bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Study of Symbiotic Genes in Pea (Pisum sativum L.) Cultivars Grown in Symbiotic Conditions
Authors: Zhukov Vladimir A. , Zhernakov Aleksandr I. , Sulima Anton S. , Kulaeva Olga A. , Kliukova Marina S. , Afonin Alexey M. , Shtark Oksana Y. , Tikhonovich Igor A.
Published: November 2021

In garden pea (Pisum sativum L.), several symbiotic genes are known to control the development of mutualistic symbioses with nodule bacteria (NB) and arbuscular mycorrhizal fungi (AMF). Here, we studied whether the allelic state of the symbiotic genes was associated with the growth parameters of pea plants under single inoculation with NB and under double inoculation with NB + AMF. Using different statistical methods, we analyzed the dataset obtained from a pot experiment that involved 99 pea cultivars, 10 of which were characterized as having shortened internodes due to the presence of the natural mutation p.A229T in the developmental gene Le. The plant’s habitus strongly influenced most of the studied growth and yield parameters and the effectiveness of the symbiotic interactions under NB and NB + AMF inoculation. Double inoculation had different effects on Le+ (normal) and le− (dwarf) plants with regard to nitrogen and phosphorus content in seeds. Regardless of the Le-status of plants, allelic states of the symbiotic gene LykX encoding the putative receptor of Nod factors (bacterial signal molecules) were shown to be associated with seed number, thousand-seed weight, and pod number at the level of FDR < 0.001, whereas associations of allelic states of the other studied symbiotic genes were less significant.
Behavioural Indicators of Intra- and Inter-Specific Competition: Sheep Co-Grazing with Guanaco in the Patagonian Steppe
Authors: Fernández Tomás , Lancaster Alex , Moraga Claudio A. , Radic-Schilling Sergio , von Hardenberg Achaz , Corti Paulo
Published: November 2021

In extensive livestock production, high densities may inhibit regulation processes, maintaining high levels of intraspecific competition over time. During competition, individuals typically modify their behaviours, particularly feeding and bite rates, which can therefore be used as indicators of competition. Over eight consecutive seasons, we investigated if variation in herd density, food availability, and the presence of a potential competitor, the guanaco (Lama guanicoe), was related with behavioural changes in domestic sheep in Chilean Patagonia. Focal sampling, instantaneous scan sampling, measures of bite and movement rates were used to quantify behavioural changes in domestic sheep. We found that food availability increased time spent feeding, while herd density was associated with an increase in vigilant behaviour and a decrease in bite rate, but only when food availability was low. Guanaco presence appeared to have no impact on sheep behaviour. Our results suggest that the observed behavioural changes in domestic sheep are more likely due to intraspecific competition rather than interspecific competition. Consideration of intraspecific competition where guanaco and sheep co-graze on pastures could allow management strategies to focus on herd density, according to rangeland carrying capacity.
Quantifying the Gap between Expected and Actual Rates of Antibiotic Prescribing in British Columbia, Canada
Authors: Saatchi Ariana , Yoo Ji-Won , Schwartz Kevin L. , Silverman Michael , Morris Andrew M. , Patrick David M. , McCormack James , Marra Fawziah
Published: November 2021

Despite decades of stewardship efforts to combat antimicrobial resistance and quantify changes in use, the quality of antibiotic use in British Columbia (BC) remains unknown. As the overuse and misuse of antibiotics drives antibiotic resistance, it is imperative to expand surveillance efforts to examine the quality of antibiotic prescriptions. In late 2019, Canadian expected rates of antibiotic prescribing were developed for common infections. These rates were utilized to quantify the gap between the observed rates of prescribing and Canadian expected rates for antibiotic use for the province of BC. The prescribing data were extracted and matched to physician billing systems using anonymized patient identifiers from 1 January 2000 to 31 December 2018. Outpatient prescribing was further subdivided into community and emergency department settings and stratified by the following age groups: <2 years, 2–18 years, and ≥19 years. The proportions of physician visits that received antibiotic prescription were compared against the Canadian expected rates to quantify the unnecessary use for 18 common indications. Respiratory tract infections (RTI), including acute bronchitis, acute sinusitis, and acute pharyngitis, reported significant levels of overprescribing. Across all ages and health care settings, prescribing for RTI indications occurred at rates 2–8 times higher than the expected rates recommended by a group of expert Canadian physicians. Understanding the magnitude of unnecessary prescribing is a first step in delineating the provincial prescribing quality. The quantification of antibiotic overuse offers concrete targets for provincial stewardship efforts to reduce unnecessary prescribing by an average of 30% across both outpatient and emergency care settings.
Immunomodulation and Antioxidant Activities as Possible Trypanocidal and Cardioprotective Mechanisms of Major Terpenes from Lippia alba Essential Oils in an Experimental Model of Chronic Chagas Disease
Authors: Espinel-Mesa Denerieth Ximena , González Rugeles Clara Isabel , Mantilla Hernández Julio César , Stashenko Elena E. , Villegas-Lanau Carlos Andrés , Quimbaya Ramírez John Jaime , García Sánchez Liliana Torcoroma
Published: November 2021

