Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting.

INTRODUCTION: Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities. METHODS: Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables. Statistical significance was set at p < 0.05. RESULTS: A total of 286 patients met inclusion criteria. Eighty-nine patients (31.1%) were underrepresented minorities (URM). Fifty-seven (64.0%) URMs presented during an EP versus 100 (50.8%) non-URMs (p = 0.037). Forty-one (46.1%) URMs were reviewed at PMDC versus 71 (36.0%) non-URMs (p = 0.10). No differences in clinical and pathologic stage between the cohorts (p = 0.28) were present. URMs took 22 days longer on average to receive treatment (66.5 days vs. 44.8 days, p = 0.003) in the EP cohort and 18 days longer in OP cohort (58.0 days vs. 40.5 days, p < 0.001) compared with non-URMs. Pancreatic Multidisciplinary Clinic enrollment in EP cohort eliminated the difference in time to treatment between cohorts (48.3 days vs. 37.0 days; p = 0.151). RESULTS: Underrepresented minorities were more likely to be diagnosed via EP and showed delayed times to treatment compared with non-URM counterparts. Our PMDC alleviated some of these observed disparities. Future studies are required to elucidate the specific factors that resulted in these findings and to identify solutions.

Adapted poling to break the nonlinear efficiency limit in nanophotonic lithium niobate waveguides.

Nonlinear frequency mixing is a method to extend the wavelength range of optical sources with applications in quantum information and photonic signal processing. Lithium niobate with periodic poling is the most widely used material for frequency mixing due to its strong second-order nonlinear coefficient. The recent development using nanophotonic lithium niobate waveguides promises to improve nonlinear efficiencies by orders of magnitude thanks to subwavelength optical confinement. However, the intrinsic nanoscale inhomogeneity of nanophotonic lithium niobate waveguides limits the coherent interaction length, leading to low nonlinear efficiencies. Here we show improved second-order nonlinear efficiency in nanophotonic lithium niobate waveguides that breaks the limit imposed by nanoscale inhomogeneity. This is realized by developing the adapted poling approach to eliminate the impact of nanoscale inhomogeneity. We realize an overall second-harmonic efficiency of 104% W-1 (without cavity enhancement), approaching the theoretical performance for nanophotonic lithium niobate waveguides. The ideal square dependence of the nonlinear efficiency on the waveguide length is recovered. Phase-matching bandwidths and temperature tuneability are improved through dispersion engineering. We finally demonstrate a conversion ratio from pump to second-harmonic power greater than 80% in a single-pass configuration with pump power as low as 20 mW. Our work therefore breaks the trade-off between the conversion ratio and pump power, offering a potential solution for highly efficient and scalable nonlinear-optical sources, amplifiers and converters.

Decreasing utilization of surgical interventions amongst patients with pancreatic neuroendocrine tumor with liver metastases.

BACKGROUND: Since 2013, North American Neuroendocrine Tumor Society (NANETS) consensus-guidelines have endorsed consideration of surgical intervention for pancreatic- neuroendocrine tumors (PNET) with liver metastases. METHODS: Patients with non-functional PNET with liver only metastases from 2010 to 2019 were identified from the National Cancer Database. RESULTS: 34.7% underwent surgical intervention (13% PNET resection, 2.1% surgical management of liver metastases (SMLM), 19.5% PNET resection â€‹+ â€‹SMLM). In multivariable analysis, government insurance, year of diagnosis>2013, increasing primary tumor size were associated with lower rate of surgical intervention. Receiving treatment at an academic center (OR 3.59, 95%CI 1.81-7.11; P â€‹< â€‹0.001) or integrated cancer network (OR 3.21, 95%CI 1.57-6.54; P â€‹= â€‹0.001) was associated with a higher rate of surgical intervention. The overall rate of surgical intervention decreased from 45.7% in 2010 to 23.0% in 2019. CONCLUSION: Despite guideline recommendations and the suggested survival benefits, only one-third of patients underwent surgical intervention, potentially influenced by the rising utilization of systemic therapy in the past decade.

Evaluation of survival outcome and prognostic factors for oral cavity cancer treated with volumetric arc therapy.

