bluuebunny/crossref_metadata_2025 huggingface dataset:
Toolbox Accelerating Glycomics (TAG): Glycan Annotation from MALDI-TOF MS Spectra and Mapping Expression Variation to Biosynthetic Pathways
Authors: Miura Nobuaki , Hanamatsu Hisatoshi , Yokota Ikuko , Okada Kazue , Furukawa Jun-Ichi , Shinohara Yasuro
Published: September 2020

Glycans present extraordinary structural diversity commensurate with their involvement in numerous fundamental cellular processes including growth, differentiation, and morphogenesis. Unlike linear DNA and protein sequences, glycans have heterogeneous structures that differ in composition, branching, linkage, and anomericity. These differences pose a challenge to developing useful software for glycomic analysis. To overcome this problem, we developed the novel Toolbox Accelerating Glycomics (TAG) program. TAG consists of three units: ‘TAG List’ creates a glycan list that is used for database searching in TAG Expression; ‘TAG Expression’ automatically annotates and quantifies glycan signals and draws graphs; and ‘TAG Pathway’ maps the obtained expression information to biosynthetic pathways. Herein, we discuss the concepts, outline the TAG process, and demonstrate its potential using glycomic expression profile data from Chinese hamster ovary (CHO) cells and mutants lacking a functional Npc1 gene (Npc1 knockout (KO) CHO cells). TAG not only drastically reduced the amount of time and labor needed for glycomic analysis but also detected and quantified more glycans than manual analysis. Although this study was limited to the analysis of N-glycans and free oligosaccharides, the glycomic platform will be expanded to facilitate the analysis of O-glycans and glycans of glycosphingolipids.
Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity
Authors: Lutkewitte Andrew J. , Finck Brian N.
Published: September 2020

Phosphatidic acid (PA) is a glycerophospholipid intermediate in the triglyceride synthesis pathway that has incredibly important structural functions as a component of cell membranes and dynamic effects on intracellular and intercellular signaling pathways. Although there are many pathways to synthesize and degrade PA, a family of PA phosphohydrolases (lipin family proteins) that generate diacylglycerol constitute the primary pathway for PA incorporation into triglycerides. Previously, it was believed that the pool of PA used to synthesize triglyceride was distinct, compartmentalized, and did not widely intersect with signaling pathways. However, we now know that modulating the activity of lipin 1 has profound effects on signaling in a variety of cell types. Indeed, in most tissues except adipose tissue, lipin-mediated PA phosphohydrolase activity is far from limiting for normal rates of triglyceride synthesis, but rather impacts critical signaling cascades that control cellular homeostasis. In this review, we will discuss how lipin-mediated control of PA concentrations regulates metabolism and signaling in mammalian organisms.
Alteration of the Fatty Acid Metabolism in the Rat Kidney Caused by the Injection of Serum from Patients with Collapsing Glomerulopathy
Authors: Soria-Castro Elizabeth , Guarner-Lans Verónica , Soto María Elena , Carmen Avila-Casado María del , Manzano Pech Linaloe , Pérez-Torres Israel
Published: September 2020

Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced alterations in fatty acid (FA) metabolism. Twenty-four female Sprague-Dawley rats were divided into four groups of six rats each: Group I, control rats (C); Group II, rats that received injections of 1 mL of 0.9% NaCl saline solution (SS); Group III, rats injected with 25 mg/mL of serum from healthy subjects (HS); and Group IV, rats injected with 25 mg/mL of serum from CG patients. In all groups, the systolic blood pressure (SBP), proteinuria, creatinine clearance (CC), cholesterol and total FA composition in the kidney and serum were evaluated. The administration of serum from CG patients to rats induced glomerular collapse, proteinuria, reduced CC and elevated SBP (p ≤ 0.01) in comparison with the C, SS and HS rats. The FA composition of the serum of rats that received the CG serum showed an increase in palmitic acid (PA) and a decrease in arachidonic acid (AA) when compared to serum from HS (p ≤ 0.02). In rats receiving the CG serum, there was also a decrease in the AA in the kidney but there was an increase in the PA in the serum and kidney (p ≤ 0.01). These results suggest that the administration of serum from CG patients to rats induces alterations in FA metabolism including changes in PA and in AA, which are precursors for the biosynthesis of the prostaglandins that are involved in the elevation of SBP and in renal injury. These changes may contribute to collapsing glomerulopathy disease.
Accuracy of the Dexcom G6 Glucose Sensor during Aerobic, Resistance, and Interval Exercise in Adults with Type 1 Diabetes
Authors: Guillot Florian H. , Jacobs Peter G. , Wilson Leah M. , Youssef Joseph El , Gabo Virginia B. , Branigan Deborah L. , Tyler Nichole S. , Ramsey Katrina , Riddell Michael C. , Castle Jessica R.
Published: September 2020

