Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonhepatic origin of notothenioid antifreeze reveals pancreatic synthesis as common mechanism in polar fish freezing avoidance

Phylogenetically diverse polar and subpolar marine teleost fishes have evolved antifreeze proteins (AFPs) or antifreeze glycoproteins (AFGPs) to avoid inoculative freezing by internalized ice. For over three decades since the first fish antifreeze (AF) protein was discovered, many studies of teleost freezing avoidance showed hepatic AF synthesis and distribution within the circulation as pivotal in preventing the blood, and therefore the fish, from freezing. We have uncovered an important twist to this long-held paradigm: the complete absence of liver synthesis of AFGPs in any life stage of the Antarctic notothenioids, indicating that the liver plays no role in the freezing avoidance in these fishes. Instead, we found the exocrine pancreas to be the major site of AFGP synthesis and secretion in all life stages, and that pancreatic AFGPs enter the intestinal lumen via the pancreatic duct to prevent ingested ice from nucleating the hyposmotic intestinal fluids. AFGPs appear to remain undegraded in the intestinal milieu, and the composition and relative abundance of intestinal AFGP isoforms are nearly identical to serum AFGPs. Thus, the reabsorption of intact pancreas-derived intestinal AFGPs, and not the liver, is the likely source of circulatory AFGPs in notothenioid fishes. We examined diverse northern fish taxa and Antarctic eelpouts with hepatic synthesis of bloodborne AF and found that they also express secreted pancreatic AF of their respective types. The evolutionary convergence of this functional physiology underscores the hitherto largely unrecognized importance of intestinal freezing prevention in polar teleost freezing avoidance, especially in the chronically icy Antarctic waters.
Influence of aging on the activity of mice Sca-1+CD31− cardiac stem cells

Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31− subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31− subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending.
Extracting multistage screening rules from online dating activity data

Significance Online activity data—for example, from dating, housing search, or social networking websites—make it possible to study human behavior with unparalleled richness and granularity. However, researchers typically rely on statistical models that emphasize associations among variables rather than behavior of human actors. Harnessing the full informatory power of activity data requires models that capture decision-making processes and other features of human behavior. Our model aims to describe mate choice as it unfolds online. It allows for exploratory behavior and multiple decision stages, with the possibility of distinct evaluation rules at each stage. This framework is flexible and extendable, and it can be applied in other substantive domains where decision makers identify viable options from a larger set of possibilities. This paper presents a statistical framework for harnessing online activity data to better understand how people make decisions. Building on insights from cognitive science and decision theory, we develop a discrete choice model that allows for exploratory behavior and multiple stages of decision making, with different rules enacted at each stage. Critically, the approach can identify if and when people invoke noncompensatory screeners that eliminate large swaths of alternatives from detailed consideration. The model is estimated using deidentified activity data on 1.1 million browsing and writing decisions observed on an online dating site. We find that mate seekers enact screeners (“deal breakers”) that encode acceptability cutoffs. A nonparametric account of heterogeneity reveals that, even after controlling for a host of observable attributes, mate evaluation differs across decision stages as well as across identified groupings of men and women. Our statistical framework can be widely applied in analyzing large-scale data on multistage choices, which typify searches for “big ticket” items.
Daily Pain, Physical Activity, and Home Fluid Intake in Pediatric Sickle Cell Disease

Objectives This study examined the temporal relationship between physical activity, fluid intake, and daily pain in children with sickle cell disease (SCD) with frequent pain. Methods A total of 30 African American children ( M age = 13.9; 53% female; 76.3% type SS) who reported pain more than or equal to once every 2 weeks and their parents completed measures of pain and anxiety/depressive symptoms. Children then completed a daily pain diary and wore a physical activity Actiwatch for 14 days at home. Results Contrary to physiological theory-based hypotheses, lower physical activity was associated with greater pain during the same day and the next day. Less pain was associated with greater physical activity the next day. There was no relationship between self-reported home fluid intake and daily pain ( p 's < .05). Conclusions Results lend support for a complex bidirectional relationship between physical activity and daily pain in pediatric SCD, and identify physical activity as a target for future research.
Novel grounded inductance simulator using single OTRA

