bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon-Based Fluorescent Nano-Biosensors for the Detection of Cell-Free Circulating MicroRNAs
Authors: Ratre Pooja , Nazeer Nazim , Kumari Roshani , Thareja Suresh , Jain Bulbul , Tiwari Rajnarayan , Kamthan Arunika , Srivastava Rupesh K. , Mishra Pradyumna Kumar
Published: February 2023

Currently, non-communicable diseases (NCDs) have emerged as potential risks for humans due to adopting a sedentary lifestyle and inaccurate diagnoses. The early detection of NCDs using point-of-care technologies significantly decreases the burden and will be poised to transform clinical intervention and healthcare provision. An imbalance in the levels of circulating cell-free microRNAs (ccf-miRNA) has manifested in NCDs, which are passively released into the bloodstream or actively produced from cells, improving the efficacy of disease screening and providing enormous sensing potential. The effective sensing of ccf-miRNA continues to be a significant technical challenge, even though sophisticated equipment is needed to analyze readouts and expression patterns. Nanomaterials have come to light as a potential solution as they provide significant advantages over other widely used diagnostic techniques to measure miRNAs. Particularly, CNDs-based fluorescence nano-biosensors are of great interest. Owing to the excellent fluorescence characteristics of CNDs, developing such sensors for ccf-microRNAs has been much more accessible. Here, we have critically examined recent advancements in fluorescence-based CNDs biosensors, including tools and techniques used for manufacturing these biosensors. Green synthesis methods for scaling up high-quality, fluorescent CNDs from a natural source are discussed. The various surface modifications that help attach biomolecules to CNDs utilizing covalent conjugation techniques for multiple applications, including self-assembly, sensing, and imaging, are analyzed. The current review will be of particular interest to researchers interested in fluorescence-based biosensors, materials chemistry, nanomedicine, and related fields, as we focus on CNDs-based nano-biosensors for ccf-miRNAs detection applications in the medical field.
SMART: A Swing-Assisted Multiplexed Analyzer for Point-of-Care Respiratory Tract Infection Testing
Authors: Zhang Li , Wang Xu , Liu Dongchen , Wu Yu , Feng Li , Han Chunyan , Liu Jiajia , Lu Ying , Sotnikov Dmitriy V. , Xu Youchun , Cheng Jing
Published: February 2023

Respiratory tract infections such as the ongoing coronavirus disease 2019 (COVID-19) has seriously threatened public health in the last decades. The experience of fighting against the epidemic highlights the importance of user-friendly and accessible point-of-care systems for nucleic acid (NA) detection. To realize low-cost and multiplexed point-of-care NA detection, a swing-assisted multiplexed analyzer for point-of-care respiratory tract infection testing (SMART) was proposed to detect multiple respiratory tract pathogens using visible loop-mediated isothermal amplification. By performing hand-swing movements to generate acceleration force to distribute samples into reaction chambers, the design of the SMART system was greatly simplified. By using different format of chips and integrating into a suitcase, this system can be applied to on-site multitarget and multi-sample testing. Three targets including the N and Orf genes of SARS-CoV-2 and the internal control were simultaneously analyzed (limit of detection: 2000 copies/mL for raw sample; 200 copies/mL for extracted sample). Twenty-three clinical samples with eight types of respiratory bacteria and twelve COVID-19 clinical samples were successfully detected. These results indicate that the SMART system has the potential to be further developed as a versatile tool in the diagnosis of respiratory tract infection.
Fabrication of P and N Co-Doped Carbon Dots for Fe3+ Detection in Serum and Lysosomal Tracking in Living Cells
Authors: Xing Yanzhi , Yang Mei , Chen Xuwei
Published: February 2023

Doping with heteroatoms allows the retention of the general characteristics of carbon dots while allowing their physicochemical and photochemical properties to be effectively modulated. In this work, we report the preparation of ultrastable P and N co-doped carbon dots (PNCDs) that can be used for the highly selective detection of Fe3+ and the tracking of lysosomes in living cells. Fluorescent PNCDs were facilely prepared via a hydrothermal treatment of ethylenediamine and phytic acid, and they exhibited a high quantum yield of 22.0%. The strong coordination interaction between the phosphorus groups of PNCDs and Fe3+ rendered them efficient probes for use in selective Fe3+ detection, with a detection limit of 0.39 μM, and we demonstrated their practicability by accurately detecting the Fe3+ contents in bio-samples. At the same time, PNCDs exhibited high lysosomal location specificity in different cell lines due to surface lipophilic amino groups, and real-time tracking of the lysosome morphology in HeLa cells was achieved. The present work suggests that the fabrication of heteroatom-doped CDs might be an effective strategy to provide promising tools for cytology, such as organelle tracking.
Susceptibility to Predation Varies with Body Mass, Foraging Niche, and Anti-Predator Responses among Bird Species
Authors: Beauchamp Guy
Published: February 2023

Predation is a major source of mortality for many avian species. Species that face more predators, and those with less effective anti-predator responses, are presumably more likely to die from predation over time. Predation rate, as a measure of susceptibility to predation, is difficult to measure in the field. Radio-tracking studies, however, allow researchers to determine the time and cause of death of marked individuals, making it possible to estimate predation rate. I used estimates of predation rates from a large number of published radio-tracking studies in birds to assess in a phylogenetic framework the effect of several potential determinants. I obtained 393 estimates of predation rates from 129 species. Predation rates were lower in areas with fewer predators, such as islands and aquatic habitats, and for species with fewer potential predators, such as larger species. The predation rate was also lower for prey species with effective anti-predator responses, such as those that forage in flocks. Radio-tracking studies provide a unique opportunity to estimate overall predation rate in the field. Broadening the range of species and the range of habitats involved in such studies will help to further elucidate the factors that affect susceptibility to predation.
Progressive Ataxia, Memory Impairments, and Seizure Episodes in Spna2 R1098Q Mouse Variant Affecting Alpha II Spectrin’s Scaffold Stability
Authors: Zalas Michał , Skrzymowska Joanna , Miążek Apolonia , Miazek Arkadiusz
Published: February 2023

