Miracle-dz/UniFAR-FTUs huggingface dataset:
Tamoxifen inhibits migration of estrogen receptor‐negative hepatocellular carcinoma cells by blocking the swelling‐activated chloride current

Tamoxifen is a triphenylethylene non‐steroidal antiestrogen anticancer agent. It also shows inhibitory effects on metastasis of estrogen receptor (EsR)‐independent tumors, but the underlying mechanism is unclear. It was demonstrated in this study that, in EsR‐negative and highly metastatic human hepatocellular carcinoma MHCC97H cells, tamoxifen‐inhibited cell migration, volume‐activated Cl− currents (ICl,vol) and regulatory volume decrease (RVD) in a concentration‐dependent manner with a similar IC50. Analysis of the relationships between migration, ICl,vol and RVD showed that cell migration was positively correlated with ICl,vol and RVD. Knockdown of the expression of ClC‐3 Cl− channel proteins by ClC‐3 shRNA or siRNA inhibited ICl,vol, and cell migration, and these inhibitory effects could not be increased further by addition of tamoxifen in the medium. The results suggest that knockdown of ClC‐3 expression may deplete the effects of tamoxifen; tamoxifen may inhibit cell migration by modulating ICl,vol and cell volume. Moreover, tamoxifen decreased the activity of protein kinase C (PKC) and the effects were reversed by the PKC activator PMA. Activation of PKC by PMA could competitively downregulate the inhibitory effects of tamoxifen on ICl,vol. PMA promoted cell migration, and knockdown of ClC‐3 expression by ClC‐3 siRNA abolished the PMA effect on cell migration. The results suggest that tamoxifen may inhibit ICl,vol by suppressing PKC activation; ICl,vol may be an EsR‐independent target for tamoxifen in the anti‐metastatic action on cancers, especially on EsR‐negative cancers. The finding may have an implication in the clinical use of tamoxifen in the treatments of both EsR‐positive and EsR‐negative cancers. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
Spatial and temporal variability of the Iberian Peninsula coastal low‐level jet

The spatial variability and the climatic characteristics of the coastal low‐level jet along the west coast of the Iberian Peninsula are presented in this study, based on a 9‐km resolution downscaling data set, produced using the weather research and forecasting model, forced by the ERA‐Interim reanalysis. The west coast of Iberia is divided into two (north and south) subareas, where the Iberian Peninsula coastal jet (IPCJ) characteristics are studied separately, and compared to the whole western Iberia. It is shown that while IPCJ occurrences are more frequent in the southern area, during summer (June–August), the jet mean wind speed maxima is highest in the northernmost area. The along‐ and cross‐coast sea surface temperature (SST) structure is studied and linked to the coastal wind speed. It is also shown that the local cross‐coast marine atmospheric boundary layer gradient at the coast is considerably higher than the synoptic one, and that this difference is responsible for the local intensification of the wind speed. The flow interaction with the three major capes along the west coast of Iberia (Finisterre, Roca, and Saint Vincent) is responsible for local higher occurrence of the IPCJ, as well as the downwind intensification of the wind speed. The along‐coast west Iberia wind speed structure due to IPCJ occurrences is shown. The diurnal cycle of the IPCJ is studied in the extended boreal summer (May–September), with higher mean IPCJ occurrences and jet wind speeds in late the afternoon.
Deep ROSAT HRI Observations of the NGC 1399/NGC 1404 Region: Morphology and Structure of the X-Ray Halo