In this paper, a method to realize a grounded inductor using single operational transresistance amplifier is presented. The simulated inductance value can be controlled independent of realizability condition. The non‐ideality analysis of the circuit is also given. The workability of the proposed simulated inductance is demonstrated through two applications namely, a band pass filter and an oscillator. PSPICE simulation and experimental results agree well with the theoretical values. Copyright © 2013 John Wiley & Sons, Ltd.
Exploring the Pharmacokinetic/Pharmacodynamic Relationship of Relebactam (MK-7655) in Combination with Imipenem in a Hollow-Fiber Infection Model

ABSTRACT Resistance to antibiotics among bacterial pathogens is rapidly spreading, and therapeutic options against multidrug-resistant bacteria are limited. There is an urgent need for new drugs, especially those that can circumvent the broad array of resistance pathways that bacteria have evolved. In this study, we assessed the pharmacokinetic/pharmacodynamic relationship of the novel β-lactamase inhibitor relebactam (REL; MK-7655) in a hollow-fiber infection model. REL is intended for use with the carbapenem β-lactam antibiotic imipenem for the treatment of Gram-negative bacterial infections. In this study, we used an in vitro hollow-fiber infection model to confirm the efficacy of human exposures associated with the phase 2 doses (imipenem at 500 mg plus REL at 125 or 250 mg administered intravenously every 6 h as a 30-min infusion) against imipenem-resistant strains of Pseudomonas aeruginosa and Klebsiella pneumoniae. Dose fractionation experiments confirmed that the pharmacokinetic parameter that best correlated with REL activity is the area under the concentration-time curve, consistent with findings in a murine pharmacokinetic/pharmacodynamic model. Determination of the pharmacokinetic/pharmacodynamic relationship between β-lactam antibiotics and β-lactamase inhibitors is complex, as there is an interdependence between their respective exposure-response relationships. Here, we show that this interdependence could be captured by treating the MIC of imipenem as dynamic: it changes with time, and this change is directly related to REL levels. For the strains tested, the percentage of the dosing interval time that the concentration remains above the dynamic MIC for imipenem was maintained at the carbapenem target of 30 to 40%, required for maximum efficacy, for imipenem at 500 mg plus REL at 250 mg.
Simulating the Flow Dynamics in Hydroentangling Nozzles: Effect of Cone Angle and Nozzle Aspect Ratio

Flow behavior in various nozzle shapes from the hydroentangling cone-capillary family is modeled in this paper. The work studies the effects of cone angle and nozzle aspect ratio (the ratio of the capillary section to its diameter) on water-jet formation. In particular, two sets of nozzles are considered. The first set consists of nozzles that have an aspect ratio of one and cone angles of 19, 15, 11, 7, and 3°, respectively. The nozzles in the second set have their inlet and outlet diameters fixed, but their aspect ratios vary from 1 to 6. The results from a two-phase axisymmetric steady-state model of turbulent nozzle flow reveal that decreasing the cone angle or increasing the nozzle aspect ratio does not affect the hydroentangling water-jet characteristics. The computational scheme is validated by comparing part of the results with the available experimental data in the literature.
A new model to estimate insulin resistance via clinical parameters in adults with type 1 diabetes

Insulin resistance (IR) is a risk factor to assess the development of micro‐ and macro‐vascular complications in type 1 diabetes (T1D). However, diabetes management in adults with T1D is limited by the difficulty of lacking simple and reliable methods to estimate insulin resistance. The aim of this study was to develop a new model to estimate IR via clinical parameters in adults with T1D.
A bioartificial dermal regeneration template promotes skin cell proliferation in vitro and enhances large skin wound healing in vivo

