bluuebunny/crossref_metadata_2025 huggingface dataset:
Oligosaccharins Alleviate Heat Stress in Greenhouse-Grown Tomatoes during the Spring-Summer Season in a Semi-Arid Climate
Authors: Hernández Virginia , Hellín Pilar , Botella M. Ángeles , Vicente Elena , Fenoll José , Flores Pilar
Published: March 2022

The use of plant biostimulants is a promising tool to stimulate crop growth and yield, as well as to promote plant defense mechanisms under abiotic stresses. The aim of the present work was to investigate the effect of oligosaccharides and their mode of application (to roots, leaves, or both) on the yield and fruit composition of tomatoes grown under greenhouse conditions. Two set-point temperatures for ventilation were established, resulting in two high-temperature levels, one higher than the other. Oligosaccharins stimulated photosynthesis and improved fruit production at both temperatures, but increased yields were more evident under lower temperature-stress. Treatments that included the application of oligosaccharins to the roots decreased the concentrations of sugars, lutein, lycopene, and most phenolic compounds in the fruit. However, when oligosaccharins were applied via the leaves, the concentration of most of the metabolites of nutritional interest in the fruit did not change. The different effects of oligosaccharins on the concentration of the different compounds may be due to a dilution effect due to increased fruit yield, and/or to the possible role of the biostimulants in reducing the stress situation in tomato plants. The results show that the application of biostimulants such as oligosaccharins can improve tomato yield under stress conditions, with the advantage that they are natural products with no negative effect on the environment.
Effects of Irrigation Schedules on Maize Yield and Water Use Efficiency under Future Climate Scenarios in Heilongjiang Province Based on the AquaCrop Model
Authors: Nie Tangzhe , Tang Yi , Jiao Yang , Li Na , Wang Tianyi , Du Chong , Zhang Zhongxue , Chen Peng , Li Tiecheng , Sun Zhongyi , Zhu Shijiang
Published: March 2022

Predicting the impact of future climate change on food security has important implications for sustainable food production. The 26 meteorological stations’ future climate data in the study area are assembled from four global climate models under two representative concentration pathways (RCP4.5 and RCP8.5). The future maize yield, actual crop evapotranspiration (ETa), and water use efficiency (WUE) were predicted by calibrated AquaCrop model under two deficit irrigation (the regulated deficit irrigation (RDI) at jointing stage(W1), filling stage(W2)), and full irrigation (W3) during the three periods (2021–2040, 2041–2060, and 2061–2080). The result showed that the maize yields under W1, W2, and W3 of RCP4.5 were 2.8%, 2.9%, and 2.5% lower than those in RCP8.5, respectively. In RCP8.5, the yield of W3 was 1.9% and 1.4% higher than W1 and W2, respectively. Under the RCP4.5, the ETa of W1, W2, and W3 was 481.32 mm, 484.94 mm, and 489.12 mm, respectively. Moreover, the ETa of W1 was significantly lower than W2 under the RCP4.5 and RCP8.5 (p > 0.05). In conclusion, regulated deficit irrigation at the maize jointing stage is recommended in the study area when considering WUE.
Is Virtual Fencing an Effective Way of Enclosing Cattle? Personality, Herd Behaviour and Welfare
Authors: Aaser Magnus Fjord , Staahltoft Søren Krabbe , Korsgaard Andreas Hein , Trige-Esbensen Adam , Alstrup Aage Kristian Olsen , Sonne Christian , Pertoldi Cino , Bruhn Dan , Frikke John , Linder Anne Cathrine
Published: March 2022

In modern nature conservation and rewilding there is a need for controlling the movements of large grazers in extensively managed areas. The inflexibility of physical fencing can be a limitation in nature management, and the physical boundaries created by physical fencing can have detrimental effects on wildlife. Virtual fencing systems provide boundaries without physical structures. These systems utilise collars with GPS technology to track animals and deliver auditory or electric cues to encourage the animals to stay within the predefined boundaries. This study aims to assess the use of virtual fencing (Nofence©) to keep twelve Angus cows (Bos taurus) within a virtual enclosure without compromising their welfare. As such, the study examines inter-individual differences between the cows as well as their herd behaviour, when reacting and learning to respond appropriately to virtual fencing. Moreover, the activity of the cows was used as an indicator of welfare. The virtual fencing was successful in keeping the herd within the designated area. Moreover, the cattle learned to avoid the virtual border and respond to auditory cues, where the cows received significantly more auditory warning and electric impulses per week throughout the first 14 days than the remaining 125 days (p < 0.001). The cows were found to express both inter-individual differences (p < 0.001) and herd behaviour. The cattle did not express any significant changes in their activity upon receiving an electrical impulse from the collar. Thus, indicating that there were little to no acute welfare implications associated with the use of virtual fencing in this study. This study clearly supports the potential for virtual fencing as a viable alternative to physical electric fencing. However, it also shows that both individual differences in personality and herd structure should be considered when selecting individuals for virtual fencing.
Improvement of Ruminal Neutral Detergent Fiber Degradability by Obtaining and Using Exogenous Fibrolytic Enzymes from White-Rot Fungi
Authors: Carrillo-Díaz María Isabel , Miranda-Romero Luis Alberto , Chávez-Aguilar Griselda , Zepeda-Batista José Luis , González-Reyes Mónica , García-Casillas Arturo César , Tirado-González Deli Nazmín , Tirado-Estrada Gustavo
Published: March 2022

