Miracle-dz/UniFAR-FTUs huggingface dataset:
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED

Objective Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis. Design We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome. Methods Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration. Results Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found. Conclusions This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms.
Comparing the 1‐year impact of preschool autism intervention programs in two Canadian provinces

Autism spectrum disorder (ASD) is associated with early differences in children's social interactions, communication, and play/interests. In many countries, considerable resources are invested in early intensive behavioral intervention (EIBI) programs for children with ASD, which aim to build adaptive skills and prevent or treat problem behavior. However, these programs vary widely in structure and delivery. Research evidence supports the efficacy of EIBI, but large knowledge gaps remain about the effectiveness of publicly funded EIBI programs. With policy‐makers as formal research partners, we compared children's progress over 1 year in public preschool programs in adjacent Canadian provinces, New Brunswick (NB) and Nova Scotia (NS). In NB, children received up to 20 hr/week of comprehensive EIBI in a publicly funded, privately provided program. In NS, children received up to 15 hr/week of Pivotal Response Treatment and Positive Behavior Support delivered through the publicly funded healthcare system. In this observational parallel cohort study, we collected parent‐reported data on 298 NB preschoolers (76.5% boys) and 221 NS preschoolers (86.9% boys) at EIBI start and 1 year later. Multilevel analysis revealed significant differences at baseline: NS children were older, with lower adaptive functioning and more severe ASD symptoms than NB children. Despite these pre‐treatment differences that favor NB, children in both provinces showed similar adaptive functioning gains and reductions of maladaptive behavior. No changes were seen in mean ASD symptom severity in either province over time. Results highlight the value of evaluating interventions in their implementation contexts, and have important implications for devising optimal ASD policy. Autism Research 2019, 12: 667–681. © 2019 International Society for Autism Research,Wiley Periodicals, Inc.
Introduction To UNIX

Introduction to UNIX has been carefully developed to meet the needs of students at the college/university level. Most other UNIX books published today are designed for the working professional. This book was written for students taking an introductory course in a UNIX based computer class. Both majors and non-majors may take this course; as there is no prior knowledge of UNIX required. Upon completion of this course, students will be able to manage most common activities in a UNIX shell account, use standard applications in an X-Windows environment and will have had some introduction to standard UNIX system administration. Table of contents Part I – UNIX BasicsChapter 1 – What is UNIX? Chapter 2 – Basic UNIX ConceptsChapter 3 – Understanding UNIX CommandsChapter 4 – The File SystemChapter 5 – Jobs and ProcessesChapter 6 – Using the ShellPart II – Working with UNIXChapter 7 – The vi EditorChapter 8 – Other Text EditorsChapter 9 – Internet ApplicationsChapter 10 – Networking IChapter 11 – Networking IIPart III – Shell ProgrammingChapter 12 – Shell Programming IChapter 13 – Shell Programming IIChapter 14 – Shell Programming IIIChapter 15 – Shell Programming IVPart IV – System AdministrationChapter 16 – Basic System Administration IChapter 17 – Basic System Administration IIChapter 18 – X WindowsChapter 19 – Running ServersPart V - AppendicesAppendix A: UNIX Command CompendiumAppendix B: GlossaryAppendix C: Common Configuration FilesAppendix D: Internet Resources
Validation of the Attention, Memory, and Frontal Abilities Screening Test (AMFAST)

The aim of this study is to validate the Attention, Memory, and Frontal Abilities Screening Test (AMFAST), a novel, 10-minute, paper-and-pencil measure developed to identify attention, processing speed, memory, and executive functioning deficits in children and adults with various conditions characterized by frontal-subcortical dysfunction. We administered the AMFAST to 186 English-speaking healthy control participants (aged 8-88 years) without reported cognitive impairment. The AMFAST was also administered to a mixed clinical sample that included 114 English-speaking individuals (aged 8-84 years) who also received comprehensive neuropsychological testing. Results indicated that total AMFAST scores in the healthy control sample were not significantly affected by education or gender. There was, however, a significant effect of age, as the 8- to 10-year-old group scored significantly lower than other age groups. Thus, only participants 11+ years were included in further analyses. The AMFAST demonstrated high test–retest and interrater reliabilities, good construct validity, and the identified optimal cutoff score of 70 had excellent sensitivity and specificity for differentiating between cognitively intact and cognitively impaired individuals. These findings demonstrate that the AMFAST is a highly effective screening test that can be used to identify attention, memory, processing speed, and executive functioning deficits in individuals from middle childhood through older adulthood.
Mutational mechanism for DAB1 (ATTTC)n insertion in SCA37: ATTTT repeat lengthening and nucleotide substitution

