bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency of HIV serodifferent couples within TB-affected households in a setting with a high burden of HIV-associated TB
Authors: Anguzu Godwin , Gupta Amanda J , Ochom Emmanuel , Tseng Ashley S. , Zhang Meixin , Barnabas Ruanne V. , Flaxman Abraham D. , Katamba Achilles , Davis J. Lucian , Ross Jennifer M.
Published: November 2022

Background

Strong epidemiological links between HIV and tuberculosis (TB) may make household TB contact investigation an efficient strategy for HIV screening and finding individuals in serodifferent partnerships at risk of HIV and linking them to HIV prevention services. We aimed to compare the proportions of HIV serodifferent couples in TB-affected households and in the general population of Kampala, Uganda.

Methods

We included data from a cross-sectional trial of HIV counselling and testing (HCT) in the context of home-based TB evaluation in Kampala, Uganda in 2016-2017. After obtaining consent, community health workers visited the homes of participants with TB to screen contacts for TB and offer HCT to household members ≥15 years. We defined index participants and their spouses and parents of the same index participant as couples, and classified couples as serodifferent if confirmed by self-reported HIV status or by HIV testing results. We used a two-sample test of proportions to compare the frequency of HIV serodifference among couples in the study to its prevalence among couples in Kampala in the 2011 Uganda AIDS Indicator Survey (UAIS).

Results

We included 323 index TB participants and 507 household contacts aged ≥18. Most index participants (55%) were male, while most (68%) adult contacts were female. There was ≥1 couple in 115/323 (35.6%) households, with most couples (98/115, 85.2%) including the index participant and spouse. The proportion of households with HIV-serodifferent couples was 18/323 (5.6%), giving a number-needed-to-screen of 18 households. The proportion of HIV serodifference among couples identified in the trial was significantly higher than among couples in the UAIS (15.7% vs 8%, p=0.039). The 18 serodifferent couples included 14 (77.8%) where the index participant was living with HIV and the spouse was HIV-negative, and 4 (22.2%) where the index partner was HIV-negative, while the spouse was living with HIV.

Conclusions

The frequency of HIV serodifference among couples identified in TB-affected households was higher than in the general population. TB household contact investigation may be an efficient strategy for identifying people with substantial exposure to HIV and linking them to HIV prevention services.
Uptake of same-day initiation of HIV treatment in Malawi, South Africa, and Zambia: the SPRINT retrospective cohort study
Authors: Huber Amy , Hirasen Kamban , Brennan Alana T , Phiri Bevis , Tchereni Timothy , Mulenga Lloyd , Haimbe Prudence , Shakwelele Hilda , Nyirenda Rose , Matola Bilaal Wilson , Gunda Andrews , Rosen Sydney
Published: November 2022

Introduction

Since 2017 global guidelines have recommended “same-day initiation” (SDI) of antiretroviral treatment (ART) for patients considered ready for treatment on the day of HIV diagnosis. Many countries in sub-Saharan Africa have incorporated a SDI option into national guidelines, but uptake of SDI is not well documented. We estimated average time to ART initiation at 12 public healthcare facilities in Malawi, 5 in South Africa, and 12 in Zambia.

Methods

We sequentially enrolled patients who were eligible to start ART between January 2018 and June 2019 and reviewed their medical records from the point of HIV treatment eligibility (HIV diagnosis or first HIV-related interaction with the clinic) to the earlier of treatment initiation or 6 months. We estimated the proportion of patients initiating ART at their original healthcare facilities on the same day or within 7, 14, 30, or 180 days of baseline, stratified by country and gender.

Results

We enrolled 826 patients in Malawi, 534 in South Africa, and 1,984 in Zambia. 88% of patients in Malawi, 57% in South Africa, and 91% in Zambia were offered and accepted SDI. In Malawi, most patients who did not receive SDI had also not initiated ART ≤ 6 months. In South Africa, an additional 13% of patients initiated ≤ 1 week, but 21% still had no record of initiation ≤ 6 months. Among those who did initiate within 6 months in Zambia, most started ≤ 1 week. There were no major differences by gender. Both WHO Stage III/IV and tuberculosis symptoms were associated with delays in ART initiation.

Discussion

As of 2020, uptake of same-day ART initiation was widespread, if not nearly universal, in Malawi and Zambia but was considerably less common in South Africa. Limitations of the study include pre-COVID-19 data that do not reflect pandemic adaptations and potentially missing data for Zambia. South Africa may be able to increase overall ART coverage by reducing numbers of patients who do not initiate ≤ 6 months.

Registration

Clinicaltrials.govNCT04468399(Malawi),NCT04170374(South Africa), andNCT04470011(Zambia).
Trajectories of host-response biomarkers and inflammatory subphenotypes in COVID-19 patients across the spectrum of respiratory support
Authors: Lu Michael , Drohan Callie , Bain William , Shah Faraaz A. , Bittner Matthew , Evankovich John , Prendergast Niall , Hensley Matthew , Suber Tomeka , Fitzpatrick Meghan , Ramanan Raj , Murray Holt , Schaefer Caitlin , Qin Shulin , Wang Xiaohong , Zhang Yingze , Nouraie Seyed M. , Gentry Heather , Kessinger Cathy , Patel Asha , Macatangay Bernard J. , Jacobs Jana , Mellors John , Lee Janet S. , Ray Prabir , Ray Anuradha , Methé Barbara , Morris Alison , McVerry Bryan J. , Kitsios Georgios D.
Published: November 2022

Purpose

Enhanced understanding of the dynamic changes in the dysregulated inflammatory response in COVID-19 may help improve patient selection and timing for immunomodulatory therapies.

