Miracle-dz/UniFAR-FTUs huggingface dataset:
Epstein–Barr virus nuclear antigen leader protein localizes to promoters and enhancers with cell transcription factors and EBNA2

Significance Epstein–Barr virus nuclear antigen (EBNA) leader protein (LP) and EBNA2 (E2) up-regulation of virus and cell gene expression is important for human B-lymphocyte conversion to continuous, potentially malignant, lymphoblast cell lines. Although the molecular mechanism(s) underlying LP and E2 regulation of cell gene expression have been partially elucidated, LP ChIP-sequencing studies have now revealed that LP and LP/E2 interact, genome-wide, with human B-cell transcription factors, mostly at or near prepatterned promoter sites, to increase cell transcription factor occupancies, increase activation-associated histone marks, and positively affect cell gene transcription. Epstein–Barr virus (EBV) nuclear antigens EBNALP (LP) and EBNA2 (E2) are coexpressed in EBV-infected B lymphocytes and are critical for lymphoblastoid cell line outgrowth. LP removes NCOR and RBPJ repressive complexes from promoters, enhancers, and matrix-associated deacetylase bodies, whereas E2 activates transcription from distal enhancers. LP ChIP-seq analyses identified 19,224 LP sites of which ∼50% were ±2 kb of a transcriptional start site. LP sites were enriched for B-cell transcription factors (TFs), YY1, SP1, PAX5, BATF, IRF4, ETS1, RAD21, PU.1, CTCF, RBPJ, ZNF143, SMC3, NFκB, TBLR, and EBF. E2 sites were also highly enriched for LP-associated cell TFs and were more highly occupied by RBPJ and EBF. LP sites were highly marked by H3K4me3, H3K27ac, H2Az, H3K9ac, RNAPII, and P300, indicative of activated transcription. LP sites were 29% colocalized with E2 (LP/E2). LP/E2 sites were more similar to LP than to E2 sites in associated cell TFs, RNAPII, P300, and histone H3K4me3, H3K9ac, H3K27ac, and H2Az occupancy, and were more highly transcribed than LP or E2 sites. Gene affected by CTCF and LP cooccupancy were more highly expressed than genes affected by CTCF alone. LP was at myc enhancers and promoters and of MYC regulated ccnd2, 23 med complex components, and MYC regulated cell survival genes, igf2r and bcl2. These data implicate LP and associated TFs and DNA looping factors CTCF, RAD21, SMC3, and YY1/INO80 chromatin-remodeling complexes in repressor depletion and gene activation necessary for lymphoblastoid cell line growth and survival.
Cumulative childhood risk and adult functioning in abused and neglected children grown up

Abstract This paper examines the relationship between childhood exposure to cumulative risk and three indicators of psychosocial adjustment in adulthood (educational attainment, mental health, and criminal behavior) and tests three different models (linear, quadratic, and interaction). Data were collected over several time points from individuals who were part of a prospective cohort design study that matched children with documented cases of abuse and/or neglect with children without such histories and followed them into adulthood. Hierarchical multiple regressions compared linear and quadratic models and then examined potential moderating effects of child abuse/neglect and gender. Exposure to a greater number of childhood risk factors was significantly related to fewer years of education, more anxiety and depression symptomatology, and more criminal arrests in adulthood. The relationship between cumulative risk and years of education demonstrated a curvilinear pattern, whereas the relationship between cumulative risk and both mental health and criminal arrests was linear. Child abuse/neglect did not moderate these relationships, although there were direct effects for both child abuse/neglect and gender on criminal arrests, with more arrests for abused/neglected individuals than controls and more for males than females. Gender interacted with cumulative risk to impact educational attainment and criminal behavior, suggesting that interventions may be more effective if tailored differently for males and females. Interventions may need to be multifaceted and designed to address these different domains of functioning.
Coffee consumption and risk of hospitalized miscarriage before 12 weeks of gestation.

