Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis.

Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results- Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39-1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86-1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63-8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73-1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99-1.54). Conclusions- In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS. Clinical Trial Registration- URL: https://www.clinicaltrials. gov. Unique identifier: NCT02313909.
Two years clinical outcomes with the state‐of‐the‐art PCI for the treatment of bifurcation lesions: A sub‐analysis of the SYNTAX II study

Bifurcation PCI is associated with a lower rate of procedural success, especially in multivessel disease patients. We aimed to determine the impact of bifurcation treatment on 2‐years clinical outcomes when a state‐of‐the‐art PCI strategy (heart team decision‐making using the SYNTAX score II, physiology guided coronary stenosis assessment, thin strut bioresorbable polymer drug‐eluting stent, and intravascular ultrasound guidance) is followed.
The efficacy of a training that combines activities on working memory and metacognition: Transfer and maintenance effects in children with ADHD and typical development

ABSTRACT Introduction: It has been demonstrated that children with attention deficit and hyperactivity disorder (ADHD) have impairments in working memory (WM), and particularly its visuospatial component, responsible for academic underachievement. Furthermore, children with ADHD have difficulty in metacognition, and consequently use inappropriate strategies to control attention and impulsive behavior. The aim of the present study was to devise a training that combined individual exercises on visuospatial WM and group metacognitive activities capable of helping children with ADHD to ameliorate their performance in executive functioning tasks, and to contain their inattentive and hyperactive/impulsive behavior. Method: A combined training that focused on visuospatial WM and metacognition was administered to 12 children with a diagnosis of ADHD and 15 typically-developing children. Tasks on executive functions and questionnaires for parents and teachers were administered before and at the end of the training, and one month after the post-test. Specific short- and long-term training gains and transfer effects were examined. Effects of the training on parents’ and teachers’ ratings were also considered. Results: Specific gains and transfer effects were found at the post-test and long-term assessments in both typically-developing children and those with ADHD. Parents’ and teachers’ ratings also indicated an improvement in the symptomatic behavior of children with ADHD. Conclusion: The results of this study have clinical and educational implications. A training that combines individual computerized visuospatial WM activities with metacognitive group reflection about useful strategies seems to produce promising results, helping children with ADHD to improve their executive functioning and behavioral problems.
Emerging Nonsteroid-Based Procedural Therapies for Alopecia Areata: A Systematic Review.

BACKGROUND Alopecia areata (AA) is a common form of patchy, nonscarring hair loss. Although intralesional steroid injections are currently the mainstay procedural therapy for AA, other nonsteroid-based procedural therapies, including platelet-rich plasma (PRP), ultraviolet radiation (UVR), and laser-based modalities, are emerging as practical options. OBJECTIVE To systematically review nonsteroid-based procedural therapies for AA and recapitulate the available clinical data. MATERIALS AND METHODS A systematic review of the literature was performed searching PubMed/MEDLINE databases identifying studies investigating PRP, UVR, and laser-based modalities for AA treatment. RESULTS Literature search yielded 644 articles encompassing PRP, UVR, and laser treatment modalities for AA. Of the 644 articles, 46 met inclusion criteria. Although numerous reports demonstrate strong potential for PRP, UVR, and laser modalities in treating AA, high-quality evidence supporting their efficacy is still lacking. CONCLUSION There is an abundance of evidence for nonsteroid-based procedural therapies in the treatment of AA. Randomized control trials comparing these treatment options head-to-head should be performed to better understand the true efficacy of these treatments.
Folic acid supplementation and risk of colorectal neoplasia during long-term follow-up of a randomized clinical trial.