Methods

We enrolled 323 COVID-19 inpatients on different levels of baseline respiratory support: i) Low Flow Oxygen (37%), ii) Non-Invasive Ventilation or High Flow Oxygen (NIV_HFO, 29%), iii) Invasive Mechanical Ventilation (IMV, 27%), and iv) Extracorporeal Membrane Oxygenation (ECMO, 7%). We collected plasma samples upon enrollment and days 5 and 10 to measure host-response biomarkers. We classified subjects into inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker and subphenotype trajectories and outcomes during hospitalization.

Results

IL-6, procalcitonin, and Angiopoietin-2 were persistently elevated in patients at higher levels of respiratory support, whereas sRAGE displayed the inverse pattern. Patients on NIV_HFO at baseline had the most dynamic clinical trajectory, with 26% eventually requiring intubation and exhibiting worse 60-day mortality than IMV patients at baseline (67% vs. 35%, p<0.0001). sRAGE levels predicted NIV failure and worse 60-day mortality for NIV_HFO patients, whereas IL-6 levels were predictive in IMV or ECMO patients. Hyper-inflammatory subjects at baseline (<10% by both models) had worse 60-day survival (p<0.0001) and 50% of them remained classified as hyper-inflammatory on follow-up sampling at 5 days post-enrollment. Receipt of combined immunomodulatory therapies (steroids and anti-IL6 agents) was associated with markedly increased IL-6 and lower Angiopoietin-2 levels (p<0.05).

Conclusions

Longitudinal study of systemic host responses in COVID-19 revealed substantial and predictive inter-individual variability, influenced by baseline levels of respiratory support and concurrent immunomodulatory therapies.
Remission and clinical patterns of systemic lupus erythematosus (SLE) in Pakistan: a retrospective cohort study
Authors: Saeed Mohammad , Pasha Aneela , Azhar Rizvi Syed Hussain , Munawar Maham , Elias Zehra Abaad , Shafi Muhammad Irfan , Gazdar Tariq , Lakhdir Maryam Ali
Published: November 2022

Objectives

Primary objective was to investigate clinical features and biomarkers associated with severe systemic lupus erythematosus (SLE). The secondary objective was to identify patterns of SLE remission. ’

Methods

A retrospective study of 200 SLE patients (2014–20) from ImmunoCure Center was conducted. Patients fulfilled ACR criteria 1997 for SLE classification. SLEDAI-2K categories mild-moderate (score <=10) and severe (score >10) were used as outcome for the primary objective. Predictors of severe SLE were evaluated by multivariate logistic regression analysis. For the secondary objective, we evaluated 94 records with follow-up time >1year. Remission status (Yes/No) was based on DORIS criteria. Survival regression was performed using Kaplan Meier curve.

Results

Significant predictors of severe SLE were male gender (OR 4.1; 95% CI: 1.2, 13.5), oral ulcers (OR 6.9; 95% CI: 2.8, 17.1), alopecia (OR 2.1; 95% CI 1.0-4.1), nephritis (OR 4.5; 95% CI: 1.9-11.4), ESR >30mm/hour (OR 2.3; 95% CI: 1.2-4.4) and aCL antibodies (OR 2.4, 95% CI 1.0 -5.9). The mean duration of follow-up was 41±19 months. Remission on treatment was achieved in 66% of 94 patients, while off treatment in 21% with a mean post-remission follow-up of 18±15 months. For every one-month increase in the duration of follow-up, the hazard of time to remission increased by 4% (95% CI 0.95-0.98;P<0.001). Factor analysis identified 4 SLE subtypes.

Conclusion

A clinical model including aCL antibodies is presented here that predicts severe SLE. Remission is possible even in severe SLE in LMIC with adequate immunosuppression and persistent follow-up.
Comparing end-tidal CO2, respiration volume per time (RVT), and average gray matter signal for mapping cerebrovascular reactivity amplitude and delay with breath-hold task BOLD fMRI
Authors: Zvolanek Kristina M. , Moia Stefano , Dean Joshua N. , Stickland Rachael C. , Caballero-Gaudes César , Bright Molly G.
Published: November 2022

