bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis
Authors: Soontararak Sirikul , Ardaum Piyathida , Senarat Napaporn , Yangtara Sarawut , Lekcharoensuk Chalermpol , Putchong Iyarath , Kashemsant Narudee , Vijarnsorn Monchanok , Chow Lyndah , Dow Steven , Lekcharoensuk Porntippa
Published: October 2022

Osteoarthritis (OA) is mostly incurable and non-regenerative with long-term complications. Autologous conditioned serum (ACS), which is enriched in Interleukin 1 receptor antagonists (IL-1RA) and growth factors, could be an alternative treatment to accelerate the positive therapeutic effects. ACS is proposed to alleviate inflammation by blocking IL-1 receptors. However, to date, there is no report focusing on the cell-mediated anti-inflammation and regenerative effect caused by ACS, especially the ACS from patients. Therefore, this study aims to investigate the therapeutic potential of ACS generated from dogs with spontaneous OA, focusing on its promising anti-inflammatory and regenerative properties in vitro compared to the matched plasma. We found that ACS prepared from ten OA dogs contained significant concentrations of IL-1RA, vascular endothelial growth factor, and transforming growth factor beta, which are key cytokines in anti-inflammation and angiogenesis. Furthermore, we found that ACS suppressed T cell activity by reducing proliferation of effector T cells and simultaneously expanding numbers of immune suppressive FOXP3+ T cells. Lastly, we showed that ACS enhanced the proliferation of osteocytes and fibroblasts and promoted extracellular matrix gene expression in primary chondrocyte culture. Therefore, these studies indicate that ACS prepared from dogs with OA is active as an immunomodulatory and regenerative strategy for use in OA management.
An Integrated Bioinformatics Approach to Identify Network-Derived Hub Genes in Starving Zebrafish
Authors: Mortazavi Amin , Ghaderi-Zefrehei Mostafa , Muhaghegh Dolatabady Mustafa , Golshan Mahdi , Nazari Sajad , Sadr Ayeh Sadat , Kadkhodaei Saeid , Imumorin Ikhide G. , Peters Sunday O. , Smith Jacqueline
Published: October 2022

The present study was aimed at identifying causative hub genes within modules formed by co-expression and protein–protein interaction (PPI) networks, followed by Bayesian network (BN) construction in the liver transcriptome of starved zebrafish. To this end, the GSE11107 and GSE112272 datasets from the GEO databases were downloaded and meta-analyzed using the MetaDE package, an add-on R package. Differentially expressed genes (DEGs) were identified based upon expression intensity N(µ = 0.2, σ2 = 0.4). Reconstruction of BNs was performed by the bnlearn R package on genes within modules using STRINGdb and CEMiTool. ndufs5 (shared among PPI, BN and COEX), rps26, rpl10, sdhc (shared between PPI and BN), ndufa6, ndufa10, ndufb8 (shared between PPI and COEX), skp1, atp5h, ndufb10, rpl5b, zgc:193613, zgc:123327, zgc:123178, wu:fc58f10, zgc:111986, wu:fc37b12, taldo1, wu:fb62f08, zgc:64133 and acp5a (shared between COEX and BN) were identified as causative hub genes affecting gene expression in the liver of starving zebrafish. Future work will shed light on using integrative analyses of miRNA and DNA microarrays simultaneously, and performing in silico and experimental validation of these hub-causative (CST) genes affecting starvation in zebrafish.
Atmospheric Mercury Concentrations in Guangzhou City, Measured by Spectroscopic Techniques
Authors: Chen Guoping , Sun Yuting , Zhang Qiang , Duan Zheng , Svanberg Sune
Published: October 2022

Atmospheric levels of atomic mercury pollution were measured using spectroscopic techniques in the city of Guangzhou, Guangdong Province, China. Assessments were mainly performed at ground level using a portable (vehicle mounted or hand carried) Zeeman modulation correlation spectrometer (Lumex RA-915M), and the results are given in easily comprehensible diagrams. Measurements were made with continuous recording in car traverses along major roads which cross the city, but also at selected spots, such as at a university campus with laboratory buildings. Further, pollution levels at different locations were recorded when walking through a major and a small hospital. While concentrations in the city in the range 3–10 ng/m3 were typical, and strongly dependent on the traffic situation, very high concentrations (up to 1300 ng/m3) were found at certain indoor hospital locations, again drawing attention to the fact that high mercury levels due to inadequate handling routines can remain undetected but could readily be eliminated by adequate measurements and subsequent sanitation.
Land Surface Albedo Estimation and Cross Validation Based on GF-1 WFV Data
Authors: Wang Zhe , Zhou Hongmin , Ma Wu , Fan Wenrui , Wang Jindi
Published: October 2022

The land surface albedo (LSA) represents the ability of the land surface to reflect solar radiation. It is one of the driving factors in the energy balance of land surface radiation and in land–air interactions. In this paper, we estimated the land surface albedo based on GF-1 WFV satellite data that have a high spatial and temporal resolution and cross-validated the albedo estimation results. The albedo estimations and validations were performed in the Ganzhou District, Zhangye City, China, and the Sindh Province, Pakistan. We used the direct estimation method which used a radiative transfer simulation to establish the relationship between the narrow band top of the atmosphere bidirectional reflectance and the land broadband albedo to estimate the albedo data. The results were validated with ground data, Landsat data, MODIS products, and GLASS products. The results show that the method can produce highly accurate albedo estimation results on different land cover types (RMSE: 0.026, R2: 0.835) and has a good consistency with the existing albedo products. This study makes a significant contribution to improving the utilization of GF data and contributes to the understanding of land–air interactions.
Analyses on the Multimodel Wind Forecasts and Error Decompositions over North China
Authors: Lyu Yang , Zhi Xiefei , Wu Hong , Zhou Hongmei , Kong Dexuan , Zhu Shoupeng , Zhang Yingxin , Hao Cui
Published: October 2022

