bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence that staphylococcal superantigens promote within-patient bacterial persistence following post-operative surgical site infection
Authors: Dufresne Karine , Tuffs Stephen W. , Walton Nicholas R. , Kasper Katherine J. , Mohorovic Ivor , Hasan Farah , Bentall Tracey , Heinrichs David E. , Delport Johan , Mele Tina S. , McCormick John K.
Published: January 2025

Staphylococcus aureus
is a predominant cause of post-operative surgical site infections and persistent bacteremia. Here, we describe a patient who experienced three episodes of
S. aureus
infection over a period of 4 months following a total knee arthroplasty. The initial bloodstream isolate (SAB-0429) was a clonal complex 5 (CC5) and methicillin-resistant
S. aureus
(MRSA), whereas two subsequent isolates (SAB-0485 and SAB-0495) were CC5 isolates but methicillin-sensitive
S. aureus
. The two latter isolates harbored a plasmid encoding three superantigen genes that were not present in the primary MRSA isolate. SAB-0485 and SAB-0495 both expressed the plasmid-encoded staphylococcal enterotoxin R exotoxin and demonstrated increased superantigen activity compared with SAB-0429. Compared to SAB-0429, the latter isolates also demonstrated an increased bacterial burden in a mouse bacteremia model that was dependent on increased interferon-γ production. Curing of the plasmid from SAB-0485 reduced this virulence phenotype. These findings suggest that the superantigen exotoxins may provide a selective advantage in chronic post-surgical infections.

IMPORTANCE

In this study, we investigated bacterial isolates from a patient who experienced three recurrent
S. aureus
infections over a 4 month period following total knee arthroplasty. Genomic and phenotypic characterization of these isolates revealed that they all belonged to clonal complex 5, yet the latter two strains contained an additional plasmid encoding superantigen exotoxins. Subsequent experimental infection experiments in mice demonstrated that the plasmid-encoded superantigens exacerbated bacteremia by promoting liver abscess formation. These experiments suggest that despite appropriate antibiotic therapy, bacterial superantigens may be able to promote persistent infection following post-surgery.
Characterization of extended-spectrum beta-lactamase-producing
Enterobacteriaceae
from recreational water in Athens, GA, using an undergraduate laboratory module
Authors: Rodriguez-Garcia Coralis , Wall Helen , Ottesen Elizabeth , Grainy Julie
Published: January 2025

We present a laboratory module that uses isolation of antibiotic-resistant bacteria from locally collected stream water samples to introduce undergraduate students to basic microbiological culture-based and molecular techniques. This module also educates them on the global public health threat of antibiotic-resistant organisms. Through eight laboratory sessions, students are involved in quality testing of water sources from their neighborhoods, followed by isolation of extended-spectrum beta-lactamase-producing
Enterobacteriaceae
. By the end of the module, students should be able to isolate
Enterobacteriaceae
from the environment using selective and differential media, identify isolates using biochemical tests, characterize antibiotic resistance phenotypes using Kirby Bauer and MIC tests, and evaluate the presence of select beta-lactamase genes of interest using PCR. To complement laboratory sessions, students participated in a weekly flipped classroom session with collaborative peer discussions and activities to reinforce concepts applied in the laboratory. Learning outcomes were measured over four semesters with concept checks, in-lecture activities, exams, and laboratory reports. We hypothesized that more than 50% of the student population would achieve each learning objective through the implementation of this authentic research laboratory module. Here, we highlight specific questions used to assess learning objective comprehension and demonstrate that each learning objective was achieved by 65%–100% of the student population. We present a ready-to-adapt module with flexible resources that can be implemented in courses across disciplines in biology, microbiology, environmental sciences, and public health.
Chromosome level genome assembly and annotation of
Hanseniaspora mollemarum
CBS 18055 strain
Authors: Bennis Nicole Xanthe , Indudhar Hanji Harshitha , van den Broek Marcel , Daran Jean-Marc
Published: January 2025

Hanseniaspora species gained attention due to the ability of these species to ferment simple sugars and to actively contribute to the development of bouquet aromas in wine and cider fermentations. We present a chromosome-level assembly of an isolate of
Hanseniaspora mollemarum
that would enhance its potential applications.
mSphere of Influence: High-throughput screens to rapidly assign function to microbial genes
Authors: Huberman Lori B.
Published: January 2025

Lori Huberman works in the field of fungal genetics, with an emphasis on investigating the genetic mechanisms fungi use to sense and respond to the nutrients and toxins in their environment. In this mSphere of Influence article, she reflects on how “Rapid quantification of mutant fitness in diverse bacteria by sequencing randomly bar-coded transposons” by K. M. Wetmore, M. N. Price, R. J. Waters, J. S. Lamson, et al. (mBio 6:e00306-15, 2015,
https://doi.org/10.1128/mBio.00306-15
) made an impact on her by establishing technologies that open realistic possibilities for developing high-throughput screening methods to correlate phenotype to genotype in diverse fungal species.
Associations of fetal and infant growth with pubertal timing
Authors: Blaauwendraad Sophia , Gaillard Romy , Gonçalves Romy , Rivadeneira Fernando , Dohle Gert , Oei Edwin , Mulders Annemarie , Jansen Pauline , Jaddoe Vincent
Published: January 2025

Objective

Impaired fetal and infant growth may cause alterations in developmental programming of the hypothalamic–pituitary–gonadal axis and subsequently pubertal development. We aimed to assess associations between fetal and infant growth and pubertal development.

