Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Colorectal Carcinoma Infiltrating B Lymphocytes Are Active Secretors of the Immunoglobulin Isotypes A, G, and M

Despite the importance of tumor infiltrating B cells (TiBc) in immunological circuits, their functional role is scarcely investigated. Here, we analyzed immunoglobulin (Ig) secretion of the subtypes IgA, IgG, and IgM of TiBc from freshly resected primary and secondary colorectal carcinomas (CRC) by FluoroSpot (n = 30 CRC) directly ex vivo. High, intermediate, and low secretion was observed in 33%, 37%, and 30% of the tumors for IgA; in 10%, 27%, and 63% for IgG; and in 21%, 36%, and 50% for IgM, respectively. These ex vivo data validate our previous findings: Most TiBc present in the CRC microenvironment are functional since they produce and actively secrete Ig (IgA > IgG > IgM). Of note, the presence of major histocompatibility complex (MHC) class II expressing cells in the tumor micromilieu only correlated with IgG secretion (p = 0.0004). Supporting recent findings in several other tumor entities, TiBc in CRC thus likely can contribute to tumor control in a dual role of sole antigen-presentation and additionally anti-tumoral Ig-production.
Role of lean leadership in the lean maturity—second-order problem-solving relationship: a mixed methods study

Objectives To investigate the relationship between lean adoption and problem-solving behaviour in nursing teams, and to explore the practices of lean leaders on nursing wards to reveal how they can stimulate second-order problem-solving within their teams. Design A mixed-methods retrospective multiple case study using semistructured interviews. Interview data were used to assess the level of lean maturity (based on a customised validated instrument) and the level of second-order problem-solving (based on scenarios). Within-case and cross-case analyses were employed to identify lean leadership practices. Setting 14 nursing teams, with different levels of lean maturity, in a Dutch hospital. Participants Three members of each nursing team were interviewed: the team leader, one nurse from the ward’s core team for the lean-based quality improvement programme and one nurse outside the core team. Interventions The nursing teams were in various phases of a lean-based quality improvement programme: ‘The Productive Ward – Releasing Time to Care’. Results A strongly significant positive relationship between lean maturity and second-order problem-solving was found: β=0.68, R2=0.46, p<0.001. Further, the results indicated a potential strengthening effect of lean leadership on this relationship. Seven lean leadership practices emerged from the data collected in a nursing ward setting: (1) convincing and setting an example; (2) unlocking individual and team potential; (3) solving problems systematically; (4) enthusing, actively participating and visualising; (5) developing self-managing teams; (6) sensing, as orchestrator, what is needed for change; and (7) listening, sharing information and appreciating. These practices have a strong link with transformational leadership. Conclusions As lean matures, nursing teams reach a higher level of second-order problem-solving. In later stages, lean leaders increasingly relinquish responsibility by developing self-managing teams.
Interleukin‐13 and interleukin‐33 mRNA are underexpressed in the duodenal mucosa of German Shepherd dogs with chronic enteropathy

Abstract Background A recent genome‐wide association study in German Shepherd dogs (GSDs) with chronic enteropathy (CE) has identified polymorphisms in the Th2 cytokine genes. Hypothesis/objective To determine if the expression of the Th2 cytokines, interleukin‐13 (IL‐13) and interleukin‐33 (IL‐33), is altered in the duodenal mucosa of GSDs with CE compared to non‐GSDs with CE and healthy dogs. Animals Twenty client‐owned dogs diagnosed with CE (10 GSDs and 10 non‐GSDs) at the Bristol Veterinary School and 8 healthy Beagle dogs from the Iowa State University Service Colony. Methods Retrospective study using archived paraffin‐embedded duodenal biopsy samples. A novel RNA in situ hybridization technology (RNAscope) was used to hybridize IL‐13 and IL‐33 mRNA probes onto at least 10 sections from duodenal biopsy samples for each dog. RNAscope signals were visualized using a microscope and semi‐quantitative assessment was performed by a single operator. Results Based on duodenal villus, subvillus, epithelial, and lamina propria average expression scores, GSDs with CE had significantly lower IL‐13 and IL‐33 mRNA expression compared to non‐GSDs with CE (IL‐13, P < .04; IL‐33, P < .02) and healthy Beagle dogs (IL‐13, P < .02; IL‐33, P < .004). Conclusions and Clinical Importance Similar to human patients with ulcerative colitis, a subtype of human inflammatory bowel disease, these data indicate that Th2 cytokines may be involved in the pathogenesis of CE in GSDs.
Exploring simulated driving performance among varsity male soccer players

