bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretreatment Plasma IL-6 and YKL-40 and Overall Survival after Surgery for Metastatic Bone Disease of the Extremities
Authors: Sørensen Michala Skovlund , Colding-Rasmussen Thomas , Horstmann Peter Frederik , Hindsø Klaus , Dehlendorff Christian , Johansen Julia Sidenius , Petersen Michael Mørk
Published: June 2021

Background: Plasma IL-6 and YKL-40 are prognostic biomarkers for OS in patients with different types of solid tumors, but they have not been studied in patients before surgery of metastatic bone disease (MBD) of the extremities. The aim was to evaluate the prognostic value of plasma IL-6 and YKL-40 in patients undergoing surgery for MBD of the extremities. Patients and Methods: A prospective study included all patients undergoing surgery for MBD in the extremities at a tertiary referral center during the period 2014–2018. Preoperative blood samples from index surgery were included. IL-6 and YKL-40 concentrations in plasma were determined by commercial ELISA. A total of 232 patients (median age 66 years, IQR 58–74; female 51%) were included. Results: Cox regression analysis was performed to identify independent prognostic factors for OS. IL-6 correlated with YKL-40 (rho = 0.46, p < 0.01). In univariate analysis (log2 continuous variable) IL-6 (HR = 1.26, 95% CI 1.16–1.37), CRP (HR = 1.20, 95% CI 1.12–1.29) and YKL-40 (HR = 1.25, 95% CI 1.15–1.37) were associated with short OS. In multivariable analysis, adjusted for known risk factors for survival, only log2(IL-6) was independently associated with OS (HR = 1.24, 95% CI 1.08–1.43), whereas CRP and YKL-40 were not. Conclusion: High preoperative plasma IL-6 is an independent biomarker of short OS in patients undergoing surgery for MBD.
Trend Shifts in Age-Specific Incidence for In Situ and Invasive Cutaneous Melanoma in Sweden
Authors: Eriksson Hanna , Nielsen Kari , Vassilaki Ismini , Lapins Jan , Mikiver Rasmus , Lyth Johan , Isaksson Karolin
Published: June 2021

Background: The incidence of invasive cutaneous melanoma (CM) is increasing in Sweden. The aim was to present age- and sex-specific trends of the age-standardised incidence and the average annual percentage change (AAPC) for in situ and invasive CM. Methods: Joinpoint regression models were used to analyse data from the Swedish Cancer Register and the Swedish Melanoma Registry 1997–2018 (N = 35,350 in situ CM; 59,932 CM). Results: The AAPC of CM for women was 4.5 (4.1–5.0; p < 0.001) for the period 1997–2018. For men, the APCC was 4.2 (3.0–5.4; p < 0.001), with a significantly higher annual percentage change (APC) for the period 2000–2018 (5.0; 4.6–5.4; p < 0.001) compared to 1997–1999. An increasing annual incidence of CM ≤ 0.6 mm and 0.7 mm Breslow tumour thickness was found for men with a significant incidence shift for the period 2006–2015, respectively. Similarly for women, with a significantly higher APC for CM ≤ 0.6 mm from 2005. The incidence of intermediate thick CM (2.1–4.0 mm) has not increased since 2011. The incidence of CM > 4.0 mm has been increasing among both sexes, with a significantly lower APC among women from 2005. Conclusions: The incidence of in situ and low-risk CM ≤ 1.0 mm in tumour thickness has been rising among both sexes since the 2000s.
RAD51D Aberrant Splicing in Breast Cancer: Identification of Splicing Regulatory Elements and Minigene-Based Evaluation of 53 DNA Variants
Authors: Bueno-Martínez Elena , Sanoguera-Miralles Lara , Valenzuela-Palomo Alberto , Lorca Víctor , Gómez-Sanz Alicia , Carvalho Sara , Allen Jamie , Infante Mar , Pérez-Segura Pedro , Lázaro Conxi , Easton Douglas F. , Devilee Peter , Vreeswijk Maaike P. G. , de la Hoya Miguel , Velasco Eladio A.
Published: June 2021

RAD51D loss-of-function variants increase lifetime risk of breast and ovarian cancer. Splicing disruption is a frequent pathogenic mechanism associated with variants in susceptibility genes. Herein, we have assessed the splicing and clinical impact of splice-site and exonic splicing enhancer (ESE) variants identified through the study of ~113,000 women of the BRIDGES cohort. A RAD51D minigene with exons 2–9 was constructed in splicing vector pSAD. Eleven BRIDGES splice-site variants (selected by MaxEntScan) were introduced into the minigene by site-directed mutagenesis and tested in MCF-7 cells. The 11 variants disrupted splicing, collectively generating 25 different aberrant transcripts. All variants but one produced negligible levels (<3.4%) of the full-length (FL) transcript. In addition, ESE elements of the alternative exon 3 were mapped by testing four overlapping exonic microdeletions (≥30-bp), revealing an ESE-rich interval (c.202_235del) with critical sequences for exon 3 recognition that might have been affected by germline variants. Next, 26 BRIDGES variants and 16 artificial exon 3 single-nucleotide substitutions were also assayed. Thirty variants impaired splicing with variable amounts (0–65.1%) of the FL transcript, although only c.202G>A demonstrated a complete aberrant splicing pattern without the FL transcript. On the other hand, c.214T>C increased efficiency of exon 3 recognition, so only the FL transcript was detected (100%). In conclusion, 41 RAD51D spliceogenic variants (28 of which were from the BRIDGES cohort) were identified by minigene assays. We show that minigene-based mapping of ESEs is a powerful approach for identifying ESE hotspots and ESE-disrupting variants. Finally, we have classified nine variants as likely pathogenic according to ACMG/AMP-based guidelines, highlighting the complex relationship between splicing alterations and variant interpretation.
VDAC1 Silencing in Cancer Cells Leads to Metabolic Reprogramming That Modulates Tumor Microenvironment
Authors: Zerbib Erez , Arif Tasleem , Shteinfer-Kuzmine Anna , Chalifa-Caspi Vered , Shoshan-Barmatz Varda
Published: June 2021

