Miracle-dz/UniFAR-FTUs huggingface dataset:
Small Molecule Agonist of Very Late Antigen-4 (VLA-4) Integrin Induces Progenitor Cell Adhesion*

Background: Activation of integrins may improve cell retention rates in stem cell transplantation. Results: The first small molecule agonist of integrin α4β1 is generated and enhances cell adhesion mechanisms in vitro. Conclusion: The agonist binds at the subunit interface, inducing ligand binding with consequent displacement of compound. Significance: The agonist may improve progenitor cell retention as an adjunct to cell-based therapy. Activation of the integrin family of cell adhesion receptors on progenitor cells may be a viable approach to enhance the effects of stem cell-based therapies by improving cell retention and engraftment. Here, we describe the synthesis and characterization of the first small molecule agonist identified for the integrin α4β1 (also known as very late antigen-4 or VLA-4). The agonist, THI0019, was generated via two structural modifications to a previously identified α4β1 antagonist. THI0019 greatly enhanced the adhesion of cultured cell lines and primary progenitor cells to α4β1 ligands VCAM-1 and CS1 under both static and flow conditions. Furthermore, THI0019 facilitated the rolling and spreading of cells on VCAM-1 and the migration of cells toward SDF-1α. Molecular modeling predicted that the compound binds at the α/β subunit interface overlapping the ligand-binding site thus indicating that the compound must be displaced upon ligand binding. In support of this model, an analog of THI0019 modified to contain a photoreactive group was used to demonstrate that when cross-linked to the integrin, the compound behaves as an antagonist instead of an agonist. In addition, THI0019 showed cross-reactivity with the related integrin α4β7 as well as α5β1 and αLβ2. When cross-linked to αLβ2, the photoreactive analog of THI0019 remained an agonist, consistent with it binding at the α/β subunit interface and not at the ligand-binding site in the inserted (“I”) domain of the αL subunit. Co-administering progenitor cells with a compound such as THI0019 may provide a mechanism for enhancing stem cell therapy.
Applying Pretrained Convolutional Neural Networks to Vehicle Classification Problem

Artificial neural networks (NN) have gained a lot of popularity in the recent years. Although basic NNs can be applied to computer vision related tasks, convolutional neural networks (CNN) have shown better suitability and results. This report gives a general overview of NNs and CNNs as well as specific CNN models. Besides, the pretrained CNN models are tested on vehicle images as classifiers.
Perioperative Complications of Total Ankle Arthroplasty

A retrospective radiographic and chart review was performed for the initial 50 patients who underwent Agility (DePuy, Warsaw IN) total ankle arthroplasty by the senior author (M.S.M.). The review focused on the perioperative complications of nerve or tendon lacerations, intraoperative fractures, acute deep infections, wound complications and component positioning. Major wound complications were defined as those requiring a soft-tissue coverage procedure. Minor wound complications did not require soft tissue coverage and included wound breakdowns, wound edge necrosis, and superficial infections. The immediate mortise and lateral postoperative radiographs were reviewed to measure component positioning. The patients were divided into two groups to compare the initial 25 patients (Group A) with the subsequent 25 patients (Group B). There were no major wound complications in either group. Minor wound complications decreased from six in Group A to two in Group B. There were four lacerations (flexor hallucis longus, posterior tibial tendon, deep peroneal nerve, and superficial peroneal nerve), all occurring in Group A. Five patients sustained intraoperative fractures in Group A, as compared with two fractures in Group B. The number of components varying greater than 4° from neutral as measured by the lateral talar, lateral tibial and mortise tibial component angles decreased by 9% from Group A to Group B. The only tibial component to be placed in more than 4° of valgus occurred in Group A. It seems that a notable learning curve exists in the performance of total ankle arthroplasty as demonstrated by a comparison of the initial 25 patients with the subsequent 25 patients performed by one orthopaedic surgeon. This improvement most likely resulted from the use of enhanced techniques and further training with the prosthesis. This information can be used as a teaching tool to decrease the incidence of complications for surgeons performing their initial arthroplasties with this potentially technically demanding procedure.
Pathway-based approach using hierarchical components of collapsed rare variants

