bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropsychiatric Manifestations of Antiphospholipid Syndrome—A Narrative Review
Authors: Man Yik Long , Sanna Giovanni
Published: January 2022

Antiphospholipid syndrome (APS) is a common autoimmune pro-thrombotic condition characterised by thrombosis and pregnancy morbidity. There are a broad range of neuropsychiatric manifestations associated with APS, from focal symptoms to more global dysfunction. Patients commonly present with transient ischaemic attacks and ischaemic strokes, with identifiable lesions on brain imaging. However, the underlying pathogenesis remains uncertain in other manifestations, such as cognitive dysfunction, seizures, headache and chorea. The aim is to provide a comprehensive review of the various neuropsychiatric manifestations associated with APS. A detailed literature search was applied to PubMed, including citations from 1983 to December 2021.
Mixed Depression: A Mini-Review to Guide Clinical Practice and Future Research Developments
Authors: Natale Antimo , Mineo Ludovico , Fusar-Poli Laura , Aguglia Andrea , Rodolico Alessandro , Tusconi Massimo , Amerio Andrea , Serafini Gianluca , Amore Mario , Aguglia Eugenio
Published: January 2022

The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.
Development of Psi Factors for Thermal Bypass Due to Insulation Gaps in Low-Slope Roofing Assemblies
Authors: Molleti Sudhakar , van Reenen David
Published: January 2022

In commercial roofs, the presence or formation of gaps could be due to improper installation, thermal expansion, and dimensional changes in the insulation boards. The heat loss from these gaps could lead to higher thermal transmittance in the roof assembly. The current research study conducted around 70 experiments to investigate the effect of gap height, gap width and gap offset on the thermal transmittance of the roofing assembly. The measured data showed that in a staggered insulation layout with a joint offset of 610 mm (24 in), formation of 6.4 mm (1/4 in) to 12.7 mm (1/2 in) gaps at the insulation joints could contribute to an average decrease of 2% to 9% in the effective R-value of the roof assembly. As the insulation thermal resistance increases or becomes thicker, the thermal losses in the roof assembly increase. Generalized gap impact curves were developed to provide the relation between gap parameters (i.e., gap widths and height) and the thermal performance of the roof assembly. The experimental data were further analyzed using the psi factor approach of linear thermal bridging generating thermal transmittance data to support the calculation of thermal bypass from gaps in the thermal roof design.
Predictors of Mortality in Patients with Advanced Cancer—A Systematic Review and Meta-Analysis
Authors: Owusuaa Catherine , Dijkland Simone A. , Nieboer Daan , van der Heide Agnes , van der Rijt Carin C. D.
Published: January 2022

To timely initiate advance care planning in patients with advanced cancer, physicians should identify patients with limited life expectancy. We aimed to identify predictors of mortality. To identify the relevant literature, we searched Embase, MEDLINE, Cochrane Central, Web of Science, and PubMed databases between January 2000–April 2020. Identified studies were assessed on risk-of-bias with a modified QUIPS tool. The main outcomes were predictors and prediction models of mortality within a period of 3–24 months. We included predictors that were studied in ≥2 cancer types in a meta-analysis using a fixed or random-effects model and summarized the discriminative ability of models. We included 68 studies (ranging from 42 to 66,112 patients), of which 24 were low risk-of-bias, and 39 were included in the meta-analysis. Using a fixed-effects model, the predictors of mortality were: the surprise question, performance status, cognitive impairment, (sub)cutaneous metastases, body mass index, comorbidity, serum albumin, and hemoglobin. Using a random-effects model, predictors were: disease stage IV (hazard ratio [HR] 7.58; 95% confidence interval [CI] 4.00–14.36), lung cancer (HR 2.51; 95% CI 1.24–5.06), ECOG performance status 1+ (HR 2.03; 95% CI 1.44–2.86) and 2+ (HR 4.06; 95% CI 2.36–6.98), age (HR 1.20; 95% CI 1.05–1.38), male sex (HR 1.24; 95% CI 1.14–1.36), and Charlson comorbidity score 3+ (HR 1.60; 95% CI 1.11–2.32). Thirteen studies reported on prediction models consisting of different sets of predictors with mostly moderate discriminative ability. To conclude, we identified reasonably accurate non-tumor specific predictors of mortality. Those predictors could guide in developing a more accurate prediction model and in selecting patients for advance care planning.
Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study
Authors: Mimori Tomoyasu , Shukuya Takehito , Ko Ryo , Okuma Yusuke , Koizumi Tomonobu , Imai Hisao , Takiguchi Yuichi , Miyauchi Eisaku , Kagamu Hiroshi , Sugiyama Tomohide , Azuma Keisuke , Namba Yukiko , Yamasaki Masahiro , Tanaka Hisashi , Takashima Yuta , Soda Sayo , Ishimoto Osamu , Koyama Nobuyuki , Kobayashi Kunihiko , Takahashi Kazuhisa
Published: January 2022

The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan–Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05–2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31–3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology.
68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data
Authors: Mapelli Paola , Ghezzo Samuele , Samanes Gajate Ana Maria , Preza Erik , Palmisano Anna , Cucchiara Vito , Brembilla Giorgio , Bezzi Carolina , Rigamonti Riccardo , Magnani Patrizia , Toninelli Elisa , Bettinardi Valentino , Suardi Nazareno , Gianolli Luigi , Scifo Paola , Briganti Alberto , De Cobelli Francesco , Esposito Antonio , Picchio Maria
Published: January 2022

