Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormone therapy and ovarian cancer.

CONTEXT Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE To assess risk of ovarian cancer in perimenopausal and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age bands included hormone exposures as time-dependent covariates. PARTICIPANTS A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE Ovarian cancer. RESULTS In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian cancers, of which 2681 were epithelial cancers, were detected. Compared with women who never took hormone therapy, current users of hormones had incidence rate ratios for all ovarian cancers of 1.38 (95% confidence interval [CI], 1.26-1.51) and 1.44 (95% CI, 1.30-1.58) for epithelial ovarian cancer. The risk declined with years since last use: 0 to 2 years, 1.22 (95% CI, 1.02-1.46); more than 2 to 4 years, 0.98 (95% CI, 0.75-1.28); more than 4 to 6 years, 0.72 (95% CI, 0.50-1.05), and more than 6 years, 0.63 (95% CI, 0.41-0.96). For current users the risk of ovarian cancer did not differ significantly with different hormone therapies or duration of use. The incidence rates in current and never users of hormones were 0.52 and 0.40 per 1000 years, respectively, ie, an absolute risk increase of 0.12 (95% CI, 0.01-0.17) per 1000 years. This approximates 1 extra ovarian cancer for roughly 8300 women taking hormone therapy each year. CONCLUSION Regardless of the duration of use, the formulation, estrogen dose, regimen, progestin type, and route of administration, hormone therapy was associated with an increased risk of ovarian cancer.
Patients with diabetes and depression may need additional support for exercise.

OBJECTIVE To examine the association between depressive symptoms and exercise-related variables among patients with type 2 diabetes. METHODS Surveys were completed by 207 primary care patients diagnosed with type 2 diabetes (52% female; 95% white; mean age = 63 years). Multiple linear regression analyses were conducted. RESULTS Lower use of relapse prevention behavior was significantly associated with higher depression scores in a multivariate model. CONCLUSIONS Patients with diabetes and depression have barriers to exercise (eg, fewer skills for relapse prevention) and may require additional support for exercise initiation and maintenance.
Prevalence of various mutations in beta thalassaemia and its association with haematological parameters.

OBJECTIVE To determine the prevalence of various mutations in beta (beta) thalassaemia and its association with haematological parameters. METHODS A descriptive cross sectional study was carried out in the Department of Haematology, Armed Forced Institute of Pathology (AFIP) from February 2009 to January 2010. A total of 515 carriers having beta thalassaemia mutations characterized by Multiplex amplification refractory mutation system (ARMS) were included in the study. Frequencies of different beta thalassaemia mutations were calculated. Mutations were analyzed for their haematological parameters which include total red blood cell count (TRBC), haemoglobin (Hb), mean cell volume (MCV), mean cell haemoglobin (MCH) and red cell distribution width (RDW). RESULTS Frame shift (Fr) 8-9 was the most common mutation found in 183 (35.5%) of patients followed by intervening sequence 1-5 (IVSI-5) in 126 (24.5%) and Fr 41-42 in 76 (14.8%) while IVSII-1 was the least common mutation found in 1 patient. Fr 8-9 was also the commonest mutation in Punjabis and Pathans. Predominant mutation in other ethnic carriers was IVSI-5. Patients with Fr 8-9 mutation had the lowest mean MCV and MCH of 63.7fl and 19.1pg, of all the mutations. Patients with CAP+1 mutation had mean TRBC, Hb, MCV, MCH and RDW of 5.5 x 1012/L, 13.5g/dl, 78.0fl, 24.7pg and 41.9fl respectively. CONCLUSION Fr 8-9 is the most common beta thalassaemia mutation with lowest red cell indices while CAP+1 mutation can present with normal red cell values therefore, a potential carrier should be screened for CAP+1 mutation by DNA analysis.
Smallest singular value of sparse random matrices

