Miracle-dz/UniFAR-FTUs huggingface dataset:
Atrial fibrillation in Brugada syndrome: Current perspectives

The incidence of atrial fibrillation (AF) in Brugada syndrome (BrS) has been reported at between 9% and 53% by different series, but the true prevalence is unknown. However, AF may be the presenting feature in some patients. The underlying mechanisms for AF may be a combination of multiple factors, genetic or acquired, that may impact upon autonomic function, atrial structure, and conduction velocities or other unknown factors. The presence of AF has been associated with a more malignant course, with a greater incidence of syncope and ventricular arrhythmias, thus acting as marker of more advanced disease. Regarding the management of patients with AF, antiarrhythmic drugs effective in preventing malignant arrhythmias in BrS such as quinidine or invasive treatment with pulmonary vein isolation (PVI) may be useful in AF treatment. In this review, we aim to present the current perspectives regarding the genetics, pathophysiology, management, and prognosis of AF in patients with BrS.
Nothing Going On? Exploring the Role of Missed Events in Changes in Subjective Well-Being and the Big Five Personality Traits.

OBJECTIVE Missed events are defined as the nonoccurrence of expected major life events within a specified time frame. We examined whether missed events should be studied in research on growth by exploring the role of missed events for changes in subjective well-being (SWB) and the Big Five personality traits. METHOD The samples were selected from two nationally representative panel studies, the German Socioeconomic Panel Innovation Sample (SOEP-IS, total N = 6,638) and the Dutch Longitudinal Internet Studies for the Social Sciences panel (LISS, Ns between 4,262 and 5,749). Rank-order stability and mean-level change were analyzed using regression and mixed models. Type I error probability was reduced by using conservative thresholds for level of significance and minimal effect size. RESULTS Expected but missed events were more frequent than actually experienced events. For SWB, rank-order stability tended to be lower among those who experienced a missed event than among those who did not. For the Big Five personality traits, significant differences between those who did and those who did not experience a missed event were rare and unsystematic. CONCLUSION Missed events merit more attention in future research on growth and personality change, but the effects are probably weak.
Emerging drugs for the treatment of vitiligo

ABSTRACT Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments. Areas covered: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localized vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy. Expert opinion: The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB.
Disentangling multiproblem behavior in male young adults: A cluster analysis

Abstract Multiproblem young adults present with major problems across key life domains, but empirical studies investigating the nature of multiproblem behavior in accordance to ecobiodevelopmental theory are scarce. To address this gap, we performed a cluster analysis on indicators spanning the key life domains addiction, mental health, social network, and justice. In a large sample (N = 680) of multiproblem young adults, we identified five subgroups labeled “severe with alcohol and cannabis problems” (4.3%), “severe with cannabis problems” (25.6%), “severe without alcohol or drug problems” (33.2%), “moderate with mental health problems” (22.9%), and “moderate without mental health problems” (14.0%). There were large differences between the severe and moderate groups in terms of childhood risk factors such as emotional and physical abuse, concerning baseline functioning such as comorbid disorders and aggressive behavior, and in the outcome measure of violent offending. Our findings indicate that multiproblem young adult behavior clusters within profiles that differ according to the severity and nature of problems. Investing in screening for clustered problems may be beneficial for early problem differentiation and selection of appropriate intervention before and during treatment programs.
Role of NPR2 mutation in idiopathic short stature: Identification of two novel mutations

C‐type natriuretic peptide (CNP, NPPC) and its receptor, natriuretic peptide receptor‐B (NPR‐B, NPR2), are critical for endochondral ossification. A monoallelic NPR2 mutation has been suggested to mildly impair long bone growth. This study was performed to identify the NPR2 mutations in Korean patients with idiopathic short stature (ISS).
Advanced Breast Cancer: A Guide to Living with Metastatic Disease

Although breast cancer has become a topic widely covered in the media, the message is almost always cheerful, emphasizing early detection and the high likelihood of "cure. " The reality of metastatic breast cancer is almost never publicly talked about, and considered “too downbeat” by mass media to attract an audience. In this chapter the social context of the disease will be examined, and the ways in which the “politics” of breast cancer isolates people dealing with metastatic and high-risk breast cancer. Psychological and social factors both play a part in the denial and fear surrounding metastatic disease. Even in the breast cancer community of advocacy and support, there is often a sense of division between those diagnosed with primary disease and those whose disease has recurred. These larger issues—fear, discomfort, isolation, discrimination—create a climate of silence that prevents the real stories of people living with metastatic disease from being told. As the stories in this book unfold, patients and their spouses and partners break this silence, speaking in depth about their lives, their families, their feelings, their hopes and their fears.
Glucocorticoids in rheumatoid arthritis: current status and future studies