The present review examines the factors and variables that should be considered to obtain, design, and evaluate EFEs that might enhance ruminal NDF degradability. Different combinations of words were introduced in Google Scholar, then scientific articles were examined and included if the reported factors and variables addressed the objective of this review. One-hundred-and-sixteen articles were included. The fungal strains and culture media used to grow white-rot fungi induced the production of specific isoforms of cellulases and xylanases; therefore, EFE products for ruminant feed applications should be obtained in cultures that include the high-fibrous forages used in the diets of those animals. Additionally, the temperature, pH, osmolarity conditions, and EFE synergisms and interactions with ruminal microbiota and endogenous fibrolytic enzymes should be considered. More consistent results have been observed in studies that correlate the cellulase-to-xylanase ratio with ruminant productive behavior. EFE protection (immobilization) allows researchers to obtain enzymatic products that may act under ruminal pH and temperature conditions. It is possible to generate multi-enzyme cocktails that act at different times, re-associate enzymes, and simulate natural protective structures such as cellulosomes. Some EFEs could consistently improve ruminal NDF degradability if we consider fungal cultures and ruminal environmental conditions variables, and include biotechnological tools that might be useful to design novel enzymatic products.
Comparison of a Point-of-Care FilmArray Test to Standard-of-Care Microbiology Test in Diagnosis of Healthcare Associated Infections in a Tertiary Care Pediatric Intensive Care Unit
Authors: El-Nawawy Ahmed A. , Antonios Manal A. , Tawfik Medhat E. , Meheissen Marwa A.
Published: March 2022

Background: Rapid and accurate identification of healthcare associated pathogens is crucial for early diagnosis and treatment of infections. This study aimed to assess the performance of a point-of-care multiplex polymerase chain reaction (PCR) in diagnosis of pathogens and their antibiotic resistance genes in bloodstream infections, pneumonia and meningitis/encephalitis in a pediatric intensive care unit (PICU). Methods: A retrospective cross-sectional study was conducted on pediatric patients diagnosed with healthcare associated infections at Alexandria University PICU, Egypt. A total of 111 samples from 98 patients were subjected simultaneously to standard-of-care microbiology testing (SOCMT) and molecular testing by BioFire multiplex PCR. Results: In comparison to SOCMT, the BioFire FilmArray® had a better diagnostic yield with broncho-alveolar lavage (BAL) (45 vs. 21) and cerebrospinal fluid (CSF) samples (five vs. none) (p ≤ 0.0001). Klebsiella pneumoniae was the most common pathogen in BAL (n = 19 by BioFire, n = 9 by SOCMT) and blood (n = 7, by SOCMT and BioFire) samples, while Streptococcus pneumoniae was the most common in CSF samples. BioFire showed 95.8% overall percent agreement, 100% positive percent agreement and 95.6% negative percent agreement with SOCMT. All phenotypically confirmed resistant isolates had resistance genes by the BioFire FilmArray® (100%). The turnaround time (TAT) of positive results by the FilmArray panels was 1–1.5 h in comparison to 48–72 h by SOCMT (p ≤ 0.001). Conclusions: The results of the current study confirm the utility of the BioFire FilmArray® in making early decisions regarding patients’ diagnosis and management of infection in the PICU, in terms of rapid TAT and appropriate antimicrobial use.
Ginsenoside Rh1 Inhibits Angiotensin II-Induced Vascular Smooth Muscle Cell Migration and Proliferation through Suppression of the ROS-Mediated ERK1/2/p90RSK/KLF4 Signaling Pathway
Authors: Huynh Diem Thi Ngoc , Jin Yujin , Van Nguyen Dung , Myung Chang-Seon , Heo Kyung-Sun
Published: March 2022

Vascular smooth muscle cell (VSMC) proliferation and migration play key roles in the progression of atherosclerosis and restenosis. A variety of ginsenosides exert various cardiovascular benefits. However, whether and how ginsenoside Rh1 (Rh1) inhibits VSMC dysfunction remain unclear. Here, we investigated the inhibitory effects of Rh1 on rat aortic smooth muscle cell (RASMC) migration and proliferation induced by angiotensin II (Ang II) and the underlying mechanisms. Cell proliferation and migration were evaluated using sulforhodamine B and wound-healing assay. The molecular mechanisms were investigated using Western blotting, quantitative reverse-transcription polymerase chain reaction analysis, immunofluorescence staining, and luciferase assay. Reactive oxygen species (ROS) production was measured using dihydroethidium and MitoSOX staining. We found that Rh1 dose-dependently suppressed Ang II-induced cell proliferation and migration. Concomitantly, Ang II increased protein levels of osteopontin, vimentin, MMP2, MMP9, PCNA, and cyclin D1, while these were reduced by Rh1 pretreatment. Notably, Ang II enhanced both the protein expression and promoter activity of KLF4, a key regulator of phenotypic switching, whereas pretreatment with Rh1 reversed these effects. Mechanistically, the effects of Rh1 on VSMC proliferation and migration were found to be associated with inhibition of ERK1/2/p90RSK signaling. Furthermore, the inhibitory effects of Rh1 were accompanied by inhibition of ROS production. In conclusion, Rh1 inhibited the Ang II-induced migration and proliferation of RASMCs by suppressing the ROS-mediated ERK1/2/p90RSK signaling pathway.
Free Final-Time Fuel-Optimal Powered Landing Guidance Algorithm Combing Lossless Convex Optimization with Deep Neural Network Predictor
Authors: Li Wenbo , Gong Shengping
Published: March 2022

