Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles.

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na+ and K+ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood. Also, because recent studies reported HCN channels have been somewhat linked with the dysfunction of photoreceptors which are affected by retinal diseases, investigating HCN channels in the retina may offer valuable insights into disease mechanisms and potentially contribute to identifying novel therapeutic targets for retinal degenerative disorders. This paper endeavors to summarize the existing literature on the distribution and function of HCN channels reported in the vertebrate retinas of various species and discuss the potential implications for the treatment of retinal diseases. Then, we recapitulate current knowledge regarding the function and regulation of HCN channels, as well as their relevance to various neurological disorders.

Usformer: A small network for left atrium segmentation of 3D LGE MRI.

Left atrial (LA) fibrosis plays a vital role as a mediator in the progression of atrial fibrillation. 3D late gadolinium-enhancement (LGE) MRI has been proven effective in identifying LA fibrosis. Image analysis of 3D LA LGE involves manual segmentation of the LA wall, which is both lengthy and challenging. Automated segmentation poses challenges owing to the diverse intensities in data from various vendors, the limited contrast between LA and surrounding tissues, and the intricate anatomical structures of the LA. Current approaches relying on 3D networks are computationally intensive since 3D LGE MRIs and the networks are large. Regarding this issue, most researchers came up with two-stage methods: initially identifying the LA center using a scaled-down version of the MRIs and subsequently cropping the full-resolution MRIs around the LA center for final segmentation. We propose a lightweight transformer-based 3D architecture, Usformer, designed to precisely segment LA volume in a single stage, eliminating error propagation associated with suboptimal two-stage training. The transposed attention facilitates capturing the global context in large 3D volumes without significant computation requirements. Usformer outperforms the state-of-the-art supervised learning methods in terms of accuracy and speed. First, with the smallest Hausdorff Distance (HD) and Average Symmetric Surface Distance (ASSD), it achieved a dice score of 93.1% and 92.0% in the 2018 Atrial Segmentation Challenge and our local institutional dataset, respectively. Second, the number of parameters and computation complexity are largely reduced by 2.8x and 3.8x, respectively. Moreover, Usformer does not require a large dataset. When only 16 labeled MRI scans are used for training, Usformer achieves a 92.1% dice score in the challenge dataset. The proposed Usformer delineates the boundaries of the LA wall relatively accurately, which may assist in the clinical translation of LA LGE for planning catheter ablation of atrial fibrillation.

Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147).

PURPOSE: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. PATIENTS AND METHODS: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms. RESULTS: Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated. CONCLUSIONS: Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.

Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study.

BACKGROUND: In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. METHODS: Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. RESULTS: 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant. CONCLUSION: In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. LEVEL OF EVIDENCE: Level III, Therapeutic Care Management.

Autonomous circadian rhythms in the human hepatocyte regulate hepatic drug metabolism and inflammatory responses.

Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, circadian rhythms play fundamental roles in maintaining organ homeostasis. Here, we established and characterized an in vitro liver experimental system in which primary human hepatocytes display self-sustained oscillations. By generating gene expression profiles of these hepatocytes over time, we demonstrated that their transcriptional state is dynamic across 24 hours and identified a set of cycling genes with functions related to inflammation, drug metabolism, and energy homeostasis. We designed and tested a treatment protocol to minimize atorvastatin- and acetaminophen-induced hepatotoxicity. Last, we documented circadian-dependent induction of pro-inflammatory cytokines when triggered by LPS, IFN-ß, or Plasmodium infection in human hepatocytes. Collectively, our findings emphasize that the phase of the circadian cycle has a robust impact on the efficacy and toxicity of drugs, and we provide a test bed to study the timing and magnitude of inflammatory responses over the course of infection in human liver.

Corrigendum: Electrically-evoked responses for retinal prostheses are differentially altered depending on ganglion cell types in outer retinal neurodegeneration caused by Crb1 gene mutation.

[This corrects the article DOI: 10.3389/fncel.2023.1115703.].

The benefits of reflecting on gratitude received at home for leaders at work: Insights from three field experiments.

