Miracle-dz/UniFAR-FTUs huggingface dataset:
Hedgehog Signaling and the Gli Code in Stem Cells, Cancer, and Metastases

Hedgehog signaling and the oncogenic load promote stem cell–like behavior and metastasis by influencing the balance between activator and repressor functions of Gli transcription factors. The Hedgehog (Hh)–Gli signaling pathway is an essential pathway involved in development and cancer. It controls the Gli code—the sum of all activator and repressor functions of the Gli transcription factors. Through the Gli code, and Gli1 in particular, it modulates the fate and behavior of stem and cancer stem cells, as well as tumor growth and survival in many human cancer types. It also affects recurrence and metastasis and is enhanced in advanced tumors, where it promotes an embryonic stem (ES) cell–like gene expression signature. A central component of this signature, Nanog, is critical for glioblastoma and cancer stem cell survival and expansion. Gli1 activity is also enhanced by several oncogenic proteins, including Ras, Myc, and Akt, and by loss of tumor suppressors, such as p53 and PTEN. The oncogenic load boosts Gli1 levels, which supports tumor progression, and promotes a critical threshold of Gli1 activity that allows cells to enter the metastatic transition. In colon cancers, this transition is defined by enhanced Hh-Gli and, surprisingly, by repressed Wnt-Tcf signaling. Together our data support a model in which the Gli code, and Gli1 in particular, acts as a key sensor that responds to both Hh signals and the oncogenic load. We hypothesize that, in turn, the Gli-regulated ES-like factors induce a reprogramming event in cancer stem cells that promotes high invasion, growth and/or metastasis. Targeting the Gli code, the autoregulatory Gli1-Nanog module and interacting partners and pathways thus offers new therapeutic possibilities.
Low miR-34a and miR-192 are associated with unfavorable prognosis in patients suffering from osteosarcoma.

BACKGROUND p53 is a well-known tumor suppressor gene involved in malignancy. Many microRNAs (miRNAs) have recently been identified as key components of p53 signaling networks, owing to the central role of p53 in many processes, these p53-regulated miRNAs may possess important role in osteosarcoma. METHODS The expression of six p53-related miRNAs (miR-34 family [including miR-34a, 34b and 34c], miR-31, miR-192, and miR-215) in 80 pairs of osteosarcoma and corresponding noncancerous bone tissues were estimated by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the associations of miRNAs expression with clinicopathological factors, p53 status, and survival of patients were analyzed. RESULTS We found that among all six miRNAs, miR-34 family, -192, and -215 had decreased levels, whereas the level of miR-31 was increased (p<0.05) in tumor compared with corresponding noncancerous bone tissues, and miR-192/215 in patients with p53 positive expression was lower than those with negative p53. Kaplan-Meier analysis demonstrated that osteosarcoma patients with low miR-34a (P=0.000) and miR-192 (P=0.022) expression had poorer disease-free survival (DFS). Moreover, disease-free survival (DFS) was shorter for patients with low miR-34a and miR-192 expression (P=0.007) and the combination of low miR-192 with p53 positive expression (P=0.000). Furthermore, the multivariate analysis identified that low miR-34a expression, the combination of low miR-34a and miR-192 expression levels and the combination of low miR-192 with p53 positive were independent biomarkers of shorter DFS. CONCLUSIONS Together, these results suggest that p53-associated miR-34a and miR-192 expression could be novel prognosis biomarkers for surgically treated osteosarcoma.
Les sols des oasis du Sahara algérien, source d’actinomycètes, rares producteurs d’antibiotiques

Les sols des oasis du Sahara algerien, bien que soumis a un climat aride, se sont reveles relativement riches en actinomycetes parfois reputes rares de par le monde et de surcroit producteurs d’antibiotiques. On les trouve non seulement dans les horizons de surface mais aussi a plus de 2 m de profondeur et en quantite appreciable. Cependant, si les horizons de surface contiennent des especes tres diversifiees, en revanche, chaque horizon profond est caracterise par la dominance nette d’une espece donnee. Au total, 727 souches ont ete isolees et rattachees a pres de 25 genres et 132 especes, des plus connus aux plus rares. Certaines souches semblent meme representer de nouvelles especes. Quelques-unes secretent des antibiotiques actifs contre plusieurs germes pathogenes. La possibilite de molecules actives originales n’est pas a ecarter, comme l’ont montre a cet effet les etudes preliminaires. Ceci montre donc a quel point les sols des oasis sahariennes restent encore a exploiter, particulierement dans le domaine des antibiotiques, et ceci surtout au vu de la recrudescence des maladies bacteriennes et fongiques observees ces dernieres annees.
Nursing frequency, gonadal function, and birth spacing among !Kung hunter-gatherers.

