Miracle-dz/UniFAR-FTUs huggingface dataset:
Anthropometric characteristics of newborns with Prader–Willi syndrome

This is a retrospective multicenter nationwide Italian study collecting neonatal anthropometric data of Caucasian subjects with Prader–Willi syndrome (PWS) born from 1988 to 2018. The aim of the study is to provide percentile charts for weight and length of singletons with PWS born between 36 and 42 gestational weeks. We collected the birth weight and birth length of 252 male and 244 female singleton live born infants with both parents of Italian origin and PWS genetically confirmed. Percentile smoothed curves of birth weight and length for gestational age were built through Cole's lambda, mu, sigma method. The data were compared to normal Italian standards. Newborns with PWS showed a lower mean birth weight, by 1/2 kg, and a shorter mean birth length, by 1 cm, than healthy neonates. Females with a 15q11‐13 deletion were shorter than those with maternal uniparental maternal disomy of chromosome 15 (p < .0001). The present growth curves may be useful as further traits in supporting a suspicion of PWS in a newborn. Because impaired prenatal growth increases risk of health problems later in life, having neonatal anthropometric standards could be helpful to evaluate possible correlations between the presence or absence of small gestational age and some clinical and metabolic aspects of PWS.
Image Content Verification based on DWT and Chaotic Map Watermarking

Image content verification is to confirm the validity of the images, i.e. . To test if the image has experienced any alteration since it was made. Computerized watermarking has turned into a promising procedure for image content verification in light of its exceptional execution and capacity of altering identification. In this study, a new scheme for image verification reliant on two dimensional chaotic maps and Discrete Wavelet Transform (DWT) is introduced. Arnold transforms is first applied to Host image (H) for scrambling as a pretreatment stage, then the scrambled host image is partitioned into sub-blocks of size 2×2 in which a 2D DWT is utilized on each sub-block to produce corresponding sub-block of DWT coefficients (LL, LH, HL and HH). Meanwhile, watermark image is encrypted using the introduced chaos-based enciphering algorithm. The watermarked image is obtained by updating the approximation coefficients (LH sub-band) of each 2×2 sub-block of DWT coefficients of the host image with the enciphered watermark image bits. Different investigational tests are performed to evaluate the act of the introduced approach. Investigation results clearly present that the proposed approach can detect and localize editing attacks perfectly.
A Derivate of Benzimidazole-Isoquinolinone Induces SKP2 Transcriptional Inhibition to Exert Anti-Tumor Activity in Glioblastoma Cells

We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.
The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating noncommunicable disease brandishing an enormous worldwide disease burden with some evidence of inherited genetic risk. Absence of measurable changes in patients’ standard blood work has necessitated ad hoc symptom-driven therapies and a dearth of mechanistic hypotheses regarding its etiology and possible cure. A new hypothesis, the indolamine-2,3-dioxygenase (IDO) metabolic trap, was developed and formulated as a mathematical model. The historical occurrence of ME/CFS outbreaks is a singular feature of the disease and implies that any predisposing genetic mutation must be common. A database search for common damaging mutations in human enzymes produces 208 hits, including IDO2 with four such mutations. Non-functional IDO2, combined with well-established substrate inhibition of IDO1 and kinetic asymmetry of the large neutral amino acid transporter, LAT1, yielded a mathematical model of tryptophan metabolism that displays both physiological and pathological steady-states. Escape from the pathological one requires an exogenous perturbation. This model also identifies a critical point in cytosolic tryptophan abundance beyond which descent into the pathological steady-state is inevitable. If, however, means can be discovered to return cytosolic tryptophan below the critical point, return to the normal physiological steady-state is assured. Testing this hypothesis for any cell type requires only labelled tryptophan, a means to measure cytosolic tryptophan and kynurenine, and the standard tools of tracer kinetics.
Quantitative analysis of chondroitin sulfate disaccharides from human and rodent fixed brain tissue by electrospray ionization-tandem mass spectrometry.