Since their first use for treating rheumatoid arthritis (RA) in the late 1940s, glucocorticoids (GCs) have been representing a substantial part of the therapeutic arsenal for RA. However, even if GCs are still widely prescribed drugs, their toxicity is discussed controversially, so obtaining consensus on their use in RA is difficult. Hence, the most recent European League Against Rheumatism and American College of Rheumatology recommendations on early arthritis and RA management advocate the use of GCs as adjunct treatment to conventional synthetic disease-modifying antirheumatic drugs, at the lowest dose possible and for the shortest time possible. However, the recommendations remain relatively vague on dose regimens and routes of administration. Here, we describe literature data on which the current recommendations are based as well as data from recent trials published since the drafting of the guidelines. Moreover, we make proposals for daily practice and provide suggestions for studies that could help clarifying the place of GCs in RA management. Indeed, numerous items, including the benefit/risk ratio of low-dose and very low-dose GCs and optimal duration of GCs as bridging therapy, remain on the research agenda, and future studies are needed to guide the next recommendations for RA.
Multimodality Cardiac Imaging in the Era of Emerging Cancer Therapies

R ecently, the field of oncology has witnessed a surge of new therapeutic agents that have collectively led to improved rates of progression-free and overall survival for many cancers. However, these advances have also led to increased morbidity attributable to treatment-related side effects, in particular, cardiac toxicities. Cancer therapeutics may negatively affect the heart in a host of ways, whether it is through direct tissue damage or indirectly by exacerbating cardiovascular risk factors. Given that cardiovascular disease is the most common cause of death among cancer survivors, increased recognition and understanding of these cardiovascular toxicities is paramount to successful management of this ever increasing survivorship population. Cardiac imaging has been essential to elucidating mechanisms for a growing number of cardiotoxicities, and its role in toxicity surveillance and management continues to evolve. Approaching this review from the perspective of treatmentrelated cardiovascular toxicities, we examine evolving applications of imaging in contemporary cardio-oncology with specific focus on the more novel and emerging anticancer therapies. In doing so, we will examine broad categories of cancer therapeutics, highlight specific agents that have been implicated in cardiotoxicity, and discuss optimal cardiac imagingmodalities for each class. We will also consider amyloidosis, in light of recent interest. Guideline-driven recommendations and position paper statements pertaining to cardiac imaging will be highlighted wherever possible. We recognize that cardiac imaging position statements are largely unavailable for certain drug categories, particularly for more novel agents. In these instances, primary literature and specific clinical cases pertaining to cardiac imaging applications for each cardiotoxicity will be reviewed. Prominent cardiotoxicities as related to cancer therapies are detailed below:
Sequential and spatial letter reversals in adults with dyslexia during a word comparison task: demystifying the “was saw” and “db” myths

ABSTRACT Whether sequential and spatial letter reversals characterize dyslexia in children has been unclear, largely due to developmental variability of these errors in children with and without dyslexia. Here we demonstrate both types of reversals for the first time in adults with dyslexia (n = 22) but not in control adults (n = 20). Participants evaluated 576 word pairs that consisted of two identical words or two words that differed subtly, by categorizing them as same or different. Two subsets of word pairs differed in sequential (e.g. “two tow”) and spatial (e.g. “cob cod”) letter reversals. The adults with dyslexia were less accurate than the controls regarding both types of word pairs. Their accuracy during left/right letter reversals was lower, compared to both up/down letter reversals (e.g. “cub cup”) and nonsymmetric letter similarities (e.g. “half halt”). Accuracy during left/right reversals was correlated with accuracy during sequential rearrangement in the word pair task as well as with a composite measure of sequential processing based on nonword repetition, nonword reading, and multisyllabic word repetition. It was also correlated with a composite measure of literacy skills. A subset of the dyslexia group who produced left/right errors during a rapid single letter naming task obtained lower accuracy than the dyslexia subgroup without such errors during both types of letter reversals, and their overall literacy skills were lower. We conclude that sequential and left/right letter reversals characterize a severe dyslexia subtype. These two types of reversal are associated, are part of a general deficit in sequential processing likely due to cerebellar deficits, and persist into adulthood.
Impact of Right Ventricular Systolic Dysfunction on Outcome in Aortic Stenosis

