bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequently arising ESX-1-associated phase variants influence
Mycobacterium tuberculosis
fitness in the presence of host and antibiotic pressures
Authors: Luna Michael J. , Oluoch Peter O. , Miao Jiazheng , Culviner Peter , Papavinasasundaram Kadamba , Jaecklein Eleni , Shell Scarlet S. , Ioerger Thomas R. , Fortune Sarah M. , Farhat Maha R. , Sassetti Christopher M. 
Published: January 2025

ABSTRACT

Mycobacterium tuberculosis
(Mtb) exhibits an impressive ability to adapt to rapidly changing environments, despite its genome’s apparent stability. Recently, phase variation through indel formation in homopolymeric tracts (HT) has emerged as a potentially important mechanism promoting adaptation in Mtb. This study examines the impact of common phase variants associated with the ESX-1 type VII secretion system, focusing on a highly variable HT upstream of the ESX-1 regulatory factor,
espR
. By engineering this frequently observed indel into an isogenic background, we demonstrate that a single nucleotide insertion in the
espR
5′UTR causes post-transcriptional upregulation of EspR protein abundance and corresponding alterations in the EspR regulon. Consequently, this mutation increases the expression of ESX-1 components in the
espACD
operon and enhances ESX-1 substrate secretion. We find that this indel specifically increases isoniazid resistance without impacting the effectiveness of other drugs tested. Furthermore, we show that two distinct observed HT indels that regulate either
espR
translation or
espACD
transcription increase bacterial fitness in a mouse infection model. The presence of multiple ESX-1-associated HTs provides a mechanism to combinatorially tune protein secretion, drug sensitivity, and host-pathogen interactions. More broadly, these findings support emerging data that Mtb utilizes HT-mediated phase variation to direct genetic variation to certain sites across the genome in order to adapt to changing pressures.

IMPORTANCE

Mycobacterium tuberculosis
(Mtb) is responsible for more deaths worldwide than any other single infectious agent. Understanding how this pathogen adapts to the varied environmental pressures imposed by host immunity and antibiotics has important implications for the design of more effective therapies. In this work, we show that the genome of Mtb contains multiple contingency loci that control the activity of the ESX-1 secretion system, which is critical for interactions with the host. These loci consist of homopolymeric DNA tracts in gene regulatory regions that are subject to high-frequency reversible variation and act to tune the activity of ESX-1. We find that variation at these sites increases the fitness of Mtb in the presence of antibiotic and/or during infection. These findings indicate that Mtb has the ability to diversify its genome in specific sites to create subpopulations of cells that are preadapted to new conditions.
c-di-GMP phosphodiesterase ProE interacts with quorum sensing protein PqsE to promote pyocyanin production in
Pseudomonas aeruginosa
Authors: Feng Qishun , Dai Xin , Wu Qiulan , Zhang Lianhui , Yang Liang , Fu Yang 
Published: January 2025

ABSTRACT

The universal bacterial second messenger bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) plays critical roles in regulating a variety of bacterial functions such as biofilm formation and virulence. The metabolism of c-di-GMP is inversely controlled by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs). Recently, increasing studies suggested that the protein-protein interactions between DGCs/PDEs and their partners appear to be a common way to achieve specific regulation. In this work, we showed that the PDE ProE can interact with PQS quorum sensing protein PqsE to regulate pyocyanin production in
Pseudomonas aeruginosa
. Our bacterial two-hybrid assay demonstrated that ProE directly interacts with PqsE, and isothermal titration calorimetry and surface plasmon resonance assay further confirmed that the binding affinity of ProE with PqsE is at micromolar level. Both ProE and PqsE negatively regulate intracellular c-di-GMP levels. Furthermore, our transcriptomic study showed that co-expression of ProE and PqsE significantly changes the gene expression profiles in
P. aeruginosa
, especially with increased expression of pyocyanin genes, and the qPCR and phenotypic results confirmed the transcriptome data. Taken together, our study suggested that the interaction between ProE and PqsE plays a critical role in regulation of pyocyanin production and highlights the importance of protein-protein interaction mediated c-di-GMP signaling in
P. aeruginosa
.