We extend probability estimates on the smallest singular value of random matrices with independent entries to a class of sparse random matrices. We show that one can relax a previously used condition of uniform boundedness of the variances from below. This allows us to consider matrices with null entries or, more generally, with entries having small variances. Our results do not assume identical distribution of the entries of a random matrix and help to clarify the role of the variances of the entries. We also show that it is enough to require boundedness from above of the $r$-th moment, $r > 2$, of the corresponding entries.
Accurate SFS Parameter Design Criterion for Inverter-Based Distributed Generation

The Sandia frequency-shift method, among all frequency-based active islanding detection methods (IDMs), is one of the most effective methods for inverter based distributed generators (DGs). The nondetection zone (NDZ) of the Sandia frequency shift (SFS) highly depends on its design parameters. If the design parameters are not properly tuned, they may result in failure of the method or deterioration of the system power quality (PQ) through injection of a high amount of harmonics. The main objective of this paper is to propose a new algorithm for SFS method parameter determination, which would add precision to the previous parameter design criterion. In this paper, also a new formula for multi-DG applications is proposed which results in optimally setting of all SFS parameters to eliminate NDZ. Using the new criterion, the negative impact of the conventional criterion on PQ is reduced, and the efficiency of the SFS IDM is increased. The simulation results show that the proposed algorithm results in more accurate detection of the islanding phenomenon in the shortest possible time. All of the simulations and NDZ analysis are carried out in the MATLAB environment.
Gender differences in long-term health consequences of physical abuse of children: data from a nationally representative survey.

OBJECTIVES This study investigated the effects of physical abuse in childhood on health problems in adulthood and assessed gender differences in these associations. METHODS We used data from 8000 men and 8000 women who were interviewed in the National Violence Against Women Survey. We used multivariate logistic regression to test for main and interactive effects and conducted post hoc probing of significant moderational effects. RESULTS Men were more likely than women to have experienced physical abuse during childhood. Whereas abuse had negative consequences for both boys and girls, it was generally more detrimental for girls. CONCLUSIONS Findings suggest the need to consider gender differences and long-term adverse health consequences in the development of intervention strategies to address physical abuse in childhood.
2‐Arachidonoylglycerol elicits neuroprotective effects on excitotoxically lesioned dentate gyrus granule cells via abnormal‐cannabidiol‐sensitive receptors on microglial cells

Endocannabinoids like 2‐arachidonoylglycerol (2‐AG) exert neuroprotective effects after brain injuries. According to current concepts, these neuroprotective effects are due to interactions between 2‐AG and cannabinoid (CB)1 receptors on neurons. Moreover, 2‐AG modulates migration and proliferation of microglial cells which are rapidly activated after brain lesion. This effect is mediated via CB2‐ and abnormal‐cannabidiol (abn‐CBD)‐sensitive receptors. In the present study, we investigated whether the abn‐CBD‐sensitive receptor on microglial cells contributes to 2‐AG‐mediated neuroprotection in organotypic hippocampal slice cultures (OHSCs) after excitotoxic lesion induced by NMDA (50 μM) application for 4 h. This lesion caused neuronal damage and accumulation of microglial cells within the granule cell layer. To analyze the role of abn‐CBD‐sensitive receptors for neuroprotection and microglial cell accumulation, two agonists of the abn‐CBD‐sensitive receptor, abn‐CBD or 2‐AG, two antagonists, 1,3‐dimethoxy‐5‐methyl‐2‐[(1R,6R)‐3‐methyl‐6‐(1‐methylethenyl)‐2‐cyclohexen1‐yl]‐benzene (O‐1918) or cannabidiol (CBD), and the CB1 receptor antagonist AM251, were applied to NMDA‐lesioned OHSC. Propidium iodide (PI) labeling was used as a marker of degenerating neurons and isolectin B4 (IB4) as a marker of microglial cells. Application of both, abn‐CBD or 2‐AG to lesioned OHSC significantly decreased the number of IB 4+ microglial cells and PI+ neurons in the dentate gyrus. In contrast to AM251, application of O‐1918 or CBD antagonized these effects. When microglial cells were depleted by preincubation of OHSC with the bisphosphonate clodronate (100 μg/mL) for 5 days before excitotoxic lesion, 2‐AG and abn‐CBD lost their neuroprotective effects. We therefore propose that the endocannabinoid 2‐AG exerts its neuroprotective effects via activation of abn‐CBD‐sensitive receptors on microglial cells. © 2008 Wiley‐Liss, Inc.
Brain arterial remodeling contribution to nonembolic brain infarcts in patients with HIV

