Miracle-dz/UniFAR-FTUs huggingface dataset:
Ubrogepant for the Treatment of Migraine.

BACKGROUND Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment. METHODS We conducted a randomized trial to evaluate the efficacy, safety, and side-effect profile of ubrogepant. We assigned adults with migraine, with or without aura, in a 1:1:1 ratio to receive an initial dose of placebo, ubrogepant at a dose of 50 mg, or ubrogepant at a dose of 100 mg for treatment of a single migraine attack, with the option to take a second dose. The coprimary efficacy end points were freedom from pain at 2 hours after the initial dose and absence of the most bothersome migraine-associated symptom at 2 hours. Secondary end points included pain relief (at 2 hours), sustained pain relief (from 2 to 24 hours), sustained freedom from pain (from 2 to 24 hours), and absence of symptoms associated with migraine (photophobia, phonophobia, and nausea) at 2 hours. RESULTS A total of 1672 participants were enrolled; 559 were assigned to receive placebo, 556 to receive 50 mg of ubrogepant, and 557 to receive 100 mg of ubrogepant. The percentage of participants who had freedom from pain at 2 hours was 11.8% in the placebo group, 19.2% in the 50-mg ubrogepant group (P = 0.002, adjusted for multiplicity, for the comparison with placebo), and 21.2% in the 100-mg ubrogepant group (P<0.001). The percentage of participants who had freedom from the most bothersome symptom at 2 hours was 27.8% in the placebo group, 38.6% in the 50-mg ubrogepant group (P = 0.002), and 37.7% in the 100-mg ubrogepant group (P = 0.002). Adverse events within 48 hours after the initial or optional second dose were reported in 12.8% of participants in the placebo group, in 9.4% in the 50-mg ubrogepant group, and in 16.3% in the 100-mg ubrogepant group. The most common adverse events were nausea, somnolence, and dry mouth (reported in 0.4 to 4.1%); these events were more frequent in the 100-mg ubrogepant group (reported in 2.1 to 4.1%). Serious adverse events reported within 30 days in the ubrogepant groups included appendicitis, spontaneous abortion, pericardial effusion, and seizure; none of the events occurred within 48 hours after the dose. CONCLUSIONS A higher percentage of participants who received ubrogepant than of those who received placebo had freedom from pain and absence of the most bothersome symptom at 2 hours after the dose. The most commonly reported adverse events were nausea, somnolence, and dry mouth. Further trials are needed to determine the durability and safety of ubrogepant for acute migraine treatment and to compare it with other drugs for migraine. (Funded by Allergan; ClinicalTrials.gov number, NCT02828020.).
Third Molar Impaction-Review

A wisdom tooth (or third molar), refers to one of the four molars in humans. Wisdom teeth generally appear between the ages of 17 and 25. Most adults have four wisdom teeth, but it is possible to have fewer or more, in which case the extras are called supernumerary teeth. Wisdom teeth commonly affect other teeth as they develop, becoming impacted or "coming in sideways". They are often extracted when this occurs. The cause of mandibular third molar impaction is said to be due to inadequate space between the distal of the second mandibular molar and the anterior border of the ascending ramus of the mandible. The amount of space is determined primarily by facial growth. This study aimed to assess whether different patterns of facial growth lead to a different incidence of mandibular third molar impaction. It was hypothesized that those with predominantly horizontal (brachyfacial) would have lower incidence of mandibular third molar impaction compared with those with a predominantly vertical growth pattern (dolichofacial).
Larger Head Displacement to Optic Flow Presented in the Lower Visual Field

Optic flow that simulates self-motion often produces postural adjustment. Although literature has suggested that human postural control depends largely on visual inputs from the lower field in the environment, effects of the vertical location of optic flow on postural responses are not well investigated. Here, we examined whether optic flow presented in the lower visual field produces stronger responses than optic flow in the upper visual field. Either expanding or contracting optic flow was presented in upper, lower, or full visual fields through an Oculus Rift head-mounted display. Head displacement and vection strength were measured. Results showed larger head displacement under the optic flow presentation in the full visual field and the lower visual field than the upper visual field, during early period of presentation of the contracting optic flow. Vection was strongest in the full visual field and weakest in the upper visual field. Our findings of lower field superiority in head displacement and vection support the notion that ecologically relevant information has a particularly important role in human postural control and self-motion perception.
Insight into Informant Discrepancies Regarding Psychosexual Functioning of Adolescents with and without Autism Spectrum Disorder.

