bluuebunny/crossref_metadata_2025 huggingface dataset:
The Intestinal Biofilm of Pseudomonas aeruginosa and Staphylococcus aureus Is Inhibited by Antimicrobial Peptides HBD-2 and HBD-3
Authors: Fusco Alessandra , Savio Vittoria , Stelitano Debora , Baroni Adone , Donnarumma Giovanna
Published: July 2021

Background: The intestinal microbiota is a very active microbial community interacting with the host in maintaining homeostasis; it acts in cooperation with intestinal epithelial cells, which protect the host from the external environment by producing a diverse arsenal of antimicrobial peptides (AMPs), including β-defensins-2 and 3 (HBD-2 and HBD-3), considered among the most studied in this category. However, there are some circumstances in which an alteration of this eubiotic state occurs, with the triggering of dysbiosis. In this condition, the microbiota loses its protective power, leading to the onset of opportunistic infections. In this scenario, the emergence of multi-drug resistant biofilms from Pseudomonas aeruginosa and Staphylococcus aureus is very frequent. Methods: We created a Caco-2 intestinal epithelial cell line stably transfected with the genes, encoding HBD-2 and HBD-3, in order to evaluate their ability to inhibit the intestinal biofilm formation of P. aeruginosa and S. aureus. Results: Both HBD-2 and HBD-3 showed anti-biofilm activity against P. aeruginosa and S. aureus. Conclusions: The exploitation of endogenous antimicrobial peptides as a new anti-biofilm therapy, in isolation or in combination with conventional antibiotics, can be an interesting prospect in the treatment of chronic and multi-drug resistant infections.
Host–Guest Inclusion Complexes of Essential Oils with Strong Antibacterial and Antifungal Features in Beta-Cyclodextrin for Solid-State Pharmaceutical Applications
Authors: Arrais Aldo , Manzoni Marta , Cattaneo Alessia , Gianotti Valentina , Massa Nadia , Novello Giorgia , Caramaschi Alice , Gamalero Elisa , Bona Elisa
Published: July 2021

Essential oils are widely recognized as natural alternatives to pharmaceutical antibacterial and antifungal agents. With respect to standard pharmaceutics, the advantages of essential oils are their (i) low production costs, (ii) lack of chemical and biochemical drawbacks that are intrinsic to the synthetic production process and (iii) good tolerance by humans. On the other hand, the liquid nature of essential oils poses concerns about their actual application in different therapeutic issues regarding their persistence and the ability to control or prolong drug release. In this study, two essential oils from oregano and winter savory showing antibacterial and antifungal features were complexed in a solid state with beta-cyclodextrin. Host–guest inclusion complexes were characterized using FT-IR spectroscopy, ESI-MS and GC-MS techniques. Manyfold terpenic and non-terpenic components of the oils could be observed and unambiguously identified as being included inside the carbohydrate hosts. Many of them provided a specific biocidal action. Indeed, essential oil host–guest inclusion products were tested against two Candida species and an S. aureus reference strain, showing that the oils effectively maintained their liquid performances. Solid-state tablets of the essential oil inclusion complexes embedded in polyvinylpyrrolidone could be obtained. These results pave the way for the solid-state application of essential oils in antibacterial and antifungal pharmaceutical treatments.
Effects of Workers Exposure to Nanoparticles Studied by NMR Metabolomics
Authors: Horník Štěpán , Michálková Lenka , Sýkora Jan , Ždímal Vladimír , Vlčková Štěpánka , Dvořáčková Štěpánka , Pelclová Daniela
Published: July 2021

In this study, the effects of occupational exposure to nanoparticles (NPs) were studied by NMR metabolomics. Exhaled breath condensate (EBC) and blood plasma samples were obtained from a research nanoparticles-processing unit at a national research university. The samples were taken from three groups of subjects: samples from workers exposed to nanoparticles collected before and after shift, and from controls not exposed to NPs. Altogether, 60 1H NMR spectra of exhaled breath condensate (EBC) samples and 60 1H NMR spectra of blood plasma samples were analysed, 20 in each group. The metabolites identified together with binning data were subjected to multivariate statistical analysis, which provided clear discrimination of the groups studied. Statistically significant metabolites responsible for group separation served as a foundation for analysis of impaired metabolic pathways. It was found that the acute effect of NPs exposure is mainly reflected in the pathways related to the production of antioxidants and other protective species, while the chronic effect is manifested mainly in the alteration of glutamine and glutamate metabolism, and the purine metabolism pathway.
Method for Calculating of Lightning Impact Level on Overhead Transmission Line
Authors: Burtsev Anton Vladimirovich , Selivanov Vasily Nikolaevich
Published: July 2021

This paper proposes a simple method for calculating the lightning impact level on overhead transmission power lines, taking into account its entire length. The method uses lightning historical data and the geographic coordinates of power line towers. It is based on calculating the distances between both arrays of lightning and of towers. The method has been tested on overhead lines in the Murmansk region of the Russian Federation and can be applied to any overhead line if a lightning dataset in the overhead line area is available. This study is useful for electric power suppliers because it provides valuable information about the most lightning-prone sections of overhead power lines. The method can also be beneficial to people selecting the optimal route (least amount of lightning strikes) for power transmission lines based on lightning density.
Two-Pass Technique for Clone Detection and Type Classification Using Tree-Based Convolution Neural Network
Authors: Jo Young-Bin , Lee Jihyun , Yoo Cheol-Jung
Published: July 2021