Cerebrovascular reactivity (CVR), defined as the cerebral blood flow response to a vasoactive stimulus, is an imaging biomarker with demonstrated utility in a range of diseases and in typical development and aging processes. A robust and widely implemented method to map CVR involves using a breath-hold task during a BOLD fMRI scan. Recording end-tidal CO2(PETCO2) changes during the breath-hold task is recommended to be used as a reference signal for modeling CVR amplitude in standard units (%BOLD/mmHg) and CVR delay in seconds. However, obtaining reliable PETCO2recordings requires equipment and task compliance that may not be achievable in all settings. To address this challenge, we investigated two alternative reference signals to map CVR amplitude and delay in a lagged general linear model (lagged-GLM) framework: respiration volume per time (RVT) and average gray matter BOLD response (GM- BOLD). In 8 healthy adults with multiple scan sessions, we compare spatial agreement of CVR maps from RVT and GM-BOLD to those generated with PETCO2. We define a threshold to determine whether a PETCO2recording has “sufficient” quality for CVR mapping and perform these comparisons in 16 datasets with sufficient PETCO2and 6 datasets with insufficient PETCO2. When PETCO2quality is sufficient, both RVT and GM-BOLD produce CVR amplitude maps that are nearly identical to those from PETCO2(after accounting for differences in scale), with the caveat they are not in standard units to facilitate between-group comparisons. CVR delays are comparable to PETCO2with an RVT regressor but may be underestimated with the average GM- BOLD regressor. Importantly, when PETCO2quality is insufficient, RVT and GM-BOLD CVR recover reasonable CVR amplitude and delay maps, provided the participant attempted the breath-hold task. Therefore, our framework offers a solution for achieving high quality CVR maps in both retrospective and prospective studies where sufficient PETCO2recordings are not available and especially in populations where obtaining reliable measurements is a known challenge (e.g., children). Our results have the potential to improve the accessibility of CVR mapping and to increase the prevalence of this promising metric of vascular health.
Inorganic polyphosphate abets silencing of a sub-telomeric gene cluster in fission yeast
Authors: Sanchez Ana M. , Garg Angad , Schwer Beate , Shuman Stewart
Published: November 2022

Inorganic polyphosphate (PolyP) is a ubiquitous polymer that plays sundry roles in cell and organismal physiology. Whereas there is evidence for polyphosphate in the cell nucleus, it is unclear whether and how physiological levels of PolyP impact transcriptional regulation in eukarya. To address this issue, we performed transcriptional profiling of fission yeastvtc4Δ cells, which lack the catalytic subunit of the Vtc4/Vtc2 polyphosphate polymerase complex and thus have no detectable intracellular PolyP. Deleting Vtc4 elicited the de-repression of four protein-coding genes –SPAC186.04c, gdt1/SPAC186.05, SPAC186.06, andSPAC750.01– located within a sub-telomeric region of the right arm of chromosome I that is known to be transcriptionally silenced by the TORC2 complex. These sub-telomeric genes were equally de-repressed invtc2Δ cells and in cells expressing polymerase-dead Vtc4, signifying that PolyP synthesis is necessary to abet TORC2-dependent locus-specific gene silencing.
Endozoicomonas-chlamydiae interactions in cell-associated microbial aggregates of the coralPocillopora acuta
Authors: Maire Justin , Tandon Kshitij , Collingro Astrid , van de Meene Allison , Damjanovic Katarina , Gøtze Cecilie Ravn , Stephenson Sophie , Philip Gayle K. , Horn Matthias , Cantin Neal E. , Blackall Linda L. , van Oppen Madeleine J. H.
Published: November 2022

Corals are associated with a variety of bacteria, which occur in the surface mucus layer, gastrovascular cavity, skeleton, and tissues. Some tissue-associated bacteria form clusters, termed cell-associated microbial aggregates (CAMAs), which are poorly studied. Here, we provide a comprehensive characterization of CAMAs in the coralPocillopora acuta. Combining imaging techniques, laser capture microdissection, and amplicon and metagenome sequencing we show that CAMAs: (i) are located in the tentacle tips and may be intracellular; (ii) containEndozoicomonas, Kistimonas(both Gammaproteobacteria), andSimkania(Chlamydiota) bacteria; (iii)Endozoicomonasmay provide vitamins to its host and use secretion systems and/or pili for colonization and aggregation; (iv)EndozoicomonasandSimkaniaoccur in distinct, but adjacent, CAMAs; (v)Simkaniamay rely on acetate and heme provided by neighboringEndozoicomonas. Our study provides detailed insight into coral endosymbionts, which will guide the assessment of their suitability for probiotic approaches to mitigate coral bleaching.
TALAIA: A 3D visual dictionary for protein structures
Authors: Alemany-Chavarria Mercè , Rodríguez-Guerra Jaime , Maréchal Jean-Didier
Published: November 2022

Graphical analysis of the molecular structure of proteins can be very complex. Full atom representations retain most of the geometric information but are generally crowded and key structural patterns can be difficult to catch. Non-full atom representations could be more instructive on physicochemical aspects but be insufficiently detailed regarding shapes (e.g., entity beans-like models in coarse grain approaches) or individualistic properties of amino acids (e.g., representation of superficial electrostatic properties). TALAIA aims at providing another layer of structural representations. It is a visual dictionary where each amino acid is represented by a unique object with differentiated shapes and colors. It makes it easier to spot important molecular information including patches of amino acids or key interactions between side chains. Most of the conventions used in TALAIA are common in chemistry and biochemistry so that experimentalists and modelers can rapidly grasp the meaning of any TALAIA depictions.

Motivation

The aim of the work is to offer a visual grammar that combines simplistic representations of amino acids while retaining their general geometry and physicochemical properties.

Results

We propose a tool that renders protein structures and encodes both structure and physicochemical aspects as a simple visual grammar. The approach is fast, highly informative, and simple, allowing the identification of possible interactions, hydrophobic patches, and other characteristic structural features at a simple glance.

