bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Simplified Point-of-Care Lung Ultrasound Protocol to Detect Coronavirus Disease 2019 in Inpatients: A Prospective Observational Study
Authors: Heyne Thomas F. , Geisler Benjamin P. , Negishi Kay , Choi Daniel , Saud Ahad A. Al , Marinacci Lucas X. , Smithedajkul Patrick Y. , Devaraj Lily R. , Little Brent P. , Mendoza Dexter P. , Flores Efren J. , Petranovic Milena , Toal Steven P. , Shokoohi Hamid , Liteplo Andrew S. 
Published: April 2021

ABSTRACTObjectivesTo assess the diagnostic performance of lung point-of-care ultrasound (POCUS) compared to either a positive nucleic acid test (NAT) or a COVID-19-typical pattern on computed tomography (CT) and to evaluate opportunities to simplify a POCUS algorithm.MethodsHospital-admitted adult inpatients with (1) either confirmed or suspected COVID-19 and (2) a completed or ordered CT within the preceding 24 hours were recruited. Twelve lung zones were scanned with a handheld POCUS machine. POCUS, CT, and X-ray (CXR) images were reviewed independently by blinded experts. A simplified POCUS algorithm was developed via machine learning.ResultsOf 79 enrolled subjects, 26.6% had a positive NAT and 31.6% had a CT typical for COVID-19. The receiver operator curve (ROC) for a 12-zone POCUS protocol had an area under the curve (AUC) of 0.787 for positive NAT and 0.820 for typical CT. A simplified four-zone protocol had an AUC of 0.862 for typical CT and 0.862 for positive NAT. CT had an AUC of 0.815 for positive NAT; CXR had AUCs of 0.793 for positive NAT and 0.733 for typical CT. Performance of the four-zone protocol was superior to CXR for positive NAT (p=0.0471). Using a two-point cutoff system, the four-zone POCUS protocol had a sensitivity of 0.920 and 0.904 compared to CT and NAT, respectively, at the lower cutoff; it had a specificity of 0.926 and 0.948 at the higher cutoff, respectively.ConclusionPOCUS outperformed CXR to predict positive NAT. POCUS could potentially replace other chest imaging for persons under investigation for COVID-19.
On whether therapeutic plasma exchange is an effective cure against severe/critical COVID-19 pneumonia
Authors: Cegolon Luca , Einollahi Behzad , Imanizadeh Sina , Rezapour Mohammad , Javanbakht Mohammad , Nikpouraghdam Mohammad , Abolghasemi Hassan , Mastrangelo Giuseppe 
Published: April 2021

ABSTRACTBackgroundThere is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill COVID-19 patients is still provisional and further investigations are needed to confirm its eventual beneficial effects.MethodsWe therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with diagnosis of COVID-19 pneumonia confirmed by real-time polymerase chain reaction (RT-PCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard of care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir); and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 liter of patients’ plasma by a solution, 50% of normal plasma and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint.ResultsDeaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of Structural Equation Modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name “severity”). Disease severity was significantly (Wilkinson rank sum test p-value=0.0000) lower among COVID-19 patients undergoing TPE (median: −2.82; range: −5.18; 7.96) as compared to those non receiving TPE (median: −1.35; range: −3.89; 8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as covariate in Cox regression models. The univariate Hazard Ratio (HR) of 0.68 (95%CI: 0.26; 1.80; p=0.441) for TPE turned to 1.19 (95%CI: 0.43; 3.29; p=0.741) after adjusting for severity.ConclusionsThe lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than TPE effects.TRIAL REGISTRATIONIRCT registration number: IRCT20080901001165N58 (Iranian Registry of Clinical Trials)Registration date: 2020-05-27, 1399/03/07 (retrospectively registered)
Analyzing the effect of relaxing restriction on the COVID-19 outbreak for some US states
Authors: Demir Mahir , Aslan ibrahim Halil , Lenhart Suzanne 
Published: April 2021

