bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations for Assessment and Deployment of Rapid Antigen Tests for Diagnosis of Coronavirus Disease 2019
Authors: Pollock Nira R , Lee Francesca , Ginocchio Christine C , Yao Joseph D , Humphries Romney M 
Published: March 2021

Abstract
Diagnostic testing is a critical tool to mitigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, but molecular testing capacity remains limited. Rapid diagnostic tests (RDTs) that detect SARS-CoV-2 protein antigens (Ag) offer the potential to substantially expand testing capacity and to allow frequent, large-scale, population screening. Testing is simple, rapid (results generally available within 15 minutes), and applicable for diagnosis at point of care. However, implementation of Ag RDTs requires a detailed understanding of test performance and operational characteristics in each testing scenario and population being evaluated. Successful implementation of Ag RDTs on a large scale should combine testing with technical oversight and with clinical and public health infrastructure, and will require production at levels much higher than presently possible. In this commentary, we provide detailed considerations for Ag RDT assessment and use cases to encourage and enable broader manufacturing and deployment.
Patterns in Rhizosolenia- and Guinardia-associated Richelia abundances in the tropical marginal seas of the western North Pacific
Authors: Tuo Sing-How , Mulholland Margaret R , Chen Yuh-Ling Lee , Chappell P Dreux , Chen Houng-Yung 
Published: March 2021

Abstract
Richelia is a widespread, heterocystous, N2-fixing cyanobacterium that occurs in oligotrophic seas. It can be symbiotic within rhizosolenoid hosts, including Rhizosolenia (R-R) and Guinardia (G-R), and occasionally occurs as free-living (FL-R) filaments. We investigated the Richelia abundances in the South China (SCS) and Philippine Seas (PS) during the northeast (NEM) and southwest monsoon (SWM) seasons between 2001 and 2016. Field results showed that G-R was most abundant in the SCS during the SWM. Both R-R and FL-R were more abundant in the PS than the SCS and during the SWM versus the NEM. In general, R-R were more abundant than G-R, except at the SCS-SWM stations where abundances were comparable. Multivariate statistical models indicate that as R-R and G-R were abundant in warmer seawaters, nitrate plus nitrite was a key factor negatively controlling R-R abundance while silicate was more positively related to G-R. Positive correlation between G-R and FL-R abundances and microscopic observations imply that like Rhizosolenia-associated Richelia, filaments released from Guinardia hosts can remain viable outside their diatom hosts for time periods on the order of days. Overall, results reveal different distribution patterns between the two rhizosolenoid-Richelia symbioses and both G-R and R-R likely contribute to FL-R in the field.
A peroxisomal β-oxidative pathway contributes to the formation of C6–C1 aromatic volatiles in poplar
Authors: Lackus Nathalie D , Schmidt Axel , Gershenzon Jonathan , Köllner Tobias G 
Published: March 2021

Abstract
Benzenoids (C6–C1 aromatic compounds) play important roles in plant defense and are often produced upon herbivory. Black cottonwood (Populus trichocarpa) produces a variety of volatile and nonvolatile benzenoids involved in various defense responses. However, their biosynthesis in poplar is mainly unresolved. We showed feeding of the poplar leaf beetle (Chrysomela populi) on P. trichocarpa leaves led to increased emission of the benzenoid volatiles benzaldehyde, benzylalcohol, and benzyl benzoate. The accumulation of salicinoids, a group of nonvolatile phenolic defense glycosides composed in part of benzenoid units, was hardly affected by beetle herbivory. In planta labeling experiments revealed that volatile and nonvolatile poplar benzenoids are produced from cinnamic acid (C6–C3). The biosynthesis of C6–C1 aromatic compounds from cinnamic acid has been described in petunia (Petunia hybrida) flowers where the pathway includes a peroxisomal-localized chain shortening sequence, involving cinnamate-CoA ligase (CNL), cinnamoyl-CoA hydratase/dehydrogenase (CHD), and 3-ketoacyl-CoA thiolase (KAT). Sequence and phylogenetic analysis enabled the identification of small CNL, CHD, and KAT gene families in P. trichocarpa. Heterologous expression of the candidate genes in Escherichia coli and characterization of purified proteins in vitro revealed enzymatic activities similar to those described in petunia flowers. RNA interference-mediated knockdown of the CNL subfamily in gray poplar (Populus x canescens) resulted in decreased emission of C6–C1 aromatic volatiles upon herbivory, while constitutively accumulating salicinoids were not affected. This indicates the peroxisomal β-oxidative pathway participates in the formation of volatile benzenoids. The chain shortening steps for salicinoids, however, likely employ an alternative pathway.
Susceptibility factor RTP1 negatively regulates Phytophthora parasitica resistance via modulating UPR regulators bZIP60 and bZIP28
Authors: Qiang Xiaoyu , Liu Xingshao , Wang Xiaoxue , Zheng Qing , Kang Lijuan , Gao Xianxian , Wei Yushu , Wu Wenjie , Zhao Hong , Shan Weixing 
Published: March 2021

