Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine

Convincing evidence accumulated over the last decades demonstrates the crucial role of epigenetic modifications for mammalian genome regulation and its flexibility. DNA methylation and demethylation is a key mechanism of genome programming and reprogramming. During ontogenesis, the DNA methylome undergoes both programmed changes and those induced by environmental and endogenous factors. The former enable accurate activation of developmental programs; the latter drive epigenetic responses to factors that directly or indirectly affect epigenetic biochemistry leading to alterations in genome regulation and mediating organism response to environmental transformations. Adverse environmental exposure can induce aberrant DNA methylation changes conducive to genetic dysfunction and, eventually, various pathologies. In recent years, evidence was derived that apart from 5-methylcytosine, the DNA methylation/demethylation cycle includes three other oxidative derivatives of cytosine—5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. 5hmC is a predominantly stable form and serves as both an intermediate product of active DNA demethylation and an essential hallmark of epigenetic gene regulation. This makes 5hmC a potential contributor to epigenetically mediated responses to environmental factors. In this state-of-the-art review, we consolidate the latest findings on environmentally induced adverse effects on 5hmC patterns in mammalian genomes. Types of environmental exposure under consideration include hypnotic drugs and medicines (i.e., phenobarbital, diethylstilbestrol, cocaine, methamphetamine, ethanol, dimethyl sulfoxide), as well as anthropogenic pollutants (i.e., heavy metals, particulate air pollution, bisphenol A, hydroquinone, and pentachlorophenol metabolites). We put a special focus on the discussion of molecular mechanisms underlying environmentally induced alterations in DNA hydroxymethylation patterns and their impact on genetic dysfunction. We conclude that DNA hydroxymethylation is a sensitive biosensor for many harmful environmental factors each of which specifically targets 5hmC in different organs, cell types, and DNA sequences and induces its changes through a specific metabolic pathway. The associated transcriptional changes suggest that environmentally induced 5hmC alterations play a role in epigenetically mediated genome flexibility. We believe that knowledge accumulated in this review together with further studies will provide a solid basis for new approaches to epigenetic therapy and chemoprevention of environmentally induced epigenetic toxicity involving 5hmC patterns.
Text-Video Completion Using Structure Repair and Texture Propagation

Today, more superimposed text is embedded within videos. Usually some text is unnecessary. Thus, one requires an approach to remove the text and complete the video. However, few conventional approaches complete the video well due to the large-sized text, structure regions, and various types of videos. In response, this study designed a text-video completion algorithm that poses text-video completion as structure repair and texture propagation. To repair the structure regions, the structure interpolation uses the new model's rotated block matching to estimate the initial location of completed regions and later refine the coordinates of completed regions. The information in the neighboring frames then fills the structure regions. To complete the structure regions without tedious manual interaction, the structure extension utilizes the spline curve estimation. Afterwards, derivative propagation realizes the texture region completion. The experiment results are based on several real TV programs, where all of the text regions were completed with spatio-temporal consistency. Additionally, comparisons present that the performance of the proposed algorithm is superior to those of conventional approaches. Its advantages include the reduction of design complexity by only integrating the structure information in multi-frame and the demonstration of structure consistency for realistic videos.
Surface Microanalysis and Chemical Imaging of Early Dentin Remineralization

Abstract This study reports physical and chemical changes that occur at early dentin remineralization stages. Extracted human third molars were sectioned to obtain dentin discs. After polishing the dentin surfaces, three groups were established: (1) untreated dentin (UD), (2) 37% phosphoric acid application for 15 s (partially demineralized dentin—PDD), and (3) 10% phosphoric acid for 12 h at 25° C (totally demineralized dentin—TDD). Five different remineralizing solutions were used: chlorhexidine (CHX), artificial saliva (AS), phosphate solution (PS), ZnCl2, and ZnO. Wettability (contact angle), ζ potential and Raman spectroscopy analysis were determined on dentin surfaces. Demineralization of dentin resulted in a higher contact angle. Wettability decreased after immersion in all solutions. ζ potential analysis showed dissimilar performance ranging from −6.21 mV (TDD + AS) up to 3.02 mV (PDD + PS). Raman analysis showed an increase in mineral components after immersing the dentin specimens, in terms of crystallinity, mineral content, and concentration. This confirmed the optimal incorporation and deposition of mineral on dentin collagen. Organic content reflected scarce changes, except in TDD that appeared partially denatured. Pyridinium, as an expression of cross-linking, appeared in all spectra except in specimens immersed in PS.
Ontogeny of Surface Texture of Limb Bones in Modern Aquatic Birds and Applicability of Textural Ageing

