bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines
Authors: Gray Mark , Turnbull Arran K. , Meehan James , Martínez-Pérez Carlos , Kay Charlene , Pang Lisa Y. , Argyle David J.
Published: July 2020

Research usingin vitrocanine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast cancer is commonly treated with radiotherapy; however, tumor response depends on both innate radiosensitivity and on tumor repopulation by cells that develop radioresistance. Comparative canine and human studies investigating the mechanisms of radioresistance may lead to novel cancer treatments that benefit both species. In this study, we developed a canine mammary cancer (REM-134) radioresistant (RR) cell line and investigated the cellular mechanisms related to the development of acquired radioresistance. We performed a comparative analysis of this resistant model with our previously developed human breast cancer radioresistant cell lines (MCF-7 RR, ZR-751 RR, and MDA-MB-231 RR), characterizing inherent differences through genetic, molecular, and cell biology approaches. RR cells demonstrated enhanced invasion/migration capabilities, with phenotypic evidence suggestive of epithelial-to-mesenchymal transition. Similarities were identified between the REM-134 RR, MCF-7 RR, and ZR-751 RR cell lines in relation to the pattern of expression of both epithelial and mesenchymal genes, in addition to WNT, PI3K, and MAPK pathway activation. Following the development of radioresistance, transcriptomic data indicated that parental MCF-7 and ZR-751 cell lines changed from a luminal A classification to basal/HER2-overexpressing (MCF-7 RR) and normal-like/HER2-overexpressing (ZR-751 RR). These radioresistant subtypes were similar to the REM-134 and REM-134 RR cell lines, which were classified as HER2-overexpressing. To our knowledge, our study is the first to generate a canine mammary cancer RR cell line model and provide a comparative genetic and phenotypic analysis of the mechanisms of acquired radioresistance between canine and human cancer cell lines. We demonstrate that the cellular processes that occur with the development of acquired radioresistance are similar between the human and canine cell lines; our results therefore suggest that the canine model is appropriate to study both human and canine radioresistant mammary cancers, and that treatment strategies used in human medicine may also be applicable to veterinary patients.
A Genetic Evaluation System for New Zealand White Rabbit Germplasm Resources Based on SSR Markers
Authors: Li Jiali , Zhao Bin , Chen Yang , Zhao Bohao , Yang Naisu , Hu Shuaishuai , Shen Jinyu , Wu Xinsheng
Published: July 2020

At present, there is an abundance of quality domestic rabbit breeds in China. However, due to the lack of technical standards for the genetic evaluation of rabbit germplasm resources, there have been a number of problems, such as poor breed conservation. By studying the genetic diversity of 130 New Zealand white rabbits (regardless of generation), we obtained the best simple sequence repeat (SSR) marker combination. We found that, when using microsatellite markers for the effective genetic evaluation of domestic rabbits, the number of records should be greater than 60 and the marker number more than 22. Through the comparative analysis of 30 combinations of 22 markers, the optimal combination of 22 markers was determined, and the 22 SSR polymorphic loci were distributed on different chromosomes. We performed a genetic analysis of 200 New Zealand white rabbits corresponding to two generations, using the best SSR polymorphic loci combination. There were no significant differences in the genetic diversity parameters between the two generations of rabbits (p > 0.05), indicating that the characteristics of this excellent rabbit germplasm have been effectively preserved. At the same time, we verified that the established method can be used to evaluate the breed conservation of rabbit germplasm resources.
Diet with a High Proportion of Rice Alters Profiles and Potential Function of Digesta-Associated Microbiota in the Ileum of Goats
Authors: Wang Kaijun , Ren Ao , Zheng Mengli , Jiao Jinzhen , Yan Qiongxian , Zhou Chuanshe , Tan Zhiliang
Published: July 2020

Effects of a high proportion of concentrate in the diet on the ileal microbiota and metabolites in small ruminants are rarely reported. This study was designed to investigate the ileal microbiota and its relationship with host metabolic function in goats and aimed to elucidate the mechanisms involving in the ileal adaptation to a diet containing a high proportion of rice. Sixteen goats were equally divided into two groups and fed a diet with a normal concentrate proportion (NC, 55% concentrate) or a high-concentrate diet (HC, 90% concentrate). Results showed that the HC diet decreased bacterial diversity and elevated the abundance of five genera (Clostridium_sensu_stricto_1, Eubacterium_nodatum_group, Ruminococcus_gauvreauii_group, Eubacterium_coprostanoligenes_group and Ruminococcus 1), but reduced the number of Anaerotruncus. Microbial functional potentials indicated that the HC diet activated the pathways related to metabolism of carbohydrate, glycan, lipid and vitamins, but inhibited the pathways associated with cell motility and signal transduction. The activities of amylase and alkaline phosphatase were greater (p < 0.05) in the intestinal digesta of the HC-fed goats. However, there were no differences in the villus height, crypt depth and the ratio of villus height to crypt depth in the ileum between the two groups. These results indicate that the HC diet alters the bacterial community and pathways related to the metabolism of dietary nutrients and cell motility and signal transduction of bacteria in the ileum of goats.
A Multicriteria Motion Planning Approach for Combining Smoothness and Speed in Collaborative Assembly Systems
Authors: Rojas Rafael A. , Wehrle Erich , Vidoni Renato
Published: July 2020

