bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of
Staphylococcus aureus
survival of trimethoprim-sulfamethoxazole-induced thymineless death
Authors: Gonsalves Lauren J. , Tran Allyson , Gardiner Tessa , Freeman Tiia , Dutta Angshita , Miller Carson J. , McNamara Sharon , Waalkes Adam , Long Dustin R. , Salipante Stephen J. , Hoffman Lucas R. , Wolter Daniel J. 
Published: October 2024

ABSTRACT

Trimethoprim-sulfamethoxazole (SXT) is commonly used to treat diverse
Staphylococcus aureus
infections, including those associated with cystic fibrosis (CF) pulmonary disease. Studies with
Escherichia coli
found that SXT impairs tetrahydrofolate production, leading to DNA damage, stress response induction, and accumulation of reactive oxygen species (ROS) in a process known as thymineless death (TLD). TLD survival can occur through the uptake of exogenous thymidine, countering the effects of SXT; however, a growing body of research has implicated central metabolism as another potentially important determinant of bacterial survival of SXT and other antibiotics. Here, we conducted studies to better understand the mechanisms of TLD survival in
S. aureus
. We found that thymidine abundances in CF sputum were insufficient to prevent TLD of
S. aureus
, highlighting the importance of alternative survival mechanisms
in vivo
. In
S. aureus
cultured
in vitro
with SXT and low thymidine, we frequently identified adaptive mutations in genes encoding carbohydrate, nucleotide, and amino acid metabolism, supporting reduced metabolism as a common survival mechanism. Although intracellular ROS levels rose with SXT treatment
in vitro
, survival was not improved in the presence of ROS scavengers, unlike in
E. coli
. SXT challenge induced the SOS response, which was alleviated by added thymidine. Finally, an inactivating mutation in the phosphotransferase gene
ptsI
conferred both limitation in cellular ATP and improved survival against TLD. Collectively, these results suggest that alterations in core metabolic functions, particularly those that reduce ATP levels, predominantly confer
S. aureus
survival and persistence during SXT treatment, potentially identifying novel targets for co-treatment.

IMPORTANCE

Staphylococcus aureus
is a ubiquitous organism and one of the leading causes of human infections, many of which are difficult to treat due to persistence, antibiotic resistance, or antibiotic tolerance. As our arsenal of effective antibiotics dwindles, the need for improved treatments becomes increasingly urgent, necessitating a better understanding of the precise mechanisms by which pathogens evade our most critical antimicrobial agents. Here, we report a systematic characterization of the mechanisms of
S. aureus
survival to treatment with the first-line antistaphylococcal antibiotic trimethoprim-sulfamethoxazole, identifying pathways and candidate targets for enhancing the efficacy of available antimicrobial agents.
Social, cultural and political conditions for advancing health equity: examples from eight country case studies (2011–2021)
Authors: van den Berg Miriam , Flavel Joanne , Schram Ashley , Friel Sharon , Gesesew Hailay Abrha , Baum Fran 
Published: October 2024

Progress in addressing systematic health inequities, both between and within countries, has been slow. However, there are examples of actions taken on social determinants of health and policy changes aimed at shaping the underlying sociopolitical context that drives these inequities.Using case study methodology, this article identifies five countries (Ethiopia, Jordan, Spain, Sri Lanka and Vietnam) that made progress on health equity during 2011–2021 and three countries (Afghanistan, Nigeria and the USA) that had not made the same gains. The case studies revealed social, cultural and political conditions that appeared to be prerequisites for enhancing health equity.Data related to population health outcomes, human development, poverty, universal healthcare, gender equity, sociocultural narratives, political stability and leadership, governance, peace, democracy, willingness to collaborate, social protection and the Sustainable Development Goals were interrogated revealing four key factors that help advance health equity. These were (1) action directed at structural determinants of health inequities, for example, sociopolitical conditions that determine the distribution of resources and opportunities based on gender, race, ethnicity and geographical location; (2) leadership and good governance, for example, the degree of freedom, and the absence of violence and terrorism; (3) a health equity lens for policy development, for example, facilitating the uptake of a health equity agenda through cross-sector policies and (4) taking action to level the social gradient in health through a combination of universal and targeted approaches.Reducing health inequities is a complex and challenging task. The countries in this study do not reveal guaranteed recipes for progressing health equity; however, the efforts should be recognised, as well as lessons learnt from countries struggling to make progress.
Systematic review of variables that moderate and/or mediate the relationship between child maltreatment and adverse outcomes: a study protocol
Authors: Colley Denise , Seidler Jenny , Rasch Lena , Gahr Britta , Küppers Lisa , Mayatepek Ertan , De Bock Freia 
Published: October 2024

