bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Accurate Multi‐Invariance ESPRIT for DOA Estimation with a Sparse Array
Authors: Gu Chen , Hong Hong , Li Yusheng , Zhu Xiaohua , He Jin
Published: February 2019

This paper proposes a multi‐invariance ESPRIT‐based method for estimation of 2D direction (MIMED) of multiple non‐Gaussian monochromatic signals using cumulants. In the MIMED, we consider an array geometry containing sparse L‐shaped diversely polarized vector sensors plus an arbitrarily‐placed single polarized scalar sensor. Firstly, we define a set of cumulant matrices to construct two matrix blocks with multi‐invariance property. Then, we develop a multi‐invariance ESPRIT‐based algorithm with aperture extension using the defined matrix blocks to estimate two‐dimensional directions of the signals. The MIMED can provide highly accurate and unambiguous direction estimates by extending the array element spacing beyond a half‐wavelength. Finally, we present several simulation results to demonstrate the superiority of the MIMED.
Vaccine Prophylaxis of Pneumococcal Infections in Children under Conditions of Severe Flood in the Amur River Basin
Authors: Chuchalin Aleksandr G. , Onishchenko Gennadiy G. , Kolosov Victor P. , Kurganova Olga P. , Zaitseva Tatiana A. , Manakov Leonid G. , Kholodok Galina N. , Perelman Juliy M. , Kozlov Roman S. , Ivakhnishina Natalia M. , Trotsenko Olga E. , Bondarenko Albina P.
Published: February 2019

Background. Pneumococcal infection being one of the dominant causes of acute respiratory diseases and exacerbation of chronic ones is a serious problem for human health and society. The flood in the Amur river basin in the summer of 2013 created a special zone and risk conditions for the formation of respiratory pathology in the Far-Eastern region of Russia. We aimed to give clinical and epidemiological assessment of the effectiveness of vaccination programs of respiratory viral and pneumococcal infections and generalization of regional experience in the organization of a set of measures aimed at their prevention in the postflood period in the Far-Eastern region. Methods. The monitoring program includes children aged 2 to 5 years in the amount of 4988 with risk factors for pneumococcal infection. The pneumococcal conjugate vaccine Prevenar-13 was used for immunization. Data on the incidence of ARVI and pneumonia in children in pre- and postvaccination periods were to be recorded. The indicators and special criteria were used to assess the effectiveness of vaccination. To study the circulation of serovariants of pneumococcus in inflammatory diseases of the respiratory tract and nasopharyngeal carrier, bacteriological and molecular genetic methods (RT-PCR in the mode of multiprime detection) were used. Results. Differences in the frequency and range of serovariants of circulating isolates of pneumococcus in the postvaccinal period and in unvaccinated children, elimination of a number of serotypes, and appearance of circulation of nonvaccinated strains were revealed. The incidence of acute respiratory diseases and pneumonia among the vaccinated population for 2 years in the region decreased by 2.5 times. The coefficient of effectiveness of vaccination according to the indicator of morbidity of children with pneumonia reaches 75-100% with direct dependence on the age of children (r=0.98). Conclusion. Comparative statistical analysis revealed a high degree of effectiveness of regional programs with the methods of immunoprophylaxis of pneumococcal infections.
Successful Initiation of Dialysis with a 20-Year-Old Buried Peritoneal Dialysis Catheter: Case Report and Literature Review
Authors: Gupta Ankur , Lavoie Susan , Blew Brian , Biyani Mohan , McCormick Brendan B.
Published: February 2019

Buried peritoneal dialysis (PD) catheters are typically inserted several weeks or months before the anticipated need for dialysis. Occasionally, renal function unexpectedly stabilizes after the surgery, and a patient may go years before the catheter is needed. We report a case of successful initiation of PD with a twenty-year-old buried catheter. We outline the steps needed to optimize the catheter function and review the benefits of the buried PD catheter.
Determination of Antimicrobial Activity of Extracts of Indigenous Wild Mushrooms against Pathogenic Organisms
Authors: Gebreyohannes Gebreselema , Nyerere Andrew , Bii Christine , Berhe Sbhatu Desta
Published: February 2019

Objective. This study has investigated the antimicrobial activity of extracts of indigenous wild mushrooms against selected organisms. Methods. Thirty-five (35) indigenous wild mushrooms were collected from Arabuko-Sokoke and Kakamega National Reserve Forests, Kenya. All mushrooms were identified and their contents were extracted and screened for their antimicrobial activities against Escherichia coli (clinical isolate), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (clinical isolate), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), MRSA (ATCC 33591), Candida albicans (clinical isolate), and Candida parapsilosis (ATCC 90018) using tetrazolium microtiter plate bioassay method. Results. Of the 35 tested mushroom extracts, extracts of three (3) mushrooms, namely, Trametes spp. (Arabuko-Sokoke forest), Trametes, and Microporus spp. (Kakamega forest), have shown promising antimicrobial activities against the tested organisms. The S. aureus (ATCC 25923), P. aeruginosa (ATCC 27853), and Methicillin-Resistant Staphylococcus aureus (MRSA) (ATCC 33591) were the most susceptible to chloroform extract of Trametes spp. collected from Arabuko-Sokoke forest. Of the tested organisms, S. aureus (ATCC 25923) was the most susceptible whereas E. coli was the most resistant organism to the hot water extract of Trametes spp. collected from Arabuko-Sokoke forest. Chloroform extract of Microporus spp. has shown the highest antibacterial activity against S. aureus (ATCC 25923), MRSA (ATCC 33591), and K. pneumoniae (ATCC 13883) but limited activity against E.coli. All extracts of the three wild mushrooms have shown the most antibacterial activities against S. aureus (ATCC 25923). Conclusion. The present study has shown that the extracts of the three wild mushrooms have shown promising antimicrobial activities against the tested organisms.
Female Urethroplasty: A Practical Guide Emphasizing Diagnosis and Surgical Treatment of Female Urethral Stricture Disease
Authors: Waterloos Marjan , Verla Wesley
Published: February 2019

