bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human papillomavirus and abnormal cervical lesions among HIV-infected women in HIV-discordant couples from Kenya
Authors: Guthrie Brandon L , Rositch Anne F , Cooper Joy Alison , Farquhar Carey , Bosire Rose , Choi Robert , Kiarie James , Smith Jennifer S 
Published: January 2020

Objective
HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies.

Methods
A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay.

Results
Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive.

Conclusion
HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance.
TRIBOLOGICAL PROPERTIES OF THE CARBON AND NITROGEN-BASED HARD FILMS SLIDING AGAINST THE NICKEL-BASED SUPERALLOY
Authors: LEI X. L. , YANG B. X. , HE Y. , SUN F. H. 
Published: January 2020

This study is focused on the tribological properties of micro- and nano-crystalline diamond (MCD and NCD), non-hydrogenated and hydrogenated diamond-like carbon (DLC and DLC-H) and nitrogen-based (CrN, TiN and TiAlN) coatings sliding against the super alloy Inconel 718, in terms of the maximal and average coefficients of frictions (COFs), the worn morphologies and the specific wear rates, by the rotating ball-on-plate configuration under dry condition. The results show that the nitrogen-based films show comparable COFs and wear rates with the WC–Co substrates. The DLC and DLC-H show lower COFs compared with the nitrogen-based films. Furthermore, their wear resistance is limited due to their low thickness compared with MCD and NCD, which have the same elemental composition. The DLC-H coating exhibits much lower wear rate compared with the DLC coating, which may be derived from the passivation of dangling bonds by the linking of H to C atoms. The MCD and NCD films show the lowest average COFs and mild wear after tribotests, due to their high hardness and low adhesive strength between pure diamond and the super alloy. Among all the tested films, the NCD film-based tribopair presents the lowest maximal and average COFs, tiny wear debris particles, mild wear of ball and plate without scratching grooves, indicating that the NCD film may be suitable to be deposited on cutting tools for super alloy machining.
Capture Steps: Robust Walking for Humanoid Robots
Authors: Missura Marcell , Bennewitz Maren , Behnke Sven 
Published: January 2020

Stable bipedal walking is a key prerequisite for humanoid robots to reach their potential of being versatile helpers in our everyday environments. Bipedal walking is, however, a complex motion that requires the coordination of many degrees of freedom while it is also inherently unstable and sensitive to disturbances. The balance of a walking biped has to be constantly maintained. The most effective ways of controlling balance are well timed and placed recovery steps — capture steps — that absorb the expense momentum gained from a push or a stumble. We present a bipedal gait generation framework that utilizes step timing and foot placement techniques in order to recover the balance of a biped even after strong disturbances. Our framework modifies the next footstep location instantly when responding to a disturbance and generates controllable omnidirectional walking using only very little sensing and computational power. We exploit the open-loop stability of a central pattern generated gait to fit a linear inverted pendulum model (LIPM) to the observed center of mass (CoM) trajectory. Then, we use the fitted model to predict suitable footstep locations and timings in order to maintain balance while following a target walking velocity. Our experiments show qualitative and statistical evidence of one of the strongest push-recovery capabilities among humanoid robots to date.
Combinatorial Studies into the Effect of Thermally Inter-Diffused Magnesium on the Kinetics of Organic Coating Cathodic Delamination from Zinc Galvanized Steel
Authors: Wint N. , Barrett Z. S. , McMurray H. N. , Williams G. 
Published: January 2020

This paper describes a high-throughput study into the role of Mg in preventing corrosion driven coating disbondment of organic coatings from Zn-Mg alloy galvanized steel. A graded Mg wedge is applied to a hot-dip zinc galvanised steel substrate using physical vapour deposition, and subsequently annealed to produce metallic inter-diffusion and formation of Mg2Zn11 intermetallic. An overcoat of electrically insulating polyvinyl butyral (PVB) is applied and corrosion is initiated from a penetrative coating defect using an aqueous electrolyte. The variation in Mg coating weight across the wedge facilitates a systematic investigation of the effect of Mg on Volta potential and the rate of corrosion driven cathodic coating disbondment using scanning Kelvin probe (SKP) potentiometry. The rate of cathodic disbondment is shown to decrease rapidly even at very low Mg coating weight (corresponding to 25 nm thickness before annealing). The results are explained in terms of the galvanic polarity of the corrosion cell formed between Zn exposed at the defect site, and the intact Zn-Mg layer at the metal-organic coating interface.
Sex differences in mitochondrial Ca2+ handling in mouse fast-twitch skeletal muscle in vivo
Authors: Watanabe Daiki , Hatakeyama Koji , Ikegami Ryo , Eshima Hiroaki , Yagishita Kazuyoshi , Poole David C. , Kano Yutaka 
Published: January 2020

