bluuebunny/crossref_metadata_2025 huggingface dataset:
mGem: A quarter century with the Pirofski–Casadevall damage response framework—a dynamic construct for understanding microbial pathogenesis
Authors: Nosanchuk Joshua D.
Published: February 2025

A quarter of a century ago, Liise-anne Pirofski and Arturo Casadevall shared their concepts of microbial pathogenesis through the lens of a damage-response framework (DRF), which characterizes disease by assessing the dynamic interactions between the host and pathogen as reflected by damage as the readout. This framework has evolved to be a powerful tool for understanding the biology of complex infectious diseases, analyzing emerging and reemerging microbes, and developing therapeutic approaches to combat infections. The DRF is also frequently used to explain research at scientific meetings and to teach microbial pathogenesis to diverse learners. This mGem reviews how the DRF came to be and provides an overview of how it is used. Without a doubt, the scientific community will continue to leverage the DRF to advance research and innovate therapeutic approaches, which is especially important as new and reemerging infectious diseases threaten global health.
mGem: The complexity of viral entry—one virus, many receptors
Authors: Dermody Terence S. , Sutherland Danica M.
Published: February 2025

Binding to cellular receptors initiates viral replication and dictates sites in the host infected by the virus. As illustrated by mammalian orthoreovirus (reovirus), viruses can bind several types of receptors using distinct capsid components to facilitate the viral entry steps of attachment, internalization, and disassembly. The outer of the two concentric capsids of reovirus virions is formed by four viral proteins, three of which bind receptors. These capsid–receptor interactions mediate stepwise entry of reovirus, dictate viral tropism in infected animals, and expand the viral host range. Engagement of independent receptors by different capsid proteins is a property of many pathogenic viruses and illustrates common themes of receptor use in viral entry and disease.
Identification of intratumoral bacteria that enhance breast tumor metastasis
Authors: Gerbec Zachary J. , Serapio-Palacios Antonio , Metcalfe-Roach Avril , Krekhno Zakhar , Bar-Yoseph Haggai , Woodward Sarah E. , Pena-Díaz Jorge , Nemirovsky Oksana , Awrey Shannon , Moreno Sebastian H. , Beatty Sean , Kong Esther , Radisavljevic Nina , Cirstea Mihai , Chafe Shawn , McDonald Paul C. , Aparicio Sam , Finlay B. Brett , Dedhar Shoukat
Published: February 2025

The central, mortality-associated hallmark of cancer is the process of metastasis. It is increasingly recognized that bacteria influence multiple facets of cancer progression, but the extent to which tumor microenvironment-associated bacteria control metastasis in cancer is poorly understood. To identify tumor-associated bacteria and their role in metastasis, we utilized established murine models of non-metastatic and metastatic breast tumors to identify bacteria capable of driving metastatic disease. We found several species of the
Bacillus
genus that were unique to metastatic tumors, and found that breast tumor cells cultured with a
Bacillus
bacterium isolated from metastatic tumors,
Bacillus thermoamylovorans
, produced nearly 3× the metastatic burden as control cells or cells cultured with bacteria from non-metastatic breast tumors. We then performed targeted metabolomics on tumor cells cultured with different bacterial species and found that
B. thermoamylovorans
differentially regulated tumor cell metabolite profiles compared to bacteria isolated from non-metastatic tumors. Using these bacteria, we performed
de novo
sequencing and tested for the presence of genes that were unique to the bacterium isolated from metastatic tumors in a patient population to provide a proof-of-concept for identifying how specific bacterial functions are associated with the metastatic process in cancer independent of bacterial species. Together, our data directly demonstrate the ability of specific bacteria to promote metastasis through interaction with cancer cells.

IMPORTANCE

Metastasis is a major barrier to long-term survival for cancer patients, and therapeutic options for patients with aggressive, metastatic forms of breast cancer remain limited. It is therefore critical to understand the differences between non-metastatic and metastatic disease to identify potential methods for slowing or even stopping metastasis. In this work, we identify a bacterial species present with metastatic breast tumors capable of increasing the metastatic capabilities of tumor cells. We isolated and sequenced this bacteria, as well as a control species which failed to promote metastasis, and identified specific bacterial genes that were unique to the metastasis-promoting species. We tested for the presence of these bacterial genes in patient tumor samples and found they were more likely to be associated with mortality. We also identified enrichment of specific bacterial functions, providing insight into possible sources of bacteria-driven increases in the metastatic potential of multiple cancer types.
C-reactive protein-induced injury in
Mycoplasma pneumoniae
-infected lung epithelial cells is mediated by the P38 MAPK/mitochondrial apoptosis pathway
Authors: Li Lianjia , Zhang Yang , Zhao Lin , Shi Yalin
Published: February 2025

