bluuebunny/crossref_metadata_2025 huggingface dataset:
DFCANet: A Novel Lightweight Convolutional Neural Network Model for Corn Disease Identification
Authors: Chen Yang , Chen Xiaoyulong , Lin Jianwu , Pan Renyong , Cao Tengbao , Cai Jitong , Yu Dianzhi , Cernava Tomislav , Zhang Xin
Published: November 2022

The identification of corn leaf diseases in a real field environment faces several difficulties, such as complex background disturbances, variations and irregularities in the lesion areas, and large intra-class and small inter-class disparities. Traditional Convolutional Neural Network (CNN) models have a low recognition accuracy and a large number of parameters. In this study, a lightweight corn disease identification model called DFCANet (Double Fusion block with Coordinate Attention Network) is proposed. The DFCANet consists mainly of two components: The dual feature fusion with coordinate attention and the Down-Sampling (DS) modules. The DFCA block contains dual feature fusion and Coordinate Attention (CA) modules. In order to completely fuse the shallow and deep features, these features were fused twice. The CA module suppresses the background noise and focuses on the diseased area. In addition, the DS module is used for down-sampling. It reduces the loss of information by expanding the feature channel dimension and the Depthwise convolution. The results show that DFCANet has an average recognition accuracy of 98.47%. It is more efficient at identifying corn leaf diseases in real scene images, compared with VGG16 (96.63%), ResNet50 (93.27%), EffcientNet-B0 (97.24%), ConvNeXt-B (94.18%), DenseNet121 (95.71%), MobileNet-V2 (95.41%), MobileNetv3-Large (96.33%), and ShuffleNetV2-1.0× (94.80%) methods. Moreover, the model’s Params and Flops are 1.91M and 309.1M, respectively, which are lower than heavyweight network models and most lightweight network models. In general, this study provides a novel, lightweight, and efficient convolutional neural network model for corn disease identification.
Aqueous Seaweed Extract Alleviates Salinity-Induced Toxicities in Rice Plants (Oryza sativa L.) by Modulating Their Physiology and Biochemistry
Authors: Chanthini Kanagaraj Muthu-Pandian , Senthil-Nathan Sengottayan , Pavithra Ganesh-Subbaraja , Malarvizhi Pauldurai , Murugan Ponnusamy , Deva-Andrews Arulsoosairaj , Janaki Muthusamy , Sivanesh Haridoss , Ramasubramanian Ramakrishnan , Stanley-Raja Vethamonickam , Ghaith Aml , Abdel-Megeed Ahmed , Krutmuang Patcharin
Published: November 2022

Around the world, salinity a critical limiting factor in agricultural productivity. Plant growth is affected by salt stress at all stages of development. The contemporary investigation focused on Chaetomorpha antennina aqueous extracts (SWEs) to decrease the effects of salt strain on rice germination, growth, yield, and the production of key biological and biochemical characters of the rice, Oryza sativa L. (Poaceae). SWE improved the germination capacities of rice seedlings by promoting their emergence 36.27 h prior to those that had been exposed to saline stress. The creation of 79.647% longer radicles by SWE treatment on salt-stressed seeds which boosted the establishment effectiveness of seeds produced under salt stress longer radicles resulted in plants that were 64.8% taller. SWE treatment was effective in revoking the levels of protein (26.9%), phenol (35.54%), and SOD (41.3%) enzyme levels that were previously constrained by salinity stress. Additionally, SWE were also efficient in retaining 82.6% of leaf water content and enhancing the production of photosynthetic pigments affected by salt exposure earlier. The improvement in plant functionality was evident from the display of increase in tiller numbers/hill (62.36%), grain yield (58.278%), and weight (56.502%). The outcome of our research shows that SWEs protected the plants from the debarring effects of salinity by enhancing the plant functionality and yield by mechanistically enriching their physiological (germination and vegetative growth) and biochemical attributes (leaf RWC, photosynthetic pigments, protein, phenol, and SOD). Despite the increase in TSS and starch levels in rice grain exposed to salinity stress, SWE improved the grain protein content thus cumulatively enhancing rice nutrition and marketability. The current investigation reveals that the extracts of C. antennina can help alleviate rice plants from salt stress in an efficient, eco-friendly, as well as economical way.
Automatic Fruit Harvesting Device Based on Visual Feedback Control
Authors: Wen Bor-Jiunn , Yeh Che-Chih
Published: November 2022

