bluuebunny/crossref_metadata_2025 huggingface dataset:
Statin Use Improves Overall Survival of Patients with Gastric Cancer after Surgery and Adjuvant Chemotherapy in Taiwan: A Nationwide Matched Cohort Study
Authors: Yang Pei-Rung , Tsai Ying-Ying , Chen Ko-Jung , Yang Yao-Hsu , Shih Wei-Tai
Published: July 2020

Background: Numerous studies have revealed that statins have antitumor effects in vivo and in vitro. However, few studies have explored the relationship between statin use and the mortality of gastric cancer (GC) patients after treatments. This study examines the relationship between statin use and the overall survival (OS) of GC patients after surgery and adjuvant chemotherapy, using data from the nationwide cohort database of Taiwan. Methods: All patients newly diagnosed with GC from 1999 to 2008 in Taiwan were identified from the Registry of Catastrophic Illness Patients Database. Through propensity score matching, statin users were matched to statin non-users at a 1:4 ratio. The relationship between statin use and the OS of patients with GC was estimated through Cox regression models. Results: The study cohort included 1835 patients with GC who had received therapies during the study period. The death numbers among statin users (defined as those who used more than 28 cumulative defined daily doses (cDDDs)) and statin non-users were 138 and 895, respectively. A dose–response association was noted between statin use and the OS of patients with GC after treatments. The adjusted hazard ratios were 0.62 (95% confidence intervals (CI), 0.50–0.78) and 0.34 (95% CI, 0.26–0.45) for statin users administered 28–167 cDDDs and >168 cDDDs, respectively, compared with no statin use (<28 cDDDs). Conclusions: This study highlights that statin use may dose-dependently improve the OS of patients with GC after surgery and adjuvant chemotherapy in Taiwan. Additional studies are required to confirm the efficacy and safety of statin use.
PKM2 Expression as Biomarker for Resistance to Oxaliplatin-Based Chemotherapy in Colorectal Cancer
Authors: Sfakianaki Maria , Papadaki Chara , Tzardi Maria , Trypaki Maria , Manolakou Stavroula , Messaritakis Ippokratis , Saridaki Zenia , Athanasakis Elias , Mavroudis Dimitrios , Tsiaoussis John , Gouvas Nikolaos , Souglakos John
Published: July 2020

The purpose of the current study is to investigate the prognostic significance of M2 isoform of pyruvate kinase (PKM2) mRNA expression loss in patients with operable colon cancer (CC). Two hundred sixty-two specimens from patients with stage-III or high-risk stage-II CC (group-A) treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy (FOLFOX), 118 specimens from metastatic CC patients (group-B) treated with FOLFOX, and 104 metastatic CC patients (group-C) treated with irinotecan-based chemotherapy were analyzed for PKM2, TS, ERCC1, MYC, and NEDD9 mRNA expression, as well as KRAS exon2 and BRAFV600E mutations. High PKM2 mRNA expression was correlated with left-sided located primaries (p = 0.001, group-A; p = 0.003, group-B; p = 0.001, group-C), high-grade tumors (p = 0.001, group-A; p = 0.017, group-B; p = 0.021, group-C), microsatellite-stable tumors (p < 0.001, group-A), pericolic lymph nodes involvement (p = 0.018, group-A), and cMYC mRNA expression (p = 0.002, group-A; p = 0.008, group-B; p = 0.006, group-C). High PKM2 mRNA expression was correlated with significantly lower disease free survival (DFS) (p = 0.002) and overall survival (OS) (p = 0.001) in the group-A. Similarly, PKM2 mRNA expression was associated with significantly decreased progression free survival (PFS) (p = 0.001) and OS (p = 0.001) in group-B. On the contrary, no significant association for the PKM2 mRNA expression has been observed with either PFS (p = 0.612) or OS (p = 0.517) in group-C. To conclude, the current study provides evidence for the prediction of PKM2 mRNA expression oxaliplatin-based treatment resistance.
Neoadjuvant Treatment Options in Soft Tissue Sarcomas
Authors: Spałek Mateusz Jacek , Kozak Katarzyna , Czarnecka Anna Małgorzata , Bartnik Ewa , Borkowska Aneta , Rutkowski Piotr
Published: July 2020

Due to the heterogeneity of soft tissue sarcomas (STS), the choice of the proper perioperative treatment regimen is challenging. Neoadjuvant therapy has attracted increasing attention due to several advantages, particularly in patients with locally advanced disease. The number of available neoadjuvant modalities is growing continuously. We may consider radiotherapy, chemotherapy, targeted therapy, radiosensitizers, hyperthermia, and their combinations. This review discusses possible neoadjuvant treatment options in STS with an emphasis on available evidence, indications for each treatment type, and related risks. Finally, we summarize current recommendations of the STS neoadjuvant therapy response assessment.
Inhibitors of Ceramide- and Sphingosine-Metabolizing Enzymes as Sensitizers in Radiotherapy and Chemotherapy for Head and Neck Squamous Cell Carcinoma
Authors: Yura Yoshiaki , Masui Atsushi , Hamada Masakazu
Published: July 2020

