Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage

Background: Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a devastating neurological condition with a high risk of associated morbidity and mortality. Inflammation has been shown to increase the risk of complications associated with aSAH such as vasospasm and brain injury in animal models and humans. The goal of this review is to discuss the inflammatory mechanisms of aneurysm formation, rupture and vasospasm and explore the role of sex hormones in the inflammatory response to aSAH. Methods: A literature review was performed using PubMed using the following search terms: “intracranial aneurysm,” “cerebral aneurysm,” “dihydroepiandrosterone sulfate” “estrogen,” “hormone replacement therapy,” “inflammation,” “oral contraceptive,” “progesterone,” “sex steroids,” “sex hormones” “subarachnoid hemorrhage,” “testosterone. ” Only studies published in English language were included in the review. Results: Studies have shown that administration of sex hormones such as progesterone and estrogen at early stages in the inflammatory cascade can lower the risk and magnitude of subsequent complications. The exact mechanism by which these hormones act on the brain, as well as their role in the inflammatory cascade is not fully understood. Moreover, conflicting results have been published on the effect of hormone replacement therapy in humans. This review will scrutinize the variations in these studies to provide a more detailed understanding of sex hormones as potential therapeutic agents for intracranial aneurysms and aSAH. Conclusion: Inflammation may play a role in the pathogenesis of intracranial aneurysm formation and subarachnoid hemorrhage, and administration of sex hormones as anti-inflammatory agents has been associated with improved functional outcome in experimental models. Further studies are needed to determine the therapeutic role of these hormones in the intracranial aneurysms and aSAH.
The other side of the coin: Hypersociability

Affiliative social motivation and behavior, that is, sociability that includes attachment, prosocial behavior (sharing, caring and helping) and empathy (the ability to understand and share the feelings of others), has high variability in the human population, with a portion of people outside of the normal range. While psychiatric disorders and autism spectrum disorders are typically associated with a deficit in social behavior, the opposite trait of hypersociability and indiscriminate friendliness are exhibited by individual with specific neurodevelopmental disorders and following early adverse care. Here we discuss both genetic and environmental factors that cause or increase the risk for developing pathological hypersociability from human to rodent models.
The Effects of Progressive Resistance Exercise on Recovery Rate of Bone and Muscle in a Rodent Model of Hindlimb Suspension

Purpose: This study aimed to examine the exercise-mediated musculoskeletal recovery following hindlimb suspension (HS) in order to identify whether bone modeling and muscle hypertrophy would eventuate in a synchronized manner during recovery stage. Methods: To identify whether 2-week HS would be sufficient to induce a significant reduction of physiological indices in both tibia and adjacent hindlimb muscles, a total of 20 rats was randomized into 2-week HS (n = 10) and age-matched control group (n = 10, CON). Another batch of rats were randomly assigned to three different groups to identify recovery intervention effects following suspension: (1) 2-week HS followed by 4-week spontaneous reloading recovery (HRE, n = 7). (2) 2-week HS followed by 4-week progressive resistance ladder climbing exercise (HEX, n = 7). (3) Age-matched control (CON, n = 7). DXA, micro-CT, and 18F-sodium fluoride (NaF) imaging, and EIA analysis were utilized to measure tibia bone indices. Hindlimb muscle wet weight and grip strength were measured to evaluate muscle mass and strength, respectively. Results: In study 1, bone quality values [bone volume/total volume (BV/TV): -27%, areal bone mineral density (aBMD): -23%, mineral contents: -7.9%, mineral density: –4.1%, and bone density: -38.9%] and skeletal muscle weight (soleus: -46.8%, gastrocnemius: -19.6%, plantaris: -20.8%, TA: -22.8%, and EDL: -9.9%) were significantly lower in HS group compared to CON group. In study 2, micro-CT and DXA-based bone morphology (bone density, BT/TV, and aBMD) were fully recovered in HRE or HEX group. However, suspension-induced dysregulation of bone mineral metabolism was returned to age-matched control group in only HEX group, but not in HRE group. A greater level of biomarkers of bone formation (P1NF) and resorption (CTX-1) was observed in only HRE group compared to CON. The hindlimb skeletal muscle mass was significantly lower in both HRE and HEX groups compared to CON group. Hindlimb grip strength was the greatest in HEX group, followed by CON and HRE groups. Conclusion: Following HS, progressive resistance exercise promotes recovery rates of bone and skeletal muscle strength without a significant increase in muscular mass, suggesting that exercise-induced reacquisition of bone and muscle strength is independent of muscle hypertrophy during early recovery stage.
CCR7 defines a precursor for murine iNKT cells in thymus and periphery

The precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets within the thymus. Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from the thymus in a Klf2 dependent manner, and undergo further maturation after reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector subsets and localization to the medulla. Parabiosis and intra-thymic transfer showed that thymic NKT1 and NKT17 were resident—they were not derived from and did not contribute to the peripheral pool. Finally, each thymic iNKT effector subset produces distinct factors that influence T cell development. Our findings demonstrate how the thymus is both a source of iNKT progenitors and a unique site of tissue dependent effector cell differentiation.
Sleep, nutrition, and physical activity interventions to prevent obesity in infancy: follow-up of the Prevention of Overweight in Infancy (POI) randomized controlled trial at ages 3.5 and 5 y.

