bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties
Authors: Joyce Kieran , Fabra Georgina Targa , Bozkurt Yagmur , Pandit Abhay 
Published: March 2021

AbstractBiomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.
The challenges characterizing the lived experience of caregiving. A qualitative study in the field of spinal cord injury
Authors: Zanini Claudia , Amann Julia , Brach Mirjam , Gemperli Armin , Rubinelli Sara 
Published: March 2021

Abstract
Study design
Qualitative exploratory study.

Objectives
To explore the lived experience of SCI caregivers, with a focus on the challenges of their role.

Setting
Caregivers of people with SCI living in the community in Switzerland.

Methods
Data were collected through semi-structured interviews. Thematic analysis was performed.

Results
The sample included 22 participants (16 women, 15 life partners) with a mean age of 61 years who had been caregivers for an average of 18 years. Caregiving in SCI seemed to be characterized by two phases. The first phase was relatively short and was central to becoming a caregiver; it was marked by challenges related to adjusting to the role of caregiver (e.g., dealing with shock, feeling unprepared). The second phase is lifelong and is characterized by a number of recurrent challenges related to balancing caregiving and personal life (e.g., having to prioritize caregiving over personal wishes, negotiating tasks and workload). Challenges related to lacking appropriate housing, facing financial uncertainty and dealing with bureaucracy were noted during both phases. Caregivers had to deal with these challenges to stay in step with life changes and newly emerging needs.

Conclusions
Informal caregivers have a major role in supporting people with SCI. But their needs are not static. Any strategy to empower them has to adapt to an evolving role characterized by multiple tasks and challenges. A functional relationship between caregivers and care recipients is based on the recognition of their individualities and the different phases of adaptation, which is also an enriching process.
Reducing FASN expression sensitizes acute myeloid leukemia cells to differentiation therapy
Authors: Humbert Magali , Seiler Kristina , Mosimann Severin , Rentsch Vreni , Sharma Katyayani , Pandey Amit V. , McKenna Sharon L. , Tschan Mario P. 
Published: March 2021

AbstractFatty acid synthase (FASN) is the only human lipogenic enzyme available for de novo fatty acid synthesis and is often highly expressed in cancer cells. We found that FASN mRNA levels were significantly higher in acute myeloid leukemia (AML) patients than in healthy granulocytes or CD34+hematopoietic progenitors. Accordingly, FASN levels decreased during all-transretinoic acid (ATRA)-mediated granulocytic differentiation of acute promyelocytic leukemia (APL) cells, partially via autophagic degradation. Furthermore, our data suggest that inhibition of FASN expression levels using RNAi or (-)-epigallocatechin-3-gallate (EGCG) accelerated the differentiation of APL cell lines and significantly re-sensitized ATRA refractory non-APL AML cells. FASN reduction promoted translocation of transcription factor EB (TFEB) to the nucleus, paralleled by activation of CLEAR network genes and lysosomal biogenesis. Together, our data demonstrate that inhibition of FASN expression in combination with ATRA treatment facilitates granulocytic differentiation of APL cells and may extend differentiation therapy to non-APL AML cells.
Dietary changes and anxiety during the coronavirus pandemic: a multinational survey
Authors: Kaufman-Shriqui Vered , Navarro Daniela Abigail , Raz Olga , Boaz Mona 
Published: March 2021

Abstract
Background/objectives
The 2020 global coronavirus pandemic is characterized by increased anxiety. Anxiety has been associated with poor diet quality and weight gain, which may lead to obesity, a risk factor for adverse COVID-19 outcomes. The present study was designed to examine associations between diet quality and anxiety levels during the COVID-19 pandemic.

Subjects/methods
This cross-sectional, international online study was conducted between March 30 and April 25, 2020 and available in seven languages: Arabic (7.6%), English (43.7%), French (0.8%), Hebrew (42.1%), Italian (3%), Russian (1.1%), and Spanish (1.6%). Diet quality was assessed using the Mediterranean Diet Score (possible range: 0–17 points) and anxiety scored using the General Anxiety Disorder 7-point scale (GAD-7). The Google Survey platform was used to conduct the survey.