Abstract Background: It is documented that male athletes display riskier behaviors while driving (as well as in life in general) than female athletes and nonathletes. However, the literature has reported that athletes show better driving ability than nonathletes. This paradox between behaviors and abilities motivated the present study to further understand the collision risk of varsity athletes. Objective: The current study estimates the performance differences between varsity male soccer players and male undergraduate nonathletes on (1) a driving task and (2) three perceptual–cognitive tasks (associated with collision risk prediction; i.e., Useful Field of View [UFOV] test). Methods: Thirty-five male undergraduate students (15 varsity soccer players, 20 undergraduate nonathletes) took part in this study. Driving performance was assessed during 14 min of urban commuting using a driving simulator. While completing the simulated driving task and UFOV test, the physiological responses were monitored using an electrocardiograph (ECG) to document heart rate variability (HRV). Results: Varsity soccer players showed more risky behaviors at the wheel compared to their nonathlete student peers. Varsity soccer players spent more time over the speed limit, committed more driving errors, and adopted fewer safe and legal behaviors. However, no difference was observed between both groups on driving skill variables (i.e., vehicle control, vehicle mobility, ecodriving). For subtests 1 and 2 of the UFOV (i.e., processing speed, divided attention), both groups performed identically (i.e., 17 ms). The nonathlete group tended to perform better on the selective attention task (i.e., subtest 3 of UFOV test; 63.2 ± 6.2 ms vs. 87.2 ± 10.7 ms, respectively; this difference was not significant, P = .76). Conclusion: Preventive driving measures should be enforced in this high-risk population to develop strategies for risk reduction in male team athletes.
Risk factors for lymph node metastasis in duodenal neuroendocrine tumors

Abstract Duodenal neuroendocrine tumors (NETs) are rare, and risk factors associated with lymph node (LN) metastasis are still not well defined. The aim of this study was to investigate risk factors of LN metastasis in duodenal NETs based on the final histopathologic results and clinical follow-up data. This study included a total of 44 duodenal NETs in 38 patients who underwent endoscopic or surgical resection between January 2008 and December 2015. Diagnosis of duodenal NETs was confirmed based on immunohistochemical staining of chromogranin A, synaptophysin, and CD56; the clinicopathologic records were collected at the time of the initial diagnosis of duodenal NETs. Most duodenal NETs were small (≤1 cm in 33 tumors), World Health Organization (WHO) grade G1 (in 32 tumors), limited to the mucosa and/or submucosa (in 40 tumors), and located at the duodenal bulb (in 32 tumors). Of 44 tumors, lymphovascular invasion was present in 4 (9.1%), and among 38 patients, LN metastasis was detected in 4 (10.5%). LN metastases were significantly associated with the non-bulb location, tumor size >10 mm, tumor invasion into the muscularis propria or deeper, WHO grade G2, and lymphovascular invasion. During the mean follow-up period of 54.5 months (range, 24–123 months), recurrence occurred in 1 patient. Non-bulb location, tumor size >10 mm, invasion beyond the submucosa, WHO grade G2, and lymphovascular invasion are risk factors of LN metastasis in duodenal NETs. These findings can help clinicians choose the appropriate therapeutic modality for duodenal NETs.
Resveratrol reduces brain injury after subarachnoid hemorrhage by inhibiting oxidative stress and endoplasmic reticulum stress

Previous studies have shown that resveratrol, a bioactive substance found in many plants, can reduce early brain injury after subarachnoid hemorrhage, but how it acts is still unclear. This study explored the mechanism using the experimental subarachnoid hemorrhage rat model established by injecting autologous blood into the cerebellomedullary cistern. Rat models were treated with an intraperitoneal injection of 60 mg/kg resveratrol 2, 6, 24 and 46 hours after injury. At 48 hours after injury, their neurological function was assessed using a modified Garcia score. Brain edema was measured by the wet-dry method. Neuronal apoptosis in the prefrontal cortex was detected by terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay. Levels of reactive oxygen species and malondialdehyde in the prefrontal cortex were determined by colorimetry. CHOP, glucose-regulated protein 78, nuclear factor-erythroid 2-related factor 2 and heme oxygenase-1 mRNA expression levels in the prefrontal cortex were measured by reverse transcription polymerase chain reaction. Tumor necrosis factor-alpha content in the prefrontal cortex was detected by enzyme linked immunosorbent assay. Immunohistochemical staining was used to detect the number of positive cells of nuclear factor-erythroid 2-related factor 2, heme oxygenase 1, glucose-regulated protein 78, CHOP and glial fibrillary acidic protein. Western blot assay was utilized to analyze the expression levels of nuclear factor-erythroid 2-related factor 2, heme oxygenase 1, glucose-regulated protein 78 and CHOP protein expression levels in the prefrontal cortex. The results showed that resveratrol treatment markedly alleviated neurological deficits and brain edema in experimental subarachnoid hemorrhage rats, and reduced neuronal apoptosis in the prefrontal cortex. Resveratrol reduced the levels of reactive oxygen species and malondialdehyde, and increased the expression of nuclear factor-erythroid 2-related factor 2, heme oxygenase-1 mRNA and protein in the prefrontal cortex. Resveratrol decreased glucose-regulated protein 78, CHOP mRNA and protein expression and tumor necrosis factor-alpha level. It also activated astrocytes. The results suggest that resveratrol exerted neuroprotective effect on subarachnoid hemorrhage by reducing oxidative damage, endoplasmic reticulum stress and neuroinflammation. The study was approved by the Animals Ethics Committee of Shandong University, China on February 22, 2016 (approval No. LL-201602022).
Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms

Background: Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers. Methods: Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. Results: Seventy-nine patients with gastroenteropancreatic (grades 1–2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6–55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6–14.2) and 102.9 months (43.3–162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1–0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11–4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3–4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months). Conclusions: CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.
The role of lipoprotein (a) in primary and secondary cardiovascular disease prevention: a systematic review of epidemiological studies.

PURPOSE OF REVIEW Lipoprotein (a) [Lp(a)] is highly suggested as an emerging risk factor in cardiovascular disease (CVD) prevention. However, there remains controversy regarding the shape of Lp(a) risk curve and the extent to which Lp(a) confers risk for CVD, independently of conventional lipid markers. This systematic review outlines the current state of knowledge regarding the role of Lp(a) in primary and secondary CVD prevention. RECENT FINDINGS Searches resulted in the selection of n = 19 studies. In the context of primary CVD prevention, n = 9 cohorts, n = 2 case-cohorts, and n = 2 retrospective studies were identified, the majority of which suggested a significant positive association between Lp(a) and CVD onset. In terms of secondary CVD prevention, n = 5 cohorts and n = 1 case-cohort were considered as eligible highlighting from a positive to a neutral association between Lp(a) and CVD progression. SUMMARY A positive association between Lp(a) and CVD seems to be supported by a large body of evidence yet it is comparatively moderate in magnitude and differentiates according to study population and the examined endpoints. This fact along with the lack of a definitive functional mechanism limits the potential connotation of Lp(a) in daily clinical practice.
Association of Daytime Napping and Diagnosed Diabetes in Middle-Aged Premenopausal, Middle-Aged Postmenopausal, and Older Postmenopausal Chinese Women

Purpose: To examine associations of daytime napping and diagnosed diabetes in middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal Chinese women. Design: Quantitative, cross-sectional. Setting: 2015 cross-sectional data from China Health and Retirement Longitudinal Study. Participants were recruited from 150 counties/districts and 450 villages/resident committees. Participants: Six thousand nine hundred and forty women aged 45 years and older (mean age = 61 years) stratified by age and menopausal status. Measures: The outcome was self-reported diagnosed diabetes. The exposure was self-reported daytime napping (0, >0-≤60, or >60 min/d). Participants were stratified to middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal women according to their age (≤60 or >60 years) and menopausal status. Analysis: One-way analysis of variance and χ2 tests were conducted to explore differences on characteristics of middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal women. Multiple logistic regressions were used to estimate adjusted odds ratios (ORs) for diagnosed diabetes according to daytime napping in the total sample, middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal Chinese women. Results: Participants’ mean self-reported daytime napping duration was 34 minutes. Women who napped more than 60 minutes were more likely to report diagnosed diabetes (OR = 1.39, 95% confidence interval (CI), 1.09-1.76) comparing to those who did not nap, after adjusting for potential confounders. No statistical significance of interaction term between daytime napping and age/menopausal status was detected (P = .602 and P = .558) among total women. The stratified analysis revealed the significant association among middle-aged postmenopausal women napping more than 60 minutes (OR = 1.81, 95% CI, 1.18-2.77). The association, however, was found to be insignificant in middle-aged premenopausal women and older postmenopausal women. Conclusions: Long daytime nap (>60 min/d) was associated with diagnosed diabetes in middle-aged postmenopausal women in China.
Suppression of alcohol-induced hypertension by dexamethasone.

