Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Infection and Elevated INR in LVAD-Associated Intracranial Hemorrhage: A Case-Crossover Study.

Despite the common occurrence left ventricular assist device (LVAD)-associated intracranial hemorrhage, the etiology of intracranial hemorrhage is uncertain. We aim to explore the impact of infection and international normalized ratio (INR) on intracranial hemorrhage in a case-crossover study. We reviewed consecutive patients with intracranial hemorrhage in a prospectively collected data of LVAD patients from a single, tertiary center from October 2004 to December 2016. Information on infection and INR values were collected at the time and 1 month before the intracranial hemorrhage as controls. Of 477 persons with LVAD, 47 (10%) developed intracranial hemorrhage (27 intracerebral, 14 subarachnoid, and six subdural hemorrhages). Of 47 (median age 58; 39 males), 27 (54%) persons had active infection at the time of intracranial hemorrhage; seven (21%) of 44 LVADs had infection at 1 month before intracranial hemorrhage. The relative risk of intracranial hemorrhage because of active infection compared with the infections at 1 month was 2.3 (95% CI: 1.5-3.4; p < 0.0001). The mean INRs at the time of intracranial hemorrhage were also significantly higher at the time of hemorrhage compared with those at 1 month (2.6 ± 1.9 vs. 1.8 ± 0.8; p = 0.01). Of 13 persons with cerebral angiogram (seven subarachnoid and six intracerebral hemorrhages), four (57%) infectious intracranial aneurysms were identified only in patients with subarachnoid hemorrhage (SAH) who also had bloodstream infections. Active infection and elevated INR were associated with LVAD-associated intracranial hemorrhage. The occurrence of both bloodstream infection and subarachnoid hemorrhage may indicate the presence of infectious intracranial aneurysm in LVAD.
Dysregulated Marginal Zone B Cell Compartment in a Mouse Model of Sjögren’s Syndrome with Ocular Inflammation

The risk of developing lymphoma in patients with Sjögren’s syndrome (SS) is 44 times higher than in the normal population with the most common lymphomas derived from marginal zone B (MZB) cells. Current understanding of the role of MZB cells in SS is primarily based on salivary gland pathology, while their contextual association with lacrimal glands and ocular manifestations largely remains unknown. We examined this possibility using a SS mouse model (thrombospondin-1 deficient (TSP1−/−)) with well-characterized ocular disease. We determined the frequency, localization, and cytokine profiles of MZB cells and their association with an antibody response in TSP1−/− mice treated with a TSP-derived peptide. A significantly increased frequency of MZB cells was detected in the spleens and lacrimal glands of TSP1−/− mice in comparison to wild-type tissues as detected by immunostaining. An altered cytokine profile of TSP1−/− MZB cells was supportive of T helper 17 (Th17)-related pathogenesis. A significantly reduced antibody response and the splenic MZB compartment against an eye-derived antigen were noted in TSP-derived peptide-treated mice. These changes correspond with the previously reported ability of the peptide to ameliorate SS-related ocular manifestations. Collectively, our results demonstrate dysregulation of MZB cells in TSP1−/− mice and highlight their role in the context of SS-related chronic ocular surface disease.
Parameter identification for piecewise Deterministic Markov Processes: a Case Study on a biochemical Network

Abstract The first part of the paper focuses on the use of Piecewise Deterministic Markov Processes (PDMP) for the modeling of biochemical networks. As a case study, the production of the peptide antibiotic B.Subtilis is considered. The second part of the paper is devoted to the problem of identifying unkown parameters of the model equations, based on experimental data. For the identification task we propose the use of Genetic Algorithms. An example demonstrates the feasibility of our aproach.
ESCRT-mediated lysosome repair precedes lysophagy and promotes cell survival