PURPOSE: This study aimed to evaluate the survival outcomes and identify prognostic factors for patients with oral cavity cancer (OCC) who underwent adjuvant treatment with volumetric arc therapy (VMAT) using simultaneous integrated boost (SIB). METHODS: Data was collected for post-operated patients of carcinoma of oral cavity who received adjuvant VMAT with SIB between June 2018 and December 2022. The data was entered and analyzed using SPSS software version 20.0. Survival rates were estimated using Kaplan Meier method. To determine survival difference between the groups, log rank test was used. Multivariate analyses were performed with Cox proportional hazard model and p value < 0.05 was considered as significant. RESULTS: A total of 178 patients were included in the study. The median follow-up period was 26 months (range 3-56 months). The 3-year OS, DFS, and LRC rates were 78% (95% CI 77-79%), 76% (95% CI 74-77%), and 81% (95% CI 80-82%), respectively. Univariate analysis identified age ≥ 50 years, lymph node involvement, extracapsular extension (ECE), and N2-N3 disease as significant adverse prognostic factors for OS, DFS, and LRC. Multivariate analysis confirmed age ≥ 50 years and nodal involvement as independent predictors of worse OS, DFS, and LRC. Additionally, ECE independently affected OS and DFS. CONCLUSION: Adjuvant treatment with VMAT using SIBin patients with OCC is effective. Age and nodal involvement had significant impact on LRC, DFSand OS while ECE on DFSand OS.

Visible-telecom tunable dual-band optical isolator based on dynamic modulation in thin-film lithium niobate.

Optical isolators are an essential component of photonic systems. Current integrated optical isolators have limited bandwidths due to stringent phase-matching conditions, resonant structures, or material absorption. Here, we demonstrate a wideband integrated optical isolator in thin-film lithium niobate photonics. We use dynamic standing-wave modulation in a tandem configuration to break Lorentz reciprocity and achieve isolation. We measure an isolation ratio of 15 dB and insertion loss below 0.5 dB for a continuous wave laser input at 1550 nm. In addition, we experimentally show that this isolator can simultaneously operate at visible and telecom wavelengths with comparable performance. Isolation bandwidths up to ∼100 nm can be achieved simultaneously at both visible and telecom wavelengths, limited only by the modulation bandwidth. Our device's dual-band isolation, high flexibility, and real-time tunability can enable novel non-reciprocal functionality on integrated photonic platforms.

Lung Imaging in COPD Part 1: Clinical Usefulness.

COPD is a condition characterized by chronic airflow obstruction resulting from chronic bronchitis, emphysema, or both. The clinical picture is usually progressive with respiratory symptoms such as exertional dyspnea and chronic cough. For many years, spirometry was used to establish a diagnosis of COPD. Recent advancements in imaging techniques allow quantitative and qualitative analysis of the lung parenchyma as well as related airways and vascular and extrapulmonary manifestations of COPD. These imaging methods may allow prognostication of disease and shed light on the efficacy of pharmacologic and nonpharmacologic interventions. This is the first of a two-part series of articles on the usefulness of imaging methods in COPD, and it highlights useful information that clinicians can obtain from these imaging studies to make more accurate diagnosis and therapeutic decisions.

Lung Imaging in COPD Part 2: Emerging Concepts.

The diagnosis, prognostication, and differentiation of phenotypes of COPD can be facilitated by CT scan imaging of the chest. CT scan imaging of the chest is a prerequisite for lung volume reduction surgery and lung transplantation. Quantitative analysis can be used to evaluate extent of disease progression. Evolving imaging techniques include micro-CT scan, ultra-high-resolution and photon-counting CT scan imaging, and MRI. Potential advantages of these newer techniques include improved resolution, prediction of reversibility, and obviation of radiation exposure. This article discusses important emerging techniques in imaging patients with COPD. The clinical usefulness of these emerging techniques as they stand today are tabulated for the benefit of the practicing pulmonologist.

The reproductive effects of the cancer chemotherapy agent, Carmofur, on Daphnia magna are mediated by its metabolite, 5-Fluorouracil.

