bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling the pandemic during the SARS-CoV-2 vaccination rollout: a modeling study
Authors: Viana João , van Dorp Christiaan H. , Nunes Ana , Gomes Manuel C. , van Boven Michiel , Kretzschmar Mirjam E. , Veldhoen Marc , Rozhnova Ganna 
Published: April 2021

AbstractThere is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point control of COVID-19 would be achieved for each scenario.
Microsampling for monitoring gentamicin in neonates
Authors: Parker Suzanne L. , Irwin Adam D. , Hosking Francine , August Deanne , Schoenmaker Brittany , Pandey Saurabh , Wallis Steven C. , Lipman Jeffrey , Roberts Jason A. , Davies Mark W 
Published: April 2021

AbstractGentamicin is recommended as first-line treatment of neonatal sepsis. The use of gentamicin is associated with toxicity which complicates neonatal dosing and necessitates therapeutic drug monitoring (TDM).In a proof-of-concept investigation, we sought to compare (1) gentamicin concentrations obtained using volumetric absorptive microsampling (VAMS) to standard TDM plasma samples, and (2) the time taken to report results obtained using VAMS compared to standard TDM by the local hospital chemical pathology service.The difference between gentamicin concentrations obtained from plasma collected for routine clinical care and calculated plasma concentrations, based on samples collected in whole blood using VAMS, was −18.0% and −0.4% for two patients. The research laboratory reported results within the time taken for the routine chemical pathology laboratory to report results. This proof-of-concept study demonstrates that the use of microsampling for TDM by pathology services can fulfil the requirements of providing an accurate gentamicin concentration in a timely manner.
Advance requests for MAiD in dementia: Policy recommendations emerging from a mixed-methods study of the views of the Canadian public and MAiD practitioners
Authors: Byram Adrian C. , Wiebe Ellen R. , Trembley-Huet Sabrina , Reiner Peter B. 
Published: April 2021

AbstractBackgroundThe Canadian public has repeatedly expressed its desire for advance requests for Medical Assistance in Dying (MAiD) after dementia diagnosis, yet MAiD practitioners’ willingness to accede to such advance requests is unknown. This study explores the extent and nature of any gap between the public’s desire for, and practitioners’ willingness to provide MAiD, and identifies policies to ameliorate such a gap.MethodsTwo complementary mixed-method surveys gathered data from convenience samples of 83 Canadian adults and 103 MAiD practitioners. The public survey asked participants which of five specific circumstances commonly encountered in dementia they would include in their advance requests. The practitioner survey queried the validation level participants would require before providing MAiD in each specific circumstance. Participants’ reasons were probed using thematic analysis of open-ended questions.ResultsOn average, 77% of public participants indicated they definitely or probably would include each of the five specific circumstances in their advance requests for MAiD. As validation level decreased from patient consent to patient assent, family assent, or advance request alone, the magnitude of the gap between the public’s desire and practitioners’ willingness increased. The practitioners’ qualitative data contained many practical insights from which emerged seven policy recommendations to ameliorate this gap and increase the likelihood of honouring patient requests.InterpretationThe study provides evidence of a gap between public desire for, and practitioner willingness to provide MAiD in dementia. The policy recommendations are relevant to consideration of legislation for advance requests for MAiD.
Body Clock: Matching Personalized Multimorbidity and Fast Aging Using Information Entropy
Authors: Salimi Shabnam , Vehtari Aki , Salive Marcel , Ferrucci Luigi 
Published: April 2021

AbstractWith aging, most older adults are at risk of having more than two diseases, conventionally defined as multimorbidity. We determined body organ disease number (BODN) as a new multimorbidity index. We measured the degree to which each disease level, from mild to severe, predicts longitudinal BODN uncoupled from chronological age. We determined Body Clock using global disease levels burden from all systems predicting longitudinal BODN for each individual, which is a proxy of the personalized rate of biological aging. Change in Body Clock predicts late-life age-related outcomes and can be used for geriatric clinics and clinical trials for precision medicine.
Pandemic effect on body composition. Single center analysis of 2.771 cases
Authors: Braga Fabrício , Zagury Roberto , Perroni Cristiane , Domecg Victor Hugo 
Published: April 2021

