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The Role of Genetic Variation in Modulating the Effects of Blended Fruits and Vegetables Versus Fruit- and Vegetable-Coated Food Products on Antioxidant Capacity, DNA Protection, and Vascular Health:A Randomized Controlled Trial
No full textBackground/Objectives: Fruits and vegetables (F&Vs) are major dietary sources of phytochemicals, crucial for preventing non-communicable diseases. However, barriers such as preparation inconvenience and a short shelf life hinder their consumption. F&V-coated foods have emerged as an alternative. This human nutrition intervention study assessed the effects of a blended F&Vs mixture versus an F&V-coated food on phytochemical absorption and chronic disease risk markers. It also explored how genetic variation influences physiological responses to these F&V products. Methods: In this randomized-controlled trial, participants were assigned to one of three dietary interventions: a blended F&V mixture ("F&V Blend"), a rice-based cereal product coated with this blend ("Coated Pearl"), or the same product without the F&V mixture ("Uncoated Pearl"). The four-week study included a two-week run-in and a two-week intervention phase, each followed by a test day. Measurements included DNA damage resistance (comet assay), plasma antioxidant status (Trolox capacity and superoxide levels), microvasculature health (retinal analysis), and plasma phytochemical concentrations (colorimetric analyses or HPLC). To assess group differences, a linear mixed model was used. Fifteen polymorphic genes related to phytochemical metabolism and oxidative stress were tested using TaqMan and PCR, with outcomes analyzed via ANOVA. Results: The F&V Blend and Coated Pearl products increased plasma carotenoid levels versus the Uncoated Pearl product. Only the F&V Blend improved retinal dilation and DNA resistance. Surprisingly, the Uncoated Pearl product enhanced antioxidant capacity, lowered superoxide levels, and improved retinal microvasculature. Genotype effects were minimal, except for HNF1A, where wildtypes in the Uncoated Pearl group showed a higher antioxidant capacity. Conclusions: Fresh F&Vs were more effective than coated alternatives in improving vascular health and DNA protection
<i>LongHealth</i>:A Question Answering Benchmark with Long Clinical Documents
No full textRecent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5090 to 6754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. We evaluated eleven open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient Generative Pre-trained Transformers-3.5 Turbo for comparison. The highest accuracy was observed for Mistral-Small-24B-Instruct-2501 and Llama-4-Scout-17B-16E-Instruct, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data. In conclusion, while LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available
Cultivating Desire:Touch and Transgressive Thrill in the Art Fair
No full textThis article builds a framework for understanding both the observable and unobservable features of art fairs and how those structures are created through material and sensorial elements. It draws on the concept of atmospheres and broader discussions of affect to analyze the transgressive thrill present at art fairs, presenting an art fair as a space of commerce masked in the appearance of a museum-like space. This article explores how emotions and lures are structurally produced within the fair and how people are encouraged to collect. Within this space, a desire is cultivated via an opportunity to transgress the familiar norms of the museum environment, which fosters the development of a relationship between a person and an object. In this deeply affective space, rational responses to objects with unclear origins may be suspended. Through focusing on why people collect and how desire is generated we can better understand markets, including criminal markets, for highly desirable objects.</p
PTSD and cognition in older adults:A systematic literature review
No full textPost-traumatic stress disorder (PTSD) is a disabling mental health disorder affecting psychosocial functioning and quality of life. This systematic review is the first to summarize existing global literature on the relationship between PTSD and specific domains of cognitive function in the general population of older adults. We searched PsycINFO, Medline and CINAHL up until November 1st 2024. Studies were included if they were longitudinal cohort or cross-sectional studies of adults aged 60 years and over with a clinical diagnosis of PTSD or subthreshold PTSD symptoms, reporting on any domain of cognitive functioning using a standardised measure. Eighteen good or satisfactory quality articles met criteria for this review, of which three were longitudinal cohort studies and fifteen were cross-sectional studies. PTSD was associated with significant accelerated general cognitive decline and possible accelerated decline in attention and memory over time. Older adults with PTSD additionally performed significantly worse on measures of global cognitive function and memory compared to those without PTSD. For executive function results were mixed; two studies showed significant negative associations, whereas four other studies showed no significant differences between individuals with and without PTSD. Proactive screening of individuals with PTSD for cognitive decline and an additional focus of PTSD treatment on cognitive functioning are needed