In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of the parasite, but are ineffective for late stage treatment and for preventing heart damage and disease progression. In vivo trypanocidal and cardioprotective activity has been reported for Lippia alba essential oils (EOs), ascribed to their two major terpenes, limonene and caryophyllene oxide. To investigate the role of antioxidant and immunomodulatory mechanisms behind these properties, chronic-T. cruzi-infected rats were treated with oral synergistic mixtures of the aforementioned EOs. For this purpose, the EOs were optimized through limonene-enrichment fractioning and by the addition of exogenous caryophyllene oxide (LIMOX) and used alone or in combined therapy with subtherapeutic doses of BNZ (LIMOXBNZ). Clinical, toxicity, inflammatory, oxidative, and parasitological (qPCR) parameters were assessed in cardiac tissue. These therapies demonstrated meaningful antioxidant and immunomodulatory activity on markers involved in CCC pathogenesis (IFN-γ, TNF-α, IL-4, IL-10, and iNOS), which could explain their significant trypanocidal properties and their noteworthy role in preventing, and even reversing, the progression of cardiac damage in chronic Chagas disease.
MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling
Authors: Chen Yung-Che , Hsu Po-Yuan , Su Mao-Chang , Chen Ting-Wen , Hsiao Chang-Chun , Chin Chien-Hung , Liou Chia-Wei , Wang Po-Wen , Wang Ting-Ya , Lin Yong-Yong , Lee Chiu-Ping , Lin Meng-Chih
Published: November 2021

The aim of this study was to identify novel microRNAs related to obstructive sleep apnea (OSA) characterized by intermittent hypoxia with re-oxygenation (IHR) injury. Illumina MiSeq was used to identify OSA-associated microRNAs, which were validated in an independent cohort. The interaction between candidate microRNA and target genes was detected in the human THP-1, HUVEC, and SH-SY5Y cell lines. Next-generation sequencing analysis identified 22 differentially expressed miRs (12 up-regulated and 10 down-regulated) in OSA patients. Enriched predicted target pathways included senescence, adherens junction, and AGE-RAGE/TNF-α/HIF-1α signaling. In the validation cohort, miR-92b-3p and miR-15b-5p gene expressions were decreased in OSA patients, and negatively correlated with an apnea hypopnea index. PTGS1 (COX1) gene expression was increased in OSA patients, especially in those with depression. Transfection with miR-15b-5p/miR-92b-3p mimic in vitro reversed IHR-induced early apoptosis, reactive oxygen species production, MAOA hyperactivity, and up-regulations of their predicted target genes, including PTGS1, ADRB1, GABRB2, GARG1, LEP, TNFSF13B, VEGFA, and CXCL5. The luciferase assay revealed the suppressed PTGS1 expression by miR-92b-3p. Down-regulated miR-15b-5p/miR-92b-3p in OSA patients could contribute to IHR-induced oxidative stress and MAOA hyperactivity through the eicosanoid inflammatory pathway via directly targeting PTGS1-NF-κB-SP1 signaling. Over-expression of the miR-15b-5p/miR-92b-3p may be a new therapeutic strategy for OSA-related depression.
Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer
Authors: Quarta Alessandra , Gaballo Antonio , Pradhan Biswajita , Patra Srimanta , Jena Mrutyunjay , Ragusa Andrea
Published: November 2021

Resveratrol is one of the most investigated polyphenols for its multiple biological activities and many beneficial effects. These are mainly related to its ability to scavenge free radicals and reduce oxidative stress. Resveratrol has also been shown to have the ability to stimulate the production of antioxidant enzymes, which interact with numerous signaling pathways involved in tumor development, and to possess side effects associated with the use of chemotherapy drugs. In this review article we summarized the main discoveries about the impact resveratrol can have in helping to prevent, as well as adjuvant treating, breast cancer. A brief overview of the primary sources of resveratrol as well as some approaches for improving its bioavailability have been also discussed.
Potential New Treatments for Knee OA: A Prospective Review of Registered Trials
Authors: Ioniţescu Marius , Vermeşan Dinu , Andor Bogdan , Dumitrascu Cristian , Al-Qatawneh Musab , Bloanca Vlad , Dumitrascu Andrei , Prejbeanu Radu
Published: November 2021

We aimed to evaluate potential new treatments for knee osteoarthritis (OA). The National Institute of Health ClinicalTrials.gov database was searched for “Osteoarthritis, Knee”. We found 565 ongoing interventional studies with a total planned enrollment of 111,276 subjects. Ongoing studies for knee OA represent a very small fraction of the registered clinical trials, but they are over a quarter of all knee trials and over two thirds of all OA studies. The most researched topic was arthroplasty, with aspects such as implant design changes, cementless fixation, robotic guidance, pain management, and fast track recovery. Intraarticular injections focused on cell therapies with mesenchymal stem cells sourced from adipose tissue, bone marrow, or umbilical cord. We could see the introduction of the first disease modifying drugs with an impact on knee OA, as well as new procedures such as geniculate artery embolization and geniculate nerve ablation.
Dual Image-Based CNN Ensemble Model for Waste Classification in Reverse Vending Machine
Authors: Yoo Taeyoung , Lee Seongjae , Kim Taehyoun
Published: November 2021

