bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylation Drivers and Prognostic Implications in Sinonasal Poorly Differentiated Carcinomas
Authors: Libera Laura , Ottini Giorgia , Sahnane Nora , Pettenon Fabiana , Turri-Zanoni Mario , Lambertoni Alessia , Chiaravalli Anna Maria , Leone Federico , Battaglia Paolo , Castelnuovo Paolo , Uccella Silvia , Furlan Daniela , Facco Carla , Sessa Fausto
Published: October 2021

Background: Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several epigenetic markers have been suggested to support the histopathological classification, predict prognosis, and guide therapeutic decision. Indeed, molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as separate entities. Identification of aberrant DNA methylation levels associated with these specific epigenetic driver genes could be useful for prognostic and therapeutic purpose. Methods: Histopathological review and immunohistochemical study was performed on 53 PDSNCs. Molecular analysis included mutational profile by NGS, Sanger sequencing, and MLPA analyses, and global DNA methylation profile using LINE-1 bisulfite-PCR and pyrosequencing analysis. Results: Nine SWI/SNF complex defective cases and five IDH2 p.Arg172x cases were identified. A significant correlation between INI-1 or IDH2 defects and LINE-1 hypermethylation was observed (p = 0.002 and p = 0.032, respectively), which were associated with a worse prognosis (p = 0.007). Conclusions: Genetic and epigenetic characterization of PDSNCs should be performed to identify distinct prognostic entities, which deserved a tailored clinical treatment.
Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants
Authors: Prakash Amol , Taylor Lorne , Varkey Manu , Hoxie Nate , Mohammed Yassene , Goo Young Ah , Peterman Scott , Moghekar Abhay , Yuan Yuting , Glaros Trevor , Steele Joel R. , Faridi Pouya , Parihari Shashwati , Srivastava Sanjeeva , Otto Joseph J. , Nyalwidhe Julius O. , Semmes O. John , Moran Michael F. , Madugundu Anil , Mun Dong Gi , Pandey Akhilesh , Mahoney Keira E. , Shabanowitz Jeffrey , Saxena Satya , Orsburn Benjamin C.
Published: October 2021

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date.
(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers
Authors: Sabol Maja , Calleja-Agius Jean , Di Fiore Riccardo , Suleiman Sherif , Ozcan Sureyya , Ward Mark P. , Ozretić Petar
Published: October 2021

Rare ovarian cancers (ROCs) are OCs with an annual incidence of fewer than 6 cases per 100,000 women. They affect women of all ages, but due to their low incidence and the potential clinical inexperience in management, there can be a delay in diagnosis, leading to a poor prognosis. The underlying causes for these tumors are varied, but generally, the tumors arise due to alterations in gene/protein expression in cellular processes that regulate normal proliferation and its checkpoints. Dysregulation of the cellular processes that lead to cancer includes gene mutations, epimutations, non-coding RNA (ncRNA) regulation, posttranscriptional and posttranslational modifications. Long non-coding RNA (lncRNA) are defined as transcribed RNA molecules, more than 200 nucleotides in length which are not translated into proteins. They regulate gene expression through several mechanisms and therefore add another level of complexity to the regulatory mechanisms affecting tumor development. Since few studies have been performed on ROCs, in this review we summarize the mechanisms of action of lncRNA in OC, with an emphasis on ROCs.
The Dual Role of Innate Lymphoid and Natural Killer Cells in Cancer. from Phenotype to Single-Cell Transcriptomics, Functions and Clinical Uses
Authors: Roma Stefania , Carpen Laura , Raveane Alessandro , Bertolini Francesco
Published: October 2021

The role of innate lymphoid cells (ILCs), including natural killer (NK) cells, is pivotal in inflammatory modulation and cancer. Natural killer cell activity and count have been demonstrated to be regulated by the expression of activating and inhibitory receptors together with and as a consequence of different stimuli. The great majority of NK cell populations have an anti-tumor activity due to their cytotoxicity, and for this reason have been used for cellular therapies in cancer patients. On the other hand, the recently classified helper ILCs are fundamentally involved in inflammation and they can be either helpful or harmful in cancer development and progression. Tissue niche seems to play an important role in modulating ILC function and conversion, as observed at the transcriptional level. In the past, these cell populations have been classified by the presence of specific cellular receptor markers; more recently, due to the advent of single-cell RNA sequencing (scRNA-seq), it has been possible to also explore them at the transcriptomic level. In this article we review studies on ILC (and NK cell) classification, function and their involvement in cancer. We also summarize the potential application of NK cells in cancer therapy and give an overview of the most recent studies involving ILCs and NKs at scRNA-seq, focusing on cancer. Finally, we provide a resource for those who wish to start single-cell transcriptomic analysis on the context of these innate lymphoid cell populations.
A Novel Method for the Evaluation of Bone Marrow Samples from Patients with Pediatric B-Cell Acute Lymphoblastic Leukemia—Multidimensional Flow Cytometry
Authors: Kárai Bettina , Tisza Katalin , Eperjesi Orsolya , Nagy Attila Csaba , Ujfalusi Anikó , Kelemen Ágnes , Szegedi István , Kiss Csongor , Kappelmayer János , Hevessy Zsuzsanna
Published: October 2021