AbstractBackgroundThe COVID-19 pandemic has led to a dramatic increase in the levels of sedentary lifestyle and unhealthy dietary habits. A worsening in populational obesity levels and body composition (BC) is strongly awaited but so far not documented.ObjectiveTo compare BC profile measured by bioelectrical impedance analysis (BIA) between pre-pandemic (P1-03/15th/2017 to 03/16th/2020) and pandemic (P2-3/17th/2020 to 3/10th/2021) period of time.Materials and MethodsBIA were grouped according to the time it was performed. Two comparisons were done: an independent sample comparison (ISC) and a paired sample comparison (PSC) considering patients with at least one BIA in P1 and P2. Age, height, gender, weight, body mass index (BMI), body fat mass (BFM), free fat mass (FFM), skeletal muscle mass (SMM), percentage of body fat (PBF), visceral fat area (VFA) were compared. Statistical significance level was defined for a p value<0.05.Results and DiscussionA total of 3.358 BIA were performed, and 2.771 and 112 were selected for IS and PS, respectively. In ISC, despite an unchanged weight, BFM, FFM, PBF and VFA increased and SSM decreased on P2(p<0.015 for all). A multivariated linear regression model using PBF as dependent variable showed P2 as an independent predictor (β=0.38 95%CI 0.19 to 0.56). In the PSC, PBF also increased from P1 to P2 (p=0.015). To our knowledge this is the first documentation of worsening BC after pandemic. Health authorities should be alert for this phenomenon and their clinical consequences in the days to come.
Risk heterogeneity in compartmental HIV transmission models of ART as prevention in Sub-Saharan Africa: A scoping review
Authors: Knight Jesse , Kaul Rupert , Mishra Sharmistha 
Published: April 2021

AbstractBackgroundTransmission models provide complementary evidence to clinical trials about the potential population-level incidence reduction attributable to ART (ART prevention impact). Different modelling assumptions about risk heterogeneity may influence projected ART prevention impacts. We sought to review representations of risk heterogeneity in compartmental HIV transmission models applied to project ART prevention impacts in Sub-Saharan Africa.MethodsWe systematically reviewed studies published before January 2020 that used non-linear compartmental models of sexual HIV transmission to simulate ART prevention impacts in Sub-Saharan Africa. We summarized data on model structure/assumptions (factors) related to risk and intervention heterogeneity, and explored multivariate ecological associations of ART prevention impacts with modelled factors.ResultsOf 1384 search hits, 94 studies were included. 64 studies considered sexual activity stratification and 39 modelled at least one key population. 21 studies modelled faster/slower ART cascade transitions (HIV diagnosis, ART initiation, or cessation) by risk group, including 8 with faster and 4 with slower cascade transitions among key populations versus the wider population. In ecological analysis of 125 scenarios from 40 studies (subset without combination intervention), scenarios with risk heterogeneity that included turnover of higher risk groups were associated with smaller ART prevention benefits. Modelled differences in ART cascade across risk groups also influenced the projected ART benefits, including: ART prioritized to key populations was associated with larger ART prevention benefits. Of note, zero of these 125 scenarios considered lower ART coverage among key populations.ConclusionAmong compartmental transmission models applied to project ART prevention impacts in Sub-Saharan Africa, representations of risk heterogeneity and projected impacts varied considerably. Inclusion/exclusion of risk heterogeneity with turnover, and intervention heterogeneity across risk groups could influence the projected impacts of ART scale-up. These findings highlight a need to capture risk heterogeneity with turnover and cascade heterogenetiy when projecting ART prevention impacts.
Urine metabolome of tuberculosis patients receiving intensive phase of treatment show diurnal variations
Authors: Faruquee Hossain Md. , Meitei Heikrujam Nilkanta , Pandey Anupama , Pahwa Falak , Thokchom Maria , Sonia Athokpam , Chaudhary Shweta , Gupta Dinesh , Singh Huidrom Lokhendro , Haobam Sunita , Haobam Reena , Nanda Ranjan Kumar 
Published: April 2021

ABSTRACTDiurnal variation in biofluid metabolome as observed in a healthy human may alter in perturbed conditions. Biofluids like urine are rich in molecular constituents including metabolites, and infectious disease conditions like tuberculosis (TB) may influence diurnal differences for which limited reports are available in the literature. In this study, we present an optimized gas chromatography coupled to a quadrupole mass spectrometry (GC-MS) method to analyze processed and trimethylsilyl (TMS) derivatized urine metabolites. Urine samples were collected at four time points (0, 6, 12 and 24 hours) of study subjects [n=15; mean age 37 (24-70) in years] including controls [n=7; mean age 29.3 (24-35) years] and culture-confirmed active TB patients [ATB; n=8; mean age 43.7 (25-70) years] receiving treatment in the intensive phase. Global urine metabolite profiling was carried out using the optimized GC-MS method. Higher urine analyte diversity was observed in ATB patients (74) than in controls (36) during the day. Diurnal variations of the parent anti-TB drugs and their breakdown products (pyrazinamide, pyrazinoic acid, 5-hydroxy pyrazinoic acid, isonicotinic acid and alpha amino butyric acid) were observed with maximum abundance at 6 h. Interestingly, urine of ATB subjects at 6 h showed the highest metabolic diversity, whereas it was at 12 h in controls. Many analytes including glycine and alanine amino-acids showed diurnal variation in ATB and controls. These changes could be attributed to the altered host metabolic activities due to disease, treatment-associated decrease in total body bacterial burden and gut microbiota dysbiosis. And the optimized spiked-in internal standard, urine sample volume and GC-MS method could be used for global urine metabolome analysis in healthy and different perturbed conditions.“For Table of Contents Only”
Denoising physiological data collected during multi-band, multi-echo EPI sequences
Authors: Bottenhorn Katherine L. , Salo Taylor , Riedel Michael C. , Sutherland Matthew T. , Robinson Jennifer L. , Musser Erica D. , Laird Angela R. 
Published: April 2021

