bluuebunny/crossref_metadata_2025 huggingface dataset:
Research agenda: Researching grammar teaching and learning in the second language classroom
Authors: Collins Laura , Ruivivar June
Published: March 2021

We propose five research tasks targeting grammar teaching and learning, focusing on extending previous research and exploring under-studied features and contexts. The first two tasks outline replications and extensions of seminal studies on pedagogical grammar, Toth (2008) and Samuda (2001), designed to advance our understanding of the teacher role in providing rich practice opportunities. Another task examines how features of peer interaction during oral communication might encourage attention to grammar among young second language (L2) classroom learners in school-based foreign language programs, a common yet under-studied context. A fourth task investigates the unique properties of spoken grammar across languages and effective approaches for its teaching and learning, and the fifth explores the (re)design and use of corpus-based tools to enhance accessibility and learner autonomy in data-driven grammar learning. Each task is designed to be feasible across a variety of classroom contexts and target languages. We highlight concrete implications for language pedagogy and include suggestions for capturing both learning outcomes and participants’ perspectives on their learning and teaching, using a range of quantitative and qualitative methodologies. We end with some thoughts on repetitive practice for learning certain features of grammar, and recommendations for collaborative research that would encourage greater replication of future studies.
A Global Flood Risk Modeling Framework Built With Climate Models and Machine Learning
Authors: Carozza David A. , Boudreault Mathieu
Published: March 2021

Large scale flood risk analyses are fundamental to many applications requiring national or international overviews of flood risk. While large‐scale climate patterns such as teleconnections and climate change become important at this scale, it remains a challenge to represent the local hydrological cycle over various watersheds in a manner that is physically consistent with climate. As a result, global models tend to suffer from a lack of available scenarios and flexibility that are key for planners, relief organizations, regulators, and the financial services industry to analyze the socioeconomic, demographic, and climatic factors affecting exposure. Here we introduce a data‐driven, global, fast, flexible, and climate‐consistent flood risk modeling framework for applications that do not necessarily require high‐resolution flood mapping. We use statistical and machine learning methods to examine the relationship between historical flood occurrence and impact from the Dartmouth Flood Observatory (1985–2017), and climatic, watershed, and socioeconomic factors for 4,734 HydroSHEDS watersheds globally. Using bias‐corrected output from the NCAR CESM Large Ensemble (1980–2020), and the fitted statistical relationships, we simulate 1 million years of events worldwide along with the population displaced in each event. We discuss potential applications of the model and present global flood hazard and risk maps. The main value of this global flood model lies in its ability to quickly simulate realistic flood events at a resolution that is useful for large‐scale socioeconomic and financial planning, yet we expect it to be useful to climate and natural hazard scientists who are interested in socioeconomic impacts of climate.
Superior survival with pediatric-style chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in older adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: analysis from CALGB 10403 and the CIBMTR
Authors: Wieduwilt Matthew J. , Stock Wendy , Advani Anjali , Luger Selina , Larson Richard A. , Tallman Martin , Appelbaum Frederick , Zhang Mei-Jie , Bo-Subait Khalid , Wang Hai-Lin , Bhatt Vijaya Raj , Dholaria Bhagirathbhai , Eapen Mary , Hamadani Mehdi , Jamy Omer , Prestidge Tim , Pulsipher Michael , Ritchie David , Rizzieri David , Sharma Akshay , Barba Pere , Sandmaier Brenda M. , de Lima Marcos , Kebriaei Partow , Litzow Mark , Saber Wael , Weisdorf Daniel
Published: March 2021

Optimal post-remission therapy for adolescents and young adults (AYAs) with Ph-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is not established. We compared overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) for patients receiving post-remission therapy on CALGB 10403 to a cohort undergoing myeloablative (MA) allogeneic hematopoietic cell transplantation (HCT) in CR1. In univariate analysis, OS was superior with chemotherapy compared to MA allogeneic HCT (3-year OS 77% vs. 53%, P < 0.001). In multivariate analysis, allogeneic HCT showed inferior OS (HR 2.00, 95% CI 1.5–2.66, P < 0.001), inferior DFS (HR 1.62, 95% CI 1.25–2.12, P < 0.001), and increased NRM (HR 5.41, 95% CI 3.23–9.06, P < 0.001) compared to chemotherapy. A higher 5-year relapse incidence was seen with chemotherapy compared to allogeneic HCT (34% vs. 23%, P = 0.011). Obesity was independently associated with inferior OS (HR 2.17, 95% CI 1.63–2.89, P < 0.001), inferior DFS (HR 1.97, 95% CI 1.51–2.57, P < 0.001), increased relapse (1.84, 95% CI 1.31–2.59, P < 0.001), and increased NRM (HR 2.10, 95% CI 1.37–3.23, P < 0.001). For AYA ALL patients in CR1, post-remission therapy with pediatric-style chemotherapy is superior to MA allogeneic HCT for OS, DFS, and NRM.
Integrated characterization of SARS-CoV-2 genome, microbiome, antibiotic resistance and host response from single throat swabs
Authors: Lu Bo , Yan Yi , Dong Liting , Han Lingling , Liu Yawei , Yu Junping , Chen Jianjun , Yi Danyang , Zhang Meiling , Deng Xin , Wang Chao , Wang Runkun , Wang Dengpeng , Wei Hongping , Liu Di , Yi Chengqi
Published: March 2021

