bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling
Authors: Liu Xiao , Guo Qingdong , Gao Guangxun , Cao Zhengcong , Guan Zhihao , Jia Bo , Wang Weizhong , Zhang Kuo , Zhang Wangqian , Wang Shuning , Li Weina , Hao Qiang , Zhang Yingqi , Li Meng , Zhang Wei , Gu Jintao 
Published: February 2023

AbstractAlthough temozolomide (TMZ) provides significant clinical benefit for glioblastoma (GBM), responses are limited by the emergence of acquired resistance. Here, we demonstrate that exosomal circCABIN1 secreted from TMZ-resistant cells was packaged into exosomes and then disseminated TMZ resistance of receipt cells. CircCABIN1 could be cyclized by eukaryotic translation initiation factor 4A3 (EIF4A3) and is highly expressed in GBM tissues and glioma stem cells (GSCs). CircCABIN1 is required for the self-renewal maintenance of GSCs to initiate acquired resistance. Mechanistically, circCABIN1 regulated the expression of olfactomedin-like 3 (OLFML3) by sponging miR-637. Moreover, upregulation of OLFML3 activating the ErbB signaling pathway and ultimately contributing to stemness reprogramming and TMZ resistance. Treatment of GBM orthotopic mice xenografts with engineered exosomes targeting circCABIN1 and OLFML3 provided prominent targetability and had significantly improved antitumor activity of TMZ. In summary, our work proposed a novel mechanism for drug resistance transmission in GBM and provided evidence that engineered exosomes are a promising clinical tool for cancer prevention and therapy.
Graphical Abstract
Prevalence and predictors of workplace violence against emergency physicians in China: a cross-sectional study
Authors: Yan Shijiao , Feng Jing , Gan Yong , Wang Rixing , Song Xingyue , Luo Zhiqian , Han Xiaotong , Lv Chuanzhu 
Published: February 2023

AbstractBackgroundWorkplace violence (WPV) is considered a global problem, particularly in the health sector; however, no studies have assessed the national prevalence of WPV against emergency physicians and the associated factors in China.MethodsA national cross-sectional survey was conducted in 31 provinces/autonomous regions/municipalities across China between July 2019 and September 2019. A total of 15 455 emergency physicians were selected using a multistage stratified random sampling method. A structured self-administered questionnaire was used to collect information on WPV and potential associated factors among emergency physicians. Descriptive and multivariable logistic regression analyses were used to identify the predictors of WPV.ResultsA total of 14 848 emergency physicians responded effectively (effective response rate: 96.07%). Of the respondents, 90.40%, 51.45%, and 90.00% reported exposure to any type of WPV, physical or nonphysical violence in the preceding year, respectively. Verbal aggression (87.25%) was the most common form of violence, followed by threat (71.09%), physical assault (48.24%), verbal sexual harassment (38.13%), and sexual assault (19.37%). Patients’ families were the main perpetrators of these incidents. Unmet patient needs, taking drugs or drinking, and long waiting times were the main contributors to WPV. Physicians who were from low-developed regions, female, and without shift work were less likely to have experienced any type of WPV. Chinese emergency physicians who were from medium-developed regions, had a bachelor’s degree, worked in a higher level hospital, had a higher professional title, with lower incomes, had a history of hypertension or coronary heart disease, were smokers or drinkers, and worked in hospitals without preventive measures or training for WPV and not encouraging to report WPV were more likely to have experienced any type of WPV. The predictors of WPV varied in different types of WPV.ConclusionsThis study shows that the prevalence of WPV against emergency physicians is high in China. Measures should be taken at the physicians, patients, hospital, and national levels to protect GPs from WPV; for example, improving physicians’ level of service and hospital’ reporting procedures. Creating a prevention strategy and providing a safer workplace environment for emergency physicians should be prioritized.
Economic costs, health-related quality of life outcomes and cost-utility of a physical and psychological group intervention targeted at older adults with neurogenic claudication
Authors: Maredza Mandy , Khan Kamran , Marian Ioana R. , Dutton Susan J. , Williamson Esther , Lamb Sarah E. , Petrou Stavros 
Published: February 2023

Abstract
Background
Emerging evidence suggests that structured and progressive exercise underpinned by a cognitive behavioural approach can improve functional outcomes in patients with neurogenic claudication (NC). However, evidence surrounding its economic benefits is lacking.