Availability

https://github.com/insilichem/talaia

Contact

jeandidier.marechal@uab.cat
Experience Alters the Timing Rules Governing Synaptic Plasticity and Learning
Authors: Jayabal Sriram , Bhasin Brandon J. , Kounga Maxwell , DiSanto Jennifer , Suvrathan Aparna , Goldman Mark S. , Raymond Jennifer L.
Published: November 2022

The brain learns about the statistical relationships between events in the world through associative synaptic plasticity, controlled by the timing between neural events. Here, we show that experience can dramatically alter the timing rules governing associative plasticity and learning. In normally reared mice, the timing requirements for short- and long-term associative plasticity at synapses in the oculomotor cerebellum are precisely matched to the 120 ms delay for visual feedback to the circuit about behavioral errors. This specialization of the plasticity rules for the constraints of a particular circuit and learning task is acquired through experience. In dark-reared mice that never experienced visual feedback about oculomotor errors, synapses defaulted to a coincidence-based plasticity rule, with a corresponding delay in the timing of learned eye movements. This temporal metaplasticity persists into adulthood; when mice reared normally from birth were moved to dark housing as adults, the task-specific timing requirements for plasticity and the temporal accuracy of learning were lost and then re-established when visual experience was restored. Computational modeling suggests two general classes of biologically plausible mechanisms, each with multiple possible implementations, that can tune plasticity to distinct features of the statistics of neural activity. Temporal metaplasticity provides a potentially general mechanism for experience-dependent improvement in the way a circuit solves the “temporal credit assignment problem” inherent in most learning tasks, thereby providing a candidate synaptic mechanism for meta-learning.
Methylmap: visualization of modified nucleotides for large cohort sizes
Authors: Coopman Elise , Van den Broeck Marleen , De Poorter Tim , Joris Geert , Dickson Dennis W , Strazisar Mojca , Rademakers Rosa , De Coster Wouter
Published: November 2022

Methylmap is a tool developed for visualization of modified nucleotide frequencies per position, especially for large numbers of samples. Various input possibilities are supported, including the standardized BAM/CRAM files containing MM and ML tags.

Availability and implementation

Methylmap is written in Python3 and available through PyPI and bioconda. The source code is released under MIT license and can be found athttps://github.com/EliseCoopman/methylmap.
Brewpitopes: a pipeline to refine B-cell epitope predictions during public health emergencies
Authors: Farriol-Duran Roc , López-Aladid Ruben , Porta-Pardo Eduard , Torres Antoni , Fernández-Barat Laia
Published: November 2022

The application of B-cell epitope identification for the development of therapeutic antibodies is well established but consuming in terms of time and resources. For this reason, in the last few years, the immunoinformatic community has developed several computational predictive tools.

While relatively successful, most of these tools only use a few properties of the candidate region to determine their likelihood of being a true B-cell epitope. However, this likelihood is influenced by a wide variety of protein features, including the presence of glycosylated residues in the neighbourhood of the candidate epitope, the subcellular location of the protein region or the three-dimensional information about their surface accessibility in the parental protein.

In this study we created Brewpitopes, an integrative pipeline to curate computational predictions of B-cell epitopes by accounting for all the aforementioned features. To this end, we implemented a set of rational filters to mimic the conditions for thein vivoantibody recognition to enrich the B-cell epitope predictions in actionable candidates. To validate Brewpitopes, we analyzed the SARS-CoV-2 proteome. In the S protein, Brewpitopes enriched the initial predictions in 5-fold on epitopes with neutralizing potential (p-value < 2e-4). Other than S protein, 4 out of 16 proteins in the proteome contain curated B-cell epitopes and hence, have also potential interest for viral neutralization, since mutational escape mainly affects the S protein. Our results demonstrate that Brewpitopes is a powerful pipeline for the rapid prediction of refined B-cell epitopes during public health emergencies.

Statement of significance

We have created Brewpitopes, a new pipeline that integrates additional important features such as glycosylation or structural accessibility, to curate B-cell epitope more likely to be functional in vivo. We have also validated Brewpitopes against SARS-CoV-2 not only for S protein but also for the entire viral proteome demonstrating that is a rapid and reliable epitope predictive tool to be implemented in present or future public health emergencies. Brewpitopes has identified 7 SARS-CoV-2 epitopes in S and epitopes allocated in 4 other proteins. Overall, offering an accurate selection of epitopes that might be scaled up to the production of new antibodies.
The Detection of COVID-19 in Chest X-Rays Using Ensemble CNN Techniques
Authors: Kuzinkovas Domantas , Clement Sandhya
Published: November 2022

Advances in the field of image classification using convolutional neural networks (CNNs) have greatly improved the accuracy of medical image diagnosis by radiologists. Numerous research groups have applied CNN methods to diagnose respiratory illnesses from chest x-rays, and have extended this work to prove the feasibility of rapidly diagnosing COVID-19 to high degrees of accuracy. One issue in previous research has been the use of datasets containing only a few hundred images of chest x-rays containing COVID-19, causing CNNs to overfit the image data. This leads to a lower accuracy when the model attempts to classify new images, as would be clinically expected of it. In this work, we present a model trained on the COVID-QU-Ex dataset, overall containing 33,920 chest x-ray images, with an equal share of COVID-19, Non-COVID pneumonia, and Normal images. The model itself is an ensemble of pre-trained CNNs (ResNet50, VGG19, VGG16) and GLCM textural features. It achieved a 98.34% binary classification accuracy (COVID-19/no COVID-19) on a balanced test dataset of 6581 chest x-rays, and 94.68% for distinguishing between COVID-19, Non-COVID pneumonia and normal chest x-rays. Also, we herein discuss the effects of dataset size, demonstrating that a 98.82% 3-class accuracy can be achieved using the model if the training dataset only contains a few thousand images, but that generalisability of the model suffers with such small datasets.
Vaccine hesitancy, reactogenicity and immunogenicity of BNT162b2 and CoronaVac in pediatric patients with neuromuscular diseases
Authors: Yu Michael Kwan Leung , Chan Hoi Shan Sophelia , Cheng Samuel , Leung Daniel , Chan Sau Man , Suen Amy Ka Yan , Wong Wilfred Hing Sang , Peiris Malik , Lau Yu Lung , Rosa Duque Jaime S
Published: November 2022

