Search Results (22)

Background: Pancreatoduodenectomy with venous resection (PDVR) may be performed to achieve tumour clearance in patients with a pancreatic ductal adenocarcinoma (PDAC) with venous involvement. This study aimed to evaluate the impact of PDVR on PDAC outcomes. Methods: In total, 435 PDAC patients with either R0 status (n = 322) or R1 status within the superior mesenteric vein groove (n = 113) were extracted from the Recurrence After Whipple’s (RAW) study dataset. PDVR patients were matched in a 1:2 ratio with standard PD patients. Comparisons were then made between the two groups (surgical radicality and survival). Results: A total of 81 PDVRs were matched with 162 PDs. Neoadjuvant chemotherapy (5.7% vs. 13.6%, p = 0.032) and R1 resection rates (17.9% vs. 42%, p < 0.001) were higher in the PDVR group. Risk factors for R1 resection included venous resection (p < 0.001 for sleeve and p = 0.034 for segmental resection), pT3 (p = 0.007), and pN1 stage (p = 0.045). PDVR patients had lower median overall survival (OS, 21 vs. 30 months (m), p = 0.023) and disease-free survival (DFS, 17 m vs. 24 m, p = 0.043). Among PDVR patients, R status did not impact on OS (R0: 23 m, R1: 21 m, p = 0.928) or DFS (R0: 18 m, R1: 17 m, p = 0.558). Irrespective of R status, systemic recurrence was higher in the PDVR group (p = 0.034). Conclusions: Independent of R status, the PDVR group had lower overall survival and higher systemic recurrence rates. Full article

Procalcitonin (PCT) is commonly used to evaluate the etiology and severity of pneumonia. PCT has been shown to be elevated at baseline in patients with obesity. The aim of this study is to determine if body mass index (BMI) has an influence on admission PCT level in patients admitted to the hospital with a diagnosis of pneumonia. We conducted a retrospective cohort study that encompassed patient visits to a tertiary care center from 2014 until September 2023. A total of 18,652 patients presented to the emergency department with a diagnosis of pneumonia. A total of 3659 were admitted to the floor, and 2246 were admitted to the MICU. Patients were grouped based on admission BMI into five categories. The Kruskal–Wallis test performed on patients admitted to the floor revealed a statistically significant difference in PCT levels among groups of different BMIs (H = 34.97, df = 4, p < 0.001). In patients admitted to the MICU, the Kruskal–Wallis test revealed a significant difference in PCT levels among groups of different BMIs (H = 32.92, df = 4, p < 0.001). BMI has a statistically significant effect on PCT in patients admitted to the hospital with pneumonia. Patients with higher BMI may exhibit less robust PCT levels, which may impact management decisions. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

Entomopathogenic fungi have been considered potential biological control agents against the fall armyworm Spodoptera frugiperda (J. E. Smith), the world’s most important pest of maize. In this study, we evaluated the natural infection, molecular characteristics, and biological activity of Metarhizium rileyi (Farlow) isolated from S. frugiperda larvae of this insect, collected from maize crops in five Mexican locations. Natural infection ranged from 23% to 90% across all locations analyzed. Twenty-four isolates were evaluated on S. frugiperda second instars at a concentration of 1.0 × 10⁸ conidia/mL, causing 70% to 98.7% mortality and 60.5% to 98.7% sporulation. Isolates T9-21, Z30-21, PP48-21, and L8-22 were selected to determine their phylogenetic relationships by β-tubulin gene analysis and to compare median lethal concentration (CL₅₀), median lethal time (LT₅₀), and larval survival. These isolates were grouped into three clades. The T9-21, PP48-21, and J10-22 isolates were closely related (clade A), but phylogenetically distant from Z30-21 (clade B) and L8-22 (clade C) isolates. These genetic differences were not always reflected in their pathogenicity characteristics since no differences were observed among the LC₅₀ values. Furthermore, isolates T9-21, J10-22, and L8-22 were the fastest to kill S. frugiperda larvae, causing lower survival rates. We conclude that native M. rileyi isolates represent an important alternative for the biocontrol of S. frugiperda. Full article

Prescription drug misuse is a global problem, especially in the United States (US). Clinician involvement is necessary in this crisis, and prescription drug monitoring programs (PDMPs) are a recommended tool for the prevention, recognition, and management of prescription opioid misuse. However, because of the plethora of differences between different PDMPs, research on their effects is mixed. Yet, despite varied evidence, policy on PDMP use is trending stricter and more comprehensive. We aimed to identify patterns in the research to inform clinicians and policy. Through a systematic review of four literature databases (CINAHL, Cochrane Database, Embase, and Medline/OVID), we found 56 experimental and quasi-experimental studies published between 2016 and 2023 evaluating PDMP effects on clinician behavior. To address study heterogeneity, we categorized studies by type of intervention and study outcome. The review suggests that more comprehensive PDMP legislation is associated with decreases in the number of opioid prescriptions overall and the number of risky prescriptions prescribed or dispensed. However, this review shows that much is still unknown, encourages improvements to PDMPs and policies, and suggests further research. Full article