BACKGROUND The Aspirin/Folate Polyp Prevention Study previously found folic acid increased risk of advanced and multiple colorectal adenomas during a surveillance colonoscopy interval starting about 3 y after randomization. OBJECTIVE We conducted secondary analyses to evaluate folic acid effects with additional follow-up after treatment was stopped. METHODS In total, 1021 participants recently diagnosed with colorectal adenomas were randomly assigned to 1 mg/d of folic acid (n = 516) or placebo (n = 505), with or without aspirin, beginning 6 July 1994. The original 3-y treatment period was extended into a subsequent colonoscopy interval, but eventually stopped prematurely on 1 October 2004. With additional post-treatment follow-up, a total of 663 participants who extended treatment completed a second colonoscopic surveillance interval after the initial 3-y follow-up. In addition, 490 participants provided information regarding a subsequent surveillance colonoscopy occurring before completion of follow-up on 31 May 2012, including 325 who had agreed to extended treatment. Study endpoints included conventional adenomas, sessile serrated adenomas/polyps (SSA/Ps), or colorectal cancer, and RRs with 95% CIs were adjusted for baseline characteristics associated with availability of follow-up. RESULTS Among those who extended treatment, any colorectal neoplasia was found in 118 (36%) participants assigned to placebo and 146 (43%) assigned to folic acid during the second surveillance interval (RR: 1.21; 95% CI: 0.99, 1.47; P = 0.06). Increased risk of SSA/P with extended folic acid supplementation was statistically significant during the second surveillance interval (RR: 1.94; 95% CI: 1.02, 3.68; P = 0.04). There was no evidence of post-treatment effects for any colorectal neoplasia (RR: 1.01; 95% CI: 0.80, 1.28; P = 0.94), and the post-treatment effect for SSA/P was no longer statistically significant (RR: 1.38; 95% CI: 0.59, 3.19; P = 0.46). CONCLUSIONS Delayed treatment effects were not observed, but folic acid may increase SSA/P risk. This trial was registered at clinicaltrials.gov as NCT00272324.
Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit

ABSTRACT Blockade of immune checkpoint pathways by programmed cell death protein 1 (PD-1) antibodies has demonstrated broad clinical efficacy against a variety of malignancies. Sintilimab, a highly selective, fully human monoclonal antibody (mAb), blocks the interaction of PD-1 and its ligands and has demonstrated clinical benefit in various clinical studies. Here, we evaluated the affinity of sintilimab to human PD-1 by surface plasmon resonance and mesoscale discovery and evaluated PD-1 receptor occupancy and anti-tumor efficacy of sintilimab in a humanized NOD/Shi-scid-IL2rgamma (null) (NOG) mouse model. We also assessed the receptor occupancy and immunogenicity of sintilimab from clinical studies in humans (9 patients with advanced solid tumor and 381 patients from 4 clinical studies, respectively). Sintilimab bound to human PD-1 with greater affinity than nivolumab (Opdivo®, MDX-1106) and pembrolizumab (Keytruda®, MK-3475). The high affinity of sintilimab is explained by its distinct structural binding mode to PD-1. The pharmacokinetic behavior of sintilimab did not show any significant differences compared to the other two anti-PD-1 mAbs. In the humanized NOG mouse model, sintilimab showed superior PD-1 occupancy on circulating T cells and a stronger anti-tumor effect against NCI-H292 tumors. The strong anti-tumor response correlated with increased interferon-γ-secreting, tumor-specific CD8+ T cells, but not with CD4+ Tregs in tumor tissue. Pharmacodynamics testing indicated a sustained mean occupancy of ≥95% of PD-1 molecules on circulating T cells in patients following sintilimab infusion, regardless of infusion dose. Sintilimab infusion was associated with 0.52% (2/381 patients) of anti-drug antibodies and 0.26% (1/381 patients) neutralizing antibodies. These data validate sintilimab as a novel, safe, and efficacious anti-PD-1 mAb for cancer immunotherapy.
Survey of full‐scale sidestream enhanced biological phosphorus removal (S2EBPR) systems and comparison with conventional EBPRs in North America: Process stability, kinetics, and microbial populations

Sidestream EBPR (S2EBPR) is an emerging alternative process to address common challenges in EBPR related to weak wastewater influent and may improve EBPR process stability. A systematic evaluation and comparison of the process performance and microbial community structure was conducted between conventional and S2EBPR facilities in North America. The statistical analysis suggested higher performance stability in S2EBPR than conventional EBPR, although possible bias associated with other plant‐specific factors might have affected the comparison. Variations in stoichiometric values related to EBPR activity and discrepancies between the observed values and current model predictions suggested a varying degree of metabolic versatility of PAOs in S2EBPR systems that warrant further investigation. Microbial community analysis using various techniques suggested comparable known candidate PAO relative abundances in S2EBPR and conventional EBPR systems, whereas the relative abundance of known candidate GAOs seemed to be consistently lower in S2EBPR facilities than conventional EBPR facilities. 16S rRNA gene sequencing analysis revealed differences in the community phylogenetic fingerprints between S2EBPR and conventional facilities and indicated statistically higher microbial diversity index values in S2EBPR facilities than those in conventional EBPRs.
Proinflammatory Histidyl–Transfer RNA Synthetase–Specific CD4+ T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies

Autoantibodies targeting histidyl–transfer RNA synthetase (HisRS; anti–Jo‐1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS in the blood and lungs of patients with IIM/antisynthetase syndrome.
Co-administration of erythropoietin and iron complex improves late-phase liver regeneration

