Miracle-dz/UniFAR-FTUs huggingface dataset:
Endovascular treatment of debilitating tinnitus secondary to cerebral venous sinus abnormalities: a literature review and technical illustration

Background and objective Pulsatile tinnitus (PT) can be debilitating and lead to significant morbidity. Cerebral venous sinus lesions, such as venous sinus stenosis, diverticula, and high-riding jugular bulb, are uncommon causes of PT, for which there is no standard treatment. Endovascular interventions have shown promising results for PT secondary to idiopathic intracranial hypertension, and may be a valid therapeutic option for isolated venous PT. Methods We conducted a systematic literature review on the outcome and safety of endovascular treatment for patients with isolated, debilitating venous PT. The venous lesion characteristics, endovascular techniques, complications, and clinical outcomes were assessed. In addition, an illustrative case of endovascular stenting for PT caused by venous sinus stenosis was included. Results A total of 41 patients (90.2% female) from 26 papers were included. The median age was 46 years (IQR 23; range 25–72 years). Focal venous sinus stenosis (20 patients) and sinus diverticula (14 patients) were the most common culprit lesions. Endovascular treatment included venous sinus stenting in 35 patients, 11 of whom had adjuvant coil embolization, and coil embolization alone in six patients. Complete resolution of the tinnitus was achieved in 95.1% of patients. There was one complication of cerebellar infarct, and no procedure-related mortality. Conclusions In patients with debilitating PT secondary to venous sinus lesions, endovascular treatment by stenting and/or coil embolization appears to be safe and effective. Prospective randomized studies with objective outcome assessments are needed to confirm the treatment benefits.
The Janus Faces of Bone Morphogenetic Protein 9 in Pulmonary Arterial Hypertension.

In the year 2000, the first link between hereditary cases of pulmonary arterial hypertension (PAH) and germline loss-of-function mutations in BMPR2, the gene encoding the BMPR-II (BMP [bone morphogenetic protein] type-II receptor), was established. This discovery promised to reveal, once and for all, the fundamental molecular causes underlying this challenging and devastating disease. Since that time, BMPR2 mutations have been identified in >70% of familial and roughly 15% of sporadic PAH cases. Reduced levels of BMPR-II protein have also been reported in tissues from patients with or without mutations, highlighting the central role for this receptor in PAH, independent of etiology. Despite these findings, there remain large gaps in our understanding of how BMPR2 mutations actually contribute to the functional and structural vascular abnormalities that are characteristic of PAH. More poignantly, as of 2019, there are no clinically approved treatments for PAH that directly target impaired BMP signaling.
On the Relative Contribution of Deep Convolutional Neural Networks for SSVEP-Based Bio-Signal Decoding in BCI Speller Applications

Brain–computer interfaces (BCI) harnessing steady state visual evoked potentials (SSVEPs) manipulate the frequency and phase of visual stimuli to generate predictable oscillations in neural activity. For BCI spellers, oscillations are matched with alphanumeric characters allowing users to select target numbers and letters. Advances in BCI spellers can, in part, be accredited to subject-specific optimization, including; 1) custom electrode arrangements; 2) filter sub-band assessments; and 3) stimulus parameter tuning. Here, we apply deep convolutional neural networks (DCNNs) demonstrating cross-subject functionality for the classification of frequency and phase encoded SSVEP. Electroencephalogram (EEG) data are collected and classified using the same parameters across subjects. Subjects fixate forty randomly cued flickering characters ( $\textsf {5} \times \textsf {8}$ keyboard array) during concurrent wet-EEG acquisition. These data are provided by an open source SSVEP dataset. Our proposed DCNN, PodNet, achieves 86% and 77% offline accuracy of classification across-subjects for two data capture periods, respectively, 6-seconds (information transfer rate = 40 bpm) and 2-seconds (information transfer rate = 101 bpm). Subjects demonstrating sub-optimal (<70%) performance are classified to similar levels after a short subject-specific training period. PodNet outperforms filter-bank canonical correlation analysis for a low volume (3-channel) clinically feasible occipital electrode configuration. The networks defined in this study achieve functional performance for the largest number of SSVEP classes decoded via DCNN to date. Our results demonstrate PodNet achieves cross-subject, calibrationless classification and adaptability to sub-optimal subject data, and low-volume EEG electrode arrangements.
Epidemiology of Surgical Site Infections and Non-Surgical Infections in Neurosurgical Polish Patients—Substantial Changes in 2003–2017

