bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors that Affect Nonmarket Fruit and Vegetable Receptions: Analyses of Two Cross-Sectional Surveys in Gunma, Japan
Authors: Machida Daisuke , Yoshida Tohru
Published: October 2019

In this study, we identified the factors that affect the frequency of receiving nonmarket fruit and vegetables (FV). For Survey 1, we conducted a cross-sectional survey using a self-administered questionnaire for men aged 50–74 living in city (A) in Gunma, Japan. Participants were asked questions on FV receiving frequency, FV gardening, social cohesion (4–20 points), and basic characteristics. For Survey 2, a similar survey was conducted for residents aged 20–74 in three areas in city (B) in Gunma, but we included more variables. Ordinal logistic regression models were used for the analysis. In Survey 1, the responses of 243 participants were analyzed. The results showed that the FV receiving frequency was positively associated with non-gardeners and social cohesion. In Survey 2, the responses of 791 participants were analyzed. Vegetable receiving frequency was positively associated with rural and suburban areas, family structure, employment status, and non-farmers. The relationship between receiving frequency and social cohesion was similar to that found in Survey 1. In conclusion, in areas with flourishing FV cultivation, it seems to be easy to obtain FV through the social networks of reception, even for individuals who are not cultivating FV themselves.
Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments
Authors: Ramirez-Acuña Jesus Manuel , Cardenas-Cadena Sergio A , Marquez-Salas Pedro A , Garza-Veloz Idalia , Perez-Favila Aurelio , Cid-Baez Miguel A , Flores-Morales Virginia , Martinez-Fierro Margarita L
Published: October 2019

Diabetic foot ulcers (DFUs) are very important diabetes-related lesions that can lead to serious physical consequences like amputations of limbs and equally severe social, psychological, and economic outcomes. It is reported that up to 25% of patients with diabetes develop a DFU in their lifetime, and more than half of them become infected. Therefore, it is essential to manage infection and ulcer recovery to prevent negatives outcomes. The available information plays a significant role in keeping both physicians and patients aware of the emerging therapies against DFUs. The purpose of this review is to compile the currently available approaches in the managing and treatment of DFUs, including molecular and regenerative medicine, antimicrobial and energy-based therapies, and the use of plant extracts, antimicrobial peptides, growth factors, ozone, devices, and nano-medicine, to offer an overview of the assessment of this condition.
Gastro-Protective and Anti-Oxidant Potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/Indomethacin-Induced Ulceration in Rats
Authors: Zaghlool Sameh S. , Abo-Seif Ali A. , Rabeh Mohamed A. , Abdelmohsen Usama Ramadan , Messiha Basim A. S.
Published: October 2019

Recently, an alternative disease treatment approach is the research of medicaments from traditional medicine. Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases. Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models, compared to reference drugs. The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential of Althaea officinalis and Solanum nigrum extracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats. Rats were divided into six groups: normal control, gastric ulcer control, two standard pretreatment groups receiving omeprazole and misoprostol, and two test pretreatment groups receiving Althaea officinalis and Solanum nigrum. Pretreatments were administrated orally for 14 days. On the 15th day, animals, excluding the normal control group, were exposed to pyloric-ligation followed by indomethacin injection. After four hours, the rat’s stomachs were removed and gastric juice and blood samples were collected. Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number, ulcer index, acid and pepsin productivity, aggressive factors, and gastric mucosal lipid-peroxide contents. Moreover, reduction in titratable acidity, gastric mucosal nitric-oxide, anti-oxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol, Althaea officinalis, and Solanum nigrum pretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats, which is hopeful for clinical examinations.
An Overall Deformation Monitoring Method of Structure Based on Tracking Deformation Contour
Authors: Chu Xi , Zhou Zhixiang , Deng Guojun , Duan Xin , Jiang Xin
Published: October 2019

In structural deformation monitoring, traditional methods are mainly based on the deformation data measured at several individual points. As a result, only the discrete deformation, not the overall one, can be obtained, which hinders the researcher from a better and all-round understanding on the structural behavior. At the same time, the surrounding area around the measuring structure is usually complicated, which notably escalates the difficulty in accessing the deformation data. In dealing with the said issues, a digital image-based method is proposed for the overall structural deformation monitoring, utilizing the image perspective transformation and edge detection. Due to the limitation on camera sites, the lens is usually not orthogonal to the measuring structure. As a result, the obtained image cannot be used to extract the deformation data directly. Thus, the perspective transformation algorithm is used to obtain the orthogonal projection image of the test beam under the condition of inclined photography, which enables the direct extraction of deformation data from the original image. Meanwhile, edge detection operators are used to detect the edge of structure’s orthogonal projection image, to further characterize the key feature of structural deformation. Using the operator, the complete deformation data of structural edge are obtained by locating and calibrating the edge pixels. Based on the above, a series of load tests has been carried out using a steel–concrete composite beam to validate the proposed method, with the implementation of traditional dial deformation gauges. It has been found that the extracted edge lines have an obvious sawtooth effect due to the illumination environment. The sawtooth effect makes the extracted edge lines slightly fluctuate around the actual contour of the structure. On this end, the fitting method is applied to minimize the fluctuation and obtain the linear approximation of the actual deflection curve. The deformation data obtained by the proposed method have been compared with the one measured by the dial meters, indicating that the measurement error of the proposed method is less than 5%. However, since the overall deformation data are continuously measured by the proposed method, it can better reflect the overall deformation of the structure, and moreover the structural health state, when compared with the traditional “point” measurements.
Ghosts in the Closet: Catastrophizing and Spectral Disability in Anne Charlotte Robertson’s Apologies
Authors: Ely Taryn Marie
Published: October 2019

