Miracle-dz/UniFAR-FTUs huggingface dataset:
Grape Seed Extract Efficacy against Azoxymethane-Induced Colon Tumorigenesis in A/J Mice: Interlinking miRNA with Cytokine Signaling and Inflammation

Colorectal cancer (CRC) is the second leading cause of cancer-associated deaths, suggesting that additional strategies are needed to prevent/control this malignancy. As CRC growth and progression involve a large window (10–15 years), chemopreventive intervention could be a practical/translational strategy. Azoxymethane (AOM)-induced colon tumorigenesis in mice resembles human CRC in terms of progression of ACF to polyps, adenoma, and carcinomas and associated molecular mechanisms. Accordingly, herein we investigated grape seed extract (GSE) efficacy against AOM-induced colon tumorigenesis in A/J mice. GSE was fed in diet at 0.25% or 0.5% (w/w) dose starting 2 weeks after last AOM injection for 18 or 28 weeks. Our results showed that GSE feeding significantly decreases colon tumor multiplicity and overall tumor size. In biomarker analysis, GSE showed significant antiproliferative and pro-apoptotic activities. Detailed mechanistic studies highlighted that GSE strongly modulates cytokines/interleukins and miRNA expression profiles as well as miRNA processing machinery associated with alterations in NF-κB, β-catenin, and mitogen-activated protein kinase (MAPK) signaling. Additional studies using immunohistochemical analyses found that indeed GSE inhibits NF-κB activation and decreases the expression of its downstream targets (COX-2, iNOS, VEGF) related to inflammatory signaling, downregulates β-catenin signaling and decreases its target gene c-myc, and reduces phosphorylated extracellular signal—regulated kinase (ERK)1/2 levels. Together, these finding suggested that inflammation, proliferation, and apoptosis are targeted by GSE to prevent CRC. In summary, this study for the first time shows alterations in the expression of miRNAs and cytokines by GSE in its efficacy against AOM-induced colon tumorigenesis in A/J mouse sporadic CRC model, supporting its translational potential in CRC chemoprevention. Cancer Prev Res; 6(7); 625–33. ©2013 AACR.
The use of cognitive testing to develop and evaluate CAHPS 1.0 core survey items. Consumer Assessment of Health Plans Study.

OBJECTIVES The main goal of the Consumer Assessments of Health Plans Study (CAHPS) is to develop an integrated set of tested, standardized surveys to obtain meaningful information from health plan enrollees about their experiences. The CAHPS project benefits from the complementary strengths of psychometric and cognitive testing. METHODS The CAHPS team conducted 150 cognitive interviews across three organizations in different geographic locations using multiple interview methods with different consumer populations. This article explains how cognitive testing was used in the CAHPS survey development process and shares the main findings from the cognitive interviews. RESULTS A modified report format is more appropriate when asking about specific aspects of plan enrollees' experiences, whereas a rating format is useful for asking about overall assessments. Specifying a longer reference period is preferable to asking about the most recent visit when capturing experiences with care, because some respondents get frustrated when they cannot include experiences other than the most recent visit. Explicit screeners and tailored inapplicable response categories are beneficial in mail questionnaires, so people know that they should not answer questions about which they have no relevant experience. CONCLUSION Cognitive testing was integral in the development and refinement of the CAHPS instrument. The cognitive testing findings contributed to an improved instrument that should capture consumers' health care and plan experiences with less response error than one not subjected to such testing. The cognitive testing process and findings can be useful to other researchers with similar survey development goals.
The Varicella-Zoster Virus Open Reading Frame 63 Latency-Associated Protein Is Critical for Establishment of Latency