Design

Population-based prospective birth cohort.

Setting

Rotterdam, the Netherlands.

Patients

5830 singleton born children.

Interventions

We estimated fetal weight in second and third trimester by ultrasound. Infant growth measures were gestational age and weight at birth and infant weight at 6, 12 and 24 months.

Main outcome measures

Pubertal timing outcomes included difference between chronological and skeletal age assessed using dual-energy X-ray absorptiometry, testicular or ovarian volumes assessed using MRI at 10 years, age at menarche and Tanner staging at 13 years.

Results

Among girls, 1-SD scores birth weight increase was associated with larger ovarian volume at 10 years (0.07 SD (95% CI 0.02 to 0.12) and later age at menarche (0.06 (0.02 to 0.11)). Among girls, increased infant growth was associated with an older skeletal age at 10 years (difference 2.67 (95% CI 2.26 to 3.08) months), earlier menarche (difference 0.10 (95% CI −0.14 to –0.06) years) and more advance breast and pubic hair development at 13 years (difference in Tanner stages 0.09 (0.05 to 0.13) and 0.07 (0.03 to 0.12)). In boys, increased infant growth was associated with an older skeletal age (3.13 (95% CI 2.58 to 3.69) months) and a larger testicular volume (0.07 (95% 0.02 to 0.12) SD) at 10 years, and with more advance pubic hair development (0.09 (95% CI 0.05 to 0.14) at 13 years).

Conclusion

Birth anthropometrics and early-life growth patterns are associated with altered pubertal development in a sex-specific manner.
Characteristics and outcomes associated with fidelity in the Family-Nurse Partnership in England: a data linkage cohort study
Authors: Clery Amanda , Cavallaro Francesca , Kennedy Eilis , Gilbert Ruth , Harron Katie L
Published: January 2025

Objectives

To determine (1) which maternal and area characteristics are associated with reaching fidelity targets (the expected number of visits mothers should receive at each stage of the programme) in the Family-Nurse Partnership (FNP), and (2) whether achieving these fidelity targets affects outcomes.

Design, setting and population

Cohort study of mothers enrolled in the FNP, aged 13–19 years, giving birth between April 2010 and January 2018 in England. Mothers were linked to their Hospital Episode Statistics and National Pupil Database records.

Outcomes

We described whether mothers reached fidelity targets for each programme stage (pregnancy, infancy and toddlerhood) and explored the characteristics associated with reaching targets. We used generalised linear models to compare child and maternal outcomes between mothers who did and did not reach fidelity targets.

Results

Of the 28 155 mothers enrolled, 58% completed the programme. Fidelity targets were met by 59% of mothers in pregnancy, 65% in infancy and 61% in toddlerhood. The median number of visits was 38 (median 43 hours contact time). Younger mothers, those with a history of unplanned hospital admissions for adversity and those with social care involvement received a greater number of visits. Meeting fidelity targets was associated with a reduction in subsequent births within 18 months and an increase in the number of children with unplanned hospital admissions for maltreatment or injury up to age 2.

Conclusions

Achieving fidelity to the FNP is challenging, but family nurses are able to engage the most vulnerable mothers in the programme. More research is needed to understand whether fidelity to programme targets is a useful measure of mothers’ experiences of intensive home visiting.
Small bowel obstruction after caesarean section: an unusual complication of surgical haemostatic agent
Authors: Sahu Nutan , Kamboj Shagun , Rana Anubhuti , Mahey Reeta
Published: January 2025

An unusual case of small bowel obstruction (SBO) due to haemostatic gelatin sponge placed during caesarean delivery is presented. A primigravida in their 30s underwent caesarean delivery at 39 weeks, and developed symptoms of SBO from the second postoperative day. Given the worsening condition of the patient and increasing abdominal girth, CT of the abdomen and pelvis was done which revealed features of SBO. Due to no improvement despite conservative management for 3 days, the decision for surgical management was taken. Exploratory laparotomy revealed adhesive obstruction with haemostatic agent with a definitive transition point in the ileum. Adhesiolysis was performed between bowel loops adhered to a gelatin sponge placed on the hysterotomy incision. The postoperative period was uneventful and she was discharged after 5 days. Physical haemostatic agents should be used judiciously and adhesions due to these agents should be kept in mind in the differential diagnosis of patients with SBO or other abdominal symptoms in the early postoperative period.
Mount Fuji sign in invasive fungal rhinosinusitis
Authors: Viskens Karolien , van Gerven Laura , Devos Johannes , Vos Robin
Published: January 2025

We report on a fatal case of invasive fungal rhinosinusitis withAspergillus fumigatusafter lung transplantation. After endoscopic treatment and adjuvant medical therapy with isavuconazole, caspofungin and an investigational antifungal drug, there was a good clinical response with absence of endoscopic and radiographic disease. However, the patient developed disease recurrence, with signs of intracranial involvement on MRI, for which urgent endoscopic sinus surgery was performed and isavuconazole was restarted. In the days following the surgery, the patient suffered from increasing headache and confusion, with CT scan displaying a Mount Fuji sign (tension pneumocephalus). Best supportive care was provided, but the patient succumbed shortly after. Autopsy demonstrated a perforation at the skull base due to locally invasive fungal infection.