SPTAN1 spectrinopathies refer to a group of rare, inherited diseases associated with damage to non-erythrocytic α-II spectrin (α-II). They are linked to a range of mild to severe neuropathologies of the central and peripheral nervous systems, such as early infantile epileptic encephalopathy type 5, cerebellar ataxia, inherited peripheral neuropathy, and spastic paraplegia. Modeling human SPTAN1 encephalopathies in laboratory animals has been challenging partially because no haploinsufficiency-related phenotypes unfold in heterozygous Spna2 deficient mice nor stable transgenic lines of mice mimicking missense human SPTAN1 mutations have been created to date. Here, we assess the motor and memory performance of a dominant-negative murine Spna2 (SPTAN1) variant carrying a spontaneous point mutation replacing an arginine 1098 in the repeat 10th of α-II with the glutamine (R1098Q). By comparing groups of heterozygous R1098Q mice at different ages, we find evidence for progressive ataxia, and age-related deterioration of motor performance and muscle strength. We also document stress-induced, long-lasting seizure episodes of R1098Q mice and their poor performance in novel object recognition memory tests. Overall, we propose that the complexity of neuropathology-related phenotypes presented by the R1098Q mice recapitulates a number of symptoms observed in human patients carrying SPTAN1 mutations affecting α-II scaffold stability. This makes the R1098Q mice a valuable animal model for preclinical research.
Microglia PKM2 Mediates Neuroinflammation and Neuron Loss in Mice Epilepsy through the Astrocyte C3-Neuron C3R Signaling Pathway
Authors: Li Xinlin , Zhou Rong , Peng Hui , Peng Jing , Li Qiaoling , Mei Meng
Published: February 2023

Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised increasing concerns and been regarded as the novel treatment strategy in epilepsy, but the target molecules require further research. Pyruvate kinase isoform 2 (PKM2) is well studied in peripheral inflammation, but its role in epilepsy neuroinflammation remains unclear. We knocked down microglia PKM2 in the hippocampus using a stereotaxic adeno-associated virus (AAV) microinjection and established a pilocarpine-induced status epilepticus (PISE) model. Racine score was used to evaluate the seizure grade. Next, we used WB, Multiplex tyramide signal amplification (TSA) staining and other methods to determine neuroinflammation and the complement component 3 (C3)–C3aR interaction in primary microglia. Results showed that microglia PKM2 knockdown reduced epilepsy grade and rescued neuron loss. Mechanistically, PKM2 knockdown inhibited microglia activation and inflammation factor secretion through suppressing p65 expression and phosphorylation. The reduced microglia C1q, TNF-α, and IL-1α were responsible for the decreased astrocyte C3 expression and the following neuron damage caused by the C3–C3aR interaction. Our data suggest that microglia PKM2 inhibition ameliorates neuroinflammation and neuron loss through C3-C3aR interaction in epilepsy, which provides an attractive target for the intervention of damaged neuron-glia crosstalk in epilepsy.
Perceiving Oneself to Be Integrated into the Peer Group: A Protective Factor against Victimization in Children with Learning Disabilities
Authors: Marini Mara , Di Filippo Gloria , Bonuomo Marika , Torregiani Giulia , Livi Stefano
Published: February 2023

Bullying is still a widespread social problem that needs serious attention. To date, research on this topic has shown that understanding the phenomenon requires a psychosocial perspective. The primary goal of the study is to identify the factors that contribute to the victimization of students with learning disabilities. The hypothesis is that the victimization experiences of this group of students can be explained by some socio-relational dynamics. Using a mediation model, this study demonstrates that perceived social integration completely mediates the association between the presence of learning disabilities and victimization experiences. This implies that students with learning disabilities are primarily victimized when they are not socially integrated into their class group. The implications for diagnosis and treatment are discussed.
Dyadic Conversation between Mandarin-Chinese-Speaking Healthy Older Adults: From Analyses of Conversation Turns and Speaking Roles
Authors: Tsai Meng-Ju
Published: February 2023

Older adults’ daily conversations with other older adults enable them to connect to their surrounding communities and improve their friendships. However, typical aging processes and fluctuations in family caring might cause conversation changes. The purpose of this study was to explore the quantitative contributions of conversation turns (CTs) and speaking roles (SRs) in Mandarin-Chinese-speaking conversation dyads between mutually familiar healthy older adults (HOAs). A total of 20 HOAs aged 65 or over were recruited. Each dyad conversed for ten minutes once a week for five weeks, five sessions per dyad, for a total of 50 sessions. The frequency and percentages of the coded CTs and SRs contributed by each HOA were individually tallied and calculated. Quantitatively symmetrical contributions of CTs and SRs occurred in Mandarin-Chinese-speaking conversation dyads between mutually familiar HOAs. Although typical aging processes might change conversations, both Mandarin-Chinese-speaking HOAs serve as active interlocutors to each other in taking CTs and SRs to co-construct their conversation processes and content in their dyadic conversation. Sufficient knowledge of conversation co-constructions might lead them to have more supportive environments to connect to surrounding communities and improve their friendships.
Photogrammetric Documentation of Stone Surface Topography Changes as a Tool in Conservation Praxis
Authors: Hodač Jindřich , Kovářová Kateřina , Cihla Michal , Matoušková Eva , Frommeltová Eva
Published: February 2023