Human–robot interaction is an important aspect of Industry 4.0, and the extended use of robotics in industrial environments will not be possible without enabling them to safely interact with humans. This imposes relevant constraints in the qualitative characterization of the motions of robots when sharing their workspace with humans. In this paper, we address the trade-off between two such constraints, namely the smoothness, which is related to the cognitive stress that a person undergoes when interacting with a robot, and the speed, which is related to normative safety requirements. Given an execution time, such an approach will allow us to plan safe trajectories without neglecting cognitive ergonomics and production efficiency aspects. We first present the methodology able to express the balance between these qualities in the form of a composite objective function. Thanks to the variational formalism, we identify the related set of optimal trajectories with respect to the given criterion and give a suitable parametrization to them. Then, we are able to formulate the safety requirements in terms of a reparametrization of the motion. Finally, numerical and experimental results are provided. This allows the identification of the preferable sets of the possible motions that satisfy the operator’s psychological well-being and the assembly process performance by complying with the safety requirements in terms of mechanical risk prevention.
Battery Management System for Future Electric Vehicles
Authors: Moulik Bedatri , Söffker Dirk
Published: July 2020

The future of electric vehicles relies nearly entirely on the design, monitoring, and control of the vehicle battery and its associated systems. Along with an initial optimal design of the cell/pack-level structure, the runtime performance of the battery needs to be continuously monitored and optimized for a safe and reliable operation and prolonged life. Improved charging techniques need to be developed to protect and preserve the battery. The scope of this Special Issue is to address all the above issues by promoting innovative design concepts, modeling and state estimation techniques, charging/discharging management, and hybridization with other storage components.
Multi-Channel Surface EMG Spatio-Temporal Image Enhancement Using Multi-Scale Hessian-Based Filters
Authors: Ullah Khalil , Khan Khalil , Amin Muhammad , Attique Muhammad , Chung Tae-Sun , Riaz Rabia
Published: July 2020

Surface electromyography (sEMG) signals acquired with linear electrode array are useful in analyzing muscle anatomy and physiology. Most algorithms for signal processing, detection, and estimation require adequate quality of the input signals, however, multi-channel sEMG signals are commonly contaminated due to several noise sources. The sEMG signal needs to be enhanced prior to the digital signal and image processing to achieve the best results. This study is using spatio-temporal images to represent surface EMG signals. The motor unit action potential (MUAP) in these images looks like a linear structure, making certain angles with the x-axis, depending on the conduction velocity of the MU. A multi-scale Hessian-based filter is used to enhance the linear structure, i.e., the MUAP region, and to suppress the background noise. The proposed framework is compared with some of the existing algorithms using synthetic, simulated, and experimental sEMG signals. Results show improved detection accuracy of the motor unit action potential after the proposed enhancement as a preprocessing step.
Validation of a Bar Linkage Model for Joint Angle Estimation during Cycling
Authors: Dieltiens Sien , Claeys Kurt , D’hondt Jordi , Devroey Henri , Juwet Marc , Demeester Eric
Published: July 2020

Measuring lower extremity joint angles during cycling is interesting to derive joint loading from contact forces at the pedals and to determine the cause of cycling injuries. Traditionally, joint angles are determined in a stationary setup with high-resolution cameras that track marker movement in a lab environment. Alternatively, joint angles can be estimated mathematically in-situ: the lower extremities, bicycle frame and pedal arms are presented as a 5 bar linkage system which is fully defined by the lower extremity segment lengths, seat height and pedal position. As most instrumented pedals for power measurements include pedal orientation measurements, the bar linkage system demands no special equipment to derive joint loadings from pedal loads. The aim of this study is to validate the bar linkage system for joint angle estimation in the sagittal plane during in-situ cycling. Ten subjects cycled on a stationary bike while the hip, knee and ankle angles were measured with a Vicon optoelectronic motion capture system and simultaneously calculated with the bar linkage system. The results were averaged to subject-specific and method-specific ensemble average curves in the function of the phase in the pedal cycle and compared by a correlation analysis, Bland Altman plot, and Spm1D paired T-test. The hip and knee angle estimation of the bar linkage system showed no statistically significant difference from the optoelectronic system. Moreover, the ankle showed a statistically significant difference in the last half of the recovery phase of the pedal cycle. As the difference was maximally 3°, it has no clinical significance when deriving joint loading from contact forces at the pedal.
Traceable Determination of Atmospheric Mercury Using Iodinated Activated Carbon Traps
Authors: Živković Igor , Berisha Sabina , Kotnik Jože , Jagodic Marta , Horvat Milena
Published: July 2020

