bluuebunny/crossref_metadata_2025 huggingface dataset:
Design Method for Reinforced Concrete Based on Bond-Slip Energy Consumption
Authors: Yang Jianhui , Yang Nianxu , Lin Xinyan , Wang Shuren , Cosgrove Tom , Hughes Peter
Published: November 2022

To reveal the energy consumption characteristics of a steel bar and all-lightweight shale ceramsite concrete (ALWSCC), focusing on hot rolled crescent ribbed bars (CRB) and hot rolled plain steel bars (PSB), a series of pull-out tests were carried out. The bonding failure modes, the contribution of the ribs to bond-slip failure and the energy consumption characteristics were analyzed based on the curves of pull-out load F-slip displacement S and energy consumption W–slip displacement S. Results show that the splitting failure is the main failure of the CRB specimen, and the pulling out failure is the main failure of the PSB one. The ratio of the total energy dissipation of splitting failure to that of the pulling out failure is less than 30%. The mechanical bite force between CRB and concrete contributes more than 95% to the bond strength. The pull-out force is divided into four stages, such as the chemical adhesive force stage (elastic and micro-elastic strain stage), the common-effect stage of mechanical bearing force and static frictional force (plastic development stage), and the frictional force stage (crushed stage). The new design is proposed to guarantee the ductility of the reinforced concrete structure, which is based on the bond-slip energy consumption rather than the traditional strength design. The conclusions provide a reference to the reinforced concrete practice.
Effect of Iron Phase on the Formation of Barium Calcium Sulphoaluminate Clinker
Authors: Zhang Bingxin , Zhang Ping , Chang Jun , Li Li
Published: November 2022

In this paper, analytically pure chemical reagents, as raw materials, were fired in barium calcium sulfoaluminate cement clinker. The effect of the iron phase on the calcination of barium calcium sulfoaluminate cement clinker was studied. The content of f-CaO in the sample was determined using the ethylene glycol method. The raw meal’s heat absorption and heat release were tested with an integrated thermal analyzer TG-DSC, and XRD and SEM measurements were used to characterize the composition and microstructure of the clinker. The results showed that the iron phase could lower the decomposition temperature of the calcium carbonate. When the calcination temperature increased, the lattice spacing of the mineral changed. The XRD pattern showed that a substitution reaction had occurred. Ba2+ replaced Ca2+ and formed a sulfoaluminate barium calcium mineral. The SEM images showed hexagonal plates or dodecahedral barium calcium sulfoaluminate minerals.
Study on the Effect of Finger Joints on the Stiffness of Fibre-Managed E. nitens Sawn Boards
Authors: Hou Jian , Taoum Assaad , Kotlarewski Nathan , Nolan Gregory
Published: November 2022

Fibre-managed E. nitens has the potential to be used as a feedstock for engineered wood products. This resource, however, has a number of strength-reducing features that need to be removed, and the board needs to be re-joint to be useful in greater lengths for timber construction. A common jointing practice is finger jointing. The suitability of the finger jointing technique for this species is crucial to the mechanical properties of the final product. This study was conducted to explore the influence of finger jointing on the stiffness of sawn boards. A strict manufacturing process of docking and re-joining timber boards in the same location without removing strength-reducing features was conducted to compare the stiffness parameters before and after finger jointing with bending tests. A statistical analysis was conducted. The results showed that the frequency of finger joints along the board did not significantly impact the edgewise stiffness; however, the average flatwise stiffness of the samples with more finger joints was improved slightly. A 10% increase in the end pressure reduced the tip gap significantly but did not influence the stiffness. The finger joint efficiency was 0.824 for the edgewise stiffness of the samples and 1.034 for flatwise stiffness of the jointed sections.
Optimized Preparation of Porous Coal Gangue-Based Geopolymer and Quantitative Analysis of Pore Structure
Authors: Wang Rui , Wang Jingsong , Song Qingchun
Published: November 2022

The purpose of study is to optimize the preparation of porous coal gangue-based geopolymer and quantitatively analyze its pore structure to establish the relationship between pore structure and mechanical properties. Porous coal gangue-based geopolymers were prepared by using coal gangue as the raw material, Na2SiO3 and NaOH as activators, H2O2 as the foaming agent and carboxymethylcellulose sodium (CMC) as the surfactant. Then response surface methodology (RSM) was used to study effects of liquid-to-solid ratio, CMC content, H2O2 content and curing temperature on compressive strength. Finally, pore number, porosity, pore size distribution and pore structure parameters were analyzed by self-developed image analysis algorithm. RSM results demonstrate that H2O2 content has the greatest effect on mechanical strength, followed by liquid-to-solid ratio, curing temperature and CMC content. Quantitative analysis of pore structure indicate that with the increase in H2O2 content, porosity could increase and pore size and pore shape could become more regular, but mechanical properties sharply deteriorate.
Easy Synthesis of Doped Graphitic Carbon Nitride Nanosheets as New Material for Enhanced DNA Extraction from Vegetal Tissues Using a Simple and Fast Protocol
Authors: Martínez-Cartagena Manuel Eduardo , Bernal-Martínez Juan , Banda-Villanueva Arnulfo , Lechuga-Islas Víctor D. , Córdova Teresa , Magaña Ilse , Torres-Lubián José Román , Fernández-Tavizón Salvador , Romero-García Jorge , Rodríguez-Hernández Ana Margarita , Díaz-de-León Ramón
Published: November 2022