The aim of the present study is to investigate and compare the performances of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent prostate cancer (PCa) after primary treatment and to explore the association of dual-tracer PET findings with clinical and histopathological characteristics. Thirty-five patients with biochemical relapse (BCR) of PCa underwent 68Ga PSMA PET/MRI for restaging purpose, with 31/35 also undergoing 68Ga-DOTA-RM2 PET/MRI scan within 16 days (mean: 3 days, range: 2–16 days). Qualitative and quantitative image analysis has been performed by comparing 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings both on a patient and lesion basis. Clinical and instrumental follow-up was used to validate PET findings. Fisher’s exact test and Mann-Whitney U test were used to investigate the association between dual-tracer PET findings, clinical and histopathological data. p-value significance was defined below the 0.05 level. Patients’ mean age was 70 years (range: 49–84) and mean PSA at time of PET/MR scans was 1.88 ng/mL (range: 0.21–14.4). A higher detection rate was observed for 68Ga-PSMA PET/MRI, with more lesions being detected compared to 68Ga-DOTA-RM2 PET/MRI (26/35 patients, 95 lesions vs. 15/31 patients, 41 lesions; p = 0.016 and 0.002). 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings were discordant in 11/31 patients; among these, 10 were 68Ga-PSMA positive (9/10 confirmed as true positive and 1/10 as false positive by follow-up examination). Patients with higher levels of PSA and shorter PSA doubling time (DT) presented more lesions on 68Ga-PSMA PET/MRI (p = 0.006 and 0.044), while no association was found between PET findings and Gleason score. 68Ga-PSMA has a higher detection rate than 68Ga-DOTA-RM2 in detecting PCa recurrence. The number of 68Ga-PSMA PET positive lesions is associated with higher levels of PSA and shorter PSA DT, thus representing potential prognostic factors.
Systemic Delivery of mLIGHT-Armed Myxoma Virus Is Therapeutic for Later-Stage Syngeneic Murine Lung Metastatic Osteosarcoma
Authors: Christie John D. , Appel Nicole , Zhang Liqiang , Lowe Kenneth , Kilbourne Jacquelyn , Daggett-Vondras Juliane , Elliott Natalie , Lucas Alexandra R. , Blattman Joseph N. , Rahman Masmudur M. , McFadden Grant
Published: January 2022

Cancers that metastasize to the lungs represent a major challenge in both basic and clinical cancer research. Oncolytic viruses are newly emerging options but successful delivery and choice of appropriate therapeutic armings are two critical issues. Using an immunocompetent murine K7M2-luc lung metastases model, the efficacy of MYXV armed with murine LIGHT (TNFSF14/CD258) expressed under virus-specific early/late promoter was tested in an advanced later-stage disease K7M2-luc model. Results in this model show that mLIGHT-armed MYXV, delivered systemically using ex vivo pre-loaded PBMCs as carrier cells, reduced tumor burden and increased median survival time. In vitro, when comparing direct infection of K7M2-luc cancer cells with free MYXV vs. PBMC-loaded virus, vMyx-mLIGHT/PBMCs also demonstrated greater cytotoxic capacity against the K7M2 cancer cell targets. In vivo, systemically delivered vMyx-mLIGHT/PBMCs increased viral reporter transgene expression levels both in the periphery and in lung tumors compared to unarmed MYXV, in a tumor- and transgene-dependent fashion. We conclude that vMyx-mLIGHT, especially when delivered using PBMC carrier cells, represents a new potential therapeutic strategy for solid cancers that metastasize to the lung.
STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death
Authors: Remy Janina , Linder Benedikt , Weirauch Ulrike , Day Bryan W. , Stringer Brett W. , Herold-Mende Christel , Aigner Achim , Krohn Knut , Kögel Donat
Published: January 2022

Glioblastoma (GBM) is a devastating disease and the most common primary brain malignancy of adults with a median survival barely exceeding one year. Recent findings suggest that the antipsychotic drug pimozide triggers an autophagy-dependent, lysosomal type of cell death in GBM cells with possible implications for GBM therapy. One oncoprotein that is often overactivated in these tumors and associated with a particularly dismal prognosis is Signal Transducer and Activator of Transcription 3 (STAT3). Here, we used isogenic human and murine GBM knockout cell lines, advanced fluorescence microscopy, transcriptomic analysis and FACS-based assessment of cell viability to show that STAT3 has an underappreciated, context-dependent role in drug-induced cell death. Specifically, we demonstrate that depletion of STAT3 significantly enhances cell survival after treatment with Pimozide, suggesting that STAT3 confers a particular vulnerability to GBM. Furthermore, we show that active STAT3 has no major influence on the early steps of the autophagy pathway, but exacerbates drug-induced lysosomal membrane permeabilization (LMP) and release of cathepsins into the cytosol. Collectively, our findings support the concept of exploiting the pro-death functions of autophagy and LMP for GBM therapy and to further determine whether STAT3 can be employed as a treatment predictor for highly apoptosis-resistant, but autophagy-proficient cancers.
The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab
Authors: Wang Jing-Houng , Chen Yen-Yang , Kee Kwong-Ming , Wang Chih-Chi , Tsai Ming-Chao , Kuo Yuan-Hung , Hung Chao-Hung , Li Wei-Feng , Lai Hsiang-Lan , Chen Yen-Hao
Published: January 2022

Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1–2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.
The Diagnostic Value of the CA19-9 and Bilirubin Ratio in Patients with Pancreatic Cancer, Distal Bile Duct Cancer and Benign Periampullary Diseases, a Novel Approach
Authors: Boyd Lenka N. C. , Ali Mahsoem , Kam Laura , Puik Jisce R. , Rodrigues Stephanie M. Fraga , Zwart Eline S. , Daams Freek , Zonderhuis Barbara M. , Meijer Laura L. , Le Large Tessa Y. S. , Giovannetti Elisa , van Laarhoven Hanneke W. M. , Kazemier Geert
Published: January 2022

Distinction of pancreatic ductal adenocarcinoma (PDAC) in the head of the pancreas, distal cholangiocarcinoma (dCCA), and benign periampullary conditions, is complex as they often share similar clinical symptoms. However, these diseases require specific management strategies, urging improvement of non-invasive tools for accurate diagnosis. Recent evidence has shown that the ratio between CA19-9 and bilirubin levels supports diagnostic distinction of benign or malignant hepatopancreaticobiliary diseases. Here, we investigate the diagnostic value of this ratio in PDAC, dCCA and benign diseases of the periampullary region in a novel fashion. To address this aim, we enrolled 265 patients with hepatopancreaticobiliary diseases and constructed four logistic regression models on a subset of patients (n = 232) based on CA19-9, bilirubin and the ratio of both values: CA19-9/(bilirubin−1). Non-linearity was investigated using restricted cubic splines and a final model, the ‘Model Ratio’, based on these three variables was fitted using multivariable fractional polynomials. The performance of this model was consistently superior in terms of discrimination and calibration compared to models based on CA19-9 combined with bilirubin and CA19-9 or bilirubin alone. The ‘Model Ratio’ accurately distinguished between malignant and benign disease (AUC [95% CI], 0.91 [0.86–0.95]), PDAC and benign disease (AUC 0.91 [0.87–0.96]) and PDAC and dCCA (AUC 0.83 [0.74–0.92]) which was confirmed by internal validation using 1000 bootstrap replicates. These findings provide a foundation to improve minimally-invasive diagnostic procedures, ultimately ameliorating effective therapy for PDAC and dCCA.
Lysine Acetylation, Cancer Hallmarks and Emerging Onco-Therapeutic Opportunities
Authors: Hu Meilan , He Fule , Thompson Erik W. , Ostrikov Kostya (Ken) , Dai Xiaofeng
Published: January 2022

Acetylation, a reversible epigenetic process, is implicated in many critical cellular regulatory systems including transcriptional regulation, protein structure, activity, stability, and localization. Lysine acetylation is the most prevalent and intensively investigated among the diverse acetylation forms. Owing to the intrinsic connections of acetylation with cell metabolism, acetylation has been associated with metabolic disorders including cancers. Yet, relatively little has been reported on the features of acetylation against the cancer hallmarks, even though this knowledge may help identify appropriate therapeutic strategies or combinatorial modalities for the effective treatment and resolution of malignancies. By examining the available data related to the efficacy of lysine acetylation against tumor cells and elaborating the primary cancer hallmarks and the associated mechanisms to target the specific hallmarks, this review identifies the intrinsic connections between lysine acetylation and cancer hallmarks and proposes novel modalities that can be combined with HDAC inhibitors for cancer treatment with higher efficacy and minimum adverse effects.
Clinical Significance and Regulation of ERK5 Expression and Function in Cancer
Authors: Monti Matilde , Celli Jacopo , Missale Francesco , Cersosimo Francesca , Russo Mariapia , Belloni Elisa , Di Matteo Anna , Lonardi Silvia , Vermi William , Ghigna Claudia , Giurisato Emanuele
Published: January 2022

Extracellular signal-regulated kinase 5 (ERK5) is a unique kinase among MAPKs family members, given its large structure characterized by the presence of a unique C-terminal domain. Despite increasing data demonstrating the relevance of the ERK5 pathway in the growth, survival, and differentiation of normal cells, ERK5 has recently attracted the attention of several research groups given its relevance in inflammatory disorders and cancer. Accumulating evidence reported its role in tumor initiation and progression. In this review, we explore the gene expression profile of ERK5 among cancers correlated with its clinical impact, as well as the prognostic value of ERK5 and pERK5 expression levels in tumors. We also summarize the importance of ERK5 in the maintenance of a cancer stem-like phenotype and explore the major known contributions of ERK5 in the tumor-associated microenvironment. Moreover, although several questions are still open concerning ERK5 molecular regulation, different ERK5 isoforms derived from the alternative splicing process are also described, highlighting the potential clinical relevance of targeting ERK5 pathways.
Experimental and Bioinformatic Approaches to Studying DNA Methylation in Cancer
Authors: Merkel Angelika , Esteller Manel
Published: January 2022

