Miracle-dz/UniFAR-FTUs huggingface dataset:
Ataxia and paresis with equine herpesvirus type 1 infection in a herd of riding school horses.

An outbreak of neurologic disease associated with serologic evidence of equine herpesvirus type 1 (EHV-1) infection occurred in a herd of 46 riding school horses. Ataxia and paresis were observed in 14 geldings and 5 barren mares. Eight affected horses had distal limb edema, 1 horse had a head tilt, and 3 others had urinary incontinence. Other clinical signs included fever, depression, and inappetance in 30 horses. Seven horses with neurologic signs were treated with acyclovir. Serum neutralizing antibody titers against EHV-1 increased 4-fold between acute and convalescent samples or exceeded 1:256 in 19 of 44 horses, confirming recent infection. A significantly greater proportion of horses that seroconverted were mares (P = .014). Of the 19 horses exhibiting ataxia and paresis, 17 made a complete recovery, 1 made a partial recovery, and 1 was euthanized.
Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer

Objectives:The primary objective was to determine the response rate in patients with metastatic pancreatic cancer treated in first line with irinotecan/docetaxel combination (Arm A) or with irinotecan/docetaxel/cetuximab combination (Arm B). Secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity, and the rate of thromboembolic events with prophylactic enoxaparin sodium. Patients and Methods:Patients were eligible who had measurable, metastatic adenocarcinoma of the pancreas, and normal bilirubin. All patients received anticoagulation. Docetaxel (35 mg/m2) and irinotecan (50 mg/m2) were administered once a week for 4 weeks followed by 2 weeks rest (Arm A) alone or with the addition of cetuximab (Arm B). The primary endpoint was response rate. Results:A total of 87 eligible patients were enrolled and treated. Grade 3/4 toxicity was observed in 74% of patients in Arm A and 76% in Arm B. The principal grade 3/4 toxicity was diarrhea. Response rates were 4.5% in Arm A and 7% in Arm B. Median PFS and OS were 3.9 and 6.5 months in Arm A and 4.5 and 5.4 months in Arm B. Conclusions:Docetaxel/irinotecan combination is associated with considerable toxicity. Objective responses were infrequent and addition of cetuximab in an unselected population was not beneficial, but PFS and OS were comparable with those achieved with other regimens. Docetaxel/irinotecan therapy is active in metastatic pancreatic cancer.
Nitric Oxide Is an Upstream Signal of Vascular Endothelial Growth Factor-induced Extracellular Signal-regulated Kinase½ Activation in Postcapillary Endothelium*

We recently demonstrated that nitric oxide (NO) significantly contributes to the mitogenic effect of vascular endothelial growth factor (VEGF), suggesting a role for the NO pathway in the signaling cascade following kinase-derivative receptor activation in vascular endothelium. The aim of this study was to investigate the intracellular pathways linked to VEGF/NO-induced endothelial cell proliferation. We assessed the activity of the mitogen-activated protein kinase (MAPK) that is specifically activated by growth factors, extracellular-regulated kinase (ERK½), on cultured microvascular endothelium isolated from coronary postcapillary venules. ERK½ was immunoprecipitated, and its activity was assessed with an immunocomplex kinase assay. In endothelial cells exposed for 5 min to the NO donor drug sodium nitroprusside at a concentration of 100 μm, ERK½ activity significantly increased. VEGF produced a time- and concentration-dependent activation of ERK½. Maximal activity was obtained after 5 min of stimulation at a concentration of 10 ng/ml. The specific MAPK kinase inhibitor PD 98059 abolished ERK½ activation and endothelial cell proliferation in a concentration-dependent manner in response to VEGF and sodium nitroprusside. The NO synthase inhibitorN ω-monomethyl-l-arginine, as well as the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, blocked the activation of ERK½ induced by VEGF, suggesting that NO and cGMP contributed to the VEGF-dependent ERK½ activation. These results demonstrate for the first time that kinase-derivative receptor activation triggers the NO synthase/guanylate cyclase pathway to activate the MAPK cascade and substantiates the hypothesis that the activation of ERK½ is necessary for VEGF-induced endothelial cell proliferation.
Nucleolin Is a Second Component of the CD154 mRNA Stability Complex That Regulates mRNA Turnover in Activated T Cells1