Conventional and commercially available DNA extraction methods have several limitations regarding, for instance, contamination, and complex and slow precipitation and recovery processes. Herein, we report the synthesis of oxygen and phosphorus-doped Graphitic carbon nitride structures (g-POCN), via a novel Zinc-catalyzed one-pot solvothermal approach, and its application in the extraction of genomic DNA (gDNA) from a vegetal matrix (P. argentatum). Experimental and molecular modeling analyses demonstrate the high affinity of gDNA with g-POCN, which provided highly efficient gDNA extraction processes, with extraction yield, as well as integrity and quality of the extracted gDNA, comparable or superior to a commercial extraction kit and isopropanol extraction. Moreover, under suitable elution conditions, this method allows the easy removal of high concentrations of gDNA from g-POCN, rendering this method as a low-cost, simple, and fast approach for the extraction of even small amounts of gDNA. Remarkably, the extracted gDNA shows no degradation, and no inhibition of the polymerase chain reaction. Therefore, g-POCN represents a promising material for the highly efficient, cost-effective, and biocompatible extraction of DNA, which could stimulate research focused on broad DNA sources, e.g., RNA extraction, plasmids, ssDNA, etc.
Low Spike Antibody Levels and Impaired BA.4/5 Neutralization in Patients with Multiple Myeloma or Waldenstrom’s Macroglobulinemia after BNT162b2 Booster Vaccination
Authors: Rosati Margherita , Terpos Evangelos , Bear Jenifer , Burns Robert , Devasundaram Santhi , Ntanasis-Stathopoulos Ioannis , Gavriatopoulou Maria , Kastritis Efstathios , Dimopoulos Meletios-Athanasios , Pavlakis George N. , Felber Barbara K.
Published: November 2022

Patients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom’s macroglobulinemia (WM, n = 20) with healthy vaccine recipients (n = 37). Patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude, including several patients lacking responses, even after a 3rd vaccine dose, whereas non-B cell depleting therapies had a lesser effect. In contrast, MM and WM cohorts off-therapy showed increased NAb with a broad response range. ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5. Compared to WA1, significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy. In contrast, the MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. Overall, the boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial even under active therapy.
Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment
Authors: Al Shareef Zainab , Ershaid Mai Nidal Asad , Mudhafar Rula , Soliman Sameh S. M. , Kypta Robert M.
Published: November 2022

Dickkopf-3 (Dkk-3) is a member of the Dickkopf family protein of secreted Wingless-related integration site (Wnt) antagonists that appears to modulate regulators of the host microenvironment. In contrast to the clear anti-tumorigenic effects of Dkk-3-based gene therapies, the role of endogenous Dkk-3 in cancer is context-dependent, with elevated expression associated with tumor promotion and suppression in different settings. The receptors and effectors that mediate the diverse effects of Dkk-3 have not been characterized in detail, contributing to an ongoing mystery of its mechanism of action. This review compares the various functions of Dkk-3 in the tumor microenvironment, where Dkk-3 has been found to be expressed by subpopulations of fibroblasts, endothelial, and immune cells, in addition to epithelial cells. We also discuss how the activation or inhibition of Dkk-3, depending on tumor type and context, might be used to treat different types of cancers.
Sex Disparity for Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Systematic Review
Authors: Tan Brandon , Seth Ishith , Fischer Olivia , Hewitt Lyndel , Melville Geoffrey , Bulloch Gabriella , Ashford Bruce
Published: November 2022

The incidence of head and neck cutaneous squamous cell carcinoma (HNcSCC) is unevenly distributed between men and women. At present, the mechanism behind this disparity remains elusive. This study conducted a systematic review and meta-analysis of proportions to investigate the disparity between sexes for patients with HNcSCC. PubMed, Scopus, EMBASE, MEDLINE, Emcare and CINAHL were searched in November 2021 and June 2022 (N > 50, English, human), and studies which examined the association between sex and HNcSCC were included. Analysis was conducted using RStudio with data and forest plots displaying males as a proportion of total patients with HNcSCC. Two independent researchers performed study selection, data extraction, data analysis and risk of bias. Eighty-two studies (1948 to 2018) comprising approximately 186,000 participants (67% male, 33% female) from 29 countries were included. Significantly more males had HNcSCC overall (71%; CI: 67–74). Males were also significantly more affected by cSCC of the ear (92%; CI: 89–94), lip (74%; CI: 66–81), and eyelid (56%; CI: 51–62). This study found HNcSCC disproportionately affected males overall and across all subtypes. Improving our understanding of sex-specific mechanisms in HNcSCC will better inform our preventive, therapeutic and prognostic practices.
Quality of Life after Risk-Reducing Hysterectomy for Endometrial Cancer Prevention: A Systematic Review
Authors: Oxley Samuel , Xiong Ran , Wei Xia , Kalra Ashwin , Sideris Michail , Legood Rosa , Manchanda Ranjit
Published: November 2022

