bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Hallmarks Define a Continuum of Plastic Cell States between Small Cell Lung Cancer Archetypes
Authors: Groves Sarah Maddox , Ireland Abbie , Liu Qi , Simmons Alan J. , Lau Ken , Iams Wade T. , Tyson Darren , Lovly Christine M. , Oliver Trudy G. , Quaranta Vito 
Published: January 2021

AbstractSmall Cell Lung Cancer (SCLC) tumors are heterogeneous mixtures of transcriptional subtypes. Understanding subtype dynamics could be key to explaining the aggressive properties that make SCLC a recalcitrant cancer. Applying archetype analysis and evolutionary theory to bulk and single-cell transcriptomics, we show that SCLC cells reside within a cell-state continuum rather than in discrete subtype clusters. Gene expression signatures and ontologies indicate each vertex of the continuum corresponds to a functional phenotype optimized for a cancer hallmark task: three neuroendocrine archetypes specialize in proliferation/survival, inflammation and immune evasion, and two non-neuroendocrine archetypes in angiogenesis and metabolic dysregulation. Single cells can trade-off between these defined tasks to increase fitness and survival. SCLC cells can easily transition from specialists that optimize a single task to generalists that fall within the continuum, suggesting that phenotypic plasticity may be a mechanism by which SCLC cells become recalcitrant to treatment and adaptable to diverse microenvironments. We show that plasticity is uncoupled from the phenotype of single cells using a novel RNA-velocity-based metric, suggesting both specialist and generalist cells have the capability of becoming destabilized and transitioning to other phenotypes. We use network simulations to identify transcription factors such as MYC that promote plasticity and resistance to treatment. Our analysis pipeline is suitable to elucidate the role of phenotypic plasticity in any cancer type, and positions SCLC as a prime candidate for treatments that target plasticity.
Genome-wide analysis of mobile element insertions in human genomes
Authors: Niu Yiwei , Teng Xueyi , Shi Yirong , Li Yanyan , Tang Yiheng , Zhang Peng , Luo Huaxia , Kang Quan ,   The Han100K Initiative, Xu Tao , He Shunmin 
Published: January 2021

AbstractMobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36,699 non-reference MEIs constructed from 5,675 genomes, comprising 2,998 Chinese samples (∼26.2X, NyuWa) and 2,677 samples from the 1000 Genomes Project (∼7.4X, 1KGP). We discovered that LINE-1 insertions were highly enriched at centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.
Do Not Attempt Resuscitation (DNAR) status in people with suspected COVID-19: Secondary analysis of the PRIEST observational cohort study
Authors: Sutton Laura , Goodacre Steve , Thomas Ben , Connelly Sarah 
Published: January 2021

AbstractBackgroundCardiac arrest is common in people admitted with suspected COVID-19 and has a poor prognosis. Do Not Attempt Resuscitation (DNAR) orders can reduce the risk of futile resuscitation attempts but have raised ethical concerns.ObjectivesWe aimed to describe the characteristics and outcomes of adults admitted to hospital with suspected COVID-19 according to their DNAR status and identify factors associated with an early DNAR decision.MethodsWe undertook a secondary analysis of 13977 adults admitted to hospital with suspected COVID-19 and included in the Pandemic Respiratory Infection Emergency System Triage (PRIEST) study. We recorded presenting characteristics and outcomes (death or organ support) up to 30 days. We categorised patients as early DNAR (occurring before or on the day of admission) or late/no DNAR (no DNAR or occurring after the day of admission). We undertook descriptive analysis comparing these groups and multivariable analysis to identify independent predictors of early DNAR.ResultsWe excluded 1249 with missing DNAR data, and identified 3929/12748 (31%) with an early DNAR decision. They had higher mortality (40.7% v 13.1%) and lower use of any organ support (11.6% v 15.7%), but received a range of organ support interventions, with some being used at rates comparable to those with late or no DNAR (e.g. non-invasive ventilation 4.4% v 3.5%). On multivariable analysis, older age (p<0.001), active malignancy (p<0.001), chronic lung disease (p<0.001), limited performance status (p<0.001), and abnormal physiological variables were associated with increased recording of early DNAR. Asian ethnicity was associated with reduced recording of early DNAR (p=0.001).ConclusionsEarly DNAR decisions were associated with recognised predictors of adverse outcome, and were inversely associated with Asian ethnicity. Most people with an early DNAR decision survived to 30 days and many received potentially life-saving interventions.RegistrationISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533
Predictive power of SARS-CoV-2 wastewater surveillance for diverse populations across a large geographical range
Authors: Melvin Richard G. , Chaudhry Nabiha , Georgewill Onimitein , Freese Rebecca , Simmons Glenn E. 
Published: January 2021

