bluuebunny/crossref_metadata_2025 huggingface dataset:
Aiding and Abetting: How the Tumor Microenvironment Protects Cancer from Chemotherapy
Authors: Fiedler Eleanor C. , Hemann Michael T.
Published: December 2018

Disease recurrence following cancer therapy remains an intractable clinical problem and represents a major impediment to reducing the mortality attributable to malignant tumors. While research has traditionally focused on the cell-intrinsic mechanisms and mutations that render tumors refractory to both classical chemotherapeutics and targeted therapies, recent studies have begun to uncover myriad roles for the tumor microenvironment (TME) in modulating therapeutic efficacy. This work suggests that drug resistance is as much ecological as it is evolutionary. Specifically, cancers resident in organs throughout the body do not develop in isolation. Instead, tumor cells arise in the context of nonmalignant cellular components of a tissue. While the roles of these cell-extrinsic factors in cancer initiation and progression are well established, our understanding of the TME's influence on therapeutic outcome is in its infancy. Here, we focus on mechanisms by which neoplastic cells co-opt preexisting or treatment-induced signaling networks to survive chemotherapy.
Taming the Heterogeneity of Aggressive Lymphomas for Precision Therapy
Authors: Young Ryan M. , Phelan James D. , Shaffer Arthur L. , Wright George W. , Huang Da Wei , Schmitz Roland , Johnson Calvin , Oellerich Thomas , Wilson Wyndham , Staudt Louis M.
Published: December 2018

Genomic analyses of diffuse large B cell lymphoma (DLBCL) are revealing the genetic and phenotypic heterogeneity of these aggressive lymphomas. In part, this heterogeneity reflects the existence of distinct genetic subtypes that acquire characteristic constellations of somatic genetic alterations to converge on the DLBCL phenotype. In parallel, functional genomic screens and proteomic analyses have identified multiprotein assemblies that coordinate oncogenic survival signaling in DLBCL. In this review, we merge these recent insights into a unified conceptual framework with implications for the design of precision medicine trials in DLBCL.
Effects of obesity and exercise on colon cancer induction and hematopoiesis in mice
Authors: Emmons Russell , Xu Guanying , Hernández-Saavedra Diego , Kriska Adam , Pan Yuan-Xiang , Chen Hong , De Lisio Michael
Published: December 2018

Obesity-induced inflammation is associated with increased risk for colorectal cancer (CRC). The role of diet and exercise in modulating increased CRC risk in obesity and the potential role of altered hematopoiesis as a contributor to these effects remain unknown. The purpose of this study was to examine how weight loss induced during CRC induction with or without exercise alters CRC initiation and its relationship to altered hematopoiesis. Mice consumed either a control (CON) or a high-fat diet to induce obesity. All mice were then placed on the control diet during CRC induction with azoxymethane (AOM). Following AOM injection, mice originally on the high-fat diet were randomized into sedentary (HF-SED) or exercise trained (HF-EX) conditions. At euthanasia, body weight and fat mass were similar among all three groups ( P < 0.05). Compared with CON and HF-EX, HF-SED developed increased content of preneoplastic lesions ( P < 0.05), and HF-SED had significantly increased markers of colon inflammation compared with CON. Compared with both CON and HF-EX, HF-SED had decreased content of short-term hematopoietic stem cells and increased content of common myeloid progenitor cells (both P < 0.05). Similarly, HF-SED had increased bone marrow adiposity compared with CON and HF-EX ( P < 0.05), and proteomics analysis revealed an increased marker of bone marrow inflammation in HF-SED compared with CON and HF-EX. Our results suggest that the early removal of a high-fat diet reduces CRC incidence when combined with an exercise training intervention. This reduction in risk was related to lower colon inflammation with anti-inflammatory changes in hematopoiesis induced by exercise.
The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes
Authors: Bond Simon T. , Moody Sarah C. , Liu Yingying , Civelek Mete , Villanueva Claudio J. , Gregorevic Paul , Kingwell Bronwyn A. , Hevener Andrea L. , Lusis Aldons J. , Henstridge Darren C. , Calkin Anna C. , Drew Brian G.
Published: December 2018

Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain mitochondrial health and function. Disruptions in mitochondrial dynamics often lead to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins, including the E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known to regulate mitochondrial dynamics; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ) during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression in vitro and in vivo alters mitochondrial function, affects cellular metabolism, and leads to differential regulation of several metabolic genes. Thus our data demonstrate an association between mitochondrial dynamics and metabolism that defines MARCH5 as a critical link between these interconnected pathways.
Comparative Studies of Pectinase Production byBacillus subtilis strain Btk 27in Submerged and Solid-State Fermentations
Authors: Oumer Oliyad Jeilu , Abate Dawit
Published: December 2018