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, poses a severe threat to humanity. Rapid and comprehensive analysis of both pathogen and host sequencing data is critical to track infection and inform therapies. In this study, we performed unbiased metatranscriptomic analysis of clinical samples from COVID-19 patients using a recently developed RNA-seq library construction method (TRACE-seq), which utilizes tagmentation activity of Tn5 on RNA/DNA hybrids. This approach avoids the laborious and time-consuming steps in traditional RNA-seq procedure, and hence is fast, sensitive, and convenient. We demonstrated that TRACE-seq allowed integrated characterization of full genome information of SARS-CoV-2, putative pathogens causing coinfection, antibiotic resistance, and host response from single throat swabs. We believe that the integrated information will deepen our understanding of pathogenesis and improve diagnostic accuracy for infectious diseases.
Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs
Authors: Todkar Kiran , Chikhi Lilia , Desjardins Véronique , El-Mortada Firas , Pépin Geneviève , Germain Marc
Published: March 2021

Most cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.
Precise regulation of the relative rates of surface area and volume synthesis in bacterial cells growing in dynamic environments
Authors: Shi Handuo , Hu Yan , Odermatt Pascal D. , Gonzalez Carlos G. , Zhang Lichao , Elias Joshua E. , Chang Fred , Huang Kerwyn Casey
Published: March 2021

The steady-state size of bacterial cells correlates with nutrient-determined growth rate. Here, we explore how rod-shaped bacterial cells regulate their morphology during rapid environmental changes. We quantify cellular dimensions throughout passage cycles of stationary-phase cells diluted into fresh medium and grown back to saturation. We find that cells exhibit characteristic dynamics in surface area to volume ratio (SA/V), which are conserved across genetic and chemical perturbations as well as across species and growth temperatures. A mathematical model with a single fitting parameter (the time delay between surface and volume synthesis) is quantitatively consistent with our SA/V experimental observations. The model supports that this time delay is due to differential expression of volume and surface-related genes, and that the first division after dilution occurs at a tightly controlled SA/V. Our minimal model thus provides insight into the connections between bacterial growth rate and cell shape in dynamic environments.
Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients
Authors: Maifeld András , Bartolomaeus Hendrik , Löber Ulrike , Avery Ellen G. , Steckhan Nico , Markó Lajos , Wilck Nicola , Hamad Ibrahim , Šušnjar Urša , Mähler Anja , Hohmann Christoph , Chen Chia-Yu , Cramer Holger , Dobos Gustav , Lesker Till Robin , Strowig Till , Dechend Ralf , Bzdok Danilo , Kleinewietfeld Markus , Michalsen Andreas , Müller Dominik N. , Forslund Sofia K.
Published: March 2021

Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
Direct observation of excitonic instability in Ta2NiSe5
Authors: Kim Kwangrae , Kim Hoon , Kim Jonghwan , Kwon Changil , Kim Jun Sung , Kim B. J.
Published: March 2021

Coulomb attraction between electrons and holes in a narrow-gap semiconductor or a semimetal is predicted to lead to an elusive phase of matter dubbed excitonic insulator. However, direct observation of such electronic instability remains extremely rare. Here, we report the observation of incipient divergence in the static excitonic susceptibility of the candidate material Ta2NiSe5 using Raman spectroscopy. Critical fluctuations of the excitonic order parameter give rise to quasi-elastic scattering of B2g symmetry, whose intensity grows inversely with temperature toward the Weiss temperature of TW ≈ 241 K, which is arrested by a structural phase transition driven by an acoustic phonon of the same symmetry at TC = 325 K. Concurrently, a B2g optical phonon becomes heavily damped to the extent that its trace is almost invisible around TC, which manifests a strong electron-phonon coupling that has obscured the identification of the low-temperature phase as an excitonic insulator for more than a decade. Our results unambiguously reveal the electronic origin of the phase transition.
Wireless battery free fully implantable multimodal recording and neuromodulation tools for songbirds
Authors: Ausra Jokubas , Munger Stephanie J. , Azami Amirhossein , Burton Alex , Peralta Roberto , Miller Julie E. , Gutruf Philipp
Published: March 2021

