bluuebunny/crossref_metadata_2025 huggingface dataset:
Image Denoising Using a Novel Deep Generative Network with Multiple Target Images and Adaptive Termination Condition
Authors: Chen Shiming , Xu Shaoping , Chen Xiaoguo , Li Fen
Published: May 2021

Image denoising, a classic ill-posed problem, aims to recover a latent image from a noisy measurement. Over the past few decades, a considerable number of denoising methods have been studied extensively. Among these methods, supervised deep convolutional networks have garnered increasing attention, and their superior performance is attributed to their capability to learn realistic image priors from a large amount of paired noisy and clean images. However, if the image to be denoised is significantly different from the training images, it could lead to inferior results, and the networks may even produce hallucinations by using inappropriate image priors to handle an unseen noisy image. Recently, deep image prior (DIP) was proposed, and it overcame this drawback to some extent. The structure of the DIP generator network is capable of capturing the low-level statistics of a natural image using an unsupervised method with no training images other than the image itself. Compared with a supervised denoising model, the unsupervised DIP is more flexible when processing image content that must be denoised. Nevertheless, the denoising performance of DIP is usually inferior to the current supervised learning-based methods using deep convolutional networks, and it is susceptible to the over-fitting problem. To solve these problems, we propose a novel deep generative network with multiple target images and an adaptive termination condition. Specifically, we utilized mainstream denoising methods to generate two clear target images to be used with the original noisy image, enabling better guidance during the convergence process and improving the convergence speed. Moreover, we adopted the noise level estimation (NLE) technique to set a more reasonable adaptive termination condition, which can effectively solve the problem of over-fitting. Extensive experiments demonstrated that, according to the denoising results, the proposed approach significantly outperforms the original DIP method in tests on different databases. Specifically, the average peak signal-to-noise ratio (PSNR) performance of our proposed method on four databases at different noise levels is increased by 1.90 to 4.86 dB compared to the original DIP method. Moreover, our method achieves superior performance against state-of-the-art methods in terms of popular metrics, which include the structural similarity index (SSIM) and feature similarity index measurement (FSIM). Thus, the proposed method lays a good foundation for subsequent image processing tasks, such as target detection and super-resolution.
Detection of Ischemic Episodes Based on Two Consecutive Declines in the JT/ST Algebraic Relationship
Authors: Šiaučiūnaitė Vaiva , Vainoras Alfonsas , Navickas Zenonas , Ragulskis Minvydas
Published: May 2021

The main objective of this paper is to explore if the JT/ST algebraic relationship could be helpful for the identification of ischemic changes in the human cardiovascular system. The suggested visualization technique highlights the specifics of complex dynamical processes in the self-organization of the heart system during the load and recovery processes. It is demonstrated that the nonlinear algebraic relationship between the duration of the JT interval and the ST amplitude can be beneficial for a deeper interpretation of dynamical processes in the human cardiovascular system. The JT/ST relationship is used for the identification of the ischemic changes and for the characterization of individual performance of the person during the load and recovery processes.
Improving Comfort and Air Conditioner Performance by Optimizing Controllers under Actual Usage Conditions
Authors: Park Taebyoung , Kim Byungsoon , Hwang Gilun , Kang Yulho , Lee Inwon , Ahn Youngchull
Published: May 2021

This study is to increase the efficiency of the air conditioning system under actual conditions of use. In order to improve the increase in energy consumption due to control without considering indoor cooling load fluctuations, we review it compared to conventional control methods in two respects. First, we examined the control method to reduce energy consumption by varying the evaporative pressure of the system according to the cooling load, and secondly, further reducing energy consumption by controlling the revolutions per minute (RPM) of the fan of the indoor unit at the same time as the pressure fluctuation under the cooling load. We found that changing the target pressure depending on the difference between the target temperature and room temperature can control temperature more efficiently and save energy than using fixed target pressure, and that the effect increases when applying the control of the air volume of the indoor air. Cleaning up the resulting values, the fan-load-control condition of the cooling-load-estimation control method showed an energy savings effect of 16.1–48.7% compared with the fixed-pressure control method and 1.2–37.7% compared with the cooling-load-estimation control method.
Binary Biocompatible CNC–Gelatine Hydrogel as 3D Scaffolds Suitable for Cell Culture Adhesion and Growth
Authors: Zoia Luca , Binda Anna , Cipolla Laura , Rivolta Ilaria , La Ferla Barbara
Published: May 2021

