bluuebunny/crossref_metadata_2025_split huggingface dataset:
The excretory–secretory antigen HcADRM1 to generate protective immunity against Haemonchus contortus
Authors: Lu Mingmin , Tian Xiaowei , Wang Wenjuan , Zhang Yang , Aimulajiang Kalibixiati , Tian Ai-Ling , Li Charles , Yan Ruofeng , Xu Lixin , Song Xiaokai , Li Xiangrui 
Published: June 2021

AbstractThe prevention, treatment and control of Haemonchus contortus have been increasingly problematic due to its widespread occurrence and anthelmintic resistance. There are very few descriptions of recombinant antigens being protective for H. contortus, despite the success of various native antigen preparations, including Barbervax. We recently identified an H. contortus excretory–secretory antigen, H. contortus adhesion-regulating molecule 1 (HcADRM1), that served as an immunomodulator to impair host T-cell functions. Given the prophylactic potential of HcADRM1 protein as a vaccine candidate, we hereby assessed the efficacies of HcADRM1 preparations against H. contortus infection. Parasitological and immunological parameters were evaluated throughout all time points of the trials, including fecal egg counts (FEC), abomasal worm burdens, complete blood counts, cytokine production profiles and antibody responses. Active vaccination with recombinant HcADRM1 (rHcADRM1) protein induced protective immunity in inoculated goats, resulting in reductions of 48.9 and 58.6% in cumulative FEC and worm burdens. Simultaneously, passive administration of anti-HcADRM1 antibodies generated encouraging levels of protection with 46.7 and 56.2% reductions in cumulative FEC and worm burdens in challenged goats. In addition, HcADRM1 preparations-immunized goats showed significant differences in mucosal and serum antigen-specific immunoglobulin G (IgG) levels, total mucosal IgA levels, haemoglobin values and circulating interferon-γ, interleukin (IL)-4 and IL-17A production compared to control goats in both trials. The preliminary data of these laboratory trials validated the immunoprophylactic effects of rHcADRM1 protein. It can be pursued as a potential vaccine antigen to develop an effective recombinant subunit vaccine against H. contortus under field conditions.
Three Men in a Boat? How the Suminokura, Caron, and the Zheng Experienced the Regime Changes in East Asia (1600–1670): An Essay in Global Microhistory
Authors: Blussé Leonard 
Published: June 2021

AbstractThis article, originally presented as a public lecture at the occasion of the Fukuoka Prize Ceremony in September 2019, approaches from biographical and microhistorical perspectives the careers of three early-modern protagonists, Suminokura Ryōi, François Caron, and Zheng Zhilong, who were all involved in the maritime trade of the Eastern Seas. It shows how these Japanese, Dutch, and Chinese entrepreneurs became entangled with the epochal changes of regime in China and Japan in the first half of the seventeenth century, and concludes with remarks on their agency, loyalty, and legacy.
Validity and reliability of the Japanese version of the Peace, Equanimity, and Acceptance in the Cancer Experience (PEACE) questionnaire
Authors: Okamura Masako , Fujimori Maiko , Hata Kotone , Mori Masanori , Mack Jennifer W. , Prigerson Holly G. , Uchitomi Yosuke 
Published: June 2021