Anne Charlotte Robertson, who died in 2012, was a Super 8 experimental filmmaker whose primarily diaristic films record her experience with a diagnosis of manic depression and the corresponding nervous breakdowns. This article specifically addresses Robertson’s film Apologies (1983–1990), which features 17 min of the filmmaker apologizing to the camera for everything from drinking non-organic coffee to returning her camera a day late to her eventual nervous breakdown in the final scene of the film. Beginning with the psychological concept of catastrophizing, this paper shows how Robertson’s film engages with larger contemporaneous philosophical conceptions of disaster, or apocalypse, and its corresponding temporality. Drawing upon Jacques Derrida and Maurice Blanchot, mental disability is shown to be more thoroughly understood through shifting and multiple temporalities, termed as ‘spectral disability’ within this paper. Apologies not only reveals the personally specific details of Robertson’s experience and identity, but also responds to a larger history of representing madness in photography and film. Robertson’s engagement with the moving image is not only related to philosophy and history, but predates similar techniques devised in psychology as well. Ultimately, through disability theorist Rosemarie Garland-Thomson’s concept of misfitting, this paper explores how Apologies exposes the creative possibilities of mental disability.
Physical Characterization of Brake-Wear Particles in a PM10 Dilution Tunnel
Authors: Mamakos Athanasios , Arndt Michael , Hesse David , Augsburg Klaus
Published: October 2019

A dilution tunnel was designed for the characterization of brake-wear particle emissions up to 10 μm on a brake dyno. The particulate matter emission levels from a single front brake were found to be 4.5 mg/km (1.5 mg/km being smaller than 2.5 μm) over a novel real-world brake cycle, for a commercial Economic Commission for Europe (ECE) pad. Particle Number (PN) emissions as defined in exhaust regulations were in the order of 1.5 to 6 × 109 particles per km per brake (#/km/brake). Concentration levels could exceed the linearity range of full-flow Condensation Particle Counters (CPCs) over specific braking events, but remained at background levels for 60% of the cycle. Similar concentrations measured with condensation and optical counters suggesting that the majority of emitted particles were larger the 300 nm. Application of higher braking pressures resulted in elevated PN emissions and the systematic formation of nano-sized particles that were thermally stable at 350 °C. Volatile particles were observed only during successive harsh braking events leading to elevated temperatures. The onset depended on the type of brakes and their prehistory, but always at relatively high disc temperatures (280 to 490 °C).
Flow Process for Ketone Reduction Using a Superabsorber-Immobilized Alcohol Dehydrogenase from Lactobacillus brevis in a Packed-Bed Reactor
Authors: Adebar Niklas , Gröger Harald
Published: October 2019

Flow processes and enzyme immobilization have gained much attention over the past few years in the field of biocatalytic process design. Downstream processes and enzyme stability can be immensely simplified and improved. In this work, we report the utilization of polymer network-entrapped enzymes and their applicability in flow processes. We focused on the superabsorber-based immobilization of an alcohol dehydrogenase (ADH) from Lactobacillus brevis and its application for a reduction of acetophenone. The applicability of this immobilization technique for a biotransformation running in a packed bed reactor was then demonstrated. Towards this end, the immobilized system was intensively studied, first in a batch mode, leading to >90% conversion within 24 h under optimized conditions. A subsequent transfer of this method into a flow process was conducted, resulting in very high initial conversions of up to 67% in such a continuously running process.
Muscular Atrophy and Sarcopenia in the Elderly: Is There a Role for Creatine Supplementation?
Authors: Dolan Eimear , Artioli Guilherme G. , Pereira Rosa Maria R. , Gualano Bruno
Published: October 2019

Sarcopenia is characterized by a loss of muscle mass, quality, and function, and negatively impacts health, functionality, and quality of life for numerous populations, particularly older adults. Creatine is an endogenously produced metabolite, which has the theoretical potential to counteract many of the morphological and metabolic parameters underpinning sarcopenia. This can occur through a range of direct and indirect mechanisms, including temporal and spatial functions that accelerate ATP regeneration during times of high energy demand, direct anabolic and anti-catabolic functions, and enhanced muscle regenerating capacity through positively impacting muscle stem cell availability. Studies conducted in older adults show little benefit of creatine supplementation alone on muscle function or mass. In contrast, creatine supplementation as an adjunct to exercise training seems to augment the muscle adaptive response to the training stimulus, potentially through increasing capacity for higher intensity exercise, and/or by enhancing post-exercise recovery and adaptation. As such, creatine may be an effective dietary strategy to combat age-related muscle atrophy and sarcopenia when used to complement the benefits of exercise training.
Pharmacology Study of the Multiple Angiogenesis Inhibitor RC28-E on Anti-Fibrosis in a Chemically Induced Lung Injury Model
Authors: Kou Xiangying , Sun Yeying , Li Shenjun , Bian Weihua , Liu Zhihao , Zhang Daolai , Jiang Jing
Published: October 2019