Mothers among ! Kung hunter-gatherers nurse briefly and frequently, with brief intervals between nursing bouts (mean +/- standard error, 13.19 +/- 1.28 minutes). The low levels of 17 beta-estradiol and progesterone in the serum of the mother are correlated with infant's age and with interbout interval, but not with total nursing time. Maternal gonadal function is apparently suppressed by a timing-dependent, prolactin-mediated effect of breast stimulation. Interbout interval may be a key variable in lactation infertility. If so, it solves the puzzle of ! Kung birth spacing.
Duplex scanning compared with intra-arterial angiography in diagnosing peripheral arterial disease: three analytical approaches.

BACKGROUND This study was undertaken to assess the reliability of duplex scanning, as compared with digital subtraction angiography, in diagnosing peripheral arterial disease of the lower limbs. PATIENTS AND METHODS 60 legs were studied. Each leg was divided in 5 arterial segments, from aortoiliac to popliteal. Duplex scanning and digital subtraction angiography were performed. The disease in each segment was assessed as significant or insignificant or classified into five categories concerning the grade of stenosis (patent vessel or no diameter reduction, mild stenosis, i.e. 1-19% diameter reduction, moderate and severe stenosis, i.e. 20-49% and 50-99% diameter reduction, respectively, and occluded vessel). Three statistical approaches were applied: calculating sensitivity and specificity, Kappa statistics, and weighted Kappa value. Median grades of arterial stenosis across different segments, according to angiography measurements, were also calculated. RESULTS The duplex sensitivity in detecting significant lesions ranged from 0.46 to 0.88. The Kappa values of agreement between duplex and angiography ranged from 0.35 to 0.64. Weighted Kappa values ranged from 0.45 to 0.72. Median grades of arterial lesions ranged from 2 (interquartile range 1-2) to 4 (3-4) and differed significantly (Kruskal-Wallis H test, p < 0.001). CONCLUSIONS The sensitivities and specificities suggested various duplex reliabilities in detecting significant arterial disease across different lower limbs segments. The Kappa values, in general, testified duplex's insufficient accuracy in grading the severity of stenosis. However, weighted Kappa values confirmed duplex's better ability to approximate the grade of stenosis. The arterial segments themselves were unevenly affected with the peripheral arterial disease.
Influence of clinical and anatomic features on treatment decisions for anterior communicating artery aneurysms.

OBJECTIVE The purpose of this study was to analyze the clinical and anatomic features involved in determining treatment modalities for anterior communicating artery (AcoA) aneurysms. METHODS The authors retrospectively evaluated 112 AcoA aneurysms with pretreatment clinical features including age, Hunt and Hess grade, medical or neurological comorbidity, and anatomical features including aneurysm size, neck size, dome-to-neck ratio, vessel incorporation, multiple lobulation, and morphologic scoring system. Post-treatment clinical results were classified according to the Glasgow Outcome Scale, and anatomic results in coiled patients were classified according to the modified Raymond scale. Using multivariate logistic regression, the probabilities for decision making between surgical clipping and coil embolization were calculated. RESULTS Sixty-seven patients (60%) were treated with surgical clipping and 45 patients (40%) with endovascular coil embolization. The clinical factor significantly associated with treatment decision was age (≥65 vs. <65 years) and anatomical factors including aneurysm size (small or large vs. medium), dome-to-neck ratio (<2 vs. ≥2), presence of vessel incorporation, multiple lobulation, and morphologic score (≥2 vs. <2). In multivariate analysis, older patients (age, >65 years) had significantly higher odds of being treated with coil embolization relative to clipping (adjusted OR=3.78; 95% CI, 1.39-10.3; p=0.0093) and higher morphological score patients (≥2) had a higher tendency toward surgical clipping than endovascular coil embolization (OR=0.23; 95% CI, 0.16-0.93; p=0.0039). CONCLUSION The optimal decision for treating AcoA aneurysms cannot be determined by any single clinical or anatomic characteristics. All clinical and morphological features need to be considered, and a collaborative neurovascular team approach to AcoA aneurysms is essential.
Transforming growth factor- (cid:1) prevents osteoblast apoptosis induced by skeletal unloading via PI3K/Akt, Bcl-2, and phospho-Bad signaling

