bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Comparison of Protocols for Recovery of High-Quality RNA from Human Islets Extracted by Laser Capture Microdissection
Authors: Cefalo Chiara M. A. , Mezza Teresa , Giaccari Andrea , Kulkarni Rohit N.
Published: April 2021

The isolation of high-quality RNA from endocrine pancreas sections represents a considerable challenge largely due to the high ribonuclease levels. Laser capture microdissection (LCM) of mammalian islets, in association with RNA extraction protocols, has emerged as a feasible approach to characterizing their genetic and proteomic profiles. However, a validated protocol to obtain high-quality RNA from LCM-derived human pancreas specimens that is appropriate for next-generation sequencing analysis is still lacking. In this study, we applied four methods (Picopure extraction kit, Qiazol protocol, Qiazol + Clean-up kit, and RNeasy Microkit + Carrier) to extract RNA from human islets obtained from both non-diabetic individuals and patients with type 2 diabetes who had undergone partial pancreatectomy, as well as handpicked islets from both non-diabetic and diabetic organ donors. The yield and purity of total RNA were determined by 260/280 absorbance using Nanodrop 100 and the RNA integrity number with a bioanalyzer. The results indicated that among the four methods, the RNeasy MicroKit + Carrier (Qiagen) provides the highest yield and purity.
Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions
Authors: Shnayder Natalia A. , Petrova Marina M. , Shesternya Pavel A. , Savinova Alina V. , Bochanova Elena N. , Zimnitskaya Olga V. , Pozhilenkova Elena A. , Nasyrova Regina F.
Published: April 2021

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.
mRNA Profiles of Porcine Parathyroid Glands Following Variable Phosphorus Supplies throughout Fetal and Postnatal Life
Authors: Oster Michael , Reyer Henry , Gerlinger Christian , Trakooljul Nares , Siengdee Puntita , Keiler Jonas , Ponsuksili Siriluck , Wolf Petra , Wimmers Klaus
Published: April 2021

Knowledge of gene expression profiles reflecting functional features and specific responsiveness of parathyroid glands (PTGs) contributes to understanding mineral homeostasis and parathyroid function in healthy and diseased conditions. The study aims to reveal effector molecules driving the maintenance of phosphorus (P) homeostasis and parathyroid hormone (PTH) responsiveness to variable P supply throughout fetal and postnatal life. In this study, a long-term dietary intervention was performed by keeping pig offspring on distinct mineral P levels throughout fetal and postnatal life. Respective adaptation processes of P homeostasis were assessed in mRNA profiles of PTGs and serum minerals. RNA sequencing data and resulting molecular pathways of PTGs showed that the PTH abundance is very strictly controlled via e.g., PIN1, CaSR, MAfB, PLC and PKA signaling to regulate PTH expression, stability, and secretion. Additionally, the observed dietary effects on collagen expression indicate shifts in the ratio between connective tissue and parenchyma, thereby affecting cell-cell contacts as another line of PTH regulation. Taken together, the mRNA profiles of porcine PTGs reflect physiological responses in-vivo following variable dietary P supplies during fetal and postnatal life. The results serve to evaluate a long-term nutrition strategy with implications for improving the mineral balance in individuals with pathological disorders.
Translational Attenuation by an Intron Retention in the 5′ UTR of ENAM Causes Amelogenesis Imperfecta
Authors: Kim Youn Jung , Lee Yejin , Zhang Hong , Wright John Timothy , Simmer James P. , Hu Jan C.-C. , Kim Jung-Wook
Published: April 2021

Amelogenesis imperfecta (AI) is a collection of rare genetic conditions affecting tooth enamel. The affected enamel can be of insufficient quantity and/or altered quality, impacting structural content, surface integrity and coloration. Heterozygous mutations in ENAM result in hypoplastic AI without other syndromic phenotypes, with variable expressivity and reduced penetrance, unlike other AI-associated genes. In this study, we recruited a Caucasian family with hypoplastic AI. Mutational analysis (using whole exome sequencing) revealed a splicing donor site mutation (NM_031889.3: c. −61 + 1G > A). Mutational effects caused by this variant were investigated with a minigene splicing assay and in vitro expression analysis. The mutation resulted in a retention of intron 1 and exon 2 (a normally skipped exon), and this elongated 5′ UTR sequence attenuated the translation from the mutant mRNA. Structure and translation predictions raised the possibility that the long complex structures—especially a hairpin structure located right before the translation initiation codon of the mutant mRNA—caused reduced protein expression. However, there could be additional contributing factors, including additional uORFs. For the first time, we determined that a mutation altered the ENAM 5′ UTR, but maintained the normal coding amino acid sequence, causing hypoplastic AI.
A Novel Fluorescent Probe for Selective Detection of Hydrazine and Its Application in Imaging
Authors: Man Ruo-Jun , Wu Meng-Ke , Yang Bing , Yang Yu-Shun
Published: April 2021

