Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivating mutations in Drosha mediate vascular abnormalities similar to hereditary hemorrhagic telangiectasia

The microRNA processing enzyme Drosha is required for blood vessel formation. Processing microRNAs for blood vessels Individuals with hereditary hemorrhagic telangiectasia (HHT) form direct and fragile connections between arteries and veins that are prone to rupture. Most HHT patients have mutations in components of the transforming growth factor–β and bone morphogenetic protein signaling pathways, which regulate blood vessel formation. Noting that the microRNA processing enzyme Drosha interacts with effector proteins in these pathways, Jiang et al. showed that Drosha-deficient zebrafish and mice with an endothelial cell–specific ablation of Drosha had vascular defects reminiscent of those found in HHT patients. Rare mutations in DROSHA were overrepresented in HHT patients who lacked the typical disease-associated mutations. Two of these mutants showed reduced activity and could not rescue the vascular phenotypes of Drosha-deficient zebrafish. Because the mutations in humans and zebrafish were global and not specific to endothelial cells, the predominantly vascular phenotypes suggest that endothelial cells are particularly sensitive to changes in microRNA abundance. The transforming growth factor–β (TGF-β) and bone morphogenetic protein (BMP) family of cytokines critically regulates vascular morphogenesis and homeostasis. Impairment of TGF-β or BMP signaling leads to heritable vascular disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-β and BMP pathway through interaction with Smads and their joint control of gene expression through miRNAs. We report that mice lacking Drosha in the vascular endothelium developed a vascular phenotype resembling HHT that included dilated and disorganized vasculature, arteriovenous fistulae, and hemorrhages. Exome sequencing of HHT patients who lacked known pathogenic mutations revealed an overrepresentation of rare nonsynonymous variants of DROSHA. Two of these DROSHA variants (P100L and R279L) did not interact with Smads and were partially catalytically active. In zebrafish, expression of these mutants or morpholino-directed knockdown of Drosha resulted in angiogenesis defects and abnormal vascular permeability. Together, our studies point to an essential role of Drosha in vascular development and the maintenance of vascular integrity, and reveal a previously unappreciated link between Drosha dysfunction and HHT.
Validade e reprodutibilidade de um questionário para medida de atividade física em adolescentes: uma adaptação do Self-Administered Physical Activity Checklist

OBJECTIVES: To evaluate test-retest reproducibility and the validity of a physical activity questionnaire for adolescents (adapted from Self-Administered Physical Activity Checklist). METHODS: The test-retest reproducibility analysis was completed by 239 adolescents (average age 16 years, SD = 1.2; 56.4% female), and the validity analysis by 70 adolescents (average age 15.7 years, SD = 1.2; 55.7% female). All adolescents were high school students in Joao Pessoa, PB, in Northeastern Brazil, in 2009. The test-retest reproducibility was determined by repeated evaluations with one week interval between them. Validity of the physical activity questionnaire was assessed by comparing the results of the questionnaire with those of four 24-hour recalls (reference method). RESULTS: The test-retest reproducibility was high (intraclass correlation coefficient: ICC = 0.88; 95%CI: 0.84 - 0.91), and the agreement was moderate for physical activity classified in two groups ( 300min/week; kappa coefficient: k = 0.52). Spearman correlation coefficient comparing the questionnaire data with those of four 24-hour recalls (reference method) was moderate (rho = 0.62; p < 0001). The agreement between these measures (questionnaire and 24-hours recalls) for physical activity classified in two groups was moderate (k = 0.59). CONCLUSIONS: The physical activity questionnaire showed high reproducibility, and moderate validity, and therefore, its use is recommended for assessing adolescents' physical activity level.
A novel IKK inhibitor suppresses heart failure and chronic remodeling after myocardial ischemia via MMP alteration

