Miracle-dz/UniFAR-FTUs huggingface dataset:
Are Psycho-Behavioral Factors Accounting for Longevity?

The general objective of this article is to critically review the state of the art regarding current factors accounting for aging, longevity and successful longevity. There are two major constructs which most authors are employing to account for longevity: genetic or intrinsic components versus environmental or extrinsic factors. This classification has important flaws: (i) From an epigenetic standpoint, such a polar classification could lead to misconceptions since both factors are interdependent through lifelong interactions. (ii) There are no specifications regarding these “environmental” factors, which include a broad heterogeneity of conditions (physical, economic, social, and cultural aspects as well as behavioral ones such as lifestyle) but do not include personal conditions, such as psychological characteristics. The review of the new paradigm called successful aging yields an important set of psycho-behavioral factors, and although population indexes such as Disability Free Life Expectancy (DFLE) or Healthy Life expectancy (HLE) have been developed, authors do not take into consideration healthy or successful longevity as a potential prolongation of the new paradigm of active or successful aging. There is a broad corpus of research literature supporting the importance of psycho-behavioral (PB) factors intervening in the ways of aging, specifically intelligence and cognitive functioning, positive emotion and control, personality traits, psychosocial, physical conditions, and lifestyles, all of which are highly associated with active aging, health, longevity, and survival. The importance of these factors accounting for longevity, and successful longevity must be taken into consideration as a pending issue in gerontology.
Association Between Atrial Fibrillation and Dementia: A Meta-Analysis

Background: A potential evidence from previous epidemiological studies remains conflicting findings regarding the association between atrial fibrillation (AF) and dementia risk. We, therefore, carried out a meta-analysis of relevant studies to investigate the magnitude of the association between AF and dementia risk. Methods: We performed a systematic literature search of PubMed, EMBASE, and Google Scholar for potential studies between January 1, 1990, and December 31, 2018, with no restriction on the publication language. All potential studies were independently assessed by two reviewers. We only included observational studies that calculated the odds ratio (OR)/hazards ratio (HR) for dementia associated with atrial fibrillation. We first assessed the heterogeneity among study-specific HRs using the Q statistic and I2 statistic. We then used the random-effects model to obtain the overall HR and its 95% CI for all studies. We also tested and corrected for publication bias by funnel plot–based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. Results: A total of 16 studies with 2,415,356 individuals, and approximately 200,653 cases of incidence dementia were included in this study. Patients with AF had a greater risk of incidence dementia than those without AF (random-effect hazard ratio HR: 1.36, 95% CI: 1.23–1.51, p < 0.0001; I2 = 83.58). Funnel plot and Egger test did not reveal significant publication bias. However, limitations of the study included high heterogeneity and varying degrees of confounder adjustment across individual studies. Conclusion: This study serves as added evidence supporting the hypothesis that AF is associated with an increased risk of dementia. More studies are needed to establish whether optimal treatment of AF can reduce or mitigate the risk of dementia.
Disorders of Puberty in Severely Neurologically Impaired Children: Is Delayed Puberty an Underestimated Problem?

Introduction: In children with disabilities, precocious puberty (PP) has been reported, however there is a paucity of studies on delayed puberty (DP) in neurologically impaired (NI) children. Patients and Methods: We retrospectively evaluated 65 patients with severe disabilities (6–18 years). DP was considered whenever the following criteria where satisfied, respectively, for girls and boys, absence of breast development by age 13 or menarche by age 15, absence of at least 4 mL testicular growth volume or 2.5 cm length by age 14. PP was defined as the presence of puberty signs at <8 and 9 years of age, respectively, for girls and boys. In all patients, a physical examination was performed and a family history of DP was obtained. A hormonal panel was evaluated when puberty disorders were detected. As a control group we evaluated 50 age-matched healthy subjects. Results: Puberty disorders were observed in 12 NI patients and in one control (18.5 vs. 2%, p < 0.01). DP was detected in 8 NI subjects (3M/5F) and in one healthy boy (p = 0.04), without differences between genders among patients from the NI group (p = 0.2), and compared with the controls (p = 0.4). In five of the eight NI subjects, Tanner stage 1 was observed; in three subjects adrenarche was present without pubertal progression for more than 2 years. Low levels of gonadotropins were detected in all NI subjects with DP. The number of subjects with a BMI <-3SDS was higher in NI patients with DP compared to NI subjects with normal puberty (p < 0.01); normal weight was detected in one healthy boy. The family history for pubertal delay was negative in all NI patients with DP and positive in the control subject. Conclusion: NI children and adolescents may experience delayed pubertal changes. An endocrinological follow-up with pubertal development monitoring is strongly recommended in order to evaluate whether targeted interventions may improve outcomes.
Spelling in Deaf, Hard of Hearing and Hearing Children With Sign Language Knowledge