With aging populations, and people′s demand for high-quality or high-unit-price fruits and vegetables, the corresponding development of automatic fruit harvesting has attracted significant attention. According to the required operating functions, based on the fruit planting environment and harvesting requirements, this study designed a harvesting mechanism to independently drive a gripper and scissor for individual tasks, which corresponded to forward or reverse rotation using a single motor. The study utilized a robotic arm in combination with the harvesting mechanism, supported by a single machine vision component, to recognize fruits by deep-learning neural networks based on a YOLOv3-tiny algorithm. The study completed the coordinate positioning of the fruit, using a two-dimensional visual sensing method (TVSM), which was used to achieve image depth measurement. Finally, impedance control, based on visual feedback from YOLOv3-tiny and the TVSM, was used to grip the fruits according to their size and rigidity, so as to avoid the fruits being gripped by excessive force; therefore, the apple harvesting task was completed with a 3.6 N contact force for an apple with a weight of 235 g and a diameter of 80 mm. During the cutting process, the contact point of the metal scissors of the motor-driven mechanism provided a shear force of 9.9 N, which was significantly smaller than the simulation result of 94 N using ADAMS and MATLAB software, even though the scissors were slightly blunt after many cuts. This study established an automatic fruit harvesting device based on visual feedback control, which can provide an automatic and convenient fruit harvest by reducing harvesting manpower.
Quantitative Carbon Changes of Selected Organic Fractions during the Aerobic Biological Recycling of Biodegradable Municipal Solid Waste (MSW) as a Potential Soil Environment Improving Amendment—A Case Study
Authors: Bekier Jakub , Jamroz Elżbieta , Dębicka Magdalena , Ćwieląg-Piasecka Irmina , Kocowicz Andrzej
Published: November 2022

The aim of the investigation was to determine the quantitative changes of selected organic compounds during composting of municipal solid wastes (MSWs). The object of the study was a differently matured compost produced according the to open pile/windrow semi-dynamic technology from selectively collected biodegradable municipal solid waste. During the experiment, the temperature and moisture of the composted wastes were monitored. In the collected samples—taken from differently matured compost—the total organic carbon (TOC) and total nitrogen (TN) were determined. The organic matter fractionation method described by Stevenson and Adani et al. was adopted, which allows to determine the carbon content of the following groups of organic compounds: hydrophobic (HSC), hydrophilic (WEOC), acidophilic (CAC), cellulose (CCEL), core-HA (ligno-humic, CALK) and residual carbon (non-hydrolysing, CR). The TOC and TN content, as well as the origin and quality of the starting materials, allow the product tested to be classified for fertiliser purposes. The most intense changes were observed during the thermophilic composting phase. In spite of the optimal technological conditions of the process, the predominance of the CR and CCEL fraction was observed, and the share of humic compounds did not exceed 30% TOC. The investigated compost met legal, ecological and economic criteria for products of biological recycling, thus can be used as a good organic amendment to improve the soil organic matter balance, stimulate the soil biodiversity and carbon sequestration.
Impacts of the Green Revolution on Rhizosphere Microbiology Related to Nutrient Acquisition
Authors: Dixon Mary , Rohrbaugh Carley , Afkairin Antisar , Vivanco Jorge
Published: November 2022

The Green Revolution (GR) involved selective breeding of cereals and the use of high fertilizer inputs with the goal of increasing crop yields to alleviate hunger. As a result of both greater use of inorganic fertilizers and the introduction of semi-dwarf cultivars, grain yield increased globally and hunger was alleviated in certain areas of the world. However, these changes in varietal selection and fertilization regimes have impacted soil fertility and the root-associated microbiome. Higher rates of inorganic fertilizer application resulted in reduced rhizosphere microbial diversity, while semi-dwarf varieties displayed a greater abundance of rhizosphere microbes associated with nitrogen utilization. Ultimately, selection for beneficial aboveground traits during the GR led to healthier belowground traits and nutrient uptake capabilities.
Establishment of a Serum-Free Hepatocyte Cryopreservation Process for the Development of an “Off-the-Shelf” Bioartificial Liver System
Authors: Lee Ji-Hyun , Park Hey-Jung , Kim Young-A , Lee Doo-Hoon , Noh Jeong-Kwon , Jung Jong-Gab , Yoon Hee-Hoon , Lee Suk-Koo , Lee Sanghoon
Published: November 2022

To use hepatocytes immediately when necessary for hepatocyte transplantation and bioartificial liver (BAL) systems, a serum-free cryopreservation protocol ensuring the high survival of hepatocytes and maintenance of their functions should be developed. We established a serum-free protocol for the cryopreservation of primary hepatocytes, hepatocyte spheroids, and hepatocyte spheroid beads in liquid nitrogen. The serum-free cryopreservation solutions showed a significantly higher performance in maintaining enhanced viability and ammonia removal, urea secretion, and the albumin synthesis of hepatocyte spheroids and spheroid beads. The serum-free thawing medium, containing human serum albumin (HSA) and N-acetylcysteine (NAC), was compared with a fetal bovine serum-containing thawing medium for the development of a serum-free thawing medium. Our results show that hepatocyte spheroids and spheroid beads thawed using a serum-free thawing medium containing HSA and NAC exhibited increased hepatocyte viability, ammonia removal, urea secretion, and albumin synthesis compared to those thawed using the serum-containing medium. Finally, we evaluated the liver functions of the cryopreserved BAL system-applied serum-free cryopreservation process compared to the fresh BAL system. The ammonia removal efficiency of the cryopreserved hepatocyte spheroids BAL was lower than or similar to that of the fresh BAL system. Additionally, the urea concentrations in the media of all three BAL systems were not significantly different during BAL system operation. This cryopreserved spheroid-based BAL system using a serum-free process will be a good candidate for the treatment of patients.
5-Fluorouracil-Immobilized Hyaluronic Acid Hydrogel Arrays on an Electrospun Bilayer Membrane as a Drug Patch
Authors: Lee Ji-Eun , Lee Seung-Min , Kim Chang-Beom , Lee Kwang-Ho
Published: November 2022