Introduction

COVID-19 causes global health and psychosocial devastation, particularly to high-risk patients such as those with neuromuscular diseases (NMDs). The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two novel COVID-19 vaccines widely used across the world that confer immune protection to healthy individuals. However, hesitancy towards COVID-19 vaccination was common for patients with NMDs early in the pandemic due to the paucity of data on the safety and efficacy in this specific patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for these patients and included the assessment of the reactogenicity and immunogenicity of these two vaccines.

Methods

Pediatric patients were screened from our NMD registry. For the vaccine hesitancy arm, those aged 8-18 years with no cognitive delay were invited to complete surveys in January and April 2022. For the reactogenicity and immunogenicity arm, patients aged 2-21 years were enrolled for COVID-19 vaccination between June 2021 to April 2022. Participants recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before BNT162b2 or CoronaVac and within 49 days after vaccination to measure their serological antibody responses as compared to healthy children and adolescents.

Results

Forty-one patients completed vaccine hesitancy surveys for both timepoints, and 22 joined our reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81-75.1,p=0.010). Pain at the injection site, fatigue and myalgia were the commonest ARs. Most ARs were mild (75.5%, n=71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of BNT162b2 or CoronaVac, although there was lower neutralization against the Omicron BA.1 variant.

Discussion

This study demonstrated vaccine hesitancy amongst patients with NMDs was influenced by family members and changed across time. BNT162b2 and CoronaVac were safe and immunogenic even for patients on low-dose corticosteroids. Future research is required to assess the durability of the COVID-19 vaccines, the effectiveness of booster doses and other routes of administration against emerging SARS-CoV-2 variants for these patients.
Factors affecting Transition Success and Satisfaction from Child to Adult Mental Health Services in the UK
Authors: Williams Paris , Willoughby Kate , Bennetts Alison , Brandt Valerie
Published: November 2022

Background

Qualitative research has identified factors affecting transition from child mental health services (CAMHS) to adult mental health services (AMHS) but it is unclear which of these factors may lead to disengagement from the young persons’ view.

Methods

N= 272 participants (mean age = 20+/-2.31, 81% females) who had experience with the UK mental healthcare system (patients, carers, health workers) attempted the survey but only participants who had been treated in CAMHS were included in this study, resulting in a total N=144 (mean age = 19.8+/-2.3, 83% female). This study used a cross-sectional, quantitative survey assessing 12 pre-transition, 16 peri-transition, and 11 post-transition variables. The Client Attachment to Therapist Scale (CATS) was used to measure client attachment to CAMHS and AMHS therapists.

Results

Successful transition from CAMHS to AMHS was significantly predicted by using a helpful care plan, continuity of treatment between CAMHS and AMHS, and being engaged in a transition service. However, few clients were aware of transition services at the time of transition. Transition satisfaction was significantly predicted by the same variables. In addition, GP support during the transition, and a more secure attachment to AMHS therapists were associated with higher transition satisfaction.

Conclusions

The results suggest clients’ transition process might be significantly improved by focusing on useful individualised care plans, and ensuring continuity of treatment. Transition success and satisfaction could also be improved by making clients aware of and engaging them in transition services, involving GPs, and working on a secure attachment on the AMHS side.
Reliability of novel centre of pressure measures of quiet standing balance in people with chronic stroke
Authors: Jagroop David , Aryan Raabeae , Schinkel-Ivy Alison , Mansfield Avril
Published: November 2022

Background

People with stroke often have asymmetric motor impairment. Investigating asymmetries in, and dynamic properties of, centre of pressure movement during quiet standing can inform how well balance is controlled.

Research question

What are the test-retest reliabilities of novel measures of quiet standing balance control in people with chronic stroke?

Methods

Twenty people with chronic stroke (>6 months post-stroke), who were able to stand for at least 30 seconds without support, were recruited. Participants completed two 30-second quiet standing trials in a standardized position. Novel measures of quiet standing balance control included: symmetry of variability in centre of pressure displacement and velocity, between-limb synchronization, and sample entropy. Root mean square of centre of pressure displacement and velocity in the antero-posterior and medio-lateral directions were also calculated. Intraclass correlation coefficients (ICCs) were used to determine test-retest reliability, and Bland-Altman plots were created to examine proportional biases.

Results

ICC3,2were between 0.79 and 0.95 for all variables, indicating ‘good’ to ‘excellent’ reliability (>0.75). However, ICC3,1for symmetry indices and between-limb synchronization were <0.75. Bland-Altman plots revealed possible proportional biases for root mean square of medio-lateral centre of pressure displacement and velocity and between-limb synchronization, with larger between-trial differences for participants with worse values.

