bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular insights into type I interferon suppression and enhanced pathogenicity by species B human adenoviruses B7 and B14
Authors: Graves Drayson , Akkerman Nikolas , Fulham Lauren , Helwer Rafe , Pelka Peter 
Published: June 2024

ABSTRACT

Human adenoviruses (HAdVs) are small DNA viruses that generally cause mild disease. Certain strains, particularly those belonging to species B HAdVs, can cause severe pneumonia and have a relatively high mortality rate. Little is known about the molecular aspects of how these highly pathogenic species affect the infected cell and how they suppress innate immunity. The present study provides molecular insights into how species B adenoviruses suppress the interferon signaling pathway. Our study shows that these viruses, unlike HAdV-C2, are resistant to type I interferon. This resistance likely arises due to the highly efficient suppression of interferon-stimulated gene expression. Unlike in HAdV-C2, HAdV-B7 and B14 sequester STAT2 and RNA polymerase II from interferon-stimulated gene promoters in infected cells. This results in suppressed interferon- stimulated gene activation. In addition, we show that RuvBL1 and RuvBL2, cofactors important for RNA polymerase II recruitment to promoters and interferon-stimulated gene activation, are redirected to the cytoplasm forming high molecular weight complexes that, likely, are unable to associate with chromatin. Proteomic analysis also identified key differences in the way these viruses affect the host cell, providing insights into species B-associated high pathogenicity. Curiously, we observed that at the level of protein expression changes to the infected cell, HAdV-C2 and B7 were more similar than those of the same species, B7 and B14. Collectively, our study represents the first such study of innate immune suppression by the highly pathogenic HAdV-B7 and B14, laying an important foundation for future investigations.

IMPORTANCE
Human adenoviruses form a large family of double-stranded DNA viruses known for a variety of usually mild diseases. Certain strains of human adenovirus cause severe pneumonia leading to much higher mortality and morbidity than most other strains. The reasons for this enhanced pathogenicity are unknown. Our study provides a molecular investigation of how these highly pathogenic strains might inactivate the interferon signaling pathway, highlighting the lack of sensitivity of these viruses to type I interferon in general while providing a global picture of how viral changes in cellular proteins drive worse disease outcomes.
Metagenomic sequences from anaerobic chloroform and dichloromethane degrading microbial communities
Authors: Bulka Olivia , Edwards Elizabeth A. 
Published: July 2024

ABSTRACT

Here, we present metagenomes from two cultures derived from an anaerobic microbial consortium used for bioremediation. One culture dechlorinates chloroform to dichloromethane, which is further mineralized to CO
2
. A second subculture was amended with only dichloromethane. We sought draft genomes of key microorganisms to identify metabolic potential in these consortia.
Metabolic model guided CRISPRi identifies a central role for phosphoglycerate mutase in
Chlamydia trachomatis
persistence
Authors: Chowdhury Niaz Bahar , Pokorzynski Nick , Rucks Elizabeth A. , Ouellette Scot P. , Carabeo Rey A. , Saha Rajib 
Published: June 2024

ABSTRACT

Upon nutrient starvation,
Chlamydia trachomatis
serovar L2 (CTL) shifts from its normal growth to a non-replicating form, termed persistence. It is unclear if persistence reflects an adaptive response or a lack thereof. To understand this, transcriptomics data were collected for CTL grown under nutrient-replete and nutrient-starved conditions. Applying K-means clustering on transcriptomics data revealed a global transcriptomic rewiring of CTL under stress conditions in the absence of any canonical global stress regulator. This is consistent with previous data that suggested that CTL’s stress response is due to a lack of an adaptive response mechanism. To investigate the impact of this on CTL metabolism, we reconstructed a genome-scale metabolic model of CTL (iCTL278) and contextualized it with the collected transcriptomics data. Using the metabolic bottleneck analysis on contextualized iCTL278, we observed that phosphoglycerate mutase (
pgm
) regulates the entry of CTL to the persistence state. Our data indicate that
pgm
has the highest thermodynamics driving force and lowest enzymatic cost. Furthermore, CRISPRi-driven knockdown of
pgm
in the presence or absence of tryptophan revealed the importance of this gene in modulating persistence. Hence, this work, for the first time, introduces thermodynamics and enzyme cost as tools to gain a deeper understanding on CTL persistence.