AbstractThe ongoing pandemic disease COVID-19 has caused worldwide social and financial disruption. As many countries are engaged in designing vaccines, the harmful second and third waves of COVID-19 have already appeared in many countries. To investigate changes in transmission rates and the effect of social distancing in the USA, we formulate a system of ordinary differential equations using data of confirmed cases and deaths in these states: California, Texas, Florida, Georgia, Illinois, Louisiana, Michigan, and Missouri in the USA to be able to investigate changes in transmission rates of the outbreak and effect of social distancing. Our models and the corresponding parameter estimations show social distancing reduces the transmission by 60% to 90%, and thus obeying the movement restriction rules plays a crucial rule to reduce the magnitudes of the outbreak waves. Our analysis shows the current management restrictions do not sufficiently slow the disease propagation.
Novel genome characteristics contribute to the invasiveness ofPhragmites australis(common reed)
Authors: Oh Dong-Ha , Kowalski Kurt P. , Quach Quynh N. , Wijesinghege Chathura , Tanford Philippa , Dassanayake Maheshi , Clay Keith 
Published: April 2021

AbstractThe rapid invasion of the non-nativePhragmites australis(Poaceae, subfamily Arundinoideae) is a major threat to native ecosystems in North America. We describe a 1.14 Gbp reference genome forP. australisand compare invasive (ssp.australis) and native (ssp.americanus) genotypes collected across the Laurentian Great Lakes to deduce genomic bases driving its invasive success. We report novel genomic features including a lineage-specific whole genome duplication, followed by gene loss and preferential retention of genes associated with transcription factors and regulatory functions in the remaining duplicates. The comparative transcriptomic analyses revealed that genes associated with biotic stress and defense responses were expressed at a higher basal level in invasive genotypes, but the native genotypes showed a stronger induction of defense responses following fungal inoculation. The reference genome and transcriptomes, combined with previous ecological and environmental data, support the development of novel, genomics-assisted management approaches for invasivePhragmites.
Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation
Authors: Aramesh Morteza , Stoycheva Diana , Sandu Ioana , Ihle Stephan J. , Zünd Tamara , Shiu Jau-Ye , Forró Csaba , Asghari Mohammad , Bernero Margherita , Lickert Sebastian , Oxenius Annette , Vogel Viola , Klotzsch Enrico 
Published: April 2021

AbstractT cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanisms by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation, and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200 nm pores, but not in 400 nm pores. Consequently, formation of TCR nanoclustered hotspots within 200 nm pores, allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.
Contrasting impacts of environmental variability on the breeding biology of two sympatric small procellariiform seabirds in south-eastern Australia
Authors: Eizenberg Yonina H. , Fromant Aymeric , Lec’hvien Arnaud , Arnould John P.Y. 
Published: April 2021

AbstractSeabirds play a vital role in marine ecosystems and are determinant sentinels of the productivity of their environments. The long-term study of their breeding biology and their responses to environmental variations can be used to monitor the effects of climate change on marine fauna. However, the ecological and physiological differences among seabirds induce a large range of responses complicating our understanding of the effects of environmental changes on marine ecosystems. The present study investigated the impact of environmental variability on breeding biology in two sympatric small Procellariiform species, the fairy prion (Pachyptila turtur) and the common diving petrel (Pelecanoides urinatrix), over four reproductive seasons (2017-2020) in Bass Strait, south-eastern Australia. Marine heatwaves had a negative effect on chick growth, breeding success, and induced a delay in laying dates in both species. While fairy prions maintained a relatively high breeding success and broadly constant breeding phenology, common diving petrels delayed the start of the breeding season by up to 50 days and experienced dramatic collapses in breeding success in years of high marine heat wave occurrence. The high wing loading and absence of stomach oils in the common diving petrel are likely to have limited the capacity of this species to increase foraging effort in years of low food availability.
Hexavalent Sperm-Binding IgG Antibody Released from Self-Dissolving Vaginal Film Enables Potent, On-Demand Non-Hormonal Female Contraception
Authors: Shrestha Bhawana , Vincent Kathleen , Schaefer Alison , Zhu Yong , Vargas Gracie , Motamedi Massoud , Swope Kelsi , Morton Josh , Simpson Carrie , Pham Henry , Brennan Miles B. , Pauly Michael H. , Zeitlin Larry , Bratcher Barry , Whaley Kevin J. , Moench Thomas R. , Lai Samuel K. 
Published: April 2021

