Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute endurance exercise stimulates circulating levels of mitochondrial derived peptides in humans.

Mitochondrial derived peptides (MDPs) humanin (HN) and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis and metabolism. Circulating levels of MDPs are altered in chronic diseases such as diabetes type 2 and chronic kidney disease. Whether acute resistance (RE) or endurance (EE) exercise modulates circulating levels of HN and MOTS-c in humans is unknown. Following familiarization, subjects were randomized to EE (n=10, 45 min cycling at 70% of estimated VO2max), RE (n=10, 4 sets x 7RM, leg press and knee extension), or control (CON, n=10). Skeletal muscle biopsies and blood samples were collected before and at 30 minutes and 3 hours following exercise. Plasma concentration of HN and MOTS-c, skeletal muscle MOTS-c as well as gene expression of exercise related genes were analyzed. Acute EE and RE promoted changes in skeletal muscle gene expression typically seen in response to each exercise modality (c-Myc, 45S pre-rRNA, PGC-1α-total and PGC-1α-ex1b). At rest, circulating levels of HN were positively correlated to MOTS-c levels and age. Plasma levels of MDPs were not correlated to fitness outcomes (VO2max, leg strength or muscle mitochondrial (mt) DNA copy number). Circulating levels of HN were significantly elevated by acute EE but not RE. MOTS-C levels showed a trend to increase after EE. These results indicate that plasma MDP levels are not related to fitness status but that acute EE increases circulating levels of MDPs, in particular HN.
Comparison of the Effects of Matching and Normalization on the Cervical Vestibular Evoked Myogenic Potential

Hypothesis: We compared two means of mitigating the effect of sternocleidomastoid (SCM) contraction strength on the cervical vestibular evoked myogenic potential (cVEMP): contraction matching and amplitude normalization. Background: SCM muscle contraction strength affects the amplitude of the cVEMP which can impact measures of inter-side asymmetry and diagnostic outcomes. Methods: In 19 normal subjects, we investigated the effect of muscle contraction variation within a cVEMP recording. We then compared cVEMP recordings on the right and left sides with matched and unmatched muscle contraction strength using raw amplitudes and amplitude ratios (i.e., normalized amplitudes). Results: Contraction variability had significant effects on small sections of a cVEMP recording, but there was no significant effect on overall cVEMP amplitude, suggesting that the cVEMP is relatively unaffected by variable effort during a recording. Matching the contraction across the two sides (d = 0.53, p = 0.016) and amplitude normalization (d = 0.43, p = 0.004) both significantly reduced inter-side asymmetry, but normalization had no additional benefit once the sides were matched (interaction effect, p = 0.019). cVEMPs recorded with matched contractions had the smallest range of asymmetry values. Conclusion: The study shows that controlling the background contraction during a cVEMP recording, either by using similar contractions for each trial or by normalizing the amplitude, reduces cVEMP asymmetry and can prevent incorrect results in the minority of subjects who make asymmetric muscle contractions.
Results of a prospective follow-up study after type A aortic dissection repair: a high rate of distal aneurysmal evolution and reinterventions.

OBJECTIVES We investigated the anatomical evolution of residual aortic dissection after type A repair and factors associated with poor prognosis at a high-volume aortic centre. METHODS Between 2017 and 2019, all type A aortic dissections were included for prospective follow-up. Patients without follow-up computed tomography (CT) scan available for radiological analysis and patients without residual aortic dissection were excluded from this study. The primary end point was a composite end point defined as dissection-related events including aneurysmal evolution (increased diameter > 5 mm/year), aortic reintervention for malperfusion syndrome, aortic diameter >55 mm, rapid aortic growth >10 mm/year or aortic rupture and death. The secondary end points were risk factors for dissection-related events and reintervention analysis. All immediate and last postoperative CT scans were analysed. RESULTS Among 104 patients, after a mean follow-up of 20.4 months (8-41), the risk of dissection-related events was 46.1% (48/104) and the risk of distal reintervention was 17.3% (18/104). Marfan syndrome (P < 0.01), aortic bicuspid valve (P = 0.038), innominate artery debranching (P = 0.025), short aortic cross-clamp time (P = 0.011), initial aortic diameter >40 mm (P < 0.01) and absence of resection of the primary entry tear (P = 0.015) were associated with an increased risk of dissection-related events or reintervention during follow-up. CONCLUSIONS Residual aortic dissection is a serious disease requiring close follow-up at an expert centre. This study shows higher reintervention and aneurysmal development rates than currently published. To improve long-term outcomes, the early demographic and anatomic poor prognostic factors identified may be used for more aggressive treatment at an early phase.
Perspectives about smoking cessation during pregnancy and beyond of Aboriginal women in Australia: A qualitative analysis using the COM‐B model