Traceable determination of atmospheric mercury (Hg) represents a major analytical problem due to low environmental concentrations. Although Hg pre-concentration on activated carbon (AC) traps is a simple method for sample collection, Hg determination is difficult due to a complex matrix that cannot be easily digested using wet chemistry. Two approaches for Hg loading on iodinated AC, the purging of elemental mercury (Hg0) and the spiking a solution of standard reference material (SRM), were used to test whether spiking SRM solution on AC can be used for the traceable determination of atmospheric mercury collected as Hg0. Mercury on AC was determined using atomic absorption spectrometry after sample combustion. The detector’s response for both loading methods was identical in a wide concentration range, indicating that the spiking of SRM on AC can, indeed, be used for the calibration of analytical systems used for the determination of atmospheric mercury. This was confirmed by the determination of Hg in a real atmospheric sample collected on an iodinated AC trap and using an SRM spiking calibration. Different ACs were compared regarding their ability to quantitatively capture Hg while having the lowest breakthrough. Use of a specific impregnating solution probably converted Hg on AC to Millon’s iodide, as estimated from the fractionation thermogram.
Energy Balances and Greenhouse Gas Emissions of Agriculture in the Shihezi Oasis of China
Authors: Yan Zhengang , Hou Fuqin , Hou Fujiang
Published: July 2020

The objective of this study was to evaluate the difference of crop and livestock products regarding energy balances, greenhouse gas (GHG) emissions, carbon economic efficiency, and water use efficiency using a life cycle assessment (LCA) methodology on farms in three sub-oases within the Shihezi Oasis of China. The three sub-oases were selected within the Gobi Desert, at Shizongchang (SZC), Xiayedi (XYD), and Mosuowan (MSW), to represent the various local oasis types: i. Oasis; ii. overlapping oasis-desert; and iii. Gobi oasis. The results indicated that crop production in XYD Oasis had higher energy balances (221.47 GJ/ha), and a net energy ratio (5.39), than in the other two oases (p < 0.01). The production of 1 kg CW of sheep in XYD Oasis resulted in significantly higher energy balances (18.31 MJ/kg CW), and an energy ratio (2.21), than in the other two oases (p < 0.01). The water use efficiency of crop production in the SZC Oasis was lower than that of the XYD and MSW oases (p < 0.05). Alfalfa production generated the lowest CO2-eq emissions (8.09 Mg CO2-eq/ha. year) and had the highest water use efficiency (45.82 MJ/m3). Alfalfa (1.18 ¥/kg CO2-eq) and maize (1.14 ¥/kg CO2-eq) had a higher carbon economic efficiency than other crops (p < 0.01). The main sources of GHG emissions for crop production were fertilizer and irrigation. The structural equation modelling (SEM) of agricultural systems in the Shihezi Oasis showed that the livestock category significantly influenced the economic income, energy, and carbon balances.
Direct and Indirect Effects of Urease and Nitrification Inhibitors on N2O-N Losses from Urea Fertilization to Winter Wheat in Southern Germany
Authors: Hu Yuncai , Gaßner Manuela P. , Weber Andreas , Schraml Martine , Schmidhalter Urs
Published: July 2020

Urea (U) is the most important nitrogen (N) fertilizer in agriculture worldwide, and as N fertilizer can result in large gaseous losses of NH3 and N2O. Thus, urease inhibitors (UIs) and nitrification inhibitors (NIs) have been coupled with U fertilizers to mitigate NH3 and N2O emissions. However, it is still unclear whether adding NIs and/or UIs to U stimulates other pollutants, while reducing one pollutant. Furthermore, part of the NH3 deposition to earth is converted to N2O, leading to indirect N2O emission. To estimate direct and indirect effect of UIs and NIs on the N2O-N and NH3-N losses from U; therefore, we analyzed multi-year field experiments from the same site during 2004 to 2005 and 2011 to 2013. The field experiments with U fertilization with or without UI (IPAT, N-isopropoxycarbonyl phosphoric acid triamide) and NI (DCD/TZ, Dicyandiamide/1H-1, 2, 4-Triazol) in winter wheat and with calcium ammonium nitrate (CAN) were conducted in southern Germany. Fluxes of NH3 or N2O emissions were determined following each split N fertilization in separate experiments on the same site. Our results showed that U with NIs considerably reduced N2O emissions, and adding UIs decreased NH3 emissions. However, the effect on N2O emissions exerted by (U + UIs) or (U + UIs + NIs) was inconsistent. In contrast to the treatment of (U + UIs + NIs), the addition of NIs alone to U stimulated NH3 emission compared to treatment with U. When 1% indirect N2O emission from NH3 (IPCC emission factor (EF4)) was considered to estimate the indirect N2O emission, total N2O emissions from (U + NIs) were approximately 29% compared to that from U alone and 36% compared to that from (U + UI), indicating that indirect N2O emission from NH3 induced by NIs may be negligible.
Reconstruction of Piecewise Smooth Multivariate Functions from Fourier Data
Authors: Levin David
Published: July 2020