Multicolor flow cytometry (FC) evaluation has a key role in the diagnosis and prognostic stratification of ALL. Our aim was to create new analyzing protocols using multidimensional dot-plots. Seventy-two pediatric patients with ALL were included in this single-center study. Data of a normal BM sample and three BM samples of patients with BCP-ALL were merged, then all B cell populations of the four samples were presented in a single radar dot-plot, and those parameters and locations were selected in which the normal and pathological cell populations differed from each other the most. The integrated profile of immunophenotype resulted in a simple, rapid, and accurate method. There were no significant differences between the percentages of lymphoblasts in the detection of minimal residual disease (MRD) by multidimensional or conventional FC method (p = 0.903 at Day 15 and p = 0.155 at Day 33). Furthermore, we found associations between the position and the number of clusters of blast cells in the radar plots and cytogenetic properties (p = 0.002 and p < 0.0001 by the position and p = 0.02 by the number of subclones). FC analysis based on multidimensional dot-plots is not only a rapid, easy-to-use method, but can also provide additional information to screen cases which require detailed genetic examination.
Neoadjuvant and Adjuvant Immunotherapy in Non-Small Cell Lung Cancer—Clinical Trials Experience
Authors: Chmielewska Izabela , Stencel Katarzyna , Kalinka Ewa , Ramlau Rodryg , Krawczyk Paweł
Published: October 2021

Across all tumor types, we observe that the role of immunotherapy has increased rapidly. Due to a number of potential advantages, it is considered in neoadjuvant treatment of localized tumors. In neoadjuvant settings, immunotherapy addresses micrometastatic diseases at the moment of their formation. However, some issues concerning neoadjuvant and adjuvant immunotherapy still has to be covered. The choice of drug and use of monotherapy or combination regimens remains unclear. The timing of surgery and preoperative evaluation of neoadjuvant immunotherapy efficacy is challenging. Although there is currently limited confirmed clinical data to support the use of immune checkpoint blockade in the neoadjuvant and adjuvant settings, there are many studies exploring this strategy in NSCLC patients.
Presence of the Human Cytomegalovirus in Glioblastomas—A Systematic Review
Authors: Peredo-Harvey Inti , Rahbar Afsar , Söderberg-Nauclér Cecilia
Published: October 2021

Glioblastoma is a malignant brain tumor with a dismal prognosis. The standard treatment has not changed in the past 15 years as clinical trials of new treatment protocols have failed. A high prevalence of the human cytomegalovirus (HCMV) in glioblastomas was first reported in 2002. The virus was found only in the tumor and not in the surrounding healthy brain tissue. Many groups have confirmed the presence of the HCMV in glioblastomas, but others could not. To resolve this discrepancy, we systematically reviewed 645 articles identified in different databases. Of these, 81 studies included results from 247 analyses of 9444 clinical samples (7024 tumor samples and 2420 blood samples) by different techniques, and 81 articles included 191 studies that identified the HCMV in 2529 tumor samples (36% of all tumor samples). HCMV proteins were often detected, whereas HCMV nucleic acids were not reliably detected by PCR methods. Optimized immunohistochemical techniques identified the virus in 1391 (84,2%) of 1653 samples. These data suggest that the HCMV is highly prevalent in glioblastomas and that optimized immunohistochemistry techniques are required to detect it.
Current Technologies for RNA-Directed Liquid Diagnostics
Authors: Martinez-Dominguez Maria Victoria , Zottel Alja , Šamec Neja , Jovčevska Ivana , Dincer Can , Kahlert Ulf Dietrich , Nickel Ann-Christin
Published: October 2021

There is unequivocal acceptance of the variety of enormous potential liquid nucleic acid-based diagnostics seems to offer. However, the existing controversies and the increased awareness of RNA-based techniques in society during the current global COVID-19 pandemic have made the readiness of liquid nucleic acid-based diagnostics for routine use a matter of concern. In this regard—and in the context of oncology—our review presented and discussed the status quo of RNA-based liquid diagnostics. We summarized the technical background of the available assays and benchmarked their applicability against each other. Herein, we compared the technology readiness level in the clinical context, economic aspects, implementation as part of routine point-of-care testing as well as performance power. Since the preventive care market is the most promising application sector, we also investigated whether the developments predominantly occur in the context of early disease detection or surveillance of therapy success. In addition, we provided a careful view on the current biotechnology investment activities in this sector to indicate the most attractive strategies for future economic success. Taken together, our review shall serve as a current reference, at the interplay of technology, clinical use and economic potential, to guide the interested readers in this rapid developing sector of precision medicine.
Obesity and Pancreatic Cancer: Insight into Mechanisms
Authors: Eibl Guido , Rozengurt Enrique
Published: October 2021