Significance

These findings suggest that centre of pressure measures extracted from a single 30-second quiet standing trial may have sufficient reliability for some research studies in chronic stroke. However, for clinical applications, the average of at least two trials may be required.
Establishing And Maintaining The Blood-Brain Barrier: Epigenetic And Signaling Determinants
Authors: Sadanandan Jayanarayanan , Thomas Sithara , Mathew Iny Elizabeth , Huang Zhen , Blackburn Spiros L , Tandon Nitin , Lokhande Hrishikesh , McCrea Pierre D , Bresnick Emery H. , Dash Pramod K , McBride Devin W , Harmanci Arif , Ahirwar Lalit K , Jose Dania , Dienel Ari C , Zeineddine Hussein A , Hong Sungha , Peeyush Kumar T
Published: November 2022

The blood-brain barrier (BBB) controls the movement of molecules into and out of the central nervous system (CNS). Since a functional BBB forms by mouse embryonic day E15.5, we reasoned that gene cohorts expressed in CNS endothelial cells (EC) at E13.5 contribute to BBB formation. In contrast, adult gene signatures reflect BBB maintenance mechanisms. Supporting this hypothesis, transcriptomic analysis revealed distinct cohorts of EC genes involved in BBB formation and maintenance. Here, we demonstrate that epigenetic regulator’s histone deacetylase 2 (HDAC2) and polycomb repressive complex 2 (PRC2) control EC gene expression for BBB development and prevent Wnt/β-catenin (Wnt) target genes from being expressed in adult CNS ECs. Low Wnt activity during development modifies BBB genes epigenetically for the formation of functional BBB. As a Class-I HDAC inhibitor induces adult CNS ECs to regain Wnt activity and BBB genetic signatures that support BBB formation, our results inform strategies to promote BBB repair.
Repurposing Vanoxerine as a new antimycobacterial drug and its impact on the mycobacterial membrane
Authors: Kingdon Alexander D. H. , Meosa John Asti-Rochelle , Batt Sarah M. , Besra Gurdyal S.
Published: November 2022

Mycobacterium tuberculosisis a deadly pathogen, currently the leading cause of death worldwide from a single infectious agent through tuberculosis infections. If the End TB 2030 strategy is to be achieved, additional drugs need to be identified and made available to supplement the current treatment regimen. In addition, drug resistance is a growing issue, leading to significantly lower treatment success rates, necessitating further drug development. Vanoxerine (GBR12909), a dopamine re-uptake inhibitor, was recently identified as having anti-mycobacterial activity. Repurposing vanoxerine or its analogues to treat tuberculosis infections may allow a faster route to clinical use than novel drug discovery. However, its effects on Mycobacteria were not well characterised. Herein, we report vanoxerine as a disruptor of the membrane potential, inhibiting mycobacterial efflux and survival, with an undetectable level of resistance. This study suggests a mechanism of action for vanoxerine, which will allow for its continued development and optimisation for pre-clinical testing.
How many ecological niches are defined by the superabundant marine microbeProchlorococcus?
Authors: Miyagi Miriam , Morrison Maike , Kirkpatrick Mark
Published: November 2022

Determining the identities, frequencies, and memberships of ecotypes inProchlorococcusand other superabundant microbes (SAMs) is essential to studies of their evolution and ecology. This is challenging, however, because the extremely large population sizes of SAMs likely cause violations of foundational assumptions made by standard methods used in molecular evolution and phylogenetics. Here we present a tree-free likelihood method to identify ecotypes, which we define as populations with genome sequences whose high similarity is maintained by purifying selection. We applied the method to 96 genomes of the superabundant marine cyanobacteriumProchlorococcusand find that this sample is comprised of about 24 ecotypes, substantially more than the five major ecotypes that are generally recognized. The method presented here may prove useful with other superabundant microbes.
A general method for the development of multicolor biosensors with large dynamic ranges
Authors: Hellweg Lars , Edenhofer Anna , Barck Lucas , Huppertz Magnus-Carsten , Frei Michelle. S. , Tarnawski Miroslaw , Bergner Andrea , Koch Birgit , Johnsson Kai , Hiblot Julien
Published: November 2022

Fluorescent biosensors enable to study cell physiology with spatiotemporal resolution, yet most biosensors suffer from relatively low dynamic ranges. Here, we introduce a family of designed Förster Resonance Energy Transfer (FRET) pairs with near quantitative FRET efficiencies based on the reversible interaction of fluorescent proteins with a fluorescently labeled HaloTag. These FRET pairs enabled the straightforward design of biosensors for calcium, ATP and NAD+with unprecedented dynamic ranges. The color of each of these biosensors can be readily tuned by either changing the fluorescent protein or the synthetic fluorophore, which enabled to monitor simultaneously free NAD+in different subcellular compartments upon genotoxic stress. Minimal modifications furthermore allow the readout of these biosensors to be switched to fluorescence intensity, lifetime or bioluminescence. These FRET pairs thus establish a new concept for the development of highly sensitive and tunable biosensors.