Traces of stone working are an integral part of natural stone objects and artefacts of historical value. Each preserved trace does not only carry a value in determining the type of tool used, but also provides information about the historic stonemason’s work process and technology. For this reason, it is desirable to assess the restoration method’s influence on the change in surface topography. The effect of restoration interventions was investigated on five stone artefacts, three of ‘opuka’, one of sandstone and one of limestone, four of which showed historic working traces. For this purpose, selected restoration methods—chemical, mechanical and laser—were used. The examined artefacts were accurately photogrammetrically captured before and after the restoration interventions in order to assess and evaluate changes in the degree of preservation of the traces. Fine results using common tools were achieved in terms of geometric quality, level of detail and the documentation’s predictive power. The models’ geometric accuracy is in the single tenths of mm, as well as the matching of the two datasets (before and after).
Numerical Simulation of the Blast Resistance of SPUA Retrofitted CMU Masonry Walls
Authors: Zhang Yi , Hu Jiahui , Zhao Wenda , Hu Feng , Yu Xiao
Published: February 2023

Through numerical simulation, the blast-resistant performance of spray polyurea elastomer (SPUA) retrofitted concrete masonry unit (CMU) masonry infill walls under far-range blast loading was studied. From an engineering perspective, the effects of boundary conditions and thickness of a SPUA layer on enhancing the blast resistance of masonry infill walls are discussed, and the blast resistance of SPUA-retrofitted and grouted CMU masonry infill walls are compared. It is concluded that the boundary constraint conditions and the anchorage length of SPUA layer have limited improvement on the blast-resistant performance of the wall; the thickness of SPUA layer can significantly improve the blast-resistant performance of the wall as the blast loading increases. In addition, SPUA retrofitting shows relatively better performance to reinforce masonry infill walls.
Asian Disease Problem Applied to Climate Change: A Study of the Impact of Framing Risk Preferences Driven by Socio-Economic Indicators for Climate-Change-Related Risks
Authors: Peterson Ted C. , Tollefson Kacey
Published: February 2023

The Asian disease problem has long been studied since first introduced by Tversky and Kahneman in 1981. This study explores the mechanics of the Asian disease problem to a scenario reflecting deaths attributed to climate change. The study examines the gain/loss frame setup of the Asian disease problem. To research the Asian disease problem, in partnership with a Qualtrics panel, we surveyed 1209 customers of Utah utilities. Through statistical tests on the survey data, we confirmed the existence of the gain/loss framing effect. Moreover, the framing effect held when separating and examining responses based on unique socio-economic characteristics (i.e., age, gender, race, marital status, income, educational attainment, political preference, living status, household size, years at current residence, and energy-saving preference). In short, like the original Asian disease problem, the framing impact varied regardless of the characteristic studied. Based on these findings, we recommend implementing the framing effects of the Asian disease problem to an expanded realm for energy- and climate-related programs, initiatives, and academic research. We believe that this framing could spur action to mitigate climate change. Moreover, we recommend an expanded empirical study of the Asian disease problem to novel and understudied realms beyond our focus area.
Carbon Fibers: From PAN to Asphaltene Precursors; A State-of-Art Review
Authors: Bisheh Hossein , Abdin Yasmine
Published: February 2023

Due to their outstanding material properties, carbon fibers are widely used in various industrial applications as functional or structural materials. This paper reviews the material properties and use of carbon fiber in various applications and industries and compares it with other existing fillers and reinforcing fibers. The review also examines the processing of carbon fibers and the main challenges in their fabrication. At present, two main precursors are primarily utilized to produce carbon fibers, i.e., polyacrylonitrile (PAN) and petroleum pitch. Each of these precursors makes carbon fibers with different properties. However, due to the costly and energy-intensive processes of carbon fiber production based on the existing precursors, there is an increasingly growing need to introduce cheaper precursors to compete with other fibers on the market. A special focus will be given to the most recent development of manufacturing more sustainable and cost-effective carbon fibers derived from petroleum asphaltenes. This review paper demonstrates that low-cost asphaltene-based carbon fibers can be a substitute for costly PAN/pitch-based carbon fibers at least for functional applications. The value proposition, performance/cost advantages, potential market, and market size as well as processing challenges and methods for overcoming these will be discussed.
Alterations in Natural Killer Cells in Colorectal Cancer Patients with Stroma AReactive Invasion Front Areas (SARIFA)
Authors: Reitsam Nic G. , Märkl Bruno , Dintner Sebastian , Sipos Eva , Grochowski Przemyslaw , Grosser Bianca , Sommer Florian , Eser Stefan , Nerlinger Pia , Jordan Frank , Rank Andreas , Löhr Phillip , Waidhauser Johanna
Published: February 2023