CD154 (CD40L) mRNA turnover is regulated in part at the posttranscriptional level by a protein complex (termed Complex I) that binds to a highly CU-rich region of the 3′UTR. Polypyrimidine tract-binding protein (PTB) has previously been identified as a major RNA-binding protein in Complex I. Nondenaturing gel filtration of total extract from Jurkat T cells demonstrated that the CD154 mRNA-binding activity migrates as a ∼200-kDa complex, indicating the presence of multiple complex-associated proteins. We have currently undertaken a biochemical approach to further characterize Complex I and observed that it segregates over DEAE-Sepharose into two subcomplexes (termed I-L and I-U). Furthermore, nucleolin was identified as a component of both subcomplexes and was shown that it is the major RNA-binding protein in I-U. To directly demonstrate the biological significance of Complex I binding to the CD154 transcript, cytoplasm from human Jurkat cells was fractionated over a sucrose gradient and the different cellular fractions subjected to immunoprecipitation with anti-PTB and anti-nucleolin Abs. RT-PCR of the immunoprecipitated products using CD154-specific primers clearly demonstrated that nucleolin and PTB are associated with CD154 mRNA in both the ribonucleoprotein and polysome fractions. These data strongly support a model whereby nucleolin and PTB are integral to the stability of CD154 mRNA and are components of the CD154 ribonucleoprotein particle associated with actively translating ribosomes.
L166P Mutant DJ-1, Causative for Recessive Parkinson's Disease, Is Degraded through the Ubiquitin-Proteasome System*

Mutations in a gene on chromosome 1, DJ-1, have been reported recently to be associated with recessive, earlyonset Parkinson's disease. While one mutation is a large deletion that is predicted to produce an effective knockout of the gene, the second is a point mutation, L166P, whose precise effects on protein function are unclear. In the present study, we show that L166P destabilizes DJ-1 protein and promotes its degradation through the ubiq-uitin-proteasome system. A double mutant (K130R, L166P) was more stable than L166P, suggesting that this lysine residue contributes to stability of the protein. Subcellular localization was broadly similar for both wild type and L166P forms of the protein, indicating that the effect of the mutation is predominantly on protein stability. These observations are reminiscent of other recessive gene mutations that produce an effective loss of function. The L166P mutation has the simple effect of promoting DJ-1 degradation, thereby reducing net DJ-1 protein within the cell.
Oxytocin and the salience of social cues

The neuropeptide oxytocin (OT) is rapidly moving from a molecule with interesting effects in model systems to an important mediator of a range of human social behaviors. In this issue of PNAS, Gamer et al. (1) report on a study in which they show that subjects given OT, relative to subjects given placebo, are more likely to make eye movements toward the eye region when viewing images of human faces, which replicates and extends previous work (2, 3). Gamer et al. (1) also use functional brain imaging to show that the amygdala is an important brain area mediating this effect. These findings have broad implications for understanding the role of OT in normal social behavior as well as the possible therapeutic impact of OT in brain disorders characterized by social dysfunction.
Aldose reductase mediates cytotoxic signals of hyperglycemia and TNF‐α in human lens epithelial cells