Female urethral strictures are rare. Guidelines on how to diagnose and treat these strictures are lacking. At present, only expert opinion is available to guide clinical practice. Once the diagnosis is suspected based on obstructive voiding symptoms and uroflowmetry, most clinicians will use in addition video-urodynamics (including urethrography), urethral calibration and cystourethroscopy for confirmation of the diagnosis. Clinical inspection and gynaecological examination are also important. Urethral dilation is usually the first-line treatment despite the lack of long-term success. Female urethroplasty is associated with higher success rates. A multitude of techniques are described but not one technique has shown superiority above another. This narrative review aims to provide a clinical guide for diagnosis and treatment to the urologist motivated to perform female urethroplasty.
Centrifugation, Storage, and Filtration of Olive Oil in an Oil Mill: Effect on the Quality and Content of Minority Compounds
Authors: Vidal Alfonso M. , Alcalá Sonia , de Torres Antonia , Moya Manuel , Espínola Francisco
Published: February 2019

Centrifugation, storage, and filtration of olive oil were evaluated in an oil mill to determine their effect on the final quality of virgin olive oil. The main functions of these processes are to clarify the olive oil by removing water, solids, and other possible suspended particles. Although some changes were detected in the oil quality parameters after these processes, all the samples were extra virgin olive oil. The phenolic and volatile compound content of the olive oil was influenced by vertical centrifugation processing. Significantly, vertical centrifugation led to a 53% reduction in ethanol content. Oil storage before filtration resulted in a significant increase of around 30% in the peroxide index, while the antioxidant capacity decreased by 78%. Comparison of the results for filtered and unfiltered oil samples revealed that the most significant change was the reduction in the photosynthetic pigment content, with a decrease of around 50% in chlorophyll. Due of all this, the conditions applied in vertical centrifugation and the time of storage of the olive oils should be further controlled, enabling cleaning and decantation but avoiding the reduction of the antioxidant capacity and the content of phenolics compounds.
Design of a Compact Ultrawideband U-Shaped Slot Etched on a Circular Patch Antenna with Notch Band Characteristics for Ultrawideband Applications
Authors: Ghimire Jiwan , Choi Dong-You
Published: February 2019

Interference between ultrawideband (UWB) antennas and other narrowband communication systems has spurred growth in designing UWB antennas with notch characteristics and complicated designs consisting of irregular etched slots and larger physical size. This article presents a simplified notched design method for existing UWB antennas exhibiting four frequency-band-rejecting characteristics. The investigation has been conducted by introducing four semicircular U-shaped slot structures based on a theoretical formulation. The formulation is validated with the equivalent LC lumped parameters responsible for yielding the notched frequency. A novel feature of our approach is that the frequency notch can be adjusted to the desired values by changing the radial length based on the value calculated using a derived formula for each semietched U-slot, which is very simple in structure and design. Additionally, by introducing the rectangular notch at the ground plane, the upper passband spectrum is suppressed while maintaining the wide impedance bandwidth of the antenna applicable for next-generation wireless communications, 5G. The measured result shows that the antenna has a wide impedance bandwidth of 149% from 2.9 to 20 GHz, apart from the four-notched frequencies at 3.49, 3.92, 4.57, and 5.23 GHz for a voltage standing wave ratio (VSWR) of <2 rejecting the Worldwide Interoperability for microwave Access (WiMAX) band at (3.38-3.7 GHz), the European C-band at (3.84-4.29 GHz), the Indian national satellite (INSAT) at (4.47-4.92 GHz), and wireless local area networks (WLANs) at (5.09-5.99 GHz). Measured and simulated experimental results reveal that the antenna exhibits nearly an omnidirectional pattern in the passband, low gain at the stopband, and good radiation efficiency within a frequency range. The LC equivalent notched frequency has been proposed by analyzing the L and C equivalent formula, and it has been validated with simulated and measured results. The measurement and simulated results correspond well at the LC equivalent notch band rejecting the existing narrowband systems.
Single- and Bicomponent Analyses of T2⁎Relaxation in Knee Tendon and Ligament by Using 3D Ultrashort Echo Time Cones (UTE Cones) Magnetic Resonance Imaging
Authors: Liu Jin , Nazaran Amin , Ma Yajun , Chen Haimei , Zhu Yanchun , Du Jiang , Li Shaolin , Zhou Quan , Zhao Yinghua
Published: February 2019

The collagen density is not detected in the patellar tendon (PT), posterior cruciate ligament (PCL), and anterior cruciate ligament (ACL) in clinic. We assess the technical feasibility of three-dimension multiecho fat saturated ultrashort echo time cones (3D FS-UTE-Cones) acquisitions for single- and bicomponent T2⁎analysis of bound and free water pools in PT, PCL, and ACL in clinic. The knees of five healthy volunteers and six knee joint samples from cadavers were scanned via 3D multiecho FS-UTE-Cones acquisitions on a clinical scanner. Single-component fitting of T2⁎Mand bicomponent fitting of short T2⁎(T2⁎S), long T2⁎(T2⁎L), short T2⁎fraction (Frac_S), and long T2⁎fraction (Frac_L) were performed within tendons and ligaments. Our results showed that biexponential fitting was superior to single-exponential fitting in PT, PCL, and ACL. For knee joint samples, there was no statistical difference among all data in PT, PCL, and ACL. For volunteers, all parameters of bicomponent fitting were statistically different across PT, PCL, and ACL, except for T2⁎S, T2⁎L, and T2⁎Mresulting in flawed measurements due to the magic angle effect. 3D multiecho FS-UTE-Cones acquisition allows high resolution T2⁎mapping in PT, PCL, and ACL of keen joint samples and PT and PCL of volunteers. The T2⁎values and their fractions can be characterized by bicomponent T2⁎analysis that is superior to single-component T2⁎analysis, except for ACL of volunteers.
Persisting Regional Disparities in Modern Contraceptive Use and Unmet Need for Contraception among Nigerian Women
Authors: Wang Chao , Cao Huimin
Published: February 2019