The prevalence of obesity in adults and children has dramatically increased over the past decades. Obesity has been declared a chronic progressive disease and is a risk factor for a number of metabolic, inflammatory, and neoplastic diseases. There is clear epidemiologic and preclinical evidence that obesity is a risk factor for pancreatic cancer. Among various potential mechanisms linking obesity with pancreatic cancer, the adipose tissue and obesity-associated adipose tissue inflammation play a central role. The current review discusses selected topics and mechanisms that attracted recent interest and that may underlie the promoting effects of obesity in pancreatic cancer. These topics include the impact of obesity on KRAS activity, the role of visceral adipose tissue, intrapancreatic fat, adipose tissue inflammation, and adipokines on pancreatic cancer development. Current research on lipocalin-2, fibroblast growth factor 21, and Wnt5a is discussed. Furthermore, the significance of obesity-associated insulin resistance with hyperinsulinemia and obesity-induced gut dysbiosis with metabolic endotoxemia is reviewed. Given the central role that is occupied by the adipose tissue in obesity-promoted pancreatic cancer development, preventive and interceptive strategies should be aimed at attenuating obesity-associated adipose tissue inflammation and/or at targeting specific molecules that mechanistically link adipose tissue with pancreatic cancer in obese patients.
Parental Origin of the RB1 Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma
Authors: Alekseeva Ekaterina A. , Babenko Olga V. , Kozlova Valentina M. , Ushakova Tatiana L. , Kazubskaya Tatiana P. , Nemtsova Marina V. , Chesnokova Galina G. , Mikhaylenko Dmitry S. , Bure Irina V. , Kalinkin Alexey I. , Kuznetsova Ekaterina B. , Tanas Alexander S. , Kutsev Sergey I. , Zaletaev Dmitry V. , Strelnikov Vladimir V.
Published: October 2021

Our aim was to identify RB1 alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an RB1 mutation affects its phenotypic expression. By NGS and MLPA, RB1 mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified RB1 mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an RB1 mutation. Additionally, in two families with retinoblastoma history, mutations were inherited by probands from unaffected parents. Overall, nine probands inherited RB1 mutations from clinically unaffected fathers and five, from mothers. Yet, we gained explanations of maternal “unaffectedness” in most cases, either as somatic mosaicism or as clinical presentation of retinomas in involution, rendering the proportion of paternal to maternal truly asymptomatic mutation carriers as 9:1 (p = 0.005). This observation supports an assumption that parental origin of an RB1 mutation influences the likelihood of developing retinoblastoma. Additionally, our study revealed a relatively high frequency of asymptomatic carriage of the RB1 mutations among the parents of retinoblastoma patients, highlighting the utmost necessity of molecular analysis among the probands’ relatives irrespective of their clinical status and family history of retinoblastoma.
Value of Assessing Peripheral Vascularization with Micro-Flow Imaging, Resistive Index and Absent Hilum Sign as Predictor for Malignancy in Lymph Nodes in Head and Neck Squamous Cell Carcinoma
Authors: de Koekkoek-Doll Petra K. , Roberti Sander , van den Brekel Michiel W. , Maas Monique , Smit Laura , Beets-Tan Regina , Castelijns Jonas
Published: October 2021

Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18–4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.
HCV Activates Somatic L1 Retrotransposition—A Potential Hepatocarcinogenesis Pathway
Authors: Sudhindar Praveen D. , Wainwright Daniel , Saha Santu , Howarth Rachel , McCain Misti , Bury Yvonne , Saha Sweta S. , McPherson Stuart , Reeves Helen , Patel Arvind H. , Faulkner Geoffrey J. , Lunec John , Shukla Ruchi
Published: October 2021

Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance.
Structural and Functional Behaviour of Ce-Doped Wide-Bandgap Semiconductors for Photo-Catalytic Applications
Authors: Forghieri Giulia , Zanardo Danny , Ghedini Elena , Menegazzo Federica , Giordana Alessia , Cerrato Giuseppina , Di Michele Alessandro , Cruciani Giuseppe , Signoretto Michela
Published: October 2021