DNA methylation is an essential epigenetic mark. Alterations of normal DNA methylation are a defining feature of cancer. Here, we review experimental and bioinformatic approaches to showcase the breadth and depth of information that this epigenetic mark provides for cancer research. First, we describe classical approaches for interrogating bulk DNA from cell populations as well as more recently developed approaches for single cells and multi-Omics. Second, we focus on the computational analysis from primary data processing to the identification of unique methylation signatures. Additionally, we discuss challenges such as sparse data and cellular heterogeneity.
Highly Photoactive Titanium Dioxide Supported Platinum Catalyst: Synthesis Using Cleaner Ultrasound Approach
Authors: Potdar Shital B. , Huang Chao-Ming , Praveen BVS , Manickam Sivakumar , Sonawane Shirish H.
Published: January 2022

Catalysts increase reaction rates; however, the surface area to volume ratio of catalysts has a vital role in catalytic activity. The noble metals such as platinum (Pt) and gold (Au) are expensive; despite this, they have proven their existence in catalysis, motivating the synthesis of supported metal catalysts. Metal catalysts need to be highly dispersed onto the support. In this investigation, an ultrasound approach has been attempted to synthesise highly photoactive titanium dioxide (TiO2) nanoparticles by the hydrolysis of titanium tetraisopropoxide in an acetone/methanol mixture. To enhance its photocatalytic activity, TiO2 was doped with Pt. The synthesised photocatalyst was characterised by techniques such as particle size analysis (PSA), XRD, FE-SEM, TEM, and EDX. The enhancement in the surface characteristics of Pt-doped TiO2 compared with bare TiO2 support was confirmed with Brunauer–Emmett–Teller (BET) analysis. The enhanced surface area and uniformity in particle size distribution at the nanoscale level were due to the effects of ultrasonic irradiation. The obtained results corroborated the size and composition of the synthesised catalysts. The size of the catalysts is in the nanometre range, and good dispersion of Pt catalysts over the TiO2 support was observed. The UV-Visible spectroscopy analysis was performed to study the optical properties of the synthesised TiO2 and Pt/TiO2 photocatalysts. An increase in the absorbance was noted when Pt was added to TiO2, which is due to the decrease in the band gap energy.
Immobilization-Stabilization of β-Glucosidase for Implementation of Intensified Hydrolysis of Cellobiose in Continuous Flow Reactors
Authors: Alvarez-Gonzalez Celia , Santos Victoria E. , Ladero Miguel , Bolivar Juan M.
Published: January 2022

Cellulose saccharification to glucose is an operation of paramount importance in the bioenergy sector and the chemical and food industries, while glucose is a critical platform chemical in the integrated biorefinery. Among the cellulose degrading enzymes, β-glucosidases are responsible for cellobiose hydrolysis, the final step in cellulose saccharification, which is usually the critical bottleneck for the whole cellulose saccharification process. The design of very active and stable β-glucosidase-based biocatalysts is a key strategy to implement an efficient saccharification process. Enzyme immobilization and reaction engineering are two fundamental tools for its understanding and implementation. Here, we have designed an immobilized-stabilized solid-supported β-glucosidase based on the glyoxyl immobilization chemistry applied in porous solid particles. The biocatalyst was stable at operational temperature and highly active, which allowed us to implement 25 °C as working temperature with a catalyst productivity of 109 mmol/min/gsupport. Cellobiose degradation was implemented in discontinuous stirred tank reactors, following which a simplified kinetic model was applied to assess the process limitations due to substrate and product inhibition. Finally, the reactive process was driven in a continuous flow fixed-bed reactor, achieving reaction intensification under mild operation conditions, reaching full cellobiose conversion of 34 g/L in a reaction time span of 20 min.
Sex Hormones, Growth Hormone, and the Cornea
Authors: McKay Tina B. , Priyadarsini Shrestha , Karamichos Dimitrios
Published: January 2022

The growth and maintenance of nearly every tissue in the body is influenced by systemic hormones during embryonic development through puberty and into adulthood. Of the ~130 different hormones expressed in the human body, steroid hormones and peptide hormones are highly abundant in circulation and are known to regulate anabolic processes and wound healing in a tissue-dependent manner. Of interest, differential levels of sex hormones have been associated with ocular pathologies, including dry eye disease and keratoconus. In this review, we discuss key studies that have revealed a role for androgens and estrogens in the cornea with focus on ocular surface homeostasis, wound healing, and stromal thickness. We also review studies of human growth hormone and insulin growth factor-1 in influencing ocular growth and epithelial regeneration. While it is unclear if endogenous hormones contribute to differential corneal wound healing in common animal models, the abundance of evidence suggests that systemic hormone levels, as a function of age, should be considered as an experimental variable in studies of corneal health and disease.
Sapienic Acid Metabolism Influences Membrane Plasticity and Protein Signaling in Breast Cancer Cell Lines
Authors: Küçüksayan Ertan , Sansone Anna , Chatgilialoglu Chryssostomos , Ozben Tomris , Tekeli Demet , Talibova Günel , Ferreri Carla
Published: January 2022