Background: Disease-related injury in any organ triggers a complex cascade of cellular and molecular responses that culminate in tissue fibrosis, inflammation, and angiogenesis simultaneously. Multiple cell angiogenesis is an essential part of the tissue damage response, which is involved in fibrosis development. RC28-E is a novel recombinant dual decoy receptor lgG1 Fc-fusion protein that can block vascular endothelial growth factor (VEGFA), platelet-derived growth factor (PDGF), and fibroblast growth factor-2 (FGF-2) simultaneously. This protein has stepped into clinical trials (NCT03777254) for the treatment of pathological neovascularization-related diseases. Here, we report on the role of RC28-E during anti-fibrosis and its potential multitarget function in regulating fibrosis. Methods: A bleomycin-induced pulmonary fibrosis C57BL/6 mouse model was established. Hematoxylin and eosin staining (HE) and Masson staining (Masson’s) were performed to evaluate the pulmonary fibrosis based on the scoring from, Ashcroft score. Fibrosis related factors and inflammatory cytokines including HYP, α-SMA, procollagen, ICAM, IL-6, IL-1, and TNF-α were also determined at the protein and mRNA levels to characterize the fibrosis. Both mRNA and protein levels of VEGF, FGF, and transforming growth factor (TGF)-β were detected by quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) analysis, respectively. Pulmonary fibrosis and related cytokines were re-evaluated in vivo after 3 doses of RC28-E (5 mg/kg, 15 mg/kg, and 50 mg/kg, ip. Tiw × 9) in comparison with a mono-target antagonist treatment (VEGF or FGF blocking). RC28-E attenuated the activation of TGF-β induced fibroblasts in vitro. Expression levels of α-SMA and collagen I, as well as proliferation and migration, were determined with the human skin fibroblast cell line Detroit 551 and primary murine pulmonary fibroblast cells. The mechanism of RC28-E via the TGF-β/Smad pathway was also investigated. Results: RC28-E exhibits significant anti-fibrosis effects on Idiopathic pulmonary fibrosis (IPF) in vivo. Moreover, TGF-β induced fibroblast activation in vitro via the inhibition of the TGF-β downstream Smad pathway, thus providing potential therapeutics for clinical disease-related fibrosis-like IPF as well as chemotherapy-induced fibrosis in cancer therapy.
Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients
Authors: Ying Yuan , Wang Hui , Xi Xinping , Ma Chengbang , Liu Yue , Zhou Mei , Du Qiang , Burrows James F. , Wei Minjie , Chen Tianbao , Wang Lei
Published: October 2019

Dermaseptins are an antimicrobial peptide family widely identified from the skin secretions of phyllomeudusinae frogs. Here, we identify Dermaseptin-PC (DM-PC), from the skin secretion of Phyllomedusa coelestis, and further investigate the properties of this peptide, and a number of rationally designed truncated derivatives. The truncated 19-mer derived from the N-terminus exhibited similar antimicrobial potency when compared to the parent peptide, but the haemolytic effect of this truncated peptide was significantly decreased. Based on previous studies, the charge and hydrophobicity of truncated derivatives can affect the bioactivity of these peptides and thus we designed a 10-mer derivative with an optimised positive charge and a cyclohexylalanine (Cha) at the C-terminus for enhancing the hydrophobicity, DMPC-10A, which retained the antimicrobial activity of the parent peptide. To further investigate the influence of Cha at the C-terminus on activity, it was substituted by alanine (Ala) to generate another derivative, DMPC-10, but this was found to be much less potent. In addition, DM-PC, DMPC-19 and DMPC-10A not only rapidly killed planktonic bacteria isolated from cystic fibrosis (CF) patient, but also effectively eradicated their biofilm matrices.
Immunotherapy of Hepatocellular Carcinoma with Magnetic PD-1 Peptide-Imprinted Polymer Nanocomposite and Natural Killer Cells
Authors: Lee Mei-Hwa , Liu Kai-Hsi , Thomas James L. , Chen Jyun-Ren , Lin Hung-Yin
Published: October 2019

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells with a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template for molecular imprinting to form magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs). The nanoparticles were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer–Emmett–Teller (BET) analysis, and superconducting quantum interference device (SQUID) analysis. Natural killer 92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and the apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found to significantly enhance the activity of natural killer cells toward HepG2 cells by increasing the expression of nuclear factor kappa B (NF-κB), caspase 8, and especially caspase 3.
Glutamine Metabolism in Brain Tumors
Authors: Natarajan Siva Kumar , Venneti Sriram
Published: October 2019

