Miracle-dz/UniFAR-FTUs huggingface dataset:
Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985–2014

Objectives To examine trends in the incidence of rheumatoid arthritis (RA) from 2005 to 2014 overall and by serological status as compared with 1995–2004 and 1985–1994. Methods We evaluated RA incidence trends in a population-based inception cohort of individuals aged ≥18 years who first fulfilled the 1987 American College of Rheumatology (ACR) criteria for RA between 1 January 1985 and 31 December 2014. Incidence rates were estimated and were age-adjusted and sex-adjusted to the white population in the USA in 2010. Trends in incidence were examined using Poisson regression methods. Results The 2005–2014 incidence cohort comprised 427 patients: mean age 55.4 years, 68% female, 51% rheumatoid factor (RF) positive and 50% anti-cyclic citrullinated peptide antibody positive. The overall age-adjusted and sex-adjusted annual RA incidence in 2005–2014 was 41/100 000 population (age-adjusted incidence: 53/100 000 in women and 29/100 000 in men). While these estimates were similar to the 1995–2004 decade, there was a decline in the incidence of RF-positive RA in 2005–2014 compared with the previous two decades (p=0.004), with a corresponding increase in RF-negative cases (p<0.001). Smoking rates declined and obesity rates increased from earlier decades to more recent years. Conclusions Significant increase in incidence of RF-negative RA and decrease in RF-positive RA in 2005–2014 compared with previous decades was found using 1987 ACR criteria. The incidence of RA overall during this period remained similar to the previous decade. The changing prevalence of environmental factors, such as smoking, obesity and others, may have contributed to these trends. Whether these trends represent a changing serological profile of RA requires further investigation.
In the wall lies the truth: a systematic review of diagnostic markers in intracranial aneurysms

Objective: Despite recent advances in molecular biology and genetics, the development of intracranial aneurysms (IA) is still poorly understood. Elucidation of the processes occurring in the IA wall is essential for a better understanding of IA pathophysiology. We sought to analyze the current evidence from histological, molecular and genetic studies of IA. Methods: We systematically searched PubMed, Scopus, Web of Science and Cochrane Library for articles published before Mar 1, 2019 reporting on different diagnostic markers in human IA specimens. Expression of the markers in IA wall (vs. healthy arterial wall) and association with the rupture status were analyzed. The quality of the included studies and the level of the evidence for the markers were incorporated into the final data assessment. Results: We included 123 studies reporting on analyses of 3476 IA (median 19 IA/study) published between 1966 and 2018. Based on microscopic, biochemical, genetic and biomechanical analyses, data on 358 diagnostic targets in the IA wall were collected. We developed a scale to distribute the diagnostic markers according to their specificity for IA or healthy arterial wall, as well as for ruptured or unruptured IA. We identified different functional pathways, which might reflect the intrinsic and extrinsic processes underlying IA pathophysiology. Conclusions: Multiple histological and molecular markers and the related functional pathways contributing to the development of IA might present promising targets for future therapeutic interventions. Because of small numbers of IA samples in each study, 89% of the analyzed diagnostic markers presented with the lowest level of evidence. This underlines the need for the initiation of a multi‐centric prospective histological IA register for pooled data analysis.
GRASP55: A Multifunctional Protein.

GRASP55 was first found as a Golgi cisternae stacking protein. Due to the crucial role of Golgi in vesicular trafficking and protein modification, GRASP55 was found to function in these two aspects. Further investigation showed that GRASP55 also participates in unconventional secretory pathway under stress. Far more than that, GRASP55 is involved in autophagy initiation and autophagosome maturation, as well as cell activity.
The association between perceived social and physical environment and mental health among older adults: mediating effects of loneliness

