bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Studies of Giant Empty and Endohedral Fullerenes
Authors: Wang Song , Chang Qing , Zhang Guizhi , Li Fukun , Wang Xingmin , Yang Shangfeng , Troyanov Sergey I.
Published: December 2020

Structure elucidations of giant fullerenes composed of 100 or more carbon atoms are severely hampered by their extremely low yield, poor solubility and huge numbers of possible cage isomers. High-temperature exohedral chlorination followed by X-ray single crystal diffraction studies of the chloro derivatives offers a practical solution for structure elucidations of giant fullerenes. Various isomers of giant fullerenes have been determined by this method, specially, non-classical giant fullerenes containing heptagons generated by the skeletal transformations of carbon cages. Alternatively, giant fullerenes can be also stabilized by encapsulating metal atoms or clusters through intramolecular electron transfer from the encapsulated species to the outer fullerene cage. In this review, we present a comprehensive overview on synthesis, separation and structural elucidation of giant fullerenes. The isomer structures, chlorination patterns of a series of giant fullerenes C2n (2n = 100-108) and heptagon-containing non-classical fullerenes derived from giant fullerenes are summarized. On the other hand, giant endohedral fullerenes bearing different endohedral species are also discussed. At the end, we propose an outlook on the future development of giant fullerenes.
Transcriptional Circuits Regulating Developmental Processes in Candida albicans
Authors: Rodriguez Diana L. , Quail Morgan M. , Hernday Aaron D. , Nobile Clarissa J.
Published: December 2020

Candida albicansis a commensal member of the human microbiota that colonizes multiple niches in the body including the skin, oral cavity, and gastrointestinal and genitourinary tracts of healthy individuals. It is also the most common human fungal pathogen isolated from patients in clinical settings.C. albicanscan cause a number of superficial and invasive infections, especially in immunocompromised individuals. The ability ofC. albicansto succeed as both a commensal and a pathogen, and to thrive in a wide range of environmental niches within the host, requires sophisticated transcriptional regulatory programs that can integrate and respond to host specific environmental signals. Identifying and characterizing the transcriptional regulatory networks that control important developmental processes inC. albicanswill shed new light on the strategies used byC. albicansto colonize and infect its host. Here, we discuss the transcriptional regulatory circuits controlling three major developmental processes inC. albicans: biofilm formation, the white-opaque phenotypic switch, and the commensal-pathogen transition. Each of these three circuits are tightly knit and, through our analyses, we show that they are integrated together by extensive regulatory crosstalk between the core regulators that comprise each circuit.
Assessment of Clinical Pharmacists' Assistance for Patients With Established Cardiovascular Diseases During the COVID-19 Pandemic: Insights From Southern India
Authors: Gona Oliver Joel , Madhan Ramesh , Shambu Sunil Kumar
Published: December 2020

Objectives: We aimed to assess the clinical pharmacist-initiated telephone-based patient education and self-management support for patients with cardiovascular disease during the nationwide lockdown during COVID-19 pandemic.

Methods: A prospective single-center telephone-based cross-sectional study was conducted among patients at the Cardiology Department and its speciality clinic at a 1,800-bed tertiary care hospital in Southern India. A validated 8-item clinical pharmacist aided on-call questionnaire with two Domains was administered during and after lockdown (15 March and 8 June 2020). Clinical pharmacist-provided educational assistance on self-management practices were in accordance with the guidelines of Indian Council of Medical Research (ICMR) and World Health Organization. Comparisons was performed using sign test and association of responses were analyzed using the Goodman and Kruskal's gamma test. All the tests were two-tailed, p < 0.05 was considered to be statistically significant.

Results: Of the 1,080 patients, 907 consented with a response rate of (83.9%) and 574 (96.36%) patients were analyzed post-intervention. Majority of the patients were male (54.7%) and had Acute Coronary Syndrome [NSTEMI (42.10%), STEMI (33.92%) and Unstable Angina (9.86)]. The majority of subjects had at least two co-morbid conditions [(Type II Diabetes (48.33%), Hypertension (50.11%)] and were rural population (82.5%) as self-employed (43.1%) with a middle-class economy (31.6%). In the Domain-1 of checklist the awareness toward complications caused by COVID-19 in cardiovascular diseases (Z = −19.698, p = 0.000) and the importance of universal safety precautions enhanced after clinical pharmacist assistance [(Z = −8.603, p = 0.000) and (Z = −21.795, p = 0.000)]. In Domain-II of checklist there was a significant improvement in patients awareness toward fatal complications caused by COVID-19 (Z = −20.543, p = 0.000), maintenance of self-hygiene (Z = −19.287, p = 0.000), practice of universal safety precautions (Z = −16.912, p = 0.000) and self-isolation (Z = −19.545, p = 0.000). The results of our study population varied from baseline evaluation (41.7%, n = 907) to post-intervention (95%, n = 574) based on Literacy, employment status and economic status.

