bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarimeters for the SPASCHARM Experiment
Authors: Semenov P. A. , Bogdanov A. A. , Bukreeva S. I. , Chetvertkov M. A. , Chetvertkova V. A. , Garkusha V. I. , Meshchanin A. P. , Mochalov V. V. , Nurushev S. B. , Nurusheva M. B. , Runtso M. F. , Ridiger A. V. , Rykov V. L. , Ryzhikov S. V. , Strikhanov M. N. , Vasiliev A. N. , Zapolsky V. N.
Published: March 2016

A beam channel of polarized protons and antiprotons produced from decays of [Formula: see text]- and anti-[Formula: see text]-hyperons for the SPASCHARM experiment is to be built at IHEP U-70 accelerator in Protvino, Russia. The methods for tagging and measuring polarization of the beam (anti)protons are discussed in this report. The fast on-line beam tagging exploits the correlations between polarization and kinematics of (anti)protons originated from (anti)[Formula: see text]-decays. In the intermediate focus of primary target, decay (anti)protons of different transverse polarizations are spatially dispersed transversely with respect to the beam axis. The tagging system, consisting of fast beam detectors with good spatial resolution, measures the momentum and trajectory of each beam particle, including its position at the intermediate focus, thus allowing instant (on-line) assignment of the transverse polarization value to each (anti)proton. This system is also extremely useful for the beam channel tuning. While being fast and convenient, the polarization tagging fully relies on computing of particle transportation in the beam channel. In order to verify the real beam polarization and operating of the tagging system and beam channel, the independent absolute beam polarimetry is to be used. It is based on measuring the spin asymmetries in elastic scattering of beam (anti)protons in Coulomb-Nuclear Interference (CNI) and diffractive kinematic regions. It is estimated that less than one week of data taking would allow measuring an absolute beam polarization at the statistical accuracy of [Formula: see text]4–5%.
Towards Polarised Antiprotons: Machine Developments for Spin-Filtering Studies
Authors: Lenisa Paolo
Published: March 2016

We address the commissioning of the experimental equipment and the machine studies required for the first spin-filtering experiment with protons at the COSY ring in Jülich (Germany) at a beam kinetic energy of 49.3 MeV. The implementation of a low-beta insertion made it possible to achieve beam lifetimes of 8000 s in the presence of a dense polarized hydrogen storage cell target. The developed techniques can be directly applied to antiproton machines and allow for the determination of the spin-dependent pbar-p cross sections via spin-filtering.
Implications of Lymphatic Transport to Lymph Nodes in Immunity and Immunotherapy
Authors: Thomas Susan N. , Rohner Nathan A. , Edwards Erin E.
Published: March 2016

Adaptive immune response consists of many highly regulated, multistep cascades that protect against infection while preserving the health of autologous tissue. The proper initiation, maintenance, and resolution of such responses require the precise coordination of molecular and cellular signaling over multiple time and length scales orchestrated by lymphatic transport. In order to investigate these functions and manipulate them for therapy, a comprehensive understanding of how lymphatics influence immune physiology is needed. This review presents the current mechanistic understanding of the role of the lymphatic vasculature in regulating biomolecule and cellular transport from the interstitium, peripheral tissue immune surveillance, the lymph node stroma and microvasculature, and circulating lymphocyte homing to lymph nodes. This review also discusses the ramifications of lymphatic transport in immunity as well as tolerance and concludes with examples of how lymphatic-mediated targeting of lymph nodes has been exploited for immunotherapy applications.
Coinhibitory Pathways in Immunotherapy for Cancer
Authors: Baumeister Susanne H. , Freeman Gordon J. , Dranoff Glenn , Sharpe Arlene H.
Published: March 2016

The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Immune responses are regulated by a number of immunological checkpoints that promote protective immunity and maintain tolerance. T cell coinhibitory pathways restrict the strength and duration of immune responses, thereby limiting immune-mediated tissue damage, controlling resolution of inflammation, and maintaining tolerance to prevent autoimmunity. Tumors exploit these coinhibitory pathways to evade immune eradication. Blockade of the PD-1 and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients with a variety of tumor types, and additional combinations are further improving response rates. In this review we discuss the immunoregulatory functions of coinhibitory pathways and their translation to effective immunotherapies for cancer.
Safety Climate in Organizations
Authors: Griffin Mark A. , Curcuruto Matteo
Published: March 2016

Safety climate is a collective construct derived from individuals' shared perceptions of the various ways that safety is valued in the workplace. Research over the past 35 years shows that safety climate is an important predictor of safety behavior and safety outcomes such as accidents and injury. We first review the conceptual foundations of safety climate and explore how the construct can be applied to different levels of analysis. We then review ways that safety climate influences individual processes of sense making, motivation, and work behavior. Next, we explore the impact of safety climate on organization-level outcomes related to both safety and productivity. We conclude with suggestions for future research and practice to support the overall safety of people and organizations.
Democracy: A Never-Ending Quest
Authors: Przeworski Adam
Published: March 2016

Most of my work focused on the functioning and the limits of democracy. I place the evolution of our understanding of this bewildering institution in the context of historical events and consider the challenges posed by its current critics. I also reflect on methods, arguing that game theory is the natural language of the social sciences. These ruminations add up to a research agenda.
Buying, Expropriating, and Stealing Votes
Authors: Mares Isabela , Young Lauren
Published: March 2016

In elections around the world, large numbers of voters are influenced by promises or threats that are contingent on how they vote. Recently, the political science literature has made considerable progress in disaggregating clientelism along two dimensions: first, in recognizing the diversity of actors working as brokers, and second, in conceptualizing and disaggregating types of clientelism based on positive and negative inducements of different forms. In this review, we discuss recent findings explaining variation in the mix of clientelistic strategies across countries, regions, and individuals and identify a few areas for future progress, particularly in explaining variation in targeting of inducements by politicians on different types of voters.
Elucidation of Degradation Factor Distribution in a Same Electrode on PEFC
Authors: Sugiura Kimihiko , Takahashi Naoya , Daigo Akihiko , Murakami Tetsuya
Published: March 2016