In the treatment of advanced head and neck squamous cell carcinoma (HNSCC), including oral SCC, radiotherapy is a commonly performed therapeutic modality. The combined use of radiotherapy with chemotherapy improves therapeutic effects, but it also increases adverse events. Ceramide, a central molecule in sphingolipid metabolism and signaling pathways, mediates antiproliferative responses, and its level increases in response to radiotherapy and chemotherapy. However, when ceramide is metabolized, prosurvival factors, such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), and glucosylceramide, are produced, reducing the antitumor effects of ceramide. The activities of ceramide- and sphingosine-metabolizing enzymes are also associated with radio- and chemo-resistance. Ceramide analogs and low molecular-weight compounds targeting these enzymes exert anticancer effects. Synthetic ceramides and a therapeutic approach using ultrasound have also been developed. Inhibitors of ceramide- and sphingosine-metabolizing enzymes and synthetic ceramides can function as sensitizers of radiotherapy and chemotherapy for HNSCC.
Hazard Curves for Tumor Recurrence and Tumor-Related Death Following Esophagectomy for Esophageal Cancer
Authors: Lindenmann Joerg , Fediuk Melanie , Fink-Neuboeck Nicole , Porubsky Christian , Pichler Martin , Brcic Luka , Anegg Udo , Balic Marija , Dandachi Nadia , Maier Alfred , Smolle Maria , Smolle Josef , Smolle-Juettner Freyja Maria
Published: July 2020

Background: The knowledge of both patterns and risk of relapse following resection for esophageal cancer is crucial for establishing appropriate surveillance schedules. The aim of this study was to evaluate the pattern of hazards for tumor recurrence and tumor-related death in the postoperative long-term follow-up after esophagectomy. Methods: Retrospective single-center analysis of 362 patients, with resected esophageal cancer. Multivariate Cox proportional hazard model was used. Results: A total of 192 (53%) had postoperative tumor recurrence. The relapse patterns of adenocarcinoma and squamous-cell carcinoma showed that each had a single peak, 12 months after surgery. After induction there was one peak at 5 months, the non-induced patients peaked 11 months, postoperatively. At 18 months, the recurrence hazard declined sharply in all cases. The hazard curves for tumor-related death were bimodal for adenocarcinoma, with two peaks at 6 and 22 months and one single peak for squamous-cell carcinoma at 18 months after surgery, showing pronounced decline later on. Conclusion: In curatively resected esophageal cancer, both tumor recurrence hazard and hazard for tumor-related death showed distinct, partly bimodal patterns. It could be justified to intensify the surveillance during the first two postoperative years by initiating a close-meshed follow-up to detect and treat tumor recurrence, as early as possible.
BMI1-Mediated Pemetrexed Resistance in Non-Small Cell Lung Cancer Cells Is Associated with Increased SP1 Activation and Cancer Stemness
Authors: Shen Huan-Ting , Chien Peng-Ju , Chen Shih-Hong , Sheu Gwo-Tarng , Jan Ming-Shiou , Wang Bing-Yen , Chang Wen-Wei
Published: July 2020

Lung cancer is the leading cause of cancer death worldwide and the therapeutic strategies include surgery, chemotherapy and radiation therapy. Non-small cell lung cancers (NSCLCs) account for around 85% of cases of lung cancers. Pemetrexed is an antifolate agent that is currently used as the second line chemotherapy drug in the treatment of advanced NSCLC patients with a response rate of 20–40%. The search for any combination therapy to improve the efficacy of pemetrexed is required. The existence of cancer stem cells (CSCs) is considered as the main reason for drug resistance of cancers. In this study, we first found that pemetrexed-resistant NSCLC cells derived from A549 cells displayed higher CSC activity in comparison to the parental cells. The expression of CSC related proteins, such as BMI1 or CD44, and the epithelial–mesenchymal transition (EMT) signature was elevated in pemetrexed-resistant NSCLC cells. We next discovered that the overexpression of BMI1 in A549 cells caused the pemetrexed resistance and inhibition of BMI1 by a small molecule inhibitor, PTC-209, or transducing of BMI1-specific shRNAs suppressed cell growth and the expression of thymidylate synthase (TS) in pemetrexed-resistant A549 cells. We further identified that BMI1 positively regulated SP1 expression and treatment of mithramycin A, a SP1 inhibitor, inhibited cell proliferation, as well as TS expression, of pemetrexed-resistant A549 cells. Furthermore, overexpression of BMI1 in A549 cells also caused the activation of EMT in and the enhancement of CSC activity. Finally, we demonstrated that pretreatment of PTC-209 in mice bearing pemetrexed-resistant A549 tumors sensitized them to pemetrexed treatment and the expression of Ki-67, BMI1, and SP1 expression in tumor tissues was observed to be reduced. In conclusion, BMI1 expression level mediates pemetrexed sensitivity of NSCLC cells and the inhibition of BMI1 will be an effective strategy in NSCLC patients when pemetrexed resistance has developed.
Risk Prediction and New Prophylaxis Strategies for Thromboembolism in Cancer
Authors: Labianca Alice , Bosetti Tommaso , Indini Alice , Negrini Giorgia , Labianca Roberto Francesco
Published: July 2020

