bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliative care national plan implementation through stakeholder analysis
Authors: Antonio Sánchez-Cárdenas Miguel , Ximena León-Delgado Marta , María Vargas-Escobar Lina , Elizabeth Muñoz Medina Sofia , Milena Buitrago Florian Paula , Andrade Fonseca David , Esteban Correa-Morales Juan 
Published: July 2024

Abstract
Background
National palliative care plans depend upon stakeholder engagement to succeed. Assessing the capability, interest, and knowledge of stakeholders is a crucial step in the implementation of public health initiatives, as recommended by the World Health Organisation. However, utilising stakeholder analysis is a strategy underused in public palliative care.

Objective
To conduct a stakeholder analysis characterising a diverse group of stakeholders involved in implementing a national palliative care plan in three rural regions of an upper-middle-income country.

Methods
A descriptive cross-sectional study design, complemented by a quantitative stakeholder analysis approach, was executed through a survey designed to gauge stakeholders’ levels of interest and capability in relation to five fundamental dimensions of public palliative care: provision of services, accessibility of essential medicines, palliative care education, financial support, and palliative care vitality. Stakeholders were categorised as promoters (high-power, high-interest), latent (high-power, low-interest), advocates (low-power, high-interest), and indifferent (low-power and low-interest). Stakeholder self-perceived category and knowledge level were also assessed.

Results
Among the 65 surveyed stakeholders, 19 were categorised as promoters, 34 as advocates, 9 as latent, and 3 as indifferent. Stakeholders’ self-perception of their category did not align with the results of the quantitative analysis. When evaluated by region and palliative care dimensions the distribution of stakeholders was nonuniform. Palliative care funding was the dimension with the highest number of stakeholders categorised as indifferent, and the lowest percentage of promoters. Stakeholders categorised as promoters consistently reported a low level of knowledge, regardless of the dimension, region, or their level of interest.

Conclusions
Assessing the capability, interest, and knowledge of stakeholders is a crucial step when implementing public health initiatives in palliative care. It allows for a data-driven decision-making process on how to delegate responsibilities, administer financial resources, and establish governance boards that remain engaged and work efficiently.
Pseudomonas aeruginosa infection correlates with high MFI donor-specific antibody development following lung transplantation with consequential graft loss and shortened CLAD-free survival
Authors: Bogyó Levente Zoltán , Török Klára , Illés Zsuzsanna , Szilvási Anikó , Székely Bálint , Bohács Anikó , Pipek Orsolya , Madurka Ildikó , Megyesfalvi Zsolt , Rényi-Vámos Ferenc , Döme Balázs , Bogos Krisztina , Gieszer Balázs , Bakos Eszter 
Published: July 2024

Abstract
Background
Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes.

Methods
A cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens.

Results
High MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival.

Conclusions
P. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.
Targeting of 3D oral cancer spheroids by αVβ6 integrin using near-infrared peptide-conjugated IRDye 680
Authors: Dirheimer L. , Pons T. , François A. , Lamy L. , Cortese S. , Marchal F. , Bezdetnaya L. 
Published: July 2024

Abstract
Background
In the treatment of oral cavity cancer, margin status is one of the most critical prognostic factors. Positive margins are associated with higher local recurrence and lower survival rates. Therefore, the universal goal of oral surgical oncology is to achieve microscopically clear margins. Near-infrared fluorescence guided surgery (FGS) could improve surgical resection using fluorescent probes. αVβ6 integrin has shown great potential for cancer targeting due to its overexpression in oral cancers. Red fluorescent contrast agent IRDye 680 coupled with anti-αVβ6 peptide (IRDye-A20) represents an asset to improve FGS of oral cancer. This study investigates the potential of IRDye-A20 as a selective imaging agent in 3D three-dimensional tongue cancer cells.

Methods
αVβ6 integrin expression was evaluated by RT-qPCR and Western Blotting in 2D HSC-3 human tongue cancer cells and MRC-5 human fibroblasts. Targeting ability of IRDye-A20 was studied in both cell lines by flow cytometry technique. 3D tumor spheroid models, homotypic (HSC-3) and stroma-enriched heterotypic (HSC-3/MRC-5) spheroids were produced by liquid overlay procedure and further characterized using (immuno)histological and fluorescence-based techniques. IRDye-A20 selectivity was evaluated in each type of spheroids and each cell population.

