Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003.

BACKGROUND The Centers for Disease Control and Prevention developed screening and diagnostic testing guidelines for chlamydia and gonorrhea at urethral, rectal, and pharyngeal sites for men who have sex with men (MSM). However, in most clinical settings, rectal chlamydial testing is not performed for MSM, and primarily sexually transmitted disease (STD) clinics alone perform routine rectal and pharyngeal gonorrhea screening for asymptomatic men. METHODS We evaluated the prevalence of rectal, urethral, and pharyngeal chlamydial and gonococcal infections among MSM seen at the municipal STD clinic and the gay men's community health center. We also determined the proportion of asymptomatic rectal infections, described the patterns of single and multiple anatomic sites of infection, and evaluated the proportion of chlamydial infections that would be missed and not treated if MSM were not routinely tested for chlamydia. We tested specimens using previously validated nucleic acid amplification tests (NAATs). RESULTS The prevalence of infection varied by anatomic site (chlamydia: rectal, 7.9%; urethral, 5.2%; and pharyngeal, 1.4%; for gonorrhea, rectal, 6.9%; urethral, 6.0%; and pharyngeal, 9.2%). Approximately 85% of rectal infections were asymptomatic supporting the need for routine screening. Because 53% of chlamydial infections and 64% of gonococcal infections were at nonurethral sites, these infections would be missed and not treated if only urethral screening was performed. In addition, >70% of chlamydial infections would be missed and not treated if MSM were tested only for gonorrhea. CONCLUSIONS Because these infections enhance both HIV transmission and susceptibility, clinical settings serving MSM should evaluate the prevalence of chlamydial and gonococcal infections by anatomic site using validated NAATs.
MnSOD-plasmid liposome gene therapy decreases ionizing irradiation-induced lipid peroxidation of the esophagus.

BACKGROUND Ionizing irradiation-induced cellular and tissue damage is mediated in part by resultant radiochemical reactions and resultant oxidative stress. Irradiation-induced reactive oxygen and nitrogen species include: superoxide, nitric oxide, hydroxyl radical and hydrogen peroxide. The biochemical combination of superoxide and nitric oxide radicals forms peroxynitrite, a potent oxidant known to induce lipid peroxidation. MATERIALS AND METHODS The antioxidant capacity and lipid peroxidation of the esophagus were determined following irradiation. RESULTS In the present studies, measurements of total antioxidant capacity did not change in the esophagus of control irradiated or control plasmid pNGVL3-PL intraesophageally-injected mice. In contrast, manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) intraesophageally-treated mice showed a significant increase in antioxidant capacity persisting for seven days. Lipid peroxidative changes induced in the control irradiated mouse esophagus decreased over seven days after irradiation of C3H/HeNHsd mice exposed to 37 Gy in a single fraction. MnSOD-PL radioprotective gene therapy administered intraorally 24 hours prior to irradiation did not significantly reduce the kinetics of induction of total peroxidated lipids over the first seven days after irradiation but did decrease lipid peroxidation at days 14 and 21. CONCLUSION These studies demonstrate the antioxidant function of MnSOD-PL gene therapy to the esophagus, which is detectable as a reduction in irradiation-induced lipid peroxidation.
Applied Machine Learning for Stochastic Local Volatility Calibration

Stochastic volatility models are a popular choice to price and risk–manage financial derivatives on equity and foreign exchange. For the calibration of stochastic local volatility models a crucial step is the estimation of the expectated variance conditional on the realized spot. The spot is given by the model dynamics. Here we suggest to use methods from machine learning to improve the estimation process. We show examples from foreign exchange.
Potential for breath test diagnosis of urease positive pathogens in lung infections