Objective: Amplification of inflammatory response in the non-infarct area plays an important role in the pathogenesis of ventricular remodeling after myocardial ischemia. Activation of nuclear factor-kappa B (NF-κB) is involved in this amplification through a positive feedback loop of pro- inflammatory cytokines. We investigated the efficacy of IKK blockade with IMD-0560, a novel inhibitor of IKK, in a rat myocardial ischemia model. Methods/results: Left coronary artery occlusion (28 days) was carried out in Sprague–Dawley rats. Daily intraperitoneal injections of IMD-0560 (5 mg/kg) were done after the operation. Treatment with IMD-0560 significantly improved cardiac function as indicated by the preservation of fractional shortening and lower serum brain natriuretic peptide level. Histological analysis showed that IMD-0560 treatment suppressed thinning in the infarcted area compared with vehicle-treated hearts. Moreover, in situ zymography showed matrix metalloprotease-9 activity was inhibited in the infarct area. Conclusion: We revealed that the IKK blockade is potent for the suppression of chronic ventricular remodeling after myocardial ischemia.
The effects of sous-vide cooking parameters on texture and cell wall modifications in two apple cultivars: A response surface methodology approach

This work aimed at evaluating the effects of sous-vide cooking parameters, such as time and temperature and their interactions, on textural attributes of ‘Mondial Gala’ and ‘Granny Smith’ apple cultivars. For this, different response surface methodology-based models were developed. This methodology proved a suitable means for the assessment of changes in textural parameters and cell wall modifications during the processing of apples. ‘Mondial Gala’ fruit displayed better aptitude for the preservation of textural properties after high-temperature processing conditions and were therefore apparently more suited to sous-vide cooking than ‘Granny Smith’ apples. Pectin methylesterase activity levels in ‘Mondial Gala’ apples were enhanced at mild temperatures and pectins in this cultivar displayed a lower degree of methylation. Therefore, the establishment of calcium-mediated linkages between cell wall polymers might have been favoured in ‘Mondial Gala’ apples, thus reinforcing tissues and improving the preservation of textural attributes, in comparison to ‘Granny Smith’ samples.
Deciphering Genetic Disease in the Genomic Era: The Model of GnRH Deficiency

Recent technical and conceptual advances presage the elucidation of the genetic causes of human disease through unbiased, patient-oriented investigations. In Pursuit of Genetic Roots The American jazz vocalist “Little” Jimmy Scott is known for his high contralto voice—and also lacks a sense of smell. These seemingly disparate characteristics are the result of Kallmann syndrome, a rare genetic disorder in which there is an isolated deficiency of gonadotropin-releasing hormone (GnRH). Normally, GnRH is secreted during puberty by specialized neurons in the hypothalamus, triggering cells in the pituitary gland to produce hormones that stimulate production of sex steroids, which in turn promote skeletal growth, secondary sexual characteristics, and fertility. GnRH biology can be disrupted at numerous points, causing reproductive failure and, at times, other characteristics. In some cases of Kallmann syndrome, for example, mutations in a certain gene prevent the olfactory tract from forming correctly; precursors of GnRH neurons normally migrate along this structure to the hypothalamus. Thus, both the ability to smell and the development of GnRH-driven characteristics are affected. Despite mutations in 16 genes being linked to isolated GnRH deficiency, most of the genetic basis of this disorder remains to be discovered. Sykiotis and colleagues review the historical path of gene discovery for GnRH deficiency, present their results from the screening of numerous candidate genes, and describe the emerging model of patient-driven gene discovery—a paradigm for uncovering the roots of complex genetic disease in general. Isolated gonadotropin-releasing hormone (GnRH) deficiency is a treatable albeit rare form of reproductive failure that has revealed physiological mechanisms controlling human reproduction, but despite substantial progress in discovering pathogenic single-gene defects, most of the genetic basis of GnRH deficiency remains uncharted. Although unbiased genetic investigations of affected families have identified mutations in previously unsuspected genes as causes of this disease in some cases, their application has been severely limited because of the negative effect of GnRH deficiency on fertility; moreover, relatively few of the many candidate genes nominated because of biological plausibility from in vitro or animal model experiments were subsequently validated in patients. With the advent of exciting technological platforms for sequencing, homozygosity mapping, and detection of structural variation at the whole-genome level, human investigations are again assuming the leading role for gene discovery. Using human GnRH deficiency as a paradigm and presenting original data from the screening of numerous candidate genes, we discuss the emerging model of patient-focused clinical genetic research and its complementarities with basic approaches in the near future.
Achievement of Self-Identified Goals by Adults With Traumatic Brain Injury: Phase I

