one of the critical interventions that have used schools as a platform to contribute to the fulfilment of their nutritional needs though the evidence to this effect is little and mixed.

Objective

This review focused on assessing the impact of school feeding programmes on reduction in underweight, thinness, and stunting among primary school children in developing countries.

Data sources

Electronic searches were carried out in PUBMED, SCORPUS and Cochrane library. The WHO clinical trials registry as well as reference lists of relevant articles were also hand searched.

Data Extraction

Data was extracted from included studies which have been published in the past 10 years (2010 – August 2021) from original research where the main intervention was the provision of school based meals.

Data analysis

Meta-analysis was conducted to determine changes in height-for-age (HAZ), weight-for-age (WAZ) and BMI-for-age (BAZ) z scores. A random effects model was applied to determine the mean difference in all outcomes of interest which were evaluated as continuous variables.

Results

Children aged 3 – 16 years were enrolled in the included studies and the number of participants ranged between 321 and 2,869 across studies. Of the included studies, the feeding intervention provided for a minimum of 30% RDA for the age group with the intervention lasting up to a maximum of 34 weeks. The impact of school feeding intervention on HAZ, BAZ and WAZ showed statistically non-significant (p>0.05) mean differences of 0.02 (95% CI, -0.06 to 0.10), 0.11 (95% CI, -0.01 to 0.23) and 0.06 (95% CI, -0.04 to 0.16) respectively

Conclusion

School feeding interventions have not shown any significant positive effect on the physical nutrition outcomes of primary school children. Short duration of intervention of studies, poor compliance to feeding and substitution of school meals could have accounted for the weak effect sizes.
Public attitudes towards COVID-19 vaccines in Africa: a systematic review
Authors: Ngangue Patrice , Pilabré Arzouma Hermann , Barro Abibata , Pafadnam Yacouba , Bationo Nestor , Soubeiga Dieudonné
Published: May 2022

Background

As COVID-19 vaccine acquisition and deployment accelerates, tensions also increase. This review aims to identify and understand the significance of population attitudes toward COVID-19 vaccines in Africa.

Methods

A systematic review was conducted. Searches were conducted in MEDLINE, CINAHL, EMBASE, and Global Health databases. Database searches began on June 23, 2021, and the last search date was June 30, 2021. The methodological quality of the studies included in this review was assessed using the Mixed methods appraisal tool.

Results

A total of 609 articles were retrieved, and 23 met the eligibility criteria. All 23 included studies were cross-sectional. Three attitudes were identified: acceptance, reluctance, and refusal to be vaccinated. Acceptance of vaccination was motivated by confidence in the accuracy of the government’s response to COVID-19 and the fact that relatives had been diagnosed with or died from COVID-19. Reluctance was based on fear of vaccine quality and side effects, and insufficient clinical trials. Finally, refusal to be vaccinated was justified by reasons such as the unreliability of clinical trials and insufficient data regarding the vaccine’s adverse effects.

Conclusion

This review revealed common attitudes of African populations toward COVID-19 vaccines. The results indicate that research needs to focus more on identifying facilitators of COVID-19 vaccination. However, they also provide essential elements for health personnel in charge of vaccination to develop strategies to achieve satisfactory coverage rates
Global and gene-specific translational regulation inEscherichia coliacross different conditions
Authors: Zhang Di , Li Sophia Hsin-Jung , King Christopher G. , Wingreen Ned S. , Gitai Zemer , Li Zhiyuan
Published: May 2022

