bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer
Authors: Powrózek Tomasz , Ochieng Otieno Michael
Published: February 2022

Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and is related to unfavorable prognosis and limited treatment strategies. Currently, there is a lack of reliable biomarkers allowing for the clinical management of TNBC. This is probably caused by a complex molecular background, leading to the development and establishment of a unique tumor phenotype. Recent studies have reported non-coding RNAs (ncRNAs) not only as the most promising class of molecular agents with a high applicability to manage human cancers, including TNBC, but also as robust and non-invasive biomarkers that are able to be monitored in blood circulation, with the application of liquid biopsy. There is a lack of papers discussing the role of blood-circulating ncRNAs as diagnostic, predictive, and prognostic biomarkers for TNBC. In this paper, we summarized the available literature reports on the utility of blood-circulating ncRNAs for TNBC management. Additionally, we supplemented this review by bioinformatics analysis, for better understanding of the role of ncRNAs’ machinery in the development of a unique TNBC phenotype.
Imaging-Based Screening of Deubiquitinating Proteases Identifies Otubain-1 as a Stabilizer of c-MYC
Authors: Moree Shannon E. , Maneix Laure , Iakova Polina , Stossi Fabio , Sahin Ergun , Catic Andre
Published: February 2022

The ubiquitin–proteasome pathway precisely controls the turnover of transcription factors in the nucleus, playing an important role in maintaining appropriate quantities of these regulatory proteins. The transcription factor c-MYC is essential for normal development and is a critical cancer driver. Despite being highly expressed in several tissues and malignancies, the c-MYC protein is also continuously targeted by the ubiquitin–proteasome pathway, which can either facilitate or inhibit c-MYC degradation. Deubiquitinating proteases can remove ubiquitin chains from target proteins and rescue them from proteasomal digestion. This study sought to determine novel elements of the ubiquitin–proteasome pathway that regulate c-MYC levels. We performed an overexpression screen with 41 human proteases to identify which deubiquitinases stabilize c-MYC. We discovered that the highly expressed Otubain-1 (OTUB1) protease increases c-MYC protein levels. Confirming its role in enhancing c-MYC activity, we found that elevated OTUB1 correlates with inferior clinical outcomes in the c-MYC-dependent cancer multiple myeloma, and overexpression of OTUB1 accelerates the growth of myeloma cells. In summary, our study identifies OTUB1 as a novel amplifier of the proto-oncogene c-MYC.
Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice
Authors: Kakudo Kennichi
Published: February 2022

Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with delicate RAS-like nuclear changes are follicular adenomas when they are noninvasive, follicular carcinomas when invasive, and follicular variant PTCs when they have fully developed PTC-type nuclear features in Asian practice. The different diagnostic threshold of PTC nuclear features resulted in a high (50–90%) incidence of BRAFV600E mutation of PTCs in most Asian countries, whereas it was low (35–50%) in most Western patient cohorts. The contamination of indolent RAS-like tumors in the malignant PTC category in Western patient cohorts explains why the BRAFV600E gene test identifies aggressive PTCs. However, the BRAFV600E test has no prognostic value for Asian PTC patients because most biologically benign or low-risk RAS-like tumors are excluded from PTC. All prognostic analyses of thyroid carcinomas before 2017 must be re-evaluated because most clinical guidelines were established based on data obtained from Western patient cohorts where a significant number of indolent RAS-like tumors were misclassified in the malignant category.
Modeled Early Longitudinal PSA Kinetics Prognostic Value in Rising PSA Prostate Cancer Patients after Local Therapy Treated with ADT +/− Docetaxel
Authors: Carrot Aurore , Elaidi Reza-Thierry , Colomban Olivier , Maillet Denis , Tod Michel , You Benoit , Oudard Stéphane
Published: February 2022

Background: In metastatic prostate cancer (PCa) patients, androgen-deprivation therapy (ADT) combined with chemotherapy or next-generation androgen receptor targeted agents is a new standard treatment. The objective of the present study is to assess longitudinal PSA kinetics during treatment using mathematical modeling, to identify the modeled PSA kinetic parameters able to exhibit early prognostic/predictive values. Methods: Phase III clinical trial dataset (NCT00764166) comparing ADT +/− docetaxel in 250 locally treated patients for PCa with rising PSA levels, who were at high risk of metastatic disease was assessed. A kinetic-pharmacodynamic (K-PD) model was used to fit PSA kinetics during the first 100 treatment days, to estimate the modeled PSA production rate K (KPROD) and elimination constant rate K (KELIM). The prognostic value of these parameters, considered as categorized (favorable vs. unfavorable) covariates regarding PSA progression-free survival (PSA-PFS) and overall survival (OS), was assessed using univariate/multivariate analyses. Results: Data from 177/250 patients was assessed. KELIM exhibited a significant prognostic value regarding PSA-PFS and KPROD regarding OS (univariate analysis). In the PSA-PFS final multivariate model, KELIM and the primary therapy type were significant. The OS multivariate model integrated both KPROD and baseline PSA doubling-time. Conclusion: In this first study assessing the modeled PSA kinetics prognostic value in PCa patients treated with systemic treatments, KELIM and KPROD exhibited respective prognostic values regarding PSA-PFS and OS.
Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases
Authors: Rhaiem Rami , Rached Linda , Tashkandi Ahmad , Bouché Olivier , Kianmanesh Reza
Published: February 2022