Background Our Prevention of Overweight in Infancy (POI) study suggested that a brief sleep intervention in infancy reduced the risk of obesity at age 2 y. In contrast, we observed no benefit from the nutrition and activity intervention. Objective The objective of the study was to determine how these interventions influenced growth at ages 3.5 and 5 y compared with usual care (Control). Design A follow-up of a parallel, 4-arm, single-blind, 2-y, randomized controlled trial in 802 women (86% European, 48% primiparous) recruited in pregnancy (58% response rate) was undertaken. All groups received standard Well-Child care with additional support for 3 intervention groups: FAB (promotion of breastfeeding, healthy eating, physical activity: 8 contacts, antenatal, 18 mo); Sleep (prevention of sleep problems: antenatal, 3 wk); Combination (both interventions). Follow-up measures were collected by staff blinded to group allocation. The primary outcome was child body mass index (BMI) z score, and secondary outcomes were prevalence of obesity (BMI ≥95th percentile), self-regulation (psychological measures), sleep, physical activity (accelerometry, questionnaires), and dietary intake (food-frequency questionnaire). Analyses were conducted through the use of multiple imputation. Results Retention was 77% at age 3.5 y and 69% at age 5 y. Children in the FAB group had significantly higher BMI z scores than did Controls at age 5 y (adjusted difference: 0.25; 95% CI: 0.04, 0.47) but not at age 3.5 y (0.15; 95% CI: -0.04, 0.34). Children who received the Sleep intervention (Sleep and Combination groups) had significantly lower BMI z scores at age 3.5 y (-0.24; 95% CI: -0.38, -0.10) and at age 5 y (-0.23; 95% CI: -0.38, -0.07) than children who did not (Control and FAB groups). Conclusions A conventional intervention had unexpected adverse long-term weight outcomes, whereas positive outcomes from a less conventional sleep intervention remained promising at age 5 y. More intensive or extended sleep intervention might have larger or longer-lasting effects and should be investigated. This trial was registered at clinicaltrials.gov as NCT00892983.
Ulinastatin Ameliorates Pulmonary Capillary Endothelial Permeability Induced by Sepsis Through Protection of Tight Junctions via Inhibition of TNF-α and Related Pathways

Background: Increased permeability of pulmonary capillary is a common consequence of sepsis that leads to acute lung injury. In this connection, ulinastatin, a urinary trypsin inhibitor (UTI), is used clinically to mitigate pulmonary edema caused by sepsis. However, the underlying mechanism of UTI in alleviating sepsis-associated pulmonary edema remains to be fully elucidated. As tight junctions (TJs) between the pulmonary microvascular endothelial cells (PMVECs) play a pivotal role in the permeability of pulmonary capillary, this study investigated the effect of UTI on expression of junctional proteins in PMVECs during sepsis. Methods: Male adult Sprague Dawley rats were subjected to cecal ligation and puncture (CLP) and divided into sham, CLP, and UTI+CLP groups. UTI was administered every 8 h for 3 days before CLP. At 48 h after surgery, Evans blue (EB) was administered to evaluate the pulmonary vascular leakage. Histological staining was used for evaluation of lung injury score. Using immunofluorescence staining and Western blot, the expression of junctional proteins (occludin, claudin-5, and ZO-1) in pulmonary endothelia was assessed. In vitro, PMVECs were divided into control, lipopolysaccharide (LPS), and UTI+LPS groups for examination of expression of junctional proteins and TNF-α as well as inhibitor of NF-κB (IκB), p38 mitogen-activated protein kinases (p38 MAPKs), c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs) signaling pathways. Additionally, the expression of various junctional proteins was determined in PMVECs of control, LPS, and TNF-α receptor antagonist-LPS groups. PMVECs were also treated with TNF-α and TNF-α receptor antagonist and the expression of various junctional proteins was assessed. Results: Compared with the CLP group, UTI markedly decreased EB leakage and lung injury score. The expression of occludin, claudin-5, and ZO-1 was decreased in both CLP rats and LPS-treated PMVECs, but it was reversed by UTI and TNF-α receptor antagonist. TNF-α expression was vigorously elevated in the lung of CLP rats and in LPS-challenged PMVECs, which were suppressed by UTI. In addition, TNF-α also reduced occludin, claudin-5, and ZO-1 expression in PMVECs, but these effects of TNF-α were antagonized by pretreatment with TNF-α receptor antagonist. Furthermore, UTI inhibited LPS-induced activation of NF-κB and mitogen-activated protein kinases (MAPKs) pathways in PMVECs. Conclusion: UTI effectively protects TJs and helps to attenuate the permeability of pulmonary capillary endothelial cells during sepsis through inhibiting NF-κB and MAPKs signal pathways and TNF-α expression.
Collective irregular dynamics in balanced networks of leaky integrate-and-fire neurons