Background. Evidence suggests that equitable provision of contraceptive services can help women achieve their reproductive goals and has significant impact on reducing the rates abortion and unintended pregnancy at large. However, regional disparities continue to persist on top of low family planning prevalence which is a critical public health challenge for fast growing populations like Nigeria. Objectives. The present study aimed to explore the prevalence of (1) nonuse of modern contraceptives, (2) unmet need for contraception, and (3) regional disparities in these two. Methods. The present study used cross-sectional data obtained from the Nigeria Demographic and Health Surveys conducted in 2003, 2008, and 2013. Participants were women of reproductive of age (15-49 years) regardless of marital status. Regional disparities of nonuse of modern contraceptives and unmet need were analysed by descriptive and multivariate regression methods. Results. In the pooled sample of 79,656 participants during 2003, 2008, and 2013, 88.6% reported not using any modern methods, and 13.5% reported having unmet need for contraception. The prevalence rates of nonuse were, respectively, 91.8%, 90.6%, and 88.6% and those of unmet need were 14.2%, 16.6%, and 13.5% in the years 2003, 2008, and 2013. Significant differences were observed in the odds of reporting nonuse and unmet need for contraception across the geopolitical zones. Conclusions. The rates of nonuse of contraception are remarkably high among women in Nigeria with significant disparities across the six geopolitical zones. Efforts should be made to address the regional disparities in order to achieve the goals of universal coverage of family planning services in the country.
Structural Behavior of Ultrahigh‐Performance Fiber‐Reinforced Concrete Thin‐Walled Arch Subjected to Asymmetric Load
Authors: Yang Jun , Zhou Jianting , Wang Zongshan , Zhou Yingxin , Zhang Hong
Published: February 2019

Ultrahigh‐performance fiber‐reinforced concrete (UHPFRC) is an innovative material in the field of bridge engineering. With superior mechanical characteristics, this new material reduced the structural self‐weight and extended the span of modern bridges. A series of tests should be conducted to establish reliable design rules for UHPFRC structures. This paper aimed at determining the compressive behavior of UHPFRC for thin‐walled arch section design and a comparison was made with a normal concrete (NC) arch. Eighteen axial compression columns for arch section design and arches under asymmetric load were tested in this paper. Behaviors of the arches were assessed using various mechanical properties, including the failure pattern, load‐deflection relationship, strain analysis, and analytical investigation. A finite element model (FEM) considering the material and geometric nonlinearity was developed to predict the behavior of the UHPFRC arch. Results indicated that a wall thickness of 50 mm with stirrups effectively restrained instability failure of the thin‐walled compression columns. The cracking load and the ultimate load of the UHPFRC arch increased by 60% and 34%, respectively, when comparing with the NC arch. It showed the UHPFRC arch had higher load capacity and outstanding durability. The failure mode of the UHPFRC arch was similar to that of the NC arch, which belonging to the destruction of multihinges. However, the appearance of the plastic hinges was delayed, and a better elastic‐plastic performance was obtained when using UHPFRC. The analytical formula for calculating the ultimate load of the UHPFRC arch was derived with high precision by using the limit equilibrium method. The results of the FEM showed good agreement with test results, and they were able to predict the behavior of the UHPFRC arches.
Qualitative and Quantitative Analysis for the Chemical Constituents of Tetrastigma hemsleyanum Diels et Gilg Using Ultra-High Performance Liquid Chromatography/Hybrid Quadrupole-Orbitrap Mass Spectrometry and Preliminary Screening for Anti-Influenza Virus Components
Authors: Ding FuJuan , Liu JiangTing , Du RuiKun , Yu QinHui , Gong LiLi , Jiang HaiQiang , Rong Rong
Published: February 2019

Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanums) is a kind of traditional folk medicinal plant which has been used widely in China for its antivirus, antitumor, and other clinical effects. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive/MS) was utilized to analyze the chemical constituents of T. hemsleyanums. Fifty-one constituents were clarified, including flavonoids, anthraquinones, esters, fatty acids, phenols, and catechins. In the subsequent quantitative analysis, the contents of ten compounds of rutin, kaempferol, astragalin, quercitrin, quercetin, vitexin-rhamnoside, isorhamnetin, vitexin, emodin-8-O-β-D-glucoside, and isoquercetin in 18 batches of T. hemsleyanums collected from different places of cultivation were determined. Meanwhile, anti-influenza virus bioactivity in vitro of the above samples was detected with Gaussia Luciferase viral titer assay. It was found that the antiviral bioactivity varied from batches to batches in accordance with content difference of the chemical constituents in T. hemsleyanums. Correlation analysis was performed with SPSS software for the association between LC-MS chemometrics and bioactivity of influenza virus inhibition, and 8 constituents of flavonoids showed positive correlation coefficient, which may provide a valuable clue for searching potential antiviral components in T. hemsleyanums.
Novel Prognostic Factors Associated with Cell Cycle Control in Sporadic Medullary Thyroid Cancer Patients
Authors: Pezzani Raffaele , Bertazza Loris , Cavedon Elisabetta , Censi Simona , Manso Jacopo , Watutantrige-Fernando Sara , Pennelli Gianmaria , Galuppini Francesca , Barollo Susi , Mian Caterina
Published: February 2019

