Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of skeletal maturity using maxillary canine, mandibular second and third molar calcification stages.

OBJECTIVE The objective of this study was to evaluate whether the calcification stages of maxillary canine, mandibular second molar, and mandibular third molar can be used for assessment of growth phase. MATERIALS AND METHODS The study group consisted of 274 subjects. Pre-treatment digital panoramic and lateral cephalometric radiographs of the patients were analysed. The patients' age was ranging from 7 to 19 years. Right maxillary canine, mandibular second molar and third molar were used as a sample. The teeth mineralization was assessed using modification of Gleiser and Hunt method. The skeletal maturation was assessed by the cervical vertebrae maturation (CVM) method. RESULTS A significant association was found between CVM stage 2 and maxillary canine (UC) stage 4, mandibular second molar (LM2) stage 4, and mandibular third molar (LM3) stage 1. CVM stage 3 corresponded with UC stage 5, LM2 stage 5, LM3 stage 2. CVM stage 4 matched with UC stage 5, LM2 stage 6 and LM3 stage 3. The highest correlations between CVM and calcification stages were in the group of the maxillary canine (r = 0.812, P < 0.01) and mandibular second molar (r = 0.824, P < 0.01). LIMITATIONS Limitation of our study was that the study sample was not very big and the distribution value in the groups was very high, so it was impossible to check more statistical parameters. CONCLUSIONS The calcification stages of UC, LM2, and LM3 as indicators of skeletal maturity could be clinically used with caution, until this method is verified with a larger sample group.
Potential of mobile technologies and applications in the detection of mild cognitive impairment among older generation groups

ABSTRACT At present, demographic changes result in the growing number of older people. This trend inevitably brings about serious social and economic issues, as well as occurrence of aging diseases. The purpose of this study is to discuss the potential of using mobile technologies and applications in the detection of aging disorders such as mild cognitive impairment. The methods used for this review study include a literature search in the world’s acknowledged databases. The findings of this study indicate that mobile applications can serve as appropriate diagnostic tools for aging disorders such as mild cognitive impairment because they seem to provide better, faster, and less costly care for older people.
A genome‐wide association study of multiple longitudinal traits with related subjects

Pleiotropy is a phenomenon that a single gene inflicts multiple correlated phenotypic effects, often characterized as traits, involving multiple biological systems. We propose a two‐stage method to identify pleiotropic effects on multiple longitudinal traits from a family‐based data set. The first stage analyses each longitudinal trait via a three‐level mixed‐effects model. Random effects at the subject‐level and at the family‐level measure the subject‐specific genetic effects and between‐subjects intraclass correlations within families, respectively. The second stage performs a simultaneous association test between a single nucleotide polymorphism and all subject‐specific effects for multiple longitudinal traits. This is performed using a quasi‐likelihood scoring method in which the correlation structure among related subjects is adjusted. Two simulation studies for the proposed method are undertaken to assess both the type I error control and the power. Furthermore, we demonstrate the utility of the two‐stage method in identifying pleiotropic genes or loci by analyzing the Genetic Analysis Workshop 16 Problem 2 cohort data drawn from the Framingham Heart Study and illustrate an example of the kind of complexity in data that can be handled by the proposed approach. We establish that our two‐stage method can identify pleiotropic effects while accommodating varying data types in the model. Copyright © 2016 John Wiley & Sons, Ltd.
Things Change: How Comparative Transcriptomics Suggest the Pallium Has Evolved at Multiple Levels of Organization