Our proposal diagnostics evaluates the PEFC’s transient response with a resistance polarization, an activation polarization and a diffusion polarization, and derives diagnostics parameters by analyzing this transient response. Because we have already clarified that this diagnostics system was able to diagnose the 25cm2 PEFC single cell, we tried to elucidate the degradation factor distribution in the same electrode by applying it to the quadrisection separator. As a result, our diagnostics was able to judge the difference of the degradation factor in each section in the same electrode such as the resistance polarization is the highest at the gas upper stream, the activation polarization is the lowest at the middle section and the diffusion polarization is the highest at the gas downstream.
Numerical Simulation of Hydrogen Absorption Process in Metal Hydride Cartridge for Mobile Devices
Authors: Katayama Noboru , Dowaki Kiyoshi , Hayase Masanori
Published: March 2016

In this study, hydrogen absorption process was analyzed by using a numerical simulation, which included heat transfer, equilibrium pressure, and heat generation from metal hydride. The dimension of the metal hydride cartridge is 50 mm x 60 mm x 5 mm. The cartridge has a serpentine channel in which metal hydride is packed. The author will fabricate a real cartridge made of stainless steel in the future work. The enthalpy and entropy are experimentally obtained from the equilibrium pressures of LmNi4.73Mn0.12Al0.15. The pressure and temperature are 0.5 MPa and 303 K, which are typical absorption condition for this metal hydride. The calculation results show the transient temperature and hydrogen content distribution. Hydrogen are filled and the temperature reaches a steady state in 240 seconds.
PICK1/calcineurin suppress ASIC1-mediated Ca2+ entry in rat pulmonary arterial smooth muscle cells
Authors: Herbert Lindsay M. , Nitta Carlos H. , Yellowhair Tracylyn R. , Browning Carly , Gonzalez Bosc Laura V. , Resta Thomas C. , Jernigan Nikki L.
Published: March 2016

Acid-sensing ion channel 1 (ASIC1) contributes to Ca2+ influx and contraction in pulmonary arterial smooth muscle cells (PASMC). ASIC1 binds the PDZ (PSD-95/Dlg/ZO-1) domain of the protein interacting with C kinase 1 (PICK1), and this interaction is important for the subcellular localization and/or activity of ASIC1. Therefore, we first hypothesized that PICK1 facilitates ASIC1-dependent Ca2+ influx in PASMC by promoting plasma membrane localization. Using Duolink to determine protein-protein interactions and a biotinylation assay to assess membrane localization, we demonstrated that the PICK1 PDZ domain inhibitor FSC231 diminished the colocalization of PICK1 and ASIC1 but did not limit ASIC1 plasma membrane localization. Although stimulation of store-operated Ca2+ entry (SOCE) greatly enhanced colocalization between ASIC1 and PICK1, both FSC231 and shRNA knockdown of PICK1 largely augmented SOCE. These data suggest PICK1 imparts a basal inhibitory effect on ASIC1 Ca2+ entry in PASMC and led to an alternative hypothesis that PICK1 facilitates the interaction between ASIC1 and negative intracellular modulators, namely PKC and/or the calcium-calmodulin-activated phosphatase calcineurin. FSC231 limited PKC-mediated inhibition of SOCE, supporting a potential role for PICK1 in this response. Additionally, we found PICK1 inhibits ASIC1-mediated SOCE through an effect of calcineurin to dephosphorylate the channel. Furthermore, it appears PICK1/calcineurin-mediated regulation of SOCE opposes PKA phosphorylation and activation of ASIC1. Together our data suggest PKA and PICK1/calcineurin differentially regulate ASIC1-mediated SOCE and these modulatory complexes are important in determining downstream Ca2+ signaling.
Bayesian Inference for Functional Dynamics Exploring in fMRI Data
Authors: Guo Xuan , Liu Bing , Chen Le , Chen Guantao , Pan Yi , Zhang Jing
Published: March 2016

This paper aims to review state-of-the-art Bayesian-inference-based methods applied to functional magnetic resonance imaging (fMRI) data. Particularly, we focus on one specific long-standing challenge in the computational modeling of fMRI datasets: how to effectively explore typical functional interactions from fMRI time series and the corresponding boundaries of temporal segments. Bayesian inference is a method of statistical inference which has been shown to be a powerful tool to encode dependence relationships among the variables with uncertainty. Here we provide an introduction to a group of Bayesian-inference-based methods for fMRI data analysis, which were designed to detect magnitude or functional connectivity change points and to infer their functional interaction patterns based on corresponding temporal boundaries. We also provide a comparison of three popular Bayesian models, that is, Bayesian Magnitude Change Point Model (BMCPM), Bayesian Connectivity Change Point Model (BCCPM), and Dynamic Bayesian Variable Partition Model (DBVPM), and give a summary of their applications. We envision that more delicate Bayesian inference models will be emerging and play increasingly important roles in modeling brain functions in the years to come.
Astaxanthin Protects Primary Hippocampal Neurons against Noxious Effects of Aβ-Oligomers
Authors: Lobos Pedro , Bruna Barbara , Cordova Alex , Barattini Pablo , Galáz Jose Luis , Adasme Tatiana , Hidalgo Cecilia , Muñoz Pablo , Paula-Lima Andrea
Published: March 2016