AbstractObjectiveThe purpose of this study was to investigate the validity and reliability of the Japanese version of the Peace, Equanimity, and Acceptance in the Cancer Experience questionnaire (PEACE-J) and to evaluate the association between the PEACE subscales and Japanese patient characteristics.MethodsA cross-sectional web-based survey was conducted among 412 patients with cancer. This survey assessed medical and demographic factors, such as the PEACE, the Coping Inventory for Stressful Situations (CISS), and the Functional Assessment of Chronic Illness Therapy — Spiritual well-being (FACIT-Sp). The forward–backward translation method was used to develop the PEACE-J. The validity of PEACE-J was evaluated by exploratory and confirmatory factor analysis, and correlation analysis between each subscale of PEACE and FACIT-Sp and CISS. The Cronbach's α and the item-total correlation of each subscale of the PEACE questionnaire were calculated to assess internal consistency reliability.ResultsThe factor analysis yielded two subscales corresponding to the original version: Cronbach's α coefficients were 0.84 and 0.86 for the Peaceful Acceptance of Illness subscale and the Struggle with Illness subscale, respectively. The PEACE subscales and the FACIT-Sp subscales and the CISS subscales were moderately associated with each other, including the Peaceful Acceptance to each subscale of FACIT (r = 0.22–0.55, p < 0.01); and the Peaceful Acceptance and the Struggle with Illness to CISS emotion-oriented coping (r = −0.36 and r = 0.45, p < 0.01, respectively). Married patients showed higher levels of peaceful acceptance than unmarried patients (p < 0.001). Poorer performance status, chemotherapy use, and recurrence or metastasis were significantly associated with higher levels of struggle with illness (p < 0.001).Significance of resultsThis study indicated that the PEACE-J is a valid and reliable measure of the patient's sense of acceptance, calmness or equanimity, and peace, as well as their sense of struggle or desperation concerning their illness.
Surfactant-guided spatial assembly of nano-architectures for molecular profiling of extracellular vesicles
Authors: Wang Zhigang , Zhao Haitao , Zhang Yan , Natalia Auginia , Ong Chin-Ann J. , Teo Melissa C. C. , So Jimmy B. Y. , Shao Huilin 
Published: June 2021

AbstractThe controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration – spatial organization and distribution – in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis.
Fast-field-cycling ultralow-field nuclear magnetic relaxation dispersion
Authors: Bodenstedt Sven , Mitchell Morgan W. , Tayler Michael C. D. 
Published: June 2021

AbstractOptically pumped magnetometers (OPMs) based on alkali-atom vapors are ultra-sensitive devices for dc and low-frequency ac magnetic measurements. Here, in combination with fast-field-cycling hardware and high-resolution spectroscopic detection, we demonstrate applicability of OPMs in quantifying nuclear magnetic relaxation phenomena. Relaxation rate dispersion across the nT to mT field range enables quantitative investigation of extremely slow molecular motion correlations in the liquid state, with time constants > 1 ms, and insight into the corresponding relaxation mechanisms. The 10-20 fT/$$\sqrt{{\rm{H}}}{\rm{z}}$$

H

z
sensitivity of an OPM between 10 Hz and 5.5 kHz 1H Larmor frequency suffices to detect magnetic resonance signals from ~ 0.1 mL liquid volumes imbibed in simple mesoporous materials, or inside metal tubing, following nuclear spin prepolarization adjacent to the OPM. High-resolution spectroscopic detection can resolve inter-nucleus spin-spin couplings, further widening the scope of application to chemical systems. Expected limits of the technique regarding measurement of relaxation rates above 100 s−1 are discussed.
An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways
Authors: Pardy Ryan D. , Valbon Stefanie F. , Cordeiro Brendan , Krawczyk Connie M. , Richer Martin J. 
Published: June 2021

AbstractZika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks.
Neoantigens elicit T cell responses in breast cancer
Authors: Morisaki Takafumi , Kubo Makoto , Umebayashi Masayo , Yew Poh Yin , Yoshimura Sachiko , Park Jae-Hyun , Kiyotani Kazuma , Kai Masaya , Yamada Mai , Oda Yoshinao , Nakamura Yusuke , Morisaki Takashi , Nakamura Masafumi 
Published: June 2021

AbstractNeoantigens are tumour-specific antigens that arise from non-synonymous mutations in tumour cells. However, their effect on immune responses in the tumour microenvironment remains unclear in breast cancer. We performed whole exome and RNA sequencing of 31 fresh breast cancer tissues and neoantigen prediction from non-synonymous single nucleotide variants (nsSNVs) among exonic mutations. Neoantigen profiles were determined by predictive HLA binding affinity (IC50 < 500 nM) and mRNA expression with a read count of ≥ 1. We evaluated the association between neoantigen load and expression levels of immune-related genes. Moreover, using primary tumour cells established from pleural fluid of a breast cancer patient with carcinomatous pleurisy, we induced cytotoxic T lymphocytes (CTLs) by coculturing neoantigen peptide-pulsed dendritic cells (DCs) with autologous peripheral lymphocytes. The functions of CTLs were examined by cytotoxicity and IFN-γ ELISpot assays. Neoantigen load ranged from 6 to 440 (mean, 95) and was positively correlated to the total number of nsSNVs. Although no associations between neoantigen load and mRNA expression of T cell markers were observed, the coculture of neoantigen-pulsed DCs and lymphocytes successfully induced CTLs ex vivo. These results suggest that neoantigen analysis may have utility in developing strategies to elicit T cell responses.
Validating quantitative PCR assays for cfDNA detection without DNA extraction in exercising SLE patients
Authors: Neuberger Elmo W. I. , Brahmer Alexandra , Ehlert Tobias , Kluge Katrin , Philippi Keito F. A. , Boedecker Simone C. , Weinmann-Menke Julia , Simon Perikles 
Published: June 2021

AbstractCirculating cell-free DNA (cfDNA) has been investigated as a screening tool for many diseases. To avoid expensive and time-consuming DNA isolation, direct quantification PCR assays can be established. However, rigorous validation is required to provide reliable data in the clinical and non-clinical context. Considering the International Organization for Standardization, as well as bioanalytical method validation guidelines, we provide a comprehensive procedure to validate assays for cfDNA quantification from blood plasma without DNA isolation. A 90 and 222 bp assay was validated to study the kinetics of cfDNA after exercise in patients with systemic lupus erythematosus (SLE). The assays showed ultra-low limit of quantification (LOQ) with 0.47 and 0.69 ng/ml, repeatability ≤ 11.6% (95% CI 8.1–20.3), and intermediate precision ≤ 12.1% (95% CI 9.2–17.7). Incurred sample reanalysis confirmed the precision of the procedure. The additional consideration of pre-analytical factors shows that centrifugation speed and temperature do not change cfDNA concentrations. In SLE patients cfDNA increases ~ twofold after a walking exercise, normalizing after 60 min of rest. The established assays allow reliable and cost-efficient quantification of cfDNA in minute amounts of plasma in the clinical setting. Additionally, the assay can be used as a tool to determine the impact of pre-analytical factors and validate cfDNA quantity and quality of isolated samples.
Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms
Authors: Valentin-Torres Alice , Day Cora , Taggart Jennifer M. , Williams Nicholas , Stubblefield Samantha R. , Roobrouck Valerie D. , Beyens Jelle , Ting Anthony E. 
Published: June 2021

AbstractDysregulation of the immune system can initiate chronic inflammatory responses that exacerbate disease pathology. Multipotent adult progenitor cells (MAPC cells), an adult adherent bone-marrow derived stromal cell, have been observed to promote the resolution of uncontrolled inflammatory responses in a variety of clinical conditions including acute ischemic stroke, acute myocardial infarction (AMI), graft vs host disease (GvHD), and acute respiratory distress syndrome (ARDS). One of the proposed mechanisms by which MAPC cells modulate immune responses is via the induction of regulatory T cells (Tregs), however, the mechanism(s) involved remains to be fully elucidated. Herein, we demonstrate that, in an in vitro setting, MAPC cells increase Treg frequencies by promoting Treg proliferation and CD4+ T cell differentiation into Tregs. Moreover, MAPC cell-induced Tregs (miTregs) have a more suppressive phenotype characterized by increased expression of CTLA-4, HLA-DR, and PD-L1 and T cell suppression capacity. MAPC cells also promoted Treg activation by inducing CD45RA+ CD45RO+ transitional Tregs. Additionally, we identify transforming growth factor beta (TGFβ) as an essential factor for Treg induction secreted by MAPC cells. Furthermore, inhibition of indoleamine 2, 3-dioxygenase (IDO) resulted in decreased Treg induction by MAPC cells demonstrating IDO involvement. Our studies also show that CD14+ monocytes play a critical role in Treg induction by MAPC cells. Our study describes MAPC cell dependent Treg phenotypic changes and provides evidence of potential mechanisms by which MAPC cells promote Treg differentiation.
Detection of SARS-CoV-2 by real-time PCR under challenging pre-analytical conditions reveals independence of swab media and cooling chain
Authors: Summer Sabrina , Schmidt Ralf , Herdina Anna Nele , Krickl Isabella , Madner Julia , Greiner Georg , Mayer Florian J. , Perkmann-Nagele Nicole , Strassl Robert 
Published: June 2021