Invasive fungal rhinosinusitis is uncommon, mainly occurs in subjects with altered host defence, requires multimodal treatment and has a poor prognosis, with tension pneumocephalus as a rare, life-threatening complication.
Analytical approaches to evaluate risk factors of multimorbidity: a systematic scoping review protocol
Authors: Song Wenbo , Birk Nick , Matsuzaki Mika , Lieber Judith , Yamanashi Hirotomo , Rogers Elliott , Aramrat Chanchanok , Wiwatkunupakarn Nutchar , Angkurawaranon Chaisiri , Lewin Alex , Kinra Sanjay , Mallinson Poppy Alice Carson
Published: January 2025

Introduction

Understanding causal risk factors that contribute to the development of multimorbidity is essential for designing and targeting effective preventive strategies. Despite a large body of research in this field, there has been little critical discussion about the appropriateness of the various analytical approaches used. This proposed scoping review aims to summarise and appraise the analytical approaches used in the published literature that evaluated risk factors of multimorbidity and to provide guidance for researchers conducting analyses in this field.

Methods and analysis

We will systematically search three electronic databases—Embase, Global Health and MEDLINE, as well as the reference lists of identified relevant review articles, from inception to September 2024. We will screen titles and abstracts using the artificial intelligence-aided software ASReview, followed by screening for eligible articles in full text and extracting data. We will then categorise the analytical approaches used across studies, provide a comprehensive overview of the methodology and discuss the potential strengths and limitations of each analytical approach.

Ethics and dissemination

We will undertake a secondary analysis of published literature; therefore, ethical approval is not required. The results will be disseminated through an open-access, peer-reviewed publication. This systematic scoping review will serve as a guide for researchers in selecting analytical approaches for aetiological multimorbidity research, thereby improving the quality and comparability of research in this field.
Comparison of the effectiveness of intra-infrapatellar fat pad and intra-articular glucocorticoid injection in knee osteoarthritis patients with Hoffa’s synovitis: protocol for a multicentre randomised controlled trial
Authors: Chen Yiwei , Lin Junqing , Lin Jiali , Gao Tao , Cai Qianying , Zhang Changqing , Zhu Hongyi , Shen Longxiang , Wang Qiuke
Published: January 2025

Introduction

The infrapatellar fat pad and synovium are the sites of immune cell infiltration and the origin of proinflammation. Studies have shown that Hoffa’s synovitis may be a sign of early-stage osteoarthritis (OA). However, there have been no effective interventions specifically for Hoffa’s synovitis.

Methods and analysis

We will conduct a multicentre, multi-blind (participant, physician, outcome assessor and data analyst blinded) randomised controlled trial to compare the effectiveness of an intra-infrapatellar fat glucocorticoid versus an intra-articular injection for Hoffa’s synovitis in patients with knee OA. We will recruit 236 knee OA patients with Hoffa’s synovitis at outpatient clinics in three centres. We will randomly allocate them to two groups in a 1:1 ratio. One group will receive ultrasound-guided injection of 40 mg (1 mL) triamcinolone acetonide into the infrapatellar fat pad; the other group will receive ultrasound-guided injection of 40 mg (1 mL) triamcinolone acetonide into the knee joint cavity. All patients will be followed up at 2, 4, 8, 12 and 24 weeks after the injection. Primary outcomes are (1) Hoffa’s synovitis improvement rate, measured with the MRI Osteoarthritis Knee Score system (superiority outcome) at 24 weeks and (2) pain intensity, measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) at 2 weeks post-injection. Secondary outcomes include Hoffa’s synovitis score at 2 weeks post-injection, pain intensity with the numerical rating scale, WOMAC questionnaire score improvements (function, joint stiffness and total score), improvement rates in effusion synovitis at 2 and 24 weeks, articular cartilage thickness changes at 2 and 24 weeks, Intermittent and Constant Osteoarthritis Pain score, quality of life measured with the EuroQol-5D, OARSI-OMERACT response indicators, co-interventions and side effects at 2, 4, 8, 12 and 24 weeks.

Ethics and dissemination

Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (2023–178). Written informed consent will be obtained from all patients prior to data collection. The findings of this research will be shared through presentations at academic conferences and publications in peer-reviewed journals.