The private nature of psychosexual functioning leads adolescents and their parents to have different perspectives, which highlights studying parent-child informant discrepancies in this domain. We investigated informant discrepancy in psychosexual functioning, using the self-report and parent report versions of the Teen Transition Inventory (TTI), of adolescents with autism spectrum disorder (ASD; 136 parent-child dyads) compared to adolescents from the general population (GP; 70 parent-child dyads). Significantly larger informant discrepancies exist in ASD dyads than GP dyads in most domains of psychosexual functioning, except for Body image, Sexual behavior, and Confidence in the future. It is important to use and pay attention to both informants, as discrepancies are relevant for both research and clinical practice regarding psychosexual functioning.
Combined phacoemulsification and sutureless vitrectomy for treatment of rhegmatogenous retinal detachment

Purpose: To report the success rate and possible complications of combined phacoemulsification and sutureless 23 gauge vitrectomy for treatment of rhegmatogenous retinal detachment (RRD). Patients and Methods: Thirty patients with RRD were included in the study. All patients were examined for the extent of detachment, number and location of retinal breaks, and degree of proliferative vitreoretinopathy (PVR). Combined phacoemulsification, intraocular lens implantation, 23 gauge vitrectomy, laser retinopexy, and 12% C3F8 injection were done for all patients. All eyes were followed for 3 months. The primary outcome measures were single operation success rate and change in best-corrected visual acuity (BCVA). Any intraoperative and postoperative complications were reported and analyzed. Results: The mean age of the patients was 43.9 ± 10.11 years; mean duration of detachment was 17.3 ± 5.53 days while mean preoperative BCVA measured by logarithm of the minimum angle of resolution (Log MAR) was 2.1 ± 0.71. Single operation success rate was achieved in 25 eyes (83.3%), 5 eyes (16.7%) showed failure of complete attachment after absorption of gas bubble. The mean postoperative BCVA was significantly better than the preoperative value (1.00, 1.1 after 6 weeks and 3 months, respectively, P < 0.01). The most common postoperative complications were reversible corneal edema that occurred in 11 eyes (36.6%), fibrinous uveitis in 8 eyes (26.6%) and posterior capsular opacification in 16 eyes (53.3%). Preoperatively, 1 eye (3.3%) had BCVA ≤1 (Log MAR) in comparison to 17 eyes (56.7%) and 18 eyes (60%) after 6 weeks and 3 months respectively. Conclusion: Combined phacoemulsification and sutureless vitrectomy with gas tamponade is safe and effective single surgical procedure for selected patients with RRD.
HELICOBACTER PYLORI INFECTION AND GASTRIC CANCER PRECURSOR LESIONS: PREVALENCE AND ASSOCIATED FACTORS IN A REFERENCE LABORATORY IN SOUTHEASTERN BRAZIL.

BACKGROUND Helicobacter pylori infection is the most important risk factor for gastric atrophy and intestinal metaplasia, both considered gastric cancer precursor lesions. Therefore, the investigation of the occurrence of H. pylori infection, precursor lesions and associated factors guides the adoption of specific strategies for the control this type of cancer. OBJECTIVE To evaluate the prevalence of H. pylori infection in patients undergoing upper digestive endoscopy, as well as the prevalence of intestinal metaplasia, atrophy and chronic inflammation and their association with H. pylori infection. METHODS A retrospective study was performed based on reports of gastric endoscopic biopsies performed in a private laboratory affiliated to the Brazilian Public Health System (SUS). Patients were evaluated for age, gender and type of health service. The samples were evaluated for the presence of H. pylori, and also of chronic inflammation, intestinal metaplasia and glandular atrophy. RESULTS Of a total of 4,604 patients (mean age 51±16.6), 63.9% were female and 63.1% coming from private health care service. The prevalence of H. pylori infection was 31.7% (n=1,459), and the percentage of infection was significantly higher in patients from public health service (42.0%) in relation to patients from private health service (25.6%). Among H. pylori (+) patients, a higher percentage of intestinal metaplasia (17.7% vs 13.3%) and glandular atrophy (17.6% vs 6.9%) were observed when compared to those H. pylori (-) (P<0.01). From the patients H. pylori (+) with at least one type of precursor lesion (n=418), 161 (38.5%) had metaplasia and chronic inflammation, 160 (38.3%) had atrophy and chronic inflammation and finally 97 (23.2%) presented metaplasia, atrophy and chronic inflammation simultaneously. CONCLUSION The present study reinforces the association of H. pylori infection with gastric cancer precursor lesions in a Brazilian population, emphasizing the importance of infection prevention measures, as well as the treatment of infected patients, especially in regions with lower socioeconomic levels that show a higher prevalence of infection by H. pylori.
The human tissue-resident CCR5+ T cell compartment maintains protective and functional properties during inflammation