Abstract Objectives: Despite growing interest in the impact of physical and social environment on mental health, data are lacking on the potential mediating effects of loneliness. We examined it in the association of several social and physical environmental characteristics with mental health among older adults in three municipalities in Flanders (Belgium). Methods: A total of 869 people aged 60 and over were interviewed. Loneliness was assessed through the De Jong Gierveld short scales for emotional and social loneliness. Social participation and social cohesion were assessed following the Neighborhood scales whereas physical environment characteristics were selected from the Neighborhood Environment Walkability Scale. Mental health was assessed through subscale psychological frailty of the Comprehensive Frailty Assessment Instrument plus (CFAI-plus). Linear regression models, including mediation analysis, were used to analyze the survey data. Results: After adjusting for individual characteristics, physical and social environment factors were significantly related to mental health with the significant mediation of emotional and social loneliness. Percentages mediated by both dimensions together were 61% for social cohesion, 43% for social participation, 35% for safety and 25% for mobility. Compared with social loneliness, emotional loneliness was a stronger mediating factor, particularly for mobility and safety. No significant associations between traffic density or basic service availability and mental health were found. Discussion: Improving the social and physical environment might result in a reduction in the prevalence of loneliness and in consequent improvement of mental health among older adults. Special attention should be paid to different types of loneliness.
Multidimensional Voice Quality Evaluation After Transoral CO2 Laser Cordectomy: A Prospective Study

Objective: To investigate voice quality changes of patients treated by transoral laser cordectomy (TLC) for early glottic cancer according to the type of cordectomies. Methods: A total of 164 consecutive male patients with an early glottic cancer were prospectively recruited from the Department of Otolaryngology—Head and Neck Surgery of the Georges Pompidou European Hospital. Depending on the tumor characteristics, patients benefited from type I to VI CO2 cordectomy regarding the European Laryngological Society classification. The following voice quality outcomes were pre- to postoperatively assessed: voice handicap index (VHI), perceptual grade of dysphonia, roughness, breathiness, maximum phonation time, and acoustic parameters. Results: Fifty-five patients with Tis, T1, or T2 vocal fold cancer completed the study (mean age: 61.7 years). Of these patients, 34 and 21 composed group 1 (types I-III TLC) and group 2 (types IV-VI TLC), respectively. Voice handicap index, grade of dysphonia, and breathiness significantly improved from pre- to 3- and 6-month posttreatment in group 1. In group 2, only VHI significantly improved from pre- to 3- and 6-month posttreatment. Acoustic and aerodynamic measurements did not change throughout the postoperative course. Patients with types I to III TLC exhibited better postoperative voice outcomes compared to those treated by types IV to VI TLC. Conclusion: Irrespective to the types of TLC, the subjective voice quality of patients treated by CO2 laser cordectomy for early glottic cancer significantly improved from pre- to 3- and 6-month posttreatment. The usefulness of aerodynamic and acoustic measurements as postoperative outcomes of voice quality changes remain controversial and require future studies considering multidimensional assessment of voice.
Changes to Ventilation, Vocalization, and Thermal Nociception in the Pink1-/- Rat Model of Parkinson's Disease.

BACKGROUND Individuals with Parkinson's disease (PD) experience significant vocal communication deficits. Findings in the Pink1-/- rat model of early-onset PD suggest that ultrasonic vocal communication is impaired early, progressively worsens prior to nigrostriatal dopamine depletion, and is associated with loss of locus coeruleus neurons, brainstem α-synuclein, and larynx pathology. Individuals with PD also demonstrate ventilatory deficits and altered sensory processing, which may contribute to vocal deficits. OBJECTIVE The central hypothesis is that ventilatory and sensory deficits are present in the early disease stages when limb and vocal motor deficits also present. METHODS Pink1-/- rats were compared to wildtype (WT) controls at longitudinal timepoints. Whole-body flow through plethysmography, was used to measure ventilation in the following conditions: baseline, hypoxia, and maximal chemoreceptor stimulation. Plantar thermal nociception, and as a follow up to previous work, limb gait and vocalization were analyzed. Serotonin density (5-HT) in the dorsal raphe was quantified post-mortem. RESULTS Baseline breathing frequencies were consistently higher in Pink1-/- rats at all time points. In hypoxic conditions, there were no significant changes between genotypes. With hypercapnia, Pink1-/- rats had decreased breathing frequencies with age. Thermal withdrawal latencies were significantly faster in Pink1-/- compared with WT rats across time. No differences in 5-HT were found between genotypes. Vocal peak frequency was negatively correlated to tidal volume and minute ventilation in Pink1-/- rats. CONCLUSION This work suggests that abnormal nociceptive responses in Pink1-/- rats and ventilatory abnormalities may be associated with abnormal sensorimotor processing to chemosensory stimuli during disease manifestation.
Cerebrospinal Fluid Characterization in Cynomolgus Monkeys, Beagle Dogs, and Göttingen Minipigs