Binary nano-biocomposite 3D scaffolds of cellulose nanocrystals (CNCs)—gelatine were fabricated without using chemical crosslinking additives. Controlled oxidative treatment allowed introducing carboxyl or carbonyl functionalities on the surface of CNCs responsible for the crosslinking of gelatine polymers. The obtained composites were characterized for their physical-chemical properties. Their biocompatibility towards different cell cultures was evaluated through MTT and LDH assays, cellular adhesion and proliferation experiments. Gelatine composites reinforced with carbonyl-modified CNCs showed the most performing swelling/degradation profile and the most promising adhesion and proliferation properties towards cell lines, suggesting their potential application in the field of tissue engineering.
On the Existence of Coupled Fractional Jerk Equations with Multi-Point Boundary Conditions
Authors: Hu Lei , Han Yaozhen , Zhang Shuqin
Published: May 2021

By coincidence degree theory due to Mawhin, some sufficient conditions for the existence of solution for a class of coupled jerk equations with multi-point conditions are established. The new existence results have not yet been reported before. Novel coupled fractional jerk equations with resonant boundary value conditions are discussed in detail for the first time. Our work is interesting and complements known results.
Simplified Iohexol-Based Method for Measurement of Glomerular Filtration Rate in Goats and Pigs
Authors: van Gelder Maaike K. , Stevens Jasper , Pieters Tobias T. , Vaessen Koen R. D. , Joles Jaap A. , Verhaar Marianne C. , Gerritsen Karin G. F.
Published: May 2021

The preclinical evaluation of novel therapies for chronic kidney disease requires a simple method for the assessment of kidney function in a uremic large animal model. An intravenous bolus of iohexol was administered to goats (13 measurements in n = 3 goats) and pigs (23 measurements in n = 5 pigs) before and after induction of kidney failure, followed by frequent blood sampling up to 1440 min. Plasma clearance (CL) was estimated by a nonlinear mixed-effects model (CLNLME) and by a one-compartmental pharmacokinetic disposition model using iohexol plasma concentrations during the terminal elimination phase (CL1CMT). A simple method (CLSM) for the calculation of plasma clearance was developed based on the most appropriate relationship between CLNLME and CL1CMT. CLSM and CLNLME showed good agreement (CLNLME/CLSM ratio: 1.00 ± 0.07; bias: 0.03 ± 1.64 mL/min; precision CLSM and CLNLME: 80.9% and 80.7%, respectively; the percentage of CLSM estimates falling within ±30% (P30) or ±10% (P10) of CLNLME: 53% and 12%, respectively). For mGFRNLME vs. mGFRSM, bias was −0.25 ± 2.24 and precision was 49.2% and 53.6%, respectively, P30 and P10 for mGFR based on CLSM were 71% and 24%, respectively. A simple method for measurement of GFR in healthy and uremic goats and pigs was successfully developed, which eliminates the need for continuous infusion of an exogenous marker, urine collection and frequent blood sampling.
Mechanisms That Activate 26S Proteasomes and Enhance Protein Degradation
Authors: Goldberg Alfred L. , Kim Hyoung Tae , Lee Donghoon , Collins Galen Andrew
Published: May 2021

Although ubiquitination is widely assumed to be the only regulated step in the ubiquitin–proteasome pathway, recent studies have demonstrated several important mechanisms that regulate the activities of the 26S proteasome. Most proteasomes in cells are inactive but, upon binding a ubiquitinated substrate, become activated by a two-step mechanism requiring an association of the ubiquitin chain with Usp14 and then a loosely folded protein domain with the ATPases. The initial activation step is signaled by Usp14’s UBL domain, and many UBL-domain-containing proteins (e.g., Rad23, Parkin) also activate the proteasome. ZFAND5 is a distinct type of activator that binds ubiquitin conjugates and the proteasome and stimulates proteolysis during muscle atrophy. The proteasome’s activities are also regulated through subunit phosphorylation. Agents that raise cAMP and activate PKA stimulate within minutes Rpn6 phosphorylation and enhance the selective degradation of short-lived proteins. Likewise, hormones, fasting, and exercise, which raise cAMP, activate proteasomes and proteolysis in target tissues. Agents that raise cGMP and activate PKG also stimulate 26S activities but modify different subunit(s) and stimulate also the degradation of long-lived cell proteins. Both kinases enhance the selective degradation of aggregation-prone proteins that cause neurodegenerative diseases. These new mechanisms regulating proteolysis thus have clear physiological importance and therapeutic potential.
From the Identification to the Dissection of the Physiological Role of the Mitochondrial Calcium Uniporter: An Ongoing Story
Authors: Pallafacchina Giorgia , Zanin Sofia , Rizzuto Rosario
Published: May 2021