Results
A total of 3797 persons were included in the present analysis. More than 75% of respondents were female; most completed the survey in English or Hebrew. Median age was 31 (IQ = 18) years. Almost 60% indicated that their pre-pandemic diet was healthier than their current diet. The median Mediterranean diet score was 9 (IQ = 3). The majority (54%) of participants reported at least mild anxiety, while 25% reported moderate anxiety or more severe. In a logistic regression model of at least moderate anxiety, Mediterranean diet score (OR 0.92, 95% CI 0.89–0.95, p < 0.0001) reduced odds of elevated anxiety, even after controlling for age, sex and other variables.

Conclusions
Though causality cannot be inferred, associations between diet quality and anxiety might suggest public health interventions including diet and stress control during future mass lockdowns.
Melanoma subpopulations that rapidly escape MAPK pathway inhibition incur DNA damage and rely on stress signalling
Authors: Yang Chen , Tian Chengzhe , Hoffman Timothy E. , Jacobsen Nicole K. , Spencer Sabrina L. 
Published: March 2021

AbstractDespite the increasing number of effective anti-cancer therapies, successful treatment is limited by the development of drug resistance. While the contribution of genetic factors to drug resistance is undeniable, little is known about how drug-sensitive cells first evade drug action to proliferate in drug. Here we track the responses of thousands of single melanoma cells to BRAF inhibitors and show that a subset of cells escapes drug via non-genetic mechanisms within the first three days of treatment. Cells that escape drug rely on ATF4 stress signalling to cycle periodically in drug, experience DNA replication defects leading to DNA damage, and yet out-proliferate other cells over extended treatment. Together, our work reveals just how rapidly melanoma cells can adapt to drug treatment, generating a mutagenesis-prone subpopulation that expands over time.
Robust nucleation control via crisscross polymerization of highly coordinated DNA slats
Authors: Minev Dionis , Wintersinger Christopher M. , Ershova Anastasia , Shih William M. 
Published: March 2021

AbstractNatural biomolecular assemblies such as actin filaments or microtubules can exhibit all-or-nothing polymerization in a kinetically controlled fashion. The kinetic barrier to spontaneous nucleation arises in part from positive cooperativity deriving from joint-neighbor capture, where stable capture of incoming monomers requires straddling multiple subunits on a filament end. For programmable DNA self-assembly, it is likewise desirable to suppress spontaneous nucleation to enable powerful capabilities such as all-or-nothing assembly of nanostructures larger than a single DNA origami, ultrasensitive detection, and more robust algorithmic assembly. However, existing DNA assemblies use monomers with low coordination numbers that present an effective kinetic barrier only for slow, near-reversible growth conditions. Here we introduce crisscross polymerization of elongated slat monomers that engage beyond nearest neighbors which sustains the kinetic barrier under conditions that promote fast, irreversible growth. By implementing crisscross slats as single-stranded DNA, we attain strictly seed-initiated nucleation of crisscross ribbons with distinct widths and twists.
Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment
Authors: Zhang Min , Luo Jin-Li , Sun Qianqian , Harber James , Dawson Alan G. , Nakas Apostolos , Busacca Sara , Sharkey Annabel J. , Waller David , Sheaff Michael T. , Richards Cathy , Wells-Jordan Peter , Gaba Aarti , Poile Charlotte , Baitei Essa Y. , Bzura Aleksandra , Dzialo Joanna , Jama Maymun , Le Quesne John , Bajaj Amrita , Martinson Luke , Shaw Jacqui A. , Pritchard Catrin , Kamata Tamihiro , Kuse Nathaniel , Brannan Lee , De Philip Zhang Pan , Yang Hongji , Griffiths Gareth , Wilson Gareth , Swanton Charles , Dudbridge Frank , Hollox Edward J. , Fennell Dean A. 
Published: March 2021

AbstractMalignant Pleural Mesothelioma (MPM) is typically diagnosed 20–50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/−3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/−22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.
Spatiotemporal single-cell RNA sequencing of developing chicken hearts identifies interplay between cellular differentiation and morphogenesis
Authors: Mantri Madhav , Scuderi Gaetano J. , Abedini-Nassab Roozbeh , Wang Michael F. Z. , McKellar David , Shi Hao , Grodner Benjamin , Butcher Jonathan T. , De Vlaminck Iwijn 
Published: March 2021