ABSTRACT Varicella-zoster virus (VZV) expresses at least six viral transcripts during latency. One of these transcripts, derived from open reading frame 63 (ORF63), is one of the most abundant viral RNAs expressed during latency. The VZV ORF63 protein has been detected in human and experimentally infected rodent ganglia by several laboratories. We have deleted >90% of both copies of the ORF63 gene from the VZV genome. Animals inoculated with the ORF63 mutant virus had lower mean copy numbers of latent VZV genomes in the dorsal root ganglia 5 to 6 weeks after infection than animals inoculated with parental or rescued virus, and the frequency of latently infected animals was significantly lower in animals infected with the ORF63 mutant virus than in animals inoculated with parental or rescued virus. In contrast, the frequency of animals latently infected with viral mutants in other genes that are equally or more impaired for replication in vitro, compared with the ORF63 mutant, is similar to that of animals latently infected with parental VZV. Examination of dorsal root ganglia 3 days after infection showed high levels of VZV DNA in animals infected with either ORF63 mutant or parental virus; however, by days 6 and 10 after infection, the level of viral DNA in animals infected with the ORF63 mutant was significantly lower than that in animals infected with parental virus. Thus, ORF63 is not required for VZV to enter ganglia but is the first VZV gene shown to be critical for establishment of latency. Since the present vaccine can reactivate and cause shingles, a VZV vaccine based on the ORF63 mutant virus might be safer.
Revisit Word Embeddings with Semantic Lexicons for Modeling Lexical Contrast

It is widely accepted that traditional word embedding models, which rely on distributional semantics hypothesis, are relatively limited for contrast meaning problem. Distributional semantics hypothesis indicates that words lying in similar contexts have similar representations in vector space. Nevertheless, synonyms and antonyms often locate in similar contexts, which means they appear close to each other in vector space. Hence, it is of great difficulty to distinguish antonyms from synonyms. To address this challenge, we propose an optimization model, named Lexicon-based Word Embedding Tuning (LWET) model. The goal of LWET is to incorporate reliable semantic lexicons to tune the distributions of pre-trained word embeddings in the vector space so as to improve their ability of distinguishing antonyms from synonyms. To speed up the training process of LWET, we propose two approximation algorithms, including positive sampling and quasi-hierarchical softmax. Compared with quasi-hierarchical softmax, positive sampling is faster, however, at the cost of worse performance. In experiments, LWET and other state-of-the-art models are tested on antonyms recognition, distinguishing antonyms from synonyms and word similarity. The results of the first two experiments show that LWET significantly improves the ability of word embeddings to detect antonyms, thus achieving the state-of-the-art performance. On word similarity, LWET gets slightly better performance than the state-of-the-art models. It means that LWET can remain and strengthen the semantic structure rather than destroy it when tuning word distributions in vector space. In general, compared with related work, LWET can not only achieve similar or even better performance, but also speed up the training process.
Matrix Metalloproteinases and Endometriosis

Retrograde menstruation represents a plausible explanation for the development of most cases of endometriosis; nevertheless, additional factors must contribute to the development of disease in only 10 to 20% of women. The discriminating factor(s) in determining the development of active endometriosis probably involves a complex array of potentially interactive influences including steroid exposure, immunological disturbances, genetic predisposition, and, perhaps, environmental toxin exposure. Matrix metalloproteinases (MMPs), enzymes that mediate normal tissue turnover including endometrial breakdown at menstruation, appear to be involved in the invasive establishment of the disease. In addition, several MMPs appear to be inappropriately expressed in the endometrium of women with this disease in association with a reduced sensitivity to progesterone. Altered regulation of endometrial MMP expression in response to steroids may represent a mechanism linking the invasive potential of refluxed endometrium to the establishment of this disease only in certain women.
Liver Transplantation in Patients With Portal Vein Thrombosis and Central Portacaval Shunts

The authors have analyzed the impact of pre-existing portal vein pathology on the outcome of orthotopic liver transplantation. The incidence was high in patients suffering from chronic active hepatitis, hypercoagulable states, trauma or previous dissection of the porta hepatis, and splenectomy. The existence of portal vein thrombosis (23 patients) or surgical central portosystemic shunt (10 patients) was documented by preoperative Doppler sonogram or angiography (26/33), or operative findings of occluded vein (7/33). Successful thrombectomy and dismantling of portacaval shunts were achieved in most cases (24/33). Only nine patients required the placement of an interposition vein graft to the superior mesenteric vein. The intraoperative course was characterized by increased blood loss and coagulopathy, significantly higher than in patients with a patent portal vein. When compared with all liver transplants, the immediate postoperative complication rate was higher for primary nonfunction (33% versus 8%), re-exploration for intraperitoneal bleeding and hematomas, and morbid infections. Rethrombosis rate of thrombectomized veins or vein graft was low (2/33). The mortality rate was 35% in the presence of portal vein thrombosis (PVT) and 30% for portacaval shuct (PCS), both significantly higher than the 12% for other orthotopic liver transplant (OLT) patients. These results are expected to improve with better patient selection, surgical experience, and anticipation of the complex postoperative course. The authors conclude that PVT or the presence of PCS are not contraindications to orthotopic liver transplantation.
DNA methylation affecting the expression of murine leukemia proviruses