Although lysosomes perform a number of essential cellular functions, damaged lysosomes represent a potential hazard to the cell. Such lysosomes are therefore engulfed by autophagic membranes in the process known as lysophagy, which is initiated by recognition of luminal glycoprotein domains by cytosolic lectins such as Galectin-3. Here we show that, under various conditions that cause injury to the lysosome membrane, components of the endosomal sorting complex required for transport (ESCRT) machinery are recruited. This recruitment occurs before that of Galectin-3 and the lysophagy machinery. Subunits of the ESCRT-III complex show a particularly prominent recruitment, which depends on the ESCRT-I component TSG101 and the TSG101- and ESCRT-III-binding protein ALIX. Interference with ESCRT recruitment abolishes lysosome repair and causes otherwise reversible lysosome damage to become cell lethal. Vacuoles containing the intracellular pathogen Coxiella burnetii show reversible ESCRT recruitment, and interference with this recruitment reduces intravacuolar bacterial replication. We conclude that the cell is equipped with an endogenous mechanism for lysosome repair which protects against lysosomal damage-induced cell death but which also provides a potential advantage for intracellular pathogens.
Decoupled taxonomic and ecological recoveries from the Permo-Triassic extinction

After the enormous Permian-Triassic mass extinction, marine animals high in the food chain recovered the most quickly. The Permian-Triassic mass extinction was the worst crisis faced by life; it killed >90% of marine species in less than 0.1 million years (Ma). However, knowledge of its macroecological impact over prolonged time scales is limited. We show that marine ecosystems dominated by non-motile animals shifted to ones dominated by nektonic groups after the extinction. In Triassic oceans, animals at high trophic levels recovered faster than those at lower levels. The top-down rebuilding of marine ecosystems was still underway in the latest Triassic, ~50 Ma after the extinction, and contrasts with the ~5-Ma recovery required for taxonomic diversity. The decoupling between taxonomic and ecological recoveries suggests that a process of vacant niche filling before reaching the maximum environmental carrying capacity is independent of ecosystem structure building.
Does High Frequency Transcutaneous Electrical Nerve Stimulation (TENS) Affect EEG Gamma Band Activity?

Background: Transcutaneous electrical nerve stimulation (TENS) is a noninvasive, inexpensive and safe analgesic technique used for relieving acute and chronic pain. However, despite all these advantages, there has been very little research into the therapeutic effects of TENS on brain activity. To the best of our knowledge, there is no evidence on the effect of high frequency TENS on the gamma band activity. Objective: Investigation of the effect of high frequency TENS on the electroencephalographic (EEG) gamma band activity after inducing ischemic pain in healthy volunteers is considered. Material and Methods: The modified version of Submaximal effort tourniquet test was carried out to induce tonic pain in 15 right-handed healthy volunteers. The high frequency TENS (150µs in duration, frequency of 100 Hz) was applied for 20 minutes. Pain intensity was assessed at using Visual Analog Scale (VAS) in two conditions (after-pain, after-TENS). EEG gamma band activity was recorded by a 19-channel EEG in three conditions (baseline, after-pain and after- TENS). The repeated measure ANOVA and paired-sample T- tests were used for data analysis. Results: EEG analysis showed an increase in gamma total power after inducing pain as compared to baseline and a decrease after the application of TENS (mean±SD: .043±.029 to .088±.042 to .038±.022 μV2 ). The analysis of VAS values demonstrated that the intensity of induced pain (mean±SD: 51.53±9.86) decreased after the application of TENS (mean±SD: 18.66±10.28). All these differences were statistically significant (p<.001). Conclusion: The results of this study revealed that the high frequency TENS can reduce the enhanced gamma band activity after the induction of tonic pain in healthy volunteers. This finding might help as a functional brain biomarker which could be useful for pain treatment, specifically for EEG-based neurofeedback approaches.
Low-Dose Quetiapine in the Treatment of SSRI-Induced Bruxism and Mandibular Dystonia: Case Series

