bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of hip fracture in meat-eaters, pescatarians, and vegetarians: a prospective cohort study of 413,914 UK Biobank participants
Authors: Webster James , Greenwood Darren C. , Cade Janet E. 
Published: July 2023

AbstractBackgroundMeat-free diets may be associated with a higher risk of hip fracture, but prospective evidence is limited. We aimed to investigate the risk of hip fracture in occasional meat-eaters, pescatarians, and vegetarians compared to regular meat-eaters in the UK Biobank, and to explore the role of potential mediators of any observed risk differences.MethodsMiddle-aged UK adults were classified as regular meat-eaters (n = 258,765), occasional meat-eaters (n = 137,954), pescatarians (n = 9557), or vegetarians (n = 7638) based on dietary and lifestyle information at recruitment (2006–2010). Incident hip fractures were identified by record linkage to Hospital Episode Statistics up to September 2021. Multivariable Cox regression models were used to estimate associations between each diet group and hip fracture risk, with regular meat-eaters as the reference group, over a median follow-up time of 12.5 years.ResultsAmong 413,914 women, 3503 hip fractures were observed. After adjustment for confounders, vegetarians (HR (95% CI): 1.50 (1.18, 1.91)) but not occasional meat-eaters (0.99 (0.93, 1.07)) or pescatarians (1.08 (0.86, 1.35)) had a greater risk of hip fracture than regular meat-eaters. This is equivalent to an adjusted absolute risk difference of 3.2 (1.2, 5.8) more hip fractures per 1000 people over 10 years in vegetarians. There was limited evidence of effect modification by BMI on hip fracture risk across diet groups (pinteraction = 0.08), and no clear evidence of effect modification by age or sex (pinteraction = 0.9 and 0.3, respectively). Mediation analyses suggest that BMI explained 28% of the observed risk difference between vegetarians and regular meat-eaters (95% CI: 1.1%, 69.8%).DiscussionVegetarian men and women had a higher risk of hip fracture than regular meat-eaters, and this was partly explained by their lower BMI. Ensuring adequate nutrient intake and weight management are therefore particularly important in vegetarians in the context of hip fracture prevention.Trial registrationNCT05554549, registered retrospectively.
Estimating the full health and economic benefits of current and future influenza vaccines
Authors: Lafond K. E. , Gharpure R. , Dugan V. G. , Azziz-Baumgartner E. 
Published: July 2023

AbstractIn the dynamic landscape of respiratory virus vaccines, it is crucial to assess the value of novel mRNA and combination influenza/COVID-19 vaccines in low- and middle-income countries. Modeling studies, such as the one conducted by Waterlow et al., provide vital information about the cost–benefit potential of these products compared to currently licensed vaccines. However, this approach only accounts for directly measured medically attended influenza-associated illnesses and has two major limitations. First, this method fails to capture the full disease burden of influenza (including non-respiratory and non-medically attended influenza illnesses), which are particularly important drivers of disease burden in infants and older adults. Second, the model does not describe the ancillary benefits of influenza vaccination such as the attenuation of severe disease, prevention of severe non-respiratory outcomes (e.g., myocardial infarctions), or reduced antibiotic use. To obtain a comprehensive understanding of the benefits of influenza vaccines, we must strive to improve the inputs for future modeling-based evaluations.
“Treated like a Human Being”: perspectives of people who inject drugs attending low-threshold HCV treatment at a syringe service program in New York City
Authors: Kapadia Shashi N. , Aponte-Melendez Yesenia , Rodriguez Alicia , Pai Melinda , Eckhardt Benjamin J. , Marks Kristen M. , Fong Chunki , Mateu-Gelabert Pedro 
Published: July 2023

Abstract
Background
Hepatitis C virus (HCV) treatment can effectively cure HCV among people who inject drugs (PWID). Perspectives of PWID treated in innovative models can reveal program features that address barriers to treatment, and guide implementation of similar models.

Methods
We interviewed 29 participants in the intervention arm of a randomized trial. The trial enrolled PWID with HCV in New York City from 2017 to 2020 and tested the effectiveness of a low-threshold HCV treatment model at a syringe services program. Participants were purposively sampled and interviewed in English or Spanish. The interview guide focused on prior experiences with HCV testing and treatment, and experiences during the trial. Interviews were inductively coded and analyzed using thematic analysis.

