Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic strategies against cancer stem cells in human colorectal cancer

Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types. Conventional therapeutics only act on proliferating and mature cancer cells, while quiescent CSCs survive and often become resistant to chemotherapy. In this review, markers of CRC-CSCs are evaluated and the recently introduced experimental therapies that specifically target these cells by inducing CSC proliferation, differentiation and sensitization to apoptotic signals via molecules including Dickkopf-1, bone morphogenetic protein 4, Kindlin-1, tankyrases, and p21-activated kinase 1, are discussed. In addition, novel strategies aimed at inhibiting some crucial processes engaged in cancer progression regulated by the Wnt, transforming growth factor β and Notch signaling pathways (pyrvinium pamoate, silibinin, PRI-724, P17, and P144 peptides) are also evaluated. Although the metabolic alterations in cancer were first described decades ago, it is only recently that the concept of targeting key regulatory molecules of cell metabolism, such as sirtuin 1 (miR-34a) and AMPK (metformin), has emerged. In conclusion, the discovery of CSCs has resulted in the definition of novel therapeutic targets and the development of novel experimental therapies for CRC. However, further investigations are required in order to apply these novel drugs in human CRC.
Epitope-Based Vaccines with the Anaplasma marginale MSP1a Functional Motif Induce a Balanced Humoral and Cellular Immune Response in Mice

Bovine anaplasmosis is a hemoparasitic disease that causes considerable economic loss to the dairy and beef industries. Cattle immunized with the Anaplasma marginale MSP1 outer membrane protein complex presents a protective humoral immune response; however, its efficacy is variable. Immunodominant epitopes seem to be a key-limiting factor for the adaptive immunity. We have successfully demonstrated that critical motifs of the MSP1a functional epitope are essential for antibody recognition of infected animal sera, but its protective immunity is yet to be tested. We have evaluated two synthetic vaccine formulations against A. marginale, using epitope-based approach in mice. Mice infection with bovine anaplasmosis was demonstrated by qPCR analysis of erythrocytes after 15-day exposure. A proof-of-concept was obtained in this murine model, in which peptides conjugated to bovine serum albumin were used for immunization in three 15-day intervals by intraperitoneal injections before challenging with live bacteria. Blood samples were analyzed for the presence of specific IgG2a and IgG1 antibodies, as well as for the rickettsemia analysis. A panel containing the cytokines’ transcriptional profile for innate and adaptive immune responses was carried out through qPCR. Immunized BALB/c mice challenged with A. marginale presented stable body weight, reduced number of infected erythrocytes, and no mortality; and among control groups mortality rates ranged from 15% to 29%. Additionally, vaccines have significantly induced higher IgG2a than IgG1 response, followed by increased expression of pro-inflammatory cytokines. This is a successful demonstration of epitope-based vaccines, and protection against anaplasmosis may be associated with elicitation of effector functions of humoral and cellular immune responses in murine model.
Chemical composition, antimicrobial and antioxidant activities of the essential oil of Tibetan herbal medicine Dracocephalum heterophyllum Benth

The essential oil of Tibetan medicine Dracocephalum heterophyllum Benth was obtained by hydrodistillation with a 0.7% (v/w) yield. The chemical composition of the essential oil was analyzed by gas chromatography–mass spectral (GC–MS). Eighty-three compounds, constituting about 89.83% of the total oil, were identified. The main compound in the oil were Cineole (14.89%), trans-nerolido (7.10%), 1-m-ethyl-2-(1-methylethyl)-benzene (4.42%), Germacrene-D (4.84%), Decahydro-1,1,4,7-tetramethyl-4aH-cycloprop[e]azulen-4a-ol (4.94%), p-menth-1-en-4-ol,acetate (4.34%), 4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol (4.10%). The antimicrobial activity of the oil was evaluated against nine bacterial, one yeast, and three fungi. The antimicrobial test result showed that the essential oil strongly inhibited the growth of test microorganisms studied. The maximal inhibition zones and MIC values for bacterial, yeast and fungi strain were in the range of 18–25 mm and 0.039–0.156 mg mL−1; *20 mm, and 0.156 mg mL−1; 8–24 mm and 0.313–2.5 mg mL−1; respectively. The antioxidant activity of the oil was determined by the malonyldialdehyde (MDA) test, measuring the MDA concentration in mouse liver cell microsomal after induced lipid peroxidation using FeSO4 and ascorbic acid, The inhibition of lipid peroxidation was 59.3% with a concentration of 0.5 mg mL−1. Result presented here may suggest that the essential oil of D. heterophyllum posses antimicrobial and antioxidant properties, and therefore, they can be one of new medicinal resources for antimicrobial agent and/or used as a natural preservative ingredient in food and cosmetics and pharmaceuticals industry.
Hypertension, an Emerging Problem in Rural Cameroon: Prevalence, Risk Factors, and Control

