bluuebunny/crossref_metadata_2025 huggingface dataset:
A Normalized HLD (HLDN) Tool for Optimal Salt-Concentration Prediction of Microemulsions
Authors: Kittithammavong Virin , Charoensaeng Ampira , Khaodhiar Sutha
Published: October 2021

Optimal condition-based microemulsion is key to achieving great efficiency in oil removal. One useful empirical equation to predict an optimal condition is a hydrophilic–lipophilic deviation (HLD). However, the K constants of each surfactant should be the same to combine the HLD equations for the mixed surfactant. Recently, a normalized hydrophilic-lipophilic deviation (HLDN) was presented to avoid this limitation. This work sought to determine the phase behaviors and predict the optimal salt concentrations, using HLDN for the mixed surfactant. Sodium dihexyl sulfosuccinate (SDHS) as an anionic surfactant, and alcohol alkyl polyglycol ether (AAE(6EO4PO)) as a nonionic surfactant, were both investigated. Alkanes and diesel were used as a model oil. The results showed that AAE(6EO4PO) enforced both the hydrophilic and the hydrophobic characteristics. The Winsor Type I-III transition was influenced by the ethylene oxide, while the propylene oxide presence affected the Winsor Type III-II inversion. For the HLDN equation, the average interaction term was 1.82 ± 0.86, which markedly showed a strong correlation with the fraction of nonionic surfactant in the mixed systems. The predicted optimal salt concentrations using HLDN of SDHS-AAE(6EO4PO) in the diesel systems were close to the experimental results, with an error of <10% that is significantly beneficial due to the shorter time required for optimal determination.
Study on the Control of Torque Distribution of 4WD Corn Harvester Operation Drive
Authors: Zhou Deyi , Hou Pengfei , Xin Yuelin , Lv Xinlei , Wu Baoguang , Yu Haiye , Zhang Jinsong , Zhang Qiang
Published: October 2021

In response to the poor adaptability of existing harvesters to complex operating conditions in the field, this study took a three-row four-wheel-drive (4WD) corn harvester as the research object, designed a traveling transmission system layout, proposed a control strategy of driving torque distribution, simulated, and analyzed each of the four states of harvester drive wheels slippage. The results showed that under the driving wheels slipping condition, after applying torque control, the adjustment time was 43.3% shorter than that without control in the case of single wheel slipping, 11.1% shorter than that without control in the case of two wheels slipping on the same axle, 41.4% shorter than that without control in the case of two wheels slipping on different axles, and 36.6% shorter than that without control in the case of three driving wheels slipping. The application of drive torque distribution control could significantly improve the traction and passing ability of the corn harvesters during operation, as well as made the harvester travel more smoothly, thus improving the harvest quality. The drive torque distribution control can be applied not only to the three-row corn harvester, but also to other types of harvesters, and self-propelled agricultural machinery to enhance their adaptability, improving their operation quality. It has a significant reference value for the development of the driving system on walking agricultural machinery.
Gap Filling and Quality Control Applied to Meteorological Variables Measured in the Northeast Region of Brazil
Authors: Costa Rafaela Lisboa , Barros Gomes Heliofábio , Cavalcante Pinto David Duarte , da Rocha Júnior Rodrigo Lins , dos Santos Silva Fabrício Daniel , Barros Gomes Helber , Lemos da Silva Maria Cristina , Luís Herdies Dirceu
Published: October 2021

In this work, we used the MICE (Multivariate Imputation by Chained Equations) technique to impute missing daily data from six meteorological variables (precipitation, temperature, relative humidity, atmospheric pressure, wind speed and insolation) from 96 stations located in the northeast region of Brazil (NEB) for the period from 1961 to 2014. We then applied tests with a quality control system (QCS) developed for the detection, correction and possible replacement of suspicious data. Both the applied gap filling technique and the QCS showed that it was possible to solve two of the biggest problems found in time series of daily data measured in meteorological stations: the generation of plausible values for each variable of interest, in order to remedy the absence of observations, and how to detect and allow proper correction of suspicious values arising from observations.
Lipid Profiles of RAS Nanoclusters Regulate RAS Function
Authors: Zhou Yong , Hancock John F.
Published: October 2021

The lipid-anchored RAS (Rat sarcoma) small GTPases (guanosine triphosphate hydrolases) are highly prevalent in human cancer. Traditional strategies of targeting the enzymatic activities of RAS have been shown to be difficult. Alternatively, RAS function and pathology are mostly restricted to nanoclusters on the plasma membrane (PM). Lipids are important structural components of these signaling platforms on the PM. However, how RAS nanoclusters selectively enrich distinct lipids in the PM, how different lipids contribute to RAS signaling and oncogenesis and whether the selective lipid sorting of RAS nanoclusters can be targeted have not been well-understood. Latest advances in quantitative super-resolution imaging and molecular dynamic simulations have allowed detailed characterization RAS/lipid interactions. In this review, we discuss the latest findings on the select lipid composition (with headgroup and acyl chain specificities) within RAS nanoclusters, the specific mechanisms for the select lipid sorting of RAS nanoclusters on the PM and how perturbing lipid compositions within RAS nanoclusters impacts RAS function and pathology. We also describe different strategies of manipulating lipid composition within RAS nanoclusters on the PM.
Pyrroloquinoline-Quinone Is More Than an Antioxidant: A Vitamin-like Accessory Factor Important in Health and Disease Prevention
Authors: Jonscher Karen R. , Chowanadisai Winyoo , Rucker Robert B.
Published: October 2021

