Miracle-dz/UniFAR-FTUs huggingface dataset:
What constitutes the fat signal detected by MRI in the spine of patients with ankylosing spondylitis? A prospective study based on biopsies obtained during planned spinal osteotomy to correct hyperkyphosis or spinal stenosis

Objective Study the MRI signal of fatty lesions (FL) by immunohistological analysis of vertebral body biopsies of patients with ankylosing spondylitis (AS) compared with degenerative disc disease (DDD). Methods Biopsies obtained during planned surgery from vertebral edges where MRI signals of FL was detected were stained with H&E. Immunofluorescence (IF) staining was performed to quantify osteoblasts and osteoclasts. Bone marrow (BM) composition, grade of cellularity and quantification of cells were analysed on six randomly chosen high-power fields (HPF; 0.125 mm2) at 200-fold magnification per patient by two experienced researchers in a blinded manner. Results Biopsies of 21 patients with AS and 18 with DDD were analysed. Adipocytes were found in the BM of 19 patients with AS (90.5%) versus 5 with DDD (27.8%) (p<0.001), while inflammatory infiltrates were found in in the BM of 8 patients with AS (38.1%) versus 14 with DDD (77.8%) (p=0.035) and fibrosis in 6 patients with AS (28.6%) versus 4 with DDD (22.2%) (p=n .s.). The most frequently detected cells were adipocytes in AS (43.3%) versus DDD (16.1%, p=0.002) and inflammatory mononuclear cells in DDD (55%) versus AS (11.0%, p=0.001). Using IF staining, there was more osteoblastic than osteoclastic activity (6.9 vs 0.17 cells/HPF) in FL as compared with inflammatory BM (1.3 vs 7.4 cells/HPF), respectively. Conclusion MRI FL correspond to presence of adipocytes, resulting to change of cellular homeostasis towards diminution of osteoclasts in the BM of patients with AS. The cross-talk between the different cell types and osteitis, fat and new bone formation needs further study.
Pharmacogenetics of anticoagulants used for stroke prevention in patients with atrial fibrillation

ABSTRACT Introduction: The inclusion of pharmacogenetics alongside clinical information in anticoagulant therapy offers the opportunity for a tailored approach to treatment according to individual patient characteristics. Areas covered: Literature was searched using PubMed database, focusing on pharmacogenetics of oral anticoagulants. Original research articles and review articles in English language were included in the literature reviewed. This article includes all information available for the genetic cause of inter-individual variability in anticoagulation response to oral anticoagulant drugs. The pharmacogenetics of VKAs and NOACs are described in detail. Expert opinion: There have been numerous studies focusing on the pharmacogenetics of VKAs, particularly warfarin. Current evidence suggests that known genetic and clinical factors explain a large proportion of the inter-individual variability in response to warfarin. Pharmacogenetic-based algorithms have been validated to determine their clinical utility with equivocal results. To date, only a limited number of mostly small studies on the pharmacogenetics of NOACs exists. The latter have highlighted genetic polymorphisms in specific genes that may affect clinical outcomes. Further evaluations of these polymorphisms are needed before firm conclusions can be drawn about the significance of pharmacogenetics on NOAC therapy.
Life after death: Posttraumatic stress disorder in survivors of cardiac arrest—Prevalence, associated factors, and the influence of sedation and analgesia