In order to analyse the association between drinking coffee in pregnancy and risk of spontaneous abortion, a case-controlled study was conducted in Milan, Northern Italy. Cases were 782 women with spontaneous abortion within the 12th week of gestation. The control group was recruited from women who gave birth at term (> 37 weeks gestation) to healthy infants on randomly selected days at the same hospitals where cases had been identified: 1543 controls were interviewed. A total of 561 (72%) cases of spontaneous abortion and 877 (57%) controls reported coffee drinking during the first trimester of the index pregnancy. The corresponding multivariate odds ratios of spontaneous abortion, in comparison with non-drinkers, were 1.2, 1.8 and 4.0, respectively, for drinkers of 1, 2 or 3, and 4 or more cups of coffee per day. No relationship emerged between maternal decaffeinated coffee, tea and cola drinking in pregnancy, as well as paternal coffee consumption, and risk of spontaneous abortion. With regard to duration in years of coffee drinking, the estimated multivariate odds ratios of spontaneous abortion were, in comparison with non-coffee drinkers, 1.1 (95% confidence interval (CI) 0.9-1.4) and 1.9 (95% CI 1.5-2.6) for women reporting a duration of coffee consumption < or = 10 or > 10 years. In conclusion, coffee drinking early in pregnancy was associated with an increased risk of abortion. This has biological implications, but epidemiological inference on the causality is difficult and still open to debate.
p35/Cdk5 pathway mediates soluble amyloid‐β peptide‐induced tau phosphorylation in vitro

Alzheimer's disease (AD) is pathologically characterized by deposition of amyloid‐β peptides (Aβ) as senile plaques and by the occurrence of neurofibrillary tangles (NFTs) composed primarily of hyperphosphorylated tau protein. Activation of cyclin‐dependent kinase 5 (Cdk5) via its potent activator p25 has recently been shown to promote phosphorylation of tau at AD‐specific phosphoepitopes, and increased cleavage of p35 to p25 has been demonstrated in AD patients, suggesting that Cdk5 may represent a pathogenic tau protein kinase. We were interested in the potential effect of soluble forms of Aβ on Cdk5‐mediated AD‐like tau phosphorylation, insofar as previous studies of human biopsies and aged canine and primate brains have shown that dystrophic neurites appear before the formation of neuritic plaques. We transfected N2a cells with a p35 vector (N2a/p35 cells) and, after differentiation, challenged these cells with Aβ1–42 peptide in soluble form (sAβ1–42). Results show that sAβ1–42 at relatively low levels (1–5 μM) dose‐dependently increases tau phosphorylation at AD‐specific phosphoepitopes in differentiated N2a/p35 cells compared with controls, an effect that is blocked by antisense oligonucleotides against p35. sAβ1–42‐induced tau phosphorylation is concomitant with an increase in both p25 to p35 ratio and Cdk5 activity (but not protein levels). Additionally, blockade of L‐type calcium channels or inhibition of calpain completely abolishes this effect. Taken together, these data indicate that sAβ is a potent activator of the p25/Cdk5 pathway, resulting in promotion of AD‐like tau phosphorylation in vitro. © 2002 Wiley‐Liss, Inc.
Two new eunicellin diterpenoids from the South China Sea gorgonian Muricella sibogae and their bioactivities

A systematic re-study on gorgonian Muricella sibogae from South China Sea yielded 10 eunicellin-based diterpenoids including two new ones, sibogins C and D (1 and 2). Their structures were elucidated by extensive spectroscopic analyses (1D and 2D NMR, IR and MS) and by comparison with data reported in literatures. All the isolates were tested for cytotoxic and antifouling activities. Compounds 3 and 5 showed significant antifouling activity against the green mussel Perna viridis, and especially 3 was suggested as a potent low-toxic antifouling agent with a large LC50/EC50 value of 18.6. This was the first report on the antifouling activity of the eunicellin-type diterpenoids against the green mussel.
Are tidal breathing indices useful in infant bronchial challenge tests?