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. More than 50% of patients with CRC will develop liver metastases (CRLM) during their disease. In the era of precision surgery for CRLM, several advances have been made in the multimodal management of this disease. Surgical treatment, combined with a modern chemotherapy regimen and targeted therapies, is the only potential curative treatment. Unfortunately, 70% of patients treated for CRLM experience recurrence. RAS mutations are associated with worse overall and recurrence-free survival. Other mutations such as BRAF, associated RAS /TP53 and APC/PIK3CA mutations are important genetic markers to evaluate tumor biology. Somatic mutations are of paramount interest for tailoring preoperative treatment, defining a surgical resection strategy and the indication for ablation techniques. Herein, the most relevant studies dealing with RAS mutations and the management of CRLM were reviewed. Controversies about the implication of this mutation in surgical and ablative treatments were also discussed.
Early Predictor Tool of Disease Using Label-Free Liquid Biopsy-Based Platforms for Patient-Centric Healthcare
Authors: Li Wei , Zhou Yunlan , Deng Yanlin , Khoo Bee Luan
Published: February 2022

Cancer cells undergo phenotypic changes or mutations during treatment, making detecting protein-based or gene-based biomarkers challenging. Here, we used algorithmic analysis combined with patient-derived tumor models to derive an early prediction tool using patient-derived cell clusters from liquid biopsy (LIQBP) for cancer prognosis in a label-free manner. The LIQBP platform incorporated a customized microfluidic biochip that mimicked the tumor microenvironment to establish patient clusters, and extracted physical parameters from images of each sample, including size, thickness, roughness, and thickness per area (n = 31). Samples from healthy volunteers (n = 5) and cancer patients (pretreatment; n = 4) could be easily distinguished with high sensitivity (91.16 ± 1.56%) and specificity (71.01 ± 9.95%). Furthermore, we demonstrated that the multiple unique quantitative parameters reflected patient responses. Among these, the ratio of normalized gray value to cluster size (RGVS) was the most significant parameter correlated with cancer stage and treatment duration. Overall, our work presented a novel and less invasive approach for the label-free prediction of disease prognosis to identify patients who require adjustments to their treatment regime. We envisioned that such efforts would promote the management of personalized patient care conveniently and cost effectively.
Targeting Mitochondrial COX-2 Enhances Chemosensitivity via Drp1-Dependent Remodeling of Mitochondrial Dynamics in Hepatocellular Carcinoma
Authors: Che Lin , Wu Jia-Shen , Du Ze-Bang , He Yu-Qiao , Yang Lei , Lin Jin-Xian , Lei Zhao , Chen Xiao-Xuan , Guo Dong-Bei , Li Wen-Gang , Lin Yu-Chun , Lin Zhong-Ning
Published: February 2022

Mitochondria are highly dynamic organelles and undergo constant fission and fusion, which are both essential for the maintenance of cell physiological functions. Dysregulation of dynamin-related protein 1 (Drp1)-dependent mitochondrial dynamics is associated with tumorigenesis and the chemotherapeutic response in hepatocellular carcinoma (HCC). The enzyme cyclooxygenase-2 (COX-2) is overexpressed in most cancer types and correlates with a poor prognosis. However, the roles played by the translocation of mitochondrial COX-2 (mito-COX-2) and the interaction between mito-COX-2 and Drp1 in chemotherapeutic responses remain to be elucidated in the context of HCC. Bioinformatics analysis, paired HCC patient specimens, xenograft nude mice, immunofluorescence, transmission electron microscopy, molecular docking, CRISPR/Cas9 gene editing, proximity ligation assay, cytoplasmic and mitochondrial fractions, mitochondrial immunoprecipitation assay, and flow cytometry analysis were performed to evaluate the underlying mechanism of how mito-COX-2 and p-Drp1Ser616 interaction regulates the chemotherapeutic response via mitochondrial dynamics in vitro and in vivo. We found that COX-2 and Drp1 were frequently upregulated and confer a poor prognosis in HCC. We also found that the proportion of mito-COX-2 and p-Drp1Ser616 was increased in HCC cell lines. In vitro, we demonstrated that the enhanced mitochondrial translocation of COX-2 promotes its interaction with p-Drp1Ser616 via PTEN-induced putative kinase 1 (PINK1)-mediated Drp1 phosphorylation activation. This increase was associated with higher colony formation, cell proliferation, and mitochondrial fission. These findings were confirmed by knocking down COX-2 in HCC cells using CRISPR/Cas9 technology. Furthermore, inhibition of Drp1 using pharmacologic inhibitors (Mdivi-1) or RNA interference (siDNM1L) decreased mito-COX-2/p-Drp1Ser616 interaction-mediated mitochondrial fission, and increased apoptosis in HCC cells treated with platinum drugs. Moreover, inhibiting mito-COX-2 acetylation with the natural phytochemical resveratrol resulted in reducing cell proliferation and mitochondrial fission, occurring through upregulation of mitochondrial deacetylase sirtuin 3 (SIRT3), which, in turn, increased the chemosensitivity of HCC to platinum drugs in vitro and in vivo. Our results suggest that targeting interventions to PINK1-mediated mito-COX-2/p-Drp1Ser616-dependent mitochondrial dynamics increases the chemosensitivity of HCC and might help us to understand how to use the SIRT3-modulated mito-COX-2/p-Drp1Ser616 signaling axis to develop an effective clinical intervention in hepatocarcinogenesis.
The Risk Analyses of Lymph Node Metastasis and Recurrence for Submucosal Invasive Colorectal Cancer: Novel Criteria to Skip Completion Surgery
Authors: Ozeki Takanori , Shimura Takaya , Ozeki Tomonori , Ebi Masahide , Iwasaki Hiroyasu , Kato Hiroyuki , Inaguma Shingo , Okuda Yusuke , Katano Takahito , Nishie Hirotada , Takahashi Satoru , Kataoka Hiromi
Published: February 2022