In some applications, one is interested in reconstructing a function f from its Fourier series coefficients. The problem is that the Fourier series is slowly convergent if the function is non-periodic, or is non-smooth. In this paper, we suggest a method for deriving high order approximation to f using a Padé-like method. Namely, we do this by fitting some Fourier coefficients of the approximant to the given Fourier coefficients of f. Given the Fourier series coefficients of a function on a rectangular domain in Rd, assuming the function is piecewise smooth, we approximate the function by piecewise high order spline functions. First, the singularity structure of the function is identified. For example in the 2D case, we find high accuracy approximation to the curves separating between smooth segments of f. Secondly, simultaneously we find the approximations of all the different segments of f. We start by developing and demonstrating a high accuracy algorithm for the 1D case, and we use this algorithm to step up to the multidimensional case.
The Role of GPR120 Receptor in Essential Fatty Acids Metabolism in Schizophrenia
Authors: Rog Joanna , Błażewicz Anna , Juchnowicz Dariusz , Ludwiczuk Agnieszka , Stelmach Ewa , Kozioł Małgorzata , Karakula Michal , Niziński Przemysław , Karakula-Juchnowicz Hanna
Published: July 2020

A growing body of evidence confirms abnormal fatty acid (FAs) metabolism in the pathophysiology of schizophrenia. Omega-3 polyunsaturated fatty acids (PUFAs) are endogenous ligands of the G protein-coupled receptors, which have anti-inflammatory properties and are a therapeutic target in many diseases. No clinical studies are concerned with the role of the GPR120 signaling pathway in schizophrenia. The aim of the study was to determine the differences in PUFA nutritional status and metabolism between patients with schizophrenia (SZ group) and healthy individuals (HC group). The study included 80 participants (40 in the SZ group, 40 in the HC group). There were no differences in serum GPR120 and PUFA concentrations and PUFA intake between the examined groups. In the HC group, there was a relationship between FAs in serum and GPR120 concentration (p < 0.05): α-linolenic acid (ALA) (R = −0.46), docosahexaenoic acid (DHA) (R = −0.54), omega-3 PUFAs (R = −0.41), arachidonic acid (AA) (R = −0.44). In the SZ group, FA serum concentration was not related to GPR120 (p > 0.05). In the HC group, ALA and DHA serum concentrations were independently associated with GPR120 (p < 0.05) in the model adjusted for eicosapentaenoic acid (EPA) and accounted for 38.59% of GPR120 variability (p < 0.05). Our results indicate different metabolisms of FAs in schizophrenia. It is possible that the diminished anti-inflammatory response could be a component connecting GPR120 insensitivity with schizophrenia.
Pain Processing in Older Adults and Its Association with Prefrontal Characteristics
Authors: Bunk Steffie , Emch Mónica , Koch Kathrin , Lautenbacher Stefan , Zuidema Sytse , Kunz Miriam
Published: July 2020

Aging is known to affect nociceptive processing, e.g., the ability to inhibit pain. This study aims to investigate whether pain responses in older individuals are associated with prefrontal characteristics, namely (i) executive functioning performance and (ii) structural brain variations in the prefrontal cortex. Heat and pressure stimuli were applied to assess pressure pain sensitivity and endogenous pain inhibition in 46 healthy older individuals. Executive functioning performance was assessed in three domains (i.e., cognitive inhibition, shifting, and updating) and structural brain variations were assessed in both gray and white matter. Overall pain responses were significantly associated with the executive functioning domains cognitive inhibition and shifting. However, no specific type of pain response showed an especially strong association. Endogenous pain inhibition specifically showed a significant association with gray matter volume in the prefrontal cortex and with variations in white matter structure of tracts connecting the prefrontal cortex with the periaqueductal gray. Hierarchical regression analyses showed that these variations in the prefrontal cortex can explain variance in pain inhibition beyond what can be explained by executive functioning. This might indicate that known deficits in pain inhibition in older individuals are associated with structural variations in prefrontal areas.
The Neuropathological Diagnosis of Alzheimer’s Disease—The Challenges of Pathological Mimics and Concomitant Pathology
Authors: King Andrew , Bodi Istvan , Troakes Claire
Published: July 2020

The definitive diagnosis of Alzheimer’s disease (AD) rests with post-mortem neuropathology despite the advent of more sensitive scanning and the search for reliable biomarkers. Even though the classic neuropathological features of AD have been known for many years, it was only relatively recently that more sensitive immunohistochemistry for amyloid beta (Aβ) and hyperphosphorylated tau (HP-tau) replaced silver-staining techniques. However, immunohistochemistry against these and other proteins has not only allowed a more scientific evaluation of the pathology of AD but also revealed some mimics of HP-tau pathological patterns of AD, including age-related changes, argyrophilic grain disease and chronic traumatic encephalopathy. It also highlighted a number of cases of AD with significant additional pathology including Lewy bodies, phosphorylated TDP-43 (p-TDP-43) positive neuronal cytoplasmic inclusions and vascular pathology. This concomitant pathology can cause a number of challenges including the evaluation of the significance of each pathological entity in the make-up of the clinical symptoms, and the threshold of each individual pathology to cause dementia. It also raises the possibility of underlying common aetiologies. Furthermore, the concomitant pathologies could provide explanations as to the relative failure of clinical trials of anti-Aβ therapy in AD patients.
MicroRNAs and Their Targetomes in Tumor-Immune Communication
Authors: Cho Sunglim , Tai Jesse W. , Lu Li-Fan
Published: July 2020