AbstractSingle-cell RNA sequencing is a powerful tool to study developmental biology but does not preserve spatial information about tissue morphology and cellular interactions. Here, we combine single-cell and spatial transcriptomics with algorithms for data integration to study the development of the chicken heart from the early to late four-chambered heart stage. We create a census of the diverse cellular lineages in developing hearts, their spatial organization, and their interactions during development. Spatial mapping of differentiation transitions in cardiac lineages defines transcriptional differences between epithelial and mesenchymal cells within the epicardial lineage. Using spatially resolved expression analysis, we identify anatomically restricted expression programs, including expression of genes implicated in congenital heart disease. Last, we discover a persistent enrichment of the small, secreted peptide, thymosin beta-4, throughout coronary vascular development. Overall, our study identifies an intricate interplay between cellular differentiation and morphogenesis.
A comprehensive influenza reporter virus panel for high-throughput deep profiling of neutralizing antibodies
Authors: Creanga Adrian , Gillespie Rebecca A. , Fisher Brian E. , Andrews Sarah F. , Lederhofer Julia , Yap Christina , Hatch Liam , Stephens Tyler , Tsybovsky Yaroslav , Crank Michelle C. , Ledgerwood Julie E. , McDermott Adrian B. , Mascola John R. , Graham Barney S. , Kanekiyo Masaru 
Published: March 2021

AbstractBroadly neutralizing antibodies (bnAbs) have been developed as potential countermeasures for seasonal and pandemic influenza. Deep characterization of these bnAbs and polyclonal sera provides pivotal understanding for influenza immunity and informs effective vaccine design. However, conventional virus neutralization assays require high-containment laboratories and are difficult to standardize and roboticize. Here, we build a panel of engineered influenza viruses carrying a reporter gene to replace an essential viral gene, and develop an assay using the panel for in-depth profiling of neutralizing antibodies. Replication of these viruses is restricted to cells expressing the missing viral gene, allowing it to be manipulated in a biosafety level 2 environment. We generate the neutralization profile of 24 bnAbs using a 55-virus panel encompassing the near-complete diversity of human H1N1 and H3N2, as well as pandemic subtype viruses. Our system offers in-depth profiling of influenza immunity, including the antibodies against the hemagglutinin stem, a major target of universal influenza vaccines.
Dynamics of fMRI patterns reflect sub-second activation sequences and reveal replay in human visual cortex
Authors: Wittkuhn Lennart , Schuck Nicolas W. 
Published: March 2021

AbstractNeural computations are often fast and anatomically localized. Yet, investigating such computations in humans is challenging because non-invasive methods have either high temporal or spatial resolution, but not both. Of particular relevance, fast neural replay is known to occur throughout the brain in a coordinated fashion about which little is known. We develop a multivariate analysis method for functional magnetic resonance imaging that makes it possible to study sequentially activated neural patterns separated by less than 100 ms with precise spatial resolution. Human participants viewed five images individually and sequentially with speeds up to 32 ms between items. Probabilistic pattern classifiers were trained on activation patterns in visual and ventrotemporal cortex during individual image trials. Applied to sequence trials, probabilistic classifier time courses allow the detection of neural representations and their order. Order detection remains possible at speeds up to 32 ms between items (plus 100 ms per item). The frequency spectrum of the sequentiality metric distinguishes between sub- versus supra-second sequences. Importantly, applied to resting-state data our method reveals fast replay of task-related stimuli in visual cortex. This indicates that non-hippocampal replay occurs even after tasks without memory requirements and shows that our method can be used to detect such spontaneously occurring replay.
ENSO modulates wildfire activity in China
Authors: Fang Keyan , Yao Qichao , Guo Zhengtang , Zheng Ben , Du Jianhua , Qi Fangzhong , Yan Ping , Li Jie , Ou Tinghai , Liu Jane , He Maosheng , Trouet Valerie 
Published: March 2021