Expressions of gratitude by leaders tend to yield positive effects in the workplace. Leaders, however, are not solely bestowers of gratitude but also recipients of it. Although leaders are often studied for their influence on others in the workplace, it is crucial to acknowledge that they are also complete individuals with personal lives outside of work that can spill over and affect their feelings and leadership behaviors at work. To advance research on leadership and gratitude, we take a whole-person view of leaders to understand the interpersonal crossover and intrapersonal spillover of gratitude. By integrating the moral affect theory of gratitude and savoring interventions research, we investigate how an intervention involving reflecting on gratitude received from family members at home motivates leaders to be more helpful and empowering toward their followers at work. We studied these ideas across three daily field experiments with 103 full-time managers from high schools, 116 leader-follower dyads from a variety of industries, and 109 leaders across various industries. Our findings demonstrate that when leaders reflected on receiving gratitude from family members at home, they felt higher prosocial impact at home, which in turn fulfilled their basic daily needs, consequently motivating them to engage in more helping and empowering behavior toward their followers at work. We also found some evidence that leaders higher in trait negative affect benefited the least from reflecting on receiving gratitude at home. We discuss how our findings provide extensions to literatures on gratitude, leadership, and work-family issues. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Lessons Learned From TranslateCovid, a Multilingual Online Resource Hub for Asian American and Pacific Islander Communities and Beyond.

The COVID-19 pandemic exacerbated health disparities among immigrant communities. Delivering accurate information and addressing misinformation on protective measures and vaccination to linguistically disadvantaged groups was critical for mitigating the effects of the pandemic. One group that was especially vulnerable to miscommunication about COVID-19 was non-native English-speaking immigrants. To address these disparities, the Asian American Studies Center and the Fielding School of Public Health at the University of California, Los Angeles, partnered to create a multilingual resource hub, TranslateCovid.org, to disseminate credible and reliable information about COVID-19 safety measures, the science behind the vaccines, and vaccine safety. We identified >1300 verified resources in 60 languages from government, academic, and nonprofit organizations and reposted them on the TranslateCovid website. We also developed public service announcement videos on handwashing, use of face masks, and social distancing in 10 languages and a fact sheet for frequently asked questions in 20 languages. We used a participatory approach to develop strategies for disseminating these resources. We discuss lessons learned, including strategies for forming government, community, and academic partnerships to support the timely development and dissemination of information. We conclude with a discussion on the unique role of universities in promoting equitable access to public health resources among immigrant communities in times of crisis.

Active Learning in Brain Tumor Segmentation with Uncertainty Sampling and Annotation Redundancy Restriction.

Deep learning models have demonstrated great potential in medical imaging but are limited by the expensive, large volume of annotations required. To address this, we compared different active learning strategies by training models on subsets of the most informative images using real-world clinical datasets for brain tumor segmentation and proposing a framework that minimizes the data needed while maintaining performance. Then, 638 multi-institutional brain tumor magnetic resonance imaging scans were used to train three-dimensional U-net models and compare active learning strategies. Uncertainty estimation techniques including Bayesian estimation with dropout, bootstrapping, and margins sampling were compared to random query. Strategies to avoid annotating similar images were also considered. We determined the minimum data necessary to achieve performance equivalent to the model trained on the full dataset (α = 0.05). Bayesian approximation with dropout at training and testing showed results equivalent to that of the full data model (target) with around 30% of the training data needed by random query to achieve target performance (p = 0.018). Annotation redundancy restriction techniques can reduce the training data needed by random query to achieve target performance by 20%. We investigated various active learning strategies to minimize the annotation burden for three-dimensional brain tumor segmentation. Dropout uncertainty estimation achieved target performance with the least annotated data.

Subjective Causes for Failure to Return to Sport After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

CONTEXT: While current literature has explored the outcomes of athletes who return to sport (RTS) after anterior cruciate ligament (ACL) injuries, less is known about the outcomes of those who are unsuccessful in returning to sport. OBJECTIVE: To determine the rate of athletes who did not RTS after primary ACL reconstruction (ACLR) and to identify the specific subjective reasons for failure to RTS. DATA SOURCES: A comprehensive search of the PubMed/MEDLINE, Scopus, and Web of Science databases was conducted through April 2021. STUDY SELECTION: Eligible studies included those explicitly reporting the rate of failure for RTS after ACLR as well as providing details on reasons for athletes' inability to return; 31 studies met the inclusion criteria. STUDY DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 2 to 4. DATA EXTRACTION: The reasons for failure to RTS referred to in our study are derived from those established previously in the studies included. Data were collected on the number of athletes, mean age, mean follow-up time, type of sport played, failure to RTS rate, and specific reasons for failure to return. RESULTS: The weighted rate of failure to RTS after ACLR was 25.5% (95% CI, 19.88-31.66). The estimated proportion of psychosocial-related reasons cited for failure to RTS was significantly greater than knee-related reasons for failure RTS (55.4% vs 44.6%, P < 0.01). The most cited reason for failure to RTS was fear of reinjury (33.0%). CONCLUSION: This study estimates the rate of failure to RTS after ACLR to be 25.5%, with the majority of athletes citing fear of reinjury as the major deterrent for returning to sports. We highlight how factors independent of surgical outcomes may impact an athlete's ability to return to play given that the predominant reason for no RTS after ACLR was unrelated to the knee.