A reverse vending machine motivates citizens to bring recyclable waste by rewarding them, which is a viable solution to increase the recycling rate. Reverse vending machines generally use near-infrared sensors, barcode sensors, or cameras to classify recycling resources. However, sensor-based reverse vending machines suffer from a high configuration cost and the limited scope of target objects, and conventional single image-based reverse vending machines usually make erroneous predictions about intentional fraud objects. This paper proposes a dual image-based convolutional neural network ensemble model to address these problems. For this purpose, we first created a prototype reverse vending machine and constructed an image dataset containing two cross-sections of objects, top and front view. Then, we chose convolutional neural network models widely used in image classification as the candidates for building an accurate and lightweight ensemble model. Considering the size and classification performance of candidates, we constructed the best-fit ensemble combination and evaluated its classification performance. The final ensemble model showed a classification accuracy higher than 95% for all target classes, including fraud objects. This result proves that our approach achieves better robustness against intentional fraud objects than single image-based models and thus can broaden the scope for target resources. The measurement results on lightweight embedded platforms also demonstrated that our model provides a short inference time that is enough to facilitate the real-time execution of reverse vending machines based on low-cost edge artificial intelligence devices.
Attention to Fires: Multi-Channel Deep Learning Models for Wildfire Severity Prediction
Authors: Monaco Simone , Greco Salvatore , Farasin Alessandro , Colomba Luca , Apiletti Daniele , Garza Paolo , Cerquitelli Tania , Baralis Elena
Published: November 2021

Wildfires are one of the natural hazards that the European Union is actively monitoring through the Copernicus EMS Earth observation program which continuously releases public information related to such catastrophic events. Such occurrences are the cause of both short- and long-term damages. Thus, to limit their impact and plan the restoration process, a rapid intervention by authorities is needed, which can be enhanced by the use of satellite imagery and automatic burned area delineation methodologies, accelerating the response and the decision-making processes. In this context, we analyze the burned area severity estimation problem by exploiting a state-of-the-art deep learning framework. Experimental results compare different model architectures and loss functions on a very large real-world Sentinel2 satellite dataset. Furthermore, a novel multi-channel attention-based analysis is presented to uncover the prediction behaviour and provide model interpretability. A perturbation mechanism is applied to an attention-based DS-UNet to evaluate the contribution of different domain-driven groups of channels to the severity estimation problem.
OntoTouTra: Tourist Traceability Ontology Based on Big Data Analytics
Authors: Mendoza-Moreno Juan Francisco , Santamaria-Granados Luz , Fraga Vázquez Anabel , Ramirez-Gonzalez Gustavo
Published: November 2021

Tourist traceability is the analysis of the set of actions, procedures, and technical measures that allows us to identify and record the space–time causality of the tourist’s touring, from the beginning to the end of the chain of the tourist product. Besides, the traceability of tourists has implications for infrastructure, transport, products, marketing, the commercial viability of the industry, and the management of the destination’s social, environmental, and cultural impact. To this end, a tourist traceability system requires a knowledge base for processing elements, such as functions, objects, events, and logical connectors among them. A knowledge base provides us with information on the preparation, planning, and implementation or operation stages. In this regard, unifying tourism terminology in a traceability system is a challenge because we need a central repository that promotes standards for tourists and suppliers in forming a formal body of knowledge representation. Some studies are related to the construction of ontologies in tourism, but none focus on tourist traceability systems. For the above, we propose OntoTouTra, an ontology that uses formal specifications to represent knowledge of tourist traceability systems. This paper outlines the development of the OntoTouTra ontology and how we gathered and processed data from ubiquitous computing using Big Data analysis techniques.
Comparison between Self-Raman Nd:YVO4 Lasers and NdYVO4/KGW Raman Lasers at Lime and Orange Wavelengths
Authors: Lee Chi-Chun , Huang Chien-Yen , Huang Hao-Yun , Chen Chao-Ming , Tsou Chia-Han
Published: November 2021

The comparison of output powers between self-Raman Nd:YVO4 lasers and Nd:YVO4/KGW Raman lasers operating at lime and orange wavelengths is presented. We exploit the LBO crystal with cutting angle θ = 90° and φ = 8° for the lime wavelengths, and then we change the angle to θ = 90° and φ = 3.9° for the orange wavelengths. In self-Raman Nd:YVO4 lasers, experimental results reveal that thermal loading can impact on the output performances, especially at the high pump power. However, by using a KGW crystal as Raman medium can remarkably share the thermal loading from gain medium. Besides, the designed coating for high reflectively at the Stokes field on the surface of KGW also improved the beam quality and reduced the lasing threshold. For self-Raman Nd:YVO4 lasers, we have achieved the output powers of 6.54 W and 5.12 W at 559 nm and 588 nm, respectively. For Nd:YVO4/KGW Raman lasers, the output powers at 559 nm and 589 nm have been increased to 9.1 W and 7.54 W, respectively. All lasers operate at a quasi-CW regime with the repetition rate 50 Hz and the duty cycle 50%.
Pseudo-Invariant Feature-Based Linear Regression Model (PIF-LRM): An Effective Normalization Method to Evaluate Urbanization Impacts on Land Surface Temperature Changes
Authors: Cai Zhengwu , Fan Chao , Chen Falin , Li Xiaoma
Published: November 2021