Intrathecal administration is an important route for drug delivery, and in pharmacology and toxicology studies, cerebrospinal fluid (CSF) collection and analysis is required for evaluating blood–brain barrier penetration and central nervous system exposure. The characteristics of CSF in commonly used nonrodent models are lacking. The purpose of this study is to evaluate and provide some insights into normal cellular and biochemical composition of CSF as well as diffusion potential following intrathecal injection across several nonrodent species. Cerebrospinal fluid samples were collected from the cerebellomedullary cistern of beagle dogs, cynomolgus monkeys, and Göttingen minipigs and analyzed for clinical chemistry and cytological evaluation. Diffusion into the intrathecal space following intrathecal injection was assessed following administration of a contrast agent using fluoroscopy. The predominant cell types identified in CSF samples were lymphocytes and monocytoid cells; however, lymphocytes were represented in a higher percentage in dogs and monkeys as opposed to monocytoid cells in minipigs. Clinical chemistry parameters in CSF revealed higher Cl− concentrations than plasma, but lower K+, Ca2+, phosphorus, glucose, creatinine, and total protein levels consistent across all 3 species. Diffusion rates following intrathecal injection of iodixanol showed some variability with dogs, showing the greatest diffusion distance; however, the longest diffusion time through the intervertebral space, followed by monkeys and minipigs. Minimal diffusion was observed in minipigs, which could have been attributed to anatomical spinal constraints that have been previously identified in this species.
The role of food parcel use on dietary intake: perception of Dutch food bank recipients - a focus group study

Abstract Objective: To gain insight in Dutch food bank recipients’ perception on the content of the food parcels, their dietary intake and how the parcels contribute to their overall dietary intake. Design: Eleven semi-structured focus group discussions were conducted. Focus group topics were based on Andersons food insecurity definition: the lack of availability of nutritionally adequate foods and the assured ability to acquire foods in socially acceptable ways. Data were coded and analysed with Atlas.ti 7.0 software, using the framework approach. Setting: Seven food banks throughout the Netherlands. Participants: A total of 44 Dutch food bank recipients. Results: Food bank recipients were not always satisfied with the amount, quality, variation and type of foods in the food parcel. For the participants who could afford to, supplementing the food parcel was reported as main reason for buying foods, and price was the most important aspect in selecting these foods. Participants were not satisfied with their dietary intake; they mainly reported not having enough to eat. The content of the food parcel importantly influenced participants’ overall dietary intake. Finally, participants reported struggling with their feelings of dissatisfaction, while also being grateful for the foods they receive. Conclusions: This study suggests that, despite their best efforts, food banks are not meeting food bank recipients’ needs. Our results provide valuable directions for improving the content of the food parcels by increasing the quantity, quality and variation in the foods supplied. Whether this also improves the dietary intake of recipients needs to be determined.
FCX‐146, a potent allosteric inhibitor of Akt kinase in cancer cells: Lead optimization of the second‐generation arylidene indanone scaffold

