Miracle-dz/UniFAR-FTUs huggingface dataset:
Examination of level of knowledge in Italian general practitioners attending an education session on diagnosis and management of the early stage of Alzheimer's disease: pass or fail?

ABSTRACT Background: We detected the general level of knowledge about the early diagnosis of Alzheimer's disease (AD) and subsequent care in general practitioners (GPs) from Southern Italy. We explored also the GP perception about their knowledge and training on diagnosis and management of AD. Methods: On a sample of 131 GPs, we administered two questionnaires: the GP-Knowledge, evaluating GPs’ expertise about AD epidemiology, differential diagnosis, and available treatments, and the GP-QUestionnaire on Awareness of Dementia (GP-QUAD), assessing the GPs’ attitudes, awareness, and practice regarding early diagnosis of dementia. Results: Specific screening tests or protocols to diagnose and manage dementia were not used by 53% of our GPs. The training on the recognition of early AD signs and symptoms was considered inadequate by 55% of the participants. Females were more likely to consider their training insufficient (58%) compared to males (53%). Female GPs were less likely to prescribe antipsychotic drugs to control neuropsychiatric symptoms (NPS) and suggest specialist advice in late stage of cognitive impairment. Multiple Correspondence Analysis (MCA) performed only on GP-QUAD suggested two dimensions explaining 26.1% (“GP attitude”) and 20.1% (“GP knowledge”) of the inertia for a total of 46.2%, Conclusion: In our survey on GP clinical practice, several problems in properly recognizing early AD symptoms and subsequently screening patients to be referred to secondary/tertiary care centers for diagnosis confirmation have emerged. In the future, specific training programs and educational projects for GPs should be implemented also in Italy to improve detection rates and management of dementia in primary care.
Surrogate Endpoint Biomarkers for Clinical Trials of Prostate Cancer Chemoprevention

Objective: In this review, we discuss the utility of fluorescence in situ hybridization (FISH) in the determination of genetic and chromosomal alterations in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as detected by FISH and other techniques. Methods and Results: FISH is a commonly used technique for the determination of gene and chromosome dosage. In tissue sections, FISH allows precise histopathologic correlation of multiple foci of normal epithelium, premalignant lesions, and carcinoma within a single specimen, including study of intratumoral heterogeneity. PIN and prostatic carcinoma foci have a similar proportion of genetic changes, but foci of carcinoma usually have more alterations. This supports the hypothesis that PIN is the most likely precursor of prostatic carcinoma. The most common genetic alterations in PIN and carcinoma are: (1) gain of chromosome 7, particularly 7q31; (2) loss of 8p and gain of 8q, and (3) loss of 10q, 16q and 18q. Inactivation of tumor suppressor genes and/or overexpression of oncogenes in these regions may be important for the initiation and progression of prostate cancer. Conclusions: FISH is a useful technique to determine genetic relationships between cancer and its precursors. PIN and prostatic carcinoma foci have a similar proportion of genetic alterations, suggesting that PIN is often a precursor of prostatic carcinoma. Genes on chromosomes 7, 8, 10, 16 and 18 may play an important role in both initiation and progression of prostatic carcinoma.
Mechanisms of Exercise-Induced Amelioration of Cardiovascular Disease pH recovery from a proton load in rat cardiomyocytes: effects of chronic exercise

Vennetia R. Danes, Josephine Anthony, Kaveh Rayani, Kenneth W. Spitzer, and Glen F. Tibbits Molecular Cardiac Physiology Group, Simon Fraser University, Burnaby, British Columbia, Canada; Cardiovascular Sciences, BC Research Institute for Children’s and Women’s Health, Vancouver, British Columbia, Canada; and Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah
Hemin Causes Lung Microvascular Endothelial Barrier Dysfunction by Necroptotic Cell Death