The development of cancer is a complex and dynamically regulated multiple-step process that involves many changes in gene expression. Over the last decade, microRNAs (miRNAs), a class of short regulatory non-coding RNAs, have emerged as key molecular effectors and regulators of tumorigenesis. While aberrant expression of miRNAs or dysregulated miRNA-mediated gene regulation in tumor cells have been shown to be capable of directly promoting or inhibiting tumorigenesis, considering the well-reported role of the immune system in cancer, tumor-derived miRNAs could also impact tumor growth through regulating anti-tumor immune responses. Here, we discuss howmiRNAs can function as central mediators that influence the crosstalk between cancer and the immune system. Moreover, we also review the current progress in the development of novel experimental approaches for miRNA target identification that will facilitate our understanding of miRNA-mediated gene regulation in not only human malignancies, but also in other genetic disorders.
Hepatocellular Carcinoma: Special Issue Highlights
Authors: Gupta Medhavi , Iyer Renuka V.
Published: July 2020

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Radiomic Texture and Shape Descriptors of the Rectal Environment on Post-Chemoradiation T2-Weighted MRI are Associated with Pathologic Tumor Stage Regression in Rectal Cancers: A Retrospective, Multi-Institution Study
Authors: Alvarez-Jimenez Charlems , Antunes Jacob T. , Talasila Nitya , Bera Kaustav , Brady Justin T. , Gollamudi Jayakrishna , Marderstein Eric , Kalady Matthew F. , Purysko Andrei , Willis Joseph E. , Stein Sharon , Friedman Kenneth , Paspulati Rajmohan , Delaney Conor P. , Romero Eduardo , Madabhushi Anant , Viswanath Satish E.
Published: July 2020

(1) Background: The relatively poor expert restaging accuracy of MRI in rectal cancer after neoadjuvant chemoradiation may be due to the difficulties in visual assessment of residual tumor on post-treatment MRI. In order to capture underlying tissue alterations and morphologic changes in rectal structures occurring due to the treatment, we hypothesized that radiomics texture and shape descriptors of the rectal environment (e.g., wall, lumen) on post-chemoradiation T2-weighted (T2w) MRI may be associated with tumor regression after neoadjuvant chemoradiation therapy (nCRT). (2) Methods: A total of 94 rectal cancer patients were retrospectively identified from three collaborating institutions, for whom a 1.5 or 3T T2w MRI was available after nCRT and prior to surgical resection. The rectal wall and the lumen were annotated by an expert radiologist on all MRIs, based on which 191 texture descriptors and 198 shape descriptors were extracted for each patient. (3) Results: Top-ranked features associated with pathologic tumor-stage regression were identified via cross-validation on a discovery set (n = 52, 1 institution) and evaluated via discriminant analysis in hold-out validation (n = 42, 2 institutions). The best performing features for distinguishing low (ypT0-2) and high (ypT3–4) pathologic tumor stages after nCRT comprised directional gradient texture expression and morphologic shape differences in the entire rectal wall and lumen. Not only were these radiomic features found to be resilient to variations in magnetic field strength and expert segmentations, a quadratic discriminant model combining them yielded consistent performance across multiple institutions (hold-out AUC of 0.73). (4) Conclusions: Radiomic texture and shape descriptors of the rectal wall from post-treatment T2w MRIs may be associated with low and high pathologic tumor stage after neoadjuvant chemoradiation therapy and generalized across variations between scanners and institutions.
The Great War of Today: Modifications of CAR-T Cells to Effectively Combat Malignancies
Authors: Zhylko Andriy , Winiarska Magdalena , Graczyk-Jarzynka Agnieszka
Published: July 2020

Immunotherapy of cancer had its early beginnings in the times when the elements of the immune system were still poorly characterized. However, with the progress in molecular biology, it has become feasible to re-engineer T cells in order to eradicate tumour cells. The use of synthetic chimeric antigen receptors (CARs) helped to re-target and simultaneously unleash the cytotoxic potential of T cells. CAR-T therapy proved to be remarkably effective in cases of haematological malignancies, often refractory and relapsed. The success of this approach yielded two Food and Drug Administration (FDA) approvals for the first “living drug” modalities. However, CAR-T therapy is not without flaws. Apart from the side effects associated with the treatment, it became apparent that CAR introduction alters T cell biology and the possible therapeutic outcomes. Additionally, it was shown that CAR-T approaches in solid tumours do not recapitulate the success in the haemato-oncology. Therefore, in this review, we aim to discuss the recent concerns of CAR-T therapy for both haematological and solid tumours. We also summarise the general strategies that are implemented to enhance the efficacy and safety of the CAR-T regimens in blood and solid malignancies.
Primary Driver Mutations in GTF2I Specific to the Development of Thymomas
Authors: Higuchi Rumi , Goto Taichiro , Hirotsu Yosuke , Yokoyama Yujiro , Nakagomi Takahiro , Otake Sotaro , Amemiya Kenji , Oyama Toshio , Mochizuki Hitoshi , Omata Masao
Published: July 2020

