bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of aztreonam–clavulanic acid exposure on gene expression and mutant selection using a multidrug-resistant
E. coli
Authors: Lin Tongtong , Zhang Jiayuan , Diao Shuo , Yan Jinke , Zhang Kexin , Cao Jichao , Huang Junyi , Wang Yaohai , Lv Zhihua , Shen Xiaopeng , Sy Sherwin K. B. , Lynch Michael , Long Hongan , Yu Mingming 
Published: February 2025

ABSTRACT

Multidrug-resistant
Escherichia coli
poses a significant threat to the healthcare system by causing treatment failure in infected patients. The use of a beta-lactam in combination with a beta-lactamase inhibitor has been shown to be an effective strategy to solve this problem.
In vitro
antimicrobial susceptibility experiments have demonstrated the antimicrobial activity of aztreonam and clavulanate. In this investigation, we conducted a transcriptomic analysis to reveal the downstream differential gene expression in
E. coli
ymmD45 (a strain newly isolated and found to carry the New Delhi metallo-β-lactamase gene) following exposure to aztreonam and clavulanate separately, as well as their combination. Differential gene expression, pathway enrichment, and gene network analyses demonstrated the polygenic nature of the response to the combination treatment, which suppressed the expression of pivotal virulence genes, disrupted two-component regulatory systems for bacteria to resist external stress, and interfered with the formation of the cellular membrane. Results from single-step mutant selection combined with deep whole-genome sequencing also revealed the spontaneous origin of the resistance mutations and confirmed action mechanisms during the combination treatment. Our study contributes valuable insights into the impact of antibiotic exposure on gene expression, laying the groundwork for understanding antibiotic resistance development in the treatment of multi-drug resistant infections through
in vitro
studies.

IMPORTANCE

Multidrug-resistant
Escherichia coli
is a major challenge in treating infections effectively. Aztreonam and clavulanate combination is promising in combating these resistant bacteria. By investigating the antimicrobial activity of aztreonam and clavulanate using transcriptomic analysis and mutant selection, this research sheds light on the mechanisms underlying antibiotic resistance and the effectiveness of combination therapies. The findings highlight how this particular antibiotic combination suppresses virulence genes, disrupts bacterial regulatory systems, and interferes with cellular functions critical for resistance. Moreover, the study lays the groundwork for understanding antibiotic resistance development in the treatment of multi-drug resistant infections through
in vitro
studies, offering insights that could inform future strategies in clinical settings. Ultimately, our findings could guide the development of better treatment strategies for multidrug-resistant infections, improving patient outcomes and helping to manage antibiotic resistance in healthcare.
Topical analgesia during needle-related procedures in children: a clinical practice guideline
Authors: Stavleu Debbie C , Mulder Renée L , Kruimer Demi M , Mensink Maarten O , Kremer Leontien CM , Tissing Wim JE , Loeffen Erik AH 
Published: February 2025

During intensive and long-lasting treatments, short-term or emergency care, children often undergo minor needle-related procedures (ie, venepuncture, venous cannulation and puncture of central venous access ports). The use of topical analgesia topical analgesia before these procedures can reduce needle-related pain. There is, however, uncertainty about the type of local anaesthetic (ie, eutectic mixture of topical analgesia (EMLA) or tetracaine-containing creams (eg, Rapydan) that should be used.Therefore, a clinical practice guideline (CPG) was developed to establish a comprehensive, evidence-based overview and provide recommendations for clinical practice.A comprehensive multidisciplinary panel was assembled, comprising 16 professionals and patient representatives in the Netherlands. A systematic literature review was performed, and after dual appraisal of all articles, results were extracted and meta-analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess, extract and summarise the evidence. An in-person meeting was held to discuss the evidence, complete an evidence-to-decision framework and formulate recommendations.In total, ten randomised controlled trials comprising 1808 children formed the evidence base for the recommendations. We recommend the use of EMLA in children who need to undergo a minor needle-related procedure, with minimal application duration of 60 min (strong recommendation, very low-quality evidence). We suggest the use of tetracaine-containing creams only when rapid cannulation/puncture (ie, within 30–60 min) is required (weak recommendation, very low-quality evidence).In this CPG, we provide recommendations regarding the choice of local anaesthetic for needle-induced pain during minor procedures in children. With these recommendations, we aim to reduce procedural pain and thereby contribute to improving care for children.
Atypical cutaneous leishmaniasis in a patient under tumour necrosis factor alpha inhibitor for psoriasis
Authors: Magalhaes Cesar , Teixeira Diogo , Coelho Andre , Malheiro Luis 
Published: February 2025

