Miracle-dz/UniFAR-FTUs huggingface dataset:
Progesterone hydroxylation by cytochromes P450 2C and 3A enzymes in marmoset liver microsomes

Abstract 1. Common marmosets (Callithrix jacchus) are potentially useful nonhuman primate models for preclinical drug metabolism studies. However, the roles of marmoset cytochrome P450 (P450) isoforms in the oxidation of endobiotic progesterone have not been fully investigated. In this study, the roles of marmoset P450 isoforms in progesterone hydroxylation were extensively determined. 2. The activities of liver microsomes from individual marmosets with respect to progesterone 21/17α- and 16α/6β-hydroxylation were significantly correlated with those for flurbiprofen 4-hydroxylation and midazolam 1′-hydroxylation, respectively, as similar correlations have been found in humans. Anti-P450 2 C and 3 A antibodies suppressed progesterone 21/17α- and 16α/6β-hydroxylation, respectively, in marmoset liver microsomes. 3. Recombinant marmoset P450 2C58 and 2C19 catalyzed progesterone to form 21-hydroxyprogesterone and 16α-hydroxyprogesterone, respectively, as major products with high maximum velocity/Km values of 0.53 and 0.089 mL/min/nmol, respectively. Recombinant marmoset P450 3A4/90 oxidized progesterone to form 6β-hydroxyprogesterone as a major product with homotropic cooperativity (>1 of Hill coefficients). 4. These results indicate that the overall activities and roles of liver microsomal P450 enzymes in marmoset livers are similar to those in humans, especially for progesterone 21/17α- and 16α/6β-hydroxylation by marmoset P450 2 C and 3 A enzymes, respectively, suggesting important roles for these P450 enzymes in the metabolism of endobiotics in marmosets.
Predialysis Cardiovascular Disease Medication Adherence and Mortality After Transition to Dialysis.

BACKGROUND Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among patients with advanced chronic kidney disease and mortality following their transition to dialysis. STUDY DESIGN Observational study. SETTING & PARTICIPANTS 32,348 US veterans who transitioned to dialysis during 2007 to 2011. PREDICTORS Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. OUTCOMES Post-dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. RESULTS Mean age of the cohort was 72±11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC>80%, there were 14,006 deaths (mortality rate, 283 [95% CI, 278-288]/1,000 patient-years]); among patients with PDC>60% to 80%, there were 3,882 deaths (mortality rate, 294 [95% CI, 285-304]/1,000 patient-years); among patients with PDC≤60%, there were 720 deaths (mortality rate, 291 [95% CI, 271-313]/1,000 patient-years). Compared with patients with PDC>80%, the adjusted HR for post-dialysis therapy initiation all-cause mortality for patients with PDC>60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC≤60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post-dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. LIMITATIONS Large number of missing values; results may not be generalizable to women or the general US population. CONCLUSIONS Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation.
Inhibition of Protein Tyrosine Phosphatase 1β by Hispidin Derivatives Isolated from the Fruiting Body of Phellinus linteus

Protein tyrosine phosphatase 1β (PTP1β) acts as a negative regulator of insulin signaling. Selective inhibition of PTP1β has served as a potential drug target for the treatment of type 2 diabetes mellitus. We evaluated the inhibitory effect of Phellinus linteus against PTP1β as part of our ongoing search for natural therapeutic and preventive agents for diabetes mellitus. Fractions of the P. linteus extract were found to exhibit significant inhibitory activities against PTP1β. In an attempt to identify bioactive components, we isolated, from the most active ethyl acetate fraction, five hispidin derivatives (phelligridimer A, davallialactone, hypholomine B, interfungins A, and inoscavin A) and four phenolic compounds (protocatechuic acid, protocatechualdehyde, caffeic acid, and ellagic acid). The chemical structures of these compounds were elucidated from spectroscopic evidence and by comparison with published data. All the compounds strongly inhibited PTP1β activity in an in vitro assay; their IC50 values ranged from 9.0 ± 0.01 to 58.2 ± 0.3 μM. Our results indicated that the hispidin skeleton may be an important moiety for inhibitory activity of the above compounds against PTP1β. Thus, hispidin derivatives could be a potent new class of natural PTP1β inhibitors.
La stéatopathie métabolique : bientôt la première cause d’hépatocarcinome ?

