bluuebunny/crossref_metadata_2025 huggingface dataset:
Two new species of Cystodermella and new combinations in Ripartitella (Agaricineae, incertae sedis) and Cystolepiota (Verrucosporaceae)
Authors: SAAR IRJA , COOPER JERRY A. , TRUDELL STEVEN A.
Published: July 2024

Two new species of Cystodermella, C. canadensis and C. rubrogranulosa, are described based on phylogenetic and morphological grounds, and compared with similar species. Four holotypes were barcoded: Agaricus terryi, Cystoderma texense, Lepiota sipariana and Melanoleuca vinosa. Two new combinations are proposed: Melanoleuca vinosa as Ripartitella vinosa, and Cystodermella contusifolia as Cystolepiota contusifolia. Cystodermella cristallifera and C. sipariana are found to be conspecific; the older name, C. sipariana, should be adopted and C. cristallifera deprecated as a later synonym. The holotypes of three species: Agaricus terryi, Cystoderma texense and Cystodermella mazahuanensis all represent Cystodermella cinnabarina, for which a neotype is selected.
Saurauia decolorata (Actinidiaceae), a new species from Mindanao, the Philippines
Authors: OLIMPOS SHIELLA MAE B. , PENNEYS DARIN S. , SALAS DARYL S. , CORITICO FULGENT P. , AMOROSO VICTOR B. , FRITSCH PETER W.
Published: July 2024

Saurauia decolorata from the Mt. Pantaron Range, Bukidnon and Mt. Balatukan Natural Park, Misamis Oriental, Mindanao Island, the Philippines, is illustrated and described as a new species. It closely resembles S. avellana and S. elegans in having branchlets, petioles, and abaxial surfaces of the leaves covered with tomentum and scales, densely clustered flowers, longitudinal anther dehiscence, and 3–4 styles. However, S. decolorata is distinguished from these species by its prominent rusty-colored tomentum and scales on branchlets and abaxial leaf surfaces, cordate leaf bases, crenate margin, 16–21 pairs of lateral veins, fascicled-cymose inflorescences that are both axillary and ramiflorous, and sparsely scaly pinkish green outer sepals. This discovery further emphasizes the unique biodiversity of the forests of the Pantaron Range and Mt. Balatukan which urgently need legislative protection and enhanced protected area management plans, respectively.
Unfolding the dynamics of driving behavior: a machine learning analysis from Germany and Belgium
Authors: Roussou Stella , Michelaraki Eva , Katrakazas Christos , Afghari Amir Pooyan , Al Haddad Christelle , Alam Md Rakibul , Antoniou Constantinos , Papadimitriou Eleonora , Brijs Tom , Yannis George
Published: July 2024

The i-DREAMS project focuses on establishing a framework known as the ‘Safety Tolerance Zone (STZ)’ to ensure drivers operate within safe boundaries. This study compares Long-Short-Term-Memory Networks and shallow Neural Networks to assess participants’ safety levels during i-DREAMS on-road trials. Thirty German drivers’ trips and Forty-Three Belgian drivers were analyzed using these methods, revealing factors contributing to risky behavior. Results indicate i-DREAMS interventions significantly enhance driving behavior, with Neural Networks displaying superior performance among the algorithms considered.
Risk factors and predictors of recurrence of febrile seizures in children in Nantong, China: a retrospective cohort study
Authors: Shen Feifei , Lu Leijuan , Wu Youjia , Suo Guihai , Zheng Yuqin , Zhong Xiuli , Wang Xu , Li Haiying
Published: July 2024

Background

Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1–3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model.

Methods

This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence.

Results

Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P < 0.001), duration of the first episode (OR = 1.03, 95% CI: 1.00, 1.06, P = 0.040), and peak temperature (OR = 0.68, 95% CI: 0.47, 0.98, P = 0.036) were identified as independent risk factors for FS recurrence. Age had the highest relative importance in predicting FS recurrence, followed by the duration of the first episode, with an area under the ROC curve of 0.717.