BACKGROUND Alcohol consumption is associated with an increased incidence of hypertension and stroke, but the triggering mechanisms are unclear. In animals, alcohol causes activation of the sympathetic nervous system and also stimulates the release of corticotropin-releasing hormone (CRH), which has sympatho-excitatory effects when administered centrally. METHODS To determine whether alcohol evokes sympathetic activation and whether such activation is attenuated by the inhibition of CRH release, we measured blood pressure, heart rate, and sympathetic-nerve action potentials (using intraneural microelectrodes) in nine normal subjects before and during an intravenous infusion of alcohol (0.5 g per kilogram of body weight over a period of 45 minutes) and for 75 minutes after the infusion. Each subject received two infusions, one after the administration of dexamethasone (2 mg per day) and one after the administration of a placebo for 48 hours. RESULTS The infusion of alcohol alone evoked a marked (P < 0.001) and progressive increase in the mean (+/- SD) rate of sympathetic discharge, from 16 +/- 3 bursts per minute at base line to 30 +/- 8 bursts per minute at the end of the two-hour period. This sympathetic activation was accompanied during the second hour by an increase in mean arterial pressure of 10 +/- 5 mm Hg (P < 0.001). After the administration of dexamethasone, the alcohol infusion had no detectable sympathetic effect. The dexamethasone-induced suppression of sympathetic activation was associated with a decrease in mean arterial pressure of 7 +/- 6 mm Hg (P < 0.001) during the alcohol infusion and with suppression of the pressor effect during the second hour. CONCLUSIONS Alcohol induces pressor effects by sympathetic activation that appear to be centrally mediated. It is possible that these alcohol-induced hemodynamic and sympathetic actions could participate in triggering cardiovascular events.
Downregulation of P2Y2 and HuD during the development of the enteric nervous system in fetal rats with anorectal malformations

Certain patients with anorectal malformations (ARMs) continue to suffer from postoperative dysphoria. The enteric nervous system (ENS) is closely associated with defecation. The purinergic receptor P2Y2 (P2Y2) and Hu antigen D (HuD) proteins contain multiple motifs that enable their activation and direct coupling to integrin and growth factor receptor signaling pathways; thus, they may serve as key points in ENS development. The aim of the present study was to investigate the expression pattern of P2Y2 and HuD proteins during anorectal development in ARM embryos. The embryogenesis of ARM in rats was induced by ethylenethiourea (ETU) on the 10th gestational day. The expression patterns of P2Y2 and HuD proteins were evaluated by immunohistochemistry and western blot analysis in normal, ETU and ARM rat embryos on embryonic days E17, E19 and E21; their mRNA levels were assessed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of the distal rectum of fetal rats. Immunohistochemistry of the distal rectum demonstrated that on E17, the expression levels of the two proteins were not different between the three groups. On E19, the expression of HuD was significantly decreased in the ARM group. On E21, the two proteins were significantly decreased in the ARM group. Additionally, the expression levels of the two proteins on E17 were significantly lower than on E21 in the ARM group. Western blotting and RT-qPCR also revealed that the P2Y2 and HuD proteins and mRNA expression levels were significantly decreased in the ARM groups when compared with the normal group on E17 and E21 (P<0.01). Thus, the present study demonstrated that downregulation of P2Y2 and HuD may partly be related to the development of the ENS in ARM embryos.
The plant product quinic acid activates Ca2+‐dependent mitochondrial function and promotes insulin secretion from pancreatic beta cells

Quinic acid (QA) is an abundant natural compound from plant sources which may improve metabolic health. However, little attention has been paid to its effects on pancreatic beta‐cell functions, which contribute to the control of metabolic health by lowering blood glucose. Strategies targeting beta‐cell signal transduction are a new approach for diabetes treatment. This study investigated the efficacy of QA to stimulate beta‐cell function by targeting the basic molecular machinery of metabolism–secretion coupling.
Ultrasonic Influence on Plasmonic Effects Exhibited by Photoactive Bimetallic Au-Pt Nanoparticles Suspended in Ethanol

The optical behavior exhibited by bimetallic nanoparticles was analyzed by the influence of ultrasonic and nonlinear optical waves in propagation through the samples contained in an ethanol suspension. The Au-Pt nanoparticles were prepared by a sol-gel method. Optical characterization recorded by UV-vis spectrophotometer shows two absorption peaks correlated to the synergistic effects of the bimetallic alloy. The structure and nanocrystalline nature of the samples were confirmed by Scanning Transmission Electron Microscopy with X-ray energy dispersive spectroscopy evaluations. The absorption of light associated with Surface Plasmon Resonance phenomena in the samples was modified by the dynamic influence of ultrasonic effects during the propagation of optical signals promoting nonlinear absorption and nonlinear refraction. The third-order nonlinear optical response of the nanoparticles dispersed in the ethanol-based fluid was explored by nanosecond pulses at 532 nm. The propagation of high-frequency sound waves through a nanofluid generates a destabilization in the distribution of the nanoparticles, avoiding possible agglomerations. Besides, the influence of mechanical perturbation, the container plays a major role in the resonance and attenuation effects. Ultrasound interactions together to nonlinear optical phenomena in nanofluids is a promising alternative field for a wide of applications for modulating quantum signals, sensors and acousto-optic devices.