bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home confinement during COVID-19 pandemic reduced physical activity but not health-related quality of life in previously active older women
Authors: do Amaral Vanessa Teixeira , Marçal Isabela Roque , da Cruz Silva Thiago , Souza Fernanda Bianchi , Munhoz Yacco Volpato , Camprigher Witzler Pedro Henrique , Soares Correa Matheus Monge , Fernandes Bianca , Ciolac Emmanuel Gomes 
Published: December 2020

ABSTRACTBackgroundTo investigate the effect of COVID-19 home confinement on levels of physical activity, sedentary behavior and health-related quality of life (HRQL) in older women previously participating in exercise and educational programs.Methods64 older women (age = 72±5 ys) who participated in a physical exercise/educational program and adhered to government home confinement recommendations have their levels of physical activity, sedentary behavior and HRQL assessed before and during (11 to 13 weeks after introduction of government recommendations to reduce virus transmission) COVID-19 pandemic.ResultsThere were significant reductions in total physical activity (−259 METs/week, P = 0.02), as a result of a ∼17.0 % reduction in walking (−30.8 min/week, P = 0.004) and ∼41.8 % reduction in vigorous-intensity activity (−29.6 min/week, P < 0.001). Sedentary behavior also increased (2.24 h/week, P < 0.001; 1.07 h/week days, P < 0.001; and 1.54 h/weekend days, P < 0.001). However, no significant change occurred in moderate-intensity physical activity, and HRQL domains and facets, except for an improvement in environment domain.ConclusionHome confinement due to COVID-19 pandemic decreased levels of physical activity and increased levels of sedentary behavior in previously active older women who participated in an educational program. However, there were no significant changes in HRQL. These results suggest that educational programs promoting healthy behaviors may attenuate the impact of home confinement in older women.
Thromboembolic risk in lung cancer patients receiving systemic therapy
Authors: Madison Cecelia J. , Melson Ryan A. , Conlin Michael J. , Gundle Kenneth R. , Thompson Reid F. , Calverley David C. 
Published: December 2020

AbstractIn this retrospective study, we investigated the influence of chemotherapy and immunotherapy on thromboembolic risk among US Veterans with lung cancer during their first six months of systemic therapy. Patients in the study cohort received treatment with common frontline agents that were divided into four groups: chemotherapy alone, immunotherapy alone, combination of chemo- and immunotherapies, and molecularly targeted therapies. The latter served as a control group of systemically treated lung cancer patients who received neither chemotherapy nor immunotherapy. The cohort experienced a 6.8% overall incidence of thromboembolic events with a median time to event of 49 days, but the analysis demonstrated significantly different rates among the different treatment groups. We explored models incorporating multiple confounding variables as well as the competing risk of death, and these results indicated that both chemotherapy and immunotherapy were associated with an increased incidence of thrombosis, either when given alone or combined, compared with the control group (6.91%, 9.09%, and 7.47% respectively versus 3.68%, p < 0.024). Both the Khorana score assessing thrombosis risk for cancer patients and the Charlson comorbidity score were found to be associated with increased risk of thrombosis in our analyses. Paradoxically, we found an association between risk of thrombosis and the use of prophylactic anticoagulation or aspirin during the first month of systemic treatment, accounting for several confounding variables including a patient’s prior history of thrombosis. Additionally, our data suggest that thromboembolic events may occur more commonly in lung cancer patients treated with immunotherapy compared with chemotherapy. Further study is warranted to better determine the drivers of thromboembolic risk and to identify ways to mitigate this risk for patients.
Analyzing the vast coronavirus literature with CoronaCentral
Authors: Lever Jake , Altman Russ B. 
Published: December 2020

