bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucosal administration of anti-bacterial antibody provides long-term cross-protection against Pseudomonas aeruginosa respiratory infection
Authors: Pitiot Aubin , Ferreira Marion , Parent Christelle , Boisseau Chloé , Cortes Mélanie , Bouvart Laura , Paget Christophe , Heuzé-Vourc’h Nathalie , Sécher Thomas
Published: July 2022

Bacterial respiratory infections, associated with acute, sometimes recurrent infections and with chronic respiratory diseases, are a major threat for human health. Mucosal administration of therapeutic antibodies (Ab), using the airways as a delivery route, has a tremendous opportunity to benefit to patients with respiratory infections, with remarkable preclinical achievements in both viral and bacterial respiratory infection models and ongoing clinical developments. The primary mode of action of anti-infective Ab delivered through the airways is pathogen neutralization and to a lesser extent, Fc-mediated direct recruitment of immune effectors to facilitate their elimination. Using a mouse model of acute pneumonia induced by P. aeruginosa, a bacterium frequently associated with multidrug resistance and a high rate of recurrence, we characterized an immunomodulatory mode of action of anti-bacterial Ab. Beyond the rapid and efficient containment of the primary infection, the anti-infective Ab delivered through the airways harnessed adaptive immunity to provide a long-term response, preventing from a secondary pathogen infection. This effect is specific and dependent on the Ab dose, intensity of infection and antigen expression by the pathogen upon primary infection. As shown by adoptive transfer experiments, it is mediated by a sustained and protective humoral immune response. Interestingly, the long-lasting response protected partially against secondary infections due to heterologous P. aeruginosa strains. Overall, our findings suggest that mucosal delivery of Ab through the airways offers a dual advantage: a rapid onset of action to neutralize respiratory bacteria and a long-term protection against secondary infections, thereby opening novel perspectives for the development of anti-infective antibody delivered to the lung mucosa, to treat respiratory infections.
Deep Proteome Profiling Reveals Signatures of Age and Sex Differences in Paw Skin and Sciatic Nerve of Naïve Mice
Authors: Xian Feng , Sondermann Julia Regina , Varela David Gomez , Schmidt Manuela
Published: July 2022

The age and sex of studied animals profoundly impact experimental outcomes in animal-based preclinical biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 14 weeks and do not assess study parameters in male and female mice in parallel. This raises concerns regarding reproducibility and neglects potentially relevant age and sex differences. Furthermore, the molecular setup of tissues in dependence of age and sex is unknown in naïve mice. Here, we employed an optimized quantitative proteomics workflow in order to deeply profile mouse paw skin and sciatic nerve (SCN) – two tissues, which are crucially implicated in nociception and pain as well as diverse diseases induced by inflammation, trauma, and demyelination. Remarkably, we uncovered significant differences when comparing (i) male and female mice, and, in parallel, (ii) adolescent mice (4 weeks) with adult mice (14 weeks). Age was identified as a major discriminator of analyzed samples irrespective of tissue type. Moreover, our analysis enabled us to decipher protein subsets and networks that exhibit differential abundance in dependence on the age and/or sex of mice. Notably, among these were proteins and signaling pathways with known relevance for (patho)physiology, such as homeostasis and epidermal signaling in skin and, in SCN, multiple myelin proteins and regulators of neuronal development. In addition, extensive comparisons with available databases revealed that we quantified approx. 50% of gene products that were implicated in distinct skin diseases and pain, many of which exhibited significant abundance changes in dependence on age and/or sex. Taken together, our study emphasizes the need for accurate age matching and uncovers hitherto unknown sex and age differences at the level of proteins and protein networks. Overall, we provide a unique systems biology proteome resource, which facilitates mechanistic insights into somatosensory and skin biology in dependence on age and sex - a prerequisite for successful preclinical studies in mouse disease models.

Graphic workflow

The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.
Single-Cell Multi-Modal GAN (scMMGAN) reveals spatial patterns in single-cell data from triple negative breast cancer
Authors: Amodio Matthew , Youlten Scott E , Venkat Aarthi , San Juan Beatriz P , Chaffer Christine , Krishnaswamy Smita
Published: July 2022

Exciting advances in technologies to measure biological systems are currently at the forefront of research. The ability to gather data along an increasing number of omic dimensions has created a need for tools to analyze all of this information together, rather than siloing each technology into separate analysis pipelines. To advance this goal, we introduce a framework called the Single-Cell Multi-Modal GAN (scMMGAN) that integrates data from multiple modalities into a unified representation in the ambient data space for downstream analysis using a combination of adversarial learning and data geometry techniques. The framework’s key improvement is an additional diffusion geometry loss with a new kernel that constrains the otherwise over-parameterized GAN network. We demonstrate scMMGAN’s ability to produce more meaningful alignments than alternative methods on a wide variety of data modalities, and that its output can be used to draw conclusions from real-world biological experimental data. We highlight data from an experiment studying the development of triple negative breast cancer, where we show how scMMGAN can be used to identify novel gene associations and we demonstrate that cell clusters identified only on the scRNAseq data occur in localized spatial patterns that reveal insights on the spatial transcriptomic images.
Duet: SNP-Assisted Structural Variant Calling and Phasing Using Oxford Nanopore Sequencing
Authors: Zhou Yekai , Leung Amy Wing-Sze , Ahmed Syed Shakeel , Lam Tak-Wah , Luo Ruibang
Published: July 2022