Objectives
To estimate the economic costs, health-related quality of life outcomes and cost-effectiveness of a physical and psychological group intervention (BOOST programme) versus best practice advice (BPA) in older adults with NC.

Methods
An economic evaluation was conducted based on data from a pragmatic, multicentre, superiority, randomised controlled trial. The base-case economic evaluation took the form of an intention-to-treat analysis conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective and separately from a societal perspective. Costs (£ 2018–2019 prices) were collected prospectively over a 12 month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit (INMB) of the BOOST programme in comparison to BPA. Sensitivity and pre-specified subgroup analyses explored uncertainty and heterogeneity in cost-effectiveness estimates.

Results
Participants (N = 435) were randomised to the BOOST programme (n = 292) or BPA (n = 143). Mean (standard error [SE]) NHS and PSS costs over 12 months were £1,974 (£118) in the BOOST arm versus £1,827 (£169) in the BPA arm (p = 0.474). Mean (SE) QALY estimates were 0.620 (0.009) versus 0.599 (0.006), respectively (p = 0.093). The probability that the BOOST programme is cost-effective ranged between 67 and 83% (NHS and PSS perspective) and 79–89% (societal perspective) at cost-effectiveness thresholds between £15,000 and £30,000 per QALY gained. INMBs ranged between £145 and £464 at similar cost-effectiveness thresholds. The cost-effectiveness results remained robust to sensitivity analyses.

Conclusions
The BOOST programme resulted in modest QALY gains over the 12 month follow-up period. Future studies with longer intervention and follow-up periods are needed to address uncertainty around the health-related quality of life impacts and cost-effectiveness of such programmes.
Trial registration This study has been registered in the International Standard Randomised Controlled Trial Number registry, reference number ISRCTN12698674. Registered on 10 November 2015.
Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker
Authors: Augustin Sebastien , Lam Marion , Lavalette Sophie , Verschueren Anna , Blond Frédéric , Forster Valérie , Przegralek Lauriane , He Zhiguo , Lewandowski Daniel , Bemelmans Alexis-Pierre , Picaud Serge , Sahel José-Alain , Mathis Thibaud , Paques Michel , Thuret Gilles , Guillonneau Xavier , Delarasse Cécile , Sennlaub Florian 
Published: February 2023

AbstractRetinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmounts, bone marrow transplantation and in vitro experiments, we show how retinal melanophages form by the transfer of melanosomes from the RPE to subretinal MPs when the “don’t eat me” signal CD47 is blocked. These melanophages give rise to hyperreflective foci in Cd47−/−-mice in vivo, and are associated with RPE dysmorphia similar to intermediate AMD. Finally, we show that Cd47 expression in human RPE declines with age and in AMD, which likely participates in melanophage formation and RPE decline. Boosting CD47 expression in AMD might protect RPE cells and delay AMD progression.
Heterogeneous effects of individual high-fat diet compositions on phenotype, metabolic outcome, and hepatic proteome signature in BL/6 male mice
Authors: Janoschek Ruth , Handwerk Marion , Hucklenbruch-Rother Eva , Schmitz Lisa , Bae-Gartz Inga , Kasper Philipp , Lackmann Jan-Wilm , Kretschmer Tobias , Vohlen Christina , Mesaros Andrea , Purrio Martin , Quaas Alexander , Dötsch Jörg , Appel Sarah 
Published: February 2023