Wireless battery free and fully implantable tools for the interrogation of the central and peripheral nervous system have quantitatively expanded the capabilities to study mechanistic and circuit level behavior in freely moving rodents. The light weight and small footprint of such devices enables full subdermal implantation that results in the capability to perform studies with minimal impact on subject behavior and yields broad application in a range of experimental paradigms. While these advantages have been successfully proven in rodents that move predominantly in 2D, the full potential of a wireless and battery free device can be harnessed with flying species, where interrogation with tethered devices is very difficult or impossible. Here we report on a wireless, battery free and multimodal platform that enables optogenetic stimulation and physiological temperature recording in a highly miniaturized form factor for use in songbirds. The systems are enabled by behavior guided primary antenna design and advanced energy management to ensure stable optogenetic stimulation and thermography throughout 3D experimental arenas. Collectively, these design approaches quantitatively expand the use of wireless subdermally implantable neuromodulation and sensing tools to species previously excluded from in vivo real time experiments.
Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial
Authors: Jagannathan Prasanna , Andrews Jason R. , Bonilla Hector , Hedlin Haley , Jacobson Karen B. , Balasubramanian Vidhya , Purington Natasha , Kamble Savita , de Vries Christiaan R. , Quintero Orlando , Feng Kent , Ley Catherine , Winslow Dean , Newberry Jennifer , Edwards Karlie , Hislop Colin , Choong Ingrid , Maldonado Yvonne , Glenn Jeffrey , Bhatt Ami , Blish Catherine , Wang Taia , Khosla Chaitan , Pinsky Benjamin A. , Desai Manisha , Parsonnet Julie , Singh Upinder
Published: March 2021

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.
Diffusion in dense supercritical methane from quasi-elastic neutron scattering measurements
Authors: Ranieri Umbertoluca , Klotz Stefan , Gaal Richard , Koza Michael Marek , Bove Livia E.
Published: March 2021

Methane, the principal component of natural gas, is an important energy source and raw material for chemical reactions. It also plays a significant role in planetary physics, being one of the major constituents of giant planets. Here, we report measurements of the molecular self-diffusion coefficient of dense supercritical CH4 reaching the freezing pressure. We find that the high-pressure behaviour of the self-diffusion coefficient measured by quasi-elastic neutron scattering at 300 K departs from that expected for a dense fluid of hard spheres and suggests a density-dependent molecular diameter. Breakdown of the Stokes–Einstein–Sutherland relation is observed and the experimental results suggest the existence of another scaling between self-diffusion coefficient D and shear viscosity η, in such a way that Dη/ρ=constant at constant temperature, with ρ the density. These findings underpin the lack of a simple model for dense fluids including the pressure dependence of their transport properties.
SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself
Authors: Ferreira-Gomes Marta , Kruglov Andrey , Durek Pawel , Heinrich Frederik , Tizian Caroline , Heinz Gitta Anne , Pascual-Reguant Anna , Du Weijie , Mothes Ronja , Fan Chaofan , Frischbutter Stefan , Habenicht Katharina , Budzinski Lisa , Ninnemann Justus , Jani Peter K. , Guerra Gabriela Maria , Lehmann Katrin , Matz Mareen , Ostendorf Lennard , Heiberger Lukas , Chang Hyun-Dong , Bauherr Sandy , Maurer Marcus , Schönrich Günther , Raftery Martin , Kallinich Tilmann , Mall Marcus Alexander , Angermair Stefan , Treskatsch Sascha , Dörner Thomas , Corman Victor Max , Diefenbach Andreas , Volk Hans-Dieter , Elezkurtaj Sefer , Winkler Thomas H. , Dong Jun , Hauser Anja Erika , Radbruch Helena , Witkowski Mario , Melchers Fritz , Radbruch Andreas , Mashreghi Mir-Farzin
Published: March 2021

The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.
Single strain control of microbial consortia
Authors: Fedorec Alex J. H. , Karkaria Behzad D. , Sulu Michael , Barnes Chris P.
Published: March 2021

The scope of bioengineering is expanding from the creation of single strains to the design of microbial communities, allowing for division-of-labour, specialised sub-populations and interaction with “wild” microbiomes. However, in the absence of stabilising interactions, competition between microbes inevitably leads to the removal of less fit community members over time. Here, we leverage amensalism and competitive exclusion to stabilise a two-strain community by engineering a strain of Escherichia coli which secretes a toxin in response to competition. We show experimentally and mathematically that such a system can produce stable populations with a composition that is tunable by easily controllable parameters. This system creates a tunable, stable two-strain consortia while only requiring the engineering of a single strain.
Topological protection versus degree of entanglement of two-photon light in photonic topological insulators
Authors: Tschernig Konrad , Jimenez-Galán Álvaro , Christodoulides Demetrios N. , Ivanov Misha , Busch Kurt , Bandres Miguel A. , Perez-Leija Armando
Published: March 2021

Topological insulators combine insulating properties in the bulk with scattering-free transport along edges, supporting dissipationless unidirectional energy and information flow even in the presence of defects and disorder. The feasibility of engineering quantum Hamiltonians with photonic tools, combined with the availability of entangled photons, raises the intriguing possibility of employing topologically protected entangled states in optical quantum computing and information processing. However, while two-photon states built as a product of two topologically protected single-photon states inherit full protection from their single-photon “parents”, a high degree of non-separability may lead to rapid deterioration of the two-photon states after propagation through disorder. In this work, we identify physical mechanisms which contribute to the vulnerability of entangled states in topological photonic lattices. Further, we show that in order to maximize entanglement without sacrificing topological protection, the joint spectral correlation map of two-photon states must fit inside a well-defined topological window of protection.
Replicating bacterium-vectored vaccine expressing SARS-CoV-2 Membrane and Nucleocapsid proteins protects against severe COVID-19-like disease in hamsters
Authors: Jia Qingmei , Bielefeldt-Ohmann Helle , Maison Rachel M. , Masleša-Galić Saša , Cooper Sarah K. , Bowen Richard A. , Horwitz Marcus A.
Published: March 2021