Abstract We extensively explore networks of weakly unbalanced, leaky integrate-and-fire (LIF) neurons for different coupling strength, connectivity, and by varying the degree of refractoriness, as well as the delay in the spike transmission. We find that the neural network does not only exhibit a microscopic (single-neuron) stochastic-like evolution, but also a collective irregular dynamics (CID). Our analysis is based on the computation of a suitable order parameter, typically used to characterize synchronization phenomena and on a detailed scaling analysis (i.e. simulations of different network sizes). As a result, we can conclude that CID is a true thermodynamic phase, intrinsically different from the standard asynchronous regime.
Cangrelor for the treatment of patients with Arterial Thrombosis

ABSTRACT Introduction: All oral P2Y12 receptor blockers are associated with some degree of delayed onset and offset of pharmacodynamic (PD) effects in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Although intravenous glycoprotein IIb/IIIa inhibitors are associated with rapid onset of action, they are also associated with delayed offset and other limitations such as elevated bleeding risk and thrombocytopenia. Areas covered: In this review, the authors focus on cangrelor, an intravenous, reversible P2Y12 receptor blocker with fast onset and offset of effects. The authors also describe the pharmacologic effects of cangrelor and its pharmacologic interaction with other P2Y12 receptor inhibitors. Finally, the authors discuss the large-scale clinical trials that compared the efficacy and safety of cangrelor with clopidogrel. Expert opinion: In ACS patients undergoing PCI, cangrelor is most desirable to effectively prevent periprocedural ischemic events and to avoid excessive bleeding. Indeed, any high-risk patient with ST-segment elevation myocardial infraction or patient who is unable to take oral medications is a potential candidate for intravenous cangrelor therapy. Furthermore, stable patients with coronary artery disease, who are considered for ad hoc PCI following coronary angiography, may be considered for treatment with cangrelor to reduce post-PCI thrombotic events.
How Does Eye Movement Desensitization and Reprocessing Therapy Work? A Systematic Review on Suggested Mechanisms of Action

Background: Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy. The high prevalence of EMDR in clinical practice and the dramatic increase in EMDR research in recent years, with more than 26 randomized controlled trials published to date, highlight the need for a better understanding of its mechanism of action. Methods: We conducted a thorough systematic search of studies published until January 2018, using PubMed, ScienceDirect, Web of Knowledge and Scopus databases that examined the mechanism of action of EMDR or provided conclusions within the framework of current theoretical models of EMDR functioning. Results: Eighty-seven studies were selected for review and classified into three overarching models; (i) psychological models (ii) psychophysiological models and (iii) neurobiological models. The evidence available from each study was analyzed and discussed. Results demonstrated a reasonable empirical support for the working memory hypothesis and for the physiological changes associated with successful EMDR therapy. Recently, more sophisticated structural and functional neuroimaging studies using high resolution structural and temporal techniques are starting to provide preliminary evidence into the neuronal correlates before, during and after EMDR therapy. Discussion: Despite the increasing number of studies that published in recent years, the research into the mechanisms underlying EMDR therapy is still in its infancy. Studies in well-defined clinical and non-clinical populations, larger sample sizes and tighter methodological control are further needed in order to establish firm conclusions.
A Comparative Analysis of Tooth Size Discrepancy between Male and Female Subjects Presenting with a Class I Malocclusion