The accuracy of continuous glucose monitoring (CGM) sensors may be significantly impacted by exercise. We evaluated the impact of three different types of exercise on the accuracy of the Dexcom G6 sensor. Twenty-four adults with type 1 diabetes on multiple daily injections wore a G6 sensor. Participants were randomized to aerobic, resistance, or high intensity interval training (HIIT) exercise. Each participant completed two in-clinic 30-min exercise sessions. The sensors were applied on average 5.3 days prior to the in-clinic visits (range 0.6–9.9). Capillary blood glucose (CBG) measurements with a Contour Next meter were performed before and after exercise as well as every 10 min during exercise. No CGM calibrations were performed. The median absolute relative difference (MARD) and median relative difference (MRD) of the CGM as compared with the reference CBG did not differ significantly from the start of exercise to the end exercise across all exercise types (ranges for aerobic MARD: 8.9 to 13.9% and MRD: −6.4 to 0.5%, resistance MARD: 7.7 to 14.5% and MRD: −8.3 to −2.9%, HIIT MARD: 12.1 to 16.8% and MRD: −14.3 to −9.1%). The accuracy of the no-calibration Dexcom G6 CGM was not significantly impacted by aerobic, resistance, or HIIT exercise.
Are People with Aphasia (PWA) Involved in the Creation of Quality of Life and Aphasia Impact-Related Questionnaires? A Scoping Review
Authors: Charalambous Marina , Kambanaros Maria , Annoni Jean-Marie
Published: September 2020

Background: Quality of Life (QoL) questionnaires are used to describe the impact of aphasia on stroke survivors’ life. People with aphasia (PWA) are traditionally excluded from research, potentially leading to a mismatch between the factors chosen in the tools and the realistic needs of PWA. The purpose of this review was to determine the direct involvement of PWA in the creation of QoL and aphasia impact-related questionnaires (AIR-Qs). Methods: A scoping review methodology was conducted by an expert librarian and two independent reviewers on health sciences based on the Preferred Reporting Items for Systematic Reviews and Metanalyses extension for Scoping Reviews (PRISMA-ScR) protocol, through a literature search in five databases: Medline Complete, PubMed, PsychINFO, Scopus, and Google Scholar. Search terms included ‘stroke’, ‘people with aphasia’, ‘communication’, ‘well-being’, and ‘quality of life’. Results: Of 952 results, 20 studies met the eligibility criteria. Of these, only four AIR-Qs studies (20%) were found reporting the direct involvement of PWA, while no QoL tools did so. Evidence showed involvement in the creation phase of AIR-Q, mainly in a consultation role. Conclusions: There is an absence of a framework for conducting and reporting the involvement of PWA in qualitative participatory research studies, which limits effectiveness to promote equitable best practice in aphasia rehabilitation.
Relationship between Psychological Factors and Social Support after Lifting of Evacuation Order in Fukushima Prefecture, Japan
Authors: Kuroda Yujiro , Koyama Yohei
Published: September 2020

We examined the relationships among social support and psychological variables and investigated the status of social support among villagers whose evacuation order had been lifted. A written questionnaire was posted to 4828 registered residents of Iitate Village; 1405 valid responses were received. The main finding (in joint assessment by local and external experts) was the “need for professional support” (191 respondents, 13.6%). A multivariate analysis found that among those living in permanent housing outside the village, the need for support was significantly more likely for those without emotional support or instrumental support than for those not providing support. The associations between perceived social support and living environment suggest the need to strengthen social support measures in areas where evacuation orders are yet to be lifted, and provide useful information for examining the effects of future support efforts.
Quantitative Review of Construction 4.0 Technology Presence in Construction Project Research
Authors: Schönbeck Pia , Löfsjögård Malin , Ansell Anders
Published: September 2020

The development of technologies associated with the fourth industrial revolution is rapid. Construction 4.0 represents the architecture, engineering, construction and operations industries exploration of new technologies, equivalent to Industry 4.0 for the manufacturing industry. These concepts address multiple perspectives besides the technological, such as management and processes. The purpose of this study was to investigate to what extent research regarding construction projects addresses information and communication, automatisation or industrialisation technologies. A scoping review was the method used to perform a quantitative analysis of over two thousand journal papers published from 2015 onwards. The results show that new technologies are addressed separately, while synergy studies are uncommon. Longitudinal analyses show that there was no significant increase in journal papers concerning new technologies from 2015 to 2019. Information and communication was the search criterion with the least number of papers found. The environmental perspective of new technologies was present but the least common from 2019 to 2020. Hence, this review shows that there is an extensive research gap regarding Construction 4.0 technologies in the context of construction projects. Studies regarding synergy and environmental effects of new technologies should increase to start the progress towards a successful entry into the fourth industrial revolution.
Preoperative or Perioperative Docetaxel, Oxaliplatin, and Capecitabine (GASTRODOC Regimen) in Patients with Locally-Advanced Resectable Gastric Cancer: A Randomized Phase-II Trial
Authors: Monti Manlio , Morgagni Paolo , Nanni Oriana , Framarini Massimo , Saragoni Luca , Marrelli Daniele , Roviello Franco , Petrioli Roberto , Fumagalli Romario Uberto , Rimassa Lorenza , Bozzarelli Silvia , Donini Annibale , Graziosi Luigina , De Angelis Verena , De Manzoni Giovanni , Bencivenga Maria , Mengardo Valentina , Parma Emilio , Milandri Carlo , Mura Gianni , Signorini Alessandra , Baiocchi Gianluca , Molfino Sarah , Sgroi Giovanni , Steccanella Francesca , Rausei Stefano , Proserpio Ilaria , Viganò Jacopo , Brugnatelli Silvia , Rinnovati Andrea , Santi Stefano , Ercolani Giorgio , Foca Flavia , Valmorri Linda , Amadori Dino , Frassineti Giovanni Luca
Published: September 2020