&NA; Hemin, the oxidized prosthetic moiety of hemoglobin, has been implicated in the pathogenesis of acute chest syndrome in patients with sickle cell disease by virtue of its endothelial‐activating properties. In this study, we examined whether hemin can cause lung microvascular endothelial barrier dysfunction. By assessing transendothelial resistance using electrical cell impedance sensing, and by directly measuring trans‐monolayer fluorescein isothiocyanate‐dextran flux, we found that hemin does cause endothelial barrier dysfunction in a concentration‐dependent manner. Pretreatment with either a Toll‐like receptor 4 inhibitor, TAK‐242, or an antioxidant, N‐acetylcysteine, abrogated this effect. Increased monolayer permeability was found to be associated with programmed cell death by necroptosis, as evidenced by Trypan blue staining, terminal deoxynucleotidyl transferase dUTP nick‐end labeling assay, Western blotting for activated forms of key effectors of cell death pathways, and studies utilizing specific inhibitors of necroptosis and apoptosis. Further studies examining the role of endothelial cell necroptosis in promoting noncardiogenic pulmonary edema during acute chest syndrome are warranted and may open a new avenue of potential treatments for this devastating disease.
FORCED MOLT IN FOUR JUVENILE YELLOW-EYED PENGUINS (MEGADYPTES ANTIPODES)

Abstract Penguins are dependent on waterproof plumage for survival. The molt in sub-Antarctic penguin species is a seasonal and catastrophic process during which the animals go through periods of fasting and high levels of stress. Their entire plumage is usually replaced in 3 wk. Attempts at consistent hormonal induction of molt in penguins have been unsuccessful. Four Yellow-eyed Penguins (Megadyptes antipodes) were referred for treatment at Wildbase, Massey University, Palmerston North, New Zealand, in late April 2014, following loss of waterproofing, feather breakage, increased body weight, pododermatitis, and damage to caudal feathers from hock sitting. Feather plucking of damaged areas to stimulate feather regrowth was attempted with poor results. Waiting 10–12 mo for a natural molt was not tenable. Catastrophic molt was induced by treatment with 10 g/kg of fresh beef thyroid gland orally once a day. The molt was complete in 18–26 d during which the animals regained full plumage and waterproofing after feather regrowth. The forced molt feathers had abnormal pigmentation but were of sufficient quality to allow release of the birds back to the wild.
An analytical study of the classification of highly skewed data

ABSTRACT This article proposes a discriminant function and an algorithm to analyze the data addressing the situation, where the data are positively skewed. The performance of the suggested algorithm based on the suggested discriminant function (LNDF) has been compared with the conventional linear discriminant function (LDF) and quadratic discriminant function (QDF) as well as with the nonparametric support vector machine (SVM) and the Random Forests (RFs) classifiers, using real and simulated datasets. A maximum reduction of approximately 81% in the error rates as compared to QDF for ten-variate data was noted. The overall results are indicative of better performance of the proposed discriminant function under certain circumstances.
Cantharidic acid induces apoptosis through the p38 MAPK signaling pathway in human hepatocellular carcinoma

Cantharidin analogs exhibit anticancer activities, including apoptosis. However, the molecular mechanisms underlying the effects of cantharidic acid (CA), a cantharidin analog, on apoptosis in hepatocellular carcinoma (HCC) cells are unclear. Thus, in this study, we evaluated the anticancer activities of CA by investigating its ability to trigger apoptosis in SK‐Hep‐1 cells. Our data demonstrated that CA effectively inhibited the proliferation of SK‐Hep‐1 cells in a dose‐dependent manner. Furthermore, CA effectively triggered cell cycle arrest and induced apoptosis, as determined by flow cytometric analysis. Western blotting revealed that CA significantly activated proapoptotic signaling including caspase‐3, −8, and −9 in SK‐Hep‐1 cells. Moreover, treatment of SK‐Hep‐1 cells with CA induced the activation of ERK, p38, and c‐Jun N‐terminal kinase. Moreover, the inhibition of p38 by specific inhibitors abolished CA‐induced cell apoptosis. In conclusion, our results indicated that CA induces apoptosis in SK‐Hep‐1 cells through a p38‐mediated apoptotic pathway and could be a new HCC therapeutic agent.
In vitro Blood Compatibility Evaluation of Cuprophan and Polyacrylonitrile Membranes