Increased reactive oxygen species (ROS) generation and the ensuing oxidative stress contribute to Alzheimer’s disease pathology. We reported previously that amyloid-βpeptide oligomers (AβOs) produce aberrant Ca2+signals at sublethal concentrations and decrease the expression of type-2 ryanodine receptors (RyR2), which are crucial for hippocampal synaptic plasticity and memory. Here, we investigated whether the antioxidant agent astaxanthin (ATX) protects neurons from AβOs-induced excessive mitochondrial ROS generation, NFATc4 activation, and RyR2 mRNA downregulation. To determine mitochondrial H2O2production or NFATc4 nuclear translocation, neurons were transfected with plasmids coding for HyperMito or NFATc4-eGFP, respectively. Primary hippocampal cultures were incubated with 0.1 μM ATX for 1.5 h prior to AβOs addition (500 nM). We found that incubation with ATX (≤10 μM) for ≤24 h was nontoxic to neurons, evaluated by the live/dead assay. Preincubation with 0.1 μM ATX also prevented the neuronal mitochondrial H2O2generation induced within minutes of AβOs addition. Longer exposures to AβOs (6 h) promoted NFATc4-eGFP nuclear translocation and decreased RyR2 mRNA levels, evaluated by detection of the eGFP-tagged fluorescent plasmid and qPCR, respectively. Preincubation with 0.1 μM ATX prevented both effects. These results indicate that ATX protects neurons from the noxious effects of AβOs on mitochondrial ROS production, NFATc4 activation, and RyR2 gene expression downregulation.
Anterior Urethral Stricture Disease Negatively Impacts the Quality of Life of Family Members
Authors: Weese Jonathan R. , Raup Valary T. , Eswara Jairam R. , Marshall Stephen D. , Chang Andrew J. , Vetter Joel , Brandes Steven B.
Published: March 2016

Purpose. To quantify the quality of life (QoL) distress experienced by immediate family members of patients with urethral stricture via a questionnaire given prior to definitive urethroplasty. The emotional, social, and physical effects of urethral stricture disease on the QoL of family members have not been previously described.Materials and Methods. A questionnaire was administered prospectively to an immediate family member of 51 patients undergoing anterior urethroplasty by a single surgeon (SBB). The survey was comprised of twelve questions that addressed the emotional, social, and physical consequences experienced as a result of their loved one.Results. Of the 51 surveyed family members, most were female (92.2%), lived in the same household (86.3%), and slept in the same room as the patient (70.6%). Respondents experienced sleep disturbances (56.9%) and diminished social lives (43.1%). 82.4% felt stressed by the patient’s surgical treatment, and 83.9% (26/31) felt that their intimacy was negatively impacted.Conclusions. Urethral stricture disease has a significant impact on the family members of those affected. These effects may last decades and include sleep disturbance, decreased social interactions, emotional stress, and impaired sexual intimacy. Treatment of urethral stricture disease should attempt to mitigate the impact of the disease on family members as well as the patient.
Synthesis and Application of a Spirocompound as Clean Viscosity-Reducer for Crude Oil
Authors: Chen Shijun , Zhao Kang , Chen Gang , Bai Li , Feng Lajun
Published: March 2016

Heavy oil transportation has become a highly technical operation facing complex difficulties. One of the major difficulties in the pipeline transportation is the high viscosity that requires efficient and economical ways to deal with. The typical polymer viscosity reducers are a negative problem during oil refinement process for their chemical properties. The objective of this study is to seek small molecular compound, different from the traditional polymers, to reduce the viscosity of the crude oil. In this work, a spirocompound, 3,9-diphenyl-2,4,8,10-tetraoxa-spiro[5.5]undecane, was synthesized catalyzed by zeolite and modified zeolite, and the product was fully characterized by NMR, MS, and TG. Then, it was used as viscosity reducer for crude oil. The factors such as dosage and temperature on the viscosity behavior have been studied. The results showed a significant viscosity reduction at different temperature, and the most economical dosage is 500 ppm. The multiphenyl groups can interact with asphaltene byπ-πstacking, and the spirostructure can fix the stacking in different direction, which can prevent the agglomeration of wax crystals.
Laparoscopic Resection of Recurrence from Hepatocellular Carcinoma after Liver Transplantation: Case Reports and Review of the Literature
Authors: Sahakyan Mushegh A. , Kazaryan Airazat M. , Pomianowska Ewa , Abildgaard Andreas , Line Pål-Dag , Bjørnbeth Bjørn Atle , Edwin Bjørn , Røsok Bård Ingvald
Published: March 2016

Background. Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) indicates a poor prognosis. Surgery is considered the only curative option for selected patients with HCC recurrence following LT. Traditionally, the preference is given to the open approach.Methods. In this report, we present two cases of laparoscopic resections (LR) for recurrent HCC after LT, performed at Oslo University Hospital, Rikshospitalet.Results. Both procedures were executed without intraoperative and postoperative adverse events. Whereas one of the patients had a recurrence one year after LR, the other patient did not have any sign of disease during 3-year follow-up.Conclusions. We argue that, in selected cases, patients with HCC recurrence following LT may benefit from LR due to its limited tissue trauma and timely start of subsequent treatment if curative resection cannot be obtained. In patients with relatively favorable prognosis, LR facilitates postoperative recovery course and avoids unnecessary laparotomy.
Time-Varying Biased Proportional Guidance with Seeker’s Field-of-View Limit
Authors: Yang Zhe , Wang Hui , Lin Defu
Published: March 2016

Traditional guidance laws with range-to-go information or time-to-go estimation may not be implemented in passive homing missiles since passive seekers cannot measure relative range directly. A time-varying biased proportional guidance law, which only uses line-of-sight (LOS) rate and look angle information, is proposed to satisfy both impact angle constraint and seeker’s field-of-view (FOV) limit. In the proposed guidance law, two time-varying bias terms are applied to divide the trajectory into initial phase and terminal phase. The initial bias is designed as a function of LOS rate and look angle to maintain the seeker’s lock-on while the final bias eliminates the deviation between the integral value of angle control bias and the expected bias amount. A switching logic is adopted to change the biases continuously so that there is no abrupt acceleration change during the engagement. Extensive simulations considering both kinematic and realistic missile models are performed to illustrate the efficiency of the proposed method.
Genotoxic Effects of Chlorpyrifos in Freshwater Fish Cirrhinus mrigala Using Micronucleus Assay
Authors: Bhatnagar Anita , Yadav Abhay Singh , Cheema Navneet
Published: March 2016