Chronic hyperglycemia and cytokines such as tumor necrosis factor α (TNF‐α) cause oxidative stress leading to dysregulated cell growth or apoptosis that contributes to the development of inflammation and secondary complications of diabetes. However, the mechanisms regulating hyperglycemic or cytokine injury are not well understood. Herein we report that inhibition of the polyol pathway enzyme aldose reductase (AR) by two structurally unrelated inhibitors—sorbinil and tolrestat—prevents, in the human lens epithelial cell line B‐3, the apoptosis and activation of caspase‐3 caused by exposure to high glucose levels or TNF‐α. Inhibition of AR attenuated TNF‐α and hyperglycemia‐induced activation of protein kinase C (PKC), phosphorylation of the inhibitory subunit of nuclear factor‐κB (NF‐κB), and stimulation of NF‐κB, but it did not prevent the activation of NF‐κB and PKC by phorbol ester. Inhibition of AR also attenuated the increase in p38 mitogen‐activated protein kinase and c‐Jun N‐terminal kinase phosphorylation. These signaling pathways were also inhibited in cells in which the expression of AR was reduced by antisense ablation. Collectively, these results identify a new participant in apoptotic signaling and suggest that AR is an obligatory mediator of the apoptotic events upstream of PKC. These observations could provide new insights into the pathophysiology of diabetes and the role of aberrant glucose metabolism in apoptotic cell death.
A Survey of Intravenous Remifentanil Use for Labor Analgesia at Academic Medical Centers in the United States

Remifentanil is most commonly offered when neuraxial labor analgesia is contraindicated. There is no consensus regarding the optimal administration, dosing strategy, or requirements for maternal monitoring, which may pose a patient safety issue. This exploratory survey evaluated the current practices regarding remifentanil use for labor analgesia at academic centers in the United States. Of 126 obstetric anesthesia directors surveyed, 84 (67%) responded. In 2014 to 2015, an estimated 36% (95% confidence interval: 25.7–46.3) of centers used remifentanil, most of which did so less than 5 times. Some serious maternal and neonatal respiratory complications occurred, emphasizing that clinical protocols and adequate monitoring are key to ensure maternal and neonatal safety.
A multi-resolution MoM analysis of multiport structures using matched terminations

This paper presents the modeling of microstrip structures involving matched terminations with multi resolution 1-D method of moment (MoM). Semi-orthogonal (SO) spline wavelets are used to obtain a sparse system while a modeling of matched terminations enables a full multiport characterization. Theoretical results involving microstrip dipoles are presented and compared with experiments.
Neoadjuvant chemoradiotherapy for locally advanced esophageal cancer: experience at a single institution.

HYPOTHESIS Patients receiving neoadjuvant chemoradiotherapy followed by surgery (CRS) undergo downstaging of their tumor and have improved survival when compared with patients undergoing surgery followed by adjuvant chemoradiotherapy (SCR). DESIGN Retrospective study. SETTING Tertiary-care university medical center. PATIENTS One hundred twenty-three patients with squamous cell carcinoma and adenocarcinoma of the esophagus underwent Ivor-Lewis esophagectomy from January 1, 1990, through December 31, 2001. Of these, 31 received CRS; 27, SCR; and 65, surgery alone. INTERVENTIONS Patients were candidates for neoadjuvant or adjuvant therapy if they had locally advanced disease (T3/T4 N0 or any T stage with N1). Neoadjuvant and adjuvant therapies were nonrandomized and based on the preference of the treating oncologist and surgeon. MAIN OUTCOME MEASUREMENTS Pathological downstaging was analyzed in the patients receiving CRS. Operative mortality, postoperative morbidity, median survival, and overall survival were compared between the CRS and SCR groups. RESULTS Pathological downstaging (as characterized by TNM staging) was observed in 20 (64%) of the patients receiving CRS. Complete pathological responses occurred in 5 (16%) of the patients undergoing CRS. No 30-day mortality was observed in either treatment group. No statistical difference in survival was observed between groups, although a trend suggested improved survival with neoadjuvant therapy (3-year survival in CRS and SCR groups was 45% and 22%, respectively; P =.15). Complete pathological responders in the CRS group had a 1-year survival of 80% compared with 29% in nonresponders (P =.25). No statistical differences were observed between groups in relation to blood loss, length of hospital stay, mortality, or morbidity. CONCLUSIONS Neoadjuvant chemoradiotherapy effectively downstages cancer in patients with locally advanced esophageal disease. Morbidity and operative mortality were not significantly different between patients receiving neoadjuvant and adjuvant therapy. The difference in overall survival between the 2 groups did not reach statistical significance, although a trend at 3 years was observed.
Spectrum of congenital heart disease in children with Down syndrome inIle-Ife, Nigeria.