Results
Before enrollment, participants reported being tested for HCV in settings such as prison, drug treatment, and emergency rooms. Treatment was delayed because of not being seen as urgent by providers. Participants reported low self-efficacy, competing priorities, and systemic barriers to treatment such as insurance, waiting lists, and criminal-legal interactions. Stigma was a major factor. Treatment during the trial was facilitated through respect from staff, which overcame stigma. The flexible care model (allowing walk-ins and missed appointments) helped mitigate logistical barriers. The willingness of the staff to address social determinants of health was highly valued.

Conclusion
Our findings highlight the need for low-threshold programs with nonjudgmental behavior from program staff, and flexibility to adapt to participants’ needs. Social determinants of health remain a significant barrier, but programs’ efforts to address these factors can engender trust and facilitate treatment.
Trial registration NCT03214679.
The prevalence of osteoporotic fractures in the elderly in China: a systematic review and meta-analysis
Authors: Meng Shilong , Tong Minghao , Yu Yang , Cao Yanguang , Tang Binbin , Shi Xiaolin , Liu Kang 
Published: July 2023

Abstract
Background
Prevalence information is the first step in developing preventive procedures or health services. This study was conducted to systematically evaluate the epidemiology of osteoporotic fractures in Chinese elderly aged ≥ 60 years and to provide evidence-based evidence for the prevention and treatment of osteoporotic fractures.

Methods
We identified relevant studies by searching the literature published in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang Data, and VIP databases from the establishment of the database until August 2022. We used a random-effects model to obtain prevalence estimates and identified sources of heterogeneity and comparisons of prevalence among different groups through subgroup analysis and sensitivity analysis.

Results
A total of 29 articles were included in this study, and the prevalence of osteoporosis fractures in elderly Chinese was high (18.9%). The prevalence has increased significantly over the past decade (from 13.2% in 2000–2010 to 22.7% in 2012–2022). The prevalence of osteoporosis is higher in women than in men (18.5% vs 14.3%) and increases with age. The northern region was higher than the southern region (20.3% vs 18.9%), and the spine, hip, and distal forearm were the most common sites of fracture.

Conclusion
The prevalence of osteoporotic fractures in the Chinese elderly is 18.9%, and timely prevention and treatment are necessary.
European Achondroplasia Forum guiding principles for the detection and management of foramen magnum stenosis
Authors: Irving Melita , AlSayed Moeenaldeen , Arundel Paul , Baujat Geneviève , Ben-Omran Tawfeg , Boero Silvio , Cormier-Daire Valérie , Fredwall Svein , Guillen-Navarro Encarna , Hoyer-Kuhn Heike , Kunkel Philip , Lampe Christian , Maghnie Mohamad , Mohnike Klaus , Mortier Geert , Sousa Sérgio B. 
Published: July 2023

AbstractForamen magnum stenosis is a serious, and potentially life-threatening complication of achondroplasia. The foramen magnum is smaller in infants with achondroplasia, compared with the general population, and both restricted growth in the first 2 years and premature closure of skull plate synchondroses can contribute to narrowing. Narrowing of the foramen magnum can lead to compression of the brainstem and spinal cord, and result in sleep apnoea and sudden death. There is a lack of clarity in the literature on the timing of regular monitoring for foramen magnum stenosis, which assessments should be carried out and when regular screening should be ceased. The European Achondroplasia Forum (EAF) is a group of clinicians and patient advocates, representative of the achondroplasia community. Members of the EAF Steering Committee were invited to submit suggestions for guiding principles for the detection and management of foramen magnum stenosis, which were collated and discussed at an open workshop. Each principle was scrutinised for content and wording, and anonymous voting held to pass the principle and vote on the level of agreement. A total of six guiding principles were developed which incorporate routine clinical monitoring of infants and young children, timing of routine MRI screening, referral of suspected foramen magnum stenosis to a neurosurgeon, the combination of assessments to inform the decision to decompress the foramen magnum, joint decision making to proceed with decompression, and management of older children in whom previously undetected foramen magnum stenosis is identified. All principles achieved the ≥ 75% majority needed to pass (range 89–100%), with high levels of agreement (range 7.6–8.9). By developing guiding principles for the detection and management of foramen magnum stenosis, the EAF aim to enable infants and young children to receive optimal monitoring for this potentially life-threatening complication.
Sexual function assessment in patients with SAPHO syndrome: a cross-sectional study
Authors: Li Chen , Jiang Haixu , Zhang Yunan , Huang Guangrui 
Published: July 2023

