Miracle-dz/UniFAR-FTUs huggingface dataset:
c-Jun N-terminal kinase inhibition attenuates early brain injury induced neuronal apoptosis via decreasing p53 phosphorylation and mitochondrial apoptotic pathway activation in subarachnoid hemorrhage rats

Early brain injury (EBI)-induced neuronal apoptosis is primarily responsible for the subsequent complications of aneurysmal subarachnoid hemorrhage (aSAH), which may increase the risk of mortality in patients with aSAH. c-Jun N-terminal kinase (JNK) has been demonstrated to be a promoter of EBI-induced cell apoptosis, although the mechanism has yet to be fully elucidated. The present study aimed to explore whether the role of JNK1 is associated with tumor protein p53 (p53), which is one of the most important factor that triggers cell apoptosis. JNK1 expression was downregulated via in vivo small interfering RNA transfection in an aSAH rat model in order to assess differences in the behavior, survival times, morphology and genetics of the experimental animals. The results revealed that JNK1 inhibition improved the neurological scores and survival times of SAH rats by interrupting cascaded neuronal apoptosis. The interruption of EBI-induced neuronal apoptosis may originate from a decrease in the level of p53 phosphorylation and deactivation of the downstream mitochondrial apoptotic pathway. Taken together, these results suggest that JNK1 may be a promising target for improving the prognosis of patients with aSAH.
Comparison of Two Approaches for Preemptive Traffic Light Control

By implementing preemptive traffic light control systems in urban areas it is possible to reduce the travel time of specific groups of vehicles such as emergency vehicles. In this paper, two approaches for preemptive traffic light control are compared by applying a microscopic simulation model. The first approach uses fixed values of vehicle arrival time and queue lengths thresholds while the second is fuzzy logic based and hence more adaptive. Both approaches are tested in six different scenarios with an use case consisting of a simulated isolated intersection based on real traffic data. Analysis of the results shows that the travel time of emergency vehicles can be reduced by up to 24 % in heavily congested conditions with a slight edge given to the fuzzy logic based approach. Both approaches show negligible negative effects on the total travel times of all vehicles in the network.
The developmental neural substrates of item and serial order components of verbal working memory

Behavioral and developmental studies have made a critical distinction between item and serial order processing components of verbal working memory (WM). This functional magnetic resonance imaging (fMRI) study determined the extent to which item and serial order WM components are characterized by specialized neural networks already in young children or whether this specialization emerges at a later developmental stage. Total of 59 children aged 7–12 years performed item and serial order short‐term probe recognition tasks in an fMRI experiment. While a left frontoparietal network was recruited in both item and serial order WM conditions, the right intraparietal sulcus was selectively involved in the serial order WM condition. This neural segregation was modulated by age, with both networks becoming increasingly separated in older children. Our results indicate a progressive specialization of networks involved in item and order WM processes during cognitive development.
A Deep Spatiotemporal Perspective for Understanding Crowd Behavior

Understanding crowd behavior is a pivotal step toward urban scene analysis. This is considered a very challenging task and has rarely been addressed to date due to the complexity of motion dynamics co-occurring across a given scene, which involves spatial and temporal dependencies. Unlike the mainstream research, which usually treats the temporal and spatial dependencies in a crowd separately, this paper presents a deep end-to-end approach that jointly considers the spatiotemporal information, leading to a rich understanding of crowd behavior. We first extract the displacement information describing crowd motion patterns from tracklets/trajectories. This information is subsequently fed into a convolutional layer to learn the underlying motion patterns and create high-level representations. The derived representations are used as inputs to a long short-term memory-based architecture to learn the underlying spatiotemporal cues in a single operation for the entire crowd in a given scene. We evaluate our approach on a widely used, large-scale benchmark datasets for three critical applications: pedestrian path forecasting, destination estimation, and holistic crowd behavior classification. The results show a drastic improvement compared to recently trending works.
Back to the future? Late Holocene marine food web structure in a warm climatic phase as a predictor of trophodynamics in a warmer South‐Western Atlantic Ocean

