Miracle-dz/UniFAR-FTUs huggingface dataset:
Dominant ELOVL1 mutation causes neurological disorder with ichthyotic keratoderma, spasticity, hypomyelination and dysmorphic features

Background Ichthyosis and neurological involvement occur in relatively few known Mendelian disorders caused by mutations in genes relevant both for epidermis and neural function. Objectives To identify the cause of a similar phenotype of ichthyotic keratoderma, spasticity, mild hypomyelination (on MRI) and dysmorphic features (IKSHD) observed in two unrelated paediatric probands without family history of disease. Methods Whole exome sequencing was performed in both patients. The functional effect of prioritised variant in ELOVL1 (very-long-chain fatty acids (VLCFAs) elongase) was analysed by VLCFA profiling by gas chromatography–mass spectrometry in stably transfected HEK2932 cells and in cultured patient’s fibroblasts. Results Probands shared novel heterozygous ELOVL1 p.Ser165Phe mutation (de novo in one family, while in the other family, father could not be tested). In transfected cells p.Ser165Phe: (1) reduced levels of FAs C24:0-C28:0 and C26:1 with the most pronounced effect for C26:0 (P=7.8×10−6 vs HEK293 cells with wild type (wt) construct, no difference vs naïve HEK293) and (2) increased levels of C20:0 and C22:0 (P=6.3×10−7, P=1.2×10−5, for C20:0 and C22:0, respectively, comparison vs HEK293 cells with wt construct; P=2.2×10−7, P=1.9×10−4, respectively, comparison vs naïve HEK293). In skin fibroblasts, there was decrease of C26:1 (P=0.014), C28:0 (P=0.001) and increase of C20:0 (P=0.033) in the patient versus controls. There was a strong correlation (r=0.92, P=0.008) between the FAs profile of patient’s fibroblasts and that of p.Ser165Phe transfected HEK293 cells. Serum levels of C20:0–C26:0 FAs were normal, but the C24:0/C22:0 ratio was decreased. Conclusion The ELOVL1 p.Ser165Phe mutation is a likely cause of IKSHD.
Morphological evaluation of gilt ovaries in relation to the quality of recovered oocytes.

The aim of the current study was to analyse the relationship between morphology of gilt’s ovary and the quantity and quality of recovered oocytes suitable for in vitro procedures. Forty ovaries of healthy 7–8 months old gilts from a local slaughterhouse divided into corpora lutea bearing (CL) and noncorpora lutea bearing (non-CL) ovaries were evaluated. Morphometric analysis (weight, length and width) of the ovaries was performed. Also, visual estimation of the number and size of follicles and presence of corpora lutea in ovaries was done. The developmental competence of recovered oocytes was evaluated by BCB test. It was found that the values of morphometric parameters of CL ovaries were higher compared to non-CL ovaries (P<0.05). Non-CL ovaries tended to bear a higher number of large and total follicles than CL, but the difference was not significant. More compact cumulus oocytes complexes (COCs) and oocytes with corona radiata (POCs) were recovered from CL than from non-CL ovaries. The BCB test showed that both types of ovaries provided more than 55% BCBpositive oocytes. In conclusion, both CL as well as non-CL ovaries from gilts aged 7–8 months could be used for recovering the developmental competent oocytes for in vitro procedures.
Processing of Emotional Faces in Patients with Chronic Pain Disorder: An Eye-Tracking Study