Abstract
Introduction
SAPHO syndrome is a group of special syndromes characterized by synovitis, acne, pustulosis, hyperostosis and osteitis. Skin lesions and joint damage are the main clinical manifestations. Among them, females mostly present with palm toe pustulosis, while males have severe acne as the main external manifestation. The bone and joint damage characterized by bone hypertrophy and osteitis is the core manifestation of SAPHO and affects all parts of the body. SAPHO syndrome causes great physical and mental suffering to patients, and it also brings a huge financial burden to the family. The purpose of this study is to explore the impact of SAPHO on the quality of sexual life of patients.

Methods
We screened and included 249 SAPHO patients (169 women and 80 men) from Peking Union Medical College Hospital (Beijing, China). First, we recorded the basic situation of the patient through questionnaires (including gender, age, SAPHO duration, BMI, smoking, drinking, marital status, educational level, occupational status and work status.). Then, the patient needed to fill in the Short Form-36 quality of life questionnaire (SF-36 QoL) to record the quality of life. For Sexual dysfunction (SD), female patients needed to fill in the Female Sexual Function Index (FSFI) to assess the quality of sexual life; while the International Index of Erectile Function (IIEF) was used to assess the SD of male patients. At the same time, we used self-esteem and relationship questionnaire (SEAR) to analyze the psychological state of SAPHO patients. Finally, we performed statistical analysis on the data obtained, and then explored the connection between SAPHO and SD.

Results
In this cross-sectional study, a total of 249 patients completed the questionnaire and constituted the study population. We found that among 169 female patients, 124 patients had FSD (73.4%); while 45 patients did not have FSD (26.6%); and among 80 male patients, 45 (56.3%) had ED; However, 35 patients did not have ED (43.7%). The results of the quality of life and mental state assessment showed that female patients with SD showed lower scores in terms of mental state. Among all male participants, we found no significant difference in quality of life and mental state among participants with or without SD. In addition, there was no significant difference in the duration of SAPHO between female and male participants with or without SD.

Conclusion
This study is the first to evaluate the SD of SAPHO patients. The incidence of SD in female SAPHO patients is higher than that in male patients; the cause of female SD may be mainly psychological factors. These results prove that it is particularly important to focus on regulating their psychological state while diagnosing and treating SAPHO patients in clinical practice.
Hyperhomocysteinemia potentiates megakaryocyte differentiation and thrombopoiesis via GH-PI3K-Akt axis
Authors: Lei Wenjing , Liu Zhuoliang , Su Zhiyuan , Meng Panpan , Zhou Chun , Chen Xiaomei , Hu Zheng , Xiao An , Zhou Miaomiao , Huang Liping , Zhang Yiyue , Qin Xianhui , Wang Junping , Zhu Fengxin , Nie Jing 
Published: July 2023