Appropriate reliance on code clones significantly reduces development costs and hastens the development process. Reckless cloning, in contrast, reduces code quality and ultimately adds costs and time. To avoid this scenario, many researchers have proposed methods for clone detection and refactoring. The developed techniques, however, are only reliably capable of detecting clones that are either entirely identical or that only use modified identifiers, and do not provide clone-type information. This paper proposes a two-pass clone classification technique that uses a tree-based convolution neural network (TBCNN) to detect multiple clone types, including clones that are not wholly identical or to which only small changes have been made, and automatically classify them by type. Our method was validated with BigCloneBench, a well-known and wildly used dataset of cloned code. Our experimental results validate that our technique detected clones with an average rate of 96% recall and precision, and classified clones with an average rate of 78% recall and precision.
Diagnosis of Obstructive Sleep Apnea from ECG Signals Using Machine Learning and Deep Learning Classifiers
Authors: Sheta Alaa , Turabieh Hamza , Thaher Thaer , Too Jingwei , Mafarja Majdi , Hossain Md Shafaeat , Surani Salim R.
Published: July 2021

Obstructive sleep apnea (OSA) is a well-known sleep ailment. OSA mostly occurs due to the shortage of oxygen for the human body, which causes several symptoms (i.e., low concentration, daytime sleepiness, and irritability). Discovering the existence of OSA at an early stage can save lives and reduce the cost of treatment. The computer-aided diagnosis (CAD) system can quickly detect OSA by examining the electrocardiogram (ECG) signals. Over-serving ECG using a visual procedure is challenging for physicians, time-consuming, expensive, and subjective. In general, automated detection of the ECG signal’s arrhythmia is a complex task due to the complexity of the data quantity and clinical content. Moreover, ECG signals are usually affected by noise (i.e., patient movement and disturbances generated by electric devices or infrastructure), which reduces the quality of the collected data. Machine learning (ML) and Deep Learning (DL) gain a higher interest in health care systems due to its ability of achieving an excellent performance compared to traditional classifiers. We propose a CAD system to diagnose apnea events based on ECG in an automated way in this work. The proposed system follows the following steps: (1) remove noise from the ECG signal using a Notch filter. (2) extract nine features from the ECG signal (3) use thirteen ML and four types of DL models for the diagnosis of sleep apnea. The experimental results show that our proposed approach offers a good performance of DL classifiers to detect OSA. The proposed model achieves an accuracy of 86.25% in the validation stage.
Day-Ahead Residential Electricity Demand Response Model Based on Deep Neural Networks for Peak Demand Reduction in the Jordanian Power Sector
Authors: Shaqour Ayas , Farzaneh Hooman , Almogdady Huthaifa
Published: July 2021

In this paper, a comprehensive demand response model for the residential sector in the Jordanian electricity market is introduced, considering the interaction between the power generators (PGs), grid operators (GOs), and service providers (SPs). An accurate day-ahead hourly short-term load forecasting is conducted, using deep neural networks (DNNs) trained on four-year data collected from the National Electric Power Company (NEPCO) in Jordan. The customer behavior is modeled by developing a precise price elasticity matrix of demand (PEMD) based on recent research on the short-term price elasticity of Jordan’s residential and the analysis of the different types of electrical appliances and their daily operational hours according to the latest surveys. First, the DNNs are fine-tuned with a detailed feature analysis to predict the day-ahead hourly electrical demand and achieved a mean absolute percentage error (MAPE) of 1.365% and 1.411% on the validation and test datasets receptively. Then the predictions are used as input to a detailed model of the Jordanian power grid market, where a day-ahead peak-time demand response policy for the residential sector is applied to the three distribution power companies in Jordan. Based on different PEMD analyses for the Jordanian residential sector, the results suggest a reduction potential of 5.4% in peak demand accompanied by a cost reduction of USD 154,505 per day for the Jordanian power sector.
Sensitivity of Simulations of Extreme Mediterranean Storms to the Specification of Sea Surface Temperature: Comparison of Cases of a Tropical-Like Cyclone and Explosive Cyclogenesis
Authors: Hagay Omer , Brenner Steve
Published: July 2021

Local air-sea interaction over the Mediterranean may amplify the effects of climate change. This study investigates the sensitivity of simulations of two different high impact weather events to changes in the specification of sea surface temperature (SST) using a regional atmospheric model. First we assess the impact of specifying SST from two reanalysis data sets with differing spatial resolution. The simulated tropical-like cyclone (TLC) is slightly stronger in the case of the lower resolution SST which is warmer over the formation region, most notably in the maximum rainfall which is ~7% higher. The differences in the two explosive cyclone simulations are negligible, most likely due to intensification occurring mainly over land. We then test the sensitivity of the storms to a range of SST anomalies. The TLC showed a clear trend of increasing storm intensity as SST rises. These results suggest that SST plays a direct role in determining the intensity of the storm. For the explosive cyclone there is no clear trend in dynamical intensity except for the highest warming anomalies. However, the rainfall increases with the magnitude of the SST anomaly. Our results suggest that extreme weather events over the Mediterranean will become more extreme if SST increases as the climate warms, assuming that upper air conditions do not change.
Role of Persistent Organic Pollutants in Breast Cancer Progression and Identification of Estrogen Receptor Alpha Inhibitors Using In-Silico Mining and Drug-Drug Interaction Network Approaches
Authors: Zainab Bibi , Ayaz Zainab , Rashid Umer , Al Farraj Dunia A. , Alkufeidy Roua M. , AlQahtany Fatmah S. , Aljowaie Reem M. , Abbasi Arshad Mehmood
Published: July 2021