Increasing the photocatalytic efficiency of earth-abundant wide-bandgap semiconductors is of high interest for the development of cheap but effective light-driven chemical conversion processes. In this study, the coupling of ZnO and TiO2 with low contents of the rare-earth Ce species aimed to assess the photo-catalytic performance of the two semiconductors (SC). Structural and optical characterizations were performed to estimate the effect of the different interactions between Zn2+, Ti4+ and Ce4+ ions, and how the photo-responsive behaviour of Ce-Ti and Ce-Zn composites was affected. Therefore, photo-catalytic tests were performed for all Ce-modified SC to assess both their photo-oxidative and photo-reductive properties. Amongst all the tested materials, only Zn-based samples resulted in being suitable for the photo-oxidation of the methylene blue (MB) organic pollutant in a synthetic-dependent fashion.
Application of Agricultural Waste as Heterogeneous Catalysts for Biodiesel Production
Authors: Khan Haris Mahmood , Iqbal Tanveer , Yasin Saima , Ali Chaudhry Haider , Abbas Muhammad Mujtaba , Jamil Muhammad Asif , Hussain Abrar , M. Soudagar Manzoore Elahi , Rahman Muhammad Muhitur
Published: October 2021

In this modern era, it has become essential to transform waste materials into valuables because of their excessive availability, along with achieving the targets of environmental protocols and waste management policies. With a growing population, the utilization and consumption of agricultural products have been increased extensively. In addition, it has increased the probability of agricultural waste generation. Waste produced from agricultural sources is considered as a viable source for synthesizing economical and ecofriendly catalysts and suitable ways for its disposal are sought. This study is targeted at agricultural waste-derived heterogeneous catalysts, which have been effectively employed for biodiesel generation. The types of agricultural waste, catalyst synthesis techniques, recent literature stated for agricultural waste-derived catalysts to produce biodiesel, the elemental composition and catalytic activity of agricultural waste ashes, the effect of reaction parameters to maximize biodiesel yield and catalyst reusability have been discussed. This work concludes that catalysts derived from agricultural waste are efficient in transesterification reaction, and they are easy to produce, and are cheap and ecofriendly. Moreover, this study encourages researchers to see the options for unexplored agricultural waste, which can be potentially converted into useful materials
Magnetically Reusable Fe3O4@NC@Pt Catalyst for Selective Reduction of Nitroarenes
Authors: Qiao Jun , Wang Tian , Zheng Kai , Zhou Enmu , Shen Chao , Jia Aiquan , Zhang Qianfeng
Published: October 2021

A novel reusable Fe3O4@NC@Pt heterogeneous catalyst was synthesized by immobilizing platinum on nitrogen-doped carbon magnetic nanostructures. It was characterized by infrared analysis (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The catalytic efficiency of Fe3O4@NC@Pt was investigated by reduction of nitro aromatic compounds. The catalyst showed good catalytic activity, wide range of substrates, and good chemical selectivity, especially for the substrates of compounds containing halide and carbonyl groups. The magnetically catalyst can readily be reused up to ten cycles without loss of catalytic activity. Moreover, the key pharmaceutical intermediate Lorlatini can be facilely achieved through this strategy.
The Effect of Preparation Method of Ni-Supported SiO2 Catalysts for Carbon Dioxide Reforming of Methane
Authors: Ren Hua-Ping , Ding Si-Yi , Ma Qiang , Song Wen-Qi , Zhao Yu-Zhen , Liu Jiao , He Ye-Ming , Tian Shao-Peng
Published: October 2021

Reforming methane to produce syngas is a subject that generates considerable interest. The process requires catalysts that possess high-performance active sites to activate stable C–H bonds. Herein, we report a facile synthetic strategy to prepare Ni-based catalysts by complexation–impregnation (Ni-G/SiO2-C) and precipitation–impregnation (Ni-G/SiO2-P) methods using glycine as a complexing agent. The particle size of Ni in both types of catalysts is decreased by adding glycine in the preparation process. Nevertheless, the preparation methods and amount of glycine play a significant role in the particle size and distribution of Ni over the Ni-based catalysts. The smaller particle size and narrower distribution of Ni were obtained in the Ni-G/SiO2-P catalyst. The catalysts were comparatively tested for carbon-dioxide reforming of methane (CDR). Ni-G/SiO2-P showed better CDR performance than Ni-G/SiO2-C and Ni/SiO2 and increased stability because of the smaller particle size and narrower distribution of Ni. Moreover, a high-performance Ni-based catalyst was prepared by optimizing the amount of glycine added. An unobservable deactivation was obtained over Ni-G-2/SiO2-P and Ni-G-3/SiO2-P for CDR during TOS = 20 h. Thus, a new promising method is described for the preparation of Ni-based catalysts for CDR.
Current Status and Future Perspectives of Supports and Protocols for Enzyme Immobilization
Authors: Cavalcante Francisco T. T. , Cavalcante Antônio L. G. , de Sousa Isamayra G. , Neto Francisco S. , dos Santos José C. S.
Published: October 2021