Despite its importance in various disciplines, a general method to assess ontogenetic ages of skeletal and fossil specimens has been lacking for birds. Although the textural ageing method was formulated to assess relative ontogenetic ages of specimens from inspection of bone surface textures, the exact correspondence of surface textures to ontogenetic stages has not yet been clear. In this study, bone surface textures of six major limb bones (humerus, ulna, carpometacarpus, femur, tibiotarsus, and tarsometatarsus) were described in postnatal ontogenies of four species of modern birds (Calonectris leucomelas, Phalacrocorax capillatus, Larus crassirostris, and Cerorhinca monocerata) from 14 to 28 individuals of known ontogenetic stages for each species. Consistently with the previous postulation, it was found that bones of chicks were characterized by rough surface textures with numerous grooves/depressions that host minute foramina. Bones of fledglings/juveniles, which are generally as large as those of adults but more slender, were characterized by the occasional presence of depressions and foramina. Histological observations confirmed that these rough surface textures were underlain by fibrolamellar bone tissue which is associated with active periosteal ossification. These results indicate that the smooth surface texture in adults is formed after the cessation of circumferential bone growth, which probably takes place between fledging and the attainment of sexual maturity. The available evidence suggests that the textural ageing is probably applicable to the entire Neognathae, a clade containing most crown‐group birds. Anat Rec, 301:1026–1045, 2018. © 2017 Wiley Periodicals, Inc.
Borderline ankle-brachial index value of 0.91-0.99 is associated with endothelial dysfunction.

BACKGROUND An ankle-brachial index (ABI) value of 0.91-0.99 is considered borderline and associated with an increased risk of cardiovascular events. However, there is no information on the relationship between borderline ABI and endothelial function. METHODS AND RESULTS We measured ABI and assessed vascular function by flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation in 389 subjects who underwent health examinations. Subjects were divided into 3 groups according to ABI (normal group: 1.00-1.40, borderline group: 0.91-0.99, abnormal group: ≤0.90 or >1.40). FMD was significantly smaller in both the borderline and the abnormal group than in the normal group. There was no significant difference in the vascular responses to nitroglycerin between the normal and borderline groups. Vascular response to nitroglycerin was significantly higher in the normal group than in the abnormal group. Borderline and abnormal ABI values were significantly associated with an increased odds ratio of low tertile of FMD levels, using the normal ABI group as the reference. Multiple logistic regression analysis for FMD revealed that age, sex, hypertension, diabetes mellitus, and borderline ABI independently remained associated with FMD. CONCLUSIONS ABI of 0.91-0.99 is associated with endothelial dysfunction. ABI examination is a simple and cost-effective method for obtaining the additional information on the initial step of atherosclerosis beyond the assessment of peripheral artery disease.
Minimum Prices for Alcohol and Educational Disparities in Alcohol-related Mortality

Background: Minimum price of alcohol is one of the proposed set of alcohol policies in many high-income countries. However, the extent to which alcohol-related harm is associated with minimum prices across socioeconomic groups is not known. Methods: Using Finnish national registers in 1988–2007, we investigated, by means of time-series analysis, the association between minimum prices for alcohol overall, as well as for various types of alcoholic beverages, and alcohol-related mortality, among men and women ages 30–79 years across three educational groups. We defined quarterly aggregations of alcohol-related deaths, based on a sample including 80% of all deaths, in accordance with information on both underlying and contributory causes of death. Results: About 62,500 persons died from alcohol-related causes during the 20-year follow-up. The alcohol-related mortality rate was more than threefold higher among those with a basic education than among those with a tertiary education. Among men with a basic education, an increase of 1% in the minimum price of alcohol was associated with a decrease of 0.03% (95% confidence interval = 0.01, 0.04%) in deaths per 100,000 person-years. Changes in the minimum prices of distilled spirits, intermediate products, and strong beer were also associated with changes in the opposite direction among men with a basic education and among women with a secondary education, whereas among the most highly educated there were no associations between the minimum prices of any beverages and mortality. Moreover, we found no evidence of an association between lower minimum prices for wine and higher rates of alcohol-related mortality in any of the population sub-groups. Conclusions: The results reveal associations between higher minimum prices and lower alcohol-related mortality among men with a basic education and women with a secondary education for all beverage types except wine.
Use of Punica granatum as an antifungal agent against candidosis associated with denture stomatitis