The endogenous, vertically transmitted proviral DNAs of the ecotropic murine leukemia virus in AKR embryo fibroblasts were found to be hypermethylated relative to exogenous AKR murine leukemia virus proviral DNAs acquired by infection of the same cells. The hypermethylated state of the endogenous AKR murine leukemia virus proviruses in these cells correlated with the failure to express AKR murine leukemia virus and the lack of infectivity of cellular DNA. Induction of the endogenous AKR murine leukemia virus proviruses with the methylation antagonist 5-azacytidine suggested a causal connection between DNA methylation and provirus expression. Also found to be relatively hypermethylated and noninfectious were three of six Moloney murine leukemia virus proviral DNAs in an unusual clone of infected rat cells. Recombinant DNA clones which derived from a methylated, noninfectious Moloney provirus of this cell line were found to be highly active upon transfection, suggesting that a potentially active proviral genome can be rendered inactive by cellular DNA methylation. In contrast, in vitro methylation with the bacterial methylases MHpaII and MHhaI only slightly reduced the infectivity of the biologically active cloned proviral DNA. Recombinant DNA clones which derived from a second Moloney provirus of this cell line were noninfectious. An in vitro recombination method was utilized in mapping studies to show that this lack of infectivity was governed by mechanisms other than methylation.
Battery State-of-Charge Estimator Using the MARS Technique

State of charge (SOC) is the equivalent of a fuel gauge for a battery pack in an electric vehicle. Determining the state of charge is thus particularly important for electric vehicles (EVs), hybrid EVs, or portable devices. The aim of this innovative study is to estimate the SOC of a high-capacity lithium iron phosphate (LiFePO4) battery cell from an experimental dataset obtained in the University of Oviedo Battery Laboratory using the multivariate adaptive regression splines (MARS) technique. An accurate predictive model able to forecast the SOC in the short term is obtained and it is a first step using the MARS technique to estimate the SOC of batteries. The agreement of the MARS model with the experimental dataset confirmed the goodness of fit for a limited range of SOC (25-90% SOC) and for a simple dynamic data profile [constant-current (CC) constant-voltage charge-CC discharge].
The Effect of Ulinastatin on Postoperative Blood Loss in Patients Undergoing Open Heart Surgery with Cardiopulmonary Bypass

This prospective, randomized, double-blind study evaluated the effect of ulinastatin on postoperative blood loss and transfusion requirements of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB) and aortic cross-clamping (ACC). CPB and ACC produce variable systemic inflammatory reactions that are associated with multiorgan dysfunction via leucocytes, especially polymorphonuclear neutrophils (PMNs). PMNs increase blood loss and transfusion requirements. Ulinastatin, a urinary trypsin inhibitor, inhibits PMN activity and reduces the systemic inflammatory response. Patients received either 5000 U/kg ulinastatin or the equivalent volume of normal saline (control group) before ACC. Postoperative blood loss and transfusion requirements were recorded. Duration of intubation and length of stay in the intensive care unit (ICU) were also noted. There were no statistically significant between-group differences in postoperative blood loss and transfusion requirements. Ulinastatin caused a non-significant decrease in duration of intubation. Patients who received ulinastatin had significantly shorter ICU stays than control patients.
The RNA Interacting Domain but Not the Protein Interacting Domain Is Highly Conserved in Ribosomal Protein P0*

