Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduced mortality associated with the use of ACE inhibitors in patients with type 2 diabetes.

OBJECTIVE ACE inhibitor therapy is widely used in lower-risk patients with type 2 diabetes to reduce mortality, despite limited evidence to support this clinical strategy. The aim of this study was to evaluate the association between ACE inhibitor use and mortality in patients with diabetes and no cardiovascular disease. RESEARCH DESIGN AND SETTINGS: Using the Saskatchewan health databases, 12,272 new users of oral hypoglycemic agents were identified between the years of 1991 and 1996. We excluded 3,202 subjects with previous cardiovascular disease. Of the remaining subjects, 1,187 "new users" of ACE inhibitors were identified (ACE inhibitor cohort). Subjects not receiving ACE inhibitor therapy throughout the follow-up period served as the control cohort (n = 4,989). Subjects were prospectively followed until death or the end of 1999. Multivariate Cox proportional hazards models were used to assess differences in all-cause and cardiovascular-related mortality between cohort groups. RESULTS Subjects were 60.7 +/- 13.7 years old, 43.6% female, and were followed for an average of 5.3 +/- 2.1 years. Mean duration of ACE inhibitor therapy was 3.6 +/- 1.8 years. We observed significantly fewer deaths in the ACE inhibitor group (102 [8.6%]) compared with the control cohort (853 [17.1%]), with an adjusted hazard ratio (HR) and 95% CI of 0.49 (0.40-0.61) (P < 0.001). Cardiovascular-related mortality was also reduced (40 [3.4%] vs. 261 [5.2%], adjusted HR, 0.63 [0.44-0.90]; P = 0.012). CONCLUSIONS The use of ACE inhibitors was associated with a significant reduction in all-cause and cardiovascular-related mortality in a broad spectrum of patients with type 2 diabetes and no cardiovascular disease.
Coordination of Cell Signaling, Chromatin Remodeling, Histone Modifications, and Regulator Recruitment in Human Matrix Metalloproteinase 9 Gene Transcription

ABSTRACT Transcriptional activation of eukaryotic genes depends on the precise and ordered recruitment of activators, chromatin modifiers/remodelers, coactivators, and general transcription factors to the promoters of target genes. Using the human matrix metalloproteinase 9 (MMP-9) gene as a model system, we investigated the sequential assembly and dynamic formation of transcription complexes on a human promoter under the influence of mitogen signaling. We find that, coincident with activation of the MMP-9 gene, activators, chromatin remodeling complexes, and coactivators are recruited to the preassembled MMP-9 promoter in a stepwise and coordinated order, which is dependent on activation of MEK-1/extracellular signal-regulated kinase and NF-κB signaling pathways. Conversely, corepressor complexes are released from the MMP-9 promoter after transcriptional activation. Histone modifications shift from repressive to permissive modifications concurrent with activation of the MMP-9 gene. Chromatin remodeling induced by Brg-1 is required for MMP-9 gene transcription, which is concomitant with initiation of transcription. Therefore, coordination of cell signaling, chromatin remodeling, histone modifications, and stepwise recruitment of transcription regulators is critical to precisely regulate MMP-9 gene transcription in a temporally and spatially dependent manner. Given the important role of MMP-9 in both normal development and pathological conditions, understanding MMP-9 gene regulation is of great relevance.
Diffuse Lewy body disease and progressive dementia

Thirty cases of diffuse Lewy body disease (DLBD) have been reported, primarily by neuropathologists, but an associated clinical syndrome has not been clearly defined. Four recent cases have led us to examine the clinicopathologic correlations. Patients are usually elderly, with symptoms lasting from 1 to 20 years. Progressive dementia or psychosis is typically the first and most prominent feature. Parkinsonian signs, initially mild or absent, become common eventually, and rigidity is usually severe. Involuntary movements, myoclonus, quadriparesis in flexion, orthostatic hypotension, and dysphagia have also been noted. Classic, concentric Lewy bodies are found profusely in the brainstem, basal forebrain, and hypothalamic nuclei, while less well defined "Lewy-like" bodies occur in limbic structures and in deep neocortical layers. In addition, focal spongiform changes in the mesial temporal lobe were found in two of our cases. We suggest that DLBD may be another specific cause of progressive dementia.
Expression of Activated Ras in Gastric Chief Cells of Mice Leads to the Full Spectrum of Metaplastic Lineage Transitions.