AbstractCollecting physiological data during fMRI experiments can improve fMRI data cleaning and contribute to our understanding of psychophysiological processes; however, these recordings are frequently fraught with artifacts from the MRI pulse sequence. Here, we assess data from BIOPAC Systems, Inc., one of the more widely-used manufacturers of physiological monitoring equipment, and evaluate their recommendations for filtering such artifacts from electrocardiogram and electrodermal activity data collected during single-band, single-echo fMRI sequences and extend these recommendations to address artifacts associated with multiband, multi-echo fMRI sequences. While the magnitude and frequencies of artifacts differ with these aspects of pulse sequences, their effects can be mitigated via application of digital filters incorporating slice collection, multiband factor, and repetition time. The implementation of these filters is provided both in interactive online notebooks and an open source denoising tool.
Tripartite networks show that keystone species can multitask
Authors: Timóteo Sérgio , Albrecht Jörg , Rumeu Beatriz , Norte Ana C. , Traveset Anna , Frost Carol M. , Marchante Elizabete , López-Núñez Francisco A. , Peralta Guadalupe , Memmott Jane , Olesen Jens M. , Costa José M. , da Silva Luís P. , Carvalheiro Luísa G. , Correia Marta , Staab Michael , Blüthgen Nico , Farwig Nina , Hervías-Parejo Sandra , Mironov Sergei , Rodríguez-Echeverría Susana , Heleno Ruben 
Published: April 2021

AbstractKeystone species are disproportionately important for ecosystem functioning (1,2). However, while all species engage in multiple interaction types with other species, the importance of keystone species is often defined based on a single dimension of their Eltonian niche (3), that is, one type of interaction (e.g., keystone predator). Therefore, it remains unclear whether the importance of keystone species is unidimensional or if it extends across interaction types. We conducted a meta-analysis of tripartite interaction networks to examine whether species importance in one dimension of their niche is mirrored in other niche dimensions, and whether this is associated with interaction outcome, intimacy, or species richness. We show that keystone species importance is positively associated across multiple ecological niche dimensions, independently of species’ abundance, and find no evidence that multidimensionality of keystone species is influenced by the explanatory variables. We propose that the role of keystone species extends across multiple ecological niche dimensions, with important implications for ecosystem resilience and conservation.Significance StatementKeystone species are often identified by focusing on a single type of interaction (e.g., predation, pollination, herbivory) which contrasts with the multiple roles that species play in biological communities. We conducted a meta-analysis of 18 tripartite interaction networks to explore if keystonness is correlated across the multiple dimensions of species Eltonian niches. Our results suggest that species importance tends to span across multiple interaction types, independently from abundance, which can be key to understand community resilience and collapse in face of multiple threats.
Bipedalism in Mexican Albian lizard (Squamata) and the locomotion type in other Cretaceous lizards
Authors: Villaseñor-Amador Damián , Suárez Nut Xanat , Cruz J. Alberto 
Published: April 2021

ABSTRACTRepresentative locomotion types in lizards include terrestrial, arboreal, grass swimmer, sand swimmer and bipedal. Few studies explain the locomotion habit of extinct lizards, and even less asses those of bipedal ones. Here, we use quantitative methods to infer the type of locomotion of two Albian Mexican lizards (Lower Cretaceous) and three Cretaceous lizards from Brazil, North America and Spain, assessing the similarities of the hindlimb-forelimb length ratio amongst extinct and extant species. Additionally, an ancestral character state reconstruction analysis was performed, to evaluate the evolution of lizard locomotion habits. The speciesHuehuecuetzpalli mixtecuswas bipedal whileTijubina ponteiwas facultative bipedal,Hoyalacerta sanzi, Tepexisaurus tepexiiandPolyglyphanodon sternbergicannot be differentiated amongst terrestrial or arboreal with the approach used in this work. The ancestral character state reconstruction analysis showed a terrestrial ancestral locomotion type, with a basal character state of hindlimbs longer than forelimbs. Equal length between hind and forelimbs appear to be a derivate state that evolved multiple times in lizard evolutionary history.
Transient induction of cell cycle promoter Fam64a improves cardiac function through regulating Klf15-dependent cardiomyocyte differentiation in mice
Authors: Hashimoto Ken , Kodama Aya , Ohira Momoko , Kimoto Misaki , Nakagawa Reiko , Usui Yuu , Ujihara Yoshihiro , Hanashima Akira , Mohri Satoshi 
Published: April 2021