Listeria monocytogenes brain abscesses presenting as contiguous, tubular rim-enhancing lesions on Magnetic Resonance Imaging: Case series and literature review.

Listeriosis has more than a 50% mortality when the central nervous system is involved, necessitating rapid diagnosis and treatment. We present four patients with brain abscesses in the setting of diagnosed neurolisteriosis, all of which demonstrated an odd presentation of multiple small, contiguous tubular lesions with rim enhancement on magnetic resonance imaging. Our review of published cases of neurolisteriosis suggests that this may be a useful pattern to identify neurolisteriosis abscesses, allowing earlier detection and therapy.

Redefining the molecular rejection states in 3230 heart transplant biopsies: Relationships to parenchymal injury and graft survival.

The first-generation Molecular Microscope (MMDx) system for heart transplant endomyocardial biopsies used expression of rejection-associated transcripts (RATs) to diagnose not only T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) but also acute injury. However, the ideal system should detect rejection without being influenced by injury, to permit analysis of the relationship between rejection and parenchymal injury. To achieve this, we developed a new rejection classification in an expanded cohort of 3230 biopsies: 1641 from INTERHEART (ClinicalTrials.gov NCT02670408), plus 1589 service biopsies added to improve the power of the machine learning algorithms. The new system used 6 rejection classifiers instead of RATs and generated 7 rejection archetypes: No rejection, 48%; Minor, 24%; TCMR1, 2.3%; TCMR2, 2.7%; TCMR/mixed, 2.7%; early-stage ABMR, 3.9%; and fully developed ABMR, 16%. Using rejection classifiers eliminated cross-reactions with acute injury, permitting separate assessment of rejection and injury. TCMR was associated with severe-recent injury and late atrophy-fibrosis and rarely had normal parenchyma. ABMR was better tolerated, seldom producing severe injury, but in later biopsies was often associated with atrophy-fibrosis, indicating long-term risk. Graft survival and left ventricular ejection fraction were reduced not only in hearts with TCMR but also in hearts with severe-recent injury and atrophy-fibrosis, even without rejection.

Wnt dose escalation during the exit from pluripotency identifies tranilast as a regulator of cardiac mesoderm.

Wnt signaling is a critical determinant of cell lineage development. This study used Wnt dose-dependent induction programs to gain insights into molecular regulation of stem cell differentiation. We performed single-cell RNA sequencing of hiPSCs responding to a dose escalation protocol with Wnt agonist CHIR-99021 during the exit from pluripotency to identify cell types and genetic activity driven by Wnt stimulation. Results of activated gene sets and cell types were used to build a multiple regression model that predicts the efficiency of cardiomyocyte differentiation. Cross-referencing Wnt-associated gene expression profiles to the Connectivity Map database, we identified the small-molecule drug, tranilast. We found that tranilast synergistically activates Wnt signaling to promote cardiac lineage differentiation, which we validate by in vitro analysis of hiPSC differentiation and in vivo analysis of developing quail embryos. Our study provides an integrated workflow that links experimental datasets, prediction models, and small-molecule databases to identify drug-like compounds that control cell differentiation.

Deep Learning Detection of Aneurysm Clips for Magnetic Resonance Imaging Safety.

Flagging the presence of metal devices before a head MRI scan is essential to allow appropriate safety checks. There is an unmet need for an automated system which can flag aneurysm clips prior to MRI appointments. We assess the accuracy with which a machine learning model can classify the presence or absence of an aneurysm clip on CT images. A total of 280 CT head scans were collected, 140 with aneurysm clips visible and 140 without. The data were used to retrain a pre-trained image classification neural network to classify CT localizer images. Models were developed using fivefold cross-validation and then tested on a holdout test set. A mean sensitivity of 100% and a mean accuracy of 82% were achieved. Predictions were explained using SHapley Additive exPlanations (SHAP), which highlighted that appropriate regions of interest were informing the models. Models were also trained from scratch to classify three-dimensional CT head scans. These did not exceed the sensitivity of the localizer models. This work illustrates an application of computer vision image classification to enhance current processes and improve patient safety.