The real-time guidance algorithm is the key technology of the powered landing. Given the lack of real-time performance of the convex optimization algorithm with free final time, a lossless convex optimization (LCvx) algorithm based on the deep neural network (DNN) predictor is proposed. Firstly, the DNN predictor is built to map the optimal final time. Then, the LCvx algorithm is used to solve the problem of fuel-optimal powered landing with the given final time. The optimality and real-time performance of the proposed algorithm are verified by numerical examples. Finally, a closed-loop simulation framework is constructed, and the accuracy of landing under various disturbances is verified. The proposed method does not need complex iterative operations compared with the traditional algorithm with free final time. Therefore, the computational efficiency can be improved by an order of magnitude.
IoT-Enabled Smart Agriculture: Architecture, Applications, and Challenges
Authors: Quy Vu Khanh , Hau Nguyen Van , Anh Dang Van , Quy Nguyen Minh , Ban Nguyen Tien , Lanza Stefania , Randazzo Giovanni , Muzirafuti Anselme
Published: March 2022

The growth of the global population coupled with a decline in natural resources, farmland, and the increase in unpredictable environmental conditions leads to food security is becoming a major concern for all nations worldwide. These problems are motivators that are driving the agricultural industry to transition to smart agriculture with the application of the Internet of Things (IoT) and big data solutions to improve operational efficiency and productivity. The IoT integrates a series of existing state-of-the-art solutions and technologies, such as wireless sensor networks, cognitive radio ad hoc networks, cloud computing, big data, and end-user applications. This study presents a survey of IoT solutions and demonstrates how IoT can be integrated into the smart agriculture sector. To achieve this objective, we discuss the vision of IoT-enabled smart agriculture ecosystems by evaluating their architecture (IoT devices, communication technologies, big data storage, and processing), their applications, and research timeline. In addition, we discuss trends and opportunities of IoT applications for smart agriculture and also indicate the open issues and challenges of IoT application in smart agriculture. We hope that the findings of this study will constitute important guidelines in research and promotion of IoT solutions aiming to improve the productivity and quality of the agriculture sector as well as facilitating the transition towards a future sustainable environment with an agroecological approach.
Study on Deformation Characteristics of Low-Highway Subgrade under Traffic Load
Authors: Qi Hui , Zhang Xuesen , Liu Jian , Zhang Tiantao , Lv Gaohang , Cui Lizhuang , Xie Quanyi
Published: March 2022

Highway subgrade bears millions of traffic loads over the years, and its strength, stiffness, and long-term stability gradually decline. In this paper, dynamic triaxial tests were carried out to study the time evolution and spatial distribution of strain and pore pressure of highway-subgrade soil under the action of traffic load. The influence of traffic load on subgrade deformation was analyzed. Furthermore, a numerical-calculation model of the subgrade was established. The deformation characteristics of subgrade under driving load were analyzed. The main conclusions can be drawn as follows: (1) With the increase in loading times, the cumulative strain and pore pressure can be roughly divided into three stages: rapid-growth stage, slow-growth stage, and equilibrium stage. (2) The influence of traffic load on the cumulative strain and pore-water pressure of subgrade soil decreases rapidly with the increase in depth. (3) The amplitude of traffic load has a tremendous influence on the strain and pore pressure of subgrade soil, especially for shallow subgrade. (4) As the distance from the subgrade surface increases, the maximum deformation appears at the edge of the subgrade.
Air Flow Study around Isolated Cubical Building in the City of Athens under Various Climate Conditions
Authors: Pavlidis Chariton L. , Palampigik Anargyros V. , Vasilopoulos Konstantinos , Lekakis Ioannis C. , Sarris Ioannis E.
Published: March 2022

This study focuses on the airflow and pollutant dispersion around an isolated cubical building located in a warm Mediterranean climate, taking into account the local microclimate conditions (of airflow, albedo of building and soil, and air humidity) using a large-eddy simulation (LES) numerical approach. To test the reliability of computations, comparisons are made against the SILSOE cube experimental data. Three different scenarios are examined: (a) Scenario A with adiabatic walls, (b) Scenario B with the same constant temperature on all the surfaces of the building, and (c) Scenario C using convective and radiative conditions imposed by the local microclimate. For the first two cases the velocity and temperature fields resulting are almost identical. In the third case, the resulting temperature on the surfaces of the building is increased by 19.5%, the center (eye) of the wake zone is raised from the ground and the maximum pollutant concentration is drastically reduced (89%).
Bootstrapped SSL CycleGAN for Asymmetric Domain Transfer
Authors: Krstanović Lidija , Popović Branislav , Janev Marko , Brkljač Branko
Published: March 2022