The importance of sapienic acid (6c-16:1), a monounsaturated fatty acid of the n-10 family formed from palmitic acid by delta-6 desaturase, and of its metabolism to 8c-18:1 and sebaleic acid (5c,8c-18:2) has been recently assessed in cancer. Data are lacking on the association between signaling cascades and exposure to sapienic acid comparing cell lines of the same cancer type. We used 50 μM sapienic acid supplementation, a non-toxic concentration, to cultivate MCF-7 and 2 triple-negative breast cancer cells (TNBC), MDA-MB-231 and BT-20. We followed up for three hours regarding membrane fatty acid remodeling by fatty acid-based membrane lipidome analysis and expression/phosphorylation of EGFR (epithelial growth factor receptor), mTOR (mammalian target of rapamycin) and AKT (protein kinase B) by Western blotting as an oncogenic signaling cascade. Results evidenced consistent differences among the three cell lines in the metabolism of n-10 fatty acids and signaling. Here, a new scenario is proposed for the role of sapienic acid: one based on changes in membrane composition and properties, and the other based on changes in expression/activation of growth factors and signaling cascades. This knowledge can indicate additional players and synergies in breast cancer cell metabolism, inspiring translational applications of tailored membrane lipid strategies to assist pharmacological interventions.
Genotoxicity Response of Fibroblast Cells and Human Epithelial Adenocarcinoma In Vitro Model Exposed to Bare and Ozone-Treated Silica Microparticles
Authors: Colafarina Sabrina , Di Carlo Piero , Zarivi Osvaldo , Aloisi Massimo , Di Serafino Alessandra , Aruffo Eleonora , Arrizza Lorenzo , Limongi Tania , Poma Anna
Published: January 2022

Indoor air pollutants (IAP), which can pose a serious risk to human health, include biological pollutants, nitric oxide (NO), nitrogen dioxide (NO2), volatile organic compounds (VOC), sulfur dioxide (SO2), carbon monoxide (CO), carbon dioxide (CO2), silica, metals, radon, and particulate matter (PM). The aim of our work is to conduct a multidisciplinary study of fine silica particles (<2.5 μm) in the presence or absence of ozone (O3), and evaluate their potential cytotoxicity using MTS, micronucleus, and the comet test in two cell lines. We analyzed A549 (human basal alveolar epithelial cell adenocarcinoma) and Hs27 (human normal fibroblasts) exposed to dynamic conditions by an IRC simulator under ozone flow (120 ppb) and in the presence of silica particles (40 μg/h). The viability of A549 and Hs27 cells at 48 and 72 h of exposure to silica or silica/ozone decreases, except at 72 h in Hs27 treated with silica/ozone. The micronucleus and comet tests showed a significant increase in the number of micronuclei and the % of DNA in the queue, compared to the control, in both lines in all treatments, even if in different cell times/types. We found that silica alone or with more O3 causes more pronounced genotoxic effects in A549 tumor cells than in normal Hs27 fibroblasts.
Extracellular HSP90α Induces MyD88-IRAK Complex-Associated IKKα/β−NF-κB/IRF3 and JAK2/TYK2−STAT-3 Signaling in Macrophages for Tumor-Promoting M2-Polarization
Authors: Fan Chi-Shuan , Chen Chia-Chi , Chen Li-Li , Chua Kee Voon , Hung Hui-Chen , Hsu John T. -A. , Huang Tze-Sing
Published: January 2022

M2-polarization and the tumoricidal to tumor-promoting transition are commonly observed with tumor-infiltrating macrophages after interplay with cancer cells or/and other stroma cells. Our previous study indicated that macrophage M2-polarization can be induced by extracellular HSP90α (eHSP90α) secreted from endothelial-to-mesenchymal transition-derived cancer-associated fibroblasts. To extend the finding, we herein validated that eHSP90α-induced M2-polarized macrophages exhibited a tumor-promoting activity and the promoted tumor tissues had significant increases in microvascular density but decreases in CD4+ T-cell level. We further investigated the signaling pathways occurring in eHSP90α-stimulated macrophages. When macrophages were exposed to eHSP90α, CD91 and toll-like receptor 4 (TLR4) functioned as the receptor/co-receptor for eHSP90α binding to recruit interleukin (IL)-1 receptor-associated kinases (IRAKs) and myeloid differentiation factor 88 (MyD88), and next elicited a canonical CD91/MyD88–IRAK1/4–IκB kinase α/β (IKKα/β)–nuclear factor-κB (NF-κB)/interferon regulatory factor 3 (IRF3) signaling pathway. Despite TLR4-MyD88 complex-associated activations of IKKα/β, NF-κB and IRF3 being well-known as involved in macrophage M1-activation, our results demonstrated that the CD91-TLR4-MyD88 complex-associated IRAK1/4−IKKα/β−NF-κB/IRF3 pathway was not only directly involved in M2-associated CD163, CD204, and IL-10 gene expressions but also required for downregulation of M1 inflammatory cytokines. Additionally, Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) were recruited onto MyD88 to induce the phosphorylation and activation of the transcription factor signal transducer and activator of transcription-3 (STAT-3). The JAK2/TYK2−STAT-3 signaling is known to associate with tumor promotion. In this study, the MyD88−JAK2/TYK2−STAT-3 pathway was demonstrated to contribute to eHSP90α-induced macrophage M2-polarization by regulating the expressions of M1- and M2-related genes, proangiogenic protein vascular endothelial growth factor, and phagocytosis-interfering factor Sec22b.
Conserved Motifs and Domains in Members of Pospiviroidae
Authors: Wüsthoff Kevin-Phil , Steger Gerhard
Published: January 2022