Aboriginal and Torres Strait Islander women (hereafter Aboriginal) and their babies experience poor health outcomes for which smoking is a major risk factor. This paper explores Aboriginal women's perspectives on and experiences of smoking cessation, within and outside pregnancy, and their use of smoking cessation services using the COM‐B (Capability, Opportunity, Motivation as determinants of Behaviour) model to understand Aboriginal women's capabilities, opportunities, and motivation for smoking cessation.
Development and in vitro characterization of nanoparticles for inner ear drug delivery

An innovative drug delivery system for inner ear therapy is based on the use of nanoparticles (NPs): they can be considered good carriers for therapeutic drugs within the inner ear, because they increase drug diffusion and are detected in all parts of the cochlea when applied near the round window. In this study liquid crystalline NPs based on glycerol monooleate were developed and conjugated with two hydrophobic drugs, coenzyme Q10 and dexamethasone, already used for inner ear therapies but limited in their efficacy by low solubility and bioavailability. These conjugated NPs were tested in vitro on two different cell lines, as models of the inner ear cell populations: thePC12 cells, neural-like cells used as a model of neuronal differentiation, and OC-k3, derived from the organ of Corti of transgenic mice as a model of inner ear sensory cells. The NPs conjugated with coenzyme Q10 or dexamethasone were tested against cisplatin (cis-diamminedichloroplatinum(II)), a cytotoxic agent widely used for treatment of solid tumors. Although effective as antitumor agent, cisplatin induces serious collateral effects, among which ototoxicity on the auditory nerve, the stria vascularis and hair cells. The results showed that NPs conjugated with drugs are well tolerated by both cells lines and are uptaken by cells in the first few hours after treatment, delivering the conjugated compounds inside the cells. Moreover, NPs conjugated with dexamethasone were able to counteract damages caused by cisplatin, preventing apoptosis in OC-k3 cells, and increased the concentration of drug uptaken by the cells compared to the free drug treatment. Based on these results, NPs have an interesting potential as inner ear drug delivery systems.
Epidemiology of adult T‐cell leukemia‐lymphoma in Japan: An updated analysis, 2012‐2013

Adult T‐cell leukemia‐lymphoma (ATL) is a T‐cell malignancy that is endemic to Japan. In this latest nationwide study of ATL, we collected the data from 4 nationwide registries of patients diagnosed in 2012‐2013; the Hematology Blood Disease, the Skin Cancer Society, the Hospital‐Based Cancer Registries, and information from the hospitals that participated in the Japanese nationwide survey of ATL in 2010‐2011. In the present study, 2614 patients with ATL were diagnosed based on the registries, and 117 departments registered 1042 patients. Among these patients, 984 were eligible for analysis. The median age at diagnosis was 69 y. A larger proportion of patients with ATL older than 70 y was diagnosed with the lymphoma subtype, and more than half of the patients with ATL in the metropolitan areas were born in the human T‐cell leukemia virus type I (HTLV‐1)‐endemic areas of Kyushu/Okinawa, which are almost identical to the findings in our 2010‐2011 study. Additionally, we identified that patients with ATL migrated from the endemic areas for HTLV‐1 to the non‐endemic metropolitan areas. The present study was able to reduce the burden of searching each hospital and to update the clinico‐epidemiological characteristics of a large number of patients with ATL in Japan, suggesting the usefulness and feasibility of the novel data collection method. The establishment of a more sophisticated database management system for ATL is necessary for future continuous surveys.
Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection.

BACKGROUND The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. METHODS KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. RESULTS Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. CONCLUSIONS The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.
Programmed Cell Death Ligand 1-Expressing Circulating Tumor Cells: A New Prognostic Biomarker in Non-Small Cell Lung Cancer.