AbstractWith global demand for SARS-CoV-2 testing ever rising, shortages in commercially available viral transport media pose a serious problem for laboratories and health care providers. For reliable diagnosis of SARS-CoV-2 and other respiratory viruses, executed by Real-time PCR, the quality of respiratory specimens, predominantly determined by transport and storage conditions, is crucial. Therefore, our aim was to explore the reliability of minimal transport media, comprising saline or the CDC recommended Viral Transport Media (HBSS VTM), for the diagnosis of SARS-CoV-2 and other respiratory viruses (influenza A, respiratory syncytial virus, adenovirus, rhinovirus and human metapneumovirus) compared to commercial products, such as the Universal Transport Media (UTM). We question the assumptions, that the choice of medium and temperature for storage and transport affect the accuracy of viral detection by RT-PCR. Both alternatives to the commercial transport medium (UTM), HBSS VTM or saline, allow adequate detection of SARS-CoV-2 and other respiratory viruses, regardless of storage temperatures up to 28 °C and storage times up to 28 days. Our study revealed the high resilience of SARS-CoV-2 and other respiratory viruses, enabling proper detection in clinical specimens even after long-time storage at high temperatures, independent of the transport medium’s composition.
Cumulene-like bridged indeno[1,2-b]fluorene π-conjugated polymers synthesized on metal surfaces
Authors: Martín-Fuentes Cristina , Urgel José I. , Edalatmanesh Shayan , Rodríguez-Sánchez Eider , Santos José , Mutombo Pingo , Biswas Kalyan , Lauwaet Koen , Gallego José M. , Miranda Rodolfo , Jelínek Pavel , Martín Nazario , Écija David 
Published: June 2021

Synthesis and characterization by scanning probe microscopy of cumulene-like bridged indeno[1,2-b]fluorene π-conjugated polymers on coinage metals.
Targeting protein phosphatase PP2A for cancer therapy: development of allosteric pharmaceutical agents
Authors: Brautigan David L. , Farrington Caroline , Narla Goutham 
Published: June 2021

Abstract
Tumor initiation is driven by oncogenes that activate signaling networks for cell proliferation and survival involving protein phosphorylation. Protein kinases in these pathways have proven to be effective targets for pharmaceutical inhibitors that have progressed to the clinic to treat various cancers. Here, we offer a narrative about the development of small molecule modulators of the protein Ser/Thr phosphatase 2A (PP2A) to reduce the activation of cell proliferation and survival pathways. These novel drugs promote the assembly of select heterotrimeric forms of PP2A that act to limit cell proliferation. We discuss the potential for the near-term translation of this approach to the clinic for cancer and other human diseases.
Promyelocytic leukemia protein: an atherosclerosis suppressor protein?
Authors: Corbett Cali B. , St. Paul Amanda K. , Autieri Michael V. 
Published: June 2021

Abstract
As many as 70% of cells in atherosclerotic plaque are vascular smooth muscle cell (VSMC) in origin, and pathways and proteins which regulate VSMC migration, proliferation, and phenotype modulation represent novel targets for rational drug design to reduce atherosclerotic vascular disease. In this volume of Clinical Science, Karle et al. demonstrate that tumor suppressor, promyelocytic leukemia protein (PML) plays an important role in regulation of VSMC phenotype and response to inflammatory stimuli (Clin Sci (2021) 135(7), 887-905; DOI: 10.1042/CS20201399). This important work demonstrates that PML, previously unrecognized as a participant in development of atherosclerosis, may represent a novel target for anti-atherosclerotic therapeutic modalities.
The Gaia-ESO Survey: Galactic evolution of lithium from iDR6
Authors: Romano D. , Magrini L. , Randich S. , Casali G. , Bonifacio P. , Jeffries R. D. , Matteucci F. , Franciosini E. , Spina L. , Guiglion G. , Chiappini C. , Mucciarelli A. , Ventura P. , Grisoni V. , Bellazzini M. , Bensby T. , Bragaglia A. , de Laverny P. , Korn A. J. , Martell S. L. , Tautvaišienė G. , Carraro G. , Gonneau A. , Jofré P. , Pancino E. , Smiljanic R. , Vallenari A. , Fu X. , Gutiérrez Albarrán M. L. , Jiménez-Esteban F. M. , Montes D. , Damiani F. , Bergemann M. , Worley C. 
Published: June 2021

