Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of atrial fibrillation and long-term oral anticoagulant use on all-cause and cardiovascular mortality: A 12-year evaluation of the prospective Brazilian Study of Stroke Mortality and Morbidity

Background Atrial fibrillation is a predictor of poor prognosis after stroke. Aims To evaluate atrial fibrillation and all-cause and cardiovascular mortality in a stroke cohort with low socioeconomic status, taking into consideration oral anticoagulant use during 12-year follow-up. Methods All-cause mortality was analyzed by Kaplan–Meier survival curve and Cox regression models to estimate hazard ratios and 95% confidence intervals (95% CI). For specific mortality causes, cumulative incidence functions were computed. A logit link function was used to calculate odds ratios (OR) with 95% CIs. Full models were adjusted by age, sex, oral anticoagulant use (as a time-dependent variable) and cardiovascular risk factors. Results Of 1121 ischemic stroke participants, 17.8% had atrial fibrillation. Overall, 654 deaths (58.3%) were observed. Survival rate was lower (median days, interquartile range-IQR) among those with atrial fibrillation (531, IQR: 46–2039) vs. non-atrial fibrillation (1808, IQR: 334–3301), p-log rank < 0.0001). Over 12-year follow-up, previous atrial fibrillation was associated with increased mortality: all-cause (multivariable hazard ratios, 1.82; 95% CI: 1.43–2.31) and cardiovascular mortality (multivariable OR, 2.07; 95% CI: 1.36–3.14), but not stroke mortality. In the same multivariable models, oral anticoagulant use was inversely associated with all-cause mortality (oral anticoagulant time-dependent effect: multivariable hazard ratios, 0.47; 95% CI: 0.30–0.50, p = 0.002) and stroke mortality (oral anticoagulant time-dependent effect ≥ 6 months: multivariable OR, 0.09; 95% CI: 0.01–0.65, p-value = 0.02), but not cardiovascular mortality. Conclusions Among individuals with low socioeconomic status, atrial fibrillation was an independent predictor of poor survival, increasing all-cause and cardiovascular mortality risk. Long-term oral anticoagulant use was associated with a markedly reduced risk of all-cause and stroke mortality.
Viscosity of sodium carboxymethylcellulose in ethylene glycol–water mixed solvent media: Separation of the influences of polyion conformation and electrostatic interactions on the reduced viscosity

Precise measurements on the viscosities of the solutions of sodium carboxymethylcellulose in water and three ethylene glycol–water mixtures containing 10, 20, and 30 mass % of ethylene glycol have been reported at 35 °C. Isoionic dilutions were performed at total ionic strengths in the range of 0.0002–0.0008 eqv L−1 using sodium chloride to obtain the intrinsic viscosities along with the Huggins constants. The influence of the medium and the ionic strength on the intrinsic viscosities have been interpreted from the points of view of the counterion condensation and expansion/contraction of the polyion chains in solution. The variations of Huggins constants, on the other hand, provided information on the intermolecular interactions in these solutions. A convenient method has been proposed to decompose the reduced viscosity of a polyelectrolyte solution into its conformational and electrostatic components. The electrostatic reduced viscosities obtained in the present study, purely from experimental considerations, quantitatively corroborates the conclusions derived from the Huggins constants. Using the Hess and Klein theoretical approach, an expression for the reduced viscosity due to the electrostatic interactions as a function of polyelectrolyte concentration could be obtained and the reported experimental electrostatic contributions could be nicely described with the help of this approach. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1196–1202, 2010
Comparison of Familial, Polygenic and Biochemical Predictors of Mortality

