Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotyping genetic variants of CYP2C19 for precision antiplatelet dosing: state of the art and future perspectives

ABSTRACT Introduction Clopidogrel is the only antiplatelet agent whose activity is significantly affected by CYP2C19 polymorphism. Areas covered This review has summarized the available evidence on the clinically significant association between CYP2C19 polymorphism and clopidogrel-based therapy; reviewed the current recommendations for clinical use of CYP2C19 genotype test results in patients on clopidogrel treatment; and discussed possible pitfalls of routine application, and future perspectives of antiplatelets pharmacogenetics. Expert opinion The available body of evidence, reflected in several meta-analyses and high-quality clinical practice guidelines, shows that the presence of CYP2C19 LOF alleles, especially CYP2C19*2, correlates with impaired activation of clopidogrel and variable platelet inhibition, followed by minimal or no antiplatelet effect, and higher risk of treatment failure. In combination with other known risk factors, CYP2C19 genetic testing could be very valuable in predicting low clopidogrel efficacy. At the same time, it could be very successful in selecting patients who will most probably benefit from the clopidogrel-based therapy, thus decreasing the pool of those who might need more expensive and otherwise riskier antiplatelet alternatives.
Why Some Mice Are Smarter than Others: The Impact of Bone Morphogenetic Protein Signaling on Cognition

Abstract Inbred mice (C57Bl/6) display wide variability in performance on hippocampal-dependent cognitive tasks. Examination of microdissected dentate gyrus (DG) after cognitive testing showed a highly significant negative correlation between levels of bone morphogenetic protein (BMP) signaling and recognition memory. Cognitive performance decline during the aging process, and the degree of cognitive decline is strongly correlated with aging-related increases in BMP signaling. Further, cognitive performance was impaired when the BMP inhibitor, noggin, was knocked down in the DG. Infusion of noggin into the lateral ventricles enhanced DG-dependent cognition while BMP4 infusion led to significant impairments. Embryonic overexpression of noggin resulted in lifelong enhancement of recognition and spatial memory while overexpression of BMP4 resulted in lifelong impairment, substantiating the importance of differences in BMP signaling in wild-type mice. These findings indicate that performance in DG-dependent cognitive tasks is largely determined by differences in levels BMP signaling in the dentate gyrus.
Risk factors for lymph node metastasis in patients with pT2 colon cancer in Denmark from 2016 to 2019—A nationwide cohort study

The majority of patients with pT2 colon cancer have no lymph node metastasis (LNM). Knowledge of risk factors for LNM in pT2 colon cancer could identify patients at low risk and thereby potential candidates for local tumour excision. The aim of this work was to identify risk factors for LNM in pT2 colon cancer and describe a subgroup of low‐risk patients.
Particles in the Lower Troposphere over the High Plains of the United States. Part III: Ice Nuclei.

Abstract One hundred and fifty-five ice nucleus (IN) spectra were measured from an aircraft at various locations over the High Plains of the United States during the springs and summers of 1975 and 1976. Frequency distributions of the IN concentrations at each test temperature reveal two modes, each of which is apparently lognormally distributed. The dominant mode occurs at high IN concentrations, and the other mode at low concentrations. The characteristic IN spectrum was represented by N(T) = 2 × 10−4 exp(−0.3ΔT), where N(T) is the concentration (per liter) of IN at temperature T and supercooling ΔT. The IN generally appear to derive from a widespread and fairly uniform ground source, which accounts for the dominant mode. However, concentrations can be increased by duststorms and industrial pollution and decreased in the vicinity of localized IN sinks (e.g., clouds and precipitation). As a consequence, IN concentrations can vary markedly during the course of a day, from day-to-day, and cyclically over p.
Electromagnetic absorption cross section of Reissner-Nordström black holes

The absorption cross section of Reissner-Nordstroem black holes for the electromagnetic field is computed numerically for arbitrary frequencies. The numerical results are in excellent agreement with the low- and high-frequency limits, which are obtained with analytical methods. Special emphasis is given to the extreme Reissner-Nordstroem black hole case.
GenPADS: Reinforcing politeness in an end-to-end dialogue system