AbstractNon-hormonal products for on-demand contraception are a global health technology gap, motivating us to pursue the use of sperm-binding monoclonal antibodies as a strategy to enable safe, effective, desirable, on-demand contraception. Here, using cGMP-compliant Nicotiana-expression system, we produce an ultra-potent sperm-binding IgG antibody possessing 6 Fab arms per molecule that bind a well-established contraceptive antigen target, CD52g. We term this hexavalent antibody “Fab-IgG-Fab” (FIF) to reflect its molecular orientation. The Nicotiana-produced FIF exhibits at least 10-fold greater sperm agglutination potency and kinetics than the parent IgG, while preserving Fc-mediated trapping of individual spermatozoa in mucus. We formulate the Nicotiana-produced FIF into a polyvinyl alcohol-based water-soluble contraceptive film, and evaluate its potency in reducing progressively motile sperm in the sheep vagina. Two minutes after vaginal instillation of human semen, no progressively motile sperm are recovered from the vaginas of sheep receiving FIF-Film. In contrast, high numbers of progressively motile sperm are recovered from sheep receiving a placebo film control. Our work supports the potential of highly multivalent contraceptive antibodies to provide safe, effective, on-demand non-hormonal contraception.
Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial
Authors: Dewey Marley J. , Milner Derek J. , Weisgerber Daniel , Flanagan Colleen L. , Rubessa Marcello , Lotti Sammi , Polkoff Kathryn M. , Crotts Sarah , Hollister Scott J. , Wheeler Matthew B. , Harley Brendan A.C. 
Published: April 2021

ABSTRACTRegenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.
Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation
Authors: Fuzo Carlos A. , Martins Ronaldo B. , Fraga-Silva Thais F.C. , Amstalden Martin K. , De Leo Thais Canassa , Souza Juliano P. , Lima Thais M. , Faccioli Lucia H. , França Suzelei C. , Bonato Vania L.D. , Arruda Eurico , Dias-Baruffi Marcelo 
Published: April 2021

AbstractThe global emergence of Covid-19 has caused huge human casualties. Clinical manifestations of the disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and non-homeostatic inflammatory response. In face of the urgent demand for effective drugs to treat Covid-19, we have searched for candidate compounds using a drug repurposing approach based onin silicoanalysis followed by biological validation. Here we identified celastrol, a pentacyclic triterpene isolated fromTripterygium wilfordiiHook F – a plant used in traditional Chinese medicine – as one of the best compounds out of 39 repurposed drug candidates. Celastrol reverted gene expression signature from SARS-CoV-2-infected cells; bound with high-affinity energy to viral molecular targets such as main protease (Mpro) and receptor-biding domain (RBD); inhibited SARS-CoV-2 replication in monkey (Vero and Vero-ACE2) and human (Caco-2 and Calu-3) cell lines; and decreased interleukin-6 (IL-6) secretion in SARS-CoV-2-infected human cell lines. Interestingly, celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity. Therefore, celastrol is a promising lead drug candidate to treat Covid-19 due to its ability to suppress SARS-CoV-2 replication and IL-6 production in infected cells, two critical events in the pathophysiology of this disease.
Structures of a deAMPylation complex rationalise the switch between antagonistic catalytic activities of FICD (14/96/109)
Authors: Perera Luke A. , Preissler Steffen , Zaccai Nathan R , Prévost Sylvain , Devos Juliette M , Haertlein Michael , Ron David 
Published: April 2021

AbstractThe endoplasmic reticulum (ER) Hsp70 chaperone BiP is regulated by AMPylation, a reversible inactivating post-translational modification. Both BiP AMPylation and deAMPylation are catalysed by a single ER-localised enzyme, FICD. Here we present long-sought crystallographic and solution structures of a deAMPylation Michaelis complex formed between mammalian AMPylated BiP and FICD. The latter, via its tetratricopeptide repeat domain, binds a surface that is specific to ATP-state Hsp70 chaperones, explaining the exquisite selectivity of FICD for BiP’s ATP-bound conformation both when AMPylating and deAMPylating Thr518. The eukaryotic deAMPylation mechanism thus revealed, rationalises the role of the conserved Fic domain Glu234 as a gatekeeper residue that both inhibits AMPylation and facilitates hydrolytic deAMPylation catalysed by dimeric FICD. These findings point to a monomerisation-induced increase in Glu234 flexibility as the basis of an oligomeric state-dependent switch between FICD’s antagonistic activities, despite a similar mode of engagement of its two substrates — unmodified and AMPylated BiP.
Expansion microscopy facilitates quantitative super-resolution studies of cytoskeletal structures in kinetoplastid parasites
Authors: Gorilak Peter , Pružincová Martina , Vachova Hana , Olšinová Marie , Varga Vladimir 
Published: April 2021

