bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of exercise and dietary habits on the association of alpha‐actinin‐3 gene polymorphisms with physical function and body composition in community‐dwelling individuals aged 60 years and older
Authors: Shiratsuchi Daijo , Taniguchi Yoshiaki , Akaida Shoma , Tateishi Mana , Kiuchi Yuto , Kuratsu Ryota , Makizako Hyuma 
Published: December 2024

AimAlpha‐actinin 3 (ACTN3) is associated with diminished physical function and muscle mass in older individuals. However, the effects of lifestyle on this relationship remain unclear. This study explored whether the association between ACTN3 polymorphisms and physical function and body composition varied based on exercise and dietary habits.MethodsA longitudinal analysis of 197 community‐dwelling individuals aged 60 years and older (mean age 72.5 ± 5.9 years, 60.9% women) in the Tarumizu study provided data on ACTN3 gene polymorphisms, with surveys completed in 2019 and 2022 (mean follow‐up 1156 ± 80.0 days). Physical performance (grip strength, walking speed) and body composition (body weight, appendicular skeletal muscle mass [ASMM], and fat mass) were assessed. Genetic polymorphisms were analyzed in oral mucosa samples and categorized into type R allele carriers and type XX alleles (homozygous for minor alleles). Median values determined exercise habits (≤4 days/week or ≥5 days/week) and dietary habits based on high‐protein‐food frequency scores.ResultsThe proportion of type XX genetic polymorphism was 26.4%. Two‐way repeated‐measures analysis of covariance showed a significant interaction between genetic polymorphism and time for ASMM (F = 10.552, P = 0.002) in the ≤4 days/week exercise habits group. Significant interactions were observed in grip strength (F = 7.013, P = 0.009) and ASMM (F = 5.347, P = 0.023) for the ≤11 score high‐protein‐intake group.ConclusionsThis association may contribute to accelerated age‐related changes in physical performance and body composition, particularly among individuals with type XX genetic polymorphism who have low exercise habits and a limited intake of high‐protein foods. Geriatr Gerontol Int 2025; 25: 173–181.
A phase 1/2 safety and efficacy study of TAK‐754 gene therapy: The challenge of achieving durable factor VIII expression in haemophilia A clinical trials
Authors: Chapin John , Álvarez Román Maria Teresa , Ayash‐Rashkovsky Mila , Diogo Dorothee , Kenniston Jon , Lopez‐Jaime Francisco‐Jose , Maggiore Caterina , Mingot‐Castellano María‐Eva , Rajavel Kavitha , Rauch Antoine , Susen Sophie , von Grotthuss Marcin , Wagoner Matt , Wang Qin 
Published: December 2024

AbstractIntroductionHaemophilia A is an X‐linked bleeding disorder resulting from a deficiency of factor VIII (FVIII). To date, multiple gene therapies have entered clinical trials with the goal of providing durable haemostatic protection from a single dose. TAK 754 (BAX 888) is an investigational AAV8‐based gene therapy containing a FVIII transgene. Reduction in CpG motifs was performed to reduce immunogenicity based on prior observations. Here, we describe the results of the first two cohorts treated with TAK 754.AimTo report clinical and translational results of the TAK‐754 phase 1/2 AAV gene therapy study for the treatment of haemophilia A.MethodsA phase 1/2 single arm open‐label dose escalation study of TAK‐754 was performed in participants with severe haemophilia A (NCT03370172). Participants were monitored for safety events, endogenous FVIII activity and bleeding rates. Glucocorticoids were implemented to preserve transgene expression. A transcriptomics analysis was performed to evaluate immunogenicity along with additional post‐hoc analyses.ResultsFour participants were dosed in two cohorts. Infusion of TAK 754 was well‐tolerated. All participants developed mild transient transaminase elevation and subsequent loss of FVIII expression within the first 12 months of treatment despite use of glucocorticoids. Transcriptomic analysis did not demonstrate significant changes in immunogenicity signals in peripheral blood. One serious adverse event of hypophosphatemia occurred in the second cohort without obvious risk factors.ConclusionsSustained FVIII expression remains a challenge in haemophilia A AAV gene therapy trials. Mechanisms of transgene expression loss require further study as clinical studies enter long term follow‐up periods.
Exploring Adolescents' Understanding, Experiences and Beliefs About Pain: A Qualitative Study
Authors: Bogard Isabelle , Ayre Julie , Smith Jenna , Pate Joshua W. , Sortwell Andrew , Gorringe Jonah , Gordon Georgia , Kamper Steven J. , Yamato Tie P. 
Published: December 2024