Graphical abstract
Biochemical-free enrichment or depletion of RNA classes in real-time during direct RNA sequencing with RISER
Authors: Sneddon Alexandra , Ravindran Agin , Shanmuganandam Somasundhari , Kanchi Madhu , Hein Nadine , Jiang Simon , Shirokikh Nikolay , Eyras Eduardo
Published: November 2022

The heterogeneous composition of cellular transcriptomes poses a major challenge for detecting weakly expressed RNA classes, as they can be obscured by abundant RNAs. Although biochemical protocols can enrich or deplete specified RNAs, they are time-consuming, expensive and can compromise RNA integrity. Here we introduce RISER, a biochemical-free technology for the real-time enrichment or depletion of RNA classes. RISER performs selective rejection of molecules during direct RNA sequencing by identifying RNA classes directly from nanopore signals with deep learning and communicating with the sequencing hardware in real time. By targeting the dominant messenger and mitochondrial RNA classes for depletion, RISER reduced their respective read counts by more than 85%, resulting in an increase in sequencing depth of up to 93% for long non-coding RNAs. We also applied RISER for the depletion of globin mRNA in whole blood, achieving a decrease in globin reads by more than 90% as well as a significant increase in non-globin reads. Furthermore, using a GPU or a CPU, RISER is faster than GPU-accelerated basecalling and mapping. RISER’s modular and retrainable software and intuitive command-line interface allow easy adaptation to other RNA classes. RISER is available athttps://github.com/comprna/riser.
The worldwide allometric relationship in anatomical structures for plant roots
Authors: Zhang Yue , Cao Jing-Jing , Yang Qing-Pei , Wu Ming-Zuo , Zhao Yong , Kong De-Liang
Published: November 2022

The anatomical structures, i.e., the cortex and stele, are fundamental for the absorptive function of plant roots. Unraveling how the allometric structures are assembled in absorptive roots is essential for our understanding the plant ecology, physiology and responses to global environmental changes. In this review study, we first compile a globally largest dataset on key root structural traits, i.e., root diameter, cortex thickness and stele radius across 512 species. Using this largest dataset, we confirm an allometric relationship of absorptive root structures in a previous study using a much smaller species pool, i.e., the cortex thickness increased much faster than the stele radius with increasing root diameter. The allometric relationship is further validated within and across different plant growth forms (woody, grass, and liana species), mycorrhiza types (arbuscular mycorrhiza, ectomycorrhiza, and orchid mycorrhizas), phylogenetic gradients (from ferns to Orchidaceae of primitive angiosperms), and environmental change scenarios (e.g., the elevation of atmospheric CO2concentration and nitrogen fertilization), supporting the universal allometric relationship in plant roots. We then summarized recent proceedings as well as possible issues on mechanisms underlying the root allometric relationship. The ecological and evolutionary implications for this allometric relationship in roots are also discussed. Finally, we propose several directions that should be stressed in future studies regarding the allometric relationship in plant roots.
Transcriptomic data reveal divergent paths of chitinase evolution underlying dietary convergence in anteaters and pangolins
Authors: Allio Rémi , Teullet Sophie , Lutgen Dave , Magdeleine Amandine , Koual Rachid , Tilak Marie-Ka , de Thoisy Benoit , Emerling Christopher A. , Lefébure Tristan , Delsuc Frédéric
Published: November 2022

Ant-eating mammals represent a textbook example of convergent evolution. Among them, anteaters and pangolins exhibit the most extreme convergent phenotypes with complete tooth loss, elongated skulls, protruding tongues, hypertrophied salivary glands producing large amounts of saliva, and powerful claws for ripping open ant and termite nests. However, comparative genomic analyses have shown that anteaters and pangolins differ in their chitinase acidic gene (CHIA) repertoires, which potentially degrade the chitinous exoskeletons of ingested ants and termites. While the southern tamandua (Tamandua tetradactyla) harbors four functionalCHIAparalogs (CHIA1-4), Asian pangolins (Manisspp.) have only one functional paralog (CHIA5). Here, we performed a comparative transcriptomic analysis of salivary glands in 33 placental species, including 16 novel transcriptomes from ant-eating species and close relatives. Our results suggest that salivary glands play an important role in adaptation to an insect-based diet, as expression of differentCHIAparalogs is observed in insectivorous species. Furthermore, convergently-evolved pangolins and anteaters express different chitinases in their digestive tracts. In the Malayan pangolin,CHIA5is overexpressed in all major digestive organs, whereas in the southern tamandua, all four functional paralogs are expressed, at very high levels forCHIA1andCHIA2in the pancreas, and forCHIA3andCHIA4in the salivary glands, stomach, liver, and pancreas. Overall, our results demonstrate that divergent molecular mechanisms within the chitinase acidic gene family underlie convergent adaptation to the ant-eating diet in pangolins and anteaters. This study highlights the role of historical contingency and molecular tinkering of the chitin-digestive enzyme toolkit in this classic example of convergent evolution.
Environmental changes associated with drying climate are expected to affect functional groups of pro- and microeukaryotes differently in temporary saline waters
Authors: Márton Zsuzsanna , Szabó Beáta , Vad Csaba F. , Pálffy Károly , Horváth Zsófia
Published: November 2022