Stable carbon and nitrogen isotope ratios in the skeletal elements of both ancient and modern marine species from the Beagle Channel were used to compare the structure of Late Holocene and modern food webs, and predict potential changes as a result of a Sea Surface Temperature (SST) increase in the region. Complementary, ancient and modern shells of limpets and mussels were isotopically analysed to explore changes in the isotopic baseline and compare marine food webs through time after an appropriate correction for baseline shifts. Results confirmed a declining pattern of marine primary productivity during the Late Holocene in the Beagle Channel. In general, the isotopic niches overlapped largely in the ancient food web in comparison to the current marine one, with the exception of that of cormorants (Phalacrocorax sp.). Our data suggest that all the species that have undergone intense human exploitation (Arctocephalus australis, Otaria flavescens and Merluccius sp.) significantly increased their trophic levels. The most important finding of this work was the very high isotopic overlap between snoek (Thyrsites atun) and hake (Merluccius sp.) during the Late Holocene. Increasing SST as a result of global warming could favour the recolonization of the southern South‐Western Atlantic Ocean by snoek from the South‐Eastern Pacific Ocean, with a potential impact on the landings of the economically important Argentine and Austral hake. These findings highlight the relevance of using zooarchaeological remains for providing predictions about marine food webs changes in the near future.
Behavior of swine hosted in facilities with different construction typologies

The aim of this study was to analyze the behavior of pigs housed in facilities with different building typologies in terms of the floor and partitions. Two treatments were compared: a pen containing an area with a depth of water, and a pen floor with leaked on the sides. Data on swine behavior were collected over seven days, and the pigs’ positions (standing, sitting, and lying down) and activities (eating, drinking, digging, interacting, walking and idling) were observed for five animals in each pen. Data were collected via visual measurement every 10 minutes and an ethogram was constructed. Measurements of environmental data were taken (dry bulb temperature, globe temperature and relative humidity), and were used to calculate the black globe temperature and humidity index. Although the pens showed differences in terms of the dry bulb temperature, this temperature can be considered thermoneutral for creation in the growth and termination phases. Animals housed in the pens with an area of water depth stood for longer, possibly due to the environmental enrichment caused by the presence of the water slide.
Effect of Dual Use of Veterans Affairs and Medicare Part D Drug Benefits on Antihypertensive Medication Supply in a National Cohort of Veterans with Dementia

OBJECTIVE To evaluate the effect of dual use of VA/Medicare Part D drug benefits on antihypertensive medication supply in older Veterans with dementia. DATA SOURCES/STUDY SETTING National, linked 2007-2010 Veterans Affairs (VA) and Medicare utilization and prescription records for 50,763 dementia patients with hypertension. STUDY DESIGN We used inverse probability of treatment (IPT)-weighted multinomial logistic regression to examine the association of dual prescription use with undersupply and oversupply of antihypertensives. DATA COLLECTION/EXTRACTION METHODS Veterans Affairs and Part D prescription records were used to classify patients as VA-only, Part D-only, or dual VA/Part D users of antihypertensives and summarize their antihypertensive medication supply in 2010: (1) appropriate supply of all prescribed antihypertensive classes, (2) undersupply of ≥1 class with no oversupply of another class, (3) oversupply of ≥1 class with no undersupply, or (4) both undersupply and oversupply. PRINCIPAL FINDINGS Dual prescription users were more likely than VA-only users to have undersupply only (aOR = 1.28; 95 percent CI = 1.18-1.39), oversupply only (aOR = 2.38; 95 percent CI = 2.15-2.64), and concurrent under- and oversupply (aOR = 2.89; 95 percent CI = 2.53-3.29), versus appropriate supply of all classes. CONCLUSIONS Obtaining antihypertensives through both VA and Part D was associated with increased antihypertensive under- and oversupply. Efforts to understand how best to coordinate dual-system prescription use are critically needed.
Special aspects of biologics treatment in psoriasis: management in pregnancy, lactation, surgery, renal impairment, hepatitis and tuberculosis

Abstract Background of the article: Biologics are modern immunomodulatory drugs, whose use in the treatment of psoriasis has led to remarkable results in psoriatic patients. The administration of these agents in special population groups, such as patients with chronic infections and renal impairment, as well as perioperative, pregnant or lactating patients, has not been thoroughly addressed, mostly because these patients are excluded from clinical studies. Materials and methods: This report is an updated systematic overview of the use of biologics in the above-mentioned types of patients and was conducted according to the PRISMA Guidelines for systematic reviews. Articles derived from the databases PubMed, EMBASE and SCOPUS, published between 1999 and 2018, were analyzed for the study. Results: Research efforts as well as clinical reporting are necessary in order to provide more insight on the management of these therapeutic dilemmas. Conclusion: The aim of this review, other than providing a summarized update on the clinical knowledge on this special topic, is also to raise awareness for the need to conduct larger systematic studies in order to adequately evaluate the use of biologics in these special patient categories and therefore draw definite conclusions on their safety profile.
Safety Velocity Tracking Control for an Omnidirectional Rehabilitative Training Walker with Uncertainty

