Miracle-dz/UniFAR-FTUs huggingface dataset:
Menopausal estrogen use and risk of breast cancer

To assess the relationship of menopausal estrogens to breast cancer risk, the authors conducted a case‐control study among 881 cases and 863 controls identified through the Breast Cancer Detection Demonstration Project (BCDDP). Use of estrogens was associated with a relative risk (RR) of 1.24 (95% C.I. 1.0–1.5), with higher risks observed among users of high‐dose preparations. Hormone effects predominated among women who received them following bilateral oophorectomy (RR = 1.54), obliterating the protective effect normally associated with the operation. In this group, risk increased with years of estrogen use, reaching risks of 2–3 for users of ten or more years. High risks were also observed among oophorectomized women who used hormones in the presence of other risk factors, including nulliparity, family history of breast cancer, and benign breast disease. These results suggest a possible, although complex, relationship between estrogen use and risk of breast cancer.
Effects of sodium butyrate on growth performance, haematological and immunological characteristics of weanling piglets.

The experiment was conducted to study the effects of sodium butyrate (SB) on growth, haematological and immunological characteristics in weanling pigs. A total of 100 male piglets (Duroc×Landrace×Yorkshire) with a body weight of 8.0 ± 0.2 kg weaned at the age of 28 days were randomly assigned to two treatments with five replicates and 10 pigs per replicate. Piglets received a basal diet (control group) or diets supplemented with 1000 mg/kg SB. The feeding trial lasted for 21 days. The results showed that dietary SB significantly decreased (p < 0.05) diarrhoea incidence of weaned piglets, but did not affect (p > 0.05) the average daily feed intake (ADFI), average daily gain (ADG) and feed to gain (F/G). Furthermore, piglets fed dietary SB had higher (p < 0.05) serum concentrations of glucose and triglycerides and lower (p < 0.05) serum concentrations of urea nitrogen, cortisol, D-lactic acid and diamine oxidase when compared with the control group. However, dietary SB did not affect concentrations of serum albumin, total protein, insulin and glucagon (p > 0.05). There were no significant (p > 0.05) treatment effects on serum IgA and IgM, whereas serum IgG concentration and IgA+ cell count in jejunum from pigs fed SB were significantly higher (p < 0.05) than in those given the basal diet. In conclusion, the present study indicated that dietary SB significantly decreased diarrhoea incidence of weaned piglets and increased the efficiency of nitrogen utilization. Also, dietary SB could regulate and enhance the immune function of piglets by increasing the serum IgG concentration and IgA+ cell count in jejunum. Our results suggest that SB may reduce some of the adverse effects of weaning stress and play an important role in maintaining the integrity of intestinal mucosa.
Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study

BACKGROUND: Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking. METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7–17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. RESULTS: The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression–Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (–0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain. CONCLUSIONS: Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.
Pulmonary Bronchiolar Cytotoxicity and Formation of Dichloroacetyl Lysine Protein Adducts in Mice Treated with Trichloroethylene