Background: Recently, our group introduced Stroma AReactive Invasion Front Areas (SARIFA) as an independent prognostic predictor for a poorer outcome in colon cancer patients, which is probably based on immunologic alterations combined with a direct tumor-adipocyte interaction: the two together reflecting a distinct tumor biology. Considering it is already known that peripheral immune cells are altered in colorectal cancer (CRC) patients, this study aims to investigate the changes in lymphocyte subsets in SARIFA-positive cases and correlate these changes with the local immune response. Methods: Flow cytometry was performed to analyze B, T, and natural killer (NK) cells in the peripheral blood (PB) of 45 CRC patients. Consecutively, lymphocytes in PB, tumor-infiltrating lymphocytes (TILs), and CD56+ and CD57+ lymphocytes at the invasion front and the tumor center were compared between patients with SARIFA-positive and SARIFA-negative CRCs. Results: Whereas no differences could be observed regarding most PB lymphocyte populations as well as TILs, NK cells were dramatically reduced in the PB of SARIFA-positive cases. Moreover, CD56 and CD57 immunohistochemistry suggested SARIFA-status-dependent changes regarding NK cells and NK-like lymphocytes in the tumor microenvironment. Conclusion: This study proves that our newly introduced biomarker, SARIFA, comes along with distinct immunologic alterations, especially regarding NK cells.
MUC1 Expressions and Its Prognostic Values in US Gastric Cancer Patients
Authors: Kim Young-Il , Pecha Robert Luke , Keihanian Tara , Mercado Michael , Pena-Munoz S. Valeria , Lang Kailash , Van Buren George , Dhingra Sadhna , Othman Mohamed O.
Published: February 2023

This study aims to evaluate the prognostic value of MUC expression in US GC patients. A total of 70 tumor specimens were collected from GC patients who underwent surgery or endoscopic resection between 2013 and 2019 at a tertiary referral center in the US. MUC expression status including MUC1, MUC2, MUC5AC, and MUC6 was evaluated by immunohistochemical staining. The positive rates of MUC1, MUC2, MUC5AC, and MUC6 were 71.4%, 78.6%, 74.3%, and 33.3%, respectively. Patients with positive MUC1 expression had a significantly higher rate of aggressive pathologic features including diffuse-type cancer (42.0% vs. 0%; p < 0.001), advanced GC (80.0% vs. 30.0%, p < 0.001), lymph node metastasis (62.0% vs. 20.0%; p = 0.001), and distant metastasis (32.0% vs. 5.0%; p = 0.017) compared with those with negative MUC1 expression. However, the differences in the pathologic features were not observed according to MUC2, MUC5AC, and MUC6 expression status. In early gastric cancer (EGC), patients with a high level of MUC1 expression showed a higher rate of lymphovascular invasion (71.4% vs. 21.4%; p = 0.026) and EGC meeting non-curative resection (85.7% vs. 42.9%; p = 0.061) than those with negative MUC1. In US GC patients, MUC1 expression is associated with aggressive pathological features, and might be a useful prognostic marker.
Body Composition in Patients with Follicular Lymphoma: Asso-Ciations between Changes in Radiomic Parameters in Patients Treated with R-CHOP-like and R-B Regimens: LyRa 01F
Authors: Esposito Fabiana , Pascale Maria Rosaria , Tesei Cristiano , Gigliotti Paola Elda , Luciano Alessandra , Angeloni Cecilia , Marinoni Massimiliano , Meconi Federico , Secchi Roberto , Patanè Alberto , Postorino Massimiliano , Cantonetti Maria , Manenti Guglielmo
Published: February 2023

In patients with follicular lymphoma (FL), therapeutic advances have led to improved survival, and within this framework, it is important to identify treatment strategies offering a better quality of life. Using (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), in patients treated with R-CHOP-like or R-Bendamustine regimens, we assessed changes in the bone mineral density (BMD), musculoskeletal index (SMI), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at disease onset and at the end of therapy. We evaluated whether the high-steroid regimen could lead to more significant radiological changes than those induced by the steroid-free regimen and whether a low BMD at disease onset is an unfavorable prognostic index. Seventy-nine patients between 60 and 80 years old with a new diagnosis of FL were included in the study. Evaluation of Delta values (pre- and post-therapy mean values) in the two immunochemotherapy regimens showed differences in radiomic parameters within the two patient cohorts. The R-CHOP-like regimen was associated with a significant reduction in BMD, an increase in SAT and VAT, and a reduction in skeletal muscle density (SMD) and SMI. Moreover, patients with high FLIPI showed a BMD below the cut-off value. This study represents the first study demonstrating a prognostic correlation between FLIPI and low BMD.
Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets
Authors: Bertin Hélios , Peries Sophie , Amiaud Jérôme , Van Acker Nathalie , Perrot Bastien , Bouvier Corinne , Aubert Sébastien , Marie Béatrice , Larousserie Frédérique , De Pinieux Gonzague , Crenn Vincent , Rédini Françoise , Gomez-Brouchet Anne
Published: February 2023

Background—The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods—We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs). We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1). The biomarkers were analyzed for their influence on progression (recurrence and metastasis), overall survival (OS), and disease-free survival (DFS). Results—A strong and significant correlation has been found between CD163 staining and lower OS and DFS. The level of CD4+ and CD8+ staining was low and non-significantly associated with survival outcomes. High levels of RANK and RANKL were found in the tumor samples and correlated with lower DFS. Conclusion—Our findings suggest that CD163+ TAMs represent markers of poor prognosis in JO. Targeting TAMs could represent a valuable therapeutic strategy in JO.
Online Adaptive MRI-Guided Radiotherapy for Primary Tumor and Lymph Node Boosting in Rectal Cancer
Authors: Kensen Chavelli , Betgen Anja , Wiersema Lisa , Peters Femke , Kayembe Mutamba , Marijnen Corrie , van der Heide Uulke , Janssen Tomas
Published: February 2023