Background

Whole genome sequencing (WGS) using the long-read Oxford Nanopore Technologies (ONT) MinION sequencer provides a cost-effective option for structural variant (SV) detection in clinical applications. Despite the advantage of using long reads, however, accurate SV calling and phasing are still challenging.

Results

We introduce Duet, an SV detection tool optimized for SV calling and phasing using ONT data. The tool uses novel features integrated from both SV signatures and single-nucleotide polymorphism (SNP) signatures, which can accurately distinguish SV haplotype from a false signal. Duet was benchmarked against state-of-the-art tools on multiple ONT sequencing datasets of sequencing coverage ranging from 8X to 40X. At low sequencing coverage of 8X, Duet performs better than all other tools in SV calling, SV genotyping and SV phasing. When the sequencing coverage is higher (20X to 40X), the F1-score for SV phasing is further improved in comparison to the performance of other tools, while its performance of SV genotyping and SV calling remains comparable or higher than other tools.

Conclusion

Duet can perform accurate SV calling, SV genotyping and SV phasing using low-coverage ONT data, making it very useful for low-coverage genomes. It has great performance when scaled to high-coverage genomes, which is adaptable to various clinical applications. Duet is open source and is available at https://github.com/yekaizhou/duet.
Sleep alterations in a mouse model of Spinocerebellar ataxia type 3
Authors: Tsimpanouli Maria-Efstratia , Ghimire Anjesh , Barget Anna J. , Weston Ridge , Paulson Henry L. , Costa Maria do Carmo , Watson Brendon O.
Published: July 2022

Background

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown.

Objectives

Using state-of-the art spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in a SCA3 transgenic mouse model with confirmed disease phenotype.

Methods

We first measured motor phenotypes in 18–31-week-old homozygous and hemizygous SCA3 YACMJD84.2 mice and non-transgenic wild-type littermate mice during lights-on and lights-off periods. We next implanted electrodes to obtain 12-hour (zeitgeber time 0-12) EEG recordings for three consecutive days when the mice were 26–36 weeks old. We then analyzed EEG-based sleep structure data to quantify differences between homozygous, hemizygous, and wild-type mice.

Results

Compared to wild-type littermates, SCA3 homozygous mice display: i) increased duration of rapid-eye movement sleep (REM) and fragmentation in all sleep and wake states; ii) higher beta power oscillations during REM and non-REM (NREM); and iii) additional spectral power band alterations during REM and wake.

Conclusions

Our data show that sleep architecture and EEG spectral power are dysregulated in homozygous SCA3 mice, indicating that common sleep-related etiologic factors may underlie mouse and human SCA3 phenotypes.
Direct Cell Extraction of Membrane Proteins for Structure-Function Analysis
Authors: Drulyte Ieva , Gutgsell Aspen Rene , Lloris-Garcerá Pilar , Liss Michael , Geschwindner Stefan , Radjainia Mazdak , Frauenfeld Jens , Löving Robin
Published: July 2022

Membrane proteins are the largest group of therapeutic targets in a variety of disease areas and yet, they remain particularly difficult to investigate. We have developed a novel one-step approach for the incorporation of membrane proteins directly from cells into lipid Salipro nanoparticles. Here, with the pannexin1 channel as a case study, we demonstrate the applicability of this method for structurefunction analysis using SPR and cryo-EM.
The FANCC-FANCE-FANCF complex is evolutionarily conserved and regulates meiotic recombination
Authors: Singh Dipesh Kumar , Gamboa Rigel Salinas , Singh Avinash Kumar , Walkemeir Birgit , Van Leene Jelle , De Jaeger Geert , Siddiqi Imran , Guerois Raphael , Crismani Wayne , Mercier Raphael
Published: July 2022