Altered metabolism is a hallmark of cancer cells. Tumor cells rewire their metabolism to support their uncontrolled proliferation by taking up nutrients from the microenvironment. The amino acid glutamine is a key nutrient that fuels biosynthetic processes including ATP generation, redox homeostasis, nucleotide, protein, and lipid synthesis. Glutamine as a precursor for the neurotransmitter glutamate, and plays a critical role in the normal functioning of the brain. Brain tumors that grow in this glutamine/glutamate rich microenvironment can make synaptic connections with glutamatergic neurons and reprogram glutamine metabolism to enable their growth. In this review, we examine the functions of glutamate/glutamine in the brain and how brain tumor cells reprogram glutamine metabolism. Altered glutamine metabolism can be leveraged to develop non-invasive imaging strategies and we review these imaging modalities. Finally, we examine if targeting glutamine metabolism could serve as a therapeutic strategy in brain tumors.
The Expression/Methylation Profile of Adipogenic and Inflammatory Transcription Factors in Adipose Tissue Are Linked to Obesity-Related Colorectal Cancer
Authors: Boughanem Hatim , Cabrera-Mulero Amanda , Hernández-Alonso Pablo , Bandera-Merchán Borja , Tinahones Alberto , Tinahones Francisco José , Morcillo Sonsoles , Macias-Gonzalez Manuel
Published: October 2019

Obesity is well accepted as crucial risk factor that plays a critical role in the initiation and progression of colorectal cancer (CRC). More specifically, visceral adipose tissue (VAT) in people with obesity could produce chronic inflammation and an altered profile expression of key transcription factors that promote a favorable microenvironment to colorectal carcinogenesis. For this, the aim of this study was to explore the relationship between adipogenic and inflammatory transcription factors in VAT from nonobese, obese, and/or CRC patients. To test this idea, we studied the expression and methylation of CCAAT-enhancer binding protein type alpha (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in VAT from non-obese control, non-obese CRC subjects, overweight/obese control, and overweight/obese CRC patients and their correlation with anthropometric and biochemical variables. We found decreased expression of C/EBP-α in overweight/obese CRC patients in comparison with overweight/obese control subjects. PGC-1α and NF-κB were overexpressed in CRC patients independently of the BMI. NF-κB promoter was hypomethylated in overweight/obese CRC patients when compared to overweight/obese control individuals. In addition, multiple significant correlations between expression, methylation, and biochemical parameters were found. Finally, linear regression analysis showed that the expression of C/EBP-α and NF-κB and that NF-κB methylation were associated with CRC and able to explain up to 55% of CRC variability. Our results suggest that visceral adipose tissue may be a key factor in tumor development and inflammatory state. We propose C/EBP-α, PGC-1α and NF-κB to be interesting candidates as potential biomarkers in adipose tissue for CRC patients.
The Role of Post-Neoadjuvant Chemotherapy Tumor Volume for Prognostication and Treatment Guidance in Loco-Regionally Advanced Nasopharyngeal Carcinoma
Authors: Chen Fo-Ping , Wen Dan-Wan , Li Feng , Lin Li , Kou Jia , Zheng Wei-Hong , Li Li , Zhou Guan-Qun , Sun Ying
Published: October 2019

The value of post-neoadjuvant chemotherapy (NACT) tumor volume for prognostication in loco-regionally advanced nasopharyngeal carcinoma (LA-NPC) is unascertained. Here, we recruited 4109 histologically proven LA-NPC (stage III-IVA) that were treated with radical chemo-intensive-modulated radiotherapy (IMRT). Post-NACT gross primary tumor (GTVp) and lymph node (GTVnd) volumes of each patient were calculated from planning computed tomography (CT). We observed similar linear association between GTVp/GTVnd and overall survival (OS); thresholds of 52 cm3 for GTVp and 12 cm3 for GTVnd were consistent for risk discretization for OS, disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). Recursive partitioning analysis (RPA) modelling incorporating T-/N-categories and GTVp/GTVnd yielded four T-N-volume (TNV) risk groupings with disparate OS (p < 0.001). TNV risk stratification outperformed GTVp/GTVnd and eighth edition TNM for predicting OS (AUC 0.643 vs. 0.541–0.591; p < 0.001), DFS (0.629 vs. 0.545–0.580; p < 0.001), and DMFS (0.652 vs. 0.522–0.621; p < 0.001). NACT + concurrent chemoradiotherapy (CCRT) over NACT + IMRT was not superior for low- and low–intermediate-risk groupings (p > 0.05 for both), but superior for intermediate- and high-risk groupings in terms of OS (HR 0.68 (95% CI 0.47–0.99) for intermediate risk, 0.73 (0.55–0.97) for high risk; both p < 0.05). Overall, GTVp/GTVnd represent effective indicators for prognostication and decision-making in LA-NPC after NACT.
Clinical Significance of Various Drug-Sensitivity Markers in Patients with Surgically Resected Pulmonary Pleomorphic Carcinoma
Authors: Imai Hisao , Shimizu Kimihiro , Kawashima Osamu , Endoh Hideki , Imaizumi Kazuyoshi , Goto Yasuhiro , Kamiyoshihara Mitsuhiro , Sugano Masayuki , Yamamoto Ryohei , Tanaka Shigebumi , Fujita Atsushi , Kogure Yoshihito , Seki Yukio , Mogi Akira , Oyama Tetsunari , Minato Koichi , Asao Takayuki , Kaira Kyoichi
Published: October 2019