The purpose of this study was to characterize the motion and define the required treatment margins of the pathological mesorectal lymph nodes (GTVln) for two online adaptive MRI-guided strategies for sequential boosting. Secondly, we determine the margins required for the primary gross tumor volume (GTVprim). Twenty-eight patients treated on a 1.5T MR-Linac were included in the study. On T2-weighted images for adaptation (MRIadapt) before and verification after irradiation (MRIpost) of five treatment fractions per patient, the GTVln and GTVprim were delineated. With online adaptive MRI-guided radiotherapy, daily plan adaptation can be performed through the use of two different strategies. In an adapt-to-shape (ATS) workflow the interfraction motion is effectively corrected by redelineation and the only relevant motion is intrafraction motion, while in an adapt-to-position (ATP) workflow the margin (for GTVln) is dominated by interfraction motion. The margin required for GTVprim will be identical to the ATS workflow, assuming each fraction would be perfectly matched on GTVprim. The intrafraction motion was calculated between MRIadapt and MRIpost for the GTVln and GTVprim separately. The interfraction motion of the GTVln was calculated with respect to the position of GTVprim, assuming each fraction would be perfectly matched on GTVprim. PTV margins were calculated for each strategy using the Van Herk recipe. For GTVln we randomly sampled the original dataset 20 times, with each subset containing a single randomly selected lymph node for each patient. The resulting margins for ATS ranged between 3 and 4 mm (LR), 3 and 5 mm (CC) and 5 and 6 mm (AP) based on the 20 randomly sampled datasets for GTVln. For ATP, the margins for GTVln were 10–12 mm in LR and AP and 16–19 mm in CC. The margins for ATS for GTVprim were 1.7 mm (LR), 4.7 mm (CC) and 3.2 mm anterior and 5.6 mm posterior. Daily delineation using ATS of both target volumes results in the smallest margins and is therefore recommended for safe dose escalation to the primary tumor and lymph nodes.
FabNet: A Features Agglomeration-Based Convolutional Neural Network for Multiscale Breast Cancer Histopathology Images Classification
Authors: Amin Muhammad , Ahn Hyunsik
Published: February 2023

The definitive diagnosis of histology specimen images is largely based on the radiologist’s comprehensive experience; however, due to the fine to the coarse visual appearance of such images, experts often disagree with their assessments. Sophisticated deep learning approaches can help to automate the diagnosis process of the images and reduce the analysis duration. More efficient and accurate automated systems can also increase the diagnostic impartiality by reducing the difference between the operators. We propose a FabNet model that can learn the fine-to-coarse structural and textural features of multi-scale histopathological images by using accretive network architecture that agglomerate hierarchical feature maps to acquire significant classification accuracy. We expand on a contemporary design by incorporating deep and close integration to finely combine features across layers. Our deep layer accretive model structure combines the feature hierarchy in an iterative and hierarchically manner that infers higher accuracy and fewer parameters. The FabNet can identify malignant tumors from images and patches from histopathology images. We assessed the efficiency of our suggested model standard cancer datasets, which included breast cancer as well as colon cancer histopathology images. Our proposed avant garde model significantly outperforms existing state-of-the-art models in respect of the accuracy, F1 score, precision, and sensitivity, with fewer parameters.
Implementation of Machine Learning Models to Ensure Radiotherapy Quality for Multicenter Clinical Trials: Report from a Phase III Lung Cancer Study
Authors: Geng Huaizhi , Liao Zhongxing , Nguyen Quynh-Nhu , Berman Abigail T. , Robinson Clifford , Wu Abraham , Nichols Jr Romaine Charles , Willers Henning , Mohammed Nasiruddin , Mohindra Pranshu , Xiao Ying
Published: February 2023

The outcome of the patient and the success of clinical trials involving RT is dependent on the quality assurance of the RT plans. Knowledge-based Planning (KBP) models using data from a library of high-quality plans have been utilized in radiotherapy to guide treatment. In this study, we report on the use of these machine learning tools to guide the quality assurance of multicenter clinical trial plans. The data from 130 patients submitted to RTOG1308 were included in this study. Fifty patient cases were used to train separate photon and proton models on a commercially available platform based on principal component analysis. Models evaluated 80 patient cases. Statistical comparisons were made between the KBP plans and the original plans submitted for quality evaluation. Both photon and proton KBP plans demonstrate a statistically significant improvement of quality in terms of organ-at-risk (OAR) sparing. Proton KBP plans, a relatively emerging technique, show more improvements compared with photon plans. The KBP proton model is a useful tool for creating proton plans that adhere to protocol requirements. The KBP tool was also shown to be a useful tool for evaluating the quality of RT plans in the multicenter clinical trial setting.
Genes and the Environment in Cancer: Focus on Environmentally Induced DNA Methylation Changes
Authors: Coppedè Fabio
Published: February 2023

Cancer has traditionally been viewed as a genetic disorder resulting from the accumulation of gene mutations, chromosomal rearrangements, and aneuploidies in somatic cells [...]
Plant-Based Copper Oxide Nanoparticles; Biosynthesis, Characterization, Antibacterial Activity, Tanning Wastewater Treatment, and Heavy Metals Sorption
Authors: Eid Ahmed M. , Fouda Amr , Hassan Saad El-Din , Hamza Mohammed F. , Alharbi Nada K. , Elkelish Amr , Alharthi Afaf , Salem Waheed M.
Published: February 2023

