Miracle-dz/UniFAR-FTUs huggingface dataset:
Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Atherosclerosis may lead to cardiovascular diseases (CVD), which are the primary cause of death globally. In addition to conventional therapeutics for CVD, use of nutraceuticals that prevents cholesterol deposition, reduce existing plaques and hence anti-atherosclerotic effects of nutraceuticals appeared to be promising. As such, in the present study we evaluated the beneficial effects of punicalagin, a phytochemical against an atherosclerotic cell model in vitro. Cytotoxicity assays were examined for 10 µM concentration of punicalagin on THP-1 macrophages. Real-time-polymerase chain reaction (RT-PCR) was used to analyze monocyte chemoattractant protein-1 (MCP-1) and Intercellular adhesion molecule (ICAM-1) expressions. Monocyte migration and cholesterol efflux assays were performed to investigate punicalagin’s further impact on the key steps of atherosclerosis. Cytotoxicity assays demonstrated no significant toxicity for punicalagin (10 µM) on THP-1 macrophages. Punicalagin inhibited the IFN-γ-induced overexpression of MCP-1 and ICAM-1 in macrophages by 10 fold and 3.49 fold, respectively, compared to the control. Punicalagin also reduced the MCP-1- mediated migration of monocytes by 28% compared to the control. Percentages of cellular cholesterol efflux were enhanced in presence or absence of IFN-γ by 88% and 84% compared to control with 58% and 62%, respectively. Punicalagin possesses anti-inflammatory and anti-atherosclerotic effects. Punicalagin also did not exhibit any cytotoxicity and therefore can be considered a safe and potential candidate for the treatment and prevention of atherosclerosis.
The Effect of Supplementation with Low Doses of a Cod Protein Hydrolysate on Satiety Hormones and Inflammatory Biomarkers in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study

Metabolic syndrome (MetS) is characterised by metabolic abnormalities that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. Altered levels of circulating ghrelin, several adipokines and inflammatory markers secreted from adipose tissue, such as leptin, adiponectin, tumor necrosis factor alpha, are observed in overweight and obese individuals. We assessed the effect of supplementation with low doses of a cod protein hydrolysate (CPH) on fasting and postprandial levels of acylated ghrelin, as well as fasting levels of adiponectin, leptin and inflammatory markers in subjects with MetS. A multicentre, double-blinded, randomized controlled trial with a parallel group design was conducted. Subjects received a daily supplement of CPH (4 g protein, n = 15) or placebo (0 g protein, n = 15). We observed no effect on fasting or postprandial levels of acylated ghrelin, fasting levels of adiponectin (p = 0.089) or leptin (p = 0.967) after supplementation with CPH, compared to placebo. Overall, our study showed that 8 weeks supplementation with a low dose of CPH in subjects with MetS had no effect on satiety hormones or most of the inflammatory markers, but the levels of high-sensitivity C-reactive protein were statistically significantly different in the CPH-group compared to placebo group. The robustness and clinical relevance of these findings should be explored in future studies with a larger sample size.
Invasive Saprochaete Infections: An Emerging Threat to Immunocompromised Patients

Saprochaete clavata and Saprochaete capitata are emerging fungal pathogens that are responsible for life threatening infections in immunocompromised patients, particularly in the setting of profound neutropenia. They have been associated with multiple hospital outbreaks mainly in Europe. In this article, we present a comprehensive review of the epidemiology, clinical presentation, diagnosis, antifungal susceptibility and treatment of these organisms. The diagnosis of invasive Saprochaete disease is challenging and relies primarily on the isolation of the fungi from blood or tissue samples. Both species are frequently misidentified as they are identical macroscopically and microscopically. Internal transcribed spacer sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry are useful tools for the differentiation of these fungi to a species level. Saprochaete spp. are intrinsically resistant to echinocandins and highly resistant to fluconazole. Current literature suggests the use of an amphotericin B formulation with or without flucytosine for the initial treatment of these infections. Treatment with extended spectrum azoles might be promising based on in vitro minimum inhibitory concentration values and results from case reports and case series. Source control and recovery of the immune system are crucial for successful therapy.
Fc γ receptor compositional heterogeneity: Considerations for immunotherapy development