AbstractHyperhomocysteinemia (HHcy) is closely associated with thrombotic diseases such as myocardial infarction and stroke. Enhanced platelet activation was observed in animals and humans with HHcy. However, the influence of HHcy on thrombopoiesis remains largely unknown. Here, we reported increased platelet count (PLT) in mice and zebrafish with HHcy. In hypertensive patients (n = 11,189), higher serum level of total Hcy was observed in participants with PLT ≥ 291 × 109/L (full adjusted β, 0.59; 95% CI 0.14, 1.04). We used single-cell RNA sequencing (scRNA-seq) to characterize the impact of Hcy on transcriptome, cellular heterogeneity, and developmental trajectories of megakaryopoiesis from human umbilical cord blood (hUCB) CD34+ cells. Together with in vitro and in vivo analysis, we demonstrated that Hcy promoted megakaryocytes (MKs) differentiation via growth hormone (GH)-PI3K-Akt axis. Moreover, the effect of Hcy on thrombopoiesis is independent of thrombopoietin (TPO) because administration of Hcy also led to a significant increase of PLT in homozygous TPO receptor (Mpl) mutant mice and zebrafish. Administration of melatonin effectively reversed Hcy-induced thrombopoiesis in mice. ScRNA-seq showed that melatonin abolished Hcy-facilitated MK differentiation and maturation, inhibited the activation of GH-PI3K-Akt signaling. Our work reveals a previously unrecognized role of HHcy in thrombopoiesis and provides new insight into the mechanisms by which HHcy confers an increased thrombotic risk.Trial Registration clinicaltrials.gov Identifier: NCT00794885.
IPSC derived cardiac fibroblasts of DMD patients show compromised actin microfilaments, metabolic shift and pro-fibrotic phenotype
Authors: Soussi Salwa , Savchenko Lesia , Rovina Davide , Iacovoni Jason S. , Gottinger Andrea , Vialettes Maxime , Pioner Josè-Manuel , Farini Andrea , Mallia Sara , Rabino Martina , Pompilio Giulio , Parini Angelo , Lairez Olivier , Gowran Aoife , Pizzinat Nathalie 
Published: July 2023

AbstractDuchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy caused by mutations in the dystrophin gene. We characterized which isoforms of dystrophin were expressed by human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts obtained from control and DMD patients. Distinct dystrophin isoforms were observed; however, highest molecular weight isoform was absent in DMD patients carrying exon deletions or mutations in the dystrophin gene. The loss of the full-length dystrophin isoform in hiPSC-derived cardiac fibroblasts from DMD patients resulted in deficient formation of actin microfilaments and a metabolic switch from mitochondrial oxidation to glycolysis. The DMD hiPSC-derived cardiac fibroblasts exhibited a dysregulated mitochondria network and reduced mitochondrial respiration, with enhanced compensatory glycolysis to sustain cellular ATP production. This metabolic remodeling was associated with an exacerbated myofibroblast phenotype and increased fibroblast activation in response to pro fibrotic challenges. As cardiac fibrosis is a critical pathological feature of the DMD heart, the myofibroblast phenotype induced by the absence of dystrophin may contribute to deterioration in cardiac function. Our study highlights the relationship between cytoskeletal dynamics, metabolism of the cell and myofibroblast differentiation and provides a new mechanism by which inactivation of dystrophin in non-cardiomyocyte cells may increase the severity of cardiopathy.
Comparing conventional treatment, single-target rTMS, or dual-target rTMS for the treatment of post-stroke cognitive impairment — clinical effects and neuroscientific insights: study protocol for a randomized controlled trial
Authors: Xu Bingshan , Lin Chunrong , Guo Cailian , Wang Hong 
Published: July 2023

Abstract
Background
Although increasing evidence suggests that repetitive transcranial magnetic stimulation may help improve cognitive impairment after stroke, its clinical efficacy is still limited. This limitation may be due to the fact that the left dorsolateral prefrontal cortex (DLPFC) is only one of several brain areas involved in post-stroke cognitive impairment (PSCI). The aim of the present study is to reveal whether dual-target stimulation is superior to single-target stimulation and usual care in the treatment of PSCI.

Methods
A single-center, single-blind, randomized controlled trial will be conducted, and fifty-seven PSCI patients will be recruited and randomly assigned to one of three groups based on the stimulating site. The primary outcome is cognitive function, measured using the Montreal Cognitive Assessment Beijing Version (MoCA-BJ) and Mini-Mental Status Examination (MMSE). The secondary outcomes are the modified Barthel Index (MBI), Trail-Making Test (TMT), and digital span test (DST). Furthermore, changes in brain activity are assessed using transcranial Doppler sonography (TCD) examination and serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) closely related to nerve and vascular repair after brain injury. All outcomes will be measured at baseline and 4 weeks after treatment.