In this study, wind forecasts derived from the European Centre for Medium-Range Weather Forecasts (ECMWF), the National Centers for Environmental Prediction (NCEP), the Japan Meteorological Agency (JMA) and the United Kingdom Meteorological Office (UKMO) are evaluated for lead times of 1–7 days at the 10 m and multiple isobaric surfaces (500 hPa, 700 hPa, 850 hPa and 925 hPa) over North China for 2020. The straightforward multimodel ensemble mean (MME) method is utilized to improve forecasting abilities. In addition, the forecast errors are decomposed to further diagnose the error sources of wind forecasts. Results indicated that there is little difference in the performances of the four models in terms of wind direction forecasts (DIR), but obvious differences occur in the meridional wind (U), zonal wind (V) and wind speed (WS) forecasts. Among them, the ECMWF and NCEP showed the highest and lowest abilities, respectively. The MME effectively improved wind forecast abilities, and showed more evident superiorities at higher levels for longer lead times. Meanwhile, all of the models and the MME manifested consistent trends of increasing (decreasing) errors for U, V and WS (DIR) with rising height. On the other hand, the main source of errors for wind forecasts at both 10 m and isobaric surfaces was the sequence component (SEQU), which rose rapidly with increasing lead times. The deficiency of the less proficient NCEP model at the 10 m and isobaric surfaces could mainly be attributed to the bias component (BIAS) and SEQU, respectively. Furthermore, the MME tended to produce lower SEQU than the models at all layers, which was more obvious at longer lead times. However, the MME showed a slight deficiency in reducing BIAS and the distribution component of forecast errors. The results not only recognized the model forecast performances in detail, but also provided important references for the use of wind forecasts in business departments and associated scientific researches.
Freezing of Solute-Laden Aqueous Solutions: Kinetics of Crystallization and Heat- and Mass-Transfer-Limited Model
Authors: Johnson Stonewall , Hall Christopher , Das Sreyashi , Devireddy Ram
Published: October 2022

Following an earlier study, we reexamined the latent heat of fusion during freezing at 5 K/min of twelve different pre-nucleated solute-laden aqueous solutions using a Differential Scanning Calorimeter (DSC) and correlated it with the amount of initially dissolved solids or solutes in the solution. In general, a decrease in DSC-measured heat release (in comparison to that of pure water, 335 mJ/mg) was observed with an increasing fraction of dissolved solids or solutes, as observed in the earlier study. In addition, the kinetics of ice crystallization was also obtained in three representative biological media by performing additional experiments at 1, 5 and 20 K/min. A model of ice crystallization based on the phase diagram of a water–NaCl binary solution and a modified Avrami-like model of kinetics was then developed and fit to the experimental data. Concurrently, a heat and mass transfer model of the freezing of a salt solution in a small container is also presented to account for the effect of the cooling rate as well as the solute concentration on the measured latent of freezing. This diffusion-based model of heat and mass transfer was non-dimensionalized, solved using a numerical scheme and compared with experimental results. The simulation results show that the heat and mass transfer model can predict (± 10%) the experimental results.
The Performance of FDA-Approved PET Imaging Agents in the Detection of Prostate Cancer
Authors: Li Mei , Zelchan Roman , Orlova Anna
Published: October 2022

Positron emission tomography (PET) incorporated with X-ray computed tomography (PET/CT) or magnetic resonance imaging (PET/MRI) is increasingly being used as a diagnostic tool for prostate cancer (PCa). In this review, we describe and evaluate the clinical performance of some Food and Drug Administration (FDA)-approved agents used for visualizing PCa: [18F]FDG, [11C]choline, [18F]FACBC, [68Ga]Ga-PSMA-11, [18F]DCFPyL, and [18F]-NaF. We carried out a comprehensive literature search based on articles published from 1 January 2010 to 1 March 2022. We selected English language articles associated with the discovery, preclinical study, clinical study, and diagnostic performance of the imaging agents for the evaluation. Prostate-specific membrane antigen (PSMA)-targeted imaging agents demonstrated superior diagnostic performance in both primary and recurrent PCa, compared with [11C]choline and [18F]FACBC, both of which target dividing cells and are used especially in patients with low prostate-specific antigen (PSA) values. When compared to [18F]-NaF (which is suitable for the detection of bone metastases), PSMA-targeted agents were also capable of detecting lesions in the lymph nodes, soft tissues, and bone. However, a limitation of PSMA-targeted imaging was the heterogeneity of PSMA expression in PCa, and consequently, a combination of two PET tracers was proposed to overcome this obstacle. The preliminary studies indicated that the use of PSMA-targeted scanning is more cost efficient than conventional imaging modalities for high-risk PCa patients. Furthering the development of imaging agents that target PCa-associated receptors and molecules could improve PET-based diagnosis of PCa.
Zinc Oxide/Phosphorus-Doped Carbon Nitride Composite as Potential Scaffold for Electrochemical Detection of Nitrofurantoin
Authors: Ahmed Faheem , Kokulnathan Thangavelu , Umar Ahmad , Akbar Sheikh , Kumar Shalendra , Shaalan Nagih M. , Arshi Nishat , Alam Mohd Gulfam , Aljaafari Abdullah , Alshoaibi Adil
Published: October 2022