Patients with
Mycoplasma pneumoniae
(MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. CRP levels were assessed in children diagnosed with
Mycoplasma pneumoniae
pneumonia (MPP) and A549 lung epithelial cells infected with MP. A549 cells were genetically modified to overexpress CRP. Effects on cell viability, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were evaluated. The expression of proteins implicated in the p38 MAPK/mitochondrial apoptotic pathway was analyzed. The protective effects of the p38 MAPK inhibitor SB203580 and the mitochondrial protector cyclosporin A (CsA) were assessed. CRP levels were elevated in both MPP patients and MP-infected A549 cells compared to controls. Increased apoptosis and reduced cell viability were observed in MP-infected cells. CRP overexpression led to upregulation of proteins in the p38 MAPK/mitochondrial apoptosis pathway, increased cytoplasmic Cyt C, decreased Tom 20 and ΔΨm, and elevated ROS. Pretreatment with SB203580 or posttreatment with CsA reduced apoptosis and mitochondrial damage and enhanced cell survival. Increased CRP levels during MP infection promote lung epithelial cell death by activating the p38 MAPK/mitochondrial apoptosis pathway. Targeting this pathway could offer therapeutic potential to reduce lung damage in MPP patients.

IMPORTANCE

This study provides critical information in understanding the pathophysiological mechanisms for MP infections concerning CRP in mediating lung epithelial cell injury. This study outlines the significant increase in MP-infected patients and shows its direct involvement in cell apoptosis through the p38 MAPK/mitochondrial apoptosis pathway. By explaining this pathway, the possibility of targeting CRP and its connected signaling mechanisms to devise therapeutic interventions for the amelioration of lung damage in MP-infected patients is brought to light. The implications of such data are not merely in the added knowledge for disease pathobiology but also it brings new promise for novel intervention strategies to result in improved clinical outcomes. The elucidation of specific molecular targets inside the apoptosis pathway heralds a new area regarding the direction of future research and clinical application for humanity in general and concerning the broader relevance and impact of this study on respiratory diseases.
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

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.
Rhegmatogenous retinal detachment with giant retinal tear masked by dense vitritis in active toxoplasma retinochoroiditis
Authors: Upadhyaya Abhishek , Cherukuri Navya , Tyagi Mudit
Published: February 2025

A male patient presented with a decreased vision in his right eye since 2 weeks. The best corrected visual acuity was a Snellen’s equivalent of 20/200 in the right eye and 20/20 in his left eye. Retinal evaluation of the right eye revealed dense vitritis and a solitary yellowish retinochoroiditis lesion. An ultrasound B scan of the right eye revealed a suspicious high amplitude membranous echo in the posterior vitreous cavity. The patient was diagnosed as having toxoplasma retinochoroiditis and was started on appropriate medical therapy. Within a week of starting treatment, the vision had dropped significantly and a rhegmatogenous retinal detachment with a giant retinal tear was noted. The patient underwent vitreoretinal surgery with silicone oil as endotamponade. The patient did well in the postoperative period maintaining a visual acuity of 20/100 at 4 weeks follow-up and also at 3 months.
AAC selection through dynamic assessment for a child with intellectual disability
Authors: Venkatraman Krupa , Harikrishnan Darshanaa , Sriramachandran Sunandha Shree
Published: February 2025

This study presents a contemporary assessment method for selecting the appropriate augmentative and alternative communication (AAC) system for children with intellectual disabilities (IDs). This involves using dynamic assessment (DA) to identify the optimal AAC system that can improve a child’s communication abilities. DA uncovers a child’s capacity to acquire new skills with specific modifications and prompts. This approach was used to select the AAC systems appropriate for a boy in his middle childhood with communication impairment secondary to ID. Three AAC scenarios were gradually introduced to the child during the assessment, and the task with which it was presented (high-tech, low-tech conventional pictures and low-tech communication book with photographs) was gradually modified. The assessment outcome revealed two essential modifications to the AAC system that facilitated the child’s functional communication. Despite the increasing popularity of advanced AAC systems, practical challenges such as accessibility, stimulus relevance and usability persist. Hence, it is crucial to consider a method such as DA to select the appropriate AAC system, considering the communication needs, language level and cognitive ability of children with ID.
Rare presentation of hypocomplementaemic urticarial vasculitis syndrome (HUVS) overlapping with systemic erythematosus lupus (SLE) and small lymphocytic lymphoma (SLL)
Authors: Chao Chen , Aksoy Merve , Varma Nidhi , Tagoe Clement E
Published: February 2025