Pyrroloquinoline quinone (PQQ) is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. In addition, PQQ attenuates clinically relevant dysfunctions (e.g., those associated with ischemia, inflammation and lipotoxicity). PQQ is novel among biofactors that are not currently accepted as vitamins or conditional vitamins. For example, the absence of PQQ in diets produces a response like a vitamin-related deficiency with recovery upon PQQ repletion in a dose-dependent manner. Moreover, potential health benefits, such as improved metabolic flexibility and immuno-and neuroprotection, are associated with PQQ supplementation. Here, we address PQQ’s role as an enzymatic cofactor or accessory factor and highlight mechanisms underlying PQQ’s actions. We review both large scale and targeted datasets demonstrating that a neonatal or perinatal PQQ deficiency reduces mitochondria content and mitochondrial-related gene expression. Data are reviewed that suggest PQQ’s modulation of lactate acid and perhaps other dehydrogenases enhance NAD+-dependent sirtuin activity, along with the sirtuin targets, such as PGC-1α, NRF-1, NRF-2 and TFAM; thus, mediating mitochondrial functions. Taken together, current observations suggest vitamin-like PQQ has strong potential as a potent therapeutic nutraceutical.
Long-Term Effects of Polystyrene Nanoplastics in Human Intestinal Caco-2 Cells
Authors: Domenech Josefa , de Britto Mariana , Velázquez Antonia , Pastor Susana , Hernández Alba , Marcos Ricard , Cortés Constanza
Published: October 2021

The increasing presence of micro- and nanoplastics (MNPLs) in the environment, and their consequent accumulation in trophic niches, could pose a potential health threat to humans, especially due to their chronic ingestion. In vitro studies using human cells are considered pertinent approaches to determine potential health risks to humans. Nevertheless, most of such studies have been conducted using short exposure times and high concentrations. Since human exposure to MNPLs is supposed to be chronic, there is a lack of information regarding the potential in vitro MNPLs effects under chronic exposure conditions. To this aim, we assessed the accumulation and potential outcomes of polystyrene nanoparticles (PSNPs), as a model of MNPLs, in undifferentiated Caco-2 cells (as models of cell target in ingestion exposures) under a relevant long-term exposure scenario, consisting of eight weeks of exposure to sub-toxic PSNPs concentrations. In such exposure conditions, culture-media was changed every 2–3 days to maintain constant exposure. The different analyzed endpoints were cytotoxicity, dysregulation of stress-related genes, genotoxicity, oxidative DNA damage, and intracellular ROS levels. These are endpoints that showed to be sensitive enough in different studies. The obtained results attest that PSNPs accumulate in the cells through time, inducing changes at the ultrastructural and molecular levels. Nevertheless, minor changes in the different evaluated genotoxicity-related biomarkers were observed. This would indicate that no DNA damage or oxidative stress is observed in the human intestinal Caco-2 cells after long-term exposure to PSNPs. This is the first study dealing with the long-term effects of PSNPs on human cultured cells.
Effective Perturbations on the Amplitude and Hysteresis of Erg-Mediated Potassium Current Caused by 1-Octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6(undecyloxy)hexyl]amino]-octanoate (SM-102), a Cationic Lipid
Authors: Cho Hsin-Yen , Chuang Tzu-Hsien , Wu Sheng-Nan
Published: October 2021

SM-102 (1-octylnonyl 8-[(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino]-octanoate) is an amino cationic lipid that has been tailored for the formation of lipid nanoparticles and it is one of the essential ingredients present in the ModernaTM COVID-19 vaccine. However, to what extent it may modify varying types of plasmalemmal ionic currents remains largely uncertain. In this study, we investigate the effects of SM-102 on ionic currents either in two types of endocrine cells (e.g., rat pituitary tumor (GH3) cells and mouse Leydig tumor (MA-10) cells) or in microglial (BV2) cells. Hyperpolarization-activated K+ currents in these cells bathed in high-K+, Ca2+-free extracellular solution were examined to assess the effects of SM-102 on the amplitude and hysteresis of the erg-mediated K+ current (IK(erg)). The SM-102 addition was effective at blocking IK(erg) in a concentration-dependent fashion with a half-maximal concentration (IC50) of 108 μM, a value which is similar to the KD value (i.e., 134 μM) required for its accentuation of deactivation time constant of the current. The hysteretic strength of IK(erg) in response to the long-lasting isosceles-triangular ramp pulse was effectively decreased in the presence of SM-102. Cell exposure to TurboFectinTM 8.0 (0.1%, v/v), a transfection reagent, was able to inhibit hyperpolarization-activated IK(erg) effectively with an increase in the deactivation time course of the current. Additionally, in GH3 cells dialyzed with spermine (30 μM), the IK(erg) amplitude progressively decreased; moreover, a further bath application of SM-102 (100 μM) or TurboFectin (0.1%) diminished the current magnitude further. In MA-10 Leydig cells, the IK(erg) was also blocked by the presence of SM-102 or TurboFectin. The IC50 value for SM-102-induced inhibition of IK(erg) in MA-10 cells was 98 μM. In BV2 microglial cells, the amplitude of the inwardly rectifying K+ current was inhibited by SM-102. Taken together, the presence of SM-102 concentration-dependently inhibited IK(erg) in endocrine cells (e.g., GH3 or MA-10 cells), and such action may contribute to their functional activities, assuming that similar in vivo findings exist.
Bullying Prevalence among Secondary School Children in Khamis Mushait City, Southwestern Saudi Arabia
Authors: Alsaleem Mohammed Abadi , Alhashem Huda Aied , Alsaleem Safar Abadi , Mahfouz Ahmed A.
Published: October 2021