At meiosis, programmed meiotic DNA double-strand breaks are repaired via homologous recombination, resulting in crossovers (COs). From a large excess of DNA double-strand breaks that are formed, only a small proportion gets converted into COs because of active mechanisms that restrict CO formation. The Fanconi anemia (FA) complex proteins AtFANCM, MHF1, and MHF2 were previously identified in a genetic screen as anti-CO factors that function during meiosis in Arabidopsis thaliana. Here, pursuing the same screen, we identify FANCC as a new anti-CO gene. FANCC was previously only identified in mammals because of low primary sequence conservation. We show that FANCC, and its physical interaction with FANCE-FANCF, is conserved from vertebrates to plants. Further, we show that FANCC, together with its subcomplex partners FANCE and FANCF, regulates meiotic recombination. Mutations of any of these three genes partially rescues CO-defective mutants, which is particularly marked in female meiosis. Functional loss of FANCC, FANCE, or FANCF results in synthetic meiotic catastrophe with the pro-CO factor MUS81. This work reveals that FANCC is conserved outside mammals and has an anti-CO role during meiosis together with FANCE and FANCF.
The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart
Authors: Taliani Valeria , Buonaiuto Giulia , Desideri Fabio , Setti Adriano , Santini Tiziana , Galfrè Silvia , Schirone Leonardo , Mariani Davide , Frati Giacomo , Valenti Valentina , Sciarretta Sebastiano , Perlas Emerald , Nicoletti Carmine , Musarò Antonio , Ballarino Monica
Published: July 2022

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes-of-action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodelling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing and whole-mountin situhybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the myocardium and ventricular hypo-trabeculation. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications.
Biochemical noise enables a single optogenetic input to control identical cells to track asymmetric and asynchronous reference signals
Authors: May Michael P , Munsky Brian
Published: July 2022

Optogenetics is a powerful technology to control synthetic gene circuits using external and computer-programmable light inputs. Like all biological processes, these systems are subject to intrinsic noise that arises from the stochastic process of gene regulation at the single-cell level. Many engineers have sought to mitigate this noise by developing more complex embedded bio-circuits, but recent work has shown that noise-exploiting stochastic controllers could enable new control strategies that take advantage of noise, rather than working against it. These noise-exploiting controllers were initially proposed to solve a single-input-multi-output stationary control problem, where symmetry was broken in a means reminiscent to the concept of Maxwell’s Demon. In this paper, we extend those results and show through computation that transient, asymmetric, and asynchronous stochastic control of the single-input-multi-output (SIMO) control problem is posible to achieve by cycling through different controllers in time. We show that such a method is able control two cells to two different periodic fates with different frequencies and different phases despite the use of only one control input.
Increased landscape disturbance and streamflow variability threaten fish biodiversity in the Red River catchment, USA
Authors: Mollenhauer Robert , Mouser Joshua B. , Roland Victor L. , Brewer Shannon K.
Published: July 2022

Aim

Stream fish distributions are hypothesized to be strongly associated with landscape characteristics at multiple scales. Variation in flow regimes and intensity of landscape disturbance are associated with stream fish distributions; however, relationships are poorly understood in many high‐diversity regions. Our objective was to identify occurrence relationships between fish distributions and streamflow and landscape characteristics in the south‐central United States.

Location

Our study area was the central Red River catchment in Oklahoma, Texas and Arkansas, USA.

Methods

We used existing fish surveys to model the occurrence of a diverse, warmwater assemblage among hydraulic response units (HRUs). We used multispecies occupancy modelling to identify variation in occurrence probability among 111 stream fishes in relation to landscape disturbance and flow regime characteristics.

Results

We found occurrence relationships with landscape disturbance and 11 metrics comprising all flow‐regime components. The relationships varied within both major species groups and some genera. Frequency and duration were the most common metrics underlying flow regime relationships. More common stream fishes tended to be positively associated with higher levels of landscape disturbance and flow regime metrics representing variability; conversely, narrow‐ranged fishes tended to be negatively associated. Occurrence relationships with flow metrics representing high‐flow events were predominately negative. As expected, many species were strongly associated with ecoregion with landscape disturbance and flow relationships held constant.

Main conclusions

Our study informs land use and water management decisions and stream fish conservation at multiple spatial scales. Collectively, the findings suggest potential homogenization of the Red River fish assemblage with increased landscape disturbance and streamflow variability. A reduction in landscape disturbance and maintenance of natural flow patterns at coarser scales may benefit endemic and narrow‐ranged fishes. Our findings also help guide finer‐scale land use and water management decisions by identifying stream network areas with a high occurrence probability of less tolerant fishes.
Nomogram for predicting in‐hospital mortality of nonagenarians with community‐acquired pneumonia
Authors: Zan Yumin , Song Weiwei , Wang Yu , Shao Jiaofang , Wang Zhiyong , Zhao Weihong , Wu Jianqing , Xu Wei
Published: July 2022

Aim

Nonagenarians with community‐acquired pneumonia (CAP) have a high mortality rate; however, appropriate tools for reliable severity assessment in this population are lacking. The current study aimed to evaluate the risk factors and establish a nomogram to predict in‐hospital mortality of nonagenarians with CAP.

Methods

In total, 304 patients aged ≥90 years who were admitted with CAP to Jiangsu Provincial People's Hospital and Jiangsu Provincial Hospital of Chinese Medicine between 2014 and 2020 were retrospectively analyzed. Clinical information, laboratory imaging results and pathogen detection were retrieved. Significant variables independently associated with CAP were identified by a logistic regression model, and a nomogram prediction model was constructed. The nomogram was compared with the widely used assessments: CURB‐65, PSI and National Early Warning Score (NEWS) scores.