What do spelling errors look like in children with sign language knowledge but with variation in hearing background, and what strategies do these children rely on when they learn how to spell in written language? Earlier research suggests that the spelling of children with hearing loss is different, because of their lack of hearing, which requires them to rely on other strategies. In this study, we examine whether, and how, different variables such as hearing degree, sign language knowledge and bilingualism may affect the spelling strategies of children with Swedish sign language, Svenskt teckenspråk, (STS) knowledge, and whether these variables can be mirrored in these children’s spelling. The spelling process of nineteen children with STS knowledge (mean age: 10.9) with different hearing degrees, born into deaf families, is described and compared with a group of fourteen hearing children without STS knowledge (mean age: 10.9). Keystroke logging was used to investigate the participants’ writing process. The spelling behavior of the children was further analyzed and categorized into different spelling error categories. The results indicate that many children showed exceptionally few spelling errors compared to earlier studies, that may derive from their early exposure of STS, enabling them to use the fingerspelling strategy. All of the children also demonstrated similar typing skills. The deaf children showed a tendency to rely on a visual strategy during spelling, which may result in incorrect, but visually similar, words, i.e., a type of spelling errors not found in texts by hearing children with STS knowledge. The deaf children also showed direct transfer from STS in their spelling. It was found that hard-of-hearing children together with hearing children of deaf adults (CODAs), both with STS knowledge, used a sounding strategy, rather than a visual strategy. Overall, this study suggests that the ability to hear and to use sign language, together and respectively, play a significant role for the spelling patterns and spelling strategies used by the children with and without hearing loss.
Exploiting Curcumin Synergy With Natural Products Using Quantitative Analysis of Dose–Effect Relationships in an Experimental In Vitro Model of Osteoarthritis

Introduction: Drug combination is widely used to treat chronic inflammatory diseases. A similar strategy might be worth of interest to design plant-derived natural products to treat inflammatory conditions. Curcumin is a natural phenolic compound which shares anti-inflammatory activity with both flavocoxid, a flavonoid mixture of baicalin and catechin, and β-caryophyllene, a bicyclic sesquiterpene. The aim of this study was to investigate the synergy potential of curcumin with both flavocoxid and β-caryophyllene in human articular chondrocytes triggered with lipopolysaccharide (LPS), in an experimental in vitro model of osteoarthritis. Materials and Methods: Human articular chondrocytes were stimulated with LPS alone or in combination with different treatments. Total RNA was extracted 4 h after treatment to study interleukin 1β (IL-1β), NF-κB, and STAT3 mRNA expression. A drug combination study was designed choosing 5 doses to demonstrate a synergistic effect of compounds, according to Chou and Talalay method. A median-effect equation was applied and finally, the combination index (CI) was used to clarify the nature of the compounds interaction (synergistic versus additive versus antagonistic inhibitory effects); CI < 1, CI = 1, and CI > 1 indicated synergistic, additive, and antagonistic effects, respectively. Results: LPS prompted IL-1β expression. Curcumin, flavocoxid and β-caryophyllene suppressed IL-1β expression with different IC50. A synergistic action for the reduction of the inflammatory phenotype in human chondrocytes was observed for the combination curcumin-flavocoxid with a percentage from 10% to 90%, and for the combination curcumin-β-caryophyllene from 50% to 90%. IC50 doses of either flavocoxid, β-caryophyllene and curcumin alone or in combination were safe and did not affect cell vitality. Moreover, the same IC50 doses reduced the transcription factors NF-κB and STAT3 mRNA expression and interestingly the effects of the combinations were greater than the natural products alone, thus suggesting that the site where the synergy takes place could be at the signal transduction level. Discussion: The results suggest that curcumin synergizes with either flavocoxid or β-caryophyllene, exerting an anti-inflammatory activity and thus strongly suggesting the potential of a dual combination of these compounds for the management of osteoarthritis and unmasking a new feature of these natural products.
Effectiveness of Noise-Attenuating Headphones on Physiological Responses for Children With Autism Spectrum Disorders