The request for enzymes in the global market is expected to rise at a fast pace in recent years. With this regard, there has been a great increase in industrial applications of pectinase owing to their significant biotechnological uses. This study was undertaken with main objectives of meeting the growing industrial demands of pectinase, by improving the yield without increasing the cost of production. In addition, this research highlights the underestimated potential of agroresidues for the production of biotechnologically important products. In this study, the maximum pectinase production attained was using wheat bran, among the tested agroresidues. The production of pectinase was improved from 10.1 ± 1.4 U/ml to 66.3 ± 1.2 U/ml in submerged fermentation whereas it was in solid state fermentation from 800.0 ± 16.2 U/g to 1272.4 ± 25.5 U/g. The maximum pectinase production was observed using YEP (submerged fermentation) and wheat bran (solid state fermentation) at initial pH of 6.5, at 37°C and by supplementing the medium with 3 mM MgSO4.7H2O.
Correlation between Transient Pupillary Light Reflex and Retinal Function Impairment in Patients with Retinitis Pigmentosa
Authors: He Yan , Tang Huanyu , Wang Gang , Ren Bangqi , Wang Yi , Liu Yong
Published: December 2018

Purpose. To investigate the relationship between transient pupillary light reflex (PLR) and visual function in patients with retinitis pigmentosa (RP). Methods. A retrospective study was performed with 137 eyes of 73 patients with RP. Transient pupillary light reflex was measured by the vision monitor system (MonColor; Metrovision, France). Dark-adapted transient PLRs were elicited by four specific levels of stimulus luminance (−5, −3, −1, and 0 log cd/m2, blue or white light). Best-corrected visual acuity (BCVA) was recorded based on Early Treatment Diabetic Retinopathy Study (ETDRS) acuity charts. Fixation stability and retinal sensitivity of radial 10° areas were measured with microperimetry. The retinal sensitivity (RS) was divided into central RS (fovea and radial 1° areas) and peripheral RS (radial 3° and 5° areas from the fovea). The patients were further classified into 2 groups (P1 > 75% and P1 < 75%) according to fixation stability. Spearman’s correlation was performed to identify significant associations between BCVA, fixation stability, RS, and PLR. Results. Under the stimuli of the same color light, relative pupillary constriction (RPC), latency, or velocity of constriction in the same patients was statistically different in multiple luminance, respectively. Under the same luminance, blue light induced greater RPC and velocity (except for −3 log cd/m2) than white light. Most patients showed varying degrees of threshold elevation and visual function deficiency. Besides, there was a statistically significant difference in the distribution of BCVA, MRS, or fixation stability under different thresholds. The correlation between pupillary constrictive area (PCA) and retinal sensitivity was mainly determined by the peripheral region. Moreover, patients with stable fixation showed a greater correlation between PCA and RS. Conclusion. PLR induced by specific colors and luminance may serve as a promising clinical approach for assessing and monitoring rod function in advanced RP patients.
Data Augmentation-Assisted Makeup-Invariant Face Recognition
Authors: Sajid Muhammad , Ali Nouman , Dar Saadat Hanif , Iqbal Ratyal Naeem , Butt Asif Raza , Zafar Bushra , Shafique Tamoor , Baig Mirza Jabbar Aziz , Riaz Imran , Baig Shahbaz
Published: December 2018

Recently, face datasets containing celebrities photos with facial makeup are growing at exponential rates, making their recognition very challenging. Existing face recognition methods rely on feature extraction and reference reranking to improve the performance. However face images with facial makeup carry inherent ambiguity due to artificial colors, shading, contouring, and varying skin tones, making recognition task more difficult. The problem becomes more confound as the makeup alters the bilateral size and symmetry of the certain face components such as eyes and lips affecting the distinctiveness of faces. The ambiguity becomes even worse when different days bring different facial makeup for celebrities owing to the context of interpersonal situations and current societal makeup trends. To cope with these artificial effects, we propose to use a deep convolutional neural network (dCNN) using augmented face dataset to extract discriminative features from face images containing synthetic makeup variations. The augmented dataset containing original face images and those with synthetic make up variations allows dCNN to learn face features in a variety of facial makeup. We also evaluate the role of partial and full makeup in face images to improve the recognition performance. The experimental results on two challenging face datasets show that the proposed approach can compete with the state of the art.
Layers of Nanocrystalline SiC as a New Type of Solid-State Hydrogen Storage
Authors: Guglya A. , Kalchenko A. , Lyubchenko E. , Marchenko Yu. , Semenov A.
Published: December 2018

This paper presents the results related to the investigation of layers of nanocrystalline silicon carbide (nc-SiC) obtained by direct ion deposition for the purpose of hydrogen accumulation. The parameters of the production process providing the largest amount of accumulated hydrogen (more than 5.5 wt.%) were determined based on the mass spectrometric data on the desorption of atomic and molecular hydrogen from nc-SiC films. Electron microscopic examination revealed the structural features that are responsible for absorption, retention, and desorption of hydrogen at relatively low temperatures and pressures. The study results suggest that the main structural elements acting as the hydrogen traps are the vacant positions of carbon in nc-SiC. The presence of a developed system of intercrystalline boundaries in investigated films promotes the hydrogen desorption at relatively low temperatures.
The Study of Large-Scale Fading Using a Wavelet Transform Method
Authors: Lu Guizhen , Cao Zhi , Jia Xingning , Liang Jingjing
Published: December 2018