IntroductionChild maltreatment (CM) is associated with adverse cognitive, behavioural, physical and social outcomes that often continue until adulthood. Systematic reviews on mediators and moderators of this relationship mostly investigate childhood adversities in general or only with regard to an adult population, single outcomes or single forms of maltreatment. The purpose of this review is to synthesise the evidence of variables that mediate and/or moderate the relationship between CM and diverse outcomes.MethodA systematic search will be performed in Scopus, PsychInfo, Medline and Web of Science until January 2022. Eligibility criteria include children under 18 years who have been maltreated and experienced adverse outcomes until the age of 21, moderators and/or mediators that influence the relationship between maltreatment and adverse outcomes must belong to the individual level and be amenable to change. After independent screening of studies by two reviewers, data extraction and study quality of included studies will be done using adapted checklists of similar reviews, the Strengthening the Reporting of Observational Studies in Epidemiology report, the COnsensus‐based Standards for the selection of health Measurement INstruments checklist and Downs and Black Checklist. The results will be presented in narrative form and, if adequate, meta-analysis.Ethics and disseminationEthics approval will not be required. The results of this systematic review will be submitted for publication in a peer-reviewed journal.PROSPERO registration numberCRD42022297982.
Major financial problems, low mental well-being and reduced HIV/STI testing among sex workers in the Netherlands during the COVID-19 pandemic: a repeated cross-sectional survey
Authors: Kloek Mariëlle , van Wees Daphne , Bakker Jane , Tyd Mischa , Rosales Julia Raxon , Geling Tomas , Spek Evelien , Hontelez Jan A C 
Published: October 2024

ObjectivesTo determine associations between the banning of sex work during the COVID-19 pandemic, and work, financial problems, mental well-being and HIV/sexually transmittable infection (STI) testing among sex workers in the Netherlands.DesignTwo cross-sectional online surveys. The first survey covered two time-periods: pre-COVID-19 (1 January 2019 to 31 December 2019) and period 1 (15 March 2020 to 1 July 2020). The second survey covered period 2 (1 January 2021 to 31 December 2021).SettingThe NetherlandsParticipantsIn total, 106 (first survey) and 196 (second survey) sex workers participated. Most of the participants in the first and second survey were cisgender women (respectively, 76.4% and 66.5%), followed by cisgender men (respectively, 12.3% and 15.7%) and the combination of transgender men, transgender women, non-binary or other (respectively, 11.3% and 17.6%). Most participants were born in the Netherlands (respectively, 61.4% and 69.7%).Primary and secondary outcome measuresWe provide descriptive statistics of self-reported work during and prior to COVID-19 measures, financial problems due to COVID-19 measures and HIV/STI testing and mental well-being during the COVID-19 pandemic. We also performed logistic and linear regression analyses to identify risk factors associated with reporting financial problems due to COVID-19 measures, not testing for HIV/STIs and lower mental well-being during the COVID-19 pandemic.ResultsIn periods 1 and 2, respectively, 69.6% and 62.0% reported financial problems due to the COVID-19 measures. Among those who reported to have had sex with clients, the percentage not HIV/STI testing was: 4.5% (95% CI: 0.9; 12.5) pre-COVID-19, 28.2% (95% CI: 15.0; 44.9) in period 1, and 15.2% (95% CI: 9.7; 22.3) in period 2. In the multivariate analysis, reported financial problems due to the COVID-19 pandemic was associated with not HIV/STI testing (OR: 12.1, p<0.001) and lower mental well-being (B: −2.7, p<0.001).ConclusionThe COVID-19 pandemic control measures in the Netherlands were associated with major financial problems, low mental well-being and reduced HIV/STI testing among sex workers.
Interventions addressing care staff views of older LGBTQ+ people in residential and homecare settings: a scoping review protocol
Authors: Moriarty Yvonne , Willis Paul 
Published: October 2024

IntroductionPrevious research has identified that lesbian, gay, bisexual, trans and queer (LGBTQ+) social care service users have concerns and/or negative experiences of their care due to staff views and attitudes about them/their sexual and gender identities. This has resulted in a number of barriers and challenges for the delivery of social care to this population. However, there is a little research relating to what types of evidence-based interventions can help overcome these barriers, enhance knowledge and promote positive attitude change in staff. The objective of this review was to systematically review current literature on interventions targeted at staff views and attitudes of LGBTQ+ older people in care and identify gaps in knowledge to inform a future theory of change and identify potential interventions to address these.Methods and analysisThis scoping review will be conducted in line with the Joanna Briggs Institute methodology for scoping reviews. We will conduct a comprehensive search of electronic databases (ie, Social Services Abstracts, Social Care online, Sociological Abstracts, PsycINFO, Medline, CINAHL, Scopus, ASSIA and Web of Science) focused on both health and social care literature to identify peer-reviewed literature as well as targeted online searches of potentially relevant grey literature. We will include literature published in the past 20 years (2003–2023) that report interventions to address care staff attitudes of LGBTQ+ populations older than 50 years who are receiving adult social care in a broad range of healthcare, residential or home settings. Citations will be screened by two independent researchers for inclusion and relevant data extracted using a bespoke template. Data will be analysed narratively and summarised to identify gaps in knowledge and aid in developing a theory of change.Ethics and disseminationEthics approval is not required. Findings will be disseminated via publication in a peer-reviewed journal.Review registrationA priori registration on Open Science Framework:https://osf.io/v76ws
Chemotherapy effects on mitochondrial function in adipose tissue in oesophageal and gastroesophageal junction adenocarcinomas with or without associated cachexia: protocol for a prospective, comparative observational study (ChiFMeOE)
Authors: Bacoeur-Ouzillou Ophélie , Guerrier Lisa , Touron Julianne , Pinel Alexandre , Pereira Bruno , Meunier Nathalie , Gillet Brigitte , Pezet Denis , Cassagnes Lucie , Malpuech-Brugère Corinne , Richard Ruddy , Gagniere Johan 
Published: October 2024

IntroductionCachexia is strongly associated with digestive cancers, particularly oesogastric cancer. Mitochondria in adipose tissue are involved in the regulation of metabolism and physiopathology of cancer cachexia in animal studies. Chemotherapeutic regimens used to control tumour development could also alter mitochondrial function in adipose tissue. We hypothesise that cachexia induces an increase in adipose tissue mitochondrial energy metabolism and that chemotherapy can mitigate this. The purpose of the ChiFMeOE study is to identify adipocyte factors involved in the energy imbalance associated with the cachectic process and their response to chemotherapeutic treatments in patients with oesogastric cancer.Methods and analysisChiFMeOE is a single-centre observational study that will prospectively include 60 patients referred to chemotherapy and surgery for oesophageal and gastro-oesophageal junction adenocarcinomas at the University Hospital of Clermont-Ferrand, France. Visceral and subcutaneous adipose tissue biopsies will be collected during surgery scheduled before and after neoadjuvant chemotherapy administration, as well as cachexia and nutritional assessment. The primary outcome is the maximum mitochondrial respiration rate (Vmax) measured by high-resolution respirometry. Secondary outcomes are other mitochondrial parameters (ie, enzymatic activities, proteins content and gene expression), tumour characteristics, nutritional status and body composition.Ethics and disseminationThe study was approved by an independent institutional review board on June 2023 (Comité de protection des personnes Sud-Méditerranée V; 2023-A00582-43) and declared to the French regulatory authority for research. Written informed consent will be obtained prior to patient inclusion. The principal investigator will be notified of any changes in patient’s health status requiring a modification of his management and/or treatment during the course of the protocol. Results will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov,NCT05954117.
Experiences across a genetic screening and testing programme pathway: a qualitative study of mammogram patient perspectives
Authors: Devine Claire , Emery Kate R , Childers Kimberly K , Brown Sandra , Gordon Ora , Roth Sarah E 
Published: October 2024