Akt, a serine‐threonine protein kinase, is regulated by class‐I PI3K signaling. Akt regulates a wide variety of cell processes including cell proliferation, survival, and angiogenesis through serine/threonine phosphorylation of downstream targets including mTOR and glycogen‐synthase‐kinase‐3‐beta (GSK3β). Targeting cancer‐specific overexpression of Akt protein could be an efficient way to control cancer‐cell proliferation. However, the ATP‐competitive inhibitors are challenged by the highly conserved ATP binding site, and by competition with high cellular concentrations of ATP. We previously developed an allosteric inhibitor, 2‐arylidene‐4, 7‐dimethyl indan‐1‐one (FXY‐1) that showed promising activity against several lung cancer models. In this work, we designed a congeneric series of molecules based on FXY‐1 and optimized lead based on computational, in vitro assays. Computational screening followed by enzyme‐inhibition and cell‐proliferation assays identified a derivative (FCX‐146) as a new lead molecule with threefold greater potency than the parent compound. FCX‐146 increased apoptosis in HL‐60 cells, mediated in part through decreased expression of antiapoptotic Bcl‐2 protein and increased levels of Bax‐2 and Caspase‐3. Molecular‐dynamic simulations showed stable binding of FCX‐146 to an allosteric (i.e., noncatalytic) pocket in Akt. Together, we propose FCX‐146 as a potent second‐generation arylidene indanone compound that binds to the allosteric pocket of Akt and potently inhibits its activation.
Randomized Controlled Trial of a Multilevel Intervention to Address Social Determinants of Refugee Mental Health.

Understanding processes that support the well-being of the unprecedented numbers of forcibly displaced people throughout the world is essential. Growing evidence documents post-migration stressors related to marginalization as key social determinants of refugee mental health. The goal of this RCT was to rigorously test a social justice approach to reducing high rates of distress among refugees in the United States. The 6-month multilevel, strengths-based Refugee Well-being Project (RWP) intervention brought together university students enrolled in a 2-semester course and recently resettled refugees to engage in mutual learning and collaborative efforts to mobilize community resources and improve community and systems responsiveness to refugees. Data collected from 290 Afghan, Great Lakes African, Iraqi, and Syrian refugees at four time points over 12 months were used to test the effectiveness of RWP to reduce distress (depression and anxiety symptoms) and increase protective factors (English proficiency, social support, connection to home and American cultures). Intention-to-treat analyses using multilevel modeling revealed significant intervention effects for all hypothesized outcomes. Results provide evidence to support social justice approaches to improving refugee mental health. Findings have implications for refugees worldwide, and for other immigrant and marginalized populations who experience inequities in resources and disproportionate exposure to trauma/stress.
Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production

Abstract Context The chronic exposure to Cadmium (Cd) constitute an risk to develop hypertension and cardiovascular diseases associated with the increase of oxidative stress. Objective In this study, we investigate the role of metabolic changes produced by exposure to Cd on the endothelial dysfunction via oxidative stress. Methods Male Wistar rats were exposed to Cd (32.5-ppm) for 2-months. The zoometry and blood pressure were evaluated, also glucose and lipids profiles in serum and vascular reactivity evaluated in isolated aorta rings. Results Rats exposed to Cd showed an increase of blood pressure and biochemical parameters similar to metabolic syndrome. Additionally, rats exposed to Cd showed a reduced relaxation in aortic rings, which was reversed after the addition of SOD and apocynin an inhibitor of NADPH. Conclusion The Cd-exposition induced hypertension and endothelial injury by that modifying the vascular relaxation and develop oxidative stress via NADPH oxidase, superoxide and loss nitric oxide bioavailability.
A Web-based Therapeutic Patient Education Intervention for Pain and Sleep for Women with Fibromyalgia: A Sequential Exploratory Mixed Methods Research Protocol.

AIMS To evaluate cognitive and behavioral factors related to pain and poor sleep quality in women diagnosed with fibromyalgia and to develop and test the effects of a web-based therapeutic education intervention on pain intensity, pain catastrophizing, chronic pain self-efficacy, sleep quality, dysfunctional beliefs and attitudes about sleep and quality of life and health status related to fibromyalgia. DESIGN The project will employ a sequential exploratory mixed methods research design. METHODS For the qualitative phase, a theoretical sample living in the community will be recruited to participate in personal, semi-structured interviews. For the quantitative phase, a sample of adult women with fibromyalgia will be recruited from secondary care centers and randomly allocated an intervention or a control group. The study protocol was approved in 2019. DISCUSSION Fibromyalgia is the most common central sensitivity syndrome and one of the principal worldwide causes of chronic widespread pain among the adult population. Poor sleep quality is a highly prevalent and troublesome symptom for patients with fibromyalgia. Psychosocial and behavioral factors have been shown to relate intimately with the symptom experiences of patients with fibromyalgia; pain catastrophizing and dysfunctional beliefs and attitudes about sleep can perpetuate those and other fibromyalgia symptoms. CONCLUSION It is imperative to reflect patients' actual symptom experiences to develop effective symptom management strategies. In the Internet era, this project's proposed web-based therapeutic education intervention could offer women with fibromyalgia a new avenue for treatment as part of standard fibromyalgia management programs in primary and secondary healthcare services. IMPACT Pain and poor sleep quality are highly prevalent and troublesome symptoms for patients with fibromyalgia. The web-based therapeutic education intervention proposed by this project could provide women with fibromyalgia a new avenue for treatment in primary and secondary healthcare services.
Repeated afternoon sleep recordings indicate first‐night‐effect‐like adaptation process in family dogs