Various drug-sensitivity markers are potentially responsible for tumor progression and chemotherapy resistance in cancer patients with both epithelial and sarcomatous components; however, the clinicopathological significance of drug-sensitivity markers in patients with pulmonary pleomorphic carcinoma (PPC) remains unknown. Here, we clarified the prognostic impact of these drug-sensitivity markers in PPC by performing immunohistochemical and clinicopathologic analyses of samples from 105 patients with surgically resected PPC in order to evaluate levels of vascular endothelial growth factor 2 (VEGFR2), stathmin 1 (STMN1), tubulin β3 class III (TUBB3), thymidylate synthetase (TS), topoisomerase II (Topo-II), glucose-regulated protein, and 78 kDa (GRP78)/binding immunoglobulin protein (BiP). We observed the rates of high expression for VEGFR2, STMN1, TUBB3, TS, Topo-II, and GRP78/BiP were 33% (39/105), 35% (37/105), 61% (64/105), 51% (53/105), 31% (33/105), and 51% (53/105) of the samples, respectively. Moreover, multivariate analysis identified VEGFR2 and GRP78/BiP as significant independent markers for predicting worse prognosis. These findings suggested elevated VEGFR2 and decreased GRP78/BiP levels as independent factors for predicting poor outcomes following surgical resection in patients with PPC.
Long Noncoding RNAs in Acute Myeloid Leukemia: Functional Characterization and Clinical Relevance
Authors: Gourvest Morgane , Brousset Pierre , Bousquet Marina
Published: October 2019

Acute Myeloid Leukemia (AML) is the most common form of leukemia in adults with an incidence of 4.3 per 100,000 cases per year. Historically, the identification of genetic alterations in AML focused on protein-coding genes to provide biomarkers and to understand the molecular complexity of AML. Despite these findings and because of the heterogeneity of this disease, questions as to the molecular mechanisms underlying AML development and progression remained unsolved. Recently, transcriptome-wide profiling approaches have uncovered a large family of long noncoding RNAs (lncRNAs). Larger than 200 nucleotides and with no apparent protein coding potential, lncRNAs could unveil a new set of players in AML development. Originally considered as dark matter, lncRNAs have critical roles to play in the different steps of gene expression and thus affect cellular homeostasis including proliferation, survival, differentiation, migration or genomic stability. Consequently, lncRNAs are found to be differentially expressed in tumors, notably in AML, and linked to the transformation of healthy cells into leukemic cells. In this review, we aim to summarize the knowledge concerning lncRNAs functions and implications in AML, with a particular emphasis on their prognostic and therapeutic potential.
Efficacy, Safety, and Tolerability of Approved Combination BRAF and MEK Inhibitor Regimens for BRAF-Mutant Melanoma
Authors: Hamid Omid , Cowey C. Lance , Offner Michelle , Faries Mark , Carvajal Richard D.
Published: October 2019

No head-to-head studies exist comparing BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) combination treatments for BRAF-mutant melanoma. A side-by-side analysis of randomized phase III trials is presented that evaluated dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib. The baseline characteristics, efficacy, and safety were compared: COMBI-v (dabrafenib/trametinib versus vemurafenib); coBRIM (vemurafenib/cobimetinib versus vemurafenib); and COLUMBUS (encorafenib/binimetinib versus encorafenib and vemurafenib). Vemurafenib was the control arm in all studies. The data sources included literature databases, European public assessment reports, U.S. Food and Drug Administration review documents, and prescribing information. The baseline characteristics were similar, except for coBRIM, which had a higher proportion of patients with elevated lactate dehydrogenase (LDH) levels. The median progression-free survival (PFS) and overall response rate (ORR) were similar across the trials, although numerically higher values were observed with encorafenib/binimetinib. In contrast, the median overall survival (OS) was numerically longer with encorafenib/binimetinib (33.6 months) compared to dabrafenib/trametinib (25.6 months) and vemurafenib/cobimetinib (22.3 months). Among vemurafenib arms, PFS, ORR, and OS were similar, despite variations in the baseline LDH. Each combination displayed a unique safety profile, with higher incidences of pyrexia with dabrafenib/trametinib and photosensitivity reactions with vemurafenib/cobimetinib. This analysis of BRAFi/MEKi combinations for BRAF-mutant melanoma, while limited as not a direct head-to-head clinical trial, highlights the differences in tolerability and efficacy that may be useful for therapeutic decision making.
The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hermida-Prado Francisco , Granda-Díaz Rocío , del-Río-Ibisate Nagore , Villaronga M. Ángeles , Allonca Eva , Garmendia Irati , Montuenga Luis M. , Rodríguez René , Vallina Aitana , Alvarez-Marcos César , Rodrigo Juan P. , García-Pedrero Juana M.
Published: October 2019

Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials.
Synergism Through WEE1 and CHK1 Inhibition in Acute Lymphoblastic Leukemia
Authors: Ghelli Luserna Di Rorà Andrea , Bocconcelli Matteo , Ferrari Anna , Terragna Carolina , Bruno Samantha , Imbrogno Enrica , Beeharry Neil , Robustelli Valentina , Ghetti Martina , Napolitano Roberta , Chirumbolo Gabriella , Marconi Giovanni , Papayannidis Cristina , Paolini Stefania , Sartor Chiara , Simonetti Giorgia , Yen Timothy J. , Martinelli Giovanni
Published: October 2019

Introduction: Screening for synthetic lethality markers has demonstrated that the inhibition of the cell cycle checkpoint kinases WEE1 together with CHK1 drastically affects stability of the cell cycle and induces cell death in rapidly proliferating cells. Exploiting this finding for a possible therapeutic approach has showed efficacy in various solid and hematologic tumors, though not specifically tested in acute lymphoblastic leukemia. Methods: The efficacy of the combination between WEE1 and CHK1 inhibitors in B and T cell precursor acute lymphoblastic leukemia (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the therapeutic strategy was tested in terms of cytotoxicity, induction of apoptosis, and changes in cell cycle profile and protein expression using B/T-ALL cell lines. In addition, the efficacy of the drug combination was studied in primary B-ALL blasts using clonogenic assays. Results: This study reports, for the first time, the efficacy of the concomitant inhibition of CHK1/CHK2 and WEE1 in ALL cell lines and primary leukemic B-ALL cells using two selective inhibitors: PF-0047736 (CHK1/CHK2 inhibitor) and AZD-1775 (WEE1 inhibitor). We showed strong synergism in the reduction of cell viability, proliferation and induction of apoptosis. The efficacy of the combination was related to the induction of early S-phase arrest and to the induction of DNA damage, ultimately triggering cell death. We reported evidence that the efficacy of the combination treatment is independent from the activation of the p53-p21 pathway. Moreover, gene expression analysis on B-ALL primary samples showed that Chek1 and Wee1 are significantly co-expressed in samples at diagnosis (Pearson r = 0.5770, p = 0.0001) and relapse (Pearson r= 0.8919; p = 0.0001). Finally, the efficacy of the combination was confirmed by the reduction in clonogenic survival of primary leukemic B-ALL cells. Conclusion: Our findings suggest that the combination of CHK1 and WEE1 inhibitors may be a promising therapeutic strategy to be tested in clinical trials for adult ALL.
Effect of Hydrazine Pretreatment on the Activity, Stability and Active Sites of Cobalt Species for Preferential Oxidation (PROX) of CO in H2-Rich Stream
Authors: Mhlaba Reineck , Mosuang Thuto , Magadzu Takalani
Published: October 2019

The as-prepared (Co3O4) and hydrazine-treated (Co3O4(H)) cobalt catalysts were prepared using the precipitation method and evaluated at a temperature range of 40–220 °C for preferential oxidation (PROX) of CO in excess hydrogen. An improved surface reducibility with smaller crystallite size was noted on hydrazine-treated cobalt species (i.e., Co3O4(H) catalyst), which indicates some surface transformation. This finding correlates with the surface roughness formation (as depicted by scanning electron microscope (SEM) and transmission electron microscope (TEM) data), which was further confirmed by an increase in the Brunauer–Emmett–Teller (BET) surface area. The mesoporous structure of the Co3O4(H) catalyst remained intact, as compared to that of the Co3O4 catalyst. Interestingly, the in situ treatment of the standalone Co3O4(H) catalyst decreased the maximum CO conversion temperature (T100%) from 160 °C (over Co3O4) to 100 °C, with good selectivity. The Co3O4(H) catalyst showed good stability, with approximately 85% CO conversion at 100 °C for 21 h, as compared to a faster deactivation of the Co3O4 catalyst. However, the Co3O4(H) catalyst was unstable in both CO2 and the moisture environment. Based on the evaluation of spent hydrazine-treated (CoO(H)) cobalt catalyst, the high PROX activity is associated with the formation of Co3+ species as confirmed by X-ray diffraction (XRD), X-ray photoelectron spectra (XPS), and temperature-programmed reduction (TPR) data.
Pulmonary Nodule in a Patient with Oral and Lung Cancer: Cryptococcus Infection
Authors: Yamagata Kenji , Hirano Chikako , Kanno Naomi , Uchida Fumihiko , Fukuzawa Satoshi , Yanagawa Toru , Bukawa Hiroki
Published: October 2019