We present the analysis of a deep (167 ks) ROSAT HRI observation of the cD galaxy NGC 1399 in the Fornax Cluster, comparing it with previous work on this galaxy and with recent Chandra data. We find, in agreement with previous observations, an extended and asymmetric gaseous halo with a luminosity (in the 0.1-2.4 keV energy band) of LX = (5.50 ± 0.04) × 1041 ergs s-1 within 46 kpc (assuming a distance of D = 19 Mpc). Using both HRI and, at larger radii, archival PSPC data, we find that the radial behavior of the X-ray surface brightness profile is not consistent with a simple β-model and suggests instead three distinct components. We use a multicomponent bidimensional model to study in detail these three components, which we identify respectively with the cooling flow region, the galactic halo, and the cluster halo. From these data we derive a binding mass distribution in agreement with that suggested by optical dynamical indicators, with an inner core dominated by luminous matter and an extended dark halo differently distributed on galactic and cluster scales. The HRI data and a preliminary analysis of Chandra public data allow us to detect significant density fluctuations in the halo. We discuss possible nonequilibrium scenarios to explain the hot halo structure, including tidal interactions with neighboring galaxies, ram stripping from the intracluster medium, and merging events. In the innermost region of NGC 1399, the comparison between the X-ray and radio emission suggests that the radio-emitting plasma is displacing and producing shocks in the hot X-ray-emitting gas. We do not detect the nuclear source in X-rays, and we pose an upper limit of ~4 × 1039 ergs s-1 (0.1-2.4 keV) to its X-ray luminosity. We found that the NGC 1404 halo is well represented by a single symmetric β-model and follows the stellar light profile within the inner 8 kpc. The mass distribution is similar to the "central" component of the NGC 1399 halo. At larger radii, ram pressure stripping from the intracluster gas produces strong asymmetries in the galactic halo. Finally, we discuss the properties of the point-source population, finding evidence of correlation between the source excess and NGC 1399.
Exercise-based rehabilitation for heart failure: systematic review and meta-analysis

Objective To update the Cochrane systematic review of exercise-based cardiac rehabilitation (CR) for heart failure. Methods A systematic review and meta-analysis of randomised controlled trials was undertaken. MEDLINE, EMBASE and the Cochrane Library were searched up to January 2013. Trials with 6 or more months of follow-up were included if they assessed the effects of exercise interventions alone or as a component of comprehensive CR programme compared with no exercise control. Results 33 trials were included with 4740 participants predominantly with a reduced ejection fraction (<40%) and New York Heart Association class II and III. Compared with controls, while there was no difference in pooled all-cause mortality between exercise CR with follow-up to 1 year (risk ratio (RR) 0.93; 95% CI 0.69 to 1.27, p=0.67), there was a trend towards a reduction in trials with follow-up beyond 1 year (RR 0.88; 0.75 to 1.02, 0.09). Exercise CR reduced the risk of overall (RR 0.75; 0.62 to 0.92, 0.005) and heart failure-specific hospitalisation (RR 0.61; 0.46 to 0.80, 0.0004) and resulted in a clinically important improvement in the Minnesota Living with Heart Failure questionnaire (mean difference: −5.8 points, −9.2 to −2.4, 0.0007). Univariate meta-regression analysis showed that these benefits were independent of the type and dose of exercise CR, and trial duration of follow- up, quality or publication date. Conclusions This updated Cochrane review shows that improvements in hospitalisation and health-related quality of life with exercise-based CR appear to be consistent across patients regardless of CR programme characteristics and may reduce mortality in the longer term. An individual participant data meta-analysis is needed to provide confirmatory evidence of the importance of patient subgroup and programme level characteristics (eg, exercise dose) on outcome.
ENIC - an improved reliable transport scheme for mobile ad hoc networks

We propose an end-to-end reliable data transport scheme to solve the issues of TCP performance degradation and packet losses due to bit errors and route failures in mobile ad hoc networks. We refer to this scheme as the explicit notification with enhanced inter-layer communication and control (ENIC) mechanism. Because of the distinct characteristics between mobile ad hoc networks and wired networks, we introduce a new design methodology - enhanced inter-layer control mechanism - to improve the reliability of data transport. Comprehensive effects of interactions among medium access control (MAC), routing and transmission control protocol (TCP) are considered. Moreover, our scheme provides a true end-to-end TCP maintenance and recovery method during route failure. A quantitative implementation is simulated and compared with the standard SACK (selective acknowledgement) TCP. Simulation results demonstrate the advantages of our scheme.
Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives.