Trial registration number

ChiCTR2400080474.
How do multiple deprivations in nuanced urban and rural settings affect health differently in South Africa? Evidence from NIDS data, 2017
Authors: Dlamini Msawenkosi , Mbonigaba Josue
Published: January 2025

Introduction/objective

Previous research on socioeconomic factors influencing health outcomes has often centred on the urban–rural divide, overlooking the nuanced variations within these categories. This study enhances our understanding by moving beyond traditional comparisons to examine the specific impacts of multiple deprivations on self-rated health across traditional authority areas, rural formal areas, urban informal areas and urban formal areas. By doing so, it captures the unique challenges and health implications associated with varying deprivation levels within these diverse contexts.

Methods

We first constructed the Provincial Index of Multiple Deprivation for each selected region using Wave 5 data from the National Income Dynamics Study, enabling an assessment of the health impacts of multiple deprivations across South Africa. During the estimation of the ordered probit model, collinearity issues emerged. To address this, we applied Principal Component Analysis (PCA) to create independent components which were then incorporated into the model. Self-reported health (SRH) was used as the dependent variable, allowing us to gain valuable insights into the relationship between health and multiple deprivation within these four contexts.

Results

The study uncovers significant disparities in deprivations, with the most deprived areas being rural formal areas and traditional authorities’ areas and the least deprived being the urban formal areas. The PCA variables in the ordered probit model suggest that traditional and rural formal areas soften the effect of multiple deprivations on SRH relative to urban areas. In contrast, informal urban areas enhance the negative effect of multiple deprivation SRH relative to urban formal areas.

Conclusion/recommendations

The interaction between multiple deprivation variables and the specific areas examined in this study reveals varying impacts on health. Greater attention should be given to finer geographical characteristics in residential contexts to ensure that interventions are tailored effectively to the specific needs of each area. This focus is particularly important, as the local context may significantly impact health—a fundamental component of life and well-being.
Rehabilitation using virtual gaming for Hospital and hOMe-Based training for the Upper limb in acute and subacute Stroke (RHOMBUS II): results of a feasibility randomised controlled trial
Authors: Butcher Tom , Warland Alyson , Stewart Victoria , Aweid Basaam , Samiyappan Arul , Kal Elmar , Ryan Jennifer , Athanasiou Dimitrios A , Baker Karen , Singla-Buxarrais Guillem , Anokye Nana , Pound Carole , Gowing Francesca , Norris Meriel , Kilbride Cherry
Published: January 2025

Objective

To investigate the safety, feasibility and acceptability of the Neurofenix platform for upper-limb rehabilitation in acute and subacute stroke.

Design

A feasibility randomised controlled trial with a parallel process evaluation.

Setting

Acute Stroke Unit and participants’ homes (London, UK).

Participants

24 adults (>18 years), acute and subacute poststroke, new unilateral weakness, scoring 9–25 on the Motricity Index (elbow and shoulder), with sufficient cognitive and communicative abilities to participate.

Interventions

Participants randomised to the intervention or control group on a 2:1 ratio. The intervention group (n=16) received usual care plus the Neurofenix platform for 7 weeks. The control group (n=8) received usual care only.

Outcomes

Safety was assessed through adverse events (AEs), pain, spasticity and fatigue. Feasibility was assessed through training and support requirements and intervention fidelity. Acceptability was assessed through a satisfaction questionnaire. Impairment, activity and participation outcomes were also collected at baseline and 7 weeks to assess their suitability for use in a definitive trial.

Randomisation

Computer-generated, allocation sequence concealed by opaque, sealed envelopes.

Blinding

Participants and assessors were not blinded; statistician blinded for data processing and analysis.

Results

192 stroke survivors were screened for eligibility, and 24 were recruited and randomised. Intervention group: n=16, mean age 66.5 years; median 9.5 days post stroke. Control group: n=8, mean age 64.6 years; median 17.5 days post stroke. Three participants withdrew before the 7-week assessment, n=21 included in the analysis (intervention group n=15; control group n=6). No significant group differences in fatigue, spasticity, pain scores or total number of AEs. The median (IQR) time to train participants was 98 (64) min over 1–3 sessions. Participants trained with the platform for a median (range) of 11 (1-58) hours, equating to 94 min extra per week. The mean satisfaction score was 34.9 out of 40.

Conclusion

The Neurofenix platform is safe, feasible and well accepted as an adjunct to usual care in acute and subacute stroke rehabilitation. There was a wide range of engagement with the platform in a cohort of stroke survivors which was varied in age and level of impairment. Recruitment, training and support were manageable and completion of data was good, indicating that a future randomised controlled trial would be feasible.

Trial registration number

ISRCTN11440079.
Successful open defecation-free intervention in low- and middle-income countries: a qualitative synthesis systematic review protocol
Authors: Yulyani Vera , Iswanto Iswanto , Daniel Daniel , Kusumaningrum Fitrina Mahardani , Tetra Dewi Fatwa Sari
Published: January 2025

Introduction

The results of open defecation-free (ODF) programmes vary greatly, especially in low- and middle-income countries (LMICs). This study will systematically investigate available qualitative research to identify the elements contributing to open defecation programmes’ effectiveness in various situations across LMICs. Furthermore, this review seeks to identify gaps in the available literature and areas that require additional investigation and action.