We investigated sex differences in mitochondrial Ca2+ handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca2+ concentration ([Ca2+]cyto) were measured in vivo using tibialis anterior muscles from male and female mice. The muscles were exposed to increasing concentrations of cyclopiazonic acid [CPA; sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitor] (from 10 to 30 to 50 μM at 10 min intervals). Thirty minutes after treatment, [Ca2+]cyto was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca2+]cyto in male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca2+ uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca2+]cyto increase. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared with males (mitochondria number: 13.1 ± 1.0 in males vs. 19.9 ± 2.3 in females; mitochondrial volume: 0.034 ± 0.004 μm3/μm3 fiber volume in males vs. 0.066 ± 0.008 μm3/μm3 fiber volume in females, both P < 0.05). There were no sex differences in the content of SR Ca2+-ATPase, mitochondrial Ca2+ uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that 1) mitochondrial Ca2+ uptake ability is greater in female than male myocytes, and 2) this superior Ca2+ uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content but not to the expression of mitochondrial proteins related to mitochondrial Ca2+ uptake. NEW & NOTEWORTHY This investigation presents evidence that female versus male fast-twitch muscle exhibits a greater mitochondrial calcium ion uptake capability that is partly conferred by the higher intermyofibrillar mitochondrial volume density.
Quantification of dynamic cerebral autoregulation and CO2 dynamic vasomotor reactivity impairment in essential hypertension
Authors: Marmarelis Vasilis Z. , Shin Dae C. , Oesterreich Mareike , Mueller Martin 
Published: January 2020

The study of dynamic cerebral autoregulation (DCA) in essential hypertension has received considerable attention because of its clinical importance. Several studies have examined the dynamic relationship between spontaneous beat-to-beat arterial blood pressure data and contemporaneous cerebral blood flow velocity measurements (obtained via transcranial Doppler at the middle cerebral arteries) in the form of a linear input-output model using transfer function analysis. This analysis is more reliable when the contemporaneous effects of changes in blood CO2 tension are also taken into account, because of the significant effects of CO2 dynamic vasomotor reactivity (DVR) upon cerebral flow. In this article, we extract such input-output predictive models from spontaneous time series hemodynamic data of 24 patients with essential hypertension and 20 normotensive control subjects under resting conditions, using the novel methodology of principal dynamic modes (PDMs) that achieves improved estimation accuracy over previous methods for relatively short and noisy data. The obtained data-based models are subsequently used to compute indexes and markers that quantify DCA and DVR in each subject or patient and therefore can be used to assess the effects of essential hypertension. These model-based DCA and DVR indexes were properly defined to capture the observed effects of DCA and VR and found to be significantly different ( P < 0.05) in the hypertensive patients. We also found significant differences between patients and control subjects in the relative contribution of three PDMs to the model output prediction, a finding that offers the prospect of identifying the physiological mechanisms affected by essential hypertension when the PDMs are interpreted in terms of specific physiological mechanisms. NEW & NOTEWORTHY This article presents novel model-based methodology for obtaining diagnostic indexes of dynamic cerebral autoregulation and dynamic vasomotor reactivity in hypertension.
Exercise-induced vasodilation is not impaired following radial artery catheterization in coronary artery disease patients
Authors: Tryfonos Andrea , Cocks Matthew , Mills Joseph , Green Daniel J. , Dawson Ellen A. 
Published: January 2020

Diagnosis and treatment for coronary artery disease (CAD) often involves angiography and/or percutaneous coronary intervention. However, the radial artery catheterization required during both procedures may result in acute artery dysfunction/damage. While exercise-based rehabilitation is recommended for CAD patients following catheterization, it is not known if there is a period when exercise may be detrimental due to catheter-induced damage. Animal studies have demonstrated exercise-induced paradoxical vasoconstriction postcatheterization. This study aimed to examine arterial responses to acute exercise following catheterization. Thirty-three CAD patients (65.8 ± 7.3 yr, 31.5 ± 6.3 kg/m2, 82% men) undergoing transradial catheterization were assessed before and 1 wk postcatheterization. Radial artery (RA) diameter and shear rate were assessed during handgrip exercise (HE), in both the catheterized (CATH) and control (CON) arms. Endothelial function was also assessed via simultaneous bilateral radial flow-mediated dilation (FMD) at both time points. We found that the increase in RA diameter and shear stress in response to HE ( P < 0.0001) was maintained postcatheterization in both the CATH and CON arms, whereas FMD following catheterization was impaired in the CATH [6.5 ± 3.3 to 4.7 ± 3.5% ( P = 0.005)] but not in the CON [6.2 ± 2.6 to 6.4 ± 3.5% ( P = 0.797)] limb. While endothelial dysfunction, assessed by FMD, was apparent 1 wk postcatheterization, the ability of the RA to dilate in response to exercise was not impaired. The impact of catheterization and consequent endothelial denudation on vascular dys/function in humans may therefore be stimulus specific, and a highly level of redundancy appears to exist that preserves exercise-mediated vasodilator responses. NEW & NOTEWORTHY Despite depressed flow-mediated endothelium-dependent dilation following catheterization-induced damage, radial artery responses to handgrip exercise were preserved. This suggests that arterial responses to catheterization may be stimulus specific and that redundant mechanisms may compensate for vasodilator impairment during exercise. This has implications for exercise-based rehabilitation after catheterization.
Impact of exercise training status on the fiber type-specific abundance of proteins regulating intramuscular lipid metabolism
Authors: Shaw C. S. , Swinton C. , Morales-Scholz M. G. , McRae N. , Erftemeyer T. , Aldous A. , Murphy R. M. , Howlett K. F. 
Published: January 2020