Abstract Mortality risk is known to be associated with many physiological or biochemical risk factors, and polygenic risk scores (PRSs) may offer an additional or alternative approach to risk stratification. We have compared the predictive value of common biochemical tests, PRSs and information on parental survival in a cohort of twins and their families. Common biochemical test results were available for up to 13,365 apparently healthy men and women, aged 17−93 years (mean 49.0, standard deviation [SD] 13.7) at blood collection. PRSs for longevity were available for 14,169 study participants and reported parental survival for 25,784 participants. A search for information on date and cause of death was conducted through the Australian National Death Index, with median follow-up of 11.3 years. Cox regression was used to evaluate associations with mortality from all causes, cancers, cardiovascular diseases and other causes. Linear relationships with all-cause mortality were strongest for C-reactive protein, gamma-glutamyl transferase, glucose and alkaline phosphatase, with hazard ratios (HRs) of 1.16 (95% CI [1.07, 1.24]), 1.15 (95% CI 1.04–1.21), 1.13 (95% CI [1.08, 1.19]) and 1.11 (95% CI [1.05, 1.88]) per SD difference, respectively. Significant nonlinear effects were found for urea, uric acid and butyrylcholinesterase. Lipid risk factors were not statistically significant for mortality in our cohort. Family history and PRS showed weaker but significant associations with survival, with HR in the range 1.05 to 1.09 per SD difference. In conclusion, biochemical tests currently predict long-term mortality more strongly than genetic scores based on genotyping or on reported parental survival.
Examining suicidal desire through the lens of the three-step theory: A cross-sectional and longitudinal investigation in a community sample.

OBJECTIVE Advancing evidence-based theories of suicide is critical to improving suicide prevention. The aim of the current study was to investigate suicidal desire through an emerging theory of suicide, the Three-Step Theory (3ST). Specifically, this study investigated the validity and predictive utility of Steps 1 and 2 of the 3ST in a Canadian community sample. METHOD Participants were 487 adults between the ages of 35 to 90 (M = 59; 64% female, 87% White) who completed self-report measures assessing suicidal ideation and attempt history, hopelessness, psychological pain, and 5 forms of social connectedness at baseline and 6 months later. RESULTS In support of 3ST predictions, cross-sectional analyses showed (a) the combination of pain and hopelessness strongly correlated with suicidal desire, and (b) connectedness was protective of suicidal desire among those high in pain and hopelessness. Regarding predictive utility, longitudinal analyses showed that pain and hopelessness were strong predictors of future suicidal desire and that connectedness was protective against future suicidal desire. These relationships of pain, hopelessness, and connectedness remained when controlling for baseline suicidal desire. CONCLUSIONS Results support the validity and predictive utility of 3ST hypotheses related to suicidal desire. Taken together with previous studies, findings suggest that Steps 1 and 2 are useful for conceptualizing suicide risk and prevention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
The Mastigamoeba balamuthi Genome and the Nature of the Free-Living Ancestor of Entamoeba

Abstract The transition of free-living organisms to parasitic organisms is a mysterious process that occurs in all major eukaryotic lineages. Parasites display seemingly unique features associated with their pathogenicity; however, it is important to distinguish ancestral preconditions to parasitism from truly new parasite-specific functions. Here, we sequenced the genome and transcriptome of anaerobic free-living Mastigamoeba balamuthi and performed phylogenomic analysis of four related members of the Archamoebae, including Entamoeba histolytica, an important intestinal pathogen of humans. We aimed to trace gene histories throughout the adaptation of the aerobic ancestor of Archamoebae to anaerobiosis and throughout the transition from a free-living to a parasitic lifestyle. These events were associated with massive gene losses that, in parasitic lineages, resulted in a reduction in structural features, complete losses of some metabolic pathways, and a reduction in metabolic complexity. By reconstructing the features of the common ancestor of Archamoebae, we estimated preconditions for the evolution of parasitism in this lineage. The ancestor could apparently form chitinous cysts, possessed proteolytic enzyme machinery, compartmentalized the sulfate activation pathway in mitochondrion-related organelles, and possessed the components for anaerobic energy metabolism. After the split of Entamoebidae, this lineage gained genes encoding surface membrane proteins that are involved in host–parasite interactions. In contrast, gene gains identified in the M. balamuthi lineage were predominantly associated with polysaccharide catabolic processes. A phylogenetic analysis of acquired genes suggested an essential role of lateral gene transfer in parasite evolution (Entamoeba) and in adaptation to anaerobic aquatic sediments (Mastigamoeba).
Repeated exposure to cocaine during adolescence enhances the rewarding threshold for cocaine‐conditioned place preference in adulthood