Supplemental Digital Content is available in the text. Background: Pulmonary hypertension is an established outcome predictor in patients with aortic stenosis (AS), but the prognostic impact of right ventricular dysfunction has not been well studied. Methods: We included 2181 patients (50.4% men; mean age, 77 years) with aortic valve area <1.3 cm2 and analyzed the occurrence of all-cause death during follow-up according to tricuspid annular plane systolic excursion (TAPSE) quartiles. Results: Patients in the lowest quartile (TAPSE <17 mm) were at a high risk of death, whereas survival was comparable for the 3 other quartiles. Five-year survival was 55±2% for TAPSE <17 mm, 72±2% for TAPSE of 17 to 20 mm, 71±2% for TAPSE of 20 to 24 mm, and 73±2% for TAPSE >24 mm (overall P<0.001). TAPSE <17 mm was associated with increased mortality after adjustment for established prognostic factors (adjusted hazard ratio [HR], 1.55 [95% CI, 1.21–1.97]) and after further adjustment for aortic valve replacement (AVR; adjusted HR, 1.47 [95% CI, 1.15–1.87]). The excess mortality risk associated with TAPSE <17 mm was noticed in both patients managed initially conservatively (adjusted HR, 1.46 [95% CI, 1.20–1.76]) and patients who underwent early (within 3 months after diagnosis) AVR (adjusted HR, 1.61 [95% CI, 1.03–2.52]). In asymptomatic patients with severe AS and preserved ejection fraction, TAPSE <17 mm was independently predictive of mortality (adjusted HR, 2.14 [95% CI, 1.31–3.51]). Early AVR was associated with similar survival benefit in TAPSE <17 and ≥17 mm (adjusted HR, 0.23 [95% CI, 0.16–0.34] for TAPSE <17 mm, adjusted HR, 0.26 [95% CI, 0.19–0.35] for TAPSE ≥17 mm; P for interaction, 0.97). Conclusions: Right ventricular dysfunction is an important and independent predictor of mortality in AS. TAPSE <17 mm at the time of AS diagnosis is a marker of poor survival under conservative management and after AVR even in asymptomatic patients with severe AS. AVR was associated with a pronounced reduction in mortality independent of TAPSE suggesting that AVR should be discussed before right ventricular dysfunction occurs in severe AS.
A comprehensive evaluation of apixaban in the treatment of venous thromboembolism

ABSTRACT Introduction: The emergence of the direct oral anticoagulants (DOACs) offers patients more convenient and accessible alternatives to warfarin or parenteral agents for the treatment of venous thromboembolism (VTE). Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is approved for the acute treatment of deep-vein thrombosis (DVT) and pulmonary embolism (PE) as well as for the reduction in the risk of recurrent DVT and PE following initial therapy. Areas covered: This article reviews results from preclinical and healthy volunteer studies, large phase III trials evaluating the safety and efficacy of apixaban, as well as key studies that led to apixaban’s current licensing. This review also will provide an overview of special populations where future areas of research are needed. Expert commentary: Apixaban offers several advantages over historical therapy for the treatment and secondary prevention of VTE. However, there are some populations in which the use of apixaban has not been extensively studied such as patients >75 years old, or those with cancer, low or high body weight, or poor renal function. Likewise, there is a dearth of data on pediatric patients and patients with a history of heparin-induced thrombocytopenia or identified forms of thrombophilia. Additional comparator studies on anticoagulation reversal involving andexanet alfa are also necessary to further assess its hemostatic efficacy and prothrombotic risk.
Multiple axes of ecological vulnerability to climate change

Observed ecological responses to climate change are highly individualistic across species and locations, and understanding the drivers of this variability is essential for management and conservation efforts. While it is clear that differences in exposure, sensitivity, and adaptive capacity all contribute to heterogeneity in climate change vulnerability, predicting these features at macroecological scales remains a critical challenge. We explore multiple drivers of heterogeneous vulnerability across the distributions of 96 vegetation types of the ecologically diverse western US, using data on observed climate trends from 1948 to 2014 to highlight emerging patterns of change. We ask three novel questions about factors potentially shaping vulnerability across the region: (a) How does sensitivity to different climate variables vary geographically and across vegetation classes? (b) How do multivariate climate exposure patterns interact with these sensitivities to shape vulnerability patterns? (c) How different are these vulnerability patterns according to three widely implemented vulnerability paradigms—niche novelty (decline in modeled suitability), temporal novelty (standardized anomaly), and spatial novelty (inbound climate velocity)—each of which uses a distinct frame of reference to quantify climate departure? We propose that considering these three novelty paradigms in combination could help improve our understanding and prediction of heterogeneous climate change responses, and we discuss the distinct climate adaptation strategies connected with different combinations of high and low novelty across the three metrics. Our results reveal a diverse mosaic of climate change vulnerability signatures across the region's plant communities. Each of the above factors contributes strongly to this heterogeneity: climate variable sensitivity exhibits clear patterns across vegetation types, multivariate climate change data reveal highly diverse exposure signatures across locations, and the three novelty paradigms diverge widely in their climate change vulnerability predictions. Together, these results shed light on potential drivers of individualistic climate change responses and may help to inform effective management strategies.
The Incredible Years Autism Spectrum and Language Delays Parent Program: A Pragmatic, Feasibility Randomized Controlled Trial