Cette revue de la litterature s’est focalisee sur les articles originaux publies entre 2013 et 2015 qui soulignent le lien croissant entre syndrome metabolique (SM), steato-hepatite metabolique (NASH) et carcinome hepatocellulaire (CHC). Bien d’autres publications pertinentes auraient pu etre citees. La steatopathie metabolique devient la 2e cause de transplantation hepatique pour hepatocarcinome [. ]
Open Versus Minimally Invasive Fixation Techniques for Thoracolumbar Trauma: A Meta-Analysis

Study Design Systematic literature review and meta-analysis of studies published in English. Objective This study evaluated differences in outcome variables between percutaneous and open pedicle screws for traumatic thoracolumbar fractures. Methods A systematic review of PubMed, Cochrane, and Embase was performed. The variables of interest included postoperative visual analog scale (VAS) pain score, kyphosis angle, and vertebral body height, as well as intraoperative blood loss and operative time. The results were pooled by calculating the effect size based on the standardized difference in means. The studies were weighted by the inverse of the variance, which included both within- and between-study error. Confidence intervals were reported at 95%. Heterogeneity was assessed using the Q statistic and I 2. Results After two-reviewer assessment, 38 studies were eliminated. Six studies were found to meet inclusion criteria and were included in the meta-analysis. The combined effect size was found to be in favor of percutaneous fixation for blood loss and operative time (p < 0.05); however, there were no differences in vertebral body height (VBH), kyphosis angle, or VAS scores between open and percutaneous fixation. All of the studies demonstrated relative homogeneity, with I 2 < 25. Conclusions Patients with thoracolumbar fractures can be effectively managed with percutaneous or open pedicle screw placement. There are no differences in VBH, kyphosis angle, or VAS between the two groups. Blood loss and operative time were decreased in the percutaneous group, which may represent a potential benefit, particularly in the polytraumatized patient. All variables in this study demonstrated near-perfect homogeneity, and the effect is likely close to the true effect.
Concerning the universality of the Noun vs. Verb distionction

L'A. examine le probleme de la distinction entre nom et verbe pour souligner la difficulte a fixer de telles categories comme applicables pour toutes les langues. Il met en evidence des situations ou cette distinction est deficiente dans certaines langues : dans certains cas, reference et predication sont interchangeables dans des structures identiques mots-choses et mots-actions et deux types de predication sont distinguees (symetrique et asymetrique). Si la distinction entre nom et verbe semble finalement valide, l'article met en valeur la fragilite de l'universalite de ces notions.
INTRA-ABDOMINAL AND ABDOMINAL PERFUSION PRESSURE IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS GRAFT SURGERY

Abstract BACKGROUND. In 2006, the International Conference of Experts on Intra-abdominal Hypertension defined abdominal perfusion pressure (APP) as the difference between mean arterial pressure (MAP) and intra-abdominal pressure (IAP). The aim of the study was to analyse changes in IAP and APP in patients undergoing elective coronary artery bypass grafting (CABG). PATIENTS AND METHODS. Fifty patients undergoing CABG with extracorporeal circulation (ECC) and normovolemic haemodilution (NH) under general anaesthesia were studied. IAP and APP were measured during CABG and in the early postoperative period. Changes in IAP and APP were analysed according to degree of normovolemic haemodilution, age, body weight, body mass index (BMI), duration of anaesthesia, surgery, ECC, aorta clamping and other haemodynamic parameters. RESULTS. The induction of anaesthesia decreased IAP. Extracorporeal circulation resulted in IAP elevation, which was dependent on the degree of blood dilution. At any time point of the postoperative period IAP higher than 12 mmHg was noted in 22 patients (44%). Abdominal perfusion pressure decreased during ECC and on the morning of the first postoperative day. Intra-abdominal pressure strongly correlated with BMI and central venous pressure. The correlation between IAP and APP and other haemodynamic parameters was poor. CONCLUSIONS. 1) The induction of anaesthesia decreased IAP. 2) ECC resulted in an increase in IAP. 3) IAP increased in 44% of patients. 4) IAP strongly correlated with BMI and central venous pressure. 5) CABG with ECC resulted in a decrease in APP. 6) Changes in APP strongly correlated with MAP and poorly correlated with other haemodynamic parameters. 7) The changes in APP demonstrated a double-phase character.
Knockdown of MTP18, a Novel Phosphatidylinositol 3-Kinase-dependent Protein, Affects Mitochondrial Morphology and Induces Apoptosis*