The market for industrial enzymes has witnessed constant growth, which is currently around 7% a year, projected to reach $10.5 billion in 2024. Lipases are hydrolase enzymes naturally responsible for triglyceride hydrolysis. They are the most expansively used industrial biocatalysts, with wide application in a broad range of industries. However, these biocatalytic processes are usually limited by the low stability of the enzyme, the half-life time, and the processes required to solve these problems are complex and lack application feasibility at the industrial scale. Emerging technologies create new materials for enzyme carriers and sophisticate the well-known immobilization principles to produce more robust, eco-friendlier, and cheaper biocatalysts. Therefore, this review discusses the trending studies and industrial applications of the materials and protocols for lipase immobilization, analyzing their advantages and disadvantages. Finally, it summarizes the current challenges and potential alternatives for lipases at the industrial level.
Rh-Catalyzed Reductive Amination of Undecanal in an Aqueous Microemulsion System Using a Non-Ionic Surfactant
Authors: Weber Ariane , Porthun Linus , Schomäcker Reinhard
Published: October 2021

The homogeneously catalyzed reductive amination of the long-chain aldehyde undecanal with diethylamine was performed in an aqueous microemulsion system using the non-ionic surfactant Marlophen NP8. The experiments showed that the used water-soluble rhodium/SulfoXantphos catalyst system is suitable for this reaction. The Rh-catalyzed formation of the alcohol by-product can be completely suppressed by the use of carbon monoxide with its stabilizing effect of the catalyst system. In addition to pressure and temperature, the most important parameters for the reaction performance of the reductive amination are the concentrations of reactants. Especially, the initial concentration of the aldehyde has a strong impact on the chemoselectivity, and the formation of aldol by-product due to the fact that both, the enamine condensation and the aldol condensation are equilibrium reactions.
Emerging Roles of N6-Methyladenosine Modification in Neurodevelopment and Neurodegeneration
Authors: Shu Liqi , Huang Xiaoli , Cheng Xuejun , Li Xuekun
Published: October 2021

N6-methyladenosine (m6A), the most abundant modification in messenger RNAs (mRNAs), is deposited by methyltransferases (“writers”) Mettl3 and Mettl14 and erased by demethylases (“erasers”) Fto and Alkbh5. m6A can be recognized by m6A-binding proteins (“readers”), such as Yth domain family proteins (Ythdfs) and Yth domain-containing protein 1 (Ythdc1). Previous studies have indicated that m6A plays an essential function in various fundamental biological processes, including neurogenesis and neuronal development. Dysregulated m6A modification contributes to neurological disorders, including neurodegenerative diseases. In this review, we summarize the current knowledge about the roles of m6A machinery, including writers, erasers, and readers, in regulating gene expression and the function of m6A in neurodevelopment and neurodegeneration. We also discuss the perspectives for studying m6A methylation.
Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology: Therapeutic Implications in Hematological Malignancies
Authors: Sidhu Ishnoor , Barwe Sonali P. , Pillai Raju K. , Gopalakrishnapillai Anilkumar
Published: October 2021

In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. Owing to their self-renewal and differentiation capacity, induced pluripotent stem cells (iPSCs) have emerged as a potential source of short in supply disease-specific human cells of the hematopoietic lineage. Patient-derived iPSCs can recapitulate the disease severity and spectrum of prognosis dictated by the genetic variation among patients and can be used for drug screening and studying clonal evolution. However, this approach lacks the ability to model the early phases of the disease leading to cancer. The advent of genetic editing technology has promoted the generation of precise isogenic iPSC disease models to address questions regarding the underlying genetic mechanism of disease initiation and progression. In this review, we discuss the use of iPSC disease modeling in hematological diseases, where there is lack of patient sample availability and/or difficulty of engraftment to generate animal models. Furthermore, we describe the power of combining iPSC and precise gene editing to elucidate the underlying mechanism of initiation and progression of various hematological malignancies. Finally, we discuss the power of iPSC disease modeling in developing and testing novel therapies in a high throughput setting.
The Role of Sodium Glucose Cotransporter-2 Inhibitors in Atherosclerotic Cardiovascular Disease: A Narrative Review of Potential Mechanisms
Authors: Barraclough Jennifer Y. , Patel Sanjay , Yu Jie , Neal Bruce , Arnott Clare
Published: October 2021

