Miracle-dz/UniFAR-FTUs huggingface dataset:
Varying proliferative and clonogenic potential in NRAS‐mutated congenital melanocytic nevi according to size

Congenital melanocytic nevi (CMN) are benign proliferations that may be associated with various consequences depending on their size. They are characterized by a specific molecular signature, namely a postzygotic somatic NRAS or BRAF mutation. We have recently reported that large CMN (lCMN), which are classically associated with an increased melanoma risk, harbour cell subpopulations with specific clonogenic and tumorigenic potential. We wished to ascertain whether cells displaying similar properties persisted postnatally in medium CMN (mCMN). Eighteen medium M1, nine large and one giant NRAS‐mutated CMN were prospectively included in the study. Subpopulations of mCMN cells expressed stem cell/progenitor lineage markers such as Sox10, nestin and Oct4, as was the case in lCMN. Nevertheless, conversely to lCMN, mCMN cells with clonogenic properties were rarer. In vitro, approximatively one in 1500 cells isolated from fresh mCMN formed colonies that could be passaged. In vivo, mCMN seemed to harbour cells with less proliferative potential than the larger lesions as lCMN biopsies displayed a threefold expansion compared to mCMN when xenografted in Rag2−/− mice. Thus, our data revealed variations in clonogenicity and tumorigenic properties in NRAS‐mutated CMN according to size.
Analgesic action of acute and chronic intraspinally administered opiate and alpha 2-adrenergic agonists in chronic neuropathic pain.

Intrathecal (IT) administration of opiate analgesics has become a popular method of pain control in patients with pain of both malignant and nonmalignant origin. Therapeutic efficacy for nonmalignant pain states might be improved by having a broader range of available pharmacologic agents for intrathecal administration. Toward this aim, we have applied a new model of neuropathic pain in the rat to evaluate the relative analgesic efficacy and potential cross tolerance of both acutely and chronically administered IT morphine (MS) and tizanidine (TZ), an alpha 2-adrenergic agonist. Under anesthesia, 225 Sprague-Dawley male rats underwent unilateral multiple partial suture ligation of the sciatic nerve. This produces a syndrome similar to human neuropathic pain. Chronic lumbar IT cannulae were placed via the cisterna magna. Seven days after surgery, animals were tested for spontaneous ambulation and paw pinch tolerance. These tests correlate with human clinical observations of chronic pain and hyperpathia. For the acute drug administration, animals were then given saline, 10, 20, or 30 micrograms IT MS or 10, 25 or 50 micrograms IT TZ and testing was repeated. Preliminary results suggest that MS, in a dose-dependent manner, significantly decreased abnormal limb withdrawal from the floor while ambulating and increased paw pinch withdrawal latency to cutoff values (p < or = 0.01 in all tests). IT MS had significant effects on pain sensation in the operated and unoperated limbs, increasing latencies to cutoff and nonspecifically inhibiting pain transmission. IT TZ had a similar effect on decreasing limb withdrawal from the floor, but paw pinch withdrawal latency was increased only to the normal range, not to cutoff values. These effects were also dose-dependent. For chronic drug administration, after baseline testing, osmotic minipumps (Alza, Palo Alto, Calif.) delivering either saline, 60 or 120 micrograms/day MS, or 75 or 150 micrograms/day TZ were attached to the IT catheter. Testing was done on days 1, 4, 7 and 14 after pump attachment. On day 14, the animals were given an IT bolus of the noninfused drug (50 micrograms tizanidine or 30 micrograms morphine) and the tests were repeated to determine degree of cross tolerance. Initially, chronic MS and TZ administration produced a similar degree of analgesia seen with results obtained with acute administration. The animals rapidly became tolerant to these agents so that by day 4, neither drug had an analgesic effect. No significant cross tolerance between MS and TZ was observed. Thus, both IT MS and TZ are analgesic in experimental chronic neuropathic pain. (ABSTRACT TRUNCATED AT 400 WORDS)
Familiarization, validity and smallest detectable difference of the isometric squat test in evaluating maximal strength