Most CycleGAN domain transfer architectures require a large amount of data belonging to domains on which the domain transfer task is to be applied. Nevertheless, in many real-world applications one of the domains is reduced, i.e., scarce. This means that it has much less training data available in comparison to the other domain, which is fully observable. In order to tackle the problem of using CycleGAN framework in such unfavorable application scenarios, we propose and invoke a novel Bootstrapped SSL CycleGAN architecture (BTS-SSL), where the mentioned problem is overcome using two strategies. Firstly, by using a relatively small percentage of available labelled training data from the reduced or scarce domain and a Semi-Supervised Learning (SSL) approach, we prevent overfitting of the discriminator belonging to the reduced domain, which would otherwise occur during initial training iterations due to the small amount of available training data in the scarce domain. Secondly, after initial learning guided by the described SSL strategy, additional bootstrapping (BTS) of the reduced data domain is performed by inserting artifically generated training examples into the training poll of the data discriminator belonging to the scarce domain. Bootstrapped samples are generated by the already trained neural network that performs transferring from the fully observable to the scarce domain. The described procedure is periodically repeated during the training process several times and results in significantly improved performance of the final model in comparison to the original unsupervised CycleGAN approach. The same also holds in comparison to the solutions that are exclusively based either on the described SSL, or on the bootstrapping strategy, i.e., when these are applied separately. Moreover, in the considered scarce scenarios it also shows competitive results in comparison to the fully supervised solution based on the pix2pix method. In that sense, it is directly applicable to many domain transfer tasks that are relying on the CycleGAN architecture.
Relationship between Subjective and Biological Responses to Comfortable and Uncomfortable Sounds
Authors: Asakura Takumi
Published: March 2022

Various kinds of biological sensors are now embedded in wearable devices and data on human biological information have recently become more widespread. Among various environmental stressors, sound has emotional and biological impacts on humans, and it is worthwhile to investigate the relationship between the subjective impressions of and biological responses to such sounds. In this study, the relationship between subjective and biological responses to acoustic stimuli with two contrasting kinds of sounds, a murmuring river sound and white noise, was investigated. The subjective and biological responses were measured during the presentation of the sounds. Compared with the murmuring river sound, the white noise had a significantly decreased EEG-related index of α-EEG and HRV-related index of SD2/SD1. The correlation between each index of subjective and biological responses indicated that α-EEG was highly correlated with the results of subjective evaluation. However, based on a more detailed analysis with clustering, some subjects showed different biological responses in each trial since they felt the sound was powerful when listening to the murmuring river sound, as well as feeling that it was beautiful. It was suggested that biological responses to sound exposure may be affected by the impression of the sound, which varies by individual.
Audiologist’s Perspective in Auditory Rehabilitation: Implications for Ethical Conduct and Decision-Making in Portugal
Authors: Marques Tatiana , Silvestre Margarida , Rosa Bárbara Santa , Miguéis António
Published: March 2022

Ethical standards in audiology have been continuously improved and discussed, leading to the elaboration of specific regulatory guidelines for the profession. However, in the field of auditory rehabilitation, audiologists are still faced with circumstances that question their ethical principles, usually associated with the support of the hearing aids industry. The study explores the decision-making process and ethical concerns in auditory rehabilitation as they relate to the practice of audiology in Portugal. An online questionnaire constructed by the authors was used and sent to the email addresses of a list of audiologists, registered with the Portuguese Association of Audiologists. The questionnaire was answered by 93 audiologists with clinical experience in auditory rehabilitation for more than one year. The collected data demonstrated that audiometric results and clinical experience are the most important factors for decision-making in auditory rehabilitation practice. Moreover, incentives from the employers or manufacturers were identified as the main cause of ethical dilemmas. This study highlights the ethical concerns regarding the clinical practice of auditory rehabilitation in Portugal, revealing that the decision-making process is complex and, specifically in this field, the current practice may not be adequate for effective compliance with professional ethical standards.
Selection of Cold Chain Logistics Service Providers Based on a Grey AHP and Grey COPRAS Framework: A Case Study in Vietnam
Authors: Nguyen Ngoc-Ai-Thy , Wang Chia-Nan , Dang Le-Thanh-Hieu , Dang Le-Thanh-Tuyen , Dang Thanh-Tuan
Published: March 2022

Choosing the most suitable cold chain logistics service providers (CLPs) is a vital strategic decision for businesses aiming to achieve an effective and sustainable cold supply chain. A sustainable CLP is one that integrates sustainable practices across its whole operation cycle to achieve product quality, on-time deliveries, and satisfied customer requirements, while preventing products from going to waste, which is especially important in the context of a developing country. This study aims to evaluate and select the best CLP regarding their sustainability performance. For this evaluation, a multi-criteria decision making (MCDM)-based framework is proposed that integrates the grey analytic hierarchy process (G-AHP) and grey complex proportional assessment (G-COPRAS) methodologies, in which grey numbers are used to express the linguistic evaluation statements of experts. Initially, the evaluation criteria based on service level, economic, environmental, and social dimensions were determined by means of a literature review and experts’ opinions to employ the MCDM approach. The G-AHP was utilized to identify the criteria weights, and then, G-COPRAS was used to select the best CLP among the alternatives. A case illustration in Vietnam is presented to exhibit the presented approach’s applicability. From the G-AHP findings, product quality, logistics costs, innovation, and effectiveness of cold chain processes, customer experience, and CO emissions of refrigerated vehicle were ranked as the five most important criteria. From the G-COPRAS analysis, Yoshida Saigon Cold Logistic (CPL-05) is the best CLP. The robustness of the applied integrated MCDM approach was also tested by conducting a comparative analysis, in which the priority rankings of the best CLPs were very similar. The assessment in this study is directed towards enabling managers, practitioners, and stakeholders of cold chain businesses to assess the most efficient CLP in the supply chain in the market and also to devise suitable strategies toward sustainable development.
Morphological and Molecular Description of Sarcocystis myodes n. sp. from the Bank Vole (Clethrionomys glareolus) in Lithuania
Authors: Rudaitytė-Lukošienė Eglė , Jasiulionis Marius , Balčiauskas Linas , Prakas Petras , Stirkė Vitalijus , Butkauskas Dalius
Published: March 2022