Previous studies have shown that adolescent exposure to cocaine increases drug use in adulthood, albeit incubation of cocaine seeking was found to be attenuated in rats trained to self‐administer cocaine during adolescence. We here hypothesize that adolescent exposure to cocaine could alter the rewarding properties of the psychostimulant in adulthood. By employing two of the most widely used animal‐experimental‐preclinical models to investigate drug addiction, we evaluated whether contingent versus non‐contingent cocaine self‐administration during adolescence modulates its rewarding threshold in adulthood evaluated by conditioned place preference (CPP). Cocaine self‐administration during adolescence increases the rewarding threshold in adulthood; CPP for cocaine was observed at the higher (20 mg/kg), but not at the lower (10 mg/kg), dose employed. Rats exposed to either contingent or non‐contingent cocaine during adolescence exhibited the same behavior in the CPP paradigm suggesting that, under our experimental conditions, cocaine rewarding properties are shaped by the psychostimulant itself and not by its motivational effects. From a mechanistic standpoint, the preference for the 20 mg/kg cocaine‐paired side in a CPP paradigm appears to depend, at least partially, upon the formation of GluA2‐lacking Ca2+‐permeable AMPA receptors and the consequent increase of αCaMKII activity in the NAc, both of which are instead reduced when the 10 mg/kg dose was used. In conclusion, contingent or non‐contingent cocaine exposure during adolescence desensitizes adult animals to a rewarding dose of cocaine (10 mg/kg) elevating the rewarding threshold necessary (20 mg/kg) to drive conditioned place preference, an effect that may predispose to higher consumption of cocaine during adulthood.
Receptor for Advanced Glycation End Products Is Involved in LPA5-Mediated Brain Damage after a Transient Ischemic Stroke

Lysophosphatidic acid receptor 5 (LPA5) has been recently identified as a novel pathogenic factor for brain ischemic stroke. However, its underlying mechanisms remain unclear. Here, we determined whether the receptor for advanced glycation end products (RAGE) could be involved in LPA5-mediated brain injuries after ischemic challenge using a mouse model of transient middle cerebral artery occlusion (tMCAO). RAGE was upregulated in the penumbra and ischemic core regions after tMCAO challenge. RAGE upregulation was greater at 3 days than that at 1 day after tMCAO challenge. It was mostly observed in Iba1-immunopositive cells of a post-ischemic brain. Suppressing LPA5 activity with its antagonist, TCLPA5, attenuated RAGE upregulation in the penumbra and ischemic core regions, particularly on Iba1-immunopositive cells, of injured brains after tMCAO challenge. It also attenuated blood–brain barrier disruption, one of the core pathogenesis upon RAGE activation, after tMCAO challenge. As an underlying signaling pathways, LPA5 could contribute to the activation of ERK1/2 and NF-κB in injured brains after tMCAO challenge. Collectively, the current study suggests that RAGE is a possible mediator for LPA5-dependent ischemic brain injury.
The Immigrant Paradox in the Problem Behaviors of Youth in the United States: A Meta-analysis.