Introduction: The objective of the analysis was to determine the epidemiology of healthcare-associated infections (HAIs) in neurosurgical patients, paying special attention to two time points, 2003 and 2017, in order to evaluate the effectiveness of a surveillance program introduced in 2003 and efforts to reduce infection rates. Materials and methods: Continuous surveillance during 2003–2017 carried out using the HAI-Net methodology allowed us to detect 476 cases of HAIs among 10,332 patients staying in a 42-bed neurosurgery unit. The intervention in this before–after study (2003–2017) comprised standardized HAI surveillance with regular analysis and feedback. Results: The HAI incidence during the whole study was 4.6%. Surgical site infections (SSIs) accounted for 33% of all HAIs with an incidence rate of 1.5%. The remaining infections were pneumonia (1.1%) and bloodstream infections (0.9%). The highest SSI incidence concerned spinal fusion (FUSN, 2.2%), craniotomy (1.9%), and ventricular shunt (5.1%) while the associated total HAI incidence rates were 4.1%, 8.0%, and 18.6%, respectively. A significant reduction was found in HAI incidence between 2003 and 2017 in regard to the most common surgery types: laminectomy (4.5% vs. 0.8%); FUSN (11.8% vs. 0.8%); and craniotomy (10.1% vs. 0.4%). Significant changes were also achieved in selected elements of the unit’s work: pre-hospitalization duration, hospital stay, and surgery length reductions. Simultaneously, the general condition of patients became significantly worse: there was an increase in patients’ age and decreases in their general condition as expressed by ASA scores (The American Society of Anesthesiologists physical status classification system). Conclusions: HAI epidemiology changed substantially during the study period. Among the main types of HAI, SSIs were slightly predominant, but non-surgical HAIs accounted for almost two thirds of all infections; this indicates the need for surveillance of infection types other than SSIs in surgical patients. The implementation of active surveillance based on regular analysis and feedback led to a significant reduction in HAI incidence.
Ethnic variation in gratitude and well-being.

Gratitude is positively associated with health and well-being. Past studies of gratitude have primarily focused on the distinct cultural context of European Americans. The current studies aimed to extend gratitude research to Latino and East Asian Americans, 2 collectivistic contexts known to differently value positive emotions. Two studies explored whether Latino and East Asian Americans varied in gratitude experience and whether the disposition toward gratitude was associated with well-being for both. In Study 1, participants completed measures of the emotional experience and expression of gratitude. Latino Americans rated the desirability, appropriateness, frequency, and intensity of their gratitude experience-expression higher than did East Asian Americans. Moreover, European Americans' gratitude experience and expression was similar to those of Latino Americans and higher than those of East Asian Americans. In Study 2, participants completed measures of gratitude disposition and indicators of well-being. Latino Americans reported a higher disposition toward gratitude than did East Asian Americans. Higher disposition toward gratitude was associated with higher self-esteem and with less loneliness and perceived stress across groups. However, the strength of the association of gratitude with subjective health and depressive symptoms varied by group in theoretically expected ways. The promising possibilities of extending research on gratitude to culturally diverse groups is discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Compromised Chondrocyte Differentiation Capacity in TERC Knockout Mouse Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

Mammalian telomere lengths are primarily regulated by telomerase, consisting of a reverse transcriptase protein (TERT) and an RNA subunit (TERC). We previously reported the generation of mouse Terc+/− and Terc−/− embryonic stem cells (ntESCs) by somatic cell nuclear transfer. In the present work, we investigated the germ layer development competence of Terc−/−, Terc+/− and wild-type (Terc+/+) ntESCs. The telomere lengths are longest in wild-type but shortest in Terc−/− ntESCs, and correlate reversely with the population doubling time. Interestingly, while in vitro embryoid body (EB) differentiation assay reveals EB size difference among ntESCs of different genotypes, the more stringent in vivo teratoma assay demonstrates that Terc−/− ntESCs are severely defective in differentiating into the mesodermal lineage cartilage. Consistently, in a directed in vitro chondrocyte differentiation assay, the Terc−/− cells failed in forming Collagen II expressing cells. These findings underscore the significance in maintaining proper telomere lengths in stem cells and their derivatives for regenerative medicine.
Eicosapentaenoic Acid Improves Hepatic Metabolism and Reduces Inflammation Independent of Obesity in High-Fat-Fed Mice and in HepG2 Cells