In this work, a novel fluorescent probe with first-time-selected thiazepine backbone, TZPzine-1, was developed for selective detection of hydrazine in water samples and living cells. Chosen from our recent anti-cancer agents, TZPzine-1 inferred structurally based advantages of the optical adjustability and the hydrazine-trapping approach. It also showed applicable properties including high sensitivity (LOD = 50 nM), wide linear range (0–15 equiv.), high selectivity (especially from competing species), rapid response (within 20 min), and practical steadiness in various pH (6.0–11.0) and temperature (15–50 °C) conditions. To satisfy the interdisciplinary requirements in environmental toxicology, TZPzine-1 was successfully applied in water samples and living cells. We hope that the information in this work, as well as the concept of monitoring the nitrogen cycle, may be referable for future research on systematic management.
Impact of Graphene or Reduced Graphene Oxide on Performance of Thermoelectric Composites
Authors: Okhay Olena , Tkach Alexander
Published: April 2021

In recent years, worldwide research has been focused on clean and sustainable energy sources that can respond to the exponentially rising energy demands of humankind. The harvesting of unused heat in relation to automotive exhaustion, industrial processes, and home heating is one possible way of enabling the transformation from a fossil fuel-based society to a low-carbon socioeconomic epoch. Thermoelectric (TE) generators can convert heat to electrical energy thanks to high-performance TE materials that work via Seebeck effects when electricity appears between the cold part and the hot part of these materials. High figure of merit (ZT) TE material is characterized by high electrical conductivity and Seebeck coefficient, together with low thermal conductivity. This article aims to summarize ZT values reported for chalcogenides, skutterudites, and metal oxides with graphene (G) or reduced graphene oxide (rGO), and intends to understand the relationship between the addition of G-rGO to composites and ZT variation. In a majority of the publications, ZT value increases with the addition of G/rGO, although the relative growth of ZT varies for different material families, as well as inside the same group of materials, with it often being related not to a G/rGO amount but with the quality of the composite.
A Neural Network Approach to Identify Glioblastoma Progression Phenotype from Multimodal MRI
Authors: Yan Jiun-Lin , Toh Cheng-Hong , Ko Li , Wei Kuo-Chen , Chen Pin-Yuan
Published: April 2021

The phenotypes of glioblastoma (GBM) progression after treatment are heterogeneous in both imaging and clinical prognosis. This study aims to apply radiomics and neural network analysis to preoperative multimodal MRI data to characterize tumor progression phenotypes. We retrospectively reviewed 41 patients with newly diagnosed cerebral GBM from 2009–2016 who comprised the machine learning training group, and prospectively included 18 patients from 2017–2018 for data validation. Preoperative MRI examinations included structural MRI, diffusion tensor imaging, and perfusion MRI. Tumor progression patterns were categorized as diffuse or localized. A supervised machine learning model and neural network-based models (VGG16 and ResNet50) were used to establish the prediction model of the pattern of progression. The diffuse progression pattern showed a significantly worse prognosis regarding overall survival (p = 0.032). A total of 153 of the 841 radiomic features were used to classify progression patterns using different machine learning models with an overall accuracy of 81% (range: 77.5–82.5%, AUC = 0.83–0.89). Further application of the pretrained ResNet50 and VGG 16 neural network models demonstrated an overall accuracy of 93.1 and 96.1%. The progression patterns of GBM are an important prognostic factor and can potentially be predicted by combining multimodal MR radiomics with machine learning.
Dosimetric Analysis of the Short-Ranged Particle Emitter 161Tb for Radionuclide Therapy of Metastatic Prostate Cancer
Authors: Bernhardt Peter , Svensson Johanna , Hemmingsson Jens , van der Meulen Nicholas P. , Zeevaart Jan Rijn , Konijnenberg Mark W. , Müller Cristina , Kindblom Jon
Published: April 2021

The aim of this study was to analyze the required absorbed doses to detectable metastases (Dreq) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4–6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The Dreq was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The Dreq for iodine-131 and yttrium-90 was high (920–3300 Gy). The Dreq for lutetium-177 was between 560 and 780 Gy and considerably lower Dreq were obtained for actinium-225 and terbium-161, with 240–330 Gy and 210–280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.
Performance Comparison of Deep Learning Autoencoders for Cancer Subtype Detection Using Multi-Omics Data
Authors: Franco Edian F. , Rana Pratip , Cruz Aline , Calderón Víctor V. , Azevedo Vasco , Ramos Rommel T. J. , Ghosh Preetam
Published: April 2021