Tumor necrosis factor (TNF) inhibitors are associated with a higher risk of infection. Cases of cutaneous leishmaniasis have been rarely reported in this population, mostly with those taking adalimumab and infliximab.A man in his 60s with chronic plaque psoriasis developed a cutaneous lesion on his leg after 2 years of adalimumab therapy. It was initially misdiagnosed and unsuccessfully treated as a bacterial ulcer, but a skin biopsy later confirmedLeishmania donovanicomplex infection. Adalimumab was discontinued, and the patient was treated with intravenous liposomal amphotericin B, leading to the resolution of the ulcers. His psoriasis worsened post-treatment but was managed with risankizumab, and 2 years later, no evidence of leishmaniasis relapse was noted.This case highlights the importance of vigilance for leishmaniasis in patients taking TNF inhibitors, especially in endemic regions, as diagnosis can be challenging. Although there is no consensus on managing leishmaniasis in this population, treatment often involves discontinuing TNF inhibitors and using systemic antileishmanial drugs.
Fate of hepatic ectopic pregnancy 1-year post-treatment: still visible
Authors: Anant Monika , Kumar Subhash , Paswan Anita , Mondal Sangeeta 
Published: February 2025

Abdominal pregnancies, 1% of all ectopic pregnancies, present diagnostic complexities with a significant risk of intraperitoneal haemorrhage and mortality. Hepatic occurrences are exceptionally uncommon, with treatment strategies less established.A woman in her early 30s and third pregnancy underwent laparotomy due to haemoperitoneum suspecting an ectopic pregnancy, but normal pelvic structures were observed. Ultrasound and MRI confirmed the hepatic location of a gestational sac of 4 cm with a live fetus at 9 weeks. Intragestational sac methotrexate was administered under ultrasound guidance along with a single intramuscular dose due to high serum β-hCG which became undetectable after 8 weeks. The patient experienced no significant complications and was followed up for a year where an avascular gestational sac of 13 mm was still imaged.Hepatic pregnancy represents an exceptionally rare subset of abdominal pregnancies, frequently challenging to diagnose due to its atypical location. This is a first-of-its-kind report of imaging follow-up until 1 year.
Bilateral medial medullary and spinal cord infarctions presenting as locked-in syndrome in an adolescent with primary antiphospholipid syndrome
Authors: Wong Gordon Sheng Xian , Ng Benjamin Wei-Liang , Jee Rou Chen 
Published: February 2025

Bilateral medial medullary infarction (BMMI) is a rare stroke subtype in the paediatric population characterised by quadriplegia, cranial nerve dysfunction and respiratory failure. MRI typically reveals a ‘heart-shaped’ sign in the medial medulla on diffusion-weighted imaging (DWI). Paediatric stroke aetiologies, including vasculopathy, thrombophilia and cardioembolic disease, differ from those in adults. Antiphospholipid syndrome (APS) is a rare but important cause of paediatric stroke.We report an adolescent male presenting with acute quadriplegia, bulbar dysfunction and respiratory failure with intact cognition, consistent with locked-in syndrome. MRI confirmed BMMI with concurrent spinal cord infarction, and APS was diagnosed based on persistently elevated anticardiolipin antibodies. Anticoagulation therapy and rehabilitation were initiated. However, minimal neurological improvement was observed at 1-year follow-up. This case highlights the rarity of BMMI in children and underscores the importance of early diagnosis and management as well as the recognition of uncommon causes such as APS.
Provocative tests of anal sphincter function correlate with symptoms and subtypes of faecal incontinence
Authors: O'Connor Alexander , Liao Donghua , Davenport Matthew , Sharma Abhiram , Vasant Dipesh H , Klarskov Niels , Drewes Asbjørn Mohr , Kiff Edward , McLaughlin John , Telford Karen 
Published: February 2025

