bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling Residential Outdoor Thermal Sensation in Hot Summer Cities: A Case Study in Chongqing, China
Authors: Liu Ying , Gao Yafeng , Shi Dachuan , Zhuang Chaoqun , Lin Zhang , Hao Zhongyu
Published: September 2022

Exposure to extreme heat is a significant public health problem and the primary cause of weather-related mortality, which can be anticipated by accurately predicting outdoor thermal sensation. Empirical models have shown better accuracy in predicting thermal sensation than the most frequently used theoretical thermal indices, which have ignored adaptability to local climate and resulted in underestimating or overestimating the neutral levels of residents. This study proposes a scheme to build an empirical model by considering the multiple linear regression of thermal sensation and microclimatic parameters during summer in Chongqing, China. Thermal environment parameters (air temperature, relative humidity, wind speed, and surface temperature) were recorded and analyzed, together with 375 questionnaire survey responses referring to different underlying surfaces. The results found that the proposed model predicted neutral sensations as warm and 19.4% of warm sensations as hot, indicating that local residents adapted to warm or even hot sensations. In addition, the empirical model could provide references for local pedestrians’ daytime path choices. Residents might feel more comfortable staying beside a pond from 8:00 to 11:00 or sheltering under trees from 08:00 to 14:00 and 17:00 to 19:00. Masonry offered a comfortable microclimate between 10:15 and 11:00, and residents on the lawns were comfortable from 17:30 to 19:00. However, asphalt should be equipped with cooling infrastructures in order to cool thermal sensation.
Alkali-Activated Binder Based on Cupola Dust of Mineral Wool Production with Mechanical Activation
Authors: Fedorov Pavel , Sinitsin Dmitry
Published: September 2022

The development of low-carbon alkali-activated binders based on production waste is one of the most sought-after areas of development of building materials science. The article examines the results of studies of the structures of cupola dust and the assessment of its ability to hydrate when exposed to alkaline activation. Technological preparation of dust by sifting it through a 0.16 mm sieve and subsequent mechanical activation for 120 s to a specific surface area of 733 m2/kg is proposed. The best results were shown by the composition of cupola dust with an alkaline activator of 50 wt.% 8.3 M NaOH and 50 wt.% Na2SiO3. After 28 days of natural hardening for this composition, the bending strength was 12.7 MPa and the compressive strength was 68.3 MPa. The analysis of the influence of hardening conditions showed that the temperature–humidity treatment of concrete at a temperature of 90 °C for 12 h accelerates the process of curing to 80–90% of natural conditions. The porosity of the samples after heating was established, which is 24–25%. The mineralogical composition of the products of the cement matrix structure’s formation, which is represented by minerals of the zeolite group, was specified.
Big Data-Based Performance Analysis of Tunnel Boring Machine Tunneling Using Deep Learning
Authors: Zhang Ye , Chen Jinqiao , Han Shuai , Li Bin
Published: September 2022

In tunnel boring machine (TBM) construction, the advance rate is a crucial parameter that affects the TBM driving efficiency, project schedule, and construction cost. During the operation process, various types of indicators that are monitored in real-time can help to control the advance rate of TBM. Although some studies have already been carried out in advance rate prediction, the research is almost all based on statistical methods and shallow machine learning algorithms, thereby having difficulties in dealing with a very large amount of monitored data and in modeling the time-dependent characteristics of the parameters. To solve this problem, a deep learning model is proposed based on the CNN architecture, bidirectional Long Short-Term Memory module, and the attention mechanism, which is called the CNN-Bi-LSTM-Attention model. In the first step, the monitored data is processed, and the CNN architecture is adopted to extract features from the data sequence. Then the Bi-LSTM module is adopted to obtain the time-dependent indicators. The significant features can be addressed by the added attention mechanism. In the model training process, the rotation speed of the cutter head (N), thrust (F), torque (T), penetration rate (P), and chamber earth pressure (Soil_P) are adopted to predict the advance rate. The influence of the training periods on the model performance is also discussed. The result shows that not only the data amount, but also the data periods have an influence on the prediction. The long-term data may lead to a failure of the advance rate of TBM. The model evaluation result on the test data shows that the proposed model cannot predict the monitored data in the starting stage, which denotes that the working state of TBM in the starting stage is not stable. Especially when the TBM starts to work, the prediction error is big. The proposed model is also compared with several traditional machine methods, and the result shows the excellent performance of the proposed model.
Short Review on the Application of Recycled Powder in Cement-Based Materials: Preparation, Performance and Activity Excitation
Authors: Yang Yonggan , Kang Zihao , Zhan Binggen , Gao Peng , Yu Qijun , Wang Jingfeng , Zhao Weiping , Zhang Yunsheng , Bi Wanqi , Yang Chongyang , Bi Yunfei , Ding Jianzhou , Chen Yuli
Published: September 2022

Recycled powder is a kind of powder particle with a particle size of less than 75 μm produced in the process of preparing recycled aggregate from construction waste with concrete and brick as the main components. It has the potential to replace part of cement as an auxiliary cementitious material. This has important engineering application value for promoting the full-component and high-quality utilization of construction waste, which meets the needs of national sustainable development. Based on the physical and chemical characteristics of recycled powder, the preparation process and basic properties of the recycled powder were systematically analyzed. Based on the low activity of recycled powder, different methods of its activity excitation were described in detail. In addition, some existing problems in the current research were also prospected.
Verification of a Novel Minimally Invasive Device for the Isolation of Rare Circulating Tumor Cells (CTC) in Cancer Patients’ Blood
Authors: Geus Paul Friedrich , Hehnen Felix , Krakowski Sophia , Lücke Klaus , Hoon Dave S. B. , Frost Nikolaj , Kertzscher Ulrich , Wendt Gabi
Published: September 2022