MOTIVATION To address 'missing heritability' issue, many statistical methods for pathway-based analyses using rare variants have been proposed to analyze pathways individually. However, neglecting correlations between multiple pathways can result in misleading solutions, and pathway-based analyses of large-scale genetic datasets require massive computational burden. We propose a Pathway-based approach using HierArchical components of collapsed RAre variants Of High-throughput sequencing data (PHARAOH) for the analysis of rare variants by constructing a single hierarchical model that consists of collapsed gene-level summaries and pathways and analyzes entire pathways simultaneously by imposing ridge-type penalties on both gene and pathway coefficient estimates; hence our method considers the correlation of pathways without constraint by a multiple testing problem. RESULTS Through simulation studies, the proposed method was shown to have higher statistical power than the existing pathway-based methods. In addition, our method was applied to the large-scale whole-exome sequencing data with levels of a liver enzyme using two well-known pathway databases Biocarta and KEGG. This application demonstrated that our method not only identified associated pathways but also successfully detected biologically plausible pathways for a phenotype of interest. These findings were successfully replicated by an independent large-scale exome chip study. AVAILABILITY AND IMPLEMENTATION An implementation of PHARAOH is available at http://statgen.snu. ac.kr/software/pharaoh/ CONTACT tspark@stats.snu. ac.kr SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
[Regulation trend of resveratrol on TNFα-,IL-1β, IL-6 expressions in bronchoalveolar lavage fluid of RSV-infected BALB/c mice].

OBJECTIVE To study the regulation trend of resveratrol on TNF-alpha, IL-1beta, IL-6 expressions in bronchoalveolar layage fluid (BALF) of RSV-infected BALB/c mice at different time points. METHOD RSV-induced BALB/c mice were orally administered with resveratrol. Their BALFs were collected at 24, 72 and 144 h after the first nasal drip with RSV to detect the level of TNF-alpha, IL-1P3, IL-6 by EILSA. RESULT The expression of TNF-alpha, IL-1Pf and IL-6 in BALF increased significantly compared with the normal group (P <0. 01) after 24 hours of RSV infection, while the expression of TNF-alpha (P < 0.01), IL-1beta (P < 0.05), IL-6 (P < 0.01) in the resveratrol group decreased notably compared with the model group. After 72 hours of infection with RSV, although the expression of TNF-alpha (P < 0.05), IL-1beta (P < 0.01) and IL-6 (P < 0.01) in BALF in model group were higher than those in the normal group, they were much more lower than at 24 h. The expression of IL-1beta and IL-6 (P < 0.05) in the resveratrol groups were down-regulated significantly, but no difference had been shown in TNF-alpha expression compared with the RSV infection group. After infection with RSV for 144 h, the expression of IL-1beta (P < 0.01) and IL-6 (P < 0.05) in BALF in the model group were higher than those in the normal group, but there was no difference in the secretion of TNF-alpha. The expression of TNF-alpha, IL-1beta and IL-6 showed also no remarkable difference between the resveratrol groups and the RSV infection group. CONCLUSION Resveratrol can inhibit the over expression of inflammatory factors TNF-alpha, IL-1beta, IL-6 in bronchoalveolar lavage fluid of RSV-induced BALB/c mice and keep them at a low level with the passing of infection time.
Food protein sensitivity with partial villous atrophy after pediatric liver transplantation with tacrolimus immunosuppression

Abstract: We report three pediatric liver transplant recipients receiving tacrolimus immunosuppression presented with vomiting, heme‐positive stools and failure to thrive, who had subtotal villous atrophy in their histology because of food protein sensitivity. Case findings and current literature of the casual relationship between tacrolimus and food allergies briefly reviewed.
Mean platelet volume as an inexpensive bio-marker of endometriosis