A heterogeneous disease such as cancer is activated through multiple pathways and different perturbations. Depending upon the activated pathway(s), the survival of the patients varies significantly and shows different efficacy to various drugs. Therefore, cancer subtype detection using genomics level data is a significant research problem. Subtype detection is often a complex problem, and in most cases, needs multi-omics data fusion to achieve accurate subtyping. Different data fusion and subtyping approaches have been proposed over the years, such as kernel-based fusion, matrix factorization, and deep learning autoencoders. In this paper, we compared the performance of different deep learning autoencoders for cancer subtype detection. We performed cancer subtype detection on four different cancer types from The Cancer Genome Atlas (TCGA) datasets using four autoencoder implementations. We also predicted the optimal number of subtypes in a cancer type using the silhouette score and found that the detected subtypes exhibit significant differences in survival profiles. Furthermore, we compared the effect of feature selection and similarity measures for subtype detection. For further evaluation, we used the Glioblastoma multiforme (GBM) dataset and identified the differentially expressed genes in each of the subtypes. The results obtained are consistent with other genomic studies and can be corroborated with the involved pathways and biological functions. Thus, it shows that the results from the autoencoders, obtained through the interaction of different datatypes of cancer, can be used for the prediction and characterization of patient subgroups and survival profiles.
Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo
Authors: Sharvit Lital , Bar-Shalom Rinat , Azzam Naiel , Yechiel Yaniv , Wasser Solomon , Fares Fuad
Published: April 2021

Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.
Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma
Authors: Uckun Fatih M.
Published: April 2021

SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, “alternatively activated” macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as promising therapeutic platforms that can be employed in various combinations as part of a rationally designed immunomodulatory strategy against an immunosuppressive tumor microenvironment (TME) in MM. These platforms provide the foundation for a new therapeutic paradigm for achieving improved survival of high-risk newly diagnosed as well as relapsed/refractory MM patients. Here we review the scientific rationale and clinical proof of concept for each of these platforms.
Mitochondrial ATP-Dependent Proteases—Biological Function and Potential Anti-Cancer Targets
Authors: Feng Yue , Nouri Kazem , Schimmer Aaron D.
Published: April 2021

Cells must eliminate excess or damaged proteins to maintain protein homeostasis. To ensure protein homeostasis in the cytoplasm, cells rely on the ubiquitin-proteasome system and autophagy. In the mitochondria, protein homeostasis is regulated by mitochondria proteases, including four core ATP-dependent proteases, m-AAA, i-AAA, LonP, and ClpXP, located in the mitochondrial membrane and matrix. This review will discuss the function of mitochondrial proteases, with a focus on ClpXP as a novel therapeutic target for the treatment of malignancy. ClpXP maintains the integrity of the mitochondrial respiratory chain and regulates metabolism by degrading damaged and misfolded mitochondrial proteins. Inhibiting ClpXP genetically or chemically impairs oxidative phosphorylation and is toxic to malignant cells with high ClpXP expression. Likewise, hyperactivating the protease leads to increased degradation of ClpXP substrates and kills cancer cells. Thus, targeting ClpXP through inhibition or hyperactivation may be novel approaches for patients with malignancy.
From Proteomic Mapping to Invasion-Metastasis-Cascade Systemic Biomarkering and Targeted Drugging of Mutant BRAF-Dependent Human Cutaneous Melanomagenesis
Authors: Giannopoulou Aikaterini F. , Velentzas Athanassios D. , Anagnostopoulos Athanasios K. , Agalou Adamantia , Papandreou Nikos C. , Katarachia Stamatia A. , Koumoundourou Dimitra G. , Konstantakou Eumorphia G. , Pantazopoulou Vasiliki I. , Delis Anastasios , Michailidi Maria T. , Valakos Dimitrios , Chatzopoulos Dimitris , Syntichaki Popi , Iconomidou Vassiliki A. , Tsitsilonis Ourania E. , Papassideri Issidora S. , Voutsinas Gerassimos E. , Hatzopoulos Polydefkis , Thanos Dimitris , Beis Dimitris , Anastasiadou Ema , Tsangaris George Th. , Stravopodis Dimitrios J.
Published: April 2021

Melanoma is classified among the most notoriously aggressive human cancers. Despite the recent progress, due to its propensity for metastasis and resistance to therapy, novel biomarkers and oncogenic molecular drivers need to be promptly identified for metastatic melanoma. Hence, by employing nano liquid chromatography-tandem mass spectrometry deep proteomics technology, advanced bioinformatics algorithms, immunofluorescence, western blotting, wound healing protocols, molecular modeling programs, and MTT assays, we comparatively examined the respective proteomic contents of WM115 primary (n = 3955 proteins) and WM266-4 metastatic (n = 6681 proteins) melanoma cells. It proved that WM115 and WM266-4 cells have engaged hybrid epithelial-to-mesenchymal transition/mesenchymal-to-epithelial transition states, with TGF-β controlling their motility in vitro. They are characterized by different signatures of SOX-dependent neural crest-like stemness and distinct architectures of the cytoskeleton network. Multiple signaling pathways have already been activated from the primary melanoma stage, whereas HIF1α, the major hypoxia-inducible factor, can be exclusively observed in metastatic melanoma cells. Invasion-metastasis cascade-specific sub-routines of activated Caspase-3-triggered apoptosis and LC3B-II-dependent constitutive autophagy were also unveiled. Importantly, WM115 and WM266-4 cells exhibited diverse drug response profiles, with epirubicin holding considerable promise as a beneficial drug for metastatic melanoma clinical management. It is the proteome navigation that enables systemic biomarkering and targeted drugging to open new therapeutic windows for advanced disease.
Late Recurrence in Breast Cancer: To Run after the Oxen or to Try to Close the Barn?
Authors: Demicheli Romano , Biganzoli Elia
Published: April 2021