IMPORTANCE

c-di-GMP is pivotal in orchestrating various bacterial functions. In P
seudomonas aeruginosa
, the nuanced balance of intracellular c-di-GMP is maintained by approximately 41 diguanylate cyclases (DGCs) and phosphodiesterases (PDEs). Emerging studies indicate that the c-di-GMP metabolic DGCs and PDEs may be involved in the signal transduction process by directly binding to the target protein, thus influencing downstream function. Despite their known importance, the precise functions of these proteins, especially their interacting partners, remain unclear. In this study, we identified that PQS quorum sensing system protein PqsE is a binding partner of c-di-GMP phosphodiesterase ProE; further analysis suggested that the ProE specifically interacts with PqsE to promote pyocyanin production. Our study extended the regulatory mechanism of the c-di-GMP signal transduction and quorum sensing in governing bacterial physiology.
Scale-up of the CRADLE Vital Signs Alert intervention to improve maternity triage in Sierra Leone: a mixed methods evaluation of device repair and maintenance
Authors: Greene Charlotte , Pearson Alice , Ridout Alexandra , Kuhrt Katy , Herm Singh Simren , Gassim Kay Jah Daniel , Momoh Francis , Sesay Tom , Shennan Andrew H 
Published: January 2025

BackgroundScale-up of the CRADLE intervention, a simple and accurate blood pressure and pulse device and focused training package, across all government maternity care facilities in Sierra Leone was completed in June 2023. Device maintenance must be prioritised to achieve sustainability.We evaluated device functionality 3 years after implementation to ensure sustainability.MethodsNon-functioning devices were collected and evaluated across five districts. Semi-structured interviews conducted with staff explored barriers and facilitators to maintenance and sustainability.Results21% (261/1257) of devices were reported as non-functioning and collected. 10% (26/261) of these devices had been damaged in storage and excluded from analysis. 75% (176/235) of non-functional devices needed a new cuff, 43% (100/235) a new inflation bulb and 18% (43/235) a new machine. Therefore, 3 years after scale-up, 82% of devices collected (192/235) and 96.5% of total devices distributed (1188/1231) could be functional after simple measures conducted within the healthcare facility.100% (18/18) of healthcare workers who use the device regularly were able to identify these specific problems and solutions. Barriers to repair included transportation and logistical challenges communicating the need for repairs. A novel training video in the local language was co-produced.ConclusionThe CRADLE device is robust and repair solutions are low cost but require logistical support at local and national levels. The majority can be fixed at the healthcare facility with minimal training if spare parts are available. The importance of implementation strategies to mitigate logistical challenges should be considered when scaling up technological innovations in similar low-resource settings.
3  Retrospective cohort study of all cause gastrointestinal illness in camp Qargha, Afghanistan in August 2020
Authors: Riley M , Makin S , Greig O , Taylor H 
Published: January 2025