Conclusions: The proactive role of clinical pharmacists in providing instructional services in collaboration with cardiologist during the pandemic circumstances increased patients understanding and mitigated infection exposure among patients, health care professionals and also assuring the continuity of care in patients with established cardiovascular diseases.
Second-Generation Digital Health Platforms: Placing the Patient at the Center and Focusing on Clinical Outcomes
Authors: Ilan Yaron
Published: December 2020

Artificial intelligence (AI) digital health systems have drawn much attention over the last decade. However, their implementation into medical practice occurs at a much slower pace than expected. This paper reviews some of the achievements of first-generation AI systems, and the barriers facing their implementation into medical practice. The development of second-generation AI systems is discussed with a focus on overcoming some of these obstacles. Second-generation systems are aimed at focusing on a single subject and on improving patients' clinical outcomes. A personalized closed-loop system designed to improve end-organ function and the patient's response to chronic therapies is presented. The system introduces a platform which implements a personalized therapeutic regimen and introduces quantifiable individualized-variability patterns into its algorithm. The platform is designed to achieve a clinically meaningful endpoint by ensuring that chronic therapies will have sustainable effect while overcoming compensatory mechanisms associated with disease progression and drug resistance. Second-generation systems are expected to assist patients and providers in adopting and implementing of these systems into everyday care.
Evidence-Based Practice in Teacher Education: The Mediating Role of Self-Efficacy Beliefs and Practical Knowledge
Authors: Georgiou Despoina , Mok Sog Yee , Fischer Frank , Vermunt Jan D. , Seidel Tina
Published: December 2020

European educational reforms call for the implementation of evidence-based teaching (EBT) in universities. Based on the evidence-based research paradigm in medical education, this study investigates the relationship between teacher educators' research experience, practical knowledge, self-efficacy beliefs, and frequency of EBT implementation. We report on survey data from N = 243 teacher educators from Germany, Austria, Switzerland, and the United Kingdom. A set of mediation analyses were run to identify the mediating role of self-efficacy beliefs and practical knowledge in the interplay among teacher educators' research experience and frequency of research evidence implementation. The results indicate that self-efficacy beliefs are a strong predictor of how frequently teacher educators implement EBT. Implications about the role of self-efficacy beliefs in teacher educators' professional learning and development along with future steps that are necessary to increase the implementation of EBT practices in teacher education will be discussed.
From Fragmented Practice to Rich Professional Learning: The Collaborative Work of Teachers of Learners With Deafblindness
Authors: Hartmann Elizabeth S.
Published: December 2020

In this study, school professionals provided a rich context for understanding how collaboration can lead to learning when educating a child with deafblindness. Analysis of the collaboration of five professionals during an academic year showed that although they thought it was critical that they learn from each other, only one sub-set engaged in ways that led to rich learning opportunities. The findings from this study suggest that professional collaboration and learning, which is a hallmark of supporting learners with dual sensory loss, may be elusive even when it is a valued and mandated practice. In addition, professional learning more readily occurs when teachers are open to educating all children yet are also focused on how to best teach children with deafblindness.
Analysis and Classification of Stormwater and Wastewater Runoff From the Tijuana River Using Remote Sensing Imagery
Authors: Ayad Mariam , Li Jingjing , Holt Benjamin , Lee Christine
Published: December 2020

Urban runoff represents the primary cause of marine pollution in the Southern California coastal oceans. This study focuses on water quality issues originating from the Tijuana River watershed, which spans the southwest border of the United States and Mexico. Frequent discharge events into the coastal ocean at this boundary include stormwater and wastewater. This study focuses on differences in spectral features, as assessed by RapidEye, Sentinel-2 A/B, and Landsat-8 satellite data, along with physical and biological in situ data, to characterize and classify plumes into four key categories: stormwater, wastewater, open ocean/no plume, and mixed (when both types of plumes are present). Key spectral differences in the visible to NIR bands showed that stormwater had elevated reflectance (0.02 to 0.09), followed by mixed (0 to 0.08), wastewater (0 to 0.05), and open ocean/no plume (0 to 0.03) events. We also examined biophysical parameters and found that stormwater events had the highest values in remote sensing based estimates of colored dissolved organic matter (CDOM) (0.98 to 2.1 m–1) and turbidity (12.4 to 45.7 FNU) and also had a large range for in situ variables of enterococcus bacteria and flow rates. This study also finds that the use of spectral features in a hierarchical cluster analysis can correctly classify stormwater from wastewater plumes when there is a dominant type. These results of this study will enable improved determination of the transport of both types of plumes and transboundary monitoring of coastal water quality across the Southern California/Baja California region.
Repurposing of Anthocyanin Biosynthesis for Plant Transformation and Genome Editing
Authors: He Yubing , Zhu Min , Wu Junhua , Ouyang Lejun , Wang Rongchen , Sun Hui , Yan Lang , Wang Lihao , Xu Meilian , Zhan Huadong , Zhao Yunde
Published: December 2020

