Miracle-dz/UniFAR-FTUs huggingface dataset:
CircRNAs: a regulator of cellular stress

Abstract Circular RNAs (CircRNAs) were first identified as a viroid and later found to also be an endogenous RNA splicing product in eukaryotes. In recent years, a series of RNA-sequencing analyses from a diverse range of eukaryotes have shed new light on these eukaryotic circRNAs, revealing dynamic expression patterns in various developmental stages and physiological conditions. In this review, we focus on circRNAs implicated in stress response pathways and explore potential mechanisms underlying their regulation. To date, circRNAs have been shown to act as scaffolds in the assembly of protein complexes, sequester proteins from native subcellular localization, activate transcription of parental genes, inhibit RNA–protein interactions, and function as regulators of microRNA activity. Although the mechanism modulating circRNA levels during stress remains unclear, circRNAs are shown to be regulated during biogenesis, degradation, and exportation. As circRNAs do not have 5′ and 3′ ends, there are no entry points for exoribonucleases to initiate degradation. Such inherent stability makes this class of RNA a strong candidate to maintain homeostasis in the face of environmental challenges.
Surface Instabilities in Compressed or Bent Rubber Blocks

Abstract Biot carried out theoretical analyses of the critical strains at which surface instabilities would be encountered in large blocks of a neo-Hookean material subjected to different degrees of compression in two directions. Three special cases are reviewed here: simple compression in one direction, compression in one direction with the perpendicular direction constrained (pure shear), and equibiaxial compression. In all cases a surface instability is predicted to occur at a moderate compressive strain, ranging from about 33% to about 55%. Because unidirectional compression occurs on the inner surface of a rubber block subjected to simple bending, a similar surface instability would be expected at a critical degree of bending, when the surface compression is about 46%. Observations on bent rubber blocks are compared with this theoretical prediction. Sharp creases occurred on the inner surface at a critical degree of bending but the critical compressive strain there was only about 35% and the bending .
Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors.

IMPORTANCE Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer. OBJECTIVE To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC. DESIGN, SETTING, AND PARTICIPANTS International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature. MAIN OUTCOMES AND MEASURES Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria. RESULTS Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP. CONCLUSIONS AND RELEVANCE Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
Perfusion CT in acute stroke: effectiveness of automatically-generated colour maps.

OBJECTIVE To evaluate the accuracy of perfusion CT (pCT) in the definition of the infarcted core and the penumbra, comparing the data obtained from the evaluation of parametric maps [cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT)] with software-generated colour maps. METHODS A retrospective analysis was performed to identify patients with suspected acute ischaemic strokes and who had undergone unenhanced CT and pCT carried out within 4.5 h from the onset of the symptoms. A qualitative evaluation of the CBV, CBF and MTT maps was performed, followed by an analysis of the colour maps automatically generated by the software. RESULTS 26 patients were identified, but a direct CT follow-up was performed only on 19 patients after 24-48 h. In the qualitative analysis, 14 patients showed perfusion abnormalities. Specifically, 29 perfusion deficit areas were detected, of which 15 areas suggested the penumbra and the remaining 14 areas suggested the infarct. As for automatically software-generated maps, 12 patients showed perfusion abnormalities. 25 perfusion deficit areas were identified, 15 areas of which suggested the penumbra and the other 10 areas the infarct. The McNemar's test showed no statistically significant difference between the two methods of evaluation in highlighting infarcted areas proved later at CT follow-up. CONCLUSION We demonstrated how pCT provides good diagnostic accuracy in the identification of acute ischaemic lesions. The limits of identification of the lesions mainly lie at the pons level and in the basal ganglia area. Qualitative analysis has proven to be more efficient in identification of perfusion lesions in comparison with software-generated maps. However, software-generated maps have proven to be very useful in the emergency setting. Advances in knowledge: The use of CT perfusion is requested in increasingly more patients in order to optimize the treatment, thanks also to the technological evolution of CT, which now allows a whole-brain study. The need for performing CT perfusion study also in the emergency setting could represent a problem for physicians who are not used to interpreting the parametric maps (CBV, MTT etc.). The software-generated maps could be of value in these settings, helping the less expert physician in the differentiation between different areas.
Effects of Silicon on Yield and Grain Quality of Wheat