Outcomes of recombinant growth hormone therapy in the traumatic brain injury population:A scoping review
No full textBackground: Post-traumatic hypopituitarism (PTHP), including growth hormone deficiency (GHD), is a prevalent and underdiagnosed complication of traumatic brain injury (TBI), resulting in substantial morbidity. Emerging evidence suggests that recombinant human growth hormone (rhGH) therapy may provide benefit for patients with confirmed GHD, and also those with growth hormone insufficiency (GHI), abnormal growth hormone secretion (AGHS), or Brain Injury Associated Fatigue and Altered Cognition (BIAFAC), even when peak growth hormone response to growth hormone stimulation testing is above traditional GHD diagnostic cutoffs in these patients. Objective: To conduct a scoping review evaluating the effects of rhGH in adults with TBI, including those classified as GHD, GHI, AGHS, or BIAFAC, on clinical, functional, and neurobiological outcomes. Methods: A comprehensive search of PubMed/MEDLINE was performed using a peer-reviewed search strategy. Studies were screened in duplicate. Eligible studies included clinical trials, observational studies, and case series, reporting rhGH use in adults with a history of TBI, with or without GHD. Outcomes included quality of life, neuropsychological performance, physical functioning, biochemical markers, and neuroimaging data. Results: Eleven studies met inclusion criteria: two double-blind, randomized, placebo-controlled trials; one double-blind, randomized, placebo-controlled crossover study; one double-blind, non-randomized, placebo-controlled trial; two non-randomized controlled trials; three retrospective cohort studies; and two open-label, single-arm trials. Across the studies reviewed, the researchers reported improvements in insulin-like growth factor-1 (IGF-1) levels, fatigue, mood, physical performance, and cognition. Structural and functional neuroimaging changes following rhGH were also reported, including increased cortical thickness and gray matter volume, and improved functional connectivity of somatosensory networks. Symptomatic improvement as well as improvements in objective measures were described among patients who did not meet diagnostic cut-point criteria for GHD. Conclusion: Evidence suggests that rhGH may confer benefit in a broad range of symptomatic TBI patients, including those with peak growth hormone values in ranges overlapping with normal, healthy controls. Larger, controlled studies are warranted to validate these findings and inform clinical guidelines
Fair Benchmarking Combinatorial Optimization Solvers in the Era of Emerging Computing Paradigms
No full textAs computational needs expand, new computing paradigms such as GPUs, FPGAs, high-performance computing clusters, digital annealers, neuromorphic computing systems, and quantum computers are emerging to complement traditional CPU-based computing models. Each paradigm offers unique capabilities for combinatorial optimization, a field concerned with finding the best solution from a finite set of possibilities. This paper addresses the challenge of fairly benchmarking the performance of combinatorial optimization solvers across these diverse paradigms. We propose a holistic approach to benchmarking that includes recommendations for fair comparisons and the introduction of new metrics. Our findings highlight the need for clear and equitable comparison criteria, particularly when contrasting digital and analogue platforms or different algorithm classes
Penetrance of Parkinson’s disease in GBA1 carriers depends on variant severity and polygenic background
No full textHeterozygous GBA1 variants increase Parkinson’s disease (PD) risk with variable penetrance. We investigated the interaction between genome-wide polygenic risk scores (PRS) and severity of pathogenic GBA1 variants (GBA1<inf>PVs</inf>) to assess their combined impact on PD risk. GBA1 variants were identified from whole exome sequencing in the UK Biobank and targeted PacBio sequencing in the Luxembourg Parkinson’s Study, with PRS calculated using genome-wide significant SNPs. GBA1<inf>PVs</inf> were present in 8.8% of PD patients in the UK Biobank and 9.9% in LuxPark, with carriers showing consistently higher PD risk across all PRS categories. In the highest PRS category, PD risk increased 2.3-fold in the UK Biobank and 1.6-fold in LuxPark. Severe and mild GBA1 variants conferred nearly double the risk of PD compared to risk variants. Our findings demonstrate the impact of PRS on GBA1<inf>PVs</inf> penetrance, highlighting implications for genetic counseling and clinical trial design in GBA1-associated PD
Artificial intelligence integration into the CT system with a focus on CT planning and scanning-review