Objective Problems in emotion processing potentially contribute to the development and maintenance of chronic pain. Theories focusing on attentional processing have suggested that dysfunctional attention deployment toward emotional information, i.e., attentional biases for negative emotions, might entail one potential developmental and/or maintenance factor of chronic pain. Methods We assessed self-reported alexithymia, attentional orienting to and maintenance on emotional stimuli using eye tracking in 17 patients with chronic pain disorder (CP) and two age- and sex-matched control groups, 17 healthy individuals (HC) and 17 individuals who were matched to CP according to depressive symptoms (DC). In a choice viewing paradigm, a dot indicated the position of the emotional picture in the next trial to allow for strategic attention deployment. Picture pairs consisted of a happy or sad facial expression and a neutral facial expression of the same individual. Participants were asked to explore picture pairs freely. Results CP and DC groups reported higher alexithymia than the HC group. HC showed a previously reported emotionality bias by preferentially orienting to the emotional face and preferentially maintaining on the happy face. CP and DC participants showed no facilitated early attention to sad facial expressions, and DC participants showed no facilitated early attention to happy facial expressions, while CP and DC participants did. We found no group differences in attentional maintenance. Conclusion Our findings are in line with the clinical large overlap between pain and depression. The blunted initial reaction to sadness could be interpreted as a failure of the attentional system to attend to evolutionary salient emotional stimuli or as an attempt to suppress negative emotions. These difficulties in emotion processing might contribute to etiology or maintenance of chronic pain and depression.
Association of Postoperative Topical Prostaglandin Analog or Beta-Blocker Use and Incidence of Pseudophakic Cystoid Macular Edema

Purpose: The purpose of this article is to determine the association of postoperative topical prostaglandin analog (PGA) or topical beta-blocker use and the incidence of pseudophakic cystoid macular edema (CME). Methods: This was a nested case-control study. All adult patients who underwent cataract surgery between January 1, 2006 and December 31, 2016 and who were enrolled in the PharMetrics Plus database were eligible for inclusion. The association between postoperative topical PGAs (bimatoprost, latanoprost, and travoprost/travoprost-z) or beta-blocker (betaxolol, levobunolol, and timolol) use and the incidence of pseudophakic CME was assessed by conditional logistic regression. Results: Five hundred eight cases and 5080 controls were included in the analyses. Incidence of pseudophakic CME was found to be statistically significantly associated with the current postoperative use of both topical PGAs [relative risk (RR), 1.86; 95% confidence interval (CI), 1.04-3.32] and topical beta-blockers (RR, 2.64; 95% CI, 1.08-6.49). Postoperative use of each of bimatoprost (RR, 2.73; 95% CI, 1.35%-5.53%) and travoprost/travoprost-z (RR, 3.16; 95% CI, 1.42-7.03) in the year before diagnosis was demonstrated to be statistically significantly associated with the incidence of pseudophakic CME. This association was not observed to be statistically significant with the postoperative use of latanoprost (RR, 1.55; 95% CI, 0.84-2.88). Conclusions: To the best of our knowledge this is the largest study that has investigated the association between postoperative topical PGA or topical beta-blocker use and the incidence of pseudophakic CME. Postoperative use of both topical PGAs and topical beta-blockers was found to be associated with the incidence of pseudophakic CME.
Provable defenses against adversarial examples via the convex outer adversarial polytope

We propose a method to learn deep ReLU-based classifiers that are provably robust against norm-bounded adversarial perturbations (on the training data; for previously unseen examples, the approach will be guaranteed to detect all adversarial examples, though it may flag some non-adversarial examples as well). The basic idea of the approach is to consider a convex outer approximation of the set of activations reachable through a norm-bounded perturbation, and we develop a robust optimization procedure that minimizes the worst case loss over this outer region (via a linear program). Crucially, we show that the dual problem to this linear program can be represented itself as a deep network similar to the backpropagation network, leading to very efficient optimization approaches that produce guaranteed bounds on the robust loss. The end result is that by executing a few more forward and backward passes through a slightly modified version of the original network (though possibly with much larger batch sizes), we can learn a classifier that is provably robust to any norm-bounded adversarial attack. We illustrate the approach on a toy 2D robust classification task, and on a simple convolutional architecture applied to MNIST, where we produce a classifier that provably has less than 8.4% test error for any adversarial attack with bounded $\ell_\infty$ norm less than $\epsilon = 0.1$. This represents the largest verified network that we are aware of, and we discuss future challenges in scaling the approach to much larger domains.
Activation of AMP-activated Protein Kinase by Metformin Induces Protein Acetylation in Prostate and Ovarian Cancer Cells*

AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription. Nucleocytosolic concentration of acetyl-CoA affects histone acetylation and links metabolism and chromatin structure. Here we show that activation of AMPK with the widely used antidiabetic drug metformin or with the AMP mimetic 5-aminoimidazole-4-carboxamide ribonucleotide increases the inhibitory phosphorylation of ACC and decreases the conversion of acetyl-CoA to malonyl-CoA, leading to increased protein acetylation and altered gene expression in prostate and ovarian cancer cells. Direct inhibition of ACC with allosteric inhibitor 5-(tetradecyloxy)-2-furoic acid also increases acetylation of histones and non-histone proteins. Because AMPK activation requires liver kinase B1, metformin does not induce protein acetylation in liver kinase B1-deficient cells. Together, our data indicate that AMPK regulates the availability of nucleocytosolic acetyl-CoA for protein acetylation and that AMPK activators, such as metformin, have the capacity to increase protein acetylation and alter patterns of gene expression, further expanding the plethora of metformin's physiological effects.
Advanced Antennas for Small Satellites

Antenna is one of the key components onboard small satellites as its design determines the performance of all the wireless systems including telemetry, tracking and control, high-speed data downlink, navigation, intersatellite communications, intrasatellite communications, wireless power transfer, radars and sensors, etc. This paper presents a review of recent development in advanced antennas for small satellites (MiniSat, MicroSat, NanoSat, CubeSat, etc.). A number of recent examples of antennas for small satellite applications are shown and discussed. A conclusion and future development in antennas for small satellites are given in the end.
Healthcare utilization and costs of children with attention deficit/hyperactivity disorder initiating atomoxetine versus extended-release guanfacine

Abstract Objectives: To compare 1-year direct healthcare costs and utilization among children and adolescents initiating non-stimulant medications atomoxetine (ATX) or extended-release guanfacine (GXR). Methods: In this retrospective, observational cohort study, children and adolescents aged 6–17 years with attention deficit/hyperactivity disorder (ADHD) who had ≥1 prescription claim for ATX or GXR between December 31, 2009 and January 1, 2011 were identified in the MarketScan Commercial or Multi-State Medicaid claims databases. The first claim was set as the index. Patients with no claims for other ADHD medications that overlapped with the days’ supply for the index therapy during the post-period were classified as initiating monotherapy. All-cause and ADHD-related utilization and costs (2011 US$) and treatment patterns (adherence and persistence) were evaluated during the 12 months following index. Propensity score adjustment accounted for differences in patient characteristics, and bootstrapping was used for comparisons. Results: A total of 13,239 children and adolescents with ADHD met the study criteria (4,411 ATX initiators and 8,828 GXR initiators). There were 2,699 ATX monotherapy patients. In propensity-score-adjusted analyses, mean all-cause total costs were significantly less for monotherapy ATX initiators than for GXR initiators ($7,553 vs $10,639; difference = –$3,086, p < .0001), as were mean ADHD-related total costs ($3,213 vs $4,544; difference = –$1,330, p < .0001). Monotherapy ATX initiators had significantly fewer all-cause and ADHD-related total medical visits and ∼22 days shorter persistence to index therapy (p < .0001). Results were similar for secondary analyses comparing all ATX with all GXR initiators, regardless of monotherapy or combination regimen, and comparing only monotherapy initiators. Conclusions: Children and adolescents with ADHD who initiated ATX monotherapy incurred lower all-cause and ADHD-related total healthcare costs than patients who initiated GXR. This was due in part to less healthcare resource utilization and slightly shorter persistence for ATX patients. These findings may aid decision-making and inform future studies, but must be tempered due to inherent observational research limitations.
Intakes of plain water, moisture in foods and beverages, and total water in the adult US population--nutritional, meal pattern, and body weight correlates: National Health and Nutrition Examination Surveys 1999-2006.