CRISPR/Cas9 gene editing technology has been very effective in editing genes in many plant species including rice. Here we further improve the current CRISPR/Cas9 gene editing technology in both efficiency and time needed for isolation of transgene-free and target gene-edited plants. We coupled the CRISPR/Cas9 cassette with a unit that activates anthocyanin biosynthesis, providing a visible marker for detecting the presence of transgenes. The anthocyanin-marker assisted CRISPR (AAC) technology enables us to identify transgenic events even at calli stage, to select transformants with elevated Cas9 expression, and to identify transgene-free plants in the field. We used the AAC technology to edit LAZY1 and G1 and successfully generated many transgene-free and target gene-edited plants at T1 generation. The AAC technology greatly reduced the labor, time, and costs needed for editing target genes in rice.
Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population
Authors: Cheng Lu , Liang Bo , Tang Xian-Fa , Cai Xin-Ying , Cheng Hui , Zheng Xiao-Dong , Zheng Jie , Wang Meng-Wei , Zhu Jun , Zhou Fu-Sheng , Li Pan , Xiao Feng-Li
Published: December 2020

Forty-nine susceptible loci have been reported to be significantly associated with vitiligo by genome-wide association studies (GWASs) in European-derived whites. To date, some of these reported susceptibility loci have not yet been validated in the Chinese Han population. The purpose of this study was to examine whether the 16 reported susceptible loci in European-derived whites were associated with vitiligo in the Chinese Han population. Imputation was performed using our previous GWAS dataset by IMPUTE v2.2.2. The 16 imputed top single-nucleotide polymorphisms (SNPs) with suggestive signals, together with the reported SNPs, were genotyped in a total of 2581 patients and 2579 controls by the Sequenom MassARRAY system. PLINK 2.0 software was used to perform association analysis. The dbSNP database, HaploReg, and eQTL data were adopted to annotate the biological function of the SNPs. Finally, four SNPs from three loci were significantly associated with vitiligo, including rs3747517 (P = 1.29 × 10–3, OR = 0.87) in 2q24.2, rs4807000 (P = 7.78 × 10–24, OR = 0.66) and rs6510827 (P = 3.65 × 10–5, OR = 1.19) in 19p13.3, and rs4822024 (P = 6.37 × 10–10, OR = 0.67) in 22q13.2. According to the dbSNP database, rs3747517 is a missense variant of IFIH1, rs4807000 and rs6510827 are located in TICAM1, and rs4822024 is located 6 kb upstream of TEF. Further bioinformatics analysis by HaploReg and eQTL found that rs4807000, rs6510827, and rs4822024 are involved in regulating gene expression. Our study revealed the strong association of 2q24.2 (rs3747517), 19p13.3 (rs4807000, rs6510827), and 22q13.2 (rs4822024) with the risk of vitiligo in the Chinese Han population, which implicates common factors for vitiligo across different ethnicities, and helps expand the understanding of the genetic basis of this disease.
No Association Between G1246A Polymorphism in HCRTR2 Gene and Risk of Cluster Headache: Evidence From an Updated Meta-Analysis of Observational Studies
Authors: Yang Jiao , Yu Si-yi , Yang Jie , Kong Jing , Liang Fan-rong , Lv Zheng-tao
Published: December 2020

Background: The hypocretin receptor 2 (HCRTR2) gene may play a pathological role in cluster headache (CH). However, the conclusions of published reports on the relationship between the G1246A polymorphism (rs2653349) in the HCRTR2 gene and risk of CH remain controversial. This purpose of this article is to comprehensively study the current evidence and assess the association between G1246A polymorphism (rs2653349) in the HCRTR2 gene and risk of CH.

Materials and Methods: Four electronic databases—ISI Web of Science, CNKI, PubMed, and EMBASE—were comprehensively searched on August 2020 to find and pinpoint all observational articles related to this study. The association between G1246A polymorphism in the HCRTR2 gene and risk of CH under five different genetic models was evaluated based on the summary odds ratio and corresponding 95 confidence interval (95% CI). Methodological quality was assessed based on the Newcastle–Ottawa Scale (NOS). To assist the analysis, RevMan 5.3 software was used to perform subgroup and sensitivity analyses. Egger's and Begg's tests were then conducted to evaluate and assess publication bias. Finally, a meta-regression was carried out by residual (restricted) maximum likelihood (REML).

Results: Eight observation studies containing 3,161 healthy controls and 1,964 patients with CH were identified and to be used for the meta-analysis. With methodological quality NOS assessment, the incorporated studies showed an average score of 6.4 stars. The pooled data didn't support the association between G1246A polymorphism in the HCRTR2 gene and CH vulnerability in the overall population (OR: 0.85, 95% CI 0.69, 1.03; p = 0.10). Subgroup analysis by ethnicity showed no significant association between G1246A and CH in either Caucasians (OR: 0.89, 95% CI 0.77, 1.01; p = 0.08) or Asians (OR: 1.65, 95% CI 0.80, 3.41; p = 0.18). The robustness of the conclusion was tested and confirmed with the leave-one-out sensitivity analysis. Meta-regression analysis showed that chronological order of publication appeared to be significantly associated with the heterogeneity (t = 2.47, p = 0.039; residual I2 = 0%, adjusted R2 = 100%).