The genotoxicity of pesticides is an issue of worldwide concern and chlorpyrifos is one of the largest selling organophosphate agrochemicals that has been widely detected in surface waters of India. The studies on long term genotoxic biomarkers are limited; therefore, present study was carried out to analyze the incidence of nuclear anomalies in the blood cells of fresh water fish Cirrhinus mrigala using micronucleus (MN) assay as a potential tool for assessment of genotoxicity. Acute toxicity of chlorpyrifos was evaluated by exposing fingerlings to different doses of chlorpyrifos (1/20, 1/10, and 1/5 of LC50) and LC50 was calculated as 0.44 mg L−1 using probit analysis. Blood samples were taken on days 2, 4, 8, 12, 21, 28, and 35. In general, significant effects for both concentration and duration of exposure were observed in treated fish. It was found that MN induction was highest on day 14 at 0.08 mg L−1 concentration of chlorpyrifos. It was concluded that chlorpyrifos is genotoxic pesticide causing nuclear anomalies in Cirrhinus mrigala.
Haploidentical versus Matched-Sibling Transplant in Adults with Philadelphia-Negative High-Risk Acute Lymphoblastic Leukemia: A Biologically Phase III Randomized Study
Authors: Wang Yu , Liu Qi-Fa , Xu Lan-Ping , Liu Kai-Yan , Zhang Xiao-Hui , Ma Xiao , Wu Mei-Qing , Wu De-Pei , Huang Xiao-Jun
Published: March 2016

Purpose: Although matched-sibling donor (MSD) hematopoietic stem-cell transplantation (HSCT) has an established role in the management of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1), the effect of haploidentical donor (HID) HSCT as post-remission treatment for this portion of patients is not defined.

Experimental Design: Transplantation outcomes from HIDs or MSDs were compared in a disease-specific, biologically phase III randomized, multicenter study. Between July 2010 and December 2013, 210 patients with Philadelphia-negative high-risk ALL in CR1 were assigned to undergo unmanipulated HIDs (121 patients) or MSDs HSCT (89 patients) according to donor availability on an intent-to-treat (ITT) basis.

Results: Overall, 24 of the 210 patients had lost transplant eligibility. Therefore, 186 of 210 (88%) patients were finally transplanted from MSD (n = 83) or HID (n = 103). Based on the ITT principle, the 3-year disease-free survival (DFS) did not differ between HID and MSD groups [61%, 95% confidence interval (CI), 52%–70%; vs. 60%, CI, 49%–71%; P = 0.91] from CR, neither did DFS differ between the two groups (68%, CI, 58%–78%; vs. 64%, CI, 52%–76%; P = 0.56) from time of the graft, with cumulative incidence of nonrelapse mortality of 13% (CI, 7%–19%) and 11% (CI, 4%–18%; P = 0.84) and relapse rates of 18% (CI, 10%–26%) and 24% (CI, 14%–34%; P = 0.30), respectively.

Conclusions: Haploidentical HSCT achieves outcomes similar to those of MSD-HSCT for Philadelphia-negative high-risk ALL patients in CR1. Such transplantation could be a valid alternative as post-remission treatment for high-risk ALL patients in CR1 lacking an identical donor. Clin Cancer Res; 22(14); 3467–76. ©2016 AACR.
Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis
Authors: Yang Jie , Qian Shihui , Cai Xueting , Lu Wuguang , Hu Chunping , Sun Xiaoyan , Yang Yang , Yu Qiang , Gao S. Paul , Cao Peng
Published: March 2016

The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antagonist of IL6 receptor via directly binding to the IL6Rα with a Kd of 663 ± 74 nmol/L and the GP130 (IL6Rβ) with a Kd of 1,660 ± 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6Rα and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6–IL6Rα–GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6Rα than to LIFR (Kd: 4,910 ± 1,240 nmol/L) and LeptinR (Kd: 4,990 ± 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. Mol Cancer Ther; 15(6); 1190–200. ©2016 AACR.
A Randomized, Placebo-Controlled, Phase II, Presurgical Biomarker Trial of Celecoxib Versus Exemestane in Postmenopausal Breast Cancer Patients
Authors: Aristarco Valentina , Serrano Davide , Gandini Sara , Johansson Harriet , Macis Debora , Guerrieri-Gonzaga Aliana , Lazzeroni Matteo , Feroce Irene , Pruneri Giancarlo , Pagani Gianmatteo , Toesca Antonio , Caldarella Pietro , DeCensi Andrea , Bonanni Bernardo
Published: March 2016

In breast cancer presurgical trials, the Ki-67 labeling index predicts disease outcome and offers clues to the preventive potential of drugs. We conducted a placebo-controlled trial to evaluate the activity of exemestane and celecoxib before surgery. The main endpoint was the change in Ki-67. Secondary endpoints were the modulation of circulating biomarkers. Postmenopausal women with histologically confirmed estrogen receptor–positive breast cancer were randomly assigned to exemestane 25 mg/day (n = 50), or celecoxib 800 mg/day (n = 50), or placebo (n = 25) for 6 weeks before surgery. Changes in biomarkers were analyzed through an ANCOVA model adjusting for baseline values. Exemestane showed a median absolute 10% reduction in Ki-67 [from 22 (interquartile range, IQR, 16–27), to 8 (IQR 5–18)], and a 15% absolute reduction in PgR expression [from 50 (IQR 3–90) to 15 (IQR −0–30)] after 6 weeks of treatment. Exemestane significantly increased testosterone [median change 0.21 ng/mL, (IQR 0.12–0.35)], decreased SHBG [median change −14.6 nmol/L, (IQR −23.1 to −8.6)], decreased total and HDL cholesterol by −10 mg/dL (IQR −21–2) and −7 mg/dL, (IQR −14 to −2), respectively. Triglycerides were reduced by both agents [median change −0.5 mg/dL (IQR −17.5–13.5) and −8 mg/dL (IQR −28–9) for celecoxib and exemestane, respectively]. Exemestane showed a remarkable antiproliferative effect on breast cancer, whereas celecoxib did not affect breast cancer proliferation. Given the proven preventive efficacy of exemestane, these findings support the use of Ki-67 to explore the optimal exemestane dose and schedule in the prevention setting. Cancer Prev Res; 9(5); 349–56. ©2016 AACR.
PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression
Authors: Xiao Xiao , Lao Xiang-Ming , Chen Min-Min , Liu Rui-Xian , Wei Yuan , Ouyang Fang-Zhu , Chen Dong-Ping , Zhao Xiao-Yu , Zhao Qiyi , Li Xue-Feng , Liu Chuan-Lu , Zheng Limin , Kuang Dong-Ming
Published: March 2016