This study was undertaken to test the hypothesis that bronchiolar damage induced by trichloroethylene (TCE) is associated with bioactivation within the Clara cells with the involvement of CYP2E1 and CYP2F2. Histopathology confirmed dose-dependent Clara cell injury and disintegration of the bronchiolar epithelium in CD-1 mice treated with TCE doses of 500 to 1000 mg/kg i.p. Immunohistochemical studies, using an antibody that recognizes dichloroacetyl lysine adducts, revealed dose-dependent formation of adducts in the bronchiolar epithelium. Localization of dichloroacetyl adducts in the Clara cells coincided with damage to this cell type in TCE-treated mice. Pretreatment of CD-1 mice with diallyl sulfone, an inhibitor of CYP2E1 and CYP2F2, abrogated the formation of the dichloroacetyl adducts and protected against TCE-induced bronchiolar cytotoxicity. Treatment of wild-type and CYP2E1-null mice with TCE (750 mg/kg i.p.) also elicited bronchiolar damage that correlated with the formation of adducts in the Clara cells. Immunoblotting, using lung microsomes from TCE-treated CD-1 mice, showed dose-dependent production of dichloroacetyl adducts that comigrated with CYP2E1 and CYP2F2. However, TCE treatment resulted in a loss of immunoreactive CYP2E1 and CYP2F2 proteins and p-nitrophenol hydroxylation, a catalytic activity associated with both cytochrome P450 enzymes. The TCE metabolite, chloral hydrate, was formed in incubations of TCE with lung microsomes from CD-1, wild-type, and CYP2E1-null mice. The levels were higher in CD-1 than in either wild-type or CYP2E1-null mice, although levels were higher in CYP2E1-null than in wild-type mice. These findings supported the contention that TCE bioactivation within the Clara cells, predominantly involving CYP2F2, correlated with bronchiolar cytotoxicity in mice.
Agri-environmental measures and farmers’ rent: evaluating the potential contribution of auctions to increase the efficiency of Agri-environmental schemes in Emilia-Romagna (Italy)

This work compares the cost-effectiveness of a simulated auction model (AM) with that of classical payment mechanisms as a marginal flat rate payment (MFR) and average flat rate payment (FR). The study provide an extension of the one-shot budget constrained auction model (BC) first introduced by Latacz-Lohmann and Van Der Hamsvoort (1997), and subsequently by Viaggi et al. (2008) and Glebe (2008). In this formulation, the model allows farmers to offer multi-dimensional bid as a combination of payment and a measure of a share of their land to commit to a hypothetical agri-environmental measure (AEM). The results show that the performance of the auction (i.e. 7.5 % and 27 % of the total UAA of the sample) is always located halfway between that of FR (i.e. 5% and 21 % of the total UAA of the sample) and that of MFR (i.e. 17% and 100% of the total UAA of the sample). According with Schillizzi and Latacz-Lohmann (2007) the flat rate option provides an amount of rents that is one and a half the auction’s rents with a lower budget and around two times greater with the higher budget level. The results confirm that the auction has the potential to reduce farmers’ information rent when compared with uniform policy instruments. However, the scale of saving depends crucially on auction design hypotheses and farmers' expectation about the maximum acceptable bid cap. The results of this research while attempting to provide a useful empirical exploration of auction theory cannot provide a comprehensive solution in most real world settings. However, it can contribute to feed the debate at EU policy level about the role of tendering instruments in agri-environmental programs to reduce the inefficiency related to the actual agri-environmental payments.
HPV self‐sampling or the Pap‐smear: A randomized study among cervical screening nonattenders from lower socioeconomic groups in France

Today in France, low attendance to cervical screening by Papanicolaou cytology (Pap‐smear) is a major contributor to the 3,000 new cervical cancer cases and 1,000 deaths that occur from this disease every year. Nonattenders are mostly from lower socioeconomic groups and testing of self‐obtained samples for high‐risk Human Papilloma virus (HPV) types has been proposed as a method to increase screening participation in these groups. In 2011, we conducted a randomized study of women aged 35–69 from very low‐income populations around Marseille who had not responded to an initial invitation for a free Pap‐smear. After randomization, one group received a second invitation for a free Pap‐smear and the other group was offered a free self‐sampling kit for HPV testing. Participation rates were significantly different between the two groups with only 2.0% of women attending for a Pap‐smear while 18.3% of women returned a self‐sample for HPV testing (p ≤ 0.001). The detection rate of high‐grade lesions (≥CIN2) was 0.2‰ in the Pap‐smear group and 1.25‰ in the self‐sampling group (p = 0.01). Offering self‐sampling increased participation rates while the use of HPV testing increased the detection of cervical lesions (≥CIN2) in comparison to the group of women receiving a second invitation for a Pap‐smear. However, low compliance to follow‐up in the self‐sampling group reduces the effectiveness of this screening approach in nonattenders women and must be carefully managed.
Differentiation and Visualization of Diverse Cellular Phenotypic Responses in Primary High-Content Screening