To generate an inexpensive readily manufactured COVID-19 vaccine, we employed the LVS ΔcapB vector platform, previously used to generate potent candidate vaccines against Select Agent diseases tularemia, anthrax, plague, and melioidosis. Vaccines expressing SARS-CoV-2 structural proteins are constructed using the LVS ΔcapB vector, a highly attenuated replicating intracellular bacterium, and evaluated for efficacy in golden Syrian hamsters, which develop severe COVID-19-like disease. Hamsters immunized intradermally or intranasally with a vaccine co-expressing the Membrane and Nucleocapsid proteins and challenged 5 weeks later with a high dose of SARS-CoV-2 are protected against severe weight loss and lung pathology and show reduced viral loads in the oropharynx and lungs. Protection correlates with anti-Nucleocapsid antibody. This potent vaccine should be safe; inexpensive; easily manufactured, stored, and distributed; and given the high homology between Membrane and Nucleocapsid proteins of SARS-CoV and SARS-CoV-2, potentially serve as a universal vaccine against the SARS subset of pandemic causing β-coronaviruses.
Highest risk abandoned, lost and discarded fishing gear
Authors: Gilman Eric , Musyl Michael , Suuronen Petri , Chaloupka Milani , Gorgin Saeid , Wilson Jono , Kuczenski Brandon
Published: March 2021

Derelict abandoned, lost and discarded fishing gear have profound adverse effects. We assessed gear-specific relative risks from derelict gear to rank-order fishing methods based on: derelict gear production rates, gear quantity indicators of catch weight and fishing grounds area, and adverse consequences from derelict gear. The latter accounted for ghost fishing, transfer of microplastics and toxins into food webs, spread of invasive alien species and harmful microalgae, habitat degradation, obstruction of navigation and in-use fishing gear, and coastal socioeconomic impacts. Globally, mitigating highest risk derelict gear from gillnet, tuna purse seine with fish aggregating devices, and bottom trawl fisheries achieves maximum conservation gains. Locally, adopting controls following a sequential mitigation hierarchy and implementing effective monitoring, surveillance and enforcement systems are needed to curb derelict gear from these most problematic fisheries. Primary and synthesis research are priorities to improve future risk assessments, produce the first robust estimate of global derelict gear quantity, and assess the performance of initiatives to manage derelict gear. Findings from this first quantitative estimate of gear-specific relative risks from derelict gear guide the allocation of resources to achieve the largest improvements from mitigating adverse effects of derelict gear from the world’s 4.6 million fishing vessels.
Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
Authors: Oveland Eystein , Ahmad Intakhar , Lereim Ragnhild Reehorst , Kroksveen Ann Cathrine , Barsnes Harald , Guldbrandsen Astrid , Myhr Kjell-Morten , Bø Lars , Berven Frode S. , Wergeland Stig
Published: March 2021

Two pathophysiological different experimental models for multiple sclerosis were analyzed in parallel using quantitative proteomics in attempts to discover protein alterations applicable as diagnostic-, prognostic-, or treatment targets in human disease. The cuprizone model reflects de- and remyelination in multiple sclerosis, and the experimental autoimmune encephalomyelitis (EAE, MOG1-125) immune-mediated events. The frontal cortex, peripheral to severely inflicted areas in the CNS, was dissected and analyzed. The frontal cortex had previously not been characterized by proteomics at different disease stages, and novel protein alterations involved in protecting healthy tissue and assisting repair of inflicted areas might be discovered. Using TMT-labelling and mass spectrometry, 1871 of the proteins quantified overlapped between the two experimental models, and the fold change compared to controls was verified using label-free proteomics. Few similarities in frontal cortex between the two disease models were observed when regulated proteins and signaling pathways were compared. Legumain and C1Q complement proteins were among the most upregulated proteins in cuprizone and hemopexin in the EAE model. Immunohistochemistry showed that legumain expression in post-mortem multiple sclerosis brain tissue (n = 19) was significantly higher in the center and at the edge of white matter active and chronic active lesions. Legumain was associated with increased lesion activity and might be valuable as a drug target using specific inhibitors as already suggested for Parkinson’s and Alzheimer’s disease. Cerebrospinal fluid levels of legumain, C1q and hemopexin were not significantly different between multiple sclerosis patients, other neurological diseases, or healthy controls.
Novel porphyrazine-based photodynamic anti-cancer therapy induces immunogenic cell death
Authors: Turubanova Victoria D. , Mishchenko Tatiana A. , Balalaeva Irina V. , Efimova Iuliia , Peskova Nina N. , Klapshina Larisa G. , Lermontova Svetlana A. , Bachert Claus , Krysko Olga , Vedunova Maria V. , Krysko Dmitri V.
Published: March 2021