In the general population, the incidence of thromboembolic events is 117 cases/100,000 inhabitants/year, while in cancer patient incidence, it is four-fold higher, especially in patients who receive chemotherapy and who are affected by pancreatic, lung or gastric cancer. At the basis of venous thromboembolism (VTE) there is the so-called Virchow triad, but tumor cells can activate coagulation pathway by various direct and indirect mechanisms, and chemotherapy can contribute to VTE onset. For these reasons, several studies were conducted in order to assess efficacy and safety of the use of anticoagulant therapy in cancer patients, both in prophylaxis setting and in therapy setting. With this review, we aim to record principal findings and current guidelines about thromboprophylaxis in cancer patients, with particular attention to subjects with additional risk factors such as patients receiving chemotherapy or undergoing surgery, hospitalized patients for acute medical intercurrent event and patients with central venous catheters. Nonetheless we added a brief insight about acute and maintenance therapy of manifested venous thromboembolism in cancer patients.
Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response
Authors: van der Kooij Monique K. , Wetzels Marjolein J.A.L. , Aarts Maureen J.B. , van den Berkmortel Franchette W.P.J. , Blank Christian U. , Boers-Sonderen Marye J. , Dierselhuis Miranda P. , de Groot Jan Willem B. , Hospers Geke A.P. , Piersma Djura , van Rijn Rozemarijn S. , Suijkerbuijk Karijn P.M. , ten Tije Albert J. , van der Veldt Astrid A.M. , Vreugdenhil Gerard , Wouters Michel W.J.M. , Haanen John B.A.G. , van den Eertwegh Alfonsus J.M. , Bastiaannet Esther , Kapiteijn Ellen
Published: July 2020

Cutaneous melanoma is a common type of cancer in Adolescents and Young Adults (AYAs, 15–39 years of age). However, AYAs are underrepresented in clinical trials investigating new therapies and the outcomes from these therapies for AYAs are therefore unclear. Using prospectively collected nation-wide data from the Dutch Melanoma Treatment Registry (DMTR), we compared baseline characteristics, mutational profiles, treatment strategies, grade 3–4 adverse events (AEs), responses and outcomes in AYAs (n = 210) and older adults (n = 3775) who were diagnosed with advanced melanoma between July 2013 and July 2018. Compared to older adults, AYAs were more frequently female (51% versus 40%, p = 0.001), and had a better Eastern Cooperative Oncology Group performance status (ECOG 0 in 54% versus 45%, p = 0.004). BRAF and NRAS mutations were age dependent, with more BRAF V600 mutations in AYAs (68% versus 46%) and more NRAS mutations in older adults (13% versus 21%), p < 0.001. This finding translated in distinct first-line treatment patterns, where AYAs received more initial targeted therapy. Overall, grade 3–4 AE percentages following first-line systemic treatment were similar for AYAs and older adults; anti-PD-1 (7% versus 14%, p = 0.25), anti-CTLA-4 (16% versus 33%, p = 0.12), anti-PD-1 + anti-CTLA-4 (67% versus 56%, p = 0.34) and BRAF/MEK-inhibition (14% versus 23%, p = 0.06). Following anti-CTLA-4 treatment, no AYAs experienced a grade 3–4 colitis, while 17% of the older adults did (p = 0.046). There was no difference in response to treatment between AYAs and older adults. The longer overall survival observed in AYAs (hazard ratio (HR) 0.7; 95% CI 0.6–0.8) was explained by the increased cumulative incidence of non-melanoma related deaths in older adults (sub-distribution HR 2.8; 95% CI 1.5–4.9), calculated by competing risk analysis. The results of our national cohort study show that baseline characteristics and mutational profiles differ between AYAs and older adults with advanced melanoma, leading to different treatment choices made in daily practice. Once treatment is initiated, AYAs and older adults show similar tumor responses and melanoma-specific survival.
Examination of Prognostic Factors Affecting Long-Term Survival of Patients with Stage 3/4 Gallbladder Cancer without Distant Metastasis
Authors: Higuchi Ryota , Yazawa Takehisa , Uemura Shuichirou , Matsunaga Yutaro , Ota Takehiro , Araida Tatsuo , Furukawa Toru , Yamamoto Masakazu
Published: July 2020

In advanced gallbladder cancer (GBC) radical resection, if multiple prognostic factors are present, the outcome may be poor; however, the details remain unclear. To investigate the poor prognostic factors affecting long-term surgical outcome, we examined 157 cases of resected stage 3/4 GBC without distant metastasis between 1985 and 2017. Poor prognostic factors for overall survival and treatment outcomes of a number of predictable preoperative poor prognostic factors were evaluated. The surgical mortality was 4.5%. In multivariate analysis, blood loss, poor histology, liver invasion, and ≥4 regional lymph node metastases (LNMs) were independent prognostic factors for poor surgical outcomes; invasion of the left margin or the entire area of the hepatoduodenal ligament and a Clavien–Dindo classification ≥3 were marginal factors. The analysis identified outcomes of patients with factors that could be predicted preoperatively, such as liver invasion ≥5 mm, invasion of the left margin or the entire area of the hepatoduodenal ligament, and ≥4 regional LNMs. Thus, the five-year overall survival was 54% for zero factors, 34% for one factor, and 4% for two factors (p < 0.05). A poor surgical outcome was likely when two or more factors were predicted preoperatively; therefore, new treatment strategies are required for such patients.
The Roles of Imprinted SLC22A18 and SLC22A18AS Gene Overexpression Caused by Promoter CpG Island Hypomethylation as Diagnostic and Prognostic Biomarkers for Non-Small Cell Lung Cancer Patients
Authors: Noguera-Uclés José Francisco , Boyero Laura , Salinas Ana , Cordero Varela Juan Antonio , Benedetti Johana Cristina , Bernabé-Caro Reyes , Sánchez-Gastaldo Amparo , Alonso Miriam , Paz-Ares Luis , Molina-Pinelo Sonia
Published: July 2020