IMPORTANCE

This study uses a metabolic model to investigate factors that contribute to the persistence of
Chlamydia trachomatis
serovar L2 (CTL) under tryptophan and iron starvation conditions. As CTL lacks many canonical transcriptional regulators, the model was used to assess two prevailing hypotheses on persistence—that the chlamydial response to nutrient starvation represents a passive response due to the lack of regulators or that it is an active response by the bacterium. K-means clustering of stress-induced transcriptomics data revealed striking evidence in favor of the lack of adaptive (i.e., a passive) response. To find the metabolic signature of this, metabolic modeling pin-pointed pgm as a potential regulator of persistence. Thermodynamic driving force, enzyme cost, and CRISPRi knockdown of pgm supported this finding. Overall, this work introduces thermodynamic driving force and enzyme cost as a tool to understand chlamydial persistence, demonstrating how systems biology-guided CRISPRi can unravel complex bacterial phenomena.
Service disruptions, trauma and burnout during the COVID-19 pandemic among healthcare providers delivering immunisation and maternal and child health services in Indonesia
Authors: Randell Madeleine , Wahyono Tri Yunis Miko , Dynes Michelle , Tinessia Adeline , Li Mu , Danchin Margie , Oktarinda  , Fitriyani Fitriyani , Saraswati Lintang Dian , Jenkins Kylie , Aung Khin Devi , Noorzad Abdul Khalil , Shetye Mrunal , Dewi Lulu , Yosephine Prima , Leask Julie , Sheel Meru 
Published: July 2024

BackgroundThe COVID-19 pandemic resulted in extreme strain on health systems including the health workforce, essential health services and vaccination coverage. We examined disruptions to immunisation and maternal and child health (MCH) services, concerns of personal well-being and delivery of healthcare during the pandemic as well as factors associated with self-reported trauma or burnout among healthcare providers (HCPs).MethodsIn March–April 2022, we conducted a cross-sectional survey among HCPs in two provinces of Indonesia. HCPs involved in COVID-19 or routine immunisation and MCH services were randomly selected from district/city health office registration lists. We descriptively analysed service disruptions experienced by HCPs as well as trauma, burnout and concerns of personal well-being and delivery of healthcare during the pandemic. Multivariate logistic regression analyses were undertaken to identify factors associated with trauma or burnout.ResultsWe recruited 604 HCPs. Mobilisation of staff from routine health services to COVID-19 response duties was a key reason for service disruptions (87.9%). Strategies such as community outreach and task shifting were implemented to overcome disruptions. Trauma or burnout during the pandemic was reported by 64.1% HCPs, with 23.5% reporting worse mental or emotional health.Factors associated with trauma or burnout included delivery of COVID-19 immunisation (adjusted OR (aOR) 2.54, 95% CI 1.08 to 5.94); and delivery of both COVID-19 immunisation and routine immunisation compared with no involvement in vaccination programmes (aOR 2.42, 95% CI 1.06 to 5.52); poor treatment in the workplace (aOR 2.26, 95% CI 1.51 to 3.38) and lower confidence to respond to patient queries on COVID-19 immunisation (aOR 1.51, 95% CI 1.03 to 2.22).ConclusionHCPs experienced service disruptions, trauma and burnout and implemented strategies to minimise disruptions to service delivery and improve patient experiences. Our study highlights the need to ensure that workforce resilience and strategies to protect and support HCPs are considered for pandemic planning, preparedness and management.
Living with mesothelioma: a systematic review of mental health and well-being impacts and interventions for patients and their informal carers
Authors: Sherborne Virginia , Ejegi-Memeh Stephanie , Tod Angela Mary , Taylor Bethany , Hargreaves Sarah , Gardiner Clare 
Published: July 2024