The problem of late recurrence in breast cancer has recently gained attention and was also addressed in an international workshop held in Toronto (ON, Canada), in which several aspects of the question were examined. This Commentary offers a few considerations, which may be useful for the ongoing investigations. A few premises are discussed: (a) clinical recurrences, especially the late ones, imply periods of tumor dormancy; (b) a structured pattern of distant metastases appearance is detectable in both early and late follow-up times; (c) the current general paradigm underlying neoplastic treatments, i.e., that killing all cancer cells is the only way to control the disease, which is strictly sprouting from the somatic mutation theory, should be re-considered. Finally, a few research approaches are suggested.
Strategies to Use Nanofiber Scaffolds as Enzyme-Based Biocatalysts in Tissue Engineering Applications
Authors: Wani Taha Umair , Rather Anjum Hamid , Khan Rumysa Saleem , Beigh Mushtaq A. , Park Mira , Pant Bishweshwar , Sheikh Faheem A.
Published: April 2021

Nanofibers are considered versatile materials with remarkable potential in tissue engineering and regeneration. In addition to their extracellular matrix-mimicking properties, nanofibers can be functionalized with specific moieties (e.g., antimicrobial nanoparticles, ceramics, bioactive proteins, etc.) to improve their overall performance. A novel approach in this regard is the use of enzymes immobilized onto nanofibers to impart biocatalytic activity. These nanofibers are capable of carrying out the catalysis of various biological processes that are essential in the healing process of tissue. In this review, we emphasize the use of biocatalytic nanofibers in various tissue regeneration applications. Biocatalytic nanofibers can be used for wound edge or scar matrix digestion, which reduces the hindrance for cell migration and proliferation, hence displaying applications in fast tissue repair, e.g., spinal cord injury. These nanofibers have potential applications in bone regeneration, mediating osteogenic differentiation, biomineralization, and matrix formation through direct enzyme activity. Moreover, enzymes can be used to undertake efficient crosslinking and fabrication of nanofibers with better physicochemical properties and tissue regeneration potential.
Highly CO Selective Trimetallic Metal-Organic Framework Electrocatalyst for the Electrochemical Reduction of CO2
Authors: Phuc Tran-Van , Chung Jin-Suk , Hur Seung-Hyun
Published: April 2021

Pd, Cu, and Zn trimetallic metal-organic framework electrocatalysts (PCZs) based on benzene-1,3,5-tricarboxylic were synthesized using a simple solvothermal synthesis. The as-synthesized PCZ catalysts exhibited as much as 95% faradaic efficiency towards CO, with a high current density, low onset potential, and excellent long-term stability during the electrocatalytic reduction of CO2.
Catalyst Modeling Challenges for Electrified Powertrains
Authors: Souliotis Thomas , Koltsakis Grigorios , Samaras Zissis
Published: April 2021

To meet the upcoming CO2 reduction challenges, the further electrification of vehicle powertrains is indispensable. In combination with the post-Euro 6 requirements for criteria pollutants, the exhaust system is expected to be more complex to allow for extremely low emissions under all driving conditions, potentially involving technologies such as electrical heating and phase-change materials. The longer ‘zero-flow’ operation of the exhaust system in hybrid applications and the associated light-out risk have demanding accuracy requirements for heat loss calculations and require additional thermal management strategies. This paper discusses the additional challenges posed with regard to catalyst modeling in the boundary conditions of electrified vehicles and the necessary improvements that go beyond the state-of-the-art techniques. Most of the necessary improvements are linked to advanced 3D modeling of the exhaust system components accounting for free convection and radiative heat transfer. Modeling of electrically assisted heating is demonstrated using a new approach involving a combined 3D electrical–thermal solver. Heat retention technologies with use of phase-change materials are also accounted for in these new-generation models. Finally, the need for a tighter integration of these high-fidelity models into a vehicle simulation framework is discussed.
Identification of 15 lncRNAs Signature for Predicting Survival Benefit of Advanced Melanoma Patients Treated with Anti-PD-1 Monotherapy
Authors: Zhou Jian-Guo , Liang Bo , Liu Jian-Guo , Jin Su-Han , He Si-Si , Frey Benjamin , Gu Ning , Fietkau Rainer , Hecht Markus , Ma Hu , Gaipl Udo S.
Published: April 2021