BACKGROUND In non-small cell lung cancer (NSCLC), analysis of programmed cell death ligand 1 (PD-L1) expression in circulating tumor cells (CTCs) is a potential alternative to overcome the problems linked to the tumor biopsy spatiotemporal heterogeneity. However, the prognostic significance of PD-L1-positive [PD-L1(+)] CTCs remains controversial. METHODS We prospectively evaluated the correlation with clinicopathological variables and prognostic value of PD-L1(+) CTCs, detected with the FDA-cleared CellSearch® system, in 54 patients with advanced NSCLC. RESULTS We detected CTCs and PD-L1(+) CTCs in 43.4% and 9.4% of patients with NSCLC. PD-L1 expression concordance between tumor tissue and CTCs was low (54%). The presence of PD-L1(+) CTC correlated with the absence of gene alterations in tumor tissue and with poor prognosis-related biological variables (anemia, hyponatremia, increased lactate dehydrogenase). In univariate analysis, absence of gene alterations, number of metastatic sites, prior systemic therapies, and presence of CTCs and PD-L1(+) CTCs were associated with worse overall survival, whereas PD-L1 expression in tumor tissue was not. In multivariate analysis, squamous cell carcinoma histology, number of prior systemic treatments, and the presence of CTC were significantly associated with overall survival. Survival was worse in patients with PD-L1(+) CTCs than in patients with PD-L1-negative CTC or without any CTC. CONCLUSIONS Our study suggests that the presence of PD-L1(+) CTCs is associated with poor prognosis in patients with advanced NSCLC. Studies with larger samples are needed to confirm our results and to determine how PD-L1(+) CTC detection could help to predict the response or resistance to anti-PD-1/PD-L1 therapies.Clinical trial registration NCT02866149.
Celebrity Suicide and Forced Responsible Reporting in the Nineteenth Century: Crown Prince Rudolf and the Absence of a Werther Effect

ABSTRACT Crown Prince Rudolf, heir to the Imperial throne of the Austro-Hungarian Empire, died by suicide in 1889. His death is a prime example of a historical celebrity suicide. Although news coverage about celebrity suicide has been shown to be linked to increases in suicides – a phenomenon known as the Werther effect –, censorship and/or journalists’ anticipatory obedience back then may have led to a form of “forced responsible reporting” that may have prevented a Werther effect. A content analysis was conducted, and civil death registers were used to identify suicides before and after Rudolf’s suicide. We compared Rudolf’s case with another historical celebrity suicide case (Colonel Redl) for which there is already empirical evidence consistent with a Werther effect. As expected, the press heavily reported on Rudolf’s death, but did not give undue prominence to suicide and rarely gave details on the method. Importantly, there was no evidence of an increase in suicides. This is in stark contrast to the Redl case in which the press reported irresponsibly. The Rudolf case emphasizes the importance of current media guidelines on responsible reporting. Thus, a high amount of news coverage does not necessarily translate into a Werther effect.
Associations between critical consciousness and well‐being in a national sample of college students during the COVID‐19 pandemic

Abstract Critical consciousness (CC) may promote well‐being, particularly during the COVID‐19 pandemic. In a national survey of 707 college students conducted in April 2020, we first validated the Short Critical Consciousness Scale (ShoCCS) among youth groups not often specifically examined in CC measurement (i.e., Asian, immigrant‐origin, LGBQ+, and women youth). Next, we examined associations between ShoCCS subscales and validated measures of both anxiety (Generalized Anxiety Disorder‐7) and hopefulness (The Individual‐Differences Measure in Hopefulness). The ShoCCS achieved measurement invariance across racial/ethnic groups and immigrant‐origin status, and partial invariance among LGBQ+ and women‐identifying youth. We found critical reflection and action associated with anxiety for the full sample, but no evidence of moderation by sociodemographic factors. ShoCCS subscales were differentially associated with hopefulness for Asian youth and LGBQ+ youth. This study contributes to the evolution of CC measurement and extends the field by identifying well‐being associations during the onset of the COVID‐19 pandemic.
The Roles of Authenticity in Relationships and Attachment in Adolescents’ Prosocial Experiences