ABSTRACTBackgroundPain is prevalent across the lifespan and contributes to significant societal and economic burdens. The public often holds misconceptions about pain and pain management. Despite this, there are no well‐resourced public health initiatives delivering information about pain and pain management to the public. Adolescence is an opportune time to educate the public about pain. Health interventions designed for adolescents should reflect their understanding, beliefs and experiences; however, no studies explore this in non‐clinical populations of adolescents. We aimed to explore adolescents' understanding, experiences and beliefs about pain to inform the development of a school‐based pain education module.MethodsWe conducted semi‐structured interviews with 25 adolescents in grades 7–10 (ages 11–16) attending Australian secondary schools. Interviews were conducted on video‐conferencing software, audio‐recorded, transcribed verbatim and analysed using Framework Analysis.ResultsWe generated three themes: (i) physical and psychological pain are distinct, (ii) psychological and contextual factors influence how someone feels or reacts to physical pain and (iii) physical pain matters if it impacts participation in meaningful activities.ConclusionsAdolescents' understanding and beliefs about pain do not always align with current scientific understanding of pain. School‐based pain education programmes should target these areas of misalignment. Addressing adolescents' misconceptions about pain through pain education could also create a more supportive school environment for adolescents experiencing pain. Interactive approaches to learning, such as discussions that encourage adolescents to reflect on their experiences of pain, could be a promising avenue for pain education.Patient or Public ContributionTwo co‐authors are part of the study population and contributed to the study design and analysis. Their input ensured the interview guide was appropriate for the target population and provided an adolescent perspective on the findings. They were remunerated for their time in accordance with consumer involvement guidelines.
Risk assessment of late biochemical recurrence after radical prostatectomy: Usefulness of ultra‐sensitive prostate‐specific antigen measurement
Authors: Kawamura Norihiko , Nakayama Masashi , Hayashi Takuji , Nagahara Akira , Nakai Yasutomo , Nishimura Kazuo 
Published: December 2024

ObjectivesThis study aimed to evaluate predictors of late biochemical recurrence in patients with no recurrence at 5 years after radical prostatectomy (RP).MethodsWe retrospectively investigated patients who underwent RP for prostate cancer in our institute from 1999 to 2016, selecting those with no biochemical recurrence at 5 years post‐RP. These patients did not receive neoadjuvant and adjuvant hormone therapy. Following RP, patients were regularly monitored using ultra‐sensitive prostate‐specific antigen (PSA) measurements, with a detection limit of 0.01 ng/mL. Biochemical recurrence was defined as PSA level ≥0.2 ng/mL, confirmed by subsequent PSA >0.2 ng/mL.ResultsAmong 581 patients who underwent RP, 312 with no biochemical recurrence at 5 years post‐RP were selected. The median follow‐up period was 123 months. The 10‐year biochemical recurrence‐free survival rate for this cohort was 89.6%. Patients with a PSA value <0.02 ng/mL at 5 years post‐RP had a 10‐year biochemical recurrence‐free survival rate of 98.5%. Multivariable regression analysis identified Grade Group ≥4 and PSA value ≥0.02 ng/mL at 5 years post‐RP as independent predictors of late biochemical recurrence (hazard ratio 2.23, 95% confidence interval 1.06–4.71, p = 0.035; hazard ratio 37.5, 95% confidence interval 11.6–121.3, p < 0.001, respectively). Patients with Grade Group of 4 or more had a significantly reduced PSA doubling time at biochemical recurrence compared to those with Grade Group of 3 or less.ConclusionsAmong patients whose PSA levels remain below 0.02 ng/mL at 5 years after RP, the risk of subsequent late biochemical recurrence is very low. Utilizing ultra‐sensitive PSA measurements at the 5‐year mark can provide useful information regarding the need for follow‐up beyond 5 years.
Characteristics and management of eosinophilic esophagitis in Australasian children: a decade of experience
Authors: Philpott Hamish , Lemberg Daniel A. , Day Andrew S. , Rosenbaum Jeremy , Singh Harveen , Rumore Sarah , Ellison Samuel , Couper Michael , Porter Jody , Roberts Amin , Thacker Kunal , Moore David , Furata Glenn , Sharma Ajay 
Published: December 2024