Herein, we present an electrocatalyst constructed by zinc oxide hexagonal prisms/phosphorus-doped carbon nitride wrinkles (ZnO HPs/P-CN) prepared via a facile sonochemical method towards the detection of nitrofurantoin (NF). The ZnO HPs/P-CN-sensing platform showed amplified response and low-peak potential compared with other electrodes. The exceptional electrochemical performance could be credited to ideal architecture, rapid electron/charge transfer, good conductivity, and abundant active sites in the ZnO HPs/P-CN composite. Resulting from these merits, the ZnO HPs/P-CN-modified electrode delivered rapid response (2 s), a low detection limit (2 nM), good linear range (0.01–111 µM), high sensitivity (4.62 µA µM−1 cm2), better selectivity, decent stability (±97.6%), and reproducibility towards electrochemical detection of NF. We further demonstrated the feasibility of the proposed ZnO HPs/P-CN sensor for detecting NF in samples of water and human urine. All the above features make our proposed ZnO HPs/P-CN sensor a most promising probe for detecting NF in natural samples.
Dose-Escalated Salvage Radiotherapy for Macroscopic Local Recurrence of Prostate Cancer in the Prostate-Specific Membrane Antigen Positron Emission Tomography Era
Authors: Tamihardja Jörg , Zehner Leonie , Hartrampf Philipp E. , Cirsi Sinan , Wegener Sonja , Buck Andreas K. , Flentje Michael , Polat Bülent
Published: October 2022

Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3–72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). Results: The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1% (95% CI: 81.1–97.8%) and the three-year metastasis-free survival rate reached 96.2% (95% CI: 91.2–100.0%). The cumulative three-year late grade 3 GU toxicity rate was 3.4%. No late grade 3 GI toxicity occurred. Conclusions: Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates.
CellCallEXT: Analysis of Ligand–Receptor and Transcription Factor Activities in Cell–Cell Communication of Tumor Immune Microenvironment
Authors: Gao Shouguo , Feng Xingmin , Wu Zhijie , Kajigaya Sachiko , Young Neal S.
Published: October 2022

(1) Background: Single-cell RNA sequencing (scRNA-seq) data are useful for decoding cell–cell communication. CellCall is a tool that is used to infer inter- and intracellular communication pathways by integrating paired ligand–receptor (L–R) and transcription factor (TF) activities from steady-state data and thus cannot directly handle two-condition comparisons. For tumor and healthy status, it can only individually analyze cells from tumor or healthy tissue and examine L–R pairs only identified in either tumor or healthy controls, but not both together. Furthermore, CellCall is highly affected by gene expression specificity in tissues. (2) Methods: CellCallEXT is an extension of CellCall that deconvolutes intercellular communication and related internal regulatory signals based on scRNA-seq. Information on Reactome was retrieved and integrated with prior knowledge of L–R–TF signaling and gene regulation datasets of CellCall. (3) Results: CellCallEXT was successfully applied to examine tumors and immune cell microenvironments and to identify the altered L–R pairs and downstream gene regulatory networks among immune cells. Application of CellCallEXT to scRNA-seq data from patients with deficiency of adenosine deaminase 2 demonstrated its ability to impute dysfunctional intercellular communication and related transcriptional factor activities. (4) Conclusions: CellCallEXT provides a practical tool to examine intercellular communication in disease based on scRNA-seq data.
Advances in Preclinical/Clinical Glioblastoma Treatment: Can Nanoparticles Be of Help?
Authors: Ruiz-Molina Daniel , Mao Xiaoman , Alfonso-Triguero Paula , Lorenzo Julia , Bruna Jordi , Yuste Victor J. , Candiota Ana Paula , Novio Fernando
Published: October 2022

Glioblastoma multiforme (GB) is the most aggressive and frequent primary malignant tumor in the central nervous system (CNS), with unsatisfactory and challenging treatment nowadays. Current standard of care includes surgical resection followed by chemotherapy and radiotherapy. However, these treatments do not much improve the overall survival of GB patients, which is still below two years (the 5-year survival rate is below 7%). Despite various approaches having been followed to increase the release of anticancer drugs into the brain, few of them demonstrated a significant success, as the blood brain barrier (BBB) still restricts its uptake, thus limiting the therapeutic options. Therefore, enormous efforts are being devoted to the development of novel nanomedicines with the ability to cross the BBB and specifically target the cancer cells. In this context, the use of nanoparticles represents a promising non-invasive route, allowing to evade BBB and reducing systemic concentration of drugs and, hence, side effects. In this review, we revise with a critical view the different families of nanoparticles and approaches followed so far with this aim.
Gene Regulatory Network Characterization of Gastric Cancer’s Histological Subtypes: Distinctive Biological and Clinically Relevant Master Regulators
Authors: Russi Sabino , Marano Luigi , Laurino Simona , Calice Giovanni , Scala Dario , Marino Graziella , Sgambato Alessandro , Mazzone Pellegrino , Carbone Ludovico , Napolitano Giuliana , Roviello Franco , Falco Geppino , Zoppoli Pietro
Published: October 2022