ObjectivesMesothelioma is an aggressive cancer predominantly affecting the lung and abdominal linings. It can have a unique impact on mental health and well-being (MHWB) due to its incurability, poor prognosis and asbestos-exposure causation. This review’s aims were to identify/synthesise international evidence on mesothelioma’s MHWB impacts; explore MHWB interventions used by patients and carers; and identify evidence of their effectiveness.DesignSystematic review.Data sourcesDatabases, searched March 2022 and March 2024, were MEDLINE; CINAHL; PsycINFO; Cochrane Library; ASSIA.Eligibility criteriaWe included study designs focusing on psychological impacts of living with mesothelioma and MHWB interventions used by patients and informal carers, published in English since January 2002.Data extraction and synthesisA team of reviewers screened included studies using standardised methods. Quality was assessed using validated tools: Mixed-Methods Appraisal tool for primary research and Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews.ResultsForty-eight studies met the inclusion criteria: 20 qualitative, 16 quantitative, nine reviews, two mixed-methods, one combined systematic review/qualitative study. UK studies predominated. Many MHWB impacts were reported, including traumatic stress, depression, anxiety and guilt. These were influenced by mesothelioma’s causation, communication issues and carer-patient relational interactions. Participants used wide-ranging MHWB interventions, including religious/spiritual practice; talking to mental-health professionals; meaning-making. Some strategies were presented as unhelpful, for example, denial. Participants reported lack of access to support.ConclusionsMost qualitative studies were rated high quality. The quality of the quantitative studies and reviews varied. The sparse literature regarding MHWB in mesothelioma means more research is needed into impacts on patients and carers, including trauma. To enable access to evidence-based support, research is recommended concerning MHWB interventions’ effectiveness in mesothelioma.PROSPERO registration numberCRD42022302187.
Assessing the efficacy of a brief universal family skills programme on child behaviour and family functioning in Gilgit-Baltistan, Pakistan: protocol for a feasibility randomised controlled trial of the Strong Families programme
Authors: El-Khani Aala , Asif Muqaddas , Shahzad Salman , Bux Majid Sain , Maalouf Wadih , Rafiq Noor ul Zaman , Khoso Ameer B , Chaudhry Imran Bashir , Van Hout Marie-Claire , Zadeh Zainab , Tahir Azam , Memon Rakhshi , Chaudhry Nasim , Husain Nusrat 
Published: July 2024

PurposeThe global burden of mental health difficulties among children underscores the importance of early prevention. This study aims to assess the efficacy, feasibility and acceptability of the Strong Families programme in enhancing child behaviour and family functioning in low-resource settings in Gilgit-Baltistan, Pakistan.Methods and analysisThis is a two-arm, multisite feasibility randomised controlled trial with an embedded process evaluation in three districts of Gilgit-Baltistan, namely Gilgit, Hunza and Skardu. 90 families living in these challenged settings, comprising a female primary caregiver aged 18 or above, and at least one child aged 8–15 years, will participate. Participants will be randomly assigned to either receive the Strong Families programme or to the waitlist group. Strong Families is a 7-hour family skills group intervention programme attended by children and their primary caregivers over 3 weeks. The waitlist group will be offered the intervention after their outcome assessment. Three raters will conduct blind assessments at baseline, 2 and 6 weeks postintervention. The primary outcome measures include the feasibility of Strong Families, as determined by families’ recruitment and attendance rates, and programme completeness (mean number of sessions attended, attrition rates). The secondary outcomes include assessment of child behaviour, parenting practices, parental adjustment and child resilience. Purposefully selected participants, including up to five caregivers from each site, researchers and facilitators delivering the intervention, will be interviewed. Descriptive statistics will be used to analyse primary and secondary outcomes. The process evaluation will be conducted in terms of programme context, reach, fidelity, dose delivered and received, implementation, and recruitment.Ethics and disseminationThis study has been approved by the UNODC Drug Prevention and Health Branch in the Headquarters office of Vienna and the National Bioethics Committee of Pakistan. Findings will be disseminated through publication in reputable journals, newsletters and presentations at conferences.Trial registration numberNCT05933850.
Acceptability and feasibility of a theatre-based wellness programme to support people living with long COVID: a single-arm feasibility study
Authors: Burton Alexandra , Bone Jessica K , Lawrence-Lunniss Kate , Philip Keir EJ 
Published: July 2024