We identified a novel human cDNA encoding a mitochondrial protein, MTP18 (mitochondrial protein, 18 kDa) as a transcriptional downstream target of phosphatidylinositol (PI) 3-kinase signaling. We demonstrate that MTP18 mRNA as well as protein expression is dependent on PI 3-kinase activity. Confocal microscopy and biochemical fractionation revealed a mitochondrial localization of MTP18. Loss-of-function analysis employing antisense molecules revealed that MTP18 is essential for cell viability in PC-3 and HaCaT cells. We show that knockdown of MTP18 protein level results in a cytochrome c release from mitochondria and consequently leads to apoptosis. In addition, HaCaT cells with reduced levels of MTP18 become more sensitive to apoptotic stimuli. This effect is accompanied by dramatic subcellular alterations. Reduction of MTP18 impairs mitochondrial morphology resulting in the formation of a highly interconnected mitochondrial reticulum in COS-7 cells. Conversely, overexpression of MTP18 induces a punctuate morphology of mitochondria suggesting also a functional role of MTP18 in maintaining the mitochondrial integrity. Hence, our data indicate an unexpected connection of PI 3-kinase signaling, apoptosis and the morphology of mammalian mitochondria.
Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Regulation of protein synthesis represents a key control point in cellular response to stress. In particular, discreet RNA regulatory elements were shown to allow to selective translation of specific mRNAs, which typically encode for proteins required for a particular stress response. Identification of these mRNAs, as well as the characterization of regulatory mechanisms responsible for selective translation has been at the forefront of molecular biology for some time. Polysome profiling is a cornerstone method in these studies. The goal of polysome profiling is to capture mRNA translation by immobilizing actively translating ribosomes on different transcripts and separate the resulting polyribosomes by ultracentrifugation on a sucrose gradient, thus allowing for a distinction between highly translated transcripts and poorly translated ones. These can then be further characterized by traditional biochemical and molecular biology methods. Importantly, combining polysome profiling with high throughput genomic approaches allows for a large scale analysis of translational regulation.
Crop specified albedo model based on the law of energy conservation and spectral invariants

A physical model for simulating crop albedo based on the law of energy conservation and spectral invariants was developed. The idea referred to the primary PARAS albedo model for forest. The developed model concerned two key problems for crop monitoring, one is the anisotropy of soil reflectance and the other is the clumping effect of crop leaves at canopy scale, which contributed to the improvement of the model accuracy. The comparison between the model results and those simulated using a Monte Carlo method shows that the calculated clumping index, soil absorptance and canopy albedo all have high accuracy, indicating that the model is able to reflect the interaction mechanism between radiation and the canopy-soil system.
Synaptic terminal coverage of primate triceps surae motoneurons

This study examined the synaptic terminal coverage of primate triceps surae (TS) motoneurons at the electron microscopic level. In three male pigtail macaques, motoneurons were labeled by retrograde transport of cholera toxin‐horseradish peroxidase that was injected into TS muscles bilaterally and visualized with tetramethylbenzidine stabilized with diamino‐benzidine. Somatic, proximal dendritic, and distal dendritic synaptic terminals were classified by standard criteria and measured. Overall and type‐specific synaptic terminal coverages and frequencies were determined.
Differential intestinal M‐cell gene expression response to gut commensals

Different rates of bacterial translocation across the gut mucosa have been reported but few studies have examined translocation of commensals at the level of the gut epithelial microfold (M) cell. We used an in vitro M‐cell model to quantify translocation and determine the transcriptional response of M cells to various commensal bacteria. The transport kinetics and gene expression profile of M cells in response to different bacterial strains, namely Lactobacillus salivarius, Escherichia coli and Bacteroides fragilis, was assessed. Bacterial strains translocated across M cells with different efficiencies; E. coli and B. fragilis translocated with equal efficiency whereas L. salivarius translocated with less efficiency. Microarray analysis of the M cell response showed both common and differential gene expression changes between the bacterial strains. In the presence of bacteria, but not control beads, up‐regulated genes were mainly involved in transcription regulation whereas pro‐inflammatory and stress response genes were primarily up‐regulated by E. coli and B. fragilis, but not L. salivarius nor beads. Translocation of bacteria and M‐cell gene expression responses were confirmed in murine M cells following bacterial challenge in vivo. These results demonstrate that M cells have the ability to discriminate between different commensal bacteria and modify subsequent immune responses.
Thermal Effects and Histologic Changes from Nd:YAG Laser Irradiation on Normal and Diseased Aortic Tissue Using a Novel Angioplasty Catheter with a Mobile Optical Fiber: An in Vitro Assessment