Discussion
If dual-target rTMS in significant improvements in cognitive function, this method could be considered as a first-line clinical treatment for PSCI. This proposed study has the potential to identify a new, evidence-based intervention that can enhance cognition and independent living in patients with cognitive impairment after stroke.

Trial registration
Chinese Clinical Trial Registry ChiCTR2200066184. It was registered on 26 November 2022.
Upregulation of Hox genes leading to caste-specific morphogenesis in a termite
Authors: Oguchi Kohei , Miura Toru 
Published: July 2023

Abstract
Background
In social insects, interactions among colony members trigger caste differentiation with morphological modifications. In termite caste differentiation, caste-specific morphologies (such as mandibles in soldiers, genital organs in reproductives or wings in alates) are well developed during post-embryonic development under endocrine controls (e.g., juvenile hormone and ecdysone). Since body part-specific morphogenesis in caste differentiation is hormonally regulated by global factors circulated throughout the body, positional information should be required for the caste-specific and also body part-specific morphogenesis. To identify factors providing the positional information, expression and functional analyses of eight Hox genes were carried out during the three types of caste differentiation (i.e., soldier, neotenic and alate differentiation) in a termite, Hodotermopsis sjostedti.

Results
Spatio-temporal patterns of Hox gene expression during caste differentiation were elucidated by real-time qPCR, showing the caste-specific upregulations of Hox genes during the differentiation processes. Among eight Hox genes, Deformed (Dfd) was upregulated specifically in mandibles in soldier differentiation, abdominal-A (abd-A) and Abdominal-B (Abd-B) were upregulated in the abdomen in neotenic differentiation, while Sex-comb reduced (Scr) and Antennapedia (Antp) were upregulated during alate differentiation. Furthermore, RNAi knockdown of Dfd in soldier differentiation and of abd-A and Abd-B in neotenic differentiation distorted the modifications of caste-specific morphologies.

Conclusions
Gene expression and functional analyses in this study revealed that, in the caste differentiation in termites, upregulation of Hox genes provide positional identities of body segments, resulting in the caste-specific morphogenesis. The acquisition of such developmental modifications would have enabled the evolution of sophisticated caste systems in termites.
Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer
Authors: Aggarwal Charu , Marmarelis Melina E. , Hwang Wei-Ting , Scholes Dylan G. , McWilliams Tara L. , Singh Aditi P. , Sun Lova , Kosteva John , Costello Michael R. , Cohen Roger B. , Langer Corey J. , Doucette Abigail , Gabriel Peter N. , Shulman Lawrence N. , Rendle Katharine A. , Thompson Jeffrey C. , Bekelman Justin E. , Carpenter Erica L. 
Published: July 2023

PURPOSE Current guidelines recommend molecular genotyping for patients newly diagnosed with metastatic nonsquamous (mNSq) non–small-cell lung cancer (NSCLC). The association between availability of molecular genotyping before first line (1L) therapy and overall survival (OS) is not known. METHODS We conducted a real-world cohort study using electronic health records in patients newly diagnosed with mNSq NSCLC. Cox proportional-hazards multivariable regression models were constructed to examine the association between OS and test result availability before 1L therapy, adjusting for covariates. Additional analyses were conducted to assess the consistency and strength of the relationship. Multivariable logistic regression models were used to examine the association between concurrent tissue and plasma testing ( v tissue alone) and result availability. RESULTS Three hundred twenty-six patients were included, 80% (261/326) with results available before 1L (available testing group), and 20% (65/326) without results available (unavailable testing group). With 14.2-month median follow-up, patients in the available testing group had significantly longer OS relative to the unavailable testing group (adjusted hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P < .0001). The adjusted odds of availability of results before 1L therapy was higher with concurrent tissue and plasma testing ( v tissue testing alone; adjusted odds ratio, 2.06; 95% CI, 1.09 to 3.90; P = .026). CONCLUSION Among patients with mNSq NSCLC in a real-world cohort, availability of molecular genotyping results before 1L therapy was associated with significantly better OS. Concurrent tissue and plasma testing was associated with a higher odds of availability of results before 1L therapy. These findings warrant renewed attention to the completion of molecular genotyping before 1L therapy.