Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

ABSTRACT We previously reported that Toll-like receptor 9 (TLR9)-CpG oligonucleotides could inhibit the establishment of hepatitis B virus (HBV) infections in hepatocytes. Our aim was to uncover the underlying mechanisms of this inhibition. HepaRG cells, RPMI-B lymphoblastoma cells, and primary plasmacytoid dendritic cells (pDCs) exposed to HBV and TLR9 ligands/agonists in various configurations were used. We observed an inhibition of HBV infection upon TLR9 stimulations only when agonist was applied during inoculation. This inhibition was independent of interleukin-6 (IL-6)/interferon-inducible protein 10 (IP-10) production as well as of TLR9 expression in hepatocytes. We further demonstrated an entry inhibition mechanism by showing a noncovalent binding of TLR9 agonist to HBV particles. Besides inhibiting HBV entry into hepatocytes, this biophysical interaction between HBV virions and TLR9 agonist was responsible for a reduction of alpha interferon (IFN-α) expression by pDCs. Interestingly, subviral particles composed of only HBsAg were able to genuinely inhibit the TLR9 pathway, without titrating TLR9 ligands. To conclude, our data suggest that synthetic TLR9-CpG oligonucleotides can strongly inhibit HBV entry by “coating” HBV virions and thereby preventing their interaction with cellular receptor. This titration effect of TLR9 agonist is also artifactually responsible for the inhibition of TLR9 engagement in pDCs, whereas a genuine inhibition of this innate pathway was confirmed with HBsAg subviral particles.
Physical fitness characteristics of Omani primary school children according to body mass index.

BACKGROUND There is evidence that children with high cardiorespiratory fitness and normal body mass index (BMI) have less risk of non-communicable diseases (NCDs), however limited research was undertaken in Omani children. Therefore the aims of the present study were to describe body composition and physical fitness of a large cohort of Omani school children of both genders, and to investigate the effects of weight status on physical fitness. METHODS Three hundred and fourteen Omani school children aged 9 to 10 years old took part in anthropometric assessments, body composition and fitness tests, including handgrip strength, the basketball chest pass, broad jump, 20-m sprint, four 10-m shuttle agility, 30-s sit-up, and multistage fitness test (MSFT). RESULTS Obese boys and girls performed worse than normal-weight children in sprint, agility and endurance. In addition, fitness measures in the overweight group and underweight groups were not significantly different from other groups, except a better handgrip strength and poorer MSFT in overweight compared to normal weight girls, and poorer agility performance in underweight girls compared to the three other groups. CONCLUSIONS Most fitness measures are lower in obese Omani children, which suggests that they will be more at risk of developing NCDs later in life.
Novel IGH and MYC Translocation Partners in Diffuse Large B‐Cell Lymphomas

Chromosomal translocations involving an immunoglobulin (IG) locus and a proto‐oncogene play a major role in diffuse large B‐cell lymphoma (DLBCL) pathogenesis. Recurrent IG translocation partners in DLBCL are the BCL6, BCL2, and MYC genes, but other rare translocation partners are also known. We studied 20 DLBCL with fluorescence in situ hybridization‐based evidence for IG heavy chain (IGH) locus‐associated translocations not involving BCL6, BCL2, MALT1, or MYC by long distance inverse PCR to identify the translocation partners. Moreover, we studied eight DLBCL with MYC translocations not involving IG or known non‐IG loci as translocation partner to search for novel MYC translocations. We identified three novel IGH‐associated translocations. Chromosomal breakpoints involved the IMMP2L gene in 7q31, the BCAS2 gene in 1p13, and the PVRL2 gene in 19q13. The latter gene, which is recurrently translocated in T‐cell lymphomas, is significantly higher expressed in the biopsy with the translocation compared to cases without this genetic aberration, indicating a pathogenetic role of PVRL2 also in DLBCL. In one case with a MYC break we obtained a novel MYC‐SOCS1 translocation representing an unusual translocation of a proto‐oncogene with a tumor suppressor gene. Indeed, we demonstrate that the oncogene was deregulated and the tumor suppressor gene inactivated. As both genes undergo aberrant somatic hypermutation in the region of the chromosomal breakpoints, this translocation likely happened as a byproduct of the hypermutation process. Overall, our study suggests that chromosomal translocations in DLBCL are more heterogeneous than previously known. © 2016 Wiley Periodicals, Inc.
Effects of Land Use/Cover Changes and Urban Forest Configuration on Urban Heat Islands in a Loess Hilly Region: Case Study Based on Yan’an City, China

