Miracle-dz/UniFAR-FTUs huggingface dataset:
Weather Impact on Acute Myocardial Infarction Hospital Admissions With a New Model for Prediction: A Nationwide Study

Introduction: Cardiovascular disease is one of the leading causes of mortality worldwide. Acute myocardial infarction (AMI) is associated with weather change. The study aimed to investigate if weather change was among the risk factors of coronary artery disease to influence AMI occurrence in Taiwan and to generate a model to predict the probabilities of AMI in specific weather and clinical conditions. Method: This observational study utilized the National Health Insurance Research Database and daily weather reports from Taiwan Central Weather Bureau to evaluate the discharge records of patients diagnosed with AMI from various hospitals in Taiwan between January 1, 2008 and December 31, 2011. Generalized additive models (GAMs) were used to estimate the effective parameters on the trend of the AMI incidence rate with respect to the weather and health factors in the time-series data and to build a model for predicting AMI probabilities. Results: A total of 40,328 discharges were listed. The minimum temperature, maximum wind speed, and antiplatelet therapy were negatively related to the daily AMI incidence; however, a drop of 1° when the air temperature was below 15°C was associated with an increase of 1.6% of AMI incidence. By using the meaningful parameters including medical and weather factors, an estimated GAM was built. The model showed an adequate correlation in both internal and external validation. Conclusion: An increase in AMI occurrence in colder weather has been evidenced in the study, but the influence of wind speed remains uncertain. Our analysis demonstrated that the novel GAM model can predict daily onset rates of AMI in specific weather conditions.
Peroxisome Proliferator–Activated Receptor α Activation Decreases Metastatic Potential of Melanoma Cells In vitro via Down-Regulation of Akt

Purpose: Peroxisome proliferator-activated receptors (PPAR) regulate lipid and glucose metabolism but their anticancer properties have been recently studied as well. We previously reported the antimetastatic activity of the PPARα ligand, fenofibrate, against melanoma tumors in vivo. Here we investigated possible molecular mechanisms of fenofibrate anti metastatic action. Experimental Design: Monolayer cultures of mouse (B16F10) and human (SkMell88) melanoma cell lines, soft agar assay, and cell migration assay were used in this study. In addition, we analyzed PPARα expression and its transcriptional activity in response to fenotibrate by using Western blots and liciferase-based reporter system. Results: Fenofibrate inhibited migration of B16F10 and SkMel188 cells in Transwell chambers and colony formation in soft agar. These effects were reversed by PPAR inhibitor, GW9662. Western blot analysis revealed time-dependent down-regulation of Akt and extracellular signal–regulated kinase l/2 phosphorylation in fenofibrate-treated cells. A B16F10 cell line stably expressing constitutively active Akt mutant was resistant to fenofibrate. In contrast, Akt gene silencing with siRNA mimicked the fenofibrate action and reduced the migratory ability of B16F1O cells. In addition, fenofibrate strongly sensitized BI6FIO cells to the proapoptotic drug staurosporine, further supporting the possibility that fenofibrate-induced down-regulation of Akt function contributes to fenofibrate-mediated inhibition of metastatic potential in this experimental model. Conclusions: Our results show that the PPAR-dependent antimetastatic activity of fenofibrate involves down-regulation of Akt phosphorylation and suggest that supplementation with this drug may improve the effectiveness of melanoma chemotherapy.
Transfection of Transforming Growth Factor-β Producing Tumor EMT6 with Interleukin‐2 Elicits Tumor Rejection and Tumor Reactive Cytotoxic T‐Lymphocytes

One mechanism by which potentially immunogenic tumors evade the immune response is production of immunosuppressive factors. The murine mammary sarcoma EMT6 has previously been demonstrated to inhibit the proliferation of B-cells, suggesting that this tumor produces immunosuppressive factors. Here, we show that supernatant from EMT6 inhibits the development of cytotoxic T-lymphocytes (CTLs) and that this inhibition can be reversed by addition of recombinant interleukin (IL)-2. Furthermore, we show that EMT6 produces high levels of the immunosuppressant factor transforming growth factor (TGF)-β. To determine if the T-cell growth factor IL-2 within the tumor microenvironment could reverse the immunosuppressive effect of EMT6, we transfected EMT6 with an expression vector containing the cDNA for murine IL-2 under the control of the β-actin promoter. These transfectants produce significant levels of IL-2 (26 U/ml). EMT6/IL-2 is rejected by mice at 100-fold higher challenge than are parental cells or control transfectants (neo-mycin resistance only). Thy-1-expressing cells purified from EMT6/IL-2 tumors show greater cytotoxicity against the parental EMT6 cells than do those from the control transfectant. Thus, IL-2 can reverse the effects of TGF-β on development and/or proliferation of CTL reactive with EMT6, allowing the establishment of mature effectors in vivo. This has significant implications for the development of CTL and immunotherapy for immunosuppressive tumors.
Inactivation of p16INK4a by CpG hypermethylation is not a frequent event in colorectal cancer