Numerous rodent species have been broadly examined for Sarcocystis parasites. Nevertheless, recent investigations on Sarcocystis spp. in voles are lacking. As many as 45 bank voles (Clethrionomys glareolus) captured in several locations in Lithuania were examined in the present study. Based on morphological, genetic, and phylogenetic results, sarcocysts detected in one bank vole were described as Sarcocystis myodes n. sp. Using light microscopy analysis, the observed sarcocysts were ribbon-shaped, 6000–3000 × 70–220 µm in size. Sarcocysts were characterized by a relatively thin (about 1 μm) and apparently smooth cyst wall. The lancet-shaped bradyzoites were 9.6–12.0 × 3.1–4.6 μm in size. By transmission electron microscopy, the sarcocyst wall was up to 1 μm thick, parasitophorous vacuolar membrane had small knob-like blebs. Based on 18S rDNA, 28S rDNA, cox1, rpoB, and ITS1 loci, S. myodes showed highest similarity with S. ratti from the black rat (Rattus rattus). According to phylogenetic placement, S. myodes was most closely related to Sarcocystis spp. that employ predatory mammals as their definitive hosts. Morphologically, sarcocysts of S. myodes have similar features to those of S. cernae, S. dirumpens, and S. montanaensis described in voles, however, they use birds of prey or snakes as their definitive hosts.
Feature Reduction for Molecular Similarity Searching Based on Autoencoder Deep Learning
Authors: Nasser Maged , Salim Naomie , Saeed Faisal , Basurra Shadi , Rabiu Idris , Hamza Hentabli , Alsoufi Muaadh A.
Published: March 2022

The concept of molecular similarity has been commonly used in rational drug design, where structurally similar molecules are examined in molecular databases to retrieve functionally similar molecules. The most used conventional similarity methods used two-dimensional (2D) fingerprints to evaluate the similarity of molecules towards a target query. However, these descriptors include redundant and irrelevant features that might impact the performance of similarity searching methods. Thus, this study proposed a new approach for identifying the important features of molecules in chemical datasets based on the representation of the molecular features using Autoencoder (AE), with the aim of removing irrelevant and redundant features. The proposed approach experimented using the MDL Data Drug Report standard dataset (MDDR). Based on experimental findings, the proposed approach performed better than several existing benchmark similarity methods such as Tanimoto Similarity Method (TAN), Adapted Similarity Measure of Text Processing (ASMTP), and Quantum-Based Similarity Method (SQB). The results demonstrated that the performance achieved by the proposed approach has proven to be superior, particularly with the use of structurally heterogeneous datasets, where it yielded improved results compared to other previously used methods with the similar goal of improving molecular similarity searching.
Benefits of Tango Therapy in Alleviating the Motor and Non-Motor Symptoms of Parkinson’s Disease Patients—A Narrative Review
Authors: Docu Axelerad Any , Stroe Alina Zorina , Muja Lavinia Florenta , Docu Axelerad Silviu , Chita Dana Simona , Frecus Corina Elena , Mihai Cristina Maria
Published: March 2022

The present study examines the efficacy of tango therapy on motor and non-motor symptomatology in Parkinson’s disease, as detailed in articles published over the previous four decades (1980–2022). All data was collected using PubMed, Google Scholar, Web of Science, and Science Direct. The present descriptive study outlines the advantages of tango in the rehabilitation of Parkinson’s disease’s motor and non-motor symptoms. Numerous studies have been conducted to determine the usefulness of tango for people with PD. Information from various research is critical for determining if tango is a useful supplementary therapy for the variety of symptoms related to Parkinson’s disease. The purpose of this review was to describe the present state of research on this subject. Thus, the objective of this review is to promote awareness of tango therapy’s therapeutic benefits for Parkinson’s disease.
CSA Antisense Targeting Enhances Anticancer Drug Sensitivity in Breast Cancer Cells, including the Triple-Negative Subtype
Authors: Filippi Silvia , Paccosi Elena , Balzerano Alessio , Ferretti Margherita , Poli Giulia , Taborri Juri , Brancorsini Stefano , Proietti-De-Santis Luca
Published: March 2022

Breast cancer (BC) is the most common cancer with the highest frequency of death among women. BC is highly heterogenic at the genetic, biological, and clinical level. Despite the significant improvements in diagnosis and treatments of BC, the high rate of cancer recurrence and resistance to treatment remains a major challenge in clinical practice. This issue is particularly relevant in Triple-Negative Breast Cancer (TNBC) subtype, for which chemotherapy remains the main standard therapeutic approach. Here, we observed that BC cells, belonging to different subtypes, including the TNBC, display an increased expression of Cockayne Syndrome group A (CSA) protein, which is involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division and that recently was found to confer cell robustness when it is up-regulated. We demonstrated that CSA ablation by AntiSense Oligonucleotides (ASOs) drastically impairs tumorigenicity of BC cells by hampering their survival and proliferative capabilities without damaging normal cells. Moreover, suppression of CSA dramatically sensitizes BC cells to platinum and taxane derivatives, which are commonly used for BC first-line therapy, even at very low doses not harmful to normal cells. Finally, CSA ablation restores drug sensitivity in oxaliplatin-resistant cells. Based on these results, we conclude that CSA might be a very attractive target for the development of more effective anticancer therapies.
Prognostic Factors in Patients with Breast Cancer Liver Metastases Undergoing Liver Resection: Systematic Review and Meta-Analysis
Authors: Galiandro Federica , Agnes Salvatore , Moschetta Giovanni , Orlandi Armando , Clarke George , Bria Emilio , Franceschini Gianluca , Treglia Giorgio , Giovinazzo Francesco
Published: March 2022