Objectives To evaluate the tooth size discrepancy and Bolton's ratios between male and female subjects with a Class I malocclusion. Materials and Methods The digital e-models of 100 male and 100 female 12-year-old southern Chinese children with a Class I malocclusion were selected. The mesiodistal widths from permanent first molar to the contralateral side first molar of the upper and lower dentitions were measured. Differences between the tooth size discrepancy, together with the anterior and overall Bolton's ratios between male and female subjects, were assessed using a two-sample t-test. A paired t-test was used to determine differences between antimetric pairs of teeth within the same arch. Results Females had statistically significant smaller teeth than males (P < 0.05) except the upper left and lower left lateral incisor and lower left and right central incisors. The mean values of anterior Bolton's ratios for males and females were 77.04 and 77.03, respectively (P > 0.05), while the mean values of overall Bolton's ratios of male and female are 90.48 and 90.65, respectively (P < 0.05). The clinical significant differences (Cohen's d > 0.2) for contralateral tooth size were shown on the maxillary canines, lateral incisors, and central incisors of males; and mandibular canines and lateral incisors of females. Conclusions Southern Chinese females presenting with Class I malocclusions have smaller mesiodistal tooth dimensions compared to males. Both males and females presented several tooth size asymmetries. There are no statistical differences in anterior and overall Bolton's ratios between the genders.
Continuous Authentication of Smartphones Based on Application Usage

An empirical investigation of active/continuous authentication for smartphones is presented by exploiting users’ unique application usage data, i.e., distinct patterns of use, modeled by a Markovian process. Specifically, variations of hidden Markov models (HMMs) are evaluated for continuous user verification, and challenges due to the sparsity of session-wise data, an explosion of states, and handling unforeseen events in the test data are tackled. Unlike traditional approaches, the proposed formulation utilizes the complete app-usage information to achieve low latency. Through experimentation, empirical assessment of the impact of unforeseen events, i.e., unknown applications and unforeseen observations, on user verification is done via a modified edit-distance algorithm for sequence matching. It is found that for enhanced verification performance, unforeseen events should be considered. For validation, extensive experiments on two distinct datasets, namely, UMDAA-02 and Securacy, are performed. Using the marginally smoothed HMM a low equal error rate (EER) of 16.16% is reached for the Securacy dataset and the same method is found to be able to detect an intrusion within ~2.5 min of application use.
The neurocognitive correlates of academic diligence in adolescent girls

ABSTRACT Academic diligence is the ability to regulate behavior in the service of goals, and a predictor of educational attainment. Here we combined behavioral, structural MRI, functional MRI and connectivity data to investigate the neurocognitive correlates of diligence. We assessed whether individual differences in diligence are related to the interplay between frontal control and striatal reward systems, as predicted by the dual-systems hypothesis of adolescent development. We obtained behavioral measures of diligence from 40 adolescent girls (aged 14-15 years) using the Academic Diligence Task. We collected structural imaging data for each participant, as well as functional imaging data during an emotional go-no-go self-control task. As predicted by the dual-systems hypothesis, we found that inferior frontal activation and gyrification correlated with academic diligence. However, neither striatal activation nor structure, nor fronto-striatal connectivity, showed clear associations with diligence. Instead, we found prominent activation of temporal areas during the go-no-go task. This suggests that academic diligence is associated with an extended network of brain regions.
Advances in risk stratification of bladder cancer to guide personalized medicine

Bladder cancer is a heterogeneous disease that poses unique challenges to the treating clinician. It can be limited to a relatively indolent papillary tumor with low potential for progression beyond this stage to muscle-invasive disease prone to distant metastasis. The former is best treated as conservatively as possible, whereas the latter requires aggressive surgical intervention with adjuvant therapies in order to provide the best clinical outcomes. Risk stratification traditionally uses clinicopathologic features of the disease to provide prognostic information that assists in choosing the best therapy for each individual patient. For bladder cancer, this informs decisions regarding the type of intravesical therapy that is most appropriate for non-muscle-invasive disease or whether or not to administer neoadjuvant chemotherapy prior to radical cystectomy. More recently, tumor genetic sequencing data have been married to clinical outcomes data to add further sophistication and personalization. In the next generation of risk classification, we are likely to see the inclusion of molecular subtyping with specific treatment considerations based on a tumor’s mutational profile.
Who Falls for Online Political Manipulation?

Social media, once hailed as a vehicle for democratization and the promotion of positive social change across the globe, are under attack for becoming a tool of political manipulation and spread of disinformation. A case in point is the alleged use of trolls by Russia to spread malicious content in Western elections. This paper examines the Russian interference campaign in the 2016 US presidential election on Twitter. Our aim is twofold: first, we test whether predicting users who spread trolls’ content is feasible in order to gain insight on how to contain their influence in the future; second, we identify features that are most predictive of users who either intentionally or unintentionally play a vital role in spreading this malicious content. We collected a dataset with over 43 million election-related posts shared on Twitter between September 16 and November 9, 2016, by about 5.7 million users. This dataset includes accounts associated with the Russian trolls identified by the US Congress. Proposed models are able to very accurately identify users who spread the trolls’ content (average AUC score of 96%, using 10-fold validation). We show that political ideology, bot likelihood scores, and some activity-related account meta data are the most predictive features of whether a user spreads trolls’ content or not.