B cells often constitute abundant cellular components in human tumors. Regulatory B cells that are functionally defined by their ability to produce IL10 downregulate inflammation and control T-cell immunity. Here, we identified a protumorigenic subset of B cells that constitutively expressed higher levels of programmed cell death-1 (PD-1) and constituted ∼10% of all B cells in advanced-stage hepatocellular carcinoma (HCC). These PD-1hi B cells exhibited a unique CD5hiCD24−/+CD27hi/+CD38dim phenotype different from the phenotype of conventional CD24hiCD38hi peripheral regulatory B cells. TLR4-mediated BCL6 upregulation was crucial for PD-1hi B-cell induction by HCC environmental factors, and that effect was abolished by IL4-elicited STAT6 phosphorylation. Importantly, upon encountering PD-L1+ cells or undergoing PD-1 triggering, PD-1hi B cells acquired regulatory functions that suppressed tumor-specific T-cell immunity and promoted cancer growth via IL10 signals. Our findings provide significant new insights for human cancer immunosuppression and anticancer therapies regarding PD-1/PD-L1.

Significance: We identify a novel protumorigenic PD-1hi B-cell subset in human HCC that exhibits a phenotype distinct from that of peripheral regulatory B cells. TLR4-mediated BCL6 upregulation is critical for induction of PD-1hi B cells, which operate via IL10-dependent pathways upon interacting with PD-L1 to cause T-cell dysfunction and foster disease progression. Cancer Discov; 6(5); 546–59. ©2016 AACR.

See related commentary by Ren et al., p. 477.

This article is highlighted in the In This Issue feature, p. 461
Photorefraktive Keratektomie bei Keratokonus
Authors: Tambe Deepali Sandeep , Ivarsen Anders , Hjortdal Jesper
Published: March 2016

Zielsetzung: Beurteilung der Wirksamkeit und Sicherheit der topografiegeführten photorefraktiven Keratektomie (PRK) bei Keratokonus und Einschätzung des Risikos einer nachfolgenden Progression. Methoden: Hierbei handelt es sich um eine retrospektive Nachbeobachtungsstudie. Zwischen 1998 und 2013 wurden 28 Augen von 23 Patienten (Alter 17-60 Jahre) mit Keratokonus im Stadium 1-3 mit einer topografiegeführten PRK behandelt. Vor dem Eingriff, 3 Monate danach und bei einer Langzeit-Nachuntersuchung im Median 7 Jahre nach dem Eingriff wurden jeweils eine Messung des korrigierten Fernvisus (corrected distance visual acuity; CDVA), Keratometrie, Pachymetrie und Hornhaut-Topografie durchgeführt. Postoperative Komplikationen einschließlich späterer Keratoplastik wurden dokumentiert. Ergebnisse: Bis zur Langzeit-Nachuntersuchung im Median 7 Jahre (Bereich 3-10 Jahre) nach der PRK war bei 5 der 28 Augen (18%) eine Hornhaut-Transplantation vorgenommen worden. Vier Augen standen für die Nachuntersuchung nicht zur Verfügung. Bei den verbleibenden 19 Augen war der CDVA in 16 Augen (84,3%) verbessert, in 2 Augen (10,5%) verschlechtert und in 1 Auge (5,2%) unverändert. Damit hatte sich der durchschnittliche CDVA von 0,49 logMAR vor der PRK auf 0,27 logMAR nach 3 Monaten und 0,24 logMAR bei der Langzeit-Nachuntersuchung verbessert. Das mittlere sphärische Äquivalent ging von -6,2 auf -3,7 dpt nach 3 Monaten und -2,1 dpt bei der Langzeit-Nachuntersuchung zurück. Ebenso verringerte sich der mittlere Zylinderwert von -4,2 auf -3,0 dpt nach 3 Monaten und bei der Langzeit-Nachuntersuchung. Schlussfolgerung: Die topografiegeführte PRK stellt bei Keratokonus potenziell eine wirksame Option zur Reduktion von Myopie und Astigmatismus sowie eine vorläufige oder dauerhafte Alternative zur Keratoplastik bei Patienten mit Keratokonus und Kontaktlinsen-Unverträglichkeit dar. In der hier vorgestellten Studie wurde ein geringes Risiko für eine Progression des Keratokonus nach einer PRK festgestellt.
Influence of Toothbrushing on the Antierosive Effect of Film-Forming Agents
Authors: Scaramucci Taís , João-Souza Samira Helena , Lippert Frank , Eckert George J. , Aoki Idalina V. , Hara Anderson T.
Published: March 2016