(1) Background: Additional surgical resection after endoscopic resection (ER) is recommended for patients with submucosal invasive colorectal cancer (pT1 CRC) who have risk factors for lymph node metastasis (LNM) (high-risk pT1 CRC). This study aimed to identify risk factors for LNM and metastatic recurrence and to determine the low-risk population for whom additional surgery can be omitted among high-risk pT1 CRCs. (2) Methods: We retrospectively identified 404 patients with pT1 CRC who underwent ER or surgery, and patients were divided into three groups: low-risk (n = 79); high-risk pT1 with ER (n = 40); and high-risk with surgery (n = 285). We also enrolled another 64 patients with high-risk pT1 CRC in an independent validation cohort. (3) Results: In the high-risk with surgery group, LNM was seen in 11.2%, and vascular and lymphatic invasions were significantly independent risk factors for LNM on multivariate analysis. No LNMs were observed in pT1 CRCs with a negative vertical margin and SM invasion depth ≤2000 µm that had no other risk factors except for budding. Five patients developed metastatic recurrence in the high-risk with surgery group, and rectal cancer and undifferentiated histology were significantly independent risk factors for poor relapse-free survival. No LNM or recurrent cases were seen in high-risk pT1 CRCs that met these criteria: differentiated adenocarcinoma, no lymphovascular invasion, colon cancer, SM invasion depth ≤2000 μm, and a negative vertical margin, which were validated in an independent validation cohort. (4) Conclusions: Completion surgery may be skipped for high-risk pT1 CRCs that meet our proposed criteria.
Long-Term Follow-Up of Elderly Patients with Acute Myeloid Leukemia Treated with Decitabine: A Real-World Study of the Apulian Hematological Network
Authors: Dargenio Michelina , Tarantini Giuseppe , Cascavilla Nicola , Pavone Enzo , Musto Pellegrino , Mazza Patrizio , Melillo Lorella , Pastore Domenico , Guarini Attilio , Buquicchio Caterina , Fina Maria Paola , Federico Vincenzo , Santeramo Teresa Maria , Urbano Marina Aurora , Leo Mariangela , Carluccio Vera , Carluccio Paola , Delia Mario , Carlino Daniela , Vergine Carolina , Gagliardi Vito Pier , Greco Giuseppina , Sibilla Silvia , Abbenante Mariachiara , Rossi Giovanni , Spinosa Giuseppina , Mazzone Annamaria , Aprile Lara , de Fazio Vincenza , Pasciolla Crescenza , Specchia Giorgina , Di Renzo Nicola
Published: February 2022

Decitabine, a DNA hypomethylating agent, was approved for use in adults with acute myeloid leukemia (AML) not eligible for standard chemotherapy and is now widely accepted as standard treatment. Although a number of clinical trials demonstrated its benefits in elderly AML patients, older adults and patients with frequent comorbidities are typically under-represented in such settings. Thus, the aim of the present study is to evaluate, in a real-world setting, the effectiveness and toxicity of decitabine administered as a single agent in unselected previously untreated elderly AML patients not eligible for intensive chemotherapy. In nine hematological departments of the Apulian Hematological Network (REP), we enrolled 199 patients (median age: 75.4 years; range: 61–91) with de novo (n = 94) or secondary/therapy-related (n = 105) AML treated with decitabine 20 mg/m2 for five days every 4 weeks. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using multivariate Cox regression. The average number of cycles administered per patient was 6.3 (SD: 6.0; median: 5 cycles). Complete response was achieved by 31 patients (15.6%) and partial response by 57 (28.6%), for a total of 88 responders overall (44.2%). After a median follow-up of 33.6 months, median OS was 8.7 months (95% CI: 7.4–10.3), and the 6-month, 1-year, and 3-year OS rates were 62.7%, 37.0%, and 7.1%, respectively. Mortality was increased in AML patients with ≥3 comorbidities (HR = 2.45; 95% CI: 1.18–5.08) vs. no comorbidities and in those with adverse karyotype (HR = 1.58; 95% CI: 1.05–2.38) vs. favourable or intermediate profile. Infection was the main registered adverse event (46.0%). In conclusion, this REP real-life study demonstrates, after a follow-up of almost 3 years, how decitabine administered to AML patients not suitable for intensive chemotherapy is effective and well tolerated, even in a population of truly elderly patients with frequent comorbidities.
Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models
Authors: Shin Ha-Yeon , Lee Eun-ju , Yang Wookyeom , Kim Hyo Sun , Chung Dawn , Cho Hanbyoul , Kim Jae-Hoon
Published: February 2022