OBJECTIVE Patients with resistant hypertension are at increased risk for cardiovascular events. Mean platelet volume (MPV) is an accepted biomarker of platelet activation and considered as a risk factor for cardiovascular disease. The aim of this study was to determine whether MPV levels are higher in resistant hypertensive (RHTN) patients than in controlled hypertensive (CHTN) patients and healthy normotensive controls. MATERIALS AND METHODS 279 consecutive patients were included in this study. Patients were divided into three groups: Resistant hypertension patient group [n=78; mean age 56.8±9.8; 42 males (53.8%)]; controlled hypertension patient group [n=121; mean age 54.1±9.6; 49 males (40.5%)]; and normotensive control group [n=80; mean age 49.8±8.5; 34 males (42.5%)]. Physical examination, laboratory work-up, and 24-hour ambulatory blood pressure measurement (ABPM) were performed in all participants. RESULTS The mean platelet volume levels were significantly higher in RHTN group than in the CHTN and normotensive groups (p<0.001). In correlation analysis office systolic and diastolic blood pressure was positively correlated with MPV. CONCLUSION Our study demonstrated that MPV, as an important indicator of platelet activation, was statistically higher in RHTN patients than in CHTN and in normotensive subjects. Elevated MPV levels may help to determine a high risk group for atherosclerosis in RHTN patients.
Recanalization of Vertebral Artery Dissection

Background and Purpose— We investigated the predictors and time course for recanalization after vertebral artery dissection. Methods— We prospectively studied 61 consecutive patients with confirmed diagnoses of vertebral artery dissection without intracerebral hemorrhage. Neuroimaging and clinical follow-up were performed at presentation and at 3, 6, and 12 months. Results— We included 61 patients with confirmed vertebral artery dissection; 19 were evaluated and followed up with conventional angiography, 24 with MR angiography, and 18 with CT angiography. Fifty-one patients had a stenotic dissection, 7 had an occlusive dissection, one had a double-lumen image, and 2 had a pseudoaneurysm. The estimated rate of complete recanalization after vertebral artery dissection was 45.9% at 3 months, 62.3% at 6 months, and 63.9% at 12 months. We found no association between outcome and complete or partial recanalization nor did we find any factors associated with recanalization. Conclusions— These results suggest that recanalization of vertebral artery dissection occurs mainly within the first 6 months after the onset of symptoms regardless of the location or pattern of the dissection.
Posterior corneal astigmatism modifications after cataract surgery and its role on total corneal astigmatism

Background: In recent years posterior corneal astigmatism and its effect on total corneal astigmatism has been studied, with research showing that this can impact total astigmatism. This study aims to ascertain if there is significant change in the posterior corneal astigmatism after cataract surgery and its impact on the total astigmatism. Methods: Analysis of 76 eyes that underwent cataract surgery with monofocal intraocular lens implantation. Corneal topography was performed with Pentacam (OCULUS ® ) pre- and post-operatively. Total corneal astigmatism was calculated with the algorithm of vergence tracing. We compared preoperative and postoperative changes in the magnitude and axis differences of anterior corneal curvature astigmatism, posterior corneal curvature astigmatism and the calculated total corneal astigmatism. We calculated the correlation between the total preoperative astigmatism and the difference between total corneal astigmatism and anterior corneal astigmatism. Results: The mean preoperative and postoperative posterior astigmatism was 0.31±0.02 D, showing no significant differences before and after surgery (P=0.989). Statistically significant differences between the calculated total corneal astigmatism and anterior corneal astigmatism were registered preoperatively and postoperatively in the with-the-rule anterior (WTR) corneal astigmatism (P=0.004, P<0.0001); against-the-rule (ATR) anterior corneal astigmatism (P<0.0001, P<0.0001) and in the oblique (P=0.026, P=0.019) subgroups. The posterior corneal astigmatism and the total corneal astigmatism correlated positively with the differences between the total corneal and anterior corneal astigmatism (R=0.378, P=0.001). Conclusions: There were statistically significant differences between the magnitude of the total astigmatism and anterior corneal astigmatism, underlining the impact of posterior corneal astigmatism. A positive correlation between the preoperative posterior astigmatism and the difference between the total corneal and the anterior corneal astigmatism suggests a specially relevant role of posterior corneal astigmatism when evaluating patients with higher degrees of astigmatism.
Early BCR Events and Antigen Capture, Processing, and Loading on MHC Class II on B Cells