The hyaluronic acid (HA) hydrogel array was employed for immobilization of 5-fluorouracil (5-FU), and the electrospun bilayer (hydrophilic: polyurethane/pluronic F-127 and hydrophobic: polyurethane) membrane was used to support the HA hydrogel array as a patch. To visualize the drug propagating phenomenon into tissues, we experimentally investigated how FITC-BSA diffused into the tissue by applying hydrogel patches to porcine tissue samples. The diffusive phenomenon basically depends on the FITC-BSA diffusion coefficient in the hydrogel, and the degree of diffusion of FITC-BSA may be affected by the concentration of HA hydrogel, which demonstrates that the high density of HA hydrogel inhibits the diffusive FITC-BSA migration toward the low concentration region. YD-10B cells were employed to investigate the release of 5-FU from the HA array on the bilayer membrane. In the control group, YD-10B cell viability was over 98% after 3 days. However, in the 5-FU-immobilized HA hydrogel array, most of the YD-10B cells were not attached to the bilayer membrane used as a scaffold. These results suggest that 5-FU was locally released and initiated the death of the YD-10B cells. Our results show that 5-FU immobilized on HA arrays significantly reduces YD-10B cell adhesion and proliferation, affecting cells even early in the cell culture. Our results suggest that when 5-FU is immobilized in the HA hydrogel array on the bilayer membrane as a drug patch, it is possible to control the drug concentration, to release it continuously, and that the patch can be applied locally to the targeted tumor site and administer the drug in a time-stable manner. Therefore, the developed bilayer membrane-based HA hydrogel array patch can be considered for sustained release of the drug in biomedical applications.
Dietary Capsaicin: A Spicy Way to Improve Cardio-Metabolic Health?
Authors: Szallasi Arpad
Published: November 2022

Today’s sedentary lifestyle with too much food and too little exercise has made metabolic syndrome a pandemic. Metabolic syndrome is a major risk factor for type-2 diabetes and cardiovascular disease. New knowledge of medical and nutraceutical intervention in the early stages of metabolic syndrome is central to prevent these deadly complications. People who eat chili pepper on a regular basis seem to stay healthier and live longer than those who do not. Animal experiments suggest a therapeutic potential for dietary capsaicin, the active principle in hot chili pepper, to reduce the risk of developing metabolic syndrome. This is an attractive theory since capsaicin has been a culinary staple for thousands of years, and is generally deemed safe when consumed in hedonically acceptable doses. The broad expression of the capsaicin receptor TRPV1 in metabolically active tissues lends experimental support to this theory. This review critically evaluates the available experimental and clinical evidence for and against dietary capsaicin being an effective dietary means to improve cardio-metabolic health. It comes to the conclusion that although a chili pepper-rich diet is associated with a reduced risk of dying due to cardiovascular disease, dietary capsaicin has no clear effect on blood glucose or lipid profiles. Therefore, the reduced mortality risk may reflect the beneficial action of digested capsaicin on gut microbiota.
Autonomous Aldosterone Secretion in Patients with Adrenal Incidentaloma
Authors: Kmieć Piotr , Zalewska Ewa , Kunicka Katarzyna , Świerblewska Ewa , Sworczak Krzysztof
Published: November 2022

In recent years, research has emphasized the significance of mild clinical and biochemical presentations of primary aldosteronism (PA) that do not meet current diagnostic criteria of the syndrome. In this study, we assessed the prevalence of autonomous aldosterone (Ald) secretion (AAS), defined as a positive (>1.2 ng/dL/mIU/L) Ald-to-renin ratio (ADRR) combined with unsuppressed Ald (>4 ng/dL), and its associations with blood pressure (BP), cardiac function, and common carotid artery (CCA) intima-media thickness (IMT) in patients with incidentally discovered adrenal adenomas (AI), who were either normo- or hypertensive but had no other cardiovascular disease. Among 332 AI patients hospitalized between November 2018 and December 2019, 63 study participants were recruited (26 normo- and 37 hypertensive), who underwent hormonal examinations, 24 h ambulatory BP measurement, transthoracic echocardiography, and CCA IMT assessment without altering chronic medications. AAS was found in approximately 25% of subjects (seven normo- and nine hypertensive); urinary aldosterone excretion (UAldE) exceeded 10 ug/day in none of the subjects. The left ventricular mass index correlated positively with UAldE in non-diabetic patients (n = 50), and negatively with renin in those without beta blocker therapy (n = 38). The study shows that a pragmatic approach to hormonal assessment (no chronic therapy modification) may reveal patients with AAS. Screening for this subclinical PA presentation is probably more effective with a permissive ADRR than UAldE in such a setting.
Impact of Wound Dressing on Mechanotransduction within Tissues of Chronic Wounds
Authors: McElvain Kelly , Klister Joshua , Ebben Alessandra , Gopalakrishnan Sandeep , Dabagh Mahsa
Published: November 2022