Gene promoter hypermethylation is common in colorectal cancer and is associated with transcriptional silencing. However, the clinicopathological significance of p16INK4a gene silencing with hypermethylation is unknown. Therefore, the aim of this study was to analyze loss of p16 expression and its relationship to hypermethylation in sporadic colorectal cancer.
Cumulative Incidence of Converting from Clinically Unilateral to Bilateral Exfoliation Syndrome

Purpose:To obtain long-term cumulative incidence estimates of time to conversion of clinically unilateral to bilateral exfoliation syndrome (ES). Methods:A retrospective, longitudinal cohort study of 35 patients with clinically unilateral ES from the private office of one author. Diagnosis of ES was made between 1968 and 1998. On return visits a careful search for ES in the nonexfoliative fellow eye was made by the same author in a semidark room using a slit lamp and maximal pupillary dilatation. Cumulative incidence of converting to bilateral ES was calculated, taking death into account as a competing risk. Results:Cumulative incidence of conversion to bilateral ES was 0.11 (95% CI, 0.03–0.25) at 5 years, 0.36 (95% CI, 0.15–0.57) at 10 years, and 0.52 (95% CI, 0.27–0.93) at 15 years when the day of examination was taken to be the day of conversion, and 0.14 (95% CI, 0.04–0.29) at 5 years and 0.52 (95% CI, 0.26–0.73) at 10 years when analysis was based on conversion taking place at the midpoint between the last two visits. The median age at conversion was 72 years (range, 66–86), and the median age of patients remaining clinically unilateral was 77 years (range, 57–90). Factors associated with time to conversion depended on the strategy of the analysis and included higher age at first visit and larger IOP difference between the involved and uninvolved eye. Conclusion:A large proportion of patients with clinically unilateral ES will not convert to bilateral involvement in long-term follow-up. Immunohistochemical studies suggest that local factors must either expedite ES or slow it down in one eye to explain the frequently longstanding asymmetric involvement, and a difference in initial aqueous outflow facility might be examined as one candidate.
NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats

The reactive oxygen species- (ROS-) induced nod-like receptor protein-3 (NLRP3) inflammasome triggers sterile inflammatory responses and pyroptosis, which is a proinflammatory form of programmed cell death initiated by the activation of inflammatory caspases. NLRP3 inflammasome activation plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated whether diabetes aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. Type 1 diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg). MI/R was induced by ligating the left anterior descending artery (LAD) for 30 minutes followed by 2 h reperfusion. H9C2 cardiomyocytes were exposed to high glucose (HG, 30 mM) conditions and hypoxia/reoxygenation (H/R) stimulation. The myocardial infarct size, CK-MB, and LDH release in the diabetic rats subjected to MI/R were significantly higher than those in the nondiabetic rats, accompanied with increased NLRP3 inflammasome activation and increased pyroptosis. Inhibition of inflammasome activation with BAY11-7082 significantly decreased the MI/R injury. In vitro studies showed similar effects, as BAY11-7082 or the ROS scavenger N-acetylcysteine, attenuated HG and H/R-induced H9C2 cell injury. In conclusion, hyperglycaemia-induced NLRP3 inflammasome activation may be a ROS-dependent process in pyroptotic cell death, and NLRP3 inflammasome-induced pyroptosis aggravates MI/R injury in diabetic rats.
High Specific Binding of [3H]GABA and [3H]Muscimol to Membranes from Dendrodendritic Synaptosomes of the Rat Olfactory Bulb

Abstract: Olfactory bulbs contain dendrodendritic synapses, which occur between granule cells and mitral cells, and γ‐aminobutyric acid (GABA) is thought to act as an inhibitory neurotransmitter at these synapses. Synaptosomes derived from the dendrodendritic synapses of the olfactory bulb were shown previously to contain considerable L‐glutamate decarboxylase activity. The subcellular distribution and binding parameters of [3H]GABA and [3H]muscimol binding sites have now been determined in the rat olfactory bulb. Of all fractions examined, crude synaptic membranes (CSM) prepared from the dendrodendritic synaptosomes were shown to have the highest specific binding activity and accounted for nearly all of the total binding activity for both ligands. The specific binding activities for [3H]GABA and for [3H]muscimol were greatly increased after treating the CSM with 0.05% Triton X‐100. Binding was shown to be Na+‐independent, reversible, pharmacologically specific, and saturable. High‐ and low‐affinity sites were detected for both ligands, and both classes of sites had appreciably lower KD values for muscimol (KD1= 3.1 nM, KD2= 25.1 nM) than for GABA (KD1= 8.6 nM; KD2= 63.7 nM). The amounts of the high‐affinity binding sites for muscimol and GABA were similar (Bmax= 1.7 and 1.5 pmol/mg protein, respectively). The results of the present experiments indicate that the GABA and muscimol binding sites represent the GABA postsynaptic receptor, presumably on mitral cell dendrites, and provide further support for the hypothesis that GABA functions as a neurotransmitter at the dendrodendritic synapses in the olfactory bulb.
Linker for Activation of T Cells Integrates Positive and Negative Signaling in Mast Cells1