AbstractChina is a key region for understanding fire activity and the drivers of its variability under strict fire suppression policies. Here, we present a detailed fire occurrence dataset for China, the Wildfire Atlas of China (WFAC; 2005–2018), based on continuous monitoring from multiple satellites and calibrated against field observations. We find that wildfires across China mostly occur in the winter season from January to April and those fire occurrences generally show a decreasing trend after reaching a peak in 2007. Most wildfires (84%) occur in subtropical China, with two distinct clusters in its southwestern and southeastern parts. In southeastern China, wildfires are mainly promoted by low precipitation and high diurnal temperature ranges, the combination of which dries out plant tissue and fuel. In southwestern China, wildfires are mainly promoted by warm conditions that enhance evaporation from litter and dormant plant tissues. We further find a fire occurrence dipole between southwestern and southeastern China that is modulated by the El Niño-Southern Oscillation (ENSO).
Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model
Authors: Driouich Jean-Sélim , Cochin Maxime , Lingas Guillaume , Moureau Grégory , Touret Franck , Petit Paul-Rémi , Piorkowski Géraldine , Barthélémy Karine , Laprie Caroline , Coutard Bruno , Guedj Jérémie , de Lamballerie Xavier , Solas Caroline , Nougairède Antoine 
Published: March 2021

AbstractDespite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.
Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites
Authors: Feng Gaoqian , Wines Bruce D. , Kurtovic Liriye , Chan Jo-Anne , Boeuf Philippe , Mollard Vanessa , Cozijnsen Anton , Drew Damien R. , Center Rob J. , Marshall Daniel L. , Chishimba Sandra , McFadden Geoffrey I. , Dent Arlene E. , Chelimo Kiprotich , Boyle Michelle J. , Kazura James W. , Hogarth P. Mark , Beeson James G. 
Published: March 2021

AbstractA highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.
Simultaneous spatiotemporal super-resolution and multi-parametric fluorescence microscopy
Authors: Sankaran Jagadish , Balasubramanian Harikrushnan , Tang Wai Hoh , Ng Xue Wen , Röllin Adrian , Wohland Thorsten 
Published: March 2021

AbstractSuper-resolution microscopy and single molecule fluorescence spectroscopy require mutually exclusive experimental strategies optimizing either temporal or spatial resolution. To achieve both, we implement a GPU-supported, camera-based measurement strategy that highly resolves spatial structures (~100 nm), temporal dynamics (~2 ms), and molecular brightness from the exact same data set. Simultaneous super-resolution of spatial and temporal details leads to an improved precision in estimating the diffusion coefficient of the actin binding polypeptide Lifeact and corrects structural artefacts. Multi-parametric analysis of epidermal growth factor receptor (EGFR) and Lifeact suggests that the domain partitioning of EGFR is primarily determined by EGFR-membrane interactions, possibly sub-resolution clustering and inter-EGFR interactions but is largely independent of EGFR-actin interactions. These results demonstrate that pixel-wise cross-correlation of parameters obtained from different techniques on the same data set enables robust physicochemical parameter estimation and provides biological knowledge that cannot be obtained from sequential measurements.
Understanding contact electrification at liquid–solid interfaces from surface electronic structure
Authors: Sun Mingzi , Lu Qiuyang , Wang Zhong Lin , Huang Bolong 
Published: March 2021

AbstractThe charge transfer phenomenon of contact electrification even exists in the liquid–solid interface by a tiny droplet on the solid surface. In this work, we have investigated the contact electrification mechanism at the liquid–solid interface from the electronic structures at the atomic level. The electronic structures display stronger modulations by the outmost shell charge transfer via surface electrostatic charge perturbation than the inter-bonding-orbital charge transfer at the liquid–solid interface, supporting more factors being involved in charge transfer via contact electrification. Meanwhile, we introduce the electrochemical cell model to quantify the charge transfer based on the pinning factor to linearly correlate the charge transfer and the electronic structures. The pinning factor exhibits a more direct visualization of the charge transfer at the liquid–solid interface. This work supplies critical guidance for describing, quantifying, and modulating the contact electrification induced charge transfer systems in triboelectric nanogenerators in future works.