Background. Despite the increasing trends suggesting that hypertension is a growing public health problem in developing countries, studies on its prevalence, associated risk factors, and extent of blood pressure control have been inequitably done in urban and rural communities in these countries. We therefore aimed to determine the prevalence of hypertension and extent of blood pressure control in rural Cameroon. Methods. This was a community-based cross-sectional study conducted in rural Cameroon (the Moliwe Health Area). Participants aged 21 years and above were recruited by a probability proportional to size multistage sampling method, using systematic sampling for household selection and random sampling for participant selection. Blood pressure, weight, and height were measured by standard methods. Hypertension was defined as BP ≥ 140/90 mmHg. Results. The prevalence of hypertension among the 733 participants recruited was 31.1% (95% CI: 27.8–34.6) and 71% (95% CI: 58.7–81.7) of these hypertensive patients were newly diagnosed. Only 21.2% (95% CI: 12.1–33.3) of known hypertensives had a well controlled BP. Age, obesity, low educational status, and being married were associated with HTN after adjusting for confounders. Conclusions. The high prevalence of hypertension and inadequate BP control among known hypertensives in rural Cameroon warrants greater sensitization and regular screening to reduce hypertension-related morbidity and mortality.
Double hashing thresholds via local weak convergence

A lot of interest has recently arisen in the analysis of multiple-choice “cuckoo hashing” schemes. In this context, a main performance criterion is the load threshold under which the hashing scheme is able to build a valid hashtable with high probability in the limit of large systems; various techniques have successfully been used to answer this question (differential equations, combinatorics, cavity method) for increasing levels of generality of the model. However, the hashing scheme analysed so far is quite utopic in that it requires to generate a lot of independent, fully random choices. Schemes with reduced randomness exists, such as “double hashing”, which is expected to provide similar asymptotic results as the ideal scheme, yet they have been more resistant to analysis so far. In this paper, we point out that the approach via the cavity method extends quite naturally to the analysis of double hashing and allows to compute the corresponding threshold. The path followed is to show that the graph induced by the double hashing scheme has the same local weak limit as the one obtained with full randomness.
Fusion of Constitutive Membrane Traffic with the Cell Surface Observed by Evanescent Wave Microscopy

Monitoring the fusion of constitutive traffic with the plasma membrane has remained largely elusive. Ideally, fusion would be monitored with high spatial and temporal resolution. Recently, total internal reflection (TIR) microscopy was used to study regulated exocytosis of fluorescently labeled chromaffin granules. In this technique, only the bottom cellular surface is illuminated by an exponentially decaying evanescent wave of light. We have used a prism type TIR setup with a penetration depth of ∼50 nm to monitor constitutive fusion of vesicular stomatitis virus glycoprotein tagged with the yellow fluorescent protein. Fusion of single transport containers (TCs) was clearly observed and gave a distinct analytical signature. TCs approached the membrane, appeared to dock, and later rapidly fuse, releasing a bright fluorescent cloud into the membrane. Observation and analysis provided insight about their dynamics, kinetics, and position before and during fusion. Combining TIR and wide-field microscopy allowed us to follow constitutive cargo from the Golgi complex to the cell surface. Our observations include the following: (1) local restrained movement of TCs near the membrane before fusion; (2) apparent anchoring near the cell surface; (3) heterogeneously sized TCs fused either completely; or (4) occasionally larger tubular-vesicular TCs partially fused at their tips.
Exposure Image Fusion of Enhancing Detail Visibility Based on Contrast Adjustment