Gastric cancer (GC) molecular heterogeneity represents a major determinant for clinical outcomes, and although new molecular classifications have been introduced, they are not easy to translate from bench to bedside. We explored the data from GC public databases by performing differential gene expression analysis (DEGs) and gene network reconstruction to identify master regulators (MRs), as well as a gene set analysis (GSA) to reveal their biological features. Moreover, we evaluated the association of MRs with clinicopathological parameters. According to the GSA, the Diffuse group was characterized by an epithelial-mesenchymal transition (EMT) and inflammatory response, while the Intestinal group was associated with a cell cycle and drug resistance pathways. In particular, the regulons of Diffuse MRs, such as Vgll3 and Ciita, overlapped with the EMT and interferon-gamma response, while the regulons Top2a and Foxm1 were shared with the cell cycle pathways in the Intestinal group. We also found a strict association between MR activity and several clinicopathological features, such as survival. Our approach led to the identification of genes and pathways differentially regulated in the Intestinal and Diffuse GC histotypes, highlighting biologically interesting MRs and subnetworks associated with clinical features and prognosis, suggesting putative actionable candidates.
Paternal Occupational Exposure to Heavy Metals and Welding Fumes and Testicular Germ Cell Tumours in Sons in France
Authors: Ahmadi Shukrullah , Guth Margot , Coste Astrid , Bouaoun Liacine , Danjou Aurélie , Lefevre Marie , Dananché Brigitte , Praud Delphine , Van Tongeren Martie , Bujan Louis , Pérol Olivia , Schüz Joachim , Charbotel Barbara , Fervers Béatrice , Olsson Ann ,   the TESTIS Study Group
Published: October 2022

Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case–control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers’ jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons.
High Neutrophil-to-Lymphocyte Ratio Facilitates Cancer Growth—Currently Marketed Drugs Tadalafil, Isotretinoin, Colchicine, and Omega-3 to Reduce It: The TICO Regimen
Authors: Kast Richard E.
Published: October 2022

This paper presents remarkably uniform data showing that higher NLR is a robust prognostic indicator of shorter overall survival across the common metastatic cancers. Myeloid derived suppressor cells, the NLRP3 inflammasome, neutrophil extracellular traps, and absolute neutrophil count tend to all be directly related to the NLR. They, individually and as an ensemble, contribute to cancer growth and metastasis. The multidrug regimen presented in this paper, TICO, was designed to decrease the NLR with potential to also reduce the other neutrophil related elements favoring malignant growth. TICO is comprised of already marketed generic drugs: the phosphodiesterase 5 inhibitor tadalafil, used to treat inadequate erections; isotretinoin, the retinoid used for acne treatment; colchicine, a standard gout (podagra) treatment; and the common fish oil supplement omega-3 polyunsaturated fatty acids. These individually impose low side effect burdens. The drugs of TICO are old, cheap, well known, and available worldwide. They all have evidence of lowering the NLR or the growth contributing elements related to the NLR when clinically used in general medicine as reviewed in this paper.
Early Mechanisms of Chemoresistance in Retinoblastoma
Authors: Zhang Michelle G. , Kuznetsoff Jeffim N. , Owens Dawn A. , Gallo Ryan A. , Kalahasty Karthik , Cruz Anthony M. , Kurtenbach Stefan , Correa Zelia M. , Pelaez Daniel , Harbour J. William
Published: October 2022

Retinoblastoma is the most common eye cancer in children and is fatal if left untreated. Over the past three decades, chemotherapy has become the mainstay of eye-sparing treatment. Nevertheless, chemoresistance continues to represent a major challenge leading to ocular and systemic toxicity, vision loss, and treatment failure. Unfortunately, the mechanisms leading to chemoresistance remain incompletely understood. Here, we engineered low-passage human retinoblastoma cells to study the early molecular mechanisms leading to resistance to carboplatin, one of the most widely used agents for treating retinoblastoma. Using single-cell next-generation RNA sequencing (scRNA-seq) and single-cell barcoding technologies, we found that carboplatin induced rapid transcriptomic reprogramming associated with the upregulation of PI3K-AKT pathway targets, including ABC transporters and metabolic regulators. Several of these targets are amenable to pharmacologic inhibition, which may reduce the emergence of chemoresistance. We provide evidence to support this hypothesis using a third-generation inhibitor of the ABCB1 transporter.
Genome-Wide DNA Methylation and Gene Expression Profiling Characterizes Molecular Subtypes of Esophagus Squamous Cell Carcinoma for Predicting Patient Survival and Immunotherapy Efficacy
Authors: Zheng Yulong , Gao Qiqi , Su Xingyun , Xiao Cheng , Yu Bo , Huang Shenglin , Sun Yifeng , Wu Sheng , Wo Yixin , Xu Qinghua , Xu Nong , Yu Hui
Published: October 2022

