Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistent high risk HPV infection associated with development of cervical neoplasia in a prospective population study

Aims: To monitor the association between the course of high risk human papillomavirus (HR-HPV) infection and the development of cervical neoplasia over time, from a baseline of normal cervical cytology. Methods: This paper presents the follow up data from a previous cross sectional analysis. Women from a screening population who had normal cytology and who were HR-HPV positive were recalled after two to three years for cytology and HPV genotyping. The development of cervical neoplasia at follow up was related to the course of HPV infection (clearance, persistence, or sequential infection) and the presence of single or multiple HPV infections at baseline. A comparator control group of women who were HPV and cytologically negative at baseline were selected from the same population. Results: Twelve cases of dyskaryosis were found in women who were HPV positive at baseline; four were high grade. Only three cases of low grade dyskaryosis were found in the control group. Women with type specific persistent infections were significantly more likely to develop cervical neoplasia than women who cleared the infection (p = 0.0001) or were sequentially infected with different types (p = 0.001). Women with multiple HPV infections at baseline were no more likely to develop cervical dyskaryosis than those with a single infection. Conclusions: Type specific persistent HR-HPV infection as monitored by genotyping can identify women at increased risk of cervical neoplasia more accurately than a single or repeated presence/absence HPV test. The cost effectiveness of such an approach should be investigated by an appropriate, large scale cost–benefit analysis.
Altered brain function in persistent postural perceptual dizziness: A study on resting state functional connectivity

This study used resting state functional magnetic resonance imaging (rsfMRI) to investigate whole brain networks in patients with persistent postural perceptual dizziness (PPPD). We compared rsfMRI data from 38 patients with PPPD and 38 healthy controls using whole brain and region of interest analyses. We examined correlations among connectivity and clinical variables and tested the ability of a machine learning algorithm to classify subjects using rsfMRI results. Patients with PPPD showed: (a) increased connectivity of subcallosal cortex with left superior lateral occipital cortex and left middle frontal gyrus, (b) decreased connectivity of left hippocampus with bilateral central opercular cortices, left posterior opercular cortex, right insular cortex and cerebellum, and (c) decreased connectivity between right nucleus accumbens and anterior left temporal fusiform cortex. After controlling for anxiety and depression as covariates, patients with PPPD still showed decreased connectivity between left hippocampus and right inferior frontal gyrus, bilateral temporal lobes, bilateral insular cortices, bilateral central opercular cortex, left parietal opercular cortex, bilateral occipital lobes and cerebellum (bilateral lobules VI and V, and left I–IV). Dizziness handicap, anxiety, and depression correlated with connectivity in clinically meaningful brain regions. The machine learning algorithm correctly classified patients and controls with a sensitivity of 78.4%, specificity of 76.9%, and area under the curve = 0.88 using 11 connectivity parameters. Patients with PPPD showed reduced connectivity among the areas involved in multisensory vestibular processing and spatial cognition, but increased connectivity in networks linking visual and emotional processing. Connectivity patterns may become an imaging biomarker of PPPD.
Extended bioreactor conditioning of mononuclear cell–seeded heart valve scaffolds

The tissue-engineered heart valve may be the ideal valve replacement option but still must overcome challenges in leaflet recellularization. This study sought to investigate the potential for leaflet matrix restoration and repopulation following mononuclear cell seeding and extended periods of bioreactor conditioning. Human aortic heart valves were seeded with mononuclear cells and conditioned in a pulsatile bioreactor for 3 days, 3 weeks, or 6 weeks. The results of this study determined that a mononuclear cell population can be readily localized within the leaflet tissue in as little as 3 days. Furthermore, as extended bioreactor condition continued to the 3- and 6-week time points, the mesenchymal stem cell subfraction proliferated and appeared to become the predominant cell phenotype. This was evident through positive expression of mesenchymal stem cell markers and no expression of mononuclear cell markers observed by immunohistochemistry in the 3- and 6-week groups. In addition, cells in the 3- and 6-week groups exhibited an up-regulation of mesenchymal stem cell–associated genes (THY1, NT5E, and ITGB1) and a down-regulation of mononuclear cell–associated genes (CD14, ICAM1, and PECAM1) compared to the initial seeded cell population. However, repopulation of the leaflet interstitium was less extensive than anticipated. Valves in the 6-week time point also exhibited retracted leaflets. Thus, while the 3-week bioreactor-conditioning period used in this study may hold some promise, a bioreactor-conditioning period of 6 weeks is not a viable option for clinical translation due to the negative impact on valve performance.
Expression of Ovol2 is related to epithelial characteristics and shows a favorable clinical outcome in hepatocellular carcinoma