Background: The role of surgical resection of liver metastases in patients with breast cancer liver metastasis (BCLM) remains controversial. A systematic review and meta-analysis of prognostic factors related to survival after BCLM resection was performed. Methods: An electronic search of relevant publications was performed. Pooled outcome measures were expressed as hazard ratios (HRs), including 95% confidence interval values (95% CIs), and calculated through a random-effects model. Heterogeneity was tested through the I2 index. Results: Thirty-five publications reported analyses on prognostic factors and survival. A total of 2782 patients who underwent liver resection for BCLM were included. Positive axillary lymph nodes at breast cancer diagnosis were an unfavorable survival factor (HR 1.74, 95% CI 1.25 to 2.41, I2 = 0%). Cumulative predictive factor HRs (multiple liver metastases, size of the metastases, short interval between primary tumor and onset of liver disease) related to the BCLM pattern were 1.32 (95% CI 1.17 to 1.48, I2 = 71%) and 1.51 (95% CI 1.15 to 1.98, I2 = 76%) for surgical and pathological features (resection margin and presence of extrahepatic disease), respectively. Conclusion: Resection of BCLM may provide a survival benefit for selected patients. For better long-term results, surgical selection should consider both primary tumor and BCLM features such as negative axillary lymph nodes at breast resection, a single hepatic lesion, a time longer than 24 months between breast and hepatic diagnosis, and a realizable R0 liver resection. However, the high heterogeneity among studies suggests the need for an RCT to validate the present findings.
The Extent of Necrosis in Brain Metastases May Predict Subtypes of Primary Cancer and Overall Survival in Patients Receiving Craniotomy
Authors: Yoo Jihwan , Cha Yoon Jin , Park Hun Ho , Park Mina , Joo Bio , Suh Sang Hyun , Ahn Sung Jun
Published: March 2022

Although necrosis is common in brain metastasis (BM), its biological and clinical significances remain unknown. We evaluated necrosis extent differences by primary cancer subtype and correlated BM necrosis to overall survival post-craniotomy. We analyzed 145 BMs of patients receiving craniotomy. Necrosis to tumor ratio (NTR) was measured. Patients were divided into two groups by NTR: BMs with sparse necrosis and with abundant necrosis. Clinical features were compared. To investigate factor relevance for BM necrosis, multivariate logistic regression, random forests, and gradient boosting machine analyses were performed. Kaplan–Meier analysis and log-rank tests were performed to evaluate the effect of BM necrosis on overall survival. Lung cancer was a more common origin for BMs with abundant necrosis (42/72, 58.33%) versus sparse necrosis (23/73, 31.51%, p < 0.01). Primary cancer subtype and tumor volume were the most relevant factors for BM necrosis (p < 0.01). BMs harboring moderately abundant necrosis showed longer survival, versus sparse or highly abundant necrosis (p = 0.04). Lung cancer BM may carry larger necrosis than BMs from other cancers. Further, moderately abundant necrosis in BM may predict a good prognosis post-craniotomy.
Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC
Authors: Rosar Florian , Neher Robert , Burgard Caroline , Linxweiler Johannes , Schreckenberger Mathias , Hoffmann Manuela A. , Bartholomä Mark , Khreish Fadi , Ezziddin Samer
Published: March 2022

In this study, we investigated upregulation of prostate-specific membrane antigen (PSMA) by enzalutamide in a cohort (n = 30) of patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Patients were examined by [68Ga]Ga-PSMA-11 PET/CT pre- and post-enzalutamide medication (mean 13 ± 7 days). Imaging results were compared based on quantification of whole-body PSMA tumor burden: total lesion PSMA (TLP) and normalized TLP values to liver (TLP-LR) and to parotid gland (TLP-PR). In addition, lesion-based analyses were performed. The median (mean) increases in TLP, TLP-LR and TLP-PR after enzalutamide medication were 10.1% (20.2%), 29.5% (34.8%) and 27.6% (24.4%), respectively. These increases were statistically significant (p = 0.002, p < 0.001, and p < 0.001), while prostate-specific antigen (PSA) serum values did not change significantly (p = 0.483). The increase was independent of prior patient exposure to enzalutamide. SUVmax increased substantially (>10%) in 49.6% of target lesions. The relative change was significantly higher in the subgroup of lesions with SUVmax < 10 (p < 0.001). In conclusion, short-term enzalutamide medication significantly increases PSMA expression in patients with mCRPC, irrespective of prior enzalutamide exposure. The relative PSMA upregulation effect seems to be more pronounced in lesions with only moderate baseline PSMA expression. Enzalutamide may provide a potential enhancer medication for PSMA-targeted radioligand therapy.
Accurate Three-Dimensional Thermal Dosimetry and Assessment of Physiologic Response Are Essential for Optimizing Thermoradiotherapy
Authors: Dewhirst Mark W. , Oleson James R. , Kirkpatrick John , Secomb Timothy W.
Published: March 2022