This article was acceptedfor publication March 28, 1998. Objective. This study sought to determine whether persons with traumatic brain injury who received outpatient occupational therapy services achieved self-identified goals related to tasks ofdaily life. Method. Sixteen participants completed the study. Occupational therapists used their usual treatment procedures to restore independence in home and community occupational functioning. The Canadian Occupational Performance Measure identified the five most important problems that interfered with independence in the roles the participant valued as well as the participant's perception ofperformance ability and satisfaction with performance. Goal Attainment Scaling documented achievement ofthe five selfidentified goals. The Independent Living Skills Evaluation (ILSE) and the Reintegration to Normal Living Scale (RNL) measured changes in overall instrumental activities ofdaily living and community reintegration. Results. The participants significantly achieved (p < .001) their goals from admission to discharge, rated themselves as performing significantly better (p < .001), and were significantly more satisfied (p = .001) with performance after treatment than before. Additionally, they improved significantly on the lLSE (p < .001) and the RNL (p < .001) from admission to discharge. There were no significant changes in performance from discharge to followup on any ofthe scales. Conclusion. Although causality cannot be inferred, it can be concluded that participants attending outpatient occupational therapy significantly improved, and improvements were sustained after discharge, but no fUrther improvement occurred spontaneously.
Chemical evaluation of the Rhynchophorus ferrugineus larvae fed on different substrates as human food source

We investigated the chemical composition of the weevil Rhynchophorus ferrugineus larvae, traditionally used as human food in Asia and known worldwide as one of the most significant pest for palm trees. Total fat content and fatty acid composition were analyzed using standard methodologies in (1) weevil larvae reared on apple fruit slices and wild specimens collected from attacked (2) Phoenix canariensis and (3) Syagrus romanzoffiana palm trees. Total fat content was extremely high in all the specimens (ranged between 57.62 and 60.03% based on dry weight). Despite sharing the same prevalent fatty acids (myristic acid, palmitic acid, stearic acid, palmitoleic acid, oleic acid, α-linoleic acid, and α-linolenic acid), fatty acid composition of the wild weevil larvae significantly differed from that of the specimens raised on apple fruit, due to the presence of other minor compounds. In general, a good balance between unsaturated fatty acids (∼53.68% of total fatty acids) and saturated fatty acids (∼43.41% of total fatty acids) and a low cholesterol content (74.61–152.32 mg/kg based on dry matter) were detected in all the specimens. Conversely, the weevil larvae did not represent a good source of α-tocopherol (14.17–26.22 mg/kg based on dry matter). The ability of the protein extracts obtained from the weevil larvae to inhibit in vitro the angiotensin-converting enzyme, the main enzyme involved in blood pressure regulation, was also investigated. To simulate gastrointestinal digestion process, protein extracts were hydrolyzed by the gastrointestinal enzymes. A significantly lower IC50 (0.588–0.623 mg/ml) was measured in all the protein extracts after enzymatic hydrolysis versus the corresponding crude protein extracts (3.270–3.752 mg/ml). Given that the weevil larvae are able to provide interesting benefits for human health, this study supports their use as human food not just in the native countries where they are traditionally consumed and farmed but also throughout the world.
PRIMARY VIRUS PNEUMONITIS WITH CYTOPLASMIC INCLUSION BODIES: STUDY OF AN EPIDEMIC INVOLVING THIRTY-TWO INFANTS, WITH NINE DEATHS