Background: Immunotherapy is recently being used to treat esophageal squamous cell carcinoma (ESCC); however, response and survival benefits are limited to a subset of patients. A better understanding of the molecular heterogeneity and tumor immune microenvironment in ESCC is needed for improving disease management. Methods: Based on the DNA methylation and gene expression profiles of ESCC patients, we identify molecular subtypes of patients and construct a predictive model for subtype classification. The clinical value of molecular subtypes for the prediction of immunotherapy efficacy is assessed in an independent validation cohort of Chinese ESCC patients who receive immunotherapy. Results: We identify two molecular subtypes of ESCC (S1 and S2) that are associated with distinct immune-related pathways, tumor microenvironment and clinical outcomes. Accordingly, S2 subtype patients had a poorer prognosis. A 15-gene expression signature is developed to classify molecular subtypes with an overall accuracy of 94.7% (89/94, 95% CI: 0.880–0.983). The response rate of immunotherapy is significantly higher in the S1 subtype than in the S2 subtype patients (68.75% vs. 25%, p = 0.028). Finally, potential target drugs, including mitoxantrone, are identified for treating patients of the S2 subtype. Conclusions: Our findings demonstrated that the identified molecular subtypes constitute a promising prognostic and predictive biomarker to guide the clinical care of ESCC patients.
An Inflammatory Signature to Predict the Clinical Benefit of First-Line Cetuximab Plus Platinum-Based Chemotherapy in Recurrent/Metastatic Head and Neck Cancer
Authors: Cavalieri Stefano , Serafini Mara Serena , Carenzo Andrea , Canevari Silvana , Lenoci Deborah , Pistore Federico , Miceli Rosalba , Vecchio Stefania , Ferrari Daris , Moro Cecilia , Sponghini Andrea , Caldara Alessia , Rocca Maria Cossu , Secondino Simona , Moretti Gabriella , Denaro Nerina , Caponigro Francesco , Vaccher Emanuela , Rinaldi Gaetana , Ferraù Francesco , Bossi Paolo , Licitra Lisa , De Cecco Loris
Published: October 2022

Epidermal growth factor receptor (EGFR) pathway has been shown to play a crucial role in several inflammatory conditions and host immune-inflammation status is related to tumor prognosis. This study aims to evaluate the prognostic significance of a four-gene inflammatory signature in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients treated with the EGFR inhibitor cetuximab plus chemotherapy. The inflammatory signature was assessed on 123 R/M HNSCC patients, enrolled in the multicenter trial B490 receiving first-line cetuximab plus platinum-based chemotherapy. The primary endpoint of the study was progression free survival (PFS), while secondary endpoints were overall survival (OS) and objective response rate (ORR). The patient population was subdivided into 3 groups according to the signature score groups. The four-genes-signature proved a significant prognostic value, resulting in a median PFS of 9.2 months in patients with high vs. 6.2 months for intermediate vs. 3.9 months for low values (p = 0.0016). The same findings were confirmed for OS, with median time of 18.4, 13.4, and 7.5 months for high, intermediate, and low values of the score, respectively (p = 0.0001). When ORR was considered, the signature was significantly higher in responders than in non-responders (p = 0.0092), reaching an area under the curve (AUC) of 0.65 (95% CI: 0.55–0.75). Our findings highlight the role of inflammation in the response to cetuximab and chemotherapy in R/M-HNSCC and may have translational implications for improving treatment selection.
Patient Selection Approaches in FGFR Inhibitor Trials—Many Paths to the Same End?
Authors: Ellinghaus Peter , Neureiter Daniel , Nogai Hendrik , Stintzing Sebastian , Ocker Matthias
Published: October 2022

Inhibitors of fibroblast growth factor receptor (FGFR) signaling have been investigated in various human cancer diseases. Recently, the first compounds received FDA approval in biomarker-selected patient populations. Different approaches and technologies have been applied in clinical trials, ranging from protein (immunohistochemistry) to mRNA expression (e.g., RNA in situ hybridization) and to detection of various DNA alterations (e.g., copy number variations, mutations, gene fusions). We review, here, the advantages and limitations of the different technologies and discuss the importance of tissue and disease context in identifying the best predictive biomarker for FGFR targeting therapies.
Tumor-Infiltrating Dendritic Cells: Decisive Roles in Cancer Immunosurveillance, Immunoediting, and Tumor T Cell Tolerance
Authors: Katopodi Theodora , Petanidis Savvas , Charalampidis Charalampos , Chatziprodromidou Ioanna , Eskitzis Panagiotis , Tsavlis Drosos , Zarogoulidis Paul , Kosmidis Christoforos , Matthaios Dimitris , Porpodis Konstantinos
Published: October 2022

The tumor microenvironment plays a key role in progression of tumorigenesis, tumor progression, and metastasis. Accumulating data reveal that dendritic cells (DCs) appear to play a key role in the development and progression of metastatic neoplasia by driving immune system dysfunction and establishing immunosuppression, which is vital for tumor evasion of host immune response. Consequently, in this review, we will discuss the function of tumor-infiltrating DCs in immune cell signaling pathways that lead to treatment resistance, tumor recurrence, and immunosuppression. We will also review DC metabolism, differentiation, and plasticity, which are essential for metastasis and the development of lung tumors. Furthermore, we will take into account the interaction between myeloid cells and DCs in tumor-related immunosuppression. We will specifically look into the molecular immune-related mechanisms in the tumor microenvironment that result in reduced drug sensitivity and tumor relapse, as well as methods for combating drug resistance and focusing on immunosuppressive tumor networks. DCs play a crucial role in modulating the immune response. Especially, as cancer progresses, DCs may switch from playing an immunostimulatory to an inhibitory role. This article’s main emphasis is on tumor-infiltrating DCs. We address how they affect tumor growth and expansion, and we highlight innovative approaches for therapeutic modulation of these immunosuppressive DCs which is necessary for future personalized therapeutic approaches.
High Presence of NETotic Cells and Neutrophil Extracellular Traps in Vaginal Discharges of Women with Vaginitis: An Exploratory Study
Authors: Zambrano Fabiola , Melo Angélica , Rivera-Concha Rodrigo , Schulz Mabel , Uribe Pamela , Fonseca-Salamanca Flery , Ossa Ximena , Taubert Anja , Hermosilla Carlos , Sánchez Raúl
Published: October 2022