The strong association between POPs and breast cancer in humans has been suggested in various epidemiological studies. However, the interaction of POPs with the ERα protein of breast cancer, and identification of natural and synthetic compounds to inhibit this interaction, is mysterious yet. Consequently, the present study aimed to explore the interaction between POPs and ERα using the molecular operating environment (MOE) tool and to identify natural and synthetic compounds to inhibit this association through a cluster-based approach. To validate whether our approach could distinguish between active and inactive compounds, a virtual screen (VS) was performed using actives (627 compounds) as positive control and decoys (20,818 compounds) as a negative dataset obtained from DUD-E. Comparatively, short-chain chlorinated paraffins (SCCPs), hexabromocyclododecane (HBCD), and perfluorooctanesulfonyl fluoride (PFOSF) depicted strong interactions with the ERα protein based on the lowest-scoring values of −31.946, −18.916, −17.581 kcal/mol, respectively. Out of 7856 retrieved natural and synthetic compounds, sixty were selected on modularity bases and subsequently docked with ERα. Based on the lowest-scoring values, ZINC08441573, ZINC00664754, ZINC00702695, ZINC00627464, and ZINC08440501 (synthetic compounds), and capsaicin, flavopiridol tectorgenin, and ellagic acid (natural compounds) showed incredible interactions with the active sites of ERα, even more convening and resilient than standard breast cancer drugs Tamoxifen, Arimidex and Letrozole. Our findings confirm the role of POPs in breast cancer progression and suggest that natural and synthetic compounds with high binding affinity could be more efficient and appropriate candidates to treat breast cancer after validation through in vitro and in vivo studies.
Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays
Authors: Perrella Fulvio , Coppola Federico , Petrone Alessio , Platella Chiara , Montesarchio Daniela , Stringaro Annarita , Ravagnan Giampietro , Fuggetta Maria Pia , Rega Nadia , Musumeci Domenica
Published: July 2021

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)—two natural stilbene polyphenols with manifold, well known biological activities—with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.
Exploration of the Activation Mechanism of the Epigenetic Regulator MLL3: A QM/MM Study
Authors: Miranda-Rojas Sebastián , Blanco-Esperguez Kevin , Tuñón Iñaki , Kästner Johannes , Mendizábal Fernando
Published: July 2021

The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new insights into the deprotonation process and the role of the catalytic machinery in the methyl-transfer reaction. Our finding suggests that the source of the activation mechanism comes from conformational restriction mediated by the formation of a network of salt-bridges between MLL3 and one of the activating subunits, which restricts and stabilizes the positioning of several residues relevant for the catalysis. New insights into the deprotonation mechanism of lysine are provided, identifying a valine residue as crucial in the positioning of the water molecule in charge of the process. Finally, a tyrosine residue was found to assist the methyl transfer from SAM to the target lysine.
Suppression of Inflammation-Associated Kidney Damage Post-Transplant Using the New PrC-210 Free Radical Scavenger in Rats
Authors: Goesch Torsten R. , Wilson Nancy A. , Zeng Weifeng , Verhoven Bret M. , Zhong Weixiong , Coumbe Gitter Maya M. , Fahl William E.
Published: July 2021

Allograft kidney transplantation, which triggers host cellular- and antibody-mediated rejection of the kidney, is a major contributor to kidney damage during transplant. Here, we asked whether PrC-210 would suppress damage seen in allograft kidney transplant. Brown Norway (BN) rat kidneys were perfused in situ (UW Solution) with or without added 30 mM PrC-210, and then immediately transplanted into Lewis (LEW) rats. 20 h later, the transplanted BN kidneys and LEW rat plasma were analyzed. Kidney histology, and kidney/serum levels of several inflammation-associated cytokines, were measured to assess mismatch-related kidney pathology, and PrC-210 protective efficacy. Twenty hours after the allograft transplants: (i) significant histologic kidney tubule damage and mononuclear inflammatory cell infiltration were seen in allograft kidneys; (ii) kidney function metrics (creatinine and BUN) were significantly elevated; (iii) significant changes in key cytokines, i.e., TIMP-1, TNF-alpha and MIP-3A/CCL20, and kidney activated caspase levels were seen. In PrC-210-treated kidneys and recipient rats, (i) kidney histologic damage (Banff Scores) and mononuclear infiltration were reduced to untreated background levels; (ii) creatinine and BUN were significantly reduced; and (iii) activated caspase and cytokine changes were significantly reduced, some to background. In conclusion, the results suggest that PrC-210 could provide broadly applicable organ protection for many allograft transplantation conditions; it could protect transplanted kidneys during and after all stages of the transplantation process—from organ donation, through transportation, re-implantation and the post-operative inflammation—to minimize acute and chronic rejection.
Spatiotemporal Dynamics of Covert Versus Overt Processing of Happy, Fearful and Sad Facial Expressions
Authors: Maffei Antonio , Goertzen Jennifer , Jaspers-Fayer Fern , Kleffner Killian , Sessa Paola , Liotti Mario
Published: July 2021