Methods and analysis

Inclusion criteria were developed considering issues related to open defecation in LMICs, sanitation interventions and behavioural change. Research examining sanitation interventions in schools, shelters, disability communities and virtual communities was excluded, as the review focused exclusively on community-based interventions. Studies published in English and Indonesian were included without limitation of the initial year until 31 January 2025. Systematic research will be carried out using ScienceDirect, PubMed, ProQuest and Scopus databases. Information from grey literature, including conference proceedings and reports from relevant organisations, will be systematically searched using Google Scholar and the websites of leading institutions, such as the WHO, UNICEF and WaterAid. This systematic review did not impose any restrictions on the place and date of publication. Two reviewers followed Joanna Briggs Institute guidelines in selecting studies, conducting critical appraisal using confidential tools and extracting data using a structured approach. Data synthesis will be performed using meta-aggregate methods to identify the themes. A ConQual Summary will be used to assess confidence in the findings.

Ethics and dissemination

The findings of the systematic review will be disseminated through a publication in a peer-reviewed journal and presented at a relevant conference. Since the data used will not contain individual patient information, ethical approval is unnecessary.

PROSPERO registration number

CRD42023408851.
Efficacy of the Foodbot Factory digital curriculum-based nutrition education intervention in improving children’s nutrition knowledge, attitudes and behaviours in elementary school classrooms: protocol for a cluster randomised controlled trial
Authors: Brown Jacqueline Marie , Tahir Saman , Franco-Arellano Beatriz , LeSage Ann , Hughes Janette , Kapralos Bill , Lou Wendy , Vogel Ellen , Farkouh Michael , Tugault-Lafleur Claire , Arcand JoAnne
Published: January 2025

Introduction

Schools are an important setting for supporting children’s development of food literacy, but minimal research has assessed which strategies are most suitable for school nutrition education. The Foodbot Factory intervention, consisting of serious game (ie, a digital game designed for education) and curriculum-based lesson plans, was developed to support teachers and children ages 8–12 with nutrition education. Pilot data have demonstrated that Foodbot Factory can significantly improve children’s nutrition knowledge, but it has not yet been evaluated in classrooms.

Methods and analysis

A single-blinded cluster randomised controlled trial was designed in 2022 by a research team based at Ontario Tech University to determine the efficacy of the Foodbot Factory intervention in improving children’s nutrition knowledge, attitudes and behaviours. 32 grade 4 and 4/5 classrooms in Ontario will be randomised to receive (1) the Foodbot Factory intervention or (2) a control nutrition education intervention using conventional materials (eg, activity sheets). The study’s primary outcome is to determine the overall nutrition knowledge acquired from the intervention. Secondary outcomes include nutrition knowledge subscores (ie, knowledge of specific food groups), nutrition attitudes, dietary intake, general nutrition behaviours (eg, eating breakfast) and intervention acceptability. An Ontario-certified teacher will deliver the intervention to both groups for 35–40 min/day for five consecutive days. Outcomes will be assessed at baseline, immediately postintervention, and 4 weeks and 3 months postintervention using the Nutrition Attitudes and Knowledge questionnaire, the Block Kids Food Screener, a modified Family Nutrition and Physical Activity screener and an acceptability questionnaire. Generalised linear mixed models will assess changes in outcomes between groups.

Ethics and dissemination

The study protocol is approved by research ethics boards at Ontario Tech University and participating school boards. Results of the trial will be published in peer-reviewed journals and lay summaries will be available to stakeholders.

Trial registration number

NCT05979259.
Remote symptom monitoring with patient-reported outcomes and nudges during lung cancer immunotherapy in China (PRO-NET): protocol for a randomised controlled trial
Authors: Xia Yiqi , Guan Xiaolong , Shi Zhenyu , Luo Yanan , He Ping
Published: January 2025

Introduction

Lung cancer is the leading cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) comprising the majority of cases. For advanced NSCLC, immunotherapy offers substantial survival benefits but is often accompanied by severe immune-related adverse events symptoms, significantly affecting health-related quality of life (HRQoL). Routinely collection of patient-reported outcomes (PROs) followed by automated alerts has been shown to improve overall survival and HRQoL for cancers. However, there is limited evidence for PRO-based symptom monitoring on advanced NSCLC during immunotherapy. This study proposes an electronic PRO-based symptom tracking intervention, integrated with reactive alerts and nudges (PRO-NET) to improve HRQoL for advanced NSCLC patients receiving immunotherapy in China. Secondary objectives include assessing the effect of PRO-symptom monitoring on survival, physical function, symptom control, mental health, cost-effectiveness and implementation fidelity.