ObjectiveCardiac arrest is possibly one of the most traumatizing conditions for patients, but to date, its influence on psychic morbidity remains unknown. Posttraumatic stress disorder is a unique symptom configuration after an extreme event consisting of intrusion re-experiencing, avoidance and numbness, and hyperarousal symptoms. We studied a) the prevalence of posttraumatic stress disorder (PTSD) in long term survivors of cardiac arrest; b) the role of specific stress factors related to cardiac arrest for the development of PTSD; and c) the influence of sedation and analgesia during or after cardiac arrest on the occurrence of PTSD. DesignProspective, cohort study. SettingUniversity teaching hospital. PatientsAnalysis was performed in cardiac arrest survivors who were discharged with favorable neurologic outcome during an 8-yr period (1991–1999). InterventionsAll patients received the Davidson Trauma Score for the assessment of PTSD and a modified German version of the EuroQol questionnaire for assessment of quality of life. Cardiac arrest circumstances and administration of sedation and analgesia were assessed. Measurements and Main ResultsOf 1,630 initially resuscitated patients, 270 patients were discharged with good neurologic outcome. A total of 226 patients were contacted, and 143 patients (63% of all eligible patients) completed the study. Mean time from cardiac arrest to follow up was 45 months (range, 24–66). Thirty-nine patients (27%; 95% confidence interval, 21% to 35%) had a Davidson Trauma Score >40 and fulfilled criteria for PTSD. Patients with PTSD had a significantly lower quality of life. The only independent risk factor for the development of PTSD was younger age. There was no difference between patients with or without PTSD regarding the use of sedation and analgesia during or after cardiac arrest. ConclusionThe prevalence of PTSD in cardiac arrest survivors is high. Besides younger age, neither clinical factors nor the use of sedation and analgesia were associated with development of PTSD.
Factors influencing adherence to home-based strength and balance exercises among older adults with mild cognitive impairment and early dementia: Promoting Activity, Independence and Stability in Early Dementia (PrAISED)

Background Older adults with dementia are at a high risk of losing abilities and of accidental falls. Promoting Activity, Independence and Stability in Early Dementia (PrAISED) is a 12-month person-centred exercise and activity programme which aims to increase activity and independence whilst reducing falls in people with early dementia. In this patient group, as well as many others, poor adherence to exercise interventions can undermine treatment effectiveness. We aimed to explore patterns of barriers and facilitators influencing PrAISED participants’ adherence to home-based strength and balance exercises. Methods Participants were a subsample of 20 individuals with mild cognitive impairment or early dementia and their carer(s) taking part in the PrAISED programme. Participants (with the support of a carer where necessary) kept a daily exercise diary. Participants’ adherence were categorised based upon reported number of times a week they undertook the PrAISED strength and balance exercises over a 4 month period (<3 times a week = low adherence, 3–4 = meeting adherence expectations, >5 = exceeding adherence expectations). Semi-structured interviews were conducted in month 4 of the PrAISED programme to explore barriers and facilitators to adherence. A mixture of deductive and inductive thematic analysis was employed with themes categorised using the Theoretical Domains Framework. Findings Participants completed on average 98 minutes of home-based strength and balance exercises per week, 3.8 sessions per week, for an average of 24 minutes per session. Five participants were categorised as exceeding adherence expectations, 7 as meeting adherence expectations, and 8 as low adherers. Analysis of interview data based on self-reported adherence revealed six interacting themes: 1) routine, 2) practical and emotional support, 3) memory support, 4) purpose, 5) past experiences of sport and exercise, and 6) belief in and experience of benefits. Conclusions Identifiable cognitive, psychological, and practical factors influence adherence to exercise, and should be addressed in future development of interventions with this population.
Investigation of chronic infection by Leptospira spp. in asymptomatic sheep slaughtered in slaughterhouse

The study aimed to evaluate the histopathological characteristics of renal lesions in chronically infected sheep and with low titers of anti-Leptospira antibodies from a slaughterhouse. In the serological analysis, 24.74% (48/194) presented seroreactivity with a titer equal to or greater than 100. Among these seroreactive sheep, titers of 100 were predominant (58.33%, 28/48), with the highest titer being 1,600 (2.08%, 1/48). Serogroup Sejroe (sv. Hardjo) was the most frequent at 35.42% (17/48). Leptospiral DNA was verified in 4.12% (8/194) of the kidney samples tested, and no urine sample was positive. All the samples corresponded to the pathogenic species L. interrogans. The eight amplicons with 202-nucleotides were identical with two mismatches (presented 100% of identity) using the PCR targeting to secY gene. Histological sections of PCR-positive kidneys were submitted to direct detection by the anti-LipL32 immunohistochemistry (IHC) technique. The Leptospira spp. antigen was evident in 62.5% (5/8) of the kidneys. Positive staining was observed in the cytoplasm of tubular cells and in the form of brownish aggregates that adhered to tubular epithelial cells and projected into the lumen. Inflammatory lymphoplasmacytic infiltrate, ranging from mild to moderate, with multifocal distribution, was the predominant finding in seroreactive animals (33.33%, 16/48). The demonstration of the leptospiral antigen lining the renal tubules through IHC of naturally infected sheep confirmed by PCR characterizes renal colonization in a species with the presence of histological changes compatible with leptospirosis.
Chronotype mediates gender differences in risk propensity and risk-taking