Behavioral and electrophysiological correlates of the influence of task demands on the processing of happy, sad, and fearful expressions were investigated in a within-subjects study that compared a perceptual distraction condition with task-irrelevant faces (e.g., covert emotion task) to an emotion task-relevant categorization condition (e.g., overt emotion task). A state-of-the-art non-parametric mass univariate analysis method was used to address the limitations of previous studies. Behaviorally, participants responded faster to overtly categorized happy faces and were slower and less accurate to categorize sad and fearful faces; there were no behavioral differences in the covert task. Event-related potential (ERP) responses to the emotional expressions included the N170 (140–180 ms), which was enhanced by emotion irrespective of task, with happy and sad expressions eliciting greater amplitudes than neutral expressions. EPN (200–400 ms) amplitude was modulated by task, with greater voltages in the overt condition, and by emotion, however, there was no interaction of emotion and task. ERP activity was modulated by emotion as a function of task only at a late processing stage, which included the LPP (500–800 ms), with fearful and sad faces showing greater amplitude enhancements than happy faces. This study reveals that affective content does not necessarily require attention in the early stages of face processing, supporting recent evidence that the core and extended parts of the face processing system act in parallel, rather than serially. The role of voluntary attention starts at an intermediate stage, and fully modulates the response to emotional content in the final stage of processing.
Apoptotic and Non-Apoptotic Modalities of Thymoquinone-Induced Lymphoma Cell Death: Highlight of the Role of Cytosolic Calcium and Necroptosis
Authors: Berehab Mimoune , Rouas Redouane , Akl Haidar , Duvillier Hugues , Journe Fabrice , Fayyad-Kazan Hussein , Ghanem Ghanem , Bron Dominique , Lewalle Philippe , Merimi Makram
Published: July 2021

Targeting non-apoptotic modalities might be therapeutically promising in diffuse large B cell lymphoma (DLBCL) patients with compromised apoptotic pathways. Thymoquinone (TQ) has been reported to promote apoptosis in cancer cells, but little is known about its effect on non-apoptotic pathways. This work investigates TQ selectivity against DLBCL cell lines and the cell death mechanisms. TQ reduces cell viability and kills cell lines with minimal toxicity on normal hematological cells. Mechanistically, TQ promotes the mitochondrial caspase pathway and increases genotoxicity. However, insensitivity of most cell lines to caspase inhibition by z-VAD-fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) pointed to a critical role of non-apoptotic signaling. In cells dying through non-apoptotic death, TQ increases endoplasmic reticulum (ER) stress markers and substantially increases cytosolic calcium ([Ca2+]c) through ER calcium depletion and activation of store-operated calcium entry (SOCE). Chelation of [Ca2+]c, but not SOCE inhibitors, reduces TQ-induced non-apoptotic cell death, highlighting the critical role of calcium in a non-apoptotic effect of TQ. Investigations showed that TQ-induced [Ca2+]c signaling is primarily initiated by necroptosis upstream to SOCE, and inhibition necroptosis by necrostatin-1 alone or with z-VAD-fmk blocks the cell death. Finally, TQ exhibits an improved selectivity profile over standard chemotherapy agents, suggesting a therapeutic relevance of the pro-necroptotic effect of TQ as a fail-safe mechanism for DLBCL therapies targeting apoptosis.
Radiomics in the Setting of Neoadjuvant Radiotherapy: A New Approach for Tailored Treatment
Authors: Nardone Valerio , Boldrini Luca , Grassi Roberta , Franceschini Davide , Morelli Ilaria , Becherini Carlotta , Loi Mauro , Greto Daniela , Desideri Isacco
Published: July 2021

Introduction: Neoadjuvant radiotherapy is currently used mainly in locally advanced rectal cancer and sarcoma and in a subset of non-small cell lung cancer and esophageal cancer, whereas in other diseases it is under investigation. The evaluation of the efficacy of the induction strategy is made possible by performing imaging investigations before and after the neoadjuvant therapy and is usually challenging. In the last decade, texture analysis (TA) has been developed to help the radiologist to quantify and identify the parameters related to tumor heterogeneity, which cannot be appreciated by the naked eye. The aim of this narrative is to review the impact of TA on the prediction of response to neoadjuvant radiotherapy and or chemoradiotherapy. Materials and Methods: Key references were derived from a PubMed query. Hand searching and ClinicalTrials.gov were also used. Results: This paper contains a narrative report and a critical discussion of radiomics approaches in different fields of neoadjuvant radiotherapy, including esophageal cancer, lung cancer, sarcoma, and rectal cancer. Conclusions: Radiomics can shed a light on the setting of neoadjuvant therapies that can be used to tailor subsequent approaches or even to avoid surgery in the future. At the same, these results need to be validated in prospective and multicenter trials.
Impact of Comorbidities, Sarcopenia, and Nutritional Status on the Long-Term Outcomes after Endoscopic Submucosal Dissection for Early Gastric Cancer in Elderly Patients Aged ≥ 80 Years
Authors: Kim Ga Hee , Choi Kee Don , Ko Yousun , Park Taeyong , Kim Kyung Won , Park Seo Young , Na Hee Kyong , Ahn Ji Yong , Lee Jeong Hoon , Jung Kee Wook , Kim Do Hoon , Song Ho June , Lee Gin Hyug , Jung Hwoon-Yong
Published: July 2021