Hypocomplementaemic urticarial vasculitis syndrome (HUVS) is a rare immune complex-mediated disorder marked by non-pruritic urticarial lesions, hypocomplementaemia (low C1q levels), leucocytoclastic vasculitis and systemic manifestations (joint pain, angio-oedema and uveitis). Complications include renal disease, lung disease and acute laryngeal oedema that can prove fatal. Distinguishing HUVS from systemic lupus erythematosus (SLE) is challenging due to overlapping symptoms and diagnostic criteria. Here, we present the case of a male who presented with uveitis, maculopapular (and urticarial) rash and facial and joint swelling. Investigation revealed atypical antineutrophil cytoplasmic antibody, elevated antinuclear antibodies, low C1q and leucocytoclastic vasculitis on skin biopsy. Renal biopsy showed diffuse mesangial focal endocapillary proliferation with full-house immunofluorescence staining concerning for HUVS versus SLE class III nephritis. The management of HUVS is complicated by a lack of FDA-approved guidelines, with therapies ranging from non-steroidal anti-inflammatory drugs to immunosuppressants. The overlapping of HUVS, SLE and small lymphocytic lymphoma necessitates a collaborative multidisciplinary approach to control disease progression and improve outcomes.
Treatment-induced neuropathy of diabetes (TIND): a hidden complication in diabetes management
Authors: Paruthi Akash , Srivastava Swati , Prasad Mohith , Sharma Prashant
Published: February 2025

Treatment-induced neuropathy of diabetes (TIND) is an under-recognised complication that arises after rapid glycaemic control in diabetic patients. It presents with acute autonomic dysfunction and/or neuropathic pain resulting from small fibre nerve damage. This case involves a woman in her 50s with type 2 diabetes who transitioned from oral hypoglycaemic agents to insulin therapy, leading to a significant drop in HbA1c from 10% to 7.2% within the last 3 months. She presented with painful sensations, orthostatic hypotension and syncope. A diagnostic workup revealed peripheral nerve and autonomic dysfunction. Symptomatic treatment, including pregabalin and intravenous fluids, led to symptom resolution. This case highlights the importance of recognising TIND in patients with rapid glycaemic control to prevent unnecessary interventions. Awareness and appropriate management, including gradual glycaemic correction, can significantly improve patient outcomes.
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.
Neonatal sepsis in a preterm infant complicated by fungal infection
Authors: Khine Hla , Iyamabo Doris
Published: February 2025

We present the case of a preterm male infant born at 23+2 weeks gestation, who developed sepsis and was subsequently found to have fungal sepsis. The case highlights the diagnostic challenges and management strategies involved in treating neonatal sepsis, particularly in the presence of fungal pathogens.
Vulval fixed drug eruption following trimethoprim use
Authors: Chong Kar Yan , Tyagi-Bhatia Jaya
Published: February 2025

This case report describes an uncommon case of a woman who developed fixed drug eruption (FDE) on her vulval area secondary to trimethoprim use. She had no known history of drug allergy. Some common culprit medications that cause FDE include antimicrobials such as co-trimoxazole and non-steroidal anti-inflammatory agents. Vulval FDE is uncommon and should remain as an important differential diagnosis in women presenting with severe vulval pain accompanied by erythema and swelling, particularly after the introduction of a new medication. Discontinuation of trimethoprim along with the adjunct use of a steroid cream led to complete resolution of the patient’s symptoms.
Oophoropexy to round ligament for recurrent ovarian torsion
Authors: Rajaraman Vaishnavi , Sumathy Sudha , Menon Rajashree , Thomas Charisma
Published: February 2025

Ovarian torsion is a gynaecological emergency commonly affecting women of reproductive age, often associated with ovarian or paraovarian masses. However, in the absence of these masses, torsion can still occur, potentially indicating an underlying anatomical abnormality that predisposes to recurrent torsion. This report presents a distinctive surgical technique used in a young girl in her early adolescence with recurrent right ovarian torsion. The patient, with a history of torsion managed by detorsion, presented again with symptoms suggestive of recurrence. Emergency diagnostic laparoscopy revealed a twisted but viable right ovary at risk of future torsion. To prevent a recurrence, a new approach was employed: the right ovarian ligament was plicated with 2–0 prolene, and the ovary was fixed to the right round ligament. The procedure successfully stabilised the ovary and prevented further torsion. Postoperative recovery was uneventful. This case demonstrates the potential of oophoropexy as an effective technique for managing recurrent ovarian torsion in adolescents.
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

Objectives

High-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.

Methods

This 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.

Results

40 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).

