Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma NOV/CCN3 Levels Are Closely Associated with Obesity in Patients with Metabolic Disorders

Objective Evidence points to a founder of the multifunctional CCN family, NOV/CCN3, as a circulating molecule involved in cardiac development, vascular homeostasis and inflammation. No data are available on the relationship between plasma NOV/CCN3 levels and cardiovascular risk factors in humans. This study investigated the possible relationship between plasma NOV levels and cardiovascular risk factors in humans. Methods NOV levels were measured in the plasma from 594 adults with a hyperlipidemia history and/or with lipid-lowering therapy and/or a body mass index (BMI) >30 kg/m2. Correlations were measured between NOV plasma levels and various parameters, including BMI, fat mass, and plasma triglycerides, cholesterol, glucose, and C-reactive protein. NOV expression was also evaluated in adipose tissue from obese patients and rodents and in primary cultures of adipocytes and macrophages. Results After full multivariate adjustment, we detected a strong positive correlation between plasma NOV and BMI (r = 0.36 p<0.0001) and fat mass (r = 0.33 p<0.0005). According to quintiles, this relationship appeared to be linear. NOV levels were also positively correlated with C-reactive protein but not with total cholesterol, LDL-C or blood glucose. In patients with drastic weight loss induced by Roux-en-Y bariatric surgery, circulating NOV levels decreased by 28% (p<0.02) and 48% (p<0.0001) after 3 and 6 months, respectively, following surgery. In adipose tissue from obese patients, and in human primary cultures NOV protein was detected in adipocytes and macrophages. In mice fed a high fat diet NOV plasma levels and its expression in adipose tissue were also significantly increased compared to controls fed a standard diet. Conclusion Our results strongly suggest that in obese humans and mice plasma NOV levels positively correlated with NOV expression in adipose tissue, and support a possible contribution of NOV to obesity-related inflammation.
Epstein–Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression

Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements.
Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells

Suberoylanilide hydroxamic acid (SAHA) as a histone deacetylase (HDAC) inhibitor has anti-cancer effect. Here, we evaluated the effect of SAHA on HDAC activity and cell growth in many normal lung and cancer cells. We observed that the HDAC activities of lung cancer cells were higher than that of normal lung cells. SAHA inhibited the growth of lung cancer cells regardless of the inhibitory effect on HDAC. This agent induced a G2/M phase arrest and apoptosis, which was accompanied by mitochondrial membrane potential (MMP: ΔΨm) loss in lung cancer cells. However, SAHA did not induce cell death in normal lung cells. All tested caspase inhibitors prevented apoptotic cell death in SAHA-treated A549 and Calu-6 lung cancer cells. Treatment with tumor necrosis factor-alpha (TNF-α) enhanced apoptosis in SAHA-treated lung cancer cells through caspase-8 and caspase-9 activations. Especially, SAHA increased the expression level of TNF-α receptor 1 (TNFR1), especially acetylation of the region of TNFR1 promoter −223/-29 in lung cancer cells. The down-regulation of TNFR1 suppressed apoptosis in TNF-α and SAHA-treated lung cancer cells. In conclusion, SAHA inhibited the growth of lung cancer cells via a G2/M phase arrest and caspase-dependent apoptosis. SAHA also enhanced apoptotic effect of TNF-α in human lung cancer cells through up-regulation of TNFR1. TNF-α may be a key to improve anti-cancer effect of HDAC inhibitors.
Improved Golgi-like Visualization in Retrogradely Projecting Neurons after EGFP-Adenovirus Infection in Adult Rat and Monkey

An adenovirus vector was generated using a neuron-specific promoter synapsin I and enhanced green fluorescent protein (EGFP) reporter (AdSynEGFP). In addition, two modifications were identified that resulted in robust and reliable retrograde transport and EGFP expression after injection of the virus into three different brain regions in adult rats (medial prefrontal cortex, posterior thalamic nuclear group, and CA1). These are post-injection survival times of 14 days and addition of high concentrations of NaCl (≥600 mM) to the injection buffer. These modifications resulted in obvious improvement in the intensity of the EGFP signal and in the number of labeled cells. Use of anti-EGFP in immunofluorescence or immunoperoxidase processing further enhanced the signal so that Golgi-like filling of dendritic spines and axon collaterals was routinely achieved. Effectiveness of the AdSynEGFP for Golgi-like filling was confirmed in one rhesus monkey with injections in visual area V4. Because of the long-term viability of the infected neurons (at least up to 28 days in rats and 22 days in monkey), this AdSynEGFP is suitable for use in microcircuitry studies in combination with other fluorescently tagged elements, including anterogradely labeled extrinsic projections. The native EGFP signal (without antibody enhancement) may be sufficient for studies involving cultured cells or slices. (J Histochem Cytochem 54:539-548, 2006)
CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma

By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven hepatocellular carcinoma model, Huang et al. identified Cdk9 as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. This study proposes CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlights the relevance of transcription elongation in the addiction of cancer cells to MYC.
High-Resolution En Face Images of Microcystic Macular Edema in Patients with Autosomal Dominant Optic Atrophy

The purpose of this study was to investigate the characteristics of microcystic macular edema (MME) determined from the en face images obtained by an adaptive optics (AO) fundus camera in patients with autosomal dominant optic atrophy (ADOA) and to try to determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL by using the advantage of AO. Six patients from 4 families with ADOA underwent detailed ophthalmic examinations including spectral domain optical coherence tomography (SD-OCT). Mutational screening of all coding and flanking intron sequences of the OPA1 gene was performed by DNA sequencing. SD-OCT showed a severe reduction in the retinal nerve fiber layer (RNFL) thickness in all patients. A new splicing defect and two new frameshift mutations with premature termination of the Opa1 protein were identified in three families. A reported nonsense mutation was identified in one family. SD-OCT of one patient showed MME in the inner nuclear layer (INL) of the retina. AO images showed microcysts in the en face images of the INL. Our data indicate that AO is a useful method to identify MME in neurodegenerative diseases and may also help determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL.
Stability of Accretion Flows with Stalled Shocks in Core-Collapse Supernovae

With an eye toward application to the theory of core-collapse supernovae, we perform a global linear analysis of the stability of spherically symmetric accretion flows through a standing shock wave onto a proto-neutron star. For the unperturbed flows, we adopt spherically symmetric, steady solutions obtained with a realistic equation of state and realistic neutrino reaction rates. These solutions are characterized by the mass accretion rate and neutrino luminosity. Then we solve the equations for linear perturbations numerically, obtaining the eigenfrequencies and eigenfunctions. We find the following: (1) The flows are stable for all modes if the neutrino luminosity is lower than a certain value, e.g., ~1 × 1052 ergs s-1 for Ṁ = 1.0 M☉ s-1. (2) For higher luminosities, nonradial instabilities are induced, probably through advective-acoustic cycles. Interestingly, modes with l = 2 and l = 3 first become unstable for relatively low neutrino luminosities, e.g., ~(2-3) × 1052 ergs s-1 for the same accretion rate, whereas the l = 1 mode is the most unstable for higher luminosities, ~(3-7) × 1052 ergs s-1. These are all oscillatory modes. (3) For still larger luminosities, ≳7 × 1052 ergs s-1 for Ṁ = 1.0 M☉ s-1, nonoscillatory modes, both radial and nonradial, become unstable. These nonradial modes are identified as convective, and their growth rates have a peak at l = 5-11, depending on the luminosity. We confirm the result from numerical simulations that the instabilities induced by advective-acoustic cycles are more important than convection for lower neutrino luminosities. Furthermore, we investigate changing the inner boundary conditions and find that while the effects are nonnegligible, the existence of the instabilities does not qualitatively change for a variety of conditions.
Underrepresentation of African-Americans in Alzheimer's Trials: A Call for Affirmative Action

Personalized medicine aims to tailor diagnosis and treatment based on an individual's personal genetic make-up and other predictive biomarkers—rather than a one-size fits all approach. African-Americans comprise 13.2% of the U.S. population (U.S. Census Bureau, 2014) and minorities (consisting of all but non-Hispanic Caucasian), now 37% of the U.S. population, are projected to reach closer to 57% in 2060 (U.S. Census Bureau, 2012). Indeed in coming decades minority population, including African-Americans, may exceed the Caucasian population in the U.S. Dementia, especially Alzheimer's disease (AD), has emerged as one of the biggest threats to public health and personal wellbeing among older adults. Epidemiological studies, by nature of their community sampling, have been able to study risk for AD in racially representative populations. In such studies, older African-Americans have been reported as being more likely than older Caucasians to develop AD and other dementias (Gurland et al., 1999; Dilworth-Anderson et al., 2008; Potter et al., 2009; Barnes and Bennett, 2014; Alzheimer's Association, 2015). Potter et al. (2009), Gurland et al. (1999), and Barnes and Bennett (2014) report that prevalence of cognitive impairment or AD among African-Americans may be two or three times higher than in Caucasians. By 2050, according to The Alzheimer's Association annual report from 2010, proportion of racial minorities with AD will increase from 20 to 42%, with African-Americans increasing from 9 to 12% (Alzheimer's Association, 2010). A more recent 2015 report suggests that 16% of African-Americans were diagnosed with AD or other dementias compared to 8% of Caucasians (Alzheimer's Association, 2015).
Effect of Periodontal Dressing on Wound Healing and Patient Satisfaction Following Periodontal Flap Surgery