AbstractThe global SARS-CoV-2 pandemic has caused a surge in research exploring all aspects of the virus and its effects on human health. The overwhelming rate of publications means that human researchers are unable to keep abreast of the research.To ameliorate this, we present the CoronaCentral resource which uses machine learning to process the research literature on SARS-CoV-2 along with articles on SARS-CoV and MERS-CoV. We break the literature down into useful categories and enable analysis of the contents, pace, and emphasis of research during the crisis. These categories cover therapeutics, forecasting as well as growing areas such as “Long Covid” and studies of inequality and misinformation. Using this data, we compare topics that appear in original research articles compared to commentaries and other article types. Finally, using Altmetric data, we identify the topics that have gained the most media attention.This resource, available athttps://coronacentral.ai, is updated multiple times per day and provides an easy-to-navigate system to find papers in different categories, focussing on different aspects of the virus along with currently trending articles.
In Vitro Safety “Clinical Trial” of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy
Authors: Charrez Bérénice , Charwat Verena , Siemons Brian , Finsberg Henrik , Miller Evan , Edwards Andrew G. , Healy Kevin E. 
Published: December 2020

AbstractDespite global efforts, there are no effective FDA-approved medicines for the treatment of SARS-CoV-2 infection. Potential therapeutics focus on repurposed drugs, some with cardiac liabilities. Here we report on a preclinical drug screening platform, a cardiac microphysiological system (MPS), to assess cardiotoxicity associated with hydroxychloroquine (HCQ) and azithromycin (AZM) polytherapy in a mock clinical trial. The MPS contained human heart muscle derived from patient-specific induced pluripotent stem cells. The effect of drug response was measured using outputs that correlate with clinical measurements such as QT interval (action potential duration) and drug-biomarker pairing.Chronic exposure to HCQ alone elicited early afterdepolarizations (EADs) and increased QT interval from day 6 onwards. AZM alone elicited an increase in QT interval from day 7 onwards and arrhythmias were observed at days 8 and 10. Monotherapy results closely mimicked clinical trial outcomes. Upon chronic exposure to HCQ and AZM polytherapy, we observed an increase in QT interval on days 4-8.. Interestingly, a decrease in arrhythmias and instabilities was observed in polytherapy relative to monotherapy, in concordance with published clinical trials. Furthermore, biomarkers, most of them measurable in patients’ serum, were identified for negative effects of single drug or polytherapy on tissue contractile function, morphology, and antioxidant protection.The cardiac MPS can predict clinical arrhythmias associated with QT prolongation and rhythm instabilities. This high content system can help clinicians design their trials, rapidly project cardiac outcomes, and define new monitoring biomarkers to accelerate access of patients to safe COVID-19 therapeutics.
Exogenous phosphatidic acid reduces acetaminophen-induced liver injury in mice by activating hepatic interleukin-6 signaling through inter-organ crosstalk
Authors: Clemens Melissa M. , Kennon-McGill Stefanie , Vazquez Joel H. , Stephens Owen W. , Peterson Erich A. , Johann Donald J. , Allard Felicia D. , Yee Eric U. , McCullough Sandra S. , James Laura P. , Finck Brian N. , McGill Mitchell R. 
Published: December 2020

AbstractWe previously demonstrated that endogenous phosphatidic acid (PA) promotes liver regeneration after acetaminophen (APAP) hepatotoxicity in mice. Based on that, we hypothesized that exogenous PA is also beneficial. To test that, we treated mice with a toxic APAP dose at 0 h, followed by PA or vehicle at multiple timepoints. We then collected blood and liver at 6, 24, and 52 h. Post-treatment with PA protected against liver injury at 6 h, and the combination of PA and N-acetyl-cysteine (NAC) further reduced injury compared to NAC alone. Interestingly, PA had no effect on major early mechanisms of APAP toxicity, including APAP bioactivation, oxidative stress, JNK activation, and mitochondrial damage. However, transcriptomics revealed that PA activated interleukin-6 (IL-6) signaling in the liver, and IL-6 was increased in serum from PA-treated mice. Furthermore, PA did not protect against APAP in IL-6-deficient mice. In addition, IL-6 expression increased 18-fold in adipose tissue after PA, indicating that adipose tissue is a likely source of the increased IL-6 due to PA treatment. Surprisingly, however, exogenous PA did not alter regeneration, despite the widely accepted role of IL-6 in liver repair. These data reinforce the protective role of IL-6 in APAP hepatotoxicity, provide new insight into the role of IL-6 in liver regeneration, and indicate that exogenous PA or PA derivatives may one day be a useful adjunct treatment for APAP overdose with NAC.
Frequency-dependent competition between strains imparts resilience to perturbations in a model ofPlasmodium falciparummalaria transmission
Authors: He Qixin , Pilosof Shai , Tiedje Kathryn E. , Day Karen P. , Pascual Mercedes 
Published: December 2020