Background: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes. Results: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening. Conclusions: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk.
Survival in Breast Cancer Patients with Bone Metastasis: A Multicenter Real-World Study on the Prognostic Impact of Intensive Postoperative Bone Scan after Initial Diagnosis of Breast Cancer (CSBrS-023)
Authors: Yang Liu , Du Wei , Hu Taobo , Liu Miao , Cai Li , Liu Qiang , Yu Zhigang , Liu Guangyu , Wang Shu
Published: November 2022

The prognostic value of intensive postoperative bone scan (BS) screening, which is performed in asymptomatic patients with breast cancer (BC) after surgery, remained unclear. Patients diagnosed with BC with bone metastasis (BM) from five medical centers in China during the years 2005–2013 were retrospectively collected. Propensity score matching (PSM) was performed to balance the baseline characteristics. The survival outcomes were overall survival (OS) and overall survival after BM (OSABM). Among 1059 eligible patients, 304 underwent intensive postoperative BS while 755 did not. During a median follow-up of 6.67 years (95%CI 6.45, 7.21), intensive postoperative BS prolonged the median OS by 1.63 years (Log-Rank p = 0.006) and OSABM by 0.66 years (Log-Rank p = 0.002). Intensive postoperative BS was an independent prognostic factor for both OS (adjusted HR 0.77, 95%CI 0.64, 0.93, adjusted p = 0.006) and OSABM (adjusted HR 0.71, 95%CI 0.60, 0.86, adjusted p < 0.001). The prognostic value of intensive postoperative BS was consistently favorable for OS among clinical high-risk patients, including those with ages younger than 50, stage II, histology grade G3 and ER-Her2- subtype. This multicenter real-world study showed that intensive postoperative BS screening improved survival for BC patients with BM and should probably be recommended for postoperative surveillance, especially for patients at clinical high-risk.
The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation
Authors: Barnett Sarah E. , Herrmann Anne , Shaw Liam , Gash Elisabeth N. , Poptani Harish , Sacco Joseph J. , Coulson Judy M.
Published: November 2022

Malignant pleural mesothelioma (MPM) has limited treatment options and poor prognosis. Frequent inactivation of the tumour suppressors BAP1, NF2 and P16 may differentially sensitise tumours to treatments. We have established chick chorioallantoic membrane (CAM) xenograft models of low-passage MPM cell lines and protocols for evaluating drug responses. Ten cell lines, representing the spectrum of histological subtypes and tumour suppressor status, were dual labelled for fluorescence/bioluminescence imaging and implanted on the CAM at E7. Bioluminescence was used to assess viability of primary tumours, which were excised at E14 for immunohistological staining or real-time PCR. All MPM cell lines engrafted efficiently forming vascularised nodules, however their size, morphology and interaction with chick cells varied. MPM phenotypes including local invasion, fibroblast recruitment, tumour angiogenesis and vascular remodelling were evident. Bioluminescence imaging could be used to reliably estimate tumour burden pre- and post-treatment, correlating with tumour weight and Ki-67 staining. In conclusion, MPM-CAM models recapitulate important features of the disease and are suitable to assess drug targets using a broad range of MPM cell lines that allow histological or genetic stratification. They are amenable to multi-modal imaging, potentially offering a time and cost-efficient, 3Rs-compliant alternative to rodent xenograft models to prioritise candidate compounds from in vitro studies.
Suppression of Calcium Entry Modulates the Expression of TRβ1 and Runx2 in Thyroid Cancer Cells, Two Transcription Factors That Regulate Invasion, Proliferation and Thyroid-Specific Protein Levels
Authors: Asghar Muhammad Yasir , Knuutinen Taru , Holm Emilia , Nordström Tommy , Nguyen Van Dien , Zhou You , Törnquist Kid
Published: November 2022

The thyroid hormone receptor beta 1 (TRβ1) is downregulated in several human cancer cell types, which has been associated with development of an aggressive tumor phenotype and the upregulation of Runt-related transcription factor 2 (Runx2). In this study, we show that the expression of TRβ1 protein is downregulated in human thyroid cancer tissues and cell lines compared with the normal thyroid tissues and primary cell line, whilst Runx2 is upregulated under the same conditions. In contrast, the expression of TRβ1 is upregulated, whereas Runx2 is downregulated, in STIM1, Orai1 and TRPC1 knockdown cells, compared to mock transfected cells. To study the functional significance of Runx2 in follicular thyroid cancer ML-1 cells, we downregulated it by siRNA. This increased store-operated calcium entry (SOCE), but decreased cell proliferation and invasion. Moreover, restoring TRβ1 expression in ML-1 cells decreased SOCE, basal and sphingosine 1-phosphate (S1P)-evoked invasion, the expression of the promigratory S1P3 receptor and pERK1/2, and at the same time increased the expression of the thyroid specific proteins thyroglobulin, thyroperoxidase, and thyroid transcription factor-1. In conclusion, we show that TRβ1 is downregulated in thyroid cancer cells and that restoration of its expression can reverse the cancer cell phenotype towards a normal thyroid cell phenotype.
Design and Experimental Setup of a Robotic Medical Instrument for Brachytherapy in Non-Resectable Liver Tumors
Authors: Tucan Paul , Vaida Calin , Horvath Daniel , Caprariu Andrei , Burz Alin , Gherman Bogdan , Iakab Stefan , Pisla Doina
Published: November 2022