BACKGROUND & AIMS Gastric cancer develops in the context of parietal cell loss, spasmolytic polypeptide-expressing metaplasia (SPEM), and intestinal metaplasia (IM). We investigated whether expression of the activated form of Ras in gastric chief cells of mice leads to the development of SPEM, as well as progression of metaplasia. METHODS We studied Mist1-CreERT2Tg/+;LSL-K-Ras(G12D)Tg/+ (Mist1-Kras) mice, which express the active form of Kras in chief cells on tamoxifen exposure. We studied Mist1-CreERT2Tg/+;LSL-KRas (G12D)Tg/+;R26RmTmG/+ (Mist1-Kras-mTmG) mice to examine whether chief cells that express active Kras give rise to SPEM and IM. Some mice received intraperitoneal injections of the Mitogen-activated protein kinase kinase (MEK) inhibitor, selumetinib, for 14 consecutive days. Gastric tissues were collected and analyzed by immunohistochemistry, immunofluorescence, and quantitative polymerase chain reaction. RESULTS Mist1-Kras mice developed metaplastic glands, which completely replaced normal fundic lineages and progressed to IM within 3-4 months after tamoxifen injection. The metaplastic glands expressed markers of SPEM and IM, and were infiltrated by macrophages. Lineage tracing studies confirmed that the metaplasia developed directly from Kras (G12D)-induced chief cells. Selumetinib induced persistent regression of SPEM and IM, and re-established normal mucosal cells, which were derived from normal gastric progenitor cells. CONCLUSIONS Expression of activated Ras in chief cells of Mist1-Kras mice led to the full range of metaplastic lineage transitions, including SPEM and IM. Inhibition of Ras signaling by inhibition of MEK might reverse preneoplastic metaplasia in the stomach.
Polymorphonuclear Leukocytes: Rickettsiacidal and Leukotoxic Activities

Rickettsia prowazekii was assessed for in vitro susceptibility to phagocytosis by rabbit polymorphonuclear leukocytes. [a-32P]adenosine triphosphate-labeled rickettsiae were used to determine phagocytosis and adsorption quantitatively. R. prowazekii was less susceptible to phagocytosis than were Escherichia coli and Neisseria gonorrhoeae. Although R. prowazekii was similar to E. coli in susceptibility to superoxide and activated halide, few phagocytized rickettsial cells were inactivated after being ingested by polymorphonuclear leukocytes, and rickettsiae were observed free in polymorphonuclear leukocyte cytoplasm. At low ratios of rickettsiae to polymorphonuclear leukocytes, PMN phagocytosis increased as a linear function of time, but at high ratios (multiplicity of infection, 50) rickettsiae were phagocytized during only the first 10 min of incubation. Polymorphonuclear leukocytes were damaged in the presence of high rickettsial multiplicities such that they released lactate dehydrogenase into the medium and lost the ability to phagocytize both rickettsiae and E. coli. The amount of leukotoxic activity in a given rickettsial sample correlated with the relative hemolytic activity of that sample. The rickettsial leukotoxin was probably not a soluble product, was active in the absence of phagocytosis, and was inhibited by inactivation of the rickettsiae or by incubation at 4°C.
Experience in 207 combined MRI examinations for acute pulmonary embolism and deep vein thrombosis.

OBJECTIVE The purpose of this study was to prospectively assess the feasibility and quality of combined MRI examinations consisting of thoracic MRI for suspected pulmonary embolism (PE) and MR venography for deep vein thrombosis (DVT), to assess the diagnostic yield of a combined examination for detecting thromboembolism compared with each component alone, and to retrospectively assess the concordance of duplex sonography and MR venography. SUBJECTS AND METHODS Two hundred twenty-one consecutive patients (119 men, 102 women; mean age, 51 years; range, 31-86 years) with suspected PE were examined using a multitechnique thoracic MRI protocol (real-time MRI using true fast imaging with steady-state precession [FISP], perfusion MRI, and MR angiography) followed by stepping-table MR venography. RESULTS Two hundred twenty-one thoracic MRI examinations were performed. Two hundred eighteen MR venography examinations were scheduled, of which five (2.3%) were not performed for clinical or technical reasons and six were not performed after negative thoracic MRI. Among 207 combined examinations, PE was diagnosed in 76 and DVT in 78 examinations. Thirteen patients without PE showed DVT; thus, MR venography detected 17% additional cases of thromboembolism. Agreement with duplex sonography was good at the upper leg (kappa = 0.87-0.89) but moderate at the pelvis (kappa = 0.59-0.65). CONCLUSION A combined "one-stop-shopping" MRI approach for PE and DVT was routinely feasible and detected 17% more cases of thromboembolism compared with separate examinations. MRI may be considered a second-line technique to avoid contraindications to CT but also a primary comprehensive technique for diagnosing thromboembolism.
Engraftment for CD34 selected stem cell products is not compromised by cryopreservation