Objective: Increased platelet activation has also been suggested to play a pivotal role in the development and progression of inflammation. Recently, mean platelet volume (MPV) has been investigated as a simple inflammatory marker in several diseases and it was found that MPV can be used as a marker of inflammatory disease. Therefore this study was designed to investigate and compare the values of MPV in patients with endometriosis and the MPV values in healthy women. Materials and methods: Patients with endometriosis (n=297) and symptom-free, healthy, age-matched controls underwent tubal ligation (n=36) were retrospectively evaluated and recruited to the study at three tertiary centers between January 2008 and December 2014. For further analysis, patients with endometriosis were divided into initial endometriosis (n=129) and advanced endometriosis (n=168) groups according to the severity of the disease. Receiver Operating Characteristic (ROC) curve and sensitivity and specificity report were performed for MPV value to evaluate differences between the groups. Results: MPV in patients with endometriosis were found to be higher than the control group (8.80±1.08 fL vs 8.11±1.03 fL, respectively; P<0.001). There was no significant difference regarding mean MPV between the patients with advanced and initial endometriosis (8.72±1.60 fL and 8.90±0.97 fL, respectively; P=0.15). ROC curve analysis suggested that the optimum MPV cutoff value for endometriosis was 8.55 fL, with a sensitivity, specificity, of 61% and 61%, respectively (AUC: 0.671). Conclusion: This study showed that significantly higher MPV levels were found in the patients with endometriosis and confirmed the previous studies indicating that endometriosis is an inflammatory process. MPV is an important, simple, inexpensive, and effortless hematological parameter and can be useful in evaluation of endometriosis
Effect of Light Treatment on Sleep and Circadian Rhythms in Demented Nursing Home Patients

OBJECTIVES To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light. DESIGN Randomized controlled trial. SETTING Two San Diego-area nursing homes. PARTICIPANTS Seventy-seven (58 women, 19 men) nursing home residents participated. Mean age +/- standard deviation was 85.7 +/- 7.3 (range 60-100) and mean Mini-Mental State Examination was 12.8 +/- 8.8 (range 0-30). INTERVENTIONS Participants were assigned to one of four treatments: evening bright light, morning bright light, daytime sleep restriction, or evening dim red light. MEASUREMENTS Improvement in nighttime sleep quality, daytime alertness, and circadian activity rhythm parameters. RESULTS There were no improvements in nighttime sleep or daytime alertness in any of the treatment groups. Morning bright light delayed the peak of the activity rhythm (acrophase) and increased the mean activity level (mesor). In addition, subjects in the morning bright light group had improved activity rhythmicity during the 10 days of treatment. CONCLUSION Increasing exposure to morning bright light delayed the acrophase of the activity rhythm and made the circadian rhythm more robust. These changes have the potential to be clinically beneficial because it may be easier to provide nursing care to patients whose circadian activity patterns are more socially acceptable.
Chronic pain in rehabilitation medicine

In this paper the chronicity of pain in non-specific pain syndromes is discussed. Experts in the study of pain with several professional backgrounds in rehabilitation are the authors of this paper. Clinical experience and literature form the basis of the paper. Non-specific low back pain and Complex Regional Pain Syndrome type I (CRPS-I) are discussed in the light of chronic pain. Many definitions of chronic pain exist. Yellow flags are important factors to identify possible chronic pain. In the acute phase of a non-specific pain complaint one should try to identify possible psychosocial inciting risk factors. Behavioural and cognitive treatment seems to be effective for chronic pain patients.
Hyperintense uterine leiomyoma at T2-weighted MR imaging: differentiation with dynamic enhanced MR imaging and clinical implications.

PURPOSE To evaluate the role of dynamic enhanced magnetic resonance (MR) imaging in differentiating leiomyomas with high signal intensity at T2-weighted imaging. MATERIALS AND METHODS Histologic features of 34 uterine leiomyomas that showed hyperintensity on T2-weighted images were compared with those of ordinary hypointense leiomyomas (n = 74). The results of treatment with gonadotropin-releasing hormone analogue were also analyzed in relation to pretreatment signal intensity. RESULTS Degenerated leiomyomas (n = 13) had higher signal intensity and heterogeneous architecture, but there was considerable overlap in signal intensity with cellular leiomyomas (n = 21). At dynamic enhanced MR imaging, cellular leiomyomas had marked contrast enhancement in the early phase, while degenerated leiomyomas showed slight or irregular enhancement. Cellular leiomyomas were reduced significantly in size after treatment (P = .02). The response in degenerated leiomyomas was minimal. CONCLUSION Evaluation of signal intensity at T2-weighted imaging and degree of contrast enhancement at dynamic enhanced MR imaging provide useful information on the nature of leiomyomas.
Non-cardiac surgery and volatile agents – Back to the future