Infectious vaginitis is a microbiological syndrome of great importance in public health that affects millions of women worldwide. However, no studies have explored the phenomenon of the production of the neutrophil extracellular traps (NETs) that are released into the female reproductive tract in these pathologies. This study aimed to determine the presence of NETosis in vaginal discharges of women with bacterial vaginosis, candidiasis, and trichomoniasis by characterizing NETs. Extracellular DNA with neutrophil elastase and citrullinated histones was identified to confirm the NET components (n = 10). The concentration, phenotypes of NETs, and number of NETotic cells were determined. The results showed an increase in NETotic cells in women with Candida albicans (CA) and Trichomonas vaginalis (TV) and an increase in NETs in TV-induced vaginitis. Samples of CA- and TV-infected women showed different NET phenotypes (diffNETs, sprNETs, and aggNETs); diffNETs were found in high concentrations in samples with CA and were increased in three types of NETs in TV infections. Samples with intermediate microbiota and bacterial vaginosis showed increased NETotic cells while the intermediate microbiota presented a higher concentration of NETs. Therefore, alterations in the microbiota and the presence of fungal and parasitic infections are important stimuli for the activation and induction of NETosis, and their cytotoxic effects could enhance tissue damage.
Facile Preparation of Ag-NP-Deposited HRGB-SERS Substrate for Detection of Polycyclic Aromatic Hydrocarbons in Water
Authors: Wang Dongmei , Hui Binyu , Zhang Xueqi , Zhu Jingyi , Gong Zhengjun , Fan Meikun
Published: October 2022

In this study, a surface-enhanced Raman scattering (SERS) substrate based on high-refractive-index reflective glass beads (HRGBs) was prepared by a facile method and successfully applied to the detection of polycyclic aromatic hydrocarbons (PAHs). The HRGB-SERS substrate was prepared by depositing silver nanoparticles (Ag NPs) onto the surface of HRGBs. The preparation procedure of the substrate was simplified by accelerating the hydrolysis of (3-Aminopropyl) trimethoxysilane (APTMS) and increasing the concentration of Ag NPs. Compared with previous methods, the HRGB-SERS substrate prepared with one round of deposition has the same detection performance, a simpler preparation process, and lower cost. Additionally, halide ions were used to modify the substrate to increase the detection sensitivity of PAHs. Adding 10 mM KBr solution to the HRGB-SERS substrate was found to achieve the best modification effect. Under the optimal modification conditions, the detection sensitivity of pyrene was improved by 3 orders of magnitude (10−7 M). Due to the HRGB-SERS substrate’s excellent performance, the rapid identification and trace detection of spiked water samples mixed with anthracene, phenanthrene, and pyrene was realized using a Raman spectrometer with only a volume of 10 μL of the water samples.
An Ascorbic Acid-Imprinted Poly(o-phenylenediamine)/AuNPs@COFTFPB-NBPDA for Electrochemical Sensing Ascorbic Acid
Authors: Chen Yaqin , Peng Xia , Song Yonghai , Ma Guangran
Published: October 2022

An electrochemical sensor based on a molecularly imprinted polymer membrane (MIP) was developed. The electrochemical sensor was prepared by electropolymerization of o-phenylenediamine (O-PD) on the surface of glassy carbon electrode (GCE), modified by AuNPs@covalent organic framework (COF) microspheres with ascorbic acid (AA) as template molecule. First, ultrasmall polyvinylpyrrolidone (PVP)-coated AuNPs were prepared by a chemical reduction method. Then, 1,3,5-tri(p-formylphenyl)benzene (TFPB) and N-boc-1,4-phenylene diamine (NBPDA) underwent an ammonaldehyde condensation reaction on PVP-coated AuNPs to form AuNPs@COFTFPB-NBPDA microspheres. The porous spherical structure of AuNPs@ COFTFPB-NBPDA could accelerate the mass transfer, enlarge the specific surface area, and enhance the catalytic activity of PVP-coated AuNPs. The electrochemical sensors, based on AuNPs@ COFTFPB-NBPDA/GCE and nMIPs/AuNPs@COFTFPB-NBPDA/GCE, were applied for the detection of AA, with a detection limit of 1.69 and 2.57 μM, as well as linear ranges of 5.07 to 60 mM and 7.81 to 60 mM. The nMIPs/AuNPs@COFTFPB-NBPDA sensor had satisfactory stability, selectivity, and reproducibility for AA detection.
From Junior to Elite in Soccer: Exploring the Relative Age Effect and Talent Selection in Spanish Youth National Teams
Authors: García-Rubio Javier , García-Vallejo Andrés , Arenas-Pareja María de los Ángeles , López-Sierra Pablo , Ibáñez Sergio J.
Published: October 2022