Tidal breathing indices have been used to assess histamine‐induced airway obstruction in adults and children. The aim of this study was to see whether they could be used to assess histamine challenge in infants. Tidal flow during quiet breathing was measured using a face mask and pneumotachograph and maximum flow at functional residual capacity (VmaxFRC) was measured from partial forced expirations in 18 sleeping, sedated infants who responded to histamine challenge and in 18 nonresponders. The tidal indices calculated were inspiratory and expiratory time (t1, and te), tidal peak expiratory flow (PEF), mean tidal expiratory flow rate (VT/te) and the expiratory time constant of the respiratory system (trs). The time to maximal expiration divided by expiratory time (tme/te) and 2 revised forms of this index (tme(a)te and tme(b)( tme(b) /te) were also calculated. Recordings of tme(a) and tme(b) were taken at 95% of peak tidal expiratory flow, before and after the peak, respectively. In nonresponders, there was an insignificant mean rise in VmaxFRC of 11.8% but no change in any tidal index. In responders, the mean percentage fall in VmaxFRC was 43.3% (range, −31 to −81%); trs fell from 0.61 s to 0.51 s (P < 0.05) and breathing frequency and mean tidal expiratory flow rate increased from 34.0 to 37.5 min−1 (P < 0.01) and from 66.6 to 72.6 mL.s−1 (P < 0.05), respectively, suggesting that infants had adopted a strategy of active expiration in response to bronchial challenge. There was no change either in tme/te, or in the revised indices after challenge. , It is therefore concluded that tme/te is an insensitive index of airflow obstruction compared to VmaxFRC and cannot be used to assess the response to bronchial challenge. Changes in other indices were small and related to a presumed pattern of active expiration after challenge. Pediatr Pulmonol. 1994; 17:225–230. © 1994 Wiley‐Liss, Inc.
Mining Human Mobility to Quantify Performance Status

Human mobility has been studied extensively in various biomedical contexts with applications in clinical rehabilitation, disease diagnosis, health risk prognosis, and general performance assessments. In this paper, we present ATOMHP (Analytical Technologies to Objectively Measure Human Performance) Kinect: a system to objectively quantify human performance using the Microsoft Kinect as a single camera sensor to capture human mobility. We explore the viability of this noninvasive performance assessment system by studying a cohort of cancer patients undergoing various therapy regimens who are assigned a performance score based on a qualitative clinical test. The ATOM-HP Kinect is a clinically usable system which consists of tools for Kinect, clinical data collection, data quality validation, and mobility feature extraction, which can be used for downstream analysis of performance. Preliminary results based on the clinical case study indicate that ATOM-HP Kinect can quantify changes in kinematic parameters, and that these features are correlated with clinically measured risk factors which could be used for early prediction of diseases, or making decision on treatment modification.
Willingness to pay for inhaled insulin: a contingent valuation approach.

PURPOSE To determine the willingness to pay (WTP) of patients with diabetes mellitus for inhaled insulin. METHODS A contingent valuation survey was administered to 96 diabetic outpatients at St. Michael's Hospital, Toronto, Canada. Standardised information about inhaled insulin and subcutaneous rapid-acting insulin was provided via video. Participants' WTP for their preferred product was elicited in Canadian dollars (Can dollars) using a 'payment-scale' method. RESULTS The mean age of participants was 51.8 years (SD 13.4). Seventy-seven patients had type 2 and 19 had type 1 diabetes. Significantly more participants preferred inhaled insulin over subcutaneous insulin (85 vs 11; p < 0.01). Mean monthly WTP for inhaled insulin (153.70 Can dollars, SD 99.90) was significantly more than the typical 50 Can dollars per month for subcutaneous insulin (p < 0.01). Significantly more participants with type 2 diabetes using oral drugs than those with type 1 diabetes and using insulin preferred inhaled insulin (98.5% vs 69%, p < 0.001). Diabetic patients who did not use insulin were willing to pay significantly more than were insulin users (p < 0.001). Multiple regression analysis showed that income was significantly associated with WTP for inhaled insulin. CONCLUSION Diabetic patients, particularly those who are not using insulin, indicated that they would prefer inhaled insulin over insulin injection and would be willing to pay a substantial amount per month to use it. An economic evaluation of inhaled insulin would provide important information to healthcare policy decision makers and private payers about its economic value.
Prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) from skin and carriage sites of dogs after treatment of their meticillin-resistant or meticillin-sensitive staphylococcal pyoderma.