AbstractExpansion microscopy (ExM) has become a powerful super-resolution method in cell biology. It is a simple, yet robust approach, which does not require any instrumentation or reagents beyond those present in a standard microscopy facility. In this study, we used kinetoplastid parasitesTrypanosoma bruceiandLeishmania major, which possess a complex, yet well-defined microtubule-based cytoskeleton, to demonstrate that this method recapitulates faithfully morphology of structures as previously revealed by a combination of sophisticated electron microscopy (EM) approaches. Importantly, we also show that due to rapidness of image acquisition and 3D reconstruction of cellular volumes ExM is capable of complementing EM approaches by providing more quantitative data. This is demonstrated on examples of less well-appreciated microtubule structures, such as the neck microtubule ofT. bruceior the pocket, cytosolic, and multivesicular tubule-associated microtubules ofL. major. We further demonstrate that ExM enables identifying cell types rare in a population, such as cells in mitosis and cytokinesis. 3D reconstruction of an entire volume of these cells provided details on morphology of the mitotic spindle and the cleavage furrow. Finally, we show that established antibody markers of major cytoskeletal structures function well in ExM, which together with the ability to visualize proteins tagged with small epitope tags will facilitate studies of the kinetoplastid cytoskeleton.
Training-Induced Circuit-Specific Excitatory Synaptogenesis is Required for Effort Control
Authors: Severino Francesco Paolo Ulloa , Lawal Oluwadamilola , Sakers Kristina , Wang Shiyi , Kim Namsoo , Friedman Alexander , Johnson Sarah , Sriworarat Chaichontat , Hughes Ryan , Soderling Scott , Kim Il Hwan , Yin Henry , Eroglu Cagla 
Published: April 2021

SummarySynaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant-conditioning via lever-press for food reward-training in mice induces excitatory synapse formation onto a subset of Anterior Cingulate Cortex neurons projecting to the dorsomedial striatum (ACC->DMS). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor α2δ-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of α2δ-1 in the adult ACC->DMScircuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation did not impact learning but instead resulted in a profound increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC->DMSneurons rescued or phenocopied the behaviors of the α2δ-1 cKO mice highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion.
Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates
Authors: Corbett Kizzmekia S. , Nason Martha C. , Flach Britta , Gagne Matthew , O’ Connell Sarah , Johnston Timothy S. , Shah Shruti N. , Edara Venkata Viswanadh , Floyd Katharine , Lai Lilin , McDanal Charlene , Francica Joseph R. , Flynn Barbara , Wu Kai , Choi Angela , Koch Matthew , Abiona Olubukola M. , Werner Anne P. , Alvarado Gabriela S. , Andrew Shayne F. , Donaldson Mitzi M. , Fintzi Jonathan , Flebbe Dillon R. , Lamb Evan , Noe Amy T. , Nurmukhambetova Saule T. , Provost Samantha J. , Cook Anthony , Dodson Alan , Faudree Andrew , Greenhouse Jack , Kar Swagata , Pessaint Laurent , Porto Maciel , Steingrebe Katelyn , Valentin Daniel , Zouantcha Serge , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Moliva Juan I. , van de Wetering Renee , Boyoglu-Barnum Seyhan , Leung Kwanyee , Shi Wei , Yang Eun Sung , Zhang Yi , Todd John-Paul M. , Wang Lingshu , Andersen Hanne , Foulds Kathryn E. , Edwards Darin K. , Mascola John R. , Moore Ian N. , Lewis Mark G. , Carfi Andrea , Montefiori David , Suthar Mehul S. , McDermott Adrian , Sullivan Nancy J. , Roederer Mario , Douek Daniel C. , Graham Barney S. , Seder Robert A. 
Published: April 2021

AbstractImmune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.One-Sentence SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.