Human CD69+CCR5+ T cells in mucosal tissues are poised to maintain barrier immunity in healthy and inflamed tissues. Tissue-resident T cells evade eviction CCR5 antagonism, explored in various disease settings, does not appear to disrupt barrier immunity. Woodward Davis et al. examined human oral mucosa to characterize CCR5+ T cells in healthy and inflamed tissues. These cells were present below the epithelia and accumulated during inflammation. They had a range of phenotypes, including TH1, TH17, and regulatory cells. Rectal biopsies from a clinical trial using a CCR5 antagonist revealed that CCR5+ T cells were retained even during treatment. These data show that tissue residency may not be perturbed by CCR5 antagonism, allowing barrier immunity to remain intact. CCR5 is thought to play a central role in orchestrating migration of cells in response to inflammation. CCR5 antagonists can reduce inflammatory disease processes, which has led to an increased interest in using CCR5 antagonists in a wide range of inflammation-driven diseases. Paradoxically, these antagonists appear to function without negatively affecting host immunity at barrier sites. We reasoned that the resolution to this paradox may lie in the CCR5+ T cell populations that permanently reside in tissues. We used a single-cell analysis approach to examine the human CCR5+ T cell compartment in the blood, healthy, and inflamed mucosal tissues to resolve these seemingly contradictory observations. We found that 65% of the CD4 tissue-resident memory T (TRM) cell compartment expressed CCR5. These CCR5+ TRM cells were enriched in and near the epithelial layer and not only limited to TH1-type cells but also contained a large TH17-producing and a stable regulatory T cell population. The CCR5+ TRM compartment was stably maintained even in inflamed tissues including the preservation of TH17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5+ TRM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5+ TRM compartment is functionally and spatially equipped to maintain barrier immunity even in the absence of CCR5-mediated, de novo T cell recruitment from the periphery.
Three-Dimensional Upper Airway Assessment in Treacher Collins Syndrome

Objectives: The purpose of this investigation was to assess the pharyngeal dimensions and the craniofacial morphology of individuals with Treacher Collins syndrome (TCS) when compared to vertical skeletal class II individuals. It is our hypothesis that the upper airways of individuals with TCS are reduced in view of the skeletal pattern and the maxillomandibular dysmorphologies. Materials and Methods: Cone-beam computed tomography scans of 26 individuals had the pharyngeal volume (V) and minimal cross-sectional area (mCSA) evaluated. Study group (TCS) was formed by 13 scans of patients with TCS (7 males and 6 females; 20.2 ± 4.7 years). Control group (CG) assembled 13 scans of nonaffected individuals with the same type of skeletal pattern (2 males and 11 females; 26.6 ± 5.4 years). Cephalometric data of maxillomandibular position, maxillomandibular dimensions, and growth pattern were assessed. Statistical analysis (P ≤ .05) included Student t test and Pearson correlation coefficient. Results: Although reduced, pharyngeal V and mCSA of TCS were not statistically different from the CG. On both groups, mCSA was mostly at the oropharyngeal level. Individuals with TCS presented retrognathic chin, reduced maxillomandibular dimensions, and increased clockwise rotation of the palatal plane. Maxillary and mandibular lengths were correlated with pharyngeal V and mCSA. Conclusions: The pharyngeal dimensions of individuals with TCS are impacted by the micrognathia and retrognathia. In association with the skeletal pattern, the reduction of the airways, although not statistically significant, may explain the increased prevalence of airways disorder in this syndrome.
Head-to-Head Comparison of Family History of Colorectal Cancer and a Genetic Risk Score for Colorectal Cancer Risk Stratification

OBJECTIVES: Family history (FH) is associated with increased risk of colorectal cancer (CRC). We aimed to examine the potential for CRC risk stratification by known common genetic variants beyond FH in a large population-based case-control study from Germany. METHODS: Four thousand four hundred forty-seven cases and 3,480 controls recruited in 2003–2016 were included for whom comprehensive interview, medical, and genomic data were available. Associations with CRC risk were estimated from multiple logistic regression models for FH and a genetic risk score (GRS) based on 90 previously identified risk variants. RESULTS: CRC in a first-degree relative was associated with a 1.71-fold (95% confidence interval 1.47–2.00) increase in CRC risk. A higher risk increase (odds ratio 2.06, 95% confidence interval 1.78–2.39) was estimated for the GRS when it was dichotomized at a cutoff yielding the same positivity rate as FH among controls. Furthermore, the GRS provides substantial additional risk stratification in both people with and especially without FH. Equal or even slightly higher risks were observed for participants without FH with a GRS in the upper 20% compared with participants with FH with a GRS below median. The observed patterns were confirmed in a replication study. DISCUSSION: In contrast to common perception, known genetic variants do not primarily reflect some minor share of the familial excess risk of CRC, but rather reflect a substantial share of risk independent of FH.
Whole Genome Expression Analyses of miRNAs and mRNAs Suggest the Involvement of miR-320a and miR-155-3p and their Targeted Genes in Lithium Response in Bipolar Disorder