Herein, the aqueous extract of Portulaca oleracea has been used as a safe, cheap, eco-friendly, and applicable scale-up method to bio-fabricate copper oxide nanoparticles (CuO-NPs). The character of CuO-NPs were determined using UV-vis spectroscopy, Fourier transform infrared (FT-IR), X-ray diffraction (XRD), Transmission electron microscopy (TEM), Energy dispersive X-ray(EDX), Dynamic light scattering (DLS), and zeta potential. Spherical and crystalline CuO-NPs with a size range of 5–30 nm at a maximum surface plasmon resonance of 275 nm were successfully fabricated. The main components of the green-synthesized particles were Cu and O with weight percentages of 49.92 and 28.45%, respectively. A Zeta-potential value of −24.6 mV was recorded for CuO-NPs, indicating their high stability. The plant-based CuO-NPs showed promising antimicrobial and catalytic activity in a dose-dependent manner. Results showed that the synthesized CuO-NPs had the efficacy to inhibit the growth of pathogens Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans with low MIC values in the ranges of 6.25–25 µg/mL. The highest decolorization percentages of tanning wastewater were attained under sunlight irradiation conditions at a concentration of 2.0 mg/mL after 200 min with percentages of 88.6 ± 1.5% compared to those which were recorded under dark conditions (70.3 ± 1.2%). The physicochemical parameters of tanning wastewater including total suspended solids (TSS), total dissolved solids (TDS), chemical oxygen demand (COD), biological oxygen demand (BOD), and conductivity under optimum conditions were significantly decreased with percentages of 95.2, 86.7, 91.4, 87.2, and 97.2%, respectively. Interestingly, the heavy metals including cobalt (Co), lead (Pb), nickel (Ni), cadmium (Cd), and chromium (Cr (VI)) decreased with percentages of 73.2, 80.8, 72.4, 64.4, and 91.4%, respectively, after treatment of tanning wastewater with CuO-NPs under optimum conditions. Overall, the plant-synthesized CuO-NPs that have antimicrobial and catalytic activities are considered a promising nano-catalyst and environmentally beneficial to wastewater treatment.
Core/Shell Nitrogen-Doped TiO2@SiO2 Nano-Catalyst as an Additive in Photocatalytic Paint for Gaseous Acetaldehyde Decomposition
Authors: Samangsri Suwapee , Areerob Thanita , Chiarakorn Siriluk
Published: February 2023

A nitrogen-doped TiO2@SiO2 core/shell nano-photocatalyst (N-TiO2@SiO2) was used as an additive in photocatalytic paint and applied for the photocatalytic degradation of gaseous acetaldehyde under light-emitting diode (LED) visible light irradiation. N-TiO2 was synthesised via the solvothermal method and then encapsulated by SiO2 via the sol-gel method. The incorporation of the N atom into the TiO2 structure was observed by X-ray photoelectron spectroscopy. The N-TiO2@SiO2 core/shell structure was determined by TEM images. The photodegradation of gaseous acetaldehyde using the prepared N-TiO2@SiO2 photocatalytic paint was examined in a closed chamber under LED light irradiation. The photodegradation of acetaldehyde by N-TiO2@SiO2 photocatalytic paint (31%) was significantly higher than that of TiO2 paint (5%) and N-TiO2 paint (20%) within 16 h. The chemical resistance and adhesion ability of N-TiO2@SiO2 photocatalytic paint were investigated following Thai Industrial Standards (TIS) no. 2321 and standard test methods for rating adhesion by tape test (ASTM D 3359-22). The N-TiO2@SiO2 paint showed good acid and alkali resistance, as well as high adhesion ability comparable with commercial paint (without a photocatalyst).
Novel Zebrafish Patient-Derived Tumor Xenograft Methodology for Evaluating Efficacy of Immune-Stimulating BCG Therapy in Urinary Bladder Cancer
Authors: Kowald Saskia , Huge Ylva , Tandiono Decky , Ali Zaheer , Vazquez-Rodriguez Gabriela , Erkstam Anna , Fahlgren Anna , Sherif Amir , Cao Yihai , Jensen Lasse D.
Published: February 2023

Background: Bacillus Calmette-Guérin (BCG) immunotherapy is the standard-of-care adjuvant therapy for non-muscle-invasive bladder cancer in patients at considerable risk of disease recurrence. Although its exact mechanism of action is unknown, BCG significantly reduces this risk in responding patients but is mainly associated with toxic side-effects in those facing treatment resistance. Methods that allow the identification of BCG responders are, therefore, urgently needed. Methods: Fluorescently labelled UM-UC-3 cells and dissociated patient tumor samples were used to establish zebrafish tumor xenograft (ZTX) models. Changes in the relative primary tumor size and cell dissemination to the tail were evaluated via fluorescence microscopy at three days post-implantation. The data were compared to the treatment outcomes of the corresponding patients. Toxicity was evaluated based on gross morphological evaluation of the treated zebrafish larvae. Results: BCG-induced toxicity was avoided by removing the water-soluble fraction of the BCG formulation prior to use. BCG treatment via co-injection with the tumor cells resulted in significant and dose-dependent primary tumor size regression. Heat-inactivation of BCG decreased this effect, while intravenous BCG injections were ineffective. ZTX models were successfully established for six of six patients based on TUR-B biopsies. In two of these models, significant tumor regression was observed, which, in both cases, corresponded to the treatment response in the patients. Conclusions: The observed BCG-related anti-tumor effect indicates that ZTX models might predict the BCG response and thereby improve treatment planning. More experiments and clinical studies are needed, however, to elucidate the BCG mechanism and estimate the predictive value.
Purification of Myosin from Bovine Tracheal Smooth Muscle, Filament Formation and Endogenous Association of Its Regulatory Complex
Authors: Wang Lu , Sobieszek Isabel J. , Seow Chun Y. , Sobieszek Apolinary
Published: February 2023