Results

Univariate and multivariate logistic regression analyses identified gender, blood urea nitrogen, C‐reactive protein‐to‐albumin ratio, Charlson Comorbidity Index and systemic immune inflammation index as independent factors that affect the prognosis. We created a nomogram for CAP based on these risk factors. The nomogram had a bootstrapped concordance index of 0.796 and was well‐calibrated in the decision analysis curve range of 0.1–0.98. The area under the curve was 0.796 (95% CI: 0.74–0.85), significantly higher than for CURB‐65, PSI and NEWS scores (P < 0.05).

Conclusions

Our nomogram model can predict the outcome of hospitalized nonagenarians with CAP and guide clinicians to provide better treatment, leading to improved prognosis and reduced mortality. Geriatr Gerontol Int 2022; 22: 635–641.
Spillover effects in Chinese carbon, energy and financial markets
Authors: Cao Guangxi , Xie Fei , Ling Meijun
Published: July 2022

As China's carbon market continues to develop, its close connection with the financial and energy markets is becoming increasingly apparent. A systematic study of the spillover effects between markets is important, as it can help prevent excessive fluctuations in carbon prices. With this in mind, this study proposes a time‐varying parameter vector autoregression with Lanne–Nyberg decomposition extended joint connectedness approach to analyze quantitatively the spillover effects in the “carbon–energy–financial” system. Empirical results show that a bidirectional spillover effect exists among markets. Not only does the carbon market have the most pronounced return (volatility) linkages with the natural gas (clean energy) market, but the information connected with the energy markets is also more closely linked than with the financial markets. We also find that market fluctuations, caused by the China–US trade conflict and the COVID‐19 pandemic, have increased spillovers in the system.
Analyst following, financial constraint, and audit opinion shopping: From the perspective of earning management
Authors: Lin Zhijun , Wang Longmei
Published: July 2022

This study examines the relationships among analyst following, financial constraint, and audit opinion shopping from the perspective of earnings management, taking a sample of Chinese A‐share firms from 2008 to 2018. We find that analyst following alleviates firm's accrued earnings management activities which restrain opinion shopping behaviors; on the other hand, it prompts real earnings management activities that encourage firm's effort to audit opinion shopping. Earnings management has a mediation effect on the positive association between analyst following and audit opinion shopping. Corporate financial constraint amplifies the positive effect of analyst following on opinion shopping.
The impact of economic hardships on the intent to migrate: Micro‐level evidence from Venezuela
Authors: Posso Alberto , Bodanac Nicholas , Palermo Facundo
Published: July 2022

We examine the impact of various hardships on individual's consideration of migration as a coping mechanism. Previous studies fail to identify the microeconomic drivers of migration during crises, lumping all the potential consequences of a crisis into singular categories. We argue that migration is one of several coping strategies available to individuals and present an empirical model that motivates this proposition. Our approach also suggests that unobserved factors, such as ability, determine both returns to migration as well as the availability of domestic (non‐migration) coping strategies, which curbs migration. We use new survey data covering over 1000 individuals in three large Venezuelan cities. This nation is undergoing a crisis caused by unprecedented levels of hyperinflation, which resulted in the worse migration crisis in Latin American history. We focus on hardships that characterise the Venezuelan situation: food insecurity; scarcity of health products/services; crime; and diminished purchasing power. We marry this information to data on stated preferences over migration. We recognise that individuals may desire to migrate temporarily or permanently and model those choices separately and subsequently treat them as competing options. Our preferred results suggest that falling victim to crime and poor health services motivate migration. We conclude with policy suggestions.
BR 287 Duplication Designed through the Methods of DNIT and MeDiNa (2020): Structural and Financial Analysis
Authors: Pascoal Paula Taiane , Chiarello Gabriéli Pires , Baroni Magnos , Pereira Deividi Da Silva , Zucchi Fernando Luiz
Published: July 2022

The paving field has experienced extensive changes due to the growth of traffic. In order to attend this evolution, it became necessary the implementation of a new methodoly for pavement designing that uses a mechanistic-empirical approach. This paper aims to compare, structurally and financially, three structures, one designed using the DNIT’s method and two through “Método de Dimensionamento Nacional – MeDiNa”. The three structures were analyzed concerning the behavior in relation to permanent deformation, fatigue life and regarding the necessary investment to pave one-kilometer duplication of an existent highway. Even though the two structures designed through MeDiNa were find to be more expensive than the one designed using DNITs precepts, when considering the cost related to the number of load requests supported by the pavement, structures designed through MeDiNa proved to be more reliable in face of layers damage and presented a good cost per supported requests.
Gaussian Stochastic Process Modeling of Blend Repaired Airfoil Modal Response Using Reduced Basis Mode Shape Approach
Authors: Brown Jeffrey M. , Kaszynski Alex A. , Gillaugh Daniel L. , Carper Emily B. , Beck Joseph A.
Published: July 2022