The antibody-binding crystallizable fragment (Fc) γ receptors (FcγRs) are expressed by leukocytes and activate or suppress a cellular response once engaged with an antibody-coated target. Therapeutic mAbs that require FcγR binding for therapeutic efficacy are now frontline treatments for multiple diseases. However, substantially fewer development efforts are focused on the FcγRs, despite accounting for half of the antibody–receptor complex. The recent success of engineered cell-based immunotherapies now provides a mechanism to introduce modified FcγRs into the clinic. FcγRs are highly heterogeneous because of multiple functionally distinct alleles for many genes, the presence of membrane-tethered and soluble forms, and a high degree of post-translational modification, notably asparagine-linked glycans. One significant factor limiting FcγR improvement is the fundamental lack of knowledge regarding endogenous receptor forms present in the human body. This review describes the composition of FcγRs isolated from primary human leukocytes, summarizes recent efforts to engineer FcγRs, and concludes with a description of potential FcγR features to enrich for enhanced function. Further understanding FcγR biology could accelerate the development of new clinical therapies targeting immune-related disease.
Dynamic hyperinflation induced by the 6-minute pegboard and ring test in hospitalized patients with exacerbated COPD

Background The six-minute pegboard and ring test (6-PBRT) has been used to evaluate functional capacity of the upper limbs in stable chronic obstructive pulmonary disease (COPD) patients. To the best of our knowledge, no studies have evaluated dynamic hyperinflation (DH) during exercise with upper limbs in the hospital setting. The aim of this study was to evaluate physiological responses and DH induced by 6-PBRT in hospitalized patients with acute exacerbation of COPD (AECOPD). Methods A cross-sectional study was conducted in a tertiary hospital enrolling patients who were hospitalized due to AECOPD. All included participants underwent an evaluation of lung function and 6-PBRT when they reached minimum clinical criteria. Ventilatory and hemodynamics parameters were monitored during 6-PBRT and until 6 minutes of rest after the test. Symptoms of dyspnea and upper limb fatigue were also measured. Results Eighteen patients (71.3±5.1 years) with a mean FEV1 of 43.2±18.3% were included in the study (11 females). Prevalence of DH after 6-PBRT was 50% (considering the drop of 150 ml or 10% of inspiratory capacity, immediately after the end of the test). There was a significant increase in respiratory rate, minute volume, dyspnea, and upper limb fatigue after the end of 6-PBRT (p<0.05). Dyspnea recovered more precociously than the perception of fatigue, being reestablished within four minutes of rest. An increase in heart rate, systolic and diastolic blood pressures was also induced by 6-PBRT (p<0.05), requiring 6 minutes of recovery to return to baseline. No adverse events were observed during 6-PBRT. We concluded that 6-PBRT induces physiological changes during its execution, at safe levels, requiring a maximum of 6 minutes for recovery. Finally, the test proved to be safe and applicable for patients hospitalized due to AECOPD.
[Risk factors for hypoglycemia in preterm infants with a gestational age of ≤32 weeks].