Thymomas are rare mediastinal tumors that are difficult to treat and pose a major public health concern. Identifying mutations in target genes is vital for the development of novel therapeutic strategies. Type A thymomas possess a missense mutation in GTF2I (chromosome 7 c.74146970T>A) with high frequency. However, the molecular pathways underlying the tumorigenesis of other thymomas remain to be elucidated. We aimed to detect this missense mutation in GTF2I in other thymoma subtypes (types B). This study involved 22 patients who underwent surgery for thymomas between January 2014 and August 2019. We isolated tumor cells from formalin-fixed paraffin-embedded tissues from the primary lesions using laser-capture microdissection. Subsequently, we performed targeted sequencing to detect mutant GTF2I coupled with molecular barcoding. We used PyClone analysis to determine the fraction of tumor cells harboring mutant GTF2I. We detected the missense mutation (chromosome 7 c.74146970T>A) in GTF2I in 14 thymomas among the 22 samples (64%). This mutation was harbored in many type B thymomas as well as type A and AB thymomas. The allele fraction for the tumors containing the mutations was variable, primarily owing to the coexistence of normal lymphocytes in the tumors, especially in type B thymomas. PyClone analysis revealed a high cellular prevalence of mutant GTF2I in tumor cells. Mutant GTF2I was not detected in other carcinomas (lung, gastric, colorectal, or hepatocellular carcinoma) or lymphomas. In conclusion, the majority of thymomas harbor mutations in GTF2I that can be potentially used as a novel therapeutic target in patients with thymomas.
Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases
Authors: Lobo-Martins Soraia , Ferreira Arlindo R. , Mansinho André , Casimiro Sandra , Leitzel Kim , Ali Suhail , Lipton Allan , Costa Luís
Published: July 2020

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.
Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm
Authors: Chakrabarti Sakti , Kamgar Mandana , Mahipal Amit
Published: July 2020

Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas that originate from the epithelial lining of the biliary tree. BTCs are characterized by presentation with advanced disease precluding curative surgery, rising global incidence, and a poor prognosis. Chemotherapy is the mainstay of the current treatment, which results in a median overall survival of less than one year, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and BRAF mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. In this review, we provide a contemporaneous appraisal of the evolving targeted therapies and the ongoing clinical trials that will likely transform the therapeutic paradigm of BTC.
Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome
Authors: Izzi Valerio , Davis Martin N. , Naba Alexandra
Published: July 2020

The extracellular matrix (ECM) is a master regulator of all cellular functions and a major component of the tumor microenvironment. We previously defined the “matrisome” as the ensemble of genes encoding ECM proteins and proteins modulating ECM structure or function. While compositional and biomechanical changes in the ECM regulate cancer progression, no study has investigated the genomic alterations of matrisome genes in cancers and their consequences. Here, mining The Cancer Genome Atlas (TCGA) data, we found that copy number alterations and mutations are frequent in matrisome genes, even more so than in the rest of the genome. We also found that these alterations are predicted to significantly impact gene expression and protein function. Moreover, we identified matrisome genes whose mutational burden is an independent predictor of survival. We propose that studying genomic alterations of matrisome genes will further our understanding of the roles of this compartment in cancer progression and will lead to the development of innovative therapeutic strategies targeting the ECM.
TP53 Mutation Analysis in Gastric Cancer and Clinical Outcomes of Patients with Metastatic Disease Treated with Ramucirumab/Paclitaxel or Standard Chemotherapy
Authors: Graziano Francesco , Fischer Nicholas W. , Bagaloni Irene , Di Bartolomeo Maria , Lonardi Sara , Vincenzi Bruno , Perrone Giuseppe , Fornaro Lorenzo , Ongaro Elena , Aprile Giuseppe , Bisonni Renato , Prisciandaro Michele , Malkin David , Gariépy Jean , Fassan Matteo , Loupakis Fotios , Sarti Donatella , Del Prete Michela , Catalano Vincenzo , Alessandroni Paolo , Magnani Mauro , Ruzzo Annamaria
Published: July 2020