The blockade of programmed cell death protein 1 (PD-1) as monotherapy has been widely used in melanoma, but to identify melanoma patients with survival benefit from anti-PD-1 monotherapy is still a big challenge. There is an urgent need for prognostic signatures improving the prediction of immunotherapy responses of these patients. We analyzed transcriptomic data of pre-treatment tumor biopsies and clinical profiles in advanced melanoma patients receiving only anti-PD-1 monotherapy (nivolumab or pembrolizumab) from the PRJNA356761 and PRJEB23709 data sets as the training and validation cohort, respectively. Weighted gene co-expression network analysis was used to identify the key module, then least absolute shrinkage and selection operator was conducted to determine prognostic-related long noncoding RNAs (lncRNAs). Subsequently, the differentially expressed genes between different clusters were identified, and their function and pathway annotation were performed. In this investigation, 92 melanoma patients with complete survival information (51 from training cohort and 41 from validation cohort) were included in our analyses. We initiallyidentified the key module (skyblue) by weighted gene co-expression network analysis, and then identified a 15 predictive lncRNAs (AC010904.2, LINC01126, AC012360.1, AC024933.1, AL442128.2, AC022211.4, AC022211.2, AC127496.5, NARF-AS1, AP000919.3, AP005329.2, AC023983.1, AC023983.2, AC139100.1, and AC012615.4) signature in melanoma patients treated with anti-PD-1 monotherapy by least absolute shrinkage and selection operator in the training cohort. These results were then validated in the validation cohort. Finally, enrichment analysis showed that the functions of differentially expressed genes between two consensus clusters were mainly related to the immune process and treatment. In summary, the 15 lncRNAs signature is a novel effective predictor for prognosis in advanced melanoma patients treated with anti-PD-1 monotherapy.
Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers
Authors: Santos Joao , Heiniö Camilla , Quixabeira Dafne , Zafar Sadia , Clubb James , Pakola Santeri , Cervera-Carrascon Victor , Havunen Riikka , Kanerva Anna , Hemminki Akseli
Published: April 2021

Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers.
Updated Mechanisms of GCN5—The Monkey King of the Plant Kingdom in Plant Development and Resistance to Abiotic Stresses
Authors: Gan Lei , Wei Zhenzhen , Yang Zuoren , Li Fuguang , Wang Zhi
Published: April 2021

Histone modifications are the main epigenetic mechanisms that regulate gene expression, chromatin structure, and plant development, among which histone acetylation is one of the most important and studied epigenetic modifications. Histone acetylation is believed to enhance DNA access and promote transcription. GENERAL CONTROL NON-REPRESSIBLE 5 (GCN5), a well-known enzymatic protein responsible for the lysine acetylation of histone H3 and H4, is a universal and crucial histone acetyltransferase involved in gene transcription and plant development. Many studies have found that GCN5 plays important roles in the different development stages of Arabidopsis. In terms of exogenous stress conditions, GCN5 is also involved in the responses to heat stress, cold stress, and nutrient element deficiency by regulating the related gene expression to maintain the homeostasis of some key metabolites (e.g., cellulose) or ions (e.g., phosphate, iron); in addition, GCN5 is involved in the phytohormone pathways such as ethylene, auxin, and salicylic acid to play various roles during the plant lifecycle. Some of the pathways involved by GCN5 also interwind to regulate specific physiological processes or developmental stages. Here, interactions between various developmental events and stress-resistant pathways mediated by GCN5 are comprehensively addressed and the underlying mechanisms are discussed in the plant. Studies with some interacting factors such as ADA2b provided valuable information for the complicated histone acetylation mechanisms. We also suggest the future focuses for GCN5 functions and mechanisms such as functions in seed development/germination stages, exploration of novel interaction factors, identification of more protein substrates, and application of advanced biotechnology-CRISPR in crop genetic improvement, which would be helpful for the complete illumination of roles and mechanisms of GCN5.
Macrophages and Immune Responses in Uterine Fibroids
Authors: Zannotti Alessandro , Greco Stefania , Pellegrino Pamela , Giantomassi Federica , Delli Carpini Giovanni , Goteri Gaia , Ciavattini Andrea , Ciarmela Pasquapina
Published: April 2021