The tumor microenvironment (TME) plays an important role in cell growth, proliferation, migration, immunity, malignant transformation, and apoptosis. Thus, better insight into tumor–host interactions is required. Most of these processes involve the metabolic reprogramming of cells. Here, we focused on this reprogramming in cancerous cells and its effect on the TME. A major limitation in the study of tumor–host interactions is the difficulty in separating cancerous from non-cancerous signaling pathways within a tumor. Our strategy involved specifically silencing the expression of VDAC1 in the mitochondria of human-derived A549 lung cancer xenografts in mice, but not in the mouse-derived cells of the TME. Next-generation sequencing (NGS) analysis allows distinguishing the human or mouse origin of genes, thus enabling the separation of the bidirectional cross-talk between the TME and malignant cells. We demonstrate that depleting VDAC1 in cancer cells led to metabolic reprogramming, tumor regression, and the disruption of tumor–host interactions. This was reflected in the altered expression of a battery of genes associated with TME, including those involved in extracellular matrix organization and structure, matrix-related peptidases, angiogenesis, intercellular interacting proteins, integrins, and growth factors associated with stromal activities. We show that metabolic rewiring upon mitochondrial VDAC1 silencing in cancer cells affected several components of the TME, such as structural protein matrix metalloproteinases and Lox, and elicited a stromal response resembling the reaction to a foreign body in wound healing. As tumor progression requires a cooperative interplay between the host and cancer cells, and the ECM is intensively remodeled during cancer progression, VDAC1 depletion induced metabolic reprogramming that targeted both tumor cells and resulted in the alteration of the whole spectrum of TME-related genes, affecting the reciprocal feedback between ECM molecules, host cells, and cancer cells. Thus, VDAC1 depletion using si-VDAC1 represents therapeutic potential, inhibiting cancer cell proliferation and also inducing the modulation of TME components, which influences cancer progression, migration, and invasion.
Asymmetric Catalytic Ketimine Mannich Reactions and Related Transformations
Authors: Xu Changgong , Reep Carlyn , Jarvis Jamielyn , Naumann Brandon , Captain Burjor , Takenaka Norito
Published: June 2021

The catalytic enantioselective ketimine Mannich and its related reactions provide direct access to chiral building blocks bearing an α-tertiary amine stereogenic center, a ubiquitous structural motif in nature. Although ketimines are often viewed as challenging electrophiles, various approaches/strategies to circumvent or overcome the adverse properties of ketimines have been developed for these transformations. This review showcases the selected examples that highlight the benefits and utilities of various ketimines and remaining challenges associated with them in the context of Mannich, allylation, and aza-Morita–Baylis–Hillman reactions as well as their variants.
Human Granulosa Cells—Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis
Authors: Dompe Claudia , Kulus Magdalena , Stefańska Katarzyna , Kranc Wiesława , Chermuła Błażej , Bryl Rut , Pieńkowski Wojciech , Nawrocki Mariusz J. , Petitte James N. , Stelmach Bogusława , Mozdziak Paul , Jeseta Michal , Pawelczyk Leszek , Jaśkowski Jędrzej M. , Piotrowska-Kempisty Hanna , Spaczyński Robert Z. , Nowicki Michał , Kempisty Bartosz
Published: June 2021

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte’s proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine.
Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells
Authors: Bhattarai Niina , Korhonen Eveliina , Mysore Yashavanthi , Kaarniranta Kai , Kauppinen Anu
Published: June 2021

Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette tar component hydroquinone causes oxidative stress in human RPE cells. In the present study, we investigated the propensity of hydroquinone to induce the secretion of interleukin (IL)-1β and IL-18. The activation of these cytokines is usually regulated by the Nucleotide-binding domain, Leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome. ARPE-19 cells were exposed to hydroquinone, and cell viability was monitored using the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt (MTT) assays. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of proinflammatory cytokines IL-1β and IL-18 as well as NLRP3, caspase-1, and poly (ADP-ribose) polymerase (PARP). Hydroquinone did not change IL-1β release but significantly increased the secretion of IL-18. Cytoplasmic NLRP3 levels increased after the hydroquinone treatment of IL-1α-primed RPE cells, but IL-18 was equally released from primed and nonprimed cells. Hydroquinone reduced the intracellular levels of PARP, which were restored by treatment with the ROS scavenger N-acetyl-cysteine (NAC). NAC concurrently reduced the NLRP3 levels but had no effect on IL-18 release. In contrast, the NADPH oxidase inhibitor ammonium pyrrolidinedithiocarbamate (APDC) reduced the release of IL-18 but had no effect on the NLRP3 levels. Collectively, hydroquinone caused DNA damage seen as reduced intracellular PARP levels and induced NLRP3-independent IL-18 secretion in human RPE cells.
Post-Effort Changes in Autophagy- and Inflammation-Related Gene Expression in White Blood Cells of Healthy Young Men
Authors: Kostrzewa-Nowak Dorota , Trzeciak-Ryczek Alicja , Wityk Paweł , Cembrowska-Lech Danuta , Nowak Robert
Published: June 2021

Acute, strenuous physical exertion requiring high levels of energy production induces the production of reactive oxygen species and metabolic disturbances that can damage the mitochondria. Thus, selective autophagic elimination of defective mitochondria may improve resistance to oxidative stress and potentially to inflammation. The main goal of this study was to evaluate the impacts of intense effort on changes in the expression of select genes related to post-effort inflammation and autophagy. Thirty-five men aged 16–21 years were recruited to the study. The impacts of both aerobic (endurance) and anaerobic (speed) efforts on selected genes encoding chemokines (CXCL5, 8–12) were analyzed. Significant increases in the expression of all studied genes excluding CXCL12 were observed. Moreover, both types of effort induced an increase in the expression of genes encoding IL-2, -4, -6, -10, IFN-γ and TNF-α, excluding IL-17A. Generally, these efforts caused a significant increase in the relative expression of apoptosis- (BCL2 and BAX) and autophagy- (BNIP3, BECN1, MAP1LC3B, ATG5, ATG7, ATG12, ATG16L1 and SQSTM1) related genes. It seems that the duration of physical activity and its bioenergetic cost has an important impact on the degree of increase in expression of this panel of autophagy-related genes. Anaerobic effort is more strenuous than aerobic effort and requires a higher bioenergetic investment. This may explain the stronger impact of anaerobic effort on the expression of the studied genes. This observation seems to support the protective role of autophagy proposed in prior studies.
NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications
Authors: Siemaszko Jagoda , Marzec-Przyszlak Aleksandra , Bogunia-Kubik Katarzyna
Published: June 2021

Natural Killer (NK) cells are natural cytotoxic, effector cells of the innate immune system. They can recognize transformed or infected cells. NK cells are armed with a set of activating and inhibitory receptors which are able to bind to their ligands on target cells. The right balance between expression and activation of those receptors is fundamental for the proper functionality of NK cells. One of the best known activating receptors is NKG2D, a member of the CD94/NKG2 family. Due to a specific NKG2D binding with its eight different ligands, which are overexpressed in transformed, infected and stressed cells, NK cells are able to recognize and attack their targets. The NKG2D receptor has an enormous significance in various, autoimmune diseases, viral and bacterial infections as well as for transplantation outcomes and complications. This review focuses on the NKG2D receptor, the mechanism of its action, clinical relevance of its gene polymorphisms and a potential application in various clinical settings.
Growth of Defect-Induced Carbon Nanotubes for Low-Temperature Fruit Monitoring Sensor
Authors: Shaalan Nagih M. , Saber Osama , Ahmed Faheem , Aljaafari Abdullah , Kumar Shalendra
Published: June 2021

Herein, a carbon nanotubes-based sensor has been grown for the purpose of ethylene detection. The prepared CNTs had a crystalline structure with a smooth surface of 11.0 nm in diameter and 10.0 µm in length. The low-intensity graphite peak (G-band) as compared to the peak of the defect (D-band) characterizes the defects in the CNTs. An MWNTs-gas sensor was fabricated for monitoring the ethylene gas. The highest response was recorded at a low operating temperature of 30 °C. The sensor was also examined at 300 ppb up to 10 ppm and it showed a response of 2% up to 28%. The sensor response and recovery time constants were varied from 60 to 300 s, depending on the gas concentration. The results that were obtained for the synthetic ethylene gas were also compared with the real measurements for banana ripening. The results confirmed that the sensor is appropriate for the monitoring of fruit ripening.
Change of Internet Use and Bedtime among Junior High School Students after Long-Term School Closure Due to the Coronavirus Disease 2019 Pandemic
Authors: Nakayama Hideki , Matsuzaki Takanobu , Mihara Satoko , Kitayuguchi Takashi , Higuchi Susumu
Published: June 2021