Bullying is a type of behavior that involves frequent, hostile activities expected to harm another person physically, mentally, or emotionally. Bullying behavior uses force, pressure, or threats to maltreat, forcefully dominate, or terrify another individual. The aim of this study was to assess the bullying prevalence and related features among secondary school pupils in Khamis Mushait city, southwestern Saudi Arabia. A cross-sectional investigation was performed among governmental and private secondary schools in Khamis Mushait city. Data were gathered from the study pupils using a pre-structured questionnaire. Bullying was assessed using the school climate bullying survey. The study included 300 secondary school students (163 females and 137 males). The overall rate of bullying was 64.7% (95% CI 59.1–69.9). The most prevalent type of bullying was verbal (41.7%, 95% CI 36.0–47.5) followed by physical (17.0%, 95% CI 12.9–21.7), and social (6.0%, 95% CI 3.6–9.3). Males had more than two times greater probability of having been bullied than females (aOR = 2.522, 95% CI 1.408–4.518). Similarly, students in first-level grade classes had more than three times greater probability of being bullied victims than those in the higher classes, i.e., second- and third-level grade classes (aOR = 3.417, 95% CI 1.159–10.07). More than half of the students tell teachers when other students are being bullied (53.7%) and tell a teacher or staff member at the school if they are being harassed (53.6%); teachers are doing anything they can to help if they are told that a student is being bothered (58.7%), and teachers are making clear to students that bullying is not tolerated (52.3%). In conclusion, in the present study, we reported a high prevalence rate of bullying among secondary school pupils in Khamis Mushait city, southwestern Saudi Arabia. Concerted efforts among teachers and health care providers in the region should be mandatory to deal with the problem.
Towards an Integrated Approach to Infrastructure Damage Assessment in the Aftermath of Natural Hazards
Authors: Nepal Madhav Prasad , Hon Carol , Lee Jinwoo (Brian) , Xiang Ziru
Published: October 2021

The world has witnessed an alarmingly increasing number of serious natural hazards. In the aftermath of a hazard, relevant authorities/agencies face, among others, the challenging tasks of rapidly evaluating and assessing the damages to infrastructures and restoring their essential functionality and operation. The availability of reliable, high-quality structural and operational/maintenance data of a structure and its health, before and after a natural hazard, can be instrumental in the rapid assessment of a damaged structure. We collectively refer, in this paper, to the existing as-built and facility operational information about a structure or an infrastructure asset represented respectively in Building Information Modeling (BIM) and Infrastructure Asset Management (IAM) systems as Product Lifecycle Data (PLD). Arguably, PLD combined with other post-hazard condition assessment data can provide a more reliable and integrated solution for a rapid damage assessment of buildings and other critical infrastructures. Unfortunately, the application of PLD in this critical area has been unexplored in the literature, and the mapping between PLD and damage assessment methods is loosely investigated. In an effort to address this research gap, this paper provides a critical analysis of the most common structural damage assessment methods and explores the potential of combining them with PLD to provide more reliable, comprehensive, and integrated solution for damage assessment. Findings from this study could be useful for practitioners in selecting the most appropriate and effective methods to conduct damage and safety assessments of critical infrastructures. The study will also assist the further theoretical developments in the integration of PLD with different damage assessment methods.
Biological Aspects of Inflamm-Aging in Childhood Cancer Survivors
Authors: Rossi Francesca , Di Paola Alessandra , Pota Elvira , Argenziano Maura , Di Pinto Daniela , Marrapodi Maria Maddalena , Di Leva Caterina , Di Martino Martina , Tortora Chiara
Published: October 2021

