bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical care demand and intensive care supply for patients in Japan with COVID-19 at the time of the state of emergency declaration in April 2020: a descriptive analysis.
Authors: Fujii Yosuke , Hirota Kiichi 
Published: June 2020

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), threatened to overwhelm Japan’s intensive care capacity due to the rising numbers of infected patients. This study aimed to determine the number of critically ill patients with COVID-19 who required intensive care, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO), during the pandemic and to compare these patient numbers with Japan’s overall intensive care capacity.MethodsJapanese Society of Intensive Care Medicine datasets were used to obtain the number of confirmed patients with COVID-19 who had undergone mechanical ventilation and ECMO between February 15 and June 4 2020, to determine and compare intensive care unit (ICU) and attending bed needs for patients with COVID-19, and to estimate peak ICU demands in Japan.ResultsIn total, 17968 ICU days, 15171 mechanical ventilation days, and 2797 ECMO days were attributable to patients with COVID-19. There was a median (interquartile range) 143 (63-255) patients in ICU, 124 (51-225) patients on mechanical ventilation, and 18 (15-36) patients on ECMO machines. During the epidemic peak in late April, 11443 patients (1.03 per 10000 adults) had been infected, 373 patients (0.034 per 10000 adults) were in ICU, 312 patients (0.028 per 10000 adults) were receiving mechanical ventilation, and 62 patients (0.0056 per 10000 adults) were on ECMO machines per day. The number of infected patients at the peak of the epidemic was 651% of total designated beds and the number of patients requiring intensive care at the peak of the epidemic was 6.0% of total ICU beds in Japan, 19.1% of total board-certified intensivists in Japan and 106% of total designated medical institutions for Category II infectious diseases in Japan, respectively.ConclusionsFollowing the state of emergency declaration on April 7 2020, the number of patients with COVID-19 and the number of critically ill patients continued to rise, exceeding the number of designated beds but not exceeding ICU capacity. Urgent nationwide and regional planning is needed to prevent an overwhelming burden on ICUs in relation to critically ill patients with COVID-19 in Japan.
Real-time image processing toolbox for all-optical closed-loop control of neuronal activities
Authors: Sheng Weihao , Zhao Xueyang , Huang Xinrui , Yang Yang 
Published: June 2020

AbstractThe development ofin vivoimaging and optogenetic tools makes it possible to control neural circuit activities in an all-optical, closed-loop manner [1], but such applications are limited by the lack of software for online analysis of neuronal imaging data. We developed an analysis software ORCA (Online Real-time activity and offline Cross-session Analysis), which performs image registration, neuron segmentation, and activity extraction at over 100 frames per second, fast enough to support real-time detection and readout of neural activity. Our active neuron detection algorithm is purely statistical, achieving much higher speed than previous methods. We demonstrated closed-loop control of neurons that were identified on the fly, without prior recording or image processing. ORCA also includes a cross-session alignment module that efficiently tracks neurons across multiple sessions. In summary, ORCA is a powerful toolbox for fast imaging data analysis, and provides a solution for all-optical closed-loop control of neuronal activity.
Glucose promotes resistance of human commensalEscherichia coliagainst contact-killing by pandemicVibrio cholerae
Authors: Crisan Cristian V , Nichols Holly , Wiesenfeld Sophia , Steinbach Gabi , Yunker Peter J , Hammer Brian K 
Published: June 2020