The notion of mitochondria being involved in the decoding and shaping of intracellular Ca2+ signals has been circulating since the end of the 19th century. Despite that, the molecular identity of the channel that mediates Ca2+ ion transport into mitochondria remained elusive for several years. Only in the last decade, the genes and pathways responsible for the mitochondrial uptake of Ca2+ began to be cloned and characterized. The gene coding for the pore-forming unit of the mitochondrial channel was discovered exactly 10 years ago, and its product was called mitochondrial Ca2+ uniporter or MCU. Before that, only one of its regulators, the mitochondria Ca2+ uptake regulator 1, MICU1, has been described in 2010. However, in the following years, the scientific interest in mitochondrial Ca2+ signaling regulation and physiological role has increased. This shortly led to the identification of many of its components, to the description of their 3D structure, and the characterization of the uniporter contribution to tissue physiology and pathology. In this review, we will summarize the most relevant achievements in the history of mitochondrial Ca2+ studies, presenting a chronological overview of the most relevant and landmarking discoveries. Finally, we will explore the impact of mitochondrial Ca2+ signaling in the context of muscle physiology, highlighting the recent advances in understanding the role of the MCU complex in the control of muscle trophism and metabolism.
Improving Performance of Salt-Grown Crops by Exogenous Application of Plant Growth Regulators
Authors: Quamruzzaman Md. , Manik S. M. Nuruzzaman , Shabala Sergey , Zhou Meixue
Published: May 2021

Soil salinity is one of the major abiotic stresses restricting plant growth and development. Application of plant growth regulators (PGRs) is a possible practical means for minimizing salinity-induced yield losses, and can be used in addition to or as an alternative to crop breeding for enhancing salinity tolerance. The PGRs auxin, cytokinin, nitric oxide, brassinosteroid, gibberellin, salicylic acid, abscisic acid, jasmonate, and ethylene have been advocated for practical use to improve crop performance and yield under saline conditions. This review summarizes the current knowledge of the effectiveness of various PGRs in ameliorating the detrimental effects of salinity on plant growth and development, and elucidates the physiological and genetic mechanisms underlying this process by linking PGRs with their downstream targets and signal transduction pathways. It is shown that, while each of these PGRs possesses an ability to alter plant ionic and redox homeostasis, the complexity of interactions between various PGRs and their involvement in numerous signaling pathways makes it difficult to establish an unequivocal causal link between PGRs and their downstream effectors mediating plants’ adaptation to salinity. The beneficial effects of PGRs are also strongly dependent on genotype, the timing of application, and the concentration used. The action spectrum of PGRs is also strongly dependent on salinity levels. Taken together, this results in a rather narrow “window” in which the beneficial effects of PGR are observed, hence limiting their practical application (especially under field conditions). It is concluded that, in the light of the above complexity, and also in the context of the cost–benefit analysis, crop breeding for salinity tolerance remains a more reliable avenue for minimizing the impact of salinity on plant growth and yield. Further progress in the field requires more studies on the underlying cell-based mechanisms of interaction between PGRs and membrane transporters mediating plant ion homeostasis.
Clinical Utility of Biosensing Platforms for Confirmation of SARS-CoV-2 Infection
Authors: Phan Le Minh Tu , Tieu My-Van , Pham Thi-Thu , Cho Sungbo
Published: May 2021

Despite collaborative efforts from all countries, coronavirus disease 2019 (COVID-19) pandemic has been continuing to spread globally, forcing the world into social distancing period, making a special challenge for public healthcare system. Before vaccine widely available, the best approach to manage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to achieve highest diagnostic accuracy by improving biosensor efficacy. For SARS-CoV-2 diagnostics, intensive attempts have been made by many scientists to ameliorate the drawback of current biosensors of SARS-CoV-2 in clinical diagnosis to offer benefits related to platform proposal, systematic analytical methods, system combination, and miniaturization. This review assesses ongoing research efforts aimed at developing integrated diagnostic tools to detect RNA viruses and their biomarkers for clinical diagnostics of SARS-CoV-2 infection and further highlights promising technology for SARS-CoV-2 specific diagnosis. The comparisons of SARS-CoV-2 biomarkers as well as their applicable biosensors in the field of clinical diagnosis were summarized to give scientists an advantage to develop superior diagnostic platforms. Furthermore, this review describes the prospects for this rapidly growing field of diagnostic research, raising further interest in analytical technology and strategic plan for future pandemics.
Nanobioengineered Sensing Technologies Based on Cellulose Matrices for Detection of Small Molecules, Macromolecules, and Cells
Authors: Divya  , Mahapatra Supratim , Srivastava Vinish Ranjan , Chandra Pranjal
Published: May 2021