A novel bioartificial dermal regeneration template has been developed using platelet-rich plasma and acellular animal skin collagen sponge for the treatment of larger area and full thickness skin wounds. This platelet-rich plasma-collagen sponge keeps native skin structure and contains huge amounts of growth factors. The effect of this bioartificial dermal regeneration template was tested in vitro and in vivo via a mimic poor wound healing process by adding collagenase I into cell culture medium or the wound area. The in vitro experimental results indicated that the rat skin cells grew faster and produced more collagen in platelet-rich plasma-collagen sponge with collagenase than those treated either with collagen sponge plus collagenase, or collagenase, or control group without treatment. The in vivo experiments were performed by large rat skin wounds, 1.5 cm diameter, treated either with collagenase, or collagenase plus collagen sponge, or collagenase plus platelet-rich plasma-collagen sponge. The wound without treatment was used as a control. The wounds treated with collagenase-containing platelet-rich plasma-collagen sponge healed 4 times faster than the untreated wounds, 6 times faster than the collagenase treated wounds, 2.4 times faster than collagenase-containing collagen sponge treated wounds. The immunostaining indicated that the healed tissues in the wound areas treated with collagenase-containing platelet-rich plasma-collagen sponge were composed of collagen type I and collagen III with blood vessels and hair follicles. The results demonstrated that this collagenase-containing platelet-rich plasma-collagen sponge works as a bioartificial dermal regeneration template. The application of this collagenase-containing platelet-rich plasma-collagen sponge promotes the traumatic skin wound healing and permits the reconstitution of the inherent barrier functions of the skin.
Microbial Diversity in the Eukaryotic SAR Clade: Illuminating the Darkness Between Morphology and Molecular Data

Despite their diversity and ecological importance, many areas of the SAR—Stramenopila, Alveolata, and Rhizaria—clade are poorly understood as the majority (90%) of SAR species lack molecular data and only 5% of species are from well‐sampled families. Here, we review and summarize the state of knowledge about the three major clades of SAR, describing the diversity within each clade and identifying synapomorphies when possible. We also assess the “dark area” of SAR: the morphologically described species that are missing molecular data. The majority of molecular data for SAR lineages are characterized from marine samples and vertebrate hosts, highlighting the need for additional research effort in areas such as freshwater and terrestrial habitats and “non‐vertebrate” hosts. We also describe the paucity of data on the biogeography of SAR species, and point to opportunities to illuminate diversity in this major eukaryotic clade. See also the video abstract here: https://youtu.be/_VUXqaX19Rw.
Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack

Background and Purpose— Limited real-world data exist comparing each non–vitamin K antagonist oral anticoagulant (NOAC) to warfarin in patients with nonvalvular atrial fibrillation who have had a previous ischemic stroke or transient ischemic attack. Methods— Using MarketScan claims from January 2012 to June 2015, we identified adults newly initiated on oral anticoagulation, with ≥2 diagnosis codes for nonvalvular atrial fibrillation, a history of previous ischemic stroke/transient ischemic attack, and ≥180 days of continuous medical and prescription benefits before anticoagulation initiation. Three analyses were performed comparing 1:1 propensity score–matched cohorts of apixaban versus warfarin (n=2514), dabigatran versus warfarin (n=1962), and rivaroxaban versus warfarin (n=5208). Patients were followed until occurrence of a combined end point of ischemic stroke and intracranial hemorrhage (ICH) or major bleed, switch/discontinuation of index oral anticoagulation, insurance disenrollment, or end of follow-up. Mean follow-up was 0.5 to 0.6 years for all matched cohorts. Results— Using Cox regression, neither apixaban nor dabigatran reduced the combined primary end point of ischemic stroke or ICH (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.33–1.48 and HR, 0.53; 95% CI, 0.26–1.07) and had nonsignificant effect on hazards of major bleeding (HR, 0.79; 95% CI, 0.38–1.64 and HR, 0.58; 95% CI, 0.26–1.27) versus warfarin. Rivaroxaban reduced the combined end point of ischemic stroke or ICH (HR, 0.45; 95% CI, 0.29–0.72) without an effect on major bleeding (HR, 1.07; 95% CI, 0.71–1.61). ICH occurred at rates of 0.16 to 0.61 events per 100 person-years in the 3 NOAC analyses, with no significant difference for any NOAC versus warfarin. Conclusions— Results from our study of the 3 NOACs versus warfarin in nonvalvular atrial fibrillation patients with a previous history of stroke/transient ischemic attack are relatively consistent with their respective phase III trials and previous stroke/transient ischemic attack subgroup analyses. All NOACs seemed no worse than warfarin in respect to ischemic stroke, ICH, or major bleeding risk.
Technical performance scores are predictors of midterm mortality and reinterventions following congenital mitral valve repair†