-To extract fine details from input bracketed images and preserve them in the final image, a novel exposure fusion method based on the nonsubsampled contourlet transform (NSCT) is presented in this paper,in which unique visual weight map is used for the detail extraction and an improved weight measurement is developed to remove the motion objects in dynamic scenes. Furthermore, a fast algorithm for contrast enhancement is applied to adjust the contrast of decomposition subbands and gain control is also introduced to modify the visibility of the blended subbands at different scales. Finally, the resulting image with more visible details is reconstructed by the inverse NSCT. Experimental results demonstrate that the proposed method can preserve fine details and produce sharper images, especially in enhancing detail visibility in the dark areas. Key-Words: Exposure fusion, NSCT, Weight map, Contrast enhancement, Gain control
Full‐Scale Experience for Nitrogen Removal from Piggery Waste

The nitrogen‐removal performances of three full‐scale piggery wastewater treatment plants, with different organic and nitrogen loads, at the capacity ranges of 95 to 130 m3/d, were compared in this study. Plants 1 and 2 can be characterized as the modification of anoxic–aerobic operating systems, while an anaerobic and anoxic–aerobic system was used in plant 3. The influent piggery wastewater concentration for plant 1 was relatively lower, but with higher organic and nitrogen loads, resulting in higher chemical oxygen demand (COD) and ammonium‐nitrogen in effluent. Plant 2 was operated with strong piggery wastewater, resulting in a higher operating temperature. The high temperature could inhibit the nitrifying activity in plant 2. Although plant 3 was operated with a higher influent total COD‐to‐total Kjeldahl nitrogen ratio (TCOD:TKN), an additional external carbon source was required to polish the final effluent to remove nitrogen. Influent COD in plant 3 was used in the anaerobic–anoxic reactor for both methane (CH4) production and denitrification. Based on various mass balances, including caloric, COD, and alkalinity, the key elements for the successful nitrogen removal from the piggery waste were reactor temperature (less than 35°C), influent TCOD:TKN (greater than 6), and alkalinity‐to‐TKN ratio (greater than 3).
The Influence of Low Doses of Zearalenone and T-2 Toxin on Calcitonin Gene Related Peptide-Like Immunoreactive (CGRP-LI) Neurons in the ENS of the Porcine Descending Colon

The enteric nervous system (ENS) can undergo adaptive and reparative changes in response to physiological and pathological stimuli. These manifest primarily as alterations in the levels of active substances expressed by the enteric neuron. While it is known that mycotoxins can affect the function of the central and peripheral nervous systems, knowledge about their influence on the ENS is limited. Therefore, the aim of the present study was to investigate the influence of low doses of zearalenone (ZEN) and T-2 toxin on calcitonin gene related peptide-like immunoreactive (CGRP-LI) neurons in the ENS of the porcine descending colon using a double immunofluorescence technique. Both mycotoxins led to an increase in the percentage of CGRP-LI neurons in all types of enteric plexuses and changed the degree of co-localization of CGRP with other neuronal active substances, such as substance P, galanin, nitric oxide synthase, and cocaine- and amphetamine-regulated transcript peptide. The obtained results demonstrate that even low doses of ZEN and T-2 can affect living organisms and cause changes in the neurochemical profile of enteric neurons.
Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial.