In this study, a new nonlinear trajectory tracking method with safety velocity constraints is proposed for omnidirectional rehabilitative training walker. The controller with safety velocity performance is formulated by considering the uncertain variable parameters based on an estimator. According to robust control technique and Lyapunov theory, the safety velocity controller can be designed to maintain stability in terms of solutions of linear matrix inequalities. The sufficient condition for the existence of such a controller with safety velocity constraints performance is derived. As an application, simulation results confirm the effectiveness of the proposed method and verify that the walker can provide safe training velocity.
Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling

Complement activation is involved in the pathogenesis of ischemia reperfusion injury (IRI), which is an inevitable process during kidney transplantation. Therefore, complement-targeted therapeutics hold great potential in protecting the allografts from IRI. We observed universal deposition of C3d and membrane attack complex in human renal allografts with delayed graft function or biopsy-proved rejection, which confirmed the involvement of complement in IRI. Using FB-, C3-, C4-, C5-, C5aR1-, C5aR2-, and C6-deficient mice, we found that all components, except C5aR2 deficiency, significantly alleviated renal IRI to varying degrees. These gene deficiencies reduced local (deposition of C3d and membrane attack complex) and systemic (serum levels of C3a and C5a) complement activation, attenuated pathological damage, suppressed apoptosis, and restored the levels of multiple local cytokines (e.g., reduced IL-1β, IL-9, and IL-12p40 and increased IL-4, IL-5, IL-10, and IL-13) in various gene-deficient mice, which resulted in the eventual recovery of renal function. In addition, we demonstrated that CRIg/FH, which is a targeted complement inhibitor for the classical and primarily alternative pathways, exerted a robust renoprotective effect that was comparable to gene deficiency using similar mechanisms. Further, we revealed that PI3K/AKT activation, predominantly in glomeruli that was remarkably inhibited by IRI, played an essential role in the CRIg/FH renoprotective effect. The specific PI3K antagonist duvelisib almost completely abrogated AKT phosphorylation, thus abolishing the renoprotective role of CRIg/FH. Our findings suggested that complement activation at multiple stages induced renal IRI, and CRIg/FH and/or PI3K/AKT agonists may hold the potential in ameliorating renal IRI.
Functional Heterogeneity of CD4+ Tumor-Infiltrating Lymphocytes With a Resident Memory Phenotype in NSCLC

Resident memory T cells (TRM) inhabit peripheral tissues and are critical for protection against localized infections. Recently, it has become evident that CD103+ TRM are not only important in combating secondary infections, but also for the elimination of tumor cells. In several solid cancers, intratumoral CD103+CD8+ tumor infiltrating lymphocytes (TILs), with TRM properties, are a positive prognostic marker. To better understand the role of TRM in tumors, we performed a detailed characterization of CD8+ and CD4+ TIL phenotype and functional properties in non-small cell lung cancer (NSCLC). Frequencies of CD8+ and CD4+ T cell infiltrates in tumors were comparable, but we observed a sharp contrast in TRM ratios compared to surrounding lung tissue. The majority of both CD4+ and CD8+ TILs expressed CD69 and a subset also expressed CD103, both hallmarks of TRM. While CD103+CD8+ T cells were enriched in tumors, CD103+CD4+ T cell frequencies were decreased compared to surrounding lung tissue. Furthermore, CD103+CD4+ and CD103+CD8+ TILs showed multiple characteristics of TRM, such as elevated expression of CXCR6 and CD49a, and decreased expression of T-bet and Eomes. In line with the immunomodulatory role of the tumor microenvironment, CD8+ and CD4+ TILs expressed high levels of inhibitory receptors 2B4, CTLA-4, and PD-1, with the highest levels found on CD103+ TILs. Strikingly, CD103+CD4+ TILs were the most potent producers of TNF-α and IFN-γ, while other TIL subsets lacked such cytokine production. Whereas, CD103+CD4+PD-1low TILs produced the most effector cytokines, CD103+CD4+PD-1++ and CD69+CD4+PD-1++ TILs produced CXCL13. Furthermore, a large proportion of TILs expressed co-stimulatory receptors CD27 and CD28, unlike lung TRM, suggesting a less differentiated phenotype. Agonistic triggering of these receptors improved cytokine production of CD103+CD4+ and CD69+CD8+ TILs. Our findings thus provide a rationale to target CD103+CD4+ TILs and add co-stimulation to current therapies to improve the efficacy of immunotherapies and cancer vaccines.
Crystallographic and Computational Characterization of Methyl Tetrel Bonding in S-Adenosylmethionine-Dependent Methyltransferases

