Miracle-dz/UniFAR-FTUs huggingface dataset:
Germline Genetic Variants and Lung Cancer Survival in African Americans

Background: African Americans have the highest lung cancer mortality in the United States. Genome-wide association studies (GWASs) of germline variants influencing lung cancer survival have not yet been conducted with African Americans. We examined five previously reported GWAS catalog variants and explored additional genome-wide associations among African American lung cancer cases. Methods: Incident non–small cell lung cancer cases (N = 286) in the Southern Community Cohort Study were genotyped on the Illumina HumanExome BeadChip. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CIs) for overall mortality. Two independent African American studies (N = 316 and 298) were used for replication. Results: One previously reported variant, rs1878022 on 12q23.3, was significantly associated with mortality (HR = 0.70; 95% CI: 0.54–0.92). Replication findings were in the same direction, although attenuated (HR = 0.87 and 0.94). Meta-analysis had a HR of 0.83 (95% CI, 0.71–0.97). Analysis of common variants identified an association between chromosome 6q21.33 and mortality (HR = 0.46; 95% CI, 0.33–0.66). Conclusions: We identified an association between rs1878022 in CMKLR1 and lung cancer survival. However, our results in African Americans have a different direction of effect compared with a prior study in European Americans, suggesting a different genetic architecture or presence of gene–environment interactions. We also identified variants on chromosome 6 within the gene-rich HLA region, which has been previously implicated in lung cancer risk and survival. Impact: We found evidence that inherited genetic risk factors influence lung cancer survival in African Americans. Replication in additional populations is necessary to confirm potential genetic differences in lung cancer survival across populations. Cancer Epidemiol Biomarkers Prev; 26(8); 1288–95. ©2017 AACR.
The activity of transient receptor potential channel C‐6 modulates the differentiation of fat cells

Previously, the V1‐3 isoforms of the transient receptor potential channel (TRP) have been shown to promote or prevent adipocyte differentiation. In the current study, the C isoforms were screened for blocking adipogenesis. The hypothesis that the TRP classic or canonical (TRPC) deters adipocyte differentiation was investigated in 3T3‐L1 cells employing the channel‐specific activator and antagonist, silencing, and overexpression techniques. Fat accumulation in cells was visualized by Oil Red O staining. Intracellular calcium inflow was estimated by confocal microscopy. A high‐fat (HF) feeding study was also performed on C57BL/6J mice to verify the findings in the cell model. Among the 6 C isoforms tested, only TRPC‐6 inhibited the differentiation of fat cells. The phytochemical quercetin induced the channel protein expression. Calcium‐imaging results also revealed that the flavonoid could trigger calcium inflow. Coadministration of quercetin (1 or 20 mg/kg body weight) in an HF diet prevented TRPC‐6 from declining and attenuated phosphorylated (p)‐PKB and PI3k, as well as the proliferation of visceral fat cells. The present study illustrated that TRPC‐6 activation could perturb adipocyte differentiation. The food f lavonoid quercetin was a TRPC‐6 inducer and activator and it could prevent adipogenesis in mice. —Tan, Y. Q. , Kwan, H. Y. , Yao, X. , Leung, L. K. The activity of transient receptor potential channel C‐6 modulates the differentiation of fat cells. FASEB J. 33, 6526–6538 (2019). www.fasebj. org
Continuous-Time Portfolio Selection and Option Pricing under Risk-Minimization Criterion in an Incomplete Market

We study option pricing with risk-minimization criterion in an incomplete market where the dynamics of the risky underlying asset are governed by a jump diffusion equation. We obtain the Radon-Nikodym derivative in the minimal martingale measure and a partial integrodifferential equation (PIDE) of European call option. In a special case, we get the exact solution for European call option by Fourier transformation methods. Finally, we employ the pricing kernel to calculate the optimal portfolio selection by martingale methods.
Subjects’ Perception in Quantifying Printed and Digital Photos of Food Portions