In 1985, Keese and Symons proposed a hypothesis on the sequence and secondary structure of viroids from the family Pospiviroidae: their secondary structure can be subdivided into five structural and functional domains and “viroids have evolved by rearrangement of domains between different viroids infecting the same cell and subsequent mutations within each domain”; this article is one of the most cited in the field of viroids. Employing the pairwise alignment method used by Keese and Symons and in addition to more recent methods, we tried to reproduce the original results and extent them to further members of Pospiviroidae which were unknown in 1985. Indeed, individual members of Pospiviroidae consist of a patchwork of sequence fragments from the family but the lengths of fragments do not point to consistent points of rearrangement, which is in conflict with the original hypothesis of fixed domain borders.
Sperm Numbers as a Paternity Guard in a Wild Bird
Authors: Rowe Melissah , van Oort Annabel , Brouwer Lyanne , Lifjeld Jan T. , Webster Michael S. , Welklin Joseph F. , Baldassarre Daniel T.
Published: January 2022

Sperm competition is thought to impose strong selection on males to produce competitive ejaculates to outcompete rival males under competitive mating conditions. Our understanding of how different sperm traits influence fertilization success, however, remains limited, especially in wild populations. Recent literature highlights the importance of incorporating multiple ejaculate traits and pre-copulatory sexually selected traits in analyses aimed at understanding how selection acts on sperm traits. However, variation in a male’s ability to gain fertilization success may also depend upon a range of social and ecological factors that determine the opportunity for mating events both within and outside of the social pair-bond. Here, we test for an effect of sperm quantity and sperm size on male reproductive success in the red-back fairy-wren (Malurus melanocephalus) while simultaneously accounting for pre-copulatory sexual selection and potential socio-ecological correlates of male mating success. We found that sperm number (i.e., cloacal protuberance volume), but not sperm morphology, was associated with reproductive success in male red-backed fairy-wrens. Most notably, males with large numbers of sperm available for copulation achieved greater within-pair paternity success. Our results suggest that males use large sperm numbers as a defensive strategy to guard within-pair paternity success in a system where there is a high risk of sperm competition and female control of copulation. Finally, our work highlights the importance of accounting for socio-ecological factors that may influence male mating opportunities when examining the role of sperm traits in determining male reproductive success.
S100A8/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation
Authors: Sprenkeler Evelien G. G. , Zandstra Judith , van Kleef Nadine D. , Goetschalckx Ines , Verstegen Bibian , Aarts Cathelijn E. M. , Janssen Hans , Tool Anton T. J. , van Mierlo Gerard , van Bruggen Robin , Jongerius Ilse , Kuijpers Taco W.
Published: January 2022

Neutrophils are the most abundant innate immune cells in the circulation and they are the first cells recruited to sites of infection or inflammation. Almost half of the intracellular protein content in neutrophils consists of S100A8 and S100A9, though there has been controversy about their actual localization. Once released extracellularly, these proteins are thought to act as damage-associated molecular patterns (DAMPs), though their mechanism of action is not well understood. These S100 proteins mainly form heterodimers (S100A8/A9, also known as calprotectin) and this heterocomplex is recognized as a useful biomarker for several inflammatory diseases. We observed that S100A8/A9 is highly present in the cytoplasmic fraction of neutrophils and is not part of the granule content. Furthermore, we found that S100A8/A9 was not released in parallel with granular content but upon the formation of neutrophil extracellular traps (NETs). Accordingly, neutrophils of patients with chronic granulomatous disease, who are deficient in phorbol 12-myristate 13-acetate (PMA)-induced NETosis, did not release S100A8/A9 upon PMA stimulation. Moreover, we purified S100A8/A9 from the cytoplasmic fraction of neutrophils and found that S100A8/A9 could induce neutrophil activation, including adhesion and CD11b upregulation, indicating that this DAMP might amplify neutrophil activation.
Wnt5A and TGFβ1 Converges through YAP1 Activity and Integrin Alpha v Up-Regulation Promoting Epithelial to Mesenchymal Transition in Ovarian Cancer Cells and Mesothelial Cell Activation
Authors: Dehghani-Ghobadi Zeinab , Sheikh Hasani Shahrzad , Arefian Ehsan , Hossein Ghamartaj
Published: January 2022