In a task-oriented dialogue setting, user’s mood and demands can change in an ongoing dialogue, which may lead to a non-informative conversation or may result in conversation drop-off. To rectify such scenarios, a conversational agent should be able to learn the user’s behaviour online, and form informative, empathetic and interactive responses. To incorporate these three aspects, we propose a novel end-to-end dialogue system GenPADS. First, we build and train two models, viz. a politeness classifier to extract polite information present in user’s and agent’s utterances and a generation model (G) to generate varying but semantically correct responses. We then incorporate both of these models in a reinforcement learning (RL) setting using two different politeness oriented reward algorithms to adapt and generate polite responses. To train our politeness classifier, we annotate recently released Taskmaster dataset into four fine-grained classes depicting politeness and impoliteness. Further, to train our generator model, we prepare a GenDD dataset using the same Taskmaster dataset. Lastly, we train GenPADS and perform automatic and human evaluation by building seven different user simulators. Detailed analysis reveals that GenPADS performs better than the two considered baselines,viz. a transformer based seq2seq generator model for user’s and agent’s utterance and a retrieval based politeness adaptive dialogue system (PADS).
Role of mass on the stability of flag/flags in uniform flow

The interaction between flag/flags and fluid is studied numerically and the time-average flow in the wake is analyzed. It is found that a zero-mass flag in uniform flow can not exhibit sustained flapping which only occurs when the mass is involved, while multiple zero-mass flags with small separation settle into sustained flapping state. Furthermore, the nonzero mass is an essential condition for flag/flags to establish the sustained flapping in the case of convectively instable wake, while it is an unnecessary condition for the case of the absolutely instable wake.
Many-body effects on the coarsening of grain boundary precipitates

The authors study the asymptotic behaviour of a diffusion-controlled coarsening of grain boundary precipitates. Using an analogy to two-dimensional particle coarsening, they consider cooperative effects among precipitates occurring via the diffusion field. They discuss the finite volume fraction effects on the form of the precipitate size distribution function and the coarsening rate.
Bad or worse? Applying critical theory to explore the impacts of Payatas dumpsite closure on the former waste pickers

Numerous garbage dumpsites worldwide have been closed down to address the safety, health and environmental hazards facing waste pickers, such as potential landsides, diseases and pollution. As a result, the environment surrounding the (former) waste pickers may have been safer and cleaner. While the closure of garbage dumpsites may be an act of social justice to protect waste pickers, however, in some cases, the incomes and living standards of former waste pickers who continue to reside at these sites have been aggravated. Drawing on critical theory, and using observations and interviews, this case study examined the post-dumpsite-closure situation of Payatas in the Philippines. This study augments previous research on critical urban and regional studies through the presentation of a meta-critical theory by expanding, critiquing and reconceptualizing critical theory to address the problematic post-dumpsite situation created through the closure of the dumpsite.
The column density and scale height of free electrons in the galactic disk

The recent discoveries of millisecond pulsars in globular clusters located far from the Galactic plane provide the first direct measurements of the total extent and column density of diffuse ionized gas within the Galactic disk. The dispersion measures of the pulsars in the clusters, 47 Tuc at z equals about -3.3 kpc and M15 at z equals about -4.3 kpc imply a column density of (0.8-1.4) x to the 20th/sq cm between the clusters and the midplane. When combined with the dispersion measures of pulsars located closer to the Galactic plane, this result indicates a free electron scale height H(e) = 1500 pc. Diffuse H(+) thus accounts for about one-quarter of the total column density of interstellar atomic hydrogen near the solar circle and appears to be the dominant state of the interstellar gas at an absolute value of z greater than 1000 pc. 46 refs.
Imperfection sensitivity due to coupled local instability: a non‐convex QP solution algorithm

The paper deals with the collapse safety of slender elastic structures subjected to local buckling interaction. Using Koiter's asymptotic approach, the mechanical problem is reduced to the search for all the local minima of an indefinite quadratic form over the unit simplex. An efficient recursive branch‐and‐cut algorithm is proposed for solving this non‐convex QP problem, allowing a numerical procedure providing statistical information about the collapse load for a given distribution of random imperfections to be set up. Copyright © 2006 John Wiley & Sons, Ltd.
Extremely high extinction ratio terahertz broadband polarizer using bilayer subwavelength metal wire-grid structure