Recent advancement has been accomplished in the field of biosensors through the modification of cellulose as a nano-engineered matrix material. To date, various techniques have been reported to develop cellulose-based matrices for fabricating different types of biosensors. Trends of involving cellulosic materials in paper-based multiplexing devices and microfluidic analytical technologies have increased because of their disposable, portable, biodegradable properties and cost-effectiveness. Cellulose also has potential in the development of cytosensors because of its various unique properties including biocompatibility. Such cellulose-based sensing devices are also being commercialized for various biomedical diagnostics in recent years and have also been considered as a method of choice in clinical laboratories and personalized diagnosis. In this paper, we have discussed the engineering aspects of cellulose-based sensors that have been reported where such matrices have been used to develop various analytical modules for the detection of small molecules, metal ions, macromolecules, and cells present in a diverse range of samples. Additionally, the developed cellulose-based biosensors and related analytical devices have been comprehensively described in tables with details of the sensing molecule, readout system, sensor configuration, response time, real sample, and their analytical performances.
Molecular and Cellular Mechanisms of Metformin in Cervical Cancer
Authors: Chen Ya-Hui , Wang Po-Hui , Chen Pei-Ni , Yang Shun-Fa , Hsiao Yi-Hsuan
Published: May 2021

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.
Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
Authors: Kang Keunsoo , Choi Yoonjung , Moon Hyeonjin , You Chaelin , Seo Minjin , Kwon Geunho , Yun Jahyun , Beck Boram , Kang Kyuho
Published: May 2021

RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.
Genetic Analysis and Operative Outcomes in Patients with Oncogene-Driven Advanced NSCLC Treated with Cytoreductive Surgery as a Component of Local Consolidative Therapy
Authors: Park Byung Jo , Shim Hyo Sup , Lee Chang Young , Lee Jin Gu , Kim Hye Ryun , Lee Sang Hoon , Hong Min Hee , Park Seong Yong
Published: May 2021

Most patients with oncogene-driven advanced non-small cell lung cancer (NSCLC) demonstrate recurrence because of the developing targeted therapy resistance. In this retrospective study, we assessed the efficacy of surgical local consolidative treatment by analyzing the operative outcomes and genetic data in 44 patients who underwent pulmonary resection for stage IIIB/C–IV NSCLC after targeted therapy. The initial mutations were in the EGFR (n = 32), ALK (n = 11), and ROS1 (n = 1) genes. The median interval from the initiation of tyrosine kinase inhibitor (TKI) therapy immediately before the surgery to the actual operation was 9.8 months. Operative mortality was absent. Four patients showed complete remission. The median follow-up period after TKI therapy initiation was 23.1 months. The Kaplan–Meier survival analysis showed that the 2-year failure-free survival and overall survival rates from the initiation of TKI were 70.8% and 95.0%, respectively. During the follow-up period, two patients died and 15 suffered from disease progression. Among the 32 patients with EGFR mutations, 12 showed additional mutations, and targeted agents were replaced in nine patients after the operation. We conclude that pulmonary resection for advanced NSCLC after targeted therapy is feasible, and the surgical specimens could be used for planning further targeted therapy.
2-[18F]FDG PET/CT as a Predictor of Microvascular Invasion and High Histological Grade in Patients with Hepatocellular Carcinoma
Authors: Sabaté-Llobera Aida , Mestres-Martí Judit , Reynés-Llompart Gabriel , Lladó Laura , Mils Kristel , Serrano Teresa , Cortés-Romera Montserrat , Bertran Esther , Fabregat Isabel , Ramos Emilio
Published: May 2021

Hepatocellular carcinoma (HCC) generally presents a low avidity for 2-deoxy-2-[18F]fluoro-d-glucose (FDG) in PET/CT although an increased FDG uptake seems to relate to more aggressive biological factors. To define the prognostic value of PET/CT with FDG in patients with an HCC scheduled for a tumor resection, forty-one patients were prospectively studied. The histological factors of a poor prognosis were determined and FDG uptake in the HCC lesions was analyzed semi-quantitatively (lean body mass-corrected standardized uptake value (SUL) and tumor-to-liver ratio (TLR) at different time points). The PET metabolic parameters were related to the histological characteristics of the resected tumors and to the evolution of patients. Microvascular invasion (MVI) and a poor grade of differentiation were significantly related to a worse prognosis. The SULpeak of the lesion 60 min post-FDG injection was the best parameter to predict MVI while the SULpeak of the TLR at 60 min was better for a poor differentiation. Moreover, the latter parameter was also the best preoperative variable available to predict any of these two histological factors. Patients with an increased TLRpeak60 presented a significantly higher incidence of poor prognostic factors than the rest (75% vs. 28.6%, p = 0.005) and a significantly higher incidence of recurrence at 12 months (38% vs. 0%, p = 0.014). Therefore, a semi-quantitative analysis of certain metabolic parameters on PET/CT can help identify, preoperatively, patients with histological factors of a poor prognosis, allowing an adjustment of the therapeutic strategy for those patients with a higher risk of an early recurrence.
Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma
Authors: Guijarro Luis G. , Sanmartin-Salinas Patricia , Pérez-Cuevas Eva , Toledo-Lobo M. Val , Monserrat Jorge , Zoullas Sofía , Sáez Miguel A. , Álvarez-Mon Miguel A. , Bujan Julia , Noguerales-Fraguas Fernando , Arilla-Ferreiro Eduardo , Álvarez-Mon Melchor , Ortega Miguel A.
Published: May 2021