Chronic wounds are significant public health problems impacting the health-related quality of individuals’ lives (due to disability, decreased productivity, and loss of independence) and an immense economic burden to healthcare systems around the world. In this study, our main objective is to investigate how mechanotransduction can impact the healing process in chronic wounds. We have developed new three-dimensional models of wound tissue to study the distribution of forces within these tissues exerted by wound dressings with different characteristics. The roles of mechanical forces on wound healing have gained significant clinical attention; the application of mechanical forces is expected to influence the physiology of tissue surrounding a wound. We aim to investigate whether the force transmission within wound tissue is impacted by the dressing characteristics and whether this impact may differ with wound tissue’s properties. Our results show that wound dressings with lower stiffnesses promote force transmission within a wound tissue. This impact is even more significant on stiffer wound tissues. Furthermore, we show that size of wound dressing alters forces that transmit within the wound tissue where dressings with 9 cm length show higher stresses. The wound tissue stiffening has been associated with healing of a wound. Our results demonstrate that wounds with stiffer tissue experience higher stresses. Taken all together, our findings suggest that low stiffness of wound dressing and its size may be introduced as a criterion to explain parameters predisposing a chronic wound to heal. This study’s findings on the role of dressings and tissue characteristics demonstrate that precision dressings are required for wound management and understanding how a dressing impacts mechanotransduction in wound tissue will lead to design of novel dressings promoting healing in chronic wounds.
A Moderated Mediation Model of Academic Supervisor Developmental Feedback and Postgraduate Student Creativity: Evidence from China
Authors: Su Weilin , Qi Qian , Yuan Shuai
Published: November 2022

Academic supervisors plays a significant role in the cultivation of postgraduate students, but little is known about how academic supervisor feedback affects their creativity. This study hypothesizes and tests a moderated mediation model to explore how and when academic supervisor developmental feedback (ASDF) affects postgraduate student creativity (PSC), including the mediating effect of intrinsic motivation and the moderating effect of creative self-efficacy. After collecting three-wave time-lagged data from 374 postgraduate students and their academic supervisors, SPSS and Amos software were used to test the research hypotheses and the whole model. The results show that ASDF is positively related to intrinsic motivation and PSC. Intrinsic motivation not only has a positive effect on PSC, but it also plays a mediating role in the relationship between ASDF and PSC. Creative self-efficacy plays a moderating role in the relationships between ASDF, intrinsic motivation, and PSC, that is, ASDF can cause postgraduate students with high creative self-efficacy to develop higher levels of intrinsic motivation than those with low creative self-efficacy, which ultimately leads to more PSC. These findings not only enrich the literature on feedback, motivation, and creativity research in the field of education, but also provide some suggestions for promoting PSC from the perspective of universities, academic supervisors, and postgraduate students.
Challenging Endocrine Sensitivity of Hormone Receptor-Positive/HER2-Negative Advanced Breast Cancer with the Combination of Eribulin and Endocrine Therapy: The REVERT Study
Authors: López González Ana , Del Barco Berrón Sonia , Grau Isabel , Galan Maria , Castelo Fernández Beatriz , Cortés Alfonso , Sánchez Rovira Pedro , Martinez-Bueno Alejandro , Gonzalez Xavier , García Almudena , Gener Petra , Mina Leonardo , Alcalá-López Daniel , Sampayo Miguel , Cortés Javier , Pérez-Garcia José Manuel , Llombart-Cussac Antonio , López-Miranda Elena
Published: November 2022

Background: Luminal advanced breast cancer (ABC) patients eventually progress on endocrine therapy. REVERT aimed to explore whether eribulin could restore endocrine sensitivity in a randomized, non-comparative phase II trial. Methods: Aromatase inhibitor (AI)-resistant patients with luminal ABC were randomized 1:1 to receive eribulin +/− AI. Patients were stratified by prior cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) treatment. The primary endpoint was an investigator-assessed overall response rate (ORR) according to RECIST version 1.1 in the eribulin + AI arm. An interim analysis was planned with 11 evaluable patients according to a two-stage Simon design. Results: Twenty-two patients were enrolled (15 eribulin + AI arm; 7 eribulin arm). The trial was terminated early in March 2021, with eight (36.4%) patients still on treatment. ORR was 26.7% in the eribulin + AI arm (95% CI, 7.8–55.1%; p = 0.0541). In the eribulin arm, two (28.6%) patients had an objective response (95% CI, 3.7–71.0%). The difference between the study arms was not significant (p = 0.918). The addition of AI to eribulin also failed to show improvement in other efficacy endpoints. A significant interaction between the treatment arm and previous CDK4/6i treatment was observed for ORR (p = 0.018) and progression-free survival (p = 0.084). Overall, the toxicity profile was consistent with the known safety profile of eribulin. No treatment-related deaths were reported. Conclusion: Eribulin + AI does not seem to improve outcomes compared with eribulin monotherapy in patients with AI-resistant luminal ABC. This chemo–endocrine approach deserves further investigation after progression to CDK4/6i-based therapy.
CT-Based Radiomic Analysis for Preoperative Prediction of Tumor Invasiveness in Lung Adenocarcinoma Presenting as Pure Ground-Glass Nodule
Authors: Kao Tzu-Ning , Hsieh Min-Shu , Chen Li-Wei , Yang Chi-Fu Jeffrey , Chuang Ching-Chia , Chiang Xu-Heng , Chen Yi-Chang , Lee Yi-Hsuan , Hsu Hsao-Hsun , Chen Chung-Ming , Lin Mong-Wei , Chen Jin-Shing
Published: November 2022