Dynamic mutations by microsatellite instability are the molecular basis of a growing number of neuromuscular and neurodegenerative diseases. Repetitive stretches in the human genome may drive pathogenicity, either by expansion above a given threshold, or by insertion of abnormal tracts in nonpathogenic polymorphic repetitive regions, as is the case in spinocerebellar ataxia type 37 (SCA37). We have recently established that this neurodegenerative disease is caused by an (ATTTC)n insertion within an (ATTTT)n in a noncoding region of DAB1. We now investigated the mutational mechanism that originated the (ATTTC)n insertion within an ancestral (ATTTT)n. Approximately 3% of nonpathogenic (ATTTT)n alleles are interspersed by AT‐rich motifs, contrarily to mutant alleles that are composed of pure (ATTTT)n and (ATTTC)n stretches. Haplotype studies in unaffected chromosomes suggested that the primary mutational mechanism, leading to the (ATTTC)n insertion, was likely one or more T>C substitutions in an (ATTTT)n pure allele of approximately 200 repeats. Then, the (ATTTC)n expanded in size, originating a deleterious allele in DAB1 that leads to SCA37. This is likely the mutational mechanism in three similar (TTTCA)n insertions responsible for familial myoclonic epilepsy. Because (ATTTT)n tracts are frequent in the human genome, many loci could be at risk for this mutational process.
Long-Term Effects of an Unguided Online Cognitive Behavioral Therapy for Chronic Insomnia.

STUDY OBJECTIVES The aim of this study was to test the efficacy of fully automated Internet-delivered cognitive behavioral therapy for insomnia (CBT-I) 18 months after the intervention period on sleep, daytime functioning, and beliefs about sleep for adults with chronic insomnia. METHODS Participants in this study had participated in a randomized controlled trial comparing the efficacy of unguided Internet CBT-I with web-based patient education. Participants who had received Internet CBT-I (n = 95) completed online questionnaires and online sleep diaries 18 months after the intervention period. We used linear mixed models to study changes from baseline to postassessment and to 18-month follow-up, and a separate mixed-models analysis to study changes from postassessment to 18-month follow-up. RESULTS Mean age of the participants was 45.5 years (standard deviation = 12.6) and 64% were females. Sixty-six participants (70%) completed the 18-month follow-up assessment. There were significant improvements from baseline to 18-month follow-up on the Insomnia Severity Index (ISI) (Cohen d = 2.04 [95% confidence interval (CI) 1.66-2.42]) and the Bergen Insomnia Scale (BIS) (d = 1.64 [95% CI 1.30-1.98]), levels of daytime fatigue (d = 0.85 [95% CI 0.59-1.11]), psychological distress (d = 0.51 [95% CI 0.29-0.73]), and beliefs about sleep (d = 1.44 [95% CI 1.15-1.73]). Moderate to large effect size improvements were also shown on the diary-derived sleep variables. All improvements from baseline to postassessment were essentially maintained to 18-month follow-up. CONCLUSIONS Unguided Internet CBT-I appears to have sustained effects on sleep, daytime functioning, and beliefs about sleep up to 18 months after the intervention period. CLINICAL TRIAL REGISTRATION This study presents long-term follow-up data of a previous clinical trial. Registry: ClinicalTrials.gov, Title: Internet-based Treatment for Insomnia in Norway, Identifier: NCT02261272, URL: https://clinicaltrials.gov/ct2/show/NCT02261272.
Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer

Abstract Background There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. Patients and methods Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan–Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. Results Median TILs was 5% (Q1–Q3 1%–15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59–0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41–0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71–1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09–2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05–1.09, P = 0.064), resulting in a significant interaction (P = 0.015). Conclusions TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.
Looking for trouble: archeology, art and interdisciplinary encounters