The immunogenicity of dying cancer cells determines the efficacy of anti-cancer therapy. Photodynamic therapy (PDT) can induce immunogenic cell death (ICD), which is characterized by the emission of damage-associated molecular patterns (DAMPs) from dying cells. This emission can trigger effective anti-tumor immunity. Only a few photosensitizers are known to induce ICD and, therefore, there is a need for development of new photosensitizers that can induce ICD. The purpose of this work was to analyze whether photosensitizers developed in-house from porphyrazines (pz I and pz III) can induce ICD in vitro and in vivo when used in PDT. We indetified the optimal concentrations of the photosensitizers and found that, at a light dose of 20 J/cm2(λex615–635 nm), both pz I and pz III efficiently induced cell death in cancer cells. We demonstrate that pz I localized predominantly in the Golgi apparatus and lysosomes while pz III in the endoplasmic reticulum and lysosomes. The cell death induced by pz I-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) but not by ferrostatin-1 and DFO (ferroptosis inhibitors) or by necrostatin-1 s (necroptosis inhibitor). By contrast, the cell death induced by pz III-PDT was inhibited by z-VAD-fmk and by the necroptosis inhibitor, necrostatin-1 s. Cancer cells induced by pz I-PDT or pz III-PDT released HMGB1 and ATP and were engulfed by bone marrow-derived dendritic cells, which then matured and became activated in vitro. We demonstrate that cancer cells, after induction of cell death by pz I-PDT or pz III-PDT, are protective when used in the mouse model of prophylactic tumor vaccination. By vaccinating immunodeficient mice, we prove the role of the adaptive immune system in protecting against tumours. All together, we have shown that two novel porphyrazines developed in-house are potent ICD inducers that could be effectively applied in PDT of cancer.
Characterization of a novel mCH3 conjugated anti-PcrV scFv molecule
Authors: Komijani Samira , Bayat Elham , Rismani Elham , Hosseini Soma , Moazzami Reza , Nematollahi Leila , Sardari Soroush , Talebkhan Yeganeh , Davami Fatemeh , Barkhordari Farzaneh , Hosseini Fakhrisadat , Jahandar Hoda
Published: March 2021

Pseudomonas aeruginosa(PA) is a leading cause of nosocomial infections and death in cystic fibrosis patients. The study was conducted to evaluate the physicochemical structure, biological activity and serum stability of a recombinant anti-PcrV single chain variable antibody fragment genetically attached to the mCH3cc domain. The stereochemical properties of scFv-mCH3 (YFL001) and scFv (YFL002) proteins as well as molecular interactions towardsPseudomonas aeruginosaPcrV were evaluated computationally. The subcloned fragments encoding YFL001 and YFL002 in pET28a were expressed within theE. coliBL21-DE3 strain. After Ni–NTA affinity chromatography, the biological activity of the proteins in inhibition of PA induced hemolysis as well as cellular cytotoxicity was assessed. In silico analysis revealed the satisfactory stereochemical quality of the models as well as common residues in their interface with PcrV. The structural differences of proteins through circular dichroism spectroscopy were confirmed by NMR analysis. Both proteins indicated inhibition of ExoU positive PA strains in hemolysis of red blood cells compared to ExoU negative strains as well as cytotoxicity effect on lung epithelial cells. The ELISA test showed the longer serum stability of the YFL001 molecule than YFL002. The results were encouraging to further evaluation of these two scFv molecules in animal models.
Experimental study on variation law of electrical parameters and temperature rise effect of coal under DC electric field
Authors: Yang Yunpeng , Wen Zhihui , Si Leilei , Xu Xiangyu
Published: March 2021

Joule heats which are generated by coals in an applied electric field are directly correlated with variation resistivity of electrical parameters of coals. Moreover, the joule heating effect is closely related with microstructural changes and relevant products of coal surface. In the present study, a self-developed applied direct current (DC) field was applied onto an experimental system of coals to investigate variation resistivity of electrical parameters of highly, moderately and lowly metamorphic coal samples. Moreover, breakdown voltages and breakdown field intensities of above three coal samples with different metamorphic grades were tested and calculated. Variation resistivity of electrical parameters of these three coal samples in 2 kV and 4 kV DC fields were analyzed. Results show that internal current of all coal samples increases continuously and tends to be stable gradually after reaching the “inflection point” at peak. The relationship between temperature rise effect on anthracite coal surface in an applied DC field and electrical parameters was discussed. The temperature rise process on anthracite coal surface is composed of three stages, namely, slowly warming, rapid warming and slow cooling to stabilize. The temperature rise effect on anthracite coal surface lags behind changes of currents which run through coal samples. There’s uneven temperature distribution on anthracite coal surface, which is attributed to the heterogeneity of coal samples. In the experiment, the highest temperature on anthracite coal surface 65.8 ℃ is far belower than the lowest temperature for pyrolysis-induced gas production of coals 200 ℃. This study lays foundations to study microstructural changes and relevant products on coal surface in an applied DC field.
Concurrent validity of the short version of Montreal Cognitive Assessment (MoCA) for patients with stroke
Authors: Feng Yali , Zhang Jiaqi , Zhou Yi , Chen Bo , Yin Ying
Published: March 2021