This article is also accessible online at: http://BioMedNet.com/karger Dear Sir, During hemodialysis (HD), human blood leukocytes come into contact with surface material of the dialyzer membrane, soluble membrane constituents, complement or other plasma products activated by the dialyzer materials, solute and microbial products in the dialysis bath, and the effect of pumping blood into the HD circuit. These interactions lead to the production of a variety of cytokines and growth factors, and the release of some cell enzymes and proteins. Several groups have demonstrated that patients dialyzed on cellulosic membranes have increased circulating interleukin-1 (IL1) before the dialysis session, further elevated at the end of the dialysis session [1, 2]. However, others failed to show significantly elevated IL-1 in the plasma of HD patients both before and after dialysis [3]. Amyloidosis of patients on chronic HD was previously related to their treatment with cellulosic/ bioincompatible membranes and increased levels of ß2-microglobulin (ß2-MG) [4]. This matter was disputed by other authors [5]. The aim of this study was to establish the effect of a cellulosic membrane (cuprophan), and a biocompatible membrane (polyacrylonitrile, PAN) on IL-1 and ß2-MG production by cultured peripheral blood mononuclear cells (PBMC). Ten patients on maintenance HD for 25– 73 (median 43) months participated in the study. PBMC were isolated from 15 ml of heparinized blood drawn at 7 a.m. before dialysis, and layered over Ficoll hypaque. Suspensions of 2 ! 106 PBMC were incubated for 48 h alone, or with cuprophan or PAN membrane fragments. Stimulation studies were performed by adding phytohemagglutinin (PHA) 30 Ìg/ml to the incubation medium. ß2-MG was determined in the medium by a radioimmunoassay kit from Phadebas (Farmacia, Sweden). For IL-1 determination, the IL-1· (125I) system from Amersham (UK), based on the competition between unlabeled IL-1 and a fixed quantity of 125I-labeled IL-1 for a limited number of binding sites on an IL-1-specific antibody, was used. A marked basal and PHA-stimulated production of both IL-1 and ß2-MG by PBMC of HD patients was demonstrated (table 1). IL-1 levels with cuprophan and PAN membranes were lower than in supernatants from control cultures; the mitogenic effect of PAN was absent. The ß2-MG level in supernatants was markedly reduced in the presence of cuprophan or PAN membrane fragments, and the mitogenic effect of PAN was absent. This study shows that cuprophan and PAN membranes do not generate an excess of IL-1 and ß2-MG in vitro and that this model cannot be used for biocompatibility testing. This simplified model lacks other blood constituents participating in a cascade of events, dialysis fluid, microbial contamination and blood pumping. ß2-MG is extensively adsorbed to the dialyzer membrane,
Social and spatial effects on genetic variation between foraging flocks in a wild bird population

Social interactions are rarely random. In some instances, animals exhibit homophily or heterophily, the tendency to interact with similar or dissimilar conspecifics, respectively. Genetic homophily and heterophily influence the evolutionary dynamics of populations, because they potentially affect sexual and social selection. Here, we investigate the link between social interactions and allele frequencies in foraging flocks of great tits (Parus major) over three consecutive years. We constructed co‐occurrence networks which explicitly described the splitting and merging of 85,602 flocks through time (fission–fusion dynamics), at 60 feeding sites. Of the 1,711 birds in those flocks, we genotyped 962 individuals at 4,701 autosomal single nucleotide polymorphisms (SNPs). By combining genomewide genotyping with repeated field observations of the same individuals, we were able to investigate links between social structure and allele frequencies at a much finer scale than was previously possible. We explicitly accounted for potential spatial effects underlying genetic structure at the population level. We modelled social structure and spatial configuration of great tit fission–fusion dynamics with eigenvector maps. Variance partitioning revealed that allele frequencies were strongly affected by group fidelity (explaining 27%–45% of variance) as individuals tended to maintain associations with the same conspecifics. These conspecifics were genetically more dissimilar than expected, shown by genomewide heterophily for pure social (i.e., space‐independent) grouping preferences. Genomewide homophily was linked to spatial configuration, indicating spatial segregation of genotypes. We did not find evidence for homophily or heterophily for putative socially relevant candidate genes or any other SNP markers. Together, these results demonstrate the importance of distinguishing social and spatial processes in determining population structure.
Techno-Economic Analysis of 5G Deployment Scenarios involving Massive MIMO HetNets over mmWave: A Case Study on the US State of Texas