Conclusions

FLIP 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

Objectives

The aim of this study was to investigate the risk of severe influenza resulting in hospitalisation among adults with type 1 diabetes (T1D).

Design

Nationwide cohort study using register data.

Settings

Data from the National Diabetes Register (NDR) linked to the Swedish Patient Register, Statistics Sweden and the Swedish Population Register.

Participants

Persons 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 outcomes

Hospitalisation 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.

Results

There 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.

Conclusions

To 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

Objectives

To 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.

Design

Purposive 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.

Setting

The research was conducted in Colombia.

Participants

A total of 17 CSL interpreters were included.

Results

We 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.

Conclusions

These 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

Introduction

Breastfeeding 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.

Methods

This 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 dissemination

Ethical 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 number

CRD42024523299.
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

Objectives

Primary 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.

Design

Cross-sectional study, online survey evaluating burn-out, moral distress and associated factors.

Setting

California 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.

Participants

FPs practising in California were eligible. The final sample included 218 physicians.

Primary and secondary outcome measures

The primary independent variable was frequency of moral distress and the primary outcome variable was worsening burn-out. Moderator variables included gender and employer support.

Results

FPs 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.

Conclusions

Female 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

Introduction

Appropriate 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 analysis

We 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 dissemination

Ethics 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 number

CRD42023413028.
Sangre Por Salud (SPS) Biobank: cohort profile
Authors: Zarrugh Emmil , Girardo Marlene E , Ryu Euijung , Bielinski Suzette , Moreno Garzon Giovanna , Hernandez Valentina , Singh Davinder , Levey Sharon , Gonzalez Crystal , Pompa Daniela B , Meagher Karen , Sharp Richard R , Shaibi Gabriel Q , Mandarino Lawrence , Thibodeau Steven , Cerhan James R , Olson Janet E , De Filippis Elena
Published: February 2025

Purpose

The Sangre Por Salud (SPS) Biobank was established to facilitate biomedical research opportunities for the Latino community by creating an easily accessible prospective cohort for scientists interested in studying health conditions and health disparities in this population.

Participants

Individuals self-identifying as Latino, aged 18–85 years, were prospectively recruited from the primary care Internal Medicine clinic at Mountain Park Health Center in Phoenix, Arizona. After obtaining informed consent, detailed medical history questionnaires were captured, and blood samples were obtained for common laboratory tests. Participants authorised the research team to access their electronic health records for research purposes. In addition, participants had serum, plasma and DNA samples isolated and stored at the Mayo Clinic Arizona Biorepository Laboratory for long-term storage and future access. As part of the study, participants consented and agreed to be contacted for potential participation in future research studies.

Findings to date

3756 participants provided informed consent, of whom 3733 completed all study questionnaires, an oral glucose tolerance test and had blood collected and stored. The SPS cohort is predominantly composed of females (72%), with a median age at time of consent of 42 years. All participants self-identified as Hispanic/Latino, 45% were married, 53% were employed for wages and 60% had less than a high school degree. Around 25% of participants met diagnostic criteria for overweight (BMI 25–29 kg/m2), and 49% met for obesity (BMI≥30 kg/m2). At time of recruitment, hypertension, hyperlipidaemia and depression affected 22%, 20% and 13% of the cohort, respectively.

Future plans

We plan to regularly update the participants’ electronic health records and self-reported health data to longitudinal research. Additionally, we plan to obtain a more comprehensive genomic analysis on the entire cohort, ensuring greater research interest and investigation into the underlying genetic factors that contribute to disease susceptibility in this cohort.
Smartphone apps for mental health: systematic review of the literature and five recommendations for clinical translation
Authors: Almuqrin Aljawharah , Hammoud Ryan , Terbagou Ilham , Tognin Stefania , Mechelli Andrea
Published: February 2025

Objectives

Providing adequate access to mental health services is a global challenge. Smartphone apps offer a potentially cost-effective, available and accessible solution for monitoring, supporting and treating mental health conditions. This systematic review describes and evaluates the usage of smartphone apps across a wide range of mental health disorders in terms of clinical effectiveness, feasibility and acceptability.

Design

This is a systematic review of studies examining treatment, self-monitoring and multipurpose smartphone apps for mental health disorders.

Data sources

Studies were identified through a comprehensive search of the Ovid and PubMed databases. Articles published up to 14 January 2024 were included based on predefined criteria.

Eligibility criteria

We included randomised controlled trials that compared mental health apps (single- or multipurpose) with treatment-as-usual or no treatment for clinical populations with mental health disorders. Studies were excluded if they focused on web-based interventions, combined apps with non-TAU treatments or targeted physical health apps.