High-throughput screening, based on subcellular imaging, has become a powerful tool in lead discovery. Through the generation of high-quality images, not only the specific target signal can be analyzed but also phenotypic changes of the whole cell are recorded. Yet analysis strategies for the exploration of high-content screening results, in a manner that is independent from predefined control phenotypes, are largely missing. The approach presented here is based on a well-established modeling technique, self-organizing maps (SOMs), which uses multiparametric results to group treatments that create similar morphological effects. This report describes a novel visualization of the SOM clustering by using an image of the cells from each node, with the most representative cell highlighted to deploy the phenotype described by each node. The approach has the potential to identify both expected hits and novel cellular phenotypes. Moreover, different chemotypes, which cause the same phenotypic effects, are identified, thus facilitating “scaffold hopping. ”
Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma

Lung carcinoma usually is advanced at the time of presentation and frequently shows metastatic spread. In recent times, prognostic factors such as c‐erbB‐2 in patients with breast carcinoma have provided useful information and beneficial therapeutic targets. The objective of this study was to evaluate angiogenesis, immune function, and telomerase expression in patients with nonsmall cell lung carcinoma (NSCLC) to determine their prognostic significance.
Role of mammalian target of rapamycin signaling in autophagy and the neurodegenerative process using a senescence accelerated mouse-prone 8 model

The mammalian target of rapamycin (mTOR) kinase is an inhibitor of autophagy, which is an intracellular system involved in the degradation of long-lived proteins and organelles in lysosomes. Recent evidence suggests that the steady incline in mTOR function during aging may be associated with the cognitive decline related to aging and may also promote development of Tau pathology. At present, the senescence accelerated mouse prone 8 (SAMP8) is an experimental model that has been proposed for the study of age-related neurodegenerative changes associated with aging. In the present study, mTOR signaling in the hippocampus of SAMP8 newborn mice and in the control-strain SAMR1 mice was investigated. Consequently, hyper phosphorylated Tau (pS199 or pS396) and upregulated mTOR activity were observed in SAMP8 when compared with SAMR1; however, 0.5 µM rapamycin administration significantly reduced the levels of phosphorylated Tau and p70S6K (pT389) in SAMP8 mice. Related to these findings, SAMP8 exhibited an increase in the neuronal loss of hippocampus that was associated with lower levels of anti-apoptotic proteins. These results indicate that mTOR signaling participates in the neurodegenerative process and rapamycin administration may protect neurons of SAMP8 mice and may have a potential role in curing cognitive decline.
Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases

Background Human tissue kallikreins are a gene family (KLK1–KLK15) encoding for 15 secretory serine proteases (hK1–hK15). Two tissue kallikrein proteins, hK5 and hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG) and appendages. hK8 was also shown to be secreted via lamellar granules and numerous KLK mRNAs were previously identified. KLKs are believed to be responsible for desquamation of corneocytes and sebum, sweat and hair maturation.
A systematic review of networked technologies supporting carers of people with dementia

Summary We conducted a systematic review of the effectiveness of networked ICT interventions in supporting carers of people with dementia. Five bibliographic databases were searched and a total of 1456 abstracts were identified as potentially relevant. From these we identified 15 papers describing five interventions: ComputerLink, AlzOnline, Caring for Others and two studies from the REACH project (TLC and CTIS). The interventions reviewed were multifaceted with elements of networked peer support. Outcomes were inconsistent but suggested that the interventions had moderate effects on improving carer stress and depression. Treatment effects were found to vary with caregiver characteristics such as ethnic groups, formal support and baseline burden. Further evaluation is needed in robust trials with good follow-up.
Alterations in interleukin-2 utilization by T-cells from rats treated with an ethanol-containing diet.