The fifth generation (5G) of mobile services envisages network heterogeneity, cell densification, and high spectral efficiency using Massive MIMO, operating at millimeter-wave frequencies. Accurately assessing the potential of financial returns for such a complex network poses to operators unique challenges including techno-economic analysis leading to the identification of decision variables most sensitive to the profitability parameters. Attempting to demystify their concerns, we evaluate the profitability potential for realistic 5G deployment scenarios over 28 GHz frequency in the State of Texas. Interestingly, we discover that the total cost of ownership for 5G network is about one-third of that for 4G LTEAdvanced (LTE-A) deployment, yielding estimated returns amounting to $482.14 million for the period 2020-2030. The sensitivity analyses predict profitability in 70% of the cases of 5G, against LTEA. For operators, the crucial levers having the maximum impact on profitability are decisions pertaining to the spectrum acquisition and the pricing of services.
Models of epigenetic age capture patterns of DNA methylation in glioma associated with molecular subtype, survival, and recurrence

Background Models of epigenetic aging (epigenetic clocks) have been implicated as potentially useful markers for cancer risk and prognosis. Using 2 previously published methods for modeling epigenetic age, Horvath's clock and epiTOC, we investigated epigenetic aging patterns related to World Health Organization grade and molecular subtype as well as associations of epigenetic aging with glioma survival and recurrence. Methods Epigenetic ages were calculated using Horvath's clock and epiTOC on 516 lower-grade glioma and 141 glioblastoma cases along with 136 nontumor (normal) brain samples. Associations of tumor epigenetic age with patient chronological age at diagnosis were assessed with correlation and linear regression, and associations were validated in an independent cohort of 203 gliomas. Contribution of epigenetic age to survival prediction was assessed using Cox proportional hazards modeling. Sixty-three samples from 18 patients with primary-recurrent glioma pairs were also analyzed and epigenetic age difference and rate of epigenetic aging of primary-recurrent tumors were correlated to time to recurrence. Results Epigenetic ages of gliomas were near-universally accelerated using both Horvath's clock and epiTOC compared with normal tissue. The 2 independent models of epigenetic aging were highly associated with each other and exhibited distinct aging patterns reflective of molecular subtype. EpiTOC was found to be a significant independent predictor of survival. Epigenetic aging of gliomas between primary and recurrent tumors was found to be highly variable and not significantly associated with time to recurrence. Conclusions We demonstrate that epigenetic aging reflects coherent modifications of the epigenome and can potentially provide additional prognostic power for gliomas.
Blind deconvolution of 3D fluorescence microscopy using depth‐variant asymmetric PSF

The 3D wide‐field fluorescence microscopy suffers from depth‐variant asymmetric blur. The depth‐variance and axial asymmetry are due to refractive index mismatch between the immersion and the specimen layer. The radial asymmetry is due to lens imperfections and local refractive index inhomogeneities in the specimen. To obtain the PSF that has these characteristics, there were PSF premeasurement trials. However, they are useless since imaging conditions such as camera position and refractive index of the specimen are changed between the premeasurement and actual imaging. In this article, we focus on removing unknown depth‐variant asymmetric blur in such an optical system under the assumption of refractive index homogeneities in the specimen. We propose finding few parameters in the mathematical PSF model from observed images in which the PSF model has a depth‐variant asymmetric shape. After generating an initial PSF from the analysis of intensities in the observed image, the parameters are estimated based on a maximum likelihood estimator. Using the estimated PSF, we implement an accelerated GEM algorithm for image deconvolution. Deconvolution result shows the superiority of our algorithm in terms of accuracy, which quantitatively evaluated by FWHM, relative contrast, standard deviation values of intensity peaks and FWHM. Microsc. Res. Tech. 79:480–494, 2016. © 2016 Wiley Periodicals, Inc.
Periacetabular osteotomy for developmental hip dysplasia with labral tears: is arthrotomy or arthroscopy required?