The coinfusion of haploidentical CD34+ selected peripheral blood stem cell products with umbilical cord blood (UCB) provides early neutrophil recovery, long‐term UCB engraftment, and a lower incidence of graft‐versus‐host disease; however, this complex transplant presents a scheduling challenge for both the cellular therapy laboratory and the clinical team. Cryopreservation of the haploidentical product can facilitate scheduling, but has been previously shown to be associated with infusion reactions and delayed platelet (PLT) engraftment in allogeneic hematopoietic progenitor cell transplant.
Body mass index and weight change attempts among adult women. The Norwegian Women and Cancer Study.

BACKGROUND Based on concern about the widespread increase in being overweight and obesity along with a substantial demand for leanness, we wanted to estimate body mass index (BMI) and the prevalence of weight change attempts in a population-based sample of Norwegian women. Furthermore, we wanted to examine how weight loss attempts are related to BMI and to age, socioeconomic status, reproductive factors, lifestyle and diet. METHODS A nationwide, cross-sectional study applying a mailed questionnaire was used. Out of a random sample of 20,000 women aged 45-69 years 10,249 women participated. RESULTS Based on self-reported data, the mean BMI was 24.6 kg m-2 and 40% of the women had a BMI of > or = 25 kg m-2. More than 50% of the women were trying to lose weight and weight loss attempts were very strongly associated with BMI. Age, education, income, smoking status and perception of diet's importance to health were also significant predictors of weight loss attempts. The effect of age, education and income on weight loss attempts was modified by the level of BMI. Women trying to lose weight reported a different diet than those not trying to lose weight, irrespective of BMI. CONCLUSION A large proportion of middle-aged women are trying to lose weight. BMI is predominant in explaining weight loss attempts. After adjusting for BMI, age, lifestyle and socioeconomic status also contribute to explaining weight loss attempts.
Increased generation of granule cells in adult Bcl‐2‐overexpressing mice: a role for cell death during continued hippocampal neurogenesis

Programmed cell death is an important mechanism during brain development in order to control neuronal cell numbers and to correctly form neuronal circuitries. Programmed cell death is also present in neurogenic regions of the adult brain, and a significant portion of the adult‐born cells is eliminated during the first months of maturation. We here address the question whether overexpression of the anti‐apoptotic protein Bcl‐2 would improve the survival of neural progenitor cells and, as a consequence, increase neurogenesis in the adult hippocampus. Transgenic animals, which express human Bcl‐2 under the neuron‐specific enolase promoter (NSE‐huBcl‐2), show a significant reduction of apoptotic cells in the hippocampal granule cell layer to about half of the wild‐type level. These apoptotic cells are almost exclusively found in the zone of hippocampal progenitor activity and frequently co‐label with the neuronal progenitor marker doublecortin (DCX). The rate of adult neurogenesis is doubled in the dentate gyrus of Bcl‐2‐overexpressing mice as demonstrated by quantification of progenitor cells using DCX and new neurons using bromodeoxyuridine (BrdU)/neuronal nuclei antigen (NeuN) double‐labelling. The effect of Bcl‐2 is limited to the late phase of progenitor maturation, as proliferation and early‐phase progenitor cells were not affected. The increased level of neurogenesis leads to a significantly higher total number of granule cells in the dentate gyrus. These results underline the importance of developmental cell death during neurogenesis in the adult brain.
Latent Demand for the Bone-Anchored Hearing Aid: The Lippy Group Experience