ABSTRACT This paper considers the difficulties and creativity involved in interdisciplinary collaboration. Based on some of the outputs generated from shared time spent at the UNESCO World Heritage site of El Kurru in Sudan, the common elements of both artistic and archaeological work are explored. By reflecting on certain methods and materials a version of our practices emerges from the assemblage of the archaeological site, one which is deeply engaged with sensorially based responses to it.
HOS15 Interacts with the Histone Deacetylase HDA9 and the Evening Complex to Epigenetically Regulate the Floral Activator GIGANTEA[OPEN]

The High Expression Of Osmotically Responsive Gene 15–Evening Complex–histone deacetylase 9 histone-modifying complex regulates photoperiodic flowering via transcriptional repression of GIGANTEA. In plants, seasonal inputs such as photoperiod and temperature modulate the plant’s internal genetic program to regulate the timing of the developmental transition from vegetative to reproductive growth. This regulation of the floral transition involves chromatin remodeling, including covalent modification of histones. Here, we report that HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE 15 (HOS15), a WD40 repeat protein, associates with a histone deacetylase complex to repress transcription of the GIGANTEA (GI)-mediated photoperiodic flowering pathway in Arabidopsis (Arabidopsis thaliana). Loss of function of HOS15 confers early flowering under long-day conditions because elevated GI expression. LUX ARRHYTHMO (LUX), a DNA binding transcription factor and component of the Evening Complex (EC), is important for the binding of HOS15 to the GI promoter. In wild type, HOS15 associates with the EC components LUX, EARLY FLOWERING 3 (ELF3), and ELF4 and the histone deacetylase HDA9 at the GI promoter, resulting in histone deacetylation and reduced GI expression. In the hos15-2 mutant, the levels of histone acetylation are elevated at the GI promoter, resulting in increased GI expression. Our data suggest that the HOS15–EC–HDA9 histone-modifying complex regulates photoperiodic flowering via the transcriptional repression of GI.
Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

The literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. SUMMARY The literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.
Pilot investigation of the mutation profile of PIK3CA/PTEN genes (PI3K pathway) in grade 3 endometrial cancer

Endometrial cancer (EC) comprises a biological and clinical heterogeneous group of tumors. Several genetic alterations are involved in the development and progression of EC, and may be used for targeted therapy, particularly in patients with advanced-stage EC. In the present study, a combined procedure was developed based on polymerase chain reaction (PCR)-high resolution melting analysis (HRMA) and Sanger sequencing for the evaluation of somatic mutations in selected phosphoinositide 3-kinase (PI3K) catalytic subunit α (PIK3CA; exons 1, 9 and 21) and phosphatase and tensin homolog (PTEN; exons 5, 6, 7 and 8) exons. This combined procedure has the specificity and sensitivity of the two techniques, and overcomes their limitations. A pilot study was performed on 18 selected homogenous EC samples, of grade 3 endometrioid subtype (G3 EEC). First, the feasibility of the combined procedure was investigated to properly identify the presence of somatic mutations on PIK3CA and PTEN, the variations identified were analyzed using Catalogue of Somatic Mutations in Cancer, PolyPhen-2 and Mutation Taster software, and the frequency of mutations/variations was determined in the selected samples. The evaluation of mutational load revealed that the majority of the G3 EEC samples exhibited PIK3CA mutations (39%) and PTEN mutations (67%), and the majority of the samples (83%) had mutations in at least one of the two genes, and 33% had mutations in the two genes. The results of the present pilot study suggested that the cost-effective combined PCR-HRMA and Sanger sequencing procedure may be suitable for identification of PTEN and PIK3CA mutations in G3 EEC and that their frequency was consistent in G3 EEC, indicating that the PI3K pathway serves a pivotal function that may have potential for defining targeted therapy for the treatment of G3 EEC.
Supplementation with omega fatty acids increases the mRNA expression level of PLA2G4A in patients with gastric cancer.

