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The health impacts of the diurnal temperature range (DTR), which may be affected by climate change, have received little attention. The objectives of this study were (1) to evaluate the association of DTR and cardiopulmonary outcomes, (2) to select the proper thresholds for a DTR warning system, and (3) to identify vulnerable groups. The weather and health records in Taiwan from 2000 to 2019, with a maximum DTR of 12.8 °C, were analyzed using generalized additive models. The health outcomes included cardiovascular (CVD) and respiratory disease (RD) categories and several sub-categories, such as ischemic heart disease, stroke, pneumonia, asthma, and chronic obstructive pulmonary disease. The results showed that the associations of DTR and cardiopulmonary outcomes were as significant as, and sometimes even stronger than, those of the daily maximum temperature and daily minimum apparent temperature in the warm and cold seasons, respectively. The significant association began at DTR of 6 °C, lower than previously reported. The identified DTR warning thresholds were 8.5 and 11 °C for the warm and cold seasons, respectively. DTR is statistically significantly associated with a 5-36% and a 9-20% increase in cardiopulmonary emergency and hospitalized cases in the warm season with a 1 °C increase above 8.5 °C, respectively. In the cold season, DTR is significantly associated with 7-41%, 4-30%, and 36-100% increases in cardiopulmonary emergency, hospitalized, and mortality with a 1 °C increase above 11 °C, respectively. People with hypertension, hyperglycemia, and hyperlipidemia had even higher risks. Vulnerable age and sex groups were identified if they had a lower DTR-health threshold than the general population, which can be integrated into a warning system. In conclusion, DTR may be increased on a local or city scale under climate change; a DTR warning system and vulnerable group identification may be warranted in most countries for health risk reduction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The two major molecular subtypes of pancreatic adenocarcinoma reportedly have differential response to FOLFIRINOX-based therapy. To promote rapid assignment of basal versus classical subtypes, an array-based single-sample classifier assay was developed and applied to 74 formalin-fixed, paraffin-embedded biopsy or resection specimens of known subtype based on transcriptomics. The Purity Independent Subtyping of Tumors (PurIST) algorithm assigns subtype based on relative expression of 16 RNAs counted by RNA sequencing (RNAseq) versus more practical array-based NanoString nCounter Elements XT technology. Subtype calls were largely concordant between RNAseq and array methods (72/74, 97% agreement). Compared with the lengthy RNAseq protocol, the array-based assay takes just 3 working days to analyze, permitting rapid reporting of tumor subtype. In conclusion, the PurIST pancreatic cancer classifier has robust performance to classify pancreatic adenocarcinoma into basal versus classical subtypes. Clinical validation studies are underway to evaluate outcome in patients whose standard-of-care chemotherapy regimen is selected on the basis of rapid subtype assignment (NCT04683315)., Competing Interests: Disclosure Statement N.U.R. and J.J.Y. are patent holders on Purity Independent Subtyping of Tumors (PurIST) technology for subtyping pancreatic ductal adenocarcinoma (US17/601,002). GeneCentric Therapeutics, Inc., had no involvement in the current study but acquired an exclusive license from the University of North Carolina at Chapel Hill related to PurIST technology., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction: Psychosocial distress screening of cancer patients is an American College of Surgeons Commission on Cancer mandate for accredited cancer programs. We evaluated psychosocial distress in breast cancer patients to characterize risk factors for high distress scores at a safety net hospital., Materials and Methods: The psychosocial distress screening form includes a list of potential issues and a distress score scaled from 1 through 10. Psychosocial distress screening results were retrospectively analyzed, along with patient demographics and clinical data. Cochran-Mantel-Haenszel test was applied to identify predictors for high distress scores, which were defined as a score of 5 and greater., Results: 775 distress screens were completed by 171 breast cancer patients. High distress scores were reported in 21.3%. Patients who had no evidence of disease at time of screening were less likely to report a high distress score compared to those who were newly diagnosed or in active treatment (odds ratio 0.51, 95% CI, 0.38-0.68, P< .0001). Patients with high distress scores were more likely to report concerns with insurance (29.1% vs. 7.6%, P< .0001), transportation (16.4% vs. 4.6%, P< .0001), housing (15.2% vs 2.1%, P< .0001), sadness/depression (63.6% vs. 14.1, P< .0001), and physical issues (89.1% vs. 52.8%, P< .0001)., Conclusion: Status of cancer at time of screening, particularly newly diagnosed cancer and active treatment of cancer were associated with high distress