Although digital photos have the potential to improve the precision of reported portions in dietary assessment, there are few studies investigating its accuracy in comparison to printed photos. The aim of this study was to evaluate the perception of adults in quantifying food portion sizes using printed and digital photos, displayed on computer-screens and tablets. In total, 1165 evaluations were performed for 60 photos of portion sizes in Brazil. Each participant (n = 58) attended two sessions in the study center, with an interval of at least one week. In each session, twelve food portions were prepared and randomly evaluated by each participant in its printed and digital forms. The mean error (difference between the estimated and true portions) was not significantly different between the printed photos (2.1 g ± 47.2) and the digital ones (−6.4 g ± 53.7). The agreement on using the printed and digital photos was 91% and 90%, respectively. Furthermore, the use of the tablet was more prone to underestimation when compared to printed and computer-screen photos (p < 0.001). Overall, participants did not present major difficulties in perceiving the portion sizes using the printed and digital photos, but the use of tablets led to less accurate results, indicating that this needs to be further evaluated.
Size-Dependent Free Vibration and Buckling of Three-Dimensional Graphene Foam Microshells Based on Modified Couple Stress Theory

In this research, the vibration and buckling of three-dimensional graphene foam (3D-GrF) microshells are investigated for the first time. In the microshells, three-dimensional graphene foams can distribute uniformly or non-uniformly through the thickness direction. Based on Love’s thin shell theory and the modified couple stress theory (MCST), size-dependent governing equations and corresponding boundary conditions are established through Hamilton’s principle. Then, vibration and axial buckling of 3D-GrF microshells are analyzed by employing the Navier method and Galerkin method. Results show that the graphene foam distribution type, size effect, the foam coefficient, the radius-to-thickness ratio, and the length-to-radius ratio play important roles in the mechanical characteristics of 3D-GrF microshells.
The Outcome of the Single Step Questionnaire in Pectus Excavatum Patients is Phase Dependent

Abstract Introduction Pectus excavatum (PE) is the most common chest wall deformity. Patients with PE may have cosmetic complaints, restricted physical capabilities, or both and may seek surgical correction. One method to assess satisfaction after surgery is the single step questionnaire (SSQ). Although the developers state that the SSQ produces a stabile score and only needs to be used once, we hypothesized that the score may depend on point in time after surgery. Materials and Methods One hundred and eight patients from a longitudinal cohort of patients undergoing a Nuss bar placement for PE were selected. Mean age was 16.0 years (range: 12–29). SSQ was completed at 6 weeks, 6 months, 1 year, and 2 years postoperatively. Mean and median scores per question and total scores were calculated on each measurement moment. Overall scores were tested using the Friedman test. Results There were significant differences in overall SSQ scores (p < 0.009) throughout the postoperative period, especially between 6 weeks and 6 months (p = 0.006). Scores on general health, exercise capacity, impact on social life, pain during hospital stay, and after discharge changed also significant in the first 2 years after Nuss bar placement. Conclusion There were significant differences in total SSQ score depending on the time of application postoperatively. However, the most clinical relevant difference was between 6 weeks and 6 months. Assessment of the overall satisfaction postoperative with the SSQ questionnaire should not be done with a single measurement but rather at different postoperative time intervals before and after 6 months postoperatively.
Functional selective ATP receptor signaling controlled by the free fatty acid receptor 2 through a novel allosteric modulation mechanism

A nonactivating allosteric modulator of free fatty acid receptor 2 (FFA2R, also called GPCR 43) turns both propionate (an orthosteric FFA2R agonist) and ATP (an agonist for the purinergic P2Y2 receptor), into potent activating ligands that trigger an assembly of the superoxide‐generating neutrophil NADPH oxidase. The ATP‐induced activation requires the participation of FFA2R, and the signaling is biased toward oxidase activation, leaving the ATP‐induced rise in intracellular Ca2+ unaffected. No NADPH oxidase activity was induced by ATP when propionate replaced the allosteric modulator. Signaling downstream of propionate‐activated FFA2Rs was insensitive to Gαq inhibition, but the crosstalk activation involving both FFA2R and P2Y2R relied on Gαq signaling. The receptor crosstalk, by which allosterically modulated FFA2Rs communicate with P2Y2Rs and generate NADPH oxidase activating signals downstream of Gαq, represent a novel mechanism by which GPCR activities can be regulated from inside the plasma membrane. Further, the finding that an allosteric FFA2R modulator sensitizes not only the response induced by orthosteric FFA2R agonists, but also the response induced by ATP (P2Y2R‐specific agonist) and formyl peptide receptor‐specific agonists, violates the receptor restriction characteristics normally defining the selectivity of allosteric GPCR modulators. —Lind, S. , Holdfeldt, A. , Mårtensson, J., Sundqvist, M. , Bjórkman, L. , Forsman, H. , Dahlgren, C. Functional selective ATP receptor signaling controlled by the free fatty acid receptor 2 through a novel allosteric modulation mechanism. FASEB J. 33, 6887–6903 (2019). www.fasebj. org
Surface Enhanced Raman Spectroscopy of Lactoferrin Adsorbed on Silvered Porous Silicon Covered with Graphene