Background. Medullary thyroid cancer (MTC) is a rare neuroendocrine-derived malignancy. It is represented by sporadic and familiar forms, and both can have RET oncogene mutations. Numerous markers can be used to define MTC; however, none is generally approved for predicting the outcome of sporadic MTC. Aim. The aim of this work was to analyze PTTG1/securin and Aurora kinase A expressions in MTC patients, both at the gene and protein levels, and to define their prognostic role in MTC assessing their association with lab and clinical parameters. Patients and Methods. Seventy-one sporadic MTC human samples were analyzed for RET mutations and by qPCR for PTTG1 and AURKA (Aurora kinase A) expression. Ki-67 levels and western blot reactivity for PTTG1 and Aurora kinase A were also determined in a selected cohort of patients. Results. RET somatic mutations were found in 48% of the patients (34/71). PTTG1 expression was statistically different among the groups with or without regional lymph node metastasis (p<0.0001) and advanced stage disease (p<0.01). PTTG1 and AURKA expressions were statistically higher than those of controls (p=0.01 and p<0.002, respectively). PTTG1 expression and Ki-67 levels were statistically different among the groups with remitted or persistent disease (p<0.05 and p<0.01, respectively). We found a significant correlation between the expressions of AURKA and PTTG1 (p<0.0002, r=0.5298) and between the expressions of PTTG1 and Ki-67 (p=0.01). Ki-67 levels were statistically different among the groups with or without metastatic lymph nodes (p=0.01) or distant metastases (p=0.003). Conclusion. The presence of an altered expression of PTTG1 and AURKA is a negative prognostic factor associated with a more aggressive course of disease, such as an advanced stage or disease persistence. It emerges as a cell cycle process mediated by the 2 factors, in addition to the RET pathway, which can be altered in MTC patients.
Neutrophil-Derived MRP14 Supports Plasma Cell Commitment and Protects Myeloma Cells from Apoptosis
Authors: Zhao Zhihong , Luo Zhonghua , Yang Qian , Chang Hongbo , Liu Pengcheng , Li Zhichao , Guo Shengli , Zhou Chunhui , Song Jian , Cao Weidong
Published: February 2019

Neutrophils have recently been proposed as cells with high functional plasticity and are involved in the pathogenesis of infections, malignancy, and autoimmune diseases. However, less is known about the role of neutrophil in humoral response. In this study, we examined the importance of neutrophils and the neutrophil-derived DAMP protein, MRP14, in antibody production. Splenic neutrophils and MRP14 that are present in the splenic peri-MZ region have a close contact with MZ B cells and promote their differentiation into plasma cells. Using neutrophil-depleting mice and an MRP14-blocking compound, we showed that the presence of neutrophil and MRP14 is required for class switch, plasma cell maintenance, and antibody production in the spleen. We found that MRP14 could also be produced by neutrophils in the bone marrow and support the maintenance of bone marrow plasma cells. MRP14 binding could enhance the effect of the BAFF signal and protect primary multiple myeloma cells from doxorubicin-induced apoptosis. Our data demonstrate the effects of neutrophils on neighboring B cells and plasma cells, which provides new insights into the connection between neutrophil and humoral responses.
MicroRNA-219 Inhibits Proliferation and Induces Differentiation of Oligodendrocyte Precursor Cells after Contusion Spinal Cord Injury in Rats
Authors: Li Fang , Zhou Mou-Wang , Liu Nan , Yang Yan-Yan , Xing Hua-Yi , Lu Yao , Liu Xiao-Xie
Published: February 2019

MicroRNA-219 (miR-219) regulates the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) during central nervous system (CNS) development. OPCs only differentiate into oligodendrocytes (OLs) in the healthy CNS, but can generate astrocytes (As) after injury. We hypothesized that miR-219 may modulate OPC proliferation and differentiation in a cervical C5 contusion spinal cord injury (SCI) model. After injury, we observed a decrease in the miR-219 level and quantity of OLs and an increase in the number of OPCs and As. Silencing of miR-219 by its antagomir in vivo produced similar results, but of greater magnitude. Overexpression of miR-219 by its agomir in vivo increased the number of OLs and suppressed generation of OPCs and As. Luxol fast blue staining confirmed that SCI caused demyelination and that the extent of demyelination was attenuated by miR-219 overexpression, but aggravated by miR-219 reduction. Monocarboxylate transporter 1 (MCT-1) may be implicated in the regulation of OPC proliferation and differentiation mediated by miR-219 following contusion SCI. Collectively, our data suggest that miR-219 may mediate SCI-induced OPC proliferation and differentiation, and MCT-1 may participate in this process as a target of miR-219.
Nicotinamide Phosphoribosyltransferase Acts as a Metabolic Gate for Mobilization of Myeloid-Derived Suppressor Cells
Authors: Travelli Cristina , Consonni Francesca Maria , Sangaletti Sabina , Storto Mariangela , Morlacchi Sara , Grolla Ambra A. , Galli Ubaldina , Tron Gian Cesare , Portararo Paola , Rimassa Lorenza , Pressiani Tiziana , Mazzone Massimiliano , Trovato Rosalinda , Ugel Stefano , Bronte Vincenzo , Tripodo Claudio , Colombo Mario P. , Genazzani Armando A. , Sica Antonio
Published: February 2019