Objective: Selective serotonin reuptake inhibitors (SSRIs) have been the most widely used psychopharmacological agents prescribed for depression worldwide. Some adverse effects of SSRI drugs on central nervous system are insomnia and bruxism. These drugs also affect sleep. Quetiapine is used as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). It is a low- dose dibenzothiazepine with more potent 5-HT2 than D2 receptor-blocking properties that can be used to manage bruxism because of its antagonist effect on the 5-HT2 receptor. Cases: The cases were 5 patients who have recently been treated with SSRIs and presented with bruxism. Low- dose quetiapine (between 25 and 50 mg daily) was prescribed for the patients, and after a few days, they reported no bruxism and continued taking the medication. Conclusion: We found that quetiapine can improve bruxism and mandibular dystonia, which are side effects of SSRIs.
Emotion Regulation in Generalized Anxiety and Social Anxiety: Examining the Distinct and Shared Use of Emotion Regulation Strategies

Objective: According to the transdiagnostic view, emotion regulation strategies are common among emotional disorders. Despite the vast majority of studies demonstrating the common role of emotion regulation strategies in emotional disorders including generalized anxiety disorder (GAD) and social anxiety disorder (SAD), distinct functions of these strategies are largely unknown. So, the aim of the present study was to assess the distinct and shared use of emotion regulation strategies in individuals with GAD and SAD symptoms. Method : Participants were recruited from a community sample of Tehran using purposive sampling method. The sample (N = 346) consisted of 269 nonclinical individuals, 47 individuals with generalized anxiety symptoms, and 30 individuals with social anxiety symptoms. Informed consent was obtained from all the participants and they were asked to fill in a series of self -report questionnaires including GAD-IV, SIAS, DERS, EQ, ACS, and RRS. Data were analyzed by discriminant function analysis using SPSS-23. Results: Findings revealed significant differences between the 3 groups in non-acceptance, focusing, shifting, brooding, and decentering (P<0.01). Results of discriminant function analysis showed 2 functions: the first accounted for 87.4% of the variance (Wilk`s Lambda = 0.81, df = 10, P<0.01, χ2 = 70.06), and the second for 12.6% of the variance (Wilk`s Lambda = 0.97, df = 4, P<0.05, χ2 = 9.43) of between group variability. Non-acceptance and focusing discriminated GAD and SAD the most. Conclusion: The findings of the present study support both splitter and lumper approaches as there were some emotion regulation strategies common between GAD and SAD, including shifting, decentering, and brooding. However, some of them were distinct, such as focusing and non-acceptance. Nevertheless, there are still inconsistencies in research about the findings, and thus examining the pathways may illuminate these findings.
Investigation of Intertriginous Mycotic and Pseudomycotic (Erythrasma) Infections and Their Causative Agents with Emphasize on Clinical Presentations

Background: Intertrigo is an erythematous inflammatory condition with multiple etiologies including fungi and bacteria. Intertrigo manifests in different clinical forms with various complaints. This study was conducted to evaluate the causative agents of intertriginous infections with emphasize on clinical presentations. Methods: This descriptive cross-sectional study was carried out in 2015–2016, on 188 patients with clinical suspicion of superficial and cutaneous intertriginous infections in Tehran, Iran. Demographic and additional related data were obtained by questionnaire from all participants. Specimens were collected by gentle scraping of the affected areas. Direct examination and culture were performed for all specimens and grown colonies were identified based on the macroscopic and microscopic features. Supplementary tests were done whenever needed. Data were analyzed in SPSS. Results: Overall, 80 (42.5%) cases with the mean age of 43.5 yr were confirmed for intertrigo. Dermatophytosis was the predominant cause in this study with 36 (45%) cases followed by erythrasma (28 cases, 35%), tinea versicolor (10 cases, 12.5%) and candidiasis (6 cases, 7.5%). Intertrigo lesions with dermatophytic agents significantly were observed in groin in comparison to different infections among body sites (P<0.05). Itching was the most common clinical presentation (57 cases, 71.3%) and also significant association between different infections and clinical manifestations were observed (P<0.05). Conclusion: Different clinical manifestations may be observed in infectious intertrigo. Regarding the significant association observed in this study, some clinical features can be used for presumptive diagnosis of diseases but further studies are required to make it clear.
Models, movements, and minds: bridging the gap between decision making and action