Genomic imprinting is a process that involves one gene copy turned-off in a parent-of-origin-dependent manner. The regulation of imprinted genes is broadly dependent on promoter methylation marks, which are frequently associated with both oncogenes and tumor suppressors. The purpose of this study was to assess the DNA methylation patterns of the imprinted solute-carrier family 22 member 18 (SLC22A18) and SLC22A18 antisense (SLC22A18AS) genes in non-small cell lung cancer (NSCLC) patients to study their relevance to the disease. We found that both genes were hypomethylated in adenocarcinoma and squamous cell carcinoma patients. Due to this imprinting loss, SLC22A18 and SLC22A18AS were found to be overexpressed in NSCLC tissues, which is significantly more evident in lung adenocarcinoma patients. These results were validated through analyses of public databases of NSCLC patients. The reversed gene profile of both genes was achieved in vitro by treatment with ademetionine. We then showed that high SLC22A18 and SLC22A18AS expression levels were significantly associated with worsening disease progression. In addition, low levels of SLC22A18AS were also correlated with better overall survival for lung adenocarcinoma patients. We found that SLC22A18 and SLC22A18AS knockdown inhibits cell proliferation in vitro. All these results suggest that both genes may be useful as diagnostic and prognostic biomarkers in NSCLC, revealing novel therapeutic opportunities.
Editorial Catalysts: Special Issue on “Microwave-Assisted Catalysis”
Authors: Salagre Pilar , Cesteros Yolanda
Published: July 2020

The concept of circular economy is based on several principles, such as the use of renewable energy resources, including those obtained from the sun, wind, or water; the use of natural raw materials; the manufacturing of products avoiding the generation of wastes and pollution; keeping products and materials in use for a longer time; or giving new applications to waste [...]
Hydrothermal Treatment of Vegetable Oils and Fats Aiming at Yielding Hydrocarbons: A Review
Authors: Zanon Costa Carolina , Falabella Sousa-Aguiar Eduardo , Peixoto Gimenes Couto Maria Antonieta , Souza de Carvalho Filho José Faustino
Published: July 2020

According to the International Air Transport Agency (IATA), the aviation industry causes 2% of GHG emissions. As a result, goals such as improving aircraft efficiency by 1.5% per year and achieving carbon-neutral growth by 2020 were established. In this circumstance, fuels produced from biomass seem to be a promising route. There are many routes available to convert biomass into renewable fuels such as pyrolysis, hydroprocessing, transesterification, hydrothermal processes, and steam reforming. In this study, one reports a review of hydrothermal technologies. This review reports recent information about hydrothermal processes using water in sub- and supercritical states. This article introduces some concepts of the hydrothermal processes, advantages, and different types of feedstock adopted. The parameters which have an influence on hydrothermal processes such as temperature, pressure, particle size, catalyst, biomass/water ratio, and reaction time are illuminated. Water characteristics in sub- and supercritical conditions are discussed as a highly reactive medium to increase the affinity for the extraction of value-added compounds. Additionally, this review splits and details the reaction schemes that take place under hydrothermal conditions. Finally, it introduces recent research and development (R&D) trends in the hydrothermal process of fatty acids and triglycerides.
The Temperature-Dependent Effectiveness of Platinum-Based Drugs Mitomycin-C and 5-FU during Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer Cell Lines
Authors: Helderman Roxan F.C.P.A. , Löke Daan R. , Verhoeff Jan , Rodermond Hans M. , van Bochove Gregor G.W. , Boon Menno , van Kesteren Sanne , Garcia Vallejo Juan J. , Kok H. Petra , Tanis Pieter J. , Franken Nicolaas A.P. , Crezee Johannes , Oei Arlene L.
Published: July 2020

Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment with curative intent for peritoneal metastasis of colorectal cancer (CRC). Currently, there is no standardized HIPEC protocol: choice of drug, perfusate temperature, and duration of treatment vary per institute. We investigated the temperature-dependent effectiveness of drugs often used in HIPEC. Methods: The effect of temperature on drug uptake, DNA damage, apoptosis, cell cycle distribution, and cell growth were assessed using the temperature-dependent IC50 and Thermal Enhancement Ratio (TER) values of the chemotherapeutic drugs cisplatin, oxaliplatin, carboplatin, mitomycin-C (MMC), and 5-fluorouracil (5-FU) on 2D and 3D CRC cell cultures at clinically relevant hyperthermic conditions (38–43 °C/60 min). Results: Hyperthermia alone decreased cell viability and clonogenicity of all cell lines. Treatment with platinum-based drugs and MMC resulted in G2-arrest. Platinum-based drugs display a temperature-dependent synergy with heat, with increased drug uptake, DNA damage, and apoptosis at elevated temperatures. Apoptotic levels increased after treatment with MMC or 5-FU, without a synergy with heat. Conclusion: Our in vitro results demonstrate that a 60-min exposure of platinum-based drugs and MMC are effective in treating 2D and 3D CRC cell cultures, where platinum-based drugs require hyperthermia (>41 °C) to augment effectivity, suggesting that they are, in principle, suitable for HIPEC.
The Role of Cutinsomes in Plant Cuticle Formation
Authors: Stępiński Dariusz , Kwiatkowska Maria , Wojtczak Agnieszka , Polit Justyna Teresa , Domínguez Eva , Heredia Antonio , Popłońska Katarzyna
Published: July 2020