Patient-derived xenografts (PDXs) are important in vivo models for the development of precision medicine. However, challenges exist regarding genetic alterations and relapse after primary treatment. Thus, PDX models are required as a new approach for preclinical and clinical studies. We established PDX models of gynecologic cancers and analyzed their clinical information. We subcutaneously transplanted 207 tumor tissues from patients with gynecologic cancer into nude mice from 2014 to 2019. The successful engraftment rate of ovarian, cervical, and uterine cancer was 47%, 64%, and 56%, respectively. The subsequent passages (P2 and P3) showed higher success and faster growth rates than the first passage (P1). Using gynecologic cancer PDX models, the tumor grade is a common clinical factor affecting PDX establishment. We found that the PDX success rate correlated with the patient’s prognosis, and also that ovarian cancer patients with a poor prognosis had a faster PDX growth rate (p < 0.0001). Next, the gene sets associated with inflammation and immune responses were shown in high-ranking successful PDX engraftment through gene set enrichment analysis and RNA sequencing. Up-regulated genes in successful engraftment were found to correlate with ovarian clear cell cancer patient outcomes via Gene Expression Omnibus dataset analysis.
Systemic Therapy for Oligoprogression in Patients with Metastatic NSCLC Harboring Activating EGFR Mutations
Authors: Rossi Antonio , Galetta Domenico
Published: February 2022

After a variable period of activity of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations develop resistance to these TKIs. In some cases, an oligoprogression is diagnosed, and its management is still controversial. The oligoprogression represents an intermediate stage of metastatic NSCLC between localized and widely disseminated disease, and is characterized by a limited number and/or sites of metastases in which a disease progression appears, together with a more indolent tumor biology. Currently, the management of oligoprogressed NSCLC involves local treatment, including radiotherapy and/or surgery, to control the progressive lesions. Systemic therapy should also be a potential approach to boost the activity of EGFR-TKIs. However, considering the lack of large trials addressing this topic, the optimal therapeutic strategies remain undefined and should be evaluated on an individualized basis. In this paper, we review the most relevant scientific evidence of continuing the systemic therapy with the same EGFR-TKI for the management of patients with NSCLC harboring EGFR mutations and oligoprogressed to first-line EGFR-TKIs, also discussing the controversies and potential future directions.
Systemic Influences of Mammary Cancer on Monocytes in Mice
Authors: Robinson Amy , Burgess Matthew , Webb Sheila , Louwe Pieter A. , Ouyang Zhengyu , Skola Dylan , Han Claudia Z. , Batada Nizar N. , González-Huici Víctor , Cassetta Luca , Glass Chris K. , Jenkins Stephen J. , Pollard Jeffery W.
Published: February 2022

There is a growing body of evidence that cancer causes systemic changes. These influences are most evident in the bone marrow and the blood, particularly in the myeloid compartment. Here, we show that there is an increase in the number of bone marrow, circulating and splenic monocytes by using mouse models of breast cancer caused by the mammary epithelial expression of the polyoma middle T antigen. Cancer does not affect ratios of classical to non-classical populations of monocytes in the circulation nor does it affect their half-lives. Single cell RNA sequencing also indicates that cancer does not induce any new monocyte populations. Cancer does not change the monocytic progenitor number in the bone marrow, but the proliferation rate of monocytes is higher, thus providing an explanation for the expansion of the circulating numbers. Deep RNA sequencing of these monocytic populations reveals that cancer causes changes in the classical monocyte compartment, with changes evident in bone marrow monocytes and even more so in the blood, suggesting influences in both compartments, with the down-regulation of interferon type 1 signaling and antigen presentation being the most prominent of these. Consistent with this analysis, down-regulated genes are enriched with STAT1/STAT2 binding sites in their promoter, which are transcription factors required for type 1 interferon signaling. However, these transcriptome changes in mice did not replicate those found in patients with breast cancer. Consequently, this mouse model of breast cancer may be insufficient to study the systemic influences of human cancer.
Effect of the Colloidal Preparation Method for Supported Preformed Colloidal Au Nanoparticles for the Liquid Phase Oxidation of 1,6-Hexanediol to Adipic Acid
Authors: Monti Eleonora , Ventimiglia Alessia , Garcia Soto Carolina Alejandra , Martelli Francesca , Rodríguez-Aguado Elena , Cecilia Juan Antonio , Sadier Achraf , Ospitali Francesca , Tabanelli Tommaso , Albonetti Stefania , Cavani Fabrizio , Wojcieszak Robert , Dimitratos Nikolaos
Published: February 2022

Supported on activated carbon gold colloidal nanoparticles have been prepared in the presence of the stabilizing polymer PVA and PVP (polyvinylalcohol, polyvinylpyrrolidone). The effect of the polymer to the Au weight ratio was investigated, for synthesizing gold nanoparticles with different particle size and particle size distribution. By varying the polymer/Au wt/wt ratio, gold nanoparticles with mean diameters from 3 to 8 nm were synthesized. The synthesized Au catalysts were studied in the liquid phase oxidation of 1,6-hexanediol (HDO) to adipic acid under base and base-free conditions. A range of experimental parameters were varied for the optimization of reaction conditions and the most promising Au catalysts were further evaluated in terms of catalytic performance. We demonstrated that the influence of choice of polymer, tuning the polymer to Au weight ratio, HDO to Au molar ratio, and use of basic conditions have an important influence in terms of catalytic activity and selectivity to adipic acid. The highest yield to adipic acid was obtained using Au-PVA catalysts (40% at 110 °C under base free conditions), however, at low HDO to Au molar ratio and lower carbon balance (70–80%). On the contrary, at higher HDO to Au molar ratio, and under basic conditions, the yield was in the range of 18–20% with a significant improvement in terms of carbon balance (88–100%).
Antimicrobial Activity of Commercial Photocatalytic SaniTise™ Window Glass
Authors: Kisand Vambola , Visnapuu Meeri , Rosenberg Merilin , Danilian Dmytro , Vlassov Sergei , Kook Mati , Lange Sven , Pärna Rainer , Ivask Angela
Published: February 2022