Abstract
The unfolded protein response (UPR) is a conserved stress adaptive signaling pathway in eukaryotic organisms activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). UPR can be elicited in the course of plant defense, playing important roles in plant–microbe interactions. The major signaling pathways of plant UPR rely on the transcriptional activity of activated forms of ER membrane-associated stress sensors bZIP60 and bZIP28, which are transcription factors that modulate expression of UPR genes. In this study, we report the plant susceptibility factor Resistance to Phytophthora parasitica 1 (RTP1) is involved in ER stress sensing and rtp1-mediated resistance against P. parasitica is synergistically regulated with UPR, as demonstrated by the simultaneous strong induction of UPR and ER stress-associated immune genes in Arabidopsis thaliana rtp1 mutant plants during the infection by P. parasitica. We further demonstrate RTP1 contributes to stabilization of the ER membrane-associated bZIP60 and bZIP28 through manipulating the bifunctional protein kinase/ribonuclease IRE1-mediated bZIP60 splicing activity and interacting with bZIP28. Consequently, we find rtp1bzip60 and rtp1bzip28 mutant plants exhibit compromised resistance accompanied with attenuated induction of ER stress-responsive immune genes and reduction of callose deposition in response to P. parasitica infection. Taken together, we demonstrate RTP1 may exert negative modulating roles in the activation of key UPR regulators bZIP60 and bZIP28, which are required for rtp1-mediated plant resistance to P. parasitica. This facilitates our understanding of the important roles of stress adaptive UPR and ER stress in plant immunity.
Retention rate and effectiveness of secukinumab vs TNF inhibitor in ankylosing spondylitis patients with prior TNF inhibitor exposure
Authors: Min Hong Ki , Kim Hae-Rim , Lee Sang-Heon , Hong Yeon Sik , Kim Moon-Young , Park Sung-Hwan , Kang Kwi Young 
Published: March 2021

Abstract

Objectives
The choice of second-line biologics for AS patients previously treated with a TNF inhibitor (TNFi) remains unclear. Here, we compared drug retention and clinical efficacy between AS patients who switched biologics to secukinumab and those who switched to a different TNFi.

Methods
AS patients enrolled in the Korean College of Rheumatology BIOlogics registry were included, and patients with non-radiographic axial spondyloarthritis were excluded. Patients with previous TNFi exposure were divided into the secukinumab group and the TNFi switching group. Drug retention and clinical efficacy [BASDAI50, Assessment of Spondylo-Arthritis International Society (ASAS)20, ASAS40, AS disease activity score (ASDAS) &lt;2.1, ASDAS clinically important improvement and ASDAS major improvement] were assessed at the 1 year follow-up. Propensity score (PS)-matched and covariate-adjusted logistic regression analyses were performed.

Results
Two hundred and forty-six had available 1 year follow-up data. Secukinumab as third- or later-line biologic was more frequent than alternative TNFi (54% vs 14%). PS-matched and multiple covariate-adjusted analyses showed that the odds ratio (OR) for drug discontinuation was comparable between the secukinumab and TNFi switching groups [OR 1.136 (95% CI 0.843, 1.531) and 1.000 (95% CI 0.433–2.308), respectively]. The proportion of patients who achieved BASDAI50 was also comparable between the two groups [OR 0.833 (95% CI 0.481, 1.441) in PS-matched analysis]. Other clinical efficacy parameters were also comparable. In the subgroup analysis of AS patients with previous TNFi discontinuation due to ineffectiveness, all clinical efficacy parameters were comparable between the two groups.