Background: Cerebrovascular disease is a cause of morbidity in HIV-infected populations. The relationship among HIV infection, brain arterial remodeling, and stroke is unclear. Methods: Large brain arteries (n = 1,878 segments) from 284 brain donors with and without HIV were analyzed to obtain media and wall thickness and lumen-to-wall ratio, and to determine the presence of atherosclerosis and dolichoectasia (arterial remodeling extremes). Neuropathologic assessment was used to characterize brain infarcts. Multilevel models were used to assess for associations between arterial characteristics and HIV. Associations between arterial characteristics and brain infarcts were examined in HIV+ individuals only. Results: Adjusting for vascular risk factors, HIV infection was associated with thicker arterial walls and smaller lumen-to-wall ratios. Cerebral atherosclerosis accounted for one-quarter of the brain infarcts in HIV+ cases, and was more common with aging, diabetes, a lower CD4 nadir, and a higher antemortem CD4 count. In contrast, a higher lumen-to-wall ratio was the only arterial predictor of unexplained infarcts in HIV+ cases. Dolichoectasia was more common in HIV+ cases with smoking and media thinning, and with protracted HIV infection and a detectable antemortem viral load. Conclusions: HIV infection may predispose to inward remodeling compared to uninfected controls. However, among HIV+ cases with protracted immunosuppression, outward remodeling is the defining arterial phenotype. Half of all brain infarcts in this sample were attributed to the extremes of brain arterial remodeling: atherosclerosis and dolichoectasia. Understanding the mechanisms influencing arterial remodeling will be important in controlling cerebrovascular disease in the HIV-infected population.
Upregulation of Bradykinin B2 Receptor Expression by Neurotrophic Factors and Nerve Injury in Mouse Sensory Neurons

Bradykinin B2 receptor mRNA was detected at low levels, both by RT-PCR and by in situ hybridization, in freshly isolated dorsal root ganglia (DRG) and in ganglia cultured in the absence of neurotrophic factors, but was strongly upregulated by culture in the presence of nerve growth factor (NGF). The effect of NGF is mediated via TrkA receptors. The related neurotrophins, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4, were ineffective in upregulating B2 mRNA, but a small upregulation was seen with the unrelated neurotrophin glial cell line-derived neurotrophic factor (GDNF). Surface membrane B2 receptor expression, detected by immunofluorescence using a B2-specific antibody, was low in outgrowing axons cultured in the absence of neurotrophic factors, but was elevated by addition of NGF or GDNF. Conditioned media prepared by incubating injured nerve, skin, or muscle had a similar effect to NGF in upregulating B2 mRNA and protein expression, and the activity was largely removed by neutralization of NGF in the conditioned medium with an anti-NGF antibody. After nerve crush injury in vivo an enhancement in B2 mRNA expression was seen, peaking after 7 days and returning to precrush levels after 14 days. In all conditions tested, the proportion of neurons expressing B2 mRNA remained the same at around 23% of small neurons, suggesting that upregulation only occurs in the B2-positive neurons. These experiments show that NGF, and to a lesser extent GDNF, upregulates the expression of bradykinin B2 mRNA and B2 receptor protein in the surface membrane of DRG neurons and that NGF is an important factor responsible for upregulating bradykinin B2 receptor expression after nerve crush injury in vivo.
Testing for inconsistencies in the estimation of UK capital structure determinants