AbstractThe multitude of obesogenic diets used in rodent studies can hardly be overviewed. Since standardization is missing and assuming that individual compositions provoke individual effects, the choice of quality, quantity and combination of diet ingredients seems to be crucial for the outcome and interpretation of obesity studies. Therefore, the present study was conducted to compare the individual effects of three commonly used obesogenic diets, mainly differing in sugar and fat content. Besides basic phenotypic and metabolic characterization, one main aspect was a comparative liver proteome analysis. As expected, the obtained results picture differentiated consequences mainly depending on fat source and/or fat- and sugar quantity. By confirming the general presumption that the choice of nutritional composition is a pivotal factor, the present findings demonstrate that a conscious selection is indispensable for obtaining reliable and sound results in obesity research. In conclusion, we strongly recommend a careful selection of the appropriate diet in advance of a new experiment, taking into account the specific research question.
Resilient phenotypes among bereaved youth: a comparison of trajectory, relative, and cross-domain approaches
Authors: Espinosa Dice Ana Lucia , Ye Xian , Kim Stephanie Gyuri , McLaughlin Katie A. , Amstadter Ananda B. , Tiemeier Henning , Denckla Christy A. 
Published: February 2023

Abstract
Background
Bereavement is a common traumatic event associated with adverse health outcomes across the life course. Despite these risks, not all bereaved individuals experience these negative effects. Limited scientific consensus exists on how to define resilience in individuals who have experienced the death of a loved one.

Methods
Using a sample of N = 3766 youth from the Avon Longitudinal Study of Parents and Children birth cohort, we identified bereavement of a family member between ages 7 and 8.5. We derived and compared three different approaches to assess resilience among bereaved youth. Trajectory-based psychological resilience identified sub-groups with similar psychological symptom profiles between ages 6 and 16 using latent growth mixture models. Relative psychological resilience at age 16 leveraged standardized residuals from a model regressing psychological symptoms on bereavement to determine better-than-expected psychological functioning relative to bereavement status. Relative cross-domain resilience around age 16 was a sum score of the residuals approach applied to eight unique domains of health. Predictive validity of each approach was assessed using depressive symptoms at age 17.5

Results
Overall, N = 877 (23%) youth were bereaved of a family member between ages 7 and 8.5. Using latent growth mixture models, a three-class solution described 84% of bereaved youth with low and stable psychological symptoms over time, 8% with worsening symptoms, and 8% with improving yet elevated symptoms. Each relative resilience score was largely concordant with the trajectory-based approach in identifying individuals as resilient or not, though relative psychological resilience demonstrated a stronger degree of concordance than the cross-domain score. Relative psychological and cross-domain resilience exhibited moderate to low correlation, depending on the domains included (r = 0.14–0.43). For each approach, resilience significantly predicted lower depressive symptoms at age 17.5, highlighting predictive validity of these measures.

Conclusions
Psychological symptom trajectories among bereaved youth aligned with those previously identified among bereaved adults. The residual-based approach to defining resilience exhibited limited utility in the context of bereavement. When identifying risk and resilience after bereavement, researchers and clinicians must address the interplay across psychosocial and physical health domains, as bereaved youth considered resilient from a mental health perspective may benefit from intervention in other domains.
Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial
Authors: Weiss Pamela F. , Sears Cora E. , Brandon Timothy G. , Forrest Christopher B. , Neu Emily , Kohlheim Melanie , Leal Jenny , Xiao Rui , Lovell Daniel 
Published: February 2023

Abstract
Background
The effectiveness of biologic therapies, primarily tumor necrosis factor inhibitors (TNFi), for children with spondyloarthritis (SpA) has made inactive disease a realistic patient outcome. However, biologic therapies are costly, primarily delivered by subcutaneous or intravenous route, and have non-trivial side effects. Many patients and families want to know if biologic medications can be discontinued after inactive disease is achieved. It remains unclear whether medication dose should remain unchanged, tapered (increase the time between doses), or discontinued once when inactive disease is attained.