The cuticle commonly appears as a continuous lipophilic layer located at the outer epidermal cell walls of land plants. Cutin and waxes are its main components. Two methods for cutin synthesis are considered in plants. One that is based on enzymatic biosynthesis, in which cutin synthase (CUS) is involved, is well-known and commonly accepted. The other assumes the participation of specific nanostructures, cutinsomes, which are formed in physicochemical self-assembly processes from cutin precursors without enzyme involvement. Cutinsomes are formed in ground cytoplasm or, in some species, in specific cytoplasmic domains, lipotubuloid metabolons (LMs), and are most probably translocated via microtubules toward the cuticle-covered cell wall. Cutinsomes may additionally serve as platforms transporting cuticular enzymes. Presumably, cutinsomes enrich the cuticle in branched and cross-linked esterified polyhydroxy fatty acid oligomers, while CUS1 can provide both linear chains and branching cutin oligomers. These two systems of cuticle formation seem to co-operate on the surface of aboveground organs, as well as in the embryo and seed coat epidermis. This review focuses on the role that cutinsomes play in cuticle biosynthesis in S. lycopersicum, O. umbellatum and A. thaliana, which have been studied so far; however, these nanoparticles may be commonly involved in this process in different plants.
PGAP3 Associated with Hyperphosphatasia with Mental Retardation Plays a Novel Role in Brain Morphogenesis and Neuronal Wiring at Early Development
Authors: Da’as Sahar I. , Aamer Waleed , Hasan Waseem , Al-Maraghi Aljazi , Al-Kurbi Alya , Kilani Houda , AlRayahi Jehan , Zamel Khaled , Stotland Mitchell A. , Fakhro Khalid A.
Published: July 2020

Recessive mutations in Post-GPI attachment to proteins 3 (PGAP3) cause the rare neurological disorder hyperphosphatasia with mental retardation syndrome 4 type (HPMRS4). Here, we report a novel homozygous nonsense mutation in PGAP3 (c.265C>T-p.Gln89*), in a 3-year-old boy with unique novel clinical features. These include decreased intrauterine fetal movements, dysgenesis of the corpus callosum, olfactory bulb agenesis, dysmorphic features, cleft palate, left ear constriction, global developmental delay, and hypotonia. The zebrafish functional modeling of PGAP3 loss resulted in HPMRS4-like features, including structural brain abnormalities, dysmorphic cranial and facial features, hypotonia, and seizure-like behavior. Remarkably, morphants displayed defective neural tube formation during the early stages of nervous system development, affecting brain morphogenesis. The significant aberrant midbrain and hindbrain formation demonstrated by separation of the left and right tectal ventricles, defects in the cerebellar corpus, and caudal hindbrain formation disrupted oligodendrocytes expression leading to shorter motor neurons axons. Assessment of zebrafish neuromuscular responses revealed epileptic-like movements at early development, followed by seizure-like behavior, loss of touch response, and hypotonia, mimicking the clinical phenotype human patients. Altogether, we report a novel pathogenic PGAP3 variant associated with unique phenotypic hallmarks, which may be related to the gene’s novel role in brain morphogenesis and neuronal wiring.
Role of Tumor-Associated Myeloid Cells in Breast Cancer
Authors: Cha Yoon Jin , Koo Ja Seung
Published: July 2020

Stromal immune cells constitute the tumor microenvironment. These immune cell subsets include myeloid cells, the so-called tumor-associated myeloid cells (TAMCs), which are of two types: tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Breast tumors, particularly those in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer and triple-negative breast cancer, are solid tumors containing immune cell stroma. TAMCs drive breast cancer progression via immune mediated, nonimmune-mediated, and metabolic interactions, thus serving as a potential therapeutic target for breast cancer. TAMC-associated breast cancer treatment approaches potentially involve the inhibition of TAM recruitment, modulation of TAM polarization/differentiation, reduction of TAM products, elimination of MDSCs, and reduction of MDSC products. Furthermore, TAMCs can enhance or restore immune responses during cancer immunotherapy. This review describes the role of TAMs and MDSCs in breast cancer and elucidates the clinical implications of TAMs and MDSCs as potential targets for breast cancer treatment.
“My Body Hates Me”: A Qualitative Analysis of the Experience of Functional Nausea in Adolescent Girls and Their Mothers
Authors: Cole Michelle A. T. , Qu’d Dima , Wild Marcus G. , Russell Alexandra C. , Caillet Aimee R. , Stone Amanda L.
Published: July 2020

Nausea is a somatic sensation typically associated with the need to vomit in order to remove a toxin from the body. When nausea occurs in the absence of a specific structural cause or toxin, it is classified as a functional gastrointestinal disorder (FGID). Functional nausea was newly recognized in 2016 as a FGID in children and little is known about its prevalence, course or patient experiences. Nausea co-occurring with functional abdominal pain in childhood has been associated with long-term risk for anxiety and ongoing somatic symptoms into young adulthood. However, few studies have focused uniquely on the experience and impact of nausea on youth. The present study aimed to qualitatively understand the experiences of adolescent girls with functional nausea and their parents. Five mother–daughter dyads were recruited from a specialized pediatric gastroenterology clinic focused on nausea and completed semi-structured interviews. Interviews were transcribed and coded using interpretive phenomenological analysis (IPA). Four main themes emerged: nausea interference, body frustration, misunderstanding of symptoms, and maternal helplessness and guilt. These themes were similar to prior studies on the experiences of youth with chronic pain but also indicated unique challenges due to nausea, such as significant food restriction and subsequent weight loss.
Research Progress of Failure Mechanism of Thermal Barrier Coatings at High Temperature via Finite Element Method
Authors: Hu Zhong-Chao , Liu Bin , Wang Liang , Cui Yu-Hang , Wang Yan-Wei , Ma Yu-Duo , Sun Wen-Wei , Yang Yong
Published: July 2020