Protein P0 interacts with proteins P1α, P1β, P2α, and P2β, and forms the Saccharomyces cerevisiaeribosomal stalk. The capacity of RPP0 genes fromAspergillus fumigatus, Dictyostelium discoideum, Rattus norvegicus, Homo sapiens, and Leishmania infantum to complement the absence of the homologous gene has been tested. In S. cerevisiae W303dGP0, a strain containing standard amounts of the four P1/P2 protein types, all heterologous genes were functional except the one from L. infantum, some of them inducing an osmosensitive phenotype at 37 °C. The polymerizing activity and the elongation factor-dependent functions but not the peptide bond formation capacity is affected in the heterologous P0 containing ribosomes. The heterologous P0 proteins bind to the yeast ribosomes but the composition of the ribosomal stalk is altered. Only proteins P1α and P2β are found in ribosomes carrying the A. fumigatus, R. norvegicus, and H. sapiens proteins. When the heterologous genes are expressed in a conditional null-P0 mutant whose ribosomes are totally deprived of P1/P2 proteins, none of the heterologous P0 proteins complemented the conditional phenotype. In contrast, chimeric P0 proteins made of different amino-terminal fragments from mammalian origin and the complementary carboxyl-terminal fragments from yeast allow W303dGP0 and D67dGP0 growth at restrictive conditions. These results indicate that while the P0 protein RNA-binding domain is functionally conserved in eukaryotes, the regions involved in protein-protein interactions with either the other stalk proteins or the elongation factors have notably evolved.
Efficacy of Dietary Arachidonic Acid Provided as Triglyceride or Phospholipid as Substrates for Brain Arachidonic Acid Accretion in Baboon Neonates

Arachidonic acid (AA) is a long-chain polyunsaturate (LCP) present in human breast milk as both triglyceride (TG) and as phospholipid (PL). There has been little attention to the metabolic consequences of lipid form of AA in infant formulas. Our objective was to investigate the efficacy of dietary TG and PL as carriers of AA for accretion in the brain and associated organs of term baboon neonates consuming a formula with LCP composition typical of human milk. TG and phosphatidylcholine (PC) with [U-13C]-AA in the sn-2 position and with unlabeled 16:0 in the remaining positions (TG-AA* or PL-AA*, respectively) were used as tracers to study the tissue AA* incorporation. Baboon neonates received a single oral dose of either TG-AA* (n = 3) or PL-AA* (n = 4) at 18–19 d of life. Tissues were obtained 10 d later (28–29 d of life) and isotopic enrichment was measured. In the brain, 4.5% of the PL-AA* dose and 2.1% of the TG-AA* dose were recovered as brain AA*, respectively, indicating that PL was about 2.1-fold more effective than TG as a substrate for brain AA accretion. Preferential incorporation of PL-derived AA* over TG source of AA* was also observed in the liver, lung, plasma, and erythrocytes. Because of the quantitative predominance of TG-AA in formula, total brain AA accretion, expressed as absolute weight, was 5.0-fold greater from TG-AA than from PL-AA. We estimate that about half of postnatal brain AA accretion is derived from dietary preformed AA in term baboon neonates consuming a formula with lipid composition similar to that of human milk.
Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered.

PURPOSE To examine the effect of single compared with repetitive (at least three) cycles of high-dose cytarabine after induction therapy for patients with acute myeloid leukemia (AML) who have the t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS Patients entered onto the study had AML and t(8;21) and attained a complete remission on four successive Cancer and Leukemia Group B studies. In these studies, either > or = three cycles of high-dose cytarabine or one cycle of high-dose cytarabine was administered, followed by sequential cyclophosphamide/etoposide and mitoxantrone/diaziquone with or without filgrastim support. Outcomes of these two groups of t(8;21) patients were compared. RESULTS A total of 50 patients with centrally reviewed AML and t(8;21) were assigned to receive one (n = 29) or > or = three cycles (n = 21) of high-dose cytarabine as postinduction therapy. The clinical features of these two groups of patients were similar. Initial remission duration for t(8;21) patients assigned to one cycle of high-dose cytarabine was significantly inferior (P =.03), with 62% of patients experiencing relapse with a median failure-free survival of 10.5 months, compared with the group of patients who received > or = three cycles, in which only 19% experienced relapse and failure-free survival is estimated to be greater than 35 months. Furthermore, overall survival was also significantly compromised (P =.04) in patients assigned to one cycle of high-dose cytarabine, with 59% having died as a consequence of AML, compared with 24% of those who received > or = three cycles of high-dose cytarabine. CONCLUSION These data demonstrate that failure-free survival and overall survival of patients with t(8;21)(q22;q22) may be compromised by treatment approaches that do not include sequential high-dose cytarabine therapy.
Cutaneous human papillomavirus genotypes in different kinds of skin lesions in Argentina