The implications of relative age grouping in sport are known as the Relative Age Effect (RAE). This study has the twofold purpose of analyzing RAE in Spanish youth national soccer teams and examining the prediction value of being selected for national youth teams to be a professional. The sample was composed of 548 players divided into five groups. A descriptive analysis of distribution and participation, frequencies, mean and standard deviation, crosstabs, Sankey charts, coefficient correlation and Cohen’s effect size criteria and two regression analyses were performed. Results established that the RAE is present in U’17 to U’21 Spanish youth national teams. Talent detection and selection programs are more reliable the closer they are to adulthood, reaching a success rate of almost 100% at the U’21 stage. The selection of players for such programs should be delayed as much as possible, thus, preventing younger players from dropping out and those selected from thinking they have already reached their goal. To this end, they should focus on long-term improvement, not short-term performance. In addition, factors such as the RAE or the maturity level of the athletes should be monitored.
Comprehensive Review: Advancements in Rainfall-Runoff Modelling for Flood Mitigation
Authors: Jehanzaib Muhammad , Ajmal Muhammad , Achite Mohammed , Kim Tae-Woong
Published: October 2022

Runoff plays an essential part in the hydrological cycle, as it regulates the quantity of water which flows into streams and returns surplus water into the oceans. Runoff modelling may assist in understanding, controlling, and monitoring the quality and amount of water resources. The aim of this article is to discuss various categories of rainfall–runoff models, recent developments, and challenges of rainfall–runoff models in flood prediction in the modern era. Rainfall–runoff models are classified into conceptual, empirical, and physical process-based models depending upon the framework and spatial processing of their algorithms. Well-known runoff models which belong to these categories include the Soil Conservation Service Curve Number (SCS-CN) model, Storm Water Management model (SWMM), Hydrologiska Byråns Vattenbalansavdelning (HBV) model, Soil and Water Assessment Tool (SWAT) model, and the Variable Infiltration Capacity (VIC) model, etc. In addition, the data-driven models such as Adaptive Neuro Fuzzy Inference System (ANFIS), Artificial Neural Network (ANN), Deep Neural Network (DNN), and Support Vector Machine (SVM) have proven to be better performance solutions in runoff modelling and flood prediction in recent decades. The data-driven models detect the best relationship based on the input data series and the output in order to model the runoff process. Finally, the strengths and downsides of the outlined models in terms of understanding variation in runoff modelling and flood prediction were discussed. The findings of this comprehensive study suggested that hybrid models for runoff modeling and flood prediction should be developed by combining the strengths of traditional models and machine learning methods. This article suggests future research initiatives that could help with filling existing gaps in rainfall–runoff research and will also assist hydrological scientists in selecting appropriate rainfall–runoff models for flood prediction and mitigation based on their benefits and drawbacks.
Preparation of the Surface of Long-Dimensional Rods of Hydro-Cylinders for Thermal Spraying Using an Abrasive Jet
Authors: Zhetessova Gulnara , Nikonova Tatyana , Gierz Łukasz , Zhunuspekov Darkhan , Yurchenko Vassiliy , Zharkevich Olga
Published: October 2022

Preliminary cleaning of the surface of hydraulic cylinder rods is of great importance for subsequent coating. The most widely used surface preparation for thermal spraying is jet-abrasive treatment. The shot blast modes provide the hardness and strength of the material being processed. The impact of the abrasive makes the surface rough, increasing the contact area. Experimental studies of jet-abrasive processing of the hydraulic cylinder rod surface, as well as its activation for the thermal spraying, were carried out. The prepared surface of the rod for thermal spraying must meet the requirements for surface roughness and the size of the hardened layer at work. The experiments made it possible to identify the optimal modes of jet-abrasive treatment, which affect surface roughness and abrasive penetration of abrasive. To obtain the desired roughness values, it is preferable to use the following: a steel shot with an abrasive particle size in the range of 0.3–1.5 mm, taking the compressed air pressure in the range of 0.4–0.7 MPa; processing time—within 3.5–5 min; counterflow angle with the surface—70–90°; consumption of abrasive particles—300–500 kg/h. A special installation for jet-abrasive processing has been designed, which makes it possible to restore the surfaces of long rods by thermal spraying directly at the site of operation of the large machines.
A Hollow Silicon Nanosphere/Carbon Nanotube Composite as an Anode Material for Lithium-Ion Batteries
Authors: Tang Hao , Xu Yuanyuan , Liu Li , Zhao Decheng , Zhang Zhen , Wu Yutong , Zhang Yi , Liu Xiang , Wang Zhoulu
Published: October 2022

Silicon possesses a high theoretical specific capacity and is a promising high-performance anode material for lithium-ion batteries (LIBs). However, it shows a poor cycling performance because of volume expansion. A hollow structure can improve Si cycling performance, and the template method is one of the most common methods for hollow micro/nanosphere preparation. A polystyrene (PS) microsphere has the advantages of having a uniform and controllable particle size, easy modification, and high stability, thus being an ideal template for preparing hollow structure material. Herein, PS microspheres are used as templates to obtain hollow silica spheres, and then obtain hollow silicon spheres with an inner pore diameter of ~50 nm by a magnesium thermal reduction method. Lithium-ion battery anode material is obtained using carbon nanotubes supporting hollow silicon spheres (Si-CNTs). Si-CNTs exhibit excellent cycling performance (1188 mAh g−1 after 200 cycles) and excellent rate capability (484 mAh g−1 at 1 A g−1). Hollow porous Si-CNTs show great potential, providing a promising idea for solving the volume expansion problem of Si.
Teleoperated Locomotion for Biobot between Japan and Bangladesh
Authors: Ariyanto Mochammad , Refat Chowdhury Mohammad Masum , Zheng Xiaofeng , Hirao Kazuyoshi , Wang Yingzhe , Morishima Keisuke
Published: October 2022