Metastasis involves epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition. Ovol2 belongs to the Ovo-like family (Ovol) of evolutionarily conserved zinc-finger transcription factors that regulate gene expression in various differentiation processes. Recent studies have demonstrated that Ovols affect mesenchymal–epithelial transition by inducing the expression of miR-200 in a range of human cancers. Downregulated Ovol2 expression is involved in the invasion and metastasis of breast and prostate cancers, but little is known about its expression and prognostic value in other cancers, including hepatocellular carcinoma (HCC). This study was designed to explore the clinical and prognostic significance of Ovol2 in patients with HCC. The expression of Ovol2 in tumor samples from patients with HCC and HCC cell lines was examined using Western blotting, real-time polymerase chain reaction, and immunohistochemistry. The expression levels of EMT-related markers, including E-cadherin, N-cadherin, and vimentin, were detected in relation to Ovol2 expression. The prognostic significance of Ovol2 in patients with HCC was statistically analyzed by Kaplan–Meier and Cox regression analyses. Ovol2 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues. Low expression of Ovol2 was detected in HCC tissues with poor histological differentiation, microvascular invasion, and cirrhosis. A significant relationship was observed between Ovol2 and EMT marker expression levels. Kaplan–Meier analysis showed that overall survival was significantly worse in patients with HCC with low Ovol2 expression, indicating that Ovol2 deletion was an independent predictor of unfavorable prognosis in patients with HCC. Elevated Ovol2 expression may suppress HCC cell invasion and metastasis via restricting EMT.
Estimating under-reporting of energy intake in dietary surveys using an individualised method

Under-reporting (UR) of energy intake (EI) by self-reported dietary methods is well-documented but the methods used to estimate UR in population-based studies commonly assume a sedentary lifestyle. We compared estimated UR using individualised estimates of energy requirements with a population cut-off based on minimum energy needs. UR was estimated for 1551 adults aged 19–64 years enrolled in the National Diet and Nutrition Survey. Physical activity diaries and 7 d weighed dietary records were completed concurrently. Mean daily EI (kJ/d) was calculated from the dietary records. Reported physical activity was used to assign each subject's activity level, and then to calculate estimated energy requirements (EER) from published equations. UR was calculated both as EER – EI with an adjustment for daily EER and EI variation, and also by a population method. By the individual method UR was approximately 27 % of energy needs in men and 29 % in women, with 75 % of men and 77 % of women classified as under-reporters; by the population method 80 and 88 % were classified as under-reporters respectively. When subjects who reported their eating being affected by dieting or illness during dietary recording were excluded, UR was 25 % of energy needs in both sexes. UR was higher in overweight and obese men and women compared with their lean counterparts (P < 0·001). UR of EI must be considered in dietary surveys. The EER method allows UR to be quantified and takes into account an individual's activity level. Measures of physical activity and questions to identify under-eating during dietary recording may help to evaluate secular trends in UR.
Macronutrient and Major Food Group Intake in a Cohort of Southern Italian Adults

Background: Dietary intake of macronutrient and foods is considered crucial to decrease the risk of diet-related non-communicable diseases. Methods: The aim of this study was to describe the intake of major food groups and macronutrients in a random sample of 1838 southern Italian adults. Results: No significant differences of macronutrient consumption between sexes were found. By contrast, younger individuals had significantly higher intake of animal protein than older ones. Men reported consuming significantly more total processed meats and less eggs than women; egg consumption significantly increased by age groups. Significantly lower intake of fruit in the younger age group compared to older ones was found. Various patterns of correlation between food groups were described. More than half of individuals reached the suggested recommendations for carbohydrate and fiber intake, and about two-thirds met the recommendations for total protein and cholesterol intake, while only a minority met for total fat intake. Total and plant protein, monounsaturated and omega-6 fatty acids, were significantly inversely related with BMI (body mass index), while trans fatty acids and cholesterol were directly correlated. A direct association with unprocessed meats and an inverse association with processed meats was also found. Conclusions: The overall findings suggest that relatively healthy dietary habits are common in southern Italy.
Optimization of differentiation time of mesenchymal-stem-cell to tenocyte under a cyclic stretching with a microgrooved culture membrane and selected measurement cells.