Anti-cancer treatments improve survival in children with cancer. A total of 80% of children treated for childhood cancer achieve 5-year survival, becoming long-term survivors. However, they undergo several chronic late effects related to treatments. In childhood cancer survivors a chronic low-grade inflammation, known as inflamm-aging, is responsible for frailty, a condition characterized by vital organ failure and by premature aging processes. Inflamm-aging is closely related to chemotherapy and radiotherapy, which induce inflammation, accumulation of senescent cells, DNA mutations, and the production of reactive oxygen species. All these conditions are responsible for the onset of secondary diseases, such as osteoporosis, cardiovascular diseases, obesity, and infertility. Considering that the pathobiology of frailty among childhood cancer survivors is still unknown, investigations are needed to better understand frailty’s biological and molecular processes and to identify inflamm-aging key biomarkers in order to facilitate the screening of comorbidities and to clarify whether treatments, normally used to modulate inflamm-aging, may be beneficial. This review offers an overview of the possible biological mechanisms involved in the development of inflamm-aging, focusing our attention on immune system alteration, oxidative stress, cellular senescence, and therapeutic strategies.
Maraviroc Prevents HCC Development by Suppressing Macrophages and the Liver Progenitor Cell Response in a Murine Chronic Liver Disease Model
Authors: Passman Adam M. , Strauss Robyn P. , McSpadden Sarah B. , Finch-Edmondson Megan , Andrewartha Neil , Woo Ken H. , Diepeveen Luke A. , Zhao Weihao , Fernández-Irigoyen Joaquín , Santamaría Enrique , Medina-Ruiz Laura , Szpakowska Martyna , Chevigné Andy , Park Hyerin , Carlessi Rodrigo , Tirnitz-Parker Janina E. E. , Blanco José R. , London Roslyn , Callus Bernard A. , Elsegood Caryn L. , Baker Murray V. , Martínez Alfredo , Yeoh George C. T. , Ochoa-Callejero Laura
Published: October 2021

Maraviroc (MVC), a CCR5 antagonist, reduces liver fibrosis, injury and tumour burden in mice fed a hepatocarcinogenic diet, suggesting it has potential as a cancer therapeutic. We investigated the effect of MVC on liver progenitor cells (LPCs) and macrophages as both have a role in hepatocarcinogenesis. Mice were fed the hepatocarcinogenic choline-deficient, ethionine-supplemented diet (CDE) ± MVC, and immunohistochemistry, RNA and protein expression were used to determine LPC and macrophage abundance, migration and related molecular mechanisms. MVC reduced LPC numbers in CDE mice by 54%, with a smaller reduction seen in macrophages. Transcript and protein abundance of LPC-associated markers correlated with this reduction. The CDE diet activated phosphorylation of AKT and STAT3 and was inhibited by MVC. LPCs did not express Ccr5 in our model; in contrast, macrophages expressed high levels of this receptor, suggesting the effect of MVC is mediated by targeting macrophages. MVC reduced CD45+ cells and macrophage migration in liver and blocked the CDE-induced transition of liver macrophages from an M1- to M2-tumour-associated macrophage (TAM) phenotype. These findings suggest MVC has potential as a re-purposed therapeutic agent for treating chronic liver diseases where M2-TAM and LPC numbers are increased, and the incidence of HCC is enhanced.
Prediction of Early Distant Recurrence in Upfront Resectable Pancreatic Adenocarcinoma: A Multidisciplinary, Machine Learning-Based Approach
Authors: Palumbo Diego , Mori Martina , Prato Francesco , Crippa Stefano , Belfiori Giulio , Reni Michele , Mushtaq Junaid , Aleotti Francesca , Guazzarotti Giorgia , Cao Roberta , Steidler Stephanie , Tamburrino Domenico , Spezi Emiliano , Del Vecchio Antonella , Cascinu Stefano , Falconi Massimo , Fiorino Claudio , De Cobelli Francesco
Published: October 2021

Despite careful selection, the recurrence rate after upfront surgery for pancreatic adenocarcinoma can be very high. We aimed to construct and validate a model for the prediction of early distant recurrence (<12 months from index surgery) after upfront pancreaticoduodenectomy. After exclusions, 147 patients were retrospectively enrolled. Preoperative clinical and radiological (CT-based) data were systematically evaluated; moreover, 182 radiomics features (RFs) were extracted. Most significant RFs were selected using minimum redundancy, robustness against delineation uncertainty and an original machine learning bootstrap-based method. Patients were split into training (n = 94) and validation cohort (n = 53). Multivariable Cox regression analysis was first applied on the training cohort; the resulting prognostic index was then tested in the validation cohort. Clinical (serum level of CA19.9), radiological (necrosis), and radiomic (SurfAreaToVolumeRatio) features were significantly associated with the early resurge of distant recurrence. The model combining these three variables performed well in the training cohort (p = 0.0015, HR = 3.58, 95%CI = 1.98–6.71) and was then confirmed in the validation cohort (p = 0.0178, HR = 5.06, 95%CI = 1.75–14.58). The comparison of survival curves between low and high-risk patients showed a p-value <0.0001. Our model may help to better define resectability status, thus providing an actual aid for pancreatic adenocarcinoma patients’ management (upfront surgery vs. neoadjuvant chemotherapy). Independent validations are warranted.
Beyond Nicotinamide Metabolism: Potential Role of Nicotinamide N-Methyltransferase as a Biomarker in Skin Cancers
Authors: Campagna Roberto , Pozzi Valentina , Sartini Davide , Salvolini Eleonora , Brisigotti Valerio , Molinelli Elisa , Campanati Anna , Offidani Annamaria , Emanuelli Monica
Published: October 2021

