Miracle-dz/UniFAR-FTUs huggingface dataset:
CD151 regulates expression of FGFR2 in breast cancer cells via PKC-dependent pathways

ABSTRACT Expression of the tetraspanin CD151 is frequently upregulated in epithelial malignancies and correlates with poor prognosis. Here, we report that CD151 is involved in regulation of the expression of fibroblast growth factor receptor 2 (FGFR2). Depletion of CD151 in breast cancer cells resulted in an increased level of FGFR2. Accordingly, an inverse correlation between CD151 and FGFR2 was observed in breast cancer tissues. CD151-dependent regulation of the FGFR2 expression relies on post-transcriptional mechanisms involving HuR (also known as ELAVL1), a multifunctional RNA-binding protein, and the assembly of processing bodies (P-bodies). Depletion of CD151 correlated with inhibition of PKC, a well-established downstream target of CD151. Accordingly, the levels of dialcylglycerol species were decreased in CD151-negative cells, and inhibition of PKC resulted in the increased expression of FGFR2. Whereas expression of FGFR2 itself did not correlate with any of the clinicopathological data, we found that FGFR2−/CD151+ patients were more likely to have developed lymph node metastasis. Conversely, FGFR2−/CD151− patients demonstrated better overall survival. These results illustrate functional interdependency between CD151 complexes and FGFR2, and suggest a previously unsuspected role of CD151 in breast tumorigenesis. Highlighted Article: The cancer-related tetraspanin protein CD151 uses novel pathways to mediate the regulation of FGFR2 expression.
Generalisation of threat expectancy increases with time

ABSTRACT Excessive fear generalisation is a feature characteristic of clinical anxiety and has been linked to its aetiology. Previous animal studies have shown that the mere passage of time increases fear generalisation and that brief exposure to training cues prior to long-term testing reverses this effect. The current study examined these phenomena in humans. Healthy participants learned the relationship between the presentation of a picture of a neutral male face and the delivery of a mild shock. One group was immediately tested with a novel picture of a somewhat different male face (generalisation test). Another group was tested one week later. A third group was also tested one week later and was additionally exposed to the training picture prior to testing. During picture presentations, shock-expectancy ratings were obtained as a measure of fear. Fear generalisation increased from the immediate test to the 1-week follow-up test. This result could not be attributed to level of neuroticism or a general increase in fear (incubation). Furthermore, the time-dependent increase in fear generalisation vanished following brief exposure to the training picture. Results indicate that human fear generalisation is a temporally dynamic process and that memory for stimulus details can be re-established following a reminder treatment.
Clinical characteristics and outcomes in acute myocardial infarction patients with versus without any cardiovascular risk factors

Background/Aims Although cardiovascular (CV) risk factors are well established, some patients experience acute myocardial infarction (AMI) even without any risk factors. Methods We analyzed total 11,390 patients (63.6 ± 12.6 years old, 8,401 males) with AMI enrolled in Korea Acute Myocardial Infarction Registry-National Institute of Health from November, 2011 to December, 2015. Patients were divided into two groups according to the presence of any CV risk factors (group I, without risk factors, n = 1,420 [12.5%]; group II, with risk factors, n = 9,970 [87.5%]). In-hospital outcomes were defined as in-hospital mortality and complications. One-year clinical outcomes were defined as the composite of major adverse cardiac events (MACE). Results Group I was older (67.3 ± 11.6 years old vs. 63.0 ± 12.7 years old, p < 0.001) and had higher prevalence of female gender (36.2% vs. 24.8%, p < 0.001) than the group II. Group I experienced less previous history of angina pectoris (7.0% vs. 9.4%, p = 0.003) and the previous history of cerebrovascular accidents (3.4% vs. 6.9%, p < 0.001). In-hospital mortality (2.6% vs. 3.0%, p = 0.450) and complications (20.6% vs. 20.0%, p = 0.647) were no differences between the groups. And 1 year clinical outcomes (5.7% vs. 5.1%, p = 0.337) were no differences between the groups. In multivariate logistic regression analysis, serum creatinine level (hazard ratio, 1.35; 95% confidence interval, 1.05 to 1.75; p = 0.021) were independent predictors of 1 year MACE in patients without any CV risk factors. Conclusions Elderly female patients were prone to develop AMI even without any modifiable CV risk factors. We suggest that more intensive care is needed in AMI patients without any CV risk factors who have high serum creatinine levels.
Therapeutic Drug Monitoring of Naltrexone and 6&bgr;-Naltrexol During Anti-craving Treatment in Alcohol Dependence: Reference Ranges