AbstractThe COVID-19 pandemic has exacerbated the disparities in healthcare delivery in the US. Many communities had, and continue to have, limited access to COVID-19 testing, making it difficult to track the spread and impact of COVID-19 in early days of the outbreak. To address this issue we monitored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA at the population-level using municipal wastewater influent from 19 cities across the state of Minnesota during the COVID-19 outbreak in Summer 2020. Viral RNA was detected in wastewater continually for 20-weeks for cities ranging in populations from 500 to >1, 000, 000. Using a novel indexing method, we were able to compare the relative levels of SARS-CoV-2 RNA for each city during this sampling period. Our data showed that viral RNA trends appeared to precede clinically confirmed cases across the state by several days. Lag analysis of statewide trends confirmed that wastewater SARS-CoV-2 RNA levels preceded new clinical cases by 15-17 days. At the regional level, new clinical cases lagged behind wastewater viral RNA anywhere from 4-20 days. Our data illustrates the advantages of monitoring at the population-level to detect outbreaks. Additionally, by tracking infections with this unbiased approach, resources can be directed to the most impacted communities before the need outpaces the capacity of local healthcare systems.
Rearrangement of T Cell Genome Architecture Regulates GVHD
Authors: Sun Yaping , Dotson Gabrielle A. , Muir Lindsey A. , Ronquist Scott , Oravecz-Wilson Katherine , Peltier Daniel , Seike Keisuke , Li Lu , Meixner Walter , Rajapakse Indika , Reddy Pavan 
Published: January 2021

AbstractThe cohesin complex modulates gene expression and cellular functions by shaping three-dimensional (3D) organization of chromatin. WAPL, cohesin’s DNA release factor, regulates 3D chromatin architecture. The 3D genome structure and its relevance to mature T cell functionsin vivois not well understood. We show thatin vivolymphopenic expansion, and allo-antigen driven proliferation, alters the 3D structure and function of the genome in mature T cells. Conditional deletion ofWaplin T cells reduced long-range genomic interactions, altered chromatin A/B compartments and interactions within topologically associating domains (TADs) of the chromatin in T cells at baseline. Comparison of chromatin structure in normal and WAPL-deficient T cells after lymphopenic and allo-antigen driven stimulation revealed reduced loop extensions with changes in cell cycling genes. WAPL-mediated changes in 3D architecture of chromatin regulated activation, cycling and proliferation of T cellsin vitroandin vivo. Finally, WAPL-deficient T cells demonstrated reduced severity of graft-versus-host disease (GVHD) following experimental allogeneic hematopoietic stem cell transplantation. These data collectively characterize 3D genomic architecture of T cellsin vivoand demonstrate biological and clinical implications for its disruption by cohesin release factor WAPL.
Identification of candidate susceptibility genes toPuccinia graminisf. sp.triticiin wheat
Authors: Henningsen Eva C. , Omidvar Vahid , Coletta Rafael Della , Michno Jean-Michel , Gilbert Erin , Li Feng , Miller Marisa E. , Myers Chad L. , Gordon Sean P. , Vogel John P. , Steffenson Brian J. , Kianian Shahryar F. , Hirsch Cory D. , Figueroa Melania 
Published: January 2021