Conclusion

Young age and duration of the first seizure are important independent risk factors for FS recurrence and are key considerations for predicting recurrence. Further research is needed to confirm the potential use of Neutrophil–lymphocyte ratio (NLR) as a predictor of FS recurrence.
A school-based food and nutrition education intervention increases nutrition-related knowledge and fruit consumption among primary school children in northern Ghana
Authors: Mogre Victor , Sefogah Promise Emmanuel , Adetunji Alaofin Wemimo , Olalekan Oni Opeyemi , Gaa Patience Kanyiri , Ayettey Anie Hannah N.G , Tayo Bamidele
Published: July 2024

Background

Providing children with the opportunity to learn about nutrition is critical in helping them establish a healthy lifestyle and eating behaviours that would remain with them till adulthood. We determined the effect of a school-based food and nutrition education (SFNE) intervention on the nutrition-related knowledge, attitudes, dietary habits, physical activity levels and the anthropometric indices (BMI-for-age z scores, %Body fat and waist circumference) of school-age children in northern Ghana.

Methods

Following a controlled before-and-after study design, we recruited school-age children in primary 4 and 5 from public and private schools and assigned them non-randomly to intervention and control groups (4 schools total). A SFNE intervention called ‘Eat Healthy, Grow Healthy (EHGH)’ was implemented in intervention schools. Components of the intervention included children, teachers, school officials, and the school environment. Nutrition education didactic sessions, active discussions, nutrition games, charades, art work, and physical activity sessions were among the teaching and learning activities implemented. At 0 and 6 months, primary (anthropometry) and secondary (fruit, vegetable, and breakfast consumption) outcomes were obtained.

Results

Mean BMI-for-age z-scores did not differ significantly between intervention and control groups (F1,261 = 0.45, P = 0.503, η2 = 0.01). However, significantly greater nutrition-related knowledge scores were recorded in the intervention group than in the control group at post-intervention (M = 6.07 SD = 2.17 vs. M = 5.22 SD = 1.92; p = 0.002). Mean number of days intervention children consumed fruits differed across time (F1, 263 = 33.04, p = 0.002, η2 = 0.04) but not between the control and intervention groups (F1, 263 = 0.28, p = 0.60, η2 = 0.00).

Conclusions

The EHGH intervention had positive effects on the nutrition-related knowledge and the consumption of fruits among children although it did not impact their anthropometric indices.
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

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

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

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

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

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

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.
SEG Summer Field Camp: Multigeophysical imaging of an aquifer in the Astara region of Azerbaijan
Authors: Jodry Clara , Abakarov Dashgin , Bayramov Zaur , Aliyev Javid , Karimova Nigar , Abdulla-Zada Murad
Published: July 2024

Groundwater faces growing pressure due to human activities and the impacts of global climate change. Therefore, it is imperative to characterize near-surface aquifers, especially those that are unconfined because they are particularly vulnerable to these challenges. In Azerbaijan, alluvial plain aquifers represent a critical facet of the nation's water resources, yet they remain largely understudied. The objective of our study is to employ a multigeophysical survey (including electrical resistivity, seismic refraction, and ground-penetrating radar) to describe the subsurface attributes of an unconfined alluvial aquifer situated within an agricultural field in Astara, Azerbaijan. These data were acquired during the 2023 SEG Summer Field Camp by global students and specialists. Based on our general knowledge of the area, we interpret our findings as a subsurface with four distinct layers. The first is an initial 1 m thick soil layer covering the second layer, which is a more permeable unconfined aquifer likely consisting of a mixture of sand, pebbles, and gravel with a silty matrix (3 m thick). The third is a potential confining layer that is possibly clayey. The fourth layer is a presumed confined aquifer at a depth of 10 m. These results shed light on previously unstudied alluvial plain aquifers and contribute to comprehension of the hydrogeologic conditions at the local scale. To provide a broader understanding at the regional scale, the survey area should be extended and linked to borehole data to improve the interpretation of the geophysical results.
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]
Dendritic Cell–Based Immunotherapy in Patients With Resected Pancreatic Cancer
Authors: van ‘t Land Freek R. , Willemsen Marcella , Bezemer Koen , van der Burg Sjoerd H. , van den Bosch Thierry P.P. , Doukas Michail , Fellah Amine , Kolijn P. Martijn , Langerak Anton W. , Moskie Miranda , van der Oost Elise , Rozendaal Nina E.M. , Baart Sara J. , Aerts Joachim G.J.V. , van Eijck Casper H.J.
Published: July 2024

PURPOSE

Immunotherapies have shown limited responses in patients with advanced pancreatic cancer. Recently, we reported that dendritic cell (DC)–based immunotherapy induced T-cell responses against pancreatic cancer antigens. The primary objective of this study was to determine the efficacy of DC-based immunotherapy to prevent recurrence of disease.