Tetrel bonds represent a category of non-bonding interaction wherein an electronegative atom donates a lone pair of electrons into the sigma antibonding orbital of an atom in the carbon group of the periodic table. Prior computational studies have implicated tetrel bonding in the stabilization of a preliminary state that precedes the transition state in SN2 reactions, including methyl transfer. Notably, the angles between the tetrel bond donor and acceptor atoms coincide with the prerequisite geometry for the SN2 reaction. Prompted by these findings, we surveyed crystal structures of methyltransferases in the Protein Data Bank and discovered multiple instances of carbon tetrel bonding between the methyl group of the substrate S-adenosylmethionine (AdoMet) and electronegative atoms of small molecule inhibitors, ions, and solvent molecules. The majority of these interactions involve oxygen atoms as the Lewis base, with the exception of one structure in which a chlorine atom of an inhibitor functions as the electron donor. Quantum mechanical analyses of a representative subset of the methyltransferase structures from the survey revealed that the calculated interaction energies and spectral properties are consistent with the values for bona fide carbon tetrel bonds. The discovery of methyl tetrel bonding offers new insights into the mechanism underlying the SN2 reaction catalyzed by AdoMet-dependent methyltransferases. These findings highlight the potential of exploiting these interactions in developing new methyltransferase inhibitors.
Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior

Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior.
Improved-Precision Time Synchronization Protocol for WSNs Based on Averaging Consensus Control

Accurate and simple time synchronization is a crucial requirement for decentralized wireless sensor networks (WSNs) to function well specially in harsh environments. The averaging consensus control protocol (ACCP), that uses single hop communication, performs well in such environments. This paper provides rigorous analysis of its time synchronization error which is by basic definition the difference between the gateway node time and the average virtual times of the other nodes in the network. Also, the paper presents a modified synchronizer protocol of the ACCP that further improves the precision of the time synchronization in WSNs. The improved time precision protocol is achieved reducing the forced response part of the time synchronization error. The proposed protocol is compared by simulations and by experiments and shown to achieve a synchronization error that is orders of magnitude less than these resulted from other known protocols which are. Finally, the proposed protocol was found to utilize the least memory and consume the least energy relative to some existing protocols.
Association of African Ancestry With Electrocardiographic Voltage and Concentric Left Ventricular Hypertrophy: The Dallas Heart Study

Importance Compared with white individuals, black individuals have increased electrocardiographic voltage and an increased prevalence of concentric left ventricular (LV) hypertrophy. Whether environmental or genetic factors lead to these racial differences is unknown. Objective To determine whether proportion of genetically determined African ancestry among self-reported black individuals is associated with increased electrocardiographic voltage and concentric LV hypertrophy (LVH). Design, Setting, and Participants The Dallas Heart Study is a probability-based cohort study of English- or Spanish-speaking Dallas County, Texas, residents, with deliberate oversampling of black individuals. Participants underwent extensive phenotyping, which included electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), and dual-energy radiography absorptiometry (DEXA) at a single center. Participants aged 18 to 65 years who enrolled in the Dallas Heart Study between July 2000 and December 2002, self-identified as black (n = 1251) or white (n = 826), and had ECG, CMR, and DEXA data were included in this analysis. Data were analyzed from June 2017 to September 2018. Exposures Proportion of African ancestry. Main Outcomes and Measures Electrocardiographic voltage (12-lead and 9-lead) and markers of concentric LVH as assessed by CMR (LV concentricity0.67 [LV mass/end-diastolic volume0.67], LV wall thickness [LVWT], and prevalent LVH [defined by LV mass/height2.7]). Results Of the 2077 participants included in the study, 1138 (54.8%) were women, and the mean (SD) age was 45.2 (9.9) years. Black race and African ancestry were individually associated with increased ECG voltage, LV concentricity0.67, LVWT, and prevalent LVH in multivariable analyses adjusting for age, sex, systolic blood pressure, antihypertensive medication use, and body composition. When African ancestry and black race were entered together into multivariable models, African ancestry but not black race remained associated with ECG voltage, LVWT, LV concentricity0.67, and prevalent LVH. Among black participants, African ancestry remained associated with these 4 phenotypes (12-lead voltage: &bgr;, 0.05; P = .04; LVWT: &bgr;, 0.05; P = .02; LV concentricty0.67: &bgr;, 0.05; P = .045; prevalent LVH: odds ratio, 1.2; 95% CI, 1.03-1.4; P = .02). Conclusions and Relevance Genetically determined African ancestry was associated with electrocardiographic voltage, measures of concentric LV remodeling, and prevalent LVH. These data support a genetic basis related to African ancestry for the increased prevalence of these cardiovascular traits in black individuals.