Most schools in Japan were closed in spring 2020 due to the novel coronavirus disease 2019 (COVID-19) pandemic. We investigated lifestyle and internet use among junior high school students across eight schools after long-term school closure and compared the data with those we obtained from previous surveys. In the summers of 2018, 2019, and 2020, we conducted questionnaire surveys on seventh-grade students from the same schools. In total, 2270 participants were analyzed. All questionnaires included items regarding background, bedtime, and internet use. The participants of the 2020 survey had significantly less sleepiness during classes and longer internet use times compared with those of the previous surveys. In the 2020 survey, the rate of problematic internet use (Young’s Diagnostic Questionnaire score, ≥5) was not significantly different from the results of previous surveys. The COVID-19 pandemic might have strongly influenced the sleepiness experienced by students in classes and increased the time spent using the internet since the summer of 2020. Our results indicate the need for attempts to encourage students to improve their sleep habits and moderate their media use.
Water Quality Threats, Perceptions of Climate Change and Behavioral Responses among Farmers in the Ethiopian Rift Valley
Authors: Godebo Tewodros R. , Jeuland Marc A. , Paul Christopher J. , Belachew Dagnachew L. , McCornick Peter G.
Published: June 2021

This work aims to assess water quality for irrigated agriculture, alongside perceptions and adaptations of farmers to climate change in the Main Ethiopian Rift (MER). Climate change is expected to cause a rise in temperature and variability in rainfall in the region, reducing surface water availability and raising dependence on groundwater. The study data come from surveys with 147 farmers living in the Ziway–Shala basin and water quality assessments of 162 samples from groundwater wells and surface water. Most groundwater samples were found to be unsuitable for long term agricultural use due to their high salinity and sodium adsorption ratio, which has implications for soil permeability, as well as elevated bicarbonate, boron and residual sodium carbonate concentrations. The survey data indicate that water sufficiency is a major concern for farmers that leads to frequent crop failures, especially due to erratic and insufficient rainfall. An important adaptation mechanism for farmers is the use of improved crop varieties, but major barriers to adaptation include a lack of access to irrigation water, credit or savings, appropriate seeds, and knowledge or information on weather and climate conditions. Local (development) agents are identified as vital to enhancing farmers’ knowledge of risks and solutions, and extension programs must therefore continue to promote resilience and adaptation in the area. Unfortunately, much of the MER groundwater that could be used to cope with declining viability of rainfed agriculture and surface water availability, is poor in quality. The use of saline groundwater could jeopardize the agricultural sector, and most notably commercial horticulture and floriculture activities. This study highlights the complex nexus of water quality and sufficiency challenges facing the agriculture sector in the region, and should help decision-makers to design feasible strategies for enhancing adaptation and food security.
Thermal Spray Multilayer Ceramic Structures with Potential for Solid Oxide Cell Applications
Authors: Vardavoulias Michail , Gkomoza Paraskevi , Arkas Michael , Niakolas Dimitrios K. , Neophytides Stylianos G.
Published: June 2021

The objective of this paper is to manufacture free-standing solid oxide cells (SOCs) through the atmospheric plasma spray process (APS), without the aid of a metallic support nor the need for a post-process heating treatment. A five-layered cell was fabricated. Fused and crushed yttria-stabilized zirconia (YSZ) powder in the 5–22 μm particle size range was used in order to achieve a dense electrolyte layer, yet still permitting satisfactory ionic diffusivity. Nickel oxide (NiO) powder that was obtained by in-house flame spray (FS) oxidation of pure nickel (Ni) powder was mixed and sprayed with the original Ni-YSZ feedstock, so as to increase the porosity content in the supporting electrode. Two transition layers were sprayed, the first between the support electrode and the electrolyte (25% (Ni/NiO)–75% YSZ) and the second at the electrolyte and the end electrode interface (50% YSZ–50% lanthanum strontium manganite (LSM)). The purpose of intercalation of these transition layers was to facilitate the ionic motion and also to eliminate thermal expansion mismatches. All the as-sprayed layers were separately tested by an in-house developed acetone permeability comparative test (APCT). Electrodes with adequate porosity (25–30%) were obtained. Concerning electrolytes, relatively thick (150–200 µm) layers derived from fused and crushed YSZ were found to be impermeable to acetone, while thinner YSZ counterparts of less than 100 µm showed a low degree of permeability, which was attributed mostly to existent microcracks and insufficient interparticle cohesion, rather than to interconnected porosity.
Numerical Simulation of Heat Mass Transfer Effects on MHD Flow of Williamson Nanofluid by a Stretching Surface with Thermal Conductivity and Variable Thickness
Authors: Islam Saeed , Ur Rasheed Haroon , Nisar Kottakkaran Sooppy , Alshehri Nawal A. , Zakarya Mohammed
Published: June 2021

The current analysis deals with radiative aspects of magnetohydrodynamic boundary layer flow with heat mass transfer features on electrically conductive Williamson nanofluid by a stretching surface. The impact of variable thickness and thermal conductivity characteristics in view of melting heat flow are examined. The mathematical formulation of Williamson nanofluid flow is based on boundary layer theory pioneered by Prandtl. The boundary layer nanofluid flow idea yields a constitutive flow laws of partial differential equations (PDEs) are made dimensionless and then reduce to ordinary nonlinear differential equations (ODEs) versus transformation technique. A built-in numerical algorithm bvp4c in Mathematica software is employed for nonlinear systems computation. Considerable features of dimensionless parameters are reviewed via graphical description. A comparison with another homotopic approach (HAM) as a limiting case and an excellent agreement perceived.
Geographic Patterns of Genetic Variation among Cacao (Theobroma cacao L.) Populations Based on Chloroplast Markers
Authors: Nieves-Orduña Helmuth Edisson , Müller Markus , Krutovsky Konstantin V. , Gailing Oliver
Published: June 2021