Circulating tumor cells (CTCs) exist in low quantities in the bloodstream in the early stages of cancers. It, therefore, remains a technical challenge to isolate them in large enough quantities for a precise diagnosis and downstream analysis. We introduce the BMProbe™, a minimally invasive device that isolates CTCs during a 30-minute incubation in the median cubital vein. The optimized geometry of the device creates flow conditions for improved cell deposition. The CTCs are isolated using antibodies that are bound to the surface of the BMProbe™. In this study, flow experiments using cell culture cells were conducted. They indicate a 31 times greater cell binding efficiency of the BMProbe™ compared to a flat geometry. Further, the functionality of isolating CTCs from patient blood was verified in a small ex vivo study that compared the cell count from seven non-small-cell lung carcinoma (NSCLC) patients compared to nine healthy controls with 10 mL blood samples. The median cell count was 1 in NSCLC patients and 0 in healthy controls. In conclusion, the BMProbe™ is a promising method to isolate CTCs in large quantities directly from the venous bloodstream without removing blood from a patient. The future step is to verify the functionality in vivo.
Tumor-Associated Neutrophils in Colorectal Cancer Development, Progression and Immunotherapy
Authors: Zheng Wei , Wu Jingjing , Peng Yao , Sun Jing , Cheng Pu , Huang Qi
Published: September 2022

The colorectal-cancer (CRC) incidence rate and mortality have remained high for several years. In recent years, immune-checkpoint-inhibitor (ICI) therapy has rapidly developed. However, it is only effective in a few CRC patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) CRC. How to improve the efficiency of ICI therapy in CRC patients with microsatellite stability (MSS) remains a huge obstacle. Tumor-associated neutrophils (TANs), which are similar to macrophages, also have N1 and N2 phenotypes. They can be recruited and polarized through different cytokines or chemokines, and then play an antitumor or tumor-promoting role. In CRC, we find that the prognostic significance of TANs is still controversial. In this review, we describe the antitumor regulation of TANs, and their mechanism of promoting tumor progression by boosting the transformation of inflammation into tumors, facilitating tumor-cell proliferation, metastasis and angiogenesis. The targeting of TANs combined with ICIs may be a new treatment model for CRC. Relevant animal experiments have shown good responses, and clinical trials have also been carried out in succession. TANs, as “assistants” of ICI treatment, may become the key to the success of CRC immunotherapy, although no significant results have been obtained.
Updates on the Management of Acute Myeloid Leukemia
Authors: Huerga-Domínguez Sofía , Villar Sara , Prósper Felipe , Alfonso-Piérola Ana
Published: September 2022

Acute myeloid leukemia is a heterogeneous disease defined by a large spectrum of genetic aberrations that are potential therapeutic targets. New targeted therapies have changed the landscape for a disease with poor outcomes. They are more effective than standard chemotherapy with a good safety profile. For “fit patients” in first-line, the combination of gemtuzumab ozogamicin or midostaurin with intensive chemotherapy or Vyxeos is now considered the “standard of care” for selected patients. On the other hand, for “unfit patients”, azacitidine-venetoclax has been consolidated as a frontline treatment, while other combinations with magrolimab or ivosidenib are in development. Nevertheless, global survival results, especially in relapsed or refractory patients, remain unfavorable. New immunotherapies or targeted therapies, such as Menin inhibitors or sabatolimab, represent an opportunity in this situation. Future directions will probably come from combinations of different targeted therapies (“triplets”) and maintenance strategies guided by measurable residual disease.
Identification of Immuno-Targeted Combination Therapies Using Explanatory Subgroup Discovery for Cancer Patients with EGFR Wild-Type Gene
Authors: Kholod Olha , Basket William , Liu Danlu , Mitchem Jonathan , Kaifi Jussuf , Dooley Laura , Shyu Chi-Ren
Published: September 2022

(1) Background: Phenotypic and genotypic heterogeneity are characteristic features of cancer patients. To tackle patients’ heterogeneity, immune checkpoint inhibitors (ICIs) represent some the most promising therapeutic approaches. However, approximately 50% of cancer patients that are eligible for treatment with ICIs do not respond well, especially patients with no targetable mutations. Over the years, multiple patient stratification techniques have been developed to identify homogenous patient subgroups, although matching a patient subgroup to a treatment option that can improve patients’ health outcomes remains a challenging task. (2) Methods: We extended our Subgroup Discovery algorithm to identify patient subpopulations that could potentially benefit from immuno-targeted combination therapies in four cancer types: head and neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD), lung squamous carcinoma (LUSC), and skin cutaneous melanoma (SKCM). We employed the proportional odds model to identify significant drug targets and the corresponding compounds that increased the likelihood of stable disease versus progressive disease in cancer patients with the EGFR wild-type (WT) gene. (3) Results: Our pipeline identified six significant drug targets and thirteen specific compounds for cancer patients with the EGFR WT gene. Three out of six drug targets—FCGR2B, IGF1R, and KIT—substantially increased the odds of having stable disease versus progressive disease. Progression-free survival (PFS) of more than 6 months was a common feature among the investigated subgroups. (4) Conclusions: Our approach could help to better select responders for immuno-targeted combination therapies and improve health outcomes for cancer patients with no targetable mutations.
EZH2 Inhibition and Cisplatin as a Combination Anticancer Therapy: An Overview of Preclinical Studies
Authors: Samaržija Ivana , Tomljanović Marko , Novak Kujundžić Renata , Trošelj Koraljka Gall
Published: September 2022