Pulmonary nodules are frequently considered to be a metastatic disease or primary lung tumors in oral cancer patients. We present a case of pulmonary cryptococcosis in a 68-year-old man with oral and lung cancer. This lung cancer was treated with thoracoscopic resection of the right inferior lobe and mediastinal lymph node dissection. Lower gingival cancer was treated with a mandibulectomy, neck dissection, and reconstruction after chemoradiotherapy. A 20 mm cavitary nodule appeared at the left lung S6 one-month after surgery, during post-operative computed tomography. Thoracoscopic partial resection of the left inferior lobe was performed under the suspicion of lung metastasis. Pathology results revealed a pseudo-epithelial granuloma with necrosis and many yeast-shaped fungi with capsules. A pathological diagnosis of Cryptococcus infection was made. The patient was prescribed the antifungal agent fosfluconazole, which was administered intravenously for 1 week and intraoral fluconazole for 12 months. No recurrence of the Cryptococcus infection has been noted after 1.5 years.
Entropy and Gravitation—From Black Hole Computers to Dark Energy and Dark Matter
Authors: Ng Y.
Published: October 2019

We show that the concept of entropy and the dynamics of gravitation provide the linchpin in a unified scheme to understand the physics of black hole computers, spacetime foam, dark energy, dark matter and the phenomenon of turbulence. We use three different methods to estimate the foaminess of spacetime, which, in turn, provides a back-door way to derive the Bekenstein-Hawking formula for black hole entropy and the holographic principle. Generalizing the discussion for a static spacetime region to the cosmos, we find a component of dark energy (resembling an effective positive cosmological constant of the correct magnitude) in the current epoch of the universe. The conjunction of entropy and gravitation is shown to give rise to a phenomenological model of dark matter, revealing the natural emergence, in galactic and cluster dynamics, of a critical acceleration parameter related to the cosmological constant; the resulting mass profiles are consistent with observations. Unlike ordinary matter, the quanta of the dark sector are shown to obey infinite statistics. This property of dark matter may lead to some non-particle phenomenology and may explain why dark matter particles have not been detected in dark matter search experiments. We also show that there are deep similarities between the problem of “quantum gravity” (more specifically, the holographic spacetime foam) and turbulence.
On the Impossibility of First-Order Phase Transitions in Systems Modeled by the Full Euler Equations
Authors: Hantke Maren , Thein Ferdinand
Published: October 2019

Liquid–vapor flows exhibiting phase transition, including phase creation in single-phase flows, are of high interest in mathematics, as well as in the engineering sciences. In two preceding articles the authors showed on the one hand the capability of the isothermal Euler equations to describe such phenomena (Hantke and Thein, arXiv, 2017, arXiv:1703.09431). On the other hand they proved the nonexistence of certain phase creation phenomena in flows governed by the full system of Euler equations, see Hantke and Thein, Quart. Appl. Math. 2015, 73, 575–591. In this note, the authors close the gap for two-phase flows by showing that the two-phase flows considered are not possible when the flow is governed by the full Euler equations, together with the regular Rankine-Hugoniot conditions. The arguments rely on the fact that for (regular) fluids, the differences of the entropy and the enthalpy between the liquid and the vapor phase of a single substance have a strict sign below the critical point.
Connection of Turbulence with Polytropic Index in the Solar Wind Proton Plasma
Authors: Livadiotis George
Published: October 2019

This paper improves our understanding of the interplay of the proton plasma turbulent heating sources of the expanding solar wind in the heliosphere. Evidence is shown of the connections between the polytropic index, the rate of the heat absorbed by the solar wind, and the rate of change of the turbulent energy, which heats the solar wind in the inner and outer heliosphere. In particular, we: (i) show the theoretical connection of the rate of a heat source, such as the turbulent energy, with the polytropic index and the thermodynamic process; (ii) calculate the effect of the pick-up protons in the total proton temperature and the relationship connecting the rate of heating with the polytropic index; (iii) derive the radial profiles of the solar wind heating in the outer and inner heliosphere; and (iv) use the radial profile of the turbulent energy in the solar wind proton plasma in the heliosphere, in order to show its connection with the radial profiles of the polytropic index and the heating of the solar wind.
Thermal Characteristics of Positive Leaders under Different Electrode Terminals in a Long Air Gap
Authors: Du Mingxing , Tang Yu , Li Min , Zou Jiayong , Ma Yigang , Sun Jinyu , Liu Lei , Zeng Qingguo
Published: October 2019

The thermal characteristics of the positive leader discharges occurring under the different electrode terminals in a 1 m rod-plate air gap were studied quantitatively using Mach–Zehnder interferometry and a high-speed video camera. When disturbed by the discharge channel, the interference fringes are distorted because of the change in the refractive index of air, which is related to the gas density. Therefore, the gas temperature and gas density distribution in the leader channel can be retrieved from the offset of the interference fringes. Based on these results, the thermal characteristics of the leader channel were studied under different electrode terminals with a radius of curvature of 2.5 mm and 5 mm for cone electrodes and a diameter of 40 mm for a spherical electrode. The results show that the gas temperature in the leader channel increased while the gas density decreased as the radius of curvature of the electrode terminal decreased. Additionally, a smaller radius of curvature leads to a larger thermal diameter, but the difference in the thermal diameter is not obvious; for the terminals used in this paper, the difference is within 2 mm.
Evaluation of Current Signature in Bearing Defects by Envelope Analysis of the Vibration in Induction Motors
Authors: Areias Isac Antônio dos Santos , Borges da Silva Luiz Eduardo , Bonaldi Erik Leandro , de Lacerda de Oliveira Levy Ely , Lambert-Torres Germano , Bernardes Vitor Almeida
Published: October 2019