AbstractIn high-transmission endemic regions, local populations ofPlasmodium falciparumexhibit vast diversity of thevargenes encoding its major surface antigen, with each parasite comprising multiple copies from this diverse gene pool. This strategy to evade the immune system through large combinatorial antigenic diversity is common to other hyperdiverse pathogens. It underlies a series of fundamental epidemiological characteristics, including large reservoirs of transmission from high prevalence of asymptomatics and long-lasting infections. Previous theory has shown that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity ofvargene repertoires (strains), in a pattern of limiting similarity that is both non-random and non-neutral. A combination of stochastic agent-based models and network analyses has enabled the development and testing of theory in these complex adaptive systems, where assembly of local parasite diversity occurs under frequency-dependent selection and large pools of variation. We show here the application of these approaches to theory comparing the resilience of the malaria transmission system to intervention when strain diversity is assembled under (competition-based) selection vs. a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections. The transmission system is considerably more resilient under NFDS, exhibiting a lower extinction probability despite comparable prevalence during intervention. We explain this pattern on the basis of the structure of strain diversity, in particular the more pronounced fraction of highly dissimilar parasites. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreasedvargene diversity reduces parasite transmission. A Principal Component Analysis of network features describing parasite similarity reveals that despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence. Given the resulting resilience to perturbations, intervention efforts will likely require longer times than the usual practice to eliminateP. falciparumpopulations. We discuss implications of our findings and potential analogies for ecological communities with non-neutral assembly processes involving frequency-dependence.
In vivo-mimicking 3D cultures secrete distinct extracellular vesicles upon cancer cell invasion
Authors: Luoto Jens C. , Coelho-Rato Leila S. , Bengs Sara H. , Roininen Jannica , Eriksson John E. , Sistonen Lea , Henriksson Eva 
Published: December 2020

AbstractExtracellular vesicles (EVs) loaded with biomolecules are important in intercellular communication and mediate local and long-range signals in cancer metastasis. However, it is currently unknown how the development of the primary tumor and onset of invasion affect the secretion and characteristics of EVs. In this study, we developed an EV production method utilizingin vivo-mimicking extracellular matrix-based 3D cultures, which allows tracking of EVs over the course of invasive development of tumor organoids. Using this method, combined with proteomic profiling, we show that PC3 human prostate cancer organoids secrete EVs with previously undefined protein cargo, which substantially differs from EV cargo of 2D cultured cells. Intriguingly, an increase in EV amounts and extensive changes in EV protein composition were detected upon invasive transition of the organoids. These results reveal that EV secretion and cargo loading are highly dependent on the developmental status of the tumor organoid, emphasizing the necessity ofin vivo-mimicking conditions for discovery of novel cancer-derived EV components, applicable as diagnostic markers for cancer.
Response of benthic macroinvertebrates to dam removal in the restoration of the Boardman River, Michigan, USA
Authors: Mahan David C. , Betts Joel T. , Nord Eric , Van Dyke Fred , Outcalt Jessica M. 
Published: December 2020