A machine learning (ML) approach is developed to predict the effect of blend repairs on airfoil frequency, modal assurance criterion (MAC), and modal displacement vectors. The method is demonstrated on a transonic research rig compressor rotor airfoil. A parametric definition of blend geometry is developed and shown to be capable of encompassing a large range of blend geometry. This blend repair geometry is used to modify the airfoil surface definition and a mesh morphing process transforms the nominal finite element model (FEM) to the repaired configuration. A multilevel full factorial sampling of the blend repair design space provides training data to a Gaussian stochastic process (GSP) regressor. The frequency and MAC results create a vector of training data for GSP calibration, but the airfoil mode shapes require further mathematical manipulation to avoid creating GSP models for each nodal displacement. This paper develops a method to significantly reduce blended airfoil mode shape emulation cost by transforming the mode shape training data into a reduced basis space using principal component analysis (PCA). The coefficients of this reduced basis are used to train a GSP that can then predict the values for new blended airfoils. The emulated coefficients are used with the reduced basis vectors in a reconstruction of blended airfoil mode shape. Validation data is computed at a full-factorial design that maximizes the distance from training points. It is found that large variations in modal properties from large blend repairs can be accurately emulated with a reasonable number of training points. The reduced basis approach of mode shape variation is shown to more accurately predict MAC variation when compared to direct MAC emulation. The added benefit of having the full modal displacement field also allows determination of other influences such as tip-timing limits and modal force values.
Differences in Accelerometer-Measured Physical Activity and Sedentary Behavior Between Middle-Aged Men and Women in Japan: A Compositional Data Analysis
Authors: Amagasa Shiho , Inoue Shigeru , Shibata Ai , Ishii Kaori , Kurosawa Sayaka , Owen Neville , Oka Koichiro
Published: July 2022

Background: Differences in accelerometer-measured sedentary behavior and different physical activity (PA) intensities between men and women have been poorly described. The authors examined gender differences in time-use activity composition and total volume of PA. Methods: A cross-sectional mail survey was conducted from 2013 to 2015 with a randomized sample of 6000 middle-aged (40–64 y) community-dwelling Japanese adults living in urban and regional cities. Participants wore Active style Pro HJA-350IT on their waist for 7 consecutive days. Gender differences in activity time use was examined using compositional data analysis to control for time spent in all activity measures. Results: In total, 757 participants (303 men, 52.3 [7.1] y) with valid data were included in the analysis. Women spent on average 12.6% less time in sedentary behavior and 23.4% more time in light-intensity PA than men, whereas no significant difference was found for moderate to vigorous PA. Women accumulated a significantly greater volume of PA than men (17.8 vs 15.0 metabolic equivalent of task h/d). Conclusions: Japanese middle-aged women showed higher levels of PA than men because they spent more time in light-intensity PA. Given the health benefits of light-intensity PA, evaluating only moderate to vigorous PA may lead to an underestimation of women’s participation in PA.
Species-Specific Molecular Barriers to SARS-CoV-2 Replication in Bat Cells
Authors: Aicher Sophie-Marie , Streicher Felix , Chazal Maxime , Planas Delphine , Luo Dongsheng , Buchrieser Julian , Nemcova Monika , Seidlova Veronika , Zukal Jan , Serra-Cobo Jordi , Pontier Dominique , Pain Bertrand , Zimmer Gert , Schwartz Olivier , Roingeard Philippe , Pikula Jiri , Dacheux Laurent , Jouvenet Nolwenn
Published: July 2022

Bats are host ancestors of several viruses that cause serious disease in humans, as illustrated by the ongoing SARS-CoV-2 pandemic. Progress in investigating bat-virus interactions has been hampered by a limited number of available bat cellular models.
Genomic Diversity across Candida auris Clinical Isolates Shapes Rapid Development of Antifungal Resistance
In Vitro
and
In Vivo
Authors: Burrack Laura S. , Todd Robert T. , Soisangwan Natthapon , Wiederhold Nathan P. , Selmecki Anna
Published: July 2022

Drug resistant
Candida auris
infections are recognized by the CDC as an urgent threat. Here, we obtained and characterized a set of clinical isolates of
C. auris
including multiple isolates from the same patient.
A Noninvasive Method for Time-Lapse Imaging of Microbial Interactions and Colony Dynamics
Authors: Molina-Santiago Carlos , Pearson John R. , Berlanga-Clavero María Victoria , Pérez-Lorente Alicia Isabel , de Vicente Antonio , Romero Diego
Published: July 2022

Communication and interactions between single cells are continuously defining the structure and composition of microbial communities temporally and spatially. Methods routinely used to study these communities at the cellular level rely on sample manipulation which makes microscopic time-lapse experiments impossible.
Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam
Authors: Zawahir Shukry , Le Hien , Nguyen Thu Anh , Beardsley Justin , Duc Anh Dang , Bernays Sarah , Viney Kerri , Cao Hung Thai , McKinn Shannon , Tran Hoang Huy , Nguyen Tu Son , Velen Kavindhran , Luong Minh Tan , Tran Thi Mai Hung , Nguyen Viet Nhung , Nguyen Viet Ha , Nguyen Thi Cam Van , Nguyen Trung Thanh , Jan Stephen , Marais Ben J , Negin Joel , Marks Guy B , Fox Gregory
Published: July 2022

Background

Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB.