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medication with broad cardiovascular benefits in those with type 2 diabetes, chronic kidney disease, and heart failure. These include reductions in major adverse cardiac events and cardiovascular death. The mechanisms that underlie their benefits in atherosclerotic cardiovascular disease (ASCVD) are not well understood, but they extend beyond glucose lowering. This narrative review summarises the ASCVD benefits of SGLT2 inhibitors seen in large human outcome trials, as well as the mechanisms of action explored in rodent and small human studies. Potential pathways include favourable alterations in lipid metabolism, inflammation, and endothelial function. These all require further investigation in large human clinical trials with mechanistic endpoints, to further elucidate the disease modifying benefits of this drug class and those who will benefit most from it.
A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment
Authors: Hofer Francesca , Di Sario Gianna , Musiu Chiara , Sartoris Silvia , De Sanctis Francesco , Ugel Stefano
Published: October 2021

Myeloid-derived suppressor cells (MDSCs) constitute a plastic and heterogeneous cell population among immune cells within the tumour microenvironment (TME) that support cancer progression and resistance to therapy. During tumour progression, cancer cells modify their metabolism to sustain an increased energy demand to cope with uncontrolled cell proliferation and differentiation. This metabolic reprogramming of cancer establishes competition for nutrients between tumour cells and leukocytes and most importantly, among tumour-infiltrating immune cells. Thus, MDSCs that have emerged as one of the most decisive immune regulators of TME exhibit an increase in glycolysis and fatty acid metabolism and also an upregulation of enzymes that catabolise essential metabolites. This complex metabolic network is not only crucial for MDSC survival and accumulation in the TME but also for enhancing immunosuppressive functions toward immune effectors. In this review, we discuss recent progress in the field of MDSC-associated metabolic pathways that could facilitate therapeutic targeting of these cells during cancer progression.
Mapping the Proximity Interaction Network of STIM1 Reveals New Mechanisms of Cytoskeletal Regulation
Authors: Gammons Jesse , Halpage Janith , Mancarella Salvatore
Published: October 2021

Stromal interaction molecule 1 (STIM1) resides primarily in the sarco/endoplasmic reticulum, where it senses intraluminal Ca2+ levels and activates Orai channels on the plasma membrane to initiate Ca2+ influx. We have previously shown that STIM1 is involved in the dynamic remodeling of the actin cytoskeleton. However, the downstream effectors of STIM1 that lead to cytoskeletal remodeling are not known. The proximity-labeling technique (BioID) can capture weak and transient protein-protein interactions, including proteins that reside in the close vicinity of the bait, but that may not be direct binders. Hence, in the present study, we investigated the STIM1 interactome using the BioID technique. A promiscuous biotin ligase was fused to the cytoplasmic C-terminus of STIM1 and was stably expressed in a mouse embryonic fibroblast (MEF) cell line. Screening of biotinylated proteins identified several high confidence targets. Here, we report Gelsolin (GSN) as a new member of the STIM1 interactome. GSN is a Ca2+-dependent actin-severing protein that promotes actin filament assembly and disassembly. Results were validated using knockdown approaches and immunostaining. We tested our results in neonatal cardiomyocytes where STIM1 overexpression induced altered actin dynamics and cytoskeletal instability. This is the first time that BioID assay was used to investigate the STIM1 interactome. Our work highlights the role of STIM1/GSN in the structure and function of the cytoskeleton.
Ischemia-Reperfusion Injury in a Simulated Lung Transplant Setting Differentially Regulates Transcriptomic Profiles between Human Lung Endothelial and Epithelial Cells
Authors: Saren Gaowa , Wong Aaron , Lu Yun-Bi , Baciu Cristina , Zhou Wenyong , Zamel Ricardo , Soltanieh Sahar , Sugihara Junichi , Liu Mingyao
Published: October 2021

Current understanding of mechanisms of ischemia-reperfusion-induced lung injury during lung preservation and transplantation is mainly based on clinical observations and animal studies. Herein, we used cell and systems biology approaches to explore these mechanisms at transcriptomics levels, especially by focusing on the differences between human lung endothelial and epithelial cells, which are crucial for maintaining essential lung structure and function. Human pulmonary microvascular endothelial cells and human lung epithelial cells were cultured to confluent, subjected to different cold ischemic times (CIT) to mimic static cold storage with preservation solution, and then subjected to warm reperfusion with a serum containing culture medium to simulate lung transplantation. Cell morphology, viability, and transcriptomic profiles were studied. Ischemia-reperfusion injury induced a CIT time-dependent cell death, which was associated with dramatic changes in gene expression. Under normal control conditions, endothelial cells showed gene clusters enriched in the vascular process and inflammation, while epithelial cells showed gene clusters enriched in protein biosynthesis and metabolism. CIT 6 h alone or after reperfusion had little effect on these phenotypic characteristics. After CIT 18 h, protein-biosynthesis-related gene clusters disappeared in epithelial cells; after reperfusion, metabolism-related gene clusters in epithelial cells and multiple gene clusters in the endothelial cells also disappeared. Human pulmonary endothelial and epithelial cells have distinct phenotypic transcriptomic signatures. Severe cellular injury reduces these gene expression signatures in a cell-type-dependent manner. Therapeutics that preserve these transcriptomic signatures may represent new treatment to prevent acute lung injury during lung transplantation.
Effects of Ankle Foot Orthoses on the Gait Patterns in Children with Spastic Bilateral Cerebral Palsy: A Scoping Review
Authors: Ricardo Diogo , Raposo Maria Raquel , Cruz Eduardo Brazete , Oliveira Raul , Carnide Filomena , Veloso António Prieto , João Filipa
Published: October 2021