It remains a challenge to preoperatively forecast whether lung pure ground-glass nodules (pGGNs) have invasive components. We aimed to construct a radiomic model using tumor characteristics to predict the histologic subtype associated with pGGNs. We retrospectively reviewed clinicopathologic features of pGGNs resected in 338 patients with lung adenocarcinoma between 2011–2016 at a single institution. A radiomic prediction model based on forward sequential selection and logistic regression was constructed to differentiate adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma. The study cohort included 133 (39.4%), 128 (37.9%), and 77 (22.8%) patients with AIS, MIA, and invasive adenocarcinoma (acinar 55.8%, lepidic 33.8%, papillary 10.4%), respectively. The majority (83.7%) underwent sublobar resection. There were no nodal metastases or tumor recurrence during a mean follow-up period of 78 months. Three radiomic features—cluster shade, homogeneity, and run-length variance—were identified as predictors of histologic subtype and were selected to construct a prediction model to classify the AIS/MIA and invasive adenocarcinoma groups. The model achieved accuracy, sensitivity, specificity, and AUC of 70.6%, 75.0%, 70.0%, and 0.7676, respectively. Applying the developed radiomic feature model to predict the histologic subtypes of pGGNs observed on CT scans can help clinically in the treatment selection process.
ERK MAP Kinase Signaling Regulates RAR Signaling to Confer Retinoid Resistance on Breast Cancer Cells
Authors: Hirota Akira , Clément Jean-Emmanuel , Tanikawa Satoshi , Nonoyama Takayuki , Komatsuzaki Tamiki , Gong Jian Ping , Tanaka Shinya , Imajo Masamichi
Published: November 2022

Retinoic acid (RA) and its synthetic derivatives, retinoids, have been established as promising anticancer agents based on their ability to regulate cell proliferation and survival. Clinical trials, however, have revealed that cancer cells often acquire resistance to retinoid therapy. Therefore, elucidation of underlying mechanisms of retinoid resistance has been considered key to developing more effective use of retinoids in cancer treatment. In this study, we show that constitutive activation of ERK MAP kinase signaling, which is often caused by oncogenic mutations in RAS or RAF genes, suppresses RA receptor (RAR) signaling in breast cancer cells. We show that activation of the ERK pathway suppresses, whereas its inhibition promotes, RA-induced transcriptional activation of RAR and the resultant upregulation of RAR-target genes in breast cancer cells. Importantly, ERK inhibition potentiates the tumor-suppressive activity of RA in breast cancer cells. Moreover, we also reveal that suppression of RAR signaling and activation of ERK signaling are associated with poor prognoses in breast cancer patients and represent hallmarks of specific subtypes of breast cancers, such as basal-like, HER2-enriched and luminal B. These results indicate that ERK-dependent suppression of RAR activity underlies retinoid resistance and is associated with cancer subtypes and patient prognosis in breast cancers.
Multi-Stage Classification-Based Deep Learning for Gleason System Grading Using Histopathological Images
Authors: Hammouda Kamal , Khalifa Fahmi , Alghamdi Norah Saleh , Darwish Hanan , El-Baz Ayman
Published: November 2022

In this work, we introduced an automated diagnostic system for Gleason system grading and grade groups (GG) classification using whole slide images (WSIs) of digitized prostate biopsy specimens (PBSs). Our system first classifies the Gleason pattern (GP) from PBSs and then identifies the Gleason score (GS) and GG. We developed a comprehensive DL-based approach to develop a grading pipeline system for the digitized PBSs and consider GP as a classification problem (not segmentation) compared to current research studies (deals with as a segmentation problem). A multilevel binary classification was implemented to enhance the segmentation accuracy for GP. Also, we created three levels of analysis (pyramidal levels) to extract different types of features. Each level has four shallow binary CNN to classify five GP labels. A majority fusion is applied for each pixel that has a total of 39 labeled images to create the final output for GP. The proposed framework is trained, validated, and tested on 3080 WSIs of PBS. The overall diagnostic accuracy for each CNN is evaluated using several metrics: precision (PR), recall (RE), and accuracy, which are documented by the confusion matrices.The results proved our system’s potential for classifying all five GP and, thus, GG. The overall accuracy for the GG is evaluated using two metrics, PR and RE. The grade GG results are between 50% to 92% for RE and 50% to 92% for PR. Also, a comparison between our CNN architecture and the standard CNN (ResNet50) highlights our system’s advantage. Finally, our deep-learning system achieved an agreement with the consensus grade groups.
C-Reactive Protein Pretreatment-Level Evaluation for Ewing’s Sarcoma Prognosis Assessment—A 15-Year Retrospective Single-Centre Study
Authors: Consalvo Sarah , Hinterwimmer Florian , Harrasser Norbert , Lenze Ulrich , Matziolis Georg , von Eisenhart-Rothe Rüdiger , Knebel Carolin
Published: November 2022