This paper presents a study regarding the design and the experimental setup of a medical robotic system for brachytherapy using tribology analysis. The robotic system is composed of a collaborative robotic arm and a multi-needle brachytherapy instrument controlled using a unified control system embedding a haptic device and force-feedback. This work is oriented towards identifying the technical characteristics of the system components to determine the accuracy of the procedure, as well as using different scenarios for needle insertion in ex vivo porcine liver tissue in order to determine the forces required for insertion and extraction of the needle and the friction coefficient that accompanies the previously mentioned forces. Subsequent to the computation of the friction forces, the normal forces and the wear during the needle insertion are determined with the scope of predicting the lifecycle of some components of the medical device.
Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers
Authors: Bou Sayuri , Takamatsu Shigeyuki , Matsumoto Sae , Asahi Satoko , Tatebe Hitoshi , Sato Yoshitaka , Kawamura Mariko , Shibata Satoshi , Kondou Tamaki , Tameshige Yuji , Maeda Yoshikazu , Sasaki Makoto , Yamamoto Kazutaka , Sunagozaka Hajime , Aoyagi Hiroyuki , Tamamura Hiroyasu , Kobayashi Satoshi , Gabata Toshifumi
Published: November 2022

We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan–Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38–90 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8–82.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient’s condition. The median follow-up of surviving patients was 63 months (range, 1–126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events ≥ grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.
Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study
Authors: De Filippi Rosaria , Marcacci Gianpaolo , Derenzini Enrico , Musso Maurizio , Donnarumma Daniela , Morelli Emanuela , Patti Caterina , Maraglino Alessio Maria Edoardo , Scalone Renato , Simeone Luigia , Becchimanzi Cristina , Mele Sara , Crisci Stefania , Morabito Fortunato , Pinto Antonio
Published: November 2022

(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6–30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients’ subsets more likely to benefit from this approach.
Oxidative Stress Correlates with More Aggressive Features in Thyroid Cancer
Authors: Muzza Marina , Pogliaghi Gabriele , Colombo Carla , Carbone Erika , Cirello Valentina , Palazzo Sonia , Frattini Francesco , Gentilini Davide , Gazzano Giacomo , Persani Luca , Fugazzola Laura
Published: November 2022

Oxidative stress (OS) can have an impact in the pathogenesis and in the progression of thyroid cancer. We investigated the levels of reactive oxygen species (ROS) in 50 malignant and benign thyroid lesions and 41 normal tissues, and correlated them with the thyroid differentiation score-TDS and the clinico-pathologic features. NOX4 expression, GPx activity and the genetic pattern of tumors were evaluated. In malignant and benign lesions, ROS generation and NOX4 protein expression were higher than in normal tissues. Follicular (FTCs) and anaplastic/poorly differentiated cancers had increased OS relative to papillary tumors (PTCs). Moreover, OS in FTCs was higher than in follicular adenomas. Mutated PTCs showed increased OS compared with non-mutated PTCs. In malignant tumors, OS was inversely correlated with TDS, and directly correlated with tumor stage and ATA risk. GPx activity was increased in tumors compared with normal tissues, and inversely correlated to OS. In conclusion, our data indicate that thyroid tumors are exposed to higher OS compared with normal tissues, while showing a compensative increased GPx activity. OS correlates with tumor aggressiveness and mutations in the MEK-ERK pathway in PTC. The inverse correlation between OS and TDS suggests that ROS may repress genes involved in thyroid differentiation.
Role of Functional MRI in Liver SBRT: Current Use and Future Directions
Authors: Tadimalla Sirisha , Wang Wei , Haworth Annette
Published: November 2022

Stereotactic body radiation therapy (SBRT) is an emerging treatment for liver cancers whereby large doses of radiation can be delivered precisely to target lesions in 3–5 fractions. The target dose is limited by the dose that can be safely delivered to the non-tumour liver, which depends on the baseline liver functional reserve. Current liver SBRT guidelines assume uniform liver function in the non-tumour liver. However, the assumption of uniform liver function is false in liver disease due to the presence of cirrhosis, damage due to previous chemo- or ablative therapies or irradiation, and fatty liver disease. Anatomical information from magnetic resonance imaging (MRI) is increasingly being used for SBRT planning. While its current use is limited to the identification of target location and size, functional MRI techniques also offer the ability to quantify and spatially map liver tissue microstructure and function. This review summarises and discusses the advantages offered by functional MRI methods for SBRT treatment planning and the potential for adaptive SBRT workflows.
MiR-101: An Important Regulator of Gene Expression and Tumor Ecosystem
Authors: Liu Ning , Yang Chunsheng , Gao Ang , Sun Meili , Lv Deguan
Published: November 2022

