Miracle-dz/UniFAR-FTUs huggingface dataset:
Etiological links between autism and difficulties in initiating and maintaining sleep: a familial co-aggregation and twin study.

BACKGROUND Difficulties initiating and maintaining sleep (DIMS) are frequent features of autism, yet little is known about why these conditions co-occur. One possibility is that they share etiological factors, yet this hypothesis remains to be tested using quantitative genetic designs. We thus investigated etiological links between autism and DIMS using familial co-aggregation and twin methods. METHODS Twins, siblings, half-siblings, and cousins of 50,097 individuals with autism were identified from Swedish population registries. Their risk of DIMS, defined through diagnoses of insomnia and/or melatonin prescriptions, was then estimated. Twin analyses conducted on 15,279 child and adolescent twin pairs investigated etiological links between DIMS and ASD. RESULTS 22.8% of autistic individuals had DIMS. Monozygotic co-twins of individuals with autism were most at risk of DIMS compared to the reference group (OR = 6.6 [2.5-17.4]), followed by dizygotic co-twins (OR = 2.6 [1.5-4.5]) and full siblings (OR = 2.5 [2.4-2.6]). Half-siblings and cousins of individuals with autism were least likely to have DIMS relative to the reference group (OR range = 1.3-1.5). Twin analyses estimated a correlation of 0.57 (0.53-0.61) between autism and DIMS, with a genetic correlation of 0.62 (0.60-0.68). These overlapping genetic factors explained 94% of the covariance between these conditions. Autistic traits also showed genetic overlap with DIMS. CONCLUSIONS Our results suggest that shared genetic mechanisms underlie autism and DIMS, which may lead them to co-occur. Untangling the etiological overlap between these conditions has potential to assist in understanding the etiology of each condition, as well as their associated outcomes.
A Scalable Bidimensional Randomization Scheme for TLC 3D NAND Flash Memories

Data randomization has been a widely adopted Flash Signal Processing technique for reducing or suppressing errors since the inception of mass storage platforms based on planar NAND Flash technology. However, the paradigm change represented by the 3D memory integration concept has complicated the randomization task due to the increased dimensions of the memory array, especially along the bitlines. In this work, we propose an easy to implement, cost effective, and fully scalable with memory dimensions, randomization scheme that guarantees optimal randomization along the wordline and the bitline dimensions. At the same time, we guarantee an upper bound on the maximum length of consecutive ones and zeros along the bitline to improve the memory reliability. Our method has been validated on commercial off-the-shelf TLC 3D NAND Flash memory with respect to the Raw Bit Error Rate metric extracted in different memory working conditions.
Transparent Exopolymer Particles in Deep Oceans: Synthesis and Future Challenges

Transparent exopolymer particles (TEP) are a class of abundant gel-like particles that are omnipresent in seawater. While versatile roles of TEP in the regulation of carbon cycles have been studied extensively over the past three decades, investigators have only recently begun to find intriguing features of TEP distribution and processes in deep waters. The emergence of new research reflects the growing attention to ecological and biogeochemical processes in deep oceans, where large quantities of organic carbon are stored and processed. Here, we review recent research concerning the role of TEP in deep oceans. We discuss: (1) critical features in TEP distribution patterns, (2) TEP sources and sinks, and (3) contributions of TEP to the organic carbon inventory. We conclude that gaining a better understanding of TEP-mediated carbon cycling requires the effective application of gel theory and particle coagulation models for deep water settings. To achieve this goal, we need a better recognition and determination of the quantities, turnover, transport, chemical properties, and microbial processing of TEP.
Psychological State after an Acute Coronary Syndrome: Impact of Physical Limitations

The aim of this study was to investigate how physical limitations after ACS influence patients’ quality of life and health perception. This was a longitudinal clinical study. We recruited 146 patients diagnosed with ACS. The patients performed a stress test (Bruce’s protocol) for the evaluation of physical limitations and were classified according to the test result: without physical limitations (more than 10 METS), with some physical limitations (7 to 9 METS), and with high physical limitations (less than 6 METS). Significant differences were found between the three groups immediately after the diagnosis of ACS and after a period of three months, regarding health perception, anxiety, depression, sexual relationships, distress, and adjustment to disease. These differences resulted larger between the group with less limitations and the group with higher limitations. After 3 months, however, there was an overall improvement in all variables. In conclusion, physical limitations after ACS seem to influence perceived quality of life determined by measuring general health, vitality, total adaptation, emotional role, social adaptation, depression, and anxiety. Therefore, the highest the physical limitations, the poorer the psychological conditions and vice versa, even 3 months after ACS diagnosis.
Microalgae–bacteria aggregates: effect of the hydraulic retention time on the municipal wastewater treatment, biomass settleability and methane potential