Methods
The Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile SpA (BACK-OFF JSpA) trial is a multicenter pragmatic trial that will randomize 198 participants ages 8–21 years old with SpA and sustained inactive disease on standard TNFi dosing to (1) continue standard TNFi dosing, (2) fixed longer dosing intervals of TNFi, or (3) stop TNFi. The trial will compare the hazard rate of protocol-defined flare and participants’ emotional health among the 3 groups over 12 months. Innovative aspects of this trial are the involvement of patient and parent stakeholders in the design and conduct of the study as well as an electronic health record-based enhanced recruitment strategy.

Discussion
This is the first randomized pragmatic trial to assess the efficacy of TNFi de-escalation strategies in children with JSpA with sustained inactive disease. This research will improve the evidence base that patients, caregivers, and rheumatologists use to make shared decisions about continued treatment versus de-escalation of TNFi therapy in this population.

Trial registration
ClinicalTrials.gov NCT04891640. Registered on 18 May 2021.
Practical guide to the diagnostics of ruminant gastrointestinal nematodes, liver fluke and lungworm infection: interpretation and usability of results
Authors: Sabatini Gustavo Adolfo , de Almeida Borges Fernando , Claerebout Edwin , Gianechini Leonor Sicalo , Höglund Johan , Kaplan Ray Matthew , Lopes Welber Daniel Zanetti , Mitchell Sian , Rinaldi Laura , von Samson-Himmelstjerna Georg , Steffan Pedro , Woodgate Robert 
Published: February 2023

AbstractThe diagnostics of ruminant parasites remains one of the cornerstones for parasite control best practices. Field veterinarians have several techniques at their disposal (fecal egg count, coproculture, FAMACHA®, plasma pepsinogen, ELISA-Ostertagia, ELISA-Fasciola, Baermann and ELISA-Lungworm) for the identification and/or quantification of gastrointestinal nematodes, lungworms and liver fluke infecting small ruminants and cattle. Each of these diagnostic tools has its own strengths and weaknesses and is more appropriate for a specific production operation and/or age of the animal (young and adults). This review focuses on the usability and interpretation of the results of these diagnostic tools. The most advanced technical information on sampling, storage, advantages and limitations of each tool for different types of production operations and animal categories is provided.Graphical abstract
Glomerulonephritis associated with systemic sclerosis: a case report
Authors: Nayebirad Sepehr , Ramandi Alireza , Nili Fatemeh , Atef-Yekta Reza , Tamartash Zahra , Salehi Samira , Kavosi Hoda 
Published: February 2023

Abstract
Background
Systemic sclerosis is a multiorgan autoimmune disease that can overlap with other rheumatologic disorders; however, co-occurrence with antineutrophil cytoplasmic antibody-associated vasculitis is rare.

Case presentation
A 39-year-old Persian female patient with systemic sclerosis according to American College of Rheumatology/European League Against Rheumatism 2013 criteria with a disease duration of 6 years was admitted to the hospital due to a rise in creatinine level in July 2021. She had complaints of nasal speech and feeling of nasal perforation. The first symptoms of antineutrophil cytoplasmic antibody-associated vasculitis had started 5 years earlier with palpable purpura in the lower limbs, hemoptysis, and positive perinuclear (p)-antibody-associated vasculitis level (> 300 AU/mL). Still, the diagnosis was not achieved due to the patient's reluctance to undergo a biopsy. She was treated with azathioprine (150 mg/day) and prednisolone (10 mg/day) during the 5-year follow-up. Her renal biopsy results showed cortical renal tissue with a cellular crescent in more than 50% of the specimen, rupture of the Bowman capsule and the glomerular basement membrane, peri-glomerular inflammation, and mild tubular atrophy in microscopic examinations. The immunofluorescence study resulted in a granular pattern of immune deposits along the glomerular basement membrane, mesangial tissue, and tubular basement membranes.

