Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex Differences in Renal Outcomes After Medical Treatment for Bilateral Primary Aldosteronism.

A higher incidence of bilateral primary aldosteronism in women is reported. Treatment of bilateral primary aldosteronism usually involves mineralocorticoid receptor antagonists. However, the impact of sex on renal outcomes is unknown. We compared renal outcomes between the sexes after mineralocorticoid receptor antagonist initiation by analyzing data obtained from 415 female and 313 male patients with bilateral primary aldosteronism who were treated with spironolactone or eplerenone in the JPAS (Japan Primary Aldosteronism Study). Over the course of 5 years, the temporal reduction in the estimated glomerular filtration rate was greater in women than in men (P<0.001). Systolic blood pressure levels were equal between the sexes, despite higher doses of antihypertensive drugs in men. The mean of the annual decline in estimated glomerular filtration rate during what we termed the late phase, or 6 to 60 months after mineralocorticoid receptor antagonist initiation, was larger in women than in men after adjusting for patient characteristics (-1.33 mL/min per 1.73 m2 per year versus -1.04 mL/min per 1.73 m2 per year, P<0.01). Female sex was a significant predictor of greater annual decline during the late phase in patients taking spironolactone but not in those taking eplerenone. Spironolactone use and diabetes were independent predictors of a greater annual decline in estimated glomerular filtration rate during the late phase in women. These findings suggest that female sex is associated with poorer renal outcomes in patients receiving mineralocorticoid receptor antagonist for bilateral primary aldosteronism.
Functional effects of vitamin D: From nutrient to immunomodulator

Abstract Vitamin D can be obtained from the endogenous synthesis in the epidermis by exposure to UVB light, and from foods and supplements in the form of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). The main metabolite used to measure vitamin D serum status is calcidiol [25(OH)D]. However, its active metabolite calcitriol [1α,25(OH)2D] performs pleiotropic effects in the cardiovascular, neurological, and adipose tissue as well as immune cells. Calcitriol exerts its effects through genomic mechanisms modulated by the nuclear vitamin D receptor (VDR)/retinoid X receptor (RXR) complex, to bind to vitamin D response elements (VDRE) in target genes of several cells such as activated T and B lymphocytes, neutrophils, macrophages, and dendritic cells; besides of its genomic mechanisms, VDR performs novel non-genomic mechanisms that involve its membrane expression and soluble form; highlighting that vitamin D could be an immunomodulatory nutrient that plays a key role during physiological and pathological events. Therefore, the aim of this comprehensive literature review was to describe the most relevant findings of vitamin D dietary sources, absorption, synthesis, metabolism, and factors that influence its serum status, signaling pathways, and biological effects of this immunonutrient in the health and disease.
The Role of Sociodemographic, Clinical and Neuropsychological Variables in Suicide Attempts in Depressed Adolescents.

Introduction In this study, we aimed to evaluate the relationship between sociodemographic, clinical and neuropsychological variables and suicide attempts by comparing adolescents with Major Depressive Disorder (MDD) with and without suicide attempt. Method 30 adolescents with and without suicide attempt were included in this study. Sociodemographic and Clinical Data Form, Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version (K-SADS-PL), The Children Depression Inventory (CDI), Beck Hopelessness Scale (BHS), Barratt Impulsivity Scale (BIS) and neuropsychological tests (Go/NoGo test, Stroop test Wisconsin Card Sorting Test) was applied to participants. Results Depressed adolescents with suicide attempt compared to adolescents without suicide attempt; motor and total impulsivity scores in BIS-11, commission errors in Go/NoGo test which measure motor inhibition, completion time and errors in Stroop 5 which measure interference inhibition and scores of perseveration in Winsconsin Card Sorting Test (WCST) which measure cognitive inhibition were found to be higher. Family history of suicide attempt (OR: 5.87), commission errors (OR: 1.37), perseverative errors (OR: 1.09) ve total impulsivity (OR: 1.05) were remained in the logistic regression model. Conclusion Results of this study suggested that family history of suicide attempt was the most important factor predicting suicide attempt in adolescents with depression. Other factors predicting suicide attempt were executive dysfunction and impulsivity.
To protect and modify double-stranded RNA – the critical roles of ADARs in development, immunity and oncogenesis