ABSTRACTEvolutionary arms races among organisms are broadly prevalent and bacteria have evolved defensive strategies against various attackers. A common microbial aggression mechanism is the Type VI Secretion System (T6SS), a contact-dependent bacterial weapon used to deliver toxic effector proteins into adjacent target cells. Sibling cells constitutively express immunity proteins that neutralize effectors. However, less is known about mechanisms that allow non-sibling bacteria to respond to external cues and survive T6SS attacks independently of immunity proteins. In this study, we show that resistance to T6SS attacks is promoted by a genetically controlled response to exogenous glucose. We observe that multiple humanEscherichia colicommensal strains lacking immunity proteins are sensitive to T6SS attacks from pandemicVibrio choleraeon nutrient-rich media. By contrast,E. colicells become resistant to attacks when co-cultured on the same media with glucose. We confirm that glucose does not impairV. choleraeT6SS activity. Instead, we find that cAMP receptor protein (CRP), which alters expression of hundreds of genes in response to glucose, controls resistance to T6SS attacks inE. colicells. Consistent with the observed resistance on media with glucose, anE. coli crpdisruption mutant survives significantly better againstV. choleraeT6SS attacks even in the absence of glucose. Finally, we also show that resistance to T6SS attacks depends on the pH of the medium and varies based on the target and killer strains.IMPORTANCEMany Gram-negative bacteria, including important pathogens, encode T6SS genes to deliver toxic effectors and eliminate competitors. Our results uncover a novel defense mechanism against T6SS attacks that is triggered by an external stimulus and mediated by a metabolic response in non-kin target cells. In microbiomes such as those in gastrointestinal tracts where T6SS activity is known to occur, signaling by metabolites like glucose may affect the efficacy of T6SS attacks and alter microbial community composition. Our findings could have vast implications for microbial interactions during pathogen colonization of hosts and survival of bacterial cells in environmental communities. Furthermore, the glucose-mediated resistance observed here might provide a novel example of an evolutionary arms race between killer T6SS cells and target bacteria.
Expert-level prenatal detection of complex congenital heart disease from screening ultrasound using deep learning
Authors: Arnaout Rima , Curran Lara , Zhao Yili , Levine Jami C. , Chinn Erin , Moon-Grady Anita J. 
Published: June 2020

AbstractCongenital heart disease (CHD) is the most common birth defect. Fetal survey ultrasound is recommended worldwide, including five views of the heart that together could detect 90% of complex CHD. In practice, however, sensitivity is as low as 30%. We hypothesized poor detection results from challenges in acquiring and interpreting diagnostic-quality cardiac views, and that deep learning could improve complex CHD detection. Using 107,823 images from 1,326 retrospective echocardiograms and surveys from 18-24 week fetuses, we trained an ensemble of neural networks to (i) identify recommended cardiac views and (ii) distinguish between normal hearts and complex CHD. Finally, (iii) we used segmentation models to calculate standard fetal cardiothoracic measurements. In a test set of 4,108 fetal surveys (0.9% CHD, >4.4 million images, about 400 times the size of the training dataset) the model achieved an AUC of 0.99, 95% sensitivity (95%CI, 84-99), 96% specificity (95%CI, 95-97), and 100% NPV in distinguishing normal from abnormal hearts. Sensitivity was comparable to clinicians’ task-for-task and remained robust on external and lower-quality images. The model’s decisions were based on clinically relevant features. Cardiac measurements correlated with reported measures for normal and abnormal hearts. Applied to guidelines-recommended imaging, ensemble learning models could significantly improve detection of fetal CHD and expand telehealth options for prenatal care at a time when the COVID-19 pandemic has further limited patient access to trained providers. This is the first use of deep learning to ∼double standard clinical performance on a critical and global diagnostic challenge.
Prelimbic-dependent activation of amygdala somatostatin interneurons signals non-aversive cues to promote discrimination
Authors: Stujenske J.M. , O’Neill P.K. , Nahmoud I , Goldberg S. , Diaz L. , Labkovich M. , Hardin W. , Bolkan S.S. , Reardon T.R. , Spellman T.J. , Salzman C.D. , Gordon J.A. , Likhtik E. 
Published: June 2020