ABSTRACT Patients with developmental dysplasia of the hip (DDH) who undergo periacetabular osteotomy (PAO) often have labral tears. The objective of this retrospective study was to compare PAO alone with PAO combined with arthrotomy or arthroscopy in DDH patients who had a full-thickness labral tear on magnetic resonance imaging. In total, 47 hips in the PAO group (PAO) were compared with 60 hips in the PAO with concomitant arthrotomy or arthroscopy (PAO-A) with respect to Hip Disability and Osteoarthritis Outcome Score (HOOS), modified Harris Hip Score (mHHS), Visual Analog Scale (VAS), clinical and radiographic outcomes at a median of 29 months. Reoperation rate and complications were compared between two groups of treatment. The PAO group was younger than the PAO-A group (25.2 ± 9.7 versus 31.3 ± 8.3). The PAO group was more likely to have worse dysplasia: lateral center edge angle (7.6°±9.63° versus 10.8°±6.85°) and anterior center edge angle (4°±12.92° versus 10.8°±9.92°). The PAO group had a higher preoperative mHHS (65.2 ± 15.3 versus 57.8 ± 14.8) and HOOS (66.3 ± 17.5 versus 55.8 ± 20.1). There were no significant differences in final functional outcome scores across treatment groups: mHHS (PAO; 86.8 ± 12.4 versus PAO-A, 83.3 ± 17.2), HOOS (86.5 ± 13.3 versus 82.5 ± 16.8) and VAS (2.5 ± 2.8 versus 2.5 ± 3.1). There was no difference in reoperation rate between two groups (6.4% versus 11.6%, P = 0.51). The overall complication rate was lower in the PAO group (26% versus 68%), but major complications were comparable. On the basis of our data, we were not able to conclusively demonstrate a clear benefit for the routine treatment of all labral tears; however, arthrotomy or arthroscopy may play a role in some conditions.
Characterization of Factors Affecting Attainment of Glycemic Control in Asian Americans With Diabetes in a Culturally Specific Program

Purpose The purpose of this study is to examine the effectiveness of a culturally specific pilot clinic for Asian Americans (AA) in reaching glycemic target and to characterize factors affecting the attainment of glycemic control in comparison with white counterparts. Methods This electronic health record review included all new AA patients with type 2 diabetes (n = 109) in a culturally specific program and a randomly selected sample of new white patients with type 2 diabetes (n = 218) in the adult clinic within the same time period and diabetes center. Results AA and whites had a comparable proportion of patients with A1C ≤7% (32.1%, 34.9%; P = .621) at baseline and after 12 months of care (48.6%, 56.0%; P = .210), with a similar A1C decline (–0.9% ± 1.6%, –0.8% ± 1.7%, P = .710) by 12 months. Factors associated with the lack of success in reaching target in AA but not in whites included older age, lower educational attainment, less likelihood of having health insurance, and a need for more educational visits. The percentage of AA reaching A1C ≤7%, as compared to whites, worsened among those with highest initial A1C when stratified by ascending quartiles (96.7% vs 85.2%, P = .101; 61.9% vs 58.9%, P = .813; 24.0% vs 37.7%, P = .230; 15.2% vs 35.4%, P = .044). Conclusion While a culturally specific diabetes program in a specialty setting achieved a similar glycemic outcome for AA compared with whites, reasons for not reaching glycemic target differed. The findings suggest that the elimination of diabetes disparities requires not only culturally and linguistically specific programs, but must also identify and address the socio-environmental differences unique to each population.
Effect of Candesartan and Verapamil on Exercise Tolerance in Diastolic Dysfunction

Diastolic dysfunction may be exacerbated by increased systolic blood pressure (SBP) during exercise. Ang II may contribute to this process. We performed a randomized, double-blind, crossover study of two weeks of candesartan (16 mg) and verapamil (SR 160 mg). The 21 subjects were 64 ± 10 years old with ejection fraction greater than 50%, no ischemia, mitral flow velocity E/A less than 1, normal resting SBP (< 150 mm Hg), and SBP greater than 200 mm Hg during exercise. Exercise tolerance was assessed using a Modified Bruce Protocol at baseline and after each two-week treatment period, separated by a two-week washout period. Quality of life (QOL) was assessed using the Minnesota Living with Heart Failure questionnaire. During exercise, Ang II levels increased from 29 ± 18 to 33 ± 18 pg/ml (P < 0.05). SBP during exercise was 213 ± 9 mm Hg at baseline and similarly reduced by candesartan (198 ± 18, P < 0.01) and verapamil (197 ± 14, P < 0.01). With candesartan, exercise time increased from 793 ± 182 seconds to 845 ± 163 seconds (P < 0.05), and QOL improved from 11 ± 14 to 5 ± 6 (P < 0.05). In contrast, verapamil did not significantly improve exercise time or QOL. In patients with mild diastolic dysfunction at rest and a hypertensive response to exercise, both Ang II receptor blockade and verapamil blunted the hypertensive response to exercise. Ang II blockade increased exercise tolerance and improved QOL.