Chondroitin sulfates (CS) are long, negatively-charged, unbranched glycosaminoglycan (GAG) chains attached to CS-proteoglycan (CSPG) core proteins that comprise the glycan component in both loose interstitial extracellular matrices (ECM) and in rigid, structured perineuronal net (PNN) scaffolds within the brain. As aberrant CS-PNN formations have been linked to a range of pathological states, including Alzheimer's disease (AD) and schizophrenia, the analysis of CS-GAGs in brain tissue at the disaccharide level has great potential to enhance disease diagnosis and prognosis. Two mass-spectrometry (MS)-based approaches were adapted to detect CS disaccharides from minute fixed tissue samples with low picomolar sensitivity and high reproducibility. The first approach employed a straightforward, quantitative direct infusion (DI)-tandem mass spectrometry (MS/MS) technique to determine the percentages of Δ4S- and Δ6S-CS disaccharides within the 4S/6S-CS ratio, while the second used a comprehensive liquid chromatography (LC)-MS/MS technique to determine the relative percentages of Δ0S- Δ4S- Δ6S- Δ4S6S-CS, and Δ2S6S-CS disaccharides, with internal validation by full chondroitin lyase activity. The quantitative accuracy of the five primary biologically-relevant CS disaccharides was validated using a developmental time course series in fixed rodent brain tissue. We then analyzed the CS disaccharide composition in formalin-fixed human brain tissue, thus providing the first quantitative report of CS sulfation patterns in human brain. The ability to comprehensively analyze the CS disaccharide composition from fixed brain tissue provides a means with which to identify alterations in the CS-GAG composition in relation to the onset and/or progression of neurological diseases.
College students’ understanding of rational exponents: a teaching experiment

The study examines first through a pre-interview the understanding five college students (at a Midwestern university) have of rational and negative exponents (including the zero exponent), and the students' justifications for their notions of exponents. A teaching intervention (experiment) is then conducted with the same students to test the strength and limitations of a conjecture for teaching rational and negative exponents, using an approach based on the concept of relative rate of growth or change (Confrey, 1994), the concept of factor of multiplication and a procedure to calculate decimal exponents. Results suggest that the definition of exponents students learn in school provide the primary lens for conceptualizing rational and negative exponents. The laws of exponents pl ay no foundational role in this process. Post-interviews with the same content as the pre-interview, held after the teaching experiment, showed improved responses on most questions.
Tailoring the Performance of Graphene Aerogels for Oil/Organic Solvent Separation by 1-Step Solvothermal Approach

Ultra-light eco-friendly graphene oxide (GO)-based aerogels are reported by simple one-step solvothermal self-assembly. The effect of varying parameters such as C/O ratio of GO; reducing agent amount; temperature; and duration on the properties of the aerogels was studied. The structural and vibrational features and hydrophobic surface properties of the obtained aerogels were obtained by XRD; FTIR; XPS; Raman; SEM; and contact angle measurements. The effect of synthesis conditions on the engine oil and organic solvent absorption properties was assessed. The results indicated that the lower the C/O ratio of GO, the better the absorption properties, with the best performance for oil uptake reaching 86 g g−1. The obtained results indicate the approach based on ice-templating and the tailoring of oxygen content in GO make the resulting aerogels potential candidates for use in oil spill and organic solvent treatments.
Cell-specific role of HDAC6 in chemotherapy-induced mechanical allodynia and loss of intraepidermal nerve fibers.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of cancer treatment with no FDA-approved medication for its prevention or management. Using RNA sequencing analysis of dorsal root ganglia (DRG) we identify critical contributions of HDAC6 and mitochondrial damage to the establishment of CIPN in a mouse model of cisplatin-induced neuropathy. We show that pharmacological inhibition of HDAC6 using ACY-1215 or global deletion of HDAC6 is sufficient to prevent cisplatin-induced mechanical allodynia, loss of intraepidermal nerve fibers (IENFs), and mitochondrial bioenergetic deficits in DRG neurons and peripheral nerves in male and female mice. The bioenergetic deficits in the neuronal cell bodies in the DRG are characterized by reduced oxidative phosphorylation, whereas the mitochondrial deficits in the nerves are due to a reduction in axonal mitochondrial content. Notably, deleting HDAC6 in sensory neurons protects against the cisplatin-induced loss of IENFs and the reduction in mitochondrial bioenergetics and content in the peripheral nerve. In contrast, deletion of HDAC6 in sensory neurons only partially and transiently prevents cisplatin-induced mechanical allodynia and does not protect against impairment of mitochondrial function in DRG neurons. We further reveal a critical role of T cells in the protective effects of HDAC6 inhibition on these signs of CIPN. In summary, we show that cisplatin-induced mechanical allodynia is associated with mitochondrial damage in DRG neurons, while the loss of IENFs is related to bioenergetic deficits in peripheral nerves. Moreover, our findings identify cell-specific contributions of HDAC6 to mechanical allodynia and loss of IENFs that characterize cisplatin-induced peripheral neuropathy.
Cytogenetic Analysis of Micronuclei in Tobacco Chewers: A Study in North Indian Population.