Despite a century of investigation [Smith, 1919; Holmgren, 1922; Johnston, 1923; Northcutt and Kaas, 1995; Karten, 1997; Butler and Hodos, 2005; Striedter, 2005], the evolutionary origins of the cerebral cortex remain intensely disputed [Karten, 1997; Wang et al., 2010; Suzuki et al., 2012; Dugas-Ford et al., 2012]. As brain tissue does not fossilize, comparative neurobiologists infer ancestral forms from living animals. Unfortunately, one of the earliest branches of the mammalian lineage, Eutriconodonta, went extinct at the end of the Cretaceous period (~145 to ~66 Mya). Thus, to gain insights into the evolutionary origin of the isocortex, which already existed in our most recent common ancestor with monotremes, we need to compare living sauropsids (birds and reptiles) and mammals, two clades separated by more than 300 million years of independent evolution in diverse ecological niches. Numerous studies have noted similarities in connectivity and gene expression between the layers of the mammalian isocortex and nuclear structures of the avian pallium [Karten, 1997; Dugas-Ford et al., 2012]. However, these similarities are seemingly inconsistent with homologies inferred from morphogenetic developmental data. Furthermore, gene expression has been used to support a wide variety of mutually contradictory homologies between isocortical laminae and various sectors of the avian pallium. It is in this context that we aimed to conduct an unbiased gene expression study using an objective analytical method [Belgard et al., 2013]. Because adult brain regions differ in their transcriptomes, we dissected several structures of both controversial and non-controversial homology in adult chickens and mice, and then sequenced and compared their transcriptomes. Although we would have liked to look throughout development, young embryonic brain regions contain so little RNA that this approach was not feasible with the then available technology. Therefore, we instead sequenced RNA from pooled samples representing several adult structures. The results of our study surprised us, and caused us to conclude that homologous developmental fields can yield staggeringly different adult forms and that highly similar adult characteristics can arise from non-homologous developmental fields. Moreover, homologous genes may underlie some of the physiologically comparable functions of these analogous adult regions. Although homologous sets of genes are usually expressed in cells that develop from homologous morphogenetic fields, this may not be the case in the pallium. We believe there may be different sets of plausible pallial homologies at two (or more) distinct levels of cellular organization: the phylogenetically continuous developmental lineage, and the key underlying genetic programs that distinguish one cell type from another. We argue that the latter level of homology is plausible but cannot be established until the underlying cause of this similar expression is understood.
Population structure and attribution of human clinical Campylobacter jejuni isolates from central Europe to livestock and environmental sources

Campylobacter jejuni is among the most prevalent causes of human bacterial gastroenteritis worldwide. Domesticated animals and, especially, chicken meat are considered to be the main sources of infections. However, the contribution of surface waters and wildlife in C. jejuni transmission to humans is not well understood. We have evaluated the source attribution potential of a six‐gene multiplex PCR (mPCR) method coupled with STRUCTURE analysis on a set of 410 C. jejuni strains isolated from environment, livestock, food and humans in central Europe. Multiplex PCR fingerprints were analysed using Subclade prediction algorithm to classify them into six distinct mPCR clades. A subset of C. jejuni isolates (70%) was characterized by multilocus sequence typing (MLST) demonstrating 74% congruence between mPCR and MLST. The correspondence analysis of mPCR clades and sources of isolation indicated three distinct groups in the studied C. jejuni population—the first one associated with isolates from poultry, the second one with isolates from cattle, and the third one with isolates from the environment. The STRUCTURE analysis attributed 7.2% and 21.7% of human isolates to environmental sources based on MLST and mPCR fingerprints, respectively.
Unexpected Role for Granzyme K in CD56bright NK Cell-Mediated Immunoregulation of Multiple Sclerosis

Functional NK cell deficiencies are associated with autoimmune diseases, including multiple sclerosis. NK cells can promote or inhibit adaptive immunity via either cytokine production or cytotoxicity toward immature dendritic cells and activated T cells. In humans, this immunoregulatory role resides in the CD56bright NK cell subset, which is selectively expanded by daclizumab, a CD25-blocking Ab that suppresses multiple sclerosis-associated inflammation. The objective of this study was to investigate the molecular mechanisms underlying the cytotoxicity of NK cells toward activated T cells. We demonstrated that NK cells induce caspase-independent apoptosis that requires NK cell degranulation and causes mitochondrial dysfunction in activated T cells. Although both granzyme A and granzyme K (GrK) can mediate this form of apoptosis, quantitatively we observed preferential transfer of GrK to target cells. Consequently, gene silencing of GrK in the NK-92 cell line, which retains functional characteristics of CD56bright NK cells, profoundly inhibited the ability of NK-92 cells to kill activated syngeneic T cells. Finally, we demonstrated that daclizumab treatment significantly enhanced this newly defined mechanism of cytotoxicity by CD56bright NK cells. Our study describes the important physiological role that GrK plays in immunoregulation of adaptive immunity in humans and indicates that therapeutic exploitation of this pathway is beneficial in controlling autoimmunity.
Neuronal Activation for Semantically Reversible Sentences