This study evaluated the influence of toothbrushing on the antierosive effect of solutions containing sodium fluoride (225 ppm/F), stannous chloride (800 ppm/Sn), sodium linear polyphosphate (2%/LPP), and their combinations, and deionized water as negative control (C). Solutions were tested in a 5-day erosion-remineralization-abrasion cycling model, using enamel and dentin specimens (n = 8). Erosion was performed 6 times/day for 5 min, exposure to the test solutions 3 times/day for 2min, and toothbrushing (or not) with toothpaste slurry 2 times/day for 2 min (45 strokes). Surface loss (SL) was determined by noncontact profilometry. Data were analyzed using three-way ANOVA (α = 0.05). Brushing caused more SL than no brushing for enamel (mean ± SD, in micrometers: 52.7 ± 6.6 and 33.0 ± 4.5, respectively), but not for dentin (28.2 ± 1.9 and 26.6 ± 1.8, respectively). For enamel without brushing, F+LPP+Sn showed the lowest SL (23.8 ± 3.4), followed by F+Sn (30.6 ± 4.9) and F+LPP (31.7 ± 1.7), which did not differ from each other. No differences were found between the other groups and C (37.8 ± 2.1). When brushing, F+LPP+Sn exhibited the lowest SL (36.7 ± 2.4), not differing from F+LPP (39.1 ± 1.8). F, F+Sn and LPP+Sn were similar (46.7 ± 2.9, 42.1 ± 2.8 and 45.3 ± 4.6, respectively) and better than C (52.7 ± 4.3). Sn (55.0 ± 2.4) and LPP (51.0 ± 4.3) did not differ from C. For dentin, neither groups differed from C, regardless of brushing. In conclusion, toothbrushing did not affect the antierosive effect of F+Sn, F+LPP and F+LPP+Sn on enamel, although overall it led to more erosion than nonbrushing. F and LPP+Sn showed a protective effect only under brushing conditions, whereas Sn and LPP did not exhibit any protection. For dentin, neither toothbrushing nor the test solutions influenced the development of erosion.
Left Adrenal Gland Analysis in Lung Cancer Patients Using the Endobronchial Ultrasound Scope: A Feasibility Trial
Authors: Crombag Laurence M.M.J. , Annema Jouke T.
Published: March 2016

Background: In lung cancer patients, the adrenal glands are predilection sites for distant metastases. Esophageal endoscopic ultrasound - fine-needle aspiration (EUS-FNA) is a minimally invasive and accurate method for left adrenal gland (LAG) analysis but requires a conventional gastrointestinal echoendoscope. Complete endobronchial and esophageal mediastinal nodal staging can be achieved by just a single endobronchial ultrasound (EBUS) scope, introducing it into the esophagus (EUS-B) following the endobronchial procedure. Whether the LAG can also be assessed with the EBUS scope is unknown. Objectives: The aim of the study was to investigate the feasibility of identifying the LAG with the EBUS scope. Methods: We conducted a retrospective analysis of lung cancer patients who underwent EBUS and EUS-B for mediastinal staging and LAG assessment between January 2013 and May 2015. Results: A total of 143 patients with (suspected) lung cancer were investigated by the combination of EBUS and EUS-B. In 68 of the 80 patients (85%) in whom an attempt was made to identify the LAG, it was feasible to transgastrically detect the LAG with the EBUS scope. In 9 patients with endosonographic signs of malignant involvement, diagnostic transgastric FNAs were obtained in all. In the 12 patients (15%) in whom the LAG was not detected, the contact between the ultrasound transducer and the gastric wall was suboptimal - the length of the scope was not a limiting factor. Conclusions: The EBUS scope allows identification of the LAG in the vast majority of lung cancer patients. Implication: In patients with (suspected) lung cancer, in addition to complete hilar and mediastinal staging, LAG assessment using just a single EBUS scope also seems feasible. Prospective studies are indicated.
Overexpression of AQP5 Was Detected in Axillary Sweat Glands of Primary Focal Hyperhidrosis Patients
Authors: Du Quan , Lin Min , Yang Ju-Hua , Chen Jian-Feng , Tu Yuan-Rong
Published: March 2016

Background: The expression of aquaporin 5 (AQP5) in human axillary sweat glands has never been studied so far. Objective: To detect the expression of AQP5 in axillary sweat glands of patients with primary focal hyperhidrosis (PFH) relative to control subjects. Methods: The morphological characteristics and the number of sweat coils in axillary sweat glands were compared between two groups by using transmission electron microscopy. The expression of AQP5 was detected by immunohistochemistry, Western blot analysis, and real-time transcription polymerase chain reaction. Results: There were no significant differences between the two groups in terms of morphological characteristics and the number of sweat coils in axillary sweat glands. The expressions of AQP5 protein and AQP5 mRNA were significantly higher in the patient group than in the control group. Conclusion: AQP5 is involved in the secretion of human axillary sweat glands. The overexpression of AQP5 in sweat glands is probably one pathogenetic mechanism underlying PFH.
Two-Port Laparoscopic Reconstructive Surgery of the Urinary Tract with Reusable Umbilical System (Hybrid Less): A Proof of Concept Study
Authors: Angulo Javier C. , Pérez Sergio , García-Tello Ana , Redondo Cristina , Meilán Elisa , Arance Ignacio
Published: March 2016

Objectives: We compared perioperative results and complications of reconstructive surgery of the urinary tract performed using a multichannel platform through the umbilicus and one additional 3.5-mm with a cohort of patients simultaneously treated with conventional 4-port laparoscopy. Materials and Methods: Matched-pair study comparing perioperative outcomes, postoperative visual analogue pain scale (VAPS) and morbidity of 2-port (n = 20) and 4-port (n = 10) laparoscopic reconstructive urological surgery. Preoperative and perioperative data compared included demographics, type of surgery, operative time, blood loss, decrease in serum hemoglobin, operative complications, length of stay and postoperative complications according to Clavien-Dindo classification. Results: There was no significant difference between groups regarding age, gender, body mass index, American Society of Anesthesiologists score, type of surgery, operative time, operative complications and intraoperative or postoperative transfusion. Estimated blood loss was lower using reduced-port approach. VAPS at postoperative day one was significantly lower for 2-port approach and so was the length of stay. Patient satisfaction with the wound was higher for 2-port surgery. Differences were not observed in number and severity of postoperative complications. Conclusions: Urological reconstructive operations can be safely performed using the hybrid laparoendoscopic single-site umbilical approach, resulting in lower blood loss, higher patient satisfaction and lower postoperative pain, which also facilitate earlier hospital discharge, than the same reconstructive procedures performed through multiport conventional laparoscopy.
Healthcare Burden and Costs Associated with Urinary Tract Infections in Type 2 Diabetes Mellitus Patients: An Analysis Based on a Large Sample of 456,586 German Patients
Authors: Wilke Thomas , Böttger Björn , Berg Björn , Groth Antje , Botteman Marc , Yu Shengsheng , Fuchs Andreas , Maywald Ulf
Published: March 2016