The cacao tree (Theobroma cacao L.) is native to the Amazon basin and widely cultivated in the tropics to produce seeds, the valuable raw material for the chocolate industry. Conservation of cacao genetic resources and their availability for breeding and production programs are vital for securing cacao supply. However, relatively little is still known about the phylogeographic structure of natural cacao populations. We studied the geographic distribution of cpDNA variation in different populations representing natural cacao stands, cacao farms in Ecuador, and breeding populations. We used six earlier published cacao chloroplast microsatellite markers to genotype 233 cacao samples. In total, 23 chloroplast haplotypes were identified. The highest variation of haplotypes was observed in western Amazonia including geographically restricted haplotypes. Two observed haplotypes were widespread across the Amazon basin suggesting long distance seed dispersal from west to east in Amazonia. Most cacao genetic groups identified earlier using nuclear SSRs are associated with specific chloroplast haplotypes. A single haplotype was common in selections representing cacao plantations in west Ecuador and reference Trinitario accessions. Our results can be used to determine the chloroplast diversity of accessions and in combination with phenotypic assessments can help to select geographically distinctive varieties for cacao breeding programs.
Lung Cancer Screening with Low-Dose CT in Smokers: A Systematic Review and Meta-Analysis
Authors: Hunger Theresa , Wanka-Pail Eva , Brix Gunnar , Griebel Jürgen
Published: June 2021

Lung cancer continues to be one of the main causes of cancer death in Europe. Low-dose computed tomography (LDCT) has shown high potential for screening of lung cancer in smokers, most recently in two European trials. The aim of this review was to assess lung cancer screening of smokers by LDCT with respect to clinical effectiveness, radiological procedures, quality of life, and changes in smoking behavior. We searched electronic databases in April 2020 for publications of randomized controlled trials (RCT) reporting on lung cancer and overall mortality, lung cancer morbidity, and harms of LDCT screening. A meta-analysis was performed to estimate effects on mortality. Forty-three publications on 10 RCTs were included. The meta-analysis of eight studies showed a statistically significant relative reduction of lung cancer mortality of 12% in the screening group (risk ratio = 0.88; 95% CI: 0.79–0.97). Between 4% and 24% of screening-LDCT scans were classified as positive, and 84–96% of them turned out to be false positive. The risk of overdiagnosis was estimated between 19% and 69% of diagnosed lung cancers. Lung cancer screening can reduce disease-specific mortality in (former) smokers when stringent requirements and quality standards for performance are met.
Expression of Neurokinin B Receptor in the Gingival Squamous Cell Carcinoma Bone Microenvironment
Authors: Yoshida Shoko , Shimo Tsuyoshi , Takabatake Kiyofumi , Murase Yurika , Obata Kyoichi , Okui Tatsuo , Kunisada Yuki , Ibaragi Soichiro , Nagatsuka Hitoshi , Sasaki Akira
Published: June 2021

Gingival squamous cell carcinoma (SCC) frequently invades the maxillary or mandibular bone, and bone destruction is known as a key prognostic factor in gingival SCCs. Recently, Neurokinin 3 receptor (NK-3R), the receptor ligand for NK-3, which is a member of the tachykinin family expressed in the central nervous system, was identified through pathway analysis as a molecule expressed in osteoclasts induced by the hedgehog signal. Although the expression of NK-3R has been detected in osteoclast and SCC cells at the bone invasion front, the relationship between NK-3R expression and the prognosis of gingival SCC patients remains unclear. In the present study, we retrospectively reviewed 27 patients with gingival SCC who had undergone surgery with curative intent. Significantly higher NK-3R expression in tumor cells was found in a case of jawbone invasion than in a case of exophytic poor jawbone invasion. On the other hand, no significant association was observed between NK-3R tumor-positive cases and tumor size, TNM stage, or tumor differentiation. The survival rate tended to be lower in NK-3R tumor-positive cases, but not significantly. However, the disease-specific survival rate was significantly lower in patients with a large number of NK-3R-positive osteoclasts than in those with a small number of them at the tumor bone invasion front. Our results suggest that NK-3R signaling in the gingival SCC bone microenvironment plays an important role in tumor bone destruction and should be considered a potential therapeutic target in advanced gingival SCC with bone destruction.
Somatostatin Receptor Subtype Expression in Patients with Acromegaly and Complicated Clinical Course
Authors: Pichler Robert , Kalev Ognian , Tomancok Berndt , Sonnberger Michael , Ehrlich Daniela , Hodolic Marina
Published: June 2021