Objective: The purpose of this study was to evaluate the proof of concept of an intervention to decrease sympathetic activation as measured by skin conductivity (electrodermal activity, EDA) in children with an autism spectrum disorder (ASD) and auditory hypersensitivity (hyperacusis). In addition, researchers examined if the intervention provided protection against the negative effects of decibel level of environmental noises on electrodermal measures between interventions. The feasibility of implementation and outcome measures within natural environments were evaluated. Method: A single-subject multi-treatment design was used with six children, aged 8–16 years, with a form of Autism (i.e., Autism, PDD-NOS). Participants used in-ear (IE) and over-ear (OE) headphones for two randomly sequenced treatment phases. Each child completed four phases: (1) a week of baseline data collection; (2) a week of an intervention; (3) a week of no intervention; and (4) a week of the other intervention. Empatica E4 wristbands collected EDA data. Data was collected on 16–20 occasions per participant, with five measurements per phase. Results: Separated tests for paired study phases suggested that regardless of intervention type, noise attenuating headphones led to a significance difference in both skin conductance levels (SCL) and frequency of non-specific conductance responses (NS-SCRs) between the baseline measurement and subsequent phases. Overall, SCL and NS-SCR frequency significantly decreased between baseline and the first intervention phase. A protective effect of the intervention was tested by collapsing intervention results into three phases. Slope correlation suggested constant SCL and NS-SCR frequency after initial use of the headphones regardless of the increase in environmental noises. A subsequent analysis of the quality of EDA data identified that later phases of data collection were associated with better data quality. Conclusion: Many children with ASD have hypersensitivities to sound resulting in high levels of sympathetic nervous system reactivity, which is associated with problematic behaviors and distress. The findings of this study suggest that the use of noise attenuating headphones for individuals with ASD and hyperacusis may reduce sympathetic activation. Additionally, results suggest that the use of wearable sensors to collect physiological data in natural environments is feasible with established protocols and training procedures.
Creating the Trans Youth Research Network: A Collaborative Research Endeavor

Abstract Purpose: This article outlines the process of establishing the Trans Youth Care Research Network, composed of four academic clinics providing care for transgender and gender-diverse (TGD) youth. The Network was formed to design and implement research studies to better understand physiologic and psychosocial outcomes of gender-affirming medical care among TGD youth. Methods: Formed in response to both the Institute of Medicine's report recommendation for an increase of data concerning sexual and gender minority populations and a transgender-specific NIH program announcement, The Center for Transyouth Health and Development at Children's Hospital Los Angeles, the Gender Management Service at Boston Children's Hospital, the Child and Adolescent Gender Center Clinic at Benioff Children's Hospital in San Francisco, and the Gender and Sex Development Program at Lurie Children's Hospital of Chicago established a collaborative research network that subsequently designed a longitudinal observational study of TGD youth undergoing medical interventions to address gender dysphoria. Results: Two cohorts, youth starting puberty blockers and youth starting gender-affirming hormones, are participating. Psychosocial measures that span multiple domains of mental and behavioral health are collected from youth and parents. Physiologic data are abstracted from patient's charts. Baseline and follow-up data of this large cohort will be disseminated through conferences, abstracts, posters, and articles. Conclusion: Since initiation of funding in 2015, a total of 497 participants have been enrolled in TYC across the four sites; gonadotropin releasing hormone analogs (GnRHa) cohort youth (n=93), GnRHa cohort parents (n=93), and gender affirming hormone cohort youth (n=311). As the network moves toward data dissemination, its lessons learned have helped strengthen the current study, as well as inform future endeavors in this field.
Association Study Between Methylation in the Promoter Regions of cGAS, MAVS, and TRAF3 Genes and the Risk of Cervical Precancerous Lesions and Cervical Cancer in a Southern Chinese Population

A case-control study was used to explore the association between the methylation status in the promoter regions of the cGAS, MAVS, and TRAF3 genes and the diseases of cervical precancerous lesions (CPL) and cervical cancer (CC) in a Southern Chinese population, and to further explore their interaction effects with high-risk human papillomavirus (hrHPV) infection and environmental factors in these diseases. The study protocol was approved by the ethics committee of The First Affiliated Hospital of Jinan University, and this study was performed in 97 healthy controls, 75 patients with CPL and 33 patients with CC, while each participant has read and signed the informed consent forms before enrolment. The promoter methylation status genes were detected from the bisulfite-treated DNA by the bisulfite sequencing PCR (BSP) technique, which was carried out using MethPrimer. The cGAS, MAVS, and TRAF3 promoter methylation levels in CPL (CPLcGAS = 35.40%, CPLMAVS = 24.26%, and CPLTRAF3 = 96.76%) were significantly higher than those in the control (ControlcGAS = 31.87%, ControlMAVS = 21.16%, and ControlTRAF3 = 96.26%, PcGAS< 0.001, PMAVS< 0.001, and PTRAF3 = 0.001); however, there was no significant differences between the CC and control. In the logistic regression model with adjusted covariates, compared with the individuals whose cGAS methylation levels were less than or equal to 31.87%, the women with the levels more than 31.87% increased the risk of CPL by 2.49 times (ORa = 2.49, 95% CI = 1.31-4.75, Pa = 0.006). The women with MAVS methylation levels above 21.16% were 1.97 times more likely to have CPL than the those with the levels less than 21.16% (ORa = 1.97, 95% CI = 1.06–3.69, Pa = 0.033). A synergistic interaction was found between hrHPV and gene promoter methylation levels of cGAS and MAVS in CPL; however, no potential interaction was observed in CC. The promoter methylation levels in cGAS, MAVS, and TRAF3 genes are higher in CPL than in control, indicating that hypermethylation might be an early event in the progression of cervical intraepithelial neoplasia (CIN). The interaction between the promoter methylation levels in cGAS and MAVS genes and hrHPV infection might play a role in the development of CPL.
Distinct Circulating Expression Profiles of Long Noncoding RNAs in Heart Failure Patients With Ischemic and Nonischemic Dilated Cardiomyopathy