Peptide Binder to Glypican-3 as a Theranostic Agent for Hepatocellular Carcinoma.

Glypican-3 (GPC3) is a membrane-associated glycoprotein that is significantly upregulated in hepatocellular carcinomas (HCC) with minimal to no expression in normal tissues. The differential expression of GPC3 between tumor and normal tissues provides an opportunity for targeted radiopharmaceutical therapy to treat HCC, a leading cause of cancer-related deaths worldwide. Methods: DOTA-RYZ-GPC3 (RAYZ-8009) comprises a novel macrocyclic peptide binder to GPC3, a linker, and a chelator that can be complexed with different radioisotopes. The binding affinity was determined by surface plasma resonance and radioligand binding assays. Target-mediated cellular internalization was radiometrically measured at multiple time points. In vivo biodistribution, monotherapy, and combination treatments with 177Lu or 225Ac were performed on HCC xenografts. Results: RAYZ-8009 showed high binding affinity to GPC3 protein of human, mouse, canine, and cynomolgus monkey origins and no binding to other glypican family members. Potent cellular binding was confirmed in GPC3-positive HepG2 cells and was not affected by isotope switching. RAYZ-8009 achieved efficient internalization on binding to HepG2 cells. Biodistribution study of 177Lu-RAYZ-8009 showed sustained tumor uptake and fast renal clearance, with minimal or no uptake in other normal tissues. Tumor-specific uptake was also demonstrated in orthotopic HCC tumors, with no uptake in surrounding liver tissue. Therapeutically, significant and durable tumor regression and survival benefit were achieved with 177Lu- and 225Ac-labeled RAYZ-8009, as single agents and in combination with lenvatinib, in GPC3-positive HCC xenografts. Conclusion: Preclinical in vitro and in vivo data demonstrate the potential of RAYZ-8009 as a theranostic agent for the treatment of patients with GPC3-positive HCC.

Intrinsic diving reflex induces potent antioxidative response by activation of NRF2 signaling.

Aims: This study aims to elucidate the underlying mechanisms of diving reflex, a powerful endogenous mechanism supporting underwater mammalian survival. Antioxidative responses, observed in marine mammals, may be contributing factors. Using a multi-organ approach, this study assesses whether acute and chronic diving reflex activate nuclear factor-erythroid-2-related factor 2 (NRF2) signaling pathways, which regulate cellular antioxidant responses. Methods: Male Sprague-Dawley rats ( n =38) underwent either a single diving session to elicit acute diving reflex, or daily diving sessions for 4-weeks to produce chronic diving reflex. NRF2 (total, nuclear, phosphorylated), NRF2-downstream genes, and malondialdehyde were assessed via Western blot, immunofluorescence, RT-PCR, and ELISA in brain, lung, kidney, and serum. Results: Diving reflex increased nuclear NRF2, phosphorylated NRF2, and antioxidative gene expression, in an organ-specific and exposure time-specific manner. Comparing organs, the brain had the highest increase of phosphorylated NRF2 expression, while kidney had the highest degree of nuclear NRF2 expression. Comparing acute and chronic sessions, phosphorylated NRF2 increased the most with chronic diving reflex, but acute diving reflex had the highest antioxidative gene expression. Notably, calcitonin gene-related peptide appears to mediate diving reflex' effects on NRF2 activation. Conclusions: Acute and chronic diving reflex activate potent NRF2 signaling in the brain and peripheral organs. Interestingly, acute diving reflex induces higher expression of downstream antioxidative genes compared to chronic diving reflex. This result contradicts previous assumptions requiring chronic exposure to diving for induction of antioxidative effects and implies that the diving reflex has a strong translational potential during preconditioning and postconditioning therapies. Key Points: Diving reflex activates potent NRF2 signaling via multiple mechanisms, including phosphorylation, nuclear translocation, and KEAP1 downregulation with both acute and chronic exposure.Diving reflex activates NRF2 via differential pathways in the brain and other organs; phosphorylated NRF2 increases more in the brain, while nuclear NRF2 increases more in the peripheral organs.Acute diving reflex exposure induces a more pronounced antioxidative effect than chronic diving reflex exposure, indicating that the antioxidative response activated by diving reflex is not dependent upon chronic adaptive responses and supports diving reflex as both a preconditioning and postconditioning treatment.