The Landsat land surface temperature (LST) product is widely used to understand the impact of urbanization on surface temperature changes. However, directly comparing multi-temporal Landsat LST is challenging, as the observed LST might be strongly affected by climatic factors. This study validated the utility of the pseudo-invariant feature-based linear regression model (PIF-LRM) in normalizing multi-temporal Landsat LST to highlight the urbanization impact on temperature changes, based on five Landsat LST images during 2000–2018 in Changsha, China. Results showed that LST of PIFs between the reference and the target images was highly correlated, indicating high applicability of the PIF-LRM to relatively normalize LST. The PIF-LRM effectively removed the temporal variation of LST caused by climate factors and highlighted the impacts of urbanization caused land use and land cover changes. The PIF-LRM normalized LST showed stronger correlations with the time series of normalized difference of vegetation index (NDVI) than the observed LST and the LST normalized by the commonly used mean method (subtracting LST by the average, respectively for each image). The PIF-LRM uncovered the spatially heterogeneous responses of LST to urban expansion. For example, LST decreased in the urban center (the already developed regions) and increased in the urbanizing regions. PIF-LRM is highly recommended to normalize multi-temporal Landsat LST to understand the impact of urbanization on surface temperature changes from a temporal point of view.
Asymmetric Differences in the Effects of Average Air Temperature and Solar Radiation on Early Rice and Late Rice Yield
Authors: Wei Shengbao , Peng Anchun , Liu Jing , Wei Dongxian , Chen Changqing
Published: November 2021

China is the world’s largest rice producer. Thus, the stability of rice production plays a decisive role in food security. Among the types of rice, double rice (including early rice and late rice) accounts for the largest proportion of rice in China. Climate change is widely expected to affect rice yields. Studying the response of double rice yield to climate change will benefit strategic decisions related to future crop adaptation. In this paper, the relationship between climate factors and the yield of double rice during 1992–2013 in south China was analysed to determine the responses of double rice yield to climate change. The results showed that the daily average air temperature during the early rice and late rice growing seasons increased by 0.34 °C and 0.68 °C, 0.29 °C and 0.67 °C, and 0.11 °C and 0.31 °C per 10-year period in the northern subtropical zone (NST), middle subtropical zone (MST) and south subtropical zone (SST), respectively, in the last 20 years. The change trend in solar radiation was not obvious, but it fluctuated greatly. A 1 °C increase in average air temperatures decreased early rice yield by 5.36% and 2.16% in SST and MST, respectively; decreased late rice yield by 0.75% and 1.43% in MST and NST, respectively; and increased late rice yield by 3.93% in SST. A solar radiation increases of 100 MJ m−2 increased early rice yield by 1.02%, 1.54% and 1.71% in SST, MST and NST, respectively, and decreased late rice yield by 0.89% in SST. We found that annual average temperatures of 17.3 °C and 18.6 °C were the early rice and late rice yield variation thresholds, respectively; in addition, above the background temperature in south China, the early rice yield will decrease and the late rice yield will increase.
Total Cross Sections for Electron and Positron Scattering on Molecules: In Search of the Dispersion Relation
Authors: Carelli Fabio , Fedus Kamil , Karwasz Grzegorz
Published: November 2021

More than one hundred years of experimental and theoretical investigations of electron scattering in gases delivered cross-sections in a wide energy range, from few meV to keV. An analogy in optics, characterizing different materials, comes under the name of the dispersion relation, i.e., of the dependence of the refraction index on the light wavelength. The dispersion relation for electron (and positron) scattering was hypothesized in the 1970s, but without clear results. Here, we review experimental, theoretical, and semi-empirical cross-sections for N2, CO2, CH4, and CF4 in search of any hint for such a relation—unfortunately, without satisfactory conclusions.
Effects of Salinity on Physiological, Biochemical and Gene Expression Parameters of Black Tiger Shrimp (Penaeus monodon): Potential for Farming in Low-Salinity Environments
Authors: Rahi Md. Lifat , Azad Khairun Naher , Tabassum Maliha , Irin Hasna Hena , Hossain Kazi Sabbir , Aziz Dania , Moshtaghi Azam , Hurwood David A
Published: November 2021