Photocatalytic and antibacterial properties of TiO2-based SaniTise™ glass by Pilkington were studied with an aim to benchmark this first commercial UVA-activated antimicrobial glass and to evaluate its efficacy in indoor-like conditions. For comparison, the antibacterial and photocatalytic activity of self-cleaning BIOCLEAN® glass and photocatalytically inactive clear float PLANICLEAR® control glass were analysed. The presence of an anatase TiO2 layer was demonstrated on the surface of SaniTise™ and BIOCLEAN®. Photocatalytic degradation of organic model dye and antibacterial activity against Escherichia coli and Staphylococcus aureus were higher on SaniTise™ than on BIOCLEAN®. In a liquid antibacterial assay corresponding to ISO 27447 format, 4 h exposure of bacteria to the SaniTise™ surface under UVA resulted in >2.8 log decrease in E. coli and >2.5 log decrease in S. aureus viable cell counts. In experiments with the more application-relevant “dry droplet method”, significantly higher antibacterial activity was observed up to the level where during 4 h at ≤50% RH complete inactivation of bacteria was observed also on PLANICLEAR® control glass. The latter raises concerns about the real-life relevancy of the standard test conditions and suggests that at low air humidity conditions, shorter exposure periods than suggested by current antimicrobial testing protocols should be targeted by photocatalytically active antibacterial surfaces.
Solution XAS Analysis for Reactions of Phenoxide-Modified (Arylimido)vanadium(V) Dichloride and (Oxo)vanadium(V) Complexes with Al Alkyls: Effect of Al Cocatalyst in Ethylene (Co)polymerization
Authors: Nomura Kotohiro , Izawa Itsuki , Kuboki Mahaharu , Inoue Kensuke , Aoki Hirotaka , Tsutsumi Ken
Published: February 2022

V K-edge XANES (XANES = X-ray Absorption Near Edge Structure) spectra of the reaction solution of V(NAr)Cl2(OAr) (1, Ar = 2,6-Me2C6H3) with halogenated Al alkyls (Me2AlCl, Et2AlCl, EtAlCl2, 50 equiv) in toluene showed low energy shifts (2.6–3.6 eV on the basis of inflection point in the photon energy) in the edge absorption accompanying slight shift to low photon energy in the pre-edge peak (λmax values); a similar spectrum was observed when the reaction of 1 with Me2AlCl was conducted in n-hexane. These results strongly suggest a formation of similar vanadium(III) species irrespective of kind of Al alkyls and solvent (toluene or n-hexane). Significant low-energy shifts in the edge absorption accompanied with diminishing the strong pre-edge absorption were also observed when VOCl3 or VO(OiPr)3 was treated with Me2AlCl (10 equiv) in toluene, clearly indicating a formation of low oxidation state vanadium species accompanied with certain structural changes (from tetrahedral to octahedral) in solution.
Activation of Small Molecules and Hydrogenation of CO2 Catalyzed by Frustrated Lewis Pairs
Authors: Pal Ranita , Ghara Manas , Chattaraj Pratim Kumar
Published: February 2022

The chemistry of frustrated Lewis pair (FLP) is widely explored in the activation of small molecules, the hydrogenation of CO2, and unsaturated organic species. A survey of several experimental works on the activation of small molecules by FLPs and the related mechanistic insights into their reactivity from electronic structure theory calculation are provided in the present review, along with the catalytic hydrogenation of CO2. The mechanistic insight into H2 activation is thoroughly discussed, which may provide a guideline to design more efficient FLP for H2 activation. FLPs can activate other small molecules like, CO, NO, CO2, SO2, N2O, alkenes, alkynes, etc. by cooperative action of the Lewis centers of FLPs, as revealed by several computational analyses. The activation barrier of H2 and other small molecules by the FLP can be decreased by utilizing the aromaticity criterion in the FLP as demonstrated by the nucleus independent chemical shift (NICS) analysis. The term boron-ligand cooperation (BLC), which is analogous to the metal-ligand cooperation (MLC), is invoked to describe a distinct class of reactivity of some specific FLPs towards H2 activation.
Low Energy Status under Methionine Restriction Is Essentially Independent of Proliferation or Cell Contact Inhibition
Authors: Koderer Corinna , Schmitz Werner , Wünsch Anna Chiara , Balint Julia , El-Mesery Mohamed , Volland Julian Manuel , Hartmann Stefan , Linz Christian , Kübler Alexander Christian , Seher Axel
Published: February 2022

Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy.
How We Manage Myelofibrosis Candidates for Allogeneic Stem Cell Transplantation
Authors: Polverelli Nicola , Farina Mirko , D’Adda Mariella , Damiani Enrico , Grazioli Luigi , Leoni Alessandro , Malagola Michele , Bernardi Simona , Russo Domenico
Published: February 2022

Moving from indication to transplantation is a critical process in myelofibrosis. Most of guidelines specifically focus on either myelofibrosis disease or transplant procedure, and, currently, no distinct indication for the management of MF candidates to transplant is available. Nevertheless, this period of time is crucial for the transplant outcome because engraftment, non-relapse mortality, and relapse incidence are greatly dependent upon the pre-transplant management. Based on these premises, in this review, we will go through the path of identification of the MF patients suitable for a transplant, by using disease-specific prognostic scores, and the evaluation of eligibility for a transplant, based on performance, comorbidity, and other combined tools. Then, we will focus on the process of donor and conditioning regimens’ choice. The pre-transplant management of splenomegaly and constitutional symptoms, cytopenias, iron overload and transplant timing will be comprehensively discussed. The principal aim of this review is, therefore, to give a practical guidance for managing MF patients who are potential candidates for allo-HCT.
Induction of Survival of Motor Neuron (SMN) Protein Deficiency in Spinal Astrocytes by Small Interfering RNA as an In Vitro Model of Spinal Muscular Atrophy
Authors: Leo Markus , Schmitt Linda-Isabell , Fleischer Michael , Steffen Rebecca , Osswald Cora , Kleinschnitz Christoph , Hagenacker Tim
Published: February 2022

Spinal muscular atrophy (SMA) is a motor neuron disorder leading to progressive loss of ventral horn neurons resulting in muscle wasting. Here we investigate the contribution of spinal astrocytes to the pathogenesis of late-onset SMA forms using a mouse model. Furthermore, we generated SMA-like astrocytes using survival of motor neuron (SMN) siRNA transfection techniques. In the SMA mouse model, the activation of spinal astrocytes and the reduction of the inward rectifier potassium channel Kir4.1 and excitatory amino acid transporter 1 (EAAT1) were observed at postnatal day (P) 28, preceding the loss of spinal motor neurons appearing earliest at P42. Using SMA-like astrocytes, we could mimic the modulation of spinal astrocytes of the mouse model in a dish and perform electrophysiological assessments and functional assays. In SMA-like astrocytes, glutamate uptake was diminished due to a reduction in EAAT1. Furthermore, patch-clamp measurements revealed reduced potassium uptake into astrocytes with membrane depolarization. Additionally, exposure of healthy spinal motor neurons to a conditioned medium of SMA-like astrocytes resulted in increased firing frequency. These data demonstrate spinal astrocytes’ crucial role in the late-onset SMA forms’ pathogenesis.
Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas
Authors: Griso Ana Belén , Acero-Riaguas Lucía , Castelo Beatriz , Cebrián-Carretero José Luis , Sastre-Perona Ana
Published: February 2022

Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies are emerging, cisplatin-based chemotherapy remains the gold standard for advanced HNSCCs, although most of the patients relapse due to the development of resistance. This review aims to condense the different mechanisms involved in the development of cisplatin resistance in HNSCCs and highlight future perspectives intended to overcome its related complications. Classical resistance mechanisms include drug import and export, DNA repair and oxidative stress control. Emerging research identified the prevalence of these mechanisms in populations of cancer stem cells (CSC), which are the cells mainly contributing to cisplatin resistance. The use of old and new CSC markers has enabled the identification of the characteristics within HNSCC CSCs predisposing them to treatment resistance, such as cell quiescence, increased self-renewal capacity, low reactive oxygen species levels or the acquisition of epithelial to mesenchymal transcriptional programs. In the present review, we will discuss how cell intrinsic and extrinsic cues alter the phenotype of CSCs and how they influence resistance to cisplatin treatment. In addition, we will assess how the stromal composition and the tumor microenvironment affect drug resistance and the acquisition of CSCs’ characteristics through a complex interplay between extracellular matrix content as well as immune and non-immune cell characteristics. Finally, we will describe how alterations in epigenetic modifiers or other signaling pathways can alter tumor behavior and cell plasticity to induce chemotherapy resistance. The data generated in recent years open up a wide range of promising strategies to optimize cisplatin therapy, with the potential to personalize HNSCC patient treatment strategies.
Protein Lipidation by Palmitate Controls Macrophage Function
Authors: Guns Jeroen , Vanherle Sam , Hendriks Jerome J. A. , Bogie Jeroen F. J.
Published: February 2022

Macrophages are present in all tissues within our body, where they promote tissue homeostasis by responding to microenvironmental triggers, not only through clearance of pathogens and apoptotic cells but also via trophic, regulatory, and repair functions. To accomplish these divergent functions, tremendous dynamic fine-tuning of their physiology is needed. Emerging evidence indicates that S-palmitoylation, a reversible post-translational modification that involves the linkage of the saturated fatty acid palmitate to protein cysteine residues, directs many aspects of macrophage physiology in health and disease. By controlling protein activity, stability, trafficking, and protein–protein interactions, studies identified a key role of S-palmitoylation in endocytosis, inflammatory signaling, chemotaxis, and lysosomal function. Here, we provide an in-depth overview of the impact of S-palmitoylation on these cellular processes in macrophages in health and disease. Findings discussed in this review highlight the therapeutic potential of modulators of S-palmitoylation in immunopathologies, ranging from infectious and chronic inflammatory disorders to metabolic conditions.
Theoretical and Experimental Investigate for the Magnetic and Optical Properties of Mn-ZnO Nanowire Microspheres
Authors: Zhang Lei , Wang Wei , Dai Rong , Ning Jing , Zhang Fuchun , Yan Junfeng
Published: February 2022