MiRNAs are small single-stranded non-coding RNAs. MiRNA contributes to the transcriptional and post-transcriptional regulation of mRNA in different cell types, including mRNA transcription inhibition and mRNA decay and phenotypes via the effect of several essential oncogenic processes and tumor microenvironment. MiR-101 is a highly conserved miRNA that was found to alter the expression in various human cancers. MiR-101 has been reported to have tumor oncogenic and suppressive effects to regulate tumorigenesis and tumor progression. In this review, we summarize the new findings about the roles of miR-101 in cancers and the underlying mechanisms of targeting genes degradation and microenvironment regulation, which will improve biological understanding and design of novel therapeutics.
Proton Beam Therapy for Pediatric Tumors of the Central Nervous System—Experiences of Clinical Outcome and Feasibility from the KiProReg Study
Authors: Peters Sarah , Frisch Sabine , Stock Annika , Merta Julien , Bäumer Christian , Blase Christoph , Schuermann Eicke , Tippelt Stephan , Bison Brigitte , Frühwald Michael , Rutkowski Stefan , Fleischhack Gudrun , Timmermann Beate
Published: November 2022

As radiotherapy is an important part of the treatment in a variety of pediatric tumors of the central nervous system (CNS), proton beam therapy (PBT) plays an evolving role due to its potential benefits attributable to the unique dose distribution, with the possibility to deliver high doses to the target volume while sparing surrounding tissue. Children receiving PBT for an intracranial tumor between August 2013 and October 2017 were enrolled in the prospective registry study KiProReg. Patient’s clinical data including treatment, outcome, and follow-up were analyzed using descriptive statistics, Kaplan–Meier, and Cox regression analysis. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 before, during, and after PBT. Written reports of follow-up imaging were screened for newly emerged evidence of imaging changes, according to a list of predefined keywords for the first 14 months after PBT. Two hundred and ninety-four patients were enrolled in this study. The 3-year overall survival of the whole cohort was 82.7%, 3-year progression-free survival was 67.3%, and 3-year local control was 79.5%. Seventeen patients developed grade 3 adverse events of the CNS during long-term follow-up (new adverse event n = 7; deterioration n = 10). Two patients developed vision loss (CTCAE 4°). This analysis demonstrates good general outcomes after PBT.
Dynamic Changes in the Extracellular Matrix in Primary, Metastatic, and Recurrent Ovarian Cancers
Authors: Gertych Arkadiusz , Walts Ann E. , Cheng Keyi , Liu Manyun , John Joshi , Lester Jenny , Karlan Beth Y. , Orsulic Sandra
Published: November 2022

Cancer-associated fibroblasts (CAFs) and their extracellular matrix are active participants in cancer progression. While it is known that functionally different subpopulations of CAFs co-exist in ovarian cancer, it is unclear whether certain CAF subsets are enriched during metastatic progression and/or chemotherapy. Using computational image analyses of patient-matched primary high-grade serous ovarian carcinomas, synchronous pre-chemotherapy metastases, and metachronous post-chemotherapy metastases from 42 patients, we documented the dynamic spatiotemporal changes in the extracellular matrix, fibroblasts, epithelial cells, immune cells, and CAF subsets expressing different extracellular matrix components. Among the different CAF subsets, COL11A1+ CAFs were associated with linearized collagen fibers and exhibited the greatest enrichment in pre- and post-chemotherapy metastases compared to matched primary tumors. Although pre- and post-chemotherapy metastases were associated with increased CD8+ T cell infiltration, the infiltrate was not always evenly distributed between the stroma and cancer cells, leading to an increased frequency of the immune-excluded phenotype where the majority of CD8+ T cells are present in the tumor stroma but absent from the tumor parenchyma. Overall, most of the differences in the tumor microenvironment were observed between primary tumors and metastases, while fewer differences were observed between pre- and post-treatment metastases. These data suggest that the tumor microenvironment is largely determined by the primary vs. metastatic location of the tumor while chemotherapy does not have a significant impact on the host microenvironment.
Vascularization of Poly-ε-Caprolactone-Collagen I-Nanofibers with or without Sacrificial Fibers in the Neurotized Arteriovenous Loop Model
Authors: Kratzer Simon , Arkudas Andreas , Himmler Marcus , Schubert Dirk W. , Schneidereit Dominik , Bauer Julian , Friedrich Oliver , Horch Raymund E. , Cai Aijia
Published: November 2022