METHODS

This was a single-center, open-label, single-arm, combined phase I/II trial. The primary end point was the 2-year recurrence-free survival (RFS) rate. A 2-year RFS rate of ≥60% was defined as a clinically meaningful improvement. We included patients with pancreatic cancer after resection and completion of standard-of-care (SOC) treatment without recurrent disease on cross-sectional imaging. Patients were treated with autologous DCs pulsed with an allogeneic mesothelioma tumor cell lysate, comprising antigens also expressed in pancreatic ductal adenocarcinoma.

RESULTS

Thirty-eight patients were included in the analysis of the primary end point (47% male, 53% female). The median age was 62 years (IQR, 55-68). Twenty-eight patients (74%) received five DC vaccinations and completed the study protocol. Three patients (8%) received four vaccinations, and seven patients (16%) received three vaccinations. After a median follow-up of 25.5 months, 26 patients (68%) had not developed recurrence of disease. The estimated 2-year RFS was 64%. Vaccination led to the enrichment of circulating activated CD4+ T cells and the detection of treatment-induced immune responses in vitro. T-cell receptor-sequencing analyses of a resected solitary lung metastasis showed influx of vaccine-specific T cells.

CONCLUSION

This study reached its primary end point of a 2-year RFS rate of ≥60% following pancreatectomy after SOC treatment and adjuvant DC-based immunotherapy in patients with pancreatic cancer. These results warrant a future randomized trial.
Piqued: Compounded Interest and the Intersubjective Scene
Authors: Moore Candace
Published: July 2024

In conversation with Silvan Tomkins, William James, Sianne Ngai, and others, “Piqued: Compounded Interest and the Intersubjective Scene” further theorizes one of the most taken-for-granted of the classic affects: interest. This essay argues that the piquing of interest is essential for projection, attachment, or resentment, even, to follow. Interest not only compounds, or accumulates with itself, sometimes sharpening or transforming into those more intense affects that we tend to associate with driving forces. It also acts combinatorially, as an elemental ingredient of all affects. Because of interest’s fundamental role in initiating momentum, combining with other affects, switching registers—in transmissible, communal, or mediated forms—it is worth confronting interest’s ubiquity to better understand how it, once provoked, functions culturally. To better demonstrate interest as a foundational, compounding affect in coexperienced dynamics and their representations, the author unpacks scenes of intersubjectivity in the television series Killing Eve (bbc America, 2018–22).
Racist Intimacies; or, The Femme Alter Ego and Her Retribution
Authors: Storti Anna M. Moncada
Published: July 2024

Cultural depictions of Asian/white miscegenation have long been a source of fascination for scholars within Asian American and sexuality studies. Such a long-standing interest has not only provided key insights into the Orientalist structure of racialized sexuality, but it has also kept our sights set, perhaps too set, on deciphering the Asian woman both in the context of romance and as an object of desire. This essay recasts the narrative of Asian/white sexuality as one of minoritarian retribution, making the argument that insofar as Asian femininity forms the object of racist desires, it can also function as the basis for feminist revenge. The author contemplates racial fetishism through twenty-first-century feminist cultural production, namely the work of mixed-race artists Chanel Matsunami Govreau and Maya Mackrandilal, showing how neoliberal multiculturalism has become further embedded within the infrastructure of everyday encounters, giving rise to something we might call the erotic life of anti-racism.
“Everything I Wanted Not to Be”: The Specter of Africa in the Trans Travel Narrative
Authors: Falek Joshua
Published: July 2024