Temporary ponds are among the most sensitive aquatic habitats to climate change. Their microbial communities have crucial roles in food webs and biogeochemical cycling, yet how their communities are assembled along environmental gradients is still understudied. This study aimed to reveal the environmental drivers of diversity (OTU-based richness, evenness, and phylogenetic diversity) and community composition from a network of saline temporary ponds, soda pans, in two consecutive spring seasons characterized by contrasting weather conditions. We used DNA-based molecular methods to investigate microbial community composition. We tested the effect of environmental variables on the diversity of prokaryotic (bacteria, cyanobacteria) and microeukaryotic functional groups (ciliates, heterotrophic flagellates and nanoflagellates, fungi, phytoplankton) within and across the years. Conductivity and the concentration of total suspended solids and phosphorus were the most important environmental variables affecting diversity patterns in all functional groups. Environmental conditions were harsher and they also had a stronger impact on community composition in the dry spring. Our results imply that these conditions, which are becoming more frequent with climate change, have a negative effect on microbial diversity in temporary saline ponds. This eventually might translate into community-level shifts across trophic groups with changing local conditions with implications for ecosystem functioning.
Single-Cell Epitope-Transcriptomics Reveal Lung Stromal and Immune Cell Response Kinetics to Nanoparticle delivered RIG-I and TLR4 Agonists
Authors: Keenum M. Cole , Chatterjee Paramita , Atalis Alexandra M , Pandey Bhawana , Jimenez Angela C , Roy Krishnendu
Published: November 2022

Lung-resident and circulatory lymphoid, myeloid, and stromal cells, expressing various pattern recognition receptors (PRRs), detect pathogen and danger-associated molecular patterns (PAMPs/DAMPs), and defend against respiratory pathogens and injuries. Here, we report the early responses of murine lungs to nanoparticle-delivered PAMPs, specifically the RIG-I agonist poly-U/UC (PUUC), with or without the TLR4 agonist monophosphoryl lipid A (MPLA). Using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we characterized the responses at 4 and 24 hours after intranasal administration. Within 4 hours, ribosome-associated transcripts decreased in both stromal and immune cells, followed by widespread interferon-stimulated gene (ISG) expression. Using RNA velocity, we show that lung-neutrophils dynamically regulate the synthesis of cytokines like CXCL-10, IL-1α, and IL-1β. Co-delivery of MPLA and PUUC increased chemokine synthesis and upregulated antimicrobial binding proteins targeting iron, manganese, and zinc in many cell types, including fibroblasts, endothelial cells, and epithelial cells. Overall, our results elucidate the early PAMP-induced cellular responses in the lung and demonstrate that stimulation of the RIG-I pathway, with or without TLR4 agonists, induces a ubiquitous microbial defense state in lung stromal and immune cells. Nanoparticle-delivered combination PAMPs may have applications in intranasal antiviral and antimicrobial therapies and prophylaxis.
The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation inClostridioides difficile
Authors: Auria Emile , Hunault Lise , England Patrick , Monot Marc , Da Fonseca Juliana Pipoli , Matondo Mariette , Duchateau Magalie , Tremblay Yannick D.N. , Dupuy Bruno
Published: November 2022

The ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms.Clostridioides difficileinfections have a high rate of recurrence and relapses and it is hypothesised that biofilms are involved in its pathogenicity and persistence. Biofilm formation byC. difficileis still poorly understood. It has been shown that specific molecules such as deoxycholate (DCA) or metronidazole induce biofilm formation, but the mechanisms involved remain elusive. In this study, we describe the role of theC. difficilelipoprotein CD1687 during DCA-induced biofilm formation. We showed that the expression ofCD1687, which is part of an operon within theCD1685-CD1689gene cluster, is controlled by multiple transcription starting sites and some are induced in response to DCA. Only CD1687 is required for biofilm formation and the overexpression of CD1687 is sufficient to induce biofilm formation. Using RNAseq analysis, we showed that CD1687 affects the expression of transporters and metabolic pathways and we identified several potential binding partners by pull-down assay, including transport-associated extracellular proteins. We then demonstrated that CD1687 is surface exposed inC. difficile, and that this localization is required for DCA-induced biofilm formation. Given this localization and the fact thatC. difficileforms eDNA-rich biofilms, we confirmed that CD1687 binds DNA in a non-specific manner. We thus hypothesize that CD1687 is a component of the downstream response to DCA leading to biofilm formation by promoting interaction between the cells and the biofilm matrix by binding eDNA.
The Loci of Insect Phenotypic Evolution
Authors: Courtier-Orgogozo Virginie
Published: November 2022

Insects are important elements of terrestrial ecosystems because they pollinate plants, destroy crops, transmit diseases to livestock and humans, and are important components of food chains. Here I used Gephebase, a manually curated database of genetic variants associated with natural and domesticated trait variation, to explore current knowledge about the genes and the mutations known to contribute to natural phenotypic variation in insects. Analysis of over 600 mutations reveals that data are concentrated towards certain species and traits and that experimental approaches have changed over time. The distribution of coding and cis-regulatory changes varies with traits, experimental approaches and identified gene loci. Recent studies highlight the important role of standing variation, repeated mutations in hotspot genes, recombination, inversions, and introgression.

Highlights

Gephebase compiles more than 600 genes and mutations contributing to insect natural variation

Our genetic knowledge is biased towards certain traits and insect species

Experimental approaches and studied insect species have changed over the years

The relative distribution of coding and cis-regulatory mutations varies with traits and genes

Clusters of causal mutations are more frequently found in insects than in other organisms