In this paper, we investigate whether Wnt5A is associated with the TGF-β1/Smad2/3 and Hippo-YAP1/TAZ-TEAD pathways, implicated in epithelial to mesenchymal transition (EMT) in epithelial ovarian cancer. We used 3D and 2D cultures of human epithelial ovarian cancer cell lines SKOV-3, OVCAR-3, CAOV-4, and different subtypes of human serous ovarian cancer compared to normal ovary specimens. Wnt5A showed a positive correlation with TAZ and TGFβ1 in high- and low-grade serous ovarian cancer specimens compared to borderline serous and normal ovaries. Silencing Wnt5A by siRNAs significantly decreased Smad2/3 activation and YAP1 expression and nuclear shuttling in ovarian cancer (OvCa) cells. Furthermore, Wnt5A was required for TGFβ1-induced cell migration and invasion. In addition, inhibition of YAP1 transcriptional activity by Verteporfin (VP) altered OvCa cell migration and invasion through decreased Wnt5A expression and inhibition of Smad2/3 activation, which was reverted in the presence of exogenous Wnt5A. We found that the activation of TGFβ1 and YAP1 nuclear shuttling was promoted by Wnt5A-induced integrin alpha v. Lastly, Wnt5A was implicated in activating human primary omental mesothelial cells and subsequent invasion of ovarian cancer cells. Together, we propose that Wnt5A could be a critical mediator of EMT-associated pathways.
Mesenchymal Stem Cell Therapy in Diabetic Cardiomyopathy
Authors: da Silva Jaqueline S. , Gonçalves Renata G. J. , Vasques Juliana F. , Rocha Bruna S. , Nascimento-Carlos Bianca , Montagnoli Tadeu L. , Mendez-Otero Rosália , de Sá Mauro P. L. , Zapata-Sudo Gisele
Published: January 2022

The incidence and prevalence of diabetes mellitus (DM) are increasing worldwide, and the resulting cardiac complications are the leading cause of death. Among these complications is diabetes-induced cardiomyopathy (DCM), which is the consequence of a pro-inflammatory condition, oxidative stress and fibrosis caused by hyperglycemia. Cardiac remodeling will lead to an imbalance in cell survival and death, which can promote cardiac dysfunction. Since the conventional treatment of DM generally does not address the prevention of cardiac remodeling, it is important to develop new alternatives for the treatment of cardiovascular complications induced by DM. Thus, therapy with mesenchymal stem cells has been shown to be a promising approach for the prevention of DCM because of their anti-apoptotic, anti-fibrotic and anti-inflammatory effects, which could improve cardiac function in patients with DM.
Expression of Lineage Transcription Factors Identifies Differences in Transition States of Induced Human Oligodendrocyte Differentiation
Authors: Raabe Florian J. , Stephan Marius , Waldeck Jan Benedikt , Huber Verena , Demetriou Damianos , Kannaiyan Nirmal , Galinski Sabrina , Glaser Laura V. , Wehr Michael C. , Ziller Michael J. , Schmitt Andrea , Falkai Peter , Rossner Moritz J.
Published: January 2022

Oligodendrocytes (OLs) are critical for myelination and are implicated in several brain disorders. Directed differentiation of human-induced OLs (iOLs) from pluripotent stem cells can be achieved by forced expression of different combinations of the transcription factors SOX10 (S), OLIG2 (O), and NKX6.2 (N). Here, we applied quantitative image analysis and single-cell transcriptomics to compare different transcription factor (TF) combinations for their efficacy towards robust OL lineage conversion. Compared with S alone, the combination of SON increases the number of iOLs and generates iOLs with a more complex morphology and higher expression levels of myelin-marker genes. RNA velocity analysis of individual cells reveals that S generates a population of oligodendrocyte-precursor cells (OPCs) that appear to be more immature than those generated by SON and to display distinct molecular properties. Our work highlights that TFs for generating iOPCs or iOLs should be chosen depending on the intended application or research question, and that SON might be beneficial to study more mature iOLs while S might be better suited to investigate iOPC biology.
A Modeling Approach on the Correction Model of the Chromatic Aberration of Scanned Wood Grain Images
Authors: Mao Jingjing , Wu Zhihui , Feng Xinhao
Published: January 2022

There always exists subjective and objective color differences between digital wood grain and real wood grain, making it difficult to replicate the color of natural timber. Therefore, we described a novel method of correcting the chromatic aberration of scanned wood grain to maximally restore the objective color information of the real wood grain. A point-to-point correction model of chromatic aberration between the scanned wood grain and the measured wood grain was established based on Circle 1 by adjusting the three channels (sR, sG, and sB) of the scanned images. A conversion of the color space was conducted using the mutual conversion formulas. The color change of the scanned images before and after the correction was evaluated through the L∗a∗b∗ color-mode-based ΔE∗. and the lαβ color-model-based CIQI (Color Image Quality Index) and CQE (Color Quality Enhancement). The experimental results showed that the chromatic aberration ΔE∗ between the scanned wood grain and the measured wood grain decreased and the colorfulness index CIQI of the scanned wood grain increased for most wood specimens after the correction. The values of ΔE∗ of the twenty kinds of wood specimens decreased by an average of 3.1 in Circle 1 and 2.3 in Circle 2, thus the correction model established based on Circle 1 was effective. The color of the scanned wood grain was more consistent with that of the originals after the correction, which would provide a more accurate color information for the reproductions of wood grain and had an important practical significance.
Synthesis, Properties and Aging of ICP-CVD SiCxNy:H Films Formed from Tetramethyldisilazane
Authors: Chagin Maksim N. , Sulyaeva Veronica S. , Shayapov Vladimir R. , Kolodin Aleksey N. , Khomyakov Maksim N. , Yushina Irina V. , Kosinova Marina L.
Published: January 2022