AbstractBackgroundThe frequency of EoE has been increasing in Northern Hemisphere cohorts, yet there is a scarcity of data in our region. Regional climatic factors, and lifestyle habits may influence the presentation of EoE, and appropriate management is crucial to prevent complications. WIth this is mind we undertook the first comprehensive multisite study of EoE in Australasian children.AimTo determine the incidence, prevalence, clinical characteristics and management of eosinophilic esophagitis (EoE) in Australasian children.MethodsRetrospective audit of endoscopic records, histology reports and case notes (ICD code) over a 10‐year period (1 January 2008 to 31 December 2018). Cases were defined as having >15 eosinophils per high‐power field (HPF) at endoscopy and oesophageal biopsy, while treatment response was defined as <5 eosinophils per HPF. Included were patients aged 0–18 years presenting to tertiary paediatric hospitals in seven capital cities (Adelaide, Auckland, Brisbane, Christchurch, Melbourne, Perth and Sydney), while those with conditions that could cause eosinophilia (organ transplantation, hyper‐eosinophilic syndrome) or taking medications that may influence tissue eosinophilia (systemic corticosteroids immunosuppressants) were excluded. Australian Bureau of Statistics and Stats NZ were used to define comparative population data. Demographics (age at diagnosis, gender, country of birth, race) comorbidities (atopic conditions, e.g. asthma, seasonal rhinitis, eczema) and treatment (diet, steroids, proton pump inhibitors) were noted.ResultsThe prevalence of EoE ranged from 15 to 54 per 100 000 children, where cases were more common in Adelaide than other localities. Incidence increased significantly in all sites across the 10 years, with peak incidence in Adelaide of 6.4 per 100 000 children in 2017. EoE was most frequent in males (male:female ratio = 3:1) and >90% were white Caucasian. Polynesian racial background in Auckland (10%) and middle eastern racial background in Sydney (10%) were the next most frequent. Treatment choice varied across sites, and greater than 30% of patients did not undergo endoscopy to assess initial treatment success.ConclusionThe prevalence of EoE in Australasian children is comparable to that observed elsewhere, and the incidence is increasing significantly. Regional differences in disease frequency, management practices and access to endoscopy warrant further study.
Sodium‐glucose cotransporter 2 inhibitors reduce albuminuria in patients with Fabry disease: a real‐world case series
Authors: Tsatsaronis Anthea , Tiong Mark , Nicholls Kathleen , Ruderman Irene 
Published: December 2024