The aim of this study was to evaluate the use of a gel containing the extract of Punica granatum as an antifungal agent against candidosis associated with denture stomatitis. Sixty patients with denture stomatitis confirmed by clinical and mycologic examination were selected. The patients were randomly allocated in two groups of 30 individuals each according to the medication prescribed: group A used miconazole (Daktarin® gel oral) and group B used a gel of P. granatum Linné (pomegranate). Both groups used the medicines three times per day for 15 days. Forty‐eight hours after finishing the treatment the patients were re‐examined and a second set of samples was collected for mycologic examination. The medicines were evaluated for their clinical response and negativity for Candida. The clinical results showed a satisfactory and regular response in 27 and 21 subjects of groups A and B, respectively. Negativity of yeasts was observed in 25 subjects of group A and 23 of group B. It can be concluded that the extract of P. granatum may be used as a topical antifungal agent for the treatment of candidosis associated with denture stomatitis.
Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

ABSTRACT Despite the growing importance of carbapenem-resistant Klebsiella pneumoniae (CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R) K. pneumoniae, and susceptible K. pneumoniae isolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of the wzi and bla KPC genes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. The bla KPC-3 gene (30%) was restricted to ST258/wzi154, whereas bla KPC-2 (70%) was observed for several wzi allele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas the K. pneumoniae susceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and the wzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted.
Susceptibility of Haemophilus influenzae Isolates from Blood and Cerebrospinal Fluid to Ampicillin, Chloramphenicol, and Trimethoprim-Sulfamethoxazole

Susceptibility to ampicillin and chloramphenicol in vitro has been determined for Haemophilus influenzae strains isolated from blood and/or cerebrospinal fluid cultures of patients admitted to two Atlanta hospitals from 1 January 1974 to 31 March 1975. Since the appearance of ampicillin-resistant strains of this organism in early 1974, chloramphenicol has been used in these hospitals as initial therapy for severe infection due to H. influenzae. Strains from five of 94 patients were resistant to ampicillin (minimum inhibitory concentration [MIC] ≥ 12.5 μg/ml), but all strains were susceptible to chloramphenicol (MIC < 2 μg/ml). The first 35 strains studied, including three resistant to ampicillin, were also tested for in vitro susceptibility to trimethoprim-sulfamethoxazole; all were highly susceptible (MIC ≤ 0.0312 μg of trimethoprim and 0.625 μg of sulfamethoxazole per ml).
The Pattern of Plasma Insulin Response to Glucose in Patients with a Previous Myocardial Infarction—The Respective Effects of Age and Disease

Plasma insulin and blood sugar variations were investigated during oral (OGTT) and intravenous (IVGTT) glucose tolerance tests in 10 patients aged 32 to 41 and 10 Patients aged 48 to 60 who had suffered a myocardial infarction at least three months previously. The results obtained in each group of patients were compared with those of ten normal subjects of corresponding age. The respective influences of age and cardio‐vascular disease on the pattern of the plasma insulin and blood sugar responses to the glucose load were dissociated on the basis of analysis of variance. —Advancing age was associated with a rise in the mean blood sugar level during OGTT and a lowering of the glucose assimilation coefficient during IVGTT, but it was not accompanied by a significant change in the plasma insulin levels during either of the two tests. —Cardiovascular disease was associated with an augmentation of the mean blood sugar level during OGTT, but also with a prolonged and excessive response in plasma insulin. During IVGTT the glucose assimilation coefficient and the plasma insulin variations were not statistically different in the patients with a previous myocardial infarction and in the normal subjects. —The previous occurrence of a myocardial infarction is thus associated with a hyperinsulinism during OGTT, but not after a rapid stimulation as realized during IVGTT. The nature of the gastrointestinal factors involved in the genesis of this hyperinsulinism remains a matter of conjecture.
Difficulties in conducting controlled trials in radical therapies for nonadvanced hepatocellular carcinoma