A wavelet method is proposed to evaluate the modeling of the first- and second-order statistics of large-scale fading from the signal strength measurement. The selection of wavelet is very important in using a wavelet method, and the steps of the wavelet method are given for the study of wave propagation loss. The path loss of measurement is analysed with different levels of wavelet decomposition and compared with an optimized Hata model. The correlation of slow fading on different scales shows that the correlation distance is related to the spatial scale.
T and N Staging of Gastric Cancer Using Dual-Source Computed Tomography
Authors: Xie Zhao-Yong , Chai Rui-Mei , Ding Guo-Cheng , Liu Yi , Ren Ke
Published: December 2018

Aim. This study is aimed at comparing gastric cancer T and N staging between virtual monochromatic energy images and fusion images generated by dual-source computed tomography (DSCT) dual-energy mode data acquisition prospectively while measuring the iodine concentration of gastric cancer and lymph nodes at different T and N stages from iodine map retrospectively. Methods. A total of 71 patients (50 males and 21 females; mean age: 59 ± 11 years) confirmed with gastric cancer by endoscopic biopsy with no neoadjuvant chemotherapy were enrolled for the CT examination before surgeries. The preoperative T and N staging results were compared between groups with pathological results as the gold standard. The iodine concentrations of the gastric lesions and LNs were measured on the iodine-based material decomposition images. All iodine concentration values were normalized against those in the abdominal aorta and defined as normalized iodine concentration (nIC) values. The short axis length of LNs and nIC values were statistically analyzed. Results. Group A was better than group B for T3 and T4 staging. No statistically significant difference in the overall accuracies for N staging was found between groups. For the late arterial and delayed phases, T3 and T4 nIC values of the extraserosal adipose tissue showed statistically significant differences. The nIC values between N0 and Nm (N1–N3) showed statistically significant differences in the portal phase only. Conclusions. T3 and T4 nIC values of the extraserosal adipose tissue showed statistically significant differences. Hence, dual-source CT may be helpful in the differential diagnosis between T3 and T4.
Baccharis trimera (Carqueja) Improves Metabolic and Redox Status in an Experimental Model of Type 1 Diabetes
Authors: do Nascimento Kaut Natália Nogueira , Rabelo Ana Carolina Silveira , Araujo Glaucy Rodrigues , Taylor Jason Guy , Silva Marcelo Eustáquio , Pedrosa Maria Lúcia , Chaves Miriam Martins , Rossoni Junior Joamyr Victor , Costa Daniela Caldeira
Published: December 2018

Diabetes mellitus is a metabolic disorder that causes severe complications due to the increased oxidative stress induced by disease. Many plants are popularly used in the treatment of diabetes, e.g., Baccharis trimera (carqueja). The aim of this study was to explore the potential application of the B. trimera hydroethanolic extract in preventing redox stress induced by diabetes and its hypoglycemic properties. Experiments were conducted with 48 female rats, divided into 6 groups, named C (control), C600 (control + extract 600 mg/kg), C1200 (control + extract 1200 mg/kg), D (diabetic), D600 (diabetic + 600 mg/kg), and D1200 (diabetic + 1200 mg/kg). Type 1 diabetes was induced with alloxan, and the animals presented hyperglycemia and reduction in insulin and body weight. After seven days of experimentation, the nontreated diabetic group showed changes in biochemical parameters (urea, triacylglycerol, alanine aminotransferase, and aspartate aminotransferase) and increased carbonyl protein levels. Regarding the antioxidant enzymes, an increase in superoxide dismutase activity was observed but in comparison a decrease in catalase and glutathione peroxidase activity was noted which suggests that diabetic rats suffered redox stress. In addition, the mRNA of superoxide dismutase, catalase, and glutathione peroxidase enzymes were altered. Treatment of diabetic rats with B. trimera extract resulted in an improved glycemic profile and liver function, decreased oxidative damage, and altered the expression of mRNA of the antioxidants enzymes. These results together suggest that B. trimera hydroethanolic extract has a protective effect against diabetes.
Factor Structure of the Ways of Coping Questionnaire in Parkinson’s Disease
Authors: Corti Emily J. , Johnson Andrew R. , Gasson Natalie , Bucks Romola S. , Thomas Meghan G. , Loftus Andrea M.
Published: December 2018

The Ways of Coping Questionnaire (WCQ) is used extensively in health research, but the measurement properties and suitability of the WCQ for people with Parkinson’s disease (PD) have not been psychometrically assessed. If the WCQ does not align with its original 8-factor structure in a PD population, the use of the WCQ subscales may not be appropriate. The present study used confirmatory factor analysis (CFA), exploratory factor analysis (EFA), and multiple-group EFA to determine the ideal factor structure of the WCQ in a PD sample. The original 8 factors of the WCQ were not reproduced. EFA revealed a 6-factor structure, including Distancing, Faith, Avoidance, Seeking Social Support, Planful Problem Solving, and Confrontive coping. As motor symptom severity may impact coping, the stability of the 6-factor structure was examined across motor symptom severity (mild and moderate), remaining consistent. Higher levels of overall motor severity were associated with increased use of faith and avoidance style coping. These findings suggest that the 6-factor structure of the WCQ may be more appropriate for assessing coping styles in PD.
Impact of Weekly Climatic Variables on Weekly Malaria Incidence throughout Thailand: A Country-Based Six-Year Retrospective Study
Authors: Kotepui Manas , Kotepui Kwuntida Uthaisar
Published: December 2018