Conclusion: Our present study showed that the G1246A polymorphism in the HCRTR2 gene did not appear to be an accomplice and associated with CH predisposition among either the Asian or Caucasian population.
Cell Type-Specific Annotation and Fine Mapping of Variants Associated With Brain Disorders
Authors: Doostparast Torshizi Abolfazl , Ionita-Laza Iuliana , Wang Kai
Published: December 2020

Common genetic variants confer susceptibility to a large number of complex brain disorders. Given that such variants predominantly localize in non-coding regions of the human genome, there is a significant challenge to predict and characterize their functional consequences. More importantly, most available computational methods, generally defined as context-free methods, output prediction scores regarding the functionality of genetic variants irrespective of the context, i.e., the tissue or cell-type affected by a disease, limiting the ability to predict the functional consequences of common variants on brain disorders. In this study, we introduce a comparative multi-step pipeline to investigate the relative effectiveness of context-specific and context-free approaches to prioritize disease causal variants. As an experimental case, we focused on schizophrenia (SCZ), a debilitating neuropsychiatric disease for which a large number of susceptibility variants is identified from genome-wide association studies. We tested over two dozen available methods and examined potential associations between the cell/tissue-specific mapping scores and open chromatin accessibility, and provided a prioritized map of SCZ risk loci for in vitro or in-vivo functional analysis. We found extensive differences between context-free and tissue-specific approaches and showed how they may play complementary roles. As a proof of concept, we found a few sets of genes, through a consensus mapping of both categories, including FURIN to be among the top hits. We showed that the genetic variants in this gene and related genes collectively dysregulate gene expression patterns in stem cell-derived neurons and characterize SCZ phenotypic manifestations, while genes which were not shared among highly prioritized candidates in both approaches did not demonstrate such characteristics. In conclusion, by combining context-free and tissue-specific predictions, our pipeline enables prioritization of the most likely disease-causal common variants in complex brain disorders.
Improved Detection of Potentially Pleiotropic Genes in Coronary Artery Disease and Chronic Kidney Disease Using GWAS Summary Statistics
Authors: Chen Haimiao , Wang Ting , Yang Jinna , Huang Shuiping , Zeng Ping
Published: December 2020

The coexistence of coronary artery disease (CAD) and chronic kidney disease (CKD) implies overlapped genetic foundation. However, the common genetic determination between the two diseases remains largely unknown. Relying on summary statistics publicly available from large scale genome-wide association studies (n = 184,305 for CAD and n = 567,460 for CKD), we observed significant positive genetic correlation between CAD and CKD (rg = 0.173, p = 0.024) via the linkage disequilibrium score regression. Next, we implemented gene-based association analysis for each disease through MAGMA (Multi-marker Analysis of GenoMic Annotation) and detected 763 and 827 genes associated with CAD or CKD (FDR < 0.05). Among those 72 genes were shared between the two diseases. Furthermore, by integrating the overlapped genetic information between CAD and CKD, we implemented two pleiotropy-informed informatics approaches including cFDR (conditional false discovery rate) and GPA (Genetic analysis incorporating Pleiotropy and Annotation), and identified 169 and 504 shared genes (FDR < 0.05), of which 121 genes were simultaneously discovered by cFDR and GPA. Importantly, we found 11 potentially new pleiotropic genes related to both CAD and CKD (i.e., ARHGEF19, RSG1, NDST2, CAMK2G, VCL, LRP10, RBM23, USP10, WNT9B, GOSR2, and RPRML). Five of the newly identified pleiotropic genes were further repeated via an additional dataset CAD available from UK Biobank. Our functional enrichment analysis showed that those pleiotropic genes were enriched in diverse relevant pathway processes including quaternary ammonium group transmembrane transporter, dopamine transport. Overall, this study identifies common genetic architectures overlapped between CAD and CKD and will help to advance understanding of the molecular mechanisms underlying the comorbidity of the two diseases.
The Integration of Genome Mining, Comparative Genomics, and Functional Genetics for Biosynthetic Gene Cluster Identification
Authors: Williams Ashley N. , Sorout Naveen , Cameron Alexander J. , Stavrinides John
Published: December 2020