Background: Cerebral palsy (CP) is the most common cause of motor disability in children and can cause severe gait deviations. The sagittal gait patterns classification for children with bilateral CP is an important guideline for the planning of the rehabilitation process. Ankle foot orthoses should improve the biomechanical parameters of pathological gait in the sagittal plane. Methods: A systematic search of the literature was conducted to identify randomized controlled trials (RCT) and controlled clinical trials (CCT) which measured the effect of ankle foot orthoses (AFO) on the gait of children with spastic bilateral CP, with kinetic, kinematic, and functional outcomes. Five databases (Pubmed, Scopus, ISI Web of SCIENCE, SciELO, and Cochrane Library) were searched before February 2020. The PEDro Score was used to assess the methodological quality of the selected studies and alignment with the Cochrane approach was also reviewed. Prospero registration number: CRD42018102670. Results: We included 10 studies considering a total of 285 children with spastic bilateral CP. None of the studies had a PEDro score below 4/10, including five RCTs. We identified five different types of AFO (solid; dynamic; hinged; ground reaction; posterior leaf spring) used across all studies. Only two studies referred to a classification for gait patterns. Across the different outcomes, significant differences were found in walking speed, stride length and cadence, range of motion, ground force reaction and joint moments, as well as functional scores, while wearing AFO. Conclusions: Overall, the use of AFO in children with spastic bilateral CP minimizes the impact of pathological gait, consistently improving some kinematic, kinetic, and spatial-temporal parameters, and making their gait closer to that of typically developing children. Creating a standardized protocol for future studies involving AFO would facilitate the reporting of new scientific data and help clinicians use their clinical reasoning skills to recommend the best AFO for their patients.
Prostate Magnetic Resonance Imaging Analyses, Clinical Parameters, and Preoperative Nomograms in the Prediction of Extraprostatic Extension
Authors: Majchrzak Natalia , Cieśliński Piotr , Głyda Maciej , Karmelita-Katulska Katarzyna
Published: October 2021

Introduction: Proper planning of laparoscopic radical prostatectomy (RP) in patients with prostate cancer (PCa) is crucial to achieving good oncological results with the possibility of preserving potency and continence. Aim: The aim of this study was to identify the radiological and clinical parameters that can predict the risk of extraprostatic extension (EPE) for a specific site of the prostate. Predictive models and multiparametric magnetic resonance imaging (mpMRI) data from patients qualified for RP were compared. Material and methods: The study included 61 patients who underwent laparoscopic RP. mpMRI preceded transrectal systematic and cognitive fusion biopsy. Martini, Memorial Sloan-Kettering Cancer Center (MSKCC), and Partin Tables nomograms were used to assess the risk of EPE. The area under the curve (AUC) was calculated for the models and compared. Univariate and multivariate logistic regression analyses were used to determine the combination of variables that best predicted EPE risk based on final histopathology. Results: The combination of mpMRI indicating or suspecting EPE (odds ratio (OR) = 7.49 (2.31–24.27), p < 0.001) and PSA ≥ 20 ng/mL (OR = 12.06 (1.1–132.15), p = 0.04) best predicted the risk of EPE for a specific side of the prostate. For the prediction of ipsilateral EPE risk, the AUC for Martini’s nomogram vs. mpMRI was 0.73 (p < 0.001) vs. 0.63 (p = 0.005), respectively (p = 0.131). The assessment of a non-specific site of EPE by MSKCC vs. Partin Tables showed AUC values of 0.71 (p = 0.007) vs. 0.63 (p = 0.074), respectively (p = 0.211). Conclusions: The combined use of mpMRI, the results of the systematic and targeted biopsy, and prostate-specific antigen baseline can effectively predict ipsilateral EPE (pT3 stage).
Performance and Fracture Analysis of Composite Interfaces for Semi-Flexible Pavement
Authors: Wu Kuanghuai , Liu Xiaoyu , Cai Xu , Huang Wenke , Yu Jinlou , Nie Guihai
Published: October 2021