A Mn-ZnO nanowire microsphere was prepared by using the hydrothermal method. The effects of Mn doping concentration and hydrothermal growth conditions on the crystal structures, morphologies, magnetic and optical properties of ZnO nanowire microsphere were studied. The characterization results showed Mn-ZnO nanowire microsphere with uniform and dense distributions along the [0001] direction with a hexagonal wurtzite structure. No impurity phases were detected in microsphere specimens. The room-temperature ferromagnetism of the Mn-ZnO nanowire microsphere was detected, with the saturation magnetization of 2.4 × 10−1 emu/g and a coercive field of 369 Oe. Furthermore, with the increase of Mn2+ ions doping concentration, the luminescence intensity of the sample decreases in both UV and visible regions, and slight blueshift in the visible light regions was observed. The theoretical results presented obvious spin polarization near the Fermi level, with strong Mn 3d and O 2p hybridization effects. The magnetic moments were mainly generated by Mn 3d and partial contribution of O 2p orbital electrons. Therefore, the Mn-ZnO nanowire microsphere can be used as a potential magneto-optical material.
Impact of Smokeless Tobacco on the Color Stability of Zirconia, Zirconia-Reinforced Lithium Silicate and Feldspathic CAD/CAM Restorative Materials: An In Vitro Study
Authors: Al Moaleem Mohammed M. , Adawi Hafiz A. , Alsharif Khalaf F. , Alhazmi Hassan A. , Alshahrani Faris A. , Abu Hadi Ramzi M. , Kara Recep , Muyidi Hussam M. , Khalid Asaad , Asiri Abdulrahman M. , Huraysi Ahmed H. , Khubrani Jabbar A. , Bhandi Shilpa , Patil Shankargouda
Published: February 2022

WHO estimates that the global number of tobacco users exceeds 1.3 billion people. Few studies have examined the effect of locally made smokeless tobacco (ST) products on the color changes of material used in dental prosthetics. Bearing the recent advances in CAD/CAM ceramic restorations material in mind, this study aimed to assess ST influence on mean color change (∆E*) values among selected CAD/CAM ceramic types: multilayer zirconia (Ceramill Zolid PS), zirconia-reinforced lithium silicate ceramic (Vita Suprinity), and feldspathic (Vita TriLuxe) restorative materials. The color changes of the ceramics were compared to VITA classical and VITA 3D-MASTER shade guides. Sixty CAD/CAM ceramic specimens (20 samples each) were fabricated from Ceramill Zolid PS, Vita TriLuxe Forte, and VITA Suprinity. Specimens were prepared and divided into two groups according to the ST type and immersed for two weeks. Basic VITA classical and VITA 3D-MASTER colors were recorded at a baseline of one week and two weeks. The highest ∆E* values were recorded in the black ST for Vita Suprinity (4.77) in the first week, followed by Vita TriLuxe (4.07) in the second week. For white ST, Vita TriLuxe (4.87), and Vita Suprinity (4.42) showed extensive color change after two weeks and one week, respectively. The color change was least in zirconia for black and white ST after one week. CAD/CAM ceramic materials showed no significant difference after 1 and 2 weeks for the tested ST types. The effects of ST on CAD/CAM ceramic material (∆E* values) were high but did not reach clinically unacceptable values. Zirconia showed the least amount of color change among all the tested materials.
Research into Carbon Dioxide Curing’s Effects on the Properties of Reactive Powder Concrete with Assembly Unit of Sulphoaluminate Cement and Ordinary Portland Cement
Authors: Cao Hongfei , Liang Zhao , Peng Xi , Cai Xin , Wang Kewei , Wang Hui , Lyu Zhongda
Published: February 2022

Excessive emissions of carbon dioxide can lead to greenhouse effect thus destroying the ecological balance. Therefore, effective measures need to be taken to reduce the emission of carbon dioxide. In this study, the influence of carbon dioxide curing on the mechanical strength and NaCl freeze-thaw deterioration of reactive powder concrete (RPC) with the assembly unit of sulphoaluminate cement and ordinary Portland cement was investigated. The ratio of sulphoaluminate cement ranged from 0% to 100% by the total mass of cement with the curing age ranging from 1 d to 28 d. The mechanical strength of RPC with 50% ordinary Portland cement and 50% sulphoaluminate cement containing the polypropylene fibers ranging from 1% to 4% by volume of RPC were investigated. Moreover, the following mass and mechanical strength loss rates, the carbonation depth, the chloride ion migration coefficient and the relative dynamic elastic modulus (RDEM) during NaCl freeze-thaw cycles were determined. Finally, the scanning electron microscope (SEM) and X-ray diffraction were applied in investigating the carbonation process of RPC. Results showed that the addition of sulphoaluminate cement could improve the mechanical strength of RPC at low curing age (lower than 7 d). However, when the cuing age reached 7 d, the sulphoaluminate cement demonstrated negative effect on the mechanical strength. Moreover, the carbon dioxide curing led to increases in the mechanical strength and when ordinary Portland cement was added the enhancing effect was more obvious. Furthermore, the carbon dioxide curing could effectively improve the resistance of NaCl freeze-thaw cycles and increase the carbonation depth. Finally, the increasing dosages of polypropylene fibers were advantageous to the mechanical strength and the resistance of NaCl freeze-thaw cycles. From the researching results of the microscopic performance, the carbon dioxide curing could improve the compactness of hydration products and reduce the content of calcium hydroxide especially at the curing age of 3 days.
Is Allergy to Titanium Bone Fixation Plates a Problem?
Authors: Niedzielska Iwona , Sitek-Ignac Natalia , Bąk Michał , Niedzielski Damian
Published: February 2022