BACKGROUND There is a surprising paucity of studies that have systematically examined the correlates of water intake in the US population. OBJECTIVE The objective was to examine the association of contributors of water intake with dietary characteristics, meal consumption, and body weight in the US population. DESIGN We used 24-h dietary recall data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (n = 12,283) and the NHANES 2005-2006 (n = 4112) to examine the independent association of intakes of plain water, beverage moisture, food moisture, and total water with sociodemographic factors, dietary characteristics (energy, nutrients, diet quality, and energy density), and meal patterns (number of eating episodes, mention of breakfast or snack) by using multiple regression methods. RESULTS In 2005-2006, American adults reported consuming 3.18 L of total water within the previous 24 h (in 1999-2004, estimated total water intake was 3.35 L), with plain water and beverages contributing 33% and 48% of the total, respectively. Plain water intake was unrelated to the intake of energy and body mass index but was positively related to dietary fiber and inversely related to beverages, sugars, and the energy density of foods; these associations were in the opposite direction for beverage moisture intake. Total water intake was inversely related to energy from fat and energy density but positively related to dietary fiber, caffeine, alcohol, and diet quality. The number of eating episodes predicted higher beverage and food moisture and total water intakes. A higher body mass index predicted higher intakes of beverage moisture and total water. CONCLUSION Various contributors of total water intake differed in their association with dietary characteristics and body weight in the adult US population.
Astrocytic IP3Rs: Contribution to Ca2+ signalling and hippocampal LTP

Astrocytes regulate hippocampal synaptic plasticity by the Ca2+ dependent release of the N‐methyl d‐aspartate receptor (NMDAR) co‐agonist d‐serine. Previous evidence indicated that d‐serine release would be regulated by the intracellular Ca2+ release channel IP3 receptor (IP3R), however, genetic deletion of IP3R2, the putative astrocytic IP3R subtype, had no impact on synaptic plasticity or transmission. Although IP3R2 is widely believed to be the only functional IP3R in astrocytes, three IP3R subtypes (1, 2, and 3) have been identified in vertebrates. Therefore, to better understand gliotransmission, we investigated the functionality of IP3R and the contribution of the three IP3R subtypes to Ca2+ signalling. As a proxy for gliotransmission, we found that long‐term potentiation (LTP) was impaired by dialyzing astrocytes with the broad IP3R blocker heparin, and rescued by exogenous d‐serine, indicating that astrocytic IP3Rs regulate d‐serine release. To explore which IP3R subtypes are functional in astrocytes, we used pharmacology and two‐photon Ca2+ imaging of hippocampal slices from transgenic mice (IP3R2−/− and IP3R2−/−;3−/−). This approach revealed that underneath IP3R2‐mediated global Ca2+ events are an overlooked class of IP3R‐mediated local events, occurring in astroglial processes. Notably, multiple IP3Rs were recruited by high frequency stimulation of the Schaffer collaterals, a classical LTP induction protocol. Together, these findings show the dependence of LTP and gliotransmission on Ca2+ release by astrocytic IP3Rs. GLIA 2017;65:502–513
Development of Tectal Connectivity across Metamorphosis in the Bullfrog (Rana catesbeiana)

In the bullfrog (Rana catesbeiana), the process of metamorphosis culminates in the appearance of new visual and visuomotor behaviors reflective of the emergence of binocular vision and visually-guided prey capture behaviors as the animal transitions to life on land. Using several different neuroanatomical tracers, we examined the substrates that may underlie these behavioral changes by tracing the afferent and efferent connectivity of the midbrain optic tectum across metamorphic development. Intratectal, tectotoral, tectotegmental, tectobulbar, and tecto-thalamic tracts exhibit similar trajectories of neurobiotin fiber label across the developmental span from early larval tadpoles to adults. Developmental variability was apparent primarily in intensity and distribution of cell and puncta label in target nuclei. Combined injections of cholera toxin subunit β and Phaseolus vulgaris leucoagglutinin consistently label cell bodies, puncta, or fiber segments bilaterally in midbrain targets including the pretectal gray, laminar nucleus of the torus semicircularis, and the nucleus of the medial longitudinal fasciculus. Developmentally stable label was observed bilaterally in medullary targets including the medial vestibular nucleus, lateral vestibular nucleus, and reticular gray, and in forebrain targets including the posterior and ventromedial nuclei of the thalamus. The nucleus isthmi, cerebellum, lateral line nuclei, medial septum, ventral striatum, and medial pallium show more developmentally variable patterns of connectivity. Our results suggest that even during larval development, the optic tectum contains substrates for integration of visual with auditory, vestibular, and somatosensory cues, as well as for guidance of motivated behaviors.
Efficacy and safety of “unboosting” atazanavir in a randomized controlled trial among HIV-infected patients receiving tenofovir DF