Aims Aim of this study was to associate concentration of naltrexone and its major active metabolite 6β-naltrexol in blood with therapeutic outcome during treatment with naltrexone in subjects with alcohol dependence. Treatment with the μ-opiate receptor antagonist naltrexone has been shown to reduce craving for alcohol and alcohol intake in patients suffering from alcohol dependence. Short summary This article shows the use of therapeutic drug monitoring in alcohol dependent patients, who are treated with naltrexone. The plasma concentrations of naltrexone and 6β-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Methods Naltrexone and 6β-naltrexol were analysed by high performance liquid chromatography with column switching and spectrophotometric detection. Alcohol craving was assessed with the Obsessive-Compulsive Drinking Scale (OCDS). Results and conclusions The study included 43 patients who were treated with naltrexone with a dose of 50 mg/day. Blood was taken for drug analysis 8 h after the last dose of the day at Week 4, 8 and 12. The plasma concentrations of naltrexone and 6β-naltrexol showed high inter-individual variability. They were predictive for treatment response, as they correlated significantly with the reduction of alcohol craving. Defining patients with OCDS reduction of 70% or higher as responders, the mean±SD concentration of naltrexone plus naltrexol was 22 ± 13 ng/ml compared to 15 ± 8 ng/ml in patients with score reductions of 1-69%. Further analyses indicated that concentrations of 17-50 ng/ml at 8 h and 7-20 ng/ml at 24 h after drug intake were required for treatment response. Conclusions Since plasma concentration of naltrexone plus 6β-naltrexol was found to be predictive for reduction of alcohol craving, it is concluded that therapeutic drug monitoring has the potential to enhance naltrexone's moderate therapeutic efficiency in patients with alcohol dependence.
Genetic Determinants of Glycemic Traits and the Risk of Gestational Diabetes Mellitus

Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Genetics of Glucose regulation in Gestation and Growth [Gen3G] and Hyperglycemia and Adverse Pregnancy Outcome [HAPO]) underwent oral glucose tolerance testing at 24–32 weeks’ gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of nonpregnant individuals. We tested for associations between these GRSs, glycemic traits in pregnancy, and GDM. In both cohorts, the fasting glucose GRS was strongly associated with fasting glucose. The insulin secretion and sensitivity GRSs were also significantly associated with these traits in Gen3G, where insulin measurements were available. The fasting insulin GRS was weakly associated with fasting insulin (Gen3G) or C-peptide (HAPO). In HAPO (207 GDM case subjects), all five GRSs (T2D, fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity) were significantly associated with GDM. In Gen3G (43 GDM case subjects), both the T2D and insulin secretion GRSs were associated with GDM; effect sizes for the other GRSs were similar to those in HAPO. Thus, despite the profound changes in glycemic physiology during pregnancy, genetic determinants of fasting glucose, fasting insulin, insulin secretion, and insulin sensitivity discovered outside of pregnancy influence GDM risk.
Safety of rectum anastomosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

In highly selected patients with peritoneal carcinomatosis, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can be an aggressive but worthwhile treatment regimen. Resection of the rectosigmoid is frequently performed with CRS. The aim of the study was to assess the safety of the rectal anastomosis in this setting.
A model of mucopolysaccharidosis type IIIB in pigs