How well mRNA transcript levels represent protein abundances has been a controversial issue. Particularly across different environments, correlations between mRNA and protein exhibit remarkable variability from gene to gene. Translational regulation is likely to be one of the key factors contributing to mismatches between mRNA level and protein abundance in bacteria. Here, we quantified genome-wide transcriptome and relative translation efficiency (RTE) under 12 different conditions inEscherichia coli. By quantifying the mRNA-RTE correlation both across genes and across conditions, we uncovered a diversity of gene-specific translational regulations, cooperating with transcriptional regulations, in response to carbon (C), nitrogen (N), and phosphate (P) limitations. Intriguingly, we found that many genes regulating translation are themselves subject to translational regulation, suggesting possible feedbacks. Furthermore, a random forest model suggests that codon usage partially predicts a gene’s cross-condition variability in translation efficiency; such cross-condition variability tends to be an inherent quality of a gene, independent of the specific nutrient limitations. These findings broaden the understanding of translational regulation under different environments, and provide novel strategies for the control of translation in synthetic biology.
Elevated plasma Complement Factor H Regulating Protein 5 is associated with venous thromboembolism and COVID-19 severity
Authors: Sanchez-Rivera Laura , Iglesias Maria Jesus , Ibrahim-Kosta Manal , Kral-Pointner Julia Barbara , Havervall Sebastian , Goumidi Louisa , Farm Maria , Munsch Gaëlle , Germain Marine , Smith Philip , Hong Mun-Gwan , Suchon Pierre , Naudin Clément , Boland Anne , Smadja David M , Holmström Margareta , Magnusson Maria , Silveira Angela , Uhlén Mathias , Renné Thomas , Martinez-Perez Angel , Emmerich Joseph , Deleuze Jean-Francois , Antovic Jovan , Assinger Alice , Fernandez Jose Manuel Soria , Thålin Charlotte , Schwenk Jochen M , Andres Juan Carlos Souto , Morange Pierre-Emmanuel , Butler Lynn Marie , Trégouët David-Alexandre , Odeberg Jacob
Published: May 2022

Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We used multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and a case-control study of patients followed up after ending anticoagulant treatment for a first VTE. With replication in 5 independent studies, together totalling 1137 patients and 1272 controls, we identify Complement Factor H Related Protein (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. Using GWAS analysis of 2967 individuals we identified a genome-wide significant pQTL signal on chr1q31.3 associated with CFHR5 levels. We showed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activationin vitro. Thrombotic complications are a frequent feature of COVID-19; in hospitalised patients we found CFHR5 levels at baseline were associated with short-time prognosis of disease severity, defined as maximum level of respiratory support needed during hospital stay. Our results indicate a clinically important role for regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.
Pediatric Diarrhea Patients Living in Urban Areas Have Higher Incidence of Clostridioides difficile Infection
Authors: Adesoji Ayodele. T. , Mgbere Osaro , Darkoh Charles
Published: May 2022

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and an unappreciated contributor to child mortality in low- and middle-income countries where diagnosis may be difficult. There is little information about the prevalence of CDI among infants, children, and adolescents in Africa. Seventy-six samples were collected from pediatric patients presenting with diarrhea, including infants (≤ 2 years old), children (2-12 years) and adolescents (13 ≤17 years) from three hospitals between January and December 2019. Demographic data, medical history and prior antibiotic use were recorded. Toxigenic culture and PCR were used to detect and validate the presence of C. difficile in the samples. A total of 29 (38.7%), 39 (52.0%) and 7 (9.3%) samples were from infants, children, and adolescents, respectively. Average age of the patients was 4.4 years. Of these samples, 31 (41%) were positive for C. difficile by culture and were verified by PCR amplification of C. difficile specific genes (tcdA and tcdB). Most positive cases were children (53.3%) and infants (40.0%) with the majority of them residing in the urban areas. Forty-nine (66.2%) of the patients had no known antibiotics exposure, whereas 29.0% and 29.7% reported use of over-the-counter antibiotics at 14 and 90 days, prior to the hospital visit, respectively. CDI is relatively common among children with diarrhea in Northern Nigeria. Therefore, for effective management and treatment, more attention should be given to testing for C. difficile as one of the causative agents of diarrhea.
Specific gait changes in prodromal hereditary spastic paraplegia type 4 - preSPG4 study
Authors: Laßmann Christian , Ilg Winfried , Schneider Marc , Völker Maximilian , Haeufle Daniel F. B. , Schüle Rebecca , Giese Martin , Schöls Ludger , Rattay Tim W.
Published: May 2022

Background

In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested.