Were Bassuoni et al.[1] the first ones to conduct a randomized controlled trial to compare volatile agents versus total intravenous anesthesia in non-cardiac surgery? Of course not. Till 2007, there were at least 79 randomized controlled trials published in peer-reviewed journals, which included 6219 patients receiving total intravenous anesthesia or volatile agents (sevoflurane or desflurane). Unfortunately, none of these studies reported adverse cardiac events or cardiac biomarker release. [2] After 2007, there was only one randomized controlled study addressing the cardioprotective properties of volatile agents in noncardiac anesthesia[3] and, probably due to the small sample size and to the low risk profile of the included patients, it found no beneficial cardioprotective effects of volatile agents.
Adaptation of existing behaviour models to unsaturated states: application to CJS model

This paper proposes a general formulation of an elastoplastic model adapted to unsaturated soils. This formulation enters within the framework of two independent state variables descriptions. The choice of a particular effective stress combined with suction is made. The definition of this effective stress is based on the formulation of an equivalent pore pressure which is an essential point of this type of models. It will be discussed in this paper.
Tenofovir/Emtricitabine Metabolites and Endogenous Nucleotide Exposures are associated with p16INK4a Expression in Subjects on Combination Therapy

Background HIV may amplify immunological, physiological and functional changes of ageing. We determined associations of frailty phenotype, a T-cell senescence marker (p16INK4a expression), age and demographics with exposures of the intracellular metabolites (IM) and endogenous nucleotides (EN) of tenofovir/emtricitabine (TFV/FTC), efavirenz (EFV), atazanavir (ATV) and ritonavir (RTV). Methods Plasma and peripheral blood mononuclear cell samples for drug, IM and EN concentrations were collected at four time points in HIV+ adults receiving TFV/FTC with EFV or ATV/RTV. Subjects underwent frailty phenotyping and p16INK4a expression analysis. Non-compartmental analysis generated an area under the curve (AUC) for each analyte. Spearman rank correlation and Kruskal–Wallis tests were used to assess associations between AUC, demographics and ageing markers, adjusting for multiple comparisons with the Holm procedure. Results Subjects (n=79) ranged in age from 22–73 years (median 48 years); 48 were African-American, 24 were female, 54 received EFV. Three subjects (range 51–60 years) demonstrated frailty, with 17 subjects (range 26–60 years) demonstrating pre-frailty. Negative associations were observed between p16INK4a expression and each of FTC-triphosphate (r=-0.45), deoxyadenosine triphosphate (dATP; r=-0.47) and deoxycytidine triphosphate (dCTP; r=-0.57) AUCs (P-values ≤0.02). TFV and FTC AUCs were larger among subjects with lower renal function or higher chronological age (P-values ≤0.05). No associations were observed for EFV, ATV or RTV AUCs. Conclusions Associations of IM/EN exposure and p16INK4a expression observed here suggest that senescence may alter drug phosphorylation, metabolism or transport. This finding warrants further mechanistic study to ensure optimal treatment in the ageing HIV+ population. Clinicaltrials.gov NCT01180075.
Hand-Eye Calibration