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18–1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2–65.8) in arm A and 40.3% (95% CI: 28.9–55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3–72.2) and 53.9% (95% CI: 35.5–69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.
Regulating Methylation at H3K27: A Trick or Treat for Cancer Cell Plasticity
Authors: Das Provas , Taube Joseph H.
Published: September 2020

Properly timed addition and removal of histone 3 lysine 27 tri-methylation (H3K27me3) is critical for enabling proper differentiation throughout all stages of development and, likewise, can guide carcinoma cells into altered differentiation states which correspond to poor prognoses and treatment evasion. In early embryonic stages, H3K27me3 is invoked to silence genes and restrict cell fate. Not surprisingly, mutation or altered functionality in the enzymes that regulate this pathway results in aberrant methylation or demethylation that can lead to malignancy. Likewise, changes in expression or activity of these enzymes impact cellular plasticity, metastasis, and treatment evasion. This review focuses on current knowledge regarding methylation and de-methylation of H3K27 in cancer initiation and cancer cell plasticity.
Oncogenic Tyrosine Phosphatases: Novel Therapeutic Targets for Melanoma Treatment
Authors: Pardella Elisa , Pranzini Erica , Leo Angela , Taddei Maria Letizia , Paoli Paolo , Raugei Giovanni
Published: September 2020

Despite a large number of therapeutic options available, malignant melanoma remains a highly fatal disease, especially in its metastatic forms. The oncogenic role of protein tyrosine phosphatases (PTPs) is becoming increasingly clear, paving the way for novel antitumor treatments based on their inhibition. In this review, we present the oncogenic PTPs contributing to melanoma progression and we provide, where available, a description of new inhibitory strategies designed against these enzymes and possibly useful in melanoma treatment. Considering the relevance of the immune infiltrate in supporting melanoma progression, we also focus on the role of PTPs in modulating immune cell activity, identifying interesting therapeutic options that may support the currently applied immunomodulating approaches. Collectively, this information highlights the value of going further in the development of new strategies targeting oncogenic PTPs to improve the efficacy of melanoma treatment.
Comparison of the Tree-Based Machine Learning Algorithms to Cox Regression in Predicting the Survival of Oral and Pharyngeal Cancers: Analyses Based on SEER Database
Authors: Du Mi , Haag Dandara G. , Lynch John W. , Mittinty Murthy N.
Published: September 2020

This study aims to demonstrate the use of the tree-based machine learning algorithms to predict the 3- and 5-year disease-specific survival of oral and pharyngeal cancers (OPCs) and compare their performance with the traditional Cox regression. A total of 21,154 individuals diagnosed with OPCs between 2004 and 2009 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Three tree-based machine learning algorithms (survival tree (ST), random forest (RF) and conditional inference forest (CF)), together with a reference technique (Cox proportional hazard models (Cox)), were used to develop the survival prediction models. To handle the missing values in predictors, we applied the substantive model compatible version of the fully conditional specification imputation approach to the Cox model, whereas we used RF to impute missing data for the ST, RF and CF models. For internal validation, we used 10-fold cross-validation with 50 iterations in the model development datasets. Following this, model performance was evaluated using the C-index, integrated Brier score (IBS) and calibration curves in the test datasets. For predicting the 3-year survival of OPCs with the complete cases, the C-index in the development sets were 0.77 (0.77, 0.77), 0.70 (0.70, 0.70), 0.83 (0.83, 0.84) and 0.83 (0.83, 0.86) for Cox, ST, RF and CF, respectively. Similar results were observed in the 5-year survival prediction models, with C-index for Cox, ST, RF and CF being 0.76 (0.76, 0.76), 0.69 (0.69, 0.70), 0.83 (0.83, 0.83) and 0.85 (0.84, 0.86), respectively, in development datasets. The prediction error curves based on IBS showed a similar pattern for these models. The predictive performance remained unchanged in the analyses with imputed data. Additionally, a free web-based calculator was developed for potential clinical use. In conclusion, compared to Cox regression, ST had a lower and RF and CF had a higher predictive accuracy in predicting the 3- and 5-year OPCs survival using SEER data. The RF and CF algorithms provide non-parametric alternatives to Cox regression to be of clinical use for estimating the survival probability of OPCs patients.
Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia
Authors: Cuatrecasas Míriam , Gorostiaga Iñigo , Riera Cristina , Saperas Esteban , Llort Gemma , Costa Irmgard , Matias-Guiu Xavier , Carrato Cristina , Navarro Matilde , Pineda Marta , Dueñas Núria , Brunet Joan , Marco Vicente , Trias Isabel , Busteros José Ignacio , Mateu Gemma , Balaguer Francesc , Fernández-Figueras María-Teresa , Esteller Manel , Musulén Eva
Published: September 2020