Dynamic regulation of myosin filaments is a crucial factor in the ability of airway smooth muscle (ASM) to adapt to a wide length range. Increased stability or robustness of myosin filaments may play a role in the pathophysiology of asthmatic airways. Biochemical techniques for the purification of myosin and associated regulatory proteins could help elucidate potential alterations in myosin filament properties of asthmatic ASM. An effective myosin purification approach was originally developed for chicken gizzard smooth muscle myosin. More recently, we successfully adapted the procedure to bovine tracheal smooth muscle. This method yields purified myosin with or without the endogenous regulatory complex of myosin light chain kinase and myosin light chain phosphatase. The tight association of the regulatory complex with the assembled myosin filaments can be valuable in functional experiments. The purification protocol discussed here allows for enzymatic comparisons of myosin regulatory proteins. Furthermore, we detail the methodology for quantification and removal of the co-purified regulatory enzymes as a tool for exploring potentially altered phenotypes of the contractile apparatus in diseases such as asthma.
Prospective Evaluation of CD45RA+/CCR7- Effector Memory T (TEMRA) Cell Subsets in Patients with Primary and Secondary Brain Tumors during Radiotherapy of the Brain within the Scope of the Prospective Glio-CMV-01 Clinical Trial
Authors: Scheer Ilka , Becker Ina , Schmitter Charlotte , Semrau Sabine , Fietkau Rainer , Gaipl Udo S. , Frey Benjamin , Donaubauer Anna-Jasmina
Published: February 2023

Radiotherapy (RT) of the brain is a common treatment for patients with high-grade gliomas and brain metastases. It has previously been shown that reactivation of cytomegalovirus (CMV) frequently occurs during RT of the brain. This causes neurological decline, demands antiviral treatment, and is associated with a worse prognosis. CMV-specific T cells are characterized by a differentiated effector memory phenotype and CD45RA+ CCR7- effector memory T (TEMRA) cells were shown to be enriched in CMV seropositive individuals. In this study, we investigated the distribution of TEMRA cells and their subsets in the peripheral blood of healthy donors and, for the first time, prospectively within the scope of the prospective Glio-CMV-01 clinical trial of patients with high-grade glioma and brain metastases during radiation therapy as a potential predictive marker. First, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of TEMRA cells in a longitudinal manner. The CMV serostatus and age were considered as influencing factors. We revealed that patients who had a reactivation of CMV have significantly higher amounts of CD8+ TEMRA cells. Further, the distribution of the subsets of TEMRA cells based on the expression of CD27, CD28, and CD57 is highly dependent on the CMV serostatus. We conclude that the percentage of CD8+ TEMRA cells out of all CD8+ T cells has the potential to serve as a biomarker for predicting the risk of CMV reactivation during RT of the brain. Furthermore, this study highlights the importance of taking the CMV serostatus into account when analyzing TEMRA cells and their subsets.
Gene-Edited Human-Induced Pluripotent Stem Cell Lines to Elucidate DAND5 Function throughout Cardiac Differentiation
Authors: Inácio José M. , Nunes Mafalda M. , Almeida Micael , Cristo Fernando , Anjos Rui , Belo José A.
Published: February 2023

(1) Background: The contribution of gene-specific variants for congenital heart disease, one of the most common congenital disabilities, is still far from our complete understanding. Here, we applied a disease model using human-induced pluripotent stem cells (hiPSCs) to evaluate the function of DAND5 on human cardiomyocyte (CM) differentiation and proliferation. (2) Methods: Taking advantage of our DAND5 patient-derived iPSC line, we used CRISPR-Cas9 gene-editing to generate a set of isogenic hiPSCs (DAND5-corrected and DAND5 full-mutant). The hiPSCs were differentiated into CMs, and RT-qPCR and immunofluorescence profiled the expression of cardiac markers. Cardiomyocyte proliferation was analysed by flow cytometry. Furthermore, we used a multi-electrode array (MEA) to study the functional electrophysiology of DAND5 hiPSC-CMs. (3) Results: The results indicated that hiPSC-CM proliferation is affected by DAND5 levels. Cardiomyocytes derived from a DAND5 full-mutant hiPSC line are more proliferative when compared with gene-corrected hiPSC-CMs. Moreover, parallel cardiac differentiations showed a differential cardiac gene expression profile, with upregulated cardiac progenitor markers in DAND5-KO hiPSC-CMs. Microelectrode array (MEA) measurements demonstrated that DAND5-KO hiPSC-CMs showed prolonged field potential duration and increased spontaneous beating rates. In addition, conduction velocity is reduced in the monolayers of hiPSC-CMs with full-mutant genotype. (4) Conclusions: The absence of DAND5 sustains the proliferation of hiPSC-CMs, which alters their electrophysiological maturation properties. These results using DAND5 hiPSC-CMs consolidate the findings of the in vitro and in vivo mouse models, now in a translational perspective. Altogether, the data will help elucidate the molecular mechanism underlying this human heart disease and potentiates new therapies for treating adult CHD.
Screen-Printed Electrodes: Fabrication, Modification, and Biosensing Applications
Authors: Paimard Giti , Ghasali Ehsan , Baeza Mireia
Published: February 2023