Administration of ethanol to Sprague-Dawley rats has been shown to produce a defect in lymphocyte proliferation in response to concanavalin A. Because a critical element in T-cell proliferation is the production of interleukin-2, experiments were designed to evaluate the influence of ethanol on the production and utilization of interleukin-2 by spleen cells from ethanol-treated animals. To ensure that changes in spleen cell responses to mitogenic stimulation were not simply caused by a loss of responding T cells, we tested nylon wool-nonadherent cells. The response to concanavalin A of isolated T cells from ethanol-treated rats was consistently less than that of equivalent numbers of cells from control animals. The addition of recombinant interleukin-2 to cultures of T cells did not correct the defect in proliferation to concanavalin A noted in cells from ethanol-treated rats. Further study results demonstrated that interleukin-2 production by T cells from ethanol-treated animals was equal to or greater than that by cells from animals given control diet. Blast cells recovered from 48-hr concanavalin A-stimulated spleen cell cultures from ethanol-treated animals, however, showed a decreased ability to proliferate in response to exogenous interleukin-2. Binding of 125I-interleukin-2 to blast cells resulting from concanavalin A stimulation, under conditions that detected high-affinity binding, was similar in cells from treated and control animals. These data indicate that the deficiency in proliferation of lymphocytes from ethanol-treated animals is not caused by a lack of interleukin-2 production by the T cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Correction of Clawtoes by the Girdlestone-Taylor Flexor-Extensor Transfer Procedure

Several techniques have been suggested for correction of clawtoe deformities in the lateral toes, ranging from multiple arthrodesis of the interphalangeal joints to phalanx resections, partial or total amputation of the impaired toes. An evaluation of the flexor-extensor transfer procedure is the basis of this study. Between 1977 and 1983, 39 feet were operated on in 31 patients, presenting a wide variation in etiology, degree of deformity, and symptoms. Average age at the time of surgery was 57.5 (16 to 80). All of the patients were available for recall and were able to return for an interview and examination. Average length of follow-up was 38 months (range, 10–80 months). The report includes a general discussion of the deformities, description of the operative technique, and the results obtained in our series. Assessment emphasized a subjective report including patient satisfaction, cosmetic result, relief of pain, and objective examination to evaluate the presence of recurrent callosities, range of movement at the metatarsophalangeal joint, and degree of residual passive mobility of the toes. Reduction of metatarsalgia and callosities with improved shape of the toes was achieved in most cases. Our experience indicates that the treatment can be recommended for use in the elderly, too, in appropriate cases. Radical procedures are rarely accepted for cosmetic as well as for functional reasons.
Accounting for dropout reason in longitudinal studies with nonignorable dropout

Dropout is a common problem in longitudinal cohort studies and clinical trials, often raising concerns of nonignorable dropout. Selection, frailty, and mixture models have been proposed to account for potentially nonignorable missingness by relating the longitudinal outcome to time of dropout. In addition, many longitudinal studies encounter multiple types of missing data or reasons for dropout, such as loss to follow-up, disease progression, treatment modifications and death. When clinically distinct dropout reasons are present, it may be preferable to control for both dropout reason and time to gain additional clinical insights. This may be especially interesting when the dropout reason and dropout times differ by the primary exposure variable. We extend a semi-parametric varying-coefficient method for nonignorable dropout to accommodate dropout reason. We apply our method to untreated HIV-infected subjects recruited to the Acute Infection and Early Disease Research Program HIV cohort and compare longitudinal CD4+ T cell count in injection drug users to nonusers with two dropout reasons: anti-retroviral treatment initiation and loss to follow-up.
Teratoma Derived From Bone Marrow Mesenchymal Stem Cells in a Diabetic Microenvironment