Salinity is one of the most important abiotic factors affecting growth, metabolism, immunity and survival of aquatic species in farming environments. As a euryhaline species, the black tiger shrimp (Penaeus monodon) can tolerate a wide range of salinity levels and is farmed between brackish to marine water conditions. The current study tested the effects of six different salinity levels (0‰, 2.5‰, 5‰, 10‰, 20‰ and 30‰) on the selected physiological, biochemical and genetic markers (individual changes in the expression pattern of selected candidate genes) in the black tiger shrimp. Experimental salinity levels significantly affected growth and survival performance (p < 0.05); the highest levels of growth and survival performance were observed at the control (20‰) salinity. Salinity reductions significantly increased free fatty acid (FFA), but reduced free amino acid (FAA) levels. Lower salinity treatments (0–10‰) significantly reduced hemolymph osmolality levels while 30‰ significantly increased osmolality levels. The five different salinity treatments increased the expression of osmoregulatory and hemolymph regulatory genes by 1.2–8-fold. In contrast, 1.2–1.6-fold lower expression levels were observed at the five salinity treatments for growth (alpha amylase) and immunity (toll-like receptor) genes. O2 consumption, glucose and serotonin levels, and expression of osmoregulatory genes showed rapid increase initially with salinity change, followed by reducing trend and stable patterns from the 5th day to the end. Hemocyte counts, expression of growth and immunity related genes showed initial decreasing trends, followed by an increasing trend and finally stability from 20th day to the end. Results indicate the farming potential of P. monodon at low salinity environments (possibly at freshwater) by proper acclimation prior to stocking with minimal effects on production performance.
Counting on COVID-19 Vaccine: Insights into the Current Strategies, Progress and Future Challenges
Authors: Kandimalla Ramesh , Chakraborty Pratik , Vallamkondu Jayalakshmi , Chaudhary Anupama , Samanta Sonalinandini , Reddy P. Hemachandra , De Feo Vincenzo , Dewanjee Saikat
Published: November 2021

The emergence of a novel coronavirus viz., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 and its subsequent substantial spread produced the coronavirus disease 2019 (COVID-19) pandemic worldwide. Given its unprecedented infectivity and pathogenicity, the COVID-19 pandemic had a devastating impact on human health, and its clinical management has been a great challenge, which has led to the development and speedy trials of several vaccine candidates against SARS-CoV-2 at an exceptional pace. As a result, several COVID-19 vaccines were made commercially available in the first half of 2021. Although several COVID-19 vaccines showed promising results, crucial insights into their epidemiology, protective mechanisms, and the propensities of reinfection are not largely reviewed. In the present report, we provided insights into the prospects of vaccination against COVID-19 and assessed diverse vaccination strategies including DNA, mRNA, protein subunits, vector-based, live attenuated, and inactivated whole/viral particle-based vaccines. Next, we reviewed major aspects of various available vaccines approved by the World Health Organization and by the local administrations to use against COVID-19. Moreover, we comprehensively assessed the success of these approved vaccines and also their untoward effects, including the possibility of reinfection. We also provided an update on the vaccines that are under development and could be promising candidates in the future. Conclusively, we provided insights into the COVID-19 vaccine epidemiology, their potency, and propensity for SARS-CoV-2 reinfection, while a careful review of their current status, strategies, success, and future challenges was also presented.
Origins and Function of VL30 lncRNA Packaging in Small Extracellular Vesicles: Implications for Cellular Physiology and Pathology
Authors: Mantziou Stefania , Markopoulos Georgios S.
Published: November 2021

Long non-coding RNAs (lncRNAs) have emerged during the post-genomic era as significant epigenetic regulators. Viral-like 30 elements (VL30s) are a family of mouse retrotransposons that are transcribed into functional lncRNAs. Recent data suggest that VL30 RNAs are efficiently packaged in small extracellular vesicles (SEVs) through an SEV enrichment sequence. We analysed VL30 elements for the presence of the distinct 26 nt SEV enrichment motif and found that SEV enrichment is an inherent hallmark of the VL30 family, contained in 36 full-length elements, with a widespread chromosomal distribution. Among them, 25 elements represent active, present-day integrations and contain an abundance of regulatory sequences. Phylogenetic analysis revealed a recent spread of SEV-VL30s from 4.4 million years ago till today. Importantly, 39 elements contain an SFPQ-binding motif, associated with the transcriptional induction of oncogenes. Most SEV-VL30s reside in transcriptionally active regions, as characterised by their distribution adjacent to candidate cis-regulatory elements (cCREs). Network analysis of SEV-VL30-associated genes suggests a distinct transcriptional footprint associated with embryonal abnormalities and neoplasia. Given the established role of VL30s in oncogenesis, we conclude that their potential to spread through SEVs represents a novel mechanism for non-coding RNA biology with numerous implications for cellular homeostasis and disease.
Somatostatin and Its Receptor System in Colorectal Cancer
Authors: Kasprzak Aldona
Published: November 2021

Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal enteroendocrine cells (EECs) restricted to the mucosa, and neurons of the submucosal and myenteric plexuses. The action of the SRIF system is based on the inhibition of endocrine and exocrine secretion, as well as the proliferative responses of target cells. The SST1–5 share common signaling pathways, and are not only widely expressed on normal tissues, but also frequently overexpressed by several tumors, particularly neuroendocrine neoplasms (NENs). Furthermore, the SRIF system represents the only peptide/G protein-coupled receptor (GPCR) system with multiple approved clinical applications for the diagnosis and treatment of several NENs. The role of the SRIF system in the histogenesis of colorectal cancer (CRC) subtypes (e.g., adenocarcinoma and signet ring-cell carcinoma), as well as diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC) and pure adenocarcinoma, is poorly understood. Moreover, the impact of the SRIF system signaling on CRC cell proliferation and its potential role in the progression of this cancer remains unknown. Therefore, this review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in CRC, aiming to evaluate the potential role of its components in CRC histogenesis, diagnosis, and potential therapy.
Sustainability Identification of Steel and Concrete Construction Frames with Respect to Triple Bottom Line
Authors: Oladazimi Amir , Mansour Saeed , Hosseinijou Seyed , Majdfaghihi Mohammad
Published: November 2021