Somatostatin analogues are considered to be the first line of treatment in acromegaly. Somatostatin analogues of the first generation mainly target the somatostatin receptor (SSTR) subtype 2 and have been proven efficient in the majority of patients with acromegaly. Pasireotide was the first somatostatin analogue also substantially targeting the SSTR subtype 5. An efficient drug for Cushing’s disease tailored to suboptimal-responding patients with acromegaly then became available. We immunohistochemically investigated SSTR subtypes expression in pituitary adenomas from operated acromegaly patients with clinical relapse and a complicated clinical course. Patients received pasireotide in the course of their disease. The predictive value of SSTR subtypes immunhistochemical analysis for the therapeutic response is discussed.
Research on a Rice Counting Algorithm Based on an Improved MCNN and a Density Map
Authors: Feng Ao , Li Hongxiang , Liu Zixi , Luo Yuanjiang , Pu Haibo , Lin Bin , Liu Tao
Published: June 2021

The thousand grain weight is an index of size, fullness and quality in crop seed detection and is an important basis for field yield prediction. To detect the thousand grain weight of rice requires the accurate counting of rice. We collected a total of 5670 images of three different types of rice seeds with different qualities to construct a model. Considering the different shapes of different types of rice, this study used an adaptive Gaussian kernel to convolve with the rice coordinate function to obtain a more accurate density map, which was used as an important basis for determining the results of subsequent experiments. A Multi-Column Convolutional Neural Network was used to extract the features of different sizes of rice, and the features were fused by the fusion network to learn the mapping relationship from the original map features to the density map features. An advanced prior step was added to the original algorithm to estimate the density level of the image, which weakened the effect of the rice adhesion condition on the counting results. Extensive comparison experiments show that the proposed method is more accurate than the original MCNN algorithm.
Interactive Feedback for Learning Mathematics in a Digital Learning Environment
Authors: Barana Alice , Marchisio Marina , Sacchet Matteo
Published: June 2021

The COVID-19 pandemic has evidenced a need for tools and methodologies to support students’ autonomous learning and the formative assessment practices in distance education contexts, especially for students from challenging backgrounds. This paper proposes a conceptualization of Interactive Feedback (IF) for Mathematics, which is a step-by-step interactive process that guides the learner in the resolution of a task after one or more autonomous tentative. This conceptualization is grounded on theories and models of automatic assessment, formative assessment, and feedback. We discuss the effectiveness of the IF for engaging students from low socio-economic contexts in closing the gap between current and reference performance through a didactic experimentation involving 299 Italian students in grade 8. Using quantitative analyses on data from the automatic assessment, we compared the results of the first and last attempts in activities with and without IF, based on algorithmic parameters so that the task changes at every attempt. We found that IF was more effective than other kinds of activities to engage learners in actions aimed at improving their results, and the effects are stronger in low socio-economic contexts.
Child-Centred Teaching: Helping Each Child to Reach Their Full Potential
Authors: Nicholas Maria , Rouse Elizabeth , Paatsch Louise
Published: June 2021

Research has shown that schoolteachers often prepare children for success in standardized reading assessments by ‘teaching to the test.’ Concurrently, research exploring children’s emergent literacies and ‘school readiness’ has shown that early childhood teachers often feel pressured to ‘prepare’ children for school and may do so by focusing on print-related literacies, to the detriment of earlier stages of the oral-to-print continuum. This raises the concern that teaching children as a group, preparing them for the next ‘stage of education,’ will disadvantage children who are working below or above expected levels of development. Our study explores the teaching approaches used with a group of foundation-year children who achieved more advanced reading outcomes than children from four adjacent classrooms in their first year of schooling. We collected the reading and letter-identification outcomes of 16 children in the teacher’s foundation-year class and interviewed her about her practices. Findings showed that the teacher used her knowledge of what the children should achieve in standardized assessments as a minimum expectation and moved beyond the content of such assessments when warranted, as determined by informal assessments. As a result, every child in the class met, and many exceeded, minimum reading standards by year’s end. We conclude that using an individualized, child-centred pedagogy, informed by a combination of standardized and informal assessments, allowed the teacher to support her students to develop a range of reading abilities and to reach their full potential.
Behavioral Analysis and Immunity Design of the RO-Based TRNG under Electromagnetic Interference
Authors: Zhang Zhiwen , Su Tao
Published: June 2021

True random-number generators based on ring oscillators (RO-based TRNG) are widely used in the field of information encryption because of their simple structure and compatibility with CMOS technology. However, radiated or conducted electromagnetic interference can dramatically deteriorate the randomness of the output bitstream of the RO-based TRNG, which poses a great threat to security. Traditional research focuses on the innovation of the means of attack and the detection of circuit states. There is a lack of research on the interference mechanism and anti-interference countermeasures. In this paper, the response of the RO array to electromagnetic interference was analyzed, and the concept of synchronous locking was proposed to describe the locking scene of multiple ROs. On the basis of synchronous locking, the RF immunity of the RO-based TRNG was modeled, which can explain the degradation mechanism of bitstream randomness under RFI. Moreover, the design method of gate-delay differentiation is presented to improve the RF immunity of the RO-based TRNG at a low cost. Both transistor-level simulation and board-level measurement proved the rationality of this scheme.
Automatic Identification Algorithm of Equivalent Electrochemical Circuit Based on Electroscopic Impedance Data for a Lead Acid Battery
Authors: Olarte Javier , Martínez de Ilarduya Jaione , Zulueta Ekaitz , Ferret Raquel , Fernández-Gámiz Unai , Lopez-Guede Jose Manuel
Published: June 2021