Conclusion
In AS patients with previous exposure to a TNFi, switching biologics to secukinumab and switching to an alternative TNFi resulted in comparable drug retention and clinical efficacy.
Structural Covariance of Cortical Gyrification at Illness Onset in Treatment Resistance: A Longitudinal Study of First-Episode Psychoses
Authors: Ajnakina Olesya , Das Tushar , Lally John , Di Forti Marta , Pariante Carmine M , Marques Tiago Reis , Mondelli Valeria , David Anthony S , Murray Robin M , Palaniyappan Lena , Dazzan Paola 
Published: March 2021

AbstractTreatment resistance (TR) in patients with first-episode psychosis (FEP) is a major cause of disability and functional impairment, yet mechanisms underlying this severe disorder are poorly understood. As one view is that TR has neurodevelopmental roots, we investigated whether its emergence relates to disruptions in synchronized cortical maturation quantified using gyrification-based connectomes. Seventy patients with FEP evaluated at their first presentation to psychiatric services were followed up using clinical records for 4 years; of these, 17 (24.3%) met the definition of TR and 53 (75.7%) remained non-TR at 4 years. Structural MRI images were obtained within 5 weeks from first exposure to antipsychotics. Local gyrification indices were computed for 148 contiguous cortical regions using FreeSurfer; each subject’s contribution to group-based structural covariance was quantified using a jack-knife procedure, providing a single deviation matrix for each subject. The latter was used to derive topological properties that were compared between TR and non-TR patients using a Functional Data Analysis approach. Compared to the non-TR patients, TR patients showed a significant reduction in small-worldness (Hedges’s g = 2.09, P &lt; .001) and a reduced clustering coefficient (Hedges’s g = 1.07, P &lt; .001) with increased length (Hedges’s g = −2.17, P &lt; .001), indicating a disruption in the organizing principles of cortical folding. The positive symptom burden was higher in patients with more pronounced small-worldness (r = .41, P = .001) across the entire sample. The trajectory of synchronized cortical development inferred from baseline MRI-based structural covariance highlights the possibility of identifying patients at high-risk of TR prospectively, based on individualized gyrification-based connectomes.
Revealing Secrets: Talismans, Healthcare and the Market of the Occult in Early Twentieth-century China
Authors: Bernardi Junqueira Luis Fernando 
Published: March 2021

Abstract
This article analyses the place and value of occult arts in the healthcare market of Republican China (1912–1949). Medical historiography has long neglected the resilience of such occult arts as talismans, astrology and divination in the context of China’s search for modernity. Focusing on the production, trade, and consumption of goods and services related to talismanic healing, I give voice to Chinese occultists by investigating the formation of a ‘market of the occult’ in the Republican era. I adopt a global perspective to clarify the changes that occult healing underwent following the popularisation of new printing technologies, mass media and transnational spiritualism in early twentieth-century China. Erstwhile embraced in secrecy, the occult was now being made public. Cheap manuals, wide-circulation newspapers and book catalogues reveal that in contrast to past studies that herald the disenchantment of the world as the hallmark of Chinese modernity, occult healing did not simply survive but thrived in the face of modern science and technology.
Continuities in State–Society Interactions across Broad Spatio-temporal Realms: Gong Tingxian as Both an Author of Popular Medical Texts and an Imperial Medical Secretary in Early Modern China
Authors: Aricanli Sare 
Published: March 2021

Abstract
Medical popularisation in late-sixteenth and early-seventeenth-century China has been understood within the context of the state’s retreat from medicine. This article points to ongoing state–societal continuities and thus suggests that the process was more complicated than it had been assumed to be. Analyses with more limited spatial or temporal frames tend to underestimate the extent of continuities forged by societal figures such as Gong Tingxian (fl. 1581–1616), an imperial medical doctor and author of popular medical texts. Gong’s self-fashioning illustrates state–society connections that are also apparent in the reception of his work and in his later legacy. These continuities crossed political, linguistic and cultural lines as Gong’s popular texts were translated to Manchu and housed in a state medical library of the ensuing dynasty. Moreover, Gong’s texts were not only transmitted in China, but reached Japan and Korea, and even found a place within a European collection by the early eighteenth century.
Metrics of sleep apnea severity: beyond the apnea-hypopnea index
Authors: Malhotra Atul , Ayappa Indu , Ayas Najib , Collop Nancy , Kirsch Douglas , Mcardle Nigel , Mehra Reena , Pack Allan I , Punjabi Naresh , White David P , Gottlieb Daniel J 
Published: March 2021