Anticancer monotherapies are often insufficient in eradicating cancer cells because cancers are driven by changes in numerous genes and pathways. Combination anticancer therapies which aim to target several cancer traits at once represent a substantial improvement in anticancer treatment. Cisplatin is a conventional chemotherapy agent widely used in the treatment of different cancer types. However, the shortcomings of cisplatin use include its toxicity and development of resistance. Therefore, from early on, combination therapies that include cisplatin were considered and used in a variety of cancers. EZH2, an epigenetic regulator, is frequently upregulated in cancers which, in general, potentiates cancer cell malignant behavior. In the past decade, numerous EZH2 inhibitors have been explored for their anticancer properties. In this overview, we present the studies that discuss the joint action of cisplatin and EZH2 inhibitors. According to the data presented, the use of cisplatin and EZH2 inhibitors may be beneficial in the treatment of lung, ovarian, and breast cancers, since there is a substantial amount of published evidence that suggests their concerted action. However, in testicular germ cell tumors, such a combination would not be recommended because cisplatin resistance seems to be associated with decreased expression of EZH2 in this tumor type.
Transformer for Gene Expression Modeling (T-GEM): An Interpretable Deep Learning Model for Gene Expression-Based Phenotype Predictions
Authors: Zhang Ting-He , Hasib Md Musaddaqul , Chiu Yu-Chiao , Han Zhi-Feng , Jin Yu-Fang , Flores Mario , Chen Yidong , Huang Yufei
Published: September 2022

Deep learning has been applied in precision oncology to address a variety of gene expression-based phenotype predictions. However, gene expression data’s unique characteristics challenge the computer vision-inspired design of popular Deep Learning (DL) models such as Convolutional Neural Network (CNN) and ask for the need to develop interpretable DL models tailored for transcriptomics study. To address the current challenges in developing an interpretable DL model for modeling gene expression data, we propose a novel interpretable deep learning architecture called T-GEM, or Transformer for Gene Expression Modeling. We provided the detailed T-GEM model for modeling gene–gene interactions and demonstrated its utility for gene expression-based predictions of cancer-related phenotypes, including cancer type prediction and immune cell type classification. We carefully analyzed the learning mechanism of T-GEM and showed that the first layer has broader attention while higher layers focus more on phenotype-related genes. We also showed that T-GEM’s self-attention could capture important biological functions associated with the predicted phenotypes. We further devised a method to extract the regulatory network that T-GEM learns by exploiting the attributions of self-attention weights for classifications and showed that the network hub genes were likely markers for the predicted phenotypes.
Role of Intracellular and Extracellular Annexin A1 in MIA PaCa-2 Spheroids Formation and Drug Sensitivity
Authors: Novizio Nunzia , Belvedere Raffaella , Morretta Elva , Tomasini Richard , Monti Maria Chiara , Morello Silvana , Petrella Antonello
Published: September 2022

Among solid tumors, pancreatic cancer (PC) remains a leading cause of death. In PC, the protein ANXA1 has been identified as an oncogenic factor acting in an autocrine/paracrine way, and also as a component of tumor-deriving extracellular vesicles. Here, we proposed the experimental protocol to obtain spheroids from the two cell lines, wild-type (WT) and Annexin A1 (ANXA1) knock-out (KO) MIA PaCa-2, this last previously obtained through CRISPR/Cas9 genome editing system. The use of three-dimensional (3D) models, like spheroids, can be useful to mimic tumor characteristics and for preclinical chemo-sensitivity studies. By using PC spheroids, we have assessed the activity of intracellular and extracellular ANXA1. Indeed, we have proved that the intracellular protein influences in vitro tumor development and growth by spheroids analysis, in addition to defining the modification about cell protein pattern in ANXA1 KO model compared to the WT one. Moreover, we have tested the response to FOLFIRINOX chemotherapy regimen whose cytostatic effect appeared notably increased in ANXA1 KO spheroids. Additionally, this study has highlighted that the extracellular ANXA1 action is strengthened through the EVs supporting spheroids growth and resistance to drug treatment, mainly affecting tumor progression. Thus, our data interestingly suggest the relevance of ANXA1 as a potential therapeutic PC marker.
Expression, Localization and Prognosis Association of MEP50 in Breast Cancer
Authors: Suresh Samyuktha , Vinet Mathilde , Dakroub Rayan , Lesage Laetitia , Ye Mengliang , Fayyad-Kazan Hussein , Nicolas André , Meseure Didier , Dubois Thierry
Published: September 2022