We registered surface enhanced Raman scattering (SERS) spectra of the human lactoferrin molecules adsorbed on a silvered porous silicon (por-Si) from 10−6–10−18 M solutions. It was found that the por-Si template causes a negative surface potential of silver particles and their chemical resistivity to oxidation. These properties provided to attract positively charged lactoferrin molecules and prevent their interaction with metallic particles upon 473 nm laser excitation. The SERS spectra of lactoferrin adsorbed from 10−6 M solution were rather weak but a decrease of the concentration to 10−10 M led to an enormous growth of the SERS signal. This effect took place as oligomers of lactoferrin were broken down to monomeric units while its concentration was reduced. Oligomers are too large for a uniform overlap with electromagnetic field from silver particles. They cannot provide an intensive SERS signal from the top part of the molecules in contrast to monomers that can be completely covered by the electromagnetic field. The SERS spectra of lactoferrin at the 10−14 and 10−16 M concentrations were less intensive and started to change due to increasing contribution from the laser burned molecules. To prevent overheating the analyte molecules on the silvered por-Si were protected with graphene, which allowed the detection of lactoferrin adsorbed from the 10−18 M solution.
Test of Everyday Attention for Children (TEA-Ch): Greek Normative Data and Discriminative Validity for Children with Combined Type of Attention Deficit-Hyperactivity Disorder

ABSTRACT We examined the utility of the Test of Everyday Attention for Children (TEA-Ch) for Greek children. Discrete and regression-based norms, controlling for demographic characteristics and intelligence, were derived from the performance of 172 children. We also assessed the ability of the TEA-Ch to differentiate children with ADHD-Combined Type (ADHD-C) from healthy matched peers. Children with ADHD-C displayed dysfunction in multiple attentional domains. Discriminant function analysis indicated that two subtests (Sky Search and Walk, Don’t Walk) correctly classified 84.2% of children with ADHD-C.
Inhibition of farnesyl pyrophosphate (FPP) and/or geranylgeranyl pyrophosphate (GGPP) biosynthesis and its implication in the treatment of cancers

Abstract Dysregulation of isoprenoid biosynthesis is implicated in numerous biochemical disorders that play a role in the onset and/or progression of age-related diseases, such as hypercholesterolemia, osteoporosis, various cancers, and neurodegeneration. The mevalonate metabolic pathway is responsible for the biosynthesis of the two key isoprenoid metabolites, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational prenylation of various proteins, including the small GTP-binding proteins (GTPases), with either FPP or GGPP is vital for proper localization and activation of these proteins. Prenylated GTPases play a critical role in cell signaling, proliferation, cellular plasticity, oncogenesis, and cancer metastasis. Pre-clinical and clinical studies strongly suggest that inhibition of protein prenylation can be an effective treatment for non-skeletal cancers. In this review, we summarize the most recent drug discovery efforts focusing on blocking protein farnesylation and/or geranylgeranylation and the biochemical and structural data available in guiding the current on-going studies in drug discovery. Furthermore, we provide a summary on the biochemical association between disruption of protein prenylation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR) signaling, and cancer.
Phylogeny, phylogeography and hybridization of Caucasian barbels of the genus Barbus (Actinopterygii, Cyprinidae)