As one of the most prominent industries in developed and developing countries, the construction industry has had substantial impacts on different aspects of the environment, society, and economy. In recent years, sustainable construction has been introduced as an approach to evaluate the various construction phases based on environmental, economic, and social dimensions, also known as the triple bottom line (TBL). To conduct a sustainability analysis of the buildings in Tehran, the capital city of Iran, two conventional construction frames were selected, namely steel frame and concrete frame. In this research, three conventional approaches for the evaluation of the TBL, namely the life cycle assessment (LCA), life cycle cost (LCC), and social life cycle assessment (SLCA), were, respectively, used for the study of environmental, economic, and social impacts. The main results of the study are summarized as the following: Overall, based on the LCA results, the concrete frame led to almost 38% more environmental pollution than steel frame. In terms of the total prices of the buildings, considering their LCC and with respect to the present value (PV) method, the steel frame was almost 152,000 USD more expensive than the concrete frame. The quantified results of the social dimension by the SLCA method showed that concrete and steel buildings had a score of 0.199 and 0.189, respectively, which indicates that concrete had a slightly better social performance based on expert opinions. A multi-criteria assessment and sensitivity analysis of the results were conducted by a graphical tool, namely the mixing triangle, and showed that the overall preference of each alternative depends mainly on the importance weights given to each aspect of the assessment. However, one of the main findings of the research was that overall, giving a high importance weight to environmental dimension leads to sustainability preference of steel over concrete frame, while giving high importance weights to economic or social dimensions leads to sustainability preference of concrete over steel frame. Findings of the study are beneficial to decision-makers in the construction industry since they can decide on the best alternative among concrete and steel frames based on their strategies.
Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides
Authors: Di Raimondo Cosimo , Han Zhen , Su Chingyu , Wu Xiwei , Qin Hanjun , Sanchez James F. , Yuan Yate-Ching , Martinez Xochiquetzal , Abdulla Farah , Zain Jasmine , Chen Chun-Wei , Rosen Steven T. , Querfeld Christiane
Published: November 2021

Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20–50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcriptional regulation of LCT-MF. Here, we investigated the miR and mRNA expression profile in lesional skin samples of patients with LCT-MF and non-LCT MF using RNA-seq analysis. We found miR-146a and miR-21 to be significantly upregulated, and miR-708 the most significantly downregulated miR in LCT-MF. Integration of miR and mRNA expression profiles revealed the miR-regulated networks in LCT-MF. Ingenuity pathway analysis (IPA) demonstrated the involvement of genes for ICOS-ICOSL, PD1-PDL1, NF-κB, E2F transcription, and molecular mechanisms of cancer signaling pathways. Quantitative real time (qRT)-PCR results of target genes were consistent with the RNA-seq data. We further identified the immunosuppressive tumor microenvironment (TME) in LCT-MF. Moreover, our data indicated that miR-146a, -21 and -708 are associated with the immunosuppressive TME in LCT-MF. Collectively, our results suggest that the key LCT-MF associated miRs and their regulated networks may provide insights into its pathogenesis and identify promising targets for novel therapeutic strategies.
MAPK Inhibition Requires Active RAC1 Signaling to Effectively Improve Iodide Uptake by Thyroid Follicular Cells
Authors: Faria Márcia , Domingues Rita , Bugalho Maria João , Matos Paulo , Silva Ana Luísa
Published: November 2021

The Sodium/Iodide Symporter (NIS) is responsible for the active transport of iodide into thyroid follicular cells. Differentiated thyroid carcinomas (DTCs) usually preserve the functional expression of NIS, allowing the use of radioactive iodine (RAI) as the treatment of choice for metastatic disease. However, a significant proportion of patients with advanced forms of TC become refractory to RAI therapy and no effective therapeutic alternatives are available. Impaired iodide uptake is mainly caused by the defective functional expression of NIS, and this has been associated with several pathways linked to malignant transformation. MAPK signaling has emerged as one of the main pathways implicated in thyroid tumorigenesis, and its overactivation has been associated with the downregulation of NIS expression. Thus, several strategies have been developed to target the MAPK pathway attempting to increase iodide uptake in refractory DTC. However, MAPK inhibitors have had only partial success in restoring NIS expression and, in most cases, it remained insufficient to allow effective treatment with RAI. In a previous work, we have shown that the activity of the small GTPase RAC1 has a positive impact on TSH-induced NIS expression and iodide uptake in thyroid cells. RAC1 is a downstream effector of NRAS, but not of BRAF. Therefore, we hypothesized that the positive regulation induced by RAC1 on NIS could be a relevant signaling cue in the mechanism underlying the differential response to MEK inhibitors, observed between NRAS- and BRAF-mutant tumors. In the present study, we found that the recovery of NIS expression induced through MAPK pathway inhibition can be enhanced by potentiating RAC1 activity in thyroid cell systems. The negative impact on NIS expression induced by the MAPK-activating alterations, NRAS Q61R and BRAF V600E, was partially reversed by the presence of the MEK 1/2 inhibitors AZD6244 and CH5126766. Notably, the inhibition of RAC1 signaling partially blocked the positive impact of MEK inhibition on NIS expression in NRAS Q61R cells. Conversely, the presence of active RAC1 considerably improved the rescue of NIS expression in BRAF V600E thyroid cells treated with MEK inhibitors. Overall, our data support an important role for RAC1 signaling in enhancing MAPK inhibition in the context of RAI therapy in DTC, opening new opportunities for therapeutic intervention.
Beyond the Usual Suspects: Hepatitis E Virus and Its Implications in Hepatocellular Carcinoma
Authors: Klöhn Mara , Schrader Jil Alexandra , Brüggemann Yannick , Todt Daniel , Steinmann Eike
Published: November 2021