Methods and analysis

The PRO-NET study is a two-arm, parallel randomised controlled trial. The study will enrol at least 300 advanced NSCLC patients undergoing immunotherapy in China. Participants will be randomly assigned to either the intervention or control group in a ratio of 1:1 via PRO-NET programme. The intervention involves weekly electronic collection of immune-related PROs and reactive alerts sent directly to patients, combined with nudges over a 6-month period. Patients in the control group will follow usual care and will not trigger the alerts. Both the intervention and control groups will receive outcome assessments at baseline, 3 months and 6 months. Primary outcome focuses on HRQoL, while secondary outcomes include survival, physical function, symptom burden, mental health, cost-effectiveness and implementation fidelity. Differences in HRQoL between the groups will be compared using general linear mixed model, accounting for potential confounding.

Ethics and dissemination

The study was approved by the Institutional Review Board of the Peking University protocol on 21 July 2024 (No. IRB 00001052-24066). This protocol is based on V2.0, 6 July 2024 of the protocol. The results of this study will be disseminated through peer-reviewed publications and academic conferences.

Trials registration number

ChiCTR2400088408.
The Protocol for the Multi-Ethnic, multi-centre raNdomised controlled trial of a low-energy Diet for improving functional status in heart failure with Preserved ejection fraction (AMEND Preserved)
Authors: Bilak Joanna M , Squire Iain , Wormleighton Joanne V , Brown Rachel L , Hadjiconstantinou Michelle , Robertson Noelle , Davies Melanie J , Yates Thomas , Asad Mehak , Levelt Eylem , Pan Jiliu , Rider Oliver , Soltani Fardad , Miller Christopher , Gulsin Gaurav Singh , Brady Emer M , McCann Gerry P
Published: January 2025

Introduction

Heart failure with preserved ejection fraction (HFpEF) is characterised by severe exercise intolerance, particularly in those living with obesity. Low-energy meal-replacement plans (MRPs) have shown significant weight loss and potential cardiac remodelling benefits. This pragmatic randomised trial aims to evaluate the efficacy of MRP-directed weight loss on exercise intolerance, symptoms, quality of life and cardiovascular remodelling in a multiethnic cohort with obesity and HFpEF.

Methods and analysis

Prospective multicentre, open-label, blinded endpoint randomised controlled trial comparing low-energy MRP with guideline-driven care plus health coaching. Participants (n=110, age ≥18 years) with HFpEF and clinical stability for at least 3 months will be randomised to receive either MRP (810 kcal/day) or guideline-driven care for 12 weeks. Randomisation is stratified by sex, ethnicity, and baseline Sodium Glucose Cotransporter-2 inhibitor (SGLT2-i) use, using the electronic database RedCap with allocation concealment. Key exclusion criteria include severe valvular, lung or renal disease, infiltrative cardiomyopathies, symptomatic biliary disease or history of an eating disorder. Participants will undergo glycometabolic profiling, echocardiography, MRI for cardiovascular structure and function, body composition analysis (including visceral and subcutaneous adiposity quantification), Kansas City Cardiomyopathy Questionnaire (KCCQ) and Six-Minute Walk Test (6MWT), at baseline and 12 weeks. An optional 24-week assessment will include non-contrast CMR, 6MWT, KCCQ score. Optional substudies include a qualitative study assessing participants’ experiences and barriers to adopting MRP, and skeletal muscle imaging and cardiac energetics using 31Phosphorus MR spectroscopy.

Statistical analysis

Complete case analysis will be conducted with adjustment for baseline randomisation factors including sex, ethnicity and baseline SGLT2-i use. The primary outcome is the change in distance walked during the 6MWT. The primary imaging endpoint is the change in left atrial volume indexed to height on cardiac MRI. Key secondary endpoints include symptoms and quality of life measured by the KCCQ score.

Ethics and dissemination

The Health Research Authority Ethics Committee (REC reference 22/EM/0215) has approved the study. The findings of this study will be published in peer-reviewed journals.

Trial registration number

NCT05887271.
Winding up to wind down: designing the end of one’s medical career with intentionality
Authors: Stoller James K , Rabalais Gerard
Published: January 2025

Background

Physicians are planful beings, spending much time imagining and trying to design their ideal careers. Yet, despite actuarial expectations that physicians may spend almost two decades in retirement, it is paradoxical that little attention is generally given to designing an ideal retirement.

Methods

The coauthors are physicians in the latter parts of their careers who both teach leadership to physicians and have thought deeply about physician transitions, including retirement. This perspective narrative is based on their observations, actual experience of colleagues who have retired well and their review of relevant literature.

Results

Several forces restrain physicians from imagining an ideal retirement: first, as with people in general, physicians may be averse to change, and second, thinking about retirement may be framed through a deficit-based lens (eg, “I am retiring because I want to avoid some unpleasant features of my current career.”) Though physicians are predisposed to deficit-based thinking by virtue of their longstanding practice of developing differential diagnoses in clinical reasoning, appreciative or asset-based thinking about retirement (eg, “I am retiring because I am attracted to activities that have not otherwise been possible in my career.”) offers richer possibilities and is encouraged. A rubric for navigating retirement regards being intentional about identity, relationships and purpose in the new state. A taxonomy for types in retirement is offered, recognising that physicians may exemplify more than one type or migrate among them. Finally, several examples of successful retirement by the authors’ colleagues are offered.