Motor current signature analysis (MCSA) enables non-invasive monitoring, without interruption of machine operation in a remote and online way, allowing the identification of various types of faults of electrical and mechanical nature without the need of accessing the motor itself, but only its supply cables. Despite its advantages, it has limitations in accurately diagnosing incipient roller bearing faults. For the detection of incipient roller bearing faults, envelope analysis of vibration signals is a well-known and stablished technique used by motor condition monitoring experts for a long time, overcoming MCSA for that purpose. Thus, it is proposed in this paper, that the fault characteristic frequencies of roller bearings are identified in the current spectrum with the aid of envelope analysis on the bearing vibration signal. After this aided identification, the fault related spectral components in the current spectrum can be correctly tracked over time for trending evaluation and decision-making. This approach can represent a significant economic value in a motor condition monitoring program, since vibration envelope analysis is performed only at a first step and, after that, its results can be applied for the MCSA monitoring of all same-model motor drivers in an industrial site. This approach is even more valuable considering the concept of the Self-Supplied Wireless Current Transducer (SSWCT) also proposed in this paper. The SSWCT is an Industrial Internet of Things (IIOT) device for MCSA application in an Industry 4.0 environment. This proposed device has wireless communication interface and wireless/battery less power supply, being supplied by the energy harvested from the magnetic field of the same currents it is transducing. So, it is a completely galvanic isolated monitoring device, without batteries and without any electric connections to the industry electric system, easily installable to the motor cables, not using precious space in the electric panels of the motor control centers and not having any physical contact to the monitored asset.
Feasibility Study of Fluctuating Wind Pressure around High-Rise Buildings as a Potential Energy-Harvesting Source
Authors: Park Jae-Chan , Kim In-Ho , Jung Hyung-Jo
Published: October 2019

As the importance of sustainable energy increases, wind power generation systems utilizing wind energy around high-rise buildings are being developed. However, in existing wind turbine systems, it is necessary to solve noise, vibration problems, and structural issues for the installation of large-sized systems. In addition, small wind turbine systems can be installed only in limited areas such as roofs and corners, because their efficiency is limited to high and stable wind speed. For this reason, the distribution of fluctuating wind pressure around high-rise buildings was analyzed, and its feasibility as an energy source was evaluated, reflecting that fluctuating wind pressure can be used in vibration-based energy-harvesters. To achieve this, firstly, experimental conditions and theories were established to check the characteristic of wind pressure around high-rise buildings. The experiment was divided into the environment without surrounding buildings and the urban environment. Next, the pressure distribution around high-rise buildings and the quantitative results obtained from the experiment were determined. Finally, based on the results obtained from the experiments, the feasibility of fluctuating wind pressure as an energy-harvesting source was analyzed. From this study, it was found that fluctuating wind pressure can be used as a new energy source at new locations of high-rise buildings that were not utilized previously.
Solar Concentrator Consisting of Multiple Aspheric Reflectors
Authors: Cao Guobin , Qin Hua , Ramachandran Rajan , Liu Bo
Published: October 2019

This paper presents an off-axis-focused solar concentrator system consisting of 190 aspheric reflectors, where the aperture radius of each reflector is 10 cm, and vertices of all reflectors are orderly arranged in the same plane. The aspheric parameters controlling the curvature of the reflectors are determined using coordinate transformations and the particle swarm optimization (PSO) algorithm. Based on these aspheric parameters, the light distribution of focal plane was calculated by the ray tracing method. The analyses show that the designed concentrator system has a spot radius of less than 1 cm and the concentration ratio over 3300:1 is achieved using only one reflection. The design results have been verified with the optical design software Zemax.
Stability Criteria for Input Filter Design in Converters with CPL: Applications in Sliding Mode Controlled Power Systems
Authors: Anderson Azzano Jorge Luis , Moré Jerónimo J. , Puleston Paul F.
Published: October 2019

Microgrids are versatile systems for integration of renewable energy sources and non-conventional storage devices. Sliding Mode techniques grant excellent features of robustness controlling power conditioning systems, making them highly suitable for microgrid applications. However, problems may arise when a converter is set to behave as a Constant Power Load (CPL). These issues manifest in the stability of internal dynamics (or Zero Dynamics), which is determined by the input filter of the power module. In this paper, a special Lyapunov analysis is conducted to address the nonlinear internal dynamics of SM controlled power modules with CPL. It takes advantage of a Liérnad-type description, establishing stability conditions and providing a secure operation region. These conditions are translated into conductance and invariant region diagrams, turning them into tools for the design of power module filters.