Numerous randomized trials have revealed that hyperthermia (HT) + radiotherapy or chemotherapy improves local tumor control, progression free and overall survival vs. radiotherapy or chemotherapy alone. Despite these successes, however, some individuals fail combination therapy; not every patient will obtain maximal benefit from HT. There are many potential reasons for failure. In this paper, we focus on how HT influences tumor hypoxia, since hypoxia negatively influences radiotherapy and chemotherapy response as well as immune surveillance. Pre-clinically, it is well established that reoxygenation of tumors in response to HT is related to the time and temperature of exposure. In most pre-clinical studies, reoxygenation occurs only during or shortly after a HT treatment. If this were the case clinically, then it would be challenging to take advantage of HT induced reoxygenation. An important question, therefore, is whether HT induced reoxygenation occurs in the clinic that is of radiobiological significance. In this review, we will discuss the influence of thermal history on reoxygenation in both human and canine cancers treated with thermoradiotherapy. Results of several clinical series show that reoxygenation is observed and persists for 24–48 h after HT. Further, reoxygenation is associated with treatment outcome in thermoradiotherapy trials as assessed by: (1) a doubling of pathologic complete response (pCR) in human soft tissue sarcomas, (2) a 14 mmHg increase in pO2 of locally advanced breast cancers achieving a clinical response vs. a 9 mmHg decrease in pO2 of locally advanced breast cancers that did not respond and (3) a significant correlation between extent of reoxygenation (as assessed by pO2 probes and hypoxia marker drug immunohistochemistry) and duration of local tumor control in canine soft tissue sarcomas. The persistence of reoxygenation out to 24–48 h post HT is distinctly different from most reported rodent studies. In these clinical series, comparison of thermal data with physiologic response shows that within the same tumor, temperatures at the higher end of the temperature distribution likely kill cells, resulting in reduced oxygen consumption rate, while lower temperatures in the same tumor improve perfusion. However, reoxygenation does not occur in all subjects, leading to significant uncertainty about the thermal–physiologic relationship. This uncertainty stems from limited knowledge about the spatiotemporal characteristics of temperature and physiologic response. We conclude with recommendations for future research with emphasis on retrieving co-registered thermal and physiologic data before and after HT in order to begin to unravel complex thermophysiologic interactions that appear to occur with thermoradiotherapy.
Quantification of Minimal Disease by Digital PCR in ALK-Positive Anaplastic Large Cell Lymphoma: A Step towards Risk Stratification in International Trials?
Authors: Damm-Welk Christine , Lovisa Federica , Contarini Giorgia , Lüdersen Jette , Carraro Elisa , Knörr Fabian , Förster Jan , Zimmermann Martin , Sala Alessandra , Vinti Luciana , Tondo Annalisa , Pillon Marta , Woessmann Wilhelm , Mussolin Lara
Published: March 2022

Minimal disseminated and residual disease (MDD/MRD) analyzed by qualitative PCR for NPM-ALK fusion transcripts are validated prognostic factors in pediatric ALK-positive anaplastic large cell lymphoma (ALCL). Although potentially promising, MDD quantification by quantitative real-time PCR in international trials is technically challenging. Quantification of early MRD might further improve risk stratification. We aimed to assess droplet digital PCR for quantification of minimal disease in an inter-laboratory setting in a large cohort of 208 uniformly treated ALCL patients. Inter-laboratory quality control showed high concordance. Using a previously described cut-off of 30 copies NPM-ALK/104 copies ABL1 (NCN) in bone marrow and peripheral blood, MDD quantification allowed identification of very high-risk patients (5-year PFS% 34 ± 5 for patients with ≥30 NCN compared to 74 ± 6 and 76 ± 5 for patients with negative or <30 NCN, respectively, p < 0.0001). While MRD positivity was confirmed as a prognostic marker for the detection of very high-risk patients in this large study, quantification of MRD fusion transcripts did not improve stratification. PFS% was 80 ± 5 and 73 ± 6 for MDD- and MRD-negative patients, respectively, versus 35 ± 10 and 16 ± 8 for MRD-positive patients with <30 and ≥30 NCN, p < 0.0001. Our results suggest that MDD quantification by dPCR enables improved patient stratification in international clinical studies and patient selection for early clinical trials already at diagnosis.
Exosome-Mediated Therapeutic Strategies for Management of Solid and Hematological Malignancies
Authors: Allegra Alessandro , Petrarca Claudia , Di Gioacchino Mario , Casciaro Marco , Musolino Caterina , Gangemi Sebastiano
Published: March 2022

Exosomes are small membrane vesicles of endocytic origin containing cytokines, RNAs, growth factors, proteins, lipids, and metabolites. They have been identified as fundamental intercellular communication controllers in several diseases and an enormous volume of data confirmed that exosomes could either sustain or inhibit tumor onset and diffusion in diverse solid and hematological malignancies by paracrine signaling. Thus, exosomes might constitute a promising cell-free tumor treatment alternative. This review focuses on the effects of exosomes in the treatment of tumors, by discussing the most recent and promising data from in vitro and experimental in vivo studies and the few existing clinical trials. Exosomes are extremely promising as transporters of drugs, antagomir, genes, and other therapeutic substances that can be integrated into their core via different procedures. Moreover, exosomes can augment or inhibit non-coding RNAs, change the metabolism of cancer cells, and modify the function of immunologic effectors thus modifying the tumor microenvironment transforming it from pro-tumor to antitumor milieu. Here, we report the development of currently realized exosome modifiers that offer indications for the forthcoming elaboration of other more effective methods capable of enhancing the activity of the exosomes.
Vitamin D Receptor Influences Intestinal Barriers in Health and Disease
Authors: Sun Jun , Zhang Yong-Guo
Published: March 2022