OBJECTIVE To investigate the risk factors for hypoglycemia after birth in preterm infants with a gestational age of ≤32 weeks. METHODS A retrospective analysis was performed for 86 neonates with hypoglycemia and a gestational age of ≤32 weeks who were admitted to the neonatal intensive care unit from January 2017 to June 2020 (hypoglycemia group). A total of 172 preterm infants with normal blood glucose who were hospitalized during the same period were randomly enrolled as the control group. Univariate analysis and multivariate logistic regression analysis were used to screen out the risk factors for hypoglycemia in preterm infants. RESULTS There were 515 preterm infants during the study, among whom 86 (16.7%) had hypoglycemia. Compared with the control group, the hypoglycemia group had significantly higher percentages of small for gestational age (SGA), cesarean section, maternal hypertension, and antenatal steroid administration (P<0.05), but significantly lower birth weight and rate of intravenous glucose use before blood glucose test (P<0.05). SGA (OR=4.311, 95%CI: 1.285-14.462, P<0.05), maternal hypertension (OR=2.469, 95%CI: 1.310-4.652, P<0.05), and antenatal steroid administration (OR=6.337, 95%CI: 1.430-28.095, P<0.05) were risk factors for hypoglycemia in preterm infants, while intravenous glucose use (OR=0.318, 95%CI: 0.171-0.591, P<0.05) was a protective factor against hypoglycemia in preterm infants. CONCLUSIONS SGA, maternal hypertension, and antenatal steroid administration may increase the risk of early hypoglycemia in preterm infants with a gestational age of ≤32 weeks, and intravenous glucose use is recommended as soon as possible after birth for preterm infants with a gestational age of ≤32 weeks to reduce the incidence rate of hypoglycemia.
Antifibrotic and Regenerative Effects of Treamid in Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by interstitial fibrosis and progressive respiratory failure. Pirfenidone and nintedanib slow down but do not stop the progression of IPF. Thus, new compounds with high antifibrotic activity and simultaneously regenerative activity are an unmet clinical need. Recently, we showed that Treamid can help restoring the pancreas and testicular tissue in mice with metabolic disorders. We hypothesized that Treamid may be effective in antifibrotic therapy and regeneration of damaged lung tissue in pulmonary fibrosis. In this study, experiments were performed on male C57BL/6 mice with bleomycin-induced pulmonary fibrosis. We applied histological and immunohistochemical methods, ELISA, and assessed the expression of markers of endothelial and epithelial cells in primary cultures of CD31+ and CD326+ lung cells. Finally, we evaluated esterase activity and apoptosis of lung cells in vitro. Our data indicate that Treamid exhibits antifibrotic activity in mice with pulmonary fibrosis and has a positive effect on capillaries of the lungs. Treamid also increases the number of endothelial progenitor cells in the lungs of animals with pulmonary fibrosis. Lastly, Treamid increases esterase activity and decreases apoptosis of CD31+ lung cells in vitro. Based on these findings, we suggest that Treamid may represent a promising compound for the development of new antifibrotic agents, which are capable of stimulating regeneration of lung endothelium in IPF patients.
A Prospective Validation and Observer Performance Study of a Deep Learning Algorithm for Pathologic Diagnosis of Gastric Tumors in Endoscopic Biopsies

Purpose: Gastric cancer remains the leading cause of cancer-related deaths in Northeast Asia. Population-based endoscopic screenings in the region have yielded successful results in early detection of gastric tumors. Endoscopic screening rates are continuously increasing, and there is a need for an automatic computerized diagnostic system to reduce the diagnostic burden. In this study, we developed an algorithm to classify gastric epithelial tumors automatically and assessed its performance in a large series of gastric biopsies and its benefits as an assistance tool. Experimental Design: Using 2,434 whole-slide images, we developed an algorithm based on convolutional neural networks to classify a gastric biopsy image into one of three categories: negative for dysplasia (NFD), tubular adenoma, or carcinoma. The performance of the algorithm was evaluated by using 7,440 biopsy specimens collected prospectively. The impact of algorithm-assisted diagnosis was assessed by six pathologists using 150 gastric biopsy cases. Results: Diagnostic performance evaluated by the AUROC curve in the prospective study was 0.9790 for two-tier classification: negative (NFD) versus positive (all cases except NFD). When limited to epithelial tumors, the sensitivity and specificity were 1.000 and 0.9749. Algorithm-assisted digital image viewer (DV) resulted in 47% reduction in review time per image compared with DV only and 58% decrease to microscopy. Conclusions: Our algorithm has demonstrated high accuracy in classifying epithelial tumors and its benefits as an assistance tool, which can serve as a potential screening aid system in diagnosing gastric biopsy specimens.
Online corrective responses following target jump in altered gravitoinertial force field point to nested feedforward and feedback control.