Biobot-based insects have been investigated so far for various applications such as search and rescue operations, environmental monitoring, and discovering the environment. These applications need a strong international collaboration to complete the tasks. However, during the COVID-19 pandemic, most people could not easily move from one country to another because of the travel ban. In addition, controlling biobots is challenging because only experts can operate the cockroach behavior with and without stimulated response. In order to solve this issue, we proposed a user-friendly teleoperation user interface (UI) to monitor and control the biobot between Japan and Bangladesh without onsite operation by experts. This study applied Madagascar hissing cockroaches (MHC) as a biobot hybrid robot. A multithreading algorithm was implemented to run multiple parallel computations concurrently on the UI. Virtual network computing (VNC) was implemented on the teleoperation UI as remote communication for streaming real-time video from Japan to Bangladesh and sending remote commands from Bangladesh to Japan. In the experiments, a remote operator successfully steered the biobot to follow a predetermined path through a developed teleoperation UI with a time delay of 275 ms. The proposed interactive and intuitive UI enables a promising and reliable system for teleoperated biobots between two remote countries.
Study of the Microstructural, Thermal, and Magnetic Properties of High-Energy Ball-Milled Nanocrystalline Fe(Al)
Authors: Ibn Gharsallah Hana , Azabou Myriam , Khitouni Mohamed , Daza Jason , Suñol Joan-Josep
Published: October 2022

In this work, structural, microstructural, thermal, and magnetic properties of a Fe-25at%Al alloy produced by high-energy mechanical milling were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and vibrating sample magnetometry (VSM) techniques. At the early stage of the milling process, three phases, namely, Fe, Al, and Fe(Al), coexist in the milled powder. After 20 h of milling, the results of the refinement of the XRD pattern reveal the formation of the supersaturated bcc-Fe(Al) solid solution with a crystallite size of 10 nm. The DSC curves show several overlapped exothermic peaks associated with the relaxation of the deformed structure and various phase transitions, such as the formation of Al13Fe4 and Fe3Al intermetallic. During milling times, the alloyed samples have a hard-ferromagnetic behavior, where Hc varies from 628 Oe to 746 Oe when the milling time increases from 4 to 40 h. The magnetic properties were related to the microstructural changes.
A Simple Method to Build High Power PCSEL Array with Isolation Pattern Design
Authors: Chang Chia-Jui , Chen Lih-Ren , Hong Kuo-Bin , Weng Wei-Chih , Chuang Bing-Hong , Kuo Hao-Chung , Lu Tien-Chang
Published: October 2022

Photonic crystal surface-emitting lasers (PCSELs) hold promising properties of both edge emitting lasers (EELs) and vertical-cavity surface-emitting lasers (VCSELs). They possess high output power while radiating light vertically, being thought of as the next generation laser source. One of the main advantages of PCSELs is their scalability of size and power, which makes them applicable to high power applications or long-distance detection. However, due to problems such as current injection and mode competition, there are limits on their dimensions. To further increase the power, the capability of two-dimensional array integration paves the way. In this work, we demonstrate a new method to fabricate PCSEL arrays by defining an isolation pattern. We also investigate the influence of aperture size and array arrangement on lasing performance.
Four-Objective Optimizations of a Single Resonance Energy Selective Electron Refrigerator
Authors: He Jinhu , Chen Lingen , Ge Yanlin , Shi Shuangshuang , Li Fang
Published: October 2022

According to the established model of a single resonance energy selective electron refrigerator with heat leakage in the previous literature, this paper performs multi-objective optimization with finite-time thermodynamic theory and NSGA-II algorithm. Cooling load (R¯), coefficient of performance (ε), ecological function (ECO¯), and figure of merit (χ¯) of the ESER are taken as objective functions. Energy boundary (E′/kB) and resonance width (ΔE/kB) are regarded as optimization variables and their optimal intervals are obtained. The optimal solutions of quadru-, tri-, bi-, and single-objective optimizations are obtained by selecting the minimum deviation indices with three approaches of TOPSIS, LINMAP, and Shannon Entropy; the smaller the value of deviation index, the better the result. The results show that values of E′/kB and ΔE/kB are closely related to the values of the four optimization objectives; selecting the appropriate values of the system can design the system for optimal performance. The deviation indices are 0.0812 with LINMAP and TOPSIS approaches for four-objective optimization (ECO¯−R¯−ε−χ¯), while the deviation indices are 0.1085, 0.8455, 0.1865, and 0.1780 for four single-objective optimizations of maximum ECO¯, R¯, ε, and χ¯, respectively. Compared with single-objective optimization, four-objective optimization can better take different optimization objectives into account by choosing appropriate decision-making approaches. The optimal values of E′/kB and ΔE/kB range mainly from 12 to 13, and 1.5 to 2.5, respectively, for the four-objective optimization.