Background/Aim: We investigated the oncologic outcomes in elderly patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) by focusing on the impact of comorbidities, sarcopenia, and nutritional status. Methods: Between 2005 and 2016, 280 patients aged ≥ 80 years with 289 EGCs underwent ESD at a tertiary care center. The short- and long-term survival outcomes were assessed. Cox regression analysis was used to identify factors associated with survival, including clinicopathologic factors and abdominal muscle area measured by computed tomography. Results: The rates of en bloc, R0, and, curative resection were 99.3%, 90.0%, and 69.2%, respectively. The rates of post-ESD bleeding and perforation rates were 2.1% and 3.1%, respectively, and no cases showed significant life-threatening adverse events. Over a median follow-up period of 70.5 months, the 3- and 5-year overall survival (OS) rates were 89.5% and 77.1%, respectively; of the114 patients who died, only four (3.5%) were due to gastric cancer. A total of 173 (61.8%) had sarcopenia, and they had lower rates of 3-year (88.4% vs. 91.4%) and 5-year (73.1% vs. 84.0%; p = 0.046) OS than did those without sarcopenia. In multivariable analyses, prognostic nutritional index (hazard ratio [HR], 0.93; 95% confidence interval [CI]: 0.90–0.98; p = 0.002) and Charlson comorbidity index (HR 1.19; 95% CI: 1.03–1.37; p = 0.018) were significant factors associated with overall survival. Conclusions: ESD was a feasible and safe therapeutic method to use in elderly patients, whose long-term survival was significantly associated with nutritional status and comorbidities. These results suggest the need for a possible extension of the curative criteria for ESD in elderly patients with EGC.
Reconsideration of the Appropriate Dissection Range Based on Japanese Anatomical Classification for Resectable Pancreatic Head Cancer in the Era of Multimodal Treatment
Authors: Nagakawa Yuichi , Nakagawa Naoya , Takishita Chie , Uyama Ichiro , Kozono Shingo , Osakabe Hiroaki , Suzuki Kenta , Nakagawa Nobuhiko , Hosokawa Yuichi , Shirota Tomoki , Honda Masayuki , Yamada Tesshi , Katsumata Kenji , Tsuchida Akihiko
Published: July 2021

Patients with resectable pancreatic cancer are considered to already have micro-distant metastasis, because most of the recurrence patterns postoperatively are distant metastases. Multimodal treatment dramatically improves prognosis; thus, micro-distant metastasis is considered to be controlled by chemotherapy. The survival benefit of “regional lymph node dissection” for pancreatic head cancer remains unclear. We reviewed the literature that could be helpful in determining the appropriate resection range. Regional lymph nodes with no suspected metastases on preoperative imaging may become areas treated with preoperative and postoperative adjuvant chemotherapy. Many studies have reported that the R0 resection rate is associated with prognosis. Thus, “dissection to achieve R0 resection” is required. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Therefore, it is possible to simulate the dissection range to achieve R0 resection preoperatively. However, it is often difficult to distinguish between areas of inflammatory changes and cancer infiltration during resection. Even if the “dissection to achieve R0 resection” range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of anatomical landmarks to determine the appropriate dissection range during surgery.
Functional Roles of Bromodomain Proteins in Cancer
Authors: Boyson Samuel P. , Gao Cong , Quinn Kathleen , Boyd Joseph , Paculova Hana , Frietze Seth , Glass Karen C.
Published: July 2021

Histone acetylation is generally associated with an open chromatin configuration that facilitates many cellular processes including gene transcription, DNA repair, and DNA replication. Aberrant levels of histone lysine acetylation are associated with the development of cancer. Bromodomains represent a family of structurally well-characterized effector domains that recognize acetylated lysines in chromatin. As part of their fundamental reader activity, bromodomain-containing proteins play versatile roles in epigenetic regulation, and additional functional modules are often present in the same protein, or through the assembly of larger enzymatic complexes. Dysregulated gene expression, chromosomal translocations, and/or mutations in bromodomain-containing proteins have been correlated with poor patient outcomes in cancer. Thus, bromodomains have emerged as a highly tractable class of epigenetic targets due to their well-defined structural domains, and the increasing ease of designing or screening for molecules that modulate the reading process. Recent developments in pharmacological agents that target specific bromodomains has helped to understand the diverse mechanisms that bromodomains play with their interaction partners in a variety of chromatin processes, and provide the promise of applying bromodomain inhibitors into the clinical field of cancer treatment. In this review, we explore the expression and protein interactome profiles of bromodomain-containing proteins and discuss them in terms of functional groups. Furthermore, we highlight our current understanding of the roles of bromodomain-containing proteins in cancer, as well as emerging strategies to specifically target bromodomains, including combination therapies using bromodomain inhibitors alongside traditional therapeutic approaches designed to re-program tumorigenesis and metastasis.
TNF-α May Exert Different Antitumor Effects in Response to Radioactive Iodine Therapy in Papillary Thyroid Cancer with/without Autoimmune Thyroiditis
Authors: Gheorghe Dan Cristian , Stanciu Marcel Marian , Zamfirescu Anca , Stanciu Adina Elena
Published: July 2021

