bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of Dual Hypothermic Oxygenated Machine Perfusion Versus Static Cold Storage in DCD Liver Transplantation
Authors: Endo Chikako , van Rijn Rianne , Huurman Volkert , Schurink Ivo , van den Berg Aad , Murad Sarwa Darwish , van Hoek Bart , de Meijer Vincent E. , de Jonge Jeroen , van der Hilst Christian S. , Porte Robert J. 
Published: October 2024

Background.
Ex situ machine perfusion of the donor liver, such as dual hypothermic oxygenated machine perfusion (DHOPE), is increasingly used in liver transplantation. Although DHOPE reduces ischemia/reperfusion-related complications after liver transplantation, data on cost-effectiveness are lacking. Our objective was to evaluate the cost-effectiveness of DHOPE in donation after circulatory death (DCD) liver transplantation.

Methods.
We performed an economic evaluation of DHOPE versus static cold storage (SCS) based on a multicenter randomized controlled trial in DCD liver transplantation (DHOPE-DCD trial; ClinicalTrials.gov number, NCT02584283). All patients enrolled in the 3 participating centers in the Netherlands were included. Costs related to the transplant procedure, hospital stay, readmissions, and outpatients treatments up to 1 y posttransplant were calculated. The cost for machine perfusion was calculated using 3 scenarios: (1) costs for machine perfusion, (2) machine perfusion costs plus costs for personnel, and (3) scenario 2 plus depreciation expenses for a dedicated organ perfusion room.

Results.
Of 119 patients, 60 received a liver after DHOPE and 59 received a liver after SCS alone. The mean total cost per patient up to 1 y posttransplant was €126 221 for the SCS group and €110 794 for the DHOPE group. The most significant reduction occurred in intensive care costs (28.4%), followed by nonsurgical interventions (24.3%). In cost scenario 1, DHOPE was cost-effective after 1 procedure. In scenarios 2 and 3, cost-effectiveness was achieved after 25 and 30 procedures per year, respectively.

Conclusions.
Compared with conventional SCS, machine perfusion using DHOPE is cost-effective in DCD liver transplantation, reducing the total medical costs up to 1 y posttransplant.
Robotic Repair of Ureteral Strictures After Kidney Transplantation
Authors: Sanz-Serra Pol , Etcheverry Begoña , Fiol Maria , Fábregas Maya , Lozano Víctor , Pérez-Reggeti José Ignacio , Buisan Óscar , Riera Lluís , Suárez José Francisco , Castells Manel , Vigués Francesc 
Published: October 2024

Background.
Approximately 5% to 10% of patients who undergo kidney transplantation develop ureteral stricture, which can be treated endoscopically or by open surgery, which is more effective but complications are common and potentially severe. Robotic surgery has begun to emerge as an alternative in reconstructive procedures. However, few studies have evaluated the role of robotic surgery in this clinical setting. The aim of this study was to assess the efficacy and safety of robotic surgery in treating ureteral stricture after kidney transplantation.

Methods.
Single-center study of patients (n = 27), who developed ureteral stricture following kidney transplantation. All patients were treated from 2018 to 2023. We describe the patients’ baseline characteristics and clinical and surgical features. We determined the success rate as a measure of efficacy and complications to measure safety.

Results.
We perform 15 pyeloureterostomies to the native ureter and 12 ureteroneocystostomies. At a median follow-up of 15 mo, the success rate was 92.6%. Fourteen patients (52%) developed treatment-related complications, mainly grade II (Clavien-Dindo classification), except for one grade IVb complication. The median length of hospital stay was 3 d [interquartile range (2–6)].

Conclusions.
These data show that robotic surgery is a safe and effective procedure for the treatment of ureteral strictures after kidney transplantation. The success rate was high with a low complication rate. To our knowledge, this is the largest series to date to evaluate robotic surgery in this clinical setting.
A systematic review to explore factors affecting participation in health research trials amongst underrepresented socio-economically disadvantaged populations in the UK and Ireland
Authors: Brandon Jakki , Bagnall Anne Marie 
Published: October 2024