Conclusion
We reported a rare case of comorbid systemic sclerosis and antineutrophil cytoplasmic antibody-associated vasculitis with nasal perforation. Her renal biopsy showed immune deposits along the glomerular basement membrane, mesangial tissue, and tubular basement membranes. Overlapping with other collagen vascular diseases can occur in rheumatology patients with uncommon manifestations. In systemic sclerosis, renal involvement in the form of glomerulonephritis is infrequent, and comorbid systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis should be considered.
Cost-effectiveness of 82-Rubidium PET myocardial perfusion imaging for the diagnosis of myocardial ischemia depending on the prevalence of coronary artery disease
Authors: Mimouni Maroua , Bulsei Julie , Darlington Meryl , Estellat Candice , Rouzet François , Hyafil Fabien , Durand-Zaleski Isabelle ,   the RUBIS Trial Group, Chequer Renata , Ducrocq Gregory , Alfaiate Toni , Regaieg Hamza , Abtan Jérémie , Leygnac Sébastien , Milliner Milan , Burg Samuel , Azzouna Rana Ben , Potier Louis , Laouénan Cédric , Quintin Caroline , Roussel Ronan , Steg Gabriel , Le Guludec Dominique , Sorbets Emmanuel , Imbert Laetitia , Marie Pierre-Yves , Hartemann Agnès , Montalescot Gilles 
Published: February 2023

Abstract
Background
82-Rubidium-Positron emission tomography myocardial perfusion imaging (Rb-PET-MPI) offers higher diagnostic performance for the detection of myocardial ischemia compared to Tc-SPECT-MPI. The aim of this economic evaluation was to perform a cost-effectiveness analysis of Rb-PET-MPI versus Tc-SPECT-MPI in patients with suspected myocardial ischemia according to pretest probabilities (PTP) of obstructive coronary artery disease based on the results of the RUBIS Trial.

Methods
Costs and effectiveness were calculated for all patients over 1 year and an incremental analysis of differences in costs and effectiveness in terms of diagnostic accuracy was performed. The uncertainty of the results was estimated using bootstrap. The analysis was conducted from the perspective of the French health care system with a time horizon of 12 months.

Results
The average cost of a Rb-PET-MPI-based strategy for the detection of myocardial ischemia was €219 lower than a SPECT-MPI-based strategy (€1192 (± 1834) vs €973 (± 1939), p < 0.01). The one-year incremental cost-effectiveness ratio was negative: − €2730 (money saved per additional accurate diagnosis) in patients presenting PTP > 15% for the Rb-PET-MPI vs. Tc-SPECT-MPI strategy. Analysis of the joint distribution of costs and outcomes found that the Rb-PET-MPI strategy had a 92% probability to be dominant (cost-saving and outcome-improving).

Conclusions
Rb-PET-MPI is cost-effective compared to Tc-SPECT-MPI for the detection of myocardial ischemia in patients with PTP > 15% of obstructive coronary artery disease.

Trial registration

RUBIS Trial registration: NCT01679886, Registered 03 September 2012, https://clinicaltrials.gov/ct2/show/NCT01679886.
Retinal determination gene networks: from biological functions to therapeutic strategies
Authors: Zhu Shuangli , Li Wanling , Zhang Hao , Yan Yuheng , Mei Qi , Wu Kongming 
Published: February 2023

AbstractThe retinal determinant gene network (RDGN), originally discovered as a critical determinator inDrosophilaeye specification, has become an important regulatory network in tumorigenesis and progression, as well as organogenesis. This network is not only associated with malignant biological behaviors of tumors, such as proliferation, and invasion, but also regulates the development of multiple mammalian organs. Three members of this conservative network have been extensively investigated, including DACH, SIX, and EYA. Dysregulated RDGN signaling is associated with the initiation and progression of tumors. In recent years, it has been found that the members of this network can be used as prognostic markers for cancer patients. Moreover, they are considered to be potential therapeutic targets for cancer. Here, we summarize the research progress of RDGN members from biological functions to signaling transduction, especially emphasizing their effects on tumors. Additionally, we discuss the roles of RDGN members in the development of organs and tissue as well as their correlations with the pathogenesis of chronic kidney disease and coronary heart disease. By summarizing the roles of RDGN members in human diseases, we hope to promote future investigations into RDGN and provide potential therapeutic strategies for patients.