ABSTRACT Mucopolysaccharidosis type IIIB (MPS IIIB) is a rare genetic disorder caused by loss-of-function mutations in the NAGLU gene. Pigs are an ideal large animal model for human diseases; however, a porcine model of MPS IIIB has not been reported. We have previously generated a heterozygous NAGLU-deficient (NAGLU+/-) Large White boar via a transgenic approach. Here we characterized phenotypes of the F1 offspring of this founder to establish a pig model for MPS IIIB. qRT-PCR revealed that the NAGLU expression level was significantly decreased in a variety of tissues in NAGLU+/− pigs. ELISA assays showed obvious deficiency of NAGLU and higher (P<0.05) glycosaminoglycan levels in multiple tissues from NAGLU+/− pigs. NAGLU+/− pigs grew at a significantly (P<0.05) slower rate than control animals (NAGLU+/+). Death, mostly sudden death, occurred at all ages in NAGLU+/− pigs, most of which died within two years. Necropsy findings included pleural adhesions, lung shrinkage and abnormalities in the pericardium and mild hepatomegaly in NAGLU+/− pigs. Notable pathological changes were observed in the sections of brain, liver, spleen and kidney from NAGLU+/− pigs. Brain atrophy, ventriculomegaly, cerebellar atrophy and abnormalities in the intracerebral capsule, parietal lobes and the thalamus were also evident in NAGLU+/− pigs. Together, NAGLU+/− pigs show typical symptoms of human MPS IIIB patients and thus represent a novel large animal model for the disease. This article has an associated First Person interview with the first author of the paper. Summary: We provide a pig model for both genetic and pathological studies of human MPS IIIB, which would contribute to timely diagnoses and better treatments of this rare disease.
Hydrogen gas reduces chronic intermittent hypoxia‐induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation

Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H 2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H 2 gas significantly improved CIH‐induced abnormal vascular relaxation. Nevertheless, inhalation of H 2 gas alone did not cause such changes. Moreover, H 2 gas‐treated rats exposed to CIH showed a significant reduction in 8‐hydroxy‐2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2.
Changes in EEG multiscale entropy and power‐law frequency scaling during the human sleep cycle

We explored changes in multiscale brain signal complexity and power‐law scaling exponents of electroencephalogram (EEG) frequency spectra across several distinct global states of consciousness induced in the natural physiological context of the human sleep cycle. We specifically aimed to link EEG complexity to a statistically unified representation of the neural power spectrum. Further, by utilizing surrogate‐based tests of nonlinearity we also examined whether any of the sleep stage‐dependent changes in entropy were separable from the linear stochastic effects contained in the power spectrum. Our results indicate that changes of brain signal entropy throughout the sleep cycle are strongly time‐scale dependent. Slow wave sleep was characterized by reduced entropy at short time scales and increased entropy at long time scales. Temporal signal complexity (at short time scales) and the slope of EEG power spectra appear, to a large extent, to capture a common phenomenon of neuronal noise, putatively reflecting cortical balance between excitation and inhibition. Nonlinear dynamical properties of brain signals accounted for a smaller portion of entropy changes, especially in stage 2 sleep.
Population Pharmacokinetics of Apixaban in Subjects With Nonvalvular Atrial Fibrillation

This analysis describes the population pharmacokinetics (PPK) of apixaban in nonvalvular atrial fibrillation (NVAF) subjects, and quantifies the impact of intrinsic and extrinsic factors on exposure. The PPK model was developed using data from phase I–III studies. Apixaban exposure was characterized by a two‐compartment PPK model with first‐order absorption and elimination. Predictive covariates on apparent clearance included age, sex, Asian race, renal function, and concomitant strong/moderate cytochrome P450 (CYP)3A4/P‐glycoprotein (P‐gp) inhibitors. Individual covariate effects generally resulted in < 25% change in apixaban exposure vs. the reference NVAF subject (non‐Asian, male, aged 65 years, weighing 70 kg without concomitant CYP3A4/P‐gp inhibitors), except for severe renal impairment, which resulted in 55% higher exposure than the reference subject. The dose‐reduction algorithm resulted in a ~27% lower median exposure, with a large overlap between the 2.5‐mg and 5‐mg groups. The impact of Asian race on apixaban exposure was < 15% and not considered clinically significant.
Assessment of Sperm Morphology, Chromatin Integrity, and Catsper Genes Expression in Hypothyroid Mice