The present report deals with a hitherto undescribed form of epidemic pulmonary disease occurring in newborn infants. Its peculiar symptomatology and pathology, as well as its epidemic character, clearly indicate the virus nature of its etiology. Characteristic cytoplasmic inclusion bodies were found in the bronchial epithelium in all fatal cases. An increasing number of reports on the subject of atypical pneumonia or virus pneumonitis in man has occurred in the literature during recent years.1That of Goodpasture and his co-workers2alone, however, deals with virus disease of the lungs in infancy. These authors reported finding intranuclear inclusion bodies in the bronchial epithelial cells in 3 cases of postmeasles pneumonia and in 1 case of postpertussis pneumonia. The differences between these cases and those reported in the present paper are detailed under the heading Differential Diagnosis. The 32 cases reported here occurred in rapid succession during the three winter
Stuart Gatehouse: A Brief Life

Stuart Gatehouse was an internationally renowned auditory scientist whose work on basic research, government policy, and clinical practice has directly improved the quality of life of adult hearing aid users. He addressed issues of relevance to the lives of hearing-impaired adults, especially on the impact of a hearing loss on an individual, the management of hearing loss, and the measurement of the benefits offered by hearing aids. He also influenced practice and service delivery and made major contributions to the delivery of audiological services in the United Kingdom, including chairing a report that directly led to their modernization in Scotland. This article describes his life and career.
Atomoxetine Versus Stimulants in the Community Treatment of Children With ADHD

Objective: To compare the morning and afternoon/evening functioning of children with ADHD treated in the community with either atomoxetine or long-acting stimulants and reported to be doing well. Method: 109 8- to 12-year-olds and their mothers participated in one of three groups: stimulants (STIM, N = 26), atomoxetine (ATMX, N = 25), or comparison (COMP, N = 58). Mothers completed morning and evening electronic diaries installed on personal digital assistants throughout an entire week, rating the child’s behaviors and moods as well as their own moods and perceptions. Results: There was no evidence that ongoing pharmacotherapy fully normalized the behaviors of children with ADHD: Mothers in both ADHD groups reported higher rates of child inattention, hyperactivity/impulsivity, oppositionality, and negative affect and lower levels of parenting efficacy and positive affect than did COMP mothers. Although the behavioral profiles were generally comparable for the STIM and ATMX groups, there were indications of better functioning in the ATMX group during mornings only. Conclusion: Children treated in the community with either STIM or ATMX appear to have similar behavioral profiles, suggesting that medication decisions be guided by other factors such as comorbid disorders, child and parent preferences, and effects on nontargeted behaviors and moods. (J. of Att. Dis. 2010; 13(4) 391-400)
An optimization based approach to the partial scan design problem

The problem of selecting flip-flops for inclusion into a partial scan path is formulated as an optimization problem. Scan flip-flops result in layout and delay overheads. Hence, scan flip-flops have to be chosen such that the net cost associated with these overheads is bounded by some user-specified limit. The problem then reduces to choosing a set of flip-flops which gives the best improvement in testability, while keeping the cost bounded. Cost functions are proposed for a standard cell design approach to model the effects of the overheads. Profit functions for three different testability criteria are proposed, and the optimization methodology for each is discussed. The optimization process is modeled on the lines of the 0/1 knapsack problem. Results for some medium-sized sequential circuits which show a very large improvement in fault coverage obtained by optimally selecting a small fraction of the flip-flops in the circuit are presented. <<ETX>>
ADHD Preschoolers With and Without ODD

Objective: To examine the impact of reinforcement on reaction time (RT) and RT variability (RT standard deviation [RTSD]) in preschoolers with ADHD with and without oppositional defiant disorder (ODD), and a typically developing (TD) comparison group. Method: Participants were administered a computerized task consisting of two conditions: simple RT (SRT) and reinforced SRT (SRTr). Data were analyzed using two-way (Group × Condition) mixed ANOVAs and followed-up using pairwise comparisons. Results: RTs were significantly shorter and less variable during the SRTr than the SRT condition. A significant Group x Condition interaction was observed for RTSD (F= 3.38, p < .05); post hoc analyses indicated that the RTSD of the ADHD + ODD group was significantly more variable than that of the TD group during the SRT condition (F = 4.81, p < .05). However, their RTSD was statistically indistinguishable from the other groups during the SRTr condition. Conclusion: Preschoolers who are oppositional/defiant and hyperactive are the most responsive to feedback/reward.
Lane detection based on improved feature map and efficient region of interest extraction