The aim of the present study was to examine the concurrent validity of 2 Chinese versions of the short version of the Montreal Cognitive Assessment (MoCA) in patients with stroke, i.e., MoCA 5-minute protocol and National Institute for Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) 5-minute Protocol. A total of 54 patients and 27 healthy controls were enrolled in this study. In this study, the Neurobehavioural Cognitive Status Examination (NCSE) was used as an external criterion of cognitive impairment. We found that the 5-min protocol did not differ from the MoCA in differentiating patients with cognitive impairments from those without (area under the receiver operating characteristic curve, AUC, of 0.948 for the MoCA 5-min protocol v.s. 0.984 for MoCA, P = 0.097). These three assessments demonstrated equal performance in differentiating patients with stroke from controls. The Chinese version of the MoCA 5-min protocol can be used as a valid screening for patients with stroke.
Inhibitory properties of Chinese Herbal Formula SanHuang decoction on biofilm formation by antibiotic-resistant Staphylococcal strains
Authors: Zhang Shaoe , Wang Peizhao , Shi Xiaotao , Tan Honglue
Published: March 2021

The aim of this study was to explore the effect of Chinese herbal SanHuang decoction (SH) on biofilm formation of antibiotic-resistant Staphylococci on titanium surface, and to explore its mechanism. Biofilm-forming ATCC 35984, ATCC 43300 and MRSE 287 were used in this study. The MICs of SH and vancomycin against Staphylococci were determined by the broth microdilution method. Six groups were designed, namely control group (bacteria cultured with medium), 1/8MIC SH group (1MIC SH was diluted by 1/8 using TSB or saline), 1/4MIC SH group, 1/2MIC SH group, 1MIC SH group and vancomycin group (bacteria cultured with 1MIC vancomycin). The inhibitory effect on bacterial adhesion and biofilm formation were observed by the spread plate method, CV staining, SEM, and CLSM. Real-time PCR was performed to determine the effect of SH on the expression levels of ica AD and ica R gene in ATCC 35984 during the biofilm formation. The strains were found to be susceptible to SH and vancomycin with MIC of 38.75 mg/ml and 2.5 μg/ml, respectively. SH with 1 MIC and 1/2 MIC could inhibit the bacteria adhesion, showing only scattered adhesion from SEM. CLSM showed that SH with 1 MIC and 1/2 MIC inhibited the biofilm formation. The quantitative results of the spread plate method and CV staining showed that there was significant differences between the SH groups (P < 0.05). Further, with an increase in SH concentration, the inhibitory effect became more obvious when compared with control group. Among the groups, vancomycin had the strongest inhibitory effect on bacterial adhesion and biofilm formation (P < 0.01). With an increase in SH concentration, the expression levels of ica AD decreased, and the expression of ica R increased correspondingly (P < 0.05). In conclusions, SH can inhibit the biofilm formation of antibiotic-resistant Staphylococci. Its probable mechanistic activity may be through the inhibition of polysaccharide intercellular adhesin synthesis by down-regulating the expression of ica AD gene.
Evaluation of isolated left ventricular noncompaction using cardiac magnetic resonance tissue tracking in global, regional and layer-specific strains
Authors: Zhang Jiamin , Jiang Mengchun , Zheng Chao , Liu Hui , Guo Yangyu , Xie Xingzhi , Zou ZhiMin , Zhou Xiaoyue , Xia Liming , Luo Meichen , Zeng Mu
Published: March 2021

We used cardiac magnetic resonance tissue tracking (CMR-TT) to quantitatively analyze the global, regional and layer-specific strain of isolated left ventricular noncompaction (ILVNC). Combined with late gadolinium enhancement (LGE), we initially explored the effect of focal myocardial fibrosis on myocardial strain. CMR was performed in 63 patients with ILVNC and 52 patients without ILVNC (i.e., the control group). The ILVNC group was divided into an LGE(+) group (29 patients) and an LGE(−) group (34 patients) according to the presence or absence of late gadalinum enhancement (LGE). CVI42 software was used to measure global and regional (basal, middle, apical) radial strain (RS), circumferential strain (CS), longitudinal strain (LS), subendocardial LS and subepicardial LS. The basal–apical strain gradient was defined as the apical mean strain minus the basal mean strain. We then compared differences between these strain parameters. The subendocardial-subepicardial LS gradient was defined as the maximum subendocardial LS minus the subepicardial LS. Compared with the control group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the ILVNC group were significantly diminished (P < 0.01). Compared with the LGE(−) group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the LGE(+) group were significantly diminished (P < 0.05). In the ILVNC group, the basal–apical CS and LS gradient, and the subendocardial-subepicardial LS gradient were significantly lower than those in the control group (P < 0.01). There were significant differences in myocardial strain between patients with and without ILVNC. ILVNC revealed a specific pattern in terms of strain change. The myocardial strain of the cardiac apex and endocardium was significantly lower than that of the cardiac base and epicardium, respectively. Myocardial strain reduction was more significant in ILVNC patients with focal myocardial fibrosis.
Synchronous facial action binds dynamic facial features
Authors: Johnston Alan , Brown Ben B. , Elson Ryan
Published: March 2021

