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Background Screening esophagogastroduodenoscopy (EGD) is recommended for all cirrhotic patients at the time of diagnosis, however, non-invasive screening practices for varices have been emerging. CT scans have demonstrated high sensitivity in the detection of esophageal varices. The purpose of this study was to evaluate the sensitivity of CT scans in detecting esophageal and gastric varices when compared to the gold standard of EGD. Methods After institutional board review was obtained, patients from any University of Florida- Jacksonville location with esophageal varices, gastric varices, or both seen on CT abdomen and pelvis, CT chest, CT chest and abdomen pelvis, or EGD were included ( n  = 470). Exclusion criteria comprised cases where medical record numbers were invalid ( n  = 239), if esophageal or gastric varices were not reported ( n  = 25), varices other than esophageal or gastric were present ( n  = 5) and if CT scans were performed after an EGD. 201 total patients were included in the analysis. Results Compared to EGD-verified varices, CT scans demonstrated a sensitivity of 38.3% (95% CI [0.312–0.457]), with scans performed within 7 days of each other improving sensitivity to 39.51% (95% CI [0.294–0.501]), and 40.1% (95% CI [0.327–0.478]), in contrasted studies. CT scans correctly detected varices in 45.90% of thrombocytopenic patients (95% CI [36.85%- 55.16%]). Conclusion Although this study’s sensitivity differs markedly from that reported in prior literature, the findings can be understood in the context of methodological limitations. More than the absolute percentages, the observed trends highlight which patient groups may derive the greatest benefit from CT scan surveillance of varices. Overall, routine CT scans may not be surrogates for dedicated radiographic variceal screening. By presenting real-world data on variceal detection rates with CT, this study underscores the potential role of routine imaging not only in risk stratification but also in guiding resource allocation, such as identifying patients who may safely defer endoscopic evaluation versus those who warrant earlier interventions. Trial registration Retrospectively registered.

Proteolysis targeting chimeric small molecules (PROTACs) offer a strategy for degrading disease-associated proteins or controlling engineered protein tags fused to therapeutic proteins, like chimeric antigen receptors (CARs). New approaches are needed that allow spatiotemporal control of PROTAC activity, restricting degrader activity to targeted cells. Photopharmacology offers a solution by enabling light-mediated spatial control of drug action. Here, we synthesize photocaged and photoswitchable PROTAC molecules and test their regulation of proteins tagged with E. coli dihydrofolate reductase (eDHFR) in tumor and CAR-T cells. Several of the molecules are derived from triazole-linked trimethoprim-PROTACs (TMP-TACtz), that degrade eDHFR fused proteins at picomolar concentrations, show degradation in cells with low cereblon E3 ligase levels, and have little off-target effects. The photocleavable compound, TMP-TAC-PC yields the best light-mediated regulation of CAR T cell cytotoxicity and cytokine secretion. This work introduces photocontrolled, tag-directed degraders for controlling protein expression in tumor cells and CAR T cells. In this work authors demonstrate how photocontrolled tag-targeted degradation enables precise, spatiotemporal control of protein expression in tumor cells and CAR T cells, offering an esapproach for regulating engineered proteins with light.

With the recent increase in phishing attacks and other kinds of malicious activities, increasing the awareness of security and privacy awareness is arguably one of the best proven ways of preventing these kinds of threats. The main challenge in security and privacy awareness is the end user’s awareness of aspects of privacy and security they give up when using the Internet. Thus, this study focuses on identifying and discussing the growing threats of Internet usage and the lack of privacy and security knowledge of the everyday person. This study presents the results of a survey conducted to determine discrepancies between what rights users think they sign away when they agree to terms of service versus what rights they actually give away. It is hypothesized that people are genuinely unaware of what rights they are giving up, especially since they are signing the terms of service without reading the fine print. In this study, the terms of service were presented to respondents, and they answered questions on what they thought they were giving up, but once they answered the questions, they were explicitly told whether they truly knew what rights they signed away. The experimental results of this study examine how much knowledge the everyday person lacks with respect to the privacy policies they sign. All of this is ultimately used to examine possible flaws in the system. The experimental results illustrate the results of the survey. Based on the total surveys completed, the average score was 62%. This means that out of 10 clauses described in a given terms of service document or privacy policy, people are truly unaware of at least 4 of these statements.