Purpose. This study aimed to evaluate climatic data, including mean temperature, relative humidity, and rainfall, and their association with malaria incidence throughout Thailand from 2012 to 2017. The correlation of climatic parameters including temperature, relative humidity, and rainfall in each province and the weekly malaria incidence was analyzed using Spearman’s rank correlation. The results showed that the mean temperature correlated with malaria incidence (p value < 0.05) in 44 provinces in Thailand. These correlations were frequently found in the western and southern parts of Thailand. Relative humidity correlated with malaria incidence (p value < 0.05) in 35 provinces. These correlations were frequently found in the northern and northeastern parts of Thailand. Rainfall correlated with malaria incidence (p value < 0.05) in 38 provinces. These correlations were frequently found in the northern parts and some western parts of Thailand. The impacts of the mean temperature, relative humidity, and rainfall were observed frequently in specific provinces, including Chiang Mai, Chiang Rai, Trat, Kanchanaburi, Ubonratchathani, and Si Sa Ket. This is the first study to report areas where climatic data are associated with malaria incidence throughout Thailand from 2012 to 2017. These results can map out the climatic change process over time and across the country, which is the foundation for effective early warning systems for malaria, public health awareness campaigns, and the adoption of proper adaption measures that will help in malaria detection, diagnosis, and treatment.
Obstructive Jaundice due to Pancreatic Involvement as an Initial Presentation of Adult Acute Lymphoblastic Leukemia
Authors: Oladiran Oreoluwa , Nwosu Ifeanyi
Published: December 2018

Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid disorders characterized by monoclonal proliferation and expansion of immature lymphoid cells in the bone marrow, blood, and other organs. It commonly presents with nonspecific symptoms such as lethargy, easy bruising, and weight loss. In this article, we present the case of a 48-year-old male who presented to the hospital with painless jaundice resulting from pancreatic infiltration, initially thought to be due to pancreatic or hepatobiliary malignancy. He was later diagnosed with ALL by lymph node biopsy and peripheral blood flow cytometry immunophenotyping and was transferred to a cancer treatment centre for unilateral bone marrow biopsy and further management. Our case highlights the rare occurrence of pancreatic infiltration in ALL.
Critical Review of Fluid Flow Physics at Micro‐ to Nano‐scale Porous Media Applications in the Energy Sector
Authors: Singh Harpreet , Myong Rho Shin
Published: December 2018

While there is a consensus in the literature that embracing nanodevices and nanomaterials helps in improving the efficiency and performance, the reason for the better performance is mostly subscribed to the nanosized material/structure of the system without sufficiently acknowledging the role of fluid flow mechanisms in these systems. This is evident from the literature review of fluid flow modeling in various energy‐related applications, which reveals that the fundamental understanding of fluid transport at micro‐ and nanoscale is not adequately adapted in models. Incomplete or insufficient physics for the fluid flow can lead to untapped potential of these applications that can be used to increase their performance. This paper reviews the current state of research for the physics of gas and liquid flow at micro‐ and nanoscale and identified critical gaps to improve fluid flow modeling in four different applications related to the energy sector. The review for gas flow focuses on fundamentals of gas flow at rarefied conditions, the velocity slip, and temperature jump conditions. The review for liquid flow provides fundamental flow regimes of liquid flow, and liquid slip models as a function of key modeling parameters. The four porous media applications from energy sector considered in this review are (i) electrokinetic energy conversion devices, (ii) membrane‐based water desalination through reverse osmosis, (iii) shale reservoirs, and (iv) hydrogen storage, respectively. Review of fluid flow modeling literature from these applications reveals that further improvements can be made by (i) modeling slip length as a function of key parameters, (ii) coupling the dependency of wettability and slip, (iii) using a reservoir‐on‐chip approach that can enable capturing the subcontinuum effects contributing to fluid flow in shale reservoirs, and (iv) including Knudsen diffusion and slip in the governing equations of hydrogen gas storage.
A National Bowel Cancer Screening Programme using FIT: Achievements and Challenges
Authors: O'Donoghue Diarmuid , Sheahan Kieran , MacMathuna Padraic , Stephens Richard B. , Fenlon Helen , Morrin Martina , Mooney Jenny , Fahy Lorraine E. , Mooney Therese , Smith Alan
Published: December 2018

Colorectal cancer accounts for 11% of all cancer-related deaths in Ireland. With the aim of diagnosing these cancers at an earlier stage, and detecting premalignant lesions, the National Screening Service (NSS) offered a fecal immunochemical test (FIT) to all individuals aged 60 to 69. All individuals in the age range were contacted by post and invited to participate in the programme. Those with a positive FIT result were offered a colonoscopy in an internationally accredited unit. From an eligible population of 488,628, 196,238 individuals participated giving an uptake of 40.2%. Commencing at a FIT threshold of 20 μg Hg/g feces, the positivity rate was 8.6%, which overwhelmed colonoscopy capacity and, thus, the threshold was increased to 45 μg, resulting in an overall 5% positivity rate. A total of 520 individuals had cancer detected (68.3% stage I or II), of which 104 were removed endoscopically (pT1s). Adenomas were present in 54.2% of all colonoscopies, 17.4% deemed high risk. Despite a lower uptake, males were twice as likely to have colorectal cancers as females and had a 59% increased rate of high-risk adenomas diagnosed. Challenges facing the programme include increasing participation, especially among males, and increasing colonoscopy capacity. The ability to alter the sensitivity of FIT to match colonoscopy capacity is a valuable option for such a programme as it ensures that the maximum public health benefit can be achieved within available resources.
Acquisition of the Recurrent Gly101Val Mutation in BCL2 Confers Resistance to Venetoclax in Patients with Progressive Chronic Lymphocytic Leukemia
Authors: Blombery Piers , Anderson Mary Ann , Gong Jia-nan , Thijssen Rachel , Birkinshaw Richard W. , Thompson Ella R. , Teh Charis E. , Nguyen Tamia , Xu Zhen , Flensburg Christoffer , Lew Thomas E. , Majewski Ian J. , Gray Daniel H.D. , Westerman David A. , Tam Constantine S. , Seymour John F. , Czabotar Peter E. , Huang David C.S. , Roberts Andrew W.
Published: December 2018