Electrospun nanofibers represent an ideal matrix for the purpose of skeletal muscle tissue engineering due to their highly aligned structure in the nanoscale, mimicking the extracellular matrix of skeletal muscle. However, they often consist of high-density packed fibers, which might impair vascularization. The integration of polyethylene oxide (PEO) sacrificial fibers, which dissolve in water, enables the creation of less dense structures. This study examines potential benefits of poly-ε-caprolactone-collagen I-PEO-nanoscaffolds (PCP) in terms of neovascularization and distribution of newly formed vessels compared to poly-ε-caprolactone -collagen I-nanoscaffolds (PC) in a modified arteriovenous loop model in the rat. For this purpose, the superficial inferior epigastric artery and vein as well as a motor nerve branch were integrated into a multilayer three-dimensional nanofiber scaffold construct, which was enclosed by an isolation chamber. Numbers and spatial distribution of sprouting vessels as well as macrophages were analyzed via immunohistochemistry after two and four weeks of implantation. After four weeks, aligned PC showed a higher number of newly formed vessels, regardless of the compartments formed in PCP by the removal of sacrificial fibers. Both groups showed cell influx and no difference in macrophage invasion. In this study, a model of combined axial vascularization and neurotization of a PCL-collagen I-nanofiber construct could be established for the first time. These results provide a foundation for the in vivo implantation of cells, taking a major step towards the generation of functional skeletal muscle tissue.
Metabolism in Cancer Stem Cells: Targets for Clinical Treatment
Authors: Wen Gui-Min , Xu Xiao-Yan , Xia Pu
Published: November 2022

Cancer stem cells (CSCs) have high tumorigenicity, high metastasis and high resistance to treatment. They are the key factors for the growth, metastasis and drug resistance of malignant tumors, and are also the important reason for the occurrence and recurrence of tumors. Metabolic reprogramming refers to the metabolic changes that occur when tumor cells provide sufficient energy and nutrients for themselves. Metabolic reprogramming plays an important role in regulating the growth and activity of cancer cells and cancer stem cells. In addition, the immune cells or stromal cells in the tumor microenvironment (TME) will change due to the metabolic reprogramming of cancer cells. Summarizing the characteristics and molecular mechanisms of metabolic reprogramming of cancer stem cells will provide new ideas for the comprehensive treatment of malignant tumors. In this review, we summarized the changes of the main metabolic pathways in cancer cells and cancer stem cells.
MAP4K4/JNK Signaling Pathway Stimulates Proliferation and Suppresses Apoptosis of Human Spermatogonial Stem Cells and Lower Level of MAP4K4 Is Associated with Male Infertility
Authors: Wan Cailin , Chen Wei , Cui Yinghong , He Zuping
Published: November 2022

Spermatogonial stem cells (SSCs) serve as a foundation for spermatogenesis and they are essential for male fertility. The fate of SSC is determined by genetic and epigenetic regulatory networks. Many molecules that regulate SSC fate determinations have been identified in mice. However, the molecules and signaling pathways underlying human SSCs remain largely unclear. In this study, we have demonstrated that MAP4K4 was predominantly expressed in human UCHL1-positive spermatogonia by double immunocytochemical staining. MAP4K4 knockdown inhibited proliferation of human SSCs and induced their apoptosis. Moreover, MAP4K4 silencing led to inhibition of JNK phosphorylation and MAP4K4 phosphorylation at Ser801. RNA sequencing indicated that MAP4K4 affected the transcription of SPARC, ADAM19, GPX7, GNG2, and COLA1. Interestingly, the phenotype of inhibiting JNK phosphorylation by SP600125 was similar to MAP4K4 knockdown. Notably, MAP4K4 protein was lower in the testes of patients with non-obstructive azoospermia than those with normal spermatogenesis as shown by Western blots and immunohistochemistry. Considered together, our data implicate that MAP4K4/JNK signaling pathway mediates proliferation and apoptosis of human SSCs, which provides a novel insight into molecular mechanisms governing human spermatogenesis and might offer new targets for gene therapy of male infertility.
Pathological Evidence for Residual SARS-CoV-2 in the Micrometastatic Niche of a Patient with Ovarian Cancer
Authors: Hayashi Takuma , Sano Kenji , Yaegashi Nobuo , Konishi Ikuo
Published: November 2022

In previous clinical studies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients has a high risk of aggravation and mortality than in healthy infected individuals. Inoculation with coronavirus disease 2019 (COVID-19) vaccine reduces the risk of SARS-CoV-2 infection and COVID-19 severity. However, vaccination-induced anti-SARS-CoV-2 antibody production is said to be lower in cancer patients than in healthy individuals. In addition, the rationale for why the condition of patients with cancer worsens with COVID-19 is not well understood. Therefore, we examined the infection status of SARS-CoV-2 in the primary tumor and micrometastasis tissues of the patient with cancer and COVID-19. In this study, the expression of angiotensin-converting enzyme 2 (ACE2) was observed, and SARS-CoV-2 particles was detected in ovarian tissue cells in contact with the micrometastatic niche of the patient with high-grade serous ovarian cancer. We believe that the severity of COVID-19 in patients with cancer can be attributed to these pathological features. Therefore, the pathological findings of patients with advanced and recurrent ovarian cancer infected with SARS-CoV-2 may help decrease COVID-19 severity in patients with other cancer types.
Yield Characteristics of Cemented Paste Backfill
Authors: Pan Andrew , Grabinsky Murray
Published: November 2022