Objective: The usefulness of the bone-anchored hearing aid (BAHA) for conductive and mixed hearing losses and recently for single-sided deafness has been well documented. Less clear is the number of patients who might benefit from the BAHA and how many would be interested in having the surgery. The purpose of this investigation is to examine these latter issues from the perspective of an otology practice. Study Design: Retrospective review. Setting: Private otology practice. Patients: Approximately 44,000 patient records were reviewed. On the basis of this review, 617 patients were sent a letter describing the BAHA and explaining that they might be candidates. One hundred sixty-two of these patients made an appointment to be evaluated for the BAHA. Methods: Patients who responded to the BAHA letter underwent an otologic and audiological evaluation to confirm their candidacy. The BAHA surgery and device were described, and interested patients tried the BAHA test band in the office. Patient responses to the BAHA were noted. Results: Approximately 1.4% of the cases reviewed (617/44,000) were considered to be potential BAHA candidates. One hundred forty-six of the 162 patients who scheduled a BAHA evaluation were confirmed to be candidates. After seeing and learning about the BAHA, 92% of the verified candidates wanted to try the BAHA test band. Most patients who tried the test band (92%) liked the BAHA, and nearly a third (30.6%) had BAHA surgery. Patients with conductive or mixed hearing loss who tried the test band were more likely to have BAHA surgery than those with single-sided deafness (45.8% versus 27.3%). The major limiting factor was infrequent or inadequate insurance coverage for the procedure or device. Conclusions: Although the percentage of patients in an otology practice who could benefit from the BAHA is small, finding and alerting potential BAHA candidates are worthwhile.
Parental Satisfaction and Outcome: A 4-Year Study in a Child and Adolescent Mental Health Service

Objective: The aim of this paper is to examine the facets of parental satisfaction and its relationship with clinician-rated outcome in a child and adolescent mental health service. Method: Patients (n = 1278) consecutively assessed between 1992 and 1996 were included in the study. When treatment ended, clinicians rated the outcome of the intervention and parents were asked to complete a satisfaction questionnaire. Results: Sixty-nine per cent of cases were rated by clinicians as having a positive outcome. Outpatients were more likely to be given a positive rating than inpatients. Satisfaction questionnaires were returned by 40% of parents; 76% of these were mostly or very satisfied. Satisfaction scores increased with the number of outpatient sessions attended but did not differ between inpatients and outpatients. There was a significant but small agreement (27% better than chance) between clinicians’ rating of outcome and parental satisfaction. Level of agreement varied according to service provided and the number of sessions attended. While rates of positive outcome increased over the study period, ratings of satisfaction were stable. Conclusions: Overall, ratings of satisfaction were comparable with those reported in other studies. Variations in concordance between parents and clinicians show that outcome and satisfaction, although related, are different constructs influenced by different factors depending on the services provided. Focusing on specific aspects of satisfaction, as opposed to global measures, may be more useful for services, although such undertakings must be supported with efforts to improve clinical outcomes.
Microalbuminuria identifies overall cardiovascular risk in essential hypertension: an artificial neural network-based approach.

Background Ultrasound (US) examination of heart and carotid arteries provides an accurate assessment of target organ damage (TOD) and may influence the stratification of the absolute cardiovascular risk profile. Microalbuminuria has recently proved to be a useful cost-effective marker of increased cardiovascular risk but is still too often neglected in clinical practice. Objective To evaluate how well artificial neural networks (ANNs) predict cardiovascular risk stratification by means of routine data and urinary albumin excretion, as compared to prediction by the clinical work-up suggested by the International Society of Hypertension (ISH), with and without ultrasound-determined TOD. Methods A group of 346 never previously treated essential hypertensives (212 men, 134 women, mean age 47 ± 9 years) was studied. Risk was stratified according to the criteria suggested by the 1999 WHO/ISH guidelines; first, by routine procedures alone, and subsequently by reassessment, using data on cardiac and vascular structures obtained by US evaluation. The ANN was trained and tested to predict the overall cardiovascular risk on the basis of routine clinical data and urinary albumin excretion (UAE). The impact of these three approaches on the determination of cardiovascular risk profile was evaluated. Results According to the first classification, 5.5% (n = 19) of patients were considered at low risk, 47.3% (n = 164) at medium, 26.7% (n = 92) at high and 20.6% (n = 71) at very high risk. A marked change in risk stratification, namely an increase in the prevalence of high- and very-high-risk patients (2.3% low, 29.8% medium, 42.8% high and 25.2% very high risk; χ2 15.201, P < 0.0001), was obtained when US examination of TOD was taken into consideration. On the basis of routine clinical data and UAE, the artificial neural network successfully predicted overall cardiovascular risk and allocated patients in different classes as accurately as the US-based evaluation. Conclusions The use of US techniques allows a more precise stratification of absolute cardiovascular risk in hypertensive patients as compared to routine clinical data. An ANN can accurately identify the patients’ risk status by using low-cost routine data and UAE. These results further emphasize the value of UAE in the stratification of cardiovascular risk.
Changing trends in the proportions of small (≤2 cm) proximal and non‐proximal gastric carcinomas treated at a high‐volume tertiary medical center in China