Previous scholarship has interrogated how transsexual autobiographies recursively construct a gender-coherent subject through travel analogies. Orientalism has been one of the predominant frames through which these trans travel narratives have been interpreted. Through a close reading of Jan Morris’s autobiography, Conundrum, this paper attends to the overwhelming anti-Blackness that scaffolds these voyages to and through the Orient. Exploring how “Black Africa” has been occluded from Orientalist analyses of trans travel narratives, the author asks what might be found by attending specifically to the role of Africa (as a metaphor for Blackened rather than Orientalized geographies) in these autobiographies. Through Black studies, trans studies, affect theory, and Kleinian object relations theory, the essay demonstrates how Blackness grounds both trans travel narratives and the scholarship about them. Through a metacritique of both Orientalism and trans studies, this paper concludes by suggesting that scholars provincialize Orientalism.
Corticosterone and glucose are correlated and show similar response patterns to temperature and stress in a free-living bird
Authors: Millanes Paola M. , Pérez-Rodríguez Lorenzo , Rubalcaba Juan G. , Gil Diego , Jimeno Blanca
Published: July 2024

Glucocorticoid (GC) hormones have traditionally been interpreted as indicators of stress, but the extent to which they provide information on physiological state remains debated. GCs are metabolic hormones that amongst other functions ensure increasing fuel (i.e. glucose) supply on the face of fluctuating energetic demands, a role often overlooked by ecological studies investigating the consequences of GC variation. Furthermore, because energy budget is limited, in natural contexts where multiple stimuli coexist, the organisms' ability to respond physiologically may be constrained when multiple triggers of metabolic responses overlap in time. Using free-living spotless starling (Sturnus unicolor) chicks, we experimentally tested whether two stimuli of different nature known to trigger a metabolic or GC response, respectively, cause a comparable increase in plasma GCs and glucose. We further tested whether response patterns differed when both stimuli occurred consecutively. We found that both experimental treatments caused increases in GCs and glucose of similar magnitude, suggesting that both variables fluctuate along with variation in energy expenditure, independently of the trigger. Exposure to the two stimuli occurring subsequently did not cause a difference in GC or glucose responses compared with exposure to a single stimulus, suggesting a limited capacity to respond to an additional stimulus during an ongoing acute response. Lastly, we found a positive and significant correlation between plasma GCs and glucose after the experimental treatments. Our results add to the increasing research on the role of energy expenditure on GC variation, by providing experimental evidence on the association between plasma GCs and energy metabolism.
Plaza Shopping e o Dilema dos Prisioneiros
Authors: Godoi Alexandra Strommer , Goldbaum Sergio
Published: July 2024

Plaza Shopping, um centro de compras regional, tem que decidir como reagir à estratégia agressiva de seu principal concorrente, o Multimall, de atrair lojistas-âncora para seu empreendimento oferecendo-se a realizar investimentos milionários nas novas lojas. Alunos assumem o papel de Felipe Medeiros, superintendente do Plaza Shopping, que precisa decidir se retalia, fazendo contrapropostas agressivas também para tentar manter seus lojistas, ou acomoda e evitar entrar em uma guerra de ofertas.
Τοπογραφοανατομική μελέτη των πυλών εισόδου στην αρθροσκοπική χειρουργική της πηχεοκαρπικής άρθρωσης
Authors: Αντώνογλου Γεώργιος
Published: July 2024