In this paper, the authors propose an efficient algorithm to detect lanes on an improved feature map based on Inverse Perspective Mapping (IPM). IPM removes the perspective effect from the road image and creates a bird's eye view of the road scene. A conventional approach to estimate the lateral offset of the lanes from the IPM image is by adding feature points column by column. However, when the vehicle is drifting from the lanes, lanes are not vertical lines anymore. In this paper, first an edge orientation histogram is calculated in the IPM image and a global lane orientation is estimated. Then, the Signal to Noise Ratio (SNR) of the feature map is improved based on the initially estimated global lane orientation by shifting and matching the feature map. Since lanes are already oriented in that direction, while lane feature points match with each other, other feature points do not. Thus, improvement in the SNR is achieved. Then, the lane marking positions are estimated by 1-D Hough transform searching lines in polar representation with a known orientation, and finally lanes are detected by fitting parabolic lane models to the feature points, in the region of interests, initialized by the Hough transform. The proposed algorithm, achieved to detect lanes with above 96% of detection ratio, tested in complex scenarios.
Self-Esteem, Self-Efficacy, and Resources in Adults With ADHD

Objective: The purpose of this study is to shed light on therapy-relevant factors, such as self-esteem, self-efficacy, and resources in adults with ADHD in comparison with a healthy control group. Method: A total of 43 adults who met Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria for ADHD in adulthood were matched with a nonclinical sample in terms of age and gender. All participants (N = 86) were assessed with self-ratings: Symptom Checklist-90–Revised (SCL-90-R), Rosenberg Self-Esteem Scale, General Perceived Self-Efficacy Scale, and Dick’s Resources Checklist. Results: Adults with ADHD showed lower levels of self-esteem and self-efficacy when compared with the control group. The authors found some, but not all, of the resources of adults with ADHD to be reduced. In other words, people with ADHD seem to possess specific resources. Conclusion: Our results have important implications for the treatment of adult ADHD and suggest that specific therapy programs should include resources-oriented modules for enhancing self-esteem, self-efficacy, and fostering strengths.
Test generation with high coverages for quiescent current test of bridging faults in combinational circuits

Two test strategies for external and internal shorts in FCMOS combinational circuits, based on current consumption monitoring, are proposed and analysed: (a) pseudorandom test with a small number of vectors, and (b) a new strategy called current testing vector generation based on stuck at Faults (CUTEGENS). Both test strategies have been experimented on a set of combinational benchmark circuits. The pseudorandom test strategy has been found efficient when testing external shorts but coverages for internal shorts are not as satisfactory. CUTEGENS provides test sets with a reduced number of vectors, which have a very high coverage for both external and internal shorts. In most of the experimented circuits, the coverage has been shown to be the highest obtainable with current consumption monitoring. <<ETX>>
Predominantly Inattentive Type of ADHD Is Associated With Social Anxiety Disorder

Objective: The aim of this study was to determine the frequency of childhood ADHD comorbidity in patients with social anxiety disorder (SAD), and the influence of this comorbidity on various demographic and clinical variables in SAD. Method: A total of 130 patients with SAD were assessed with K-SADS-PL’s (Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version) behavioral disorders module to determine the childhood diagnosis of ADHD. Patients with or without a comorbid childhood ADHD were compared in terms of clinical characteristics and rating scores. Results: The mean age at onset of SAD was lower, and lifetime major depressive disorder and bipolar disorder (BD) comorbidity were higher in the SAD–ADHD group than in the SAD–without ADHD group. Conclusion: We have found high ADHD comorbidity in patients with SAD. Presence of comorbid ADHD was associated with increased severity, functional impairment, and BD comorbidity.