growth factor- prevents osteoblast apoptosis induced by skeletal unloading via PI3K/ Akt, Bcl-2, and phospho-Bad signaling. Am J Physiol Endocrinol Metab 294: E794–E801, 2008; doi:10.1152/ajpendo.00791. 2007. — Loss of mechanical loading induces rapid bone loss resulting from reduced osteoblastogenesis and decreased bone formation. The signaling mechanisms involved in this deleterious effect on skeletal metabolism remain poorly understood. We have previously shown that hindlimb suspension in rats increases osteoblast apoptosis associated with decreased phosphatidylinositol 3-kinase (PI3K) signaling. In this study, we investigated whether transforming growth factor (TGF)- (cid:1) 2 may prevent the altered signaling and osteoblast apoptosis induced by skeletal unloading in vivo. Hindlimb suspension-induced decreased bone volume was associated with reduced (cid:2) 5 (cid:1) 1 -integrin protein levels and PI3K/Akt signaling in unloaded bone. Continuous administration of TGF- (cid:1) 2 using osmotic minipumps prevented the decreased (cid:2) 5 (cid:1) 1 -integrin expression and the reduced PI3K/Akt signaling in unloaded bone, resulting in the prevention of osteoblast apoptosis. We also show that TGF- (cid:1) 2 prevented the decreased Bcl-2 levels induced by unloading, which suggests that TGF- (cid:1) 2 targets Bcl-2 via PI3K/Akt to prevent osteoblast apoptosis in unloaded bone. Further-more, we show that TGF- (cid:1) 2 prevented the decrease in phosphorylated Bad, the inactive form of the proapoptotic protein Bad, induced by unloading. These results identify a protective role for TGF- (cid:1) 2 in osteoblast apoptosis induced by mechanical unloading via the (cid:2) 5 (cid:1) 1 / PI3K/Akt signaling cascade and downstream Bcl-2 and phospho-Bad survival proteins. We thus propose a novel role for TGF- (cid:1) 2 in protection from unloading-induced apoptosis in vivo.
Évaluation de la technique de sexage et de foetométrie par échographie chez la chèvre du sahel

Le succes de l’application de l’echographie en production animale est en grande partie lie a sa sensibilite et sa specificite au diagnostic. Les protocoles de validation de la technique, bien que nombreux n’ont pas encore ete appliques aux organes genitaux apres abattage. Cette etude vise a evaluer la technique pour la determination du sexe et la foetometrie a partir d’uterus gravides collectes apres abattage. Pour cela, les resultats echographiques de determination du sexe (n=52) et de mesures de la longueur du dos (n= 44) ont ete compares aux observations faites apres dissection des uterus. L’evaluation de la technique a ete realisee par le calcul de la valeur predictive et de la sensibilite. Les donnees ont ete analysees au moyen du test de correlation de Pearson et par regression lineaire. Les valeurs predictives ont ete de 69,23% et de 30,76% pour les diagnostics des sexes mâle et femelle, respectivement. La sensibilite a ete de 75%. L’equation de regression a ete de LDO = 1,056LDE - 0,450 (r= 0,936, p = 0,008) (LDO et LDE en millimetre). La technique de l’echographie est valide pour la determination du sexe et les mesures de longueur de dos chez la chevre sahelienne. Mots cles: chevre, echographie, foetus, sensibilite, sexe.
Vulvodynia—An Evidence‐Based Literature Review and Proposed Treatment Algorithm

We searched the medical literature from the last 15 years (1998 to 2013) relating to the etiology, diagnosis, and treatment of vulvodynia. The evidence was reviewed supporting the therapeutic proposals currently in use and propose the incorporation of novel, minimally invasive, interventional therapies, within the context of a multidisciplinary approach.
Properties of a novel carbenicillin-hydrolyzing beta-lactamase (CARB-4) specified by an IncP-2 plasmid from Pseudomonas aeruginosa

CARB-4, a novel carbenicillin-hydrolyzing beta-lactamase with an isoelectric point of 4.3, was discovered in a strain of Pseudomonas aeruginosa from France. It was determined by a multiresistant transmissible plasmid belonging to the P-2 incompatibility group.
Continuous monitoring of circadian glycemic patterns in patients receiving prednisolone for COPD.