This article analyses the determinants of the capital structure of 1054 UK companies from 1991 to 1997, and the extent to which the influence of these determinants are affected by time-invariant firm-specific heterogeneity. Comparing the results of pooled OLS and fixed effects panel estimation, significant differences in the results are found. While the OLS results are generally consistent with prior literature, the results of our fixed effects panel estimation contradict many of the traditional theories of the determinants of corporate financial structure. This suggests that results of traditional studies may be biased owing to a failure to control for firm-specific, time-invariant heterogeneity. The results of the fixed effects panel estimation find larger companies to have higher levels of both long-term and short-term debt than do smaller firms, profitability to be negatively correlated with the level of gearing, although profitable firms tend to have more short-term bank borrowing than less profitable firms, and tangibility to positively influence the level of short-term bank borrowing, as well as all long-term debt elements. However, the level of growth opportunities appears to have little influence on the level of gearing, other than short-term bank borrowing, where a significant negative relationship is observed.
Retrospective analysis of post-exposure to human anti-rabies treatment in Botucatu, São Paulo State, Brazil

This analysis aimed to identify characteristics of accidents that would, probably, provoke rabies infection. A total of 14,409 survey questionnaires for surveillance of human rabies from the Brazilian Information System for Disease Notification (SINAN), from 2000 to 2005, were analyzed. Regarding demographics, it was observed that 7,377 (51.5%) of the victims were white, 4,458 (30.93%) were children and 8,008 (55.58%) were males. Urban cases were prevalent (88.10%) while dogs were the animals most frequently involved in accidents, in 11,700 cases (81.19%). Bites (84.35%) and scratches (19.15%) were the most prevalent exposure types, and occurred predominantly on victims' extremities (38.79%). The prophylactic measure taken in 6,179 cases comprised anti-rabies vaccine; of these victims, 421 (2.92%) showed systemic reactions while 693 (4.80%) reported no response. The importance of developing awareness in professionals that should correctly report post-exposure immunoprophylaxis cases is emphasized given the high number of individuals who receive this type of treatment annually.
Polycomb Repressive Complex 2 Confers BRG1 Dependency on the CIITA Locus

CIITA (or MHC2TA) coordinates constitutive and IFN-γ–induced expression of MHC class II genes. IFN-γ responsiveness of CIITA requires BRG1 (SMARCA4), the ATPase engine of the chromatin remodeling SWI/SNF complex (also called BAF). SWI/SNF is defective in many human cancers, providing a mechanism to explain IFN-γ resistance. BRG1 dependency is mediated through remote elements. Short CIITA reporters lacking these elements respond to IFN-γ, even in BRG1-deficient cells, suggesting that BRG1 counters a remote repressive influence. The nature of this distal repressor is unknown, but it would represent a valuable therapeutic target to reactivate IFN-γ responsiveness in cancer. In this article, we show that the polycomb repressive complex 2 (PRC2) components EZH2 and SUZ12, as well as the associated histone mark H3K27me3, are codetected at interenhancer regions across the CIITA locus. IFN-γ caused a BRG1-dependent reduction in H3K27me3, associated with nucleosome displacement. SUZ12 knockdown restored IFN-γ responsiveness in BRG1-null cells, and it mimicked the ability of BRG1 to induce active histone modifications (H3K27ac, H3K4me) at the −50-kb enhancer. Thus, PRC2 confers BRG1 dependency on the CIITA locus. Our data suggest that, in addition to its known roles in promoting stemness and proliferation, PRC2 may inhibit immune surveillance, and it could be targeted to reactivate CIITA expression in SWI/SNF deficient cancers.
Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression.