BACKGROUND The use of microalgae–bacteria systems is particularly attractive for wastewater treatment, and the generated biomass can be further used for methane production. The aim of this study was to evaluate the influence of the hydraulic retention time (HRT) on the organic matter, nutrient removal, settling properties and the biochemical methane potential using a granular microalgae–bacteria system in a high rate algal pond. RESULTS The primary microorganisms present in the system were constituted by diatoms, green filamentous microalgae and bacteria. At 2 d of HRT the system showed the lowest performance while high chemical oxygen demand (COD) (>92%), ammonium (>85%) and phosphorus (up to 30%) removal was observed at 6 and 10 d of HRT. High settling velocities (up to 8 m h−1) were observed due to agglomerates and granules as dominant structures. The highest methane yield and production rates (348 mL CH4 g−1 VS and 56 mL CH4 g−1 VS d−1) were observed with the biomass obtained at 10 d of HRT. CONCLUSION Flocs and granules were the dominant structures in the system. High settling velocities and low effluent total suspended solids concentrations were obtained at higher HRT. An inverse relationship between HRT and the biochemical methane potential was observed. © 2016 Society of Chemical Industry
An adamantamine derivative as a drug candidate for the treatment of visceral leishmaniasis.

BACKGROUND This study aimed to investigate compounds acting on the host cell machinery to impair parasite installation with the possible advantage of limiting drug resistance. The strategy therefore consisted of selecting compounds that are poorly active on the axenic parasite, but very active on the intramacrophage form of Leishmania. OBJECTIVES To identify a drug candidate from focused screening of adamantamine derivatives that can inhibit the development of Leishmania infantum in macrophages. METHODS In vitro screening was performed on a library of 142 adamantamine derivatives with axenic and intramacrophage forms of L. infantum, as well as cytotoxicity assays, allowing selection of the most promising compound. Absorption, distribution, metabolism and excretion (ADME) experiments, including pharmacokinetics and microsomal stability, were performed and finally the physicochemical stability of the compound was investigated to assess its suitability for further drug development. RESULTS VP343 was identified first in vitro, with a CC50 value of 63.7 μM and an IC50 value of 0.32 μM for L. infantum intramacrophage amastigotes and then in vivo, with a 59% reduction of the liver parasite burden after oral administration at 10 mg/kg/day for 5 days. In addition, the ADME data were compatible with moving this compound further through the antileishmanial drug candidate pipeline. CONCLUSIONS VP343 has the properties of a good drug candidate and merits further investigations.
Transcriptomic and Epigenomic Landscape in Rett Syndrome

Rett syndrome (RTT) is an extremely invalidating, cureless, developmental disorder, and it is considered one of the leading causes of intellectual disability in female individuals. The vast majority of RTT cases are caused by de novo mutations in the X-linked Methyl-CpG binding protein 2 (MECP2) gene, which encodes a multifunctional reader of methylated DNA. MeCP2 is a master epigenetic modulator of gene expression, with a role in the organization of global chromatin architecture. Based on its interaction with multiple molecular partners and the diverse epigenetic scenario, MeCP2 triggers several downstream mechanisms, also influencing the epigenetic context, and thus leading to transcriptional activation or repression. In this frame, it is conceivable that defects in such a multifaceted factor as MeCP2 lead to large-scale alterations of the epigenome, ranging from an unbalanced deposition of epigenetic modifications to a transcriptional alteration of both protein-coding and non-coding genes, with critical consequences on multiple downstream biological processes. In this review, we provide an overview of the current knowledge concerning the transcriptomic and epigenomic alterations found in RTT patients and animal models.
Fine Mapping of a Major Pleiotropic QTL Associated with Sesamin and Sesamolin Variation in Sesame (Sesamum indicum L.)

Deciphering the genetic basis of quantitative agronomic traits is a prerequisite for their improvement. Herein, we identified loci governing the main sesame lignans, sesamin and sesamolin variation in a recombinant inbred lines (RILs, F8) population under two environments. The content of the two lignans in the seeds was investigated by HPLC. The sesamin and sesamolin contents ranged from 0.33 to 7.52 mg/g and 0.36 to 2.70 mg/g, respectively. In total, we revealed 26 QTLs on a linkage map comprising 424 SSR markers, including 16 and 10 loci associated with sesamin and sesamolin variation, respectively. Among them, qSmin_11. 1 and qSmol_11. 1 detected in both the two environments explained 67.69% and 46.05% of the phenotypic variation of sesamin and sesamolin, respectively. Notably, qSmin11-1 and qSmol11-1 were located in the same interval of 127–127.21 cM on LG11 between markers ZMM1776 and ZM918 and acted as a pleiotropic locus. Furthermore, two potential candidate genes (SIN_1005755 and SIN_1005756) at the same locus were identified based on comparative transcriptome analysis. Our results suggest the existence of a single gene of large effect that controls expression, both of sesamin and sesamolin, and provide genetic information for further investigation of the regulation of lignan biosynthesis in sesame.
In-Silico Modeling of Tumor Spheroid Formation and Growth