Objectives

Identification of specific movement abnormalities before manifestation of gait impairment and quantification of disease progression in the prodromal phase.

Methods

70 subjects participated in gait assessment, including 30 prodromal SPAST mutation carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy controls. Gait was assessed by an infrared-camera-based motion capture system to analyze features like range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale (SPRS) and neurofilament light chain (NfL) as a fluid biomarker indicating neurodegeneration.

Results

Compared to healthy controls, we found an altered gait pattern in prodromal mutation carriers during the swing phase in segmental angles of the lower leg (p<0.05) and foot (p<0.01), and in heel ground clearance (p<0.01). Furthermore, ranges of motion of segmental angles were reduced for foot (p<0.001) and lower leg (p<0.01). These changes occurred in prodromal mutation carriers without quantified leg spasticity in clinical examination. Gait features correlated with NfL levels and SPRS score.

Conclusion

Gait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages.
Systematic review of food insecurity and violence against women and girls: mixed methods findings from low- and middle-income settings
Authors: Hatcher Abigail M , Page Sabrina , Aletta van Eck Lele , Pearson Isabelle , Fielding-Miller Rebecca , Mazars Celine , Stöckl Heidi
Published: May 2022

Introduction

Violence against women and girls (VAWG) is a global human rights and public health concern. Food insecurity is a sign of severe poverty, and likely to heighten women’s vulnerability to VAWG and men’s perpetration of it. However, the extent of the association and the multiple pathways between food insecurity and VAWG are not well understood.

Methods

We systematically assessed peer reviewed quantitative and qualitative literature to explore this in low- and middle-income countries (LMIC). Fixed effects meta-analysis was used to synthesize quantitative evidence. Qualitative data was analyzed using thematic analysis.

Results

We identified 23 quantitative and 19 qualitative or mixed-methods peer-reviewed manuscripts. In a meta-analysis of 21 cross-sectional studies with 20,378 participants, food insecurity was associated with doubled odds of reported VAWG (odds ratio [OR]=2.38, 95% confidence interval [CI]=1.82-3.10). This finding was consistent for both women’s experience or male perpetration of VAWG. Qualitative and mixed-methods papers offered insight that underlying conditions of inequitable gender norms, economic deprivation, and social isolation frame both food insecurity and VAWG. Food insecurity may trigger survival behaviors due to household stress and lack of meeting expected gender roles, which leads to VAWG. VAWG exposure may lead to food insecurity if women are more impoverished after leaving a violent household. Potential protective factors include financial stability, the involvement of men in VAWG programming, transformation of gender norms, and supporting women to develop new networks and social ties.

Conclusion

Strong evidence exists for a relationship between food security and IPV. Future funding should target causal directions and preventive options through longitudinal and interventional research. Strategies to ensure households have access to sufficient food and safe relationships are urgently needed to prevent VAWG.
Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD
Authors: Kamal Farooq , Morrison Cassandra , Maranzano Josefina , Zeighami Yashar , Dadar Mahsa ,   Alzheimer’s Disease Neuroimaging Initiative
Published: May 2022

Background

White matter hyperintensities (WMHs) are pathological changes that develop with increased age and are associated with cognitive decline. Most research on WMHs has neglected to examine regional differences and instead focuses on using a whole-brain approach. This study examined regional WMH differences between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Another goal was to examine whether WMH burden was associated with declines in different cognitive domains in each of the groups.

Methods

Participants were selected from the Alzheimer’s Disease Neuroimaging Initiative and included if they had at least one WMH measurement and cognitive scores examining global cognition, executive functioning, and memory. MCI and AD participants were included only if they were amyloid positive. A total of 1573 participants with 7381 follow-ups met inclusion criteria. Linear mixed-effects models were completed to examine group differences in WMH burden and the association between WMH burden and cognition in aging, MCI, and AD.