The phylogenetic relationships and the phylogeography of seven species of Caucasian barbels of the genus Barbus s. str. were studied based on extended geographic coverage and the use of mtDNA and nDNA markers. Based on the 26 species studied, matrilineal phylogeny of the genus Barbus is composed of two clades: a) West European clade, and b) Central and East European clade. The latter comprises two subclades: b1) Balkanian subclade, and b2) Ponto-Caspian subclade, which includes 11 lineages mainly from Black and Caspian Sea drainages. Caucasian barbels are not monophyletic and are subdivided into two groups. The Black Sea group encompasses species from tributaries of the Black Sea, including the reinstalled B. rionicus, except for B. kubanicus. The Caspian group includes B. ciscaucasicus, B. cyri (with B. goktschaicus, which might be synonymized with B. cyri), B. lacerta from the Tigris-Euphrates basin and B. kubanicus from the Kuban basin. The genetic structure of Black Sea barbels was influenced by glaciation-deglaciation periods accompanied by freshwater phases, periods of migration and the colonization of Black Sea tributaries. Intra- and intergeneric hybridization among Caucasian barbines was revealed for the first time. In the present study, we report the discovery of B. escherichii in the Kuban basin, where only B. kubanicus was known to inhabit. Hybrids of these two species were detected based on both mtDNA and nDNA markers. Remarkably, the Kuban population of B. escherichii is distant to closely located conspecific populations, and we consider it as a relic. We reveal the intergeneric hybridization between evolutionary tetraploid (2n=100) B. goktschaicus and evolutionary hexaploid (2n=150) Capoeta sevangi in Lake Sevan.
TLR4 Receptor Induces 2-AG–Dependent Tolerance to Lipopolysaccharide and Trafficking of CB2 Receptor in Mast Cells

Mast cells (MCs) contribute to the control of local inflammatory reactions and become hyporesponsive after prolonged TLR4 activation by bacterial LPS. The molecular mechanisms involved in endotoxin tolerance (ET) induction in MCs are not fully understood. In this study, we demonstrate that the endocannabinoid 2-arachidonoylglycerol (2-AG) and its receptor, cannabinoid receptor 2 (CB2), play a role in the establishment of ET in bone marrow–derived MCs from C57BL/6J mice. We found that CB2 antagonism prevented the development of ET and that bone marrow–derived MCs produce 2-AG in a TLR4-dependent fashion. Exogenous 2-AG induced ET similarly to LPS, blocking the phosphorylation of IKK and the p65 subunit of NF-κB and inducing the synthesis of molecular markers of ET. LPS caused CB2 receptor trafficking in Rab11-, Rab7-, and Lamp2-positive vesicles, indicating recycling and degradation of the receptor. 2-AG also prevented LPS-induced TNF secretion in vivo, in a MC-dependent model of endotoxemia, demonstrating that TLR4 engagement leads to 2-AG secretion, which contributes to the negative control of MCs activation. Our study uncovers a functional role for the endocannabinoid system in the inhibition of MC-dependent innate immune responses in vivo.
Enhanced Anti-Allergic Activity of Milk Casein Phosphopeptide by Additional Phosphorylation in Ovalbumin-Sensitized Mice

The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as suppression of allergy-associated cytokine and antigen-specific immune response. This study was conducted to assess whether oral intake of additionally phosphorylated CPP-III (P-CPP) attenuates ovalbumin (OVA)-induced IgE-mediated allergic reactions because of the additional phosphate groups. Female BALB/c mice were intraperitoneally sensitized with OVA twice at intervals of 14 days and then orally fed native CPP-III (N-CPP), P-CPP, and dephosphorylated CPP-III (D-CPP) for 6 weeks. Next, the mice were orally challenged with 50 mg of OVA. Oral administration of P-CPP suppressed total and specific IgE levels in the serum. Mice fed P-CPP exhibited low levels of OVA-specific IgG1 and increased OVA-specific IgG2a. P-CPP also suppressed IL-4 production, while D-CPP showed similar a level compared to that of the control. Further, P-CPP increased the population of the T follicular helper (Tfh) cell in the spleen. These results suggest that additional phosphorylation of CPP can enhance the attenuation of allergen-specific IgE-modulated allergic reactions in a murine food allergy model.
Advances in Capacitive Micromachined Ultrasonic Transducers

Capacitive micromachined ultrasonic transducer (CMUT) technology has enjoyed rapid development in the last decade. Advancements both in fabrication and integration, coupled with improved modelling, has enabled CMUTs to make their way into mainstream ultrasound imaging systems and find commercial success. In this review paper, we touch upon recent advancements in CMUT technology at all levels of abstraction; modeling, fabrication, integration, and applications. Regarding applications, we discuss future trends for CMUTs and their impact within the broad field of biomedical imaging.
The time course of muscle-tendon properties and function responses of a five-minute static stretching exercise