The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), precursor lesions of gastrointestinal (71) and extra-gastrointestinal origin (9), and benign neoplasms (8) from different organs of 71 patients suspicious of being LS due to MSH2 alterations. LS was confirmed in 68 patients, 53 with MSH2 mutations and 15 with EPCAM 3′-end deletions. Tissue microarrays were constructed with human normal tissues and their malignant counterparts to assist in the evaluation of EPCAM staining. Among 154 MSH2-negative lesions, 17 were EPCAM-negative, including 10 CRC and 7 colorectal polyps, and 5 of them showed only isolated negative glands. All lesions showing a lack of EPCAM expression belonged to patients with EPCAM 3′-end deletions. EPCAM IHC is a useful screening tool, with 100% specificity to identify LS patients due to EPCAM 3′-end deletions in MSH2-negative CRC and MSH2-negative colorectal polyps.
Cells in Cardiovascular Disease: Using Diversity to Confront Adversity
Authors: Martínez-González José , García de Frutos Pablo
Published: September 2020

The present Special Issue on “Cells in Cardiovascular Disease” wants to offer a general overview of current cardiovascular research and illustrate how advances in the molecular characterization at the cellular level are providing unique insights into pathologies of the circulatory system [...]
Stem Cell-Based Disease Modeling and Cell Therapy
Authors: Bai Xiaowen
Published: September 2020

Stem cell science is among the fastest moving fields in biology, with many highly promising directions for translatability. To centralize and contextualize some of the latest developments, this Special Issue presents state-of-the-art research of adult stem cells, induced pluripotent stem cells (iPSCs), and embryonic stem cells as well as cancer stem cells. The studies we include describe efficient differentiation protocols of generation of chondrocytes, adipocytes, and neurons, maturation of iPSC-derived cardiomyocytes and neurons, dynamic characterization of iPSC-derived 3D cerebral organoids, CRISPR/Cas9 genome editing, and non-viral minicircle vector-based gene modification of stem cells. Different applications of stem cells in disease modeling are described as well. This volume also highlights the most recent developments and applications of stem cells in basic science research and disease treatments.
snR30/U17 Small Nucleolar Ribonucleoprotein: A Critical Player during Ribosome Biogenesis
Authors: Vos Timothy John , Kothe Ute
Published: September 2020

The small nucleolar RNA snR30 (U17 in humans) plays a unique role during ribosome synthesis. Unlike most members of the H/ACA class of guide RNAs, the small nucleolar ribonucleoprotein (snoRNP) complex assembled on snR30 does not direct pseudouridylation of ribosomal RNA (rRNA), but instead snR30 is critical for 18S rRNA processing during formation of the small subunit (SSU) of the ribosome. Specifically, snR30 is essential for three pre-rRNA cleavages at the A0/01, A1/1, and A2/2a sites in yeast and humans, respectively. Accordingly, snR30 is the only essential H/ACA guide RNA in yeast. Here, we summarize our current knowledge about the interactions and functions of snR30, discuss what remains to be elucidated, and present two non-exclusive hypotheses on the possible molecular function of snR30 during ribosome biogenesis. First, snR30 might be responsible for recruiting other proteins including endonucleases to the SSU processome. Second, snR30 may contribute to the refolding of pre-rRNA into a required conformation that serves as a checkpoint during ribosome biogenesis facilitating pre-rRNA cleavage. In both scenarios, the snR30 snoRNP may have scaffolding and RNA chaperoning activity. In conclusion, the snR30 snoRNP is a crucial player with an unknown molecular mechanism during ribosome synthesis, posing many interesting future research questions.
Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease
Authors: Mo Dingding , Li Xinping , Raabe Carsten A. , Rozhdestvensky Timofey S. , Skryabin Boris V. , Brosius Juergen
Published: September 2020

Alzheimer’s disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (Aβ) play a crucial role in the pathology of AD. In familial AD, Aβ are generated from the full-length amyloid beta precursor protein (APP) via dysregulated proteolytic processing; however, in the case of sporadic AD, the mechanism of Aβ biogenesis remains elusive. circRNAs are a class of transcripts preferentially expressed in brain. We identified a circRNA harboring the Aβ-coding region of the APP gene termed circAβ-a. This circular RNA was detected in the brains of AD patients and non-dementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circAβ-a is efficiently translated into a novel Aβ-containing Aβ175 polypeptide (19.2 KDa) in both cultured cells and human brain. Furthermore, Aβ175 was shown to be processed into Aβ peptides—a hallmark of AD. In summary, our analysis revealed an alternative pathway of Aβ biogenesis. Consequently, circAβ-a and its corresponding translation product could potentially represent novel therapeutic targets for AD treatment. Importantly, our data point to yet another evolutionary route for potentially increasing proteome complexity by generating additional polypeptide variants using back-splicing of primary transcripts that yield circular RNA templates.
Conditioned Medium from Cells Overexpressing TDP-43 Alters the Metabolome of Recipient Cells
Authors: Hergesheimer Rudolf , Lanznaster Débora , Bourgeais Jérôme , Hérault Olivier , Vourc’h Patrick , Andres Christian R. , Corcia Philippe , Blasco Hélène
Published: September 2020