BACKGROUND Although statin therapy is known to increase concentrations of PCSK9, whether this effect is related to the magnitude of LDL reduction is uncertain. This study was undertaken to understand the extent of this effect and examine the relationship between PCSK9 and LDL cholesterol (LDL-C) reduction. METHODS We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 500 men and 500 women participating in the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial that randomly allocated participants to rosuvastatin 20 mg daily or placebo. We also evaluated rs11591147, a single nucleotide polymorphism known to have an impact on plasma PCSK9 concentrations. RESULTS At baseline, median (interquartile range) PCSK9 concentrations were higher in women [73 (62-90)] ng/mL than in men [69 (57-81) ng/mL] (P<0.005). During 1 year, there was no change in PCSK9 concentrations in the placebo arm, suggesting stability in time. In contrast, the rosuvastatin increased PCSK9 by 35% in women [101 (82-117) ng/mL] and 28% in men [89 (71-109) ng/mL] (P<0.0001). Among those allocated to rosuvastatin, greater reductions in LDL-C were associated with greater increases in PCSK9 on both absolute and relative scales (r=-0.15, P<0.0005). Furthermore PCSK9 (rs11591147) did not alter the magnitude of LDL-C reduction associated with rosuvastatin use. CONCLUSIONS In this randomized trial, rosuvastatin increased plasma concentration of PCSK9 in proportion to the magnitude of LDL-C reduction; the LDL-C response to statin could not be inferred by PCSK9 concentrations.
Autoethnography: Critical Appreciation of an Emerging Art

In this article, the author discusses how she applied autoethnography in a study of the design of hypermedia educational resources and shows how she addressed problematic issues related to autoethnographic legitimacy and representation. The study covered a 6-year period during which the practitioner's perspective on the internal and external factors influencing the creation of three hypermedia CD-ROMs contributed to an emerging theory of design. The author highlights the interrelationship between perception and reality as vital to qualitative approaches and encourages researchers to investigate their reality more fully by practicing the art of autoethnography.
Comparative Transcriptional Profiling of Borrelia burgdorferi Clinical Isolates Differing in Capacities for Hematogenous Dissemination

ABSTRACT Borrelia burgdorferi, the etiologic agent of Lyme disease, is genetically heterogeneous. Previous studies have shown a significant association between the frequency of hematogenous dissemination in Lyme disease patients and the genotype of the infecting B. burgdorferi strain. Comparative transcriptional profiling of two representative clinical isolates with distinct genotypes (BL206 and B356) was undertaken. A total of 78 open reading frames (ORFs) had expression levels that differed significantly between the two isolates. A number of genes with potential involvement in nutrient uptake (BB0603, BBA74, BB0329, BB0330, and BBB29) have significantly higher expression levels in isolate B356. Moreover, nearly 25% of the differentially expressed genes are predicted to be localized on the cell surface, implying that these two isolates have cell surface properties that differ considerably. One of these genes, BBA74, encodes a protein of 257 amino acid residues that has been shown to possess porin activity. BBA74 transcript level was >20-fold higher in B356 than in BL206, and strain B356 contained three- to fivefold more BBA74 protein. BBA74 was disrupted by the insertion of a kanamycin resistance cassette into the coding region. The growth rates of both wild-type and mutant strains were essentially identical, and cultures reached the same final cell densities. However, the mutant strains consistently showed prolonged lags of 2 to 5 days prior to the induction of log-phase growth compared to wild-type strains. It is tempting to speculate that the absence of BBA74 interferes with the enhanced nutrient uptake that may be required for the entry of cells into log-phase growth. These studies demonstrate the value of comparative transcriptional profiling for identifying differences in the transcriptomes of B. burgdorferi clinical isolates that may provide clues to pathogenesis. The 78 ORFs identified here are a good starting point for the investigation of factors involved in the hematogenous dissemination of B. burgdorferi.
Surgical Management of Wilms Tumor with Intravascular Extension: A Single-Institution Experience