Antimicrobial resistance is a worldwide health crisis for which new antibiotics are needed. One strategy for antibiotic discovery is identifying unique antibiotic biosynthetic gene clusters that may produce novel compounds. The aim of this study was to demonstrate how an integrated approach that combines genome mining, comparative genomics, and functional genetics can be used to successfully identify novel biosynthetic gene clusters that produce antimicrobial natural products. Secondary metabolite clusters of an antibiotic producer are first predicted using genome mining tools, generating a list of candidates. Comparative genomic approaches are then used to identify gene suites present in the antibiotic producer that are absent in closely related non-producers. Gene sets that are common to the two lists represent leading candidates, which can then be confirmed using functional genetics approaches. To validate this strategy, we identified the genes responsible for antibiotic production inPantoea agglomeransB025670, a strain identified in a large-scale bioactivity survey. The genome of B025670 was first mined with antiSMASH, which identified 24 candidate regions. We then used the comparative genomics platform, EDGAR, to identify genes unique to B025670 that were not present in closely related strains with contrasting antibiotic production profiles. The candidate lists generated by antiSMASH and EDGAR were compared with standalone BLAST. Among the common regions was a 14 kb cluster consisting of 14 genes with predicted enzymatic, transport, and unknown functions. Site-directed mutagenesis of the gene cluster resulted in a reduction in antimicrobial activity, suggesting involvement in antibiotic production. An integrated approach that combines genome mining, comparative genomics, and functional genetics yields a powerful, yet simple strategy for identifying potentially novel antibiotics.
A Roadmap Toward the Definition of Actionable Tumor-Specific Antigens
Authors: Minati Robin , Perreault Claude , Thibault Pierre
Published: December 2020

The search for tumor-specific antigens (TSAs) has considerably accelerated during the past decade due to the improvement of proteogenomic detection methods. This provides new opportunities for the development of novel antitumoral immunotherapies to mount an efficient T cell response against one or multiple types of tumors. While the identification of mutated antigens originating from coding exons has provided relatively few TSA candidates, the possibility of enlarging the repertoire of targetable TSAs by looking at antigens arising from non-canonical open reading frames opens up interesting avenues for cancer immunotherapy. In this review, we outline the potential sources of TSAs and the mechanisms responsible for their expression strictly in cancer cells. In line with the heterogeneity of cancer, we propose that discrete families of TSAs may be enriched in specific cancer types.
Pre-Exposure to Defibrotide Prevents Endothelial Cell Activation by Lipopolysaccharide: An Ingenuity Pathway Analysis
Authors: Orlando Nicoletta , Babini Gabriele , Chiusolo Patrizia , Valentini Caterina Giovanna , De Stefano Valerio , Teofili Luciana
Published: December 2020

Defibrotide (DFB) effects on different endothelial cell pathways have been investigated focusing on a limited number of genes or molecules. This study explored the modulation of the gene expression profile of steady-state or lipopolysaccharide (LPS)-activated endothelial cells, following the DFB exposure. Starting from differentially regulated gene expression datasets, we utilized the Ingenuity Pathway Analysis (IPA) to infer novel information about the activity of this drug. We found that effects elicited by LPS deeply differ depending on cells were exposed to DFB and LPS at the same time, or if the DFB priming occurs before the LPS exposure. Only in the second case, we observed a significant down-regulation of various pathways activated by LPS. In IPA, the pathways most affected by DFB were leukocyte migration and activation, vasculogenesis, and inflammatory response. Furthermore, the activity of DFB seemed to be associated with the modulation of six key genes, including matrix-metalloproteinases 2 and 9, thrombin receptor, sphingosine-kinase1, alpha subunit of collagen XVIII, and endothelial-protein C receptor. Overall, our findings support a role for DFB in a wide range of diseases associated with an exaggerated inflammatory response of endothelial cells.
Neutrophils From Patients With Invasive Candidiasis Are Inhibited by Candida albicans Biofilms
Authors: Kernien John F. , Johnson Chad J. , Bayless Meg L. , Chovanec Jack F. , Nett Jeniel E.
Published: December 2020

Invasive candidiasis frequently involves medical device placement. On the surfaces of these devices, Candida can form biofilms and proliferate in adherent layers of fungal cells surrounded by a protective extracellular matrix. Due in part to this extracellular matrix, biofilms resist host defenses and antifungal drugs. Previous work (using neutrophils from healthy donors) found that one mechanism employed to resist host defenses involves the inhibition of neutrophil extracellular traps (NET) formation. NETs contain nuclear DNA, as well as antimicrobial proteins that can ensnare pathogens too large or aggregated to be effectively killed by phagocytosis. Given that these neutrophil structures are anticipated to have activity against the large aggregates of C. albicans biofilms, understanding the role of this inhibition in patients could provide insight into new treatment strategies. However, prior work has not included patients. Here, we examine NET formation by neutrophils collected from patients with invasive candidiasis. When compared to neutrophils from healthy participants, we show that patient neutrophils exhibit a heightened background level of NET release and respond to a positive stimulus by producing 100% more NETs. However, despite these physiologic differences, patient neutrophil responses to C. albicans were similar to healthy neutrophils. For both groups, planktonic cells induce strong NET release and biofilms inhibit NET formation. These results show that a mechanism of immune evasion for fungal biofilms translates to the clinical setting.
Angiogenesis in Lymph Nodes Is a Critical Regulator of Immune Response and Lymphoma Growth
Authors: Menzel Lutz , Höpken Uta E. , Rehm Armin
Published: December 2020