PURPOSE There is a need for efficient stem cell-to-tenocyte differentiation techniques for tendon tissue engineering. More than 1 week is required for tenogenic differentiation with chemical stimuli, including co-culturing. Research has begun to examine the utility of mechanical stimuli, which reduces the differentiation time to several days. However, the precise length of time required to differentiate human bone marrow-derived mesenchymal stem cells (hBMSCs) into tenocytes has not been clarified. Understanding the precise time required is important for future tissue engineering projects. Therefore, in this study, a method was developed to more precisely determine the length of time required to differentiate hBMSCs into tenocytes with cyclic stretching stimulus. METHODS First, it had to be determined how stretching stimulation affected the cells. Microgrooved culture membranes were used to suppress cell orientation behavior. Then, only cells oriented parallel to the microgrooves were selected and evaluated for protein synthesis levels for differentiation. RESULTS The results revealed that growing cells on the microgrooved membrane and selecting optimally-oriented cells for measurement improved the accuracy of the differentiation evaluation, and that hBMSCs differentiated into tenocytes in approximately 10 h. CONCLUSIONS The differentiation time corresponded to the time required for cellular cytoskeleton reorganization and cellular morphology alterations. This suggests that cells, when subjected to mechanical stimulus, secrete mRNAs and proteins for both cytoskeleton reorganization and differentiation.
Research on the Premotor Symptoms of Parkinson’s Disease: Clinical and Etiological Implications

Background: The etiology and natural history of Parkinson’s disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years. Objectives: We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications. Methods: This review was based on a workshop, Parkinson’s Disease Premotor Symptom Symposium, held 7–8 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. Discussion: Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood. Conclusion: This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis. Citation: Chen H, Burton EA, Ross GW, Huang X, Savica R, Abbott RD, Ascherio A, Caviness JN, Gao X, Gray KA, Hong JS, Kamel F, Jennings D, Kirshner A, Lawler C, Liu R, Miller GW, Nussbaum R, Peddada SD, Comstock Rick A, Ritz B, Siderowf AD, Tanner CM, Tröster AI, Zhang J. 2013. Research on the premotor symptoms of Parkinson’s Disease: clinical and etiological implications. Environ Health Perspect 121:1245–1252; http://dx.doi. org/10.1289/ehp.1306967
Nutritional and other influences in childhood as predictors of adult obesity

It has been proposed that there are critical periods during childhood that influence the development of obesity, including gestation and early infancy, the period of adiposity rebound that occurs between ages 5 and 7 years, and adolescence. Despite an extensive literature, there is to date only modest evidence for most of the factors such as nutrition, physical activity and other behavioural factors that are suspected as playing a role in the development of obesity. A recent review of this evidence (Parsons et al. 1999) showed, however, a consistent relationship between socio-economic status (SES) of origin and adult obesity, whereby those from lower SES backgrounds were fatter subsequently in adulthood. This association appeared to apply to both men and women, a finding that contrasts with the trends observed in cross-sectional studies, of an association with SES for women only. There are several potential explanations for the SES of origin–adult obesity relationship. SES of origin may be confounded by parental body size; studies to date provide insufficient evidence of an independent association with SES after allowing for parental body size. Alternatively, environment in early life (for which SES of origin is a proxy measure) may have a long-term impact on obesity later in adulthood, through one or more of several processes. Three major potential explanations can be identified: (1) nutrition in infancy and childhood, either over- or undernutrition, followed subsequently by overnutrition; (2) psychological factors, possibly involving emotional deprivation in childhood; (3) cultural or social norms regarding dietary restraint and attitudes to fatness that may be acquired during childhood.
Recognition of hand motions via surface EMG signal with rough entropy

The rough entropy (RoughEn) is developed based on the rough set theory. It has the advantage of low computational complexity, because there is no parameter to set in RoughEn. In this paper, we characterized the feature of surface electromyography (SEMG) signal with RoughEn and then used support vector machine to classify six different hand motions. The sample entropy, wavelet entropy and approximate entropy were compared with RoughEn to evaluate the performance of characterizing SEMG signals. The experimental results indicated that the RoughEn-based classification outperformed other entropy based methods for recognizing six hand motions from four-channel SEMG signals with the best recognition accuracy of 95.19 ± 2.99%. The results suggest that RoughEn has the potential to be used in the SEMG-based prosthetic control as a method of feature extraction.
Development of a multipurpose scaffold for the display of peptide loops