B cells are efficient antigen-presenting cells (APCs), relying on antigen uptake through the B cell receptor (BCR). The mechanism of antigen recognition remains a topic of debate; while the prevalent view holds that antigens need to be multivalent for BCR activation, monovalent antigens can also initiate B cell responses. In this review, we describe the steps required for antigen uptake, processing, and loading of peptides onto MHC Class II compartments in B cells for efficient presentation to CD4 T cells, with a special focus in the initial steps of BCR recognition of antigen.
Effect of newer oral antiviral agents on future therapy of chronic hepatitis B

Long-term therapy with oral nucleoside/nucleotide analogues (NAs) is a favoured approach to the treatment of patients with chronic hepatitis B (CHB); however, all oral agents currently approved for the treatment of such patients are associated with some risk for drug resistance. This can lead to a rebound in HBV levels and, eventually, progressive liver disease. Combination therapy is one strategy that has the potential for enhanced antiviral effects and diminished or delayed resistance. The disadvantages of combination therapy include increased cost, the potential for drug interactions and increased toxicity. Additional therapeutic efficacy from combination therapy has not been demonstrated in clinical trials of HBV, and this approach might be less relevant now that potent NAs with excellent drug resistance profiles are available. However, it might be possible to identify subsets of patients (for example, those with extremely high viraemia or low baseline alanine aminotransferase levels) who derive added benefit from combination therapy. This review examines efficacy and resistance data for new low resistance oral NAs and clinical experience to date with de novo combination therapy in patients with CHB. The application of combination therapy in select populations of patients with CHB is also discussed.
Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8+ Memory T Cells

ABSTRACT The majority of acute hepatitis C virus (HCV) infections progress to chronicity and progressive liver damage. Alpha interferon (IFN-α) antiviral therapy achieves the highest rate of success when IFN-α is administered early during the acute phase, but the underlying mechanisms are unknown. We used a panel of major histocompatibility complex class I tetramers to monitor the phenotypic and functional signatures of HCV-specific T cells during acute HCV infection with different infection outcomes and during early IFN therapy. We demonstrate that spontaneous resolution correlates with the early development of polyfunctional (IFN-γ- and IL-2-producing and CD107a+) virus-specific CD8+ T cells. These polyfunctional T cells are distinguished by the expression of CD127 and Bcl-2 and represent a transitional memory T-cell subset that exhibits the phenotypic and functional signatures of both central and effector memory T cells. In contrast, HCV-specific CD8+ T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery. Early therapeutic intervention with pegylated IFN-α rescued polyfunctional memory T cells expressing high levels of CD127 and Bcl-2. These cells were detectable for up to 1 year following discontinuation of therapy. Our results suggest that the polyfunctionality of HCV-specific T cells can be predictive of the outcome of acute HCV infection and that early therapeutic intervention can reconstitute the pool of long-lived polyfunctional memory T cells.
Geographic variation in sperm traits reflects predation risk and natural rates of multiple paternity in the guppy

Guppies (Poecilia reticulata) are models for understanding the interplay between natural and sexual selection. In particular, predation has been implicated as a major force affecting female sexual preferences, male mating tactics and the level of sperm competition. When predation is high, females typically reduce their preferences for showy males and engage more in antipredator behaviours, whereas males exploit these changes by switching from sexual displays to forced matings. These patterns are thought to account for the relatively high levels of multiple paternity in high‐predation populations compared to low‐predation populations. Here, we assess the possible evolutionary consequences of these patterns by asking whether variation in sperm traits reflect differences in predation intensity among four pairs of Trinidadian populations: four that experience relatively low levels of predation from a gape‐limited predator and four that experience relatively high levels of predation from a variety of piscivores. We found that males in high‐predation populations had faster swimming sperm with longer midpieces compared to males in low‐predation populations. However, we found no differences among males in high‐ and low‐predation populations with respect to sperm number, sperm head length, flagellum length and total sperm length.
Risk factors contributing to weaning failure from continuous positive airway pressure to high flow nasal cannula in neonates with respiratory distress syndrome