Cemented paste backfill (CPB) plays an increasingly important role in the mining industry due to its operational and environmental benefits. CPB is placed in the mined-out stope to form a self-supporting structure. The strength and stability of the CPB is of great concern in its engineering applications. Indeed, CPB must remain stable during the extraction of adjacent stopes to ensure the safety of the mine operations. Although significant research has been conducted on the shear properties of CPB, there are limited studies on its post-failure behavior, in particular the yield characteristics of CPB. This paper presents the finding on the post-peak and yield property of CPB. The study is conducted on three cemented contents and six stress intervals based on the mining practice and field study. The results show that CPB exhibits dilative behavior under strain softening and contractive property under strain hardening conditions. Our study demonstrates that pure frictional resistance could exceed the cohesion strength at high stress levels.
Microstructural Evaluation of Graphene-Reinforced Nickel Matrix Ni-P-Gr Coating on Ti-6Al-4V Alloy by the Electroless Coating Method
Authors: Gunduz Hatice , Karslioglu Ramazan , Ozturk Fahrettin
Published: November 2022

Titanium alloys are widely used in many industrial applications, from aerospace to automotive, and from defense to medical, as they combine superior properties such as high strength and low density. Still, titanium and its alloys are insufficient in environments with friction and wear because of their weak tribological properties. In the literature, numerous research works on improving the surface quality of titanium alloys have been conducted. Electroless coatings, on the other hand, are one of the most widely used surface improvement methods due to its homogeneous thickness achievement, high hardness, and good corrosion resistance. The autocatalytic reduction in the coating process enhances the surface quality of the material or alloy considerably. In addition, many studies in the literature aim to carry the properties of electroless coatings to a higher point by creating a composite coating with the addition of extra particles. In this study, graphene-reinforced nickel matrix Ni-P-Gr coating was applied to the surface of Ti-6Al-4V alloy, in order to enhance weak tribological behaviors, by the electroless coating method. Moreover, the coated and uncoated, heat-treated, and non-heat-treated specimens were subjected to abrasion in linear reciprocating ball-on-plate configuration to observe tribological properties. Microstructure examination of the samples was performed using a scanning Electron Microscope (SEM), X-ray Diffractometer (XRD), X-ray Photon Spectrometry (XPS), and Raman Spectroscopy. Specific wear rates of specimens were calculated using microstructural analysis and the hardness of the produced samples was measured using the Vickers hardness test. Results indicate that both the coating and the heat treatment improved the microstructure and tribological properties significantly. With the graphene-reinforced Ni-P coating via electroless coating process, the hardness of the substrate increased by about 34%, while it increased by approximately 73% using subjected heat treatment. Furthermore, the wear rate of the Ti-6Al-4V substrate was approximately 98% higher than that of the heat-treated nanocomposite coating. The highest wear resistance was obtained at the heat-treated nanocomposite coating.
Photoluminescent and Photocatalytic Properties of Eu3+-Doped MgAl Oxide Coatings Formed by Plasma Electrolytic Oxidation of AZ31 Magnesium Alloy
Authors: Stojadinović Stevan , Radić Nenad , Vasilić Rastko
Published: November 2022

The synthesis of Eu3+-doped MgAl oxide coatings containing MgO and MgAl2O4 was accomplished through plasma electrolytic oxidation of AZ31 magnesium alloy in aluminate electrolyte with the addition of Eu2O3 particles in various concentrations. Their morphological, structural, and above all, photoluminescent (PL) and photocatalytic activity (PA) were thoroughly investigated. PL emission spectra of MgAl oxide coatings feature characteristic emission peaks, which are ascribed to f–f transitions of Eu3+ ions from excited level 5D0 to lower levels 7FJ. The charge transfer state of Eu3+ or direct excitation of the Eu3+ ground state 7F0 into higher levels of the 4f-manifold are both attributed to the PL peaks that appear in the excitation PL spectra of the obtained coatings. The fact that the transition 5D0 → 7F2 (electrical dipole transition) in Eu3+-doped MgAl oxide coatings is considerably stronger than the transition 5D0 → 7F1 (magnetic dipole transition) indicates that Eu3+ ions occupied sites with non-inversion symmetry. Because of oxygen vacancy formation, the Eu3+-doped MgAl oxide coatings had a higher PA in the degradation of methyl orange than the pure MgAl oxide coating. The highest PA was found in Eu3+-doped MgAl oxide coating formed in an aluminate electrolyte with 4 g/L of Eu2O3 particles. The PA, morphology, and phase of Eu3+-doped MgAl oxide coatings did not change after several consecutive runs, indicating outstanding stability of these photocatalysts.
The Effect of the Dilution Level on Microstructure and Wear Resistance of Fe-Cr-CV Hardfacing Coatings Deposited by PTA-P
Authors: Passos Thais Andrezza , Costa Henara , Luz Felipe Kevin Correa , Pintaude Giuseppe
Published: November 2022