Tumor-induced remodeling of the microenvironment in lymph nodes (LNs) includes the formation of blood vessels, which goes beyond the regulation of metabolism, and shaping a survival niche for tumor cells. In contrast to solid tumors, which primarily rely on neo-angiogenesis, hematopoietic malignancies usually grow within pre-vascularized autochthonous niches in secondary lymphatic organs or the bone marrow. The mechanisms of vascular remodeling in expanding LNs during infection-induced responses have been studied in more detail; in contrast, insights into the conditions of lymphoma growth and lodging remain enigmatic. Based on previous murine studies and clinical trials in human, we conclude that there is not a universal LN-specific angiogenic program applicable. Instead, signaling pathways that are tightly connected to autochthonous and infiltrating cell types contribute variably to LN vascular expansion. Inflammation related angiogenesis within LNs relies on dendritic cell derived pro-inflammatory cytokines stimulating vascular endothelial growth factor-A (VEGF-A) expression in fibroblastic reticular cells, which in turn triggers vessel growth. In high-grade B cell lymphoma, angiogenesis correlates with poor prognosis. Lymphoma cells immigrate and grow in LNs and provide pro-angiogenic growth factors themselves. In contrast to infectious stimuli that impact on LN vasculature, they do not trigger the typical inflammatory and hypoxia-related stroma-remodeling cascade. Blood vessels in LNs are unique in selective recruitment of lymphocytes via high endothelial venules (HEVs). The dissemination routes of neoplastic lymphocytes are usually disease stage dependent. Early seeding via the blood stream requires the expression of the homeostatic chemokine receptor CCR7 and of L-selectin, both cooperate to facilitate transmigration of tumor and also of protective tumor-reactive lymphocytes via HEV structures. In this view, the HEV route is not only relevant for lymphoma cell homing, but also for a continuous immunosurveillance. We envision that HEV functional and structural alterations during lymphomagenesis are not only key to vascular remodeling, but also impact on tumor cell accessibility when targeted by T cell–mediated immunotherapies.
B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients
Authors: Sosa-Hernández Víctor A. , Torres-Ruíz Jiram , Cervantes-Díaz Rodrigo , Romero-Ramírez Sandra , Páez-Franco José C. , Meza-Sánchez David E. , Juárez-Vega Guillermo , Pérez-Fragoso Alfredo , Ortiz-Navarrete Vianney , Ponce-de-León Alfredo , Llorente Luis , Berrón-Ruiz Laura , Mejía-Domínguez Nancy R. , Gómez-Martín Diana , Maravillas-Montero José L.
Published: December 2020

Background

SARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity.

Methods

Using a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data.

Results

The frequency of CD19+ B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations.

Conclusions

The severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.
Open Data, Collaborative Working Platforms, and Interdisciplinary Collaboration: Building an Early Career Scientist Community of Practice to Leverage Ocean Observatories Initiative Data to Address Critical Questions in Marine Science
Authors: Levine Robert M. , Fogaren Kristen E. , Rudzin Johna E. , Russoniello Christopher J. , Soule Dax C. , Whitaker Justine M.
Published: December 2020

Ocean observing systems are well-recognized as platforms for long-term monitoring of near-shore and remote locations in the global ocean. High-quality observatory data is freely available and accessible to all members of the global oceanographic community—a democratization of data that is particularly useful for early career scientists (ECS), enabling ECS to conduct research independent of traditional funding models or access to laboratory and field equipment. The concurrent collection of distinct data types with relevance for oceanographic disciplines including physics, chemistry, biology, and geology yields a unique incubator for cutting-edge, timely, interdisciplinary research. These data are both an opportunity and an incentive for ECS to develop the computational skills and collaborative relationships necessary to interpret large data sets. Here, we use observatory data to demonstrate the potential for these interdisciplinary approaches by presenting a case study on the water-column response to anomalous atmospheric events (i.e., major storms) on the shelf of the Mid-Atlantic Bight southwest of Cape Cod, United States. Using data from the Ocean Observatories Initiative (OOI) Pioneer Array, we applied a simple data mining method to identify anomalous atmospheric events over a four-year period. Two closely occurring storm events in late 2018 were then selected to explore the dynamics of water-column response using mooring data from across the array. The comprehensive ECS knowledge base and computational skill sets allowed identification of data issues in the OOI data streams and technologically sound characterization of data from multiple sensor packages to broadly characterize ocean-atmosphere interactions. An ECS-driven approach that emphasizes collaborative and interdisciplinary working practices adds significant value to existing datasets and programs such as OOI and has the potential to produce meaningful scientific advances. Future success in utilizing ocean observatory data requires continued investment in ECS education, collaboration, and research; in turn, the ECS community provides feedback, develops knowledge, and builds new tools to enhance the value of ocean observing systems. These findings present an argument for building a community of practice to augment ECS ocean scientist skills and foster collaborations to extend the context, reach, and societal utility of ocean science.
Whale Watching in the Pelagos Sanctuary: Status and Quality Assessment
Authors: Tepsich Paola , Borroni Anna , Zorgno Margherita , Rosso Massimiliano , Moulins Aurélie
Published: December 2020