Endurance training enhances the capacity for fat oxidation during exercise due to increased utilization of intramuscular lipid (IMCL). This study quantitatively investigated the impact of exercise training status on muscle fiber type-specific abundance of regulatory proteins involved in IMCL utilization. Endurance-trained [ n = 7 subjects, peak oxygen consumption (V̇o2peak) 62.6 ± 4.1 (SD) mL·min−1·kg−1] and non-endurance-trained ( n = 8 subjects, V̇o2peak 44.9 ± 5.3 mL·min−1·kg−1) young men completed an incremental exercise test to determine maximal fat oxidation (MFO) and maximal oxygen uptake. Fiber type-specific IMCL content and protein abundance were assessed with immunofluorescence microscopy and immunoblot analysis of pooled single muscle fibers and whole muscle. Endurance-trained individuals displayed a higher MFO rate (0.45 ± 0.15 vs. 0.19 ± 0.07 g/min, P < 0.05), a greater proportion of type I muscle fibers, and higher IMCL content compared with untrained individuals ( P < 0.05). Adipose triglyceride lipase, hormone-sensitive lipase, perilipin 2, perilipin 5, and hydroxyacyl-coenzyme A dehydrogenase abundances were ~2–3-fold higher in type I muscle fibers compared with type IIa fibers ( P < 0.05). Correspondingly, these lipid proteins and oxidative enzymes were higher in endurance-trained individuals when assessed in whole muscle. MFO rate was strongly related to the proportion of type I fibers ( R = 0.81, P < 0.01). The abundance of proteins involved in the regulation of IMCL storage and oxidation is highly muscle fiber type specific. The increased capacity for fat oxidation in endurance-trained individuals corresponded with increased IMCL content and elevated abundance of lipolytic and oxidative enzymes in combination with a greater proportion of type I muscle fibers. NEW & NOTEWORTHY We have utilized contemporary techniques to compare the fiber type-specific characteristics of skeletal muscle from endurance-trained athletes and untrained individuals. We show that type I muscle fibers have a coordinated upregulation of proteins controlling intramuscular lipid storage, mobilization, and oxidation. Furthermore, the enhanced capacity for intramuscular lipid storage and utilization in endurance-trained individuals is related to the increased expression of lipid regulatory proteins combined with a greater proportion of type I muscle fibers.
Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218
Authors: Alvarez Secord Angeles , Bell Burdett Kirsten , Owzar Kouros , Tritchler David , Sibley Alexander B. , Liu Yingmiao , Starr Mark D. , Brady J. Chris , Lankes Heather A. , Hurwitz Herbert I. , Mannel Robert S. , Tewari Krishnansu S. , O'Malley David M. , Gray Heidi , Bakkum-Gamez Jamie N. , Fujiwara Keiichi , Boente Matthew , Deng Wei , Burger Robert A. , Birrer Michael J. , Nixon Andrew B. 
Published: January 2020

AbstractPurpose:GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses.Experimental Design:Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell–derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates.Results:Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS (P = 0.007) and OS (P = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS (P &lt; 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo.Conclusions:The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.
Targeting the Complement Alternative Pathway Permits Graft Versus Leukemia Activity while Preventing Graft Versus Host Disease
Authors: Nguyen Hung , Alawieh Ali , Bastian David , Kuril Sandeepkumar , Dai Min , Daenthanasanmak Anusara , Zhang Mengmeng , Iamsawat Supinya , Schutt Steven D. , Wu Yongxia , Sleiman M. Mahdi , Shetty Akshay , Atkinson Carl , Sun Shaoli , Varela Juan Carlos , Tomlinson Stephen , Yu Xue-Zhong 
Published: January 2020