Objectives: We examined the real-world treatment of urinary tract infections (UTIs) in a type 2 diabetes mellitus (T2DM) population, evaluated UTI-related healthcare resource use and direct treatment costs, and assessed factors that may predict UTI-related costs. Methods: We analyzed an anonymized dataset from a regional German healthcare fund (2010-2012). UTI-associated resource use was described by the number of UTI-associated outpatient visits, the number and length of UTI-related acute hospital visits, and the number of UTI-related antibiotics prescriptions. UTI-related direct treatment costs were studied both based on these resource use numbers and, additionally, based on a comparison of all-cause annual healthcare costs of T2DM-patients who were or were not affected by a UTI. To identify factors that might predict direct treatment costs related to UTI treatment, we conducted generalized linear regression model analyses (based on gamma distribution) using sociodemographic and clinical characteristics of observed patients as available in the database as independent variables. Results: A total of 456,586 T2DM-patients were included with a mean age of 73.8, a percentage of 56.3 female patients, and a mean Charlson comorbidity index of 7.3. In our database, we observed 48,337 UTI events. The direct mean resource-based costs were €315.90 per UTI event. Older age, higher comorbidity status, at least one previous non-UTI infection, and poorer renal function were associated with higher costs, while female gender and at least one previous UTI event were associated with lower costs. In the all-cause cost analysis, healthcare costs per patient year were €3,916 higher in the UTI group than in the non-UTI group. Conclusion: Our study confirms that UTI is a common complication in patients with T2DM. Patients with T2DM who have had previous infections, who are older, and who are male, as well as patients who have more comorbidities or severe renal insufficiency, face above-average UTI treatment costs. These patient groups, therefore, should receive special attention in the real-world treatment of T2DM, which should include a regular screening of UTI risk.
МЕДИКО-СОЦІАЛЬНА ЕФЕКТИВНІСТЬ МЕДИЧНОЇ РЕАБІЛІТАЦІЇ У ХВОРИХ НА ОСТЕОАРТРОЗ
Authors: БАКАЛЮК Т.Г.
Published: March 2016

Мета: визначення медико-соціальної ефективності застосування програми медичної реабілітації у хворих на остеоартроз.

Матеріали і методи. В основу роботи покладені особисті дослідження лікування 158 хворих на остеоартроз І та ІІ клініко-рентгенологічної стадії на санаторно-курортному етапі реабілітації; групу контролю склали 80 пацієнтів, які лікувались амбулаторно.

Результати. Проаналізовані різні аспекти реабілітаційного лікування хворих на остеоартроз та вивчена їх ефективність: повторна звертальність пацієнтів за медичною допомогою знизилась в 4,7 разу у порівнянні із дореабілітаційним періодом, шпиталізація хворих зменшилась у 5,6 разу, тимчасова непрацездатність знизилась у 3,8 разу.

Висновки. Отримані результати свідчать про безсумнівні переваги санаторно-курортного лікування, яке має одночасно як саногенетичну, так і патогенетичну спрямованість і дозволяє реалізувати комплекс реабілітаційних засобів в оптимальному об’ємі та в необхідній послідовності, забезпечити індивідуальний підхід до лікування хворого, а також суттєво підвищити медичну та економічну ефективність відновного лікування.

КЛЮЧОВІ СЛОВА: медична реабілітація, остеоартроз, медико-соціальна ефективність.
ТЕНДЕНЦІЇ ТА ПРОГНОЗ ПОШИРЕНОСТІ СТЕНОКАРДІЇ ТА ІНФАРКТУ МІОКАРДА В УКРАЇНІ
Authors: ТЕРЕНДА Н.О.
Published: March 2016

Мета: вивчити динаміку показників поширеності та захворюваності населення України внаслідок стенокардії та інфаркту міокарда (ІМ) у регіональному аспекті протягом 1996–2014 років та спрогнозувати їх зміни до 2025 року.

Матеріали і методи. Матеріалом дослідження слугували дані Центру медичної статистики МОЗ України про рівень первинної захворюваності та поширеності стенокардії та ІМ серед населення України. У роботі використано епідеміологічний, демографічний, статистичний методи дослідження.

Результати. З використанням методу демографічного районування проведено оцінку змін захворюваності й поширеності стенокардії та ІМ в Україні та окремих її районах протягом 1996–2014 років. Спрогнозовано тенденцію подальшого зростання даних патологій, як в Україні, так і в деяких її районах.

Висновки. Протягом останніх 18 років в Україні істотно зросла поширеність (у 2,9 разу) та захворюваність (у 1,5 разу) на стенокардію. Найбільше ці показники змінилися у Південному районі України. Дещо менше зросла поширеність ІМ – на 96,4%. Прогнозні показники щодо захворюваності та поширеності стенокардії та ІМ свідчать про тенденцію їх зростання, особливо у Південно-Східному та Південному районах.

КЛЮЧОВІ СЛОВА: стенокардія, інфаркт міокарда, поширеність, первинна захворюваність, прогноз.
КОНТРМІРА ЕВТАНАЗІЇ – ПАЛІАТИВНЕ ЛІКУВАННЯ
Authors: КОВАЛЬ М.І.
Published: March 2016

Мета: висвітлити засади біоетики, якими повинні керуватися медичні працівники у наданні допомоги невиліковно хворим.