Open reduction and internal fixation (ORIF) with titanium fixation plates is the gold standard for maxillofacial fracture treatment. Titanium is considered a fully compatible material. However, reports of allergic reactions to titanium implants do occur. The aim of this work is to answer the question whether titanium devices used in the treatment of fractures in the craniofacial region can cause allergic reactions. The study comprised 50 subjects treated surgically for maxillofacial injuries with the use of titanium composite devices. Allergic tests were performed by the patch method. The control group consisted of 20 healthy people who did not have any titanium elements. There were no skin changes to titanium and its compounds in both the test and control groups. Only one patient had a positive skin test which showed an allergic reaction to silver nitrate. Titanium fixing elements, as well as titanium dental implants, according to our research, do not show allergic skin reactions.
Synthesis, Characterization, and Antimicrobial of MnO and CdO Nanoparticles by Using a Calcination Method
Authors: Al-Fakeh Maged S. , Alsaedi Roaa O. , Amiri Nesrine , Allazzam Gadah A.
Published: February 2022

Nano-sized manganese oxide and cadmium oxide were formed quantitatively via chemical routes, using calcination from an aqueous solution containing metal chloride as a precursor, to create polyvinyl alcohol and para-aminobenzoic acid complexes with the following formulae: [Mn (PVA)(P-ABA) (H2O)3] H2O and [Cd (PVA)(P-ABA) (H2O)3]. The synthesized complexes and metal oxide nanoparticles were characterized using elemental analysis, thermal analyses (TGA and DTA), FT-IR spectroscopy, XRD analysis, UV-vis spectra, and SEM and TEM electron microscopes. The kinetic and thermodynamic parameters (∆H*, ∆G* and ∆S*) for the Mn(II) and Cd(II) coordination compounds were calculated. The antimicrobial properties of the samples were assessed using five bacterial strains and three fungal strains. Three strains of (G+) bacteria, two strains of (G−) bacteria, one stain of yeast-like fungi, and two molds were used in this study.
Wettability and Stability of Naproxen, Ibuprofen and/or Cyclosporine A/Silica Delivery Systems
Authors: Wiącek Agnieszka Ewa , Przykaza Kacper
Published: February 2022

The characteristics of the wetting process of the porous surface of silica gel when penetrated by base liquids (water and n-octane), ethanol and stable drug systems (naproxen, ibuprofen and cyclosporine A), as biologically active substances in two ethanol concentrations, were determined by the wetting rate vs. time. The tests were performed for contacted and non-contacted plates with the vapours of the wetting liquid. Thin-layer liquid chromatography was used to determine the penetration rate of the SiO2-coated plates, taking into account the linear dependence consistent with the Washburn equation. Additionally, the changes in the adhesive tension ΔG were determined for the tested drugs. Drug stability tests were conducted using the dynamic light scattering technique and microelectrophoresis. The penetration time of the plate depends on the properties and structure of the wetting liquid droplets. The types of interactions (dispersive, electrostatic and hydrogen bonding) formed between the silanol surface groups of the silica gel and the groups contained in the adsorbate particles are also very important factors. The greater the impact force, the slower the wetting process due to the strong penetration of the liquid into the pores of the substrate. The characteristics of the drug wetting/stability process may contribute to the development of their new forms, creating delivery systems with greater efficiency and lower side effects.
Acknowledgment to Reviewers of Cryptography in 2021
Authors:   Cryptography Editorial Office
Published: February 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Fabrication and Investigation of Spectral Properties of a Dielectric Slab Waveguide Photonic Crystal Based Fano-Filter
Authors: Khan Yousuf , Rehman Atiq Ur , Batool Bibi A. , Noor Mahain , Butt Muhammad A. , Kazanskiy Nikolay L. , Khonina Svetlana N.
Published: February 2022

In this paper, we discuss the fabrication of a dielectric photonic crystal (PhC)-based Fano-filter device, as well as a numerical investigation of its spectral characteristics. The process parameters affecting the structural and physical properties of the fabricated device are discussed in detail, along with their influence on the spectral properties of the filter. The considered experimental problem is a three-layered PhC structure, fabricated using focused ion-beam (FIB) technology, designed to operate in the near-infrared (NIR) range. The studied parameters include the shape of PhC elements, depth of the structures, cladding layer thicknesses, and the refractive index of the material. Numerical design and simulations are performed using an open-source python-based Finite-difference time-domain (FDTD) simulation tool. The proposed optical filter device operates based on the principle of guided-mode resonance, and achieved a maximum quality factor value in the range of 800.