There is an evident relationship between the fertilizing capacity of sperm and the normal morphology, quality chromatin, and motility of sperm. It is well known that thyroid hormones are the important regulators of testicular function. A correlation was found between the hypothyroidism and sperm damages. The present study was conducted to investigate the effects of hypothyroidism on sperm morphology, chromatin quality, and motility. For this purpose, 20 male mice were divided into the control and the hypothyroid groups that received 0.05% 6- n -propyl-2-thiouracil (PTU) for 35 days. Sperm morphology with Papanicolaou staining and sperm chromatin quality with both Aniline Blue (AB) and Toluidine blue (TB) staining were assessed. Besides, immunohistochemistry and real-time PCR were performed to evaluate the changes of cation sperm channel (CatSper) genes. A significant increase in the sperm chromatin condensation was found in the hypothyroid mice compared to the control mice (p < 0.05). Furthermore, a significant decrease was observed in the morphology of normal sperm in hypothyroid mice compared to the controls (p < 0.05). The results showed that Hypothyroidism could downregulate the expression of CatSper genes. Immunohistochemical data confirmed the real time-PCR results. Furthermore, the results showed that hypothyroidism could adversely affect sperm morphology, sperm chromatin condensation, and CatSper gene expression in mice and these abnormalities may be related to the excessive production of reactive oxygen species (ROS) in a hypothyroid state.
Incidence and prevalence of MS in children

Objective To validate a case definition of multiple sclerosis (MS) in the pediatric population using administrative (health claims) data, and to estimate the incidence and prevalence of MS in the pediatric population for Ontario, Canada. Methods We used population-based administrative data to identify persons aged ≤18 years with MS. We assessed the performance of multiple administrative case definitions using a clinical reference cohort including children with MS, children with monophasic demyelinating syndromes, and healthy children; we report sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We applied 2 preferred case definitions to estimate the incidence and prevalence of MS from 2003 to 2014. Results The Canadian Chronic Disease Surveillance System definition of ≥1 hospitalization or ≥5 physician claims for MS within 2 years had a sensitivity of 81.1%, specificity of 100%, PPV of 100%, and NPV of 86%. The Marrie definition of ≥3 hospital or physician claims for MS ever had a sensitivity of 89.2%, specificity of 100%, PPV of 100%, and NPV of 91.5%. Depending on the administrative case definition used, in 2014, the annual age-standardized annual incidence of MS in the pediatric population ranged from 0.99 to 1.24 per 100,000 population, and the age-standardized prevalence ranged from 4.03 to 6.8 per 100,000 population. The prevalence of MS rose over time. Conclusion Administrative data provide a feasible, valid means of estimating the incidence and prevalence of MS in the pediatric population. MS prevalence in the Ontario pediatric population is among the highest reported in pediatric populations worldwide.
Satellite Imagery Multiscale Rapid Detection with Windowed Networks

Detecting small objects over large areas remains a significant challenge in satellite imagery analytics. Among the challenges is the sheer number of pixels and geographical extent per image: a single DigitalGlobe satellite image encompasses over 64 km2 and over 250 million pixels. Another challenge is that objects of interest are often minuscule (~10pixels in extent even for the highest resolution imagery), which complicates traditional computer vision techniques. To address these issues, we propose a pipeline (SIMRDWN) that evaluates satellite images of arbitrarily large size at native resolution at a rate of > 0.2 km2/s. Building upon the TensorFlow Object Detection API paper, this pipeline offers a unified approach to multiple object detection frameworks that can run inference on images of arbitrary size. The SIMRDWN pipeline includes a modified version of YOLO (known as YOLT), along with the models of the TensorFlow Object Detection API: SSD, Faster R-CNN, and R-FCN. The proposed approach allows comparison of the performance of these four frameworks, and can rapidly detect objects of vastly different scales with relatively little training data over multiple sensors. For objects of very different scales (e.g. airplanes versus airports) we find that using two different detectors at different scales is very effective with negligible runtime cost. We evaluate large test images at native resolution and find mAP scores of 0.2 to 0.8 for vehicle localization, with the YOLT architecture achieving both the highest mAP and fastest inference speed.
The Prevalence of Psychiatric Comorbidity in Patients with Prurigo Nodularis