BACKGROUND Sleep effects of antidepressants are important clinically and for elucidating mechanism of action: selective serotonin reuptake inhibitors disturb sleep and 5-HT(2) receptor-blocking compounds may enhance sleep quality. AIMS To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression. METHOD Forty patients with depression were randomised to take paroxetine 20-40 mg/day or nefazodone 400-600 mg/day for 8 weeks. Objective and subjective quality of sleep and depression measures were assessed throughout. RESULTS Nefazodone significantly increased objective sleep efficiency and total sleep time, and improved subjective sleep on days 3 and 10. Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8. Paroxetine but not nefazodone produced marked suppression of rapid eye movement (REM) sleep. CONCLUSIONS Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression. These effects are seen within the first 2 weeks of treatment and diminish thereafter.
Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes

After sarcoplasmic reticulum (SR) Ca2+ depletion in intact ventricular myocytes, electrical activity promotes SR Ca2+ reloading and recovery of twitch amplitude. In ferret, recovery of twitch and caffeine‐induced contracture required fewer twitches than in rabbit or rat. In rat, there was no difference in action potential duration at 90% repolarization (APD90) at steady state (SS) versus at the first post‐depletion (PD) twitch. The SS APD90 was similar in ferret and rabbit (but longer than in rat). However, compared to SS, the PD APD90 was lengthened in ferret, but shortened in rabbit. When rabbit myocytes were subjected to AP‐clamp patterns during SR Ca2+ reloading (ferret‐ or rabbit‐type APs), reloading was much faster using the ferret AP templates. We conclude that the faster SR Ca2+ refilling in ferret is due to the increased Ca2+ influx during the longer PD AP. The PD versus SS APD90 difference was suppressed by thapsigargin in ferret (indicating Ca2+ dependence). In rabbit, the PD AP shortening depended on the preceding diastolic interval (rather than Ca2+), because rest produced the same AP shortening, and SS APD90 increased as a function of frequency (in contrast to ferret). Transient outward current (Ito) was larger and recovered from inactivation much faster in ferret than in rabbit. Moreover, slow Ito recovery (τ∼ 3 s) in rabbit was a much larger fraction of Ito. Our data and a computational model (including two Ito components) suggest that in rabbit the slowly recovering Ito is responsible for short post‐rest and PD APs, for the unusual frequency dependence of APD90, and ultimately for the slower post‐depletion SR Ca2+ reloading.
Relative and combined performance of mammography and ultrasonography for breast cancer screening in the general population: a pilot study in Tochigi Prefecture, Japan.

BACKGROUND Breast cancer screening by mammography is thought to be effective in reducing breast cancer mortality while ultrasonography is not accepted as a population screening modality, although the latter has been suggested to be useful in detection of cancer in the dense breast, relatively more typical for a younger woman. METHODS Mammography with medio-lateral oblique view was offered on trial in 1999-2000 for 3453 female residents in Tochigi prefecture who also underwent clinical breast examination and ultrasonography. The municipalities that provided cancer screening were informed of the final diagnosis for women with positive findings in the screening trial by doctors who performed the diagnostic evaluation. Linkage was also made between the list of participants in the trial and registrations at Tochigi Cancer Registry for breast cancer cases diagnosed during 1999-2001. RESULTS Thirteen cases with breast cancer were identified during a 2-year follow-up period: 10 were diagnosed subsequent to positive finding in the trial; two were negative in the trial and diagnosed 23 and 24 months after, respectively; and one had a positive finding at the trial but was undiagnosed at first and then diagnosed 18 months after the trial. Among the 11 cases judged as positive in the trial, four were judged only by mammography while three were judged only by ultrasonography. Those mammography alone-detected cases were relatively young, at 36, 40, 47 and 54 years of age, respectively, while the ultrasonography alone-detected cases were aged 50, 55 and 68, respectively. CONCLUSIONS Combined screening with mammography and ultrasonography may be feasible. A larger study is required to evaluate relative performance of mammography and ultrasonography in detail by characteristics of examinees and their breasts.