In this study Yan’an City, a typical hilly valley city, was considered as the study area in order to explain the relationships between the surface urban heat island (SUHI) and land use/land cover (LULC) types, the landscape pattern metrics of LULC types and land surface temperature (LST) and remote sensing indexes were retrieved from Landsat data during 1990–2015, and to find factors contributed to the green space cool island intensity (GSCI) through field measurements of 34 green spaces. The results showed that during 1990–2015, because of local anthropogenic activities, SUHI was mainly located in lower vegetation cover areas. There was a significant suburban-urban gradient in the average LST, as well as its heterogeneity and fluctuations. Six landscape metrics comprising the fractal dimension index, percentage of landscape, aggregation index, division index, Shannon’s diversity index, and expansion intensity of the classified LST spatiotemporal changes were paralleled to LULC changes, especially for construction land, during the past 25 years. In the urban area, an index-based built-up index was the key positive factor for explaining LST increases, whereas the normalized difference vegetation index and modified normalized difference water index were crucial factors for explaining LST decreases during the study periods. In terms of the heat mitigation performance of green spaces, mixed forest was better than pure forest, and the urban forest configuration had positive effects on GSCI. The results of this study provide insights into the importance of species choice and the spatial design of green spaces for cooling the environment.
Overexpression of HHLA2, a member of the B7 family, is associated with worse survival in human colorectal carcinoma

Background Colorectal carcinoma (CRC) is one of the most common malignancies, and immunotherapy has opened a new field of cancer treatment in recent years. Generally, CRC does not benefit from immunotherapy. HHLA2, a member of the B7 family, is a novel immune checkpoint molecule, and the prognostic value of HHLA2 in CRC patients and the association between HHLA2 expression and clinicopathological characteristics remains unknown. Materials and methods This study included 63 patients diagnosed with CRC, and their resected specimens were obtained and constructed as a tissue microarray. Expression of HHLA2 and CD8 was detected by the double immunohistochemistry method. Based on follow-up data, correlations of HHLA2 expression and clinicopathological features, including overall survival, in CRC patients were evaluated. Results High HHLA2 expression was detected in CRC tumor tissues, compared to the adjacent noncancerous tissues. HHLA2 expression level was significantly related to the depth of invasion (P=0.044) and CD8+ T-cell infiltration status (P=0.016), and predicted high mortality rate (P=0.035). HHLA2 acted as an independent predictive factor in the overall survival of CRC patients (P=0.039, hazard ratio=2.162, 95% CI 1.041–3.084). Conclusion HHLA2 expression is upregulated in CRC patients, and HHLA2 is an independent prognostic factor of overall survival of CRC patients. High HHLA2 expression is closely correlated with CD8 T-cell infiltration status and can predict poor prognosis in CRC patients.
Kidney exchange match rates in a large multicenter clearinghouse

Kidney paired donation (KPD) can facilitate living donor transplantation for candidates with an incompatible donor, but requires waiting for a match while experiencing the morbidity of dialysis. The balance between waiting for KPD vs desensitization or deceased donor transplantation relies on the ability to estimate KPD wait times. We studied donor/candidate pairs in the National Kidney Registry (NKR), a large multicenter KPD clearinghouse, between October 2011 and September 2015 using a competing‐risk framework. Among 1894 candidates, 52% were male, median age was 50 years, 66% were white, 59% had blood type O, 42% had panel reactive antibody (PRA)>80, and 50% obtained KPD through NKR. Median times to KPD ranged from 2 months for candidates with ABO‐A and PRA 0, to over a year for candidates with ABO‐O or PRA 98+. Candidates with PRA 80‐97 and 98+ were 23% (95% confidence interval , 6%‐37%) and 83% (78%‐87%) less likely to be matched than PRA 0 candidates. ABO‐O candidates were 67% (61%‐73%) less likely to be matched than ABO‐A candidates. Candidates with ABO‐B or ABO‐O donors were 31% (10%‐56%) and 118% (82%‐162%) more likely to match than those with ABO‐A donors. Providers should counsel candidates about realistic, individualized expectations for KPD, especially in the context of their alternative treatment options.
Cardiorespiratory responses during and after water exercise in pregnant and non-pregnant women.