Data extraction and synthesis

Two independent reviewers screened and selected studies, with a third reviewer resolving inconsistencies. Extracted data included study details, participant characteristics, app information and outcome measures related to effectiveness, feasibility and acceptability. A risk-of-bias assessment for each study was conducted.

Results

Out of 4153 non-duplicate articles screened, 31 studies met full-text eligibility criteria. These included 6 studies on treatment apps, 4 on self-monitoring apps and 21 on multipurpose apps for a range of mental health disorders. Fifteen were identified as having between some and high concern on the risk-of-bias assessment. While smartphone apps were generally effective and acceptable, their feasibility appeared to decline over time.

Conclusions

Smartphone apps are promising tools for mental healthcare, demonstrating effectiveness and acceptability. However, challenges such as reduced feasibility over time, potential biases and underrepresented demographics require further research. This review proposes five recommendations for improving clinical translation in future studies.
Nurture-U student mental health longitudinal survey: a study protocol
Authors: Marshall Ellen , Duffy Anne C , Chamberlain Samuel R , Dooley Jemima , Dorey Lucy , Forty Liz , Matlock Kevin A , Newbold Alexandra , Quinn Anthony , Rees Sarah , Robinson Lucy J , Saunders Kate E , Watkins Edward R
Published: February 2025

Introduction

University life represents a critical period for young adults, providing opportunities for personal growth and development of coping skills but also posing significant mental health challenges. Recent trends indicate rising mental health concerns among university students, exacerbated by the COVID-19 pandemic and its aftermath. This study aims to address gaps in longitudinal data on student mental health in the UK and to identify risk and protective factors across diverse student populations.

Methods and analysis

The current Nurture-U survey is developed from the U-Flourish biannual survey study piloted at Queen’s and Oxford universities in Canada and the UK, respectively. Nurture-U is a longitudinal survey study conducted at five UK universities, aiming to create a comprehensive data set from over 5000 students. The study will collect data at the start and completion of each academic year, using validated measures to assess well-being, mental health symptoms, lifestyle factors and access to support. Recruitment will target all students, with an emphasis on first-year students, to track their mental health trajectory from university entry through subsequent years.

Ethics and dissemination

Ethical approval has been obtained from relevant committees at each participating university. Students will provide informed consent prior to participation, with risk messages and support information provided for those indicating self-harm or suicidal thoughts. Data will be de-identified and securely stored, with results disseminated through academic publications, social media and student engagement activities.
Cognitive behavioural therapy plus Kiesler Circle Training (CBT+) versus CBT only for patients with interpersonal problems: study protocol for a randomised controlled feasibility trial
Authors: Ollrogge Karen , Schulze Daniel , Sterzer Philipp , Köhler Stephan , Friedel Eva , Romanczuk-Seiferth Nina , Siegerist Anna-Lena , Brakemeier Eva-Lotta , Guhn Anne
Published: February 2025

Introduction

Interpersonal problems are a transdiagnostic risk factor for the development and maintenance of various psychiatric disorders, including anxiety and depression. Interventions that address these interpersonal challenges could therefore play a crucial role in enhancing mental health. This study aims to evaluate the efficacy and feasibility of a transdiagnostic group intervention, the Kiesler Circle Training (KCT), in improving interpersonal skills.

Methods and analysis

In a prospective randomised controlled trial (RCT), 156 outpatients with a primary diagnosis of either depression or anxiety disorder according to DSM-5, and significant interpersonal problems, will be investigated. All patients will receive individual, state-of-the-art cognitive behavioural therapy (CBT) during the study. They will be randomly assigned to one of two conditions: the experimental group will receive the KCT in group sessions, in addition to individual CBT, while the control group will receive only individual CBT. The KCT intervention consists of 1 introductory individual session and 12 weekly group sessions, each lasting 100 min, with groups of up to 10 patients. KCT includes five sequential modules: the interpersonal circle, nonverbal communication, verbal communication, conflict resolution and empathy training. It is hypothesised that the experimental group will show (a) greater reduction in interpersonal problems from pre-assessment to post-assessment and (b) greater symptomatic improvement regarding the primary diagnosis. Child maltreatment is expected to moderate the trajectory of interpersonal problems. This study aims to provide evidence for the feasibility of KCT as a modular transdiagnostic add-on approach for patients with interpersonal difficulties.

Ethics and dissemination

This study obtained approval from the ethics committees at the Charité Berlin, the Medical School of Berlin and the University of Greifswald. All results will be disseminated through peer-reviewed articles in scientific journals and contributions to national and international conferences.

Trial registration number

DRKS00032467,NCT06170801(see Supplementary Material).