AbstractPurpose:Application of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with hematologic disorders is limited by the development of GVHD. Separation of GVHD and graft-versus-leukemia (GVL) remains a great challenge in the field. We investigated the contribution of individual pathways involved in the complement cascade in GVH and GVL responses to identify specific targets by which to separate these two processes.Experimental Design:We used multiple preclinical murine and human-to-mouse xenograft models involving allo-HCT recipients lacking components of the alternative pathway (AP) or classical pathway (CP)/lectin pathway (LP) to dissect the role of each individual pathway in GVHD pathogenesis and the GVL effect. For translational purposes, we used the AP-specific complement inhibitor, CR2-fH, which localizes in injured target organs to allow specific blockade of complement activation at sites of inflammation.Results:Complement deposition was evident in intestines of mice and patients with GVHD. In a preclinical setting, ablation of the AP, but not the CP/LP, significantly improved GVHD outcomes. Complement activation through the AP in host hematopoietic cells, and specifically dendritic cells (DC), was required for GVHD progression. AP deficiency in recipients decreased donor T-cell migration and Th1/Th2 differentiation, while increasing the generation of regulatory T cells. This was because of decreased activation and stimulatory activity of recipient DCs in GVHD target organs. Treatment with CR2-fH effectively prevented GVHD while preserving GVL activity.Conclusions:This study highlights the AP as a new therapeutic target to prevent GVHD and tumor relapse after allo-HCT. Targeting the AP by CR2-fH represents a promising therapeutic approach for GVHD treatment.
Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment
Authors: Chen Peiwen , Hsu Wen-Hao , Chang Andrew , Tan Zhi , Lan Zhengdao , Zhou Ashley , Spring Denise J. , Lang Frederick F. , Wang Y. Alan , DePinho Ronald A. 
Published: January 2020

Abstract

Glioblastoma (GBM) is a lethal brain tumor containing a subpopulation of glioma stem cells (GSC). Pan-cancer analyses have revealed that stemness of cancer cells correlates positively with immunosuppressive pathways in many solid tumors, including GBM, prompting us to conduct a gain-of-function screen of epigenetic regulators that may influence GSC self-renewal and tumor immunity. The circadian regulator CLOCK emerged as a top hit in enhancing stem-cell self-renewal, which was amplified in about 5% of human GBM cases. CLOCK and its heterodimeric partner BMAL1 enhanced GSC self-renewal and triggered protumor immunity via transcriptional upregulation of OLFML3, a novel chemokine recruiting immune-suppressive microglia into the tumor microenvironment. In GBM models, CLOCK or OLFML3 depletion reduced intratumoral microglia density and extended overall survival. We conclude that the CLOCK–BMAL1 complex contributes to key GBM hallmarks of GSC maintenance and immunosuppression and, together with its downstream target OLFML3, represents new therapeutic targets for this disease.

Significance:
Circadian regulator CLOCK drives GSC self-renewal and metabolism and promotes microglia infiltration through direct regulation of a novel microglia-attracting chemokine, OLFML3. CLOCK and/or OLFML3 may represent novel therapeutic targets for GBM.
This article is highlighted in the In This Issue feature, p. 327
Can the Help Match the Hype? KRASG12C-Specific Inhibitors and Beyond
Authors: Klempner Samuel J. , Hata Aaron N. 
Published: January 2020

Abstract

Summary:
Hallin and colleagues demonstrate the preclinical activity of the KRASG12C-specific inhibitor MRTX849 in a series of in vitro and in vivo studies with supporting pilot clinical efficacy. Variable responsiveness despite effective KRASG12C inhibition highlights both the promise and potential need for combinatorial strategies to optimally target KRASG12C-driven cancers.
See related article by Hallin et al., p. 54.
Lessons from the A2A Adenosine Receptor Antagonist–Enabled Tumor Regression and Survival in Patients with Treatment-Refractory Renal Cell Cancer
Authors: Sitkovsky Michail V. 
Published: January 2020

Abstract

Summary:
In this issue of Cancer Discovery, Fong and colleagues describe the encouraging observations of tumor regression, disease control, and survival of patients with otherwise refractory renal cell cancer with progressive disease after treatment with the conceptually novel oral antagonist of the A2A adenosine receptor (A2AR), ciforadenant. A2AR antagonists may represent the until now missing but critically important part of more effective immunotherapies of cancer, because they prevent the inhibition of tumor-reactive T and natural killer cells by blocking the immunosuppressive hypoxia–A2A–adenosinergic signaling, which represents an emerging immunosuppressive hallmark of tumors that are the most resistant to therapies.
See related article by Fong et al., p. 40.