The BCL2 inhibitor venetoclax induces high rates of durable remission in patients with previously treated chronic lymphocytic leukemia (CLL). However, despite continuous daily treatment, leukemia recurs in most patients. To investigate the mechanisms of secondary resistance, we analyzed paired pre-venetoclax and progression samples from 15 patients with CLL progression enrolled on venetoclax clinical trials. The novel Gly101Val mutation in BCL2 was identified at progression in 7 patients, but not at study entry. It was first detectable after 19 to 42 months of therapy, and its emergence anticipated clinical disease progression by many months. Gly101Val reduces the affinity of BCL2 for venetoclax by ∼180-fold in surface plasmon resonance assays, thereby preventing the drug from displacing proapoptotic mediators from BCL2 in cells and conferring acquired resistance in cell lines and primary patient cells. This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse.

Significance:

Why CLL recurs in patients who achieve remission with the BCL2 inhibitor venetoclax has been unknown. We provide the first description of an acquired point mutation in BCL2 arising recurrently and exclusively in venetoclax-treated patients. The mutation reduces venetoclax binding and is sufficient to confer resistance.

See related commentary by Thangavadivel and Byrd, p. 320.

This article is highlighted in the In This Issue feature, p. 305
CD16+NKG2Ahigh Natural Killer Cells Infiltrate Breast Cancer–Draining Lymph Nodes
Authors: Frazao Alexandra , Messaoudene Meriem , Nunez Nicolas , Dulphy Nicolas , Roussin France , Sedlik Christine , Zitvogel Laurence , Piaggio Eliane , Toubert Antoine , Caignard Anne
Published: December 2018

Tumor-draining lymph nodes (TD-LNs) are the first site of metastasis of breast cancer. Natural killer (NK) cells that infiltrate TD-LNs [including noninvaded (NI) or metastatic (M)-LNs from breast cancer patients] and NK cells from healthy donor (HD)-LNs were characterized, and their phenotype analyzed by flow cytometry. Low percentages of tumor cells invaded M-LNs, and these cells expressed ULBP2 and HLA class I molecules. Although NK cells from paired NI and M-LNs were similar, they expressed different markers compared with HD-LN NK cells. Compared with HD-LNs, TD-LN NK cells expressed activating DNAM-1, NKG2C and inhibitory NKG2A receptors, and exhibited elevated CXCR3 expression. CD16, NKG2A, and NKp46 expression were shown to be increased in stage IIIA breast cancer patients. TD-LNs contained a large proportion of activated CD56brightCD16+ NK cells with high expression of NKG2A. We also showed that a subset of LN NK cells expressed PD-1, expression of which was correlated with NKp30 and NKG2C expression. LN NK cell activation status was evaluated by degranulation potential and lytic capacity toward breast cancer cells. NK cells from TD-LNs degranulated after coculture with breast cancer cell lines. Cytokine-activated TD-LN NK cells exerted greater lysis of breast cancer cell lines than HD-LN NK cells and preferentially lysed the HLA class Ilow MCF-7 breast cancer cell line. TD-LNs from breast cancer patients, thus, contained activated lytic NK cells. The expression of inhibitory receptor NKG2A and checkpoint PD-1 by NK cells infiltrating breast cancer–draining LNs supports their potential as targets for immunotherapies using anti-NKG2A and/or anti–PD-1.
Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function
Authors: Clavijo Paul E. , Friedman Jay , Robbins Yvette , Moore Ellen C. , Smith Ernest , Zauderer Maurice , Evans Elizabeth E. , Allen Clint T.
Published: December 2018