Background: A pathological/inflamed cellular microenvironment state is an additional risk factor for any cancer type. The importance of a chronic inflammation state in most diffuse types of tumour has already been analysed, except for in Ewing’s sarcoma. It is a highly malignant blue round cell tumour, with 90% of cases occurring in patients aged between 5 and 25 years. Worldwide, 2.9 out of 1,000,000 children per year are affected by this malignancy. The aim of this retrospective study was to analyse the role of C-reactive protein (CRP) as a prognostic factor for Ewing’s sarcomas. Methods: This retrospective study at Klinikum rechts der Isar included 82 patients with a confirmed Ewing’s sarcoma diagnosis treated between 2004 and 2019. Preoperative CRP determination was assessed in mg/dL with a normal value established as below 0.5 mg/dL. Disease-free survival time was calculated as the time between the initial diagnosis and an event such as local recurrence or metastasis. Follow-up status was described as death of disease (DOD), no evidence of disease (NED) or alive with disease (AWD). The exclusion criteria of this study included insufficient laboratory values and a lack of information regarding the follow-up status or non-oncological resection. Results: Serum CRP levels were significantly different in patients with a poorer prognosis (DOD) and in patients who presented distant metastasis (p = 0.0016 and p = 0.009, respectively), whereas CRP levels were not significantly different in patients with local recurrence (p = 0.02). The optimal breakpoint that predicted prognosis was 0.5 mg/dL, with a sensitivity of 0.76 and a specificity of 0.74 (AUC 0.81). Univariate CRP analysis level >0.5 mg/dL revealed a hazard ratio of 9.5 (95% CI 3.5–25.5). Conclusions: In Ewing’s sarcoma cases, we consider a CRP pretreatment value >0.5 mg/dL as a sensitive prognostic risk factor indication for distant metastasis and poor prognosis. Further research with more data is required to determine more sensitive cutoff levels.
Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures
Authors: Klebowski Bartosz , Stec Malgorzata , Depciuch Joanna , Panek Agnieszka , Krzempek Dawid , Komenda Wiktor , Gałuszka-Bulaga Adrianna , Pajor-Swierzy Anna , Baran Jarek , Parlinska-Wojtan Magdalena
Published: November 2022

Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ~30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.
The Study of the Extracellular Matrix in Chronic Inflammation: A Way to Prevent Cancer Initiation?
Authors: Marangio Asia , Biccari Andrea , D’Angelo Edoardo , Sensi Francesca , Spolverato Gaya , Pucciarelli Salvatore , Agostini Marco
Published: November 2022

Bidirectional communication between cells and their microenvironment has a key function in normal tissue homeostasis, and in disease initiation, progression and a patient’s prognosis, at the very least. The extracellular matrix (ECM), as an element of all tissues and cellular microenvironment, is a frequently overlooked component implicated in the pathogenesis and progression of several diseases. In the inflammatory microenvironment (IME), different alterations resulting from remodeling processes can affect ECM, progressively inducing cancer initiation and the passage toward a tumor microenvironment (TME). Indeed, it has been demonstrated that altered ECM components interact with a variety of surface receptors triggering intracellular signaling that affect cellular pathways in turn. This review aims to support the notion that the ECM and its alterations actively participate in the promotion of chronic inflammation and cancer initiation. In conclusion, some data obtained in cancer research with the employment of decellularized ECM (dECM) models are described. The reported results encourage the application of dECM models to investigate the short circuits contributing to the creation of distinct IME, thus representing a potential tool to avoid the progression toward a malignant lesion.
Survival and Prognostic Factors of Ultra-Central Tumors Treated with Stereotactic Body Radiotherapy
Authors: Salvestrini Viola , Duijm Marloes , Loi Mauro , Nuyttens Joost J.
Published: November 2022

Introduction: Stereotactic body radiotherapy (SBRT) reported excellent outcomes and a good tolerability profile in case of central lung tumors, as long as risk-adapted schedules were adopted. High grade toxicity was more frequently observed for tumors directly touching or overlapping the trachea, proximal bronchial tree (PBT), and esophagus. We aim to identify prognostic factors associated with survival for Ultra-Central (UC) tumors. Methods: We retrospectively evaluated patients treated with SBRT for primary or metastatic UC lung tumors. SBRT schedules ranged from 45 to 60 Gy. Results: A total number of 126 ultra-central lung tumors were reviewed. The Median follow-up time was 23 months. Median Overall Survival (OS) and Progression Free Survival (PFS) was 29.3 months and 16 months, respectively. Local Control (LC) rates at 1 and 2 were 86% and 78%, respectively. Female gender, age < 70 years, and tumor size < 5 cm were significantly associated with better OS. The group of patients with tumors close to the trachea but further away from the PBT also correlated with better OS. The acute G2 dysphagia, cough, and dyspnea were 11%, 5%, and 3%, respectively. Acute G3 dyspnea was experienced by one patient. Late G3 toxicity was reported in 4% of patients. Conclusion: risk-adaptive SBRT for ultra-central tumors is safe and effective, even if it remains a high-risk clinical scenario.
The Influence of Vaginal HPV Self-Sampling on the Efficacy of Populational Screening for Cervical Cancer—An Umbrella Review
Authors: Tatara Tomasz , Wnuk Katarzyna , Miazga Wojciech , Świtalski Jakub , Karauda Dagmara , Mularczyk-Tomczewska Paulina , Religioni Urszula , Gujski Mariusz
Published: November 2022