Semantically reversible sentences are prone to misinterpretation and take longer for typically developing children and adults to comprehend; they are also particularly problematic for those with language difficulties such as aphasia or Specific Language Impairment. In our study, we used fMRI to compare the processing of semantically reversible and nonreversible sentences in 41 healthy participants to identify how semantic reversibility influences neuronal activation. By including several linguistic and nonlinguistic conditions within our paradigm, we were also able to test whether the processing of semantically reversible sentences places additional load on sentence-specific processing, such as syntactic processing and syntactic-semantic integration, or on phonological working memory. Our results identified increased activation for reversible sentences in a region on the left temporal–parietal boundary, which was also activated when the same group of participants carried out an articulation task which involved saying “one, three” repeatedly. We conclude that the processing of semantically reversible sentences places additional demands on the subarticulation component of phonological working memory.
Multifactorial Evolution: Toward Evolutionary Multitasking

The design of evolutionary algorithms has typically been focused on efficiently solving a single optimization problem at a time. Despite the implicit parallelism of population-based search, no attempt has yet been made to multitask, i.e., to solve multiple optimization problems simultaneously using a single population of evolving individuals. Accordingly, this paper introduces evolutionary multitasking as a new paradigm in the field of optimization and evolutionary computation. We first formalize the concept of evolutionary multitasking and then propose an algorithm to handle such problems. The methodology is inspired by biocultural models of multifactorial inheritance, which explain the transmission of complex developmental traits to offspring through the interactions of genetic and cultural factors. Furthermore, we develop a cross-domain optimization platform that allows one to solve diverse problems concurrently. The numerical experiments reveal several potential advantages of implicit genetic transfer in a multitasking environment. Most notably, we discover that the creation and transfer of refined genetic material can often lead to accelerated convergence for a variety of complex optimization functions.
Perceived Demands of Schooling, Stress and Mental Health: Changes from Grade 6 to Grade 9 as a Function of Gender and Cognitive Ability

The link between perceived demands of school, stress and mental health in relation to gender is complex. The study examined, with two waves of longitudinal data at age 13 and age 16, how changes in perceived academic demands relate to changes in perceived stress, taking into account gender and cognitive ability, and to investigate how these factors affect the level of psychosomatic and depressive symptoms at the age of 16. A nationally representative sample including about 9000 individuals from the Swedish longitudinal Evaluation Through Follow up database born in 1998 was included. A growth modelling approach was applied to examine relations over time. The results show girls to have a considerably higher self-reported level of mental health problems at the end of compulsory school than boys. This gender difference is entirely accounted for by perceived school demands and stress in grades 6 and 9. Students who were stronger in inductive than vocabulary ability reported lower levels of perceived academic demands and less stress in grade 6. There is a need to develop interventions for minimizing the consequences of stress among adolescents and modify those particular aspects of academic demands which cause stress and poor mental health, especially among girls. Copyright © 2016 John Wiley & Sons, Ltd.
One year change of knee cartilage morphology in the first release of participants from the Osteoarthritis Initiative progression subcohort: association with sex, body mass index, symptoms and radiographic osteoarthritis status

Objective: The Osteoarthritis Initiative (OAI) is a multicentre study targeted at identifying biomarkers for evaluating the progression and risk factors of symptomatic knee OA. Here cartilage loss using 3 Tesla (3 T) MRI is analysed over 1 year in a subset of the OAI, together with its association with various risk factors. Methods: An age- and gender-stratified subsample of the OAI progression subcohort (79 women and 77 men, mean (SD) age 60.9 (9.9) years, body mass index (BMI) 30.3 (4.7)) with both frequent symptoms and radiographic OA in at least one knee was studied. Coronal FLASHwe (fast low angle shot with water excitation) MRIs of the right knee were acquired at 3 T. Seven readers segmented tibial and femoral cartilages blinded to order of acquisition. Segmentations were quality controlled by one expert. Results: The reduction in mean cartilage thickness (ThC) was greater (p = 0.004) in the medial than in the lateral compartment, greater (p = 0.001) in the medial femur (−1.9%) than in the medial tibia (−0.5%) and greater (p = 0.011) in the lateral tibia (−0.7%) than in the lateral femur (0.1%). Multifactorial analysis of variance did not reveal significant differences in the rate of change in ThC by sex, BMI, symptoms and radiographic knee OA status. Knees with Kellgren–Lawrence grade 2 or 3 and with a BMI >30 tended to display greater changes. Conclusions: In this sample of the OAI progression subcohort, the greatest, but overall very modest, rate of cartilage loss was observed in the weight-bearing medial femoral condyle. Knees with radiographic OA in obese participants showed trends towards higher rates of change than those of other participants, but these trends did not reach statistical significance.
Semifluorinated Alkane Eye Drops for Treatment of Dry Eye Disease Due to Meibomian Gland Disease