AbstractBackgroundThose with the greatest health inequalities and highest burden of poor-health have the lowest representation in health research. Meaning that diseases which are known to have higher prevalence in disadvantaged populations are being studied in healthier populations, so findings will be inappropriately applied to those that face the greatest challenges to their health. This systematic review is concerned with those defined as socioeconomic-deprived, gypsy/traveller/Roma communities, and homeless people.ObjectivesTo understand the barriers or facilitators to research participation in specific underserved groups to inform how equality, diversity and inclusion in research trials can be improved.MethodsA systematic review of etiology of quantitative and qualitative primary research conducted in the UK and Ireland in the previous 10 years, to produce a narrative synthesis of the themes identified.ResultsKey themes of barriers and facilitators were identified across the groups. All facilitators reported were common to all the groups. The value of peer-researchers, gatekeepers, community relationships and participatory approaches was a prominent feature within the facilitators. Reporting of barriers overall was lower, with fewer commonalities seen across the groups. The SE deprived group had the fewest barriers reported.ConclusionThe lack of identified barriers suggests that more work should be done to learn what these may be for specific groups, particularly in the SE deprived group. It seems likely that barriers exist in this group. The fact that these were not reported may indicate lack of reach to the most deprived sections of this population. Therefore, more research needs to be done to fully explore the barriers in the most deprived groups. By developing engagement approaches in a way which is tailored to separate underserved groups this will address barriers and help to shape the future of research.
The G3BP Stress-Granule Proteins Reinforce the Translation Program of the Integrated Stress Response
Authors: Smith Jarrett , Bartel David P. 
Published: October 2024

ABSTRACTWhen mammalian cells are exposed to extracellular stress, they coordinate the condensation of stress granules (SGs) through the action of key nucleating proteins G3BP1 and G3BP2 (G3BPs) and, simultaneously, undergo a massive reduction in translation.1–5Although SGs and G3BPs have been linked to this translation response, their overall impact has been unclear. Here, we investigate the longstanding question of how, and indeed whether, G3BPs and SGs shape the stress translation response. We find that SGs are enriched for mRNAs that are resistant to the stress-induced translation shutdown. Although the accurate recruitment of these stress-resistant mRNAs does require the context of stress, a combination of optogenetic tools and spike-normalized ribosome profiling demonstrates that G3BPs and SGs are necessary and sufficient to both help prioritize the translation of their enriched mRNAs and help suppress cytosolic translation. Together these results support a model in which G3BPs and SGs reinforce the stress translation program by prioritizing the translation of their resident mRNAs.
Kidney Dialysis Service: Experiences of Consumer and Provider and Quality of Life of End Stage Kidney Disease Patients in Parbat, Nepal
Authors: Dhakal Mamta , Sharma Prabin , P.C. Anjali , Sharma Suman 
Published: October 2024

AbstractBackground/ObjectivesThe kidney dialysis patients and service providers possess a wide range of experience relating to the service, and quality of life is an important measure to evaluate holistic approach to chronic disease management such as kidney disease. This study was conducted to find out the experience of kidney dialysis patients and service providers and quality of life of end stage kidney disease patients.MethodsA qualitative study was conducted, from March 2024 to August 2024, among 20 end stage kidney disease patients visiting Parbat hospital for dialysis and 7 dialysis service providers, doctor and nurses, using in-depth interview guidelines, kidney disease quality of life-36 instrument (for end stage kidney disease patients) and job satisfaction survey tool (for service providers). Thematic analysis was performed from the transcribed and translated recorded information to carry out the actual theme.ResultNine (9) themes were extracted for experiences of kidney dialysis patients. They were (i) perception on end-stage kidney disease, (ii) perception on free kidney dialysis service at the hospital, (iii) administrative process for free dialysis service, (iv) feasibility with the schedules of dialysis session, (v) quality of care and response of service providers (vi) duration of dialysis session (vii) desires and challenges towards kidney transplantation, (viii) on recommending the dialysis site and (ix) further expectations for improvement. The quality of life of end-stage kidney disease patients was found to be moderate. Similarly, nine (9) themes were extracted for experiences of service providers. They were (i) patient personalized care and understanding patients’ behavior (ii) addressing queries and concerns of the patients (iii) rewarding aspect of the job (iv) learning acceptance and witnessing positivity (v) availability of safety measures and protective protocols (vi) training and professional development experience (vii) reflection on job security (viii) challenging aspect of the job (ix) further expectations and requests. The kidney dialysis service providers were found to be ambivalent, neither satisfied nor dissatisfied with the job.ConclusionPatients share an overall good experience of free kidney dialysis service at Parbat hospital while the service providers also have a positive experience working in the dialysis section. However, expectations for provision of free medications and availability of nephrologist by the end stage kidney disease patients direct towards the reforms for improved service delivery. The doctor and nurses should be provided with more opportunities for professional development and safety should be a priority. These respective vigilance and actions for, shall address the quality of life and job satisfaction as well.
C-Reactive Protein Drives Potent Clearance of Blood Bacteria in the Liver by Activating the Complement System
Authors: Chen Danyu , Hu Jiao , Zhu Mengran , Xie Yufeng , Yao Hantian , An Haoran , Meng Yumin , Wang Juanjuan , Huang Xueting , Shao Zhujun , Xiang Ye , Qi Jianxun , Gao George Fu , Zhang Jing-Ren 
Published: October 2024