Amorphous hydrogenated silicon carbonitride films were synthesized on Si(100), Ge(111), and fused silica substrates using the inductively coupled plasma chemical vapor deposition technique. 1,1,3,3-tetramethyldisilazane (TMDSN) was used as a single-source precursor. The effect of the precursor’s pressure in the initial gas mixture, the substrate temperature, the plasma power, and the flow rate of nitrogen gas as an additional reagent on the film growth rate, element composition, chemical bonding, wettability of film surface, and the optical and mechanical properties of a-SiCxNy:H films was investigated. In situ diagnostic studies of the gas phase have been performed by optical emission spectroscopy during the film deposition process. The long-term stability of films was studied over a period of 375 days. Fourier-transform infrared (FTIR) and X-ray energy dispersive spectroscopy (EDX), and wettability measurements elucidated the oxidation of the SiCxNy:H films deposited using TMDSN + N2 mixture. Films obtained from a mixture with argon had high stability and maintained the stability of element composition after long-term storage in ambient air.
Exploring the Genetic Diversity among Weedy Rice Accessions Differing in Herbicide Tolerance and Allelopathic Potential
Authors: Shrestha Swati , Sharma Gourav , Stallworth Shandrea , Redona Edilberto D. , Tseng Te Ming
Published: January 2022

Increasing agricultural productivity is indispensable to meet future food demand. Crop improvement programs rely heavily on genetic diversity. The success of weeds in the ecosystem can be attributed to genetic diversity and plasticity. Weedy rice, a major weed of rice, has diverse morphology and phenology, implying wide genetic diversity. Study was conducted to genotype weedy rice accessions (n = 54) previously phenotyped for herbicide tolerance and allelopathic potential using 30 SSR markers. Cultivated rice (CL163, REX) and allelopathic rice (RONDO, PI312777, PI338047) were also included in the study. Nei’s genetic diversity among weedy rice (0.45) was found to be higher than cultivated rice (0.24) but less than allelopathic rice (0.56). The genetic relationship and population structure based on herbicide tolerance and allelopathic potential were evaluated. Herbicide-tolerant and susceptible accessions formed distinct clusters in the dendrogram, indicating their genetic variation, whereas no distinction was observed between allelopathic and non-allelopathic weedy rice accessions. Weedy rice accession B2, which was previously reported to have high allelopathy and herbicide tolerance, was genetically distinct from other weedy rice. Results from the study will help leverage weedy rice for rice improvement programs as both rice and weedy rice are closely related, thus having a low breeding barrier.
Consistent Grime’s CSR Strategy of Daisy Fleabane Erigeron annuus (L.) Pers. despite Its High Morphological Variability—A Case Study from Zagreb and Medvednica Mt., Croatia
Authors: Levačić Damjana , Jelaska Sven D.
Published: January 2022

Alongside the direct destruction of natural habitats and changes in land use, invasive species are considered one of the greatest threats to global biodiversity. Daisy fleabane Erigeron annuus (L.) Pers. is among the most widespread invasive plants in Croatia. Invasions of E. annuus may be aided by morphological variability, which this study investigates. The variability of life traits (stem height, fresh and dry leaf mass, length, width and leaf area, specific leaf area, and leaf dry matter content) was examined among 18 locations throughout Zagreb and Medvednica Mt. Overall, 87 plant specimens and 435 leaves were measured and analysed using univariate and multivariate statistics. Viable populations were recorded in diverse habitat types, mostly with marked human impact. We determined Grime’s CR plant life strategies for all, except for two localities with C/CR plant strategies. Two populations with a more pronounced competitive strategy had high leaf dry matter content, with smaller leaves and medium height stems. Significant differences between the localities were found, with the specific leaf area (SLA) and plant height being the most diverse. Despite its high morphological variability, daisy fleabane had a consistent CSR strategy, which likely enables its widespread invasions across variable habitats.
Unrecognized Ant Megadiversity in Monsoonal Australia: Diversity and Its Distribution in the Hyperdiverse Monomorium nigrius Forel Group
Authors: Andersen Alan N. , Brassard François , Hoffmann Benjamin D.
Published: January 2022

We document diversity and its distribution within the hyperdiverse Monomorium nigrius Forel group of the Australian monsoonal tropics, an unrecognized global centre of ant diversity. The group includes a single described species, but several distinct morphotypes each with multiple clearly recognizable taxa are known. Our analysis is based on 401 CO1-sequenced specimens collected from throughout the Australian mainland but primarily in the monsoonal north and particularly from four bioregions: the Top End (northern third) of the Northern Territory (NT), the Sturt Plateau region of central NT, the Kimberley region of far northern Western Australia, and far North Queensland. Clade structure in the CO1 tree is highly congruent with the general morphotypes, although most morphotypes occur in multiple clades and are therefore shown as polyphyletic. We recognize 97 species among our sequenced specimens, and this is generally consistent (if not somewhat conservative) with PTP analyses of CO1 clustering. Species turnover is extremely high both within and among bioregions in monsoonal Australia, and the monsoonal fauna is highly distinct from that in southern Australia. We estimate that the M. nigrius group contains well over 200 species in monsoonal Australia, and 300 species overall. Our study provides further evidence that monsoonal Australia should be recognized as a global centre of ant diversity.