scores in this patient group. While there should be an emphasis to ensure patients with these risk factors receive psychosocial distress screening, routine periodic screening for all patients should continue to be implemented to ensure quality cancer care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Backgound and Aims: We aimed at determining the effects of statin use on coronary artery disease (CAD) and stroke risks in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS)., Methods: We retrospectively enrolled patients with ACOS treated with (N = 916) and without (N = 6338) statins. The cumulative incidence of CAD and stroke (ischemic and hemorrhagic) was analyzed through time-dependent Cox proportional regression. After adjustment for sex, age, comorbidities, inhaled corticosteroid steroid (ICS) use, and oral steroid (OS) use, we calculated the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for CAD or stroke in the statin users (long-term [>600 days] and short-term [≤600 days]) compared with the non-users., Results: Among the statin users, aHRs (95% CIs) for CAD and stroke were 0.50 (0.41-0.62) and 0.83 (0.63-1.09), respectively; moreover, aHRs were 0.30 (0.09-0.99) and 0.90 (0.68-1.20) for ischemic and hemorrhagic stroke, respectively. aHRs (95% CIs) for CAD and stroke were 0.58 (0.47-0.71) and 0.93 (0.70-1.23), respectively, in the short-term users and 0.23 (0.13-0.41) and 0.42 (0.19-0.89), respectively, in the long-term users., Conclusions: CAD risk was lower in all statin users, regardless of the duration of use, whereas ischemic stroke risk was lower only in the long-term statin users. No association was observed between hemorrhagic stroke risk and statin use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wild type (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed. We established that DAT-KO results in a chronic anxiety-like state, seen as an increase in bottom-dwelling and thigmotaxis. Similar effects were produced by aging and acute cocaine administration, both leading to reduction in DAT mRNA abundance (qPCR). Inhibition of D1 activity counteracted the anxiety-like effects associated with DAT deficit, independent of its origin. Inhibition of D2/D3 receptors reduced anxiety in young DAT-KO, and enhanced the anxiogenic effects of cocaine in WT, but did not affect aged WT or DAT-KO fish. These findings provide new evidence that the dopaminergic system plays a critical role in anxiety-like states, and suggest that adult zebrafish provide a sensitive diurnal vertebrate model for elucidating the molecular mechanisms of anxiety and a platform for anxiolytic drug screens., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: We compared the accuracy of shorter-time dual-phase (18)F-FDG PET/CT in evaluating 94 different lung nodules classified as solid or ground-glass nodules (GGNs)., Materials and Methods: Early and delayed maximum standardized uptake values (SUV(max)) as well as the retention index (RI) of each nodule were determined in 75 solid nodules and 19 GGNs., Results: In solid nodules, early SUV(max), delayed SUV(max), and RI were higher in malignant than in benign lesions. In GGNs, these values were not significantly lower in the malignant than in the benign lesions., Conclusion: In the patient group with solid nodules, shorter-time dual-phase (18)F-FDG PET/CT could significantly differentiate the malignant from the benign ones., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF Ab. Of the 2 TF-positive lines, only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, < 5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor-bearing and control mice in an inferior vena cava stenosis model. The results of the present study using a xenograft mouse model suggest that tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis.

P-selectin expression has been shown in Helicobacter pylori-infected persons, an infection that has been clinically associated with platelet-related diseases, such as idiopathic thrombocytopenic purpura. However, the role of P-selectin expression during H pylori infection remains unclear. In this study, we hypothesized that P-selectin expression was associated with platelet aggregation during H pylori infection. Using flow cytometry, we examined the levels of adhesion between H pylori and platelets as well as the levels of P-selectin expression and platelet phosphatidylserine (PS) expression during H pylori infection. Significantly high levels of adhesion between pro-aggregatory bacteria and platelets were observed. We identified that H pylori IgG is required for bacteria to induce P-selectin expression and that a significant release of P-selectin is essential for H pylori to induce aggregation. In addition, cellular apoptotic signs, such as membrane blebbing, were observed in platelet aggregates. PS expression was also detected in platelets during infection with both pro-aggrogatory and nonaggregatory strains of H pylori. These results suggest that the decrease in platelet counts seen during H pylori infection is the result of P-selection-dependent platelet aggregation and PS expression induced by the bacteria.

Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.