Abstract The current study examined prosocial experiences in 165 girls and boys (M age = 14.87). Two aspects of relationships, parental attachment and parent and peer authenticity in relationships, were explored as predictors of prosocial experiences. The results indicated that girls reported higher levels of prosocial experiences compared to boys. Path analyses found that, for both genders, secure attachment and authenticity with peers predicted prosocial experiences. In addition, there were interactions between secure attachment and dismissing attachment with authenticity with peers, with authenticity with peers buffering the effects of low secure attachment and low dismissive attachment on prosocial experiences. These results highlight the importance of examining adolescents’ prosocial experiences within the context of relationships.
Hippocampal volume is related to olfactory impairment in Parkinson's disease

Recent evidence has suggested that hyposmia in patients with Parkinson's disease (PD) may be due to impaired central processing. Furthermore, the hippocampus has been regarded as a critical structure linking olfactory impairment and cognitive impairment in PD patients. This study aimed to identify significant structural alterations of the hippocampus in PD patients with hyposmia, and to determine whether these structural changes are significantly associated with olfactory impairment severity.
Depressive symptoms and associated factors among HIV positive patients attending public health facilities of Dessie town: A cross-sectional study.

BACKGROUND Depressive symptoms are the most common psychiatric complication of Human Immunodeficiency Virus (HIV) infection. They are associated with poor drug adherence, treatment failure, and increase the risk for suicide. There was limited evidence of depressive symptoms among HIV-positive patients in the study area. So, this study aimed to determine the prevalence of depressive symptoms and associated factors among HIV-positive patients attending public health facilities of Dessie town, North-central Ethiopia, 2019. METHOD A cross-sectional study was conducted on 380 HIV-positive patients attending ART clinics in Dessie town, North-central Ethiopia, 2019. Samples were selected using systematic random sampling and the data were collected by using structured, pretested, and interviewer-administered questionnaires. Patient Health Questionnaire (PHQ-9) at a cut-off point of 5 was used to assess depressive symptoms. The data were entered by Epi data version 3.1 and analyzed by SPSS version 25. A binary logistic regression model was used to identify factors associated with depressive symptoms. The Adjusted Odds Ratio (AOR) along with a 95% Confidence Interval (CI) was estimated to measure the association. The level of significance was declared at a p-value of less than 0.05. RESULT The prevalence of depressive symptoms among HIV positive patients was 15.5% (95% CI: (12.4%, 19.2%)). Age 40-49 years compared to 30-39 years (AOR = 2.96, 95% CI: (1.01, 8.68)), age ≥50 years compared to 30-39 years (AOR = 3.81, 95% CI: (1.05, 13.8)), having perceived stigma (AOR = 10.2, 95%CI: (4.26, 24.4)) taking medication other than Antiretroviral Therapy (ART) (AOR = 2.58, 95% CI: (1.25, 5.33)) and history of opportunistic infections (AOR = 5.17, 95% CI: (1.31, 20.4)) were factors associated with depressive symptoms. CONCLUSION The prevalence of depressive symptoms was low compared to previous studies. Age, perceived stigma, taking medication other than ART, and history of opportunistic infections were factors associated with depressive symptoms. Health education and counseling programs should be strengthened and target older patients, patients who took medications other than ART, patients who experienced perceived stigma and patients with a history of history opportunistic infections.
The Sympathetic Nervous System in Hypertension: Roadmap Update of a Long Journey

Abstract The present paper will provide an update on the role of sympathetic neural factors in the development and progression of essential hypertension by reviewing data collected in the past 10 years. This will be done by discussing the results of the published studies in which sympathetic neural function in essential hypertension and related disease has been investigated via sophisticated and highly sensitive techniques, such as microneurographic recording of sympathetic nerve traffic and regional norepinephrine spillover. First, the relevance of the pathophysiological background of the neurogenic alterations will be discussed. It will be then examined the behavior of the sympathetic neural function in specific clinical phenotypes, such as resistant hypertension, pseudoresistant hypertension, and hypertensive states displaying elevated resting heart values. This will be followed by a discussion of the main results of the meta-analytic studies examining the behavior of sympathetic nerve traffic in essential hypertension, obesity, metabolic syndrome, and chronic renal failure. The sympathetic effects of renal denervation and carotid baroreceptor stimulation as well as the possible involvement of sympathetic neural factors in the determination of the so-called “residual risk” of the treated hypertensive patients will be finally discussed.
Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19

Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19 and provide insights into viral entry inhibition, immune regulation, and drug optimisation strategies. The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus’ pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.