A field experiment was performed to investigate the effects of silicon(Si) on the plant morphological characters,grain quality,yield and its components in two spring wheat genotypes of Longmai 26 and Kehan 16 under basal fertilizer application with Si at 0 to 75 kg·hm-2.The results showed that appropriate dosage of silicon fertilizer increased grain yield of wheat,with more increase for Longmai 26 than that for Kehan 16.The yield increase for Longmai 26 and Kehan 16 resulted from the increase of grain number per spike and spike number,respectively.There was no significant effect of silicon fertilizer on plant height and stem base diameter of wheat,but the spike length of Longmai 26 increased at varying degrees.There was no significant effect of silicon fertilizer on grain quality parameters of 1000 grain weight,test weight and grain protein content,but the content of wet gluten,water absorption of flour and fracture time of paste were greatly enhanced for Longmai 26,and the extension quality of paste was improved.It suggested that 30 kg·hm-2 and 60 kg·hm-2 silicon were appropriate for Longmai 26 and Kehan 16,respectively,and more silicon was not favorable for the formation of,wheat yield and quality.
ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self‐limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
Association of Circulating Wnt Antagonists With Severe Abdominal Aortic Calcification in Elderly Women

Context: There is great interest in the biology of vascular calcification. Wnt/β-catenin signaling is an important mediator of mineralization and may play a role in vascular calcification. Objective: We assessed the association between circulating Wnt antagonists and abdominal aortic calcification (AAC) severity in elderly women. Design: This was a cross-sectional analysis of the Calcium Intake Fracture Outcome Study. Setting: The participants were recruited from the community-dwelling elderly population. Participants: We examined 768 women aged over 70 years. Interventions: We collected blood samples, and lateral spine images captured during bone density assessment were used to score AAC with a validated 24-point scale. Main Outcome Measures: We tested the hypothesis that low Wnt antagonist levels of Dickkopf-1 (DKK1), secreted frizzled related protein 3 (sFRP3), and Wnt inhibitory factor 1 (WIF1) are associated with severe AAC (AAC24 score > 5). Results: Severe AAC was present in 146 women (19%). Lower levels of DKK1, but not WIF1 and sFRP3, were associated with higher odds of severe AAC. Per standard deviation decrease in DKK1 was associated with increased multivariable-adjusted odds ratio (OR) of severe AAC [OR, 1.26; 95% confidence interval (CI), 1.04 to 1.52; P = 0.017]. In quartile analyses, the lowest and second-lowest quartiles of DKK1 had increased multivariable-adjusted odds of severe AAC vs the highest quartile (OR, 2.05; 95% CI, 1.18 to 3.56; P = 0.011 and OR, 1.83; 95% CI, 1.05 to 3.19; P = 0.035). Conclusions: In elderly women, DKK1, but not sFRP3 or WIF1, is associated with severe AAC. This study supports the concept that Wnt/β-catenin signaling is an important regulator of vascular mineral metabolism and is independent of other risk factors.
Antibiotic-Resistant Infection Treatment Costs Have Doubled Since 2002, Now Exceeding $2 Billion Annually.

Antibiotic-resistant infections are a global health care concern. The Centers for Disease Control and Prevention estimates that 23,000 Americans with these infections die each year. Rising infection rates add to the costs of health care and compromise the quality of medical and surgical procedures provided. Little is known about the national health care costs attributable to treating the infections. Using data from the Medical Expenditure Panel Survey, we estimated the incremental health care costs of treating a resistant infection as well as the total national costs of treating such infections. To our knowledge, this is the first national estimate of the costs for treating the infections. We found that antibiotic resistance added $1,383 to the cost of treating a patient with a bacterial infection. Using our estimate of the number of such infections in 2014, this amounts to a national cost of $2.2 billion annually. The need for innovative new infection prevention programs, antibiotics, and vaccines to prevent and treat antibiotic-resistant infections is an international priority.
Glomerular Density and Volume in Renal Biopsy Specimens of Children with Proteinuria Relative to Preterm Birth and Gestational Age.