Breast cancer is composed of distinct subgroups, triple-negative breast cancer (TNBC), human epidermal growth factor receptor-2 (HER2), luminal A, and luminal B, which are associated with different prognosis. MEP50 is the main partner of the arginine methyltransferase PRMT5 required for its enzymatic activity. Here, we examined MEP50 expression in the different breast cancer subgroups from the transcriptomic data obtained on human breast cancer samples and on normal breast tissues in two cohorts (Curie, n = 141; The Cancer Genome Atlas—TCGA, n = 788). We observed higher levels of MEP50 mRNA in TNBC (Curie, n = 41; TCGA, n = 106) compared to the other breast cancer subgroups and normal breast tissues. Using an online KM-plotter database, which allows survival analyses in a larger number of breast cancer patients, we found that high MEP50 mRNA levels were associated with a more favorable recurrence-free survival (RFS) in TNBC (n = 953, p = 1.2 × 10−4) and luminal B (n = 1353, p = 0.013) tumors, whereas high PRMT5 mRNA levels were associated with worse RFS in these two subgroups (TNBC: n = 442, p = 1.0 × 10−4; luminal B: n = 566, p = 6.8 × 10−3). We next determined the expression and the subcellular localization of MEP50 protein by immunohistochemistry (IHC) in our Curie cohort of breast cancer (n = 94) and normal tissues (n = 7) using a validated MEP50 antibody. MEP50 was more expressed in breast tumors compared to normal breast tissues (p = 0.02). MEP50 was more localized to the cytosol in breast cancer cells compared to normal breast tissue (p = 4 × 10−4), and was more found at the plasma membrane in normal tissues compared to breast tumors (p = 0.01). We also evaluated PRMT5 activity by IHC in our Curie cohort using a validated antibody (H4R3me2s) detecting histone H4 symmetrically dimethylated on Arg3. High levels of H4R3me2s were found in normal breast tissues, whereas the lowest levels of H4R3me2s were observed in TNBC and HER2 breast cancer subgroups. Altogether, our study reports the expression of the PRMT5 cofactor (MEP50) and substrate (H4R3me2s) in breast cancer and highlights the association of PRMT5 and MEP50 mRNA with prognosis in luminal B and TNBC breast cancer subgroups and certain TNBC subtypes.
Potassium Ion Channels in Malignant Central Nervous System Cancers
Authors: Boyle Yasmin , Johns Terrance G. , Fletcher Emily V.
Published: September 2022

Malignant central nervous system (CNS) cancers are among the most difficult to treat, with low rates of survival and a high likelihood of recurrence. This is primarily due to their location within the CNS, hindering adequate drug delivery and tumour access via surgery. Furthermore, CNS cancer cells are highly plastic, an adaptive property that enables them to bypass targeted treatment strategies and develop drug resistance. Potassium ion channels have long been implicated in the progression of many cancers due to their integral role in several hallmarks of the disease. Here, we will explore this relationship further, with a focus on malignant CNS cancers, including high-grade glioma (HGG). HGG is the most lethal form of primary brain tumour in adults, with the majority of patient mortality attributed to drug-resistant secondary tumours. Hence, targeting proteins that are integral to cellular plasticity could reduce tumour recurrence, improving survival. This review summarises the role of potassium ion channels in malignant CNS cancers, specifically how they contribute to proliferation, invasion, metastasis, angiogenesis, and plasticity. We will also explore how specific modulation of these proteins may provide a novel way to overcome drug resistance and improve patient outcomes.
Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors
Authors: McClellan Kristen , Chen Emerson Y. , Kardosh Adel , Lopez Charles D. , Del Rivero Jaydira , Mallak Nadine , Rocha Flavio G. , Koethe Yilun , Pommier Rodney , Mittra Erik , Pegna Guillaume J.
Published: September 2022

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogenous group of malignancies originating from neuroendocrine cells of the gastrointestinal tract, the incidence of which has been increasing for several decades. While there has been significant progress in the development of therapeutic options for patients with advanced or metastatic disease, these remain limited both in quantity and durability of benefit. This review examines the latest research elucidating the mechanisms of both up-front resistance and the eventual development of resistance to the primary systemic therapeutic options including somatostatin analogues, peptide receptor radionuclide therapy with lutetium Lu 177 dotatate, everolimus, sunitinib, and temozolomide-based chemotherapy. Further, potential strategies for overcoming these mechanisms of resistance are reviewed in addition to a comprehensive review of ongoing and planned clinical trials addressing this important challenge.
Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma
Authors: Whisenant Thomas C. , Nigam Sanjay K.
Published: September 2022

(1) Background: Many transporters of the SLC22 family (e.g., OAT1, OAT3, OCT2, URAT1, and OCTN2) are highly expressed in the kidney. They transport drugs, metabolites, signaling molecules, antioxidants, nutrients, and gut microbiome products. According to the Remote Sensing and Signaling Theory, SLC22 transporters play a critical role in small molecule communication between organelles, cells and organs as well as between the body and the gut microbiome. This raises the question about the potential role of SLC22 transporters in cancer biology and treatment. (2) Results: In two renal cell carcinoma RNA-seq datasets found in TCGA, KIRC and KIRP, there were multiple differentially expressed (DE) SLC22 transporter genes compared to normal kidney. These included SLC22A6, SLC22A7, SLC22A8, SLC22A12, and SLC22A13. The patients with disease had an association between overall survival and expression for most of these DE genes. In KIRC, the stratification of patient data by pathological tumor characteristics revealed the importance of SLC22A2, SLC22A6, and SLC22A12 in disease progression. Interaction networks combining the SLC22 with ADME genes supported the centrality of SLC22 transporters and other transporters (ABCG2, SLC47A1) in disease progression. (3) Implications: The fact that many of these genes are uric acid transporters is interesting because altered uric acid levels have been associated with kidney cancer. Moreover, these genes play key roles in processing metabolites and chemotherapeutic compounds, thus making them potential therapeutic targets. Finally, our analyses raise the possibility that current approaches may undertreat certain kidney cancer patients with low SLC22 expression and only localized disease while possibly overtreating more advanced disease in patients with higher SLC22 expression. Clinical studies are needed to investigate these possibilities.
HSP27/Menin Expression as New Prognostic Serum Biomarkers of Prostate Cancer Aggressiveness Independent of PSA
Authors: Bourefis Asma , Berredjem Hajira , Djeffal Omar , Le Thi Khanh , Giusiano Sophie , Rocchi Palma
Published: September 2022