Whenever a sensor is mounted on a robot hand, it is important to know the relationship between the sensor and the hand. The problem of determining this relationship is referred to as the hand-eye calibration problem. Hand-eye calibration is impor tant in at least two types of tasks: (1) map sensor centered measurements into the robot workspace frame and (2) tasks allowing the robot to precisely move the sensor. In the past some solutions were proposed, particularly in the case of the sensor being a television camera. With almost no exception, all existing solutions attempt to solve a homogeneous matrix equation of the form AX = X B. This article has the following main contributions. First we show that there are two possible formulations of the hand-eye calibration problem. One formu lation is the classic one just mentioned. A second formulation takes the form of the following homogeneous matrix equation: MY = M'YB. The advantage of the latter formulation is that the extrinsic and intrinsic parameters of the camera need not be made explicit. Indeed, this formulation directly uses the 3 x4 perspective matrices ( M and M' ) associated with two positions of the camera with respect to the calibration frame. Moreover, this formulation together with the classic one covers a wider range of camera-based sensors to be calibrated with respect to the robot hand: single scan-line cameras, stereo heads, range finders, etc. Second, we develop a common mathematical framework to solve for the hand-eye calibration problem using either of the two formulations. We represent rotation by a unit quaternion and present two methods: (1) a closed-form solution for solving for rotation using unit quaternions and then solving for translation and (2) a nonlinear technique for simultane ously solving for rotation and translation. Third, we perform a stability analysis both for our two methods and for the lin ear method developed by Tsai and Lenz (1989). This analysis allows the comparison of the three methods. In light of this comparison, the nonlinear optimization method, which solves for rotation and translation simultaneously, seems to be the most robust one with respect to noise and measurement errors.
Expression analysis of extracellular matrix components in brush biopsies of oral lesions.

BACKGROUND Oral brush biopsies have proved to be a promising new non-invasive methodology in the diagnosis of oral lesions. The extracellular matrix (ECM) molecules gamma2 chain of laminin-5 (L5gamma2), tenascin-c (Tn-C) and the fibronectin isoform containing EDB (EDB-fn) are involved in matrix remodeling during malignant transformation in oral carcinoma. MATERIALS AND METHODS Expression of L5gamma2, Tn-C and EDB-fn was analysed in brush biopsy-obtained cells of benign inflammatory or hyperproliferative lesions and primary oral squamous cell carcinoma (OSCC) using the Roche LightCycler 2.0 System. RESULTS AND CONCLUSION Oral carcinoma are detectable with mRNA resynthesis of the ECM molecules L5gamma2 and Tn-C in oral brush biopsies. EDB-fn mRNA was not detected--the stroma myofibroblasts are apparently a preferential source of EDB-fn and sampling by oral brush biopsy harvests epithelial cells and does not reach the cells which do express EDB-fn. The performance of gene expression analysis in brush biopsies is limited by a high RNase activity in the oral cavity.
Growth after Renal Transplantation in Prepubertal Children: Impact of Various Treatment Modalities

ABSTRACT: A retrospective study evaluated posttrans-plant growth of 70 prepubertal children during the first 2 y after renal transplantation (RTx). Immunosuppressive treatment consisted of prednisone administered either daily or on alternate days in combination with either azathioprine or cyclosporin A. The increment in height standard deviation score for chronologic age during the first 2 y after RTx was less than 0.5 SD for 70% of the study population. The predictive factors for posttransplant growth were determined by evaluating several factors and treatment modalities singly and simultaneously in a multiple regression analysis. Patients with the most severe growth retardation at RTx appeared to have the most pronounced growth spurt after RTx, but even they never had complete catchup growth, and 2 y after RTx they were still shorter than those with less severe growth retardation at RTx. Alternate-day instead of daily prednisone administration had a significantly positive influence, whereas a high cumulative dose of prednisone, azathioprine instead of cyclosporin A therapy, and a persistently reduced GFR (GFR < 50 mL/ min/1.73 m2) had a significantly negative influence on catch-up growth during the 2 y after RTx. Other factors, such as gender, chronologic and bone age at RTx, primary renal disease, duration of initial dialysis, repeat RTx, and target height SD score for chronologic age, whether evaluated singly or simultaneously with other significant factors, appeared to have no significant influence on post-RTx growth. Thus, 70% of the prepubertal children do not experience appreciable catch-up growth during the first 2 y after RTx. Optimization of pretransplant height appears very important. Immunosuppressive treatment with cyclosporin therapy in combination with a minimal dose of alternate-day prednisone would then result in optimal post-transplant growth, particularly if the GFR remains above 50 mL/min/1.73 m2).