Uterine fibroids represent the most common benign tumors of the uterus. They are considered a typical fibrotic disorder. In fact, the extracellular matrix (ECM) proteins—above all, collagen 1A1, fibronectin and versican—are upregulated in this pathology. The uterine fibroids etiology has not yet been clarified, and this represents an important matter about their resolution. A model has been proposed according to which the formation of an altered ECM could be the result of an excessive wound healing, in turn driven by a dysregulated inflammation process. A lot of molecules act in the complex inflammatory response. Macrophages have a great flexibility since they can assume different phenotypes leading to the tissue repair process. The dysregulation of macrophage proliferation, accumulation and infiltration could lead to an uncontrolled tissue repair and to the consequent pathological fibrosis. In addition, molecules such as monocyte chemoattractant protein-1 (MCP-1), granulocyte macrophage-colony-stimulating factor (GM-CSF), transforming growth factor-beta (TGF-β), activin A and tumor necrosis factor-alfa (TNF-α) were demonstrated to play an important role in the macrophage action within the uncontrolled tissue repair that contributes to the pathological fibrosis that represents a typical feature of the uterine fibroids.
Fast-Onset Diffuse Interstitial Lung Disease in Anti-MDA5 Antibodies-Associated Amyopathic Dermatomyositis
Authors: Aissaoui Houari , Alsibai Kinan Drak , Khayath Naji
Published: April 2021

Anti-MDA5 antibodies-associated amyopathic dermatomyositisis a rare autoimmune disease that involve polyarthritis, cutaneous and pulmonary manifestations. The development of rapidly progressing interstitial lung disease is a life-threatening complication. We report the case of a 45-year-old woman without medical history, who was addressed to the Pulmonary Department for a polyarthritis with dry cough and hypoxemic dyspnea. Initially there was neither cutaneous manifestation nor interstitial lung disease on chest CT scan. After a few days, the patient developed fatal acute respiratory failure with diffuse ground glass opacities. Identification of anti-MDA5 antibodies allowed establishing diagnosis, despite the fact that the first immunological assessment was negative. Corticosteroid bolus of 1 g for three days and immunosuppressive treatment by cyclophosphamide was only initiated at the acute respiratory distress syndrome stage. Given the rapidly unfavorable prognosis of this entity of amyopathic dermatomyositis, the testing for anti-MDA5 antibodies should be recommended in case of progressive pulmonary symptoms associated with joint signs in order to identify this disease at an early stage and to begin rapid and adequate management.
The Effect of Modified Lysozyme Treatment on the Microflora, Physicochemical and Sensory Characteristics of Pork Packaged in Preservative Gas Atmospheres
Authors: Cegielska-Radziejewska Renata , Szablewski Tomasz , Radziejewska-Kubzdela Elżbieta , Tomczyk Łukasz , Biadała Agata , Leśnierowski Grzegorz
Published: April 2021

The aim of the study was to investigate the effect of modified lysozyme on the microflora, physicochemical and sensory characteristics of pork loin packaged in modified atmospheres and stored at 4 ± 1 °C. Different gas compositions (M1 65:25:10 O2:CO2:N2; M2 50:40:10 O2:CO2:N2; M3 80:20 O2:CO2) were used. The microbiological parameters (APC, Enterobacteriaceae, Pseudomonas spp., lactic acid bacteria), physicochemical indexes (pH, colour) as well as a sensory attribute, i.e., aroma were analysed. Meat samples were tested after five, 12, 19, 23, and 28 days of storage. Changes in the qualities of pork were determined throughout the storage. The proportions of polymeric forms, hydrolytic activity and hydrophobicity were determined in the lysozyme preparation. Modified lysozyme exhibited higher hydrophobicity and lower hydrolytic activity than lysozyme monomer. The colour parameters L* and a* were not considerably affected by the addition of modified lysozyme. The sample with the modified lysozyme was given the highest score for aroma. In comparison with the monomer, the modified lysozyme exhibited greater antibacterial effect, especially against Pseudomonas and Enterobacteriaceae. Microbial growth rates in the sample with modified lysozyme, packaged in an atmosphere with the highest content of CO2 (total plate count 4.59 log CFU/cm2; moulds and yeasts 2.17 log CFU/cm2) were lower than those observed in the sample without lysozyme packed under M1 and M3 (20−25% CO2). The use of an atmosphere with gas composition and modified lysozyme considerably extended the shelf life of pork. The combination of the atmosphere with the highest content of carbon dioxide (50% O2, 40% CO2, 10% N2) and modified lysozyme resulted in the best effect. This strategy extended the shelf-life by more than 20%, as compared with the control sample without lysozyme, packaged in an atmosphere of 50:40:10 O2:CO2:N2.
Microstructural and Erosive Wear Characteristics of a High Chromium Cast Iron
Authors: Fortini Annalisa , Suman Alessio , Vulpio Alessandro , Merlin Mattia , Pinelli Michele
Published: April 2021