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the progressive death of both upper and lower motor neurons. The disease presents a poor prognosis, and patients usually die 2–5 years after the onset of symptoms. The hallmark of this disease is the presence of phosphorylated and ubiquitinated aggregates containing trans-active response DNA-binding protein-43 (TDP-43) in the cytoplasm of motor neurons. TDP-43 pathology has been associated with multiple pathways in ALS, such as metabolic dysfunction found in patients and in in vivo models. Recently, it has been described as a “prion-like” protein, as studies have shown its propagation in cell culture from ALS brain extract or overexpressed TDP-43 in co-culture and conditioned medium, resulting in cytotoxicity. However, the cellular alterations that are associated with this cytotoxicity require further investigation. Here, we investigated the effects of conditioned medium from HEK293T (Human Embryonic Kidney 293T) cells overexpressing TDP-43 on cellular morphology, proliferation, death, and metabolism. Although we did not find evidence of TDP-43 propagation, we observed a toxicity of TDP-43-conditioned medium and altered metabolism. These results, therefore, suggest (1) that cells overexpressing TDP-43 produce an extracellular environment that can perturb other cells and (2) that TDP-43 propagation alone may not be the only potentially cytotoxic cell-to-cell mechanism.
HbF Levels in Sickle Cell Disease Are Associated with Proportion of Circulating Hematopoietic Stem and Progenitor Cells and CC-Chemokines
Authors: Minniti Caterina P. , Tolu Seda S. , Wang Kai , Yan Zi , Robert Karl , Zhang Shouping , Crouch Andrew S. , Uehlinger Joan , Manwani Deepa , Bouhassira Eric E.
Published: September 2020

The concentration of circulating hematopoietic stem and progenitor cells has not been studied longitudinally. Here, we report that the proportions of Lin-CD34+38- hematopoietic multipotent cells (HMCs) and of Lin-CD34+CD38+ hematopoietic progenitors cells (HPCs) are highly variable between individuals but stable over long periods of time, in both healthy individuals and sickle cell disease (SCD) patients. This suggests that these proportions are regulated by genetic polymorphisms or by epigenetic mechanisms. We also report that in SCD patients treated with hydroxyurea, the proportions of circulating HMCs and HPCs show a strong positive and negative correlation with fetal hemoglobin (HbF) levels, respectively. Titration of 65 cytokines revealed that the plasma concentration of chemokines CCL2, CCL11, CCL17, CCL24, CCL27, and PDGF-BB were highly correlated with the proportion of HMCs and HPCs and that a subset of these cytokines were also correlated with HbF levels. A linear model based on four of these chemokines could explain 80% of the variability in the proportion of circulating HMCs between individuals. The proportion of circulating HMCs and HPCs and the concentration of these chemokines might therefore become useful biomarkers for HbF response to HU in SCD patients. Such markers might become increasingly clinically relevant, as alternative treatment modalities for SCD are becoming available.
Perspectives Regarding the Intersections between STAT3 and Oxidative Metabolism in Cancer
Authors: Chun Kyung-Soo , Jang Jeong-Hoon , Kim Do-Hee
Published: September 2020

Signal transducer and activator of transcription 3 (STAT3) functions as a major molecular switch that plays an important role in the communication between cytokines and kinases. In this role, it regulates the transcription of genes involved in various biochemical processes, such as proliferation, migration, and metabolism of cancer cells. STAT3 undergoes diverse post-translational modifications, such as the oxidation of cysteine by oxidative stress, the acetylation of lysine, or the phosphorylation of serine/threonine. In particular, the redox modulation of critical cysteine residues present in the DNA-binding domain of STAT3 inhibits its DNA-binding activity, resulting in the inactivation of STAT3-mediated gene expression. Accumulating evidence supports that STAT3 is a key protein that acts as a mediator of metabolism and mitochondrial activity. In this review, we focus on the post-translational modifications of STAT3 by oxidative stress and how the modification of STAT3 regulates cell metabolism, particularly in the metabolic pathways in cancer cells.
Apoptosis, Induced by Human α-Synuclein in Yeast, Can Occur Independent of Functional Mitochondria
Authors: Akintade Damilare D. , Chaudhuri Bhabatosh
Published: September 2020

Human α-synuclein expression in baker’s yeast reportedly induces mitochondria-dependent apoptosis. Surprisingly, we find that, under de-repressing conditions of the inducible MET25/GAL1 promoters, yeast cells expressing chromosomally-integrated copies of the human α-synuclein gene are not killed, but spontaneously form respiration-deficient rho-minus (ρ−) petites. Although yeast cells can undergo cell death (apoptosis) from loss of mitochondrial function, they can also survive without functional mitochondria. Such cells are referred to as ρ0 or ρ− petites. This study reports that minimal expression of human α-synuclein in yeast, from MET25/GAL1 promoter, gives rise to ρ− petites. Interestingly, the full expression of α-synuclein, from the same promoters, in α-synuclein-triggered ρ− petites and also in ρ0 petites (produced by treating ρ+ cells with the mutagen ethidium bromide) initiates apoptosis. The percentages of petites increase with increasing α-synuclein gene copy-number. ρ− petites expressing α-synuclein from fully-induced MET25/GAL1 promoters exhibit increased ROS levels, loss of mitochondrial membrane potential, and nuclear DNA fragmentation, with increasing copies of α-synuclein. Our results indicate that, for the first time in yeast, α-synuclein-triggered apoptosis can occur independently of functional mitochondria. The observation that α-synuclein naturally forms petites and that they can undergo apoptosis may have important implications in understanding the pathogenesis of Parkinson’s disease.
Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness
Authors: Parackova Zuzana , Zentsova Irena , Bloomfield Marketa , Vrabcova Petra , Smetanova Jitka , Klocperk Adam , Mesežnikov Grigorij , Casas Mendez Luis Fernando , Vymazal Tomas , Sediva Anna
Published: September 2020

COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host–pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.
Cell Death in the Tumor Microenvironment: Implications for Cancer Immunotherapy
Authors: Gadiyar Varsha , Lahey Kevin C. , Calianese David , Devoe Connor , Mehta Dhriti , Bono Kristy , Desind Samuel , Davra Viralkumar , Birge Raymond B.
Published: September 2020

The physiological fate of cells that die by apoptosis is their prompt and efficient removal by efferocytosis. During these processes, apoptotic cells release intracellular constituents that include purine nucleotides, lysophosphatidylcholine (LPC), and Sphingosine-1-phosphate (S1P) that induce migration and chemo-attraction of phagocytes as well as mitogens and extracellular membrane-bound vesicles that contribute to apoptosis-induced compensatory proliferation and alteration of the extracellular matrix and the vascular network. Additionally, during efferocytosis, phagocytic cells produce a number of anti-inflammatory and resolving factors, and, together with apoptotic cells, efferocytic events have a homeostatic function that regulates tissue repair. These homeostatic functions are dysregulated in cancers, where, aforementioned events, if not properly controlled, can lead to cancer progression and immune escape. Here, we summarize evidence that apoptosis and efferocytosis are exploited in cancer, as well as discuss current translation and clinical efforts to harness signals from dying cells into therapeutic strategies.
Frequency Associations between East Asian Jet Streams and the Temperature over the Barents–Kara Sea Region/Arctic Oscillation in Winter
Authors: Li Yuefeng , Zhu Yuxiang , Song Wei
Published: September 2020

The frequency associations between jet streams over East Asia and the Arctic key temperature at 2 m (AKT2m) in the Barents–Kara Sea region (40°–75° E, 66°–82° N) and the Arctic Oscillation in winter are investigated using continuous wavelet transform, cross-wavelet transform, and wavelet coherence. The cross-wavelet transforms between the AKT2m/Arctic Oscillation and the East Asian polar front jet stream (EAPJ) suggest that the EAPJ is closely related to the AKT2m and Arctic Oscillation on an interannual (3–5-year band) timescale, but the variation in the phase angle denotes a complex frequency connection between the EAPJ and Arctic Oscillation. The squared wavelet coherence suggests that weakening of the EAPJ is associated with the rise in AKT2m during the period of abrupt climate change in East Asia. The EAPJ contains more forced components from the Arctic than the East Asian subtropical jet stream. By comparison, the relationship between AKT2m and the EAPJ is closer than that between the Arctic Oscillation and EAPJ, especially during the period of abrupt climate change in East Asia. This suggests that the EAPJ serves as a bridge for Arctic warming to affect the weather and climate over East Asia in winter. By contrast, the Arctic Oscillation does not play an important part, although it also contains information about the Arctic.
Microstructure and Corrosion Behavior of Cold-Sprayed Zn-Al Composite Coating
Authors: Zhao Zhipo , Tang Junrong , Tariq Naeem ul Haq , Wang Jiqiang , Cui Xinyu , Xiong Tianying
Published: September 2020

A Zn–Al composite coating was successfully deposited on Q235 steel by cold spray technology for the corrosion protection in the marine atmosphere. The microstructure and corrosion behavior of the prepared coating was studied byScanning Electron Microscope (SEM), X-ray Diffraction (XRD), salt spray test and electrochemical experiments. A 2400-h neutral salt spray corrosion test (with a corrosion medium of 3.5% sodium chloride solution) showed that the prepared cold-sprayed Zn-Al composite coating has excellent anti-corrosion properties. Based on the microstructure evolution and corrosion products analysis, droplets’ flow-driven ‘synergistic corrosion effect’ was proposed to explain the co-corrosion behavior of Zn and Al particles in the composite coating.
Electrodeposition of ZnO/Cu2O Heterojunctions on Ni-Mo-P Electroless Coating
Authors: Rosas-Laverde Nelly , Pruna Alina , Cembrero Jesus , Busquets-Mataix David
Published: September 2020

Electroless Ni-Mo-P coatings were deposited onto ceramic tiles in order to be employed as electrodes for the electrodeposition of ZnO and Cu2O heterojunction layers. Varying conditions, such as duration, annealing of the electroless coating and applied potential, and duration for ZnO electrodeposition were studied in order to optimize the properties of the ZnO/Cu2O heterojunctions toward improved photoelectrical performance. The coatings were evaluated in terms of morphology, crystalline structure, and by electrochemical and photoelectrical means. The obtained results indicated that a prolonged annealing treatment at low temperature is beneficial to improve the roughness and electrical conductivity of the Ni-Mo-P coating to further enhance the electrodeposition of ZnO. The morphology analysis revealed continuous and homogeneous Ni-Mo-P coatings. The formation of cube-like Cu2O crystals with larger grain size was induced by increasing the deposition duration of ZnO. The properties of ZnO layer are much improved when a higher cathodic potential is applied (−0.8 V) for 1 h, resulting in optimum photoelectric parameters as 1.44 mA·cm−2 for the JSC and 760.23 µV for the VOC value, respectively, for the corresponding heterojunction solar cell.
Causal Modeling of Twitter Activity during COVID-19
Authors: Gencoglu Oguzhan , Gruber Mathias
Published: September 2020