IntroductionCamp Qargha (QAA), a British led NATO base in Kabul, had a history of gastrointestinal outbreaks. August 2020 saw an outbreak identified. Controlling outbreaks and understanding their causes is vital for preserving operational effectiveness. We describe the outbreak and use a retrospective cohort study to test the hypothesis that two-person-rooms are a potential risk factor.MethodData collected for clinical and outbreak management was described. Organisms were detected using BioFire® Film Array® Gastrointestinal Panel. Using Stata v.17, we conducted univariate and multivariable binomial logistic regression (MVA) for all GI illness and for specific pathogens detected to estimate adjusted risk ratios (aRRs) with 95% confidence Intervals (CI).Results36 presentations of gastrointestinal illness in 33 service-personnel during a 24-day outbreak saw 132 working days lost. Diarrhoeagenic e. coli, cryptosporidium, norovirus, and shigella were identified as potential causative organisms, with symptomatic duration, isolation and impact on operational effectiveness greatest in those with shigella or cryptosporidium. On MVA we did not find being in a two person room to be a risk factor (aRR 1.5; 95%CI 0.7-3.2). We did find risk of any GI illness increased 1.7 (95%CI; 0.9-3.0) times, and 1.2 (95%CI 1.0-1.4) times for being part of operational team 1 or living adjacent to another case respectively. Being part of operational team 1 was also a risk factor for enteropathogenic and enterotoxigenic E.coli infection.ConclusionTwo-person rooms weren’t a significant risk factor for gastrointestinal outbreaks. This is an important negative finding to inform the balance of outbreak control and operational wellbeing where social isolation can be detrimental. Targeted behavioural control measure education should be considered for identified at risk groups in the future. In terms of operational impact, cryptosporidium was the most significant cause of days lost. Further research by military enteric diseases specialists into cryptosporidium illness and spread in deployed settings is recommended.
Pharmacist-Directed Transition of Care Services Decrease Readmissions at a Safety-Net Hospital
Authors: Carboni Shannon , Tawfik Monika , Menon Brooke , Rhodes Heather , Brigino Ann 
Published: January 2025

Background: Limited data exist describing the influence of pharmacist-led transition of care (TOC) services in safety-net hospital settings. Objective: This analysis assessed the impact of pharmacist-led TOC services on hospital readmissions in a high-risk managed Medicaid population impacted by housing instability, substance use disorder (SUD), and mental health issues. Methods: A retrospective evaluation of patients who received safety-net hospital-based TOC pharmacy services between January 1, 2022, and December 31, 2022, was conducted. Patients 18 years and older, insured by a select managed Medicaid plan, and admitted to an inpatient medicine service were included. Patients were excluded if they were admitted from or discharged to a facility or hospice, discharged before medically ready, or died within 30 days of discharge. Interventions included an initial visit, discharge medication delivery and education, and a post-discharge follow-up phone call within 24 to 72 hours. Patients were provided with a number to call for medication-related questions post-discharge. The primary outcome was 30-day hospital readmissions. Secondary outcomes included time to and reason for readmission and a description of TOC services. Results: There were 292 patients engaged in pharmacist-led TOC services. Nearly 1 in 6 patients were experiencing homelessness and almost 40% were struggling with SUD during the index admission. The median readmission performance in the target population 6 months prior to TOC service implementation was 20.2% and fell to 12.3% post-intervention. Substance use disorder was the leading contributor to re-hospitalization, accounting for 58% of readmissions. Six (16.7%) readmissions were medication-related; 5 of 6 were complicated by SUD. There were no preventable medication-related readmissions. There are limitations to this study; not all patients received all TOC program components. Prospective, randomized-controlled studies are needed to show cause and effect. Conclusion and Relevance: This evaluation suggests pharmacist-led TOC discharge services may lead to hospital readmission reduction in a socially complex managed Medicaid population in a safety-net hospital setting.
COVID-19 health distress among autistic adults: Does psychological flexibility explain effects of health distress on mental health concerns?
Authors: Aller Ty B , Kelley Heather H , Juhasz Audrey , Covington Benjamin 
Published: January 2025