Κατά την αρθροσκόπηση του καρπού, η άρθρωση του καρπού μπορεί πλέον να προβληθεί ουσιαστικά από οποιαδήποτε οπτική γωνία, μέσω ενός συνδυασμού τυπικών ραχιαίων και παλαμιαίων αρθροσκοπικών πυλών. Αυτή η πτωματική μελέτη στοχεύει στη σύγκριση όλων των πυλών του καρπού που περiγράφηκαν, ως προς τη ζώνη ασφαλείας τους, προκειμένου αυτές να ταξινομηθούν ανάλογα με την απόσταση από την πλησιέστερη δομή που διατρέχει κίνδυνο, για τις αρθροσκοπικές επεμβάσεις του καρπού. Εξετάστηκε ένα δείγμα είκοσι εννέα παρασκευσμάτων πτωματικών άνω άκρων, χωρίς διαθέσιμα κλινικά ιστορικά των πτωμάτων. Βελόνες εισήχθησαν στις θέσεις των ραχιαίων (1-2, 3-4, 4-5, 6-R, 6-U, MC-R, MC-U) και παλαμιαίων (VR, VU, VC-RC, VC-MC) πυλών στην κερκιδοκαρπική και μεσοκάρπια άρθρωση αναλόγως, σχηματίζοντας τις πύλες της αρθροσκόπησης του καρπού. Κατά την ανατομική παρασκευή που ακολούθησε, αποστάσεις μετρήθηκαν ως τη μικρότερη δυνατή απόσταση από τις βελόνες που τοποθετήθηκαν στις προαναφερθείσες πύλες, έως τις αντίστοιχες βελόνες που τοποθετήθηκαν στα πλησιέστερα ευγενή στοιχεία σε κίνδυνο για κάθε πύλη. Έπειτα από στατιστική ανάλυση των αποτελεσμάτων, καθορίστηκαν ζώνες ασφαλείας για όλες τις πύλες και προτάθηκε η ταξινόμηση ασφάλειας των αρθροσκοπικών πυλών του καρπού, κατατάσσοντας αυτές από τις πιο ασφαλείς στις πιο επικίνδυνες. Ειδικότερα, με ζώνη ασφαλείας μεγαλύτερη των 6 mm, οι ραχιαίες πύλες MC-U, MC-R, 4-5 και η παλαμιαία πύλη VC-RC εντάχθηκαν στην Κατηγορία Α. Με ζώνη ασφαλείας μεταξύ 2 mm και 6 mm, οι ραχιαίες πύλες 6-R, 3-4 και οι παλαμιαίες πύλες VC-MC, VU εντάχθηκαν στην Κατηγορία Β. Τέλος, με ζώνη ασφαλείας μικρότερη των 2 mm, οι ραχιαίες πύλες 1-2, 6-U και η παλαμιαία πύλη VU εντάχθηκαν στην Κατηγορία Γ. Εφαρμόζοντας την προτεινόμενη ταξινόμηση ασφάλειας στην αρθροσκοπική πρακτική, δύναται να πραγματοποιείται η αρθροσκόπηση του καρπού χωρίς ιατρογενείς επιπλοκές προερχόμενες από τη διενέργεια των πυλών εισόδου.
Μηχανές δημιουργίας γεωμετρικών καμπυλών και εφαρμογή τους στη διδακτική πράξη
Authors: Ντόντος Γεώργιος
Published: July 2024