Autoimmune thyroiditis (AIT) may impair radioiodine (131I) uptake in papillary thyroid cancer (PTC). Finding the mechanisms that govern immune cells during 131I therapy of PTC with concomitant AIT (PTC + AIT) could provide a rationale. Our study aimed to evaluate the effects of 131I on anti-thyroglobulin antibodies (TgAb), matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor TIMP-1 and tumor necrosis factor-α (TNF-α) and its receptors TNFR1 and TNFR2, in PTC and PTC + AIT patients. Peripheral blood was collected from 56 female patients with PTC and 32 with PTC + AIT before and 4 days after 131I (3.7 GBq). The serum levels of TgAb, MMP-9, TIMP-1, TNF-α, TNFR1 and TNFR2 were measured by ELISA. The mean radioactivity of blood samples collected after 131I intake was higher in the PTC + AIT group than in PTC (p < 0.001). In the PTC + AIT group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios decreased by 0.38-fold and 0.32-fold after 131I and were positively correlated with the MMP-9/TIMP-1 ratio (r = 0.48, p = 0.005, and r = 0.46, p = 0.007). In the PTC group, TNF-α/TNFR1 and TNF-α/TNFR2 ratios increased by 3.17-fold and 3.33-fold and were negatively correlated with the MMP-9/TIMP-1 ratio (r = −0.62, p < 0.001 and r = −0.58, p < 0.001). Our results demonstrate that TNF-α may exert different antitumor effects in response to 131I therapy depending on the patient’s immune profile.
An Investigation into the Bulk and Surface Phase Transformations of Bimetallic Pd-In/Al2O3 Catalyst during Reductive and Oxidative Treatments In Situ
Authors: Smirnova Nadezhda S. , Khramov Evgeny V. , Baeva Galina N. , Markov Pavel V. , Bukhtiyarov Andrey V. , Zubavichus Yan V. , Stakheev Aleksander Y.
Published: July 2021

A series of oxidative treatments of PdIn-supported intermetallic nanoparticles at different temperatures were performed. The bulk and surface structure of catalyst during phase transformation was investigated by bulk- and surface-sensitive techniques (in situ XAFS, DRIFTS of adsorbed CO). It was found that comparison of palladium and indium fractions in bulk and on the surface suggests the formation of a «core-shell» structure. According to obtained results, the core consists of In-depleted intermetallic compound or inhomogeneous bimetallic phase with the inner core of metallic Pd, when a mixture of indium oxide, metallic palladium and small part of PdIn is present on the surface.
HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy
Authors: De Giovanni Carla , Landuzzi Lorena , Palladini Arianna , Nicoletti Giordano , Nanni Patrizia , Lollini Pier-Luigi
Published: July 2021

Rhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features allow for distinction between subtypes: morphology and presence/absence of a translocation between the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy. HER family members could be exploited for therapeutic approaches in two ways: blocking the HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting expressed HER members to vehiculate toxins or immune effectors.
New Data on Organization and Spatial Localization of B-Chromosomes in Cell Nuclei of the Yellow-Necked Mouse Apodemus flavicollis
Authors: Karamysheva Tatyana , Romanenko Svetlana , Makunin Alexey , Rajičić Marija , Bogdanov Alexey , Trifonov Vladimir , Blagojević Jelena , Vujošević Mladen , Orishchenko Konstantin , Rubtsov Nikolay
Published: July 2021

The gene composition, function and evolution of B-chromosomes (Bs) have been actively discussed in recent years. However, the additional genomic elements are still enigmatic. One of Bs mysteries is their spatial organization in the interphase nucleus. It is known that heterochromatic compartments are not randomly localized in a nucleus. The purpose of this work was to study the organization and three-dimensional spatial arrangement of Bs in the interphase nucleus. Using microdissection of Bs and autosome centromeric heterochromatic regions of the yellow-necked mouse (Apodemus flavicollis) we obtained DNA probes for further two-dimensional (2D)- and three-dimensional (3D)- fluorescence in situ hybridization (FISH) studies. Simultaneous in situ hybridization of obtained here B-specific DNA probes and autosomal C-positive pericentromeric region-specific probes further corroborated the previously stated hypothesis about the pseudoautosomal origin of the additional chromosomes of this species. Analysis of the spatial organization of the Bs demonstrated the peripheral location of B-specific chromatin within the interphase nucleus and feasible contact with the nuclear envelope (similarly to pericentromeric regions of autosomes and sex chromosomes). It is assumed that such interaction is essential for the regulation of nuclear architecture. It also points out that Bs may follow the same mechanism as sex chromosomes to avoid a meiotic checkpoint.
Distinctive Prognostic Value and Cellular Functions of Osteopontin Splice Variants in Human Gastric Cancer
Authors: Hao Chengcheng , Cui Yuxin , Lane Jane , Jia Shuqin , Ji Jiafu , Jiang Wen G.
Published: July 2021