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.
Global Chromatin Changes Resulting from Single-Gene Inactivation—The Role of SMARCB1 in Malignant Rhabdoid Tumor
Authors: Kenny Colin , O’Meara Elaine , Ulaş Mevlüt , Hokamp Karsten , O’Sullivan Maureen J.
Published: May 2021

Human cancer typically results from the stochastic accumulation of multiple oncogene-activating and tumor-suppressor gene-inactivating mutations. However, this process takes time and especially in the context of certain pediatric cancer, fewer but more ‘impactful’ mutations may in short order produce the full-blown cancer phenotype. This is well exemplified by the highly aggressive malignant rhabdoid tumor (MRT), where the only gene classically showing recurrent inactivation is SMARCB1, a subunit member of the BAF chromatin-remodeling complex. This is true of all three presentations of MRT including MRT of kidney (MRTK), MRT of the central nervous system (atypical teratoid rhabdoid tumor—ATRT) and extracranial, extrarenal rhabdoid tumor (EERT). Our reverse modeling of rhabdoid tumors with isogenic cell lines, either induced or not induced, to express SMARCB1 showed widespread differential chromatin remodeling indicative of altered BAF complex activity with ensuant histone modifications when tested by chromatin immunoprecipitation followed by sequencing (ChIP-seq). The changes due to reintroduction of SMARCB1 were preponderantly at typical enhancers with tandem BAF complex occupancy at these sites and related gene activation, as substantiated also by transcriptomic data. Indeed, for both MRTK and ATRT cells, there is evidence of an overlap between SMARCB1-dependent enhancer activation and tissue-specific lineage-determining genes. These genes are inactive in the tumor state, conceivably arresting the cells in a primitive/undifferentiated state. This epigenetic dysregulation from inactivation of a chromatin-remodeling complex subunit contributes to an improved understanding of the complex pathophysiological basis of MRT, one of the most lethal and aggressive human cancers.
Damage-Associated Molecular Patterns Modulation by microRNA: Relevance on Immunogenic Cell Death and Cancer Treatment Outcome
Authors: Lamberti María Julia , Nigro Annunziata , Casolaro Vincenzo , Rumie Vittar Natalia Belén , Dal Col Jessica
Published: May 2021

Immunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy.
Mitochondrial Dynamics and Liver Cancer
Authors: Hernández-Alvarez María Isabel , Zorzano Antonio
Published: May 2021

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Due to its rising incidence and limited therapeutic options, HCC has become a leading cause of cancer-related death worldwide, accounting for 85% of all deaths due to primary liver cancers. Standard therapy for advanced-stage HCC is based on anti-angiogenic drugs such as sorafenib and, more recently, lenvatinib and regorafenib as a second line of treatment. The identification of novel therapeutic strategies is urgently required. Mitochondrial dynamics describes a group of processes that includes the movement of mitochondria along the cytoskeleton, the regulation of mitochondrial morphology and distribution, and connectivity mediated by tethering and fusion/fission events. In recent years, mitochondrial dynamic processes have emerged as key processes in the maintenance of liver mitochondrial homeostasis. In addition, some data are accumulating on the role played by mitochondrial dynamics during cancer development, and specifically on how such dynamics act directly on tumor cells or indirectly on cells responsible for tumor aggression and defense. Here, we review the data that suggest mitochondrial dynamics to be involved in the development of liver tumors.
Immobilization of an Iridium(I)-NHC-Phosphine Catalyst for Hydrogenation Reactions under Batch and Flow Conditions
Authors: Kovács Henrietta , Orosz Krisztina , Papp Gábor , Joó Ferenc , Horváth Henrietta
Published: May 2021

Na2[Ir(cod)(emim)(mtppts)] (1) with high catalytic activity in various organic- and aqueous-phase hydrogenation reactions was immobilized on several types of commercially available ion-exchange supports. The resulting heterogeneous catalyst was investigated in batch reactions and in an H-Cube flow reactor in the hydrogenation of phenylacetylene, diphenylacetylene, 1-hexyne, and benzylideneacetone. Under proper conditions, the catalyst was highly selective in the hydrogenation of alkynes to alkenes, and demonstrated excellent selectivity in C=C over C=O hydrogenation; furthermore, it displayed remarkable stability. Activity of 1 in hydrogenation of levulinic acid to γ-valerolactone was also assessed.
Thermogravimetry of the Steam Gasification of Calluna vulgaris: Kinetic Study
Authors: Encinar José María , González Juan Félix , Nogales-Delgado Sergio
Published: May 2021