Carmofur is an antineoplastic agent that inhibits ceramidase, a key enzyme in the sphingolipid pathway. Previous research suggests carmofur represses reproductive maturity in Daphnia magna. The purpose of this experiment was to confirm carmofur's effects on fecundity and reproductive maturity over two generations. A chronic toxicity test found reproductive maturity was delayed from 9 to 19 days by 0.80 µM carmofur with a 99.7% drop in reproduction, probably caused by delayed ovarian development. Second generation effects were even greater with 0% reproductive success at 0.40 µM. To our surprise, carmofur was not measured in the media by HPLC 24 h after exposure. Previous research indicated that carmofur is unstable in water and hydrolyzed into 5-fluorouracil (5-FU). Therefore, the chronic toxicity study was repeated with 5-FU and similar effects on reproductive maturity were observed at similar concentrations despite very different acute toxicities (48 h carmofur LC50 = 1.93 µM; 5-FU LC50 = 207 µM). 5-FU delayed reproductive maturity from 9 to 21 days with a 71.12% drop in reproduction at 0.80 µM and greater effects in the 2nd generation similar to carmofur. 5-FU was found stable in aquatic media and HPLC confirmed 5-FU was hydrolyzed from carmofur within 24 h. In conclusion, carmofur and 5-FU reduce fecundity because they delay reproductive maturity and ovarian development in Daphnia magna. We conclude that the reproductive effects observed after carmofur treatment are primarily mediated by its breakdown product, 5-FU. This further underscores the importance of measuring chemical concentrations and evaluating chemical metabolism and decomposition when determining toxicity, especially of chemotherapeutic agents.Clinical trials registration Not applicable.

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice.

Background: Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. Methods: Using hydrodynamic tail-vein injection, we overexpress Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli. Results: In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that overexpression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury, independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease-promoting and interferon (IFN)-related genes, including Ackr2 and Cxcl11. Conclusions: We demonstrate that, in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select IFN signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.

Smartphone-based Fluoride-specific Sensor for Rapid and Affordable Colorimetric Detection and Precise Quantification at Sub-ppm Levels for Field Applications.

Higher levels of fluoride (F-) in groundwater constitute a severe problem that affects more than 200 million people spread over 25 countries. It is essential not only to detect but also to accurately quantify aqueous F- to ensure safety. The need of the hour is to develop smart water quality testing systems that would be effective in location-based real-time water quality data collection, devoid of professional expertise for handling. We report a cheap, handheld, portable mobile device for colorimetric detection and rapid estimation of F- in water by the application of the synthesized core-shell nanoparticles (near-cubic ceria@zirconia nanocages) and a chemoresponsive dye (xylenol orange). The nanomaterial has been characterized thoroughly, and the mechanism of sensing has been studied in detail. The sensor system is highly selective toward F- and shows unprecedented sensitivity in the range of 0.1-5 ppm of F-, in field water samples, which is the transition regime, where remedial measures may be needed. It addresses multiple issues expressed by indicator-based metal complexes used to determine F- previously. Consistency in the performance of the sensing material has been tested with synthetic F- standards, water samples from F- affected regions, and dental care products like toothpastes and mouthwash using a smartphone attachment and by the naked eye. The sensor performs better than what was reported by prior works on aqueous F- sensing.

Cross-sectional study on smokeless tobacco use, awareness and expenditure in an urban slum of Bhavnagar, western India.

Background: Data are sparse on smokeless tobacco (SLT) use in Bhavnagar. We assessed the prevalence and awareness of and expenditure on SLT use in Bhavnagar. Methods: We conducted a community-based, cross- sectional study in an urban slum of Bhavnagar on a sample of 260 SLT users for a period of three months in 2017. Results: The prevalence of SLT use in Bhavnagar was 27.3% (95% CI 25%-30%). Mawa, a preparation of tobacco flakes mixed with areca nut and lime, was the most commonly chewed form of tobacco; commonly kept in the buccal mucosa. The mean age ofstarting SLT use was 25 years; the mean number of years since chewing was 15 years; the mean time tobacco was kept in the mouth per consumption was 5 minutes and the mean number of packets of tobacco consumed per day was five. The mean expenditure on SLT use per month was ?536. All SLT users were aware that tobacco consumption led to oral cancer. Peer influence was the most common (75%) reason for starting SLT use, and addiction was the most common (74%) reason for its continued use. Among SLT users, 47% had made at least one attempt to quit; of them, 98% had tried self-control for quitting but did not succeed. The most common (72%) reason given by those not able to quit (n=119) was addiction to SLT use. Among the 260 study participants, 72% had read the warnings on packets of tobacco; 59% wished to chew tobacco even after reading the warnings and 62% opined on banning the sale and consumption of tobacco. Ninety-two per cent of SLT users were not comfortable with the idea that imitating them, their children too would start chewing tobacco. Conclusions: Every third person in the urban slum of Bhavnagar was a SLT user. Even though SLT users knew about the harmful effects of tobacco, only a handful were able to quit due to addiction to it. This burden on health services, in addition to the expenditure on purchase of tobacco, requires a comprehensive tobacco cessation programme at the community level.