In 2001 Italy, France, and Principality of Monaco instituted a protected area for marine mammals in northwestern Mediterranean Sea, named thePelagosSanctuary. The agreement foresees the commitment by signing parties to manage human activities in the area, with a special mention to whale watching. Whale watching is a form of wildlife tourism which has considerably grown in the last decades. Understanding the profile of whale watchers and their satisfaction toward the activity, is the first step toward a sustainable and effective management of this touristic activity. In this work we provide the first analysis of the whale watching activity in thePelagosSanctuary, focusing on commercial whale watching tours departing from Italian harbors in Liguria. We provide a census of the activity and the results of close-ended questionnaires filled by whale watchers during trips in summer 2016 and 2017. The aim of the questionnaires was to understand the level of awareness of experienced and new whale watchers regarding thePelagosSanctuary and some conservation initiative going on in the area. Finally, we analyzed the satisfaction level, with the aim of evidencing weakness and strengths of the service offered. Our results evidence a growth in the activity in the last 15 years, with a wider differentiation of offers and impacting a larger area than previously found. Whale watchers in the area come from a variety of countries, demonstrating the importance of the Pelagos as a hot spot for this activity. A high level of satisfaction has been evidenced, with no difference among new and experienced whale watchers. At the same time, more effort is needed to increase awareness of Pelagos and its conservation initiative both at a national and international level. This study provides useful information for the start of an effective management of whale watching in this protected area.
Surface Functionalization of Three Dimensional-Printed Polycaprolactone-Bioactive Glass Scaffolds by Grafting GelMA Under UV Irradiation
Authors: Ghorbani Farnaz , Sahranavard Melika , Mousavi Nejad Zohre , Li Dejian , Zamanian Ali , Yu Baoqing
Published: December 2020

In this study, bioactive glass nanoparticles (BGNPs) with an average diameter of less than 10 nm were synthesized using a sol-gel method and then characterized by transmission electron microscopy (TEM), differential scanning calorimetric (DSC), Fourier transforms infrared spectroscopy (FTIR), and x-ray spectroscopy (XRD). Afterward, three dimensional (3D)-printed polycaprolactone (PCL) scaffolds along with fused deposition modeling (FDM) were incorporated with BGNPs, and the surface of the composite constructs was then functionalized by coating with the gelatin methacryloyl (GelMA) under UV irradiation. Field emission scanning electron microscopy micrographs demonstrated the interconnected porous microstructure with an average pore diameter of 260 µm and homogeneous distribution of BGNPs. Therefore, no noticeable shrinkage was observed in 3D-printed scaffolds compared with the computer-designed file. Besides, the surface was uniformly covered by GelMA, and no effect of surface modification was observed on the microstructure while surface roughness increased. The addition of the BGNPs the to PCL scaffolds showed a slight change in pore size and porosity; however, it increased surface roughness. According to mechanical analysis, the compression strength of the scaffolds was increased by the BGNPs addition and surface modification. Also, a reduction was observed in the absorption capacity and biodegradation of scaffolds in phosphate-buffered saline media after the incorporation of BGNPs, while the presence of the GelMA layer increased the swelling potential and stability of the composite matrixes. Moreover, the capability of inducing bio-mineralization of hydroxyapatite-like layers, as a function of BGNPs content, was proven by FE-SEM micrographs, EDX spectra, and x-ray diffraction spectra (XRD) after soaking the obtained samples in concentrated simulated body fluid. A higher potential of the modified constructs to interact with the aqueous media led to better precipitation of minerals. According to in-vitro assays, the modified scaffolds can provide a suitable surface for the attachment and spreading of the bone marrow mesenchymal stem cells (BMSCs). Furthermore, the number of the proliferated cells confirms the biocompatibility of the scaffolds, especially after a modification process. Cell differentiation was verified by alkaline phosphatase activity as well as the expression of osteogenic genes such as osteocalcin and osteopontin. Accordingly, the scaffolds showed an initial potential for reconstruction of the injured bone.
Prevalence and Risk Factors for COPD at High Altitude: A Large Cross-Sectional Survey of Subjects Living Between 2,100–4,700 m Above Sea Level
Authors: Guo Yanfei , Xing Zhenzhen , Shan Guangliang , Janssens Jean-Paul , Sun Tieying , Chai Di , Liu Weiming , Wang Yuxia , Ma Yali , Tong Yaqi , Huang Yilin , Cao Yang , Wang Chen
Published: December 2020

Aim of Study: Four hundred million people live at high altitude worldwide. Prevalence and risk factors for COPD in these populations are poorly documented. We examined the prevalence and risk factors for COPD in residents living at an altitude of 2,100–4,700 m.

Methods: We performed a cross-sectional survey in Xinjiang and Tibet autonomous region. A multistage stratified sampling procedure was used to select a representative population aged 15 years or older from eight high altitude regions. All participants underwent pre- and post-bronchodilator measurement of forced expiratory volumes. COPD was diagnosed according to 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.