Results
αVβ6 integrin was overexpressed in 2D HSC-3 cancer cells but not in MRC-5 fibroblasts and consistently, only HSC-3 were labelled with IRDye-A20. Round shaped spheroids with an average diameter of 400 μm were produced with a final ratio of 55%/45% between HSC-3 and MRC-5 cells, respectively. Immunofluorescence experiments demonstrated an uniform expression of αVβ6 integrin in homotypic spheroid, while its expression was restricted to cancer cells only in heterotypic spheroid. In stroma-enriched 3D model, Cytokeratin 19 and E-cadherin were expressed only by cancer cells while vimentin and fibronectin were expressed by fibroblasts. Using flow cytometry, we demonstrated that IRDye-A20 labeled the whole homotypic spheroid, while in the heterotypic model all cancer cells were highly fluorescent, with a negligible fluorescence in fibroblasts.

Conclusions
The present study demonstrated an efficient selective targeting of A20FMDV2-conjugated IRDye 680 in 3D tongue cancer cells stroma-enriched spheroids. Thus, IRDye-A20 could be a promising candidate for the future development of the fluorescence-guided surgery of oral cancers.

Graphical Abstract
Role of plasma fatty acid in age-related macular degeneration: insights from a mendelian randomization analysis
Authors: Han Guoge , Wei Pinghui , He Meiqin , Jia Lanbo , Su Qi , Yang Xiru , Hao Rui 
Published: July 2024

Abstract
Background
An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes.

Methods
We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides.

Results
Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66–0.92) and dry AMD (0.85, 0.74–0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03–1.56) and dry AMD (1.18, 1.02–1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82–0.98; FADS2, 0.88, 0.81–0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02–1.20; FADS2, 1.11, 1.03–1.20) suggests causal effects of these factors on wet AMD.

Conclusions
The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.
Long-term outcomes of TEVAR for thoracic aortic diseases: a retrospective single-center study
Authors: Deniz Gokay , Kasımzade Ferit , Ozcınar Evren , Yazicioglu Levent , Eryılmaz Sadik 
Published: July 2024

Abstract
Background
The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive endovascular experience, focusing on exploring the outcome in long term follow-up.

Methods
From 2006 to 2018, we conducted TEVAR on 97 patients presenting with various aortic pathologies. This retrospective cohort study was designed primarily to assess graft durability and secondarily to evaluate mortality causes, complications, reinterventions, and the impact of comorbidities on survival using Kaplan-Meier and Cox regression analyses.

Results
The most common indication was thoracic aortic aneurysm (n = 52). Ten patients had aortic arch variations and anomalies, and the bovine arch was observed in eight patients. Endoleaks were the main complications encountered, and 10 of 15 endoleaks were type I endoleaks. There were 18 reinterventions; the most of which was TEVAR (n = 5). The overall mortality was 20 patients, with TEVAR-related causes accounting for 12 of these deaths, including intracranial bleeding in three patients. Multivariant Cox regression revealed chronic renal diseases (OR = 11.73; 95% CI: 2.04–67.2; p = 0.006), previous cardiac operation (OR = 14.26; 95% CI: 1.59-127.36; p = 0.01), and chronic obstructive pulmonary diseases (OR = 7.82; 95% CI: 1.43–42.78; p = 0.001) to be independent risk factors for 10-year survival. There was no significant difference in the survival curves of the various aortic pathologies. In the follow-up period, two non-symptomatic intragraft thromboses and one graft infection were found.

Conclusion
Comorbidities can increase the risk of TEVAR-related mortality without significantly impacting endoleak rates. TEVAR is effective for severe aortic pathologies, though long-term graft durability may be compromised by its thrombosis and infection.
Striving for the perfect diet? The mediating role of perfectionism in the relationship between obsessive compulsive symptoms and traits of Orthorexia Nervosa
Authors: Greville-Harris Maddy , Vuillier Laura , Goodall Summer , Talbot Catherine V. , Walker Cliona , Appleton Katherine M. 
Published: July 2024

Abstract
Background
Orthorexia Nervosa (ON) is a disordered eating style involving an unhealthy obsession with ‘healthy’ or ‘clean’ eating. Its aetiology is still poorly understood and is not yet recognised in diagnostic manuals. While ON has been associated with Obsessive Compulsive (OC) symptoms and perfectionism, no study to date has looked at the relationship between OC symptoms and ON tendencies via perfectionism, or the influence of two facets of perfectionism in this relationship, namely evaluative concern and achievement striving. Examining the potential role of perfectionism helps to understand the aetiology of ON as well as inform potential treatments tailored specifically for ON and comorbid OC symptoms.