ObjectivesHigh-resolution anorectal manometry (HRAM) is the established investigation in faecal incontinence (FI). However, provocative tests (functional lumen imaging probe (FLIP) and anal acoustic reflectometry (AAR)) have been proposed as alternatives. This study uniquely explores all three methods in correlation with FI symptoms and subtypes.MethodsThis was a prospective observational study of patients with FI attending a tertiary pelvic floor unit between August 2022 and January 2024. Patients underwent HRAM, FLIP and AAR with the order randomised. FI severity was assessed with the Vaizey score and quality-of-life with the Manchester Health Questionnaire.Results40 patients (39 women, median age: 62 (range: 38–85)) were recruited with 27 (67.5%) reporting urge FI, 8 (20%) mixed and 5 (12.5%) passive incontinence. FLIP squeeze measurements correlated with the Vaizey score, including incremental squeeze pressure at 40 mL (rs=−0.412; p=0.008) and 50 mL (rs=−0.414; p=0.009) and the pressure-diameter volume loop at 50 mL (rs=−0.402; p=0.011). Incremental squeeze opening pressure with AAR correlated with the Vaizey score (rs=−0.339; p=0.032). There was no correlation between symptom severity and HRAM parameters, or any parameter and quality-of-life scores. Resting parameters with all three modalities were lower in passive FI: mean resting pressure (HRAM; p=0.010), yield pressure (FLIP; p=0.031) and opening pressure (AAR; p=0.006). With FLIP, there was a trend towards reduced squeeze function in the urge group (pressure-diameter volume loop at 50 mL; p=0.295).ConclusionsFLIP and AAR correlate better with FI symptoms compared with HRAM. Therefore, these provocative tests could be used to guide the management of FI in prospective studies.
Hospitalisation from seasonal influenza among persons with type 1 diabetes: a cohort study from the Swedish National Diabetes Register
Authors: Kjölhede Elin Allansson , Carlsen Hanne Krage , Martyn Oliver , Svensson Lena , Gisslén Magnus , Eliasson Björn , Eeg-Olofsson Katarina 
Published: February 2025

ObjectivesThe aim of this study was to investigate the risk of severe influenza resulting in hospitalisation among adults with type 1 diabetes (T1D).DesignNationwide cohort study using register data.SettingsData from the National Diabetes Register (NDR) linked to the Swedish Patient Register, Statistics Sweden and the Swedish Population Register.ParticipantsPersons with T1D in the Swedish NDR n=35 596 and control persons from the Swedish Population Register matched on age, sex and county of residence, n=155 590.Primary and secondary outcomesHospitalisation from seasonal influenza from October 2013 to December 2019. Season-wise incidence and HRs were analysed in the T1D group compared with controls. Secondary outcomes were associations between clinical variables and hospitalisation due to seasonal influenza for persons with T1D.ResultsThere were 347 (1.0%) influenza admissions in persons with T1D and 332 (0.2%) in the control group. The overall incidence rate was 16.9/10 000 person-years in the T1D group and 3.6/10 000 person-years for the control group. Persons with T1D had an unadjusted HR 4.7 (95% CI 4.0 to 5.5) for risk of hospitalisation from influenza during the study period and HR 3.4 (95% CI 2.9 to 4.0) when adjusted for age, sex, socioeconomic factors and chronic medical conditions at baseline. Within the T1D cohort, individuals hospitalised due to influenza were older, were more often smokers, had lower glomerular filtration rate and more often had a previous history of ischaemic heart disease and stroke.ConclusionsTo our knowledge, this is the first large study to highlight that persons with T1D have a threefold higher risk of hospitalisation due to seasonal influenza compared with matched controls from the general population. It is important for healthcare professionals to acknowledge this excess risk, particularly in older persons with T1D, who have cardiovascular risk factors and reduced kidney function.
Key components in the professional ethics of sign language interpreters in healthcare contexts: a qualitative study in Colombia
Authors: Izquierdo Martínez Laura Catalina , Groce Nora Ellen , Hurst Samia , Martínez-R Angela , Cuculick Jessica , Rivas Velarde Minerva C 
Published: February 2025