Abstract Protein–protein interactions (PPIs) determine a wide range of biological processes and analysis of these dynamic networks is increasingly becoming a mandatory tool for studying protein function. Using the globular ATPase domain of recombinase RadA as a scaffold, we have developed a peptide display system (RAD display), which allows for the presentation of target peptides, protein domains or full-length proteins and their rapid recombinant production in bacteria. The design of the RAD display system includes differently tagged versions of the scaffold, which allows for flexibility in the protein purification method, and chemical coupling for small molecule labeling or surface immobilization. When combined with the significant thermal stability of the RadA protein, these features create a versatile multipurpose scaffold system. Using various orthogonal biophysical techniques, we show that peptides displayed on the scaffold bind to their natural targets in a fashion similar to linear parent peptides. We use the examples of CK2β/CK2α kinase and TPX2/Aurora A kinase protein complexes to demonstrate that the peptide displayed by the RAD scaffold can be used in PPI studies with the same binding efficacy but at lower costs compared with their linear synthetic counterparts.
Modulating the endocannabinoid system in human health and disease – successes and failures

The discovery of the endocannabinoid system, comprising the G‐protein coupled cannabinoid 1 and 2 receptors (CB1/2), their endogenous lipid ligands or endocannabinoids, and synthetic and metabolizing enzymes, has triggered an avalanche of experimental studies implicating the endocannabinoid system in a growing number of physiological/pathological functions. These studies have also suggested that modulating the activity of the endocannabinoid system holds therapeutic promise for a broad range of diseases, including neurodegenerative, cardiovascular and inflammatory disorders; obesity/metabolic syndrome; cachexia; chemotherapy‐induced nausea and vomiting; and tissue injury and pain, amongst others. However, clinical trials with globally acting CB1 antagonists in obesity/metabolic syndrome, and other studies with peripherally‐restricted CB1/2 agonists and inhibitors of the endocannabinoid metabolizing enzyme in pain, have introduced unexpected complexities, suggesting that a better understanding of the pathophysiological role of the endocannabinoid system is required to devise clinically successful treatment strategies.
No Evidence of Genetic Mediation in the Association Between Birthweight and Academic Performance in 2,413 Danish Adolescent Twin Pairs

Abstract Evidence of a positive association between birthweight and IQ has been established in several studies. Analyses of within twin pair differences in birthweight and IQ have been used to shed light on the basis of the association. The strength of this approach is the possibility of controlling for both unmeasured common childhood–environmental factors as well as genetic factors shared by the co-twins. Two twin studies suggest the existence of genetic mediation between birthweight and IQ, that is, common genetic factors influence both fetal growth and IQ in childhood, while two other twin studies find no evidence of such mediation. In the present study we use a large population-based national register study of 2,413 Danish twin-pairs from birth cohorts 1986–1990, of which we have zygosity information on 74%. We perform individual level as well as intra-pair analyses of birthweight and school achievements at age 16. For both sexes we observed a monotonic increase in academic performance with increasing percentiles of birthweight. However, we did not find that this association is due to genetic mediation.
n (cid:1) 3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO 2 Study 1–3

Background: Knowledge of the influence of nutritional intake on bone health is limited. Polyunsaturated fatty acids have been suggested to influence bone growth and modeling in humans, although data are sparse. Objective: The objective was to investigate the role of fatty acids in bone accumulation and the attainment of peak bone mass in young men. Design: The cohort studied consisted of 78 healthy young men with a mean age of 16.7 y at baseline. Bone mineral density (BMD; in g/cm 2 ) of total body, hip, and spine was measured at baseline and at 22 and 24 y of age. Fatty acid concentrations were measured in the phospholipid fraction in serum at 22 y of age. Results: Concentrations of n (cid:1) 3 fatty acids were positively associated with total BMD ( r (cid:2) 0.27, P (cid:2) 0.02) and spine BMD ( r (cid:2) 0.25, P (cid:2) 0.02) at 22 y of age. A positive correlation between n (cid:1) 3 fatty acid concentrations and the changes in BMD at the spine ( r (cid:2) 0.26, P (cid:2) 0.02) was found between 16 and 22 y of age. Concentrations of docosahexaenoic acid (DHA, 22:6n (cid:1) 3) were positively associated with total BMD ( r (cid:2) 0.32, P (cid:2) 0.004) and BMD at the spine ( r (cid:2) 0.30, P (cid:2) 0.008)at22yofage.Apositivecorrelationwasalsofound between DHA concentrations and the changes in BMD at the spine ( r (cid:2) 0.26, P (cid:2) 0.02) between 16 and 22 y of age. Conclusion: The results showed that n (cid:1) 3 fatty acids, especially DHA, are positively associated with bone mineral accrual and, thus, with peak BMD in young men. Am J Clin Nutr 2007;85:803–7.