PURPOSE to compare the blood pressure and oxygen consumption (VO(2)) responses between pregnant and non-pregnant women, during cycle ergometer exercise on land and in water. METHODS ten pregnant (27 to 29 weeks of gestation) and ten non-pregnant women were enrolled. Two cardiopulmonary tests were performed on a cycle ergometer (water and land) at the heart rate corresponding to VO(2), over a period of 30 minutes each. Exercise measurements consisted of recording blood pressure every five minutes, and heart rate and VO(2) every 20 seconds. Two-way ANOVA was used and α=0.05 (SPSS 17.0). RESULTS there was no difference in cardiovascular responses between pregnant and non-pregnant women during the exercise. The Pregnant Group demonstrated significant differences in systolic (131.6±8.2; 142.6±11.3 mmHg), diastolic (64.8±5.9; 74.5±5.3 mmHg), and mean blood pressure (87.0±4.1; 97.2±5.7 mmHg), during water and land exercise, respectively. The Non-pregnant women Group also had a significantly lower systolic (130.5±8.4; 135.9±8.7 mmHg), diastolic (67.4±5.7; 69.0±10.1 mmHg), and mean blood pressure (88.4±4.8; 91.3±7.8 mmHg) during water exercise compared to the land one. There were no significant differences in VO(2) values between water and land exercises or between pregnant and non-pregnant women. After the first five-minute recovery period, both blood pressure and VO(2) were similar to pre-exercise values. CONCLUSIONS for pregnant women with 27 to 29 weeks of gestation, water exercise at the heart rate corresponding to VO(2) is physiologically appropriate. These women also present a lower blood pressure response to exercise in water than on land.
Pan‐cancer analysis of copy number changes in programmed death‐ligand 1 (PD‐L1, CD274) – associations with gene expression, mutational load, and survival

Inhibition of the PD‐L1 (CD274) – PD‐1 axis has emerged as a powerful cancer therapy that prevents evasion of tumor cells from the immune system. While immunohistochemical detection of PD‐L1 was introduced as a predictive biomarker with variable power, much less is known about copy number alterations (CNA) affecting PD‐L1 and their associations with expression levels, mutational load, and survival. To gain insight, we employed The Cancer Genome Atlas (TCGA) datasets to comprehensively analyze 22 major cancer types for PD‐L1 CNAs. We observed a diverse landscape of PD‐L1 CNAs, which affected focal regions, chromosome 9p or the entire chromosome 9. Deletions of PD‐L1 were more frequent than gains (31% vs. 12%) with deletions being most prevalent in melanoma and non‐small cell lung cancer. Copy number gains most frequently occurred in ovarian cancer, head and neck cancer, bladder cancer, cervical and endocervical cancer, sarcomas, and colorectal cancers. Fine‐mapping of the genetic architecture revealed specific recurrently amplified and deleted core regions across cancers with putative biological and clinical consequences. PD‐L1 CNAs correlated significantly with PD‐L1 mRNA expression changes in many cancer types, and tumors with PD‐L1 gains harbored significantly higher mutational load compared to non‐amplified cases (median: 78 non‐synonymous mutations vs. 40, P = 7.1e‐69). Moreover, we observed that, in general, both PD‐L1 amplifications and deletions were associated with dismal prognosis. In conclusion, PD‐L1 CNAs, in particular PD‐L1 copy number gains, represent frequent genetic alterations across many cancers, which influence PD‐L1 expression levels, are associated with higher mutational loads, and may be exploitable as predictive biomarker for immunotherapy regimens. © 2016 Wiley Periodicals, Inc.
The Neurotoxic Role of Extracellular Tau Protein

Tauopathies are a class of neurodegenerative diseases associated with the microtubule-associated protein tau, with Alzheimer’s disease (AD) being the most prevalent related disorder. Neurofibrillary tangles (NFTs) are one of the neuropathological hallmarks present in the brains of AD patients. Because NFTs are aberrant intracellular inclusions formed by hyperphosphorylated tau, it was initially proposed that phosphorylated and/or aggregated intracellular tau protein was causative of neuronal death. However, recent studies suggest a toxic role for non-phosphorylated and non-aggregated tau when it is located in the brain extracellular space. In this work, we will discuss the neurotoxic role of extracellular tau as well its involvement in the spreading of tau pathologies.
Influence of the ER,CR:YSGG laser and different irrigation methods on push-out bond strength of fiber post

Abstract Er,Cr:YSGG lasers are currently being investigated for disinfecting the root canal treatment. The aim of this study was to compare the effects of various irrigation protocols on push-out bond strength of fiber posts. Fifty maxillary anterior teeth were divided into five groups (n = 10) according to the protocol that applied into the post space. Group-1: distilled water, Group-2: 5% NaOCl, Group-3: 2% CHX, Group-4: Er,Cr:YSGG laser (1.5 W, 20 Hz, 85 air, 75 water, 26.7 J/cm2), Group-5: Er,Cr:YSGG laser (1.25 W, 50 Hz, 34 air, 24 water, 12.7 J/cm2). Fiber posts were cemented with resin cement. The remaining part of the root, three slices were obtained from each specimen and push-out test was performed. One-way ANOVA and Duncan’s test at a 5% level of significance were used for the statistical analysis. Post space irradiation with Er,Cr:YSGG laser (1.5 W 20 Hz, 85 air, 75 water, 26.7 J/cm2) increases push-out bond strength of fiber post to root canal dentin. Further investigations are needed to establish and optimize ER,Cr:YSGG laser parameters to increase the push-out bond strength of fiber posts.
Anisotropic Mechanical Properties of Pure Magnesium Analyzed by In Situ Nanoindentation