Risk-taking is a complex form of decision-making that involves calculated assessments of potential costs and rewards that may be immediate or delayed. Thus, making predictions about inter-individual variation in risk-taking due to personality traits, decision styles or other attributes can be difficult. The association of risk-taking with gender is well-supported; males report higher propensity for risk-taking and show higher risk-taking on tasks measuring actual risk-taking behavior. Risk-taking also appears to be associated with circadian phenotypes (chronotypes), with evening-types reporting higher levels of risk-taking—but this association may be confounded by the fact that, in certain age groups, males are more likely to be evening-types. Here, we test for gender by chronotype effects on risk-taking in young adults (n = 610) using a self-reported risk propensity questionnaire, the health domain of the DOSPERT, and a behavioral task measuring risk-taking, the Balloon Analog Risk Task (BART). Our results show that males report and take significantly more risks than females in this population. In addition, evening-type individuals have significantly higher self-reported risk propensity and tend to take more risks on the BART. Interestingly, there is no significant difference in risk propensity or risk-taking behavior across male circadian phenotypes, but evening-type females significantly report and take more risk than female intermediate and morning types. In regression analyses, we found both gender and chronotype predict risk propensity and risk-taking. Path analysis confirms that chronotype has an indirect effect on gender differences in both risk propensity and risk-taking. Furthermore, we found that trait anxiety (STAI) and sleep disturbance (PROMIS), significantly correlate with chronotype and gender in the complete dataset, but do not independently predict differences in female risk-taking. These results suggest that chronotype mediates gender effects on risk-taking and that these effects are driven primarily by morning-type females, but are not related to gender-specific differences in trait anxiety or sleep quality.
Caregivers’ Experiences With Food Insecurity Screening and Impact of Food Insecurity Resources

We explored caregivers’ experiences with food insecurity screening in a primary care setting and the impact of resources provided. English- and Spanish-speaking food insecure caregivers of children aged 1 to 5 years were recruited. In-depth individual semistructured interviews were conducted (n = 17) eliciting caregivers’ experiences with food insecurity, clinic screening, and resources provided. Interviews were audio-recorded and transcribed verbatim. Interviews were double-coded and thematic analysis was used to identify themes and subthemes. All caregivers described multiple and repeat experiences with food insecurity. Food insecurity screening was acceptable, but families were not always connected with resources. Caregivers described WIC (Women, Infants, and Children) as the most commonly used program to address food insecurity and infrequently utilized other food insecurity resources. Screening for food insecurity in primary care was generally well accepted by this sample of food insecure caregivers. Future studies are needed to determine how to improve connecting resources with families most in need.
Nuclear Phospho-SOD1 Protects DNA from Oxidative Stress Damage in Amyotrophic Lateral Sclerosis