ABSTRACTPlasma C-reactive protein (CRP) is widely used as a biomarker for bacterial infections due to its massive induction during infections, however, the precise function of CRP in bacterial infections remains undefined. Here we show that CRP enables Kupffer cells (liver macrophages) to capture and eliminate a wide range of encapsulated bacteria from the bloodstream of mice and thereby provides rapid and effective immunity. Mechanistically, CRP binds to the structurally diverse capsular polysaccharides of major Gram-positive and -negative pathogens, and thereby activates complement C3 at the bacterial surface. The C3-opsonized microbes are in turn captured by C3 receptors on the surface of Kupffer cells, and eliminated in the liver sinusoids. Since CRP principally shares the functional features of antibodies in pathogen recognition/execution, CRP-based defense combines the broad spectrum of the innate immunity with the swiftness, potency and specificity of the adaptive immunity, which helps explain massive rise of CRP during systemic bacterial infections.
Genetic Determinants of Bone Microarchitecture and its Association with Health Outcomes: A Genome-wide Association and Mendelian Randomization Study on Trabecular Bone Score
Authors: Guo Sijia , Zhang Jiping , Li Huiwu , Lin Guan Ning , Cheng Cheng-Kung , Zhang Jingwei 
Published: October 2024

SummaryBackgroundBone microarchitecture is a critical determinant of bone strength and fracture risk, yet its genetic basis and relationship to systemic health remain largely unexplored. This study aimed to identify genetic determinants of bone microarchitecture using trabecular bone score (TBS) and investigate the causal relationships between bone microarchitecture and various health outcomes.MethodsWe conducted a genome-wide association study (GWAS) of TBS in 25,268 UK Biobank participants to identify genetic loci associated with bone microarchitecture. Two-sample Mendelian randomization (MR) was employed to assess the causal relationships between systemic health risk factors and bone microarchitecture, as well as the impact of bone microarchitecture on musculoskeletal disorders.FindingsThe GWAS identified 75 significant single nucleotide polymorphisms (SNPs) across 19 genomic loci, with an estimated heritability of TBS at 24.5%. Many of these loci (18/19) were also associated with bone mineral density (BMD) and fractures, indicating a shared genetic basis for bone microarchitecture and bone mass. MR analysis revealed that rheumatoid arthritis has a significant causal effect on the deterioration of bone microarchitecture (β = -0.003, P = 1.14×10-4). Suggestive associations were found between bone microarchitecture deterioration and inflammatory bowel disease, cardiovascular disease, and depression (P < 0.05). Moreover, genetically predicted TBS was significantly associated with fracture risk (OR = 0.003, P = 1.89×10-8) and suggestively associated with osteonecrosis (OR = 0.002, P = 0.040).InterpretationThis study identified novel genetic determinants of bone microarchitecture and demonstrated its association with various systemic diseases, highlighting the critical role of bone microarchitecture in skeletal health. The results advocate for the clinical use of TBS to better assess the risk of osteoporosis and fractures and to improve bone and overall health assessments. The causal effect of rheumatoid arthritis on microarchitectural deterioration underscores the need for increased monitoring of bone health in this population.FundingThis work supported by Shanghai "Rising Stars of Medical Talent" Youth Development Program, Youth Medical Talents-Specialist Program (grant number SHHWRS 2023-62), the Fundamental Research Funds for the Central Universities (grant number AF0820060), Outstanding Research-oriented Doctor Cultivation Program at the Ninth People’s Hospital affiliated with the School of Medicine, Shanghai Jiao Tong University, National Natural Science Foundation of China (grant number 31900941).
Plant genotype and microbial strain combinations strongly influence the transcriptome under heavy metal stress conditions
Authors: Sharma Reena , Chakraborty Sanhita , Bhat Aditi , Clear Michael , Xie Meng , Pueyo José J. , Paape Timothy 
Published: October 2024