AbstractDam removal is an increasingly important method of stream restoration, but most removal efforts are under-studied in their effects. In order to better understand the effects of such removals on the stream ecosystem, we examined changes in stream macroinvertebrate communities from 2011-2016 above, below, and before and after the October 2012 removal of the Brown Bridge Dam on the Boardman River in Michigan (USA), and to new channel sites created in its former reservoir (2013-2015). Using linear mixed-effect models on the percent abundance of ecologically sensitive taxa (% Ephemeroptera, Plecoptera, Trichoptera (EPT)), total density of all macroinvertebrates, and overall taxa richness, along with multivariate analyses on the community matrix, we examined differences in community composition among sites and years. EPT declined downstream of the dam immediately after dam removal, but recovered in the second year, becoming dominant within 2-4 years. Downstream sites before removal had different community composition than upstream sites and downstream sites after removal (p<0.001), while upstream and downstream sites after removal converged towards similarity. New channel (restored) %EPT, density, and taxa richness were not different from upstream sites in any year following removal, but new channel sites were the most distinct in community composition, possessing multiple indicator taxa characteristic of unique new conditions. The invasive New Zealand mud snail (Potamopyrgus antipodarum) was absent from all sites prior to dam removal, but appeared at low densities in upstream sites in 2013, had spread to all sites by 2015, and showed large increases at all sites by 2016. Managers employing dam removal for stream restoration should include post-removal monitoring for multiple years following removal and conduct risk analysis regarding potential effects on colonization of invasive invertebrate species.
Fish-released kairomones affectCuliseta longiareolataoviposition and larval life history
Authors: Silberbush Alon 
Published: December 2020

AbstractSeveral species of mosquitoes respond to the presence of kairomones released by larval predators during oviposition habitat selection and larval development. These responses may differ among mosquito species and do not always correlate with larval survival. This study examined the responses of the mosquitoCuliseta longiareolataMacquart to kairomones released by three species of fish during oviposition,Gambusia affinisBaird and Girard,Aphanius mentoHeckel andGarra rufaHeckel. In addition, the study examined the effects of kairomones released byG. affinison larval development. Results show that ovipositing female avoided cues from larvivorous, but not algivorous fish. In addition, developing larvae metamorphosed slower and showed increased mortality when exposed to fish-released kairomones. Results suggest that the responses of this mosquito species to fish-released kairomones may be explained by its competitive ability.
The transcription factor FoxO1 is required for the establishment of the human definitive endoderm
Authors: Nord Joshua , Schill Daniel , Pulakanti Kirthi , Rao Sridhar , Cirillo Lisa Ann 
Published: December 2020

AbstractThe transcription factor FoxO1 has been shown to dynamically regulate cell fate across diverse cell types. Here, we employ a human induced pluripotent stem cell (hiPSC)-to-hepatocyte differentiation system that recapitulates the process of hepatocyte specification and differentiation in the human embryo to investigate FoxO1 as a participant in the molecular events required to execute the initial stages of liver development. We demonstrate that FoxO1 is expressed in hiPSC and at all stages of hepatocyte differentiation: definitive endoderm, specified hepatocytes, immature hepatoblasts, and mature hepatocyte-like cells. Disruption of FoxO1 activity by addition of the small molecule inhibitor AS1842856 at the beginning of the differentiation protocol abolishes the formation of definitive endoderm, as indicated by the loss of endoderm gene expression and the gain in expression of multiple mesoderm genes. Moreover, we show that FoxO1 binds to the promoters of two genes with important roles in endoderm differentiation whose expression is significantly downregulated in AS1842856 treated versus untreated cells. These findings reveal a new role for FoxO1 as an essential transcriptional regulator for the establishment of definitive endoderm in humans.
Protein substrates engage the lumen of O-GlcNac transferase’s tetratricopeptide repeat domain in different ways
Authors: Joiner Cassandra M. , Hammel Forrest A. , Janetzko John , Walker Suzanne 
Published: December 2020