The purpose of this study was to retrospectively analyze the clinical presentation, treatment, and outcomes of children with Wilms tumor (WT) and intravascular extension who were treated at a single institution. A retrospective review was conducted of medical records of all children with Wilms tumor and intravascular extension treated at Virgen del Rocio Children's Hospital between 1992 and 2010. Seven patients (median age 3.4 years, range 2–8.1 years) were identified. At diagnosis, 6 of the 7 patients (85.7%) presented with tumor thrombus that reached the right atrium (RA) and 1 patient with infrahepatic inferior vena cava (IVC) thrombus. All patients received neoadjuvant chemotherapy (SIOP 2001 protocol) with vincristine, doxorubicin, and actinomycin D. Regression of the intravascular extension of the tumor was documented in all patients. Postchemotherapy level of extension was suprahepatic IVC in 1 patient, infrahepatic IVC in 2 patients, renal vein (RV) in 1 patient, and RA in 3 patients. Nephrectomy and thrombectomy were performed in all cases, requiring cardiopulmonary bypass for the 4 patients who presented with suprahepatic IVC and RA thrombus. The other 3 patients with infrahepatic IVC and RV involvement underwent cavotomy and thrombus extraction. Computed tomography, ultrasonography, and echocardiography were used for diagnosis and follow-up. All patients remain disease-free with a median follow-up of 6.3 years (range, 2–19 years). Neoadjuvant chemotherapy for WT with intravascular extension may facilitate the resection by decreasing the extent of the tumor thrombus. Cardiopulmonary bypass is indicated for suprahepatic IVC and RA involvement. Accurate diagnostic imaging is necessary.
Online Evaluation of Coreference Resolution

This paper presents the design of an online evaluation service for coreference resolution in texts. We argue that coreference, as an equivalence relation between referring expressions (RE) in texts, should be properly distinguished from anaphora and has therefore to be evaluated separately. The annotation model for coreference is based on links between REs. The program presented in this article compares two such annotations, which may be the output of coreference resolution tools or of human judgement. In order to evaluate the agreement between the two annotations, the evaluator first converts the input annotation format into a pivot format, then abstracts equivalence classes from the links and provides five scores representing in different ways the similarity between the two partitions: MUC, B3, Kappa, Core-discourse-entity, and Mutual-information. Although we consider that the identification of REs (i.e. the elements of the partition) should not be part of coreference resolution properly speaking, we propose several solutions for the frequent case when the input files do not agree on the elements of the text to consider as REs.
Child and genetic variables associated with maternal adaptation to fragile X syndrome: A multidimensional analysis

One hundred eight carrier mothers (95 premutation, 13 full mutation) of children with the full mutation fragile X syndrome completed seven scales to assess maternal stress, depressive symptoms, anger, anxiety, quality of life, hope, and optimism. A wide range of responses was found on each measure, with most mothers scoring in the non‐clinical range on any individual measure. However, nearly half of the mothers scored in the clinically significant range on at least one measure and 25% on two or more measures. High stress and low quality of life were the most common domains of concern. Mothers with the full mutation generally did not differ from mothers with the premutation. CGG repeat length was not associated with responses on any of the measures completed by mothers with the premutation. Severity of the child's delay was not associated with any of the outcome measures, but child behavior problems accounted for significant variance in stress, depressive symptoms, anxiety, anger, and quality of life. Maternal adaptation appears to be a multidimensional phenomenon experienced in unique ways by each mother. Most mothers experienced positive adaptation, but a subset appear to be more vulnerable, especially those with children who have significant behavior problems. Future research needs to identify family, child, and support factors associated with maternal vulnerability and how adaptation changes over time in response to these factors. © 2008 Wiley‐Liss, Inc.
Whiteside Effect of experience levels in voice quality ratings : 1 Effect of experience levels on voice quality ratings

1 Introduction Measuring interrater-and intrarater reliability is an important way of validating perceptual judgments of voice quality. One of the fields of research for which this validation is particularly important, is that which attempts to establish correlations between perceptual measures of voice on the one hand, and physiologic or acoustic parameters on the other. If reliability of a perceptual label or judgement is low, interpretation of a correlation with a perceptual parameter is complicated.
A distributed simplex algorithm and the multi-agent assignment problem

In this paper we propose a novel distributed algorithm to solve degenerate linear programs on asynchronous networks. Namely, we propose a distributed version of the well known simplex algorithm. We prove its convergence to the global lexicographic minimum for possibly fully degenerate problems and provide simulations supporting the conjecture that the completion time scales linearly with the diameter of the graph. The algorithm can be interpreted as a dual version of the constraints consensus algorithm proposed in [1] to solve abstract programs when the last is applied to linear programs. Finally, we study a multi-agent task assignment problem and show that it can be solved by means of our distributed simplex algorithm.