Mathematical modeling has significant potential for understanding of biological models of cancer and to accelerate the progress in cross-disciplinary approaches of cancer treatment. In mathematical biology, solid tumor spheroids are often studied as preliminary in vitro models of avascular tumors. The size of spheroids and their cell number are easy to track, making them a simple in vitro model to investigate tumor behavior, quantitatively. The growth of solid tumors is comprised of three main stages: transient formation, monotonic growth and a plateau phase. The last two stages are extensively studied. However, the initial transient formation phase is typically missing from the literature. This stage is important in the early dynamics of growth, formation of clonal sub-populations, etc. In the current work, this transient formation is modeled by a reaction–diffusion partial differential equation (PDE) for cell concentration, coupled with an ordinary differential equation (ODE) for the spheroid radius. Analytical and numerical solutions of the coupled equations were obtained for the change in the radius of tumor spheroids over time. Human glioblastoma (hGB) cancer cells (U251 and U87) were spheroid cultured to validate the model prediction. Results of this study provide insight into the mechanism of development of solid tumors at their early stage of formation.
Ethnicity-Specific Normative Models of Quadruple Test as a Screening Test for Down Syndrome

Background and Objectives: To establish normative models for median levels of serum biomarkers of the second trimester quad test (alpha-fetoprotein: AFP; free beta-human gonadotropins: hCG; inhibin-A; and unconjugated estriol: uE3) specific to Thai women and to compare multiples of the median (MoMs) derived from ethnicity-specific models and those derived from Caucasian models with ethnic correction. Materials and Methods: A cross-sectional study was undertaken in a tertiary, medical teaching center among low-risk pregnant Thai women between 14 and 21 weeks of gestation to measure the levels of the four serum biomarkers. The measured values of each biomarker were analyzed using the multivariable factorial polynomial technique for quantile regression as a function of gestational age and maternal weight. Results: The Thai-specific normative models for the four biomarkers were generated and available for use. The MoMs of all individuals generated from our models were significantly different from conventional (Caucasian) models with ethnic correction (Wilcoxon signed-rank test; p < 0.0001 for all biomarkers). The MoMs of AFP and hCG from both methods were in agreement, but those from Thai-specific models were significantly higher. However, those of inhibin-A and uE3 were markedly different and ethnic correction was unlikely to be useful. Conclusions: The Thai-specific normative models of the quad test as a function of gestational age and maternal weight were constructed using multivariable factorial polynomial models, better than simple quantile regression or log-linear regression used in earlier decades. The analysis of MoMs supports the use of ethnicity-specific models instead of Caucasian models with ethnic correction.
Availability, Nutritional Profile and Processing Level of Food Products Sold in Vending Machines in a Spanish Public University

Background. Given the lack of data about the nutritional value and other determinants of the consumption of foods and drinks sold in vending machines in European universities and the relevance of this sector in Spain, it is necessary to obtain scientific data on this topic. The present study aimed to assess the availability, nutritional profile and processing level of food products from vending machines at a Spanish public university and to investigate differences in nutritional profile according to the cost and promotion. Methods. Cross-sectional descriptive study. Data from all products available (3894) were collected and analysed using the criteria of the Spanish Agency for Consumption, Food Safety and Nutrition and the United Kingdom nutrient profiling model. The items were also classified according to the degree of industrial processing through the NOVA system. Promotion was assessed, taking into account where products were displayed in vending machines. Results. The most common products were sweets (23.4% of the total options), coffee (20.3%) and salty snacks (11.7%). According to the combination of the two criteria used to assess nutritional profile, 48.6% of the products were classified as with low nutritional quality (LNQ). In addition, 73.8% of the items were categorised as “ultra-processed”. Foods (β = 0.31, 95% CI 0.24, 0.39, p < 0.001) and hot drinks (β = 0.46, 95% CI 0.39, 0.52, p < 0.001) with high nutritional quality (HNQ) were more likely to have higher prices than alternatives with LNQ. Both foods and cold drinks that support healthy dietary recommendations were promoted to a lesser extent than those with LNQ (p < 0.001). Conclusion. Almost half of the products were of LNQ and three-quarters had a high level of processing. Moreover, foods and cold drinks with LNQ were less expensive and more often promoted than alternatives with HNQ.
Psychological Stress among Students in Health-Related Fields during the COVID-19 Pandemic: Results of a Cross-Sectional Study at Selected Munich Universities