The COVID-19 pandemic caused significant health distress among autistic adults in the United States. While there is considerable evidence that autistic adults’ COVID-19 health distress was related to increases in mental health concerns (e.g. depression, anxiety, and stress), there is a less clear understanding of the possible mechanisms by which this process occurs. Accordingly, our participatory action research team assessed whether psychological flexibility, a strengths-based mechanism from acceptance and commitment therapy, mediated the association between COVID-19-related health distress and mental health concerns (e.g. depression, anxiety, and stress). We found that among 281 autistic adults the positive relationship between COVID-19 health distress and mental health concerns was partially mediated by values progress (a component of psychological flexibility) and values obstruction (a component of psychological inflexibility). Results provide preliminary support that the strengths-based mechanism of psychological flexibility might be a salient therapeutic target to improve mental health among autistic adults experiencing health distress. Lay Abstract What is already known? In the United States, the COVID-19 Pandemic caused many autistic adults to be fearful and worried about their health. There is a lot of research that says that when autistic adults experience health distress it can worsen their mental health. We do not know, however, what might explain how experiencing health distress negatively affects mental health. Because of this, our participatory action research team wanted to understand if there are strengths-based processes that help us understand the relationship between health distress and mental health concerns. What does this paper add? We examined among 281 autistic adults how a strengths-based construct from acceptance and commitment therapy called psychological flexibility might explain the relationship between health distress and mental health concerns. We found that for adults that had more values progress, doing the things that mattered to them, was associated with better mental health even while experiencing health distress. We also found that values obstruction, getting stuck on uncomfortable thoughts and feelings and trying to avoid them, explained worse mental health for autistic adults experiencing health distress. Implications for research and practice? The findings of this study provide initial support that psychological flexibility can explain the relationship between health distress and mental health concerns among autistic adults. Interventions that seek to improve psychological flexibility, like acceptance and commitment therapy, might be useful in improving autistic adults’ mental health while they are experiencing health distress.
The acceptability of a novel seismocardiography device for measuring VO2 max in a workplace setting: a mixed methods approach
Authors: Carter Anouska M , Humphreys Liam , Beswick Alison , Kesterton Sue , Bugg Alex , Platts Katharine 
Published: January 2025

Abstract

Background
Workplace health screening rarely includes measures of cardiorespiratory fitness, despite it being a greater predictor of cardiovascular disease and all-cause mortality than other routinely measured risk factors. This study aimed to determine the comparative acceptability of using a novel seismocardiography device to measure cardiorespiratory fitness via VO2 max during a workplace health check.

Methods
Participants were invited to participate in workplace health screening sessions where VO2 max was assessed by both seismocardiography at rest and sub-maximal exercise testing, in order for acceptability of both to be compared across multiple domains. Questionnaires and focus group guides for participants and practitioners were developed based on the Theoretical Framework of Acceptability. Data were analysed using t-tests and deductive thematic analysis.

Results
There was a significant difference in the acceptability domain of ‘affective attitude’ between the novel SCG device (M = 9.06 ± 1.14) and the sub-maximal exercise testing (M = 7.94 ± 1.79); t = 3.296, p = .001, d = 0.50, and in the domain of ‘burden’ between the novel SCG device (M = 9.16, ± 0.55) and the sub-maximal exercise testing (M = 7.41 ± 1.45); t = 7.033, p = < 0.001, d = 1.45. Practitioners and employees highlighted the potential of seismocardiography to create a more inclusive and accessible workplace offer, allowing those with restricted mobility or those with differing physical or emotional needs to participate in wellness testing; yet there was a lack of understanding in both groups around intervention effectiveness and coherence.

Conclusions
Seismocardiography may offer an acceptable route to cardiorespiratory fitness testing in the workplace, due to the low effort requirement and simplicity of administration. This study suggests that practitioners delivering such services have a critical role to play in acceptability of health interventions at work, as employees will be heavily influenced by practitioner beliefs around coherence and effectiveness. Comprehensive delivery training is important for the adoption of new health-related technologies such as seismocardiography into workplace health screening.
Posterior instrumented correction and fusion of Scheuermann´s results in physiological reconstruction of sagittal alignment and excellent overall clinical outcome- clinical trail of 73 patients
Authors: Jensch M.-L. , Platz U. , Quante M. , Köszegvary M. , Thomsen B. , Gliemroth J. , Berlin C. , Halm H. 
Published: January 2025

Abstract

Purpose
The aim was to assess the clinical outcomes after posterior spinal fusion (PSF) in patients with Scheuermann’s disease (SD).