AbstractBackgroundFabry disease is a rare X‐linked multisystem disease, with progressive proteinuric kidney disease contributing significantly to morbidity and mortality of these patients. Evidence shows that sodium‐glucose cotransporter 2 inhibitors (SGLT2Is) can reduce proteinuria and slow progression to end‐stage kidney disease in both diabetic and non‐diabetic kidney disease.AimEvaluate the effects of SGLT2I on kidney function and albuminuria in patients with Fabry disease.MethodsSingle‐centre real‐world case series reviewing electronic medical records of patients with Fabry disease who initiated therapy with dapagliflozin or empagliflozin (n = 11). Changes in urine albumin–creatinine ratio (uACR) and creatinine before and after treatment with SGLT2I were analysed using Wilcoxon signed‐rank test. Two‐tailed P‐values <0.05 were considered significant.ResultsEleven patients were followed for up to 19 months after commencement of SGLT2I. An overall significant reduction in albuminuria (P = 0.05) was seen with SGLT2I use in the Fabry cohort. Median uACR before SGLT2I was 76 mg/mmol (interquartile range (IQR) 47–141) and after SGLT2I was 39 mg/mmol (IQR 18–95) (P = 0.05). All patients with uACR >100 mg/mmol had reduction in albuminuria over the study period. SGLT2Is were well tolerated overall, with only one case resulting in cessation of treatment due to adverse effects.ConclusionThese results suggest SGLT2Is can significantly reduce albuminuria in a portion of patients with Fabry‐related kidney disease and offer additional treatment for Fabry nephropathy. Given the nature of the study design and small case numbers, further long‐term controlled studies are required to evaluate the long‐term efficacy of this medication class in both cardiac and renal outcomes in Fabry disease.
Excipient induced allergies in oral medications: unravelling the covert threat – a systematic review
Authors: Seth Shrey , Lukose Lipin , Sud Kamal , Goh Jing Xin , Tesfaye Wubshet , Small Fatima , Sridhar Sathvik B. , Castelino Ronald L. 
Published: December 2024

AbstractExcipients have been identified as ‘inert’ substances that often enhance the non‐pharmacological aspects of a medication. However, recent clinical evidence elucidates their potential in inducing anaphylaxis and indicates that they are often overlooked as potential allergens in routine clinical practice. The aim of the study was to assimilate published evidence on excipient‐induced allergies associated with the use of oral medications and to underline their potential as potent allergens. A systematic literature search of MEDLINE, EMBASE and International Pharmaceutical Abstracts databases was performed for case reports published from inception to June 2024. Studies were excluded if they were animal and laboratory studies or not published in English, full‐text articles were unavailable, and they lacked essential information. This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines. Polyethylene glycol was the most prevalent allergenic excipient, followed by colouring agents. Clinical manifestations exhibited wide variability ranging from mild to life‐threatening reactions, and the most common presentations were urticaria and angioedema. Most patients recovered spontaneously after withdrawal of the offending agent with less than half necessitating additional drug interventions and only a single instance of reported fatality, which cannot be attributed to the excipient alone. Despite being labelled as inert, excipients pose a significant threat for the development of allergic reactions. Simple measures such as increased awareness among patients and healthcare professionals, comprehensive history taking, reviewing medication compositions and improved patient awareness regarding potentially allergenic excipients can aid in avoiding these readily preventable reactions.
The Impacts of Second Victim Experiences on Nurses' Absenteeism and Intention to Leave: A Multi‐Site Cross‐Sectional Study
Authors: Alfar Zainab , Hakamy Essa , Innab Adnan 
Published: December 2024

ABSTRACTAimAdverse events impact patients as primary victims including their families, while healthcare providers are impacted as second victims. These incidents have serious psychological and physical impacts on healthcare providers' quality of life and their ability to execute their jobs. As no studies have been conducted in the Middle East to explore the experiences of second victims among nurses, this study examined the relationship between nurses' second victim experiences, turnover and absenteeism.DesignDescriptive, correlational, cross‐sectional study.MethodsA convenience sample of 117 nurses was recruited from secondary‐ and tertiary‐level hospitals across 13 regions in Saudi Arabia. The Second Victim Experience and Support Tool was used to assess second victim experiences and their impact on turnover and absenteeism.ResultsSecond victim trauma affected over half of the participants. ‘The mental weight of my experience is exhausting’ and ‘My colleagues can be indifferent to the impact these situations have had on me’ obtained the highest mean scores. Healthcare providers who stated that these situations had improved their quality of care were found to have the lowest scores. Second victim experiences had significant relationships with turnover and absenteeism. Further, healthcare providers' length of experience did not affect absenteeism, while second victim experiences significantly predicted absenteeism. Additionally, a strong relationship was observed between turnover and absenteeism. Overall, those with a second victim experience had a greater turnover intention.ConclusionsThe results underscore the physical and psychological distress that healthcare providers endure, increasing the likelihood of them leaving the profession. These problems are worsened by inadequate institutional support, emphasising the need for efforts to stabilise second victims and avoid unfavourable organisational outcomes.Reporting MethodThe study adheres to the STROBE reporting guidelines.Patient or Public ContributionNo patient or public contribution.
Childhood and Adulthood Predictors of Community Participation by Autistic Adults With and Without Intellectual Disability
Authors: Cameron Lauren A. , Tonge Bruce J. , Howlin Patricia , Einfeld Stewart L. , Stancliffe Roger J. , Gray Kylie M. 
Published: December 2024