Background: Congenital heart disease is a significant morbidity and determinant of mortality in persons with Down syndrome, the most prevalent human chromosomal anomaly. Yet, dearth of literature persists about its spectrum in Nigerian children. Objective: To determine the spectrum and outcome of congenital heart disease among children with Down syndrome in the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. Methods: A prospective study of all children diagnosed with Down syndrome seen over a 21 month period. Data obtained and analysed included age, sex, parental ages, birth order, anthropometry, echocardiography diagnoses, complications, treatments and outcomes. Results: Of the 70 children with Down syndrome, 53 (75.7%) had congenital heart disease of which 24 (45.3%) had solitary lesions with atrio-ventricular canal defect being the most common while 29 (54.7%) had multiple lesions of which the combination of ventricular septal defect with atrial septal defect was the most common. However, when all individual lesions were summed together, the most prevalent was atrial septal defect. The mean maternal and paternal ages were 31.4 and 41.2 years respectively. Over half were 1st or 2nd born. Higher proportion of those with congenital heart disease than those without were undernourished (67.9% versus 35.3%; p=0.035). Only 4 (7.5%) have had definitive corrective interventions, 26.4% developed pulmonary arterial hypertension and 18.9% had left ventricular dysfunction. Conclusion: The occurrence of congenital heart disease in these Nigerian children with Down syndrome is high the pattern being comparable with that in the literature with atrio-ventricular canal defect and other septal defects being most common. Presentation is late and the level of definitive care is poor. Routine and early cardiologic evaluation of all children suspected with Down syndrome is advocated.
Intelligent evolutionary design: A new approach to optimizing complex engineering systems and its application to designing heat exchangers

A new method for optimizing complex engineering designs is presented that is based on the Learnable Evolution Model (LEM), a recently developed form of non‐Darwinian evolutionary computation. Unlike conventional Darwinian‐type methods that execute an unguided evolutionary process, the proposed method, called LEMd, guides the evolutionary design process using a combination of two methods, one involving computational intelligence and the other involving encoded expert knowledge. Specifically, LEMd integrates two modes of operation, Learning Mode and Probing Mode. Learning Mode applies a machine learning program to create new designs through hypothesis generation and instantiation, whereas Probing Mode creates them by applying expert‐suggested design modification operators tailored to the specific design problem. The LEMd method has been used to implement two initial systems, ISHED1 and ISCOD1, specialized for the optimization of evaporators and condensers in cooling systems, respectively. The designs produced by these systems matched or exceeded in performance the best designs developed by human experts. These promising results and the generality of the presented method suggest that LEMd offers a powerful new tool for optimizing complex engineering systems. © 2006 Wiley Periodicals, Inc. Int J Int Syst 21: 1217–1248, 2006.
The effect of ingestion of inulin on blood lipids and gastrointestinal symptoms in healthy females

The effect of a daily intake of 14g inulin added to a low-fat spread on fasting blood lipids and gastrointestinal symptoms was investigated in sixty-four young healthy women in a randomized double-blind crossover study involving two periods of 4 weeks. The test spread with and without inulin replaced habitual spread during the test periods. No significant differences between the test periods in plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triacylglycerol concentrations were observed. Gastrointestinal symptoms assessed with questionnaires showed that in the inulin period there was a significantly (P<0·05) higher degree of discomfort from flatulence and other gastrointestinal symptoms than in the control period. In general, there was no indication of intestinal adaptation to this level of intake of inulin.
Free internet as agent of community transformation

Does the internet empower communities or perpetuate the status quo? Can universal internet access resolve education, employment, and other social gaps? We report on our longitudinal assessment of low income community access to free internet in New Zealand, in terms of new internet users (1) community belonging, (2) internet connectedness, and (3) civic engagement. Findings show internet connectedness may have only a minimal impact on community capacity due to constraints such as family transience, difficult domestic circumstances, inadequate project resourcing, and poor literacy. Internet ubiquity may not be a strategically useful social objective unless contextual limitations are recognised and addressed.
ON SEGMENTED MULTIVARIATE REGRESSION