We report a broadband terahertz (THz) polarizer exhibiting extremely high polarization extinction ratio and the method to fabricate it. The polarizer consists of a bilayer subwavelength Au wire-grid structure fabricated on Si substrate by one step etching and metal formation. The THz time domain spectroscopy (THz-TDS) measurement reveals an extremely high extinction ratio of 84.9 dB at 1.67 THz, close to the detection limit of THz-TDS system, and an average extinction ratio of 69.9 dB in 0.6–3 THz frequency range. The fabricated bilayer wire-grid polarizer shows greatly enhanced performance over conventional single layer wire-grid THz polarizer.
Ambient precipitation determines the sensitivity of soil respiration to precipitation treatments in a marsh

The effects in field manipulation experiments are strongly influenced by amplified interannual variation in ambient climate as the experimental duration increases. Soil respiration (SR), as an important part of the carbon cycle in terrestrial ecosystems, is sensitive to climate changes such as temperature and precipitation changes. A growing body of evidence has indicated that ambient climate affects the temperature sensitivity of SR, which benchmarks the strength of terrestrial soil carbon–climate feedbacks. However, whether SR sensitivity to precipitation changes is influenced by ambient climate is still not clear. In addition, the mechanism driving the above phenomenon is still poorly understood. Here, a long‐term field manipulation experiment with five precipitation treatments (−60%, −40%, +0%, +40%, and +60% of annual precipitation) was conducted in a marsh in the Yellow River Delta, China, which is sensitive to soil drying–wetting cycle caused by precipitation changes. Results showed that SR increased exponentially along the experimental precipitation gradient each year and the sensitivity of SR (standardized by per 100 mm change in precipitation under precipitation treatments) exhibited significant interannual variation from 2016 to 2021. In addition, temperature, net radiation, and ambient precipitation all exhibited dramatic interannual variability; however, only ambient precipitation had a significant negative correlation with SR sensitivity. Moreover, the sensitivity of SR was significantly positively related to the sensitivity of belowground biomass (BGB) across 6 years. Structural equation modeling and regression analysis also showed that precipitation treatments significantly affected SR and its autotrophic and heterotrophic components by altering BGB. Our study demonstrated that ambient precipitation determines the sensitivity of SR to precipitation treatments in marshes. The findings underscore the importance of ambient climate in regulating ecosystem responses in long‐term field manipulation experiments.
Could serum ACE2 levels predict infarct size in acute phase of ST-segment elevation myocardial infarction: a comparative study with classical biomarkers.

OBJECTIVE Serum ACE2 level in the acute phase of ST-segment elevation myocardial infarction may be an indicator of heart failure, however, limited studies have reported conflicting results. Therefore, in our study, we aimed to evaluate the relationship between serum ACE2 level and infarct size in the acute phase of ST-segment elevation myocardial infarction and compare the predictive value of ACE2 level with classical biomarkers. PATIENTS AND METHODS Sixty-six patients after the primary percutaneous coronary intervention were included in the study. For the measurement of serum ACE2 levels, blood samples were taken twice from the patients: in the first 24 hours and on the 5th day of the infarction, and once from 30 healthy volunteers. hs-cTnT, BNP, and CRP levels were measured daily, and their peak values were taken. On the 7th day of ST-segment elevation myocardial infarction, gSPECT was used with the 99mTc-MIBI method for assessment of infarct size. RESULTS Baseline ACE2 values were found to be higher in patients compared to controls, and ACE2 values obtained on the 5th day were found to be higher than the baseline values in the patients. There was no significant correlation between serum ACE2 levels and the RSS (%), while peak levels of hs-cTnT, BNP, and CRP were assessed as predictive factors for the RSS (%). CONCLUSIONS Although serum ACE2 levels increased in the acute phase of ST-segment elevation myocardial infarction, this increase was not associated with infarct size. Serum ACE2 level did not provide additional benefit to classical biomarkers for infarct size-related prognosis prediction.
The Jet and Filaments in Cygnus A