AbstractWheat stem rust disease caused byPuccinia graminisf. sp.tritici(Pgt) is a global threat to wheat production. Fast evolving populations ofPgtlimit the efficacy of plant genetic resistance and constrain disease management strategies. Understanding molecular mechanisms that lead to rust infection and disease susceptibility could deliver novel strategies to deploy crop resistance through genetic loss of disease susceptibility. We used comparative transcriptome-based and orthology-guided approaches to characterize gene expression changes associated withPgtinfection in susceptible and resistantTriticum aestivumgenotypes as well as the non-hostBrachypodium distachyon. We targeted our analysis to genes with differential expression inT. aestivumand genes suppressed or not affected inB. distachyonand report several processes potentially linked to susceptibility toPgt, such as cell death suppression and impairment of photosynthesis. We complemented our approach with a gene co-expression network analysis to identify wheat targets to deliver resistance toPgtthrough removal or modification of putative susceptibility genes.
Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus
Authors: Ehrenberg Alexander J. , Moehle Erica A. , Brook Cara E. , Doudna Cate Andrew H. , Witkowsky Lea B. , Sachdeva Rohan , Hirsh Ariana , Barry Kerrie , Hamilton Jennifer R. , Lin-Shiao Enrique , McDevitt Shana , Valentin-Alvarado Luis , Letourneau Kaitlyn N. , Hunter Lauren , Keller Amanda , Pestal Kathleen , Frankino Phillip A. , Murley Andrew , Nandakumar Divya , Stahl Elizabeth C. , Tsuchida Connor A. , Gildea Holly K. , Murdock Andrew G. , Hochstrasser Megan L. , O’Brien Elizabeth , Ciling Alison , Tsitsiklis Alexandra , Worden Kurtresha , Dugast-Darzacq Claire , Hays Stephanie G. , Barber Colin C. , McGarrigle Riley , Lam Emily , Ensminger David , Bardet Lucie , Sherry Carolyn ,   the IGI SARS-CoV-2 Testing consortium, Harte Anna , Nicolette Guy , Giannikopoulos Petros , Hockemeyer Dirk , Petersen Maya , Urnov Fyodor D. , Ringeisen Bradley R. , Boots Mike , Doudna Jennifer A. 
Published: January 2021

SummaryRegular surveillance testing of asymptomatic individuals for SARS-CoV-2 has played a vital role in SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants’ experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.
Comparison of Carotid Intima Media Thickness between Women with History of Preeclampsia and Normal Pregnancy: A Meta-Analysis of Systematic Review
Authors: Pikir Budi Susetyo , Subagjo Agus , Wardhani Deasy Eka , Andrianto  , Oktaviono Yudi Her , Nugraha Ricardo Adrian 
Published: January 2021

ABSTRACTBackgroundWomen with a history of preeclampsia are twice as likely to experience long term cardiovascular disease (CVD) compared to women with unaffected pregnancy. The pathophysiology of preeclampsia is not well understood, however there is general agreement that, similar to cardiovascular disease, endothelial dysfunction plays a crucial role. On a clinical level, preeclampsia and atherosclerotic cardiovascular disease share common risk factors. Carotid intima media thickness (CIMT) is ultrasound-based imaging, non-invasive, simple and reproducible method of subclinical atherosclerosis evaluation. Nowadays, there were studies concerning of CIMT among preeclamptic women, although the results were different.ObjectiveTo prove that CIMT among women with histories of preeclampsia was greater compared to normal pregnancy.MethodsWe conducted a meta-analysis of studies that reported CIMT, in women who had preeclampsia and had normal pregnancy. Studies were identified through three databases: PubMed, Google Scholar dan SAGE Journals with publication year of 2010- 2020. Heterogeneity was assessed using the I2 statistic. Standardized mean difference was used as measured of effect size.ResultsNine eligible studies were included in the meta-analysis. This meta-analysis consisted of 439 women with preeclampsia histories and 526 women with normal pregnancy histories. Women who had preeclampsia had significantly higher CIMT compared to those with normal pregnancy with standardized mean difference −0.38 and 95% confidence interval (CI) −0.68 to −0.07 (p=0.02).ConclusionCIMT was greater among women with histories of preeclampsia compared to normal pregnancy.Prospero registration numberID 228825.
Impact of gastric resection and enteric anastomotic configuration on delayed gastric emptying after pancreaticoduodenectomy: a network meta-analysis of randomized trials
Authors: Varghese Chris , Bhat Sameer , Wang Tim , O’Grady Gregory , Pandanaboyana Sanjay 
Published: January 2021