Surface material loss due to erosive wear is responsible for the increased cost of maintenance and downtime in industries. Hence, hardfacing is one of the most valuable and effective techniques employed to improve the wear resistance of heavy-duty components. The present paper investigates the microstructural and erosive wear characteristics of a hypereutectic high-chromium cast iron, considering the erosion resistance, resulting from the impact of micro-sized particles, of both as-received and heat-treated conditions. Micro-sized particles involve the erosion-resistant characteristics of carbide and matrix, contemporary. Due to this, the enhancement of the matrix strength could improve the mechanical support to withstand cracking deformation and spalling. Accordingly, the effect of a destabilization heat treatment on the microstructure was firstly investigated by hardness tests, X-ray diffraction analyses, optical and scanning electron microscopy. Specifically designed erosive tests were carried out using a raw meal powder at an impingement angle of 90°. The resulting superior wear resistance of the heat-treated samples was relayed on the improved matrix microstructure: consistent with the observed eroded surfaces, the reduced matrix/carbides hardness difference of the heat-treated material is pivotal in enhancing the erosion resistance of the hardfacing. The present results contribute to a better understanding of the microstructure–property relationships concerning the erosive wear resistance.
A Review of Pharmaceutical Nano-Cocrystals: A Novel Strategy to Improve the Chemical and Physical Properties for Poorly Soluble Drugs
Authors: Tan Jianbing , Liu Jianhao , Ran Liling
Published: April 2021

Nowadays, many commercial drugs have poor solubility and bioavailability. Cocrystals are formulated to modulate active pharmaceutical ingredients’ properties with improved solubility, dissolution, and bioavailability compared to their pristine individual components in the pharmaceutical industry. Nano-cocrystals, crystals in the nano range, can further enhance these properties because of not only the cocrystal structure, but also the large surface to volume ratio of nanocrystals. Even though there are many studies on cocrystals, the research of pharmaceutical nano-cocrystals is still in the initial stage. Thus, it is necessary to conduct a systematic study on pharmaceutical nano-cocrystals. In this review, the possible preparation approaches of nano-cocrystals have been reported. To have a comprehensive understanding of nano-cocrystals, some analytical techniques and characterizations will be discussed in detail. In addition, the feasible therapeutic application of nano-cocrystals will be presented. This work is expected to provide guidance to develop new nano-cocrystals with commercial value in the pharmaceutical industry.
Effect of Ni2+ on Lithium-Ion Diffusion in Layered LiNi1−x−yMnxCoyO2 Materials
Authors: Zhu Yuanyuan , Huang Yang , Du Rong , Tang Ming , Wang Baotian , Zhang Junrong
Published: April 2021

LiNi1−x−yMnxCoyO2 materials are a typical class of layered cathode materials with excellent electrochemical performance in lithium-ion batteries. Molecular dynamics simulations are performed for LiNi1−x−yMnxCoyO2 materials with different transition metal ratios. The Li/Ni exchange ratio, ratio of anti-site Ni2+ to total Ni2+, and diffusion coefficient of Li ions in these materials are calculated. The results show that the Li-ion diffusion coefficient strongly depends on the ratio of anti-site Ni2+ to total Ni2+ because their variation tendencies are similar. In addition, the local coordination structure of the Li/Ni anti-site is analyzed.
Thermostable Heptaplex PCR Assay for the Detection of Six Respiratory Bacterial Pathogens
Authors: Nik Zuraina Nik Mohd Noor , Goni Mohammed Dauda , Amalina Khazani Nur , Hasan Habsah , Mohamad Suharni , Suraiya Siti
Published: April 2021

A thermostabilized, multiplex polymerase chain reaction (mPCR) assay was developed in this study for the detection of six respiratory bacterial pathogens. Specific primers were designed for an internal amplification control (IAC) and six target sequences from Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Haemophilus influenzae. The resultant seven-band positive amplification control (PAC) of this heptaplex PCR assay corresponded to 105 base pairs (bp) of IAC, 202 bp of K. pneumoniae, 293 bp of S. aureus, 349 bp of S. pneumoniae, 444 bp of P. aeruginosa, 505 bp of M. tuberculosis, and 582 bp of H. influenzae. Results found that 6% (w/v) of the stabilizer was optimum to preserve the functional conformation of Taq DNA polymerase enzyme. This assay was stable at ambient temperature for at least 6 months. The sensitivity and specificity of this assay were both 100% when testing on the intended target organisms (n = 119) and non-intended species (n = 57). The mPCR assay developed in this study enabled accurate, rapid, and simple detection of six respiratory bacteria.
Neurofilaments as Emerging Biomarkers of Neuroaxonal Damage to Differentiate Behavioral Frontotemporal Dementia from Primary Psychiatric Disorders: A Systematic Review
Authors: Davy Vincent , Dumurgier Julien , Fayosse Aurore , Paquet Claire , Cognat Emmanuel
Published: April 2021