On a obtenu des cartes detaillees de Cyg A a partir d'observations VLA a 1,4 et 5 GHz. Un jet radio s'etend du noyau au lobe nord-ouest. On a identifie deux nouveaux points chauds. La pression du gaz de l'amas dans lequel se trouve Cyg A semble insuffisante pour confiner soit le jet, soit les filaments. Le jet est probablement relativiste. La brillance de surface du jet est elevee dans l'absolu, mais la puissance totale rayonnee par le jet n'est que 10 −3 de celle de la source entiere
Resection margin status evaluation in gastric cancer surgery by intraoperative flow cytometry

We have read with a great interest the recent report by Watanabe et al., published in Journal of Surgical Oncology, that contributes towards our understanding on the impact of resection margin status in gastric cancer surgery. Gastric Cancer is the fifth most common cancer type and the fourth cause of cancer‐associated mortality. Several factors contribute toward this dismal figure, that include surgical management. Positive resection margins are strongly associated with poor prognosis. In the state‐of‐the‐art report by Watanabe et al., the authors evaluated the role of intraoperative frozen section (IFS) analysis of resection margins (RMs). The study included 377 patients, 16% of which has positive RMs. IFS analysis has been applied in 34% of the patients and has found to significantly contribute towards negative RMs and improved overall survival. The authors conclude that further application of IFS may prove impactful in high‐risk patients and support the further use of this interesting technique. To our opinion this is a proof of concept on the impact of intraoperative methods that evaluate cancer cells and margin status. Recently we have been developing an intraoperative cancer cell evaluation technique, namely intraoperative flow cytometry (iFC), that has been applied in the identification of tumor biology and RMs of several solid tumors, such as brain, head and neck, liver, breast, gynecological, colorectal, and bladder cancer. The rationale of iFC is based on DNA content analysis that permits simultaneous assessment of the cell cycle phases and the ploidy status of neoplastic cells. IFC is fast and allows results acquisition within 5–6min. Intraoperative flow cytometry has a considerably low cost, tissue requirements are minutest. Significantly, iFC methodology has exhibited high reproducibility and high accuracy (>90%) in detecting cancer cells. The calculated sensitivity and specificity of our assay was in most cases above 90%–95%. Lately, we have registered for a clinical protocol for iFC evaluation of RMs during gastric cancer surgery. An iFC evaluation from our ongoing study is depicted in Figure 1. The rationale of iFC is based on the precise and rapid DNA content analysis. In that manner, proliferating cancer cells are distinguished from those of normal tissue, leading to an accurate characterization of surgical margins status (Figure 1). Our data from our previous reports and our ongoing research support that intraoperative flow cytometry would significantly increase the rate of R0 resections in surgical oncology, including gastric cancer surgery. IFS and iFC analysis are paradigms of next‐generation margin evaluation techniques. Results so far are encouraging for the future performance of iFC and analogous techniques such as IFS in the operating theater. We believe that the implementation of individual or simultaneous assessment of margin status by techniques such as IFS and iFC has the potential to
Regression of Hepatic Fibrosis After Endoscopic Gastric Plication in Nonalcoholic Fatty Liver Disease

