Miracle-dz/UniFAR-FTUs huggingface dataset:
TNM supplement 1993. A commentary on uniform use

The TNM Classification, a publication of the TNM Project of the International Union Against Cancer (UICC), provides common definitions for the anatomic extent of disease and for staging’,* Although it is used widely clinically and pathologically, some of the definitions and rules for assigning TNM categories for individual sites are not detailed sufficiently and may lead to inconsistencies in staging. Therefore, the TNM Project Committee has prepared a new publication, the TNM Supplement 1993,3 designed to facilitate the uniform application of the TNM Classification. The Supplement provides explanations and examples that can help solve problems encountered in assigning the TNM categories. Many of these examples and explanations are based on comments and suggestions from cancer registrars and individual users. For example, in the chapters concerning explanatory nodes, the definitions of anatomic sites and subsites, regional lymph nodes, and the T, N, and M categories that have been perceived as generic or ambiguous are described more precisely. The Supplement considers practical questions encountered in the everyday use of TNM. For example, how to classify a 4-mm tumor nodule that resembles a lymph node found in the mesentery adjacent to a primary colon carcinoma but does not contain lymphoid tissue-it is coded as a regional lymph node metastasis; and the translation of the clinical description “frozen pelvis” in a case of invasive carcinoma of the uterine cervix into a TNM category (T3b). The Supplement contains recommendations for pathologic classification (pT, pN) of individual tumor sites and selected entities. For example, it considers the staging of an ad-
Cost-effectiveness of upper gastrointestinal endoscopy according to the appropriateness of the indication

Objective. Application of appropriate indications for upper endoscopy (EGD) should conserve limited endoscopic resources. The cost-effectiveness of current guidelines for the detection of gastro-oesophageal cancer is unknown. The aim of this study was to assess the clinical and economic impact of ASGE and EPAGE guidelines in selecting patients referred for upper endoscopy relative to the detection of gastro-oesophageal cancer. Material and methods. A decision analysis model was constructed to compare a strategy of not referring patients for EGD (with either an appropriate or inappropriate indication) with a policy of carrying out the requested EGD. Cancer prevalence in appropriate and inappropriate EGDs was estimated using a systematic review of the literature. Costs of EGD and cancer care were estimated from Medicare reimbursement data. Results. The number of appropriate and inappropriate EGDs required to detect one case of cancer was 41 and 753, respectively, and to prevent one gastro-oesophageal cancer-related death the numbers were 571 and 11,111, respectively. The incremental cost-effectiveness ratios of appropriate and inappropriate EGDs as compared to a policy of not referring patients for endoscopy were $16,577 and $301,203, respectively, per life-year gained. Conclusions. For inappropriate EGD, the very low likelihood of cancer and the relatively high costs associated with this procedure argue against endoscopic referral.
Specificity of autonomic arousal to anxiety in children with autism spectrum disorder

Anxiety is one of the most concerning comorbidities in autism spectrum disorder (ASD) due to its high prevalence, negative impact on physical and psychological well‐being, and interaction with core deficits of ASD. Current assessment and treatment of anxiety, which rely on the observation of behavior and self‐reports, are often ineffective as ASD is associated with deficits in communication and diminished introspective ability. In this light, autonomic nervous system (ANS) activity has been suggested as a marker of physiological arousal associated with anxiety. However, physiological arousal measured by ANS indices also occurs with other cognitive and emotional processes, and it is unclear whether anxiety‐related arousal can be differentiated from that related to other cognitive processes. To address this gap, we investigated the use of linear and nonlinear classification techniques for differentiating anxiety‐related arousal from arousal due to three cognitive processes (attention, inhibitory control, and social cognition) and physical activity based on electrocardiography signal features. Our results indicate that over 80% classification accuracy can be achieved, suggesting that ANS response can be used as a specific marker of anxiety‐related arousal in a subgroup of children with ASD who demonstrate an increase in heart rate in response to anxiogenic stimuli. Autism Res 2016, 9: 491–501. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging Technologies