Skin cancers (SC) collectively represent the most common type of malignancy in white populations. SC includes two main forms: malignant melanoma and non-melanoma skin cancer (NMSC). NMSC includes different subtypes, namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma (MCC), and keratoacanthoma (KA), together with the two pre-neoplastic conditions Bowen disease (BD) and actinic keratosis (AK). Both malignant melanoma and NMSC are showing an increasing incidence rate worldwide, thus representing an important challenge for health care systems, also because, with some exceptions, SC are generally characterized by an aggressive behavior and are often diagnosed late. Thus, identifying new biomarkers suitable for diagnosis, as well as for prognosis and targeted therapy is mandatory. Nicotinamide N-methyltransferase (NNMT) is an enzyme that is emerging as a crucial player in the progression of several malignancies, while its substrate, nicotinamide, is known to exert chemopreventive effects. Since there is increasing evidence regarding the involvement of this enzyme in the malignant behavior of SC, the current review aims to summarize the state of the art as concerns NNMT role in SC and to support future studies focused on exploring the diagnostic and prognostic potential of NNMT in skin malignancies and its suitability for targeted therapy.
The Microbiome in Childhood Acute Lymphoblastic Leukemia
Authors: Oldenburg Marina , Rüchel Nadine , Janssen Stefan , Borkhardt Arndt , Gössling Katharina L.
Published: October 2021

For almost 30 years, the term “holobiont” has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.
Cholecystokinin Receptor Antagonist Improves Efficacy of Chemotherapy in Murine Models of Pancreatic Cancer by Altering the Tumor Microenvironment
Authors: Malchiodi Zoe X. , Cao Hong , Gay Martha D. , Safronenka Anita , Bansal Sunil , Tucker Robin D. , Weinberg Benjamin A. , Cheema Amrita , Shivapurkar Narayan , Smith Jill P.
Published: October 2021

Pancreatic cancer is resistant to chemotherapy in part due to the dense desmoplastic fibrosis surrounding the tumor, the immunosuppressive cells in the tumor microenvironment (TME), and the early rate of metastases. In this study, we examined the effects of a CCK receptor antagonist, proglumide, alone and in combination with gemcitabine in murine models of pancreatic cancer. Tumor growth rate, metastases, and survival were assessed in mice bearing syngeneic murine or human pancreatic tumors treated with PBS (control), gemcitabine, proglumide, or the combination of gemcitabine and proglumide. Excised tumors were evaluated histologically for fibrosis, immune cells, molecular markers, and uptake of chemotherapy by mass spectroscopy. Peripheral blood was analyzed with a microRNAs biomarker panel associated with fibrosis and oncogenesis. Differentially expressed genes between tumors of mice treated with gemcitabine monotherapy and combination therapy were compared by RNAseq. When given in combination the two compounds exhibited inhibitory effects by decreasing tumor growth rate by 70%, metastases, and prolonging survival. Proglumide monotherapy altered the TME by decreasing fibrosis, increasing intratumoral CD8+ T-cells, and decreasing arginase-positive cells, thus rendering the tumor sensitive to chemotherapy. Proglumide altered the expression of genes involved in fibrosis, epithelial–mesenchymal transition, and invasion. CCK-receptor antagonism with proglumide renders pancreatic cancer susceptible to chemotherapy.
RAC1 Alterations Induce Acquired Dabrafenib Resistance in Association with Anaplastic Transformation in a Papillary Thyroid Cancer Patient
Authors: Bagheri-Yarmand Rozita , Busaidy Naifa L. , McBeath Elena , Danysh Brian P. , Evans Kurt W. , Moss Tyler J. , Akcakanat Argun , Ng Patrick K. S. , Knippler Christina M. , Golden Jalyn A. , Williams Michelle D. , Multani Asha S. , Cabanillas Maria E. , Shaw Kenna R. , Meric-Bernstam Funda , Shah Manisha H. , Ringel Matthew D. , Hofmann Marie Claude
Published: October 2021

