Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years

Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high‐quality magnetic resonance imaging [MRI] scans; mean inter‐scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high‐quality scans; mean inter‐scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8‐year period. This initial analysis includes between one and three high‐quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. Autism Res 2015, 8: 82–93. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
Empathic Embarrassment Accuracy in Autism Spectrum Disorder

Empathic accuracy refers to the ability of perceivers to accurately share the emotions of protagonists. Using a novel task assessing embarrassment, the current study sought to compare levels of empathic embarrassment accuracy among individuals with autism spectrum disorders (ASD) with those of matched controls. To assess empathic embarrassment accuracy, we compared the level of embarrassment experienced by protagonists to the embarrassment felt by participants while watching the protagonists. The results show that while the embarrassment ratings of participants and protagonists were highly matched among controls, individuals with ASD failed to exhibit this matching effect. Furthermore, individuals with ASD rated their embarrassment higher than controls when viewing themselves and protagonists on film, but not while performing the task itself. These findings suggest that individuals with ASD tend to have higher ratings of empathic embarrassment, perhaps due to difficulties in emotion regulation that may account for their impaired empathic accuracy and aberrant social behavior. Autism Res 2015, 8: 241–249. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Individual medicine in inflammatory bowel disease: Monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies

Antibody constructs targeting tumour necrosis factor-alpha (TNF) have become important in the management of several chronic immunoinflammatory diseases. Four recombinant anti-TNF drugs are currently approved for clinical use in patients with various chronic inflammatory diseases, three of which are effective in chronic inflammatory bowel disease. These proteins can dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favourably to anti-TNF antibodies. For example, patients suffering from Crohn's disease do not benefit from etanercept, and some patients treated with the other anti-TNF constructs either do not respond at all (primary response failure), or they respond initially but have later relapses (secondary response failure) despite increased dosage and/or more frequent administration of the drugs. The reason(s) for these response failures are not clear but inter-individual and even intra-individual differences in bioavailability and pharmacokinetics may contribute. Furthermore, immunogenicity of the drugs, causing patients to develop anti-drug antibodies (ADAs), contributes to treatment failure. Monitoring patients for circulating levels of functional anti-TNF drugs and ADAs is therefore warranted so that treatment can be tailored to the individual patient (individual medicine or personal medicine) in order that effective and economical long-term therapy can be given with minimal risks to the patients.
Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1

Objective. Serine proteases and the matrix metalloproteinases (MMPs) are key factors in the proteolytic cascade and participate in extracellular matrix (ECM) degradation. Fibrinolytic activators and inhibitors may have an effect on inflammatory cells, thereby modulating the inflammatory response. It is reasonable to assume that they may be implicated in the tissue injury in acute appendicitis that subsequently leads to appendix perforation. The purpose of this study was to investigate the expression and distribution of urokinase-type plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in appendicitis. Material and methods. Expression of uPA and expression of PAI-1 were measured in tissue specimens from patients with appendicitis (n=30) and in control specimens (n=9), using the quantitative ELISA technique. Distribution of enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the subgroups of appendicitis and controls were compared. Results. The overall expressions of uPA and PAI-1 were greater in appendicitis than in control specimens (p <0.001 and p<0.0001, respectively). Expressions of uPA and PAI-1 in phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all higher than those in controls (n=9), (p<0.01). Moreover, the PAI-1 level was elevated in perforated appendicitis compared with phlegmonous appendicitis (p<0.01). uPA staining was observed in connection with vascular endothelial cells and the serosa stained intensely in specimens from perforated appendicitis. Conclusions. The expression of uPA and especially the over-expression of PAI-1 seem to correlate to the progression of local inflammatory response in acute appendicitis.
Anxiety but Not Social Stressors Predict 12-Month Depression and Pain Severity