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental condition. Symptoms of ASD cover the spectrum from mild qualitative differences in social interaction to severe communication and social and behavioral challenges that require lifelong support. Attempts at understanding the pathophysiology of ASD have been hampered by a multifactorial etiology that stretches the limits of current behavioral and cell based models. Recent progress has implicated numerous autism‐risk genes but efforts to gain a better understanding of the underlying biological mechanisms have seen slow progress. This is in part due to lack of appropriate models for complete molecular and pharmacological studies. The advent of induced pluripotent stem cells (iPSC) has reinvigorated efforts to establish more complete model systems that more reliably identify molecular pathways and predict effective drug targets and candidates in ASD. iPSCs are particularly appealing because they can be derived from human patients and controls for research purposes and provide a technology for the development of a personalized treatment regimen for ASD patients. The pluripotency of iPSCs allow them to be reprogrammed into a number of CNS cell types and phenotypically screened across many patients. This quality is already being exploited in protocols to generate 2‐dimensional (2‐D) and three‐dimensional (3‐D) models of neurons and developing brain structures. iPSC models make powerful platforms that can be interrogated using electrophysiology, gene expression studies, and other cell‐based quantitative assays. iPSC technology has limitations but when combined with other model systems has great potential for helping define the underlying pathophysiology of ASD. Autism Res 2016, 9: 513–535. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Variants in several genomic regions associated with asperger disorder

Asperger disorder (ASP) is one of the autism spectrum disorders (ASD) and is differentiated from autism largely on the absence of clinically significant cognitive and language delays. Analysis of a homogenous subset of families with ASP may help to address the corresponding effect of genetic heterogeneity on identifying ASD genetic risk factors. To examine the hypothesis that common variation is important in ASD, we performed a genome‐wide association study (GWAS) in 124 ASP families in a discovery data set and 110 ASP families in a validation data set. We prioritized the top 100 association results from both cohorts by employing a ranking strategy. Novel regions on 5q21.1 (P = 9.7 × 10−7) and 15q22.1–q22.2 (P = 7.3 × 10−6) were our most significant findings in the combined data set. Three chromosomal regions showing association, 3p14.2 (P = 3.6 × 10−6), 3q25–26 (P = 6.0 × 10–5) and 3p23 (P = 3.3 × 10−4) overlapped linkage regions reported in Finnish ASP families, and eight association regions overlapped ASD linkage areas. Our findings suggest that ASP shares both ASD‐related genetic risk factors, as well as has genetic risk factors unique to the ASP phenotype.
Differences in age‐dependent neural correlates of semantic processing between youths with autism spectrum disorder and typically developing youths

Individuals with autism spectrum disorders (ASD) have aberrant neural activity during semantic judgments. We aimed to examine age‐dependent neural correlates of semantic processing in boys with ASD as compared to typically developing boys (TD). We used functional MRI to investigate 37 boys with ASD (mean age = 13.3 years, standard deviation = 2.4) and 35 age‐, sex‐, Intelligence quotient (IQ)‐ and handedness‐matched TD boys (mean age = 13.3 years, standard deviation = 2.7) from age 8 to 18 years. Participants had to indicate whether pairs of Chinese characters presented visually were related in meaning. Group (ASD, TD) × Age (Old, Young) ANOVA was used to examine the difference of age‐related changes. Direct comparisons between the adolescent group and the child group were also performed. The behavioral results showed that the ASD group had lower accuracy in the related condition relative to the TD group. The neuroimaging results showed greater activation in the cuneus and less activation in the left inferior frontal gyrus in boys with ASD than TD boys. Children with ASD produced greater activation in the cuneus than TD children. Adolescents with ASD showed reduced left IFG activation as compared to TD adolescents. Our findings suggest that TD boys may engage more in higher‐level processing of retrieving or selecting semantic features while boys with ASD may rely more on lower‐level visual processing during semantic judgments. The findings imply different functional organizations of the semantic system between the two groups. Autism Res 2016, 9: 1263–1273. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Personal space regulation in childhood autism: Effects of social interaction and person's perspective

Studies in children with Typical Development (TD) and with Autism Spectrum Disorder (ASD) revealed that autism affects the personal space regulation, influencing both its size (permeability) and its changes depending on social interaction (flexibility). Here, we investigate how the nature of social interaction (Cooperative vs. Uncooperative) and the person perspective influence permeability and flexibility of interpersonal distance. Moreover, we tested whether the deficit observed in ASD children, reflects the social impairment (SI) in daily interactions. The stop‐distance paradigm was used to measure the preferred distance between the participant and an unfamiliar adult (first‐person perspective, Experiment 1), and between two other people (third‐person perspective, Experiment 2). Interpersonal distance was measured before and after the interaction with a confederate. The Wing Subgroups Questionnaire was used to evaluate SI in everyday activities, and each ASD participant was accordingly assigned either to the lower (children with low social impairment [low‐SI ASD]), or to the higher SI group (children with high social impairment [high‐SI ASD]). We observed larger interpersonal distance (permeability) in both ASD groups compared to TD children. Moreover, depending on the nature of social interaction, a modulation of interpersonal distance (flexibility) was observed in TD children, both from the first‐ and third‐person perspective. Similar findings were found in low‐SI but not in high‐SI ASD children, in Experiment 1. Conversely, in Experiment 2, no change was observed in both ASD groups. These findings reveal that SI severity and a person's perspective may account for the deficit observed in autism when flexibility, but not permeability, of personal space is considered. Autism Res 2017, 10: 144–154. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Adipose tissue and cardiovascular and metabolic diseases