Background Many lines of evidence suggest that arachidonic acid (AA)-based eicosanoid signaling pathway involved in development and progression of human cancers. Cytosolic phospholipase A2-α (cPLA2α) encoded by the PLA2G4A gene acts as an upstream regulator of eicosanoid signaling pathway through providing intracellular AA. The current study aimed to evaluate the effect of omega fatty acids on mRNA expression level of PLA2G4A in patients with gastric cancer (GC) and to assess the possible relation between its expression and clinicopathological features. Methods According to treatment strategy, 34 chemotherapy-naive patients were randomly divided into two groups including, treatment group I (17 subjects received cisplatin alone) and treatment group II (17 individuals received cisplatin plus omega fatty acids) in a double-blind manner. The gastric biopsies specimens were taken from subjects before and after treatment and then mRNA expression level of PLA2G4A was evaluated by quantitative real-time PCR procedure. Results The expression of the PLA2G4A gene at the protein level in the gastric biopsies samples was also determined by immunohistochemistry. Our findings revealed a significantly up-regulated expression of PLA2G4A mRNA in treatment group II after receiving cisplatin plus omega fatty acid compared to before treatment (P=0.003). In treatment group I, there was no significant difference in mRNA expression levels of PLA2G4A before and after treatment (P=0.790). We also found that mRNA expression of PLA2G4A in treatment group II was significantly associated with tumor size (P=0.007) and familial history (P=0.006). Conclusions This study provides evidence that supplementation with omega fatty acids increases the mRNA expression level of PLA2G4A in patients with GC and may be crucial in guarding the cell from transformation and carcinogenesis.
The Effect of Selective Laser Melting Process Parameters on the Microstructure and Mechanical Properties of Al6061 and AlSi10Mg Alloys

Additive manufacturing (AM) offers customization of the microstructures and mechanical properties of fabricated components according to the material selected and process parameters applied. Selective laser melting (SLM) is a commonly-used technique for processing high strength aluminum alloys. The selection of SLM process parameters could control the microstructure of parts and their mechanical properties. However, the process parameters limit and defects obtained inside the as-built parts present obstacles to customized part production. This study investigates the influence of SLM process parameters on the quality of as-built Al6061 and AlSi10Mg parts according to the mutual connection between the microstructure characteristics and mechanical properties. The microstructure of both materials was characterized for different parts processed over a wide range of SLM process parameters. The optimized SLM parameters were investigated to eliminate internal microstructure defects. The behavior of the mechanical properties of parts was presented through regression models generated from the design of experiment (DOE) analysis for the results of hardness, ultimate tensile strength, and yield strength. A comparison between the results obtained and those reported in the literature is presented to illustrate the influence of process parameters, build environment, and powder characteristics on the quality of parts produced. The results obtained from this study could help to customize the part’s quality by satisfying their design requirements in addition to reducing as-built defects which, in turn, would reduce the amount of the post-processing needed.
Electronic cigarettes in Italy: a tool for harm reduction or a gateway to smoking tobacco?

Introduction More than a decade after electronic cigarettes (e-cigarette) hit the European market, we are still debating whether they may help or hinder tobacco control. It is therefore useful to explore the potential net effect of e-cigarette use in the general population. Methods We annually conduct a face-to-face survey on smoking in Italy on a representative sample of the general population aged 15 years or over (52.4 million). A total of 15 406 subjects were interviewed in 2014–2018. We investigated the consequences of using e-cigarettes on tobacco smoking behaviour among ever and regular e-cigarette users. Results In all, 5.7% of our sample reported ever e-cigarette use. Multivariate analyses showed more use by men, ex-smokers and current smokers. E-cigarette use decreased with age and increased with education and calendar year. Only 1.1% of subjects were regular e-cigarette users. This prevalence rose from 0.4% in 2014–2015 to 1.8% in 2016–2017 and was 1.3% in 2018. Among 522 ever users, 13.2% stopped smoking after trying e-cigarettes and 22.2% started smoking or relapsed after using e-cigarettes. The corresponding estimates among regular users were 24.7% and 28.0%, respectively. Conclusions Among Italian e-cigarette users, those (re)starting smoking after using e-cigarettes outnumber those who stop smoking after using e-cigarettes. From a public health point of view, e-cigarettes may have an unfavourable net effect. Consequently, if we are not able to prevent sales of e-cigarettes to non-smokers, this product will more likely stimulate smoking tobacco than reduce harm.