Tumor infiltration by immunosuppressive myeloid cells, such as myeloid-derived suppressor cells (MDSCs), causes resistance to immunotherapy. Semaphorin4D, originally characterized for its axonal guidance properties, also contributes to endothelial cell migration and survival and modulates global immune cytokine profiles and myeloid cell polarization within the tumor microenvironment. Here, we show how a therapeutic murine Sema4D mAb improves responses to immune-checkpoint blockade (ICB) in two murine carcinoma models. Treatment of tumor-bearing mice with Sema4D mAb abrogated Ly6Ghi PMN-MDSC recruitment through reducing MAPK-dependent chemokine production by tumor cells in Murine oral cancer-1 (MOC1) tumors. PMN-MDSC suppressive capacity was reduced through inhibition of Sema4D-driven arginase expression. These changes led to enhanced tumor infiltration by CD8+ TIL and activation of tumor-draining lymph node T lymphocytes in response to tumor antigen. Sema4D mAb in combination with either CTLA-4 or PD-1 blockade enhanced rejection of tumors or tumor growth delay, resulting in prolonged survival with either treatment. This function of Sema4D mAb provides a rationale for its evaluation in combination with ICB to treat tumors with immunosuppressive myeloid infiltration.
Postoperative Late-Onset Endophthalmitis Caused by Leishmania donovani: A Case Report
Authors: Kozomara Bojan , Potkonjak Ernesta , Lazic Ratimir , Savicic Sanja , Gabric Nikica
Published: December 2018

Leishmania donovani is a human blood parasite that belongs to the genus Leishmania. We would like to present a case of late Leishmania donovani endophthalmitis in one eye of a patient that underwent simultaneous bilateral grade 3 cataract surgery.
Tetraparesis following an Anterior Circulation Stroke: A Case Report
Authors: Saleh Christian , Michel-de Cazotte Elvire , Hund-Georgiadis Margret
Published: December 2018

The azygos anterior cerebral artery (AACA) is a large single anterior cerebral artery that supplies both medial territories of the anterior cerebral hemispheres. Occlusion of the AACA can result, therefore, in bifrontal infarction. We report a patient who suffered from a tetraparesis following a bilateral anterior cerebral artery territory infarction due to an occluded AACA and provide a brief review of the literature.
miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer
Authors: Zhu Xiangyu , Ma Si-ping , Yang Dongxiang , Liu Yanlong , Wang Yong-peng , Lin Tao , Li Yan-xi , Yang Shi-hua , Zhang Wan-chuan , Wang Xin-ling
Published: December 2018

Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.
Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors
Authors: Kaneko Yuji , Tuazon Julian P. , Ji Xunming , Borlongan Cesario V.
Published: December 2018

Background/Aims: The endogenous neurotrophic peptides pituitary adenylate cyclase-activating polypeptides (PACAP-27/38) protect against stroke, but the molecular mechanism remains unknown. Methods: Primary rat neural cells were exposed to PACAP-27 or PACAP-38 before induction of experimental acute ischemic stroke via oxygen-glucose deprivation-reperfusion (OGD/R) injury. To reveal PACAP’s role in neuroprotection, we employed fluorescent live/dead cell viability and caspase 3 assays, optical densitometry of mitochondrial dehydrogenase and cell growth, glutathione disulfide luciferase activity, ELISA for high mobility group box1 extracellular concentration, ATP bioluminescence, Western blot analysis of PACAP, NMDA subunits, apoptosis regulator Bcl-2, social interaction hormone oxytocin, and trophic factor BDNF, and immunocytochemical analysis of PACAP. Results: Both PACAP-27 and PACAP-38 (PACAP-27/38) increased cell viability, decreased oxidative stress-induced cell damage, maintained mitochondrial activity, prevented the release of high mobility group box1, and reduced cytochrome c/caspase 3-induced apoptosis. PACAP-27/38 increased the protein expression levels of BDNF, Bcl-2, oxytocin, and precursor PACAP. N-methyl-D-aspartate receptor (NMDAR)-induced excitotoxicity contributes to the cell death associated with stroke. PACAP-27/38 modulated the protein expression levels of NMDAR subunits. PACAP-27/38 increased the protein expression levels of the GluN1 subunit, and decreased that of the GluN2B and GluN2D subunits. PACAP-27, but not PACAP-38, increased the expression level of the GluN2C subunit. Conclusion: This study provides evidence that PACAP regulated NMDAR subunits, affording neuroprotection after OGD/R injury.
Ficcionalidade: uma prática cultural e seus contextos
Authors:   Universidade de São Paulo. Faculdade de Filosofia, Letras e Ciências Humanas
Published: December 2018

Com intuito de preencher uma lacuna nos debates sobre a teoria literária, foi organizada, em março de 2013, a conferência internacional “Ficção em contextos históricos e culturais” que reuniu, na Universidade de São Paulo, cerca de cinquenta pesquisadores do Brasil e de mais oito países. As contribuições desta obra foram, sobretudo, apresentadas naquele congresso. A coletânea conta com os trabalhos selecionados que foram organizados em três eixos: 1) o desenvolvimento histórico da ficcionalidade literária na Europa; 2) algumas perspectivas interessantes sobre a ficção latino-americana; e 3) contribuições que versam sobre aspectos gerais da ficcionalidade relacionados à filosofia estética, à sociologia e à psicologia.
Impact of Frailty on Mortality and Hospitalization in Chronic Heart Failure: A Systematic Review and Meta‐Analysis
Authors: Yang Xiaobo , Lupón Josep , Vidán Maria T. , Ferguson Caleb , Gastelurrutia Paloma , Newton Phillip J. , Macdonald Peter S. , Bueno Héctor , Bayés‐Genís Antoni , Woo Jean , Fung Erik
Published: December 2018

Background

Although frailty has been associated with increased risks for hospitalization and mortality in chronic heart failure, the precise average effect remains uncertain. We performed a systematic review and meta‐analysis to summarize the hazards for mortality and incident hospitalization in patients with heart failure and frailty compared with those without frailty and explored the heterogeneity underlying the effect size estimates.