Methods
SD undergoing PSF were retrospectively analyzed. Clinical outcome was determined using SRS-22- and Eq. 5D-questionaires preop and after 3, 12, 24 months after surgery. Whole spine x-rays were analyzed (preop, postop, after 6, 12, 24 months): sagittal and coronary Cobb angles, and pelvic parameters were evaluated; ideal lumbar lordosis (LL) was calculated using formula of le Huec (LL = 0.54*PI + 27.6). Surgical time, complications and blood loss were compared. Postop appearance of proximal (PJF) and distal junction failure (DJF) were calculated. Values were given as mean. Comparison with significance α = 0.05.

Results
73 patients were included. SRS-22 total score and EQ5D showed significant increase from preop to two-year FU (each p < 0.001). Preop Thoracic kyphosis (TK) was 75.1° with significant correction to 48.5° (p < 0.001). LL showed mean correction from 68.2° to 46.7° (p < 0.001). Difference between ideal and measured LL showed improvement from − 17.2° preop to -3.3° 6 month postop, good spontaneous correction of hyperlordosis. 63% had < 10° deviation from ideal LL 6 month postoperatively, whereas only 21.4% were in this range preoperatively. No significant changes for spinopelvic parameters during FU. Complications occurred in 13,7% of cases. A low revision rate for PJF (2,7%) was necessary. Subscore mental health showed a correlation to preop TK (p < 0.05).

Conclusion
Physiological reconstruction of sagittal alignment could be achieved in most cases (63%). Clinical FU results were convincing with significant improvement of patient’s satisfaction. Complication rate was moderate and risk of PJF after PSF low.
Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration
Authors: Zhang Ping-Wu , Wan Zi-He , Li Weifeng , Vats Abhishek , Mehta Kunal , Fan Laura , Zhou Lingli , Li Sean , Li Gloria , Keuthan Casey J. , Berlinicke Cynthia , Qian Cheng , Esumi Noriko , Duh Elia J , Zack Donald J. 
Published: January 2025

Abstract

Background
The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival and function in a mouse model of light damage (LD)-induced PR degeneration.

Methods
LD was induced by exposing mice to 4000 lx of light for 2–4 hours (h). IBU (100 or 200 mg/kg) or vehicle was administered by daily intraperitoneal injection. Retinal structure and function were evaluated by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG). Cell death genes were analyzed at 24 and 72 h after LD using the Mouse Pan-Cell Death Pathway PCR Array (88 genes). The cellular location and protein expression of key necroptosis genes were assessed by immunohistochemistry.

Results
Retinal outer nuclear layer (ONL) thickness in vehicle-injected LD animals was 8.7 ± 0.6% of retinas without LD (p < 0.0001). In IBU 200 mg/kg treated mice, central ONL thickness was 74.9 ± 7.7% of untreated retinas (p < 0.001). A-wave and b-wave ERG amplitudes were significantly preserved in IBU-treated animals. IBU significantly inhibited retinal inflammation. Twenty-four hour after LD, retinal mRNA expression for the inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1B), and C-C motif chemokine ligand 2 (Ccl2) increased by 10-, 17-, and 533-fold, respectively; in IBU-treated animals, the expression levels of these inflammatory factors were not significantly different from no-LD controls. Expression of key necroptosis genes, including Ripk3 and Mlkl, were upregulated in LD vehicle-treated mice, but dramatically reduced to near no LD levels in LD IBU-treated mice. Microglia activation and MLKL protein upregulation were observed primarily in photoreceptors 12 h after LD, as assessed by immunohistochemistry. IBU reduced the upregulation of MLKL protein and microglia migration in the ONL and outer plexiform layer (OPL) of treated retinas.

Conclusions
Systemic administration of the anti-inflammatory drug IBU partially protected mouse retinas from light-induced photochemical damage and inhibited both inflammation and the necroptosis cell death pathways. Our results suggest that NSAIDs may provide a promising therapeutic approach for treatment of the human retinal degenerative diseases.