BACKGROUND Meticillin-resistant staphylococci are significant pathogens in veterinary dermatology, yet longitudinal studies of the impact of routine antimicrobial therapy on emergence or resolution of resistance are lacking. OBJECTIVES To determine the prevalence of meticillin-resistant staphylococci on skin and carriage sites in dogs with bacterial pyoderma and evaluate the prevalence of meticillin-resistant Staphylococcus pseudintermedius (MRSP) colonization after successful treatment of pyoderma. ANIMALS One hundred and seventy-three dogs that presented to a dermatology referral service with pyoderma and 41 healthy control dogs. METHODS Skin, nasal and rectal swabs for bacterial culture were collected at the time of referral and after clinical resolution of the pyoderma. Meticillin resistance was confirmed by demonstration of penicillin binding protein 2a antigen. RESULTS Initially, skin cultures yielded MRSP in 70 (40.5%) dogs, meticillin-resistant Staphylococcus aureus (MRSA) in three (1.7%) and meticillin-resistant Staphylococcus schleiferi ssp. coagulans (MRSScoag) in five (2.9%). Samples collected from the nose and rectum (carriage sites) yielded MRSP in 59 (34.1%) dogs, MRSA in 11 (6.4%) and MRSScoag in seven (4.0%). One hundred and two dogs were available for follow-up cultures after clinical cure. Of 42 dogs initially diagnosed with MRSP pyoderma, MRSP was isolated at follow-up from skin in 19 (45.2%) and carriage sites in 20 (47.6%). Of 60 dogs that did not have MRSP pyoderma initially, MRSP was isolated post-treatment from the skin in 17 (28.3%), and MRSP from carriage sites increased from 7.8% (initially) to 26.7% (P = 0.0022). CONCLUSIONS AND CLINICAL IMPORTANCE Colonization by MRSP often persists after resolution of MRSP pyoderma. Acquisition of MRSP during treatment appears to be common.
Evaluation of Impression Accuracy for Implant at Various Angulations

Purpose:The purpose of this study was to compare 2 splinted impression transfer techniques for implant-supported prostheses. Materials:A metal matrix (control) with 4 implants was used. The implants were positioned at 90, 80, 75, and 65 degrees in relation to the surface of the matrix. Squared impression copings were splinted with self-curing acrylic resin in group 1 (n = 10) and with condensation silicone in group 2 (n = 10). A computer software was used to measure the implants/analogs inclinations. Data were analyzed by 2-way analysis of variance and Tukey test (&agr; <0.05). Results:There was significant difference between groups, implant/analog inclinations, and interaction between them (P < 0.05). Group 1 had no significant difference from the control (P > 0.05) nor from group 2 (P > 0.05) regardless implant/analog inclinations. Considering implant/analog inclinations, both techniques did not differ from control group (P > 0.05), except for 75 degrees implant/analog inclinations (P < 0.05). Conclusion:The results suggest that condensation silicone may not be used as an alternative splinting material. Furthermore, implant inclination may affect master cast accuracy.
A Coordinate System associated to a Point Cloud issued from a Manifold: Definition, Properties and Applications. (Un système de coordonnées associé à un échantillon de points d'une variété: définition, propriétés et applications)

Surfaces and manifolds represented by a set of discrete points are encountered in various application areas. In this thesis, we define a coordinate system on the manifold associated to such a point set which is a generalization of Sibson's natural neighbor coordinates. We show its fundamental mathematical properties as well as its application to scattered data interpolation on manifolds. Furthermore, we introduce the notion of Voronoi atlas defined as a collection of Voronoi cells that approximate the Voronoi diagram restricted to the manifold. We describe its application in surface reconstruction and re-meshing. In addition, we show the basic properties of natural neighbor coordinates in power diagrams and we survey the interpolation methods based on natural neighbor coordinates. This survey details some proofs that are omitted in the original papers.
Sublethal effects of methylmercury on fecal metabolites of testosterone, estradiol, and corticosterone in captive juvenile white ibises (Eudocimus albus)

Methylmercury (MeHg) is a globally distributed neurotoxin, endocrine disruptor, and teratogen, and its effects on birds are poorly understood, especially within an environmentally relevant exposure range. In an effort to understand the potential causal relationship between MeHg exposure and endocrine development, we established four dietary exposure groups (0 [control], 0.05, 0.1, and 0.3 mg/kg wet wt/d of MeHg) of postfledging white ibises (Eudocimus albus) in a divided, free‐flight aviary that spanned the estimated range of environmental exposure for this species. Fecal samples were collected from individually identified ibises over six months in 2005 and processed for hormone evaluation. Significant sex‐related differences in fecal estradiol concentrations, though unpredicted in direction, suggest that this steroid could be related to juvenile development in this species. Using repeated‐measures general linear models, we tested a set of candidate models to explain variation in endocrine expression. We found that MeHg exposure led to significant differences in fecal estradiol concentrations between the control and medium‐dose groups, whereas differences in fecal corticosterone concentrations were observed between the control and both the low‐ and high‐dose groups. These results suggest highly nonlinear dose‐response patterns for MeHg. Many endocrine‐disrupting contaminants are theorized to affect multiple endpoints in a nonlinear manner, making results difficult to interpret using a traditional toxicological approach. The evidence presented here suggests that endocrine effects of MeHg exposure could behave similarly.
Comparative effectiveness of prostate cancer treatments: evaluating statistical adjustments for confounding in observational data.