Results

People with MCI and AD had increased total and regional WMH burden compared to cognitively healthy older adults. An association between WMH and cognition was observed for global cognition, executive functioning, and memory in NCs in all regions of interest. A steeper decline (stronger association between WMH and cognition) was observed in MCI compared to NCs for all cognitive domains in all regions. A steeper decline was observed in AD compared to NCs for global cognition in only the temporal region.

Conclusion

These results suggest WMH burden increases from aging to AD. A strong association is observed between all cognitive domains of interest and WMH burden in healthy aging and MCI, while those with AD only had a few associations between WMH and memory and WMH and global cognition. These findings suggest that WMH burden is associated with changes in cognition in healthy aging and early cognitive decline, but other biological changes may have a stronger impact on cognition with AD.
A pipeline for tabular dataset formation from unstructured data provided by ACR Appropriateness Criteria guidelines
Authors: Eduardo Anderson A. , Loureiro Rafael M. , Tachibana Adriano , Netto Pedro V. , de Almeida Tatiana F. , Monteiro Luiz Henrique Alves , Santos André P. dos
Published: May 2022

Currently, data performns a critical concept for disparate human activities, from law to technology. Among data-centric technologies, clinical decision support systems (CDSS) figures out as one of the most promising for healthcare. Despite the technological advances facilitating its implementation, the maintainance of knowledge base for CDSS remains open to improvements. Here, we argue that the Appropriateness Criteria provided by ACR guidelines can be used as a open data-source that, combined with appropriate algorithms, can push forward basic research and technological developments regarding knowledge base for CDSS. Therefore, we developed a pipeline capable of forming tabular datasets from ACR guidelines, stored in a web site as textual PDF files. We also experimentally demonstrate that the proposed pipeline successfully recorvers the interested contents, and the best composition, in terms of its component algorithms, is discussed. Future research focused on algorithms flexibility in the face of PDF template updates could improve our work.
Minimal algorithms for knowledge representation in clinical decision support systems research: a theoretical and empirical analysis
Authors: Eduardo Anderson A. , Loureiro Rafael M. , Tachibana Adriano , Netto Pedro V. , Almeida Tatiana F. de , Monteiro Luiz Henrique Alves , Santos André P. dos
Published: May 2022

Clinical decision support systems (CDSS) figures out as one of the most promising technologies for data-centered and AI-prompted healthcare. Its current developments are mainly guided by two disparate mindsets, namely a machine learning-centered framework and a classical rule-based framework. These respective approaches presents contrastive pros and cons. In the present study we provide an analysis showing that these two mindsets are actually related to each other, and straightforward algorithms are feasible by combining current standards for machine learning and classic decision tables algorithms. A theoretical analysis are provided, as well a computational implementation (in python). A real case scenario on radiological immaging exam prescription is used to ilustrate the successfully application of our results. Future work on benchmarking the proposed algorithms embodied in a fully operational clinical decision support system could extend our findings towards daily used systems.
Assessing Depression and Suicidality Among Recently Unemployed Persons with Obstructive Sleep Apnea and Socioeconomic Inequality
Authors: Singh Vijay , Haynes Patricia L. , Quan Stuart F.
Published: May 2022

Background

Obstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder that often is associated with several psychiatric conditions. Job loss is a stressful life event that can also affect mental health and socioeconomic status (SES). We investigated whether there was an association between the prevalence of OSA and several psychiatric conditions within a cohort of persons who recently became unemployed and whether SES was a contributing factor.

Methods

Data from 292 participants who completed the screening evaluation of the Assessing Daily Activity Patterns through occupational Transitions (ADAPT) Study were used to assess the association between the prevalence of OSA, and current and past depression, and past suicidality. A type III sleep home sleep monitor was used to identify the presence of OSA and assess its severity. Depression and suicidality were ascertained using the Mini-international neuropsychiatric interview. Years of education was used as a proxy for SES.