AbstractThe introduction of fetal or neonatal signatures such as cell cycle promoting genes into damaged adult hearts has been vigorously pursued as a promising strategy for stimulating proliferation and regeneration of adult cardiomyocytes, which normally cannot divide. However, cell division of cardiomyocytes requires preceding dedifferentiation with sarcomere disassembly and calcium dysregulation, which, in principle, compromises contractile function. To overcome this intrinsic dilemma, we explored the feasibility of optimizing the induction protocol of the cell cycle promoter in mice. As a model of this approach, we used Fam64a, a fetal-specific cardiomyocyte cell cycle promoter that we have recently identified. We first analyzed transgenic mice maintaining long-term cardiomyocyte-specific expression of Fam64a after birth, when endogenous expression was abolished. Despite having an enhanced proliferation of postnatal cardiomyocytes, these mice showed age-related cardiac dysfunction characterized by sustained cardiomyocyte dedifferentiation, which was reminiscent of the dilemma. Mechanistically, Fam64a inhibited glucocorticoid receptor-mediated transcriptional activation of Klf15, a key regulator that drives cardiomyocyte differentiation, thereby directing cardiomyocytes toward immature undifferentiated states. In contrast, transient induction of Fam64a in cryoinjured wildtype adult mice hearts improved functional recovery with augmented cell cycle activation of cardiomyocytes. These data indicate that optimizing the intensity and duration of the stimulant to avoid excessive cardiomyocyte dedifferentiation could pave the way toward developing efficient strategy for successful heart regeneration.
Alveolar macrophages strictly rely on GM-CSF from alveolar epithelial type 2 cells before and after birth
Authors: Gschwend Julia , Sherman Samantha , Ridder Frederike , Feng Xiaogang , Liang Hong-Erh , Locksley Richard M. , Becher Burkhard , Schneider Christoph 
Published: April 2021

ABSTRACTPrograms defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and non-immune cells, and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular crosstalk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoieticCsf2and basophil depletion. Instead, AT2 lineage-specific constitutive and inducibleCsf2deletion revealed the non-redundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.
Technical advances in the development of zonation liverin vitrosystems that incorporate localized Wnt activating signals
Authors: Valle-Encinas Eider , Dawes Michael , Martinez Carmen Velasco , McSweeney Kate , Müller Miryam , Bird Tom , Dale Trevor 
Published: April 2021

AbstractA Wnt microenvironment sustained by the hepatic central vein is essential for the segregation of liver functions into zones. Current liver culture systems lack localized Wnt cues and as a consequence fail to maintain the hepatocyte functional heterogeneity that is observed in the intact organ. In this study, organoid models and 2D-culture systems were used to identify cellular sources and Wnt presentation methods that could support the future development of zonated liverin vitrosystems. Using soluble ligands, we show that primary hepatocyte (PH)-derived organoids but not bile duct (BD)-derived organoids may be used to recapitulate the resting liver. We provide evidence that differentiation of PH-organoids in the presence of Wnt9b and Rspo3 induce pericentral maturation. Finally, we show that immobilization of Rspo3 onto beads in combination with soluble Wnt9b may be a valid strategy to recreate the central vein Wnt microenvironmentin vitro.
The natural design for harvesting far-red light: the antenna increases both absorption and quantum efficiency of Photosystem II
Authors: Mascoli Vincenzo , Bhatti Ahmad Farhan , Bersanini Luca , van Amerongen Herbert , Croce Roberta 
Published: April 2021

AbstractCyanobacteria carry out photosynthetic light-energy conversion using phycobiliproteins for light harvesting and the chlorophyll-rich photosystems for photochemistry. While most cyanobacteria only absorb visible photons, some of them can acclimate to harvest far-red light (FRL, 700-800 nm) by integrating chlorophyllfanddin their photosystems and producing red-shifted allophycocyanin. Chlorophyllfinsertion enables the photosystems to use FRL but slows down charge separation, reducing photosynthetic efficiency. Here we demonstrate with time-resolved fluorescence spectroscopy that charge separation in chlorophyll-f-containing Photosystem II becomes faster in the presence of red-shifted allophycocyanin antennas. This is different from all known photosynthetic systems, where additional light-harvesting complexes slow down charge separation. Based on the available structural information, we propose a model for the connectivity between the phycobiliproteins and Photosystem II that qualitatively accounts for our spectroscopic data. This unique design is probably important for these cyanobacteria to efficiently switch between visible and far-red light.