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, concurrent with increased obesity. Thus, there is urgent need for research that can lead to effective NAFLD prevention/treatment strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA), improve inflammation- and dyslipidemia-related metabolic disorders; however, mechanisms mediating the benefits of n-3 PUFAs in NAFLD treatment are less understood. We previously reported that EPA reversed obesity-induced hepatic steatosis in high-fat (HF)-fed B6 mice. Utilizing a combination of biochemical analyses of liver tissues from HF and HF-EPA-fed mice and a series of in vitro studies in tumor necrosis factor-alpha (TNF-α)-stimulated HepG2 cells, we dissect the mechanistic effects of EPA in reducing hepatic steatosis, including the role of EPA-targeted microRNAs (miRNA). With EPA, hepatic lipid metabolism was improved in HF-EPA mice, as indicated by decreased protein and messenger RNA (mRNA) levels of fatty acid synthase (FASN) and acetyl-CoA carboxylase (Acaca) gene, and increased mRNA levels for the peroxisome proliferator activated receptor-α (Pparα), and carnitine palmitoyltransferase (Cpt) 1a and 2 genes in the HF-EPA mice. Additionally, inflammation was reduced, as shown by decreased tumor necrosis factor-alpha (Tnfα) gene expression. Accordingly, EPA also significantly reduced FASN and ACACA mRNAs in human HepG2 cells. Glycolysis, estimated by extracellular acidification rate, was significantly reduced in HepG2 cells treated with EPA vs. vehicle. Furthermore, we identified several miRNAs that are regulated by EPA in mouse liver, including miR-19b-3p, miR-21a-5p, and others, which target lipid metabolism and inflammatory pathways. In conclusion, our findings provide novel mechanistic evidence for beneficial effects of EPA in NAFLD, through the identification of specific genes and miRNAs, which may be further exploited as future NAFLD therapies.
Inflammatory mediators and dual depression: Potential biomarkers in plasma of primary and substance-induced major depression in cocaine and alcohol use disorders

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1β, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to “Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision” (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p<0.05) and CCL11 (p<0.05), and higher IL-1β (p<0.01) concentrations than the control group. In contrast, the alcohol group showed higher IL-1β (p<0.01) and lower CXCL12 (p<0.01) concentrations than the control group. Regarding MDD, we only observed alterations in the cocaine group. Thus, CUD/MDD patients showed lower IL-1β (p<0.05), CXCL12 (p<0.05) and CCL11 (p<0.05), and higher CXC3CL1 (p<0.05) concentrations than CUD/non-MDD patients. Moreover, while CUD/primary MDD patients showed higher CCL11 (p<0.01) concentrations than both CUD/non-MDD and CUD/cocaine-induced MDD patients, CUD/cocaine-induced MDD patients showed lower CXCL12 (p<0.05) concentrations than CUD/non-MDD patients. Finally, a logistic regression model in the cocaine group identified CXCL12, CCL11 and sex to distinguish primary MDD from cocaine-induced MDD providing a high discriminatory power. The present data suggest an association between changes in inflammatory mediators and the diagnosis of primary and substance-induced MDD, namely in CUD patients.
Adaptations in Mitochondrial Enzymatic Activity Occurs Independent of Genomic Dosage in Response to Aerobic Exercise Training and Deconditioning in Human Skeletal Muscle

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I–IV activities were increased by 51% and 46–61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e., cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I–IV activities by 29–36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.
DNA methylation changes associated with Parkinson’s disease progression: outcomes from the first longitudinal genome-wide methylation analysis in blood