An exploration of mechanisms underlying Desemzia incerta colonization resistance to methicillin-resistant Staphylococcus aureus on the skin.

Colonization of human skin and nares by methicillin-resistant Staphylococcus aureus (MRSA) leads to the community spread of MRSA. This spread is exacerbated by the transfer of MRSA between humans and livestock, particularly swine. Here, we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial species Desemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in an in vivo murine skin model. Using parallel genomic and biochemical investigation, we discovered that D. incerta secretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis of D. incerta and MRSA cocultures, we found that exposure to D. incerta leads to decreased MRSA biofilm production. These results emphasize the value of exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as an increased understanding of microbial competition.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) causes a significant healthcare burden and can be spread to the human population via livestock transmission. Members of the skin microbiome can prevent MRSA colonization via a poorly understood phenomenon known as colonization resistance. Here, we studied the colonization resistance of S. aureus by bacterial inhibitors previously identified from a porcine skin model. We identify a pig skin commensal, Desemzia incerta, that reduced MRSA colonization in a murine model. We employ a combination of genomic, proteomic, and transcriptomic analyses to explore the mechanisms of inhibition between D. incerta and S. aureus. We identify 24 candidate antimicrobial proteins secreted by D. incerta that could be responsible for its antimicrobial activity. We also find that exposure to D. incerta leads to decreased S. aureus biofilm formation. These findings show that the livestock transmission of MRSA can be exploited to uncover novel mechanisms of MRSA colonization resistance.

Development of a Culinary Medicine Curriculum to Support Nutrition Knowledge for Gastroenterology Fellows and Faculty.

Gastroenterologists encounter many nutrition-related disorders in their practice, yet the nutritional needs of patients with chronic gastrointestinal (GI) and liver disease are largely unaddressed by treating physicians, due to suboptimal nutrition education. To address this gap, we developed and piloted a culinary medicine course for a GI fellowship training program. The objective of this study is to describe the development, implementation, and acceptability of the course. A registered dietitian, a chef instructor, and a gastroenterology clinical professor trained in culinary medicine developed the four-class tailored curriculum and delivered the classes remotely. Each class had a theme related to commonly encountered GI disorders and included hands-on meal preparation, a nutrition lecture, and a patient case study discussion. Post-course feedback surveys were disseminated. Twenty-three GI physicians enrolled in the course and the attendance rates in classes 1-4 were 83%, 65%, 61%, and 48%, respectively. Among 15 completed feedback surveys, 80% reported that the class contents were either moderately or extremely useful and all endorsed the curriculum for other gastroenterologists. Future studies of culinary medicine programs tailored to medical specialties should identify strategies to maintain engagement and assess the impact on nutrition knowledge, competencies, and translation of these new skills to clinical practice.

Multiparametric Radiogenomic Model to Predict Survival in Patients with Glioblastoma.

BACKGROUND: Clinical, histopathological, and imaging variables have been associated with prognosis in patients with glioblastoma (GBM). We aimed to develop a multiparametric radiogenomic model incorporating MRI texture features, demographic data, and histopathological tumor biomarkers to predict prognosis in patients with GBM. METHODS: In this retrospective study, patients were included if they had confirmed diagnosis of GBM with histopathological biomarkers and pre-operative MRI. Tumor segmentation was performed, and texture features were extracted to develop a predictive radiomic model of survival (<18 months vs. ≥18 months) using multivariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regularization to reduce the risk of overfitting. This radiomic model in combination with clinical and histopathological data was inserted into a backward stepwise logistic regression model to assess survival. The diagnostic performance of this model was reported for the training and external validation sets. RESULTS: A total of 116 patients were included for model development and 40 patients for external testing validation. The diagnostic performance (AUC/sensitivity/specificity) of the radiomic model generated from seven texture features in determination of ≥18 months survival was 0.71/69.0/70.3. Three variables remained as independent predictors of survival, including radiomics (p = 0.004), age (p = 0.039), and MGMT status (p = 0.025). This model yielded diagnostic performance (AUC/sensitivity/specificity) of 0.77/81.0/66.0 (training) and 0.89/100/78.6 (testing) in determination of survival ≥ 18 months. CONCLUSIONS: Results show that our radiogenomic model generated from radiomic features at baseline MRI, age, and MGMT status can predict survival ≥ 18 months in patients with GBM.