Obtaining tools to analyze and predict the performance of batteries is a non-trivial challenge because it involves non-destructive evaluation procedures. At the research level, the development of sensors to allow cell-level monitoring is an innovative path, and electrochemical impedance spectrometry (EIS) has been identified as one of the most promising tools, as is the generation of advanced multivariable models that integrate environmental and internal-battery information. In this article, we describe an algorithm that automatically identifies a battery-equivalent electrochemical model based on electroscopic impedance data. This algorithm allows in operando monitoring of variations in the equivalent circuit parameters that will be used to further estimate variations in the state of health (SoH) and state of charge (SoC) of the battery based on a correlation with experimental aging data corresponding to states of failure or degradation. In the current work, the authors propose a two-step parameter identification algorithm. The first consists of a rough differential evolution algorithm-based identification. The second is based on the Nelder–Mead Simplex search method, which gives a fine parameter estimation. These algorithm results were compared with those of the commercially available Z-view, an equivalent circuit tool estimation that requires expert human input.
New Indirect Tire Pressure Monitoring System Enabled by Adaptive Extended Kalman Filtering of Vehicle Suspension Systems
Authors: Lee Dong-Hoon , Yoon Dal-Seong , Kim Gi-Woo
Published: June 2021

This paper presents a new indirect tire pressure monitoring system (TPMS) based on adaptive extended Kalman filtering with unknown input (AEKF-UI) estimation of vehicle suspension systems. The suggested methodology is based on the explicit correlation between tire pressure and tire stiffness and is available in real time. AEKF-UI is used to simultaneously estimate the time-varying parameter (tire stiffness) of vehicle suspension systems and the road roughness using an unknown input estimator. Simulation studies demonstrate that the proposed algorithm can simultaneously estimate tire stiffness (i.e., tire inflation pressure) variation and unknown road roughness input. The feasibility and effectiveness of the proposed estimation algorithm are verified through a laboratory-level experiment. This study offers a potential application for an alternative indirect TPMS and the estimation of unknown road roughness used for automotive controller design.
AutoCoach: An Intelligent Driver Behavior Feedback Agent with Personality-Based Driver Models
Authors: Marafie Zahraa , Lin Kwei-Jay , Wang Daben , Lyu Haoyu , Liu Yanan , Meng Yu , Ma Jiaao
Published: June 2021

Nowadays, AI has many applications in everyday human activities such as exercise, eating, sleeping, and automobile driving. Tech companies can apply AI to identify individual behaviors (e.g., walking, eating, driving), analyze them, and offer personalized feedback to help individuals make improvements accordingly. While offering personalized feedback is more beneficial for drivers, most smart driver systems in the current market do not use it. This paper presents AutoCoach, an intelligent AI agent that classifies drivers’ into different driving-personality groups to offer personalized feedback. We have built a cloud-based Android application to collect, analyze and learn from a driver’s past driving data to provide personalized, constructive feedback accordingly. Our GUI interface provides real-time user feedback for both warnings and rewards for the driver. We have conducted an on-the-road pilot user study. We conducted a pilot study where drivers were asked to use different agent versions to compare personality-based feedback versus non-personality-based feedback. The study result proves our design’s feasibility and effectiveness in improving the user experience when using a personality-based driving agent, with 61% overall acceptance that it is more accurate than non-personality-based.
Wash Analyses of Flexible and Wearable Printed Circuits for E-Textiles and Their Prediction of Damages
Authors: Zaman Shahood uz , Tao Xuyuan , Cochrane Cédric , Koncar Vladan
Published: June 2021

The development of specific user-based wearable smart textiles is gaining interest. The reliability and washability of e-textiles, especially electronic-based components of e-textiles, are under particular investigation nowadays. This is because e-textiles cannot be washed like normal textile products and washing electronic products is not common practice in our daily life. To adopt the e-textile products in our daily life, new standards, based on product usage, should be developed especially for flexibility and washability. The wearable motherboards are the main component for e-textile systems. They should be washing reliable and flexible for better adoption in the system. In this manuscript, flexible wearable PCBs were prepared with different conductive track widths and protected with silicone coatings. The samples were washed for 50 washing cycles in the household washing machine, and provoked damages were investigated. The PCBs were also investigated for bending tests (simulating mechanical stresses in the washing machine), and resultant damages were discussed and co-related with washing damages. The bending test was performed by bending the FPCBs at 90° over the circular rod and under the known hanging load.
Performance Tradeoff Analysis of Hybrid Signaling SWIPT Systems with Nonlinear Power Amplifiers
Authors: Chen Linlin , Wu Xiaofang , Wang Xin , Qi Wen , Hong Xuemin , Shi Jianghong , Hu Jie , Yang Kun
Published: June 2021