Abstract The purpose of this study was to investigate the time course of the changes of muscle-tendon mechanical properties and the function responses of the plantar flexor muscles following 5 × 60 s of static stretching. Fourteen healthy volunteers were tested on four separate days in a random order with three different rest times (0, 5, 10 min) after 5 × 60 s of stretching or following a control period without stretching. During each test, the dorsiflexion range of motion (RoM), passive resistive torque (PRT), and maximum voluntary contraction (MVC) were measured with a dynamometer. Ultrasonography of the gastrocnemius medialis (GM) muscle-tendon junction displacement and motion capture allowed us to determine the length changes in the tendon and muscle, respectively, and hence to calculate their stiffness. We observed an increase in RoM and decrease in MVC at 0, 5, and 10 min post-stretching. This could be attributed to an increase in muscle elongation which lasted at least 10 min. A decrease in muscle-tendon stiffness was observed immediately, but not 5 or 10 min after the stretching. A decrease in PRT and muscle stiffness was observed up to 5 min after the stretching. No changes were detected in tendon stiffness or in any variable in the control group. The effects of a 5 × 60 s static stretching exercise changes the muscle-tendon functions (RoM, MVC), which are related to mechanical changes of the muscle but not the tendon structure, respectively. Although the functional changes last for at least 10 min, changes in muscle stiffness were only observed up to 5 min after the stretching exercise.
Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity

The nicotine metabolite ratio (NMR; 3‐hydroxycotinine/cotinine) is an index of CYP2A6 activity. CYP2A6 is responsible for nicotine's metabolic inactivation and variation in the NMR/CYP2A6 is associated with several smoking behaviors. Our aim was to integrate established alleles and novel genome‐wide association studies (GWAS) signals to create a weighted genetic risk score (wGRS) for the CYP2A6 gene for European‐ancestry populations. The wGRS was compared with a previous CYP2A6 gene scoring approach designed for an alternative phenotype (C2/N2; cotinine‐d2/(nicotine‐d2 + cotinine‐d2)). CYP2A6 genotypes and the NMR were assessed in European‐ancestry participants. The wGRS training set included N = 933 smokers recruited to the Pharmacogenetics of Nicotine Addiction and Treatment clinical trial [NCT01314001]. The replication cohort included N = 196 smokers recruited to the Quit 2 Live clinical trial [NCT01836276]. Comparisons between the two CYP2A6 phenotypes and with fractional clearance were made in a laboratory‐based pharmacokinetic study (N = 92 participants). In both the training and replication sets, the wGRS, which included seven CYP2A6 variants, explained 33.8% (P < 0.001) of the variance in NMR, providing improved predictive power to the NMR phenotype when compared with other CYP2A6 gene scoring approaches. NMR and C2/N2 were strongly correlated to nicotine clearance (ρ = 0.70 and ρ = 0.79, respectively; P < 0.001), and to one another (ρ = 0.82; P < 0.001); however reduced function genotypes occurred in slow NMR but throughout C2/N2. The wGRS was able to predict smoking quantity and nicotine intake, to discriminate between NMR slow and normal metabolizers (AUC = 0.79; P < 0.001), and to replicate previous NMR‐stratified cessation outcomes showing unique treatment outcomes between metabolizer groups.
The further development of out‐of‐office BP monitoring: Japan's ImPACT Program Project's achievements, impact, and direction

New guidelines for the management of hypertension were recently released by the European Society of Hypertension/European Society of Cardiology (the 2018 ESH/ESC guidelines) and the American College of Cardiology/American Heart Association (the 2017 ACC/AHA guidelines). 1,2 These guidelines stress the importance of out‐of‐office blood pressure (BP) values over that of office BP values. In Japan and other Asian countries, we have highlighted the use of the out‐of‐office BP‐guided management of hypertension.3‐5 Ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) are the two standard measurements of out‐of‐office BP. Their use can detect masked (uncontrolled) hy‐ pertension (normotension in office BP and hypertension in out‐ of‐office BP) in individuals at the highest risk of cardiovascular events.6‐8 There are three clinical phenotypes of masked hyper‐ tension: morning hypertension, daytime hypertension, and noc‐ turnal hypertension.9