AbstractThe amygdala and prelimbic cortex (PL) communicate during fear discrimination retrieval, but how they coordinate to discriminate a non-threatening stimulus is unknown. Here, we show that somatostatin interneurons (SOM) in the basolateral amygdala (BLA) become active specifically during learned non-threatening cues, when they block sensory-evoked phase resetting of theta-oscillations. Further, we show that SOM activation is PL-dependent, and promotes discrimination of non-threat. Thus, fear discrimination engages PL-dependent coordination of BLA SOM responses to non-threatening stimuli.
Response of Regulatory Genetic Variation in Gene Expression to Environmental Change inDrosophila melanogaster
Authors: Huang Wen , Carbone Mary Anna , Lyman Richard F. , Anholt Robert H. H. , Mackay Trudy F. C. 
Published: June 2020

AbstractThe genetics of phenotypic responses to changing environments remains elusive. Using whole genome quantitative gene expression as a model, we studied how the genetic architecture of regulatory variation in gene expression changed in a population of fully sequenced inbredDrosophila melanogasterstrains when flies developed at different environments (25 °C and 18 °C). We found a substantial fraction of the transcriptome exhibited genotype by environment interaction, implicating environmentally plastic genetic architecture of gene expression. Genetic variance in expression increased at 18 °C relative to 25 °C for most genes that had a change in genetic variance. Although the majority of expression quantitative trait loci (eQTLs) for the gene expression traits in the two environments were shared and had similar effects, analysis of the environment-specific eQTLs revealed enrichment of binding sites for two transcription factors. Finally, although genotype by environment interaction in gene expression could potentially disrupt genetic networks, the co-expression networks were highly conserved across environments. Genes with higher network connectivity were under stronger stabilizing selection, suggesting that stabilizing selection on expression plays an important role in promoting network robustness.
Non-invasive Amelioration of Essential Tremor via Phase-Locked Disruption of its Temporal Coherence
Authors: Schreglmann Sebastian R. , Wang David , Peach Robert , Li Junheng , Zhang Xu , Latorre Anna , Rhodes Edward , Panella Emanuele , Boyden Edward S. , Barahona Mauricio , Santaniello Sabato , Bhatia Kailash P. , Rothwell John , Grossman Nir 
Published: June 2020

AbstractAberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be noninvasively suppressed via electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained after the end of the stimulation and can be phenomenologically predicted. Finally, using feature-based statistical-learning and neurophysiological-modelling we show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the oscillation via perturbation of the tremor generating a cascade of synchronous activity in the olivocerebellar loop. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may represent a powerful neuromodulatory strategy to treat brain disorders.
A hybrid additive manufacturing platform to create bulk and surface composition gradients on scaffolds for tissue regeneration
Authors: Sinha Ravi , Cámara-Torres Maria , Scopece Paolo , Falzacappa Emanuele Verga , Patelli Alessandro , Moroni Lorenzo , Mota Carlos 
Published: June 2020

AbstractScaffolds with gradients of physico-chemical properties and controlled 3D architectures are crucial for engineering complex tissues. These can be produced using multi-material additive manufacturing (AM) techniques. However, they typically only achieve discrete gradients using separate printheads to vary compositions. Achieving continuous composition gradients, to better mimic tissues, requires material dosing and mixing controls. No such AM solution exists for most biomaterials. Existing AM techniques also cannot selectively modify scaffold surfaces to locally stimulate cell adhesion. We report a hybrid AM solution to cover these needs. On one platform, we combine a novel dosing- and mixing-enabled, dual-material printhead with an atmospheric pressure plasma jet to selectively activate/coat scaffold filaments during manufacturing. We fabricated continuous composition gradients in both 2D hydrogels and 3D thermoplastic scaffolds. We demonstrated an improvement in mechanical properties of continuous gradients compared to discrete gradients in the 3D scaffolds, and the ability to selectively enhance cell adhesion.
IMPACT OF PHENOLIC ACIDS ON THE ENERGY METABOLISM AND LONGEVITY INC. ELEGANS
Authors: Dilberger Benjamin , Weppler Selina , Eckert Gunter P 
Published: June 2020