In the past decades, the durability of thermal barrier coatings (TBCs) has been extensively studied. The majority of researches emphasized the problem of oxidation, corrosion, and erosion induced by foreign object damage (FOD). TBCs with low thermal conductivity are usually coated on the hot-section components of the aircraft engine. The main composition of the TBCs is top-coat, which is usually regarded as a wear-resistant and heat-insulating layer, and it will significantly improve the working temperature of the hot-section components of the aircraft engine. The application of TBCs are serviced under a complex and rigid environment. The external parts of the TBCs are subjected to high-temperature and high-pressure loading, and the inner parts of the TBCs have a large thermal stress due to the different physical properties between the adjacent layers of the TBCs. To improve the heat efficiency of the hot-section components of aircraft engines, the working temperature of the TBCs should be improved further, which will result in the failure mechanism becoming more and more complicated for TBCs; thus, the current study is focusing on reviewing the failure mechanism of the TBCs when they are serviced under the actual high temperature conditions. Finite element simulation is an important method to study the failure mechanism of the TBCs, especially under some extremely rigid environments, which the experimental method cannot realize. In this paper, the research progress of the failure mechanism of TBCs at high temperature via finite element modeling is systematically reviewed.
Pharmaceutical Salts of Enrofloxacin with Organic Acids
Authors: Pang Hong , Sun Yu-Bin , Zhou Jun-Wen , Xie Meng-Juan , Lin Hao , Yong Yan , Chen Liang-Zhu , Fang Bing-Hu
Published: July 2020

Enrofloxacin is a poorly soluble antibacterial drug of the fluoroquinolones class used in veterinary medicine. The main purpose of this work was to investigate the structural and pharmaceutical properties of new enrofloxacin salts. Enrofloxacin anhydrate and its organic salts with tartaric acid, nicotinic acid and suberic acid formed as pure crystalline anhydrous solids. All the crystals were grown from a mixed solution by slow evaporation at room temperature. These products were then characterized by field-emission scanning electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Further, X-ray single crystal diffraction analysis was used to study the crystal structure. The intermolecular interactions and packing arrangements in the crystal structures were studied, and the solubility of these salts in water was determined using high-performance liquid chromatography. The results show that the new salts of enrofloxacin developed in this study exhibited excellent water solubility.
Compression of the Lateral Antebrachial Cutaneous Nerve due to Leakage of Iron after an Intravenous Iron Infusion
Authors: Kwak Soyoung , Chang Min Cheol
Published: July 2020

Skin staining due to iron leakage into the subcutaneous tissue can sometimes occur during intravenous iron infusion. We describe a case of lateral antebrachial cutaneous nerve (LACN) entrapment due to extravasated iron after an intravenous iron infusion. A 41-year-old woman received an intravenous ferric carboxymaltose infusion for iron deficiency anemia. However, during the infusion, extravasation of iron occurred and brown pigmentation developed on the lateral side of the cubital fossa. Sixteen months later, the patient still had some staining in her anterolateral elbow and proximal forearm. In addition, she complained of tingling pain over her left forearm. Ultrasonography (US) revealed a lateral antebrachial cutaneous nerve (LACN) under the stained area. When we swept the stained area with the US transducer, she reported a tingling pain on her left lateral forearm, the region innervated by the left LACN. Therefore, we considered that the pain resulted from the compression of the left LACN by the leaked iron during the intravenous infusion. Leaked iron can compress the cutaneous nerve and result in neuropathic pain and cosmetic problems. When patients with skin staining after iron infusion have neuropathic pain, clinicians should consider the possibility of entrapment of the cutaneous nerves.
A Comparative Systematic Literature Review on Knee Bone Reports from MRI, X-Rays and CT Scans Using Deep Learning and Machine Learning Methodologies
Authors: Khalid Hafsa , Hussain Muzammil , Al Ghamdi Mohammed A. , Khalid Tayyaba , Khalid Khadija , Khan Muhammad Adnan , Fatima Kalsoom , Masood Khalid , Almotiri Sultan H. , Farooq Muhammad Shoaib , Ahmed Aqsa
Published: July 2020

The purpose of this research was to provide a “systematic literature review” of knee bone reports that are obtained by MRI, CT scans, and X-rays by using deep learning and machine learning techniques by comparing different approaches—to perform a comprehensive study on the deep learning and machine learning methodologies to diagnose knee bone diseases by detecting symptoms from X-ray, CT scan, and MRI images. This study will help those researchers who want to conduct research in the knee bone field. A comparative systematic literature review was conducted for the accomplishment of our work. A total of 32 papers were reviewed in this research. Six papers consist of X-rays of knee bone with deep learning methodologies, five papers cover the MRI of knee bone using deep learning approaches, and another five papers cover CT scans of knee bone with deep learning techniques. Another 16 papers cover the machine learning techniques for evaluating CT scans, X-rays, and MRIs of knee bone. This research compares the deep learning methodologies for CT scan, MRI, and X-ray reports on knee bone, comparing the accuracy of each technique, which can be used for future development. In the future, this research will be enhanced by comparing X-ray, CT-scan, and MRI reports of knee bone with information retrieval and big data techniques. The results show that deep learning techniques are best for X-ray, MRI, and CT scan images of the knee bone to diagnose diseases.
AZGP1 Protein Expression in Hormone-Naïve Advanced Prostate Cancer Treated with Primary Androgen Deprivation Therapy
Authors: Winther Mads Dochedahl , Kristensen Gitte , Stroomberg Hein Vincent , Berg Kasper Drimer , Toft Birgitte Grønkær , Brooks James D. , Brasso Klaus , Røder Martin Andreas
Published: July 2020