ABSTRACT Isometric multi-joint tests are considered reliable and have strong relationships with 1RM performance. However, limited evidence is available for the isometric squat in terms of effects of familiarization and reliability. This study aimed to assess, the effect of familiarization, stability reliability, determine the smallest detectible difference, and the correlation of the isometric squat test with 1RM squat performance. Thirty-six strength-trained participants volunteered to take part in this study. Following three familiarization sessions, test–retest reliability was evaluated with a 48-hour window between each time point. Isometric squat peak, net and relative force were assessed. Results showed three familiarizations were required, isometric squat had a high level of stability reliability and smallest detectible difference of 11% for peak and relative force. Isometric strength at a knee angle of ninety degrees had a strong significant relationship with 1RM squat performance. In conclusion, the isometric squat is a valid test to assess multi-joint strength and can discriminate between strong and weak 1RM squat performance. Changes greater than 11% in peak and relative isometric squat performance should be considered as meaningful in participants who are familiar with the test.
Can we predict suicide?

In 2008, national guidelines for suicide prevention in mental health care were published in Norway (1). A milestone in suicide prevention work, these guidelines have, however, been criticised, partly because some mental health professionals believe that suicide risk assessments are not useful and may even be harmful (2, 3). It has also been maintained that it is not possible to predict suicide, even among high-risk individuals (3), and that several studies have demonstrated this (4–7). Claims like these can create uncertainty among clinicians as to what they should do.
Tumor Angiogenesis as a Prognostic Predictor in Colorectal Carcinoma with Special Reference to Mode of Metastasis and Recurrence

Tumor angiogenesis has proved to be a useful prognostic determinant for patients with various solid tumors. In this study, we investigated the quantitative expression of angiogenesis in colorectal carcinoma to determine how angiogenesis correlates with clinicopathologic factors and prognosis. One hundred twenty-seven specimens resected from patients with primary colorectal carcinoma were investigated immunohistochemically using a polyclonal antibody against factor-VIII-related antigen, and areas with the highest vascular density at the invasive tumor margin were counted at 200 times magnification. The microvessel count, defined as angiogenesis density (AD), became significantly higher with increase in histologic grade (p = 0.02) and Dukes stage (p = 0.001). AD was also significantly higher in patients with lymph node metastasis (p = 0.005), lymphatic invasion (p = 0.042), vascular invasion (p < 0.001), and liver metastasis (p = 0.0004) than in those without. In addition, patients with synchronous distant hematogenous metastasis in stage D disease showed significantly higher AD than patients with nonhematogenous metastasis (p = 0.006). When 27 cases of disease recurrence after surgical resection with curative intent were stratified according to mode of spread, AD in cases with a hematogenous pattern of relapse proved to be significantly higher than in cases with nonhematogenous spread (p < 0.001). No significant differences were, however, found in AD when they were subdivided as to operative nodal status (p = 0.39 and 0.08 in the node-negative and the node-positive group, respectively). Multivariate analysis indicated that AD was an independent prognostic factor (p = 0.0004) in colorectal carcinoma. Quantitative evaluation of tumor angiogenesis at the invasive tumor margin is suggested to be a good prognostic indicator and a useful predictor for hematogenous spread and recurrence in patients with colorectal carcinoma.
Discovery and recognition of motion primitives in human activities

We present a novel framework for the automatic discovery and recognition of motion primitives in videos of human activities. Given the 3D pose of a human in a video, human motion primitives are discovered by optimizing the ‘motion flux’, a quantity which captures the motion variation of a group of skeletal joints. A normalization of the primitives is proposed in order to make them invariant with respect to a subject anatomical variations and data sampling rate. The discovered primitives are unknown and unlabeled and are unsupervisedly collected into classes via a hierarchical non-parametric Bayes mixture model. Once classes are determined and labeled they are further analyzed for establishing models for recognizing discovered primitives. Each primitive model is defined by a set of learned parameters. Given new video data and given the estimated pose of the subject appearing on the video, the motion is segmented into primitives, which are recognized with a probability given according to the parameters of the learned models. Using our framework we build a publicly available dataset of human motion primitives, using sequences taken from well-known motion capture datasets. We expect that our framework, by providing an objective way for discovering and categorizing human motion, will be a useful tool in numerous research fields including video analysis, human inspired motion generation, learning by demonstration, intuitive human-robot interaction, and human behavior analysis.
Serum Concentrations of Tissue Polypeptide Antigen in Patients with Vulvar Intraepithelial Neoplasia and Vulvar Cancer

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker tissue polypeptide antigen (TPA) in patients with vulvar cancer. This retrospective study comprises 41 patients with vulvar cancer FIGO stages I–III, 17 patients with vulvar intraepithelial neoplasia (VIN) III, and 40 healthy female controls. Serum concentrations of TPA were measured using a microparticle enzyme immunoassay. Results were correlated to clinical data. Median serum concentrations of TPA in healthy female controls, patients with VIN III, and patients with vulvar cancer were 42 U/l (range 12–192), 53 U/l (range 17–127.9) and 57 U/l (range 4.2–423), respectively (Mann-Whitney U test, p = 0.8). Serum concentrations of TPA were not associated with stage of disease, histological grade, and age at the time of diagnosis. In vulvar cancer patients, elevated serum concentrations of TPA prior to therapy were not associated with a shortened disease-free or overall survival (log-rank test: p = 0.5 and p = 0.9, respectively). In a multivariate Cox regression model comprising tumor stage and TPA, tumor stage, but not TPA revealed a statistically significant influence on disease-free (Cox proportional hazard regression model, p = 0.05 and p = 0.6, respectively) and overall (Cox proportional hazard regression model, p = 0.04 and p = 0.8, respectively) survival of patients with vulvar cancer. We conclude that cytokeratin expression, as reflected by serum concentrations of TPA, does not play a role in the natural history of vulvar cancer. The evaluation of serum concentrations of TPA prior to therapy is not recommended.
Handrub Consumption Mirrors Hand Hygiene Compliance

We assessed handrub consumption as a surrogate marker for hand hygiene compliance from 2007 to 2014. Handrub consumption varied substantially between departments but correlated in a mixed effects regression model with the number of patient-days and the observed hand hygiene compliance. Handrub consumption may supplement traditional hand hygiene observations. Infect Control Hosp Epidemiol 2016;37:707–710
Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia.

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials. gov as #NCT01976416.
Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm2) then analysed by RNA‐Seq at different time points post‐UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time‐ and dose‐dependent changes in gene expression that was different from melanocytes. The early UVB‐responsive gene set (4 h post‐UVR) differed significantly from delayed UVB‐responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin.
Recombinant human erythropoietin in patients with myelodysplastic syndrome and myelofibrosis.

In a dose titration study we tested the efficacy and tolerance of recombinant human erythropoietin (rhEPO) in 10 patients with myelodysplasia (MDS) and 2 patients with idiopathic myelofibrosis. Patients with a haemoglobin level < 100 g/l were treated as out-patients for 12 weeks with daily doses ranging from 30 U/kg body weight (BW) up to 240 U/kg BW in non-responders. Of the 10 patients with MDS, 6 were suffering from refractory anaemia with sideroblasts (RAS) and 4 from refractory anaemia with an excess of blasts. The median age was 73 years (range 41-81). Two patients with RAS responded with a rise in haemoglobin concentration to > 130 g/l. They had not been transfusion-dependent prior to treatment. Both patients had relatively low serum concentrations of immunoreactive EPO. There was neither a rise in haemoglobin nor a reduction in transfusion dependence in any of the other patients. It may be concluded that rhEPO is possibly effective in a subgroup of MDS patients where the disease is less advanced. None of the transfusion-dependent patients benefited.
Drug metabolism and liver disease: a drug–gene–environment interaction

Abstract Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug–gene–environment interaction. This requires an integration of knowledge of the drug’s properties, knowledge of the gene products involved in its metabolism, and knowledge of the pathophysiology of its disposition. This will enhance the level of predictability of drug disposition and toxicity for a drug of interest in an individual patient. It is our contention that advances in pharmacology, pharmacogenomics, and hepatology, together with concerted interests in the academic, regulatory, and pharmaceutical industry communities provide an ideal immediate environment to move from a qualitative reactive approach to quantitative proactive approach in individualizing patient therapy in liver disease.
Exercise Training and the Progression of Chronic Renal Failure

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, We regret that Eidemak et al. [1] failed to mention and discuss our investigation [2] which we feel is relevant to the subject they studied. We have demonstrated that repeated physical exertion under optimal environmental conditions produced a rise in GFR in sham-operated and uninephrectomized mice. By contrast, no change in GFR was demonstrated following a similar procedure in uremic animals. We suggest that our results in the latter group are more indicative than those of the two studies mentioned [3, 4] since in these studies the imposed physical activity consisted of swimming and involved water immersion and exposure to a high environmental temperature (37 °C). Each of those two elements triggered a chain of physiological events, such as a rise in central blood volume and activation of various relevant hormonal systems, which could alter the pure effect of physical activity on GFR. Moreover, our results strongly suggest that the magnitude of the initial GFR determines the capacity to mobilize ‘reserve’ renal function by exercise. The lower the GFR, the smaller would be the reserve capacity. We therefore conclude that under identical experimental conditions results obtained in humans [1] and mice are similar. OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO
Effect of superoxide dismutase on liver ischemia-reperfusion injury in the rat: a biochemical monitoring.