Background: Prurigo nodularis (PN) is a chronic, recalcitrant itchy dermatosis. It is supposed to be associated with psychological factors, but research in this area is scarce. Objectives: To study the prevalence and determinants of psychiatric morbidity, and the phenomenology of itch in PN. Materials and Methods: This study was carried out in the outpatient service of the Department of Dermatology. Purposive sampling was used to recruit 50 patients each with PN, chronic urticaria (CU), and vitiligo (V). A one-time cross-sectional assessment was carried out on the participants. Psychiatric morbidity was assessed using Mini-International Neuropsychiatric Interview and Patient Health Questionnaire-9. Results: The three groups were comparable on socio-demographic parameters. The prevalence of any psychiatric disorder (current or lifetime) was 48%, 42%, and 58% in the PN, CU, and V groups, respectively (P = 0.27). Limitations: The limitations of this study include the small sample size and the purposive, non-blind nature of assessments. Conclusion: Our study suggests that there is significant psychiatric morbidity in PN which is comparable to that seen in CU and V.
Comparative binding of kaempferol and kaempferide on inhibiting the aggregate formation of mutant (G85R) SOD1 protein in familial amyotrophic lateral sclerosis: A quantum chemical and molecular mechanics study

Mutation in Cu/Zn superoxide dismutase (SOD1) at position 85 from glycine to arginine was found to be a prominent cause of aggregation characterized by an increased content of β-sheets in familial amyotrophic lateral sclerosis (fALS). Various literatures reported that natural polyphenols could act as a β-sheet breaker and therefore, treated as a potential therapeutics against various aggregated proteins involved in neurodegenerative disorders. Through computational perspective, molecular docking, quantum chemical studies, and discrete molecular dynamics were implemented to study the binding and structural effect of natural polyphenols, kaempferol, and kaempferide on mutant SOD1. Kaempferol exhibited significant binding and greater residual energy contribution with mutant SOD1 than kaempferide. More interestingly, kaempferol was found to reduce the β-sheet content augmenting the mutant conformational stability and flexibility relative to that of kaempferide. Hence, the inhibition of mutant SOD1 aggregation by kaempferol was explored, thereby suggesting kaempferol could act as a drug candidate for the design of the natural therapeutics against fALS. © 2018 BioFactors, 44(5):431-442, 2018.
Going online to stay connected: Online social participation buffers the relationship between pain and depression.

Objectives Maintaining offline social participation (i.e. face-to-face social interaction) is key for healthy aging, but older adults who experience pain tend to restrict their social activity outside of the home. The onset of pain may set off a downward spiral where lowered social participation increases the risk of depression and vice versa. This study thus assesses whether online social participation (i.e., the use of online social network sites) moderates the effect of pain on depression, possibly functioning as a compensatory mechanism for reduced offline social participation for those in pain. Method Logistic regression models with a lagged dependent variable were used with panel data from the National Health and Aging Trends Study. An interaction term was included to assess the moderating effect of online social participation. Results We find that online social participation buffers the detrimental effect of pain on depression. However, the effect of pain on online social participation was not statistically significant. Discussion Findings show that online social participation can alleviate the negative effects of pain on mental well-being, and suggest that online social participation can supplement attempts to maintain offline social participation in later life, especially for those whose social activity may be limited by pain.