The screening of PCa is based on two tests, the total PSA test and the rectal examination. However, PSA is not specific for PCa stage confirmation, leading in false positive result and involving PCa over-diagnosis and over-treatment. HSP27 and Menin have been found to be overexpressed in a wide range of human cancers. Recent studies showed how HSP27 interacts with and stabilizes Menin to lead PCa progression and treatment resistance. The purpose of our study was to evaluate the correlation of HSP27 and Menin molecular expression, and their prognosis value in PCa with respect to clinicopathological features. Elisa was employed to measure serum HSP27 and Menin concentrations in 73 PCa patients and 80 healthy individuals. Immunohistochemistry (IHC) was used to determine HSP27 and Menin tissue expression in 57 tumors and 4 Benign Prostatic Hyperplasia (BPH) tissues. Serum HSP27 expression correlated with its tissue expression in all PCa patients, whereas serum Menin expression correlated only with tissue expression in aggressive PCa patients. Moreover, the results showed a positive correlation between HSP27 and Menin either in serum (r = 0.269; p = 0.021) or in tissue (r = 0.561; p < 0.0001). In aggressive PCa, serum expression of HSP27 and Menin was positively correlated (r = 0.664; R = 0.441; p = 0.001). The correlation between HSP27 and Menin expression in tissue was found only in patients with aggressive PCa (r = 0.606; R = 0.367; p = 0.004). Statistical analysis showed that the expression of both biomarkers was positively correlated with the hormone resistance or sensitivity, tumor aggressiveness, metastasis, Gleason Score, death and did not significantly correlate with age and PSA. Survival was illustrated by Kaplan–Meier curves; increased HSP27 and Menin expression correlated with shorter survival of PCa patients (p = 0.001 and p < 0.0001, respectively). Accuracy in predicting aggressiveness was quantified by the Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC). We demonstrated that the combination of HSP27/Menin was statistically greater than PSA; it achieved an AUC of 0.824 (95% CI, 0.730–0.918; p < 0.0001). However, HSP27/Menin/PSA combination decreased the diagnostic value with an AUC of 0.569 (95% CI, 0.428–0.710; p = 0.645). Our work suggests the potential role of HSP27/Menin as diagnostic and prognostic biomarkers.
Management of Optic Pathway Glioma: A Systematic Review and Meta-Analysis
Authors: Yousefi Omid , Azami Pouria , Sabahi Mohammadmahdi , Dabecco Rocco , Adada Badih , Borghei-Razavi Hamid
Published: September 2022

Background: OPG accounts for 3–5% of childhood central nervous system (CNS) tumors and about 2% of pediatric glial lesions. Methods: Article selection was performed by searching PubMed, Web of Science, and Cochrane databases. Results: The pooled mortality rate was 0.12 (95%CI 0.09–0.14). Due to the unrepresentative data, improved and not changed outcomes were classified as favorable outcomes and worsened as unfavorable. Meta-analyses were performed to determine the rate of clinical and radiological favorable outcomes. In terms of visual assessment, the pooled rate of a favorable outcome in chemotherapy, radiotherapy, and surgery was 0.74, 0.81, and 0.65, respectively, and the overall pooled rate of the favorable outcome was 0.75 (95%CI 0.70–0.80). In terms of radiological assessment, the rate of a favorable outcome following chemotherapy, radiotherapy, and surgery was 0.71, 0.74, and 0.67, respectively, and the overall pooled rate of the favorable outcome is 0.71 (95%CI 0.65–0.77). The subgroup analysis revealed no significant difference in the rate of clinical and radiological favorable outcomes between the different treatment modalities (p > 0.05). Conclusion: Our analyses showed that each therapeutic modality represents viable treatment options to achieve remission for these patients.
Magnetoreceptory Function of European Robin Retina: Electrophysiological and Morphological Non-Homogeneity
Authors: Rotov Alexander Yu. , Goriachenkov Arsenii A. , Cherbunin Roman V. , Firsov Michael L. , Chernetsov Nikita , Astakhova Luba A.
Published: September 2022