Conclusions

We endorse physicians’ being as planful and intentional about retirement as they are about designing their careers. Our hope is that the described issues and approach enhance physicians’ likelihood to achieve the fulfilment and impact in retirement that they seek.
Settlement characteristics and evaluation approach of embankment widening over soft clay
Authors: Zheng Gang , Wang Jiawei , Zhou Haizuo , Xia Boyang , Bui Phu Doanh
Published: January 2025

Embankment widening alongside an existing embankment causes additional stress and differential settlement on the foundation beneath the embankment, which may have adverse effects on pavements. The settlement profiles of the existing and widened foundations beneath an embankment are governed by several geometric and physical parameters related to embankment widening. An accurate settlement evaluation method is essential for the determination of an appropriate ground improvement technique. In this paper, a simplified method for predicting the settlement of the soft foundation induced by embankment widening is proposed. A validated finite element method model was first employed to quantify the effect of geometric parameters and soil properties on the settlement characteristics. Furthermore, a simplified model based on the bi-Gaussian function was developed to illustrate the settlement profiles. The results obtained by the proposed model are in good agreement with previously reported centrifuge test results and a generated numerical database, demonstrating that the proposed model has satisfactory accuracy. The developed prediction model offers an alternative approach for the preliminary design of embankment widening.
Compatibility of Commercial Fungicide Formulations with Plant-Associated Methylobacterium
Authors: Palberg Daniel , Emery Neil RJ
Published: January 2025

Symbiotic Methylobacterium comprise a significant part of the plant microbiome and are known to benefit host plant growth, development, tolerance to abiotic stress, and enhanced disease resistance. The wide application of commercial broad-spectrum fungicide formulations in contemporary agriculture practices has necessitated the investigation of compatibility between popular pesticide products and bacterial endophytes, especially as the Methylobacterium are increasingly considered for agronomic use including biocontrol of phytopathogens.
This study provides an evaluation of compatibility between a extensive inventory of 40 Methylobacterium strains in response to commercial pesticide formulations, each containing different agtive ingredients: DYNASTY® and QUADRIS® (azoxystrobin), MAXIM®480 (fludioxonil), and APRON XL® LS (metalaxyl-M). Using a diffusion disk assay, no sensitivity of tested Methylobacterium strains could be detected against any fungicide product, at doses within and above the recommended therapeutic window (1-100 µg). Potency of formulations across the same range were confirmed using the sensitive phytopathogen Fusarium graminearum.
As Methylobacterium spp. continue to emerge as suitable candidates for various roles in biotechnology including agriculture, a better understanding on the compatibility between this important genus and commercial fungicide products has become a relevant consideration for integrated pest management practices.
Sequence-based identification of polyamine oxidase genes in Sorghum bicolor L.
Authors: Ebeed Heba T. , El-Zonkorany Mohamed , Habib Eman , Ali Esraa , Zahran Ahmed , Ragab Aya Hamdy
Published: January 2025

Polyamine oxidases (PAOs) are enzymes associated with polyamine catabolism and play important roles in growth and development and stress tolerance of plants. In the present study, genome-wide discovery and analysis of the PAO family in sorghum was done utilizing model PAO of Arabidopsis. Six PAO genes were found using publicly available genomic data. Sorghum has the PAO gene representatives distributed throughout four chromosomes (chr1, chr3, chr6, and chr7), and most members have eight to nine exons. The molecular weights of PAO proteins range from 53 to 63 kDa. PAO proteins have a theoretical PI between 5.2 and 8.1. The identification and characterization of PAO gene members in sorghum lay the foundation for further experimental studies elucidating their roles in growth, development, and stress responses, ultimately contributing to our understanding of plant biology, with significant implications for plant breeding by providing valuable insights into potential targets for enhancing stress tolerance and improving crop performance.
Phenomenology of the dark matter sector in the 2HDM extended with complex scalar singlet
Authors: Dutta Juhi , Moortgat-Pick Gudrid , Schreiber Merle
Published: January 2025

The two-Higgs-doublet model augmented with a complex scalar singlet (2HDMS) is a well-motivated candidate for Beyond Standard Model (BSM) Physics. We investigate the dark matter phenomenology of the 2HDMS with the complex scalar singlet as the dark matter candidate. We perform a study of the parameter space allowed by existing theoretical and experimental constraints from dark matter, flavour physics and collider searches. Further, we discuss a few benchmark scenarios to test the discovery potential for the 2HDMS at the HL-LHC and at future high-energy

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colliders.
Report on ReAnimate'24: 2024 Summer School on Retro Gaming History, Critic, and Development
Authors: Guéhéneuc Yann-Gaël , Ullmann Gabriel C. , Politowski Cristiano , Petrillo Fabio , Therrien Carl
Published: January 2025

For many years, there has been an interest in ''old'' games, either real old games or recent games with an ''old'' look and feel. The retro gaming community has grown from very niche to mainstream, following the general gaming trend. Retro gaming has also entered the general psyche with books, movies, documentaries, articles, etc. becoming mainstream. However, despite this mainstream status and some recent books, retro gaming remains under-studied in academia and existing research rarely enters mass media.