On account of the continuous decrease in oil reserves, as well as the promotion of sustainable policies, there is an increasing interest in biomass conversion processes, which imply the search for new raw materials as energy sources, like forestry and agricultural wastes. On the other hand, gasification seems to be a suitable thermal conversion process for this purpose. This work studied the thermogravimetry of the steam gasification of charcoal from heather (Calluna vulgaris) in order to determine the kinetics of the process under controlled reaction conditions. The variables studied were temperature (from 750 to 900 °C), steam partial pressure (from 0.26 to 0.82 atm), initial charcoal mass (from 50 to 106 mg), particle size (from 0.4 to 2.0 mm), N2 and steam volumetric flows (from 142 to 446 mL·min−1) and catalyst (K2CO3) concentration (from 0 to 10% w/w). The use of the shrinking core model and uniform conversion model allowed us to determine the kinetic parameters of the process. As a result, a positive influence of catalyst concentration was found up to 7.5% w/w. The kinetic study of the catalytic steam gasification showed activation energies of 99.5 and 114.8 kJ·mol−1 and order of reactions (for steam) of 1/2 and 2/3.
Two Types of PPARγ Ligands Identified in the Extract of Artemisia campestris
Authors: Hasegawa Tokio , Osaka Mayo , Miyamae Yusaku , Nishino Katsutoshi , Isoda Hiroko , Kawada Kiyokazu , Neffati Mohamed , Irie Kazuhiro , Nagao Masaya
Published: May 2021

The 70% ethanol extract of Artemisia campestris was screened to find PPARγ ligands using the PPARγ ligand-responsive chimera luciferase reporter system. Capillartemisin B was identified as a PPARγ ligand that stimulated lipid accumulation in 3T3-L1 cells. By further purification of PPARγ ligands from a large-scale preparation of the methanol extract of Artemisia campestris, we isolated and identified eupatilin and santaflavone as PPARγ ligands. Weak PPARγ ligand activity of eupatilin or santaflavone in reporter assay was enhanced by a PPARγ antagonist, GW9662, suggesting that santaflavone or eupatilin and GW9662 bound simultaneously to the multiple sub-pockets of the PPARγ ligand-binding domain (LBD) and cooperatively activated PPARγ. Docking simulation suggested that eupatilin binds to the Ω-pocket but not to the AF-2 pocket of Y-shaped PPARγ LBD where artepillin C that differs from capillartemisin B at the C-5′ position without hydroxy group binds. Eupatilin or santaflavone with or without GW9662 did not stimulate lipid accumulation in differentiated 3T3-L1 cells, suggesting that binding of each compound alone or with GW9662 to the Ω-pocket which stimulated the PPARγ-responsive reporter expression was not enough to stimulate lipid accumulation. The PPARγ ligands found in this study have a potential to design the fragment-based drug design of a novel PPARγ ligand that cover the Y-shaped PPARγ LBD.
Ru-Doped Single Walled Carbon Nanotubes as Sensors for SO2 and H2S Detection
Authors: Kuganathan Navaratnarajah , Chroneos Alexander
Published: May 2021

Carbon nanotubes are of great interest for their ability to functionalize with atoms for adsorbing toxic gases such as CO, NO, and NO2. Here, we use density functional theory in conjunction with dispersion correction to examine the encapsulation and adsorption efficacy of SO2 and H2S molecules by a (14,0) carbon nanotube and its substitutionally doped form with Ru. Exoergic encapsulation and adsorption energies are calculated for pristine nanotubes. The interaction of molecules with pristine nanotube is non-covalent as confirmed by the negligible charge transfer. The substitutional doping of Ru does not improve the encapsulation significantly. Nevertheless, there is an important enhancement in the adsorption of molecules by Ru-doped (14,0) nanotube. Such strong adsorption is confirmed by the strong chemical interaction between the nanotube and molecules. The promising feature of Ru-doped nanotubes can be tested experimentally for SO2 and H2S gas sensing.
Lung Cancer Inequalities in Stage of Diagnosis in Ontario, Canada
Authors: Lofters Aisha K. , Gatov Evgenia , Lu Hong , Baxter Nancy N. , Guilcher Sara J. T. , Kopp Alexander , Vahabi Mandana , Datta Geetanjali D.
Published: May 2021