Obesity is a major contributor to the rising prevalence of cardiovascular and metabolic diseases in both the developed and developing world. Increased adipose tissue mass is associated with changes to the structure and function of the cardiovascular system to ensure circulatory requirements are met. Adipose tissue is a metabolically active endocrine organ that is capable of synthesizing and releasing a variety of signal proteins (adipokines), many of which impact unfavorably on both the cardiovascular system and metabolism. The extent of adiposity, location of fat deposits and variations in the secretion of adipokines, along with other factors, determine whether a particular obese person develops complications, including type 2 diabetes, coronary artery disease, congestive heart failure, hypertension, obstructive sleep apnea syndrome, and non-alcoholic fatty liver disease. This review will discuss the relationship between obesity and cardiovascular and metabolic diseases and will explore how complications of obesity impact on mortality, while healthy lifestyle may prevent them. Biomedical Reviews 2006; 17: 89-104.
Qutenza (Capsaicin) 8% Patch Onset and Duration of Response and Effects of Multiple Treatments in Neuropathic Pain Patients

Introduction:Qutenza (capsaicin) 8% patch is used to treat various neuropathic indications, including postherpetic neuralgia (PHN) and human immunodeficiency virus-associated neuropathy (HIV-AN). Objectives:We conducted a meta-analysis of Qutenza studies to describe clinical phenomena of effects of Qutenza treatment better, such as onset and duration of pain relief, and the need for retreatments. Methods:The meta-analyses combined individual patient data (1313 participants with PHN and 801 with HIV-AN) from 7 completed randomized, double-blind, controlled studies. Studies had similar designs, and all used the Qutenza patch (8% capsaicin) and a low-dose control patch (0.04% capsaicin). A 30% response was defined as a ≥30% decrease in mean pain intensity score during week 2 to end of follow-up; complete pain relief was defined as an average pain intensity ⩽1 during week 2 to end of follow-up. Duration of response was calculated using the data from long-term studies as the time from onset of response to offset of response, retreatment, or end of follow-up (whichever occurred first). Results:Overall 44% of PHN and 41% of HIV-AN patients had a 30% response, and 11% and 7%, respectively, had complete pain relief 2 to 12 weeks after treatment with Qutenza. The mean (median) onset of response to Qutenza was 3.4 (1) days for PHN and 6.5 (4) days for HIV-AN (delayed due to an initial increase in discomfort). The mean (median) duration of response after 1 Qutenza treatment was 5 (3) months. Of the patients followed-up for 12 months, 40% PHN and 36% HIV-AN patients had a 30% response, and 9% and 10%, respectively, had complete pain relief from week 2 to end of follow-up. Conclusions:Qutenza is effective in a high proportion of patients. In patients who respond to Qutenza, analgesia starts within a few days of treatment and lasts on average 5 months.
Audition‐specific temporal processing deficits associated with language function in children with autism spectrum disorder

Sensory processing alterations are highly prevalent in autism spectrum disorder (ASD). Neurobiologically‐based theories of ASD propose that abnormalities in the processing of temporal aspects of sensory input could underlie core symptoms of ASD. For example, rapid auditory temporal processing is critical for speech perception, and language difficulties are central to the social communication deficits defining the disorder. This study assessed visual and auditory temporal processing abilities and tested their relation to core ASD symptoms. 53 children (26 ASD, 27 TD) completed visual and auditory psychophysical gap detection tasks to measure gap detection thresholds (i.e., the minimum interval between sequential stimuli needed for individuals to perceive an interruption between the stimuli) in each domain. Children were also administered standardized language assessments such that the relation between individual differences in auditory gap detection thresholds and degree of language and communication difficulties among children with ASD could be assessed. Children with ASD had substantially higher auditory gap detection thresholds compared to children with TD, and auditory gap detection thresholds were correlated significantly with several measures of language processing in this population. No group differences were observed in the visual temporal processing. Results indicate a domain‐specific impairment in rapid auditory temporal processing in ASD that is associated with greater difficulties in language processing. Findings provide qualified support for temporal processing theories of ASD and highlight the need for future research testing the nature, extent, and universality of auditory temporal processing deficits in this population. Autism Res 2017, 10: 1845–1856. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Click‐evoked auditory brainstem responses and autism spectrum disorder: A meta‐analytic review

Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click‐evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well‐characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta‐analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically‐developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedges's g) for at least one ABR latency component (I, III, V, I‐III, III‐V, I‐V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random‐effects regressions to generate component‐specific estimates. ASD was associated with longer ABR latencies for Waves III (g = 0.5, 95% CI 0.1, 0.9), V (g = 0.7, 95% CI 0.3, 1.1), I‐III (g = 0.7, 95% CI 0.2, 1.2), and I‐V (g = 0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ≤8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium‐to‐large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co‐occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018, 11: 916–927. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
Noninvasive Prenatal Testing: Implications for Muslim Communities

Noninvasive prenatal testing (NIPT), a new technology that uses cell-free fetal DNA in maternal plasma to detect fetal aneuploidies, is currently entering clinical practice. NIPT offers great clinical benefits as it is much more accurate than current screening, allows earlier testing, and eliminates the risk of miscarriage associated with amniocentesis and chorionic villus sampling (CVS). In the future, it may become accurate enough to replace invasive testing. To date, no attention has been given in the literature to the role that earlier testing through NIPT might play in the context of religious traditions with particular attitudes toward abortion, such as in Muslim communities. This article presents some Islamic views regarding fetal development and abortion as well as some recent legislative developments surrounding abortion for fetal conditions, focusing on Iran and Saudi Arabia. It then offers a discussion of possible implications of NIPT for Muslim communities, such as its potential to allow access to diagnostic information before “ensoulment,” the point of fetal development at which the fetus is bestowed the moral status of a human being. The possible impact of early access to information on the evolution of legislation surrounding abortion for fetal conditions is also discussed. Finally, we suggest future research directions based on empirical studies with women, partners, health professionals, and religious authorities in Muslim countries and in countries with a Muslim majority in order to explore their preferences and attitudes regarding the future implementation of NIPT within those communities.
Importance of daily electronic portal imaging in radiotherapy *

An audit was conducted on 20 randomly selected patients who had daily electronic portal imaging during the course of their radiotherapy treatment. The daily images were reviewed to determine whether they were within tolerance according to departmental protocol. If they were not, the actions that were taken were documented. Four treatment areas (spine, chest, breast and prostate) were compared among five patients belonging to each of these categories. The patients were also categorized according to their treatment intent (radical or palliative). A total of 889 electronic portal images of 475 fractions were audited and 33.5% of all fractions were outside tolerance. It was found that 95% of patients needed an action during their treatment and 80% of the patients needed a treatment centre move during the course of their treatment. We found that errors occurred throughout the treatment and it was not possible to predict patients who could have daily imaging omitted. Concordance between radiation therapists and radiation oncologists for identification of error was also investigated. Despite the use of familiar electronic portal imaging protocols, image reviewers (radiation therapists and radiation oncologists) disagreed in interpretation 10% of the time. Our results support the hypothesis that daily imaging may be a useful tool for patients undergoing radiotherapy and that imaging may be ideally carried out before each fraction. Image assessments would be ideally carried out by a team approach, with all images reviewed by both radiation therapists and radiation oncologists. This approach has significant resource implications and may require review of current Medicare and Health Program Grant reimbursements.
High diagnostic yield by CSF-PCR for entero- and herpes simplex viruses and TBEV serology in adults with acute aseptic meningitis in Stockholm

Acute aseptic meningitis (AAM) affects 10–20/100,000 inhabitants per years in Sweden. Up to the beginning of the 1980s the diagnoses were made by virus isolation and/or determination of viral antibodies in serum. The development of PCR for detection of viruses in CSF samples has increased the sensitivity and diagnostic efficiency considerably. We investigated the aetiology of AAM and the diagnostic efficiency in an adult population in Stockholm, using a limited first-line combination of microbiological assays. CSF and serum samples, consecutively collected in 419 patients with clinical symptoms of AAM in northern Stockholm during 1999–2004, were included. PCR assays for herpes simplex virus (HSV) DNA and enterovirus (EV) RNA in the CSF as well as ELISA for IgM in serum to tick-borne encephalitis virus (TBEV) were performed routinely. A viral diagnosis was obtained in 255 of the 419 cases (62%) with these routinely performed assays. Clinical findings in combination with additional diagnostic tests resulted in an overall aetiological yield of 72%. EV was the major causative agent (27%) followed by TBEV (21%) and HSV-2 (19%). We conclude that consistent use of CSF-PCR for EV and HSV and TBEV serology established a diagnosis in the majority of AAM patients.