We already demonstrated that in peripheral blood mononuclear cells (PBMCs) of sporadic amyotrophic lateral sclerosis (sALS) patients, superoxide dismutase 1 (SOD1) was present in an aggregated form in the cytoplasmic compartment. Here, we investigated the possible effect of soluble SOD1 decrease and its consequent aggregation. We found an increase in DNA damage in patients PBMCs characterized by a high level of aggregated SOD1, while we found no DNA damage in PBMCs with normal soluble SOD1. We found an activation of ataxia-telangiectasia-mutated (ATM)/Chk2 and ATM and Rad3-related (ATR)/Chk1 DNA damage response pathways, which lead to phosphorylation of SOD1. Moreover, data showed that phosphorylation allows SOD1 to shift from the cytoplasm to the nucleus, protecting DNA from oxidative damage. Such pathway was finally confirmed in our cellular model. Our data lead us to suppose that in a sub-group of patients this physiologic pathway is non-functional, leading to an accumulation of DNA damage that causes the death of particularly susceptible cells, like motor neurons. In conclusion, during oxidative stress SOD1 is phosphorylated by Chk2 leading to its translocation in the nuclear compartment, in which SOD1 protects DNA from oxidative damage. This pathway, inefficient in sALS patients, could represent an innovative therapeutic target.
The Composition, Diversity, and Distribution of Mosquito Fauna (Diptera: Culicidae) in Kosovo

ABSTRACT: The aim of this study is to identify the mosquito species that currently exist and their distributions in Kosovo in order to determine current potential endemic zones and areas at a higher risk for future epidemics. These scientific data will be shared with public health authorities for implementing mosquito control programs. During a two-year period of monitoring in 48 localities in 23 provinces in Kosovo, a total of 1,604 mosquitoes representing 13 species and six genera were collected and morphologically identified. Members of species complexes were also classified to species using DNA barcoding. In total, 13 species were identified with Culex pipiens s.l. , the predominant species with an abundance rate of 39%. The remaining 12 species identified were grouped into five genera: Anopheles, Aedes, Coquillettidia, Culiseta, Uranotaenia, including species that are vectors of arboviruses in other parts of the world.
Is more emotional clarity always better? An examination of curvilinear and moderated associations between emotional clarity and internalising symptoms

ABSTRACT Low emotional clarity has been a target for psychological interventions due to its association with increased internalising symptoms. However, theory suggests that very high emotional clarity may also lead to increased symptoms, particularly in combination with high levels of neuroticism. As an initial empirical test of this hypothesis, the present study examined curvilinear associations of emotional clarity with internalising symptoms (i.e. dysphoria, social anxiety, panic, traumatic intrusions) and a moderating role of neuroticism/negative affect in the association across two student samples and two clinical samples (total N = 920). Evidence of curvilinear associations and moderation varied across samples, with some supporting evidence in three samples. Specifically, neuroticism/negative affect moderated the curvilinear association of emotional clarity with traumatic intrusions in Clinical Sample 2 as well as the linear association between emotional clarity and dysphoria in Student Sample 2 and Clinical Sample 1. Simple slope analyses indicated that high emotional clarity was not consistently associated with lower symptoms. Also, the hypothesised quadratic effects of emotional clarity were found in Student Sample 2 and Clinical Sample 1 for panic, and in Clinical Sample 1 for dysphoria. Implications and limitations of these findings for conceptualisations of emotional clarity and current treatments were discussed.
Guide to the Assessment of Mature Liver Gene Expression in Stem Cell-Derived Hepatocytes

Differentiation of stem cells to hepatocyte-like cells (HLCs) holds great promise for basic research, drug and toxicological investigations, and clinical applications. There are currently no protocols for the production of HLCs from stem cells, such as embryonic stem cells or induced pluripotent stem cells, that produce fully mature hepatocytes with a wide range of mature hepatic functions. This report describes a standard method to assess the maturation of stem cell-derived HLCs with a moderately high-throughput format, by analysing liver gene expression by quantitative RT-qPCR. This method also provides a robust data set of the expression of 62 genes expressed in normal liver, generated from 17 fetal and 25 mature human livers, so that investigators can quickly and easily compare the expression of these genes in their stem cell-derived HLCs with the values obtained in authentic fetal and mature human liver. The simple methods described in this study will provide a quick and accurate assessment of the efficacy of a differentiation protocol and will help guide the optimization of differentiation conditions.
The GNAS SNP c.393C>T (rs7121) as a marker for disease progression and survival in cancer.