AbstractHeavy metals such as cadmium (Cd) and mercury (Hg) pose significant threats to plant health and food safety as they are absorbed from the environment. Legumes are generally considered sensitive to heavy metals but possess standing genetic variation for accumulation and tolerance to toxic ions. We conducted a transcriptomic analysis on hydroponically and soil grownMedicago truncatulaplants to investigate gene expression responses to Cd and Hg exposure in roots, leaves, and nodules. By using plant genotypes with varying metal tolerance or accumulation levels, we observed distinct clustering of gene ontologies, indicating tissue-specific, genotype-specific, and metal-specific gene expression patterns. Considering the symbiotic relationship between legumes and nitrogen-fixing bacteria, we further examined plant phenotypes and transcriptomes of plant genotypes with contrasting Hg accumulation levels and inoculated them with high or low Hg-tolerantSinorhizobium medicaestrains that have presence-absence variation for a mercury reductase (Mer) operon. Host plants inoculated with the Hg-tolerant rhizobia strain possessing a Mer operon exhibited less reduction in nodule number and plant biomass. A smaller reduction in iron (Fe) distribution in nodules after Hg stress was measured using X-ray Fluorescence (XRF) imaging. Dual transcriptome (host plant and bacteria) analysis of nodules revealed a remarkable decrease in the number of differentially expressed genes (DEGs) and clustering of gene ontologies in plants inoculated with the Hg-tolerant rhizobia strain, including symbiosis related genes. This suggests the Hg-tolerant rhizobia strain has the potential to mitigate Hg stress in host plants. Furthermore, we observed genotype-by-genotype interactions between the high Hg accumulating plant genotype and the Hg-tolerant rhizobia strain. These findings provide insights into enhancing plant resilience in contaminated environments through optimizing legume-rhizobia interactions for heavy metal tolerance, as well as identification of genetic mechanisms that can reduce transport to edible plant parts.HighlightsGenetic variation in tolerance to heavy metals affects responses in plant tissuesSymbiosis with Hg tolerant rhizobia strain reduced stress response in host plantDual-transcriptomics in nodules identified metal stress and symbiosis responsesGenotype by genotype interaction significantly affected symbiosis gene expressionRhizobia strain possessing Mer operon suggests genetic basis affecting responses
A Novel Dataset for Nuclei and Tissue Segmentation in Melanoma with baseline nuclei segmentation and tissue segmentation benchmarks
Authors: Schuiveling Mark , Liu Hong , Eek Daniel , Breimer Gerben E. , Suijkerbuijk Karijn P.M. , Blokx Willeke A.M. , Veta Mitko 
Published: October 2024

AbstractBackgroundMelanoma is an aggressive form of skin cancer in which tumor-infiltrating lymphocytes (TILs) are a biomarker for recurrence and treatment response. Manual TIL assessment is prone to interobserver variability, and current deep learning models are not publicly accessible or have low performance. Deep learning models, however, have the potential of consistent spatial evaluation of TILs and other immune cell subsets with the potential of improved prognostic and predictive value. To make the development of these models possible, we created the Panoptic Segmentation of nUclei and tissue in advanced MelanomA (PUMA) dataset and assessed the performance of several state-of-the-art deep learning models. In addition, we show how to improve model performance further by using heuristic post-processing in which nuclei classes are updated based on their tissue localization.ResultsThe PUMA dataset includes 155 primary and 155 metastatic melanoma H&E stained regions of interest with nuclei and tissue annotations from a single melanoma referral institution. The Hover-NeXt model, trained on the PUMA dataset, demonstrated the best performance for lymphocyte detection, approaching human interobserver agreement. In addition, heuristic post-processing of deep learning models improve the detection of non-common classes, such as epithelial nuclei.ConclusionThe PUMA dataset is the first melanoma specific dataset that can be used to develop melanoma-specific nuclei and tissue segmentation models. These models can, in turn, be used for prognostic and predictive biomarker development. Incorporating tissue and nuclei segmentation is a step towards improved deep learning nuclei segmentation performance. We will use this dataset to organize the PUMA challenge in which the goal is to further improve model performance.
Frontline maintenance olaparib therapy for BRCA/HRD-positive advanced epithelial ovarian cancer: real-world data analysis in matched population
Authors: Rumyantsev Alexey A. , Glazkova Elena V. , Tikhomirova Tatiana E. , Pokataev Ilya A. , Ignatova Ekaterina O. , Knyazev Rostislav I. , Tyulyandina Alexandra S. , Tjulandin Sergey A. 
Published: October 2024