The avian magnetic compass allows orientation during migration and is shown to function properly under short-wavelength but not long-wavelength visible light. Therefore, the magnetoreceptive system is assumed to be light- and wavelength-dependent and localized in the retina of the eye. Putative candidates for the role of primary magnetosensory molecules are the cryptochromes that are known to be expressed in the avian retina and must be able to interact with phototransduction proteins. Previously, we reported that in migratory birds change in magnetic field direction induces significant effects on electroretinogram amplitude in response to blue flashes, and such an effect was observed only in the nasal quadrant of the retina. Here, we report new electroretinographic, microscopic and microspectrophotometric data on European robins, confirming the magnetosensitivity of the retinal nasal quadrant after applying the background illumination. We hypothesized that magnetoreceptive distinction of this region may be related to its morphology and analyzed the retinal distribution and optical properties of oil droplets, the filtering structures within cones. We found that the nasal quadrant contains double cones with the most intensely colorized oil droplets compared to the rest of the retina, which may be related to its magnetosensory function.
Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma
Authors: Kapoor-Narula Upasana , Lenka Nibedita
Published: September 2022

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, displays a highly infiltrative growth pattern and remains refractory to chemotherapy. Phytochemicals carrying specificity and low cytotoxicity may serve as potent and safer alternatives to conventional chemotherapy for treating GBM. We have evaluated the anticancer effects of Oltipraz (Olt), a synthetic dithiolethione found in many vegetables, including crucifers. While Olt exposure was non-toxic to the HEK-293 cell line, it impaired the cell growth in three GBM cell lines (LN18, LN229, and U-87 MG), arresting those at the G2/M phase. Olt-exposed GBM cells induced the generation of reactive oxygen species (ROS), mitochondrial depolarization, caspase 3/7-mediated apoptosis, nuclear condensation, and DNA fragmentation, and decreased glutathione, a natural ROS scavenger, as well as vimentin and β-catenin, the EMT-associated markers. Its effect on a subpopulation of GBM cells exhibiting glioblastoma stem cell (GSCs)-like characteristics revealed a reduced expression of Oct4, Sox2, CD133, CD44, and a decrease in ALDH+, Nestin+ and CD44+ cells. In contrast, there was an increase in the expression of GFAP and GFAP+ cells. The Olt also significantly suppressed the oncosphere-forming ability of cells. Its efficacy was further validated in vivo, wherein oral administration of Olt could suppress the ectopically established GBM tumor growth in SCID mice. However, there was no alteration in body weight, organ ratio, and biochemical parameters, reflecting the absence of any toxicity otherwise. Together, our findings could demonstrate the promising chemotherapeutic efficacy of Olt with potential implications in treating GBM.
Pro-Inflammatory Chemokines CCL5, CXCL12, and CX3CL1 Bind to and Activate Platelet Integrin αIIbβ3 in an Allosteric Manner
Authors: Takada Yoko K. , Fujita Masaaki , Takada Yoshikazu
Published: September 2022

Activation of platelet integrin αIIbβ3, a key event for hemostasis and thrombus formation, is known to be mediated exclusively by inside-out signaling. We showed that inflammatory chemokines CX3CL1 and CXCL12 in previous studies, and CCL5 in this study, bound to the allosteric binding site (site 2) of vascular integrin αvβ3, in addition to the classical ligand binding site (site 1), and allosterically activated integrins independent of inside-out signaling. Since αIIbβ3 is exposed to inflammatory chemokines at increased concentrations during inflammation (e.g., cytokine/chemokine storm) and platelet activation, we hypothesized that these chemokines bind to and activate αIIbβ3 in an allosteric activation mechanism. We found that these chemokines bound to αIIbβ3. Notably, they activated soluble αIIbβ3 in 1 mM Ca2+ by binding to site 2. They activated cell-surface αIIbβ3 on CHO cells, which lack machinery for inside-out signaling or chemokine receptors, quickly (<1 min) and at low concentrations (1–10 ng/mL) compared to activation of soluble αIIbβ3, probably because chemokines bind to cell surface proteoglycans. Furthermore, activation of αIIbβ3 by the chemokines was several times more potent than 1 mM Mn2+. We propose that CCL5 and CXCL12 (stored in platelet granules) may allosterically activate αIIbβ3 upon platelet activation and trigger platelet aggregation. Transmembrane CX3CL1 on activated endothelial cells may mediate platelet–endothelial interaction by binding to and activating αIIbβ3. Additionally, these chemokines in circulation over-produced during inflammation may trigger αIIbβ3 activation, which is a possible missing link between inflammation and thrombosis.
Rab GTPases as Modulators of Vascular Function
Authors: Raghavan Somasundaram , Brishti Masuma Akter , Leo M. Dennis
Published: September 2022

Rab GTPases, the largest family of small GTPases, are ubiquitously expressed proteins that control various aspects of cellular function, from cell survival to exocytosis. Rabs cycle between the GDP-bound inactive form and the GTP-bound active form. When activated, specific Rab GTPase-positive vesicles mediate cellular networks involved in intracellular trafficking, recycling, and/or exocytosis of cargo proteins. Dysfunctional Rab signaling pathways have been implicated in various disease processes. The precise cellular functions of several members of the Rab GTPase family are still unknown. A lack of pharmacological tools and the lethality of gene knockouts have made more detailed characterizations of their protein interaction networks difficult. Nevertheless, available evidence suggests that these proteins are vital for normal cell function. Endothelial and smooth muscle cells control vascular lumen diameter and modulate blood flow. Endothelial cells also secrete several pro- and antithrombotic factors and vasoactive substances to coordinate local inflammatory responses and angiogenesis. Rab GTPase function in endothelial cells has been relatively well-explored, while only a handful of reports are available on these proteins in vascular smooth muscle. This review summarizes the present knowledge on Rab GTPases in the vasculature.
Pyrotinib Targeted EGFR-STAT3/CD24 Loop-Mediated Cell Viability in TSC
Authors: Han Xiao , Zhang Yupeng , Li Yin , Lin Zhoujun , Pei Xiaolin , Feng Ya , Yang Juan , Li Fei , Li Tianjiao , Fu Zhenkun , Wang Changjun , Li Chenggang
Published: September 2022

Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor, designed for the therapy of HER2-positive breast cancers. Inhibition of the epidermal growth factor receptor (EGFR, HER family) efficiently and selectively suppresses the proliferation of human TSC2-deficient smooth muscle cells and reverses lung changes in LAM/TSC. Our pilot study indicated that pyrotinib dramatically restrained the vitality of TSC2-deficient cells compared to its limited impact on TSC2-expression cells. Pyrotinib induced G1-phase arrest and triggered apoptosis by blocking abnormally activated CD24 in TSC2-deficient cells. CD24 is not only an important immune checkpoint, but is also involved in the regulation of signaling pathways. Pyrotinib inhibited the nuclear import of pEGFR and restrained the pEGFR/pSTAT3 signals, which directly boosted the transcriptional expression of CD24 by binding to its promoter region. In reverse, CD24 enhanced pEGFR function by directly binding. Pyrotinib specifically targeted TSC2-deficient cells, inhibited tumor cell viability and induced apoptosis through EGFR-STAT3/CD24 Loop in vivo and in vitro. Thus, pyrotinib may be a promising new therapeutic drug for TSC treatment.
Hyaluronic Acid-Coated Bovine Milk Exosomes for Achieving Tumor-Specific Intracellular Delivery of miRNA-204
Authors: Li Dan , Gong Liang , Lin Han , Yao Surui , Yin Yuan , Zhou Zhifang , Shi Jie , Wu Zhimeng , Huang Zhaohui
Published: September 2022

Cell type-specific drug delivery is a straightforward strategy to achieve targeted cancer therapy and reduce side effects. Hyaluronic acid (HA), an U.S. Food and Drug Administration (FDA)-approved biocompatible carbohydrate polymer, has been extensively employed as a targeting ligand for a drug delivery system due to its natural ability to bind to tumor cells overexpressing cluster of differentiation 44 (CD44) receptors. Here, we report the preparation and antitumor efficacy of HA-coated bovine milk exosomes (HA-mExo) for tumor-specific delivery of microRNA-204-5p mimics (miR-204). The exosome-based delivery formulation was prepared with miR-204 encapsulated inside the lumen and HA displayed outside the membrane. The resultant formulation of HA-mExo-miR204 was able to specifically target CD44-positive cancer cells, with a concomitant increase in the intracellular uptake of miR-204. Compared to the uncoated mExo-miR204 formulation, HA-mExo-miR204 showed significantly increased antitumor efficacy both in vitro and in vivo. Importantly, HA-mExo-miR204 showed excellent biocompatibility and did not cause significant systemic toxicity. Given that both HA and bovine milk exosomes are low-cost and highly accessible biogenic materials with broad biomedical applications, HA-decorated bovine milk exosomes can be proven to be a practical drug delivery system of RNA drugs for targeted cancer therapy.
Pancreatic Ductal Adenocarcinoma: Molecular Pathology and Predictive Biomarkers
Authors: Taherian Mehran , Wang Hua , Wang Huamin
Published: September 2022

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis due to the lack of methods or biomarkers for early diagnosis and its resistance to conventional treatment modalities, targeted therapies, and immunotherapies. PDACs are a heterogenous group of malignant epithelial neoplasms with various histomorphological patterns and complex, heterogenous genetic/molecular landscapes. The newly proposed molecular classifications of PDAC based on extensive genomic, transcriptomic, proteomic and epigenetic data have provided significant insights into the molecular heterogeneity and aggressive biology of this deadly disease. Recent studies characterizing the tumor microenvironment (TME) have shed light on the dynamic interplays between the tumor cells and the immunosuppressive TME of PDAC, which is essential to disease progression, as well as its resistance to chemotherapy, newly developed targeted therapy and immunotherapy. There is a critical need for the development of predictive markers that can be clinically utilized to select effective personalized therapies for PDAC patients. In this review, we provide an overview of the histological and molecular heterogeneity and subtypes of PDAC, as well as its precursor lesions, immunosuppressive TME, and currently available predictive molecular markers for patients.
Safe from Harm? Massive Attack Nuclear Worst-Case Scenario for Civil Protection in Germany Regarding High-Risk Zones of Exposure, Vulnerability, and Safe Havens
Authors: Fekete Alexander
Published: September 2022