Although various laser angioplasty devices are currently being examined, thermal damage and perforation of the vessel wall remains the major acute complication of vascular laser recanalization. Consequently, the aim of this study was to investigate the thermal effects and histologic changes from laser irradiation (Nd:YAG, 1064 nm) on normal and diseased aortic tissue using a novel angioplasty device. During laser emission the coaxially guided optical fiber tip was positioned in reference to the end hole of the metallic capped probe as follows: (1) at the end hole (metal-cap position), (2) protruding 10 mm from that end hole (bare-fiber position), (3) withdrawn 5 mm into the metal cap's lumen (hot-tip position). In total, 96 laser impacts (25 joule: 5 W, 5 s, each) were produced on normal and atherosclerotic aorta in air through a 0.2-mm-core-diameter silica quartz fiber, with direct contact on the intimal surface of the target tissue by both the fiber and the metal cap and by either the fiber or the metal cap (n = 32 each). Tissue temperature was measured by means of special sensors positioned opposite the irradiated intimal spot in direct contact with the adventitial surface. Morphohistologic evaluation of lesions was performed and injury indexes were determined. Thermal injury (on normal aorta) for the metal-cap position was 0.063 ± 0.02 versus 0.42 ± 14 and 0.13 ± 0.03 for bare-fiber and hot-tip position, respectively (p< 0.001). In the metal-cap position of the optical fiber tip the metal cap appears to act as a "heat sink" to decrease the lateral spread of thermal injury and thereby reduce the risk of perforation and enhance the safety of tissue ablation for potential vascular laser recanalization.
The Leading Practices of Green Mobile Telecommunication Base Station Design

The aim of this study is to identify the green mobile telecommunication base station design practices as adopted by leading cases, four cases were analyzed; Ericsson, ZTE, Huawei, and Bharti. The data were collected from the published data. This study reveals that; the design attributes could be classified to; primary and secondary design attributes. A lot of relationships are reported between the design attributes. This study helps the academics in understanding the relationship between design attributes and actions, so they can use the reported model of this study for teaching purposes or for further extended survey study. The base stations developer and mobile communication services providers have a good insight about the sustainable design alternatives. The green operations practices are still new and the research contribution is limited, the research contribution of green mobile telecommunication base station deign is very limited.
Psychopharmacologic Strategies for the Treatment of Aggression in Juveniles

ABSTRACT Maladaptive aggression in youth is one of the most common and troublesome reasons for referrals to child psychiatrists. It has a complex relationship with psychopathology. There are several syndromes, which are primary disturbances of clustered maladaptive aggression, most notably oppositional defiant disorder and conduct disorder. However, problems with aggression also appear in a wide range of other disturbances, such as bipolar disorder, posttraumatic stress disorder, and mood disorders. Additionally, aggression is normative, serves an adaptive purpose and can be situationally induced. These complexities need to be carefully addressed before targeting maladaptive aggression psychopharmacologically. We summarize the literature on the psychopharmacology of maladaptive aggression in youth, focusing on disorders without cognitive impairment. We delineate the subtypes of aggression which are most likely to respond to medication (reactive-affective-defensive-impulsive in their acute and chronic form) and conclude with a discussion of specific medication strategies which are supported by controlled clinical trials and clinical experience.
The Surface Composition of Charon: Tentative Identification of Water Ice

The 3 March 1987 Charon occultation by Pluto was observed in the infrared at 1.5, 1.7, 2.0, and 2.35 micrometers. Subtraction of fluxes measured between second and third contacts from measurements made before and after the event has yielded individual spectral signatures for each body at these wavelengths. Charon's surface appears depleted in methane relative to Pluto. Constancy of flux at 2.0 micrometers throughout the event shows that Charon is effectively black at this wavelength, which is centered on a very strong water absorption band. Thus, the measurements suggest the existence of water ice on Pluto's moon.
Menstrual patterns leading to the final menstrual period

ObjectiveTo characterize premenopausal menstrual regularity and the patterns of divergence from regularity associated with the approach of the final menstrual period. DesignTwo samples of individual cycle length sequences contributed by participants in a population-based longitudinal study of the menopausal transition were examined. The first sample, of “early” sequences, is used to characterize menstrual regularity. The second shows how cycle length patterns change as the final menstrual period (FMP) is approached. Regression slopes are used to measure trend in cycle length, and changes in cycle length variability are registered by a simply calculated measure, the “running range. ” ResultsSequences in the early cycles sample rarely varied outside the 21–35 day range and did not show a rising or falling trend. In contrast, pre-FMP sequences generally became increasingly variable in length, while rising above 35 days in mean during the last 10 cycles. The variability measure remained below 40 days throughout the early sequences, but characteristically rose above 42 days during sequences including the last 20 pre-FMP cycles. In early sequences, but not in pre-FMP sequences, long and short cycles tended to alternate. ConclusionsIncreased variability is the dominant feature of cycle length pattern for most women as their final menstrual period approaches. Underlying this is a steady trend toward mean cycle lengths above 35 days. An indicator of the approach of menopause is a rise in running range of cycle lengths to 42 days.