Cancer induces alteration of hematopoiesis to fuel disease progression. We report that in tumor-bearing mice the macrophage colony-stimulating factor elevates the myeloid cell levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway, which acts as negative regulator of the CXCR4 retention axis of hematopoietic cells in the bone marrow. NAMPT inhibits CXCR4 through a NAD/Sirtuin 1–mediated inactivation of HIF1α-driven CXCR4 gene transcription, leading to mobilization of immature myeloid-derived suppressor cells (MDSC) and enhancing their production of suppressive nitric oxide. Pharmacologic inhibition or myeloid-specific ablation of NAMPT prevented MDSC mobilization, reactivated specific antitumor immunity, and enhanced the antitumor activity of immune checkpoint inhibitors. Our findings identify NAMPT as a metabolic gate of MDSC precursor function, providing new opportunities to reverse tumor immunosuppression and to restore clinical efficacy of immunotherapy in patients with cancer.

Significance:

These findings identify NAMPT as a metabolic gate of MDSC precursor function, providing new opportunities to reverse tumor immunosuppression and to restore clinical efficacy of immunotherapy in cancer patients.
Genetic and Environmental Determinants of Immune Response to Cutaneous Melanoma
Authors: Poźniak Joanna , Nsengimana Jérémie , Laye Jonathan P. , O’Shea Sally J. , Diaz Joey Mark S. , Droop Alastair P. , Filia Anastasia , Harland Mark , Davies John R. , Mell Tracey , Randerson-Moor Juliette A. , Muralidhar Sathya , Hogan Sabrina A. , Freiberger Sandra Nicole , Levesque Mitchell P. , Cook Graham P. , Bishop D. Timothy , Newton-Bishop Julia
Published: February 2019

The immune response to melanoma improves the survival in untreated patients and predicts the response to immune checkpoint blockade. Here, we report genetic and environmental predictors of the immune response in a large primary cutaneous melanoma cohort. Bioinformatic analysis of 703 tumor transcriptomes was used to infer immune cell infiltration and to categorize tumors into immune subgroups, which were then investigated for association with biological pathways, clinicopathologic factors, and copy number alterations. Three subgroups, with “low”, “intermediate”, and “high” immune signals, were identified in primary tumors and replicated in metastatic tumors. Genes in the low subgroup were enriched for cell-cycle and metabolic pathways, whereas genes in the high subgroup were enriched for IFN and NF-κB signaling. We identified high MYC expression partially driven by amplification, HLA-B downregulation, and deletion of IFNγ and NF-κB pathway genes as the regulators of immune suppression. Furthermore, we showed that cigarette smoking, a globally detrimental environmental factor, modulates immunity, reducing the survival primarily in patients with a strong immune response. Together, these analyses identify a set of factors that can be easily assessed that may serve as predictors of response to immunotherapy in patients with melanoma.

Significance:

These findings identify novel genetic and environmental modulators of the immune response against primary cutaneous melanoma and predict their impact on patient survival.

See related commentary by Anichini, p. 2457
A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children's Oncology Group Phase I and Pilot Consortium (ADVL0921)
Authors: Mossé Yael P. , Fox Elizabeth , Teachey David T. , Reid Joel M. , Safgren Stephanie L. , Carol Hernan , Lock Richard B. , Houghton Peter J. , Smith Malcolm A. , Hall David , Barkauskas Donald A. , Krailo Mark , Voss Stephan D. , Berg Stacey L. , Blaney Susan M. , Weigel Brenda J.
Published: February 2019

Purpose:

Aurora A kinase (AAK) plays an integral role in mitotic entry, DNA damage checkpoint recovery, and centrosome and spindle maturation. Alisertib (MLN8237) is a potent and selective AAK inhibitor. In pediatric preclinical models, antitumor activity was observed in neuroblastoma, acute lymphoblastic leukemia, and sarcoma xenografts. We conducted a phase 2 trial of alisertib in pediatric patients with refractory or recurrent solid tumors or acute leukemias (NCT01154816).

Patients and Methods:

Alisertib (80 mg/m2/dose) was administered orally, daily for 7 days every 21 days. Pharmacogenomic (PG) evaluation for polymorphisms in the AURK gene and drug metabolizing enzymes (UGT1A1*28), and plasma pharmacokinetic studies (PK) were performed. Using a 2-stage design, patients were enrolled to 12 disease strata (10 solid tumor and 2 acute leukemia). Response was assessed after cycle 1, then every other cycle.

Results:

A total of 139 children and adolescents (median age, 10 years) were enrolled, 137 were evaluable for response. Five objective responses were observed (2 complete responses and 3 partial responses). The most frequent toxicity was myelosuppression. The median alisertib trough concentration on day 4 was 1.3 μmol/L, exceeding the 1 μmol/L target trough concentration in 67% of patients. No correlations between PG or PK and toxicity were observed.

Conclusions:

Despite alisertib activity in pediatric xenograft models and cogent pharmacokinetic-pharmacodynamic relationships in preclinical models and adults, the objective response rate in children and adolescents receiving single-agent alisertib was less than 5%.
ЗМІНИ ФІБРИНОЛІТИЧНОЇ АКТИВНОСТІ КРОВІ У ПАЦІЄНТІВ З ІШЕМІЧНОЮ ХВОРОБОЮ СЕРЦЯ І СУПУТНІМ ЦУКРОВИМ ДІАБЕТОМ 2 ТИПУ ЗАЛЕЖНО ВІД КОМПЕНСАЦІЇ
Authors: Zolotukhina Yu. O.
Published: February 2019

Порушення в системі гемостазу мають серйозний вплив на перебіг захворювання і наявність ускладнень у пацієнтів із коморбідним перебігом ішемічної хвороби серця (ІХС) та цукрового діабету (ЦД) 2 типу.