AbstractIntroductionDelayed gastric emptying (DGE) is frequent after pancreaticoduodenectomy (PD). Several randomised controlled trials (RCTs) have explored operative strategies to minimise DGE, however, the optimal combination of gastric resection approach, anastomotic route, and configuration, role of Braun enteroenterostomy remains unclear.MethodsMEDLINE, Embase, and CENTRAL databases were systematically searched for RCTs comparing gastric resection (Classic Whipple, pylorus-resecting, and pylorus-preserving), anastomotic route (antecolicvsretrocolic) and configuration (Billroth IIvsRoux-en-Y), and enteroenterostomy (Braunvsno Braun). A random-effects, Bayesian network meta-analysis with non-informative priors was conducted to determine the optimal combination of approaches to PD for minimising DGE.ResultsTwenty-four RCTs, including 2526 patients and 14 approaches were included. There was some heterogeneity, although inconsistency was low. The overall incidence of DGE was 25.6% (n = 647). Pylorus-resecting, antecolic, Billroth II with Braun enteroenterostomy was associated with the lowest rates of DGE and ranked the best in 35% of comparisons. Classic Whipple, retrocolic, Billroth II with Braun ranked the worst for DGE in 32% of comparisons. Pairwise meta-analysis of retrocolicvsantecolic route of gastro-jejunostomy found increased risk of DGE with the retrocolic route (OR 2.1, 95% CrI; 0.92 - 4.7). Pairwise meta-analysis of Braun enteroenterostomy found a trend towards lower DGE rates with Braun compared to no Braun (OR 1.9, 95% CrI; 0.92 - 3.9). Having a Braun enteroenterostomy ranked the best in 96% of comparisons.ConclusionBased on existing RCT evidence, a pylorus-resecting, antecolic, Billroth II with Braun enteroenterostomy may be associated with the lowest rates of DGE.
Mathematical Relationship between Reproduction Number and Epidemic Curve of Daily Cases
Authors: Caudana Bruno 
Published: January 2021

AbstractThe strict mathematical relationship between Rt and the curve of daily cases f (t) is shown. Up to date and statistically robust Rt from the curve of daily cases can be estimated as soon as new cases are added to the curve. That is equivalent to estimating Rt by averaging all detected cases of infection, without any distortion induced by the difficulty of following and weighting trees of secondary cases from original ones, and without needing to wait for secondary cases to manifest infection. With this method, if Rt scaled numbers are of interest, only the average duration of subjects’ infectivity has to be estimated directly, but independently of linking secondary cases to primary ones. A new index, Instantaneous Reproduction Number Rist is introduced, which is mathematically tied to Rt and does not depend on the duration of infectivity of subjects. Rist, Rt and the doubling/halving time of the epidemic may be estimated by simple computations at the very detection time of new daily cases. Any smoothed curve of daily cases gives smooth Rt and Rist. No phase lag on Rt estimate is introduced by this method.
Discerning amyloid network in plants
Authors: Y.Gahane Avinash , Sinha Nabodita , Zahra Talat , K.Thakur Ashwani 
Published: January 2021

AbstractAmyloids are proteinaceous fibrillar structures and are known for their pathogenic and functional roles across the kingdoms. Besides proteinaceous deposits, amyloid-like structures are present in small metabolite assemblies and fibrillar hydrogels. Recent cryoelectron microscopy studies have shed light on the heterogeneous nature of the amyloid structures and their association with carbohydrate or lipid molecules, suggesting that amyloids are not exclusively proteinaceous. The association of amyloids with carbohydrates is further supported because the gold-standard dye of amyloid detection, Congo red, also binds to carbohydrates, probably due to similar stacking interactions. We name the association between amyloids, carbohydrates and other biomolecules as amyloid-network and propose that plants might contain such structures. Specifically, we hypothesize that cereal seeds containing glutamine-repeat-rich granules of storage proteins may have amyloid-like structures. This is because, polyQ repeats are associated with protein aggregation and amyloid formation in humans and are linked to multiple neurodegenerative conditions. Also seed storage proteins and seed cell wall proteins possess carbohydrate affinity. Thus, plant seeds might contain an intercalated network of proteins and carbohydrates, lending strength, stability and dynamics to these structures. In this paper, we show that, plant seeds have a mesh-like network that shows apple-green birefringence on staining with Congo red, a characteristic of amyloids. This congophilic network is more prominent in protein-rich seed sections of wheat and lentils, as compared to starch-rich compartments of potato. The findings suggest an amyloid network in the seeds and might be extended to other plant tissues. Further investigation with mass spectrometry and other techniques would detail the exact compositional analysis of these networks.
Postdiction: when temporal regularity drives space perception through pre-stimulus alpha oscillations
Authors: Grabot Laetitia , Kayser Christoph , van Wassenhove Virginie 
Published: January 2021