BRAF-activating mutations are the most frequent driver mutations in papillary thyroid cancer (PTC). Targeted inhibitors such as dabrafenib have been used in advanced BRAF-mutated PTC; however, acquired resistance to the drug is common and little is known about other effectors that may play integral roles in this resistance. In addition, the induction of PTC dedifferentiation into highly aggressive KRAS-driven anaplastic thyroid cancer (ATC) has been reported. We detected a novel RAC1 (P34R) mutation acquired during dabrafenib treatment in a progressive metastatic lesion with ATC phenotype. To identify a potential functional link between this novel mutation and tumor dedifferentiation, we developed a cell line derived from the metastatic lesion and compared its behavior to isogenic cell lines and primary tumor samples. Our data demonstrated that RAC1 mutations induce changes in cell morphology, reorganization of F-actin almost exclusively at the cell cortex, and changes in cell adhesion properties. We also established that RAC1 amplification, with or without mutation, is sufficient to drive cell proliferation and resistance to BRAF inhibition. Further, we identified polyploidy of chromosome 7, which harbors RAC1, in both the metastatic lesion and its derived cell line. Copy number amplification and overexpression of other genes located on this chromosome, such as TWIST1, EGFR, and MET were also detected, which might also lead to dabrafenib resistance. Our study suggests that polyploidy leading to increased expression of specific genes, particularly those located on chromosome 7, should be considered when analyzing aggressive thyroid tumor samples and in further treatments.
A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
Authors: Romano Mariele , Bravin Alberto , Mittone Alberto , Eckhardt Alicia , Barbone Giacomo E. , Sancey Lucie , Dinkel Julien , Bartzsch Stefan , Ricke Jens , Alunni-Fabbroni Marianna , Hirner-Eppeneder Heidrun , Karpov Dmitry , Giannini Cinzia , Bunk Oliver , Bouchet Audrey , Ruf Viktoria , Giese Armin , Coan Paola
Published: October 2021

The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques.
HER2/neu-Based Peptide Vaccination-Pulsed with B-Cell Epitope Induced Efficient Prophylactic and Therapeutic Antitumor Activities in TUBO Breast Cancer Mice Model
Authors: Nordin Muhammad Luqman , Mohamad Norpi Abdin Shakirin , Ng Pei Yuen , Yusoff Khatijah , Abu Nadiah , Lim Kue Peng , Azmi Fazren
Published: October 2021

Breast cancer is the most common invasive cancer diagnosed among women. A cancer vaccine has been recognized as a form of immunotherapy with a prominent position in the prevention and treatment of breast cancer. The majority of current breast cancer vaccination strategies aim to stimulate antitumor T-cell responses of the HER2/neu oncogene, which is abnormally expressed in breast cancer cells. However, the role of the B-cell humoral response is often underappreciated in the cancer vaccine design. We have advanced this idea by elucidating the role of B-cells in cancer vaccination by designing a chimeric antigenic peptide possessing both cytotoxic T lymphocytes (GP2) and B-cell (P4) peptide epitopes derived from HER2/neu. The chimeric peptide (GP2–P4) was further conjugated to a carrier protein (KLH), forming a KLH–GP2–P4 conjugate. The immunogenicity of KLH–GP2–P4 was compared with KLH–GP2 (lacking the B-cell epitope) in BALB/c mice. Mice immunized with KLH–GP2–P4 elicited more potent antigen-specific neutralizing antibodies against syngeneic TUBO cells (cancer cell line overexpressing HER2/neu) that was governed by a balanced Th1/Th2 polarization in comparison to KLH–GP2. Subsequently, these immune responses led to greater inhibition of tumor growth and longer survival in TUBO tumor-bearing mice in both prophylactic and therapeutic challenge experiments. Overall, our data demonstrated that the B-cell epitope has a profound effect in orchestrating an efficacious antitumor immunity. Thus, a multi-epitope peptide vaccine encompassing cytotoxic T-lymphocytes, T-helper and B-cell epitopes represents a promising strategy in developing cancer vaccines with a preventive and therapeutic modality for the effective management of breast cancer.
A Highly Reliable Convolutional Neural Network Based Soft Tissue Sarcoma Metastasis Detection from Chest X-ray Images: A Retrospective Cohort Study
Authors: Wallner Christoph , Alam Mansoor , Drysch Marius , Wagner Johannes Maximilian , Sogorski Alexander , Dadras Mehran , von Glinski Maxi , Reinkemeier Felix , Becerikli Mustafa , Heute Christoph , Nicolas Volkmar , Lehnhardt Marcus , Behr Björn
Published: October 2021

Introduction: soft tissue sarcomas are a subset of malignant tumors that are relatively rare and make up 1% of all malignant tumors in adulthood. Due to the rarity of these tumors, there are significant differences in quality in the diagnosis and treatment of these tumors. One paramount aspect is the diagnosis of hematogenous metastases in the lungs. Guidelines recommend routine lung imaging by means of X-rays. With the ever advancing AI-based diagnostic support, there has so far been no implementation for sarcomas. The aim of the study was to utilize AI to obtain analyzes regarding metastasis on lung X-rays in the most possible sensitive and specific manner in sarcoma patients. Methods: a Python script was created and trained using a set of lung X-rays with sarcoma metastases from a high-volume German-speaking sarcoma center. 26 patients with lung metastasis were included. For all patients chest X-ray with corresponding lung CT scans, and histological biopsies were available. The number of trainable images were expanded to 600. In order to evaluate the biological sensitivity and specificity, the script was tested on lung X-rays with a lung CT as control. Results: in this study we present a new type of convolutional neural network-based system with a precision of 71.2%, specificity of 90.5%, sensitivity of 94%, recall of 94% and accuracy of 91.2%. A good detection of even small findings was determined. Discussion: the created script establishes the option to check lung X-rays for metastases at a safe level, especially given this rare tumor entity.
Synergistic Effects of Curcumin and Nano-Curcumin against Toxicity, Carcinogenicity, and Oxidative Stress Induced by Tartrazine at Normal and Cancer Cell Levels
Authors: El-Desoky Gaber E. , Wabaidur Saikh M. , Habila Mohamed A. , AlOthman Zeid A.
Published: October 2021