New risk geographies are emerging with war and conflict resurfacing, including nuclear threats. This poses challenges to civil protection for conducting risk-informed preparedness planning. A spatial assessment of Germany and Europe is conducted using a geographic information system. Buffer circles of nuclear explosion effects and fallout buffers show potentially exposed areas around major cities. Different scenarios indicate shrinking areas safe from exposure. However, even in a densely populated country, rural areas and smaller cities can be identified that could provide sites for evacuation shelters. Changing wind directions poses a challenge for civil protection planning because fallout risk covers most German territory even when few cities are attacked. However, wind speeds and topography can help identify suitable shelter areas. More knowledge about the temporal development of a nuclear explosion and its specific forms of harm can also help to improve risk knowledge and planning. While nuclear warfare at first seems to render useless any option for safe areas and survival, the spatial risk assessment shows that exposure does not occur at all places at all times. Being safe from harm will be difficult in such a worst-case scenario, but avoiding large city perimeters and being informed can also help reduce risk.
ADAM10 and ADAM17 as Biomarkers Linked to Inflammation, Metabolic Disorders and Colorectal Cancer
Authors: Sikora-Skrabaka Magdalena , Walkiewicz Katarzyna Weronika , Nowakowska-Zajdel Ewa , Waniczek Dariusz , Strzelczyk Joanna Katarzyna
Published: September 2022

ADAM10 and ADAM17 have a role in inflammation and diseases associated with inflammation, such as diabetes, cardiovascular diseases (CVD) or cancer, e.g., colorectal cancer (CRC). The aim of this study was to evaluate whether ADAM10 and ADAM17 could be biomarkers of CRC. To achieve this goal, CRC tumors and a surgical margin from 72 patients with CRC were collected. The concentration of ADAM proteins was measured by the ELISA method. Results were analyzed statistically and compared with selected clinical parameters. We found that ADAM17 protein concentration in the tumor samples was higher in patients with diabetes mellitus type 2 (DMT2) (0.28 vs. 0.2 ng/µg protein; p = 0.01) and in the surgical margin was higher both in patients with coexisting DMT2 (0.22 vs. 0.16 ng/µg protein; p < 0.05) and CVD (0.21 vs. 0.13 ng/µg protein; p < 0.01). The concentration of ADAM10 was higher in the surgical margin than in the tumor (249.34 vs. 228.82 pg/µg protein), and the concentration of ADAM17 was higher in the tumor than in the margin (0.23 vs. 0.18 ng/µg protein), but results were not statistically significant. In conclusion, the results of our study indicate that ADAM10 and ADAM17 may be potential biomarkers in cancer linked with DMT2 and CVD as diseases associated with inflammation.
Temperature and Residential Electricity Demand for Heating and Cooling in G7 Economies: A Method of Moments Panel Quantile Regression Approach
Authors: Emenekwe Chukwuemeka Chinonso , Emodi Nnaemeka Vincent
Published: September 2022

The global energy system is highly vulnerable to climate variability and change. This results in a vast range of impacts on the energy demand sector and production and supply channels. This article aims to estimate the impacts of variables such as heating and cooling temperatures, income, population, and price on residential electricity demand in G7 countries. Methodologically, this study uses the second-generation panel unit root and cointegration approaches (which are robust in the presence of cross-sectional dependence), a panel fixed effects model with Driscoll–Kraay standard errors, and a novel method of moments quantile regression (MM-QR) to determine long-run elasticities. The results suggest that the residential electricity demand of G7 countries is statistically and positively responsive to cold days rather than hot days. This study also presents some policy-relevant issues based on the results.
Tribological Behavior of High Entropy Alloy Coatings: A Review
Authors: Luo Dawei , Zhou Qing , Huang Zhuobin , Li Yulong , Liu Yulin , Li Qikang , He Yixuan , Wang Haifeng
Published: September 2022

As engineering equipment is applied in a harsh environment with a heavy load, cyclic stress, and a wide range of temperatures, the reliability of the equipment becomes a challenge, especially when wear contact is involved. Hence, the design and exploitation of an advanced alloy surface may hold the key to control and minimize friction and wear in the transmission system for safety-critical applications. High entropy alloys (HEAs) or multi-component alloys have been proved to have outstanding mechanical properties, corrosion resistance, and high-temperature oxidation resistance with potential use as wear resistance and friction reduction coatings. In this paper, the properties and development status of HEAs coating systems for tribological applications were reviewed to gain a better understanding of their advantages and limitations obtained by different preparation methods. Specifically, focus was paid to magnetron sputtering, laser cladding, and thermal spraying since these three deposition methods were more widely used in wear-resistant and friction-reducing coatings. Building upon this, the correlation between composition, mechanical properties, and friction as well as wear characteristics of these coatings are summarized. Finally, the key problems to be solved to move the field forward and the future trend of tribology application for HEA coatings are outlined.
Study of the Passivation Film on S32750 Super-Duplex Stainless Steel Exposed in a Simulated Marine Atmosphere
Authors: Yang Lijing , Du Wenwen , Wu Minghua , He Jin , Yu Guohong , Wang Shuchang , Song Zhenlun
Published: September 2022

The corrosion behavior and passivation mechanism of S32750 super-duplex stainless steel exposed in a simulated marine atmosphere were studied using electrochemical methods, XPS and SEM. Passivation and local corrosion occurred on the metal surface when S32750 SDSS was exposed in the simulated marine atmospheric environment. The passivation film is composed of two chromium-enriched layers. The outer layer is a very thin film at the metal/atmosphere interface of the specimen surface with higher chromium content, whereas the chromium in the inner layer seems a little depleted. The outer and inner layers had similar Fe components, and Fe3+ oxide/hydroxide was the primary oxide in the film. The outer layer contains CrO3, whereas the inner layer has Cr3+ as its primary oxide. Pitting occurred when exposure time exceeded 24 d, and the Cr content of the specimen decreased. Therefore, S32750 SDSS exposed for 24 d exhibited the best corrosion resistance.