The transmembrane adapter linker for activation of T cells (LAT) is thought to couple immunoreceptors to intracellular signaling pathways. In mice, its intracytoplasmic domain contains nine tyrosines which, when phosphorylated upon receptor aggregation, recruit Src-homology 2 domain-containing cytosolic enzymes and adapters. The four distal tyrosines are critical for both TCR and FcεRI signaling. Unexpectedly, knock-in mice expressing LAT with a point mutation of the first or of the last three of these tyrosines exhibited an abnormal T cell development characterized by a massive expansion of TH2-like αβ or γδ T cells, respectively. This phenotype suggests that, besides positive signals, LAT might support negative signals that normally regulate terminal T cell differentiation and proliferation. We investigated here whether LAT might similarly regulate mast cell activation, by generating not only positive but also negative signals, following FcR engagement. To this end, we examined IgE- and/or IgG-induced secretory and intracellular responses of mast cells derived from knock-in mice expressing LAT with combinations of tyrosine mutations (Y136F, Y(175, 195, 235)F, or Y(136, 175, 195, 235)F). A systematic comparison of pairs of mutants enabled us to dissect the respective roles played by the five proximal and the four distal tyrosines. We found that LAT tyrosines differentially contribute to exocytosis and cytokine secretion and differentially regulate biological responses of mucosal- and serosal-type mast cells. We also found that, indeed, both positive and negative signals may emanate from distinct tyrosines in LAT, whose integration modulates mast cell secretory responses.
Dynamics-aware numerical coarsening for fabrication design

The realistic simulation of highly-dynamic elastic objects is important for a broad range of applications in computer graphics, engineering and computational fabrication. However, whether simulating flipping toys, jumping robots, prosthetics or quickly moving creatures, performing such simulations in the presence of contact, impact and friction is both time consuming and inaccurate. In this paper we present Dynamics-Aware Coarsening (DAC) and the Boundary Balanced Impact (BBI) model which allow for the accurate simulation of dynamic, elastic objects undergoing both large scale deformation and frictional contact, at rates up to 79 times faster than state-of-the-art methods. DAC and BBI produce simulations that are accurate and fast enough to be used (for the first time) for the computational design of 3D-printable compliant dynamic mechanisms. Thus we demonstrate the efficacy of DAC and BBI by designing and fabricating mechanisms which flip, throw and jump over and onto obstacles as requested.
Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer.

PURPOSE To determine the effect of elevation of serum HER-2/neu on response to hormone therapy. PATIENTS AND METHODS Seven hundred nineteen metastatic patients with estrogen receptor-positive (ER(+)), progesterone receptor-positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels. RESULTS Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with non-elevated and 23% in 217 patients with elevated serum HER-2/neu levels (P <.0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with non-elevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P <.0001). CONCLUSION Patients with ER(+) and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER(+) and serum HER-2/neu-negative patients. Their survival duration is also shorter.
Independent component analysis for face recognition based on two dimension symmetrical image matrix

The new face recognition method based on the matrix of symmetrical face image ICA is put forward for the problem that the influence of the light on the face recognition and high dimensional small sample exists in traditional independent component analysis (ICA)in face recognition. At the same time, in order to improve the human face recognition efficiency, the ICA face recognition method based on the matrix of symmetrical face image is put forward. The method uses the natural characteristics with mirror symmetry of face. According to parity decomposition principle, the odd and even symmetrical samples are created. And symmetrical face image is used as training sample. The principal component analysis (PCA) is used to remove second order relevant and reduce dimension, and then the handled sample is feature extracted by ICA. According to the theory analysis and experimental proof, the influence caused by view, light, face expression, the posture change factors on the face is effective reduced by the new algorithm. Meanwhile, the algorithm increases the size of training sample and reduces the complexity of calculation. In the meantime, the algorithm solves the problem of small sample and improve face recognition rate.
Assessment of skeletal muscle proteolysis and the regulatory response to nutrition and exercise