This meta-analysis synthesizes the empirical data on problem behaviors among foreign- (G1) and U.S-born (G2+) youth and explores the effects of immigrant status on youth internalizing and externalizing problems. A random effects meta-regression with robust variance estimates summarized effect sizes for internalizing and externalizing problems across 91 studies (N = 179,315, Mage = 13.98). Results indicated that G1 youth reported significantly more internalizing problems (g = .06), and fewer externalizing problems than G2+ youth (g = -.06). Gender and sample type moderated the effects. The findings provide a first-step toward reconciling mixed support for the immigrant paradox by identifying for whom and under what conditions the immigrant experience serves as a risk or protective factor for youth.
Melt- vs. Non-Melt Blending of Complexly Processable Ultra-High Molecular Weight Polyethylene/Cellulose Nanofiber Bionanocomposite

The major hurdle in melt-processing of ultra-high molecular weight polyethylene (UHMWPE) nanocomposite lies on the high melt viscosity of the UHMWPE, which may contribute to poor dispersion and distribution of the nanofiller. In this study, UHMWPE/cellulose nanofiber (UHMWPE/CNF) bionanocomposites were prepared by two different blending methods: (i) melt blending at 150 °C in a triple screw kneading extruder, and (ii) non-melt blending by ethanol mixing at room temperature. Results showed that melt-processing of UHMWPE without CNF (MB-UHMWPE/0) exhibited an increment in yield strength and Young’s modulus by 15% and 25%, respectively, compared to the Neat-UHMWPE. Tensile strength was however reduced by almost half. Ethanol mixed sample without CNF (EM-UHMWPE/0) on the other hand showed slight decrement in all mechanical properties tested. At 0.5% CNF inclusion, the mechanical properties of melt-blended bionanocomposites (MB-UHMWPE/0.5) were improved as compared to Neat-UHMWPE. It was also found that the yield strength, elongation at break, Young’s modulus, toughness and crystallinity of MB-UHMWPE/0.5 were higher by 28%, 61%, 47%, 45% and 11%, respectively, as compared to the ethanol mixing sample (EM-UHMWPE/0.5). Despite the reduction in tensile strength of MB-UHMWPE/0.5, the value i.e., 28.4 ± 1.0 MPa surpassed the minimum requirement of standard specification for fabricated UHMWPE in surgical implant application. Overall, melt-blending processing is more suitable for the preparation of UHMWPE/CNF bionanocomposites as exhibited by their characteristics presented herein. A better mechanical interlocking between UHMWPE and CNF at high temperature mixing with kneading was evident through FE-SEM observation, explains the higher mechanical properties of MB-UHMWPE/0.5 as compared to EM-UHMWPE/0.5.
No evidence for increased loss of old carbon in a temperate organic soil after 13 years of simulated climatic warming despite increased CO2 emissions

Determining the temperature sensitivity of terrestrial carbon (C) stores is an urgent priority for predicting future climate feedbacks. A key aspect to solve this long‐standing research gap is to determine whether warmer temperatures will increase autotrophic activities leading to greater C storage or promote heterotrophic activities that will drive these systems to become C sources. We experimentally addressed this critical question by subjecting intact plant‐soil systems in a UK upland ecosystem to simulated climate warming under natural field conditions. We report the results of a 13‐year field‐based climate manipulation experiment combining in situ respiration measurements with radiocarbon (14C) analyses of respired CO2, dissolved organic carbon (DOC), soil and the tissue contents of the dominant soil fauna (enchytraeids). We found that warming during the growing season produced the largely expected increases in ecosystem respiration (63%) and leaching of DOC (19%) with no evidence for thermal acclimation or substrate exhaustion over the whole 13‐year experimental period. Contrary to expectations, we found no evidence to support an increased release of old soil C after more than a decade of simulated climatic change, and indeed, 14C analyses indicated that warming caused a significant shift towards mineralisation of more recent plant‐derived C inputs. Further support came from the radiocarbon analyses of the enchytraeid tissues, which showed a greater assimilation of the more recent (plant‐derived) C sources following warming. Therefore, in contrast to subarctic ecosystems, our results suggest that changes in C storage in this UK upland soil are strongly coupled to plant activities and that increasing temperatures will drive the turnover of organic material fixed only within recent years, without resulting in the loss of existing old carbon stores.
Atomic layer depostion of TiO2/Al2O3 films for optical applications