BackgroundPopulation-based genetic screening and testing programmes have substantial potential to improve cancer-related outcomes through early detection and cancer prevention. Yet, genetic testing for cancer risk remains largely underused. This study aimed to describe barriers and facilitators to patient engagement at each stage of a California-based genetic screening programme, from completing the electronic screener to receiving the test and to identify potential improvements that could support precision medicine-based approaches to patient care.MethodsWe conducted 26 semistructured interviews among programme participants who did not complete the screener (n=9), those who did not receive the recommended test (n=7) and those who received a genetic test (n=10). Interviewees were selected from patients who recently received a mammogram through one of the participating Southern California clinics. Interviews were transcribed and coded using Atlas.ti. The study used a qualitative descriptive approach to identify similar and contrasting themes among the participant groups.ResultsThis study found that barriers and facilitators to engagement were largely the same regardless of how far participants had moved through the process towards getting a genetic test. We identified four overarching themes: participants wanted clear communication of personal benefits at each stage; participants needed additional information and knowledge to navigate genetic screening and testing; a trusted provider could be instrumental in participants following a recommendation; and repetition and timing strongly impacted participants’ likelihood to engage.ConclusionsProviding education about the benefits of genetic screening and testing to patients and their families, as well as clear communication about what each step entails may help patients engage with similar programmes. Strategies aimed at increasing coordination among a patient’s healthcare team can also help ensure information reaches patients in multiple ways, from multiple providers, to increase the likelihood that recommendations for testing come from trusted sources, which supports the uptake of genetic testing.
Temporal trends and practice variation of paediatric diagnostic tests in primary care: retrospective analysis of 14 million tests
Authors: Thomas Elizabeth T , Withrow Diana R , Drakesmith Cynthia Wright , Gill Peter J , Perera-Salazar Rafael , Heneghan Carl 
Published: October 2024

ObjectiveThe primary objective was to investigate temporal trends and between-practice variability of paediatric test use in primary care.Methods and analysisThis was a descriptive study of population-based data from Clinical Practice Research Datalink Aurum primary care consultation records from 1 January 2007 to 31 December 2019. Children aged 0–15 who were registered to one of the eligible 1464 general practices and had a diagnostic test code in their clinical record were included. The primary outcome measures were (1) temporal changes in test rates measured by the average annual percent change, stratified by test type, gender, age group and deprivation level and (2) practice variability in test use, measured by the coefficient of variation.Results14 299 598 diagnostic tests were requested over 27.8 million child-years of observation for 2 542 101 children. Overall test use increased by 3.6%/year (95% CI 3.4 to 3.8%) from 399/1000 child-years to 608/1000 child-years, driven by increases in blood tests (8.0%/year, 95% CI 7.7 to 8.4), females aged 11–15 (4.0%/year, 95% CI 3.7 to 4.3), and children from the most socioeconomically deprived group (4.4% /year, 95% CI 4.1 to 4.8). Tests subject to the greatest temporal increases were faecal calprotectin, fractional exhaled nitric oxide and vitamin D. Tests classified as high-use and high-practice variability were iron studies, coeliac testing, vitamin B12, folate, and vitamin D.ConclusionsIn this first nationwide study of paediatric test use in primary care, we observed significant temporal increases and practice variability in testing. This reflects inconsistency in practice and diagnosis rates and a scarcity of evidence-based guidance. Increased test use generates more clinical activity with significant resource implications but conversely may improve clinical outcomes. Future research should evaluate whether increased test use and variability are warranted by exploring test indications and test results and directly examine how increased test use impacts on quality of care.
Modular A4 symmetry in 3+1 active–sterile neutrino masses and mixings
Authors: Singh Mayengbam Kishan , Singh S. Robertson , Singh N. Nimai 
Published: October 2024