ObjectivesTo identified the core components of professional ethics for medical sign language interpreters and develop a framework based on empirical data from Colombian sign language (CSL) interpreters.DesignPurposive and snowball sampling methods were used in this qualitative study, which involved conducting semistructured interviews to CSL interpreters. Inductive data analysis was performed using the constant comparative method, where data collection and analysis occurred simultaneously. Transcriptional coding was performed line by line, and the data results were organised into themes and subthemes.SettingThe research was conducted in Colombia.ParticipantsA total of 17 CSL interpreters were included.ResultsWe identified key themes (confidentiality, privacy, professionalism, business practices and professional development). Our data analyses show the need for codes of conduct and establishment of professional codes of ethics for sign language interpreters working in a health context. The proposed framework addresses the challenges within the professional ethics of sign language interpreters in healthcare.ConclusionsThese findings offer unique insights into the ethical experiences of CSL interpreters. This framework can be a valuable reference for interpreters facing ethical dilemmas. The clarity of ethical considerations is crucial for overcoming barriers to healthcare for the D/deaf population. The identified ethical issues underscore the necessity of education, training and the establishment of codes of ethics and legislation for sign language interpreters. These findings can serve as a foundational reference for crafting ethical guidelines for sign language interpreters in other low- and middle-income countries.
Impact of mother’s own milk expression practices and processing treatments on infant health and growth outcomes: a systematic review protocol
Authors: Gandino Serena , Giribaldi Marzia , Smith Carolyn , Cassidy Tanya , Cavallarin Laura , Karcz Karolina , Peila Chiara , Klotz Daniel , Bzikowska-Jura Agnieszka , Walczak Bartłomiej , Wesolowska Aleksandra 
Published: February 2025

IntroductionBreastfeeding is the biological norm for infant nutrition. In certain scenarios, feeding at the breast is not possible, because of either maternal or neonatal reasons. In those cases, infants can still receive expressed mother’s own milk (MOM) and its beneficial properties. Mothers can express their milk using a variety of methods, while applying different hygiene practices, in different settings; moreover, expressed milk might receive processing before it is fed to the infant, particularly to reduce transmission of viruses such as cytomegalovirus to premature infants. The present protocol was designed to gather the evidence on the effect that the expression method, the hygiene regimen and setting and any processing used on expressed MOM can have on the clinical outcomes of recipient infants.MethodsThis systematic review will follow the methodological recommendations of the Cochrane Collaboration, in accordance with WHO recommendations and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will apply a hybrid search strategy, by combining structured database search with predefined snowballing searches. We will include primary research studies only, without restrictions on the type and including observational studies; no publication time, setting or language restriction will be applied, provided the abstract is available in English. Studies evaluating different methods of MOM expression, hygiene practices or settings during expression, processing of MOM and reporting clinical outcomes on recipient infants will be eligible. The searches have been planned to be performed in April–May 2024. Two reviewers will independently perform the reference screening, data extraction and risk of bias analysis of eligible studies, by using standardised tools specific for each study design. Quantitative and thematic narrative data synthesis will be performed and statistical heterogeneity between studies tested. Meta-analyses of extracted data will be performed where applicable. For relevant outcomes, certainty of the evidence will be tested by using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval is not required for this study since no original data will be collected. There is patient and public involvement throughout this research process. The results of this review will be disseminated through publication in a peer-reviewed journal and through conference presentations. Moreover, this systematic review will inform recommendations on milk banking of the WHO Department of Nutrition and Food Safety.PROSPERO registration numberCRD42024523299.
Impact of moral distress on burn-out: a cross-sectional survey of front-line family physicians during the initial wave of the COVID-19 pandemic
Authors: Fischer Avital Sabrina , Fenning Reece , Robb John Michael , Slater Allison , Mai Uyen , Lam Tien , De La Cruz Jan Paolo , Billimek John , Shapiro Johanna , Nguyen Tan , Haq Cynthia 
Published: February 2025