The whitemarked tussock moth (WMTM), Orgyia leucostigma (J.E. Smith) (Lepidoptera: Erebidae), is an economic pest in Nova Scotia, Canada, where it undergoes periodic outbreaks defoliating several tree species of economic value, including balsam fir, Abies balsamea (L.) Miller (Pinaceae). Herein is described a releasing device for the WMTM sex pheromone (Z,Z)-6, 9-heneicosadien-11-one based on a rubber septum, which converts pheromone precursors, such as acetals, namely (Z,Z)-11,11-dimethoxy-6,9-heneicosadiene and (Z,Z)-6,9-heneicosadien-11-one ethylene ketal, to the pheromone itself by the action of acetic acid and releases it over time. The pheromone is unstable in nature and, consequently, lures made with this compound will only attract WMTM for a day or two. The two pheromone precursors, however, are more stable, and are converted slowly into the pheromone by acetic acid impregnated in the releasing device, or by acidic conditions in the environment. The two pheromone precursors were synthesized in 2019 using a modified, previously published approach. Field trapping studies conducted from 2019–22 showed that traps baited with rubber septa loaded with either (Z,Z)-11,11-dimethoxy-6,9-heneicosadiene by itself or (Z,Z)-6,9-heneicosadien-11-one ethylene ketal plus acetic acid consistently caught significantly more WMTM than traps baited with blank septa in most experiments. Full article

Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of Artemisia dracunculus L., termed PMI5011, improves blood glucose and insulin sensitivity via skeletal muscle, rather than fat, and may therefore spare bone. Here, we examine the effects of PMI5011 and an identified active compound within PMI5011 (2′,4′-dihydroxy-4-methoxydihydrochalcone, DMC-2) on pre-osteoblasts. We hypothesized that PMI5011 and DMC-2 will not inhibit osteogenesis. To test our hypothesis, MC3T3-E1 cells were induced in osteogenic media with and without PMI5011 or DMC-2. Cell lysates were probed for osteogenic gene expression and protein content and were stained for osteogenic endpoints. Neither compound had an effect on early stain outcomes for alkaline phosphatase or collagen. Contrary to our hypothesis, PMI5011 at 30 µg/mL significantly increases osteogenic gene expression as early as day 1. Further, osteogenic proteins and cell culture mineralization trend higher for PMI5011-treated wells. Treatment with DMC-2 at 1 µg/mL similarly increased osteogenic gene expression and significantly increased mineralization, although protein content did not trend higher. Our data suggest that PMI5011 and DMC-2 have the potential to promote bone health via improved osteoblast maturation and activity. Full article

Background: β-cryptoxanthin is a dietary carotenoid for which there have been few studies on the safety and pharmacokinetics following daily oral supplementation. Methods: 90 healthy Asian women between 21 and 35 years were randomized into three groups: 3 and 6 mg/day oral β-cryptoxanthin, and placebo. At 2, 4, and 8 weeks of supplementation, plasma carotenoid levels were measured. The effects of β-cryptoxanthin on blood retinoid-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition were investigated. Results: β-cryptoxanthin supplementation for 8 weeks (3 and 6 mg/day) was found to be safe and well tolerated. Plasma β-cryptoxanthin concentration was significantly higher in the 6 mg/day group (9.0 ± 4.1 µmol/L) compared to 3 mg/day group (6.0 ± 2.6 µmol/L) (p < 0.03), and placebo (0.4 ± 0.1 µmol/L) (p < 0.001) after 8 weeks. Plasma all-trans retinol, α-cryptoxanthin, α-carotene, β-carotene, lycopene, lutein, and zeaxanthin levels were not significantly changed. No effects were found on blood retinol-dependent gene expression, mood, physical activity and sleep, metabolic parameters, and fecal microbial composition. Conclusions: Oral β-cryptoxanthin supplementation over 8 weeks lead to high plasma concentrations of β-cryptoxanthin, with no impact on other carotenoids, and was well tolerated in healthy women. Full article

There is a lack of investigations assessing the performance of systemic inflammation indices as outcome predictive tools in African Americans with prostate cancer. This study aims to assess the relationships between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation (SII), and systemic inflammation response index (SIRI) with survival outcomes among 680 diverse men with prostate cancer. Routine blood results were collected from self-identified African American and European American patients. We applied multivariable Cox regression modeling to examine the associations of systemic inflammation indices with overall and prostate cancer-specific survival. The median survival follow-up was 5.9 years, with 194 deaths. NLR, SII, and SIRI, but not PLR, showed associations with all-cause and prostate cancer-specific mortality when coded as dichotomized and continuous variables. NLR and SIRI were significantly associated with prostate cancer-specific mortality among all men (hazard ratio (HR) 2.56 for high vs. low NLR; HR 3.24 for high vs. low SIRI) and African American men (HR 2.96 for high vs. low NLR; HR 3.19 for high vs. low SIRI). Among European Americans, only SII showed an association with prostate cancer-specific survival. These observations suggest that inflammation indices merit further study as predictors of prostate cancer mortality. Full article