No full textFor many years, the development of CT has been driven by technological advances in CT scanners to improve their performance, reduce radiation dose, and expand their clinical capabilities. Meanwhile, another focus of CT development has emerged—on improving and automating the scanning workflow and on approaches to better display the clinical information of CT images, supported by artificial intelligence (AI). In this review, we provide an overview of AI-driven functionalities integrated into the CT system. We discuss 3D camera-based patient positioning, patient characterization, and scan guidance, and automated scan range definition based on the localizer scan. We present approaches to automatically predict patient-specific individual scan delays for CT angiographic scans, and we discuss algorithms for AI-supported initial image quality checks. Finally, we present modern approaches that enable automatic calculation of anatomically aligned reconstructions and advanced visualizations directly on the scanner. We focus on clinically established methods, but we also present some prototype algorithms as a glimpse into the future.</p
Association of Pelvic Structure Involvement and Tumor Morphology at MRI with Prognosis Following Resection in Locally Recurrent Rectal Cancer
No full textPurpose To determine the influence of location, extent of tissue invasion, and tumor morphology at MRI on the resectability of locally recurrent rectal cancer (LRRC) and postresection oncologic outcomes of LRRC. Materials and Methods This retrospective observational study included consecutive patients diagnosed with LRRC who underwent surgery with curative intent at the Catharina Hospital Eindhoven and Karolinska University Hospital Stockholm between January 2003 and December 2017. Two expert radiologists reviewed available MR images while adhering to a standardized reviewing checklist. The effect of pelvic structure involvement, tumor morphology on the primary outcome of resection margin status, and secondary outcomes of overall survival and disease-free survival were assessed using univariable and multivariable logistic regression and Cox proportional hazard analyses. Results The final analysis included 328 patients with LRRC (mean age ± SD, 64.9 years ± 9.6; 126 female, 202 male). Resection margins were negative in 217 (66.2%) patients and positive in 111 patients (33.8%). Tumor size, tumor type, and border type on MR images were all associated with resectability. Central recurrences were associated with the lowest likelihood of positive resection margins (odds ratio [OR], 0.45; 95% CI: 0.28, 0.71; P < .001), whereas lateral recurrences were associated with the highest likelihood (OR, 2.00; 95% CI: 1.25, 3.19: P = .004). Similarly, central recurrences were associated with better disease-free survival compared with lateral recurrences (hazard ratio [HR], 0.69; 95% CI: 0.53, 0.90; P = .006 vs HR, 1.49; 95% CI: 1.14, 1.94; P = .003, respectively). Similar findings were observed after correcting for resection margin status. Conclusion Standardized MRI assessment of tumor characteristics in patients with LRRC resulted in the identification of specific prognostic factors. Central compartment involvement and well-defined tumors were associated with improved prognosis, whereas lateral compartment involvement and fibrotic spiculated tumors were associated with a worse prognosis after surgical resection. Keywords: Rectum, MR-Imaging, Abdomen/GI, Oncology, Surgery, Locally Recurrent Rectal Cancer, Tumor Biology Supplemental material is available for this article.</p
Gene expression analysis of primary graft dysfunction in adult heart transplant recipients:A cohort study
No full textBACKGROUND: Cardiac transplantation remains the primary treatment for advanced heart failure, with primary graft dysfunction (PGD) being the leading cause of early mortality. While PGD's exact pathogenesis is unclear, ischemia/reperfusion injury is a key factor. Donor hearts undergo multiple stresses, such as brain death, hypothermia, and ischemia, contributing to PGD and reduced graft survival. Many centers are studying PGD's pathophysiology through epidemiological, biomarker, and transcriptome analyses. This study aims to evaluate, via transcriptomic analysis of myocardial biopsies, the gene expression profile of patients with PGD and compare it with those without PGD. METHODS: Adult heart transplant patients were included in the study after signing the Informed Consent. The diagnosis of PGD followed the International Society for Heart and Lung Transplant criteria. Clinical and laboratory data from donors and recipients were evaluated. We included 20 consecutive heart transplant patients in the protocol. Gene expression analysis was performed via biopsies at donor heart implantation. RESULTS: Eleven genes had their expression significantly different in patients with PGD, with MYL4 the less expressed gene, and related to the myosin function and the gene B3GALT 5 the most expressed one and associated with the inflammatory response. CONCLUSIONS: The gene expression in patients with PGD is different when compared to patients without PGD. MYL4 gene was much less expressed in these patients and B3GALT5 was overexpressed. Future studies regarding gene expression on PGD may clarify the pathophysiology and provide possible biomarkers of the disease