The COVID-19 pandemic has been a challenging period of upheaval for higher education students. This study aims to assess the factors associated with psychological stress during the COVID-19 pandemic among a sample of students in health-related fields at Munich universities in Germany. Students (n = 623) from KSH Munich and LMU Munich completed an online cross-sectional survey. Information on demographics and academic and everyday difficulties due to the COVID-19 pandemic as well as data on physical and mental health were collected. Multivariable logistic regression analyses were performed to identify factors associated with the outcome. The prevalence for higher psychological stress was 44% among the study population. Factors associated with higher psychological stress were: lower overall life satisfaction (p < 0.0001), worsened health situation (p < 0.0001), lack of social support (p = 0.0301) and social interaction (p = 0.0115), worries about financial difficulties due to loss of income (p = 0.0134), stressful thoughts about a second wave (p < 0.0001), feeling unable to positively influence the situation (p = 0.0262) and study-related effects, such as perceived study burden (p = 0.0003) and likely delay in studies (p = 0.0178)). The COVID-19 pandemic is having a significant negative impact on the mental health of students in health-related fields. Proactive efforts to support the mental health and well-being of students are needed.
Roles of Hostility and Depression in the Association between the MAOA Gene Polymorphism and Internet Gaming Disorder

The metabolism of bioamine in the central nervous system contributes to the development of addiction. We examined the roles of hostility and depression in the association between internet gaming disorder (IGD) and monoamine oxidase-A (MAOA) EcoRV polymorphism (rs1137070). A total of 69 adults with IGD and 138 without IGD were recruited through diagnostic interviewing. We evaluated participants for rs1137070, depression, and hostility. The participants with the TT genotype of rs1137070 had a higher odds ratio of 2.52 (1.37–4.64) for IGD compared with the C carriers. Expressive hostility behavior and hostility cognition mediated the association between rs1137070 and IGD. Indicating lower MAOA activity, the TT genotype predicted IGD and higher expressive hostility behavior and hostility cognition. Expressive hostility behavior and hostility cognition may underline the association between rs1137070 and IGD. Assessment of and intervention for hostility behavior and cognition should be provided to attenuate the risk of IGD, particularly in those with the TT genotype. Further brain imaging or neurobiological studies are required to elucidate the possible mechanism underlying the association between MAOA activity and IGD.
Effects of a Modified Tap Dance Program on Ankle Function and Postural Control in Older Adults: A Randomized Controlled Trial

Older adults are at a high risk of falling due to age-related degradations in physical fitness. This study aimed to examine the effects of a modified tap dance program (MTD) on ankle function and postural control in older adults. Forty-four healthy older adults (mean age = 64.1 years, with 9 men) were recruited from local communities and were randomly divided into the MTD group and the control (CON) group. The MTD group received 12 weeks of MTD training 3 times per week for 30 min per session. Outcomes were measured using the five times sit-to-stand test (FTSST) for ankle strength, the universal goniometer for ankle range of motion, and the Footscan® to trace the center of pressure. Results revealed significant improvements in FTSST in the MTD group (mean difference = 1.01), plantar flexion (left = 9.10, right = 10.0). In addition, the MTD group displayed significantly more improvements at midtest than the CON group in FTSST (mean difference = 1.51) and plantar flexion (mean difference: left = 6.10; right = 4.5). Therefore, the MTD can be an effective exercise program for ankle function improvement, but it has limited effects on improving postural control among healthy older adults.
Coupling of the engineered DNA “mutator” to a biosensor as a new paradigm for activation of silent biosynthetic gene clusters in Streptomyces

Abstract DNA replication fidelity in Streptomyces bacteria, prolific producers of many medically important secondary metabolites, is understudied, while in Escherichia coli it is controlled by DnaQ, the ϵ subunit of DNA polymerase III (DNA PolIII). Manipulation of dnaQ paralogues in Streptomyces lividans TK24, did not lead to increased spontaneous mutagenesis in this bacterium suggesting that S. lividans DNA PolIII uses an alternative exonuclease activity for proofreading. In Mycobacterium tuberculosis, such activity is attributed to the DnaE protein representing α subunit of DNA PolIII. Eight DnaE mutants designed based on the literature data were overexpressed in S. lividans, and recombinant strains overexpressing two of these mutants displayed markedly increased frequency of spontaneous mutagenesis (up to 1000-fold higher compared to the control). One of these ‘mutators’ was combined in S. lividans with a biosensor specific for antibiotic coelimycin, which biosynthetic gene cluster is present but not expressed in this strain. Colonies giving a positive biosensor signal appeared at a frequency of ca 10–5, and all of them were found to produce coelimycin congeners. This result confirmed that our approach can be applied for chemical- and radiation-free mutagenesis in Streptomyces leading to activation of orphan biosynthetic gene clusters and discovery of novel bioactive secondary metabolites.
Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.