Atomic layer deposition (ALD) is an important technology for depositing functional coatings on accessible, reactive surfaces with precise control of thickness and nanostructure. Unlike conventional chemical vapour deposition, where growth rate is dependent on reactant flux, ALD employs sequential surface chemical reactions to saturate a surface with a (sub-) monolayer of reactive compounds such as metal alkoxides or covalent halides, followed by reaction with a second compound such as water to deposit coatings layer-by-layer. A judicious choice of reactants and processing conditions ensures that the reactions are self-limiting, resulting in controlled film growth with excellent conformality to the substrate. This paper investigates the deposition and characterisation of multi-layer TiO2 /Al2O3 films on a range of substrates, including silicon , soda glass and polycarbonate, using titanium tetrachloride/water and trimethylaluminium/water as precursor couples. Structure-property correlations were established using a suite of analytical tools, including transmission electron microscopy (TEM), secondary ion mass spectrometry (SIMS), X-ray reflectometry (XRR) and spectroscopic ellipsometry (SE). The evolution of nanostructure and composition of multi-layer high/low refractive index stacks are discussed as a function of deposition parameters.
Cross-talk of insulin-like peptides, juvenile hormone, and 20-hydroxyecdysone in regulation of metabolism in the mosquito Aedes aegypti

Significance In hematophagous female mosquitoes, each reproductive cycle is linked to a separate blood intake, serving as a foundation for the transmission of dangerous human diseases. During each reproductive cycle, female mosquitoes sequentially feed on carbohydrates and protein (blood). Metabolic flux is alternated to support the reproductive cyclicity. We have established that insulin-like peptides (ILPs), critical for regulating metabolism, are genetically controlled by juvenile hormone (JH) and 20-hydroxyecdysone (20E), the key hormones governing the reproduction of female mosquitoes. CRISPR gene-tagging experiments revealed that the JH and 20E pathways coordinate the production of ILPs. This study has uncovered the link between ILPs and JH and 20E pathways in controlling mosquito metabolism during reproduction of the Aedes aegypti mosquito. Female mosquitoes feed sequentially on carbohydrates (nectar) and proteins (blood) during each gonadotrophic cycle to become reproductively competent and effective disease vectors. Accordingly, metabolism is synchronized to support this reproductive cyclicity. However, regulatory pathways linking metabolism to reproductive cycles are not fully understood. Two key hormones, juvenile hormone (JH) and ecdysteroids (20-hydroxyecdysone, 20E, is the most active form) govern female mosquito reproduction. Aedes aegypti genome codes for eight insulin-like peptides (ILPs) that are critical for controlling metabolism. We examined the effects of the JH and 20E pathways on mosquito ILP expression to decipher regulation of metabolism in a reproducing female mosquito. Chromatin immunoprecipitation assays showed genomic interactions between ilp genes and the JH receptor, methoprene-tolerant, a transcription factor, Krüppel homolog 1 (Kr-h1), and two isoforms of the ecdysone response early gene, E74. The luciferase reporter assays showed that Kr-h1 activates ilps 2, 6, and 7, but represses ilps 4 and 5. The 20E pathway displayed the opposite effect in the regulation of ilps. E74B repressed ilps 2 and 6, while E74A activated ilps 4 and 5. Combining RNA interference, CRISPR gene tagging and enzyme-linked immunosorbent assay, we have shown that the JH and 20E regulate protein levels of all eight Ae. aegypti ILPs. Thus, we have established a regulatory axis between ILPs, JH, and 20E in coordination of metabolism during gonadotrophic cycles of Ae. aegypti.
Combination of Lenvatinib and Pembrolizumab Is an Effective Treatment Option for Anaplastic and Poorly Differentiated Thyroid Carcinoma

Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14–24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1–90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with long-term (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%. Conclusions: Our results implicate that the combination of lenvatinib and pembrolizumab might be safe and effective in patients with ATC/PDTC and can result in complete and long-term remissions. The combination treatment is now being systematically examined in a phase II clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab [ATLEP]) in ATC/PDTC patients.