Background: Osteopontin (OPN) splice variants are identified as predictors of tumour progression and therapeutic resistance in certain types of solid tumours. However, their roles in gastric cancer (GC) remain poorly characterized. The current study sought to assess the prognostic value of the three OPN splice variants (namely OPN-a, OPN-b, and OPN-c) in gastric cancer and their potential functions within gastric cancer cells. Methods: RNA extraction and reverse transcription were performed using our clinical cohort of gastric carcinomas and matched normal tissues (n = 324 matched pairs). Transcript levels were determined using real-time quantitative PCR. Three OPN splice variants overexpressed cell lines were created from the gastric cancer cell line HGC-27. Subsequently, biological functions, including cell growth, adhesion, migration, and invasion, were studied. The potential effects of OPN isoforms on cisplatin and 5-Fu were evaluated by detecting cellular reactive oxygen species (ROS) levels in the HGC-27-derived cell lines. Results: Compared with normal tissues, the expression levels of three splice variants were all elevated in gastric cancer tissues in an order of OPN-a > OPN-b > OPN-c. The OPN-a level significantly increased with increasing TNM staging and worse clinical outcome. There appeared to be a downregulation for OPN-c in increasing lymph node status (p < 0.05), increasing TNM staging, and poor differentiation. High levels of OPN-a and OPN-b were correlated with short overall survival and disease-free survival of gastric cancer patients. However, the low expression of OPN-c was significantly associated with a poor prognosis. Functional analyses further showed that ectopic expression of OPN-c suppressed in vitro proliferation, adhesiveness, migration, and invasion properties of HGC-27 cells, while the opposite role was seen for OPN-a. Cellular ROS detection indicated that OPN-a and OPN-c significantly promoted ROS production after treatment with 5-Fu comparing to OPN-vector, while only OPN-a markedly induced ROS production after treatment with cisplatin. Conclusion: Our results suggest that OPN splice variants have distinguished potential to predict the prognosis of gastric cancer. Three OPN variants exert distinctive functions in gastric cancer cells. Focusing on specific OPN isoforms could be a novel direction for developing diagnostic and therapeutic approaches in gastric cancer.
Structural, Optical, and Electrical Properties of Copper Oxide Films Grown by the SILAR Method with Post-Annealing
Authors: Lee Wen-Jen , Wang Xin-Jin
Published: July 2021

Copper oxides are widely used in photocatalysts, sensors, batteries, optoelectronic, and electronic devices. In order to obtain different material properties to meet the requirements of different application fields, varied technologies and process conditions are used to prepare copper oxides. In this work, copper oxide films were grown on glass substrates by a successive ionic layer adsorption and reaction (SILAR) method with subsequent annealing under an atmospheric environment. The films were characterized by using an X-ray diffractometer, Raman spectrometer, Scanning electron microscope, UV-Visible-NIR spectrophotometer, and Hall Effect measurement. The results show that the as-deposited film has a Cu2O crystal structure, which begins to transform into Cu2O-CuO mixed crystal and CuO crystal structure after annealing at 300 °C for a period of time, resulting in the bandgap of being reduced from 1.90 to 1.34 eV. The results show that not only are the crystal structure and bandgap of the films affected by the post-annealing temperature and time, but also the resistivity, carrier concentration, and mobility of the films are varied with the annealing conditions. In addition, the film with a Cu2O-CuO mixed crystal shows a high carrier mobility of 93.7 cm2·V−1·s−1 and a low carrier concentration of 1.8 × 1012 cm−3 due to the formation of a Cu2O-CuO heterojuction.
Drying of a Colloidal Suspension Deposited on a Substrate: Experimental and Numerical Studies
Authors: Olivi-Tran Nathalie , Bonnet Laurent , Etienne Pascal
Published: July 2021

We studied a colloidal suspension of polystyrene beads deposited on a glass substrate. The glass substrate contained either straight rough areas on the borders of an open channel or only straight rough areas. The drying of the suspension was observed with an optical microscope, the light bulb of which acted as an energy source to evaporate the suspension. Moreover, the light bulb of the microscope provided optical pressure due to light. We observed that the colloidal particles were trapped on the rough areas of the substrate and not in the open channel at the end of the drying process. In order to understand the experimental results, we modeled numerically the drying of the suspension using a Molecular Dynamics program. The forces imposed on the substrate by the particles are their weight, the optical pressure due to the light bulb of the optical microscope, the attractive Van der Waals force and the repulsive diffuse layer force. The forces acting between two particles are the attractive Van der Waals forces, the repulsive diffuse layer force and the capillary force. The Gaussian random force (linked to Brownian motion) and the particle liquid viscous drag force (also linked to Brownian motion) are horizontal and applied on one particle. The relation between the normal forces N (forces acting by the particles on the substrate) and the horizontal forces F is Amontons’ third law of friction F≤μkN; in rough areas of the substrate, μk is larger than in smooth areas. This explains that particles are trapped in the areas with high roughness.
Bacterial Number and Genetic Diversity in a Permafrost Peatland (Western Siberia): Testing a Link with Organic Matter Quality and Elementary Composition of a Peat Soil Profile
Authors: Aksenov Andrey S. , Shirokova Liudmila S. , Kisil Oksana Ya. , Kolesova Sofiia N. , Lim Artem G. , Kuzmina Darya , Pouillé Sophie , Alexis Marie A. , Castrec-Rouelle Maryse , Loiko Sergey V. , Pokrovsky Oleg S.
Published: July 2021