This paper concerns segmented multivariate regression models, models which have different linear forms in different subdomains of the domain of an in- dependent variable. Without knowing that number and their boundaries, we first estimate the number of these subdomains using a modified Schwarz criterion. The estimated number of regions proves to be weakly consistent under fairly general conditions. We then estimate the subdomain boundaries ("thresholds") and the regression coefficients within subdomains by minimizing the sum of squares of the residuals. We show that the threshold estimates converge (at rates, 1/n and n −1/2 , respectively at the model's threshold points of discontinuity and continuity) and that the regression coefficients as well as the residual variances are asymptotically normal. The basic condition on the error distribution required for the veracity of our asymptotic results is satisfied by any distribution with zero mean and a mo- ment generating function (having bounded second derivative around zero). As an illustration, a segmented bivariate regression model is fitted to real data and the relevance of the asymptotic results is examined via simulations. Many practical situations involve a response variable which depends on some independent variables through a function whose form cannot be uniformly well approximated by the leading terms of a single Taylor expansion. Consequently, the usual linear regression model is not applicable and the simplicity of the methodology is lost. However a segmented linear model has much of the simplicity of the classi- cal linear methodology, and more flexibility. It may be regarded as a piecewise linear approximation deriving from different Taylor expansions in different sub- domains. We require that a certain independent variable be selected and used to partition the domain of the independent variables into subdomains. The rela- tionship between the response and independent variables is allowed to vary from subdomain-to-subdomain. The partitioning variable may be suggested by extraneous considerations. The positive correlation of the production rate on the composition of the chemical agents involved reverses when the temperature exceeds a certain threshold (or
Psychometric properties of the Postgraduate Hospital Educational Environment Measure in an Iranian hospital setting

Background Students’ perceptions of the educational environment are an important construct in assessing and enhancing the quality of medical training programs. Reliable and valid measurement, however, can be problematic – especially as instruments developed and tested in one culture are translated for use in another. Materials and method This study sought to explore the psychometric properties of the Postgraduate Hospital Educational Environment Measure (PHEEM) for use in an Iranian hospital training setting. We translated the instrument into Persian and ensured its content validity by back translation and expert review prior to administering it to 127 residents of Urmia University of Medical Science. Results Overall internal consistency of the translated measure was good (a=0.94). Principal components analysis revealed five factors accounting for 52.8% of the variance. Conclusion The Persian version of the PHEEM appears to be a reliable and potentially valid instrument for use in Iranian medical schools and may find favor in evaluating the educational environments of residency programs nationwide.
RNA polymerase mutations that facilitate replication progression in the rep uvrD recF mutant lacking two accessory replicative helicases

We observed that cells lacking Rep and UvrD, two replication accessory helicases, and the recombination protein RecF are cryo‐sensitive on rich medium. We isolated five mutations that suppress this Luria–Bertani (LB)‐cryo‐sensitivity and show that they map in the genes encoding the RNA polymerase subunits RpoB and RpoC. These rpoB (D444G, H447R and N518D) and rpoC mutants (H113R and P451L) were characterized. rpoBH447R and rpoBD444G prevent activation of the Prrn core promoter in rich medium, but only rpoBH447R also suppresses the auxotrophy of a relA spoT mutant (stringent‐like phenotype). rpoCH113R suppresses the thermo‐sensitivity of a greA greB mutant, suggesting that it destabilizes stalled elongation complexes. All mutations but rpoCP451L prevent R‐loop formation. We propose that these rpo mutations allow replication in the absence of Rep and UvrD by destabilizing RNA Pol upon replication–transcription collisions. In a RecF+ context, they improve growth of rep uvrD cells only if DinG is present, supporting the hypothesis that Rep, UvrD and DinG facilitate progression of the replication fork across transcribed sequences. They rescue rep uvrD dinG recF cells, indicating that in a recF mutant replication forks arrested by unstable transcription complexes can restart without any of the three known replication accessory helicases Rep, UvrD and DinG.