CONTEXT Endogenous glucocorticoid excess (Cushing's syndrome) predominantly increases postprandial glucose concentration. The pattern of hyperglycemia induced by prednisolone has not been well characterized. OBJECTIVE Our objective was to define the circadian effect of prednisolone on glucose concentration to optimize management of prednisolone-induced hyperglycemia. DESIGN AND SETTING This was a cross-sectional study in a teaching hospital. PARTICIPANTS Participants included 60 consecutive consenting subjects with chronic obstructive pulmonary disease admitted to hospital: 13 without known diabetes admitted for other indications and not treated with glucocorticoids (group 1), 40 without known diabetes admitted with an exacerbation of chronic obstructive pulmonary disease and treated with prednisolone (group 2, prednisolone = 30 ± 6 mg/d), and seven with known diabetes treated with prednisolone (group 3, prednisolone = 26 ± 9 mg/d). MAIN OUTCOME MEASURE Interstitial glucose concentration was assessed during continuous glucose monitoring. RESULTS Significantly more subjects in group 2 [21 of 40 (53%), P = 0.02] and group 3 [seven of seven (100%), P = 0.003] recorded a glucose of at least 200 mg/dl (≥11.1 mmol/liter) during continuous glucose monitoring than in group 1 [one of 13 (8%)]. The mean glucose concentration between 2400-1200 h for group 3 (142 ± 36 mg/dl) was significantly greater than in the other two groups (P < 0.005), whereas mean glucose concentrations between 2400-1200 h in group 1 (108 ± 16 mg/dl) and group 2 (112 ± 22 mg/dl) were not significantly different. In contrast, the mean glucose concentrations between 1200-2400 h for group 2 (142 ± 25 mg/dl) and group 3 (189 ± 32 mg/dl) were both significantly greater than group 1 (117 ± 14 mg/dl, P < 0.05 for both comparisons). CONCLUSIONS Prednisolone predominantly causes hyperglycemia in the afternoon and evening. Treatment of prednisolone-induced hyperglycemia should be targeted at this time period.
Analysis of Herpes Simplex Virus Type 1 DNA Packaging Signal Mutations in the Context of the Viral Genome

ABSTRACT The minimal signal required for the cleavage and packaging of replicated concatemeric herpes simplex virus type 1 (HSV-1) DNA corresponds to an approximately 200-bp fragment, Uc-DR1-Ub, spanning the junction of the genomic L and S segments. Uc and Ub occupy positions adjacent to the L and S termini and contain motifs (pac2 and pac1, respectively) that are conserved near the ends of other herpesvirus genomes. We have used homologous Red/ET recombination in Escherichia coli to introduce wild-type and specifically mutated Uc-DR1-Ub fragments into an ectopic site of a cloned HSV-1 genome from which the resident packaging signals had been previously deleted. The resulting constructs were transfected into mammalian cells, and their abilities to replicate and become encapsidated, generate Uc- and Ub-containing terminal fragments, and give rise to progeny virus were assessed. In general, the results obtained agree well with previous observations made using amplicons and confirm roles for the pac2 T element in the initiation of DNA packaging and for the GC-rich motifs flanking the pac1 T element in termination. In contrast to a previous report, the sequence of the DR1 element was also crucial for DNA packaging. Following repair of the resident packaging signals in mammalian cells, recombination occurred at high frequency in progeny virus between the repaired sequences and mutated Uc-DR1-Ub inserts. This restored the ability of mutated Uc-DR1-Ub inserts to generate terminal fragments, although these were frequently larger than expected from simple repair of the original lesion.
Health screening in a general practice by opportunistic recruitment.