Roles for urease in virulence are accepted for Helicobacter pylori and urinary tract pathogens. However, urease is widely expressed by bacterial and fungal lung pathogens causing emerging and opportunistic lung infections, organisms causing acute exacerbations of chronic bronchitis, mycobacterial lung diseases such as tuberculosis (TB), and ventilator associated pneumonia and health care associated pneumonia. Detection of urease provides a method for rapid in vivo detection of these lung pathogens by inhaled 13C- breath test, and this review discusses the range of lung pathogens that might be amenable to rapid diagnosis.
Predicting Essential Proteins by Integrating Network Topology, Subcellular Localization Information, Gene Expression Profile and GO Annotation Data

Essential proteins are indispensable for maintaining normal cellular functions. Identification of essential proteins from Protein-protein interaction (PPI) networks has become a hot topic in recent years. Traditionally biological experimental based approaches are time-consuming and expensive, although lots of computational based methods have been developed in the past years; however, the prediction accuracy is still unsatisfied. In this research, by introducing the protein sub-cellular localization information, we define a new measurement for characterizing the protein's subcellular localization essentiality, and a new data fusion based method is developed for identifying essential proteins, named TEGS, based on integrating network topology, gene expression profile, GO annotation information, and protein subcellular localization information. To demonstrate the efficiency of the proposed method TEGS, we evaluate its performance on two <inline-formula><tex-math notation="LaTeX">$Saccharomyces cerevisiae$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>S</mml:mi><mml:mi>a</mml:mi><mml:mi>c</mml:mi><mml:mi>c</mml:mi><mml:mi>h</mml:mi><mml:mi>a</mml:mi><mml:mi>r</mml:mi><mml:mi>o</mml:mi><mml:mi>m</mml:mi><mml:mi>y</mml:mi><mml:mi>c</mml:mi><mml:mi>e</mml:mi><mml:mi>s</mml:mi><mml:mi>c</mml:mi><mml:mi>e</mml:mi><mml:mi>r</mml:mi><mml:mi>e</mml:mi><mml:mi>v</mml:mi><mml:mi>i</mml:mi><mml:mi>s</mml:mi><mml:mi>i</mml:mi><mml:mi>a</mml:mi><mml:mi>e</mml:mi></mml:mrow></mml:math><inline-graphic xlink:href="zhang-ieq1-2916038.gif"/></alternatives></inline-formula> datasets and compare with other seven state-of-the-art methods (DC, BC, NC, PeC, WDC, SON, and TEO) in terms of true predicted number, jackknife curve, and precision-recall curve. Simulation results show that the TEGS outperforms the other compared methods in identifying essential proteins. The source code of TEGS is freely available at <uri>https://github.com/wzhangwhu/TEGS</uri>.
Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation

Significance Influenza A virus (IAV) is a major cause of respiratory infections. We show that mice lacking the N-terminal domain of α-dystroglycan (α-DGN) exhibit significantly higher viral titers in the lungs after IAV infection. In addition, we show that overexpression of α-DGN in the lungs, both prior and during IAV infection, significantly reduces viral load and that recombinant α-DGN disrupts hemagglutination mediated by the influenza virus. Collectively, we uncover a protective role for α-DGN in IAV proliferation, suggesting it may have antiviral properties and could potentially be used as a treatment for IAV infection. As α-DGN levels are altered in more (inflammatory) disease states, this insight opens new avenues of investigation into the role of α-DGN in inflammation. α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Notably, α-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted α-DGN remains unknown. Here, we show that mice lacking α-DGN exhibit significantly higher viral titers in the lungs after Influenza A virus (IAV) infection (strain A/Puerto Rico/8/1934 H1N1), suggesting an inability to control virus load. Consistent with this, overexpression of α-DGN before infection or intranasal treatment with recombinant α-DGN prior and during infection, significantly reduced IAV titers in the lungs of wild-type mice. Hemagglutination inhibition assays using recombinant α-DGN showed in vitro neutralization of IAV. Collectively, our results support a protective role for α-DGN in IAV proliferation.
RADIOFREQUENCY EXPOSURE FROM WIRELESS LANS UTILIZING WI-FI TECHNOLOGY