Abstract Adenosine deaminases that act on RNA (ADARs) are present in all animals and function to both bind double-stranded RNA (dsRNA) and catalyze the deamination of adenosine (A) to inosine (I). As inosine is a biological mimic of guanosine, deamination by ADARs changes the genetic information in the RNA sequence and is commonly referred to as RNA editing. Millions of A-to-I editing events have been reported for metazoan transcriptomes, indicating that RNA editing is a widespread mechanism used to generate molecular and phenotypic diversity. Loss of ADARs results in lethality in mice and behavioral phenotypes in worm and fly model systems. Furthermore, alterations in RNA editing occur in over 35 human pathologies, including several neurological disorders, metabolic diseases, and cancers. In this review, a basic introduction to ADAR structure and target recognition will be provided before summarizing how ADARs affect the fate of cellular RNAs and how researchers are using this knowledge to engineer ADARs for personalized medicine. In addition, we will highlight the important roles of ADARs and RNA editing in innate immunity and cancer biology. Graphical Abstract
Transcanal Endoscopic Management of Glomus Tympanicum: Multicentric Case Series

Objective: The aim of this study was to report a multicentric surgical experience in the exclusive endoscopic management of glomus tympanicum (GT). Study Design: Retrospective case series review at two institutions. Setting: Tertiary referral centers. Patients: The study included 30 patients who underwent exclusive transcanal excision of GT between 2010 and 2017 at the two referral centers. Interventions: Exclusive endoscopic transcanal excision of GT type A1, A2, and B1 (modified Fisch-Mattox classification). All surgical procedures were performed by two senior surgeons (L.P.; M.B.). Main Outcome Measures: For each procedure, intraoperative features of the disease, postoperative complications, and functional outcomes were evaluated. Recurrent or residual diseases were clinically and radiologically assessed during the follow-up period. Results: None of the patients treated with transcanal endoscopic approach (TEA) experienced intraoperative complications, nor required conversion to microscopic approach. Gross total resection (GTR) was obtained in 90% of the cases, while a near total resection was advocated when the residual pathology had a close relationship with the internal carotid artery. Mean hospitalization time was 1.6 (±0.8 SD) days and no postoperative complications were reported. No recurrences were reported in the GTR group after a mean follow-up period of 38.1 (±28.7 SD) months. Conclusions: Middle ear paragangliomas with no mastoid involvement (Class A1, A2, and B1) can be safely managed by means of a transcanal endoscopic approach. Low rate of postoperative complications, short hospitalization, and high rate of gross total resection demonstrate that TEA is a safe and effective procedure.
Utility of Basophil Activation Test in a Case of Daisaikoto- and Yokukansan-induced Lung Injury

Drug-induced lung injury is defined as a respiratory disorder. The usefulness of the basophil activation test (BAT) for drug allergy-related cases was recently reported. The patient was an 82-year-old woman who had been taking Daisaikoto and Yokukansan (herbal medicines) 3 months before developing dry cough. She was admitted to our hospital with an initial diagnosis of pneumonia with elevated serum LDH, KL-6, and IgE. Chest CT showed bilateral ground-glass opacities. Her bronchoalveolar lavage fluid showed increased eosinophils. Finally, a BAT was positive for both medications. Based on the findings, the patient was diagnosed with Daisaikoto- and Yokukansan-induced lung injury. The current case suggests that the BAT may be useful for the diagnosis of drug-induced lung injury.
Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample

Objective To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI. Methods We studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression. Results Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, β [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, −0.12 [0.05], p = 0.010; percentage, −0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts. Conclusion Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.
RPGR isoform imbalance causes ciliary defects due to exon ORF15 mutations in X-linked retinitis pigmentosa (XLRP)

Abstract Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause severe retinal ciliopathy, X-linked retinitis pigmentosa. Although two major alternatively spliced isoforms, RPGRex1-19 and RPGRORF15, are expressed, the relative importance of these isoforms in disease pathogenesis is unclear. Here, we analyzed fibroblast samples from eight patients and found that all of them form longer cilia than normal controls, albeit to different degrees. Although all mutant RPGRORF15 messenger RNAs (mRNAs) are unstable, their steady-state levels were similar or higher than those in the control cells, suggesting there may be increased transcription. Three of the fibroblasts that had higher levels of mutant RPGRORF15 mRNA also exhibited significantly higher levels of RPGRex1-19 mRNA. Four samples with unaltered RPGRex1-19 levels carried mutations in RPGRORF15 that resulted in this isoform being relatively less stable. Thus, in all cases, the RPGRex1-19/RPGRORF15 isoform ratio was increased, and this was highly correlative to the cilia extension defect. Moreover, overexpression of RPGRex1-19 (mimicking the increase in RPGRex1-19 to RPGRORF15 isoform ratio) or RPGRORF15 (mimicking reduction of the ratio) resulted in significantly longer or shorter cilia, respectively. Notably, the cilia length defect appears to be attributable to both the loss of the wild-type RPGRORF15 protein and to the higher levels of the RPGRex1-19 isoform, indicating that the observed defect is due to the altered isoform ratios. These results suggest that maintaining the optimal RPGRex1-9 to RPGRORF15 ratio is critical for cilia growth and that designing strategies that focus on the best ways to restore the RPGRex1-19/RPGRORF15 ratio may lead to better therapeutic outcomes.
Comment On "500 Minimally Invasive Robotic Pancreatoduodenectomies: One Decade of Optimizing Performance".