Understanding the characteristics of public attention and sentiment is an essential prerequisite for appropriate crisis management during adverse health events. This is even more crucial during a pandemic such as COVID-19, as primary responsibility of risk management is not centralized to a single institution, but distributed across society. While numerous studies utilize Twitter data in descriptive or predictive context during COVID-19 pandemic, causal modeling of public attention has not been investigated. In this study, we propose a causal inference approach to discover and quantify causal relationships between pandemic characteristics (e.g., number of infections and deaths) and Twitter activity as well as public sentiment. Our results show that the proposed method can successfully capture the epidemiological domain knowledge and identify variables that affect public attention and sentiment. We believe our work contributes to the field of infodemiology by distinguishing events that correlate with public attention from events that cause public attention.
Dinuclear Silver(I) Nitrate Complexes with Bridging Bisphosphinomethanes: Argentophilicity and Luminescence
Authors: Baranova Kristina F. , Titov Aleksei A. , Filippov Oleg A. , Smol’yakov Alexander F. , Averin Alexey A. , Shubina Elena S.
Published: September 2020

Two silver nitrate complexes with bisphosphines were obtained and characterized: [Ag(dcypm)]2(NO3)2 (1; dcypm = bis(dicyclohexylphosphino)methane) and [Ag(dppm)]2(Me2PzH)n(NO3)2 (n = 1, 2a; n = 2, 2b; dppm = bis(diphenylphosphino)methane, Me2PzH = 3,5-dimethylpyrazole). The steric repulsions of bulky cyclohexyl substituents prevent additional ligand coordination to the silver atoms in 1. Compounds obtained feature the bimetallic eight-member cyclic core [AgPCP]2. The intramolecular argenthophilic interaction (d(Ag···Ag) = 2.981 Å) was observed in complex 1. In contrast, the coordination of pyrazole led to the elongation of Ag···Ag distance to 3.218(1) Å in 2a and 3.520 Å in 2b. Complexes 1 and 2a possess phosphorescence both in the solution and solid state. Time-dependent density-functional theory (TD-DFT) calculations demonstrate the origin of their different emission profile. In the case of 1, upon excitation, the electron leaves the Ag–P bonding orbital and locates on the intramolecular Ag···Ag bond (metal-centered character). Complex 2a at room temperature exhibits a phosphorescence originating from the 3(M + LP+N)LPhCT state. At 77 K, the photoluminescence spectrum of complex 2a shows two bands of two different characters: 3(M + LP+N)LPhCT and 3LCPh transitions. The contribution of Ag atoms to the excited state in both complexes 2a and 2b decreased relative to 1 in agreement with the structural changes caused by pyrazole coordination.
Broadband Multichannel Optical Vortex Generators via Patterned Double-Layer Reverse-Twist Liquid Crystal Polymer
Authors: Zhang Hanqing , Duan Wei , Wei Ting , Xu Chunting , Hu Wei
Published: September 2020

The capacity of an optical communication system can be greatly increased by using separate orbital angular momentum (OAM) modes as independent channels for signal transmission and encryption. At present, a transmissive OAM mode generator compatible with wavelength division multiplexing is being highly pursued. Here, we introduce a specific double-layer reverse-twist configuration into liquid crystal polymer (LCP) to overcome wavelength dependency. With this design, broadband-applicable OAM array generators are proposed and demonstrated. A Damman vortex grating and a Damman q-plate were encoded via photopatterning two subsequent LCP layers adopted with oppositely handed chiral dopants. Rectangular and hexagonal OAM arrays with mode conversion efficiencies exceeding 40.1% and 51.0% in the ranges of 530 to 930 nm, respectively, are presented. This provides a simple and broadband efficient strategy for beam shaping.
A Multi-Center, Real-Life Experience on Liquid Biopsy Practice for EGFR Testing in Non-Small Cell Lung Cancer (NSCLC) Patients
Authors: Cortiula Francesco , Pasello Giulia , Follador Alessandro , Nardo Giorgia , Polo Valentina , Scquizzato Elisa , Del Conte Alessandro , Miorin Marta , Giovanis Petros , D’Urso Alessandra , Girlando Salvator , Settanni Giulio , Picece Vincenzo , Veccia Antonello , Corvaja Carla , Indraccolo Stefano , De Maglio Giovanna
Published: September 2020