Methods and Results

MEDLINE
,
EMBASE,
and Cochrane databases were queried for articles published between January 1966 and March 2018. Predefined selection criteria were used. Hazard ratios (
HRs
) were pooled for meta‐analyses, and where odds ratios were used previously, original data were recalculated for
HR
. Overlapping data were consolidated, and only unique data points were used. Study quality and bias were assessed. Eight studies were included for mortality (2645 patients), and 6 studies were included for incident hospitalization (2541 patients) during a median follow‐up of 1.82 and 1.12 years, respectively. Frailty was significantly associated with an increased hazard for mortality (
HR
, 1.54; 95% confidence interval, 1.34–1.75;
P
<0.001) and incident hospitalization (
HR
, 1.56; 95% confidence interval, 1.36–1.78;
P
<0.001) in chronic heart failure. The Fried phenotype estimated a 16.9% larger effect size than the combined Fried/non‐Fried frailty assessment for the end point of mortality (
HR
, 1.80; 95% confidence interval, 1.41–2.28;
P
<0.001), but not for hospitalization (
HR
, 1.57; 95% confidence interval, 1.30–1.89;
P
<0.001). Study heterogeneity was found to be low (I
2
=0%), and high quality of studies was verified by the Newcastle‐Ottawa scale.

Conclusions

Overall, the presence of frailty in chronic heart failure is associated with an increased hazard for death and hospitalization by ≈1.5‐fold.
Young Women With Coronary Artery Disease Exhibit Higher Concentrations of Interleukin‐6 at Baseline and in Response to Mental Stress
Authors: Sullivan Samaah , Hammadah Muhammad , Wilmot Kobina , Ramadan Ronnie , Pearce Brad D. , Shah Amit , Kaseer Belal , Gafeer Mohamad Mazen , Lima Bruno B. , Kim Jeong Hwan , Ward Laura , Ko Yi‐An , Lewis Tené T. , Hankus Allison , Elon Lisa , Li Lian , Bremner J. Douglas , Raggi Paolo , Quyyumi Arshed , Vaccarino Viola
Published: December 2018

Background

Young women with coronary artery disease (
CAD
), a group with high psychosocial burden, were previously shown to have higher levels of interleukin‐6 (
IL
‐6) compared with men of similar age. We sought to examine
IL
‐6 response to acute stress in
CAD
patients across sex and age, and contrast results to healthy controls and other biomarkers known to increase with mental stress (monocyte chemoattractant protein‐1 and matrix metallopeptidase‐9) and known limited stress‐reactivity (high‐sensitivity C‐reactive protein).

Methods and Results

Inflammatory biomarkers were measured at rest and 90 minutes after mental stress (speech task) among 819 patients with
CAD
and 89 healthy controls. Repeated‐measures models were used to investigate age (continuous) and sex differences across time, before and after adjusting for demographics,
CAD
risk factors, depressive symptoms, medication use, and
CAD
severity. Among patients with
CAD
, the mean age was 60 years (range, 25–79) and 31% were women. Younger women with
CAD
had significantly higher concentrations of
IL
‐6 at rest, 90 minutes after mental stress, as well as a higher response to stress, compared with similarly aged men (
P
<0.05 for sex by age interactions). In contrast,
IL
‐6 increased with age, and there were no sex differences in
IL
‐6 levels or response to stress among controls. Inflammatory responses to stress for high‐sensitivity C‐reactive protein, monocyte chemoattractant protein‐1, and matrix metallopeptidase‐9 among
CAD
patients were similar in women and men.

Conclusions

IL
‐6 response to mental stress are higher in young women with
CAD
than men of similar age.
Eye Movements in the “Morris Maze” Spatial Working Memory Task Reveal Deficits in Strategic Planning
Authors: Hodgson Timothy L. , Hermens Frouke , Pennington Kyla , Pickering Jade S. , Ezard Gemma , Clarke Richard , Sharma Jagdish , Owen Adrian M.
Published: December 2018

Analysis of eye movements can provide insights into processes underlying performance of cognitive tasks. We recorded eye movements in healthy participants and people with idiopathic Parkinson disease during a token foraging task based on the spatial working memory component of the widely used Cambridge Neuropsychological Test Automated Battery. Participants selected boxes (using a mouse click) to reveal hidden tokens. Tokens were never hidden under a box where one had been found before, such that memory had to be used to guide box selections. A key measure of performance in the task is between search errors (BSEs) in which a box where a token has been found is selected again. Eye movements were found to be most commonly directed toward the next box to be clicked on, but fixations also occurred at rates higher than expected by chance on boxes farther ahead or back along the search path. Looking ahead and looking back in this way was found to correlate negatively with BSEs and was significantly reduced in patients with Parkinson disease. Refixating boxes where tokens had already been found correlated with BSEs and the severity of Parkinson disease symptoms. It is concluded that eye movements can provide an index of cognitive planning in the task. Refixations on locations where a token has been found may also provide a sensitive indicator of visuospatial memory integrity. Eye movement measures derived from the spatial working memory task may prove useful in the assessment of executive functions as well as neurological and psychiatric diseases in the future.
Drawing on students’ funds of knowledge
Authors: Folk Amanda
Published: December 2018