Methods

A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs’ referral.

Results

In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan.

Conclusions

Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings.
Protocol for an intervention development and pilot implementation evaluation study of an e-health solution to improve newborn care quality and survival in two low-resource settings, Malawi and Zimbabwe: Neotree
Authors: Wilson Emma , Gannon Hannah , Chimhini Gwendoline , Fitzgerald Felicity , Khan Nushrat , Lorencatto Fabiana , Kesler Erin , Nkhoma Deliwe , Chiyaka Tarisai , Haghparast-Bidgoli Hassan , Lakhanpaul Monica , Cortina Borja Mario , Stevenson Alexander G. , Crehan Caroline , Sassoon Yali , Hull-Bailey Tim , Curtis Kristina , Chiume Msandeni , Chimhuya Simbarashe , Heys Michelle
Published: July 2022

Introduction

Every year 2.4 million deaths occur worldwide in babies younger than 28 days. Approximately 70% of these deaths occur in low-resource settings because of failure to implement evidence-based interventions. Digital health technologies may offer an implementation solution. Since 2014, we have worked in Bangladesh, Malawi, Zimbabwe and the UK to develop and pilot Neotree: an android app with accompanying data visualisation, linkage and export. Its low-cost hardware and state-of-the-art software are used to improve bedside postnatal care and to provide insights into population health trends, to impact wider policy and practice.

Methods and analysis

This is a mixed methods (1) intervention codevelopment and optimisation and (2) pilot implementation evaluation (including economic evaluation) study. Neotree will be implemented in two hospitals in Zimbabwe, and one in Malawi. Over the 2-year study period clinical and demographic newborn data will be collected via Neotree, in addition to behavioural science informed qualitative and quantitative implementation evaluation and measures of cost, newborn care quality and usability. Neotree clinical decision support algorithms will be optimised according to best available evidence and clinical validation studies.

Ethics and dissemination

This is a Wellcome Trust funded project (215742_Z_19_Z). Research ethics approvals have been obtained: Malawi College of Medicine Research and Ethics Committee (P.01/20/2909; P.02/19/2613); UCL (17123/001, 6681/001, 5019/004); Medical Research Council Zimbabwe (MRCZ/A/2570), BRTI and JREC institutional review boards (AP155/2020; JREC/327/19), Sally Mugabe Hospital Ethics Committee (071119/64; 250418/48). Results will be disseminated via academic publications and public and policy engagement activities. In this study, the care for an estimated 15 000 babies across three sites will be impacted.

Trial registration number

NCT0512707; Pre-results
Protocol for a process evaluation: face-to-face physiotherapy compared with a supported home exercise programme for the management of musculoskeletal conditions: the REFORM trial
Authors: Withers Hannah G , Liu Hueiming , Glinsky Joanne V , Chu Jackie , Jennings Matthew D , Hayes Alison J , Starkey Ian J , Palmer Blake A , Szymanek Lukas , Cruwys Jackson J , Wong David , Duong Kitty , Barnett Anne , Tindall Matthew J , Lucas Barbara R , Lambert Tara E , Taylor Deborah A , Sherrington Catherine , Ferreira Manuela L , Maher Christopher G , Zadro Joshua R , Harvey Lisa A
Published: July 2022

Introduction

The REFORM (REhabilitation FOR Musculoskeletal conditions) trial is a non-inferiority randomised controlled trial (n=210) designed to determine whether a supported home exercise programme is as good or better than a course of face-to-face physiotherapy for the management of some musculoskeletal conditions. The trial is currently being conducted across Sydney government hospitals in Australia. This process evaluation will run alongside the REFORM trial. It combines qualitative and quantitative data to help explain the trial results and determine the feasibility of rolling out supported home exercise programmes in settings similar to the REFORM trial.

Methods and analysis

Two theoretical frameworks underpin our process evaluation methodology: the Realist framework (context, mechanism, outcomes) considers the causal assumptions as to why a supported home exercise programme may be as good or better than face-to-face physiotherapy in terms of the context, mechanisms and outcomes of the trial. The RE-AIM framework describes the Reach, Effectiveness, Adoption, Implementation and Maintenance of the intervention. These two frameworks will be broadly used to guide this process evaluation using a mixed-methods approach. For example, qualitative data will be derived from interviews with patients, healthcare professionals and stakeholders, and quantitative data will be collected to determine the cost and feasibility of providing supported home exercise programmes. These data will be analysed iteratively before the analysis of the trial results and will be triangulated with the results of the primary and secondary outcomes.