AIM Oral cancer ranks in top three of all cancers in India and accounts for over 30% of all cancers reported in the country. The present study aims at an in vivo cytogenetic analysis to assess the applicability of the micronucleus test in diagnosing early detection of dysplastic changes. MATERIALS AND METHODS Exfoliated scrape smears were collected from 75 patients suffering from premalignant lesions. The wet-fixed smears were stained by adopting Papanicolaou's staining protocol. The analysis of variance (ANOVA) test was used to analyze the data statistically. RESULTS The results of the above study give a fair assessment of the amount of nuclear alterations seen in individuals exposed to genotoxic agents, such as tobacco, and also to a certain extent, an insight into the expected biological behavior of the lesions present in such individuals. Detection of micronuclei and their assay is an upcoming research domain in the field of cancer detection and therapeutics. These miniature nuclear offshoots if properly identified can turn out to be important biomarkers with huge potential for screening and predicting patients with oral precancers and also can act as risk assessors in patient's ongoing treatment for invasive cancers. CONCLUSION The frequency of micronucleated cells has been observed to be in increasing order with the increase in the age-groups and from control to precancerous cases significantly in both sexes.
ARGONAUTE1 and ARGONAUTE4 Regulate Gene Expression and Hypoxia Tolerance1[OPEN]

RNA-silencing pathways contribute to low-oxygen signaling in Arabidopsis. In plants, hypoxia can be induced by submergence, and the lack of oxygen impairs mitochondrial respiration, thus affecting the plant’s energy status. Hypoxia has major effects on gene expression; these changes induce key responses that help meet the needs of the stressed plant. However, little is known about the possible role of RNA signaling in the regulation of gene expression under limited oxygen availability. Here, we report the contribution of ARGONAUTE1 (AGO1) to hypoxia-induced gene regulation in Arabidopsis (Arabidopsis thaliana). Submergence induced changes in levels of the microRNAs miR2936 and miR398, but this had no obvious effects on their putative target mRNA levels. However, we found that ago1-27 plants are intolerant to submergence and transcriptome analysis identified genes whose regulation requires functional AGO1. Analysis of mutants affected in various branches of RNA signaling highlighted the convergence of AGO1 signaling with the AGO4-dependent RNA-directed DNA methylation (RdDM) pathway. AGO4-dependent RdDM represses the expression of HOMOLOG OF RPW8 4 (HR4) and alters its response to submergence. Remarkably, methylation of the second exon of HR4 is not only reduced in ago4-1 but also in plants overexpressing a constitutively stable version of the oxygen sensor RELATED TO APETALA2 12 (RAP2.12), indicating convergence of oxygen signaling with epigenetic regulation of gene expression. Therefore, our results identify a role for AGO1 and AGO4 RNA-silencing pathways in low-oxygen signaling in Arabidopsis.
The experimental dose ranges influence the LETd dependency of the proton minimum RBE (RBEmin)

Cell experiments have shown the proton relative biological effectiveness (RBE) to vary with dose and linear energy transfer (LET), which has led to development of variable RBE models. The RBE is normally estimated from two independent functions, the RBEmax and RBEmin, describing the extreme RBE at low and high doses. While there is consensus that RBEmax increases with increasing LET, the RBEmin is not uniformly defined and its dependency on LET is deviating. In this work, we analysed this dependency and its sensitivity to variations of the experimental dose range. We performed a literature search to find data from existing monoenergetic proton cell survival experiments with (α/β)x values below 5 Gy and dose averaged LET (LETd) values below 20 keV µm−1. From the experiments the doses and their corresponding survival data were extracted. Based on these data, multiple restricted databases were generated by sequential exclusion of low dose data in the experiments followed by a linear-quadratic (LQ) fit. The quadratic component from the LQ-fit was used to estimate RBEmin. The LETd dependency of RBEmin was determined by fitting a linear function to the RBEmin values estimated from the restricted databases. Our analysis showed the LETd dependency of RBEmin to be significantly influenced by the experimental dose range. By including experiments with doses below 1 Gy in the database, we found that RBEmin increased with increasing LETd. By excluding the low dose experiments in our database, the RBEmin became constant for all LETd values. For an LETd value of 5 keV µm−1, a restricted database including the data with the lowest doses gave an RBEmin of 1.4 ± 0.1, while databases with only high dose data (>2 Gy) gave an RBEmin of 1.0 ± 0.1. None of our restricted databases gave a decreasing RBEmin with increasing LETd. Our study showed that RBEmin has a small yet significant dependency on LETd for tissues with low (α/β)x ratio. The LETd dependency of RBEmin varied substantially with the experimental dose range. Including experiments with high minimum dose in RBE models may lead to underestimation of the RBE.
Differential Impact of an Education-Based Intervention for Patients with Type 2 Diabetes Mellitus in Rural China