Abstract
Obstructive sleep apnea (OSA) is thought to affect almost 1 billion people worldwide. OSA has well established cardiovascular and neurocognitive sequelae, although the optimal metric to assess its severity and/or potential response to therapy remains unclear. The apnea-hypopnea index (AHI) is well established; thus, we review its history and predictive value in various different clinical contexts. Although the AHI is often criticized for its limitations, it remains the best studied metric of OSA severity, albeit imperfect. We further review the potential value of alternative metrics including hypoxic burden, arousal intensity, odds ratio product, and cardiopulmonary coupling. We conclude with possible future directions to capture clinically meaningful OSA endophenotypes including the use of genetics, blood biomarkers, machine/deep learning and wearable technologies. Further research in OSA should be directed towards providing diagnostic and prognostic information to make the OSA diagnosis more accessible and to improving prognostic information regarding OSA consequences, in order to guide patient care and to help in the design of future clinical trials.
Regional brain metabolism differs between narcolepsy type 1 and idiopathic hypersomnia
Authors: Trotti Lynn Marie , Saini Prabhjyot , Crosson Bruce , Meltzer Carolyn C , Rye David B , Nye Jonathon A 
Published: March 2021

AbstractStudy ObjectivesDaytime sleepiness is a manifestation of multiple sleep and neurologic disorders. Few studies have assessed patterns of regional brain metabolism across different disorders of excessive daytime sleepiness. One such disorder, idiopathic hypersomnia (IH), is particularly understudied.MethodsPeople with IH, narcolepsy (NT1), and non-sleepy controls underwent [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) with electroencephalography (EEG). Participants were instructed to resist sleep and were awoken if sleep occurred. Voxel-wise parametric analysis identified clusters that significantly differed between each pair of groups, with a minimum cluster size of 100 voxels at a cluster detection threshold of p &lt; 0.005. Correlations between glucose metabolism and sleep characteristics were evaluated.ResultsParticipants (77% women) had IH (n = 16), NT1 (n = 14), or were non-sleepy controls (n = 9), whose average age was 33.8 (±10.7) years. Compared to controls, NT1 participants demonstrated hypermetabolism in fusiform gyrus, middle occipital gyrus, superior and middle temporal gyri, insula, cuneus, precuneus, pre- and post-central gyri, and culmen. Compared to controls, IH participants also demonstrated hypermetabolism in precuneus, inferior parietal lobule, superior and middle temporal gyri, and culmen. Additionally, IH participants demonstrated altered metabolism of the posterior cingulate. Most participants fell asleep. Minutes of N1 during uptake was significantly negatively correlated with metabolism of the middle temporal gyrus.ConclusionNT1 and IH demonstrate somewhat overlapping, but distinct, patterns of regional metabolism.
A New Method for Integrating Ecological Niche Modeling with Phylogenetics to Estimate Ancestral Distributions
Authors: Guillory Wilson X , Brown Jason L 
Published: March 2021

Abstract
Ancestral range estimation and projection of niche models into the past have both become common in evolutionary studies where the ancient distributions of organisms are in question. However, these methods are hampered by complementary hurdles: discrete characterization of areas in ancestral range estimation can be overly coarse, especially at shallow timescales, and niche model projection neglects evolution. Phylogenetic niche modeling accounts for both of these issues by incorporating knowledge of evolutionary relationships into a characterization of environmental tolerances. We present a new method for phylogenetic niche modeling, implemented in R. Given past and present climate data, taxon occurrence data, and a time-calibrated phylogeny, our method constructs niche models for each extant taxon, uses ancestral character estimation to reconstruct ancestral niche models, and projects these models into paleoclimate data to provide a historical estimate of the geographic range of a lineage. Models either at nodes or along branches of the phylogeny can be estimated. We demonstrate our method on a small group of dendrobatid frogs and show that it can make inferences given species with restricted ranges and little occurrence data. We also use simulations to show that our method can reliably reconstruct the niche of a known ancestor in both geographic and environmental space. Our method brings together fields as disparate as ecological niche modeling, phylogenetics, and ancestral range estimation in a user-friendly package. [Ancestral range estimation; ancestral state reconstruction; biogeography; Dendrobatidae; ecological niche modeling; paleoclimate; phylogeography; species distribution modeling.]
Comparative efficacy of commercially available deoxynivalenol detoxifying feed additives on growth performance, total tract digestibility of components, and physiological responses in nursery pigs fed diets formulated with naturally contaminated corn1
Authors: Mwaniki Alice W , Buis Quincy R , Trott David , Huber Lee-Anne , Yang Chengbo , Kiarie Elijah G 
Published: March 2021