AbstractIntroductionAging represents one of the major risk factors for metabolic diseases, such as diabetes and obesity, or neurodegeneration. Polyphenols and its metabolites, especially simple phenolic acids, have gained more and more attention as a preventive strategy for age-related, non-communicable diseases, due to their hormetic potential. Using the nematodeCaenorhabditis elegans(C. elegans) we investigate the effect of protocatechuic, gallic and vanillic acid to improve mitochondrial function and health associated parameters as a preventive measure.MethodsLifespan, heat-stress resistance and chemotaxis ofC. elegansstrain PX627, as a specific model for aging, were assessed in 2-day and 10-day old nematodes. Mitochondrial membrane potential (ΔΨm) and ATP generation of young and aged nematodes were measured. mRNA expression levels of longevity and energy metabolism-related genes were determined using qRT-PCR.ResultsAll phenolic acids were able to significantly increase the nematodes lifespan, heat-stress resistance and chemotaxis at micromolar concentrations. While ΔΨm was only affected by age, vanillic acid significantly decreased ATP concentrations in aged nematodes. Genetic analysis revealed increased glycolytic activity mediated through vanillic acid, suggesting improved thermogenesis.ConclusionWhile life- and health-span parameters are positively affected by the investigated phenolic acids, the concentrations applied were unable to impact mitochondrial performance, suggesting hormesis. In contrast to the other phenolic acids, vanillic acid showed potential in regulating glucose homeostasis, making it a prime candidate for future diabetes and obesity focused approaches.
Fatty acid photodecarboxylase is an ancient photoenzyme responsible for hydrocarbon formation in the thylakoid membranes of algae
Authors: Moulin Solène , Beyly Audrey , Blangy Stéphanie , Légeret Bertrand , Floriani Magali , Burlacot Adrien , Sorigué Damien , Li-Beisson Yonghua , Peltier Gilles , Beisson Fred 
Published: June 2020

ABSTRACTFatty acid photodecarboxylase (FAP) is one of the three enzymes that require light for their catalytic cycle (photoenzymes). FAP has been first identified in the green microalgaChlorella variabilisNC64A and belongs an algae-specific subgroup of the glucose-methanol-choline oxidoreductase family. While the FAP fromChlorellaand itsChlamydomonas reinhardtiihomolog CrFAP have demonstratedin vitroactivity, their activity and physiological function have not been studiedin vivo. Besides, the conservation of FAP activity beyond green microalgae remains hypothetical. Here, using aChlamydomonasFAP knockout line (fap), we show that CrFAP is responsible for the formation of 7-heptadecene, the only hydrocarbon present in this alga. We further show that CrFAP is associated to the thylakoids and that 90% of 7-heptadecene is recovered in this cell fraction. In thefapmutant, photosynthesis activity was not affected under standard growth conditions but was reduced after cold acclimation. A phylogenetic analysis including sequences from Tara Ocean identified almost 200 putative FAPs and indicated that FAP was acquired early after primary endosymbiosis. Within Bikonta, FAP was kept in photosynthetic secondary endosymbiosis lineages but absent in those that lost the plastid. Characterization of recombinant FAPs from various algal genera (Nannochloropsis, Ectocarpus, Galdieria, Chondrus) provided experimental evidence that FAP activity is conserved in red and brown algae and is not limited to unicellular species. These results thus indicate that FAP has been conserved during evolution of most algal lineages when photosynthesis was kept and suggest that its function is linked to photosynthetic membranes.One sentence summaryFAP is present in thylakoids and conserved beyond green algae.
CRISPR-targeted display of functional T cell receptors enables engineering of enhanced specificity and prediction of cross-reactivity
Authors: Vazquez-Lombardi Rodrigo , Jung Johanna S. , Bieberich Florian , Kapetanovic Edo , Aznauryan Erik , Weber Cédric R. , Reddy Sai T. 
Published: June 2020