Behavior problems in children with autism spectrum disorders (ASD) are common and particularly stressful for parents. This study aimed to examine the feasibility of delivering a parenting program in existing services, and the feasibility of conducting a future large‐scale Randomized Controlled Trial evaluation of the effectiveness of the intervention. Parents of children aged 3–8 years with a diagnosis of ASD, or strongly suspected ASD were eligible to participate. A multicenter, pragmatic, feasibility randomized controlled trial was conducted in four specialist children's services in Wales. Families were randomly assigned to receive the Incredible Years® Autism Spectrum and Language Delays (IY‐ASLD) parent program immediately or to a wait‐list, treatment as usual control condition. IY‐ASLD sessions were delivered once a week for 12 weeks. The primary outcomes related to feasibility (recruitment, retention, fidelity, and acceptability). Preliminary outcome analyses were conducted using covariance models controlling for study site and baseline scores. From October 5 to December 19, 2016, 58 families were randomized, 29 to IY‐ASLD and 29 to control. Three parents did not attend any sessions while 19 (73%) completed the program. Fidelity of delivery was high (88%), as was satisfaction with the program. Fifty‐three (91%) completed the follow‐up measures. All 95% CIs for effect sizes included zero in exploratory outcome analyses. This study supports the feasibility of delivering the IY‐ASLD in existing services with good levels of acceptability and fidelity evident. A larger randomized controlled trial is required to examine the effectiveness of the program. Autism Res 2020, 13: 1011‐1022. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.
Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in the early stages of hypoxia, we established a cell hypoxia–reoxygenation model and orthotopic left lung ischemia–reperfusion model. Rat alveolar epithelial cells stably expressing GFP‐LC3 were treated with an autophagy inhibitor (3‐MA) or an autophagy promoter (rapamycin), followed by hypoxia–reoxygenation treatment for 2, 4, and 6 hr in vitro. In vivo, 20 male Sprague Dawley rats were randomly divided into four groups (model group: No blocking of the hilum in the left lung; control group: Blocking of the hilum in the left lung for 1 hr with dimethyl sulfoxide lavage; 3‐MA group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of 3‐MA (5 μmol/L) solution lavage; and rapamycin group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of rapamycin (250 nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the nuclear factor kappa B signaling pathway and limited the expression of proinflammatory factors. A contrary result was found after the 3‐MA pretreatment. These findings indicate that autophagy reduces ischemia–reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia–reperfusion injury.
Identification of a minimal region of loss on chromosome 6q27 associated with poor survival of high-risk neuroblastoma patients

ABSTRACT Patients with high-risk neuroblastoma (HR-NB) often initially respond to therapy, but afterward they become resistant and disease recurred. Unfortunately, it does not exist one or more specific chromosome defects associated with relapse or refractory NB. Recently, genomic evidence from primary tumors indicated that the distal region of chromosome 6q is loss in HR-NB patients with fatal outcome. We identified a minimal common region of loss of chromosome 6q27 spanning an area of 2.09 Mb by high-resolution DNA copy number data of a small cohort of HR-NB samples carrying 6q loss. This region of loss harbored five genes T, SFT2D1, RPS6KA2, FGFR1OP, and UNC93A. We found that low SFT2D1, RPS6KA2, and FGFR1OP gene expression predicted poor outcome in HR-NB patients using public R2 Platform. Further functional studies will be essential to confirm the presumed tumor suppressor gene(s) located within 6q27 region. These results suggest that SFT2D1, RPS6KA2, and FGFR1OP genes may be responsible for poor prognosis of HR-NB tumors with 6q27 loss, and their haploinsufficiency may be crucial in accelerating tumor progression.