Loss of p53 promotes vascular endothelial growth factor (VEGF)-A up-regulation and the angiogenic potential of cancer cells. We investigated TP53 somatic mutations in 110 primary gastric adenocarcinomas of two retrospective metastatic series including 48 patients treated with second-line Ramucirumab/Paclitaxel and 62 patients who received first-line chemotherapy with Cisplatin or Oxaliplatin plus 5-Fluorouracil. Missense mutations were classified by tumor protein p53 (TP53) mutant-specific residual transcriptional activity scores (TP53RTAS) and used to stratify patients into two groups: transcriptionally TP53Active and TP53Inactive. The primary endpoint was overall survival (OS). An additional analysis was addressed to measure VEGF/VEGF receptor 2 (VEGFR2) expression levels in relation to the TP53RTAS. In the Ramucirumab/Paclitaxel group, 29/48 (60.4%) patients had TP53 mutations. Ten patients with TP53Inactive mutations showed better OS than carriers of other TP53 mutations. This effect was retained in the multivariate model analysis (Hazard Ratio = 0.29, 95% confidence interval = 0.17–0.85, p = 0.02). In the chemotherapy group, 41/62 (66%) patients had TP53 mutations, and the 11 carriers of TP53Inactive mutations showed the worst OS (Hazard Ratio = 2.64, 95% confidence interval = 1.17–5.95, p = 0.02). VEGF-A mRNA expression levels were significantly increased in TP53Inactive cases. Further studies are warranted to explore the effect of TP53Inactive mutations in different anti-cancer regimens. This information would lead to new tailored therapy strategies for this lethal disease.
Soybean Protein Extraction by Alcalase and Flavourzyme, Combining Thermal Pretreatment for Enteral Feeding Product
Authors: Anh Truong Le Que , Hoa Nguyen Thi Quynh , Nguyen Pham Dinh Thanh , Thanh Hoang Van , Nguyen Pham Bao , Anh Le Thi Hong , Dao Dong Thi Anh
Published: July 2020

Soybean is one of the essential ingredients when formulating a tube feeding formula. In this study, we initially focused on determining which enzyme is suitable for hydrolyzing soy and comparing the soy protein enzymatic hydrolysis of three different enzymes at the same enzyme content: Flavourzyme, Protamex, and Alcalase. The result showed that Flavourzyme attained the highest soluble protein recovery efficiency (SPRE). Secondly, the study determined the effect of thermal treatment conditions such as thermal treatment duration, and then it showed that when combining the thermal treatment and enzymatic hydrolysis, the yield reached (61.44 ± 0.22)%, which was much higher than only using enzymatic hydrolysis (52.57 ± 0.27)%. Next, optimizing the enzymatic hydrolysis (combining thermal treatment) using Flavourzyme and Alcalase, Flavourzyme achieved (62.47 ± 0.12)%, while Alcalase attained (41.32 ± 0.13)%. The soy hydrolyzate using Flavourzyme achieved an average molecular size of 3.19 kDa at the following optimizing conditions: enzyme concentration, 16.09 U·g−1; pH, 7.02; temperature, 45.8 °C; and beans/water ratio, 1:3. In contrast, when using Alcalase, the soy hydrolyzate achieved an average molecular size of 1.52 kDa at the following optimizing conditions: enzyme concentration, 28.01 U·g−1; pH, 7.2; temperature, 56.5 °C; beans/water ratio, 1:4.6. Soy protein hydrolyzate of suitable viscosity and particle size flow through the inhaler with branched-chain amino acids achieved a BCAA (Branched Amino Acid) ratio of 2:1:1 for Alcalase and 4:1:1 for Flavourzyme. Soybean hydrolyzate using both enzymes attained a high SPRE and was suitable for the digestive ability of patients recovering from surgery. Soy protein is divided into amino acids, di- and tri-amino acids, and peptides to create a soluble protein source that helps feed patients with a sonde tube easily. In addition, the molecular weight of peptides will reduce viscosity significantly when passing through a sonde tube, preventing tube congestion.
Entrapping Immobilisation of Lipase on Biocomposite Hydrogels toward for Biodiesel Production from Waste Frying Acid Oil
Authors: Muanruksa Papasanee , Dujjanutat Praepilas , Kaewkannetra Pakawadee
Published: July 2020

A new application of biocomposite hydrogels named gelatin-alginate (GA) and pectin alginate (PA) enables the use of the hydrogels as carriers for lipase entrapment during biodiesel production. Waste frying acid oil (WFAO), a raw material, was converted to biodiesel via an esterification reaction catalysed by two different immobilised biocatalysts: gelatin-alginate lipase (GAL) and pectin-alginate lipase (PAL). The highest immobilisation yield of GAL and PAL beads was achieved at 97.61% and 98.30%, respectively. Both of them gave biodiesel yields in the range of 75–78.33%. Furthermore, capability and reusability of biocatalysts were improved such that they could be reused up to 7 cycles. Moreover, the predicted biodiesel properties met the European biodiesel standard (EN14214). Interestingly, entrapped lipase on composite hydrogels can be used as an alternative catalyst choice for replacing the chemical catalyst during the biodiesel production.
Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition
Authors: Khalili Bita , Lovelace Hailey D. , Rutkowski David M. , Holz Danielle , Vavylonis Dimitrios
Published: July 2020