Studies on goal-directed arm movements have shown a close link between feedforward and feedback control in protocols where both planning and online control processes faced a similar type of perturbation, either mechanical or visual. This particular context might have facilitated the use of an adapted internal model by feedforward and feedback control. Here we considered this link in a context where after feedforward control was adapted through proprioception-based processes, feedback control was tested under visual perturbation. We analyzed the response of the reaching hand to target displacements following adaptation to an altered force field induced by rotating participants at constant velocity. Reaching corrections were assessed through variables related to the accuracy (lateral and longitudinal endpoint errors) and kinematics (movement time, peak velocity) of the corrective movements. The electromyographic activity of different arm muscles (pectoralis, deltoid, biceps and triceps brachii) was analyzed. Statistical analyses revealed that accuracy and kinematics of corrective movements were strikingly alike between normal and altered gravitoinertial force fields. However, pectoralis and biceps muscle activities recorded during corrective movements were significantly modified to counteract the effect of rotation-induced Coriolis and centrifugal forces on the arm. Remarkably, feedback control was functional from the very first time participants encountered a target jump in the altered force field. Overall, the present results demonstrate that feedforward control enables immediate functional feedback control even when applied to distinct sensorimotor processes.
Anticarsia gemmatalis Nucleopolyhedrovirus from Soybean Crops in Tamaulipas, Mexico: Diversity and Insecticidal Characteristics of Individual Variants and their Co-Occluded Mixtures

Abstract In 1999, Anticarsia gemmatalis nucleopolyhedrovirus (AgMNPV) was introduced into a major soybean-growing region in Tamaulipas, Mexico, for control of its lepidopteran host, Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae). The virus introduction proved to be highly successful in controlling this agronomically important pest. In order to determine the genotypic diversity and insecticidal traits of Mexican AgMNPVs, we obtained 30 field-collected isolates from Tamaulipas State. Five distinct variants (genotypes 1–5) were identified from plaques replicated in A. gemmatalis larvae by examination of restriction profiles using HindIII. Initial screening indicated that none of the variants, or co-occluded mixtures of variants in different proportions, was more pathogenic than the 30 field isolates mixture or a reference variant from Brazil (AgMNPV-2D). Mean occlusion body production also was similar among genotype variants, the mixture of 30 field isolates and AgMNPV-2D treatments, but was significantly reduced in 1 co-occluded mixture. Speed of kill also was similar among variants (except genotype 1) and their mixtures. Lethal concentration metrics indicated that these results were unlikely due to selection of variants with reduced pathogenicity during the plaque purification process. We conclude that the mixture of 30 field isolates most likely would prove suitable for use as a biological insecticide in the soybean-growing region of Mexico.
Double-Hybrid DFT Functionals for the Condensed Phase: Gaussian and Plane Waves Implementation and Evaluation

Intermolecular interactions play an important role for the understanding of catalysis, biochemistry and pharmacy. Double-hybrid density functionals (DHDFs) combine the proper treatment of short-range interactions of common density functionals with the correct description of long-range interactions of wave-function correlation methods. Up to now, there are only a few benchmark studies available examining the performance of DHDFs in condensed phase. We studied the performance of a small but diverse selection of DHDFs implemented within Gaussian and plane waves formalism on cohesive energies of four representative dispersion interaction dominated crystal structures. We found that the PWRB95 and ωB97X-2 functionals provide an excellent description of long-ranged interactions in solids. In addition, we identified numerical issues due to the extreme grid dependence of the underlying density functional for PWRB95. The basis set superposition error (BSSE) and convergence with respect to the super cell size are discussed for two different large basis sets.
Analysis of Arterial Stiffness and Sexual Function after Adding on PCSK9 Inhibitor Treatment in Male Patients with Familial Hypercholesterolemia: A Single Lipid Center Real-World Experience