BACKGROUND AND OBJECTIVES A low total nephron number, which is associated with low birth weight (LBW), may indicate increased susceptibility to early-onset renal diseases in children. However, few studies have assessed renal biopsy findings in LBW children. We examined the relationship between LBW and glomerular density (GD) and/or glomerular volume (GV) in renal biopsy samples as a surrogate for total nephron number. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Renal biopsy findings of children of LBW were compared with those of age-matched control subjects of normal birth weight (NBW) who were histopathologically diagnosed with FSGS or minimal change nephrotic syndrome (MCNS) from 1995 to 2011. The GD and GV were estimated on the basis of measurements obtained by computerized image analysis. RESULTS A total of 31 subjects (mean age 11 years; eight with low birth weight-FSGS [LBW-FSGS], 10 with normal birth weight-FSGS [NBW-FSGS], and 13 with normal birth weight-minimal change nephrotic syndrome [NBW-MCNS]) were analyzed. The mean birth weight of each group was 777 g (629-1000), 3110 g (2888-3358), and 3120 g (2748-3398), respectively (median [25th-75th percentile]). Age, body mass index, BP, and degrees of globally sclerotic glomeruli at biopsy were comparable between the groups. The GD was lower (LBW-FSGS, 1.4±0.6/mm2; NBW-FSGS, 3.3±1.2/mm2; and NBW-MCNS, 3.6±1.1/mm2; P<0.05) and the GV was greater (LBW-FSGS, 4.1 [3.1-5.1]×106µm3; NBW-FSGS, 1.6 [1.5-2.1]×106µm3; and NBW-MCNS, 1.3 [1.1-1.8]×106µm3 [median, (25th-75th percentile)]; P<0.05) in patients with LBW-FSGS than in the other patient groups. The GD showed close positive correlations with birth weight (r=0.48) and gestational age (r=0.54), independent of renal function and degree of global glomerular sclerosis. CONCLUSIONS A low GD together with marked glomerular enlargement characterizes renal biopsy samples of children born with a LBW at an early stage of gestation.
Rare genetic variants in GATA transcription factors in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a very heterogeneous disease. Although primarily caused by mutations in genes encoding sarcomeric proteins, other genes might explain that heterogeneity. Potential candidate genes are GATA transcription factors that regulate the expression of proteins associated with HCM. Exons of GATA2, GATA4, and GATA6 genes were sequenced in 212 patients with unrelated HCM previously analyzed for genes encoding the most frequently mutated sarcomeric proteins. Functional effects of variants were predicted by in silico analyses. 3 potentially pathogenic variants were identified: c. -77G>A in GATA2, p.Ala343Thr (rs370588269) in GATA4, and p.Pro555Ala (rs146243018) in GATA6. Multivariate analyses showed that angina was more frequent in patients carrying sarcomeric and GATA rare variants (55% vs 23.2% in non-carriers of GATA rare variants, OR (95% CI) 7.12 (1.23 to 41.27), p=0.029). Among patients without a known causal mutation, GATA rare variants were associated with a greater maximum posterior wall thickness (16.4±4.4 vs 14.0±3.1 mm in non-carriers, p=0.021). Thus, variants having a putative effect on GATA genes would alter the expression of their target genes and could modify the hypertrophic response. Therefore, although relatively infrequent in patients with HCM, they may represent a novel insight into the molecular mechanisms related to the pathogenesis of HCM.
Spacecraft Thermal Control Coatings References

The successful thermal design of spacecraft depends in part on a knowledge of the solar absorption and hemispherical emittance of the thermal control coatings used in and on the spacecraft. Goddard Space Flight Center has had since its beginning a group whose mission has been to provide thermal/optical properties data of thermal control coatings to thermal engineers. This handbook represents a summary of the data and knowledge accumulated over many years at GSFC.
Progressive recruitment of contralesional cortico‐reticulospinal pathways drives motor impairment post stroke