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), with distinct long-term prognosis and responses to treatment, are two major problems that lead to heart failure (HF) ultimately. In this study, we investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expressions in the plasma of patients with DCM and ICM and analyzed the different lncRNA profile between the two groups. The microarray analysis identified 3,222 and 1,911 significantly differentially expressed lncRNAs and mRNAs between DCM and ICM group. The most enriched upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling and regulation of cellular localization, while the top 10 downregulated genes mainly consisted of acid secretion and myosin heavy chain binding. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed lncRNA-coexpressed mRNAs between DCM and ICM group were significantly enriched in the natural killer cell mediated cytotoxicity and ras signaling pathway respectively. Quantitative real-time PCR confirmed 8 of 12 lncRNAs were upregulated in DCM group compared to ICM group which was consistent with the initial microarray results. The lncRNA/mRNA coexpression network indicated the possible functions of the validated lncRNAs. These findings revealed for the first time the specific expression pattern of both protein-coding RNAs and lncRNAs in plasma of HF patients due to DCM and ICM which may provide some important evidence to conveniently identify the etiology of myocardial dysfunctions and help to explore a better strategy for future HF prognosis evaluation.
Academic Performance in Adolescent Students: The Role of Parenting Styles and Socio-Demographic Factors – A Cross Sectional Study From Peshawar, Pakistan

Academic performance is among the several components of academic success. Many factors, including socioeconomic status, student temperament and motivation, peer, and parental support influence academic performance. Our study aims to investigate the determinants of academic performance with emphasis on the role of parental styles in adolescent students in Peshawar, Pakistan. A total of 456 students from 4 public and 4 private schools were interviewed. Academic performance was assessed based on self-reported grades in the latest internal examinations. Parenting styles were assessed through the administration of the Parental Bonding Instrument (PBI). Regression analysis was conducted to assess the influence of socio-demographic factors and parenting styles on academic performance. Factors associated with and differences between “care” and “overprotection” scores of fathers and mothers were analyzed. Higher socio-economic status, father’s education level, and higher care scores were independently associated with better academic performance in adolescent students. Affectionless control was the most common parenting style for fathers and mothers. When adapted by the father, it was also the only parenting style independently improving academic performance. Overall, mean “care” scores were higher for mothers and mean “overprotection” scores were higher for fathers. Parenting workshops and school activities emphasizing the involvement of mothers and fathers in the parenting of adolescent students might have a positive influence on their academic performance. Affectionless control may be associated with improved academics but the emotional and psychosocial effects of this style of parenting need to be investigated before recommendations are made.
Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection

Current influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the context of an emerging pandemic strain. Here we explore the production of recombinant influenza haemagglutinin using the ciliated protozoan Tetrahymena thermophila. For the first time we were able to produce haemagglutinin from both seasonal influenza A and B strains. This ciliate derived material was immunogenic, inducing an antibody response in both mice and non-human primates. Mice immunized with ciliate derived haemagglutinin were protected against challenge with homologous influenza A or B viruses. The antigen could also be combined with submicron particles containing a Nod2 ligand, significantly boosting the immune response and reducing the dose of antigen required. Thus, we show that Tetrahymena can be used as a manufacturing platform for viral vaccine antigens.
Cis-Acting Relaxases Guarantee Independent Mobilization of MOBQ4 Plasmids

Plasmids are key vehicles of horizontal gene transfer and contribute greatly to bacterial genome plasticity. In this work, we studied a group of plasmids from enterobacteria that encode phylogenetically related mobilization functions that populate the previously non-described MOBQ4 relaxase family. These plasmids encode two transfer genes: mobA coding for the MOBQ4 relaxase; and mobC, which is non-essential but enhances the plasmid mobilization frequency. The origin of transfer is located between these two divergently transcribed mob genes. We found that MPFI conjugative plasmids were the most efficient helpers for MOBQ4 conjugative dissemination among clinically relevant enterobacteria. While highly similar in their mobilization module, two sub-groups with unrelated replicons (Rep_3 and ColE2) can be distinguished in this plasmid family. These subgroups can stably coexist (are compatible) and transfer independently, despite origin-of-transfer cross-recognition by their relaxases. Specific discrimination among their highly similar oriT sequences is guaranteed by the preferential cis activity of the MOBQ4 relaxases. Such a strategy would be biologically relevant in a scenario of co-residence of non-divergent elements to favor self-dissemination.