Мета дослідження – оцінити та проаналізувати показники фібринолізу в різних групах пацієнтів з ішемічною хворобою серця та супутнім цукровим діабетом 2 типу залежно від стадії компенсації останнього.

Матеріали і методи. В ході дослідження фібринолітичної системи обстежено 52 хворих, яких госпіталізовано в кардіологічне та ендокринологічне відділення Київської клінічної лікарні на залізничному транспорті № 2 з клінічними ознаками ІХС. Пацієнтів поділили на три групи: перша – 27 осіб із ІХС у поєднанні з ЦД 2 типу в стадії субкомпенсації, друга – 14 хворих у стадії компенсації та третя 11 пацієнтів у стадії декомпенсації.

Результати досліджень та їх обговорення. Проаналізувавши дані, ми виявили знижений рівень плазміногену при субкомпенсації на 15,5 % (р<0,001), при компенсації – на 13 (р<0,001), при декомпенсації – на 17,2 % (р<0,05), а також значне підвищення активності показників Хагеманзалежного фібринолізу (в 2,09 раза (р<0,001), 2,2 (р<0,001), 2,3 раза (р<0,001) відповідно) та інгібітора активатора плазміногену-1 (на 20 % (р<0,001), 19,8 % (р<0,001), 26 % (р<0,001). І як наслідок, при виявлених змінах показників фібринолізу ми спостерігаємо значне подовження частково-еуглобулінового лізису: на 49,8 % (р<0,001) при субкомпенсації, на 55,4 % (р<0,001) при компенсації, на 55,7 % (р<0,001) при декомпенсації.

Висновки. У пацієнтів із коморбідним перебігом ІХС та ЦД 2 типу на різних стадіях компенсації ми спостерігали пригнічення активності фібринолітичного потенціалу крові. Але у хворих на ЦД 2 типу в стадії декомпенсації він найвираженіший, що можливо є причиною частого розвитку мікро- та макросудинних ускладнень у цій групі хворих.
Evaluation of Glomerular Hemodynamic Function by Empagliflozin in Diabetic Mice Using In Vivo Imaging
Authors: Kidokoro Kengo , Cherney David Z.I. , Bozovic Andrea , Nagasu Hajime , Satoh Minoru , Kanda Eiichiro , Sasaki Tamaki , Kashihara Naoki
Published: February 2019

Background:

Sodium glucose cotransporter 2 inhibitors may reduce kidney hyperfiltration, thereby preventing diabetic kidney disease progression, which may in turn reduce cardiovascular risk, including heart failure. However, the mechanisms that regulate renal function responses to sodium glucose cotransporter 2 inhibition are not yet fully understood. We explored the renal protective effects of sodium glucose cotransporter 2 inhibition with empagliflozin, with a focus on glomerular hemodynamic effects and tubuloglomerular feedback using in vivo multiphoton microscopy imaging techniques.

Methods:

C57BL/6 mice and spontaneously diabetic

Ins2
+/Akita

mice were studied. The mice were treated with empagliflozin (20 mg·kg
–1
·d
–1
) and insulin for 4 weeks, and the single-nephron glomerular filtration rate was measured using multiphoton microscope. A neuronal nitric oxide synthase inhibitor (7-nitroindazole, 20 mg·kg
–1
·d
–1
) or a cyclooxygenase-2 inhibitor (SC58236, 6 mg/L), or an A1 adenosine receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 1 mg·kg
–1
·d
–1
) was administered to elucidate the mechanisms of tubuloglomerular feedback signaling and single-nephron glomerular filtration rate regulation.

Results:

The urinary excretion of adenosine, nitric oxide metabolites, and the prostanoid prostaglandin E2 was also quantified. The single-nephron glomerular filtration rate in the

Ins2
+/Akita

group was higher than in controls (C57BL/6; 4.9±1.3 nL/min versus

Ins2
+/Akita

; 15.8±6.8 nL/min) and lower in

Ins2
+/Akita

/empagliflozin to 8.0±3.3 nL/min (
P
<0.01). In vivo imaging also revealed concomitant afferent arteriolar dilation (
P
<0.01) and increased glomerular permeability of albumin in the

Ins2
+/Akita

group. Empagliflozin ameliorated these changes (
P
<0.01). Urinary adenosine excretion in the

Ins2
+/Akita

/empagliflozin group was higher than in

Ins2
+/Akita

(

Ins2
+/Akita

; 3.4±1.4 nmol/d,

Ins2
+/Akita

/empagliflozin; 11.2±3.0 nmol/d,
P
<0.05), whereas nitric oxide metabolites and prostaglandin E2 did not differ. A1 adenosine receptor antagonism, but not neuronal nitric oxide synthase or cyclooxygenase-2 inhibition, blocked the effect of empagliflozin on renal function. Empagliflozin increased urinary adenosine excretion and reduced hyperfiltration via afferent arteriolar constriction, effects that were abolished by A1 adenosine receptor blockade.

Conclusions:

Adenosine/A1 adenosine receptor pathways play a pivotal role in the regulation of the single-nephron glomerular filtration rate via tubuloglomerular feedback mechanisms in response to sodium glucose cotransporter 2 inhibition, which may contribute to renal and cardiovascular protective effects reported in clinical trials.
Associations of Unhealthy Food Environment With the Development of Coronary Artery Calcification: The CARDIA Study
Authors: Kelman Julie , Pool Lindsay R. , Gordon‐Larsen Penny , Carr J. Jeffrey , Terry James G. , Rana Jamal S. , Kershaw Kiarri N.
Published: February 2019

Background

While prior studies have linked the neighborhood environment and development of subclinical atherosclerosis, it is unknown whether living in neighborhoods with greater availability of “unhealthy” food outlets (fast‐food chain restaurants and convenience stores) is associated with risk of developing coronary artery calcification (CAC).