Activation of the shoulder abductor muscles in the arm opposite a unilateral brain injury causes involuntary increases in elbow, wrist and finger flexion in the same arm, a phenomenon referred to as the flexion synergy. It has been proposed that flexion synergy expression is related to reduced output from ipsilesional motor cortex and corticospinal pathways. In this human subjects study, we provide evidence that the magnitude of flexion synergy expression is instead related to a progressive, task‐dependent recruitment of contralesional cortex. We also provide evidence that recruitment of contralesional cortex may induce excessive activation of ipsilateral reticulospinal descending motor pathways that cannot produce discrete movements, leading to flexion synergy expression. We interpret these findings as an adaptive strategy that preserves low‐level motor control at the cost of fine motor control.
Divide-and-conquer checkpointing for arbitrary programs with no user annotation

Classical reverse-mode automatic differentiation (AD) imposes only a small constant-factor overhead in operation count over the original computation, but has storage requirements that grow, in the worst case, in proportion to the time consumed by the original computation. This storage blowup can be ameliorated by checkpointing, a process that reorders application of classical reverse-mode AD over an execution interval to tradeoff space vs. time. Application of checkpointing in a divide-and-conquer fashion to strategically chosen nested execution intervals can break classical reverse-mode AD into stages which can reduce the worst-case growth in storage from linear to sublinear. Doing this has been fully automated only for computations of particularly simple form, with checkpoints spanning execution intervals resulting from a limited set of program constructs. Here we show how the technique can be automated for arbitrary computations. The essential innovation is to apply the technique at the level of the language implementation itself, thus allowing checkpoints to span any execution interval.
Genetic variation in the shape of cold‐survival curves in a single fly population suggests potential for selection from climate variability

Temperature variation is one of the primary challenges facing ectotherms, and the ability to tolerate a range of thermal environments is critical for setting current and future species distributions. Low temperature is particularly challenging for ectotherms because winter conditions have strong latitudinal and temporal variation. Lower lethal temperature (LLT) is a common metric of cold tolerance used in studies of local adaptation and plasticity. Comparisons of LLT across groups typically assume parallel S‐shaped survival curves, but genetic variation in the shape of survival vs. temperature curves has not been assessed. Here, we measured the ability of 36 lines of the Drosophila Genetic Reference Panel (DGRP) to survive a 1‐h cold shock at seven ecologically relevant low temperatures (−1 to −7 °C) to create a high‐resolution response curve for each genotype. We observed surprising variation both in the magnitude of survival and in the shapes of the response curves, with the curves clustering into four distinct shapes. To encompass variation in the shapes of these survival curves, we developed a new cold tolerance metric, cumulative cold tolerance (CCT). By comparing our survival data with climatological data, we propose that variation in the shapes of cold‐survival curves arose from weak selection pressure to survive intermediate subzero temperatures in this mid‐latitude population of flies. Using publicly available genome sequence and transcript expression data for these lines, we identified several candidate genes associated with CCT, and using transgenic RNAi, we confirmed a functional role for many of these genes.
Behavioral therapy for Tourette syndrome and chronic tic disorders.

Purpose of review To summarize behavioral interventions for the treatment of primary tic disorders. Recent findings Although tics were attributed to a disordered weak volition, the shift towards neurobiological models of tic disorders also transformed nonpharmacologic treatment practices. Current international guidelines recommend habit reversal training, comprehensive behavioral intervention, and exposure and response prevention as first-line therapies for tics. Appropriate patient selection, including age and presence of comorbidities, are salient clinical features that merit consideration. Evidence for further behavioral interventions is also presented. Summary Currently recommended behavioral interventions view tics as habitual responses that may be further strengthened through negative reinforcement. Although availability and costs related to these interventions may limit their effect, Internet-based and telehealth approaches may facilitate wide accessibility. Novel nonpharmacologic treatments that take different approaches, such as autonomic modulation or attention-based interventions, may also hold therapeutic promise.