OBJECTIVES The Technical Performance Score (TPS) has been shown to be predictive of postoperative mortality, morbidities and reinterventions following various cardiac procedures in children. We hypothesized that TPS is also a predictor of mitral valve repair outcomes. METHODS A review of patients who underwent mitral valve repair from January 2000 to December 2013 was performed. Primary repair of complete atrioventricular defect was excluded. The scores were determined according to previously published criteria based on the need for reintervention and predischarge echocardiograms: Class 1 (no residua), Class 2 (minor residua) or Class 3 (pacemaker implantation, major residua or reintervention for major residua prior to discharge). Cox proportional hazard models and Kaplan-Meier estimator were used. RESULTS A total of 587 patients underwent mitral repair (median age 2.6 years). Median follow-up duration was 3 years. There were 125 (21.3%) post-discharge mitral reinterventions and freedom from reintervention was 85.2%, 78.2% and 69.4% at 1, 2 and 5 years, respectively. Both TPS Class 2 [hazard ratio (HR) 3.6, 95% confidence interval (CI) 1.4-10.0; P = 0.02] and Class 3 (HR 8.7, 95% CI 3.0-25.1; P < 0.001) were associated with post-discharge reinterventions. There were 31 late deaths/transplantations, and transplant-free survival at 1, 2 and 5 years was 97.8%, 95.3% and 93.2%. TPS 3 was associated with decreased post-discharge transplant-free survival (HR 5.5, 95% CI 1.2-25.0; P = 0.03). Post-discharge mitral reintervention was not associated with increased mortality. CONCLUSIONS The TPS is a strong predictor of midterm mortality and post-discharge mitral reintervention in congenital patients who underwent mitral repair.
CoinFold: a web server for protein contact prediction and contact-assisted protein folding

CoinFold (http://raptorx2.uchicago.edu/ContactMap/) is a web server for protein contact prediction and contact-assisted de novo structure prediction. CoinFold predicts contacts by integrating joint multi-family evolutionary coupling (EC) analysis and supervised machine learning. This joint EC analysis is unique in that it not only uses residue coevolution information in the target protein family, but also that in the related families which may have divergent sequences but similar folds. The supervised learning further improves contact prediction accuracy by making use of sequence profile, contact (distance) potential and other information. Finally, this server predicts tertiary structure of a sequence by feeding its predicted contacts and secondary structure to the CNS suite. Tested on the CASP and CAMEO targets, this server shows significant advantages over existing ones of similar category in both contact and tertiary structure prediction.
Nitrite as a pharmacological intervention for the successful treatment of crush syndrome

Crush syndrome is characterized by ischemia/reperfusion injury (IRI). The protective effect of nitrite on experimentally induced IRI has been demonstrated in the heart, kidney, liver, and skeletal muscle. IRI in tissues and systemic organs occurs due to the massive generation of reactive oxygen species and subsequent systemic inflammation. Therefore, ischemic pre and postconditioning are performed in clinical practice. Intravenous administration of nitrite inhibits IRI through nitric oxide‐mediated mechanisms. In this paper, we discuss the utility of nitrite as a pharmacological postconditioning agent in the treatment of crush syndrome.
Evaluation of a Powered Stapler System with Gripping Surface Technology on Surgical Interventions Required During Laparoscopic Sleeve Gastrectomy

Abstract Background: Transection of gastric tissue during laparoscopic sleeve gastrectomy (LSG) can be challenging. Reinforcing the staple line may decrease the incidence of issues requiring intervention. Methods: The objective of this study was to compare the number of intraoperative surgical interventions for a surgical stapler and reload system with Gripping Surface Technology (GST) to standard reloads in patients who underwent LSG. Patients who underwent elective LSG were enrolled. The study was conducted in two stages. For Stage 1, procedures were performed using a powered stapler and standard reloads. For Stage 2, a reload system with GST was used. The primary endpoint was surgical interventions for bleeding and/or staple line issues during transection of the greater curvature of the stomach. Propensity score matching was applied to create two groups similar in baseline characteristics and risk factors. Results: A total of 111 subjects were enrolled across four centers. Propensity-matched procedures were completed with the standard (n = 38) or GST reloads (n = 38). The mean number of interventions in the standard group was 1.9 (1.29) versus 1.1 (1.45) in the GST group. Nonparametric comparisons were statistically significant, indicating a reduction in the distribution of interventions for GST subjects (P = .0036 for matched pair data). Tissue slippage during transection was low for both groups. Intraoperative leak testing was negative in all procedures, and no procedures were converted to open. Conclusions: Use of the GST stapling system reduces the need for staple line interventions in LSG. Both stapling systems had an acceptable safety profile.
H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin– Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair.