Miracle-dz/UniFAR-FTUs huggingface dataset:
Myogenic determination occurs independently in somites and limb buds.

Gene targeting has indicated that the bHLH transcription factors Myf-5 and MyoD are required for myogenic determination because skeletal myoblasts and myofibers are entirely ablated in mouse embryos lacking both Myf-5 and MyoD. Entrance into the skeletal myogenic program during development occurs following the independent transcriptional induction of either Myf-5 or MyoD. To identify sequences required for the de novo induction of MyoD transcription during development, we investigated the expression patterns of MyoD-lacZ transgenes in embryos deficient in both Myf-5 and MyoD. We observed that a 258-bp fragment containing the core of the -20-kb MyoD enhancer activated expression in newly formed somites and limb buds in compound mutant embryos lacking both Myf-5 and MyoD. Importantly, Myf-5- and MyoD-deficient presumptive muscle precursor cells expressing beta-galactosidase were observed to assume nonmuscle fates primarily as precartilage primordia in the trunk and the limbs, suggesting that these cells were multipotential. Therefore, cells are recruited into the MyoD-dependent myogenic lineage through activation of the -20-kb MyoD enhancer and this occurs independently in somites and limb buds.
Inhibition of human natural killer cell activity by (14R,15S)-14,15-dihydroxy-5Z,8Z,10E,12E- icosatetraenoic acid.

The interactions between products of the 15-lipoxygenase cascade and human natural killer (NK) cell activity have been studied. Addition of human leukocyte-derived (14R,15S)-14,15-dihydroxy-5Z,8Z,10E,12E-ic osatetraenoic acid (14,15-DiHETE) to the NK cytotoxicity assay against K562 target cells resulted in inhibition of NK cell activity, whereas addition of other 15-lipoxygenase-associated metabolites [i.e., (15S)-15-hydroperoxy-5Z,8Z,11Z,13E-icosatetra eno ic acid, (15S)-15-hydroxy-5Z,8Z,11Z,13E-icosatetraenoic acid, and (8R,15S)- and (8S,15S)-8,15-dihydroxy-5Z,9E,-11E,13E-icosat etr aenoic acid isomers] resulted in little or no inhibition of NK function. Dose-response studies indicate that leukocyte-derived 14,15-DiHETE and 14,15-DiHETE methyl ester, at micromolar concentrations, inhibit NK function even in the presence of 2.5% fetal calf serum. Synthetic 14,15-DiHETE prepared by total organic synthesis displayed similar biological activities over identical dose ranges. These icosanoids do not inhibit NK target cell binding and they exert only a variable effect in either antibody-dependent cytotoxicity or cytotoxic T-lymphocyte assays. These results demonstrate that the 14,15-DiHETE inhibits NK cell function in vitro. Moreover, they suggest that activation of the 15-lipoxygenase cascade and formation of 14,15-DiHETE in vivo may provide a mode of immune regulation.
The Diverse Molecular Basis and Hematological Features of Hb H and AEBart’s Diseases in Northeast Thailand

We defined the molecular basis and correlated the hematological phenotypes with the globin genotypes in 52 patients with Hb H disease and 29 patients with AEBart’s disease of northeast Thailand. Among the former group, the most prevalent molecular defect was found to be the interaction of α-thalassemia 1 (SEA type) with the Hb Constant Spring (Hb CS; 35 of 52 patients), followed by the deletion of three α-globin genes with the SEA type α-thalassemia 1 and the 3.7- or 4.2-kb deletion of α-thalassemia 2 (14 of 52 patients) and the interaction of the SEA α-thalassemia 1 with the Hb Paksé which was found in the remaining 3 patients. Among the 29 patients of the latter group, in 18 disease was caused by interactions of Hb E heterozygotes with the SEA α-thalassemia 1 and Hb CS. Interaction of Hb E heterozygotes with a deletional form of Hb H disease was detected in 7 patients and the Hb Paksé AEBart’s disease was found in another 3 patients. A remaining patient with an unusually severe form of AEBart’s disease with a lower Hb E level and observable Hb H was associated with a hitherto undescribed condition, the interaction of Hb E heterozygote with α-thalassemia 1 and an α2 codon 30 (GAG) deletion. Hematological characterization of the patients demonstrated that although disease in most of them was associated with thalassemia intermedia phenotypes, it was apparent that association with the nondeletional form of α-thalassemia 2 produced a more severe phenotype than that of the deletional one. Therefore, α-globin gene analysis of Hb H and AEBart’s disease patients would be useful for predicting the clinical outcome and improving genetic counseling.
Characterization of adrenal tumors by chemical shift fast low-angle shot MR imaging: comparison of four methods of quantitative evaluation.

OBJECTIVE The aim of our study was to assess quantitative methods of distinguishing adenomas from malignant adrenal lesions using chemical shift fast low-angle shot MR imaging. MATERIALS AND METHODS We assessed 102 adrenal tumors in 88 patients (27 hyperfunctioning and 44 nonhyperfunctioning adenomas, 19 metastases, nine pheochromocytomas, and three other adrenal tumors) using chemical shift MR imaging. On the chemical shift imaging, signal intensity index, calculated as [(signal intensity on in-phase imaging - signal intensity on opposed-phase imaging) / (signal intensity on in-phase imaging)] x 100%, was compared with the adrenal-to-spleen ratio, adrenal-to-muscle ratio, and adrenal-to-liver ratio for signal change on opposed-phase fast low-angle shot MR imaging. The tissues in the spleen, paraspinal muscle, and liver were reference tissues. RESULTS The signal intensity index had several advantages over the other three parameters calculated. We found no overlap in indexes between adenomas and metastatic tumors. The accuracy in distinguishing adenomas from metastatic tumors was 100% if the cutoff value of the signal intensity index selected was 11.2-16.5%. CONCLUSION The signal intensity index is the most reliable evaluation method for differentiating adrenal adenomas from metastatic adrenal tumors.
Young suicide attempters: a comparison between a clinical and an epidemiological sample.

OBJECTIVE To compare risk factors for self-harm in 2 groups: hospitalized adolescents who had attempted suicide and adolescents reporting suicide attempts in a community survey. METHOD All suicide attempters aged 13 to 19 years admitted to medical wards (n = 91) in a region of Norway were assessed and interviewed. Risk factors were identified by comparisons with a general population sample participating in a questionnaire study in the same community (n = 1,736). In this population sample, a separate analysis of risk factors for reporting deliberate self-harm (n = 141) was performed, applying bivariate and multivariate logistic regression models. RESULTS Adjusted risk factors for suicide attempts in hospitalized adolescents were depression (odds ratio [OR] = 4.7), disruptive disorders (OR = 9.4), low self-worth (OR = 1.3), infrequent support from parents (OR = 3.3) or peers (OR = 3.3), parents' excessive drinking (OR = 4.3), and low socioeconomic status (OR = 2.4). For adolescents who self-reported self-harm, depression (OR = 3.1) and loneliness (OR = 1.13) were significant adjusted risk factors (p < .001). Low self-worth, low socioeconomic status, and little support from parents or peers characterized hospitalized suicidal adolescents compared with those who were not hospitalized. CONCLUSIONS The risk factors were more powerful for hospitalized than for nonhospitalized adolescents. Prevention efforts should target the same factors for both groups, at a population level for nonhospitalized adolescents and at an individual level for hospitalized adolescents, with a focus on depression, low self-esteem, and family communication.
Development and Psychometric Properties of the Nursing Critical Thinking in Clinical Practice Questionnaire

Background and Aim: A complex healthcare environment, with greater need for care based on the patient and evidence‐based practice, are factors that have contributed to the increased need for critical thinking in professional competence. At the theoretical level, Alfaro‐LeFevre (2016) put forward a model of critical thinking made up of four components. And although these explain the construct, instruments for their empirical measurement are lacking. The purpose of the study was to develop and validate the psychometric properties of an instrument, the Nursing Critical Thinking in Clinical Practice Questionnaire (N‐CT‐4 Practice), designed to evaluate the critical thinking abilities of nurses in the clinical setting. Methods: A cross‐sectional survey design was used. A pool of items was generated for evaluation by a panel of experts who considered their validity for the new instrument, which was finally made up of 109 items. Following this, validation was carried out using a sample of 339 nurses at a hospital in Barcelona, Spain. Reliability was determined by means of internal consistency and test–retest stability over time, although the validity of the construct was assessed by means of confirmatory factor analysis. Results: The content validity index of the N‐CT‐4 Practice was . 85. Cronbach's alpha coefficient for the whole instrument was . 96. The intraclass correlation coefficient was . 77. Confirmatory factor analysis showed that the instrument was in line with the four‐dimensional model proposed by Alfaro‐LeFevre (2016). Linking Evidence to Action: The psychometric properties of theN‐CT‐4 Practice uphold its potential for use in measuring critical thinking and in future research related with the examination of critical thinking.
The IARC TP53 database: New online mutation analysis and recommendations to users

Mutations in the tumor suppressor gene TP53 are frequent in most human cancers. Comparison of the mutation patterns in different cancers may reveal clues on the natural history of the disease. Over the past 10 years, several databases of TP53 mutations have been developed. The most extensive of these databases is maintained and developed at the International Agency for Research on Cancer. The database compiles all mutations (somatic and inherited), as well as polymorphisms, that have been reported in the published literature since 1989. The IARC TP53 mutation dataset is the largest dataset available on the variations of any human gene. The database is available at www.iarc. fr/P53/. In this paper, we describe recent developments of the database. These developments include restructuring of the database, which is now patient‐centered, with more detailed annotations on the patient (carcinogen exposure, virus infection, genetic background). In addition, a new on‐line application to retrieve somatic mutation data and analyze mutation patterns is now available. We also discuss limitations on the use of the database and provide recommendations to users. Hum Mutat 19:607–614, 2002. © 2002 Wiley‐Liss, Inc.
Assessment of third degree tears using three‐dimensional anal endosonography with combined anal manometry: a novel technique

Three‐dimensional anal endosonography has enabled sagittal and coronal reconstructions of the anal canal to be matched with longitudinal pressure data, to present a combined picture of structure and function. This novel technique has been applied to a group of women with a clinical diagnosis of a third degree tear. Endosonography showed that only 68% of women had ultrasound evidence of sphincter damage. Anal canal anatomy and pressure profile did not differ significantly between those with and those without sphincter damage, but the anterior external anal sphincter and the puborectalis tended to be shorter and the pressures were lower in those with sphincter disruption.
Perspective on BVDV control programs

Abstract Programs for control and eradication of bovine viral diarrhea virus (BVDV) are often considered prudent when the expense of a control program within a specified time frame effectively prevents loss due to disease and the expense of control does not exceed the costs associated with infection. In some geographic areas, concerns about animal welfare or desires to reduce antibiotic usage may motivate BVDV control even when control programs are associated with a lack of financial return on investment. In other geographic areas, concerns about financial return on investment may be the key motivating factor in considering implementation of BVDV control programs. Past experiences indicate that systematic, well-coordinated control programs have a clear potential for success, while voluntary control programs in cultures of distributed decision-making often result in notable initial progress that ultimately ends in dissolution of efforts. Segmentation of the cattle industry into cow–calf producers, stocker/backgrounders, and feedlot operators amplifies the distribution of decision-making regarding control programs and may result in control measures for one industry segment that are associated with significant costs and limited rewards. Though the host range of BVDV extends well beyond cattle, multiple eradication programs that focus only on testing and removal of persistently infected (PI) cattle have proven to be effective in various countries. While some individuals consider education of producers to be sufficient to stimulate eradication of BVDV, research surrounding the adoption of innovative health care procedures suggests that the process of adopting BVDV control programs has a social element. Collegial interactions and discussions may be crucial in facilitating the systematic implementation necessary to optimize the long-term success of control programs. Compulsory control programs may be considered efficient and effective in some regions; however, in a nation where individual identification of cattle remains voluntary, the likelihood of effective compulsion to control BVDV within a farm or ranch appears to be very unlikely. While currently available diagnostic tests are sufficient to support BVDV eradication via systematic, well-coordinated programs, the development of a diagnostic procedure to safely and consistently detect the gestation of a PI fetus after 5 months of gestation would be a valuable research breakthrough. This desired testing modality would allow diagnosis of PI calves, while the dam continues to provide biocontainment of the infected fetus. This development could speed the progress of control programs in achieving the goal of BVDV control and eventual eradication.
Single Image Super Resolution - When Model Adaptation Matters

In the recent years impressive advances were made for single image super-resolution. Deep learning is behind a big part of this success. Deep(er) architecture design and external priors modeling are the key ingredients. The internal contents of the low resolution input image is neglected with deep modeling despite the earlier works showing the power of using such internal priors. In this paper we propose a novel deep convolutional neural network carefully designed for robustness and efficiency at both learning and testing. Moreover, we propose a couple of model adaptation strategies to the internal contents of the low resolution input image and analyze their strong points and weaknesses. By trading runtime and using internal priors we achieve 0.1 up to 0.3dB PSNR improvements over best reported results on standard datasets. Our adaptation especially favors images with repetitive structures or under large resolutions. Moreover, it can be combined with other simple techniques, such as back-projection or enhanced prediction, for further improvements.
Interleukin‐4 and Interferon‐γ: The Quintessence of a Mutual Antagonistic Relationship

The two cytokines interleukin (IL)‐4 and interferon (IFN)‐γ play major roles in the generation and regulation of immune responses. Central in this respect is their mutually antagonistic functions. First, IL‐4 promotes T helper cell type 2 (Th2) differentiation and stability and inhibits Th1‐cell differentiation. A direct role of IFN‐γ in Th1‐cell differentiation is debatable, whereas inhibition of Th2‐cell differentiation and roles in Th1‐cell stabilization are well established functions of IFN‐γ. Secondly, IL‐4 and IFN‐γ also affect antibody class switch and expression of Fc receptors differentially, which strongly affect the effector mechanisms following antibody production. Thirdly, macrophage activities induced or enhanced by IFN‐γ, such as expression of certain cytokines, surface molecules and enzymes, are antagonized by IL‐4. Together, these functions of IL‐4 and IFN‐γ place the two cytokines at cardinal positions in the regulation of immune reactions. In this review the known molecular mechanisms underlying the observed functions of IL‐4 and IFN‐γ are presented and discussed.
Diuretic effect of frusemide in patients with nephrotic syndrome: is it potentiated by intravenous albumin?

We investigated the claim that infusion of albumin potentiates the diuretic effect of frusemide in patients with the nephrotic syndrome.1 We selected 12 inpatients with the nephrotic syndrome according to two criteria: (a) failure to lose weight after bed rest and a 40 mmol sodium diet and (b) presence of minimal lesions or a well preserved glomerular histology on renal biopsy. We gave each patient three treatments randomly from 8 am to noon, at intervals of at least two days—infusion of albumin 0.5 g/kg given as a 20% solution for four hours; infusion of frusemide 60 mg bolus followed by 40 mg/h for four hours; and a combined treatment of both types of infusion. We collected urine on the treatment days from 8 am to 2 pm and …
A prospective comparison of surgical and pathological outcomes obtained after robot‐assisted or pure laparoscopic partial nephrectomy in moderate to complex renal tumours: results from a French multicentre collaborative study

Nephron‐sparing surgery has become the standard of care for small renal masses because it allows for the same oncological control as radical nephrectomy and achieves better overall survival, while lowering the risk of subsequent chronic renal failure. Mini‐invasive surgical approaches have also been developed, e.g. laparoscopic partial nephrectomy (LPN) and robot‐assisted laparoscopic PN (RAPN), which result in less bleeding, reduced postoperative pain, shorter length of stay (LOS) and shorter recovery time. LPN requires advanced surgical skill, has a longer learning curve and requires perseverance, which limits its large diffusion. From this prospective comparative study, we can now claim that RAPN is not inferior to pure LPN in terms of perioperative outcomes (i.e. blood loss, operative duration, warm ischaemia time, LOS).
GMP synthase is essential for viability and infectivity of Trypanosoma brucei despite a redundant purine salvage pathway

The causative agent of human African trypanosomiasis, Trypanosoma brucei, lacks de novo purine biosynthesis and depends on purine salvage from the host. The purine salvage pathway is redundant and contains two routes to guanosine‐5′‐monophosphate (GMP) formation: conversion from xanthosine‐5′‐monophosphate (XMP) by GMP synthase (GMPS) or direct salvage of guanine by hypoxanthine‐guanine phosphoribosyltransferase (HGPRT). We show recombinant T. brucei GMPS efficiently catalyzes GMP formation. Genetic knockout of GMPS in bloodstream parasites led to depletion of guanine nucleotide pools and was lethal. Growth of gmps null cells was only rescued by supraphysiological guanine concentrations (100 μM) or by expression of an extrachromosomal copy of GMPS. Hypoxanthine was a competitive inhibitor of guanine rescue, consistent with a common uptake/metabolic conversion mechanism. In mice, gmps null parasites were unable to establish an infection demonstrating that GMPS is essential for virulence and that plasma guanine is insufficient to support parasite purine requirements. These data validate GMPS as a potential therapeutic target for treatment of human African trypanosomiasis. The ability to strategically inhibit key metabolic enzymes in the purine pathway unexpectedly bypasses its functional redundancy by exploiting both the nature of pathway flux and the limited nutrient environment of the parasite's extracellular niche.
Modeling the Time Course of CD4 T-Lymphocyte Counts According to the Level of Virologic Rebound in HIV-1–Infected Patients on Highly Active Antiretroviral Therapy

Objective To study the influence of the level of virologic rebound during combination antiretroviral therapy on the time course of the CD4 count. Methods Between January 1997 and December 1999, we enrolled 3736 patients from the French Hospital HIV Database who had an undetectable viral load on a first course of highly active antiretroviral therapy (HAART). Four levels of virologic rebound were defined on the basis of viral load values during the year following initial undetectability on HAART: group 1, all viral loads <500 copies/mL; group 2, all viral loads <5000 copies/mL; group 3, all viral loads <10,000 copies/mL; and group 4, at least 1 viral load >10,000 copies/mL. We developed a continuous time-homogeneous Markov process with 5 reversible stages defined by CD4 count intervals. Results CD4 counts increased continuously over time in each group. The smaller the virologic rebound, the stronger was the increase in the CD4 count (P < 0.0001). The mean CD4 cell count increments between months 2 and 6 were 26, 20, 11, and 2 cells/mm3 in groups 1, 2, 3, and 4, respectively. The rate of gain fell after month 6 and was almost nil in group 4. Conclusion After achieving an undetectable viral load on HAART, immunologic reconstitution is possible whatever the subsequent level of viral replication, except among patients with high-level rebound, meaning that in patients with a long history of antiretroviral therapy and a reduced choice of antiretroviral drugs due to acquisition of resistances, delay in antiretroviral therapy switch can be possible in patients with low or intermediate rebound.
Tumor necrosis factor links chronic obstructive pulmonary disease and K-ras mutant lung cancer through induction of an immunosuppressive pro-tumor microenvironment

ABSTRACT Tumor necrosis factor (TNF) is known as an important regulator of tumor microenvironment and inflammation. TNF levels are markedly elevated in the bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), which is an independent risk factor for lung cancer. We have previously shown that COPD-like airway inflammation promotes lung cancer in a K-ras mutant mouse model (CC-LR mouse). This was associated with a significant increase of neutrophils in BALF, accompanied by a marked increase in TNF level, suggesting a link between COPD, TNF, and lung cancer promotion. Therefore, we first overexpressed TNF in the airway epithelium of CC-LR mice, which promoted lung cancer by ∼2-fold. This was associated with increased numbers of Ki67 and CD31 positive cells in lung tumors of CC-LR/TNF-Tg mice. We also found a robust increase in NF-κB activation, and numbers of neutrophils and myeloid-derived suppressor cells (MDSCs) in lung. Accordingly, we depleted MDSCs in CC-LR/TNF-Tg mice, which lead to significant tumor suppression emphasizing on the role of TNF-induced MDSCs in K-ras induced lung tumorigenesis. Finally, we targeted TNF expression by crossing CC-LR mice with TNF knock-out mice (CC-LR/TNF-KO), which resulted in a significant decrease in lung tumor burden in the absence or presence of COPD-like airway inflammation. Interestingly, there were less MDSCs and lower Ki67 and CD31 expression in the lung of the CC-LR/TNF-KO mice. We conclude that TNF links COPD to lung cancer promotion by induction of an immunosuppressive MDSC response, and subsequent amplification of proliferation and angiogenesis in tumors.