This survey measured radiofrequency (RF) fields from wireless local area networks (WLANs) using Wi-Fi technology against a background of RF fields in the environment over the frequency range 75 MHz–3 GHz. A total of 356 measurements were conducted at 55 sites (including private residences, commercial spaces, health care and educational institutions, and other public spaces) in four countries (U.S., France, Germany, Sweden). Measurements were conducted under conditions that would result in the higher end of exposures from such systems. Where possible, measurements were conducted in public spaces as close as practical to the Wi-Fi access points. Additional measurements were conducted at a distance of approximately 1 m from a laptop while it was uploading and downloading large files to the WLAN. This distance was chosen to allow a useful comparison of fields in the far-field of the antenna in the laptop, and give a representative measure of the exposure that a bystander might receive from the laptop. The exposure to the user, particularly if the antenna of the client card were placed against his or her body, would require different measurement techniques beyond the scope of this study. In all cases, the measured Wi-Fi signal levels were very far below international exposure limits (IEEE C95.1-2005 and ICNIRP) and in nearly all cases far below other RF signals in the same environments. An Appendix discusses technical aspects of the IEEE 802.11 standard on which WLANs operate that are relevant to determining the levels of RF energy exposure from WLANs. Important limiting factors are the low operating power of client cards and access points, and the low duty cycle of transmission that normally characterizes their operation.
Turtles maintain mitochondrial integrity but reduce mitochondrial respiratory capacity in the heart after cold acclimation and anoxia

ABSTRACT Mitochondria are important to cellular homeostasis, but can become a dangerous liability when cells recover from hypoxia. Anoxia-tolerant freshwater turtles show reduced mitochondrial respiratory capacity and production of reactive oxygen species (ROS) after prolonged anoxia, but the mechanisms are unclear. Here, we investigated whether this mitochondrial suppression originates from downregulation of mitochondrial content or intrinsic activity by comparing heart mitochondria from (1) warm (25°C) normoxic, (2) cold-acclimated (4°C) normoxic and (3) cold-acclimated anoxic turtles. Transmission electron microscopy of heart ventricle revealed that these treatments did not affect mitochondrial volume density and morphology. Furthermore, neither enzyme activity, protein content nor supercomplex distribution of electron transport chain (ETC) enzymes changed significantly. Instead, our data imply that turtles inhibit mitochondrial respiration rate and ROS production by a cumulative effect of slight inhibition of ETC complexes. Together, these results show that maintaining mitochondrial integrity while inhibiting overall enzyme activities are important aspects of anoxia tolerance. Summary: Inhibition of mitochondrial respiration rate and production of reactive oxygen species during cold acclimation and anoxia, while preserving mitochondrial content and morphology, is central to the anoxia tolerance of freshwater turtle hearts.
Impact of residential area on the management of rheumatoid arthritis patients initiating their first biologic DMARD

Abstract Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area. We described differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residential area type. Cross-sectional analysis of 793 adult RA patients in the longitudinal Ontario Best Practices Research Initiative (OBRI) registry initiating their first bDMARD <30 days prior to or anytime post-enrolment. Patient residential and clinic areas (rural vs. urban) were classified using 2 methods: postal codes and Statistics Canada population centres. Sociodemographics, disease characteristics, and RA medications (tumor necrosis factor inhibitor [TNFi] vs. non-TNFi, concurrent use of conventional synthetic DMARDs [csDMARDs], and intravenous [IV] vs. subcutaneous [SC] bDMARD) at initiation of first bDMARD were contrasted between residential area types. Other than marital status, first language, and race (higher proportion of married, English speaking, Caucasian patients in rural areas), no significant differences were observed in the demographic and disease characteristics of patients living in rural and urban areas. In multivariate analysis, there was no association between residential area type and type of bDMARD use, concurrent csDMARD(s) use or route of bDMARD. However, patients living farther from their treating clinic were significantly less likely to initiate IV bDMARD. Female rheumatologist and rural clinic location were independently associated with lower odds of IV bDMARD use. The use of SC vs. IV bDMARD was associated with being seen in a clinic located in a rural area, being treated by a female rheumatologist, and living farther from treating clinic. These results suggest possible prescription bias in bDMARD selection and/or patient preferences due to convenience.
Optimization of a flow cytometry‐based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrow

To study the biology of rare bone marrow (BM) multipotent mesenchymal stromal cells (MSCs), recognized protocols are needed. Colony‐forming unit‐fibroblast (CFU‐F) assays have historically been used for the enumeration of MSCs. However, the need to isolate and further analyze MSCs requires new strategies based on cell surface markers. The purpose of this work was to verify the phenotype of BM MSCs in vivo and to develop flow cytometry‐based methods for their evaluation.
Joint machine-type device selection and power allocation for buffer-aided cognitive M2M communication

In this paper, a cognitive machine-to-machine (M2M) communication network is considered, in which a cellular network shares the spectrum with the M2M communication network with M machine-type devices (MTDs), one half-duplex relay, and one MTD gateway for data gathering. One key challenge is that in the future 5G wireless networks, there will be billions of those small MTDs, and therefore, a MTD selection protocol is required for managing data transmission between MTDs. A joint buffer-aided MTD selection and power allocation protocol is proposed to maximize the MTDs' sum-rate provided that the induced interference to the cellular network is limited. In particular, in the proposed scheme, at each time slot and each subcarrier, the cognitive M2M network optimally decides on whether to be silent or to select either the relay or one of the MTDs for data transmission. To this end, for each MTD, there exists a buffer at the relay to avoid data loss. The closed-form expressions for the power coefficients of MTDs are calculated. Simulation results show that the proposed policy improves the sum-rate of the MTDs in comparison with the other proposed schemes for M2M communication without buffer.
Targeted Notch1 inhibition with a Notch1 antibody, OMP‐A2G1, decreases tumor growth in two murine models of prostate cancer in association with differing patterns of DNA damage response gene expression

Notch plays a protumorigenic role in many cancers including prostate cancer (PCa). Global notch inhibition of multiple Notch family members using γ‐secretase inhibitors has shown efficacy in suppressing PCa growth in murine models. However, global Notch inhibition is associated with marked toxicity due to the widespread function of many different Notch family members in normal cell physiology. Accordingly, in the current study, we explored if specific inhibition of Notch1 would effectively inhibit PCa growth in a murine model. The androgen‐dependent VCaP and androgen‐independent DU145 cell lines were injected subcutaneously into mice. The mice were treated with either control antibody 1B7.11, anti‐Notch1 antibody (OMP‐A2G1), docetaxel or the combination of OMP‐A2G1 and docetaxel. Tumor growth was measured using calipers. At the end of the study, tumors were assessed for proliferative response, apoptotic response, Notch target gene expression, and DNA damage response (DDR) expression. OMP‐A2G1 alone inhibited tumor growth of both PCa cell lines to a greater extent than docetaxel alone. There was no additive or synergistic effect of OMP‐A2G1 and docetaxel. The primary toxicity was weight loss that was controlled with dietary supplementation. Proliferation and apoptosis were affected differentially in the two cell lines. OMP‐A2G1 increased expression of the DDR gene GADD45α in VCaP cells but downregulated GADD45α in Du145 cells. Taken together, these data show that Notch1 inhibition decreases PCa xenograft growth but does so through different mechanisms in the androgen‐dependent VCaP cell line vs the androgen‐independent DU145 cell line. These results provide a rationale for further exploration of targeted Notch inhibition for therapy of PCa.
Microneedle-Assisted Transdermal Delivery of Etanercept for Rheumatoid Arthritis Treatment