We asked how dynamic facial features are perceptually grouped. To address this question, we varied the timing of mouth movements relative to eyebrow movements, while measuring the detectability of a small temporal misalignment between a pair of oscillating eyebrows—an eyebrow wave. We found eyebrow wave detection performance was worse for synchronous movements of the eyebrows and mouth. Subsequently, we found this effect was specific to stimuli presented to the right visual field, implicating the involvement of left lateralised visual speech areas. Adaptation has been used as a tool in low-level vision to establish the presence of separable visual channels. Adaptation to moving eyebrows and mouths with various relative timings reduced eyebrow wave detection but only when the adapting mouth and eyebrows moved asynchronously. Inverting the face led to a greater reduction in detection after adaptation particularly for asynchronous facial motion at test. We conclude that synchronous motion binds dynamic facial features whereas asynchronous motion releases them, allowing adaptation to impair eyebrow wave detection.
Higher exercise tolerance early after allogeneic hematopoietic stem cell transplantation is the predictive marker for higher probability of later social reintegration
Authors: Hamada Ryota , Arai Yasuyuki , Kondo Tadakazu , Harada Kazuhiro , Murao Masanobu , Miyasaka Junsuke , Yoshida Michiko , Yonezawa Honami , Nankaku Manabu , Ouchi Sayako , Kitakubo Wakako , Wadayama Tomoko , Kanda Junya , Takaori-Kondo Akifumi , Ikeguchi Ryosuke , Matsuda Shuichi
Published: March 2021

As the proportion of long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is on the rise, it is essential to consider the significance of quality of life (QOL), including reintegration with society (returning to school or work). This retrospective cohort study aims to illustrate the precise epidemiology of social reintegration later after allo-HSCT and determine its predictive indicators. We enrolled 56 patients, and 40 patients (71%) attained social reintegration at 2 years post-HSCT. Reintegration failure markedly correlated with an inferior performance status and concurrent chronic graft-versus-host disease. In non-reintegrated patients, the physical function at discharge measured by the 6-min walking distance (6MWD) was markedly decreased. On the multivariate risk analyses, sex (female; odds ratio (OR) 0.07; 95% confidence interval (CI) 0.01–0.54; p = 0.01), HCT-CI (≥ 2; OR 0.10; 95% CI 0.01–0.84; p = 0.03), and change in 6MWD (per 5% increase; OR 1.47; 95% CI 1.01–2.13; p = 0.04) were significant predictors of later social reintegration. This study suggests that a multidisciplinary strategy including rehabilitation is essential, especially in patients with poor predictive markers at an early phase, and we should consider suitable rehabilitation programs to prevent a decline in exercise tolerance and improve social reintegration and overall QOL in patients after allo-HSCT.
Low HDL and high triglycerides predict COVID-19 severity
Authors: Masana Lluís , Correig Eudald , Ibarretxe Daiana , Anoro Eva , Arroyo Juan Antonio , Jericó Carlos , Guerrero Carolina , Miret Marcel·la , Näf Silvia , Pardo Anna , Perea Verónica , Pérez-Bernalte Rosa , Plana Núria , Ramírez-Montesinos Rafael , Royuela Meritxell , Soler Cristina , Urquizu-Padilla Maria , Zamora Alberto , Pedro-Botet Juan ,   the STACOV-XULA research group, Rodríguez-Borjabad Cèlia , Andreychuk Natalia , Malo Ana , Matas Laia , del Señor Cortes-Fernandez Maria , Mauri Marta , Borrallo Rosa M. , Pedragosa Àngels , Gil-Lluís Pilar , Lacal-Martínez Ana , Barragan-Galló Patricia , Vives-Masdeu Glòria , Arto-Fernández Carmen , Boutrouki Omar El , Vázquez-Escobales Andrea , Antón-Alonso Maria Cristina , Rivero-Santana Sergio , Gómez Albert , García Sara , Rial-Lorenzo Núria , Ruiz-Ortega Lourdes , Alonso-Gisbert Oriol , Méndez-Martínez Ana Inés , Iglesias-López Hada , Climent Elisenda , Güerri Roberto , Soldado Jade , Fanlo Marta , Taboada Alicia , Gutierrez Liliana
Published: March 2021