Oxygen free radicals have been implicated in the pathogenesis of postischemic liver injury. High-dose superoxide dismutase (SOD), a radical scavenging enzyme, has been investigated in a rat model of liver ischemia reperfusion by biochemical monitoring. Blood vessels to the median and left lobe were clamped for 1 h and then reperfusion was allowed. The indices used were serial venous blood levels of AST, ALT, calcium, and ATP determination in liver tissue. In SOD-treated animals (7,5000 U i.v.) a significant attenuation of the rise in enzyme levels was observed as well as the absence of the decrease in calcium level in the early phase after reperfusion as compared with control rats, and furthermore ATP restoration was significantly increased.
Entitled vengeance: A meta-analysis relating narcissism to provoked aggression.

Narcissism has long been used to predict aggressive or vengeful responses to provocations from others. The strength of this relation can, however, vary widely from study to study. Narcissism and revenge were examined in 84 independent samples (N = 11297), along with the moderating role of sample type (i.e., child/adolescent, prisoner, undergraduate, or general samples), type of narcissism measure used (i.e., Narcissistic Personality Inventory, Psychological Entitlement Scale, Short D3, etc.), the nature of the provocation, and the type of provoked aggression examined. Narcissism was positively related to provoked aggression across studies (ρ = .25), but that relation was stronger in child/adolescent samples (ρ = .36) and when measures of entitlement or vulnerable narcissism were employed (ρ = .29). Implications for practical research, as well as neglected areas of research on narcissism and provoked aggression are discussed. Aggr. Behav. 42:362-379, 2016. © 2015 Wiley Periodicals, Inc.
Psychopathological Profile of Tinnitus Sufferers: Evidence Concerning the Relationship between Tinnitus Features and Impact on Life

This study involving 281 French tinnitus sufferers sought to investigate possible correlations between psychopathological profile and scores obtained from three tinnitus questionnaires. The patients all completed a French version of the Mini-Mult – a shortened Minnesota Multiphasic Personality Inventory – and French translations of three questionnaires designed especially for the clinical assessment of tinnitus: Tinnitus Reaction Questionnaire (TRQ), Subjective Tinnitus Severity Scale (STSS) and Tinnitus Handicap Questionnaire (THQ). Significant correlations were found (p < 0.0001) between scores on various Mini-Mult scales and total or factor 1 THQ and total TRQ scores. No significant correlation was found between the STSS and any Mini-Mult score.
A Model to Detect Autochthonous Group 1 and 2 Brazilian Vaccinia virus Coinfections: Development of a qPCR Tool for Diagnosis and Pathogenesis Studies

Vaccinia virus (VACV) is the etiological agent of bovine vaccinia (BV), an emerging zoonosis that has been associated with economic losses and social effects. Despite increasing reports of BV outbreaks in Brazil, little is known about the biological interactions of Brazilian VACV (VACV-BR) isolates during coinfections; furthermore, there are no tools for the diagnosis of these coinfections. In this study, a tool to co-detect two variants of VACV was developed to provide new information regarding the pathogenesis, virulence profile, and viral spread during coinfection with VACV-BR isolates. To test the quantitative polymerase chain reactions (qPCR) tool, groups of BALB/c mice were intranasally monoinfected with Pelotas virus 1—Group II (PV1-GII) and Pelotas virus 2—Group I (PV2-GI), or were coinfected with PV1-GII and PV2-GI. Clinical signs of the mice were evaluated and the viral load in lung and spleen were detected using simultaneous polymerase chain reactions (PCR) targeting the A56R (hemagglutinin) gene of VACV. The results showed that qPCR for the quantification of viral load in coinfection was efficient and highly sensitive. Coinfected mice presented more severe disease and a higher frequency of VACV detection in lung and spleen, when compared to monoinfected groups. This study is the first description of PV1 and PV2 pathogenicity during coinfection in mice, and provides a new method to detect VACV-BR coinfections.