To the Editor: In a recent paper, Carroccio et al 1 showed that patients with celiac disease (CD) may have an abnormal serum elevation of amylase and/or lipase and that this elevation regresses after treatment of the CD. The authors suggested that this increase of serum pancreatic enzymes in subjects with CD may be a result of subclinical autoimmune pancreatic damage. Prompted by these findings, in this study, we attempted to see whether subjects with asymptomatic, apparently benign pancreatic hyperenzymemia have laboratory findings indicating the presence of CD. To diagnose this disease, we measured serum IgA and IgG tissue transglutaminase antibodies, highly sensitive and specific tests for the diagnosis of CD.
Diagnostic role of serum glypican‐3 in differentiating hepatocellular carcinoma from non‐malignant chronic liver disease and other liver cancers

Background and Aims: The role of glypican‐3 (GPC3), a novel serum marker, in differentiating hepatocellular carcinoma (HCC) from non‐malignant chronic liver disease and other malignant space‐occupying lesions in the liver is largely unknown. The aims of this study were to evaluate its diagnostic role and clinical correlations in patients with HCC.
Regulatory Forum Commentary* Counterpoint

High-dose selection for 6-month carcinogenicity studies of pharmaceutical candidates in Tg.rasH2-transgenic mice currently primarily relies on (1) estimation of a maximum tolerated dose (MTD) from the results of a 1-month range-finding study, (2) determination of the maximum dose administrable to the animals (maximum feasible dose [MFD]), (3) demonstration of a plateau in systemic exposure, and (4) use of a limit dose of 1,500 mg/kg/day for products with human daily doses not exceeding 500 mg. Eleven 6-month Tg.rasH2 carcinogenicity studies and their corresponding 1-month range-finding studies conducted at Merck were reviewed. High doses were set by estimation of the MTD in 6, by plateau of exposure in 3, and by MFD in 2 cases. For 4 of 6 studies where MTD was used for high-dose selection, the 1-month study accurately predicted the 6-month study tolerability whereas in the remaining 2 studies the high doses showed poorer tolerability than expected. The use of 3 or more drug-treated dose levels proved useful to ensure that a study would successfully and unambiguously demonstrate that a drug candidate was adequately evaluated for carcinogenicity at a minimally toxic high dose level, especially when the high dose may be found to exceed the MTD.
Rate of and Risks for Regression of Cervical Intraepithelial Neoplasia 2 in Adolescents and Young Women

OBJECTIVE: To describe the natural history of cervical intraepithelial neoplasia (CIN) 2 in a prospective study of adolescents and young women, and to examine the behavioral and biologic factors associated with regression and progression. METHODS: Adolescents and women aged 13 to 24 years who were referred for abnormal cytology and were found to have CIN 2 on histology were evaluated at 4-month intervals. Risks for regression were defined as three consecutive negative cytology and histology visits, and progression to CIN 3 was estimated using Cox proportional hazards regression models. RESULTS: Ninety-five patients with a mean age of 20.4 years (±2.3) were entered into the analysis. Thirty-eight percent resolved by year 1, 63% resolved by year 2, and 68% resolved by year 3. Multivariable analysis found that recent Neisseria gonorrhoeae infection (hazard ratio 25.27; 95% confidence interval [CI] 3.11–205.42) and medroxyprogesterone acetate use (per month) (hazard ratio 1.02; 95% CI 1.003–1.04) were associated with regression. Factors associated with nonregression included combined hormonal contraception use (per month) (hazard ratio 0.85; 95% CI 0.75–0.97) and persistence of human papillomavirus (HPV) of any type (hazard ratio 0.40; 95% CI 0.22–0.72). Fifteen percent of patients showed progression by year 3. HPV 16/18 persistence (hazard ratio 25.27; 95% CI 2.65–241.2; P=.005) and HPV 16/18 status at last visit (hazard ratio 7.25; 95% CI 1.07–49.36; P<.05) were associated with progression Because of the small sample size, other covariates were not examined. CONCLUSION: The high regression rate of CIN 2 supports clinical observation of this lesion in adolescents and young women. LEVEL OF EVIDENCE: II