Simultaneous wireless information and power transfer (SWIPT) is a promising technology to achieve wide-area energy transfer by sharing the same radio frequency (RF) signal and infrastructure of legacy wireless communication systems. To enlarge the effective range of energy transfer in practice, it is desirable to have a hybrid signaling SWIPT scheme, which combines a high-power multitone energy signal with a low-power broadband information signal. This paper presents a systematic study on the performance of hybrid signaling SWIPT systems with memoryless nonlinear transmitter power amplifiers (PAs). Using PA efficiency and signal-to-noise-and-distortion ratio (SNDR) as the metrics to measure the efficiency of energy transfer and information transmission, respectively, we derive the tradeoff between these two metrics for two PA classes, two nonlinear PA models, and two SNDR definitions. Our results reveal insights into the fundamental performance tradeoff inherent in SWIPT systems using hybrid signaling schemes.
Comparative Chloroplast Genomics of Litsea Lam. (Lauraceae) and Its Phylogenetic Implications
Authors: Zhang Yunyan , Tian Yongjing , Tng David Y. P. , Zhou Jingbo , Zhang Yuntian , Wang Zhengwei , Li Pengfu , Wang Zhongsheng
Published: June 2021

Litsea Lam. is an ecological and economic important genus of the “core Lauraceae” group in the Lauraceae. The few studies to date on the comparative chloroplast genomics and phylogenomics of Litsea have been conducted as part of other studies on the Lauraceae. Here, we sequenced the whole chloroplast genome sequence of Litsea auriculata, an endangered tree endemic to eastern China, and compared this with previously published chloroplast genome sequences of 11 other Litsea species. The chloroplast genomes of the 12 Litsea species ranged from 152,132 (L. szemaois) to 154,011 bp (L. garrettii) and exhibited a typical quadripartite structure with conserved genome arrangement and content, with length variations in the inverted repeat regions (IRs). No codon usage preferences were detected within the 30 codons used in the chloroplast genomes, indicating a conserved evolution model for the genus. Ten intergenic spacers (psbE–petL, trnH–psbA, petA–psbJ, ndhF–rpl32, ycf4–cemA, rpl32–trnL, ndhG–ndhI, psbC–trnS, trnE–trnT, and psbM–trnD) and five protein coding genes (ndhD, matK, ccsA, ycf1, and ndhF) were identified as divergence hotspot regions and DNA barcodes of Litsea species. In total, 876 chloroplast microsatellites were located within the 12 chloroplast genomes. Phylogenetic analyses conducted using the 51 additional complete chloroplast genomes of “core Lauraceae” species demonstrated that the 12 Litsea species grouped into four sub-clades within the Laurus-Neolitsea clade, and that Litsea is polyphyletic and closely related to the genera Lindera and Laurus. Our phylogeny strongly supported the monophyly of the following three clades (Laurus–Neolitsea, Cinnamomum–Ocotea, and Machilus–Persea) among the above investigated “core Lauraceae” species. Overall, our study highlighted the taxonomic utility of chloroplast genomes in Litsea, and the genetic markers identified here will facilitate future studies on the evolution, conservation, population genetics, and phylogeography of L. auriculata and other Litsea species.
MaxEnt Modeling Based on CMIP6 Models to Project Potential Suitable Zones for Cunninghamia lanceolata in China
Authors: Zhou Yichen , Zhang Zengxin , Zhu Bin , Cheng Xuefei , Yang Liu , Gao Mingkun , Kong Rui
Published: June 2021

Cunninghamia lanceolata (Lamb.) Hook. (Chinese fir) is one of the main timber species in Southern China, which has a wide planting range that accounts for 25% of the overall afforested area. Moreover, it plays a critical role in soil and water conservation; however, its suitability is subject to climate change. For this study, the appropriate distribution area of C. lanceolata was analyzed using the MaxEnt model based on CMIP6 data, spanning 2041–2060. The results revealed that (1) the minimum temperature of the coldest month (bio6), and the mean diurnal range (bio2) were the most important environmental variables that affected the distribution of C. lanceolata; (2) the currently suitable areas of C. lanceolata were primarily distributed along the southern coastal areas of China, of which 55% were moderately so, while only 18% were highly suitable; (3) the projected suitable area of C. lanceolata would likely expand based on the BCC-CSM2-MR, CanESM5, and MRI-ESM2-0 under different SSPs spanning 2041–2060. The increased area estimated for the future ranged from 0.18 to 0.29 million km2, where the total suitable area of C. lanceolata attained a maximum value of 2.50 million km2 under the SSP3-7.0 scenario, with a lowest value of 2.39 million km2 under the SSP5-8.5 scenario; (4) in combination with land use and farmland protection policies of China, it is estimated that more than 60% of suitable land area could be utilized for C. lanceolata planting from 2041–2060 under different SSP scenarios. Although climate change is having an increasing influence on species distribution, the deleterious impacts of anthropogenic activities cannot be ignored. In the future, further attention should be paid to the investigation of species distribution under the combined impacts of climate change and human activities.