Objectives: It has been claimed that periodontal dressing reduces the risk of wound infection, bleeding and granulation tissue formation and improves tissue healing. This study sought to assess the effect of periodontal dressing on wound healing and patient satisfaction following periodontal flap surgery. Materials and Methods: This clinical trial was conducted on 33 patients presenting to Hamadan University, School of Dentistry in 2012 whose treatment plan included two periodontal surgical procedures on both quadrants of the maxilla or mandible. The variables evaluated were severity of pain, bleeding, facial swelling and ease of nutrition experienced by patient during the first 3 days after surgery and inflammation, granulation tissue formation and gingival color at 7 and 14 days. Obtained data were analyzed using SPSS version 16.0 and R software and chi-square and t-tests. Results: The mean (±SD) pain score was 1.73±1.153 and 2.79±1.933 in surgical sites with and without periodontal dressing, respectively and this difference was statistically significant (P=0.005). No significant difference was noted between sites with and without periodontal dressing in terms of swelling, bleeding, gingival consistency, granulation tissue formation, gingival color and ease of nutrition (P>0.05). Conclusion: According to the results of the present study, patients did not experience more bleeding, facial swelling or nutritional problems without periodontal dressing; however, the level of pain experienced was lower after surgeries with the use of periodontal dressing.
The Incidence of Positional Plagiocephaly: A Cohort Study

OBJECTIVE: The objective of this study was to estimate the incidence of positional plagiocephaly in infants 7 to 12 weeks of age who attend the 2-month well-child clinic in Calgary, Alberta, Canada. METHODS: A prospective cohort design was used to recruit 440 healthy full-term infants (born at ≥37 weeks of gestation) who presented at 2-month well-child clinics for public health nursing services (eg, immunization) in the city of Calgary, Alberta. The study was completed in 4 community health centers (CHCs) from July to September 2010. The CHCs were selected based on their location, each CHC representing 1 quadrant of the city. Argenta's (2004) plagiocephaly assessment tool was used to identify the presence or absence of plagiocephaly. RESULTS: Of the 440 infants assessed, 205 were observed to have some form of plagiocephaly. The incidence of plagiocephaly in infants at 7 to 12 weeks of age was estimated to be 46.6%. Of all infants with plagiocephaly, 63.2% were affected on the right side and 78.3% had a mild form. CONCLUSIONS: To our knowledge, this is the first population-based study to investigate the incidence of positional plagiocephaly using 4 community-based data collection sites. Future studies are required to corroborate the findings of our study. Research is required to assess the incidence of plagiocephaly using Argenta's plagiocephaly assessment tool across more CHCs and to assess prevalence at different infant age groups. The utility of using Argenta's plagiocephaly assessment tool by public health nurses and/or family physicians needs to be established.
Certain class I HLA alleles and haplotypes implicated in susceptibility play a role in determining specific features of the psoriatic arthritis phenotype

Objectives Psoriatic arthritis (PsA) susceptibility is associated with several different class I alleles, suggesting separate patterns of MHC effect. This exploratory study was based on the hypothesis that heterogeneity of the clinical phenotype of PsA might be explained by differing associations of clinical features with these susceptibility genes. Methods The clinical phenotype of 282 PsA patients in a cohort previously studied for associations with human leukocyte antigen (HLA)-B and HLA-C genotypes was first preliminarily assessed by univariate associations of susceptibility genes with specific clinical characteristics. To explore the potential genotypic effects of pairwise combinations of different HLA-B and C alleles/haplotypes, we created a series of allele/haplotype risk scores combining single alleles/haplotypes separately associated with being in the highest PsA severity propensity tertile based on the features studied by univariate analysis. Results In exploratory univariate analyses, B*27:05:02 was positively associated with enthesitis, dactylitis and symmetric sacroiliitis, whereas B*08:01:01-C*07:01:01and its component alleles were positively associated with joint fusion and deformities, asymmetrical sacroiliitis, and dactylitis. HLA-C*06:02:01 was negatively associated with asymmetrical sacroiliitis. The highest propensity score for severe PsA was with B*27:05:02-C*02:02:02, B*08:01:01-C*07:01:01 and B*37:01:01-C*06:02:01, but not the B*27:05:02-C*01:01:01 or B*57:01:01-C*06:02:01 haplotypes. In contrast, B*44 haplotypes were associated with presence of milder disease, and in univariate analysis with a decreased frequency of enthesitis, joint fusion, deformities and dactylitis. Conclusions Different HLA susceptibility genes were associated with particular features that defined the PsA phenotype of a given patient. Additive interactions between different susceptibility HLA alleles defined the propensity for a more severe or milder musculoskeletal phenotype.
On the precision of social and information networks