Familial hypercholesterolemia (FH) subjects have high low-density lipoprotein cholesterol (LDL-C) and may be at high risk of erectile dysfunction and atherosclerotic cardiovascular diseases. We evaluated the effect of PCSK9-i on sexual function evaluated by the Male Sexual Health Questionnaire (MSHQ) and the International Index of Erectile Function (IIEF-5) questionnaire and on pulse wave velocity (PWV) in FH male subjects. In this prospective observational study, we evaluated 30 FH male patients on high-intensity statins plus ezetimibe and with an LDL-C off-target. All patients added PCSK9-i treatment and obtained clinical assessment at baseline and after six months of PCSK9-i. As expected, LDL-C significantly decreased after adding-on PCSK9-i (−48.73%, p < 0.001). MSHQ and PWV significantly improved after adding-on PCSK9-i (for MSHQ 93.63 ± 6.28 vs. 105.41 ± 5.86, p < 0.05; for PWV 9.86 ± 1.51 vs. 7.7 ± 1.42, p < 0.05); no significant change of IIEF-5 was found. Finally, a simple regression showed that ∆ MSHQ was significantly associated with ∆ LDL-C and ∆ PWV (p value for both <0.05). In conclusion, PCSK9-i therapy significantly improves lipid profile, PWV, and sexual function in FH male patients; our results support the favorable function of PCSK9-i on these parameters.
Caustic-Side Solvent Extraction: Extended Equilibrium Modeling of Cesium and Potassium Distribution Behavior

An extension of the model developed in FY01 for predicting equilibrium distribution ratios in the Caustic-Side Solvent Extraction (CSSX) process is presented here. Motivation for extending the model arose from the need to predict extraction performance of the recently optimized solvent composition and the desire to include additional waste components. This model involves the extraction of cesium and potassium from different cesium, potassium, and sodium media over a large range of concentrations. Those different media include a large variety of anions such as nitrate, hydroxide, nitrite, chloride, fluoride, sulfate, and carbonate. The model was defined based on several hundreds of experimental data points and predicted satisfactorily the cesium extraction from five different SRS waste simulants. This process model encompassed almost exclusively 1:1:1 metal:anion:ligand species. Fluoride, sulfate, and carbonate species were found to be very little extractable, and their main impact is reflected through their activity effects. This model gave a very good cesium and potassium extraction prediction from sodium salts, which is what is needed when trying to predict the behavior from actual waste. However, the extraction from potassium or cesium salts, and the extraction of sodium could be improved, and some additional effort was devoted to improve the thermodynamic rigor of the model. Toward this end, more detailed anion-specific models were developed based on the cesium, potassium, and sodium distribution ratios obtained with simple systems containing single anions, but it has not yet proven possible to combine those models to obtain better predictions than provided by the process model.
Quantitative Evaluation of the Echo Intensity of Paraneural Area and Myofascial Structure around Median Nerve in Carpal Tunnel Syndrome

The aim of this study was to investigate whether the echo intensity (EI) of the paraneural area (PA), the median nerve (MN) at the carpal tunnel, the EI of the myofascial structure (MS) around MN, the ‘PA and MN’ at the mid-forearm, and the MN transversal displacement at both sites differs between persons with carpal tunnel syndrome (CTS) and control subjects. Methods: In total, 16 CTS patients and 16 controls, age- and gender-matched, were recruited. Cross-sectional ultrasound images of MN were obtained to evaluate the EI of the PA, the MN at carpal tunnel, the EI of MS, and the ‘PA and MN’ at the mid-forearm in a natural position, then images were taken after a whole-hand grasp movement, to evaluate MN transversal displacement. Inter-rater and intra-rater reliability in control, and differences in the EI and MN displacement between CTS and control, were analyzed. In addition, the correlations between ultrasound parameters and MN displacement were evaluated. Results: The quantitative EI of PA, MN, EI of MS, ‘PA and MN’ had high inter-rater and intra-rater reliability in the control. The EI of PA, MS and ‘PA and MN’ were significantly higher in CTS subjects (p < 0.01), whilst there was no significant difference in the EI of MN at the carpal tunnel. MN displacement was significantly decreased both at the carpal tunnel and the mid-forearm in CTS subjects (p < 0.01). In addition, there were negative correlations among the EI of PA (rs = −0.484, p = 0.004), EI of MS (rs = −0.479, p = 0.002), EI of ‘PA and MN’ (rs = −0.605, p < 0.001) and MN transversal displacement. Conclusions: The higher EI of PA and MS around MN in CTS may indicate greater fibrosis along the course of MN, reducing fascial adaptability, influencing the synergy and coordination of the MS, and increasing the shear stress between MS and MN, and it may further increase the abnormal pressure on the MN not only at the carpal tunnel, but also at the mid-forearm. These results may partly explain the role of PA and MS in CTS pathogenesis.