As electrochemical measuring instruments, screen-printed electrodes (SPEs) are constructed via a technology called thick film deposition onto plastic or ceramic substrates, allowing for simple, inexpensive, and rapid on-site analysis with high reproducibility, sensitivity, and accuracy. Numerous substances such as gold, silver, platinum, and carbon are applied for electrode construction, enabling the analyst to design the best device based on its purpose to determine an analyte’s selectivity and sensitivity. Thus, in the current review, we report the latest results and analyses conducted over the past eight years (2015–2022) on the expansion of SPE electrochemical biosensors, including aptasensors, immunosensors, DNA sensors, and enzymatic biosensors. Such expansion has resulted in new possibilities for the identification, distinction, and quantification of biocompounds, drugs, enzymes, etc. Therefore, in this paper, we review the role of different nanomaterials in manufacturing on-screen electrode methods as well as strategies for the future stable diagnosis of biorecognition elements.
A Sensitive Immunochromatographic Test Strip Based on Hydrophobic Quantum Dots Incorporated into Mg/Fe Nanoflowers for HCG Detection
Authors: Liu Hao , Zhang Qing , Bao Ning , Ding Shou-Nian
Published: February 2023

As the most widely used disposable paper-based diagnostic tool in the world, immunochromatographic test strips (ICTS) have occupied more and more positions in the field of rapid diagnosis due to their ease of operation and affordability. Therefore, the development of an easily prepared, sensitive, and accurate signal reporter is of great significance for the detection of some low-abundance biomarkers in clinical diagnosis. Herein, Mg/Fe layered double hydroxide nanoflowers (MF NFs) were selected as adsorption templates and sulfhydryl-functionalized, followed by one-step loading of hydrophobic CdSe/ZnS quantum dots in the organic phase via a metal-thiol covalent bond. After coating the reporter with branched polyethyleneimine (PEI), a novel ICTS fluorescent reporter was prepared. The modification of PEI not only improved the hydrophilicity of MF@CdSe/ZnS NFs but also introduced amino functional groups on the surface of the reporter for subsequent conjugation with antibodies. X-ray photoelectron spectroscopy, UV-vis absorption, X-ray diffraction, fluorescence spectroscopy, and infrared spectroscopy were used to characterize the composition of MF@CdSe/ZnS NFs. Under the optimal experimental conditions, the detection range of MF@CdSe/ZnS@PEI-ICTS for the model analyte HCG was 0.1–500 mIU/mL, and the limit of detection (LOD) reached was 0.1 mIU/mL. The potential for practical application was validated by the detection of HCG in spiked healthy human serum, showing overall recoveries between 90.48 and 116.1% with coefficients of variation that ranged from 3.66 to 12.91%.
Pyrene-Based Fluorescent Probe for “Off-on-Off” Sequential Detection of Cu2+ and CN− with HeLa Cells Imaging
Authors: Shellaiah Muthaiah , Venkatesan Parthiban , Thirumalaivasan Natesan , Wu Shu-Pao , Sun Kien-Wen
Published: February 2023

The novel pyrene-appended Schiff base probe L with aggregation-induced emissions (AIE) relevant to an increase in water fractions (0–90%) is synthesized and applied in sequentially detecting Cu2+ and CN−. The pyrene-based probe L firstly induces the excimer formation in the presence of Cu2+. However, the process can be reversed by sequentially adding CN−, which is demonstrated using the fluorescence “Off-On-Off” response in semi-aqueous media ethanol water (v/v = 7/3) under physiological pH (5 mM HEPES, pH 7.0). The Job’s plot, mass analysis, 1H NMR titrations, and density functional theory (DFT) interrogations confirm the 2:1 stoichiometry of excimer complex L–Cu2+-L*, preferential binding atoms, and CN− tuned complex reversibility. Based on the photoluminescence (PL) titration, the association constant of L to Cu2+ is determined as 4.95 × 106 M−1. From standard deviation and linear fittings, the detection limits (LODs) of Cu2+ and CN− are estimated as 219 nM and 580 nM, respectively. The practicality of Cu2+ and CN− detection is demonstrated using a TLC plate and a blended polymer membrane through which significant color changes under a UV lamp can be monitored. Moreover, utility of the designed probe L towards biological application with low toxicity is demonstrated by detecting Cu2+ and CN− inside HeLa cells. The responses of the probe to Cu(II) ions were also verified using living HeLa cells imaging.
Cross-Linked SnO2 Nanosheets Modified by Ag Nanoparticles for Formaldehyde Vapor Detection
Authors: Weng Huaipeng , Dong Xumeng , Sun Yufeng , Ren Haibo , Huang Jiarui , Joo Sang Woo
Published: February 2023

Ag@SnO2 nanosheets were prepared through a hydrothermal method followed by heat treatment and a liquid reduction process. Many Ag nanoparticles (Ag NPs) were dispersed uniformly over the surface of the SnO2 nanosheets. The thickness of the SnO2 nanosheets was approximately 10 nm. After decoration with Ag NPs, the Ag@SnO2 nanosheet sensors exhibited improved gas-sensing behaviors compared to the pure SnO2 nanosheet sensor. The response of cross-linked SnO2 nanosheets decorated by Ag NP sensors for 100 ppm formaldehyde vapor was up to 101.4, which was double that (45.5) of the pure SnO2 nanosheet sensor. The response and recovery times of the Ag@SnO2 sensor were 21 s and 23 s, respectively. The Ag@SnO2 nanosheet sensors showed reasonable cycling stability, as demonstrated by testing with 100 ppm formaldehyde 10 times. The superior gas-sensing behaviors of the Ag@SnO2 sensor were due to the large specific surface area, cross-linked nanostructure, and synergistic effect of the Ag NPs with huge sensitizing active sites and numerous SnO2 nanosheets.