Hepatitis E virus infections are the leading cause of viral hepatitis in humans, contributing to an estimated 3.3 million symptomatic cases and almost 44,000 deaths annually. Recently, HEV infections have been found to result in chronic liver infection and cirrhosis in severely immunocompromised patients, suggesting the possibility of HEV-induced hepatocarcinogenesis. While HEV-associated formation of HCC has rarely been reported, the expansion of HEV’s clinical spectrum and the increasing evidence of chronic HEV infections raise questions about the connection between HEV and HCC. The present review summarizes current clinical evidence of the relationship between HEV and HCC and discusses mechanisms of virus-induced HCC development with regard to HEV pathogenesis. We further elucidate why the development of HEV-induced hepatocellular carcinoma has so rarely been observed and provide an outlook on possible experimental set-ups to study the relationship between HEV and HCC formation.
Synergistic Anti-Tumor Effect of Simvastatin Combined to Chemotherapy in Osteosarcoma
Authors: Mangelinck Adèle , Habel Nadia , Mohr Audrey , Gaspar Nathalie , Stefanovska Bojana , Fromigué Olivia
Published: November 2021

Context: Osteosarcoma is the most common primary solid malignancy of the bone, mainly affecting pediatric patients. The main clinical issues are chemoresistance and metastatic spread, leading to a survival rate stagnating around 60% for four decades. Purpose: Here, we investigated the effect of simvastatin as adjuvant therapy on chemotherapy. Methods: Cell viability was assessed by the MTT test, and a combination index was evaluated by an isobologram approach. Cell motility was assessed by wound-healing assay. Cell-derived xenograft models were established in mice. FFPE tumor samples were assessed by immunohistochemistry. Results: In vitro experiments indicate that simvastatin synergized the conventional chemotherapy drugs’ inhibitory effect on cell viability. Functional assays reveal that simvastatin supplementation favored the anticancer mechanism of action of the tested chemotherapy drugs, such as DNA damage through intercalation or direct alkylation and disorganization of microtubules. Additionally, we show that even though simvastatin alone did not modify tumor behavior, it potentiated the inhibitory effect of doxorubicin on primary tumor growth (+50%, p < 0.05) and metastatic spread (+50%, p < 0.05). Our results provide evidence that simvastatin exerted an anti-tumor effect combined with chemotherapy in the preclinical murine model and represents valuable alternative adjuvant therapy that needs further investigation in clinical trials.
Revisiting Gas to Solids Ratio for Activated Sludge Clarification by Electrolytic Hydrogen Bubbles: Theoretical and Experimental Evaluations
Authors: Kim Jiseon , Chung Chong Min , Cho Kangwoo , Chung Tai Hak
Published: November 2021

Molecular hydrogen (H2), as the green energy carrier from water electrolysis, can be utilized for separation of suspended micro-particles as electroflotation (EF). This study provides practical guidelines for the gas to solids (G/S) ratio as the governing parameter in EF, based on theoretical estimations and experiments for clarification of activated sludge. The G/S ratio in EF was controlled linearly by current density (j), under quasi-consistent current efficiency (at j > 8 mA/cm2) for H2 (~1) and O2 (~0.4) bubble generations on Ti cathode and IrTaOx anode, respectively. Based on the measured sizes of bubbles (approximated to 35 µm) and biological flocs (discretized to mean sizes of 22.5, 40, 60, 135, and 150 µm), batch flotation experiments estimated the maximum collision-attachment efficiency of 0.057. The rise velocities of floc-bubble aggregate were computed to derive the limiting G/S ratio to overcome the given influent hydraulic loading. Consequently, the estimates (5.23 × 10−4 and 5.92 × 10−4 at hydraulic loading of 0.87 and 1.73 cm/min, respectively) were compatible with the continuous EF experiments.
Treatable Traits in Chronic Respiratory Disease: A Comprehensive Review
Authors: Lee Yong Qin , Selvakumar Asvin , See Kay Choong
Published: November 2021