Objectives: To assess safety and efficacy of a switch to unboosted atazanavir (ATV) among HIV-infected adults receiving ATV/ritonavir (r) and tenofovir disoproxil fumarate (TDF). Methods: HIV-infected adults with viral load (VL) <40 copies/mL at screening and <150 copies/mL consistently for ≥3 months while receiving a regimen including ATV/r and TDF were randomized to continue ATV/r 300/100 mg daily (control) or change to ATV 400 mg daily (switch), while maintaining their TDF backbone. The primary outcome was proportion of subjects without treatment failure (regimen switch or VL > 200 copies/mL twice consecutively) at 48 weeks. Results: Fifty participants (46 male, median age 47 years) were randomized, 25 to each arm. At week 48, treatment success occurred in 76% in the control arm and 92% in the switch arm (ITT, p = 0.25). ATV trough levels at week 9 were higher in controls (median 438 ng/mL) than in the switch arm (median 124 ng/mL) (p = 0.003), as was total bilirubin at week 48 (median 38 μmol/L and 28 μmol/L, respectively; p = 0.02). Estimated glomerular filtration rate (eGFR) decreased in the control arm (p = 0.007), but did not change in the switch arm. At week 48, eGFR was higher in the switch arm (median 96 mL/min) than in the control arm (median 85 mL/min) (p = 0.035), but the arms were similar with respect to fasting glucose, C-reactive protein, and lipid parameters. Conclusions: Switching from ATV/r to unboosted ATV appears to be safe and effective in selected virologically suppressed patients receiving TDF-containing regimens, and may have favorable effects on bilirubin and renal function.
Are Children With Type 1 Diabetes Consuming a Healthful Diet?

Purpose The purpose of this study is to review the literature on usual dietary intake in children with type 1 diabetes (T1D) and to discuss approaches to promote dietary change with potential efficacy. Methods Search strategies included a MEDLINE search for English-language articles that estimated usual dietary intake in children with T1D and a screening of the reference lists from original studies. The keywords used were diet, dietary intake, nutrition, type 1 diabetes, children, adolescents, and youth. Studies were included if they were observational, contained a sample of children with T1D, and estimated usual dietary intake. Results Nine studies fulfilled the criteria (6 US, 3 European). Of the 4 studies with a control group, 3 reported that both total fat and saturated fat intake were higher in the children with T1D. Six studies examined the percent of total calories from saturated fat; mean intake ranged from 11 to 15%, exceeding ADA recommendations (< 7%). Fruit, vegetable, and fiber intakes were low among children with T1D. No prior studies have addressed dietary change in this population. The behavior-change literature suggests that nutrition education alone is unlikely to be adequate, but that incorporation of behavioral approaches offers potential efficacy in promoting healthful dietary change. Conclusions Children with T1D are not meeting dietary guidelines, and in some areas their diets are less healthful than children without diabetes. As these dietary behaviors may affect the risk of long-term complications, the incorporation of behavioral approaches promoting healthy eating into routine clinical practice is warranted.
Convolutional Geometric Matrix Completion

Geometric matrix completion~(GMC) has been proposed for recommendation by integrating the relationship~(link) graphs among users/items into matrix completion~(MC) . Traditional \mbox{GMC} methods typically adopt graph regularization to impose smoothness priors for \mbox{MC}. Recently, geometric deep learning on graphs~(\mbox{GDLG}) is proposed to solve the GMC problem, showing better performance than existing GMC methods including traditional graph regularization based methods. To the best of our knowledge, there exists only one GDLG method for GMC, which is called \mbox{RMGCNN}. RMGCNN combines graph convolutional network~(GCN) and recurrent neural network~(RNN) together for GMC. In the original work of RMGCNN, RMGCNN demonstrates better performance than pure GCN-based method. In this paper, we propose a new \mbox{GMC} method, called \underline{c}onvolutional \underline{g}eometric \underline{m}atrix \underline{c}ompletion~(CGMC), for recommendation with graphs among users/items. CGMC is a pure GCN-based method with a newly designed graph convolutional network. Experimental results on real datasets show that CGMC can outperform other state-of-the-art methods including RMGCNN.