Semi-flexible pavement is widely used in pavement engineering due to its excellent rutting resistance; however, it mainly fails due to cracking. Therefore, it is important to understand the properties of the aggregate–mortar–asphalt interfacial transition zone, to better understand the cracking mechanism of the semi-flexible pavement. In this work, we used pull-off tests and digital image analysis technology to compare and analyze the interfacial tensile strength and granite–bitumen–mortar interactions in three types of asphalt (70# matrix asphalt, PG76-22 modified asphalt and S-HV modified asphalt) at different curing ages. The analysis results showed that, for the three different bitumen materials, with settled mortar, the peak interfacial tensile strength values all occurred at approximately 14 d of curing. In addition, the order of the tensile strength followed the order of asphalt penetration degree; the order of the interfacial water damage resistance from weak to strong was 70# asphalt cementation specimen, PG76-22 modified asphalt cementation specimen, and S-HV modified asphalt cementation specimen. The results of this analysis highlight the original contributions of the optimum curing time for the composite interface of semi-flexible pavement materials prepared with different asphalts to reach optimum crack resistance.
Engineering Nanostructured Antimony-Based Anode Materials for Sodium Ion Batteries
Authors: Luo Wen , Ren Jingke , Feng Wencong , Chen Xingbao , Yan Yinuo , Zahir Noura
Published: October 2021

Sodium-ion batteries (SIBs) are considered a potential alternative to lithium-ion batteries (LIBs) for energy storage due to their low cost and the large abundance of sodium resources. The search for new anode materials for SIBs has become a vital approach to satisfying the ever-growing demands for better performance with higher energy/power densities, improved safety and a longer cycle life. Recently, antimony (Sb) has been extensively researched as a promising candidate due to its high specific capacity through an alloying/dealloying process. In this review article, we will focus on different categories of the emerging Sb based anode materials with distinct sodium storage mechanisms including Sb, two-dimensional antimonene and antimony chalcogenide (Sb2S3 and Sb2Se3). For each part, we emphasize that the novel construction of an advanced nanostructured anode with unique structures could effectively improve sodium storage properties. We also highlight that sodium storage capability can be enhanced through designing advanced nanocomposite materials containing Sb based materials and other carbonaceous modification or metal supports. Moreover, the recent advances in operando/in-situ investigation of its sodium storage mechanism are also summarized. By providing such a systematic probe, we aim to stress the significance of novel nanostructures and advanced compositing that would contribute to enhanced sodium storage performance, thus making Sb based materials as promising anodes for next-generation high-performance SIBs.
Black-Hole Optimization Applied to the Parametric Estimation in Distribution Transformers Considering Voltage and Current Measures
Authors: Arenas-Acuña Camilo Andres , Rodriguez-Contreras Jonathan Andres , Montoya Oscar Danilo , Rivas-Trujillo Edwin
Published: October 2021

The problem of parametric estimation in single-phase transformers is addressed in this research from the point of view of metaheuristic optimization. The parameters of interest are the series resistance and reactance as well as the magnetization resistance and reactance. To obtain these parameters considering only the voltage and the currents measured in the terminals of the transformer, a nonlinear optimization model that deals with the minimization of the mean square error among the measured and calculated voltage and current variables is formulated. The nonlinear programming model is solved through the implementation of a simple but efficient metaheuristic optimization technique known as the black-hole optimizer. Numerical simulations demonstrate that the proposed optimization method allows for the reduction in the estimation error among the measured and calculated variables when compared with methods that are well established in the literature such as particle swarm optimization and genetic algorithms, among others. All the simulations were carried out in the MATLAB programming environment.
IoTSAS: An Integrated System for Real-Time Semantic Annotation and Interpretation of IoT Sensor Stream Data
Authors: Sejdiu Besmir , Ismaili Florije , Ahmedi Lule
Published: October 2021

Sensors and other Internet of Things (IoT) technologies are increasingly finding application in various fields, such as air quality monitoring, weather alerts monitoring, water quality monitoring, healthcare monitoring, etc. IoT sensors continuously generate large volumes of observed stream data; therefore, processing requires a special approach. Extracting the contextual information essential for situational knowledge from sensor stream data is very difficult, especially when processing and interpretation of these data are required in real time. This paper focuses on processing and interpreting sensor stream data in real time by integrating different semantic annotations. In this context, a system named IoT Semantic Annotations System (IoTSAS) is developed. Furthermore, the performance of the IoTSAS System is presented by testing air quality and weather alerts monitoring IoT domains by extending the Open Geospatial Consortium (OGC) standards and the Sensor Observations Service (SOS) standards, respectively. The developed system provides information in real time to citizens about the health implications from air pollution and weather conditions, e.g., blizzard, flurry, etc.