Vitamin D receptor (VDR) executes most of the biological functions of vitamin D. Beyond this, VDR is a transcriptional factor regulating the expression levels of many target genes, such as genes for tight junction proteins claudin-2, -5, -12, and -15. In this review, we discuss the progress of research on VDR that influences intestinal barriers in health and disease. We searched PubMed and Google Scholar using key words vitamin D, VDR, tight junctions, cancer, inflammation, and infection. We summarize the literature and progress reports on VDR regulation of tight junction distribution, cellular functions, and mechanisms (directly or indirectly). We review the impacts of VDR on barriers in various diseases, e.g., colon cancer, infection, inflammatory bowel disease, and chronic inflammatory lung diseases. We also discuss the limits of current studies and future directions. Deeper understanding of the mechanisms by which the VDR signaling regulates intestinal barrier functions allow us to develop efficient and effective therapeutic strategies based on levels of tight junction proteins and vitamin D/VDR statuses for human diseases.
Color Genesis and Compositional Characteristics of Color-Change Sapphire from Fuping, China
Authors: Wang Hui , Yu Xiao-Yan , Liu Fei , Alam Masroor , Wu Gai-Chao
Published: March 2022

The color-change sapphire occurs in sillimanite-biotite gneiss in Fuping County Hebei province, China, is one of most famous sapphire deposits in China. However, the color genesis, mechanisms of color changing and compositional characteristics of the sapphire remain enigmatic. In this contribution, the coloration in the Fuping sapphire, color changing mechanisms and, compositional characteristics were studied by conventional gemological instruments in conjunction with ultraviolet-visible spectroscopy and Laser ablation inductively coupled plasma mass spectrometer. The results show that the Fuping sapphire is characterized by purple-blue-to-purple-red changed effect and column-shaped, waist drum-shaped with higher degree of euhedral crystal. Reddish brown rutile inclusions with 120° crossed cleavage are commonly observed. The dominant coloring element of the Fuping sapphire is Fe3+, and subordinate elements are Fe2+, Cr3+ and V3+. The color-change effect is caused by trace elements Cr3+ and V3+. The chemical compositions of Fuping color-change sapphires are analogous to those of metamorphic blue sapphires. When geochemically compared with sapphires from Isalo/Ilakaka deposit in Madagascar, Ratnapura deposit in Sri Lanka and Mogok in Myanmar, the Fuping color-change sapphires have distinctly higher rare element contents of Fe, Cr and Ga.
Chronic Appendicitis—From Ambiguous Clinical Image to Inconclusive Imaging Studies
Authors: Brodzisz Agnieszka , Kuczyńska Maryla , Zbroja Monika , Cyranka Weronika , Cielecki Czesław , Woźniak Magdalena Maria
Published: March 2022

A six-year-old boy visits a general practitioner due to diarrhea and abdominal pain with a moderate fever of up to 39 °C for 2 days. Treatment is initiated; however, the recurrence of abdominal pain is observed. Physical examination of the child at the emergency department reveals abdominal guarding and visible, palpable, painful intestinal loops in the left iliac and hypogastric regions—this is referred to as an ‘acute abdomen’. An X-ray shows single levels of air and fluid indicative of bowel obstruction. Ultrasound reveals distended, fluid-filled intestinal loops with diminished motility. The intestinal wall is swollen. Laboratory tests indicate increased inflammatory indices. Contrast-enhanced computed tomography examination of the abdominal cavity and lesser pelvis shows intestinal dilation. The loops were filled with liquid content and numerous collections of gas. The patient is qualified for a laparotomy. An intraoperative diagnosis of perforated gangrenous appendicitis with autoamputation was made. In addition, numerous interloop and pelvic abscesses, excessive adhesions, signs of small intestine micro-perforation, and diffuse peritonitis are found. The patient’s condition and laboratory parameters significantly improve during the following days of hospitalization. Despite the implementation of multidirectional, specialized diagnostics in the case of acute abdomen, in everyday practice we still encounter situations where the final diagnosis is made intraoperatively only.
The Application of Sonovaginography for Implementing Ultrasound Assessment of Endometriosis and Other Gynaecological Diseases
Authors: Arezzo Francesca , Cormio Gennaro , La Forgia Daniele , Kawosha Adam Abdulwakil , Mongelli Michele , Putino Carmela , Silvestris Erica , Oreste Donato , Lombardi Claudio , Cazzato Gerardo , Cicinelli Ettore , Loizzi Vera
Published: March 2022

Sonovaginography is a way of assessing gynaecological diseases that can be described as cheap yet accurate and non-invasive. It consists of distention of the vagina with ultrasound gel or saline solution while performing transvaginal sonography to clearly visualize and assess a host of local cervical, as well as any vaginal, disorders. With endometriosis being a steadily growing gynaecological pathology affecting 8–15% of women of fertile age, transvaginal sonography (TVS) can be considered as one of the most accurate and comprehensive imaging techniques in its diagnosis. Nevertheless, the accuracy may vary depending on scan sites. The purpose of this narrative review is to assess the performance of sonovaginography in detecting endometriosis in those sites where TVS has a low sensitivity.