AbstractDuring postdiction, the last stimulus of a sequence changes the perception of the preceding ones: in therabbitillusion, a three-flash series presented regularly in time, but not in space, is – illusory - perceived as spatially regular. Such a reorganization of (spatial) perception could be driven by internal priors, e.g. favoring slow motion for therabbitillusion. Although postdiction is a ubiquitous phenomenon, its neural underpinnings remain poorly understood. Here, we focused on the role of priors during postdiction and hypothesized that these could be reflected by alpha oscillations (8-12Hz), previously observed to correlate with idiosyncratic biases. We presented human participants with ambiguous visual stimuli that elicited therabbitillusion on about half the trials, allowing us to contrast MEG-EEG brain responses to the same physical events causing distinct percepts. Given that a strong prior will increase the overall probability of perceiving the illusion, we used the percentage of perceived illusion as a proxy for an individual’s prior. We found that high fronto-parietal alpha power was associated with perceiving the sequence according to individual biases: participants with high susceptibility to the illusion would report the illusion, while participants with low susceptibility would report the veridical sequence. Additionally, we found that pre-stimulus alpha phase in occipital and frontal areas dissociated illusory from non-illusory trials. These results point to a dissociated relation of the power and timing of alpha band activity to illusory perception, with power reflecting prior expectations and phase influencing behavioral performance, potentially due to the modulation of sensory uncertainty.Significance StatementLate events may sometimes influence how earlier events are perceived, as if the arrow of time was reversed in the brain. This surprising phenomenon, called postdiction, is observed in the rabbit illusion, and highlights a predominant mechanism for perceptual processes. Perception builds up from the combination of prior expectations with incoming sensory evidence, which takes time. We showed that pre-stimulus neural activity, and more specifically alpha oscillations (8-12Hz), play a double role in postdiction. Fronto-parietal alpha power reflects individual prior expectation, while occipital and frontal alpha phase predicts illusory perception. Postdiction might actually be a means of compensating for the neural delays inherent in perceptual processes, so that the arrow of perceptual time matches the arrow of physical time.
Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant
Authors: Reuschl Ann-Kathrin , Thorne Lucy G. , Zuliani-Alvarez Lorena , Bouhaddou Mehdi , Obernier Kirsten , Hiatt Joseph , Soucheray Margaret , Turner Jane , Fabius Jacqueline M. , Nguyen Gina T. , Swaney Danielle L. , Rosales Romel , White Kris M. , Avilés Pablo , Kirby Ilsa T. , Melnyk James E. , Shi Ying , Zhang Ziyang , Shokat Kevan M. , García-Sastre Adolfo , Jolly Clare , Towers Gregory J. , Krogan Nevan J. 
Published: January 2021

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal and economic burden. Recently, a new variant of SARS-CoV-2, known as B.1.1.7, was first detected in the United Kingdom and is spreading in several other countries, heightening public health concern and raising questions as to the resulting effectiveness of vaccines and therapeutic interventions. We and others previously identified host-directed therapies with antiviral efficacy against SARS-CoV-2 infection. Less prone to the development of therapy resistance, host-directed drugs represent promising therapeutic options to combat emerging viral variants as host genes possess a lower propensity to mutate compared to viral genes. Here, in the first study of the full-length B.1.1.7 variant virus, we find two host-directed drugs, plitidepsin (aplidin; inhibits translation elongation factor eEF1A) and ralimetinib (inhibits p38 MAP kinase cascade), as well as remdesivir, to possess similar antiviral activity against both the early-lineage SARS-CoV-2 and the B.1.1.7 variant, evaluated in both human gastrointestinal and lung epithelial cell lines. We find that plitidepsin is over an order of magnitude more potent than remdesivir against both viruses. These results highlight the importance of continued development of host-directed therapeutics to combat current and future coronavirus variant outbreaks.