ABSTRACTT cell receptor (TCR) gene therapy is a promising cell therapy approach for the treatment of cancer. However, most naturally occurring TCRs display low affinities to their peptide-MHC targets, and engineering of TCRs for enhanced affinity is complicated by the risk of introducing cross-reactivity and the poor correlation between affinity and function. Here we report the establishment of the TCR-accepting T cell (TnT) platform through five sequential CRISPR-Cas9 genome editing steps of a human T cell line, and demonstrate its application for functional engineering of TCRs and prediction of cross-reactivity. Using the TnT platform, we profile the mutational landscapes of tumor-specific TCRs at high-throughput to reveal a substantial discordance between antigen binding and antigen-induced signaling. Furthermore, we combine CRISPR-targeting, functional selection and deep sequencing to screen TCR mutagenesis libraries and identify variants with enhanced recognition of the cancer-testis antigen MAGE-A3. Finally, functional cross-reactivity profiling using TnT cells was able to accurately predict off-targets and identify engineered TCRs with exquisite specificity to MAGE-A3. Thus, the TnT platform represents a valuable technology for the engineering of TCRs with enhanced functional and safety profiles.
A Computer-aided Method for Identifying the Presence of Softwood Growth Ring Boundaries
Authors: Lin Qi-Zhao , He Tuo , Sun Yong-Ke , He Xin , Qiu Jian 
Published: June 2020

ABSTRACTThe objective of this study was to develop a computer-aided method to quantify the obvious degree of growth ring boundaries of softwood species, based on data analysis with some image processing technologies. For this purpose, a 5× magnified cross-section color micro-image of softwood was cropped into 20 sub-images, then every image is binarized as a gray image according to an automatic threshold value. After that, the number of black pixels in the gray image was counted row by row and the number of black pixels was binarized to 0 or 100. Finally, a transition band from earlywood to latewood on the sub-image was identified. If this was successful, the growth ring boundaries of the sub-image are distinct, otherwise they were indistinct or absent. If 10 of the 20 sub-images are distinct, with the majority voting method, the growth ring boundaries of softwood are distinct, otherwise they are indistinct or absent. The proposed method has been visualized as a growth-ring-boundary detecting system based on the .NET Framework. A sample of 100 micro-images (Supplementary Images) of softwood cross-sections were selected for evaluation purposes. In short, this detecting system computes the obvious degree of growth ring boundaries of softwood species by image processing involved image importing, image cropping, image reading, image grayscale, image binarization, data analysis. The results showed that the method used avoided mistakes made by the manual comparison method of identifying the presence of growth ring boundaries, and it has a high accuracy of 98%.
Nuclear lamin A/C promotes cancer cell survival and lung metastasis without restricting transendothelial migration
Authors: Roncato Francesco , Regev Ofer , Feigelson Sara W. , Yadav Sandeep Kumar , Kaczmarczyk Lukasz , Levi Nehora , Drago-Garcia Diana , Ovadia Samuel , Kizner Marina , Addadi Yoseph , Sabino João C. , Ovadya Yossi , de Almeida Sérgio F. , Feldmesser Ester , Gerlitz Gabi , Alon Ronen 
Published: June 2020

AbstractThe mechanisms by which the nuclear lamina of tumor cells controls their migration and survival are poorly understood. Lamin A and its variant lamin C are key nuclear lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C levels in two metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, elevated nuclear deformability and reduced heterochromatin. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown. Both cancer cells with lamin A/C knockdown grew normally in primary tumors and in vitro on rigid surfaces. Strikingly, however, both lamin A/C deficient melanoma and breast cancer cells grew poorly in 3D spheroids expanded in soft agar cultures. Experimental lung metastasis of both lamin A/C knockdown cells was also markedly reduced. Taken together, our results suggest that high content of lamin A/C in multiple cancer cells promotes cancer cell survival and ability to generate lung metastasis without compromising cancer cell emigration from lung vessels.