Erythropoietin and iron have individually shown beneficial effects on early-phase liver regeneration following partial hepatectomy (PHx); however, there are limited data on the combined effect on late-phase liver regeneration after PHx. Here we examined combined effects of recombinant human erythropoietin (rhEPO, 3,000 IU/kg) and iron isomaltoside (IIM, 40 mg/kg) on late-phase liver regeneration following PHx and investigated the possible underlying mechanism. Rats administrated with rhEPO showed significantly higher liver mass restoration, interleukin-6 (IL-6, a hepatocyte mitogen) levels, and Ki-67-positive hepatocytes on day 7 after PHx than saline-treated controls. These beneficial effects were further enhanced on days 7 and 14 by co-treatment with IIM. This combination also significantly improved liver function indices, such as increased albumin production and decreased bilirubin levels, but did not alter serum levels of toxic parameters, such as aspartate transaminase and alanine transaminase. This study demonstrates that the combination of rhEPO and IIM synergistically improves late-phase liver regeneration and function after PHx, probably by promoting IL-6-mediated hepatocyte proliferation without adverse effects. Thus, this combination treatment can be a potential therapeutic strategy for patients undergoing resection for hepatic malignancies.
In Vitro Efficacy of Chlorhexidine and a riboflavin/UVA Combination on Fungal Agents of Keratitis

ABSTRACT Purpose Mycotic keratitis is a global ophthalmological problem because it is difficult to diagnose and treat. The aim of the current study was to evaluate the efficiency of using antifungal agents amphotericin B (AMB), voriconazole (VRC), 0.02% chlorhexidine (CHX), and a combination of riboflavin and UVA treatment against two fungal genera (Aspergillus and Fusarium) responsible for keratitis. Methods We evaluated antifungal efficiencies of riboflavin/UVA and the antifungal drugs VRC, AMB, and CHX (alone and in combination) against fungal inocula at four concentrations. We recorded colony counts of isolates for Aspergillus terreus, A. flavus, A. fumigatus, Fusarium falciforme, F. proliferatum, and F. solani on Mueller-Hinton agar plates. Results Fungal suspensions exposed to the following treatment combinations did not allow fungal growth: riboflavin/UVA and VRC, riboflavin/UVA and AMB, riboflavin/UVA and CHX, and CHX alone. We observed a statistically significant reduction (P < .05) in the number of colonies on agar plates when fungal suspensions were treated with riboflavin/UVA, VRC, and AMB only. Conclusions Riboflavin/UVA treatment in combination with AMB, VRC, and CHX are capable of killing keratitis-inducing fungi (P < .05). The antiseptic CHX exerted a considerable antifungal effect on all strains we examined. Therefore, we recommend CHX as additional therapy against mycotic keratitis, particularly when keratitis is caused by multi-resistant members of Fusarium.
Reevaluation of genetic variants previously associated with arrhythmogenic right ventricular cardiomyopathy integrating population‐based cohorts and proteomics data

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the most common causes of sudden cardiac death in young people. Patients diagnosed with ARVC may experience increased likelihood of development of anxiety and depression, emphasizing the need for accurate diagnosis. To assist future genetic diagnosis and avoidance of misdiagnosis, we evaluated the reported monogenic disease‐causing variants in ARVD/C Genetic Variants Database, Human Gene Mutation Database, and ClinVar. Within the aforementioned databases, 630 monogenic disease‐causing variants from 18 genes were identified. In the genome Aggregation Database, 226 of these were identified; 68 of which were found at greater than expected prevalence. Furthermore, 37/226 genetic variants were identified amongst the 409 000 UK biobank participants, 23 were not associated with ARVC. Among the 14 remaining variants, 13 were previously found with greater than expected prevalence for a monogenic variant. Nevertheless, they were associated with serious cardiac phenotypes, suggesting that these 13 variants may be disease‐modifiers of ARVC, rather than monogenic disease‐causing. In summary, more than 10% of variants previously reported to cause ARVC were found unlikely to be associated with highly penetrant monogenic forms of ARVC. Notably, all variants in OBSCN and MYBPC3 were found, making these unlikely to be monogenic causes of ARVC.
Patterns of co‐altered brain structure and function underlying neurological soft signs in schizophrenia spectrum disorders