Biomarkers for predicting the risk of castration-resistant prostate cancer (CRPC) in men treated with primary androgen deprivation therapy (ADT) are lacking. We investigated whether Zinc-alpha 2 glycoprotein (AZGP1) expression in the diagnostic biopsies of men with hormone-naïve prostate cancer (PCa) undergoing primary ADT was predictive of the development of CRPC and PCa-specific mortality. The study included 191 patients who commenced ADT from 2000 to 2011. The AZGP1 expression was evaluated using immunohistochemistry and scored as high or low expression. The risks of CRPC and PCa-specific mortality were analyzed using stratified cumulative incidences and a cause-specific COX regression analysis for competing risk assessment. The median follow-up time was 9.8 (IQR: 6.1–12.7) years. In total, 94 and 97 patients presented with low and high AZGP1 expression, respectively. A low AZGP1 expression was found to be associated with a shorter time to CRPC when compared to patients with a high AZGP1 expression (HR: 1.5; 95% CI: 1.0–2.1; p = 0.03). However, the multivariable analysis demonstrated no added benefit by adding the AZGP1 expression to prediction models for CRPC. No differences for PCa-specific mortality between the AZGP1 groups were observed. In conclusion, a low AZGP1 expression was associated with a shorter time to CRPC for PCa patients treated with first-line ADT but did not add any predictive information besides well-established clinicopathological variables.
Improving the Wearing Rate of Mouthguards in the Youth Rugby Category Affects the Total Future Mouthguard Wearing Rate
Authors: Hayashi Kairi , Churei Hiroshi , Tanabe Gen , Togawa Kaito , Chowdhury Ruman Uddin , Ueno Toshiaki
Published: July 2020

The aim of this study is to consider the hypothesis that wearing mouthguards (MGs) from a young age helps to shape players’ habit of continuing to wear MGs as adults. In addition, we consider the mandatory rule of wearing mouthguards in the youth category on the future wearing rates of mouthguards. Eighty-five Japanese male amateur rugby players were included in this study. We examined the relationship between the wearing rates of mouthguards when participants were high school students and as adults (in 2018) using a questionnaire. Collected data were classified into categories (age, mouthguard type, and applied mandatory rule or not), and their relationships were analyzed. The wearing rate of mouthguards in high school was significantly related to the wearing rate of mouthguards in adulthood (χ2 = 12.1, p < 0.01). The mandatory rule to wear mouthguards at high school was related to the wearing rates of mouthguards as adults, but not significantly (χ2 = 3.42, p = 0.06). Participants’ mouthguard wearing rates as adults were affected by their high school wearing rates. The mandatory rule of wearing mouthguards in the youth category may be somewhat effective for improving mouthguard wearing rates; however, it is more important to provide knowledge about their importance.
The Complex Adaptive Delta-Modulator in Sliding Mode Theory
Authors: Almakhles Dhafer
Published: July 2020

In this paper, we consider the stability and various dynamical behaviors of both discrete-time delta modulator (Δ-M) and adaptive Δ-M. The stability constraints and conditions of Δ-M and adaptive Δ-M are derived following the theory of quasi-sliding mode. Furthermore, the periodic behaviors are explored for both the systems with steady-state inputs and certain parameter values. The results derived in this paper are validated using simulated examples which confirms the derived stability conditions and the existence of periodicity.
Automatic Recognition of Human Interaction via Hybrid Descriptors and Maximum Entropy Markov Model Using Depth Sensors
Authors: Jalal Ahmad , Khalid Nida , Kim Kibum
Published: July 2020

Automatic identification of human interaction is a challenging task especially in dynamic environments with cluttered backgrounds from video sequences. Advancements in computer vision sensor technologies provide powerful effects in human interaction recognition (HIR) during routine daily life. In this paper, we propose a novel features extraction method which incorporates robust entropy optimization and an efficient Maximum Entropy Markov Model (MEMM) for HIR via multiple vision sensors. The main objectives of proposed methodology are: (1) to propose a hybrid of four novel features—i.e., spatio-temporal features, energy-based features, shape based angular and geometric features—and a motion-orthogonal histogram of oriented gradient (MO-HOG); (2) to encode hybrid feature descriptors using a codebook, a Gaussian mixture model (GMM) and fisher encoding; (3) to optimize the encoded feature using a cross entropy optimization function; (4) to apply a MEMM classification algorithm to examine empirical expectations and highest entropy, which measure pattern variances to achieve outperformed HIR accuracy results. Our system is tested over three well-known datasets: SBU Kinect interaction; UoL 3D social activity; UT-interaction datasets. Through wide experimentations, the proposed features extraction algorithm, along with cross entropy optimization, has achieved the average accuracy rate of 91.25% with SBU, 90.4% with UoL and 87.4% with UT-Interaction datasets. The proposed HIR system will be applicable to a wide variety of man–machine interfaces, such as public-place surveillance, future medical applications, virtual reality, fitness exercises and 3D interactive gaming.
Cointegration and Structure in Norwegian Wage–Price Dynamics
Authors: Gjelsvik Marit , Nymoen Ragnar , Sparrman Victoria
Published: July 2020