Methods and Results

We included 2706CARDIAstudy (Coronary Artery Risk Development in Young Adults) participants who underwentCACmeasurement during follow‐up years 15 (2000–2001), 20 (2005–2006), and 25 (2010–2011). Neighborhood features examined included percentage of all food outlets that were convenience stores and fast‐food chain restaurants within a 3‐km Euclidean buffer distance from each participant's residence. Econometric fixed effects models, which by design control for all time‐invariant covariates, were used to model the longitudinal association between simultaneous within‐person change in percentage food outlet and change inCAC. At baseline (year 15), 9.7% of participants had prevalentCAC. During 10 years of follow‐up, 21.1% of participants developedCAC. Each 1‐SD increase in percentage of convenience stores was associated with a 1.34 higher odds of developingCAC(95%CI: 1.04, 1.72) after adjusting for individual‐ and neighborhood‐level covariates; however, there was no significant association between increased percentage of fast‐food chain restaurants and developingCAC(odds ratio=1.15; 95%CI: 0.96, 1.38). There were no significant associations between increases in either food outlet percentage and progression ofCAC.

Conclusions

Our findings suggest that increases in the relative availability of convenience stores in participants' neighborhoods is related to the development ofCACover time.
Religion and the Arts: History and Method
Authors: Apostolos-Cappadona Diane
Published: February 2019

In Religion and the Arts: History and Method, Diane Apostolos-Cappadona presents an overview of the 19th century origins of this discrete field of study and its methodological journey to the present-day through issues of repatriation, museum exhibitions, and globalization. Apostolos-Cappadona suggests that the fluidity and flexibility of the study of religion and the arts has expanded like an umbrella since the 1970s—and the understanding that art was simply a visual exegesis of texts—to now support the study of material, popular, and visual culture, as well as gender. She also delivers a careful analysis of the evolution of thought from traditional iconographies to the transformations once scholars were influenced by response theory and challenged by globalization and technology. Religion and the Arts: History and Method offers an indispensable introduction to the questions and perspectives essential to the study of this field.
Seven new species of Systaria Simon, 1897 from Southeast Asia (Araneae, Clubionidae, Systariinae)
Authors: DANKITTIPAKUL PAKAWIN , SINGTRIPOP TIPPAWAN
Published: February 2019

The male of Systaria cervina (Simon, 1897) is newly described; the female internal genitalia are illustrated for the first time. Seven new species are described from Southeast Asia: S. decidua sp. nov. and S. lanna sp. nov. from northern Thailand; S. insolita sp. nov. from northeastern Thailand; S. bifida sp. nov. from southern Thailand and Myanmar; S. acuminata sp. nov. from southern Thailand and Indonesia; S. convolutiva sp. nov. from Indonesia; S. deelemanae sp. nov. from the Philippines. Two additional characters are recognized among Systaria species and considered synapomorphies for the genus: the base of the cymbium on retrolateral side is provided with a sharply pointed cymbial tubercle or an elevated, oblique ridge; the anterior bursae of the internal female genitalia are distinctly sclerotized.
Jardamarekia enigma, a new Early Devonian tryblidioidean from Royal Creek area (Yukon Territory, Canada), and paleobiogeography of the Early Devonian of northwestern Canada
Authors: FRÝDA JIŘÍ , BLODGETT ROBERT B. , LENZ ALFRED C. , FRÝDOVÁ BARBORA
Published: February 2019

The Tryblidia (= Monoplacophora) represents the conchiferan class with the fewest Recent taxa in the phylum Mollusca (Haszprunar 2008) and its phylogeny is still poorly known. This group is known already in Cambrian strata (Early Paleozoic) more than 500 Ma ago. Present-day tryblidian species are known mainly from hadal environments (Schwabe 2008, but see also Wilson et al. 2009) in contrast to Paleozoic species, which have been described only from shallow environments of continental shelves of many paleocontinents (e.g., Horný 1962). A typical feature of fossil as well as living tryblidian species is their rarity. The vast majority of species are known only from several specimens (Haszprunar 2008). Furthermore, description of Paleozoic tryblidian molluscs is strongly underrepresented in the literature, despite the existence of diverse material. This is also true for fossils described in the present study based on a diverse silicified molluscan fauna of mostly gastropods collected from Lower Devonian strata of the Royal Creek area, Yukon Territory (Fig. 1) by Alfred C. Lenz and David G. Perry from 1970–1980. Lists of all hitherto described molluscan species as well as detailed information on their age and locality can be found in Lenz (1977a), Blodgett et al. (2001, 2010) and Frýda et al. (2008). Prior to our studies of the Royal Creek tryblidian and gastropod fauna, no descriptions or illustrations were available for Lower Devonian molluscs of north-western Canada, although a short discussion and faunal lists were provided by Blodgett et al. (1988) for Lower Devonian tryblidians and gastropods from the relatively nearby Delorme Formation of Northwest Territories, and early Emsian (late Early Devonian) tryblidians and gastropods from the Mt. Lloyd George area, northeastern British Columbia. The poor knowledge of Paleozoic tryblidians and gastropods faunas of Laurentia (North America) caused difficulties in the evaluation of Early Devonian paleobiogeography (Blodgett et al. 1999). The present paper is focused on the taxonomy of a new Devonian tryblidian limpet, but it provides also useful data for paleobiogeography and biostratigraphy of the Lower Devonian of western Canada.
World review of Laricobius (Coleoptera: Derodontidae)
Authors: LESCHEN RICHARD A. B.
Published: February 2019