Permafrost peatlands, containing a sizable amount of soil organic carbon (OC), play a pivotal role in soil (peat) OC transformation into soluble and volatile forms and greatly contribute to overall natural CO2 and CH4 emissions to the atmosphere under ongoing permafrost thaw and soil OC degradation. Peat microorganisms are largely responsible for the processing of this OC, yet coupled studies of chemical and bacterial parameters in permafrost peatlands are rather limited and geographically biased. Towards testing the possible impact of peat and peat pore water chemical composition on microbial population and diversity, here we present results of a preliminary study of the western Siberia permafrost peatland discontinuous permafrost zone. The quantitative evaluation of microorganisms and determination of microbial diversity along a 100 cm thick peat soil column, which included thawed and frozen peat and bottom mineral horizon, was performed by RT-PCR and 16S rRNA gene-based metagenomic analysis, respectively. Bacteria (mainly Proteobacteria, Acidobacteria, Actinobacteria) strongly dominated the microbial diversity (99% sequences), with a negligible proportion of archaea (0.3–0.5%). There was a systematic evolution of main taxa according to depth, with a maximum of 65% (Acidobacteria) encountered in the active layer, or permafrost boundary (50–60 cm). We also measured C, N, nutrients and ~50 major and trace elements in peat (19 samples) as well as its pore water and dispersed ice (10 samples), sampled over the same core, and we analyzed organic matter quality in six organic and one mineral horizon of this core. Using multiparametric statistics (PCA), we tested the links between the total microbial number and 16S rRNA diversity and chemical composition of both the solid and fluid phase harboring the microorganisms. Under climate warming and permafrost thaw, one can expect a downward movement of the layer of maximal genetic diversity following the active layer thickening. Given a one to two orders of magnitude higher microbial number in the upper (thawed) layers compared to bottom (frozen) layers, an additional 50 cm of peat thawing in western Siberia may sizably increase the total microbial population and biodiversity of active cells.
Influence of Geographical and Climatic Factors on Quercus variabilis Blume Fruit Phenotypic Diversity
Authors: Gao Shuang , Ren Yue , Masabni Joseph , Zou Feng , Xiong Huan , Zhu Jingle
Published: July 2021

Quercus variabilis Blume is one of the most ecologically valuable tree species in China and is known to have adaptive mechanisms to climate change. Our objective was to quantify the variation pattern in the fruit morphology of Q. variabilis. Fruit samples were collected from 43 natural populations in autumn of 2019. Our results indicated that the coefficient of variation (CV) of the fruit length (FL) and fruit width (FW) were 10.08% and 11.21%, respectively. There were significant differences in the FL, FW, and fruit length-to-width ratios (FL/FW) among the studied populations. Also, there was a significant positive correlation between the FW and FL. The FL decreased with increasing precipitation in the wettest quarter (PWQ). A concave trend was observed in the variations in FL with the equivalent latitude (ELAT), longitude (LON), annual mean air temperature (MAT), and annual precipitation (AP). A similar concave trend was observed for the FL/FW with LON, MAT, and AP. A positive correlation was observed between the FW, FL and FL/FW, and the ELAT. The cluster analysis revealed five groups of the 43 natural populations. Our study findings suggests that Q. variabilis has high levels of phenotypic plasticity for geographical and climatic factors.
Effect of Cothurnia variabilis and Epistylis gammari (Ciliophora: Peritrichia) on Metabolic Rate of the Crayfish Cambarellus (Cambarellus) montezumae
Authors: Ramírez-Ballesteros Mireya , Cárdenas-Vázquez René , Lugo-Vázquez Alfonso , Mayén-Estrada Rosaura
Published: July 2021

Peritrichs usually settle on the external surface and gills of crustaceans. However, their physiological effect on the host has not been studied. Respiratory rate is a susceptible index for some factors that affect an organism. To test if ciliates attached to the crustacean gills have a physiological effect, we measured crustacean oxygen consumption in a closed system. Crayfish Cambarellus (Cambarellus) montezumae were collected in Lago Xochimilco in Mexico City and were isolated in chambers. Two peritrich species, Cothurnia variabilis (32.5%) and Epistylis gammari (67.5%), were observed on the gills. The metabolic rate was evaluated by oxygen consumption with a polarimetric oximeter. Statistical analyses demonstrated that a density of ciliates attached to the gills of the crayfish above ~50 individuals increased oxygen consumption with a positive correlation to epibiont density. We conclude that C. variabilis and E. gammari ciliate epibionts attached to the gill of the crayfish Cambarellus (Cambarellus) montezumae cause an increase in metabolic rate.