The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation.
View Article and Find Full Text PDFWildfires are impacting communities globally, with California wildfires often breaking records of size and destructiveness. Knowing how communities are affected by these wildfires is vital to understanding recovery. We sought to identify impacted communities' post-wildfire needs and characterize how those needs change over time.
View Article and Find Full Text PDFIntroduction: Surgery is a cognitive discipline whose practitioners characteristically use technology during operations for patients. With accelerating technological innovation throughout society and healthcare, we sought to develop a shared position for Irish surgery via a commissioned work programme by the Royal College of Surgeons in Ireland.
Methods: Using Stanford design principles, representative clinical specialty and academic leads and higher trainee representatives across 15 specialties were surveyed regarding sentiments, perspectives and concerns regarding now and near future technology in clinical practice, career considerations and training/education.
Integration of multi-omic data for the purposes of biomarker discovery can provide novel and robust panels across multiple biological compartments. Appropriate analytical methods are key to ensuring accurate and meaningful outputs in the multi-omic setting. Here, we extensively profile the proteome and transcriptome of patient pancreatic cyst fluid (PCF) (n = 32) and serum (n = 68), before integrating matched omic and biofluid data, to identify biomarkers of pancreatic cancer risk.
View Article and Find Full Text PDFDespite an increased understanding of the underlying biology of the disease, pancreatic ductal adenocarcinoma (PDAC) remains a challenging condition with poor outcomes and a 5-year survival rate, even at an early stage, of less than 10%. This dismal prognosis is due in part to biological aggressiveness, the lack of early diagnosis, suboptimal surgical selection, and the need for effective neoadjuvant and adjuvant therapies. However, progress is being made with significant advancements in the diagnosis, staging, and treatment of PDAC, with a focus on precision therapy, improved surgical care, and supportive care, coupled with a deeper understanding of PDAC's biology.
View Article and Find Full Text PDFBackground: Adrenal myelolipomas are rare, benign, tumours of the adrenal cortex.
Aims: This study reports the experience of a tertiary adrenal surgery referral centre's approach to the management of patients with adrenal myelolipoma.
Methods: A retrospective observational cohort study was conducted on all adult patients (> 18 years age) diagnosed with adrenal myelolipoma from January 1, 2014, to December 30, 2022.
Introduction: Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined.
View Article and Find Full Text PDFBrand names can be used to hold plastic companies accountable for their items found polluting the environment. We used data from a 5-year (2018-2022) worldwide (84 countries) program to identify brands found on plastic items in the environment through 1576 audit events. We found that 50% of items were unbranded, calling for mandated producer reporting.
View Article and Find Full Text PDFThe Rhynonyssid mesostigmatic mite, , is a well-documented endoparasitic hematophagous arthropod of the respiratory tracts of multiple avian species, particularly Estrildid finches and canaries. In this retrospective study, 175 medical and 278 pathology records for the Gouldian finch () population (N = 377) at the San Diego Zoo between 2013 and 2021 were analyzed to evaluate the effectiveness of ivermectin-based prophylaxis. A multivariable negative binomial regression model was constructed to evaluate the population effects of monthly treatments on morbidity or mortality associated with respiratory mites.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2024
Future climate change can cause more days with poor air quality. This could trigger more alerts telling people to stay inside to protect themselves, with potential consequences for health and health equity. Here, we study the change in US air quality alerts over this century due to fine particulate matter (PM), who they may affect, and how they may respond.
View Article and Find Full Text PDFBackground: Debate exists regarding the optimal treatment for painful chronic pancreatitis (CP). This meta-analysis aims to determine the outcomes of surgical intervention as compared to endoscopy in patients with painful CP.
Methods: A systematic review and meta-analysis including studies from PubMed, Embase, Web of Science, and Cochrane Databases (1995 onwards) was done by two independent reviewers using PRISMA guidelines.
Background: Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody, in patients with advanced solid tumors.
Methods: This phase I/Ib study had two dose-escalation arms: single-agent NIZ985 administered subcutaneously thrice weekly (TIW, 2 weeks on/2 weeks off) or once weekly (QW, 3 weeks on/1 week off), and NIZ985 TIW or QW administered subcutaneously plus spartalizumab (400 mg intravenously every 4 weeks (Q4W)).
Background: Obesity, sarcopenia, and myosteatosis in inflammatory bowel disease may confer negative outcomes, but their prevalence and impact among patients with Crohn's disease (CD) have not been systematically studied. The aim of this study was to assess nutritional status and body composition among patients undergoing resectional surgery for CD and determine impact on operative outcomes.
Methods: Consecutive patients with CD undergoing resection from 2000 to 2018 were studied.
Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier in a non-inflammatory state. However, the intracellular mechanisms that regulate distinct transcriptional profiles and functional diversity of Th17 cells remain unclear. Here we show Raftlin1, a lipid raft protein, specifically upregulates and forms a complex with RORγt in pathogenic Th17 cells.
View Article and Find Full Text PDFObjective: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery.
Summary Background Data: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines.
To describe demographic and social characteristics of US communities exposed to wildfire smoke. Using satellite-collected data on wildfire smoke with the locations of population centers in the coterminous United States, we identified communities potentially exposed to light-, medium-, and heavy-density smoke plumes for each day from 2011 to 2021. We linked days of exposure to smoke in each category of smoke plume density with 2010 US Census data and community characteristics from the Centers for Disease Control and Prevention's Social Vulnerability Index to describe the co-occurrence of smoke exposure and social disadvantage.
View Article and Find Full Text PDFBackground: The clinical course of chronic pancreatitis is unpredictable and there is no globally accepted score to predict the disease course. We developed a clinical score to estimate pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis.
Methods: We conducted a retrospective cohort study using two clinical chronic pancreatitis databases held in tertiary referral centres in Dublin, Ireland, and in Tarragona, Spain.
Introduction: The beneficial effects of exercise and physical activity (PA) have been demonstrated in many chronic inflammatory diseases. Knowledge on PA levels is unknown in the chronic pancreatitis population, and there are currently no specific PA recommendations for this condition.
Methods: PA was measured objectively over a 7-day period in 17 individuals with chronic pancreatitis using an accelerometer (ActiGraph) and in 15 controls, matched for age, sex, and body mass index.
Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix GeneChip miRNA 4.0 array.
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