The Holarctic genus Laricobius (Derodontidae) is reviewed and a key to the species provided. There are 21 known species and those with known life history are predators of adelgids. The type specimen of L. minutus Nikitsky was lost prior to this study and types of L. caucasicus Rost were never located, though one specimen which lacks the abdomen is attributed to this species. One new species is described (Laricobius naganoensis n. sp.) and lectotypes were designated for L. erichsonii Rosenhauer and L. sahlberg Reitter. Europe has one described species, North America 3, and Asia 17. A cladistic analysis, based on 20 species, resulted in two broad groups, one which is confined to south-eastern Asia and Himalaya and has more shortened species with a narrower pronotum lacking explanate margins, and a more widespread Holarctic group, which is more typical of the genus type, being more elongate, with a transverse, fully explanate pronotum. The latter group includes four Asian species without ocelli, collected from Tsuga (hemlock) infested with Adelges tsugae Annand.
Revision of the Mexican subgenus Carabomimus Kolbe, 1895 (Coleoptera: Carabidae: Calosoma Weber, 1801): C. depressicolle, C. flohri and C. digueti species groups
Authors: HÄCKEL MARTIN , HEINZ WALTER , SEHNAL ROSTISLAV
Published: February 2019

It is revised the central Mexican species of the C. (Carabomimus) depressicolle species complex, included in the subgenus Carabomimus Kolbe, 1895, genus Calosoma Weber, 1801. The complex is divided into two species groups, depressicolle and flohri. A key to all species groups of the subgenus Carabomimus (depressicolle, digueti, flohri, politum and striatulum) inhabiting this area is included, whereas C. bulleri (Beheim & Breuning, 1943) was left unassigned. Another key to all five species of the complex (species groups depressicolle and flohri) is likewise included. It is described C. flohri zirostense ssp. n. (México: Michoacán), and the previously synonymized C. lesnei Breuning, 1931 and C. gebieni Breuning, 1931 are restablished as valid taxa. C. asper (Jeannel, 1940) is downgraded as subspecies of C. depressicolle Chaudoir, 1869, whereas C. altipeta (Jeannel, 1940) and C. sylvestre (Lassalle, 2009) are ranked as species. C. digueti colimaense (Lassalle 2009) is considered to be a subspecies of C. flohri.
Hydroporus esseri sp. n., a new diving beetle from southern Turkey (Coleoptera, Dytiscidae, Hydroporinae)
Authors: FERY HANS , HENDRICH LARS
Published: February 2019

Hydroporus esseri sp. n. is described from the Köprülü Canyon near Sagirin in southern Turkey (Antalya province), where it was found in a backwater pool of the Köprülü River. It is the smallest species of the genus Hydroporus Clairville, 1806 recorded so far from Turkey. Morphologically the new species is very close to Hydroporus umbrosus (Gyllenhal, 1808), which is widespread in North and Central Europe, Siberia and Far East. H. esseri sp. n. can be separated from H. umbrosus chiefly by its smaller size, the shape of the median lobe and surface colour. The aedeagi and habitus of both species are illustrated. Notes on their distribution and life habitats are given. Hydroporus memnonius Nicolai, 1822 is recorded for the first time from Turkey, and H. umbrosus for the first time from Slovakia. Altogether 180 species of the genus Hydroporus are now reported world-wide and 34 from Turkey.
A new species of the genus Macrosaldula Leston et Southwood, 1964 (Hemiptera: Heteroptera: Saldidae) from Northwestern China
Authors: LUO ZHAOHUI , VINOKUROV NIKOLAI N.
Published: February 2019

Macrosaldula bogdashana Luo et Vinokurov sp. n. is described from Bogda Shan Range, Northwestern China. The new species is most similar in size and vestiture to M. oblonga oblonga (Stål, 1858) but differs in the color pattern of forewings (Fig. 1-3) and male genitalia structure (Figs. 11–14). M. bogdashana is also similar to M. tadzhika (Kiritshenko, 1912) in the same vestiture, but can be distinguished from the latter by the shorter body (see Table), shape of pale spots on corium (Figs. 6–9), and the male genitalia structure (Figs. 15–18).
Johngarthia cocoensis, a new species of Gecarcinidae MacLeay, 1838 (Crustacea, Decapoda, Brachyura) from Cocos Island, Costa Rica
Authors: PERGER ROBERT , VARGAS RITA , WALL ADAM
Published: February 2019

A new species of Gecarcinidae MacLeay, 1838, Johngarthia cocoensis n. sp. from Cocos Island (Costa Rica) is described and illustrated. The new species closely resembles J. malpilensis (Faxon, 1893), from which it can be separated by the inner apical lobes of the third maxilliped meri mostly separated from each other in resting position, palp of third maxilliped merus partly exposed and epistomial carapace tooth completely exposed.
A blue-eyed Leptobrachium (Anura: Megophryidae) from Arunachal Pradesh, India
Authors: SONDHI SANJAY , OHLER ANNEMARIE
Published: February 2019

A new species of Megophryidae, Leptobrachium bompu is described from Eaglenest Wildlife Sanctuary, Arunachal Pradesh, India. It is a medium sized member of the genus Leptobrachium. In life, the frog is distinguished by the combination of a series of morphological characters from its congeners. Its entirely greyish-blue coloured eyes differentiate the species from all other species in the genus but Leptobrachium waysepuntiense. The morphological comparison is based on a table of 16 characters discriminant in Leptobrachium species.