Context. After more than 50 years, astronomical research still struggles to reconstruct the history of lithium enrichment in the Galaxy and to establish the relative importance of the various 7Li sources in enriching the interstellar medium (ISM) with this fragile element.
Aims. To better trace the evolution of lithium in the Milky Way discs, we exploit the unique characteristics of a sample of open clusters (OCs) and field stars for which high-precision 7Li abundances and stellar parameters are homogeneously derived by the Gaia-ESO Survey (GES).
Methods. We derive possibly un-depleted 7Li abundances for 26 OCs and star forming regions with ages from young (∼3 Myr) to old (∼4.5 Gyr), spanning a large range of galactocentric distances, 5 < RGC/kpc < 15, which allows us to reconstruct the local late Galactic evolution of lithium as well as its current abundance gradient along the disc. Field stars are added to look further back in time and to constrain 7Li evolution in other Galactic components. The data are then compared to theoretical tracks from chemical evolution models that implement different 7Li forges.
Results. Thanks to the homogeneity of the GES analysis, we can combine the maximum average 7Li abundances derived for the clusters with 7Li measurements in field stars. We find that the upper envelope of the 7Li abundances measured in field stars of nearly solar metallicities (−0.3 < [Fe/H]/dex < +0.3) traces very well the level of lithium enrichment attained by the ISM as inferred from observations of cluster stars in the same metallicity range. We confirm previous findings that the abundance of 7Li in the solar neighbourhood does not decrease at super-solar metallicity. The comparison of the data with the chemical evolution model predictions favours a scenario in which the majority of the 7Li abundance in meteorites comes from novae. Current data also seem to suggest that the nova rate flattens out at later times. This requirement might have implications for the masses of the white dwarf nova progenitors and deserves further investigation. Neutrino-induced reactions taking place in core-collapse supernovae also produce some fresh lithium. This likely makes a negligible contribution to the meteoritic abundance, but could be responsible for a mild increase in the 7Li abundance in the ISM of low-metallicity systems that would counterbalance the astration processes.
Current Concepts of Pathogenesis and Treatment of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms
Authors: Zeeh Franziska C. , Meyer Sara C. 
Published: June 2021

AbstractPhiladelphia chromosome-negative myeloproliferative neoplasms are hematopoietic stem cell disorders characterized by dysregulated proliferation of mature myeloid blood cells. They can present as polycythemia vera, essential thrombocythemia, or myelofibrosis and are characterized by constitutive activation of JAK2 signaling. They share a propensity for thrombo-hemorrhagic complications and the risk of progression to acute myeloid leukemia. Attention has also been drawn to JAK2 mutant clonal hematopoiesis of indeterminate potential as a possible precursor state of MPN. Insight into the pathogenesis as well as options for the treatment of MPN has increased in the last years thanks to modern sequencing technologies and functional studies. Mutational analysis provides information on the oncogenic driver mutations in JAK2, CALR, or MPL in the majority of MPN patients. In addition, molecular markers enable more detailed prognostication and provide guidance for therapeutic decisions. While JAK2 inhibitors represent a standard of care for MF and resistant/refractory PV, allogeneic hematopoietic stem cell transplantation remains the only therapy with a curative potential in MPN so far but is reserved to a subset of patients. Thus, novel concepts for therapy are an important need, particularly in MF. Novel JAK2 inhibitors, combination therapy approaches with ruxolitinib, as well as therapeutic approaches addressing new molecular targets are in development. Current standards and recent advantages are discussed in this review.