Rheumatoid arthritis (RA) is a complicated autoimmune disease. The clinical applications of etanercept (EN), a TNF-α inhibitor, can efficiently halt the development of RA. EN is mainly administrated by subcutaneous injection, which may cause low compliance, side effects, and infection risk. In this study, a hyaluronic acid crosslinked microneedle system (MN) was constructed as the transdermal alternative to deliver EN. We describe the formulation, fabrication, characterization, and transdermal insertion study of MN. In vitro bioactivity of EN was conducted and analyzed by dynamic light scattering and circular dichroism spectrum. In vivo evaluation of MN was studied on adjuvant-induced arthritis mice. The MN possessed sufficient mechanical strength, good biocompatibility, little influence on the bioactivity of EN, and high anti-inflammatory efficacy. This work represents a successful example of delivering macromolecule therapeutic treatment by MN for RA treatment. The transdermal delivery of EN by MN offers a new treatment option for RA patients.
4-Hydroxyglutamate is a novel predictor of pre-eclampsia

Abstract Background Pre-term pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. A multi-centre randomized–controlled trial has shown that first-trimester screening followed by treatment of high-risk women with aspirin reduces the risk of pre-term pre-eclampsia. However, the biomarkers currently employed in risk prediction are only weakly associated with the outcome. Methods We conducted a case–cohort study within the Pregnancy Outcome Prediction study to analyse untargeted maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age (wkGA) in women with pre-eclampsia delivering at term (n = 165) and pre-term (n = 29), plus a random sample of the cohort (n = 325). We used longitudinal linear mixed models to identify candidate metabolites at 20/28 wkGA that differed by term pre-eclampsia status. Candidates were validated using measurements at 36 wkGA in the same women. We then tested the association between the 12-, 20- and 28-wkGA measurements and pre-term pre-eclampsia. We externally validated the association using 24- to 28-wkGA samples from the Born in Bradford study (25 cases and 953 controls). Results We identified 100 metabolites that differed most at 20/28 wkGA in term pre-eclampsia. Thirty-three of these were validated (P < 0.0005) at 36 wkGA. 4-Hydroxyglutamate and C-glycosyltryptophan were independently predictive at 36 wkGA of term pre-eclampsia. 4-Hydroxyglutamate was also predictive (area under the receiver operating characteristic curve, 95% confidence interval) of pre-term pre-eclampsia at 12 (0.673, 0.558–0.787), 20 (0.731, 0.657–0.806) and 28 wkGA (0.733, 0.627–0.839). The predictive ability of 4-hydroxyglutamate at 12 wkGA was stronger than two existing protein biomarkers, namely PAPP-A (0.567, 0.439–0.695) and placenta growth factor (0.589, 0.463–0.714). Finally, 4-hydroxyglutamate at 24–28 wkGA was positively associated with pre-eclampsia (term or pre-term) among women from the Born in Bradford study. Conclusions 4-hydroxyglutamate is a novel biochemical predictor of pre-eclampsia that provides better first-trimester prediction of pre-term disease than currently employed protein biomarkers.
Associations of Community Structure and Functions of Benthic Invertebrates with Nickel Concentrations: Analyses from Field Surveys

Field surveys provide valuable empirical information about the effects of heavy metals on the biological integrity of river ecosystems. To evaluate the effect of nickel (Ni) on aquatic organisms, we conducted field surveys of benthic invertebrates and Ni concentrations at 45 sites in 19 rivers in Japan. We examined the relationships between 11 structural or functional measures of benthic invertebrate communities and free Ni ion concentrations with a 90th quantile regression model. Among the measures, Ephemeroptera, Plecoptera, and Trichoptera (EPT) richness, total wet biomass of all invertebrates, and total abundance of filter feeders were negatively associated with free Ni ion concentrations. The total abundance of mud burrowers and their percentage contribution to the abundance of all invertebrates as well as the total abundances of collector‐gatherers and predators were positively associated with the Ni ion concentrations. The free ion concentrations of Ni associated with a 5% reduction of one of the 3 measures from its 90th quantile value at reference sites (EC5) were estimated to be 0.2 to 7.6 µg/L. The point estimates of EC5 were similar in order of magnitude to the environmental quality standard for Ni in the European Union. However, the usefulness of simple point estimates of effective concentrations based on quantile regression lines should be carefully examined because the uncertainties in our EC5 values were large. Environ Toxicol Chem 2019;38:1728–1737. © 2019 SETAC