Neurological soft signs (NSS) comprise a broad range of subtle neurological deficits and are considered to represent external markers of sensorimotor dysfunction frequently found in mental disorders of presumed neurodevelopmental origin. Although NSS frequently occur in schizophrenia spectrum disorders (SSD), specific patterns of co‐altered brain structure and function underlying NSS in SSD have not been investigated so far. It is unclear whether gray matter volume (GMV) alterations or aberrant brain activity or a combination of both, are associated with NSS in SSD. Here, 37 right‐handed SSD patients and 37 matched healthy controls underwent motor assessment and magnetic resonance imaging (MRI) at 3 T. NSS were examined on the Heidelberg NSS scale. We used a multivariate data fusion technique for multimodal MRI data—multiset canonical correlation and joint independent component analysis (mCCA + jICA)—to investigate co‐altered patterns of GMV and intrinsic neural fluctuations (INF) in SSD patients exhibiting NSS. The mCCA + jICA model indicated two joint group‐discriminating components (temporoparietal/cortical sensorimotor and frontocerebellar/frontoparietal networks) and one modality‐specific group‐discriminating component (p < .05, FDR corrected). NSS motor score was associated with joint frontocerebellar/frontoparietal networks in SSD patients. This study highlights complex neural pathomechanisms underlying NSS in SSD suggesting aberrant structure and function, predominantly in cortical and cerebellar systems that critically subserve sensorimotor dynamics and psychomotor organization.
Gabapentin for Perioperative Pain Management for Uterine Aspiration: A Randomized Controlled Trial.

OBJECTIVE To evaluate the effect of oral gabapentin in conjunction with usual oral pain management regimens of lorazepam, ibuprofen, oxycodone, and acetaminophen for surgical abortion on pain 5 minutes postprocedure. METHODS This was a randomized, double-blind, placebo-controlled trial of patients from 6 0/7-14 6/7 weeks of gestation scheduled to undergo surgical abortion at the Duke Family Planning Clinic. Participants were administered 600 mg of oral gabapentin compared with placebo with usual oral pain management. Pain score was assessed using a 100-mm visual analog scale, with the primary outcome being pain score 5 minutes after the procedure. The effect of gabapentin was assessed using a linear regression model controlling for baseline pain. We also measured pain perception 24 hours after the procedure. Secondary outcome measures included anxiety, side effects, and usage of opiate pain medication in the 24-hour postoperative period. RESULTS Out of 113 women screened for this study; 96 women were recruited, enrolled, and randomized to study treatment arm from August 2016 to June 2018. Pain at 5 minutes after the procedure was similar between the gabapentin and placebo groups (β=3.40; 95% CI -8.20 to 15.0; P=.56). Gabapentin and placebo were well tolerated, with no statistically significant difference in side effects or anxiety levels. Although prescription of opioids after the procedure was not standardized among patients, 73% of women received a short-term prescription for oxycodone. A lower percentage of women in the gabapentin group self-reported taking opioids in the 24 hours postprocedure (18% vs 47%; odds ratio 0.26; 95% CI 0.09-0.75). CONCLUSION The addition of gabapentin to usual oral pain management regimens with paracervical block did not reduce postoperative pain for patients undergoing outpatient surgical abortion. Although the addition of gabapentin was well tolerated and reduced oral opiate use 24 hours postprocedure, it did not affect the experience of pain during and immediately after the procedure. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT02725710.
Direct Cup-to-Disc Ratio Estimation for Glaucoma Screening via Semi-Supervised Learning

Glaucoma is a chronic eye disease that leads to irreversible vision loss. The Cup-to-Disc Ratio (CDR) serves as the most important indicator for glaucoma screening and plays a significant role in clinical screening and early diagnosis of glaucoma. In general, obtaining CDR is subjected to measuring on manually or automatically segmented optic disc and cup. Despite great efforts have been devoted, obtaining CDR values automatically with high accuracy and robustness is still a great challenge due to the heavy overlap between optic cup and neuroretinal rim regions. In this paper, a direct CDR estimation method is proposed based on the well-designed semi-supervised learning scheme, in which CDR estimation is formulated as a general regression problem while optic disc/cup segmentation is cancelled. The method directly regresses CDR value based on the feature representation of optic nerve head via deep learning technique while bypassing intermediate segmentation. The scheme is a two-stage cascaded approach comprised of two phases: unsupervised feature representation of fundus image with a convolutional neural networks (MFPPNet) and CDR value regression by random forest regressor. The proposed scheme is validated on the challenging glaucoma dataset Direct-CSU and public ORIGA, and the experimental results demonstrate that our method can achieve a lower average CDR error of 0.0563 and a higher correlation of around 0.726 with measurement before manual segmentation of optic disc/cup by human experts. Our estimated CDR values are also tested for glaucoma screening, which achieves the areas under curve of 0.905 on dataset of 421 fundus images. The experiments show that the proposed method is capable of state-of-the-art CDR estimation and satisfactory glaucoma screening with calculated CDR value.