Στην παρούσα έρευνα γίνεται αρχικά μία σύντομη ιστορική αναδρομή των μαθηματικών μηχανών και μηχανισμών, εστιάζοντας τελικά στους δύο ιστορικούς παραβολογράφους του 17ου αιώνα που σχεδιάστηκαν και κατασκευάστηκαν από τον Bonaventura Franciscus Cavalieri και τον Frans van Schooten. Οι δύο μηχανισμοί αναλύθηκαν, προσομοιώθηκαν και ανακατασκευάστηκαν. Μέσω λογισμικού δυναμικής γεωμετρίας αναζητήθηκαν προεκτάσεις και δυνατότητες των μηχανισμών που δεν είναι εμφανείς. Με εμφανή στοιχεία του παραβολογράφου van Schooten υπολογίστηκε η τοπική καμπυλότητα του χαρασσόμενου παραβολικού τόξου, Διατυπώθηκε το αντίστροφο εφαπτομενικό πρόβλημα που επιλύει γεωμετρικά ο παραβολογράφος van Schooten, ουσιαστικά επιλύοντας την αντίστοιχη διαφορική εξίσωση. Επιβεβαιώθηκε μηχανολογικά η ισοδυναμία των ορισμών της παραβολής που ενσωματώνουν, καθιστώντας τους μηχανολογικά ισοδύναμους, Με την διαμεσολάβηση των δύο μηχανισμών διδάχτηκε η έννοια της παραβολής σε τμήμα της Β΄λυκείου το οποίο χωρίστηκε σε δύο ομάδες. Πραγματοποιήθηκαν δύο σχεδιασμένες τετράωρες πειραματικές διδασκαλίες στον χώρο του σχολείου φοίτησης. Τα ατομικά αποτελέσματα αναλύθηκαν ποιοτικά και ποσοτικά, εστιάζοντας σε δύο γνωστικούς δείκτες και σε τρεις δείκτες γνωστικής δομής μέσω δραστηριοτήτων, που αρχικά μετετράπησαν σε διατακτικές μεταβλητές χωρίς ιδιαίτερη στάθμιση. Επίσης, για κάθε ομάδα πραγματοποιήθηκε μη παραμετρικός έλεγχος της διαμέσου κάθε ενός από τους πέντε ποιοτικούς δείκτες. Πραγματοποιήθηκε και μη παραμετρικός έλεγχος συσχέτισης των γνωστικών δεικτών με τους δείκτες των δραστηριοτήτων της κάθε ομάδας. Οι δύο γνωστικοί δείκτες και οι τρεις δείκτες γνωστικής δομής μέσω δραστηριοτήτων, έδωσαν μία πληρέστερη εικόνα του επιπέδου κατανόησης κάθε μαθητή και μαθήτριας, αλλά και μία πληρέστερη διαδικασία αξιολόγησης του τρόπου που κατανοούν. Αναδεικνύεται ο ρόλος των μαθηματικών μηχανών, που αποτελούνται από άκαμπτες αρθρωτές ράβδους, καθώς και του λογισμικού δυναμικής γεωμετρίας, ως γνωστικών γεφυρών μεταξύ της εμπειρικής δικαιολόγησης και της παραγωγικής συλλογιστικής. Οι μηχανικές συνδέσεις (linkages) και οι δυναμικές προσομοιώσεις τους αναδεικνύονται ως κατάλληλα πλαίσια γεφύρωσης εμπειρικών και παραγωγικών συλλογισμών, καθώς και ως εργαλεία ισόρροπης σύνδεσης στην διδασκαλία Άλγεβρας και Γεωμετρίας τουλάχιστον στην δευτεροβάθμια εκπαίδευση.
Reformy instytucjonalne Unii Gospodarczej i Walutowej po 2010 r. – ocena zasadności i efektywności wprowadzonych rozwiązań na gruncie teorii optymalnych obszarów walutowych
Authors: Wajda-Lichy Marta
Published: July 2024

INSTITUTIONAL REFORMS OF THE ECONOMIC AND MONETARY UNION IMPLEMENTED AFTER 2010: THE EFFECTIVENESS OF NEW ARRANGEMENTS ON THE GROUNDS OF THE THEORY OF OPTIMUM CURRENCY AREAS
The economic shocks over the last 15 years revealed low effectiveness of macroeconomic adjustment mechanisms, as manifested by growing imbalances in the current accounts, public finances, and labour markets of the euro zone economies. The essence of the institutional reforms introduced after 2010 was to improve the mechanisms for stabilizing macroeconomic balances, as well as to increase the resilience of the EMU economies to future disturbances, especially those of a systemic nature. New solutions have a strong basis in the theory of optimum currency areas, as well as in institutional economics. The effects of the new institutional arrangements indicate a substantial improvement in the resilience of credit institutions to economic shocks, however, other macroeconomic risks remain.
Reformy i ewolucja Wspólnej Polityki Bezpieczeństwa i Obrony Unii Europejskiej w latach 2016-2023
Authors: Fiszer Józef M.
Published: July 2024

REFORMS AND EVOLUTION OF THE EU’S COMMON SECURITY AND DEFENCE POLICY
2016-2023: Achievements and Failures The aim of the article is to analyze the reforms of the Common Security and Defence Policy (CSDP) of the European Union, with particular emphasis on the new EU External Security Strategy adopted in 2016 and its evolution, achievements and failures in the years 2016-2023. In addition, the European Union’s position on Russia’s aggression against Ukraine on 24 February 2022 and its impact on the evolution and reforms of the CSDP and the necessary changes to the EU’s foreign policy and security strategy for Europe will be shown. The main thesis here is that the previous reforms of the European Union’s WSDiO have been defensive in nature and should be radically changed in view of the current international situation. Among other things, the EU’s soft power policy should be supplemented with hard power measures. The decision making process on matters relating to the EU’s foreign and security policy should also change, and in particular the use of the EU veto requires urgent reform. This will not be easy to achieve, but it is necessary for the European Union to be able to respond quickly and effectively to emerging threats to the security of its members and peace in Europe.