To the Editor: O ver the past decade, numerous studies have demonstrated that robotic pancreaticoduodenectomy (RPD) is safe and feasible for well-selected patients. However, for patients with borderline resectable tumors, received neoadjuvant therapy, or requiring a vascular resection, RPD should be carefully performed by experienced surgeons in high volume centers. We read with great interest the article by Zureikat et al, titled ‘‘500 Minimally Invasive Robotic Pancreatoduodenectomies: One Decade of Optimizing Performance. ’’ In this study, the authors conducted a retrospective review of the outcomes of the patients who underwent PRD between 2008 and 2017 at the University of Pittsburgh. Results demonstrated that RPD was safe and effective and the clinical outcomes were not adversely affected by expansion of selection criteria or integration of trainees. We commend the authors for conducting the largest analysis of RPD, which provided us with the benchmarks when adopting PRD and a structured robotics training program for wider dissemination. However, we would like to discuss certain aspects of this article. First, the study reported that 3 patients (3%) developed a CR-POPF (Grade B/C) in the last 100 RPDs. To my knowledge, it is the
The influence of nanodelivery systems on the antioxidant activity of natural bioactive compounds

Abstract Bioactive compounds may lose their antioxidant activity (e.g., phenolic compounds) at elevated temperatures, enhanced oxidative conditions and severe light exposures so they should be protected by various strategies such as nano/microencapsulation methods. Encapsulation technology has been employed as a proper method for using antioxidant ingredients and to provide easy dispersibility of antioxidants in all matrices including food and pharmaceutical products. It can improve the food fortification processes, release of antioxidant ingredients, and extending the shelf-life and bioavailability of them when ingested in the intestine. In this study, our main goal is to have an overview of the influence of nanoencapsulation on the bioactivity and bioavailability, and cellular activities of antioxidant ingredients in different delivery systems. Also, the effect of encapsulation process conditions, storage conditions, carrier wall materials, and release profile on the antioxidant activity of different natural bioactives are explained. Finally, analytical techniques for measuring antioxidant activity of nanoencapsulated ingredients will be covered.
Ketone Ester Treatment Improves Cardiac Function and Reduces Pathologic Remodeling in Preclinical Models of Heart Failure

Supplemental Digital Content is available in the text. Background: Accumulating evidence suggests that the failing heart reprograms fuel metabolism toward increased utilization of ketone bodies and that increasing cardiac ketone delivery ameliorates cardiac dysfunction. As an initial step toward development of ketone therapies, we investigated the effect of chronic oral ketone ester (KE) supplementation as a prevention or treatment strategy in rodent heart failure models. Methods: Two independent rodent heart failure models were used for the studies: transverse aortic constriction/myocardial infarction (MI) in mice and post-MI remodeling in rats. Seventy-five mice underwent a prevention treatment strategy with a KE comprised of hexanoyl-hexyl-3-hydroxybutyrate KE (KE-1) diet, and 77 rats were treated in either a prevention or treatment regimen using a commercially available β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG; KE-2) diet. Results: The KE-1 diet in mice elevated β-hydroxybutyrate levels during nocturnal feeding, whereas the KE-2 diet in rats induced ketonemia throughout a 24-hour period. The KE-1 diet preventive strategy attenuated development of left ventricular dysfunction and remodeling post-transverse aortic constriction/MI (left ventricular ejection fraction±SD, 36±8 in vehicle versus 45±11 in KE-1; P=0.016). The KE-2 diet therapeutic approach also attenuated left ventricular dysfunction and remodeling post-MI (left ventricular ejection fraction, 41±11 in MI-vehicle versus 61±7 in MI-KE-2; P<0.001). In addition, ventricular weight, cardiomyocyte cross-sectional area, and the expression of ANP (atrial natriuretic peptide) were significantly attenuated in the KE-2–treated MI group. However, treatment with KE-2 did not influence cardiac fibrosis post-MI. The myocardial expression of the ketone transporter and 2 ketolytic enzymes was significantly increased in rats fed KE-2 diet along with normalization of myocardial ATP levels to sham values. Conclusions: Chronic oral supplementation with KE was effective in both prevention and treatment of heart failure in 2 preclinical animal models. In addition, our results indicate that treatment with KE reprogrammed the expression of genes involved in ketone body utilization and normalized myocardial ATP production following MI, consistent with provision of an auxiliary fuel. These findings provide rationale for the assessment of KEs as a treatment for patients with heart failure.
A Correlative Study on Amyloid-β Variants Exhibit Different Cytotoxicities Depending on Ratio of β40 to Aβ42 and Their Interaction Time and Implication of Aβ40 as a Primary Determinant for the Variable Cytotoxicities in Wild-type, Flemish and Dutch