Despite programmes and initiatives intended to enable access to higher education for underrepresented students, higher education in the United States suffers from a persistent social class achievement gap. Although research exists about the social and academic factors that contribute to the social class achievement gap, one ubiquitous practice in higher education has been neglected – the research assignment. In this article, I share a subset of findings from a qualitative study that explores first-generation college students’ experiences with research assignments in college. In particular, I present four case studies of participants who relied on their identities and prior knowledge to successfully a complete research assignment. Finally, I introduce the funds of knowledge concept, which honours students’ identities and lived experiences, to provide a conceptual approach for engaging underrepresented and minoritised students through research assignments.
Examining student perceptions of their knowledge, roles, and power in the information cycle
Authors: Rush Lucinda
Published: December 2018

This project report describes a collaborative effort between librarians, staff, local journalists and students at Old Dominion University (Norfolk, VA) to provide a venue for a discussion about ‘fake news’. Post-event questionnaire results are analysed to explore what students learned as a result of attending the event as well as student perceptions of their own understanding and ownership of the roles that they can play in the information cycle.
Myrcia auxotelica, a new southeastern Brazilian Myrtaceae
Authors: SOBRAL MARCOS , ANTUNES KELLY
Published: December 2018

The American genus Myrcia De Candolle (1827: 406) comprises about 850 species (Lucas et al. 2018), from which about 260 occur in Brazil (BFG 2015). Along the examination of some unidentified specimens we spotted a singular Myrcia from southeastern Brazil that we here propose as new. Herbaria are cited according to Thiers (2018); measurements are in the order length × width, and when only one measurement is presented it refers to length except otherwise stated.
A taxonomic monograph of Myrcia sect. Sympodiomyrcia (Myrteae, Myrtaceae)
Authors: SANTOS MATHEUS F. , LUCAS EVE , SANO PAULO T.
Published: December 2018

Myrcia contains nearly 800 species and is divided into nine sections, one of them, Myrcia sect. Sympodiomyrcia, has recently been recognized and formally described. This study presents a taxonomic monograph of the group and revises its literature and taxonomic history. Myrcia sect. Sympodiomyrcia is mainly characterized by the presence of cataphylls at the base of internodes, sympodial branching at the base of inflorescences and free and deciduous calyx lobes. Myrcia sect. Sympodiomyrcia is distributed between the Guiana Shield and the central-eastern portion of Brazil (Atlantic Forest and Cerrado Domains). Morphological characterization of organs and structures is provided, as well as distribution statements, morphological differences with other sections of Myrcia and an identification key. A full taxonomic treatment as well as conservation status and images of representative specimens of each species are provided. Twenty one species are here accepted in Myrcia sect. Sympodiomyrcia: Myrcia ascendens, M. attenuata, M. bicarinata, M. bicolor, M. cataphyllata, M. costeira, M. densa, M. foveolata, M. insigniflora, M. lenheirensis, M. mucugensis, M. mutabilis, M. nitida, M. plusiantha, M. rupestris, M. subavenia, M. subcordata, M. subterminalis, M. summa, M. tenuifolia and M. truncata.
A Review of the Jumping Spider Fauna (Araneae: Salticidae) of Chile
Authors: RICHARDSON BARRY J.
Published: December 2018

The salticid fauna of Chile is relatively small, consisting of 21 known species in eight genera. The male and female morphology of each species for which material was available is shown. Two new species, Dendryphantes villarrica n. sp. and Euophrys flordellago n.sp. are described. Euophrys pehuenche Galiano, 1968 is synonymised with Euophrys rapida C. L. Koch, 1846. As well, three little known species, Euophrys saitiformis Simon, 1901, Euophrys laetata Simon, 1904 and Euophrys rapida C. L. Koch, 1846 are redescribed from the types. The female of Dendryphantes fulvipes is described for the first time. Several earlier described species remain unidentifiable from modern material. Eighteen names are listed as species inquirenda as the descriptions are inadequate and the location of the types unknown. Keys to the genera and known species are provided. Remarks on the biology and distribution of each species are given.La fauna chilena de saltícidos es relativamente pobre, siendo de 21 especies ubicadas en ocho géneros. Se presenta la morfología del macho y de la hembra de cada una de las especies a las cuales se disponía de material. Se describen dos especies nuevas: Dendryphantes villarrica n. sp. y Euophrys flordellago n.sp. Euophrys pehuenche Galiano, 1968 es reducido a estado de sinónimo con Euophrys rapida C.L. Koch, 1846. Adicionalmente, tres especies poco conocidas― Euophrys saitiformis Simon, 1901, Euophrys laetata Simon, 1904 y Euophrys rapida C.L. Koch, 1846― se vuelven a describir a base de los ejemplares tipos. Por primera veza se decribe la hembra de Dendrophantes fulvipes. Varias especies, posiblemente legítimas, se desconocen en colecciones modernas. Se considera 18 nombres como species inquirenda, ya que sus descripciones originales son inadecuadas y se desconoce la ubicación de los ejemplares tipos. Se presentan llaves para la identificación de los géneros y de las especies conocidas. Se aporta información sobre la biología y distribución de cada especie.