The diffusion of information on online social and information networks has been a popular topic of study in recent years, but attention has typically focused on speed of dissemination and recall (i.e. the fraction of users getting a piece of information). In this paper, we study the complementary notion of the precision of information diffusion. Our model of information dissemination is "broadcast-based'', i.e., one where every message (original or forwarded) from a user goes to a fixed set of recipients, often called the user's ``friends'' or ``followers'', as in Facebook and Twitter. The precision of the diffusion process is then defined as the fraction of received messages that a user finds interesting. On first glance, it seems that broadcast-based information diffusion is a "blunt" targeting mechanism, and must necessarily suffer from low precision. Somewhat surprisingly, we present preliminary experimental and analytical evidence to the contrary: it is possible to simultaneously have high precision (i.e. is bounded below by a constant), high recall, and low diameter! We start by presenting a set of conditions on the structure of user interests, and analytically show the necessity of each of these conditions for obtaining high precision. We also present preliminary experimental evidence from Twitter verifying that these conditions are satisfied. We then prove that the Kronecker-graph based generative model of Leskovec et al. satisfies these conditions given an appropriate and natural definition of user interests. Further, we show that this model also has high precision, high recall, and low diameter. We finally present preliminary experimental evidence showing Twitter has high precision, validating our conclusion. This is perhaps a first step towards a formal understanding of the immense popularity of online social networks as an information dissemination mechanism.
Asymptotic Convergence Properties of EM-Type Algorithms

We analyze the asymptotic convergence properties of a general class of EM type algorithms for es timating an unknown parameter via alternating estimation and maximization As examples this class includes ML EM penalized ML EM Green s OSL EM and many other approximate EM al gorithms A theorem is given which provides conditions for monotone convergence with respect to a given norm and speci es an asymptotic rate of convergence for an algorithm in this class By investigating di erent parameterizations the condition for monotone convergence can be used to establish norms under which the distance between successive iterates and the limit point of the EM type algorithm approaches zero monotonically We apply these results to a modi ed ML EM algorithm with stochastic complete incomplete data mapping and establish global monotone conver gence for a linear Gaussian observation model We then establish that in the nal iterations the unpenalized and quadratically penalized ML EM algorithms for PET image reconstruction converge monotonically relative to two di erent norms on the logarithm of the images
The role of MALAT1 correlates with HPV in cervical cancer

Cervical cancer, the second most common type of cancer in women worldwide, is responsible for >275,100 mortalities each year and is associated with high-risk human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA originally identified in non-small cell lung cancer. Previous studies have revealed that MALAT1 is expressed in numerous tissue types, and is significant in maintaining the normal function of the body. However, it also appeared to be notably upregulated in numerous carcinoma types compared with adjacent non-cancerous tissues. In the present study, it was identified that MALAT1 expression was upregulated in cervical cancer cell lines compared with normal cervical squamous cell samples. Further study into the effect of MALAT1 on cellular phenotype revealed that MALAT1 was able to promote cell migration and proliferation. Of note, it was revealed that the expression of MALAT1 was decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the investigations in clinical samples also revealed that MALAT1 was expressed in HPV-positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells. These results indicate that HPV correlates with MALAT1 deregulation in cervical cancer.
Medication adsorption into contemporary extracorporeal membrane oxygenator circuits.

OBJECTIVE This study was conducted to evaluate the amount of medication adsorbed into extracorporeal membrane oxygenation (ECMO) circuits with a polymethylpentane membrane oxygenator and heparin-coated polyvinyl chloride tubing. METHODS An ECMO circuit with the aforementioned components was set up ex vivo and primed with expired blood. Midazolam, lorazepam, morphine, and fentanyl were administered to the circuit. Fifteen minutes after medication administration, 60 mL of blood were removed and stored in a 60-mL syringe to serve as a control. Medication levels were drawn from the ECMO circuit (test) and control syringe (control) 15 minutes, 24 hours, and 48 hours after the medications were administered. ECMO circuit medication levels were compared to their corresponding syringe control medication levels. Descriptive statistics were used to determine the percentage of medication remaining in the blood and compare it to the control value. RESULTS Except for morphine, there was a large decline in medication levels over the 48-hour period. Compared to control values, 17.2% of midazolam, 41.3% of lorazepam, 32.6% of fentanyl, and 102% of morphine remained in the ECMO circuit. CONCLUSION Despite the use of newer components in ECMO circuits, a large quantity of medication is adsorbed into the ECMO circuit. Midazolam, lorazepam, and fentanyl all showed reductions in medication levels greater than 50%. Morphine may have advantages for patients on ECMO, as its concentration does not appear to be affected.