We proposed a summer school dedicated to retro gaming, which invited both the humanities and engineering fields to provide unique insights on retro gaming, both theoretical and practical, and opportunities for cross-fertilization among research fields.

This summer school welcomed anyone interested in retro gaming. In particular, students in the humanities learned about general game development and the particularities of retro games while students in engineering learned about the history of gaming and theories about games and game design.

This summer school, supported by the ACM SIGSOFT and Cloanto, featured lectures in the mornings and practical, hands-on sessions in the afternoon given by experts on (retro) games as well as site visits, panels, and discussions to foster exchanges, create a community, and promote the studies of retro games.
A Responsible and Inclusive Technology Framework for Attending to Business-to-Business Contexts
Authors: Becerra Sandoval Juana Catalina , Figueredo de Santana Vagner , Berger Sara , Thomas Quigley Lauren , Hobson Stacy
Published: January 2025

Technology development practices in industry are often primarily focused on business results, which risks creating unbalanced power relations between corporate interests and the needs or concerns of people who are affected by technology implementation and use. These practices, and their associated cultural norms, may result in uses of technology that have direct, indirect, short-term, and even long-term negative effects on groups of people and/or the environment. This is especially critical in B2B (business-to-business) settings due to the potential for responsibility gaps to emerge in such contexts where technologies are sold to one or more third party company obfuscating downstream impacts. This paper contributes a formative framework -the Responsible and Inclusive Technology Framework- that orients critical reflection around the social contexts of technology creation and use; the power dynamics between self, business, and societal stakeholders; the impacts of technology on various communities across past, present, and future dimensions; and the practical decisions that imbue technological artifacts with cultural values. The framework and its components were iteratively developed based on observations of 10 internal exploratory workshops conducted with a total of 49 participants across the company. We expect that the use of the Responsible and Inclusive Technology framework, especially in B2B industry settings, will serve as a catalyst for more intentional and socially-grounded practices, thus bridging the responsibility and principles-to-practice gap.
Blockchain for Large Language Model Security and Safety: A Holistic Survey
Authors: Geren Caleb , Board Amanda , Dagher Gaby G. , Andersen Tim , Zhuang Jun
Published: January 2025

With the growing development and deployment of large language models (LLMs) in both industrial and academic fields, their security and safety concerns have become increasingly critical. However, recent studies indicate that LLMs face numerous vulnerabilities, including data poisoning, prompt injections, and unauthorized data exposure, which conventional methods have struggled to address fully. In parallel, blockchain technology, known for its data immutability and decentralized structure, offers a promising foundation for safeguarding LLMs. In this survey, we aim to comprehensively assess how to leverage blockchain technology to enhance LLMs' security and safety. Besides, we propose a new taxonomy of blockchain for large language models (BC4LLMs) to systematically categorize related works in this emerging field. Our analysis includes novel frameworks and definitions to delineate security and safety in the context of BC4LLMs, highlighting potential research directions and challenges at this intersection.Through this study, we aim to stimulate targeted advancements in blockchain-integrated LLM security.
FG-SMOTE: Towards Fair Node Classification with Graph Neural Network
Authors: Wang Zichong , Yin Zhipeng , Zhang Yuying , Yang Liping , Zhang Tingting , Pissinou Niki , Cai Yu , Hu Shu , Li Yun , Zhao Liang , Zhang Wenbin
Published: January 2025

Graph generative models have become increasingly prevalent across various domains due to their superior performance in diverse applications. However, as their application rises, particularly in high-risk decision-making scenarios, concerns about their fairness are intensifying within the community. Existing graph-based generation models mainly focus on synthesizing minority nodes to enhance the node classification performance. However, by overlooking the node generation process, this strategy may intensify representational disparities among different subgroups, thereby further compromising the fairness of the model. Moreover, existing oversampling methods generate samples by selecting instances from corresponding subgroups, risking overfitting in those subgroups owing to their underrepresentation. Furthermore, they fail to account for the inherent imbalance in edge distributions among subgroups, consequently introducing structural bias when generating graph structure information. To address these challenges, this paper elucidates how existing graph-based sampling techniques can amplify real-world bias and proposes a novel framework, Fair Graph Synthetic Minority Oversampling Technique (FG-SMOTE), aimed at achieving a fair balance in representing different subgroups. Specifically, FG-SMOTE starts by removing the identifiability of subgroup information from node representations. Subsequently, the embeddings for simulated nodes are generated by sampling from these subgroup-information-desensitized node representations. Lastly, a fair link predictor is employed to generate the graph structure information. Extensive experimental evaluations on three real graph datasets show that FG-SMOTE outperforms the state-of-the-art baselines in fairness while also maintaining competitive predictive performance.