Ethics and dissemination

This trial will be conducted in accordance with the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (2018) and the Note for Good Clinical Practice (CPMP/ICH-135/95). Ethical approval was obtained on 17 March 2017 from the Northern Sydney Local Health District Human Research Ethics Committee (trial number: HREC/16HAWKE/431-RESP/16/287) with an amendment for the process evaluation approved on 4 February 2020. The results of the process evaluation will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences.

Trial registration number

ACTRN12619000065190.
Gift of time: learning together to embed a palliative approach to care in long-term care
Authors: Sarakbi Diana , Graves Elan , King Gillian , Webley Jane , Crick Shelly , Quinn Christine
Published: July 2022

Background

Embedding a Palliative Approach to Care (EPAC) is a model that helps shift the culture in long-term care (LTC) so that residents who could benefit from palliative care are identified early. Healthcare Excellence Canada supported the implementation of EPAC in seven teams from across Canada between August 2018 and September 2019.

Objective

To identify effective strategies for supporting the early identification of palliative care needs to improve the quality of life of residents in LTC.

Intervention

Training methods on the EPAC model included a combination of face-to-face education (national and regional workshops), online learning (webinars and access to an online platform) and expert coaching. Each team adapted EPAC based on their organisational context and jurisdictional requirements for advance care planning.

Measures

Teams tracked their progress by collecting monthly data on the number of residents who died, date of their most recent goals of care (GOCs) conversation, location of death and number of emergency department (ED) transfers in the last 3 months of life. Teams also shared their implementation strategies including successes, barriers and lessons.

Results

Implementation of EPAC required leadership support and dedicated time for changing how palliative care is perceived in LTC. Based on 409 resident deaths, 89% (365) had documented GOC conversations; 78% (318) had no transfers to the ED within the last 3 months of life; and 81% (333) died at home. A monthly review of the results showed that teams were having earlier GOC conversations with residents. Teams also reported improvements in the quality of care provided to residents and their families.

Conclusion

EPAC was successfully adapted and adopted to the organisational contexts of homes participating in the collaborative.
Parents and school-aged children’s mental well-being after prolonged school closures and confinement during the COVID-19 pandemic in Mexico: a cross-sectional online survey study
Authors: Leon Rojas Daniela , Castorena Torres Fabiola , Garza-Ornelas Barbara M , Castillo Tarquino Angie Milady , Salinas Silva Cynthia Anahí , Almanza Chanona José Luis , Rodríguez-de-Ita Julieta
Published: July 2022

Objective

This study aimed to determine parents’ and school-aged children’s mental well-being after experiencing confinement and prolonged school closures during the COVID-19 pandemic.

Design

Using a cross-sectional design, an online survey was applied to parents of school-aged children inquiring about their mental well-being and COVID-19 pandemic changes in their home and working lives. To assess the presence of depression, anxiety and stress in parents, the participants responded to the Depression, Anxiety and Stress Scale - 21 scale. To assess psychosocial dysfunction and sleep disturbances in children, participants responded to the Pediatric Symptom Checklist and the Children Sleep Habits Questionnaire.

Results

A total of 209 parents answered the questionnaire, most of them were female (87.1%) with a mean age of 40 years. The prevalence of anxiety, stress and parental depression symptoms were 35.9%, 28.2% and 25.4%, respectively. Children’s mean age was 8.9 years, the prevalence of children’s psychosocial dysfunction was 12%, while their sleep disturbance symptoms were 59.8%. 10.5% of children were suffering both outcomes. We found a bidirectional relationship between parents’ and children’s mental health outcomes. Parental depression symptoms were associated with experiencing COVID-19 infection within the household, having children with pre-existing medical diagnoses, children’s psychosocial dysfunction and sleep disturbances. Children’s psychosocial dysfunction was associated with parental depression and changes in their school routine. Children’s sleep disturbances were associated with parental anxiety, younger age, increased use of electronic devices, night-time awakenings and shorter sleep time.

Conclusion

Our results support the impact of long confinement and school closure due to the COVID-19 pandemic in Mexican children and parents’ mental well-being. We advocate for specific mental health interventions tailored to respond to parents and children at risk of mental well-being distress.
Acute pancreatitis in children – morbidity and outcomes at 1 year
Authors: Bhanot A , Majbar AA , Candler Toby , Hunt LP , Cusick E , Johnson Paul R V , Shield Julian PH
Published: July 2022

Objective

To establish short-term and medium-term complications 1-year postdiagnosis, of acute pancreatitis (AP) in children aged 0–14 years.

Design

One-year follow-up of a prospective monthly surveillance of new cases of AP in children under 15 years through the British Paediatric Surveillance Unit (BPSU) from April 2013 to April 2014.