Results

There were no significant associations between severity of OSA, SES and current depression, past depression, and suicidality. Past suicidality was noted to be more common among those who were single/widowed (17.4%) or those who were divorced or separated (11.1%) (p=0.027). Current depression was more common among Hispanics in comparison to non-Hispanics. Furthermore, prevalence rates of both depression and past suicidality were higher than previous reports in general populations.

Conclusions

Within a cohort of individuals who experienced recent job loss, there was no association between OSA and depression or past suicidality. Prevalence rates of both depression and past suicidality were higher than previous reports in the general population.
Mitochondrial effects on fertility and longevity in Tigriopus californicus contradict predictions of the mother’s curse hypothesis
Authors: Watson Eric T. , Flanagan Ben A. , Pascar Jane A. , Edmands Suzanne
Published: May 2022

Strict maternal inheritance of mitochondria favors the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The “mother’s curse” hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila, where support for the predictions of mother’s curse has been mixed. We investigated the impact of mother’s curse mutations in Tigriopus californicus, a minute crustacean. Using nonrecombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context-dependent, being influenced by the nuclear-background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mother’s curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favoring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus.
A benchmark of Hi-C scaffolders using reference genomes and de novo assemblies
Authors: Sur Aakash , Noble William Stafford , Myler Peter J.
Published: May 2022

Background

Studying a new species using high-throughput sequencing requires a high-quality reference genome. However, assembling chromosome length sequences remains challenging. Recent advances in chromatin conformation capture (Hi-C) have provided a new approach to scaffolding genome assemblies, and the last ten years have seen a proliferation of such methods. However, to our knowledge no comprehensive benchmarking of Hi-C scaffolders has been conducted to date.

Results

Through a literature review we identified the most popular Hi-C scaffolders – Lachesis, HiRise, 3d-dna, SALSA, and AllHiC. We tested their ability to scaffold four well studied genomes – S. cerevisiae, L. tarentolae, A. thaliana, and H. sapiens. Scaffolders were tasked with both scaffolding fragmented versions of the reference genome as well as de novo assemblies derived from long read datasets. We found that all scaffolders can exceed 80% accuracy under ideal circumstances but that their performance quickly deteriorates under more challenging conditions. Surprisingly, many scaffolders also showed poor performance on the best assemblies, where contigs are near chromosome length. Overall, we found that HiRise and Lachesis offer the best performance on average across all conditions.

Conclusions

We compare the performance of five Hi-C scaffolders using multiple reference species under both ideal and real-life conditions, thereby illuminating their strengths and weaknesses.
The association of ubiquitin-associated protein 2-like and Ras-GTP-activating protein SH3 domain binding protein 1 mediated by small nucleolar RNA is essential for stress granule formation
Authors: Asano-Inami Eri , Yokoi Akira , Sugiyama Mai , Hyodo Toshinori , Hamaguchi Tomonari , Kajiyama Hiroaki
Published: May 2022

Stress granules (SGs) are dynamic, non-membranous structures composed of non-translating mRNAs and various proteins and play critical roles in cell survival under stressed conditions. Extensive proteomics analyses have been performed to identify proteins in SGs; however, the molecular functions of these components in SG formation remain unclear. In this report, we show that ubiquitin-associated protein 2-like (UBAP2L) is a novel component of SGs. UBAP2L localized to SGs in response to various stresses, and its depletion significantly suppressed SG organization. Proteomics and RNA sequencing analyses found that UBAP2L formed a protein-RNA complex with Ras-GTP-activating protein SH3 domain binding protein 1 (G3BP1) and small nucleolar RNAs (snoRNAs). In vitro binding analysis demonstrated that snoRNAs were required for UBAP2L association with G3BP1. In addition, decreased expression of snoRNAs reduced the interaction between UBAP2L and G3BP1 and suppressed SG formation. Our results reveal a critical role of a novel SG component, the UBAP2L/snoRNA/G3BP1 protein-RNA complex, and provide new insights into the regulation of SG assembly.