The importance of dogs (Canis familiaris) in sleep research is primarily based on their comparability with humans. In spite of numerous differences, dogs' comparable sleep pattern, as well as several phenotypic similarities on both the behavioural and neural levels, make this species a most feasible model in many respects. Our aim was to investigate whether the so‐called first‐night effect, which in humans manifests as a marked macrostructure difference between the first and second sleep occasions, can be observed in family dogs. We used a non‐invasive polysomnographic method to monitor and compare the characteristics of dogs' (N = 24) 3‐hr‐long afternoon naps on three occasions at the same location. We analysed how sleep macrostructure variables differed between the first, second and third occasions, considering also the effects of potential confounding variables such as the dogs' age and sleeping habits. Our findings indicate that first‐night effect is present in dogs' sleep architecture, although its specifics somewhat deviate from the pattern observed in humans. Sleep macrostructure differences were mostly found between occasions 1 and 3; dogs slept more, had less wake after the first drowsiness episode, and reached drowsiness sleep earlier on occasion 3. Dogs, which had been reported to sleep rarely not at home, had an earlier non‐rapid eye movement sleep, a shorter rapid eye movement sleep latency, and spent more time in rapid eye movement sleep on occasion 3, compared with occasion 1. Extending prior dog sleep data, these results help increase the validity of further sleep electroencephalography investigations in dogs.
Effects of MIneralocorticoid and AT1 Receptor Antagonism on The Aldosterone-Renin Ratio (ARR) In Primary Aldosteronism-EMIRA Study.

CONTEXT The withdrawal of mineralocorticoid-receptor antagonist (MRA) and renin-angiotensin system blockers recommended in current guidelines for case detection of primary aldosteronism (PA) can worsen hypokalemia and control of high blood pressure (BP) values. OBJECTIVE To investigate if aldosterone/renin ratio (ARR) values were affected by the MRA canrenone and/or by canrenone plus olmesartan treatment in patients with PA. DESIGN Within-patient study. SETTING The European Society of Hypertension center of excellence at the University of Padua. PATIENTS Consecutive patients with an unambiguous diagnosis of PA subtyped by adrenal vein sampling (AVS). INTERVENTIONS Patients were treated for one-month treatment with canrenone (50-100 mg orally), and a further month with canrenone plus olmesartan (10-20 mg orally). Canrenone and olmesartan were up-titrated over the first two weeks until BP values and hypokalemia were controlled. Patients with unilateral PA were adrenalectomized; those with bilateral PA were treated medically. MAIN OUTCOME MEASURES BP, plasma levels of sodium and potassium, renin, and aldosterone. RESULTS Canrenone neither lowered plasma aldosterone nor did raise renin, thus leaving the high ARR and true positive rate unaffected. Addition of the angiotensin type 1 receptor blocker raised renin and slightly lowered aldosterone, thus reducing the ARR and increasing the false negative rate. CONCLUSIONS At doses that effectively controlled serum potassium and BP values, canrenone did not preclude an accurate diagnosis in patients with PA. Addition of the angiotensin type 1 receptor blocker olmesartan slightly raised the false negative rate. Hence, MRA did not seem to endanger the accuracy of the diagnosis of PA.