Cutaneous human papillomaviruses (HPVs) comprise a large and highly heterogeneous virus group. Some of the cutaneous HPVs of the genus Beta have been suggested as a co‐factor in the development of non‐melanoma skin cancer (NMSC). The aim of this study was to determine cutaneous HPV prevalence and type‐specific distribution in different kinds of skin lesions from Argentine patients visiting Dermatology Departments of three hospitals from Buenos Aires. A cross‐sectional analysis was performed. HPV DNA was analyzed in (i) 3 patients with Epidermodysplasia verruciformis (EV) harboring benign lesions (BL) (n = 1) and squamous cell carcinoma (SCC) (n = 4); (ii) 240 non‐EV patients harboring: (a) BL (n = 38), (b) Actinic Keratosis (AK) (n = 83), (c) SCC (n = 74), and (d) basal cell carcinoma (BCC) (n = 96). Detection and genotyping of 35 cutaneous HPV DNA was carried out by BGC‐PCR and GP5+/6 + PCR followed by reverse line blot assay. In EV patients, Beta types were found in all lesions (5/5), including the potentially high‐risk HPV types 5 and 8, mostly in multiple infections. In non‐EV patients, cutaneous types were found in 50.0% of BL, 43.4% of AK, 31.1% of SCC, and 16.7% of BCC. Beta HPVs were the most frequently found in all lesions, being present in all AK and SCC cases that were positive for HPV. No type‐specific correlation with lesion severity was found. In our series, a wide spectrum of cutaneous HPV types was detected in different skin lesions. A possible role for these HPVs in skin carcinogenesis deserves further study. J. Med. Virol. 89:352–357, 2017. © 2016 Wiley Periodicals, Inc.
Synaptic inhibition by glycine acting at a metabotropic receptor in tiger salamander retina

Glycine is the lone fast neurotransmitter for which a metabotropic pathway has not been identified. In retina, we found a strychnine‐insensitive glycine response in bipolar and ganglion cells. This glycine response reduced high voltage‐activated calcium current. It was G‐protein mediated and protein kinase A dependent. The EC50 of the metabotropic glycine response is 3 μm, an order of magnitude lower than the ionotropic glycine receptor in the same retina. The bipolar cell glutamatergic input to ganglion cells was suppressed by metabotropic glycine action. The synaptic output of about two‐thirds of bipolar cells and calcium current in two‐thirds of ganglion cells are sensitive to the action of glycine at metabotropic receptors, suggesting this signal regulates specific synaptic pathways in proximal retina. This study resolves the curious absence of a metabotropic glycine pathway in the nervous system and reveals that the major fast inhibitory neurotransmitters, GABA and glycine, both activate G‐protein‐coupled pathways as well.
Prevalence and Symptoms of Delirium Superimposed on Dementia

Delirium is a frequent syndrome among patients who are elderly. People who are older with cognitive impairment who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. This study goal was to describe the effect of severity of prior cognitive impairment on delirium prevalence and symptom presentation among patients who were older and were newly admitted to an acute care hospital. A total of 104 were included in this descriptive study and screened for delirium. The results showed that the prevalence of delirium increased according to the severity of the patients’ prior cognitive impairment. Except for disorganized thinking, all symptoms of delirium were similar among patients with mild, moderate, and severe prior cognitive impairment. The study concluded that training nurses to recognize subtle changes in mental status among those patients who were older with prior cognitive impairment may prevent the underdetection of delirium.