Objectives:To determine whether baseline anxiety and social stressors as well their early change (first 3 months) predict 12-month depression and pain severity. Methods:We analyzed data from the Stepped Care for Affective Disorders and Musculoskeletal Pain study, a randomized clinical trial of a combined medication-behavioral intervention for primary care patients with chronic musculoskeletal pain and depression. Using multivariable linear regression modeling, we examined the independent association of baseline anxiety and social stressors with depression and pain severity at 12 months. In addition, we modeled whether changes in anxiety and social stressors predicted 12-month depression and pain severity. Results:Overall, the sample (N=250) was 52.8% women with a mean age of 55.5 years, and a racial distribution of 60.4% white, 36.4% black, and 3.2% other. Depression and pain were moderately severe at baseline (mean SCL-20 depression=1.9 and Brief Pain Inventory pain severity=6.15) and similar across intervention and usual care arms. Baseline anxiety symptoms predicted both depression (t score=2.13, P=0.034) and pain severity (t score=2.75, P=0.007) at 12 months. Also, early change in anxiety predicted 12-month depression (t score=−2.47, P=0.014), but not pain. Neither baseline nor early change in social stressors predicted depression or pain severity. Conclusions:Anxiety, but not social stressors predict 12-month depression and pain severity. The presence of comorbid anxiety should be considered in the assessment and treatment of patients with musculoskeletal pain and depression, particularly as a factor that may adversely affect treatment response.
Ascites: Pathogenesis and therapeutic principles

Ascites is a classic complication of advanced cirrhosis and it often marks the first sign of hepatic decompensation. Ascites occurs in more than 50% of patients with cirrhosis, worsens the course of the disease, and reduces survival substantially. Portal hypertension, splanchnic vasodilatation, liver insufficiency, and cardiovascular dysfunction are major pathophysiological hallmarks. Modern treatment of ascites is based on this recognition and includes modest salt restriction and stepwise diuretic therapy with spironolactone and loop-diuretics. Tense and refractory ascites should be treated with large volume paracentesis followed by plasma volume expansion or transjugular intrahepatic portosystemic shunt. Ascites complicated by spontaneous bacterial peritonitis requires adequate treatment with antibiotics. New potential treatment strategies include the use of vasopressin V2-receptor antagonists and vasoconstrictors. Since formation of ascites is associated with a poor prognosis, and treatment of fluid retention does not substantially improve survival, such patients should always be considered for liver transplantation.
Diabetes Mellitus: A Fundamental and Clinical Text

Another diabetes text? Is there something else to know besides controlling blood sugars? According to Mayer B. Davidson, president-elect of the American Diabetes Association, 16 million Americans have diabetes mellitus. It is the most expensive disease in the Western world and the fourth leading cause of death by disease in the United States. The annual cost to the American public is $92 billion dollars, exceeding $11 000 per patient. Diabetes is the leading cause of adult blindness, kidney disease requiring dialysis, and nontraumatic amputations and is a major contributor to heart disease and stroke. Diabetes is among the "big four" for managed care organizations, the others being asthma, prenatal care, and psychiatric disorders. All four are relatively inexpensive when well managed, extraordinarily expensive when out of control. But do we need a new textbook on diabetes? Diabetes Mellitus , edited by LeRoith, Taylor, and Olefsky, takes a uniquely integrated approach. In
Deficient visuospatial working memory functions and neural correlates of the default‐mode network in adolescents with autism spectrum disorder

In addition to the essential features of autism spectrum disorder (ASD), namely social communication deficits and repetitive behaviors, individuals with ASD may suffer from working memory deficits and an altered default‐mode network (DMN). We hypothesized that an altered DMN is related to working memory deficits in those with ASD. A total of 37 adolescents with ASD and 36 age‐ and IQ‐matched typically developing (TD) controls were analyzed. Visuospatial working memory performance was assessed using pattern recognition memory (PRM), spatial recognition memory (SRM), and paired‐associates learning (PAL) tasks. The intrinsic functional connectivity (iFC) of the DMN was indexed by the temporal correlations between the resting‐state functional magnetic resonance imaging signals of pairs of DMN regions, including those between the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) and between the PCC and parahippocampi (PHG). The corresponding structural connectivity of the DMN was indexed by the generalized fractional anisotropy (GFA) of the dorsal and ventral cingulum bundles on the basis of diffusion spectrum imaging data. The results showed that ASD adolescents exhibited delayed correct responses in PRM and SRM tasks and committed more errors in the PAL task than the TD controls did. The delayed responses during the PRM and SRM tasks were negatively correlated with bilateral PCC–mPFC iFCs, and PAL performance was negatively correlated with right PCC–PHG iFC in ASD adolescents. Furthermore, ASD adolescents showed significant lower GFA in the right cingulum bundles than the TD group did; the GFA value was negatively correlated with SRM performance in ASD. Our results provide empirical evidence for deficient visuospatial working memory and corresponding neural correlates within the DMN in adolescents with ASD. Autism Res 2016, 9: 1058–1072. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Lack of replication of previous autism spectrum disorder GWAS hits in European populations

Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome‐wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family‐based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case‐control association study in five European populations of ASD patients and gender‐matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta‐analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI = 0.84–1.32) for rs10513025, 1.0002 (95% CI = 0.93–1.08) for rs4141463 and 1.01 (95% CI = 0.92–1.1) for rs4307059, with no significant P‐values (rs10513025, P = 0.73; rs4141463, P = 0.95; rs4307059, P = 0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. Autism Res 2017, 10: 202–211. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Snus and risk of gastroesophageal reflux. A population-based case-control study: the HUNT study

Abstract Objective: Tobacco smoking is a risk factor for gastroesophageal reflux, but whether other tobacco products increase the risk is unclear. The aim of this study was to investigate if snus increases the risk of gastroesophageal reflux symptoms (GERS). Material and methods: The study was based on the third Nord-Trøndelag health study (HUNT3), a population-based study of all adult residents in Nord-Trøndelag County, Norway, performed in 2006–2009. The association between self-reported severe heartburn/regurgitation and snus use was assessed by logistic regression. Results: Compared to never snus users, daily snus users had a reduced risk of GERS (OR 0.77, 95% confidence interval [CI] 0.64–0.93), while previous snus users and those using <2 boxes of snus/month had an increased risk (OR 1.20, 95% CI 1.00–1.46 and OR 1.41, 95% CI 1.02–1.96, respectively). There was no association between age when starting using snus and GERS. Snus users who started using snus to quit or cut down on cigarette smoking, who started using both snus and cigarettes or cigarettes alone had an increased risk of GERS. Snus users <30 years of age had an increased risk of GERS (OR 1.49, 95% CI 1.02–2.16), while those aged between 50–60 and 60–70 years had a reduced risk (OR 0.67, 95% CI 0.49–0.93 and OR 0.51, 95% CI 0.28–0.94, respectively). Conclusions: Daily snus users had a reduced risk of GERS. However, previous snus users and subgroups of snus users had an increased risk of GERS indicating reverse causality, such that snus use could increase the risk of GERS.
Randomised controlled trial comparing two school furniture configurations in the printing performance of young children with cerebral palsy.

AIM This randomised controlled trial compared the same-session effects of two different school furniture configurations on printing legibility. METHODS A total of 30 school-age children with ambulatory cerebral palsy participated in this study. Each child provided one near-point printing sample of up to 34 letters while positioned on Mandal-type specialty school furniture and on standard school furniture. An assessor who was unaware of the intervention assignment scored printing errors. RESULTS No significant difference in legibility score mean values between the interventions was detected and the effect size was small. CONCLUSIONS Compared with standard school furniture, the use of specialty school furniture did not lead to immediate gains in printing legibility and other printing performance areas for children with cerebral palsy. Further study of the influence of functional abilities, other contextual factors and the longer-term use of school furniture on handwriting performance is recommended.
Worldwide Clinical Experience with aDown‐Sized Active Can ImplantableCardioverier Defibrillator in 162 ConsecutivePatients