Introduction: Early detection of cervical cancer is a matter of great importance as the prognosis depends on the stage of the disease. The objective of the study consisted in the assessment of the impact of HPV self-sampling on the efficacy of populational screening programs aimed at early CC detection. Methods: The analysis was performed taking into account the Cochrane Collaboration guidelines for systematic reviews. The analyzed articles were searched for in the following databases: Medline (PubMed), Embase (Ovid), and Cochrane Library. Results: From a total of 60 citations, 16 studies were included in this review. The HPV test is highly sensitive and specific although the diagnostic accuracy of tests carried out in self-collected samples is slightly lower than that of tests carried out in samples collected by clinicians. The results of meta-analyses for HPV tests performed on self-collected samples indicate that the sensitivity for detecting CIN2+ ranges from 74% to 86% (depending on the publication and the analyzed population), and for CIN3+ from 75% to 86%. One publication showed a clearly lower sensitivity of 42% in detecting CIN3+, but the result is for a high-risk population and comes from only 1 RCT. The specificity of the assay exceeds 80% and 79.5% with regard to the detection of CIN2+ and CIN3+, respectively. As shown by the studies included in the review, both the offering of HPV self-sampling kits to patients and the mailing of such kits significantly increase the uptake of and participation in cervical cancer screening programs. In addition, self-sampling was found to be acceptable by the female subjects. Conclusions: HPV self-sampling is an innovative and cost-effective way to perform screening tests. In addition, self-sampling significantly increases the willingness to participate in screening programs among female subjects.
Ciliary Neurotrophic Factor Modulates Multiple Downstream Signaling Pathways in Prostate Cancer Inhibiting Cell Invasiveness
Authors: Tossetta Giovanni , Fantone Sonia , Gesuita Rosaria , Goteri Gaia , Senzacqua Martina , Marcheggiani Fabio , Tiano Luca , Marzioni Daniela , Mazzucchelli Roberta
Published: November 2022

Background: Prostate cancer (PCa) remains the most common diagnosed tumor and is the second-leading cause of cancer-related death in men. If the cancer is organ-confined it can be treated by various ablative therapies such as RP (radical prostatectomy), RT (radiation therapy), brachytherapy, cryosurgery or HIFU (High-Intensity Focused Ultrasound). However, advanced or metastatic PCa treatment requires systemic therapy involving androgen deprivation, but such patients typically progress to refractory disease designated as castration-resistant prostate cancer (CRPC). Interleukin-6 (IL-6) has been established as a driver of prostate carcinogenesis and tumor progression while less is known about the role of ciliary neurotrophic factor (CNTF), a member of the IL-6 cytokine family in prostate cancer. Moreover, MAPK/ERK, AKT/PI3K and Jak/STAT pathways that regulate proliferative, invasive and glucose-uptake processes in cancer progression are triggered by CNTF. Methods: We investigate CNTF and its receptor CNTFRα expressions in human androgen-responsive and castration-resistant prostate cancer (CRPC) by immunohistochemistry. Moreover, we investigated the role of CNTF in proliferative, invasive processes as well as glucose uptake using two cell models mimicking the PCa (LNCaP cell line) and CRPC (22Rv1 cell line). Conclusions: Our results showed that CNTF and CNTFRa were expressed in PCa and CRPC tissues and that CNTF has a pivotal role in prostate cancer environment remodeling and as a negative modulator of invasion processes of CRPC cell models.
The Cytotoxic Effects of Cannabidiol and Cannabigerol on Glioblastoma Stem Cells May Mostly Involve GPR55 and TRPV1 Signalling
Authors: Lah Tamara T. , Majc Bernarda , Novak Metka , Sušnik Ajda , Breznik Barbara , Porčnik Andrej , Bošnjak Roman , Sadikov Aleksander , Malavolta Marta , Halilčević Selma , Mlakar Jernej , Zomer Roby
Published: November 2022

Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60–70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion receptor protein transporters TRPs. First, we found up-regulated CNR1, GPR55, and TRPV1 expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples. CNR1 and GPR55 did not correlate with glioma grade, whereas TRPV1 negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of TRPV1. With respect to markers of GBM stem cells, preferred targets of therapy, TRPV1 and GPR55, but not CNR1, strongly correlated with different sets of stemness gene markers: NOTCH, OLIG2, CD9, TRIM28, and TUFM and CD15, SOX2, OCT4, and ID1, respectively. This is in line with the higher expression of TRPV1 and GPR55 genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy.
Long Intergenic Non-Protein Coding RNA 173 in Human Cancers
Authors: Mao Wei , Liao Yi , Tang Liling
Published: November 2022