Lung cancer is the most common cancer and cause of cancer death in Canada, with approximately 50% of cases diagnosed at stage IV. Sociodemographic inequalities in lung cancer diagnosis have been documented, but it is not known if inequalities exist with respect to immigration status. We used multiple linked health-administrative databases to create a cohort of Ontarians 40–105 years of age who were diagnosed with an incident lung cancer between 1 April 2012 and 31 March 2017. We used modified Poisson regression with robust standard errors to examine the risk of diagnosis at late vs. early stage among immigrants compared to long-term residents. The fully adjusted model included age, sex, neighborhood-area income quintile, number of Aggregated Diagnosis Group (ADG) comorbidities, cancer type, number of prior primary care visits, and continuity of care. Approximately 62% of 38,788 people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. Immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents (63.5% vs. 62.0%, relative risk (RR): 1.01 (95% confidence interval (CI): 0.99–1.04), adjusted relative risk (ARR): 1.02 (95% CI: 0.99–1.05)). However, in fully adjusted models, people with more comorbidities were less likely to have a late-stage diagnosis (adjusted relative risk (ARR): 0.82 (95% CI: 0.80–0.84) for those with 10+ vs. 0–5 ADGs). Compared to adenocarcinoma, small cell carcinoma was more likely to be diagnosed at a late stage (ARR: 1.29; 95% CI: 1.27–1.31), and squamous cell (ARR: 0.89; 95% CI: 0.87–0.91) and other lung cancers (ARR: 0.93; 95% CI: 0.91–0.94) were more likely to be diagnosed at an early stage. Men were also slightly more likely to have late-stage diagnosis in the fully adjusted model (ARR: 1.08; 95% CI: 1.05–1.08). Lung cancer in Ontario is a high-fatality cancer that is frequently diagnosed at a late stage. Having fewer comorbidities and being diagnosed with small cell carcinoma was associated with a late-stage diagnosis. The former group may have less health system contact, and the latter group has the lung cancer type most closely associated with smoking. As lung cancer screening programs start to be implemented across Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care should be system priorities.
A Case of Pathological Complete Response and Resolution of Dermatomyositis Following Neoadjuvant Chemotherapy in HER2-Positive Early Breast Cancer
Authors: Piras Marta , Panebianco Martina , Garibaldi Matteo , Roberto Michela , Merlonghi Gioia , Pellegrini Patrizia , Marchetti Paolo
Published: May 2021

Introduction. Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) mainly characterized by subacute muscle weakness and skin rash sometimes associated with malignancy. Case Presentation. A 61-year-old female was admitted to our hospital because of progressive proximal muscular weakness, heliotropic rash and left breast rash. Muscle biopsy findings were consistent with dermatomyositis (DM). A full panel of myositis associated (MAA) and specific antibodies (MSA) revealed the presence of anti-nuclear antibodies (1:160, speckled), Anti-Ro52 and anti TIF1-γ antibodies. A whole body Computed Tomography Scan showed three left mammary nodules and homolateral axillary lymphadenopathy. The breast biopsy confirmed the diagnosis of ductal carcinoma. Patient was initiated to neoadjuvant chemotherapy followed by surgery for cancer, and corticosteroid and intravenous immunoglobulins for DM with a complete resolution of muscle weakness and pathological complete response of breast cancer. Discussion and conclusion. Similar cases in literature are commonly referred to a first-line surgery and the role of neoadjuvant chemotherapy is debatable.
The Chairside Periodontal Diagnostic Toolkit: Past, Present, and Future
Authors: Ko Tae-Jun , Byrd Kevin M. , Kim Shin Ae
Published: May 2021

Periodontal diseases comprise a group of globally prevalent, chronic oral inflammatory conditions caused by microbial dysbiosis and the host immune response. These diseases specifically affect the tooth-supporting tissues (i.e., the periodontium) but are also known to contribute to systemic inflammation. If left untreated, periodontal diseases can ultimately progress to tooth loss, lead to compromised oral function, and negatively impact the overall quality of life. Therefore, it is important for the clinician to accurately diagnose these diseases both early and accurately chairside. Currently, the staging and grading of periodontal diseases are based on recording medical and dental histories, thorough oral examination, and multiple clinical and radiographic analyses of the periodontium. There have been numerous attempts to improve, automate, and digitize the collection of this information with varied success. Recent studies focused on the subgingival microbiome and the host immune response suggest there is an untapped potential for non-invasive oral sampling to assist clinicians in the chairside diagnosis and, potentially, prognosis. Here, we review the available toolkit available for diagnosing periodontal diseases, discuss commercially available options, and highlight the need for collaborative research initiatives and state-of-the-art technology development across disciplines to overcome the challenges of rapid periodontal disease diagnosis.
Towards Accurate Diagnosis of Skin Lesions Using Feedforward Back Propagation Neural Networks
Authors: Moldovanu Simona , Obreja Cristian-Dragos , Biswas Keka C. , Moraru Luminita
Published: May 2021