Temporal control of protein levels in cells and living animals can be used to improve our understanding of protein function. In addition, control of engineered proteins could be used in therapeutic applications. PRoteolysis-TArgeting Chimeras (PROTACs) have emerged as a small-molecule-driven strategy to achieve rapid, post-translational regulation of protein abundance via recruitment of an E3 ligase to the target protein of interest. Here, we develop several PROTAC molecules by covalently linking the antibiotic trimethoprim (TMP) to pomalidomide, a ligand for the E3 ligase, Cereblon. These molecules induce degradation of proteins of interest (POIs) genetically fused to a small protein domain, E. coli dihydrofolate reductase (eDHFR), the molecular target of TMP. We show that various eDHFR-tagged proteins can be robustly degraded to 95% of maximum expression with PROTAC molecule 7c . Moreover, TMP-based PROTACs minimally affect the expression of immunomodulatory imide drug (IMiD)-sensitive neosubstrates using proteomic and biochemical assays. Finally, we show multiplexed regulation with another known degron-PROTAC pair, as well as reversible protein regulation in a rodent model of metastatic cancer, demonstrating the formidable strength of this system. Altogether, TMP PROTACs are a robust approach for selective and reversible degradation of eDHFR-tagged proteins in vitro and in vivo. The ability to control proteins in cells and animals is important for experimental research and may have therapeutic applications. Here, the authors developed a new set of heterobifunctional small molecules based on the antibiotic trimethoprim that can degrade proteins that are genetically tagged with E. coli dihydrofolate reductase (eDHFR).

Objectives With advances in antiretroviral therapy, the life expectancy of individuals living with human immunodeficiency virus infection has significantly improved. Consequently, non–acquired immunodeficiency syndrome-related conditions, particularly chronic liver disease, have become increasingly prominent causes of mortality. Methods A retrospective analysis was conducted using mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database spanning 1999 to 2020. We identified deaths among adults aged 25 years and older in which both human immunodeficiency virus infection and chronic liver disease were listed as causes of death. Data were grouped by gender, age, race, and region. Age-adjusted mortality rates were calculated per 1 million adults in the United States. Annual percent changes were computed using Joinpoint regression. Results From 1999 to 2020, there were 13,447 deaths in the United States in which both human immunodeficiency virus infection and chronic liver disease were listed as causes of death, with an overall age-adjusted mortality rate of 2.49. Males had higher age-adjusted mortality rates (3.85) than females (1.08). Non-Hispanic Black population had a higher age-adjusted mortality rate (8.71) than Hispanics (3.3) and non-Hispanic whites (2.29). Conclusion Mortality in which both human immunodeficiency virus infection and chronic liver disease were listed as causes of death has declined, but racial disparities persist, particularly among non-Hispanic Black individuals. Addressing these disparities will require policies that improve care access and reduce liver disease-related risks among people living with human immunodeficiency virus infection.

Spring-mediated distraction enterogenesis has been studied as a novel treatment for short bowel syndrome (SBS). Previous approaches are limited by multiple surgeries to restore intestinal continuity. Purely endoluminal devices require a period of intestinal attachment for enterogenesis. The purpose of this study is to modify the device to prevent premature spring migration in a porcine model. Two models were created in juvenile mini-Yucatan pigs for the placement of three-dimensionally printed springs. (1) Two Roux-en-y jejunojenostomies with two Roux limbs were made. A spring with bidirectional hooked surface features was placed in one Roux limb and a spring with smooth surface was placed in the other Roux limb. (2) The in-continuity model had both hooked and smooth surface springs placed directly in intestinal continuity. Spring location was evaluated by weekly radiographs, and the intestine was retrieved after 2 to 4 weeks. Springs with smooth surfaces migrated between 1 to 3 weeks after placement in both porcine models. Springs with bidirectional hooked surface features were anchored to the intestine for up to 4 weeks without migration. Histologically, the jejunal architecture showed significantly increased crypt depth and muscularis thickness compared to normal jejunum. Bidirectional features printed on springs prevented the premature migration of endoluminal springs. These novel spring anchors allowed for their endoluminal placement without any sutures. This approach may lead to the endoscopic placement of the device for patients with SBS.