Methods
In this cross sectional study, we tested 507 participants (n = 70 males, n = 69 at risk of ON) on questionnaires measuring OC symptoms, perfectionism and ON symptoms. We ran two mediation analyses to look at the overall relationship between perfectionism and OC and ON symptoms (Model 1) as well as the specific contribution of evaluative concern and achievement striving in the relationship between OC and ON symptoms (Model 2).

Results
We found that perfectionism partially mediated the relationship between OC and ON symptoms. Specifically, we found that while achievement striving and evaluative concern were associated with OC symptoms, only achievement striving was significantly associated with ON symptoms, mediating the relationship between OC and ON symptoms.

Conclusions
This study highlighted the role of one key facet of perfectionism (achievement striving) in the aetiology of ON. The role of achievement striving was indicated as a transdiagnostic construct explaining the link between ON and OC symptoms. These findings are discussed in terms of their implications for treatment models, specifically in terms of the potential role of targeting perfectionism in ON treatment.
Association of baseline inflammatory biomarkers and clinical outcomes in patients with advanced renal cell carcinoma (aRCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Yildirim Ahmet , Wei Mengting , Liu Yuan , Goswamy Rohit Vivek , Choi Yujin , Brown Jacqueline T , Nazha Bassel , Martini Dylan J. , Hartman Caitlin , McClintock Greta Russler , Zhuang Tony , Kissick Haydn , Harris Wayne B. , Carthon Bradley Curtis , Kucuk Omer , Master Viraj A. , Bilen Mehmet Asim 
Published: July 2024

4548 Background: Multiple inflammatory biomarkers such as modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), and neutrophil to eosinophil ratio (NER) have been identified in RCC. We analyzed those biomarkers in patients with aRCC treated with ICIs to assess the association with treatment outcomes. Methods: A retrospective analysis was conducted on adult patients with aRCC treated with ICIs at Emory Winship Cancer Institute between 2018 and 2023. Clinical benefit (CB) is determined by stable disease, partial response, and complete response. mGPS (combining albumin and CRP), NLR, MLR, PLR, and NER data were collected from the baseline bloodwork. Multivariate and univariate analyses were conducted on PFS, OS, and CB. MVA was built by controlling the age, gender, race, BMI, smoking status, IMDC risk group, clear cell histology, prior treatment, liver metastases, ECOG performance score, and number of distant metastases, which were subject to backward elimination at the significant level of p < 0.2 Results: Our analysis included a total of 401 patients (118:283 F:M, median age: 66). On univariate analysis, high mGPS, NLR, MLR, PLR, and NER were related to inferior CB; hazard ratios (HR) (95% CI, p value) were 3.03 (1.35-6.77, p=0.005), 1.86 (1.14-3.03, p=0.013), 1.83 (1.10-3.02, p=0.019), 2.37 (1.52-3.71, p <.001), 1.93 (1.22-3.05, p=0.005) respectively. On multivariate analysis, NLR, PLR, NER had statistically significant correlation with CB, HR (95% CI) were 1.75 (1.01-3.04, p=0.047), 2.21 (1.33-3.66, p=0.002), 2.07 (1.24-3.47, p=0.006). Conclusions: The results demonstrated that high systemic inflammatory biomarkers may be related to worse clinical outcomes with ICI treatment. Prospective studies are needed for further validation. [Table: see text]
Associations of dietary fructose with survival of patients (pts) with metastatic cancer of the urothelium (UC) and renal cell carcinoma (RCC) on immune checkpoint blockade (ICB).
Authors: Badri Anas , Guercio Brendan John , Ratna Neha , Gavrilov David , Metzker Nicholina , Duzgol Cihan , Teo Min Yuen , Regazzi Ashley M. , Supplice Lauren , Funt Samuel A , Aggen David H , Voss Martin H , Carlo Marie Isabel , Shah Neil J. , Motzer Robert J. , Bajorin Dean F. , Rosenberg Jonathan E. , Lee Chung-Han , Kotecha Ritesh R , Iyer Gopa 
Published: July 2024