ObjectivesPrimary care clinicians are especially prone to burn-out. The primary objective of this study was to investigate factors contributing to burn-out and moral distress and their relationship among practising family physicians (FPs) in California early in the COVID-19 pandemic.DesignCross-sectional study, online survey evaluating burn-out, moral distress and associated factors.SettingCalifornia FPs between July and August 2020 practising in community health centres, hospital systems, private clinics and university systems were surveyed with a 22-item online questionnaire.ParticipantsFPs practising in California were eligible. The final sample included 218 physicians.Primary and secondary outcome measuresThe primary independent variable was frequency of moral distress and the primary outcome variable was worsening burn-out. Moderator variables included gender and employer support.ResultsFPs experiencing higher burn-out and moral distress were more likely to report concerns regarding personal COVID-19 risk and lack of personal protective equipment. Practising self-care and personal wellness were associated with decreased moral distress. Female physicians were 3.86-fold more likely to report worsening burn-out compared with male physicians. Employer support was associated with a 59% reduced burn-out risk and 54% reduction in frequent moral distress. Frequent moral distress was associated with a 3.12- fold higher burn-out risk. Gender moderated the relationship between moral distress and burn-out. Moral distress was associated with a 3.55-fold increase in burn-out risk among females.ConclusionsFemale FPs experienced greater levels of moral distress and burn-out than male physicians. Moral distress was differentially associated with increased burn-out among female physicians. Employer support was a protective factor against moral distress and burn-out.
Effectiveness of educational interventions to promote safe handling of pesticides: protocol for a systematic review and meta-analysis
Authors: Sánchez-Gervacio Belén Madeline , Alvarado-Castro Víctor Manuel , Legorreta-Soberanis José , Paredes-Solís Sergio , Flores-Moreno Miguel , Rios-Rivera Claudia Erika , Saldaña-Almazán Janet , Cockcroft Anne , Andersson Neil 
Published: February 2025

IntroductionAppropriate use of pesticides minimises harm to human health and the environment. Despite regulations and restrictions on use, however, many farmers still use highly toxic pesticides in ways that endanger their health and the environment. Many pesticide users know little about the health effects of these chemicals or how to handle them safely. A systematic review will collate evidence of the effectiveness of educational interventions among farmers regarding health hazards and the safe handling of pesticides. The review aims to summarise the impact of educational interventions on knowledge and reported behaviour of pesticide users and to identify characteristics of more effective interventions.Methods and analysisWe will search MEDLINE, LILACS, AGRICOLA, IMBIOMED, SciELO, Web of Science, Scopus, Embase databases and from the grey literature, Open Grey and WHO to identify potentially eligible studies. We will consider randomised and non-randomised controlled trials that evaluated the impact of educational interventions among farmers about the safe use of pesticides. We will include studies published between 2000 and 2024 in English, Spanish and Portuguese and consider outcomes of knowledge about pesticide health effects, knowledge about safe handling of pesticides and reported behaviour when handling pesticides. A meta-analysis of eligible studies, using a random-effects model, will estimate the impact of educational interventions on the outcomes as the difference between the intervention group and the control group at the last point of measurement. We will assess heterogeneity using the χ2test and I2statistic, conduct a sensitivity analysis by removing each study from the meta-analysis and evaluate publication bias with a funnel plot and Begg and Egger tests. Subgroup analyses will examine the impact of different kinds of educational interventions.Ethics and disseminationEthics approval is not required as no information from individuals are collected. The results will be published in a peer-reviewed journal or disseminated at relevant conferences.PROSPERO registration numberCRD42023413028.