BACKGROUND Using observational data to assess the relative effectiveness of alternative cancer treatments is limited by patient selection into treatment, which often biases interpretation of outcomes. We evaluated methods for addressing confounding in treatment and survival of patients with early-stage prostate cancer in observational data and compared findings with those from a benchmark randomized clinical trial. METHODS We selected 14 302 early-stage prostate cancer patients who were aged 66-74 years and had been treated with radical prostatectomy or conservative management from linked Surveillance, Epidemiology, and End Results-Medicare data from January 1, 1995, through December 31, 2003. Eligibility criteria were similar to those from a clinical trial used to benchmark our analyses. Survival was measured through December 31, 2007, by use of Cox proportional hazards models. We compared results from the benchmark trial with results from models with observational data by use of traditional multivariable survival analysis, propensity score adjustment, and instrumental variable analysis. RESULTS Prostate cancer patients receiving conservative management were more likely to be older, nonwhite, and single and to have more advanced disease than patients receiving radical prostatectomy. In a multivariable survival analysis, conservative management was associated with greater risk of prostate cancer-specific mortality (hazard ratio [HR] = 1.59, 95% confidence interval [CI] = 1.27 to 2.00) and all-cause mortality (HR = 1.47, 95% CI = 1.35 to 1.59) than radical prostatectomy. Propensity score adjustments resulted in similar patient characteristics across treatment groups, although survival results were similar to traditional multivariable survival analyses. Results for the same comparison from the instrumental variable approach, which theoretically equalizes both observed and unobserved patient characteristics across treatment groups, differed from the traditional multivariable and propensity score results but were consistent with findings from the subset of elderly patient with early-stage disease in the trial (ie, conservative management vs radical prostatectomy: for prostate cancer-specific mortality, HR = 0.73, 95% CI = 0.08 to 6.73; for all-cause mortality, HR = 1.09, 95% CI = 0.46 to 2.59). CONCLUSION Instrumental variable analysis may be a useful technique in comparative effectiveness studies of cancer treatments if an acceptable instrument can be identified.
Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid

Objective. To investigate the effect of a chewing gum containing probiotic bacteria on gingival inflammation and the levels of selected inflammatory mediators in gingival crevicular fluid (GCF). Material and Methods. Forty-two healthy adults with moderate levels of gingival inflammation entered a double-blind placebo-controlled study design. The subjects were randomly assigned to one of three parallel arms: Group A/P was given one active and one placebo gum daily, Group A/A received two active chewing gums, and Group P/P two placebo gums. The chewing gums contained two strains of Lactobacillus reuteri: ATCC 55730 and ATCC PTA 5289 (1×108 CFU/gum, respectively). The subjects were instructed to chew the gums for 10 min over the course of 2 weeks. Bleeding on probing (BOP) and GCF sampling were conducted at baseline and after 1, 2 and 4 weeks. The levels of IL-1β, TNF-α, IL-6, IL-8 and IL-10 were determined using luminex technology and multiplex immunoassay kits. Results. BOP improved and GCF volume decreased in all groups during the chewing period, but the results were statistically significant (p<0.05) only in Groups A/P and A/A. The levels of TNF-α and IL-8 decreased significantly (p<0.05) in Group A/A compared with baseline after 1 and 2 weeks, respectively. A non-significant decreasing tendency was also observed concerning IL-1β during the chewing period. The levels of IL-6 and IL-10 were unaffected in all groups after 1 and 2 weeks. Conclusions. The reduction of pro-inflammatory cytokines in GCF may be proof of principle for the probiotic approach combating inflammation in the oral cavity.