Decision making is a fundamental cognitive function, which not only determines our day‐to‐day choices but also shapes the trajectories of our movements, our lives, and our societies. While immense progress has been made in recent years on our understanding of the mechanisms underlying decision making, research on this topic is still largely split into two halves. Good‐based models largely state that decisions are made between representations of abstract value associated with available options; while action‐based models largely state that decisions are made at the level of action representations. These models are further divided between those that state that a decision is made before an action is specified, and those that regard decision making as an evolving process that continues until movement completion. Here, we review computational models, behavioral findings, and results from neural recordings associated with these frameworks. In synthesizing this literature, we submit that decision making is best understood as a continuous, graded, and distributed process that traverses a landscape of behaviorally relevant options, from their presentation until movement completion. Identifying and understanding the intimate links between decision making and action processing has important implications for the study of complex, goal‐directed behaviors such as social communication, and for elucidating the underlying mechanisms by which decisions are formed.
Evidence in focus: Nusinersen use in spinal muscular atrophy

Objective To identify the level of evidence for use of nusinersen to treat spinal muscular atrophy (SMA) and review clinical considerations regarding use. Methods The author panel systematically reviewed nusinersen clinical trials for patients with SMA and assigned level of evidence statements based on the American Academy of Neurology's 2017 therapeutic classification of evidence scheme. Safety information, regulatory decisions, and clinical context were also reviewed. Results Four published clinical trials were identified, 3 of which were rated above Class IV. There is Class III evidence that in infants with homozygous deletions or mutations of SMN1, nusinersen improves the probability of permanent ventilation-free survival at 24 months vs a well-defined historical cohort. There is Class I evidence that in term infants with SMA and 2 copies of SMN2, treatment with nusinersen started in individuals younger than 7 months results in a better motor milestone response and higher rates of event-free survival than sham control. There is Class I evidence that in children aged 2–12 years with SMA symptom onset after 6 months of age, nusinersen results in greater improvement in motor function at 15 months than sham control. Nusinersen was safe and well-tolerated. Clinical context Evidence of efficacy is currently highest for treatment of infantile- and childhood-onset SMA in the early and middle symptomatic phases. While approved indications for nusinersen use in North America and Europe are broad, payer coverage for populations outside those in clinical trials remain variable. Evidence, availability, cost, and patient preferences all influence decision-making regarding nusinersen use.
Suppression of testosterone production by nanoparticulate TiO2 is associated with ERK1/2–PKA–PKC signaling pathways in rat primary cultured Leydig cells

Background Nanoparticulate titanium dioxide (nano-TiO2) enters the body through various routes and causes organ damage. Exposure to nano-TiO2 is reported to cause testicular injury in mice or rats and decrease testosterone synthesis, sperm number, and motility. Importantly, nano-TiO2 suppresses testosterone production by Leydig cells (LCs) and impairs the reproductive capacity of animals. Methods In an attempt to establish the molecular mechanisms underlying the inhibitory effect of nano-TiO2 on testosterone synthesis, primary cultured rat LCs were exposed to varying concentrations of nano-TiO2 (0, 10, 20, and 40 µg/mL) for 24 hours, and alterations in cell viability, cell injury, testosterone production, testosterone-related factors (StAR, 3βHSD, P450scc, SR-BI, and DAX1), and signaling molecules (ERK1/2, PKA, and PKC) were investigated. Results The data show that nano-TiO2 crosses the membrane into the cytoplasm or nucleus, triggering cellular vacuolization and nuclear condensation. LC viability decreased in a time-dependent manner at the same nano-TiO2 concentration, nano-TiO2 treatment (10, 20, and 40 µg/mL) decreased MMP (36.13%, 45.26%, and 79.63%), testosterone levels (11.40% and 44.93%), StAR (14.7%, 44.11%, and 72.05%), 3βHSD (26.56%, 50%, and 79.69%), pERK1/2 (27.83%, 63.61%, and 78.89%), PKA (47.26%, 70.54%, and 85.61%), PKC (30%, 50%, and 71%), SR-BI (16.41%, 41.79%, and 67.16%), and P450scc (39.41%, 55.26%, and 86.84%), and upregulated DAX1 (1.31-, 1.63-, and 3.18-fold) in primary cultured rat LCs. Conclusion Our collective findings indicated that nano-TiO2-mediated suppression of testosterone in LCs was associated with regulation of ERK1/2–PKA–PKC signaling pathways.
Maternal age at menarche and pubertal development in sons and daughters: a Nationwide Cohort Study