Cells polarize for growth, motion, or mating through regulation of membrane-bound small GTPases between active GTP-bound and inactive GDP-bound forms. Activators (GEFs, GTP exchange factors) and inhibitors (GAPs, GTPase activating proteins) provide positive and negative feedbacks. We show that a reaction–diffusion model on a curved surface accounts for key features of polarization of model organism fission yeast. The model implements Cdc42 membrane diffusion using measured values for diffusion coefficients and dissociation rates and assumes a limiting GEF pool (proteins Gef1 and Scd1), as in prior models for budding yeast. The model includes two types of GAPs, one representing tip-localized GAPs, such as Rga3; and one representing side-localized GAPs, such as Rga4 and Rga6, that we assume switch between fast and slow diffusing states. After adjustment of unknown rate constants, the model reproduces active Cdc42 zones at cell tips and the pattern of GEF and GAP localization at cell tips and sides. The model reproduces observed tip-to-tip oscillations with periods of the order of several minutes, as well as asymmetric to symmetric oscillations transitions (corresponding to NETO “new end take off”), assuming the limiting GEF amount increases with cell size.
Mercury Exposure and Health Problems of the Students Using Skin-Lightening Cosmetic Products in Makassar, South Sulawesi, Indonesia
Authors: Abbas Hasriwiani Habo , Sakakibara Masayuki , Sera Koichiro , Nurgahayu  , Andayanie Ella
Published: July 2020

Despite legal and safety issues, skin-lightening cosmetic products—including hazardous mercury-containing cosmetics—are in increasing demand in Indonesia. Perceptions of beauty may result in desires to have lighter skin tones, regardless of the safety of these cosmetics, which block the production of melanin and thus lighten skin tone. This study investigated Hg exposure of students using skin-lightening cosmetics and assessed the health issues. A total of 105 female students were given a questionnaire regarding their use of cosmetics; a further 43 students formed a non-cosmetic-user control group. Their scalp hair and cosmetic products were analyzed by particle-induced X-ray emission (PIXE) spectroscopy. The geometric-mean hair Hg concentration for the cosmetics-using students was 6.7 µg g−1—three times that of the control group (2.3 µg g−1). Of twenty-seven cosmetic samples were analyzed, twenty had Hg concentrations of 0.12–7834.4 µg g−1 (mean 554.6 µg g−1), and seven had no detectable Hg. The hair Hg concentrations exhibited a statistically significant correlation with cosmetic Hg concentration. The health assessments indicated only rigidity & ataxia and irregular eye movement were prevalent in the cosmetic-using students with less than 7% occurrences.
Influence of Phosphorus Addition on the Stress Rupture Properties of Direct Aged IN706 Superalloy
Authors: Zhang Sha , Zhang Anwen , Xue Chaochao , Jia Dan , Zhang Weiwei , Wang Weiyang , Xin Xin , Sun Wenru
Published: July 2020

This study investigated the influence of phosphorus (P) addition on the stress rupture properties of direct aged IN706 superalloy. The results showed that P slightly improved the stress rupture life of the superalloy when added in the range between 0.002% and 0.008%; however, it significantly reduced the stress rupture life when added in the range between 0.013% and 0.017%. Microstructure characterization indicated that the precipitation of γ′, γ″, and η phases was not significantly affected by the addition of P. Phosphides precipitated in the alloy containing 0.017% P after aging at 980 °C for 10 min. Compared to a similar study previously made on IN706 superalloy, it was found that the optimum P concentration in the as-solutioned state for improving the stress rupture properties was not definite. Furthermore, the relationship between the amount of P segregated at the grain boundary and the role of P on the stress rupture properties was discussed.
Hyperuricemia Is Associated with Left Ventricular Dysfunction and Inappropriate Left Ventricular Mass in Chronic Kidney Disease
Authors: Chiu Tai-Hua , Wu Pei-Yu , Huang Jiun-Chi , Su Ho-Ming , Chen Szu-Chia , Chang Jer-Ming , Chen Hung-Chun
Published: July 2020

Background. Hyperuricemia is common in patients with chronic kidney disease (CKD), and this may lead to poor cardiovascular (CV) outcomes. The aim of this cross-sectional study was to assess associations among serum uric acid (UA) and echocardiographic parameters, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity (baPWV) in patients with CKD. Methods. A total of 418 patients with CKD were included. The echocardiographic measurements included left atrial diameter (LAD), left ventricular ejection fraction (LVEF) and the ratio of observed to predict left ventricular mass (LVM). ABI, baPWV and medical records were obtained. Results. Multivariable forward logistic regression analysis showed that a high UA level was significantly associated with LAD > 47 mm (odds ratio [OR], 1.329; p = 0.002), observed/predicted LVM > 128% (OR, 1.198; p = 0.008) and LVEF < 50% (OR, 1.316; p = 0.002). No significant associations were found between UA and ABI < 0.9 or baPWV > 1822 cm/s. Multivariate stepwise linear regression analysis showed that a high UA level correlated with high LAD (unstandardized coefficient β, 0.767; p < 0.001), high observed/predicted LVM (unstandardized coefficient β, 4.791; p < 0.001) and low LVEF (unstandardized coefficient β, −1.126; p = 0.001). No significant associations between UA and low ABI and high baPWV were found. Conclusion. A high serum UA level was associated with a high LAD, high observed/predicted LVM and low LVEF in the patients with CKD. A high serum UA level may be correlated with abnormal echocardiographic parameters in patients with stage 3–5 CKD.