Background: circulating tumor DNA (ctDNA) is a source of tumor genetic material for EGFR testing in NSCLC. Real-word data about liquid biopsy (LB) clinical practice are lacking. The aim of the study was to describe the LB practice for EGFR detection in North Eastern Italy. Methods: we conducted a multi-regional survey on ctDNA testing practices in lung cancer patients. Results: Median time from blood collection to plasma separation was 50 min (20–120 min), median time from plasma extraction to ctDNA analysis was 24 h (30 min–5 days) and median turnaround time was 24 h (6 h–5 days). Four hundred and seventy five patients and 654 samples were tested. One hundred and ninety-two patients were tested at diagnosis, with 16% EGFR mutation rate. Among the 283 patients tested at disease progression, 35% were T790M+. Main differences in LB results between 2017 and 2018 were the number of LBs performed for each patient at disease progression (2.88 vs. 1.2, respectively) and the percentage of T790M+ patients (61% vs. 26%).
Association of Major Histocompatibility Complex Class I Related Chain A/B Positive Microparticles with Acute Myocardial Infarction and Disease Severity
Authors: Haohan Songpol , Pussadhamma Burabha , Jumnainsong Amonrat , Leuangwatthananon Wit , Makarawate Pattarapong , Leelayuwat Chanvit , Komanasin Nantarat
Published: September 2020

Background: Various cell types undergo activation and stress during atherosclerosis resulting in the development of acute myocardial infarction (AMI) in coronary artery disease (CAD). Major histocompatibility complex class I related chain A and B (MICA/B) can be expressed on the surface of activated and stressed cells and released into blood circulation in several forms including microparticles (MICA/B+ MPs) from various cell types. We aimed to investigate the association of these MICA/B+ MPs with the presence of AMI. Fifty-one AMI and 46 age-matched control subjects were recruited. Methods: Levels of MICA/B+ MPs derived from various parent cells including endothelial cells, platelets, monocytes, neutrophils, and T lymphocytes were determined by flow cytometry. Results: The levels and proportion of MICA/B+ MPs from all types of cell origin were significantly increased in AMI patients compared to those of the controls. A multivariate regression model showed an independent association between MICA/B+ MPs and AMI (OR = 11.6; 95% CI = 2.8, 47.3). Interestingly, based on the disease severity, we found that the levels of MICA/B+ MPs were significantly elevated in the ST-segment elevation myocardial infarction (STEMI) compared to the non-STEMI (NSTEMI) patients. Moreover, an independent association of MICA/B+ MPs with the occurrence of STEMI was also demonstrated (OR = 4.1; 95% CI = 1.5, 16.7). Conclusions: These results suggest that MICA/B+ MPs are associated with AMI and disease severity. They may act as mediators contributing to the pathological process of AMI. Alternatively, they are the results of various cell activations contributing to AMI.
Real-World Experience Measurement of Liver Iron Concentration by R2 vs. R2 Star MRI in Hemoglobinopathies
Authors: Abou Zahr Riad , Burkhardt Barbara E. U. , Ehsan Lubaina , Potersnak Amanda , Greil Gerald , Dillenbeck Jeanne , Rogers Zora , Hussain Tarique
Published: September 2020

Background: Non-invasive determination of liver iron concentration (LIC) is a valuable tool that guides iron chelation therapy in transfusion-dependent patients. Multiple methods have been utilized to measure LIC by MRI. The purpose of this study was to compare free breathing R2* (1/T2*) to whole-liver Ferriscan R2 method for estimation of LIC in a pediatric and young adult population who predominantly have hemoglobinopathies. Methods: Clinical liver and cardiac MRI scans from April 2016 to May 2018 on a Phillips 1.5 T scanner were reviewed. Free breathing T2 and T2* weighted images were acquired on each patient. For T2, multi-slice spin echo sequences were obtained. For T2*, a single mid-liver slice fast gradient echo was performed starting at 0.6 ms with 1.2 ms increments with signal averaging. R2 measurements were performed by Ferriscan analysis. R2* measurements were performed by quantitative T2* map analysis. Results: 107 patients underwent liver scans with the following diagnoses: 76 sickle cell anemia, 20 Thalassemia, 9 malignancies and 2 Blackfan Diamond anemia. Mean age was 12.5 ± 4.5 years. Average scan time for R2 sequences was 10 min, while R2* sequence time was 20 s. R2* estimation of LIC correlated closely with R2 with a correlation coefficient of 0.94. Agreement was strongest for LIC < 15 mg Fe/g dry weight. Overall bias from Bland–Altman plot was 0.66 with a standard deviation of 2.8 and 95% limits of agreement −4.8 to 6.1. Conclusion: LIC estimation by R2* correlates well with R2-Ferriscan in the pediatric age group. Due to the very short scan time of R2*, it allows imaging without sedation or anesthesia. Cardiac involvement was uncommon in this cohort.
Performance of Targeted Library Preparation Solutions for SARS-CoV-2 Whole Genome Analysis
Authors: Klempt Petr , Brož Petr , Kašný Martin , Novotný Adam , Kvapilová Kateřina , Kvapil Petr
Published: September 2020

Single next-generation sequencing (NGS) proved to be an important tool for monitoring the SARS-CoV-2 outbreak at the global level Until today, thousands of SARS-CoV-2 genome sequences have been published at GISAID (Global Initiative on Sharing All Influenza Data) but only a portion are suitable for reliable variant analysis. Here we report on the comparison of three commercially available NGS library preparation kits. We discuss advantages and limitations from the perspective of required input sample quality and data quality for advanced SARS-CoV-2 genome analysis.