ABSTRACT Parkinson’s Disease (PD) is a common neurodegenerative disorder currently diagnosed based on the presentation of characteristic movement symptoms. Unfortunately, patients exhibiting these symptoms have already undergone significant dopaminergic neuronal loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetic mechanisms, which are modified by both environment and disease pathophysiology, are emerging as important components of neurodegeneration. Alterations to the PD methylome have been reported in epigenome-wide association studies. However, the extent to which methylation changes correlate with disease progression has not yet been reported; nor the degree to which methylation is affected by PD medication. We performed a longitudinal genome-wide methylation study surveying ~850,000 CpG sites in whole blood from 189 well-characterized PD patients and 191 control individuals obtained at baseline and at a follow-up visit ~2 y later. We identified distinct patterns of methylation in PD cases versus controls. Importantly, we identified genomic sites where methylation changes longitudinally as the disease progresses. Moreover, we identified methylation changes associated with PD pathology through the analysis of PD cases that were not exposed to anti-parkinsonian therapy. In addition, we identified methylation sites modulated by exposure to dopamine replacement drugs. These results indicate that DNA methylation is dynamic in PD and changes over time during disease progression. To the best of our knowledge, this is the first longitudinal epigenome-wide methylation analysis for Parkinson’s disease and reveals changes associated with disease progression and in response to dopaminergic medications in the blood methylome.
Coherence between subjective experience and physiology in emotion: Individual differences and implications for well-being.

Emotion theorists have characterized emotions as involving coherent responding across various emotion response systems (e.g., covariation of subjective experience and physiology). Greater response system coherence has been theorized to promote well-being, yet very little research has tested this assumption. The current study examined whether individuals with greater coherence between physiology and subjective experience of emotion report greater well-being. We also examined factors that may predict the magnitude of coherence, such as emotion intensity, cognitive reappraisal, and expressive suppression. Participants (N = 63) completed self-report measures of well-being, expressive suppression, and cognitive reappraisal. They then watched a series of emotionally evocative film clips designed to elicit positive and negative emotion. During the films, participants continuously rated their emotional experience using a rating dial, and their autonomic physiological responses were recorded. Time-lagged cross-correlations were used to calculate within-participant coherence between intensity of emotional experience (ranging from neutral to very negative or very positive) and physiology (composite of cardiac interbeat interval, skin conductance, ear pulse transit time, finger pulse transit time and amplitude, systolic and diastolic blood pressure). Results indicated that individuals with greater coherence reported greater well-being. Coherence was highest during the most emotionally intense film and among individuals who reported lower expressive suppression. However, coherence was not associated with reappraisal. These findings provide support for the idea that greater emotion coherence promotes well-being and also shed light on factors that are associated with the magnitude of coherence. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Adalimumab provides long-lasting clinical improvement in refractory mucocutaneous Behçet's disease without formation of antidrug antibodies.

OBJECTIVES The TNF-blocker adalimumab can be effective in Behçet's disease (BD), a multisystem auto-inflammatory disorder. Unfortunately, the therapeutic efficacy of TNF-blockers can be hampered by the formation of anti-drug antibodies. We present an observational study of adalimumab in refractory BD with measurement of anti-drug antibodies. METHODS The effect of fortnightly 40mg adalimumab in nine patients with therapy refractory mucocutaneous, non-ocular or organ threatening BD was studied up to 60 months. Primary endpoint was a decrease in disease activity, measured by the BD Current Activity Form (BDCAF) within 6 months. Secondary endpoints included serum cytokines and the long-term formation of anti-adalimumab antibodies. RESULTS BDCAF improved significantly in all nine patients from 5.4 (SD=1.4) to 2.4 (SD=1.4) (p=0.007) within one month up to 6 months and after prolonged follow up of 5 years. All patients could either taper or stop concomitant therapy. Symptoms of mucocutaneous lesions, erythema nodosum and joint involvement decreased or disappeared. Serum TNF-alpha levels were elevates in five patients and decreased upon treatment (p=0.017). Adalimumab was save and none of the patients experienced therapy failure or antibodies against adalimumab. CONCLUSIONS We present an observational study on patients with BD treated with adalimumab and provide a basis for long-term use in refractory mucocutaneous BD. These findings show that adalimumab can safely be administered yielding sustainable clinical effects in refractory BD patients with mucocutaneous disease without formation of anti-adalimumab antibodies, even after long follow up.