Guided by the recently established histological criteria of the gastroesophageal junction (GEJ), we aimed to investigate and compare trends in the proportions of small (≤2 cm) proximal gastric carcinoma (PGC) vs non‐PGC (NPGC) in Chinese patients over an 8‐year period.
Incorporating covariates in mapping heterogeneous traits: a hierarchical model using empirical Bayes estimation

Complex genetic traits are inherently heterogeneous, i.e., they may be caused by different genes, or non‐genetic factors, in different individuals. So, for mapping genes responsible for these diseases using linkage analysis, heterogeneity must be accounted for in the model. Heterogeneity across different families can be modeled using a mixture distribution by letting each family have its own heterogeneity parameter denoting the probability that its disease‐causing gene is linked to the marker map under consideration. A substantial gain in power is expected if covariates that can discriminate between the families of linked and unlinked types are incorporated in this modeling framework. To this end, we propose a hierarchical Bayesian model, in which the families are grouped according to various (categorized) levels of covariate(s). The heterogeneity parameters of families within each group are assigned a common prior, whose parameters are further assigned hyper‐priors. The hyper‐parameters are obtained by utilizing the empirical Bayes estimates. We also address related issues such as evaluating whether the covariate(s) under consideration are informative and grouping of families. We compare the proposed approach with one that does not utilize covariates and show that our approach leads to considerable gains in power to detect linkage and in precision of interval estimates through various simulation scenarios. An application to the asthma datasets of Genetic Analysis Workshop 12 also illustrates this gain in a real data analysis. Additionally, we compare the performances of microsatellite markers and single nucleotide polymorphisms for our approach and find that the latter clearly outperforms the former. Genet. Epidemiol. 2007. © 2007 Wiley‐Liss, Inc.
Variation in Estimated Ozone-Related Health Impacts of Climate Change due to Modeling Choices and Assumptions

Background: Future climate change may cause air quality degradation via climate-induced changes in meteorology, atmospheric chemistry, and emissions into the air. Few studies have explicitly modeled the potential relationships between climate change, air quality, and human health, and fewer still have investigated the sensitivity of estimates to the underlying modeling choices. Objectives: Our goal was to assess the sensitivity of estimated ozone-related human health impacts of climate change to key modeling choices. Methods: Our analysis included seven modeling systems in which a climate change model is linked to an air quality model, five population projections, and multiple concentration–response functions. Using the U.S. Environmental Protection Agency’s (EPA’s) Environmental Benefits Mapping and Analysis Program (BenMAP), we estimated future ozone (O3)-related health effects in the United States attributable to simulated climate change between the years 2000 and approximately 2050, given each combination of modeling choices. Health effects and concentration–response functions were chosen to match those used in the U.S. EPA’s 2008 Regulatory Impact Analysis of the National Ambient Air Quality Standards for O3. Results: Different combinations of methodological choices produced a range of estimates of national O3-related mortality from roughly 600 deaths avoided as a result of climate change to 2,500 deaths attributable to climate change (although the large majority produced increases in mortality). The choice of the climate change and the air quality model reflected the greatest source of uncertainty, with the other modeling choices having lesser but still substantial effects. Conclusions: Our results highlight the need to use an ensemble approach, instead of relying on any one set of modeling choices, to assess the potential risks associated with O3-related human health effects resulting from climate change.