In this work, correlation between nanomechanical properties and crystallographic orientation of grains in 99.9 % magnesium is presented. Crystallographic orientation of individual grains was obtained by scanning electron microscope (SEM) equipped with electron backscatter diffraction (EBSD) detector. Hardness and elastic modulus of grains with known orientation were subsequently determined by in situ nanoindentation in SEM. We show that hardness decreases with increasing angle between the direction of indentation and the c-axis of grains, while elastic modulus varies non-monotonically.
Rectified Gaussian Scale Mixtures and the Sparse Non-Negative Least Squares Problem

In this paper, we develop a Bayesian evidence maximization framework to solve the sparse non-negative least squares (S-NNLS) problem. We introduce a family of probability densities referred to as the rectified Gaussian scale mixture (R-GSM) to model the sparsity enforcing prior distribution for the solution. The R-GSM prior encompasses a variety of heavy-tailed densities such as the rectified Laplacian and rectified Student's t-distributions with a proper choice of the mixing density. We utilize the hierarchical representation induced by the R-GSM prior and develop an evidence maximization framework based on the expectation-maximization (EM) algorithm. Using the EM based method, we estimate the hyper-parameters and obtain a point estimate for the solution. We refer to the proposed method as rectified sparse Bayesian learning (R-SBL). We provide four R-SBL variants that offer a range of options for computational complexity and the quality of the E-step computation. These methods include the Markov chain Monte Carlo EM, linear minimum mean-square-error estimation, approximate message passing, and a diagonal approximation. Using numerical experiments, we show that the proposed R-SBL method outperforms existing S-NNLS solvers in terms of both signal and support recovery performance, and is also very robust against the structure of the design matrix.
Cardiovascular afferent signals and drinking in response to hypotension in dogs.

Arterial hypotension stimulates increases in plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake in conscious dogs. We have previously reported that increasing left atrial but not right atrial pressure completely blocks the increase in plasma AVP and PRA induced by hypotension. The goal of the present study was to examine the effect of increasing right or left atrial pressure on water intake induced by arterial hypotension. Dogs were prepared with occluding cuffs on the thoracic inferior vena cava, the pulmonary artery, and the ascending aorta. We reduced mean arterial pressure (MAP) 25% below control by either inferior vena cava constriction (IVCC), pulmonary artery constriction (PAC), or ascending aorta constriction (AAC) and measured water intake over a 2-h period. Cumulative water intake during IVCC ( n = 6) and PAC ( n = 6) was 7.8 ± 2.0 and 6.7 ± 2.6 ml/kg, respectively. There was no difference between either the latency or the volume consumed between the two treatments. In contrast, none of the dogs drank during hypotension induced by AAC ( n = 5). Because the degree of arterial baroreceptor unloading was the same in each treatment by design, we conclude that stimulation of left atrial receptors inhibits drinking in response to arterial hypotension but that stimulation of right atrial receptors has no effect on the response in dogs.
Knowledge, Skills, and Attitudes Regarding the Use of Medical Cannabis in the Hospice Population: An Educational Intervention

Background: Currently, 28 states and the District of Columbia have legalized cannabis for medical use despite its remaining Schedule I federally. Benefits of medical cannabis (MC) have been demonstrated in nausea/vomiting associated with chemotherapy, cachexia associated with HIV/AIDS, and certain types of neuropathic pain. However, it is unclear how comfortable hospice providers are with the concept of MC. Objective: The aim of this study is to determine changes in knowledge, self-perceived skills, and attitudes (KSA) of hospice providers regarding MC after an online educational intervention. Methods: The educational intervention consisted of 3 learning modules covering information from 6 learning domains. Participants took a pre- and postcourse survey to assess changes in KSA. Participant demographics were analyzed using descriptive statistics. To detect any differences between pre- and postsurvey answers, a paired t test was used to reduce intersubject variability. Results: Attitudes about the importance of cannabis knowledge were overall positive and did not change significantly after the intervention (N = 94). Both self-perceived skills and knowledge increased significantly, with providers reporting more positive skills, and >75% of respondents answering questions correctly after the intervention. There was a significant difference in attitudes in all domains in the postsurvey between participants who have practiced in hospice <3 years or ≥4 years, but no difference in perceived skills or knowledge. Conclusion: Providers’ attitudes regarding the importance of MC knowledge were strong and the same before and after. Both the self-perception of skills and direct knowledge were significantly increased after the educational intervention.
Cancer‐associated fecal microbial markers in colorectal cancer detection

Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case–control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa‐C+ diffusely adherent Escherichia coli harboring the afa‐1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a “high‐risk” microbial pattern to other further diagnostic procedures such as colonoscopy.