Chronic respiratory diseases are major contributors to the global burden of disease. While understanding of these diseases has improved, treatment guidelines have continued to rely on severity and exacerbation-based approaches. A new personalised approach, termed the “treatable traits” approach, has been suggested to address the limitations of the existing treatment strategies. We aim to systematically review the current evidence regarding treatable traits in chronic respiratory diseases and to identify gaps in the current literature. We searched the PubMed and Embase databases and included studies on treatable traits and chronic respiratory diseases. We then extracted information on prevalence, prognostic implications, treatment options and benefits from these studies. A total of 58 papers was included for review. The traits identified were grouped into five broad themes: physiological, biochemical, psychosocial, microbiological, and comorbidity traits. Studies have shown advantages of the treatable traits paradigm in the clinical setting. However, few randomised controlled trials have been conducted. Findings from our review suggest that multidisciplinary management with therapies targeted at treatable traits has the potential to be efficacious when added to the best practices currently implemented. This paradigm has the potential to improve the holistic care of chronic respiratory diseases.
Treatment Considerations for Obstructive Sleep Apnea in Pediatric Down Syndrome
Authors: Gastelum Erica , Cummins Marcus , Singh Amitoj , Montoya Michael , Urbano Gino , Tablizo Mary
Published: November 2021

Children with Down syndrome (DS) are at high risk for developing obstructive sleep apnea (OSA) compared to children without DS. The negative impact of OSA on health, behavior, and cognitive development in children with DS highlights the importance of timely and effective treatment. Due to the higher prevalence of craniofacial and airway abnormalities, obesity, and hypotonia in patients with DS, residual OSA can still occur after exhausting first-line options. While treatment commonly includes adenotonsillectomy (AT) and continuous positive airway pressure (CPAP) therapy, additional therapy such as medical management and/or adjuvant surgical procedures need to be considered in refractory OSA. Given the significant comorbidities secondary to untreated OSA in children with DS, such as cardiovascular and neurobehavioral consequences, more robust randomized trials in this patient population are needed to produce treatment guidelines separate from those for the general pediatric population of otherwise healthy children with OSA. Further studies are also needed to look at desensitization and optimization of CPAP use in patients with DS and OSA.
Pediatric and Adult Low-Grade Gliomas: Where Do the Differences Lie?
Authors: Greuter Ladina , Guzman Raphael , Soleman Jehuda
Published: November 2021

Two thirds of pediatric gliomas are classified as low-grade (LGG), while in adults only around 20% of gliomas are low-grade. However, these tumors do not only differ in their incidence but also in their location, behavior and, subsequently, treatment. Pediatric LGG constitute 65% of pilocytic astrocytomas, while in adults the most commonly found histology is diffuse low-grade glioma (WHO II), which mostly occurs in eloquent regions of the brain, while its pediatric counterpart is frequently found in the infratentorial compartment. The different tumor locations require different skillsets from neurosurgeons. In adult LGG, a common practice is awake surgery, which is rarely performed on children. On the other hand, pediatric neurosurgeons are more commonly confronted with infratentorial tumors causing hydrocephalus, which more often require endoscopic or shunt procedures to restore the cerebrospinal fluid flow. In adult and pediatric LGG surgery, gross total excision is the primary treatment strategy. Only tumor recurrences or progression warrant adjuvant therapy with either chemo- or radiotherapy. In pediatric LGG, MEK inhibitors have shown promising initial results in treating recurrent LGG and several ongoing trials are investigating their role and safety. Moreover, predisposition syndromes, such as neurofibromatosis or tuberous sclerosis complex, can increase the risk of developing LGG in children, while in adults, usually no tumor growth in these syndromes is observed. In this review, we discuss and compare the differences between pediatric and adult LGG, emphasizing that pediatric LGG should not be approached and managed in the same way as adult LCG.
Effects of Live Music Therapy on Autonomic Stability in Preterm Infants: A Cluster-Randomized Controlled Trial
Authors: Yakobson Dana , Gold Christian , Beck Bolette Daniels , Elefant Cochavit , Bauer-Rusek Sofia , Arnon Shmuel
Published: November 2021

Unbuffered stress levels may negatively influence preterm-infants’ autonomic nervous system (ANS) maturation, thus affecting neurobehavior and psycho-emotional development. Music therapy (MT) is an evidence-based treatment modality in neonatal care. When coupled with skin-to-skin care (SSC), it may reduce stress responses in both preterm infants and their parents and enhance family-centered care. Accordingly, we aimed to compare the effects of combined MT and SSC and SSC alone on ANS stabilization in preterm infants. In a single-center, cluster-randomized trial design, ten two-month time-clusters were randomized to either combined MT and SSC or SSC alone. Families of preterm infants were offered two sessions of the allocated condition in the NICU, and a three-month follow up session at home. The primary outcome variable was stabilization of the ANS, defined by change in the high frequency (HF) power of heart rate variability (HRV) during the second session. Secondary outcomes included other HRV measures, parent–infant attachment, and parental anxiety at each session. Sixty-eight families were included. MT combined with SSC improved infants’ ANS stability, as indicated by a greater increase in HF power during MT compared to SSC alone (mean difference 5.19 m2/Hz, SE = 1.27, p < 0.001) (95% confidence interval 0.87 to 2.05). Most secondary outcomes were not significantly different between the study groups. MT contributes to preterm-infants’ autonomic stability, thus laying an important foundation for neuro-behavioral and psycho-emotional development. Studies evaluating longer-term effects of MT on preterm infants’ development are warranted.