4571 Background: The gut microbiome is a modifiable determinant of ICB efficacy. Dietary fiber is associated with longer progression-free survival (PFS) on ICB in melanoma and UC, putatively via effects on the gut microbiome. Other dietary factors may also impact ICB efficacy. Fructose promotes adverse health effects and induces ICB resistance in pre-clinical models via upregulation of the antiapoptotic enzyme heme oxygenase-1. Thus, we set out to explore effects of fructose intake on ICB efficacy. Methods: In a retrospective analysis of a prospectively collected cohort, we leveraged dietary data collected with the validated Harvard Willett Food Frequency Questionnaire from pts with advanced UC and RCC initiating ICB at Memorial Sloan Kettering to assess for associations between baseline dietary fructose and PFS and overall survival (OS). Tumor mutational burden (TMB) was estimated via MSK-IMPACT. Associations of fructose with clinical outcomes were evaluated using univariate (UV) and multivariable (MV) Cox proportional hazards regression. Fructose was normalized via log transformation and treated as a continuous variable. MV models adjusted for fiber intake and prior ICB exposure. UC models adjusted for TMB and Bellmunt risk score and RCC models for histology and IMDC score. Results: From 2/2021-6/2022, 88 eligible pts enrolled. Median follow-up was 10.2 and 17.0 months among pts with UC (n = 40) and RCC (n = 48), respectively; 32 RCC pts (67%) were IMDC intermediate/poor risk and 21 UC pts (52%) had visceral metastases. High fructose and fiber intake correlated (rho 0.66). Among UC pts, higher fructose was associated with shorter PFS after adjusting for covariables (Table). In the MV model, high fiber was associated with longer PFS (HR 0.2, 95% CI 0.07-0.62, p = .004). Among RCC pts, fructose was not associated with PFS. Fructose was associated with OS in the RCC UV model, but this association was not statistically significant in the MV model (Table). In an exploratory model for PFS pooling all pts, a test for interaction between fructose intake and disease type (UC vs RCC) showed p = .01. Conclusions: Dietary fructose is associated with shorter PFS in UC pts treated with ICB, but not RCC pts. Discrepant results between UC and RCC require further study and may be attributable to differences in therapy or cancer biology. Our findings provide insights into potentially beneficial dietary interventions. Efforts to characterize effects of fructose on the gut microbiome are ongoing. [Table: see text]
Inferring PDL-1 status from H&E images using digital pathology to identify patients responsive to anti-PD(L)-1 immuno-oncology therapy for bladder cancer trials.
Authors: Ramon Albert Juan , Ginley Brandon , Saranadasa Madhawa , Parmar Chaitanya , Beeharry Neil , Thomas Shibu , Linghu Bolan , Greshock Joel , Standish Kristopher 
Published: July 2024

4579 Background: Programmed death ligand-1 (PDL-1) expression has been established as a biomarker for response to immune checkpoint inhibitors in bladder cancer. Targeted therapies that inhibit the PDL-1 pathway improve therapeutic response, but immunohistochemistry (IHC) testing is required to assess PDL-1 expression. In order to ease identification of patients who have high potential to respond to anti-PD(L)-1 therapies, we explore the use of a computer vision algorithm to infer PDL-1 expression from patients routine H&E images. Methods: We pretrained a Foundational Model on ~55k unlabeled WSIs from various sources (multiple scanners, hospitals, diseases, tissues..). We then finetuned it on a train set (n=1546) of PDL-1 labeled H&E images to infer expression. Labels were defined as PDL1-High or PDL1-Low based on the most sensible threshold for the various included antibodies (e.g., TPS>=10% on 22C3 antibody, CPS>=1% on 28-8 antibody, etc..). We applied this model to WSIs from 1) a holdout split (n=388) and 2) an independent dataset (n=93) to evaluate the performance at inferring PDL1-High vs. PDL1-Low, quantified by the Area Under ROC Curve (AUC). We then applied the model to a third dataset (n=27) containing WSIs from bladder cancer patients taken prior to start of anti-PD(L)-1 treatment (i.e., pembrolizumab) and evaluated treatment response (quantified by overall survival) for the two stratified groups based on the model outputs (PDL1-High vs. PDL1-Low). Results were compared to patients stratified based on IHC pathology readouts (i.e., TPS>=10% vs. TPS<10%). Results: For PD-L1 status inference, the model achieved AUC=0.82 and AUC=0.8 on holdout and independent datasets respectively. The table below shows survival analysis results upon pembrolizumab treatment (n=27) when stratifying patients based on the algorithm (AI-based PDL1-High vs. PDL1-Low) compared to IHC-based stratification. Note that the survival probability for PDL1-High patients is higher than PDL1-Low patients. Conclusions: We developed a computer vision algorithm to infer PDL-1 expression from routine H&E images. The algorithm shows strong performance at classifying PDL-1 status and proficiency in inferring outcomes to anti-PD(L)-1 therapy in a small bladder cancer data set. This tool represents a novel, rapid means to assess whether a patient may respond to anti-PD(L)-1 therapies from common H&E-stained images and has the potential to guide patient care decisions in clinic. [Table: see text]