ABSTRACTGlycosylation of nuclear and cytoplasmic proteins is an essential post-translational modification in mammals. O-GlcNAc transferase (OGT), the sole enzyme responsible for this modification, glycosylates over a thousand unique nuclear and cytoplasmic substrates. How OGT selects its substrates is a fundamental question that must be answered to understand OGT’s unusual biology. OGT contains a long tetratricopeptide repeat (TPR) domain that has been implicated in substrate selection, but there is almost no information about how changes to this domain affect glycosylation of individual substrates. Here, we used proteome-wide glycosylation profiling and probed glycosylation of selected purified substrates to show that asparagine and aspartate ladders that extend the full length of OGT’s TPR lumen control substrate glycosylation. We also found that substrates with glycosylation sites close to the C-terminus bypass lumenal binding. Our findings demonstrate that substrates can engage OGT in a variety of different ways for glycosylation.
Grammatical category and the neural processing of phrases
Authors: Burroughs Amelia , Kazanina Nina , Houghton Conor 
Published: December 2020

AbstractThe interlocking roles of lexical, syntactic and semantic processing in language comprehension has been the subject of longstanding debate. Recently, the cortical response to a frequency-tagged linguistic stimulus has been shown to track the rate of phrase and sentence, as well as syllable, presentation. This could be interpreted as evidence for the hierarchical processing of speech, or as a response to the repetition of grammatical category. To examine the extent to which hierarchical structure plays a role in language processing we recorded EEG from human participants as they listen to isochronous streams of monosyllabic words. Comparing responses to sequences in which grammatical category is strictly alternating and chosen such that two-word phrases can be grammatically constructed —cold food loud room— or is absent —rough give ill tell— showed cortical entrainment at the two-word phrase rate was only present in the grammatical condition. Thus, grammatical category repetition alone does not yield entertainment at higher level than a word. On the other hand, cortical entrainment was reduced for the mixed-phrase condition that contained two-word phrases but no grammatical category repetition —that word send less— which is not what would be expected if the measured entrainment reflected purely abstract hierarchical syntactic units. Our results support a model in which word-level grammatical category information is required to build larger units.
Sustained expression ofunc-4/Hoxandunc-37/Grouchoin postmitotic neurons specifies the spatial organization of the cholinergic synapses inC. elegans
Authors: Kurashina Mizuki , Wang Jane , Lee Kathy Kyungeun , Johal Arpun , Mizumoto Kota 
Published: December 2020

AbstractNeuronal cell fate determinants establish the identities of neurons by controlling gene expression to regulate neuronal morphology and synaptic connectivity. However, it is not understood if neuronal cell fate determinants have postmitotic functions in synapse pattern formation. Here we identify a novel role for UNC-4 homeobox protein and its corepressor UNC-37/Groucho, in tiled synaptic patterning of the cholinergic motor neurons inCaenorhabditis elegans. We show thatunc-4is not required during neurogenesis but is required in the postmitotic neurons for proper synapse patterning. In contrast,unc-37is required in both developing and postmitotic neurons. The synaptic tiling defects ofunc-4mutants are suppressed bybar-1/β-cateninmutation, which positively regulates the expression ofceh-12/Hb9. Ectopicceh-12expression partly underlies the synaptic tiling defects ofunc-4andunc-37mutants. Our results reveal a novel postmitotic role of neuronal cell fate determinants in synapse pattern formation through inhibiting the canonical Wnt signaling pathway.
15-PGDH Regulates Hematopoietic and Gastrointestinal Fitness During Aging
Authors: Ho Won Jin , Smith Julianne N.P. , Park Young Soo , Hadiono Matthew , Christo Kelsey , Jogasuria Alvin , Zhang Yongyou , Broncano Alyssia V. , Kasturi Lakshmi , Dawson Dawn M. , Gerson Stanton L. , Markowitz Sanford D. , Desai Amar B. 
Published: December 2020

ABSTRACTEmerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cells’ regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss ofHpgdexpression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness.ARTICLE SUMMARY15-PGDH as a Driver of Age-Related Tissue Dysfunction