Treatment with an ICD is the first‐line treatmentfor survivors of sudden cardiac death. More recently, evidence accumulates that prophylactic ICD therapy may be beneficial for selected subgroups of patients after myocardial infarction. Particularly for future studies on the value of prophylactic ICD therapy, downsized devices are needed to allow easy pectoral implantation with a single lead configuration and featuring extended memory capabilities.Accordingly, this study assesses the clinical performance of a downsized fourth‐generation ICD in 162consecutive patients. All devices could be successfully implanted pectorally, in 96% with a single leadconfiguration with a low defibrillation threshold of 10.6 ± 5.2 J. During a 3‐month follow‐up, 26% of thepatients received ICD therapy. Twenty percent had appropriate therapy for ventricular fibrillation (n= 9) and VT (n = 23), which was effective in all cases. Of the 450 episodes of VT, 426 were terminated by an‐titachycardia pacing. Fourteen patients (9%) had inappropriate ICD therapy mainly due to atrial fibrillation or sinus tachycardia, which could be reliably diagnosed by the ICD stored intracardiac electrograms.
Setting up a student clinical ethics committee

Although medical ethics and law teaching is a required element of the medical undergraduate curriculum, there is a need to ensure that theoretical knowledge is translated into relevant decision-making skills. With at least 85 clinical ethics committees (CECs) providing support for ethical dilemmas arising in clinical practice, might the development of a student clinical ethics committee (SCEC) facilitate both ethical awareness and competency? The SCEC established at King’s College London, School of Medicine (KCLSM) aims to raise awareness and facilitate discussion of ethical issues encountered by students in clinical practice while supplementing current core ethics teaching. In addition, the SCEC introduces students to the workings of a CEC. As medical students do come across ethical dilemmas frequently within their clinical placements, it might be reasonable to suggest that a student forum for ethical discussion, a SCEC, would be a useful adjunct to more theory-based ethics teaching. Just as clinical placements seek to root the sciences of anatomy, physiology, pharmacology (and so on) in the practical medical management of patients, a SCEC could help students reconcile potentially complex moral reasoning with ethically sound patient care. It might be assumed that as medical students progress through their undergraduate training, their ethical awareness and ethical decision-making skills improve as a result of teaching and clinical exposure. However, studies have shown a worrying trend of ethical erosion in medical students’ capability to identify and manage ethical dilemmas as they progress through their undergraduate education. – 5 Unresolved ethical dilemmas encountered by students may erode their ethical principles and ‘ethical self-identities’ and inhibit development in moral reasoning. The reasons for this include lack of time for reflection and a focus on scientific medical knowledge. The SCEC seeks to tackle these deficiencies by offering time for ethical reflection and, by purposefully taking a narrative approach to discussion, considers the perspectives of the patient and others involved in the case.
The implementation of an effective aerobic walking program based on Ottawa panel guidelines for older individuals with mild to moderate osteoarthritis: a participant exercise preference pilot randomized clinical trial protocol design.

kinesiology and the members in rheumatology and biostatistics. A charter governing the process and the frequency of the DSMB meeting, as well as content of the reports, will be determined as part of the study start-up in conjunction with the DSMB and principal investigators. ABSTRACT Aims: Osteoarthritis is the most common disabling disorder affecting particularly knees. A recent systematic review demonstrated the efficacy of walking programs for improving pain, functional status, endurance, and quality of life, in the management of knee osteoarthritis. Even though evidence suggests that walking provides numerous clinical benefits, older people diagnosed with osteoarthritis avoid physical activity. General objective is to evaluate the effect of participants’ exercise preference. We expect to encourage osteoarthritis participants to adhere successfully to a proven effective walking program. Study Design: This is a 9-month supervised walking program with a 3-month follow-up period using a preference trial design which consists of three single blind randomized clinical trials, based on a participant exercise preference model, to elicit preferences independently of randomization. Methodology: A total of 69 participants with a confirmed diagnosis of osteoarthritis of the knee will be recruited from the general public from the Ottawa area. We are implementing a knowledge translation strategy, in order to improve adherence and consequently ensure the maintenance of pain relief, functional status and quality of life, among older individuals diagnosed with mild to moderate osteoarthritis. This article summarizes the study protocol of the walking study, by explaining the methods and interventions selected and discussing on the need for this trial. Conclusion: This proposed pilot randomized controlled trial will address a new knowledge gap by concentring on questions of clinical and scientific importance to improve the understanding related to the efficacy of strategies to promote the adoption and long-term adherence of community-based walking programs.