Formation of amyloid- () aggregates is a core process in the pathogenesis of Alzheimer's disease. Importance of interaction of the length variants, and in the process and consequent cytotoxicity has been pointed out for wild-type previously. In addition to confirming the findings, the current study demonstrates that the potential interaction is also important for cytotoxicity of the Flemish and Dutch sequence variants. The interaction could strengthen or inhibit cytotoxicity of mixture, depending on interaction time of the length variants as well as the ratio and amyloidogenic property. The inhibitory effect was prominent at the early stage of aggregate formation in less amyloidogenic Flemish mixture, while strengthened cytotoxicity was exhibited at the stage in potently amyloidogenic Dutch variant and at the later stage in wild-type and the Flemish variant. The samples showing relatively robust cytotoxicity were those enriched in protofibril-like structures, implying strong correlation of the structure with cytotoxicity. The different consequence of the interaction on sequence variants is likely due to differential amyloidogenic property of each variant, rather than that of , because aggregation rates and levels of variants are greatly variable depending on the sequence, compared to variants. These studies may highlight a potential role of in the cytotoxicity, providing a novel mechanistic insight into the pathogenesis of each FAD-associated variant.
Internalized Weight Bias, Teasing, and Self-Esteem in Children with Overweight or Obesity.

Background: Although 2/3 of US adults and nearly 1/3 of US children have overweight or obesity, weight stigma is common. Many with overweight or obesity ascribe negative ideas to themselves, resulting in internalized weight bias (IWB). In adults, IWB has been associated with psychosocial problems; however, this relationship has been studied little in children. This study aims to describe IWB in children with overweight and obesity and to study the association of children's IWB with experienced weight bias, self-esteem, and their parents' IWB. Methods: Children ages 9-18 with overweight or obesity completed the Weight Bias Internalization Scale (WBIS), Rosenberg Self-Esteem Scale, and Perception of Teasing Scale; parents completed the Weight Bias Internalization Scale-Modified and the Perceived Weight Discrimination Scale. Descriptive statistics were used to assess IWB, self-esteem, and experienced weight stigma. Chi-square and t-tests were used to examine associations between categorical and continuous variables, respectively. Multivariate linear regression was used to identify correlates of IWB in children. Results: Of 111 child participants, the median WBIS score was 2.8 out of 7. Higher IWB was associated with more peer teasing (p < 0.001) and lower self-esteem (p < 0.001). IWB in children was not associated with child BMI z-score (p = 0.590) or higher parent IWB (p = 0.287). Conclusions: Children with overweight and obesity who have experienced more teasing by peers or who have lower self-esteem are more likely to have a higher IWB. However, increasing child BMI z-score and parent IWB are not associated with higher child IWB.
Coronavirus Endoribonuclease Ensures Efficient Viral Replication and Prevents Protein Kinase R Activation

Coronaviruses can emerge from animal reservoirs into naive host species to cause pandemic respiratory and gastrointestinal diseases with significant mortality in humans and domestic animals. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal, and reproductive systems, causing millions of dollars in lost revenue worldwide annually. ABSTRACT Coronavirus (CoV) nsp15 is an endoribonuclease conserved throughout the CoV family. The enzymatic activity and crystal structure of infectious bronchitis virus (IBV) nsp15 are undefined, and the protein’s role in replication remains unclear. We verified the uridylate-specific endoribonuclease (EndoU) activity of IBV and found that the EndoU active sites were located in the C terminus of nsp15 and included His223, His238, Lys278, and Tyr334. We further constructed an infectious clone of the IBV-rSD strain (rSD-wild type [WT]) and EndoU-deficient IBVs by changing the codon for the EndoU catalytic residues to alanine. Both the rSD-WT and EndoU-deficient viruses propagated efficiently in embryonated chicken eggs. Conversely, EndoU-deficient viral propagation was severely impaired in chicken embryonic kidney cells, which was reflected in the lower viral mRNA accumulation and protein synthesis. After infecting chickens with the parental rSD-WT strain and EndoU-deficient viruses, the EndoU-deficient virus-infected chickens presented reduced mortality, tissue injury, and viral shedding. IMPORTANCE Coronaviruses can emerge from animal reservoirs into naive host species to cause pandemic respiratory and gastrointestinal diseases with significant mortality in humans and domestic animals. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal, and reproductive systems, causing millions of dollars in lost revenue worldwide annually. Mutating the viral endoribonuclease resulted in an attenuated virus and prevented protein kinase R activation. Therefore, EndoU activity is a virulence factor in IBV infections, providing an approach for generating live attenuated vaccine candidates for emerging coronaviruses.