Abstract Purpose: Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction. Methods: Seventy-two patients with Meibomian gland disease and associated dry eye received 1 drop of perfluorohexyloctane 4 times daily during an observational, prospective, multicenter, 6–8-week study. Clinical assessment included best-corrected visual acuity, intraocular pressure, Schirmer test I, tear film breakup time, anterior and posterior blepharitis assessment, number of expressible Meibomian glands, meibum quality and quantity, ocular surface fluorescein staining, lid margin and symptom assessment, and Ocular Surface Disease Index (OSDI©). Results: From the 72 patients recruited, 61 completed the trial per protocol. Nine patients did not apply the medication as recommended and 2 patients were lost to follow-up. Tear film breakup time, corneal and conjunctival fluorescein staining, number of expressible Meibomian glands, and severity of anterior and posterior blepharitis significantly improved after 6–8 weeks of perfluorohexyloctane application. In addition, symptoms improved as demonstrated by a significant decrease of OSDI-values from 37 (±13) to 26 (±16). Conclusions: In concordance with previous findings, 6–8 weeks of topical application of perfluorohexyloctane significantly improves clinical signs of Meibomian gland disease and associated mild to moderate DED.
FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence.

BACKGROUND A common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. METHODS Forty-nine patients with PTSD and AD were admitted for 4 weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. RESULTS FAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. CONCLUSIONS This is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.
Access control management with provenance in healthcare environments

Provenance, describes how a data item came to be its current state. A Directed Acyclic Graph, nature of the provenance poses challenges to access control models and querying languages. Access control policies are needed to protect the security of data provenance. In this paper, we apply proposed notions of regular expression for provenance as the structure of a provenance graph is very large. We use an extending access control language for data provenance, and semantic Web technologies to effectively query provenances. Finally, we tailored an access control language by using the regular expressions through a medical example.
The anterior temporal lobes and the functional architecture of semantic memory

Abstract Recently, three accounts have emerged on the role of the anterior temporal lobes (ATLs) in semantic memory. One account claims that the ATLs are domain-general semantic hubs, another claims that they underlie knowledge of unique entities specifically, and yet another account claims that they support social conceptual knowledge generally. Here, we review neuropsychological and neuroimaging studies that bear on these three accounts and offer suggestions for future research to elucidate the roles of the ATLs in semantic memory. (JINS, 2009, 15, 645–649.)
Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration

Caloric restriction (CR), fasting, and exercise have long been recognized for their neuroprotective and lifespan-extending properties; however, the underlying mechanisms of these phenomena remain elusive. Such extraordinary benefits might be linked to the activation of sirtuins. In mammals, the sirtuin family has seven members (SIRT1–7), which diverge in tissue distribution, subcellular localization, enzymatic activity, and targets. SIRT1, SIRT2, and SIRT3 have deacetylase activity. Their dependence on NAD+ directly links their activity to the metabolic status of the cell. High NAD+ levels convey neuroprotective effects, possibly via activation of sirtuin family members. Mitochondrial sirtuin 3 (SIRT3) has received much attention for its role in metabolism and aging. Specific small nucleotide polymorphisms in Sirt3 are linked to increased human lifespan. SIRT3 mediates the adaptation of increased energy demand during CR, fasting, and exercise to increased production of energy equivalents. SIRT3 deacetylates and activates mitochondrial enzymes involved in fatty acid β-oxidation, amino acid metabolism, the electron transport chain, and antioxidant defenses. As a result, the mitochondrial energy metabolism increases. In addition, SIRT3 prevents apoptosis by lowering reactive oxygen species and inhibiting components of the mitochondrial permeability transition pore. Mitochondrial deficits associated with aging and neurodegeneration might therefore be slowed or even prevented by SIRT3 activation. In addition, upregulating SIRT3 activity by dietary supplementation of sirtuin activating compounds might promote the beneficial effects of this enzyme. The goal of this review is to summarize emerging data supporting a neuroprotective action of SIRT3 against Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.