AIMS this study aims to assess the effectiveness of opportunistic recruitment into a general practice health screening programme and subsequent improvement in screening rates. METHODS a study group of 754 patients aged 30-69 years (345 men, 409 women) in a Wanganui general practice were invited by the doctor when attending the surgery to return for a preventive health check. The check included a self administered screening questionnaire, selected examination items performed by the practice nurse, and a consultation with the doctor to review the findings. RESULTS over the three year study period 327 of the men and 392 of the women attended the surgery. An invitation to return for a health check was offered to 307 men and 329 women with completion of health checks by 294 men and 317 women, resulting in a screening rate in the study group of 85% for men and 78% for women. Selected screening indicators showed improvement with blood pressure recording increasing from 48% to 85% for men, and cervical cancer screening improving from 45% to 87% for women. CONCLUSION opportunistic recruitment by the doctor's personal invitation proved an effective approach to health screening in this practice with significant improvement in selected screening indicators.
Functional cDNA library for efficient expression of measles virus-specific gene products in primate cells

A cDNA library designed for high-level expression of measles virus-specific gene products in mammalian cells was generated. From this library, functional clones which contained the entire protein-coding sequences of the nucleocapsid (N) and the phosphoprotein (P) genes were isolated. By DNA-mediated gene transfer into a line of simian virus 40-transformed monkey kidney cells, the N-specific cDNA was expressed into a single polypeptide of about 60,000 Mr, which was immunoprecipitated by monoclonal antibodies against the measles virus N protein. In contrast, the P-specific cDNA could be expressed into either one or two species of polypeptides of 75,000 or 70,000 Mr, both of which were immunoprecipitated by monoclonal antibodies against the measles virus P protein.
Fine needle aspiration cytology in feline skeletal muscle as a diagnostic tool for extramedullary plasmacytoma

Extramedullary noncutaneous plasmacytoma (ENP) is a myeloproliferative disorder of plasma cells that rarely affects cats. This paper describes an ENP case revealed by fine needle aspiration cytology (FNAC) of the mass in the skeletal muscle of an 8-month-old, male, mixed breed cat, which had a nodule in the left hind limb. The rapid immunoassay test confirmed the presence of feline leukemia virus (FeLV). The animal necropsy macroscopically showed the nodule came from the semimembranosus muscle. Histopathological examination ratified the cytological findings. Thus, this paper alerts to the existence of plasmacytoma located in the skeletal muscle of feline species. FNAC is a quick and efficient method for diagnosis of ENP.
Characteristic Impedance Extraction Using Calibration Comparison

A robust line impedance identification method is presented. It determines the characteristic impedance of on-wafer TLR standards measured after an initial off-wafer LRM or TLR calibration. The only assumption made is that the obtained trans-wafer error boxes are a cascade of a symmetric probe related disturbance and a change in reference impedance. The proposed method yields an unbiased estimate of the complex characteristic impedance. Results from coplanar lines on a high resistivity silicon substrate support the made assumption.
PolInSAR Coherence Set Theory and Application

In this paper we investigate coherence sets in polarimetric SAR interferometry. The coherence set is closely related to the numerical range (field of values). This paper aims to bring the numerical range to the attention of the radar research community. The mathematical understanding of the numerical range helps to understand theoretical and physical properties of coherence and coherency matrix. This paper presents a structured hierarchy of coherence sets and corresponding numerical ranges. Different applications which are related to numerical ranges are reviewed. An example of the inverse analysis of the coherence set is performed to obtain information about the coherency matrix. Finally, a generalization of the coherence set applications is presented.
Compilation of human mtDNA control region sequences

This paper describes the organisation of a database for human mitochondrial control-region sequences. The data are divided into three ASCII files that contain aligned sequences from the hypervariable region I (HVRI), from the hypervariable region II (HVRII), and the available information about the individuals, from whom the sequences stem. The current collection comprises 4079 HVRI and 969 HVRII sequences. From 728 individuals sequences of both HVRI and HVRII are available. For easy access, the collection is made available to the scientific community via World Wide Web at URL http://www.zi. biologie.uni-muenchen.de/[symbol: see text]meyers/mtdna.html
Expressions of programmed death (PD)‐1 and PD‐1 ligand (PD‐L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status

The programmed death 1/programmed death 1 ligand (PD‐1/PD‐L1) pathway can decrease the immune clearance effects of antigen‐presenting cells and T lymphocytes to promote immune evasion of cervical cancer cells. However, the effects of this pathway on cervical intraepithelial neoplasia (CIN) progression and squamous cell carcinoma (SCC) metastasis are not clear. We herein investigated whether human papillomavirus infection could affect PD‐1 and PD‐L1 expression in CIN, and whether their expression is associated with CIN progression and SCC metastasis.