In this study, the cellular synergistic and antagonistic effects of mixing tartrazine (TZ) with curcumin (CUR) or curcumin-nanoparticles (CUR-NPs) were investigated. The in vivo administration of TZ, CUR, CUR-NPs, and TZ mixed with CUR or CUR-NPs at 75:25 or 50:50 ratios were tested. The results indicated that CUR and CUR -NPs reduced the cytotoxicity effects of TZ on skin fibroblast BJ-1 (ATCC® CRL-2522™) normal cells. However, among the tested materials, CUR-NPs had highest in vitro and in vivo antioxidant activity compared to TZ. Furthermore, CUR-NPs and CUR exhibited anticancer activity against HepG-2 liver cancer cells via apoptosis induction. The key apoptosis protein genes Caspase-3, p53, and Bax were upregulated, whereas Bc-2, which exhibits anti-apoptosis activity, was downregulated. Our results indicated that the nano-formulation of CUR alters its physicochemical properties, including the size and shape, and increases its antioxidant and anticancer properties. CUR-NPs also overcome the side effect of using TZ as a yellow color and food preservative additive, due to its reduced toxicity, oxidative stress, and carcinogenicity. In agreement with our previous findings, CUR and CUR-NPs were able to protect against cellular oxidative stress by stimulating endogenous antioxidant defense enzymes, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione-S-transferase (GST). We conclude that the nano-formulation of CUR exhibits economic benefits as a new strategy to use CUR as a food additive at the cellular level.
How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease
Authors: Habibe Jayron J. , Clemente-Olivo Maria P. , de Vries Carlie J.
Published: October 2021

Susceptibility to complex pathological conditions such as obesity, type 2 diabetes and cardiovascular disease is highly variable among individuals and arises from specific changes in gene expression in combination with external factors. The regulation of gene expression is determined by genetic variation (SNPs) and epigenetic marks that are influenced by environmental factors. Aging is a major risk factor for many multifactorial diseases and is increasingly associated with changes in DNA methylation, leading to differences in gene expression. Four and a half LIM domains 2 (FHL2) is a key regulator of intracellular signal transduction pathways and the FHL2 gene is consistently found as one of the top hyper-methylated genes upon aging. Remarkably, FHL2 expression increases with methylation. This was demonstrated in relevant metabolic tissues: white adipose tissue, pancreatic β-cells, and skeletal muscle. In this review, we provide an overview of the current knowledge on regulation of FHL2 by genetic variation and epigenetic DNA modification, and the potential consequences for age-related complex multifactorial diseases.
Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer
Authors: Wang Bin , Guo Hanfei , Xu Haiyang , Yu Hongquan , Chen Yong , Zhao Gang
Published: October 2021

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and has high morbidity and mortality rates. Central nervous system (CNS) metastasis is one of the most frequent complications in patients with NSCLC and seriously affects the quality of life (QOL) and overall survival (OS) of patients, with a median OS of untreated patients of only 1–3 months. There are various treatment methods for NSCLC CNS metastasis, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, which do not meet the requirements of patients in terms of improving OS and QOL. There are still many problems in the treatment of NSCLC CNS metastasis that need to be solved urgently. This review summarizes the research progress in the treatment of NSCLC CNS metastasis to provide a reference for clinical practice.
Nuclear Dynamics and Chromatin Structure: Implications for Pancreatic Cancer
Authors: Flores Luis F. , Tader Brooke R. , Tolosa Ezequiel J. , Sigafoos Ashley N. , Marks David L. , Fernandez-Zapico Martin E.
Published: October 2021

Changes in nuclear shape have been extensively associated with the dynamics and functionality of cancer cells. In most normal cells, nuclei have a regular ellipsoid shape and minimal variation in nuclear size; however, an irregular nuclear contour and abnormal nuclear size is often observed in cancer, including pancreatic cancer. Furthermore, alterations in nuclear morphology have become the ‘gold standard’ for tumor staging and grading. Beyond the utility of altered nuclear morphology as a diagnostic tool in cancer, the implications of altered nuclear structure for the biology and behavior of cancer cells are profound as changes in nuclear morphology could impact cellular responses to physical strain, adaptation during migration, chromatin organization, and gene expression. Here, we aim to highlight and discuss the factors that regulate nuclear dynamics and their implications for pancreatic cancer biology.
A Preliminary Study of the Treatment Outcomes of Paediatric Dental Patients Referred for General Anaesthesia or Sedation at a Regional Hospital in Trinidad
Authors: Percival Tricia , Bhagoutie Reshma
Published: October 2021