In the automatic detection framework, there have been many attempts to develop models for real-time melanoma detection. To effectively discriminate benign and malign skin lesions, this work investigates sixty different architectures of the Feedforward Back Propagation Network (FFBPN), based on shape asymmetry for an optimal structural design that includes both the hidden neuron number and the input data selection. The reason for the choice of shape asymmetry was based on the 5–10% disagreement between dermatologists regarding the efficacy of asymmetry in the diagnosis of malignant melanoma. Asymmetry is quantified based on lesion shape (contour), moment of inertia of the lesion shape and histograms. The FFBPN has a high architecture flexibility, which indicates it as a favorable tool to avoid the over-parameterization of the ANN and, equally, to discard those redundant input datasets that usually result in poor test performance. The FFBPN was tested on four public image datasets containing melanoma, dysplastic nevus and nevus images. Experimental results on multiple benchmark data sets demonstrate that asymmetry A2 is a meaningful feature for skin lesion classification, and FFBPN with 16 neurons in the hidden layer can model the data without compromising prediction accuracy.
Relationship between Retinal Microvasculature, Cardiovascular Risk and Silent Brain Infarction in Hypertensive Patients
Authors: Forés Rosa , Manresa Josep M. , López-Lifante Victor M. , Heras Antonio , Delgado Pilar , Vázquez Xose , Ruiz Susana , Alzamora Maria Teresa , Toran Pere
Published: May 2021

Objective: The aims of this study are to analyze the role of artery-vein ratio AVR assessment using VesselMap 2 software (Imedos Systems) and cardiovascular risk evaluation by means of REGICOR in the prediction of silent brain infarction (SBI) in middle-age hypertensive patients from the ISSYS study. Material and Methods: A cross-sectional study with 695 patients with hypertension aged 50 to 70 years who participated in the project Investigating Silent Strokes in HYpertensives: a Magnetic Resonance Imaging Study (ISSYS), was conducted in two Primary Care Centres of Barcelona. Participants agreed to a retinography and an MRI to detect silent brain infarction (SBI). The IMEDOS software was used for the semiautomatic caliber measurement of retinal arteries and veins, and the AVR was considered abnormal when <0.66. The REGICOR score was calculated for all patients. Results: Multivariate logistic regression analysis was used to evaluate the impact of AVR and REGICOR scores on SBI. The OR (odds ratio) for a high REGICOR score and an abnormal AVR were 3.16 and 4.45, respectively. When analysing the interaction of both factors, the OR of an abnormal AVR and moderate REGICOR score was 3.27, whereas with a high REGICOR score it reached 13.07. Conclusions: The measurement of AVR in patients with hypertension and with a high REGICOR score can contribute to the detection of silent brain infarction.
The Association of Lumbar Disc Herniation with Lumbar Volumetric Bone Mineral Density in a Cross-Sectional Chinese Study
Authors: Geng Jian , Wang Ling , Li Qing , Huang Pengju , Liu Yandong , Blake Glen M. , Tian Wei , Cheng Xiaoguang
Published: May 2021

Little is known about the effect of lumbar intervertebral disc herniation (LDH) on lumbar bone mineral density (BMD), and few previous studies have used quantitative computed tomography (QCT) to assess whether the staging of LDH correlates with lumbar vertebral trabecular volumetric bone mineral density (Trab.vBMD). To explore the relationship between lumbar Trab.vBMD and LDH, seven hundred and fifty-four healthy participants aged 20–60 years were enrolled in the study from an ongoing study on the degeneration of the spine and knee between June 2014 and 2017. QCT was used to measure L2–4 Trab.vBMD and lumbar spine magnetic resonance images (MRI) were performed to assess the incidence of disc herniation. After 9 exclusions, a total of 322 men and 423 women remained. The men and women were divided into younger (age 20–39 years) and older (age 40–60 years) groups and further into those without LDH, with a single LDH segment, and with ≥2 segments. Covariance analysis was used to adjust for the effects of age, BMI, waistline, and hipline on the relationship between Trab.vBMD and LDH. Forty-one younger men (25.0%) and 59 older men (37.3%) had at least one LDH segment. Amongst the women, the numbers were 46 (22.5%) and 80 (36.4%), respectively. Although there were differences in the characteristics data between men and women, the difference in Trab.vBMD between those without LDH and those with single and ≥2 segments was not statistically significant (p > 0.05). These results remained not statistically significant after further adjusting for covariates (p > 0.05). No associations between lumbar disc herniation and vertebral trabecular volumetric bone mineral density were observed in either men or women.