G-protein receptor signaling plays a key role in multiple signal transduction pathways. Aberrant activity of the stimulatory Gsα subunit has been frequently associated with cancer. GNAS sequence alterations and conformational changes of Gsα can both enhance or diminish its function and change downstream effects of G-protein receptor signaling. In this review and meta-analysis, we focus on the synonymous SNP rs7121 (FokI, c.393C>T), which is associated with either tumor progression or prolonged survival in cancer patients (overall hazard ratio = 2.256; p < 0.001). We finally point out the relevance of GNAS rs7121 as a promising biomarker and a prediction tool for therapy response and the need of further experiments to implement it into routine clinical diagnostics.
Effect of RNA splicing machinery gene mutations on prognosis of patients with MDS

Abstract Background: Gene mutations with important prognostic role have been identified in patients with myelodysplastic syndrome (MDS). We performed a meta-analysis to investigate the effects of RNA splicing machinery gene mutations on prognosis of MDS patients. Methods: We searched English database including PubMed, Embase, Cochrane Library for literatures published within recent 10 years on the effect of RNA splicing machinery genes in MDS. Revman version 5.2 software was used for all the statistical processing. We calculated risk ratio and 95% confidence interval (CI) of continuous variables, and find hazard ratio (HR) and 95% CI of time-to-event data. Results: We included 19 studies enrolling 4320 patients. There is a significant superior overall survival (OS) in splicing factor 3b, subunit 1 (SF3B1)-mutation group compared to unmutated group (HR = 0.58, 95% CI: 0.5–0.67, P < .00001); OS decreased significantly in serine/arginine-rich splicing factor 2/ U2 auxiliary factor protein 1 (SRSF2/U2AF1) mutation group compared to unmutated group, (HR = 1.62, 95% CI: 1.34–1.97, P < .00001 and HR = 1.61, 95% CI: 1.35–1.9, P < .00001, respectively). In terms of leukemia-free survival (LFS), the group with SF3B1 mutation had better outcome than unmutated group, HR = 0.63 (95% CI: 0.53–0.75, P < .00001). Other RNA splicing gene mutation group showed significant poor LFS than unmutated groups, (HR = 1.89, 95% CI: 1.6–2.23, P < .00001; HR = 2.77, 95% CI: 2.24–3.44, P < .00001; HR = 1.48, 95% CI: 1.08–2.03, P < .00001; for SRSF2, U2AF1, and zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2 [ZRSR2], respectively). As for subgroup of low- or intermediate-1-IPSS risk MDS, SRSF2, and U2AF1 mutations were related to poor OS. (HR = 1.83, 95% CI: 1.43–2.35, P < .00001; HR = 2.11, 95% CI: 1.59–2.79, P < .00001 for SRSF2 and U2AF1, respectively). SRSF2 and U2AF1 mutations were strongly associated with male patients. SF3B1 mutation was strongly associated with disease staging. Conclusion: This meta-analysis indicates a positive effect of SF3B1 and an adverse prognostic effect of SRSF2, U2AF1, and ZRSR2 mutations in patients with MDS. Mutations of RNA splicing genes have important effects on the prognosis of MDS.
Different Ways to Get There: Evidence of a Variable Female Sexual Response Cycle

Research has suggested women’s sexual response cycle may vary more than previously thought. We asked 769 sexually active women between the ages of 18–70 to report on their sexual desire and arousal patterns during their last sexual experience. Using a latent class mixture model from retrospective sexual response data, we found six classes of desire and arousal patterns (Low, Middle Steady, High Fluctuation, Low Fluctuation, Upper Steady, High). We examined how these patterns were related to demographics, outcomes during the sexual experience, and outcomes for the global relationship. The Low sexual response class (8% of women) was significantly different from other classes in duration of the sexual experience, orgasms, and overall satisfaction with the sexual experience. Most sexual response patterns were associated with healthy relational and sexual outcomes. All classes except for the Low arousal and desire class showed associations with a neutral or positive sexual satisfaction evaluation. The non-problematic variation of women’s sexual experience is an important concept to consider as it impacts determinations of dysfunction and women’s self-evaluations. Not all women need to experience high levels of arousal throughout the sexual experience or to have desire at the outset in order to have positive sexual experiences and sexual outcomes.