General anaesthesia and sedation are known to be useful adjuncts in the care of paediatric dental patients. There are several challenges that prevent patients from receiving care. Aim: To assess the treatment outcomes of paediatric dental patients seen at an emergency facility who were referred for treatment under sedation or general anaesthesia at a regional hospital in Trinidad. Methods: Records of patients seen at the Child Dental Health Unit Emergency clinic at the University of The West Indies Dental School from 2012 to 2017 were assessed. The parents of children referred for general anaesthesia or sedation at the regional hospital were then interviewed via telephone. Results: Most children (53.4%) were younger than 6 years old and the most common reasons for referral were the treatment of multiple carious teeth and behaviour management. Furthermore, 66.1% of cases did not receive treatment and had a mean waiting time of 4.7 years, and 61.7% of referred cases needed emergency care while awaiting general anaesthesia or sedation. Limited access to these services and the high cost of treatment were the main reasons for non-treatment. Conclusion: There is significant need for the timely treatment of paediatric dental patients referred for general anaesthesia or sedation. Improved availability and accessibility of these services could improve patients’ quality of life.
Constructions of Beyond-Birthday Secure PRFs from Random Permutations, Revisited
Authors: Nan Jiehui , Zhang Ping , Hu Honggang
Published: October 2021

In CRYPTO 2019, Chen et al. showed how to construct pseudorandom functions (PRFs) from random permutations (RPs), and they gave one beyond-birthday secure construction from sum of Even-Mansour, namely SoEM22 in the single-key setting. In this paper, we improve their work by proving the multi-key security of SoEM22, and further tweaking SoEM22 but still preserving beyond birthday bound (BBB) security. Furthermore, we use only one random permutation to construct parallelizable and succinct beyond-birthday secure PRFs in the multi-key setting, and then tweak this new construction. Moreover, with a slight modification of our constructions of tweakable PRFs, two parallelizable nonce based MACs for variable length messages are obtained.
Nationality as an Influential Variable with Regard to the Social Skills and Academic Success of Immigrant Students
Authors: Fernández-Leyva Christian , Tomé-Fernández María , Ortiz-Marcos José Manuel
Published: October 2021

This study aims to expand the existing scientific, theoretical and empirical knowledge about the influence of the variables age, gender, nationality and place of residence on the probability of developing social skills that generate social wellbeing, and, in addition, to identify the relationship between the most influential variable and the academic success of immigrant students. We hope that the educational community, in an intercultural context, can benefit from and apply this knowledge to assist immigrant students. In this study, a sample of n = 749 students aged between 12 and 18, of 41 different nationalities, is analyzed using the Social Skills Scale for Young Immigrants (SSSYI). Data analysis is performed with the SPSS and STATA statistical programs. Multiple linear regression (MLR) analyses verify that nationality is the most influential variable. In addition, when calculating the Pearson correlation, high and positive correlations are found between social skills, nationality and students’ grades, with which academic success was measured. In conclusion, we find that students who emigrated from the European continent present better social skills, better social wellbeing and greater academic success.
A Velocity Estimation Technique for a Monocular Camera Using mmWave FMCW Radars
Authors: Pandya Aarav , Jha Ajit , Cenkeramaddi Linga Reddy
Published: October 2021

Perception in terms of object detection, classification, and dynamic estimation (position and velocity) are fundamental functionalities that autonomous agents (unmanned ground vehicles, unmanned aerial vehicles, or robots) have to navigate safely and autonomously. To date, various sensors have been used individually or in combination to achieve this goal. In this paper, we present a novel method for leveraging millimeter wave radar’s (mmW radar’s) ability to accurately measure position and velocity in order to improve and optimize velocity estimation using a monocular camera (using optical flow) and machine learning techniques. The proposed method eliminates ambiguity in optical flow velocity estimation when the object of interest is at the edge of the frame or far away from the camera without requiring camera–radar calibration. Moreover, algorithms of various complexity were implemented using custom dataset, and each of them successfully detected the object and estimated its velocity accurately and independently of the object’s distance and location in frame. Here, we present a complete implementation of camera–mmW radar late feature fusion to improve the camera’s velocity estimation performance. It includes setup design, data acquisition, dataset development, and finally, implementing a lightweight ML model that successfully maps the mmW radar features to the camera, allowing it to perceive and estimate the dynamics of a target object without any calibration.
Autonomous Trajectory Planning and Control of Anti-Radiation Loitering Munitions under Uncertain Conditions
Authors: Bai Linyuan , Luo Hongchuan , Ling Haifeng
Published: October 2021

As an autonomous system, an anti-radiation loitering munition (LM) experiences uncertainty in both a priori and sensed information during loitering because it is difficult to accurately know target radar information in advance, and the sensing performance of the seeker is affected by disturbance and errors. If, as it does in the state of the art, uncertainties are ignored and the LM travels its planned route, its battle effectiveness will be severely restricted. To tackle this problem, this paper studies the method of autonomous planning and control of loitering routes using limited a priori information of target radar and real-time sensing results. We establish a motion and sensing model based on the characteristics of anti-radiation LMs and use particle filtering to iteratively infer the target radar information. Based on model predictive control, we select a loitering path to minimize the uncertainty of the target information, so as to achieve trajectory planning control that is conducive to the acquisition of target radar information. Simulation results show that the proposed method can effectively complete the autonomous trajectory planning and control of anti-radiation LMs under uncertain conditions.