Soil preparation tools are subject to severe abrasion. The wear resistance of various industrial components can be improved using the hardfacing technique. The improvement in hardfacing wear resistance depends on the microstructure, i.e., the chemical composition of the alloys, the method of overlay, and the parameters of the selected process. The Plasma Transferred Arc with Powder (PTA-P) welding process is interesting as a hardfacing technique since it promotes very low dilution of the substrate in the coating. In this article, the PTA-P welding process was used for the deposition of Fe-Cr-C-based hard coatings with the addition of vanadium onto cheap and relatively soft low-carbon steel substrates. Rubber-wheel abrasion tests were performed to compare the abrasion resistance between commercial anti-wear steel and weld-deposited Fe-Cr-C-V hard coatings. In addition, the microstructure, dilution, and wear mechanisms were investigated. The dilution of the coatings affected the microstructure, in particular, the free mean path of the vanadium carbides, but it only affected abrasion resistance when the wear mechanism involved rolling abrasion. The deposited coatings proved to be at least three times stronger than a commercial abrasion-resistant steel due to the distribution and morphology of the vanadium carbides formed in the coatings.
Regulatory Processes in Populations of Forest Insects (A Case Study of Insect Species Damaging the Pine Pinus sylvestris L. in Forests of SIBERIA)
Authors: Soukhovolsky Vladislav , Ovchinnikova Tamara , Tarasova Olga , Ivanova Yulia , Kovalev Anton
Published: November 2022

The present study addresses the population dynamics of five species of phyllophagous forest insects in five habitats located in the Krasnoturansk pine forest (south Middle Siberia). Based on the data of insect surveys obtained during 1979–2016, autoregressive (AR) models of population dynamics have been proposed, with the current population density being dependent on population densities of the preceding years. Methods of calculation of the autoregression order and coefficients of AR equations have been presented. The study shows that, for different insect species in different habitats, the lags between the current population density and the densities of the previous years are not the same. AR equations characterize positive and negative feedbacks regulating population dynamics. By using AR equations, up to 90% of population density variance can be taken into account. Stability margin, which is calculated from coefficients of AR models, has been proposed as a parameter to assess the stability of population dynamics. A small stability margin indicates a high risk of outbreak of an insect species.
A Waveform Dataset in Continuous Mode of the Montefeltro Seismic Network (MF) in Central-Northern Italy from 2018 to 2020
Authors: Megna Antonella , Cimini Giovanni Battista , Marchetti Alessandro , Pagliuca Nicola Mauro , Santini Stefano
Published: November 2022

The Montefeltro seismic network (FDSN Network code: 1S) was deployed in the Apennines area of northern Marche and southern Emilia-Romagna regions (central Italy). A temporary network was set up in December 2018 and continues to operate, with an array consisting of stations equipped with dynamic digitizers and three-component short/extended/broad band seismometers (Guralp CMG/20s and 30s, Lennartz 3D/5s, Sara SS20 3D/0.5s sensors). The network records in continuous mode at 100 sps. The data are used to analyze the seismic activity and the spatiotemporal evolution of small seismic sequences occurring in the considered area and surrounding zones, strongly clustered in time and space. The data of dataset files are mini-seed formatted and subdivided by the following tree: (1) the dataset is divided by years; (2) the dataset is then subdivided by stations; (3) finally, the data are divided by days of each year in every station folder.
Experimental and Nonlinear Finite Element Analysis Data for an Innovative Buckling Restrained Bracing System to Rehabilitate Seismically Deficient Structures
Authors: Karzad Abdul Saboor , Al-Sadoon Zaid A. , Sagheer Abdullah , AlHamaydeh Mohammad
Published: November 2022

This article presents experimental data and nonlinear finite element analysis (NLFEA) modeling for an innovative buckling restrained bracing (BRB) system. The data were collected from qualification testing of introduced BRBs per the AISC 341 test provision and finite element modeling. The BRB is made of three parts: core bar, restraining unit, and end units, in which duplicates of three different core bar cross sections (i.e., fully threaded, threaded notched, and smooth shaved) were tested. The BRBs introduced in this research come with innovative end parts, so-called fingers. These fingers provide the longitudinal gap required in every BRB system and simultaneously prevent buckling of the core bar at the end regions at both ends of the BRB sample, thus facilitating an easy core replacement if it gets damaged in the event of an earthquake. The measured parameters were the applied cyclic load and the corresponding displacement. Analysis of the acquired data illustrated an almost symmetric hysteric behavior with a little higher capacity under compression but a noticeable overall ductility of 4. Moreover, finite element modeling data for one type of core bar (fully threaded) were curated. The data presented in this paper will be valuable for fabricating BRBs in practice and further research on the topic considered.