ABSTRACTBackgroundFew studies have explored community participation for autistic adults, with or without intellectual disability. This study aims to investigate how autistic adults participate in the community, and the childhood and adulthood factors that predict community participation in adulthood.MethodEighty‐four autistic adults (mean age 34 years; 67% with co‐occurring intellectual disability) initially recruited as children and adolescents, participated in the current study. Community participation frequency and variety were measured in adulthood. Childhood and adulthood predictors of community participation were investigated.ResultsParticipants engaged in the community an average of 18.2 times (range 0–49) over the previous 30‐day period, in an average of 6.3 different activities (range 0–13). Childhood and adulthood factors (autism symptoms, intellectual disability, living arrangements) were associated with community participation.ConclusionAreas for additional support and resources were identified.
Implementing Pretraining to Optimise Learning in Immersive Virtual Reality
Authors: Delgado Cynthia Y. , Mayer Richard E. 
Published: December 2024

ABSTRACTBackgroundIn recent years, immersive virtual reality in education has garnered attention, however, there have been mixed findings on the efficacy of IVR in education. Thus, exploring which strategies are effective in transferring learning from IVR to real‐world applications is imperative.ObjectiveThis study aims to investigate the efficacy of the pretraining principle for acquiring procedural knowledge and skills in an IVR setting that will transfer to real‐world environments.MethodsNinety‐three participants were randomly assigned to either a pretraining or no‐pretraining group. The pretraining group watched a video before the IVR lesson, providing the names and characteristics of the physical objects and actions of a micropipette, while the no‐pretraining group did not receive this video. During the IVR lesson, participants completed a training phase, followed by a four‐step serial dilution test. Afterwards, all participants completed a modified serial dilution test in a real‐life setting, along with a knowledge test and assessment on cognitive load, presence, self‐efficacy and demographic information.Results and ConclusionsAnalyses demonstrated the pretraining group scored significantly higher on the knowledge test and committed fewer errors in the real‐life serial dilution task compared to the no‐pretraining group. The pretraining group also reported lower cognitive load, with no observable differences in presence, self‐efficacy ratings or errors during the virtual serial dilution task between groups. Theoretical and practical implications are discussed.
Leveraging Large Language Models to Generate Course‐Specific Semantically Annotated Learning Objects
Authors: Lohr Dominic , Berges Marc , Chugh Abhishek , Kohlhase Michael , Müller Dennis 
Published: December 2024

ABSTRACTBackgroundOver the past few decades, the process and methodology of automatic question generation (AQG) have undergone significant transformations. Recent progress in generative natural language models has opened up new potential in the generation of educational content.ObjectivesThis paper explores the potential of large language models (LLMs) for generating computer science questions that are sufficiently annotated for automatic learner model updates, are fully situated in the context of a particular course and address the cognitive dimension understand.MethodsUnlike previous attempts that might use basic methods such as ChatGPT, our approach involves more targeted strategies such as retrieval‐augmented generation (RAG) to produce contextually relevant and pedagogically meaningful learning objects.Results and ConclusionsOur results show that generating structural, semantic annotations works well. However, this success was not reflected in the case of relational annotations. The quality of the generated questions often did not meet educational standards, highlighting that although LLMs can contribute to the pool of learning materials, their current level of performance requires significant human intervention to refine and validate the generated content.