Lithium is the mainstay in the maintenance of bipolar disorder (BD) and the most efficacious pharmacological treatment in suicide prevention. Nevertheless, its use is hampered by a high interindividual variability and important side effects. Genetic and epigenetic factors have been suggested to modulate lithium response, but findings so far have not allowed identifying molecular targets with predictive value. In this study we used next generation sequencing to measure genome-wide miRNA expression in lymphoblastoid cell lines from BD patients excellent responders (ER, n = 12) and non-responders (NR, n = 12) to lithium. These data were integrated with microarray genome-wide expression data to identify pairs of miRNA/mRNA inversely and significantly correlated. Significant pairs were prioritized based on strength of association and in-silico miRNA target prediction analyses to select candidates for validation with qRT-PCR. Thirty-one miRNAs were differentially expressed in ER vs. NR and inversely correlated with 418 genes differentially expressed between the two groups. A total of 331 of these correlations were also predicted by in-silico algorithms. miR-320a and miR-155-3p, as well as three of their targeted genes (CAPNS1 (Calpain Small Subunit 1) and RGS16 (Regulator of G Protein Signaling 16) for miR-320, SP4 (Sp4 Transcription Factor) for miR-155-3p) were validated. These miRNAs and mRNAs were previously implicated in psychiatric disorders (miR-320a and SP4), key processes of the central nervous system (CAPNS1, RGS16, SP4) or pathways involved in mental illnesses (miR-155-3p). Using an integrated approach, we identified miRNAs and their targeted genes potentially involved in lithium response in BD.
Direct and indirect effects of mindfulness, PTSD, and depression on self-stigma of mental illness in OEF/OIF veterans.

OBJECTIVE Two of the most common and costly mental health diagnoses among military veterans who served in the post-9/11 conflicts in Afghanistan and Iraq are posttraumatic stress disorder (PTSD) and depression, but over half of veterans who screen positive for these problems do not seek treatment. A key barrier is self-stigma of mental illness. Mindfulness has shown promise as an explanatory variable in the context of mental health symptoms and self-stigma, but these associations are underexplored in the veterans' literature. This study examines direct and indirect effects among mindfulness, PTSD and depression, and self-stigma in post-9/11-era military veterans. METHOD A sample of 577 veterans from 3 large American cities completed surveys capturing mindfulness, symptoms of PTSD and depression, and self-stigma. A structural equation modeling approach was used to examine direct and indirect effects among study variables. RESULTS Mindfulness was associated with less PTSD and depression and indirectly with less self-stigma through the PTSD pathway. PTSD was associated with more depression and self-stigma, and depression was not significantly associated with self-stigma. CONCLUSION PTSD is strongly associated with self-stigma in military veterans, many of whom do not seek mental health treatment. Findings show that mindfulness is a promising intervention target for reducing symptoms of PTSD directly and reducing associated self-stigma of mental illness indirectly. Additional investigation of links between mindfulness, PTSD and depressive symptoms, and self-stigma in military veterans is warranted. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
The Prognostic Role of β-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only

Supplemental Digital Content is available in the text Objective: This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients. Summary of Background Data: The majority of sporadic DTF tumors harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types. Methods: A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used. Results: Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded a P-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48–1.42), 0.37 (95% CI 0.12–1.14), and 0.44 (95% CI 0.21–0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence. Conclusions: Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.
Cross-cultural adaptation of the Danish version of the Big Five Inventory – a dual-panel approach

Abstract Background and aims Assessing personality in research can be of importance, especially due to the potential relationship between different personality traits and the manifestation of symptoms in different clinical conditions. Therefore, it is important to have valid and reliable tools that allow for the assessment of personality traits. In this study, the aim was to translate and culturally adapt the Big Five Inventory (BFI) to the Danish language. Methods A dual panel approach, consisting of a 4-person bilingual panel and an 8-person panel with laymen, was used to translate and culturally adapt the questionnaire. A third 9-person panel consisting of people with different medical diagnosis was used to assess the face validity. Internal consistency (Cronbach’s α) and test-retest reliability (intraclass correlation coefficients (ICC)) were tested amongst 96 subjects. Results The translated version demonstrated adequate internal consistency (0.66–0.84) and good-excellent test-retest reliability (0.86–0.95). The smallest detectable change is between 1.13–1.70 for the five subscales. Both the healthy and patient panels of laymen considered the questionnaire too long. Conclusion This translated version of the Big Five Inventory demonstrated high to very high test-retest reliability and, for most parts, an acceptable internal consistency. The construct validity was however different from versions translated into languages geographically and culturally similar to Danish. Implications Assessing the Big Five personality traits in Danish populations can be valuable for many reasons, e.g. when assessing people in pain in both clinical and experimental settings. Improved knowledge of the underlying driver of pain conditions is important. Here, understanding how personality may interact with pain can help researchers and clinicians.