The study aimed to assess the impact of an education-based intervention to improve vertical integration and management of type 2 diabetes mellitus in primary care in rural China. Patients with type 2 diabetes mellitus in three townships in Jingjiang county, Jiangsu Province were randomly divided into intervention and control groups. Participants in the intervention group received an education-based intervention. Patients’ data including the fasting blood glucose (FBG) level, health-related quality of life (HRQoL), and sociodemographic characteristics were collected at baseline (2015) and follow-up (2016). The FBG levels decreased significantly in the intervention group compared to the control group in the overall analysis. In the stratified analysis, FBG levels and some aspects of HRQoL improved in the intervention group more for females, married persons, those with low education, and those in farming or house working. Participants in the control group deteriorated in FBG levels but improved in some aspects of HRQoL. The intervention improved in FBG levels and some aspects of HRQoL among participants. Furthermore, the intervention seemed to differentially benefit females, married persons, lowly educated persons, and those in farming or house working more than other groups. (Trial registration: ISRCTN, ISRCTN13319989. Retrospectively registered 4 April 2017).
Diterpenoid Lactones with Anti-Inflammatory Effects from the Aerial Parts of Andrographis paniculata

Andrographis paniculata (AP) has been widely used in China for centuries to treat various diseases, and especially to treat inflammation. Diterpenoid lactones are the main anti-inflammatory components of AP. However, systematic chemical composition and biological activities, as well as key pharmacophores, of these diterpenoid lactones from AP have not yet been clearly understood. In this study, 17 diterpenoid lactones, including 2 new compounds, were identified by spectroscopic methods, and most of them attenuated the generation of TNF-α and IL-6 in LPS-induced RAW 274.7 cells examined by ELISA. Pharmacophores of diterpenoid lactones responsible for the anti-inflammatory activities were revealed based on the quantitative structure-activity relationship (QSAR) models. Moreover, new compounds (AP-1 and AP-4) exerted anti-inflammatory activity in LPS microinjection-induced zebrafish, which might be correlated with the inhibition of the translocation of NF-κB p65 from cytoplasm to nucleus. Our study provides guidelines for future structure modification and rational drug design of diterpenoid lactones with anti-inflammatory properties in medical chemistry.
A well-balanced scheme for chemotactic travelling waves at the mesoscopic scale

We investigate numerically a model consisting in a kinetic equation for the biased motion of bacteria following a run-and-tumble process, coupled with two reaction-diffusion equations for chemical signals. This model exhibits asymptotic propagation at a constant speed. In particular, it admits travelling wave solutions. To capture this propagation, we propose a well-balanced numerical scheme based on Case's elementary solutions for the kinetic equation, and L-splines for the parabolic equations. We use this scheme to explore the Cauchy problem for various parameters. Some examples far from the diffusive regime lead to the coexistence of two waves travelling at different speeds. Numerical tests support the hypothesis that they are both locally asymptotically stable. Interestingly, the exploration of the bifurcation diagram raises counter-intuitive features.
Preparation and antiplasmodial activity of 3',4'‐dihydro‐1'H‐spiro(indoline‐3,2'‐quinolin)‐2‐ones

A series of 3',4'‐dihydro‐1'H‐spiro(indoline‐3,2'‐quinolin)‐2‐ones were prepared by the inverse‐electron‐demand aza‐Diels–Alder reaction (Povarov reaction) of imines derived from isatin and substituted anilines, and the electron‐rich alkenes trans‐isoeugenol and 3,4‐dihydro‐2H‐pyran. These compounds were assessed for in vitro antiplasmodial activity against drug‐sensitive and drug‐resistant forms of the P. falciparum parasite. Three compounds derived from 3,4‐dihydro‐2H‐pyran and four compounds derived from trans‐isoeugenol showed antiplasmodial activity in the low micromolar range against the drug‐resistant FCR‐3 strain (1.52–4.20 µM). Only compounds derived from trans‐isoeugenol showed antiplasmodial activity against the drug‐sensitive 3D7 strain (1.31–1.80 µM).
Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC)

Objectives Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium. Methods We pooled 11 case–control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses. Results ORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses. Conclusions In this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.