Results: Between June, 2015 and August 2016, 4,967 subjects were included. Median age was 38.0 years (range: 15–91 years; inter-quartile range: 28–49 years); 51.4% participants were female. Overall prevalence of spirometry-defined COPD was 8.2% (95% CI 7.4–8.9%): 9.3% in male (95% CI 8.2–10.4%), and 7.1% in female (95% CI 6.1–8.2%). By multivariable logistic regression analysis, COPD was significantly associated with being aged ≥40 years (odds ratio: 2.25 [95% CI 1.72–2.95], P < 0.0001), exposure to household air pollution (OR: 1.34 [95% CI 1.01–1.79], P = 0.043), and a history of tuberculosis (OR: 1.79 [95% CI 1.23–2.61], P = 0.030), while living at a higher altitude (OR: 0.45 [95% CI 0.33–0.61], P < 0.0001) and having a higher educational level (OR: 0.64 [95% CI 0.43–0.95], P = 0.025) were associated with a lower prevalence of COPD.

Conclusions: Our results show that the spirometry-defined COPD is a considerable health problem for residents living at high altitudes and COPD prevalence was inversely correlated with altitude. Preventing exposure to household air pollution and reducing the incidence of tuberculosis should be public health priorities for high altitude residents.
Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan
Authors: Al-Mudares Faeq , Reddick Samuel , Ren Jenny , Venkatesh Akshaya , Zhao Candi , Lingappan Krithika
Published: December 2020

Growth Differentiation Factor 15 (GDF15) is a divergent member of transforming growth factor-beta (TGF-β) superfamily and is ubiquitously expressed, under normal physiological conditions. GDF15 expression increases during many pathological states and serves a marker of cellular stress. GDF15 has multiple and even paradoxical roles within a pathological condition, as its effects can be dose- and time-dependent and vary based on the targeted tissues and downstream pathways. GDF15 has emerged as one of the most recognized proteins as part of the senescence associated secretory phenotype. Cellular senescence plays a major role in many lung diseases across the life-span from bronchopulmonary dysplasia in the premature neonate to COPD and idiopathic pulmonary fibrosis in aged adults. GDF15 levels have been reported to be as a useful biomarker in chronic obstructive pulmonary disease, lung fibrosis and pulmonary arterial hypertension and predict disease severity, decline in lung function and mortality. Glial-cell-line-derived neurotrophic factor family receptor alpha-like (GFRAL) in the brain stem has been identified as the only validated GDF15 receptor and mediates GDF15-mediated anorexia and wasting. The mechanisms and pathways by which GDF15 exerts its pulmonary effects are being elucidated. GDF15 may also have an impact on the lung based on the changes in circulating levels or through the central action of GDF15 activating peripheral metabolic changes. This review focuses on the role of GDF15 in different lung diseases across the lifespan and its role in cellular senescence.
How ICU Patient Severity Affects Communicative Interactions Between Healthcare Professionals: A Study Utilizing Wearable Sociometric Badges
Authors: Kawamoto Eiji , Ito-Masui Asami , Esumi Ryo , Imai Hiroshi , Shimaoka Motomu
Published: December 2020

Numerous factors affecting the interactions between healthcare professionals in the workplace demand a comprehensive understanding if the quality of patient healthcare is to be improved. Our previous cross-sectional analysis showed that patient severity scores [i.e., Acute Physiology and Chronic Health Evaluation (APACHE) II] in the 24 h following admission positively correlated with the length of the face-to-face interactions among ICU healthcare professionals. The present study aims to address how the relationships between patient severity and interaction lengths can change over a period of time during both admission and treatment in the ICU. We retrospectively analyzed data prospectively collected between 19 February to 17 March 2016 from an open ICU in a University Hospital in Japan. We used wearable sensors to collect a spatiotemporal distribution dataset documenting the face-to-face interactions between ICU healthcare professionals, which involved 76 ICU staff members, each of whom worked for 160 h, on average, during the 4-week period of data collection. We studied the longitudinal relationships among these interactions, which occurred at the patient bedside, vis-à-vis the severity of the patient's condition [i.e., the Sequential Organ Failure Assessment (SOFA) score] assessed every 24 h. On Day 1, during which a total of 117 patients stayed in the ICU, we found statistically significant positive associations between the interaction lengths and their SOFA scores, as shown by the Spearman's correlation coefficient value (R) of 0.447 (p < 0.01). During the course of our observation from Day 1 to Day 10, the number of patients (N) who stayed in the ICU gradually decreased (N = 117, Day1; N = 10, Day 10), as they either were discharged or died. The statistically significant positive associations of the interaction lengths with the SOFA scores disappeared from Days 2 to 6, but re-emerged on Day 7 (R = 0.620, p < 0.05) and Day 8 (R = 0.625, p < 0.05), then disappearing again on Days 9 and 10. Whereas all 6 SOFA sub-scores correlated well with the interaction lengths on Day 1, only a few of the sub-scores (coagulation, cardiovascular, and central nervous system scores) did so; specifically, those on Days 7 and 8. The results suggest that patient severity may play an important role in affecting the interactions between ICU healthcare professionals in a time-related manner on ICU Day 1 and on Days 7/8.