Wage coordination plays an important role in macroeconomic stabilization. Pattern wage bargaining systems have been common in Europe, but in different forms, and with different degrees of success in terms of actual coordination reached. We focus on wage formation in Norway, a small open economy, where it is custom to regard the manufacturing industry as the wage leader. We estimate a model of wage formation in manufacturing and in two other sectors. Deciding cointegration rank is an important step in the analysis, economically as well statistically. In combination with simultaneous equation modelling, the cointegration analysis provides evidence that collective wage negotiations in manufacturing have defined wage norms for the rest of the economy over the period 1980(1)–2014(4).
Security in Low Powered Wide Area Networks: Opportunities for Software Defined Network-Supported Solutions
Authors: Pathak Gaurav , Gutierrez Jairo , Rehman Saeed Ur
Published: July 2020

The Internet of things (IoT) has revolutionized the use of connectivity and has given birth to new transmission technologies to satisfy the requirements of diverse IoT applications. Low powered wide area networks (LPWAN) is one of those transmission technologies, and is becoming exceptionally useful for IoT applications. The nodes use energy-efficient mechanisms for long-range data transmission (10–20 km), lasting in hostile environments for years and making them suitable for IoT applications such as environmental monitoring, automated billing systems, smart homes, smart offices, and patient monitoring. However, LPWAN devices have minimal resources, which makes it challenging to provide promising security to devices and data in the network. In this paper, we discuss the security mechanisms used in current LPWAN technologies along with their vulnerabilities and possible attacks on them. A detailed literature review is conducted on existing solutions on the security of constrained IoT networks similar to LPWAN using different networking frameworks. The reviewed literature is then compared based on various network security measures addressed by them. In addition, the emergence of software defined network (SDN) architecture for security in IoT is explained based on literature. Finally, the applicability of SDN in LPWAN security, its opportunities, and challenges in implementation are discussed.
A Security Monitoring Framework for Mobile Devices
Authors: Lima António , Rosa Luis , Cruz Tiago , Simões Paulo
Published: July 2020

Quite often, organizations are confronted with the burden of managing mobile device assets, requiring control over installed applications, security, usage profiles or customization options. From this perspective, the emergence of the Bring Your Own Device (BYOD) trend has aggravated the situation, making it difficult to achieve an adequate balance between corporate regulations, freedom of usage and device heterogeneity. Moreover, device and information protection on mobile ecosystems are quite different from securing other device assets such as laptops or desktops, due to their specific characteristics and limitations—quite often, the resource overhead associated with specific security mechanisms is more important for mobile devices than conventional computing platforms, as the former frequently have comparatively less computing capabilities and more strict power management policies. This paper presents an intrusion and anomaly detection framework specifically designed for managed mobile device ecosystems, that is able to integrate into mobile device and management frameworks for complementing conventional intrusion detection systems. In addition to presenting the reference architecture for the proposed framework, several implementation aspects are also analyzed, based on the lessons learned from developing a proof-of-concept prototype that was used for validation purposes.
On the DC Offset Current Generated during Biphasic Stimulation: Experimental Study
Authors: Aiello Orazio
Published: July 2020

This paper deals with the DC offset currents generated by a platinum electrode matrix during biphasic stimulation. A fully automated test bench evaluates the nanoampere range DC offset currents in a realistic and comprehensive scenario by using platinum electrodes in a saline solution as a load for the stimulator. Measurements are performed on different stimulation patterns for single or dual hexagonal stimulation sites operating simultaneously and alternately. The effectiveness of the return electrode presence in reducing the DC offset current is considered. Experimental results show how for a defined nominal injected charge, the generated DC offset currents differ depending on the stimulation patterns, frequency, current amplitude, and pulse width of a biphasic signal.
Deep Learning with Limited Data: Organ Segmentation Performance by U-Net
Authors: Bardis Michelle , Houshyar Roozbeh , Chantaduly Chanon , Ushinsky Alexander , Glavis-Bloom Justin , Shaver Madeleine , Chow Daniel , Uchio Edward , Chang Peter
Published: July 2020

(1) Background: The effectiveness of deep learning artificial intelligence depends on data availability, often requiring large volumes of data to effectively train an algorithm. However, few studies have explored the minimum number of images needed for optimal algorithmic performance. (2) Methods: This institutional review board (IRB)-approved retrospective review included patients who received prostate magnetic resonance imaging (MRI) between September 2014 and August 2018 and a magnetic resonance imaging (MRI) fusion transrectal biopsy. T2-weighted images were manually segmented by a board-certified abdominal radiologist. Segmented images were trained on a deep learning network with the following case numbers: 8, 16, 24, 32, 40, 80, 120, 160, 200, 240, 280, and 320. (3) Results: Our deep learning network’s performance was assessed with a Dice score, which measures overlap between the radiologist’s segmentations and deep learning-generated segmentations and ranges from 0 (no overlap) to 1 (perfect overlap). Our algorithm’s Dice score started at 0.424 with 8 cases and improved to 0.858 with 160 cases. After 160 cases, the Dice increased to 0.867 with 320 cases. (4) Conclusions: Our deep learning network for prostate segmentation produced the highest overall Dice score with 320 training cases. Performance improved notably from training sizes of 8 to 120, then plateaued with minimal improvement at training case size above 160. Other studies utilizing comparable network architectures may have similar plateaus, suggesting suitable results may be obtainable with small datasets.