Setting

A monthly surveillance of >3700 consultant paediatricians and paediatric surgeons in the UK and Ireland using the BPSU.

Patients

Children aged 0–14 years with a new diagnosis of AP.

Main outcome measures

The outcomes following AP, including the incidence of complications and comorbidity at diagnosis and at 1 year.

Results

Of the 94 new confirmed cases of AP identified in the UK during the study period, 90 cases (96%) were included in the 1-year follow-up. 30 patients (32%) developed further episode(s) of AP. Over one-fifth of patients developed one or more major complication. At initial admission, the most common of these was pancreatic necrosis (n=8, 9%), followed by respiratory failure (n=7, 7%). Reported complications by 1 year were pseudocyst formation (n=9, 10%), diabetes requiring insulin therapy (n=4, 4%) and maldigestion (n=1, 1%). At 1-year postdiagnosis, only 59% of children made a full recovery with no acute or chronic complications or recurrent episodes of AP. Two patients died, indicating a case fatality of ~2.0%.

Conclusions

AP in childhood is associated with significant short-term and medium-term complications and comorbidities including risk of recurrence in approximately a third of cases.
High-intensity functional exercise does not cause persistent elevations in augmentation index in young men and women
Authors: Landers-Ramos Rian Q. , Lawal Ibukun , Imery Ian , Siok Dakota , Addison Odessa , Zabriskie Hannah A. , Dondero Kathleen , Dobrosielski Devon A.
Published: July 2022

Elevations in central augmentation index (AIx) are predictive of cardiovascular disease. The objective of this study was to examine AIx immediately and 24 h following an acute bout of high-intensity functional training (HIFT) in apparently healthy young adults. A second aim compared the exercise-induced AIx recovery response between men and women. Thirty-two recreationally active younger adults ( n = 16 men) were tested. Baseline central hemodynamic measures were assessed, followed by a single bout of bodyweight HIFT. The HIFT included 4 rounds of burpees, jump squats, split squats, and walking lunges. Assessments were repeated 5, 10, 15, and 24 h post-exercise. AIx was normalized to a heart rate of 75 bpm (AIx75). There was a significant main effect of time on AIx75 across all groups ( P < 0.001) with AIx75 increasing at all acute time points compared with baseline and returning to resting values 24 h post-exercise. When examining sex differences after covarying for height and body fat percentage, the authors found no time × sex interaction ( P = 0.62), or main effect for sex ( P = 0.41), but the significant main effect of time remained ( P < 0.001). The AIx75 response to HIFT follows a similar recovery pattern as previously studied modes of exercise with no residual effects 24 h later and no differences between men and women indicating no persistent cardiovascular strain in younger adults participating in this mode of exercise.
Revealing the influence of temperature on benzene oxidation by palladium oxide via ReaxFF molecular dynamics simulations
Authors: Wu Sheng , Wei Mingrui , Guo Guanlun , Ju Hongling
Published: July 2022

For catalytic reactions, temperature has a great influence on reaction rate and reaction mechanism. The oxidation processes of soot precursors (C6H6) at different temperatures are simulated using reactive force field molecular dynamics to investigate the effect of temperature on the oxidation process. The reaction products at different temperatures and the effect of temperature are discussed. The results show that the intermediate species C3 and C4 are more and existed longer at 1400 K than at 2000 K, while hardly existed at 2000 K, indicating that as the temperature increases, the oxidation reaction takes place more completely and the products formed are more stable. The effect of temperature on the oxidation mechanism is then explored; the results show that the main reaction pathway at 1400 K is basically the same as that at 2000 K, while the final product contains less hydrogen and more oxygen atoms at 2000 K. The C6 components with two, three, and four oxygen atoms are found easier to be decomposed at both 1400 and 2000 K. It shows that temperature mainly affects the catalytic reaction process by affecting the hydrogen and oxygen content of the decomposed C6 component. This may be helpful to understand the effect of temperature on the C6H6 oxidation from the perspective of basic research.
Drivers’ ability to distinguish consecutive horizontal curves
Authors: Sil Gourab , Maji Avijit , Majumdar Bandhan Bandhu , Maurya Akhilesh Kumar
Published: July 2022

Driver error in distinguishing preceding and upcoming horizontal curves can lead to single-vehicle fatal crashes. The 3D perspective views of different horizontal curve stimuli were used to examine a representative sample of volunteering drivers’ ability to distinguish consecutive horizontal curves. A probit model, developed using the recorded responses, revealed that differences in radius and deflection angle between the consecutive curves are more likely to influence, whereas radius and deflection angle of reference curve are less likely to influence drivers in distinguishing consecutive curves. The sensitivity analysis of the model parameters indicated a difference in radius between the consecutive curves as the most and deflection angle of reference curve as the least sensitive parameters. The estimated marginal effects are useful for evaluating the design and safety of consecutive curves from the drivers’ perspective. Finally, nomograms were developed for relevant applications.