Lipids are indispensable in the SARS-CoV-2 infection process. The clinical significance of plasma lipid profile during COVID-19 has not been rigorously evaluated. We aim to ascertain the association of the plasma lipid profile with SARS-CoV-2 infection clinical evolution. Observational cross-sectional study including 1411 hospitalized patients with COVID-19 and an available standard lipid profile prior (n: 1305) or during hospitalization (n: 297). The usefulness of serum total, LDL, non-HDL and HDL cholesterol to predict the COVID-19 prognosis (severe vs mild) was analysed. Patients with severe COVID-19 evolution had lower HDL cholesterol and higher triglyceride levels before the infection. The lipid profile measured during hospitalization also showed that a severe outcome was associated with lower HDL cholesterol levels and higher triglycerides. HDL cholesterol and triglyceride concentrations were correlated with ferritin and D-dimer levels but not with CRP levels. The presence of atherogenic dyslipidaemia during the infection was strongly and independently associated with a worse COVID-19 infection prognosis. The low HDL cholesterol and high triglyceride concentrations measured before or during hospitalization are strong predictors of a severe course of the disease. The lipid profile should be considered as a sensitive marker of inflammation and should be measured in patients with COVID-19.
A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy
Authors: Tan Chen , Jia Fan , Zhang Peng , Sun Xinghuai , Qiao Yunsheng , Chen Xueli , Wang Youxiang , Chen Junyi , Lei Yuan
Published: March 2021

Polydopamine–polyethylenimine nanoparticles (PDA/PEI NPs) have been successfully applied as miRNA carriers, and PDA/PEI NPs/miR-21-5p plays a role in increasing the aqueous humor drainage and lowering the intraocular pressure.
A signal-on fluorescence-based strategy for detection of microRNA-21 based on graphene oxide and λ exonuclease-based signal amplification
Authors: Ai Xiaojuan , Zhao Han , Hu Tingting , Yan Ying , He Hailun , Ma Changbei
Published: March 2021

A facile fluorescence method has been developed for the detection of miRNA-21 based on graphene oxide and λ exonuclease-assisted signal amplification.
Baicalin ameliorates Mycoplasma gallisepticum-induced inflammatory injury in the chicken lung through regulating the intestinal microbiota and phenylalanine metabolism
Authors: Wang Jian , Ishfaq Muhammad , Li Jichang
Published: March 2021

Baicalin shows excellent protective effects against Mycoplasma gallisepticum (MG) induced inflammatory injury as discussed in our previous studies.
Reversible magnetism switching of iron oxide nanoparticle dispersions by controlled agglomeration
Authors: Müssig Stephan , Kuttich Björn , Fidler Florian , Haddad Daniel , Wintzheimer Susanne , Kraus Tobias , Mandel Karl
Published: March 2021

Defined agglomeration of iron oxide nanoparticle dispersions was induced by temperature. The changes were characterized by magnetic particle spectroscopy in situ and revealed that the agglomerates' size distribution affected magnetic properties.
Anisotropic bacterial cellulose hydrogels with tunable high mechanical performances, non-swelling and bionic nanofluidic ion transmission behavior
Authors: Zhang Minghao , Chen Shiyan , Sheng Nan , Wang Baoxiu , Wu Zhuotong , Liang Qianqian , Wang Huaping
Published: March 2021

Our new strategy of the fossilization process and design of unique nanofiber-network-self-reinforced structure to construct anisotropic high-strength and water-rich hydrogels are scalable.
From spherical compartments to polymer films: exploiting vesicle fusion to generate solid supported thin polymer membranes
Authors: Kyropoulou Myrto , Yorulmaz Avsar Saziye , Schoenenberger Cora-Ann , Palivan Cornelia G. , Meier Wolfgang. P.
Published: March 2021

Schematic overview of the thiol assisted polymersome attachment and formation of solid supported planar polymer membranes.
Ceria doping boosts methylene blue photodegradation in titania nanostructures
Authors: Alberoni Chiara , Barroso-Martín Isabel , Infantes-Molina Antonia , Rodríguez-Castellón Enrique , Talon Aldo , Zhao Haiguang , You Shujie , Vomiero Alberto , Moretti Elisa
Published: March 2021

The photocatalytic activity of titania nanotubes and nanoparticles toward methylene blue (MB) can be enhanced through addition of a small amount of Ce. MB acts as a hole scavenger, fastening the photocatalytic process.
Bioplastic films with unusually good oxygen barrier properties based on potato fruit-juice
Authors: Poulose Simi , Jönkkäri Ilari , Hedenqvist Mikael S. , Kuusipalo Jurkka
Published: March 2021

Valorization of potato fruit juice, a potato starch industry by-product, by developing biopolymer films that could replace petroleum based alternatives in packaging, providing a greener and sustainable solution to industrial waste management.
Novel procedure of CO2 capture of the CaO sorbent activator on the reaction of one-part alkali-activated slag
Authors: Zheng Hao , He Yan , Zhu Yuqing , Liu Leping , Cui Xuemin
Published: March 2021

The proposed strategy builds a bridge between the alkali-activated cement and CaO-based CO2 sorbents, and this study provides a facile and cost-effective method for controlling the reaction rate of alkali-activated slag.