Long non-coding RNAs belong to non-coding RNAs (ncRNAs) with a length of more than 200 nucleotides and limited protein-coding ability. Growing research has clarified that dysregulated lncRNAs are correlated with the development of various complex diseases, including cancer. LINC00173 has drawn researchers’ attention as one of the recently discovered lncRNAs. Aberrant expression of LINC00173 affects the initiation and progression of human cancers. In the present review, we summarize the recent considerable research on LINC00173 in 11 human cancers. Through the summary of the abnormal expression of LINC00173 and its potential molecular regulation mechanism in cancers, this article indicates that LINC00173 may serve as a potential diagnostic biomarker and a target for drug therapy, thus providing novel clues for future related research.
CDK4/6 Inhibition Enhances the Efficacy of Standard Chemotherapy Treatment in Malignant Pleural Mesothelioma Cells
Authors: Terenziani Rita , Galetti Maricla , La Monica Silvia , Fumarola Claudia , Zoppi Silvia , Alfieri Roberta , Digiacomo Graziana , Cavazzoni Andrea , Cavallo Delia , Corradi Massimo , Tiseo Marcello , Petronini Pier Giorgio , Bonelli Mara
Published: November 2022

Background: The loss of the CDKN2A/ARF (cyclin-dependent kinase inhibitor 2A/alternative reading frame) gene is the most common alteration in malignant pleural mesothelioma (MPM), with an incidence of about 70%, thus representing a novel target for mesothelioma treatment. In the present study, we evaluated the antitumor potential of combining the standard chemotherapy regimen used for unresectable MPM with the CDK4/6 (cyclin-dependent kinase 4 or 6) inhibitor abemaciclib. Methods: Cell viability, cell death, senescence, and autophagy induction were evaluated in two MPM cell lines and in a primary MPM cell culture. Results: The simultaneous treatment of abemaciclib with cisplatin and pemetrexed showed a greater antiproliferative effect than chemotherapy alone, both in MPM cell lines and in primary cells. This combined treatment induced cellular senescence or autophagic cell death, depending on the cell type. More in detail, the induction of cellular senescence was related to the increased expression of p21, whereas autophagy induction was due to the impairment of the AKT/mTOR signaling. Notably, the effect of the combination was irreversible and no resumption in tumor cell proliferation was observed after drug withdrawal. Conclusion: Our results demonstrated the therapeutic potential of CDK4/6 inhibitors in combination with chemotherapy for the treatment of MPM and are consistent with the recent positive results in the MiST2 arm in abemaciclib-treated patients.
Radiotherapy of the Primary Disease for Synchronous Metastatic Cancer: A Systematic Review
Authors: Ghannam Youssef , Laville Adrien , Kirova Youlia , Latorzeff Igor , Levy Antonin , Zhou Yuedan , Bourbonne Vincent
Published: November 2022

In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of the concept of oligometastatic and oligopersistent diseases, the advent of new systemic therapies enabling longer overall survival with an enhanced quality of life, a better understanding of the biologic history of metastatic spread, and technical advances in radiation therapy are revolutionizing the management of patients with de novo metastatic cancer. The prognosis of these patients has been markedly improved and many studies have investigated the survival benefits from the local treatment of various primary tumors in cases of advanced disease at the time of diagnosis or in the case of oligopersistence. This article provides an update on the place of irradiation of the primary tumor in cancer with synchronous metastases, and discusses its interest through published or ongoing trials.
Intercommunication between Voltage-Gated Calcium Channels and Estrogen Receptor/Estrogen Signaling: Insights into Physiological and Pathological Conditions
Authors: Subbamanda Yashashwini Dinesh , Bhargava Anamika
Published: November 2022

Voltage-gated calcium channels (VGCCs) and estrogen receptors are important cellular proteins that have been shown to interact with each other across varied cells and tissues. Estrogen hormone, the ligand for estrogen receptors, can also exert its effects independent of estrogen receptors that collectively constitute non-genomic mechanisms. Here, we provide insights into the VGCC regulation by estrogen and the possible mechanisms involved therein across several cell types. Notably, most of the interaction is described in neuronal and cardiovascular tissues given the importance of VGCCs in these electrically excitable tissues. We describe the modulation of various VGCCs by estrogen known so far in physiological conditions and pathological conditions. We observed that in most in vitro studies higher concentrations of estrogen were used while a handful of in vivo studies used meager concentrations resulting in inhibition or upregulation of VGCCs, respectively. There is a need for more relevant physiological assays to study the regulation of VGCCs by estrogen. Additionally, other interacting receptors and partners need to be identified that may be involved in exerting estrogen receptor-independent effects of estrogen.
Survival by Mediastinal Chest Drain Due to Pneumomediastinum Resulting from COVID-19
Authors: Lingens Johanna Elisabeth , Lingens Jan Berend , Gutersohn Achim , Hönemann Christian
Published: November 2022

Pneumomediastinum, pneumothorax, and subcutaneous emphysema may occur as rare complications of COVID-19. They are associated with worsened prognosis and survival from SARS-CoV-2 pneumonia. The treatment of pneumomediastinum involves supportive care and management of underlying diseases. Our case presents a female patient suffering from COVID-19 pneumonia with life-threatening mediastinal emphysema. According to guidelines, literature, and other clinical sources, no further therapy options were recommended, and survival was improbable. During an interdisciplinary case discussion, we decided to establish a mediastinal drain and tracheal cannula. This achieved a significant reduction of emphysema as well as an improvement in the patient’s clinical condition and long-term survival. This case demonstrates a rarely used invasive therapy for pneumomediastinum. Furthermore, it demonstrates the importance of cooperation with other centers, interdisciplinary teamwork, and of presenting case reviews—especially when guidelines are unavailable.