Background Respiratory distress syndrome (RDS) is one of the most frequent causes of mortality and morbidity in neonates. High flow nasal canule (HFNC) is a step ladder modality of alternative oxygen therapy for weaning to reduce the workload of breathing and the need for intubation. Objective To identify the risk factors contributing to weaning failure from continuous positive airway pressure (CPAP) to HFNC in neonates with RDS. Methods This study was a retrospective observational study in neonates aged less than 36 weeks weighing less than 2500 grams who underwent CPAP to HFNC weaning from 2019 to 2021 in Dr. Kariadi Hospital, Semarang, Central Java, Indonesia. Results There were 108 patients included in this study. Our bivariate analysis found significant differences in gestational age, age at the start of weaning, body weight at the start of weaning, FiO2 levels, history of maternal chorioamnionitis, patent ductus arteriosus (PDA), anemia, apnea of prematurity (AOP), and sepsis in neonates with RDS. Multivariate analysis showed that the most dominant factors were FiO2 levels of more than 25% at the start of weaning (OR11.16; 95%CI 1.83 to 63.12; P=0.009), anemia (OR 7.70; 95%CI 1.39 to 42.67; P=0.019), AOP (OR 19.64; 95%CI 4.27 to 90.35; P<0.001), and sepsis (OR 10.93; 95%CI 2.37 to 45.53; P=0.002) Conclusion FiO2 setting of more than 25% at the start of weaning, anemia, AOP, and sepsis produce a significant probability of HFNC weaning failure.
Pharmacogenomic Discovery to Function and Mechanism: Breast Cancer as a Case Study

Biomedical research is undergoing rapid change, with the development of a series of analytical omics techniques that are capable of generating Biomedical Big Data. These developments provide an unprecedented opportunity to gain novel insight into disease pathophysiology and mechanisms of drug action and response—but they also present significant challenges. Pharmacogenomics is a discipline within Clinical Pharmacology that has been at the forefront in defining, taking advantage of, and dealing with the opportunities and challenges of this aspect of the Post‐Genome Project world. This overview will describe the evolution of germline pharmacogenomic research strategies as we have moved from an era of candidate genes to agnostic genome‐wide association studies (GWAS) coupled with the functional and mechanistic pursuit of GWAS signals. Germline pharmacogenomic studies of breast cancer endocrine therapy will be used to illustrate research strategies that are being applied broadly to omics studies of drug response phenotypes.
Encourage Teacher Innovative Behavior : The Interaction Role of Cognitive Flexibility and Teacher Self-Efficacy

This study aims to analyze the interaction role of cognitive flexibility and teacher self-efficacy in teacher innovative behavior in the context of curriculum change in Indonesian schools. This study used a quantitative survey method. Three instruments were used, namely the Teacher Innovative Behavior Scale, the Cognitive Flexibility Inventory, and the Teachers’ Sense of Efficacy Scale. Data were collected from 322 teachers from three educational levels in Jabodetabek. Descriptive analyses, correlation analyses, and moderation analyses were conducted. The findings revealed that cognitive flexibility, as a whole construct, and each dimension (the control and alternative dimension), positively predicts teacher innovative behavior. Specifically, only the alternative dimension that significantly interacts with teacher self-efficacy positively predicts teacher innovative behavior. In other words, teacher self-efficacy is significant as a moderator. The findings highlight the importance of addressing cognitive flexibility and teacher self-efficacy, which were not extensively researched before, in enhancing teachers’ innovative behavior. Innovative behavior is crucial for teachers, especially in the current era of change.