ObjectivesTo determine acceptability and feasibility of a theatre-based wellness programme to support the health and well-being of people with long COVID.DesignSingle-group, repeated-measures feasibility study.SettingCommunity centre and online.ParticipantsAdults with diagnosed long COVID experiencing breathlessness, pain and/or loneliness.InterventionSix-week participatory creative programme delivered to one online and one in-person group facilitated by movement, voice and drama consultants using breathing, visualisation, singing, poetry, storytelling and movement exercises.Primary outcome measuresProgramme acceptability and feasibility measured via uptake, reasons for non-attendance and barriers to engagement.Secondary outcome measuresFeasibility of recruitment and data collection procedures measured through proportion of missing data and follow-up rates, mechanisms of action of the programme identified through qualitative interviews, changes in mental health, well-being, quality of life, loneliness, social support, fatigue, breathlessness and post-COVID-19 functional status at 8-week follow-up.Results21 people expressed interest in participating, 20 people took part in the programme, 19 completed baseline and 16 completed follow-up assessments. Participants attended an average of 4.8 of 6 sessions (SD=1.5, range 2–6). Exploratory analyses demonstrated significant improvements in self-rated health (t-test mean difference=0.12, 95% CI=0.00, 0.23, p=0.04) and chronic fatigue symptoms (mean difference=−3.50, 95% CI=−6.97, –0.03, p=0.05) at 8 weeks. Key mechanisms of action that supported health and well-being included: increased sense of community, illness acceptance, experiencing joy, increased confidence in managing everyday life, increased ability to relax and reconnection with previous identity. Barriers to engagement included: activities being outside of the participant's comfort zone, ongoing long COVID symptoms, emotional consequences of sharing experiences and connectivity and connecting online.ConclusionsA 6-week theatre-based programme was perceived as acceptable to most participants and resulted in some positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development and scale-up of this and related arts programmes to support people living with long COVID.
Cross-sectional study to investigate the seroprevalence and risk factors ofToxoplasma gondiiamong women attending the antenatal clinic in Namwala, Zambia
Authors: Daka Victor , Mukosha Moses , Zimba Sharon D , Phiri Andrew M 
Published: July 2024

BackgroundToxoplasmosis is a zoonotic parasitic disease caused byToxoplasma gondii (T. gondii). It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to undesirable pregnancy outcomes such as congenital malformations, miscarriage, premature birth and stillbirth. This study investigated the seroprevalence ofT. gondiiinfection among pregnant women attending the antenatal clinic at Namwala District Hospital in Southern Zambia.MethodsThis was a cross-sectional study where blood was collected, and the serum was tested forToxoplasmaIgG and IgM. A questionnaire was administered to participants on demographic characteristics and risk factors. Data were entered in Microsoft Excel and exported to STATA version 14 for analysis.ResultsA total of 401 women were enrolled in the study from 3 March to 5 August 2021. The seroprevalence ofToxoplasmaIgG was 4.2% (n=17), while the seroprevalence ofToxoplasmaIgM was 0.7% (n=3). The median age was 27 (IQR: 24–30) years, and a larger proportion had primary-level education (n=223, 55.6%). The majority (81.6%) of the women were married. None of the risk factors investigated in this study were significant forT. gondiiinfection.ConclusionThere was a low seroprevalence ofT. gondiiinfection among pregnant women in the Namwala district of Southern Province, Zambia, and regular screening may not be warranted in this population. Continued research on toxoplasmosis is recommended to understand its epidemiology across Zambia.
Impact of tonsillectomy on the efficacy of Alt-RAMEC/PFM treatment protocols in children with class III malocclusion and tonsillar hypertrophy: protocol for a cluster randomised controlled trial
Authors: Guo Feiyang , Li Qiujing , Ngan Peter , Guan Guoqiang , Chen Xiong , Yang Xiuping , Lv Chenxing , Hua Fang , Zhao Tingting , He Hong 
Published: July 2024

IntroductionOrthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy.Methods and analysisThis is a two-arm, parallel-group, superiority cluster randomised controlled trial, with four clinics randomly assigned to the surgery-first arm and the orthodontic-first arm in a 1:1 ratio. The Alt-RAMEC protocol involves alternate activation and deactivation of the expander’s jet screw over 6 weeks to stimulate maxillary suture distraction. Patients will be instructed to wear the PFM for a minimum of 14 hours per day. The primary outcomes are changes in Wits appraisal and the degree of maxillary advancement from baseline to the end of orthodontic treatment. Lateral cephalometric radiographs, polysomnography, Obstructive Sleep Apnoea-18 questionnaire and Oral Health Impact Profile-14 questionnaire will be traced, collected and measured. We will recruit 96 patients intofor the study. To assess differences, repeated multilevel linear mixed modelling analyses will be used.Ethics and disseminationThis study has been granted ethical approval by the Ethics Committee of the School & Hospital of Stomatology, Wuhan University (approval No. 2023-D10). Written informed consent will be obtained from the participants and their guardians. The results of the trial will be disseminated through academic conferences and journal publications.Trial registration numberChiCTR2300078833.
Are the content and usability of a new direct observation tool adequate for assessing competency in delivering person-centred care: a think-aloud study with patients and healthcare professionals in Sweden
Authors: Ekman Nina , Fors Andreas , Moons Philip , Boström Eva , Taft Charles 
Published: July 2024

ObjectiveTo evaluate the content and usability of a new direct observation tool for assessing competency in delivering person-centred care based on the Gothenburg Centre for Person-Centred Care (gPCC) framework.DesignThis is a qualitative study using think-aloud techniques and retrospective probing interviews and analyzed using deductive content analysis.SettingSessions were conducted remotely via Zoom with participants in their homes or offices.Participants11 participants with lengthy experience of receiving, delivering and/or implementing gPCC were recruited using purposeful sampling and selected to represent a broad variety of stakeholders and potential end-users.ResultsParticipants generally considered the content of the four main domains of the tool, that is, person-centred care activities, clinician manner, clinician skills and person-centred care goals, to be comprehensive and relevant for assessing person-centred care in general and gPCC in particular. Some participants pointed to the need to expand person-centred care activities to better reflect the emphasis on eliciting patient resources/capabilities and psychosocial needs in the gPCC framework. Think-aloud analyses revealed some usability issues primarily regarding difficulties or uncertainties in understanding several words and in using the rating scale. Probing interviews indicated that these problems could be mitigated by improving written instructions regarding response options and by replacing some words. Participants generally were satisfied with the layout and structure of the tool, but some suggested enlarging font size and text spacing to improve readability.ConclusionThe tool appears to satisfactorily cover major person-centred care activities outlined in the gPCC framework. The inclusion of content concerning clinician manner and skills was seen as a relevant embellishment of the framework and as contributing to a more comprehensive assessment of clinician performance in the delivery of person-centred care. A revised version addressing observed content and usability issues will be tested for inter-rater and intra-rater reliability and for feasibility of use in healthcare education and quality improvement efforts.