Матеріали і методи. За допомогою бібліографічного та герменевтичного методів проведено аналіз нормативних документів та етичних актів.

Результати. В статті розглядаються ставлення до смерті, яке служить характеристикою цивілізації, а також недоторканість людського життя в контексті Божого Закону «Не вбий!». Висвітлюється евтаназія як акт вбивства, який не можна дозволити за будь-яких умов. Розкривається паліативне лікування як цілковита опіка над особистістю людини, а також принципи біоетики, які вимагають від лікаря особистої відповідальності за життя та здоров’я пацієнта.

Висновки. Евтаназія і добре здійснювана паліативна опіка є не тільки різними – вони знаходяться в радикальній опозиції. Органи державного управління повинні подбати про відповідне законодавче врегулювання цієї проблеми, впроваджуючи замість евтаназії паліативну терапію – пом’якшення страждань невиліковно хворої людини.

Ключові слова: евтаназія, паліативне лікування, принципи біоетики.
ПРОЗАПАЛЬНИЙ ЦИТОКІН ЕНДОТЕЛІАЛЬНИЙ МОНОЦИТАКТИВУЮЧИЙ ПЕПТИД ІІ: ВМІСТ У СИРОВАТЦІ КРОВІ ПРИ ЦУКРОВОМУ ДІАБЕТІ
Authors: Mohylnytska L. A. , Tuzova O. V.
Published: March 2016

РЕЗЮМЕ. Досліджували вміст ендотеліального моноцитактивуючого пептиду ІІ (ЕМАР-ІІ) у сироватці крові при цукровому діабеті 1-го та 2-го типів, встановлювали можливий зв’язок з показниками вуглеводного обміну. Виявлено підвищення вмісту ЕМАР-ІІ у сироватці крові при цукровому діабеті 1-го та 2-го типів. Рівень пептиду прямо корелював з вмістом глікозильованого гемоглобіну, глюкози крові. Підвищення вмісту ЕМАР-ІІ може бути одним з проявів ендотеліальної дисфункції при цукровому діабеті 1-го та 2-го типів, а порушення вуглеводного обміну може впливати на розвиток виявлених зрушень.

 
КЛЮЧОВІ СЛОВА: ендотеліальний моноцитактивуючий пептид ІІ, цукровий діабет, ендотеліальна дисфункція
Хірургічне лікування нирковоклітинного раку з внутрішньовенозним розповсюдженням та імплантацією тромбу в стінку нижньої порожнистої вени
Authors: Rusin V. I. , Korsak V. V. , Boiko S. O. , Popovych Y. M.
Published: March 2016

У роботі представлено результати хірургічного лікування нирковоклітинного раку з внутрішньовенозним розповсюдженням та імплантацією тромбу в стінку нижньої порожнистої вени. У 3 випадках виконано протезування нижньої порожнистої вени протезами Gore Tex чи ПТФЕ (2 – вище ниркових вен, 1 – нижче ниркових вен). Гістологічно підтверджена інвазія пухлинного тромбу при нирковоклітинному раку в стінку нижньої порожнистої вени є показанням до резекції стінки чи ділянки нижньої порожнистої вени, яка відновлюється за допомогою протезування.
АКТУАЛЬНІ ПРОБЛЕМИ НЕВІДКЛАДНОЇ ХІРУРГІЇ КОЛОРЕКТАЛЬНОГО РАКУ
Authors: MATVIYCHUK B. O. , MATVIYCHUK О. В. , FETSYCH M. T.
Published: March 2016

Здійснено ретроспективний аналіз результатів лікування 136 хворих на ускладнений рак товстої кишки, оперованих у клініці в 2008–2014 рр. Вік пацієнтів перебував у межах 36–94 років (середній – (68,8±12,1 року). У більшості хворих РТК діагностовано в клініці у зв’язку з виникненням того чи іншого ускладнення – 117 (86 %). Домінуючим ускладненням колоректального раку виявилась гостра обтураційна непрохідність – ізольовано у 105 (77,2 %) хворих, у поєднанні з перфорацією пухлини, перитонітом – у 24 (17,6 %) пацієнтів, кишковою кровотечею – в 1 (0,8 %) хворого. Перфорацію пухлини, перитоніт констатовано у 3 (2,2 %) хворих, гостру кишкову кровотечу – в 3 (2,2 %) пацієнтів. У 81,1 % спостережень перитоніт мав дифузний характер. Радикальні операції виконано у 68 (50 %) хворих, паліативні – у 18 (13,2 %), симптоматичні – в 50 (36,8 %) пацієнтів. Відповідно до класифікацією TNM, І стадію пухлини встановлено у 0,7 % оперованих, ІІ стадію – у 31 % хворих, ІІІ і IV стадії, відповідно, – у 31,4 та 37,0 % пацієнтів. Післяопераційні ускладнення розвинулись у 10 хворих (7,3 %) і мали в основному гнійно-септичний характер. Появу третинного перитоніту було визнано у 17 (12,5 %) прооперованих. Релапаротомії виконано 21 хворому (15,4 %), здебільшого з причини перитоніту, ретракції колостом. Середній ліжкодень склав 16,2±7,7. Померли 23 хворі – післяопераційна летальність – 16,9 %. Третинний перитоніт призвів до летального кінця в 15 пацієнтів (88,2 %). Основною причиною смерті визнано поліорганну недостатність як прояв тяжкого сепсису. Основними аспектами проблеми ускладненого раку товстої кишки (УРТК), які потребують комплексного вирішення, є зростання захворюваності, запізніла госпіталізація пацієнтів, потенційований ризик венозних тромбозів та емболій, третинний перитоніт, підвищення фахової онкологічної підготовки хірургів.