AbstractBackgroundintroduction of the poly(ADP-ribose) polymerase (PARP) inhibitors to clinical practice remarkably improved outcomes for advanced epithelial ovarian cancer (EOC) patients. We conducted this study to evaluate efficacy of frontline maintenance olaparib therapy in BRCA-mutated and/or HRD-positive EOC patients in real-world practice setting.Patients and methodswe enrolled patients with FIGO stage III-IV high-grade serous or endometrioid EOC with BRCA1/2 mutations and/or HRD-positive status with complete or partial response to frontline therapy, who were treated in 2014-2024. Main objective of this trial was to compare progression-free survival (PFS) of HRD+/BRCA-mutant advanced EOC patients treated with or without maintenance olaparib in well-balanced treatment arms. Cardinality matching was considered to ensure balancing of the study arms with 1:1 ratio of patients in trial arms. The groups were balanced according to the presence of residual tumor after initial treatment, platinum-free interval duration after frontline therapy, secondary local therapy for recurrent disease, treatment with platinum drugs for relapse and subsequent bevacizumab. The primary endpoint of the study was PFS.Resultscardinality matching with 1:1 ratio resulted in 282 matched patients for the analysis. Groups were well balanced in all baseline characteristics. Median age in both treatment arms was 50 years with no differences in patients’ age, surgical outcomes, prevalence of BRCA-mutated or HRD-positive disease and response to initial platinum-based therapy. With a median follow up of 37.2 mo. median PFS was 38.0 in the olaparib arm and 13.7 mo. in the control arm, respectively (HR 0.32; 95% CI 0.23-0.43; p<0.001). Estimated 3-year PFS was 50.9% and 11.5%, respectively. Median PFS2 was 49.5 mo. in the olaparib arm compared to 34.3 mo. in the control arm (HR 0.58; 95% CI 0.39-0.85; p=0.005).Conclusionthis study confirms the benefits of olaparib maintenance therapy in patients with HRD- -positive and/or BRCA-mutated advanced EOC in real-world setting.HighlightsUsing cardinality matching two cohorts of patients after frontline therapy were made (treated with maintenance olaparib vs not);Median PFS was 38.0 in the olaparib arm and 13.7 mo. in the control arm, respectively (HR 0.32; 95% CI 0.23-0.43; p<0.001);This data confirms efficacy of maintenance olaparib for BRCA/HRD-positive advanced epithelial ovarian cancer in routine clinical practice.
Estimated dietary intakes of vitamin A5
Authors: Bohn Torsten , Despotovic Marta , Vahid Farhad , Rühl Ralph 
Published: October 2024

AbstractA new vitamin concept, termed vitamin A5, was recently identified. Furthermore, dietary recommendations in the range of 1,1 (0,5 – 1,8) mg vitamin A5 / day were suggested by an international expert consortium. The ensuing question arises as to the current daily dietary intake amounts in the Western civilization. Addressing this answer included calculating the intake based on known amounts of vitamin A5 in frequently consumed food items of the human diet high in this vitamin as well as the known daily dietary intake amounts of those selected food components in Westernized countries. Regarding food items, amounts of vitamin A5 in the form of provitamin A5 (i.e. 9-cis-beta-carotene (9CBC)), the predominant form in the diet, were found to range from 0,1 to 39 µg 9CBC / g for individual fruits and vegetables, with highest concentrations in leafy vegetables. The average intake amounts of vitamin A5 in adults of the general population following a Western lifestyle in Europe, averaged 0,9 with a range of 0,5 (for Austria) – 1,3 (for Italy) mg 9CBC / day. Furthermore, based on our calculations, large parts, i.e. ∼ 2/3rd of the population are low, even too low (<1.1 mg/day), in daily vitamin A5 intake. In addition to the importance of nudging the population towards a regrettably non-well accepted higher intake of fruits and vegetables, an additional fortification and supplementation of vitamin A5 could be considered, similar as to other micronutrients that are low a Westernized diet.