The behavioral variant of frontotemporal dementia (bvFTD) is a clinical syndrome resulting from various causes of neuronal demises associated with frontotemporal lobar degeneration. Symptoms include behavioral and personality changes, social cognitive impairment, and executive function deficits. There is a significant clinical overlap between this syndrome and various primary psychiatric disorders (PPD). Structural and functional neuroimaging are considered helpful to support the diagnosis of bvFTD, but their sensitivity and specificity remain imperfect. There is growing evidence concerning the potential of neurofilaments as biomarkers reflecting axonal and neuronal lesions. Ultrasensitive analytic platforms have recently enabled neurofilament light chains’ (NfL) detection not only from cerebrospinal fluid but also from peripheral blood samples in FTD patients. In this short review, we present recent advances and perspectives for the use of NfL assessments as biomarkers of neuroaxonal damage to differentiate bvFTD from primary psychiatric disorders.
Attitude towards Telemonitoring in Orthodontists and Orthodontic Patients
Authors: Dalessandri Domenico , Sangalli Linda , Tonni Ingrid , Laffranchi Laura , Bonetti Stefano , Visconti Luca , Signoroni Alberto , Paganelli Corrado
Published: April 2021

The purpose of this study was to analyze the attitude of dentists and patients towards the use of Dental MonitoringTM (DM), an orthodontic telemonitoring software. Thus, two different specially prepared specific questionnaires were administered to 80 dentists (40 were general dentists and 40 orthodontists) and 80 orthodontic patients. All dentists judged positively telemonitoring, as 96.25% of them considered telemonitoring indicative of high tech and high-quality treatment; 100% considered it a way to reduce the number of in-office visits; 17.5% agreed on a weekly telemonitoring frequency, 40% on a biweekly, and 42.5% on a lower frequency. Further, 97.5% of patients judged positively telemonitoring; 81.25% of them considered telemonitoring indicative of high-tech treatment; 81.25% declared to be interested in reducing the number of in-office visits through telemonitoring; 27.5% agreed on taking self-picture every week, 57.5% every two weeks, and 15% on a lower frequency. Both patients and dentists positively judged telemonitoring, considering it a technologically advanced tool increasing the perception of quality and accuracy of the treatment. Both groups were interested in reducing the number of in-office visits, although not all of them revealed to be ready to invest more money and time in it.
Entanglement Dynamics Induced by a Squeezed Coherent Cavity Coupled Nonlinearly with a Qubit and Filled with a Kerr-Like Medium
Authors: Mohamed Abdel-Baset A. , Eleuch Hichem
Published: April 2021

An analytical solution for a master equation describing the dynamics of a qubit interacting with a nonlinear Kerr-like cavity through intensity-dependent coupling is established. A superposition of squeezed coherent states is propped as the initial cavity field. The dynamics of the entangled qubit-cavity states are explored by negativity for different deformed function of the intensity-dependent coupling. We have examined the effects of the Kerr-like nonlinearity and the qubit-cavity detuning as well as the phase cavity damping on the generated entanglement. The intensity-dependent coupling increases the sensitivity of the generated entanglement to the phase-damping. The stability and the strength of the entanglement are controlled by the Kerr-like nonlinearity, the qubit-cavity detuning, and the initial cavity non-classicality. These physical parameters enhance the robustness of the qubit-cavity entanglement against the cavity phase-damping. The high initial cavity non-classicality enhances the robustness of the qubit-cavity entanglement against the phase-damping effect.
Limit Theorems as Blessing of Dimensionality: Neural-Oriented Overview
Authors: Kreinovich Vladik , Kosheleva Olga
Published: April 2021

As a system becomes more complex, at first, its description and analysis becomes more complicated. However, a further increase in the system’s complexity often makes this analysis simpler. A classical example is Central Limit Theorem: when we have a few independent sources of uncertainty, the resulting uncertainty is very difficult to describe, but as the number of such sources increases, the resulting distribution gets close to an easy-to-analyze normal one—and indeed, normal distributions are ubiquitous. We show that such limit theorems often make analysis of complex systems easier—i.e., lead to blessing of dimensionality phenomenon—for all the aspects of these systems: the corresponding transformation, the system’s uncertainty, and the desired result of the system’s analysis.
Security Analysis and Improvement of an Image Encryption Cryptosystem Based on Bit Plane Extraction and Multi Chaos
Authors: Zhu Shuqin , Zhu Congxu
Published: April 2021

This paper analyzes the security of image encryption systems based on bit plane extraction and multi chaos. It includes a bit-level permutation for high, 4-bit planes and bit-wise XOR diffusion, and finds that the key streams in the permutation and diffusion phases are independent of the plaintext image. Therefore, the equivalent diffusion key and the equivalent permutation key can be recovered by the chosen-plaintext attack method, in which only two special plaintext images and their corresponding cipher images are used. The effectiveness and feasibility of the proposed attack algorithm is verified by a MATLAB 2015b simulation. In the experiment, all the key streams in the original algorithm are cracked through two special plaintext images and their corresponding ciphertext images. In addition, an improved algorithm is proposed. In the improved algorithm, the generation of a random sequence is related to ciphertext, which makes the encryption algorithm have the encryption effect of a “one time pad”. The encryption effect of the improved algorithm is better than that of the original encryption algorithm in the aspects of information entropy, ciphertext correlation analysis and ciphertext sensitivity analysis.