INTRODUCTION: Fibrosis stage is the strongest predictor of mortality in patients with nonalcoholic fatty liver disease (NAFLD). There is currently no approved therapy that specifically targets fibrosis. This study aims to assess the effect of endoscopic gastric plication on hepatic fibrosis in patients with underlying NAFLD. METHODS: This is a retrospective analysis of prospectively collected registry of patients with obesity and NAFLD with clinically significant hepatic fibrosis (≥F2) who underwent endoscopic gastric plication. Full-thickness plications were placed in the gastric body using a commercially available platform to reduce the gastric volume. The primary outcome included various noninvasive tests (NITs) of hepatic fibrosis based on clinical chemistry and/or imaging. The secondary outcomes included NITs of hepatic steatosis, other metabolic outcomes, including hemoglobin A1c, insulin resistance, and total weight loss (TWL), and adverse events. RESULTS: Forty-five patients (age 51 ± 13 years and body mass index 40.7 ± 6.9 kg/m2) were included. All patients underwent endoscopic gastric plication successfully. At 6–12 months, there were significant reductions in biochemistries (alanine aminotransferase: 49.7 ± 36.8 U/L to 24.2 ± 12.0 U/L [P < 0.0001], aspartate aminotransferase: 39.1 ± 24.1 U/L to 24.1 ± 10.0 U/L [P < 0.0001]), composite fibrosis score (NAFLD fibrosis score: 0.48 ± 1.51 to −1.18 ± 1.56 [P < 0.0001], fibrosis-4 index: 1.4 ± 1.2 to 1.2 ± 0.7 [P = 0.03]), and imaging-based markers of fibrosis (vibration-controlled transient elastography: 13.9 ± 7.5 kPa to 8.9 ± 4.8 kPa (P < 0.0001) and Agile 3+: 0.53 ± 0.28 to 0.37 ± 0.28 [P = 0.001]). There were significant reductions in controlled attenuation parameter, Homeostatic Model Assessment for Insulin Resistance, and hemoglobin A1c (P < 0.05 for all). At 12 months, patients experienced 15.5% ± 7.9% TWL, with 63% reaching at least 10% TWL. DISCUSSION: Endoscopic gastric plication seems effective at treating NAFLD, with significant reduction in NITs of hepatic fibrosis even in patients with cirrhosis.
Effects of Reynolds number and adverse pressure gradient on a turbulent boundary layer developing on a rough surface

A detailed experimental study of turbulent boundary layers developing over rough surfaces subjected to both zero and adverse pressure gradients was undertaken. Two rough surfaces constituted by distributed random elements have been chosen. The experiments were conducted in the range of the Reynolds number R θ based upon the momentum thickness varying from 2200 to 5800 and 3200 to 3800, respectively, with and without pressure gradient. The roughness Reynolds number h + characteristic of the rough surfaces grew from about 25 to 80 in both zero and adverse pressure gradient, which corresponds to Reynolds number based upon the equivalent sand grain ranging from 75 to 225. The boundary layer was probed with a single hot wire. Skin friction coefficient was obtained from the semi-logarithmic profiles of the mean velocity. The aim of this work is to assess the relevance of the “equivalent sand grain” concept, and more precisely if the equivalent sand grain height only depends upon the surface characteristics or also upon the flow regime. The present study confirms that the equivalent sand grain height is far from being constant for a given surface, although this is often assumed in computational fluid dynamics. Significant changes in the equivalent sand grain height are evidenced as well for zero pressure gradient, transitional flow as for adverse pressure gradient, fully rough flow. Therefore, the roughness topology as well as the nature of flow should be accounted for to evaluate an equivalent sand grain roughness.
NeiyiKangfu tablets control the progression of endometriosis through inhibiting RAF/MEK/ERK signal pathway by targeting RKIP

Abstract Background NeiyiKangfu tablets (NYKF) are widely used clinically for the treatment of endometriosis (EMS), whose mechanism of action has been extensively studied. Researchers have found that NYKF may control the development of ectopic lesions by inhibiting angiogenesis and inflammatory cytokine secretion. Nevertheless, NYKF’s mechanism of action remains unclear. Methods In the present study, the function of NYKF in the progression of EMS and the associated underlying mechanism was investigated by in vivo and in vitro experiments. EMS model mice were treated with NYKF and the pro-inflammatory factors and apoptosis of ectopic endometrium as well as RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling activation were assessed. In addition, human endometriosis-derived immortalized entopic stromal (hEM15A) cells transfected with or without RAF kinase inhibitor protein (RKIP)-small-interfering RNA (siRNA) were also treated with NYKF and the proliferation, migration, apoptosis, and RAF/MEK/ERK signaling activation were measured by Cell Counting Kit-8 (CCK-8), flow cytometry, Transwell, and western blot, respectively. Results Results showed that NYKF increased the expression of RKIP, inhibited RAF/MEK/ERK signaling activation, and induced apoptosis while inhibiting proliferation and migration both in EMS mice and hEM15A cells. RKIP knockdown could inhibit the effect of NYKF treatment, leading to the activation of RAF/MEK/ERK signaling and the proliferation and migration of hEM15A cells. Conclusions In conclusion, these results suggest that NYKF treatment promotes apoptosis and inhibits proliferation and migration in EMS by inhibiting the RAF/MEK/ERK signaling pathway by targeting RKIP.