STUDY QUESTION Is maternal age at menarche associated with pubertal development in sons and daughters? SUMMARY ANSWER Maternal age at menarche was associated with pubertal development in both sons and daughters. WHAT IS KNOWN ALREADY Studies have shown that age at menarche is greatly inherited from mother to daughter, but it remains largely unknown to what extent age at menarche in mothers is associated with timing of puberty in sons. STUDY DESIGN, SIZE, DURATION In this population-based study we used data from the Puberty Cohort nested within the Danish National Birth Cohort. Live-born singletons aged 11 were followed from 2012 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 15 822 children (7697 sons and 8125 daughters) gave half-yearly information on puberty from the age of 11 years until full sexual maturity or 18 years of age through self-administrated questionnaires (participation rate 71%). Information on maternal age at menarche was reported by the mothers during pregnancy. Maternal age at menarche was used both as a continuous and as a categorical variable (earlier, same time or later than peers). A multivariable regression model for interval-censored data was used. MAIN RESULTS AND THE ROLE OF CHANCE Maternal age at menarche was positively associated with timing of genital development, pubic hair development, first ejaculation of semen, voice break, axillary hair development and acne in sons, and with timing of breast development, pubic hair development, menarche, axillary hair development and acne in daughters. In sons, the associations were of similar strength for all pubertal markers, whereas in daughters, the associations were strongest for breast development and menarche. LIMITATIONS, REASONS FOR CAUTION Age at menarche was recalled during pregnancy. However, studies indicate that age at menarche is recalled moderately in adulthood. Information on puberty was self-reported, but inaccuracy of data would probably cause non-differential misclassification. WIDER IMPLICATIONS OF THE FINDINGS Early maternal age at menarche was associated with earlier pubertal development, and late maternal age at menarche was associated with later pubertal development in both sons and daughters. The largest effect-estimates were for the associations between maternal age at menarche and the daughters' age at menarche and age at breast development. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the Danish Council for Independent Research (4183-00152). There are no competing interests. TRIAL REGISTERATION NUMBER N/A.
The role of COMT gene Val108/158Met polymorphism in suicidal behavior: systematic review and updated meta-analysis

Background It is accepted that there is a genetic factor that influences the risk of suicidal behavior. The catechol-O-methyltransferase (COMT) gene, especially the Val108/158Met polymorphism, has been associated with suicide; however, no conclusive outcome has been attained. Therefore, the aim of the present study was to assess the role of COMT Val108/158Met in suicidal behavior throughout an updated meta-analysis. Methods We performed an online search using PubMed and Web of Science (up to March 2017). Our systematic review included case-control studies of individuals who attempted suicide and completed suicide. We tested allelic, homozygous, heterozygous, dominant, and recessive inheritance models. The meta-analysis was performed in accordance with the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results The meta-analysis comprised 17 studies, which included 3,282 cases and 3,774 controls, and showed that when evaluating the overall population, the Val108/158Met polymorphism of COMT was not associated with suicidal behavior in any of the inheritance models; however, the subanalyses showed that this polymorphism exhibits a risk factor in males and a protective effect in females. Additionally, it conveyed a risk factor in Asian populations when using the allelic (OR 1.25; CI: 1.04–1.51) and recessive models (OR 1.32; CI: 1.03–1.68). Conclusion Our updated meta-analysis suggests a possible association between COMT Val108/158Met and suicidal behavior in Asian populations. However, in view of the small number of studies, these results should be considered exploratory. We recommend that more studies be performed with larger samples.