Motivated by the significance of modular symmetry in generating neutrino masses and flavor mixings, we apply the modular [Formula: see text] symmetry in a [Formula: see text] scheme of active–sterile neutrino mixings. Neutrino oscillation observables in the 3[Formula: see text] range are successfully reproduced through the vacuum expectation value of the modulus [Formula: see text]. We also study phenomenologies related to the effective neutrino masses [Formula: see text] in tritium beta decay and [Formula: see text] in neutrinoless double beta decay. Mixings between active neutrinos and eV scale sterile neutrino are analyzed in detail. The model also predicts the Dirac CP-violating phase [Formula: see text] and Majorana phases [Formula: see text] and [Formula: see text]. The best-fit values of the neutrino mixing angles and ratios of two mass-squared differences are determined using minimum [Formula: see text] analysis. The best-fit values of the neutrino oscillation observables are predicted as [Formula: see text] [Formula: see text] [Formula: see text] and [Formula: see text] for NH while [Formula: see text] [Formula: see text] [Formula: see text] and [Formula: see text] for IH. We also observe that the predictions of effective neutrino mass parameters in the [Formula: see text] scheme are significantly different from the three neutrino paradigm.
Broviac Catheter–Related Aortic Valve Infective Endocarditis Complicated With Massive Aortic Regurgitation Requiring Emergency Surgery: A Case Report
Authors: Wilawer Małgorzata , Elikowski Waldemar , Fertała Natalia , Włodarski Arkadiusz , Szczęśniewski Patryk , Ratajska Paulina Anna , Bugajski Paweł 
Published: October 2024

Introduction: Broviac catheter is a type of central venous catheter (CVC) used for long‐term parenteral nutrition in specific patients, e.g., diagnosed with intestinal failure as short bowel syndrome (SBS). The way of the catheter insertion is conceived to minimalize the risk of infections. However, CVC‐related blood stream infections (CVC‐BSIs), including infective endocarditis (IE), remain most important complications associated with Broviac catheter. Staphylococcus epidermidis stands out as a prevalent pathogen. The increasing number of CVCs results in an increased incidence of healthcare‐associated IE. Complete parenteral treatment is an independent risk that increases the likelihood of IE. Treatment of IE is mainly based on antibiotic therapy, but in certain cases, surgical treatment is needed.Presentation of Case: A 71‐year‐old female with SBS who had been receiving total parenteral nutrition through the Broviac catheter for several months was admitted in a serious condition with significant weakness, increasing shortness of breath, deteriorating cough, fever, low blood pressure, and heart palpitations. Echocardiography revealed severe aortic valve IE with a large, longitudinal, highly mobile vegetation (up to 40 mm) and massive aortic regurgitation with pulmonary edema. Fast pathogen detection in the patients’ blood (S. epidermidis) was obtained using PCR‐based multiplex test. Due to life‐threatening conditions, emergency surgery with aortic valve replacement was performed. Consistent rehabilitation resulted in good condition achievement. Follow‐up echocardiography showed normal function of the aortic valve bioprosthesis.Conclusion: The use of CVC, including Broviac catheter, is associated with an increased risk of infections, including IE. Treatment‐resistant severe HF complicating IE requires emergency surgery.