I read with great interest and more than a little dismay the article by Myers, Gregor, and Marotta1 on the cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C. While I found the article to be very well written and thorough, I find the premise for the article to be totally unacceptable. Are we to withhold a simple vaccination from our patients, knowing that they run the risk of severe morbidity or death simply because it may not be “cost effective” in a population study? This article calls to mind a story that was recently played out in the courts in the United States. There was once a large automobile manufacturer that produced a vehicle it knew was unsafe. Not only did they know that it was unsafe, they also knew how to fix the problem to render the vehicle safe. However, rather than do the right thing and fix the vehicle (at a cost of $11 per vehicle), they embarked on a course similar to Myers et al. They first calculated the cost of correcting the defect and then compared it with the cost they may incur if the defect was not corrected. They used data from the federal government and that the National Highway Traffic Safety Administration made available to them. They calculated the average damage per person killed by their vehicle. They added medical costs, property damage, insurance administration, legal and court costs, employer losses, victim pain and suffering, and funeral bills as well as “other costs. ” When they found that this cost would be less than the cost of correcting the defect on the vehicle, they elected to take their chances in court. Their strategy ultimately landed them in court and resulted in one of the largest settlements in the American legal system. The ethics involved in their decision-making process was headline news throughout the nation. The parallels between this story and the conclusions drawn from this article I find to be quite remarkable. I can see myself in the future consoling Mrs. X upon the death of her husband from hepatitis A superimposed on hepatitis C, a disease that could have been prevented by a simple vaccination, by handing her the article and saying, “but as you can see here, clearly it would not have been cost effective for me to have given your husband a simple vaccine. ” I was surprised that this article did not provoke more editorial comments from the editors of HEPATOLOGY and I certainly hope that the ACIP does not reconsider its stance on vaccinating all patients with hepatitis C with the hepatitis A vaccine.
Integration of a Class-E low DV/DT rectifer in a wireless power transfer system

This paper presents the integration of a Class-E rectifier into a high frequency semi-resonant inductive power transfer system. The rectifier is used to rectify the 5.56 MHz ac output of the resonant receiving coil. End to end efficiency's exceeding 69 % are demonstrated while transferring 120 W with 30 cm coil spacing. Rectifier topologies were reviewed with their applicability to high frequency resonant IPT as a focus. A voltage driven series inductor low dv/dt resonant Class-E rectifier was selected for integration into an existing inductive power transfer system. System and rectifier efficiency is shown at 30 cm and 40 cm coil separation. Rectifier efficiency is estimated as 90.9% on the basis of the loss in overall system efficiency when using the rectifier.
Impact of Cost Reduction Programs on Short-Term Patient Outcome and Hospital Cost of Total Knee Arthroplasty

Background: During the 1990s, cost reduction programs were developed to decrease the hospital cost of total knee arthroplasty. The purpose of this study was to evaluate the impact of hospital cost reduction programs for total knee arthroplasty on patient outcome at our hospital.Methods: We evaluated 159 patients who had undergone unilateral primary total knee arthroplasty for the treatment of osteoarthritis at the Lahey Clinic. The results of fifty-six knee replacements performed in 1992 without a clinical pathway or a knee-implant standardization program (the control group) were compared with the results of 103 knee replacements performed in 1995 with a clinical pathway and a knee-implant standardization program (the study group). Before the operation, the two patient populations were similar in terms of age, pain score on a visual analog scale, and clinical knee scores; the groups were also similar with regard to the surgical approach and the time in the operating room. The minimum duration of follow-up was eight years for the control group and five years for the study group.Results: All patients in both groups had excellent relief of pain and improvement in function. There were no differences in clinical outcome between the patient groups. The rate of patient satisfaction was 98% in the control group and 99% in the study group. Implementation of the clinical pathway was associated with a reduction in the average length of the stay in the hospital from 6.79 days in 1992 to 4.16 days in 1995. Implementation of the knee-implant standardization program was associated with increased use of all-polyethylene tibial components in 1995. Hospital cost adjusted for medical inflation was reduced 19% with the implementation of the clinical pathway and the knee-implant standardization program.Conclusions: The clinical pathway and the knee-implant standardization program reduced resource utilization and hospital cost for total knee arthroplasty without affecting short-term patient outcome in our hospital. Orthopaedic surgeons should carefully evaluate cost reduction programs, which may affect their patients, in order to maintain high-quality orthopaedic care and consistently successful patient outcomes.