The importance of genomic surveillance on emerging diseases continues to be highlighted with the ongoing SARS-CoV-2 pandemic. Here, we present an analysis of a new bat-borne mumps virus (MuV) in a captive colony of lesser dawn bats (Eonycteris spelaea). This report describes an investigation of MuV-specific data originally collected as part of a longitudinal virome study of apparently healthy, captive lesser dawn bats in Southeast Asia (BioProject ID PRJNA561193) which was the first report of a MuV-like virus, named dawn bat paramyxovirus (DbPV), in bats outside of Africa. More in-depth analysis of these original RNA sequences in the current report reveals that the new DbPV genome shares only 86% amino acid identity with the RNA-dependent RNA polymerase of its closest relative, the African bat-borne mumps virus (AbMuV). While there is no obvious immediate cause for concern, it is important to continue investigating and monitoring bat-borne MuVs to determine the risk of human infection. Full article

The interaction between leukocytes and cytokine-activated retinal endothelium is an initiating step in non-infectious uveitis involving the posterior eye, mediated by cell adhesion molecules. However, because cell adhesion molecules are required for immune surveillance, therapeutic interventions would ideally be employed indirectly. Using 28 primary human retinal endothelial cell isolates, this study sought to identify transcription factor targets for reducing levels of the key retinal endothelial cell adhesion molecule, intercellular adhesion molecule (ICAM)-1, and limiting leukocyte binding to the retinal endothelium. Five candidate transcription factors—C2CD4B, EGR3, FOSB, IRF1, and JUNB—were identified by differential expression analysis of a transcriptome generated from IL-1β- or TNF-α-stimulated human retinal endothelial cells, interpreted in the context of the published literature. Further filtering involved molecular studies: of the five candidates, C2CD4B and IRF1 consistently demonstrated extended induction in IL-1β- or TNF-α-activated retinal endothelial cells and demonstrated a significant decrease in both ICAM-1 transcript and ICAM-1 membrane-bound protein expression by cytokine-activated retinal endothelial cells following treatment with small interfering RNA. RNA interference of C2CD4B or IRF1 significantly reduced leukocyte binding in a majority of human retinal endothelial cell isolates stimulated by IL-1β or TNF-α. Our observations suggest that the transcription factors C2CD4B and IRF1 may be potential drug targets for limiting leukocyte–retinal endothelial cell interactions in non-infectious uveitis involving the posterior eye. Full article

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents. Full article

Urinary PGE-M is a stable metabolite of prostaglandin E2 (PGE2). PGE2 is a product of the inflammatory COX signaling pathway and has been associated with cancer incidence and metastasis. Its synthesis can be inhibited by aspirin. We investigated the association of PGE-M with lethal prostate cancer in a case–control study of African American (AA) and European American men. We measured urinary PGE-M using mass-spectrometry. Samples were obtained from 977 cases and 1022 controls at the time of recruitment. We applied multivariable logistic and Cox regression modeling to examine associations of PGE-M with prostate cancer and participant survival. Median survival follow-up was 8.4 years, with 246 deaths among cases. Self-reported aspirin use over the past 5 years was assessed with a questionnaire. Race/ethnicity was self-reported. Urinary PGE-M levels did not differ between men with prostate cancer and population-based controls. We observed no association between PGE-M and aggressive disease nor prostate-cancer-specific survival. However, we observed a statistically significant association between higher (>median) PGE-M and all-cause mortality in AA cases who did not regularly use aspirin (HR = 2.04, 95% CI 1.23–3.37). Among cases who reported using aspirin, there was no association. Our study does not support a meaningful association between urinary PGE-M and prostate cancer. Moreover, PGE-M levels were not associated with aggressive prostate cancer. However, the observed association between elevated PGE-M and all-cause mortality in AA non-aspirin users reinforces the potential benefit of aspirin to reduce mortality among AA men with prostate cancer. Full article

Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeO_xNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeO_xNPs present in the environment. We, therefore, analysed the potential toxicity of FeO_xNPs of different forms (Fe₃O₄, α-Fe₂O₃ and γ-Fe₂O₃) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeO_x-mix). A preliminary in vitro study indicated Fe₃O₄ and FeO_x-mix were more cytotoxic than either form of Fe₂O₃ in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague–Dawley rats, nose-only exposure, 50 µg/m³ and 500 µg/m³, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects. Full article