Skeletal muscle proteolysis is highly regulated, involving complex intramuscular proteolytic systems that recognize and degrade muscle proteins, and recycle free amino acid precursors for protein synthesis and energy production. Autophagy‐lysosomal, calpain, and caspase systems are contributors to muscle proteolysis, although the ubiquitin proteasome system (UPS) is the primary mechanism by which actomyosin fragments are degraded in healthy muscle. The UPS is sensitive to mechanical force and nutritional deprivation, as recent reports have demonstrated increased proteolytic gene expression and activity of the UPS in response to resistance and endurance exercise, and short‐term negative energy balance. However, consuming dietary protein alone (or free amino acids), or as a primary component of a mixed meal, may attenuate intramuscular protein loss by down‐regulating proteolytic gene expression and the catabolic activity of the UPS. Although these studies provide novel insight regarding the intramuscular regulation of skeletal muscle mass, the role of proteolysis in the regulation of skeletal muscle protein turnover in healthy human muscle is not well described. This article provides a contemporary review of the intramuscular regulation of skeletal muscle proteolysis in healthy muscle, methodological approaches to assess proteolysis, and highlights the effects of nutrition and exercise on skeletal muscle proteolysis. © 2014 IUBMB Life, 66(7):478–484, 2014
Round Window Stimulation of the Cochlea

Mixed hearing loss associated with a sensorineural component and an impaired conductive mechanism for sound from the external ear canal to the cochlea represents a challenge for rehabilitation using either surgery or traditional hearing amplification. Direct stimulations of the ossicular chain and the round window (RW) membrane have allowed an improved hearing in this population. The authors review the developments in basic and clinical research that have allowed the exploration of new routes for inner ear stimulation. Similar changes occur in the electrophysiological measures in response to auditory stimulation through the traditional route and direct mechanical stimulation of the RW. The latter has proven to be very effective as a means of hearing rehabilitation in a group of patients with significant difficulties with hearing and communication.
Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis

Objectives: A systematic review and meta-analysis was performed to evaluate the potential prognostic role of serum uric acid (SUA) in patients with chronic heart failure (CHF). Methods: The Embase, PubMed, Web of Science and Cochrane Library databases were searched up to 5 April 2021 for relevant publications. Random effects model was used to pool data. STATA15.0 software was used to perform meta-analysis. Heterogeneity was assessed using the Cochran Q statistic (significance level of P < 0.10) and I2 statistics (significance level of 50%). Results: Ultimately, 18 publications reporting adverse events in CHF patients were included. The results indicate reveal associations between a high level of SUA and the risk of all-cause mortality (HR 2.24, 95% CI 1.49–3.37), cardiovascular mortality (HR 1.14, 95% CI 1.06–1.23), and the composite of death or cardiac events (HR 1.26, 95% CI 1.01–1.56) in CHF patients. A 1 mg/dL increase in serum uric acid led to 4% (HR 1.04, 95% CI 1.02–1.05) and 9% (HR 1.09, 95% CI 1.03–1.17) increases in the risk of all-cause mortality and the composite endpoint of death or cardiac events in CHF patients, respectively. Conclusion: Serum uric acid is positively associated with the risk of adverse events in CHF patients. This study protocol has been registered at PROSPERO as CRD42021247084 (https://www.crd.york.ac.uk/PROSPERO). Systematic Review Registration: https://www.crd. york.ac. uk/PROSPERO.
Structure of Negative Symptoms in Schizophrenia: An Unresolved Issue

Background: Negative symptoms are core features of schizophrenia and very challenging to be treated. Identification of their structure is crucial to provide a better treatment. Increasing evidence supports the superiority of a five-factor model (alogia, blunted affect, anhedonia, avolition, and asociality as defined by the NMIH-MATRICS Consensus); however, previous data primarily used the Brief Negative Symptoms Scale (BNSS). This study, including a calibration and a cross-validation sample (n = 268 and 257, respectively) of participants with schizophrenia, used the Clinical Assessment Interview for Negative Symptoms (CAINS) to explore the latent structure of negative symptoms and to test theoretical and data-driven (from this study) models of negative symptoms. Methods: Exploratory factor analysis (EFA) was carried out to investigate the structure of negative symptoms based on the CAINS. Confirmatory factor analysis (CFA) tested in a cross-validation sample four competing theoretical (one-factor, two-factor, five-factor, and hierarchical factor) models and two EFA-derived models. Result: None of the theoretical models was confirmed with the CFA. A CAINS-rated model from EFA consisting of five factors (expression, motivation for recreational activities, social activities, vocational, and close/intimate relationships) was an excellent fit to the data (comparative fix index = 0.97, Tucker–Lewis index = 0.96, and root mean square error of approximation = 0.07). Conclusions: This study cannot support recent data on the superiority of the five-factor model defined by the NMIH-MATRICS consensus and suggests that an alternative model might be a better fit. More research to confirm the structure of negative symptoms in schizophrenia, and careful methodological consideration, should be warranted before a definitive model can put forward and shape diagnosis and treatment of schizophrenia.