Abstract
Comparative efficacy of deoxynivalenol (DON) detoxifying feed additives (FA) was evaluated in growth performance (exp. 1) and apparent total tract digestibility (ATTD; exp. 2) nursery pig studies. Six corn–soybean meal-based diets were used: 1) positive control (PC, formulated with &lt;1.5 ppm DON corn), negative control (NC, formulated with 5.5 ppm DON corn), NC + FA1 (clay plus yeast cell wall extract), NC + FA2 (aluminosilicate), NC + FA3 (aluminosilicate plus fungal extract), and NC + FA4 (sodium metabisulfite, SMB). In exp. 1, 144 pigs (body weight [BW], 10.2 ± 0.1kg) were housed (4 pigs/pen), allocated to diets (n = 6) based on BW, and fed for 4-wk. The BW and feed intake were monitored weekly. On d 7, one pig/pen was bled for plasma and euthanized for organ weight and tissue samples. Assayed DON concentration in PC, NC, NC + FA4 was 0.29, 2.86, and 1.21 ppm, respectively. In wk-1, the average daily gain (ADG) of pigs fed NC + FA4 was not different (P &gt; 0.05) to that of pigs fed PC diet but greater (P = 0.01) than for pigs fed NC without or with other FA. Pigs fed NC and NC + FA2 had lower (P = 0.026) average daily feed intake (ADFI) than pigs fed PC and NC + FA3. Pigs fed NC + FA4 had greater (P = 0.003) G:F than pigs fed the other diets. Diets had no effect (P &gt; 0.05) on ADG, ADFI, and G: F after first week, plasma concentration of urea and creatinine or liver and spleen weight. Pigs fed NC diets had greater (P = 0.01) jejunal mRNA expression of superoxide dismutase 1 relative to pigs fed PC or NC plus FA. Jejunal histomorphology and mRNA expression of nutrient transporters, inflammatory cytokines, and tight junction proteins and ceca digesta concentration of short-chain fatty acids were not affected (P &gt; 0.05) by the diet. In exp. 2, 24 barrows (BW 10.2 ± 0.3 kg) were individually placed in metabolism crates and allocated to four diets: PC, NC, NC + FA3, and NC + FA4 (n = 6) containing TiO2 as digestibility marker. Pigs were adjusted to diets for 5 d, followed by a 2-d grab fecal sample collection. Pigs fed PC and NC + FA4 diets had higher ATTD of dry matter, gross energy, and crude protein than NC fed pigs. The FA3 was intermediate in digestibility response. In conclusion, FA containing sequestering component plus fungal extract or SMB in DON-contaminated feed resulted in commensurate nursery pig performance to PC. The tested FA mitigated intestinal oxidative stress through decreased expression of genes for superoxide dismutase.
Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age
Authors: Nwanaji-Enwerem Jamaji C , Laan Lars Van Der , Avakame Elorm F , Scott Kristan A , Burris Heather H , Cardenas Andres 
Published: March 2021

ABSTRACT

Background
Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes—potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang’s mortality score (ZMS).

Methods
Mortality measures were calculated from previously published HumanMethylationEPIC BeadChip data from 44 Brazilian children aged 5–40 months (18 with ZIKV-associated microcephaly; 7 normocephalic, exposed to ZIKV in utero; and 19 unexposed controls). We used linear models adjusted for chronological age, sex, methylation batch and white blood cell proportions to evaluate ZIKV and mortality marker relationships.

Results
We observed significant decreases in GrimAge-component plasminogen activator inhibitor-1 [PAI-1; β = −2453.06 pg/ml, 95% confidence interval (CI) −3652.96, −1253.16, p = 0.0002], and ZMS-site cg14975410 methylation (β = −0.06, 95% CI −0.09, −0.03, p = 0.0003) among children with microcephaly compared to controls. PAI-1 (β = −2448.70 pg/ml, 95% CI −4384.45, −512.95, p = 0.01) and cg14975410 (β = 0.01, 95% CI −0.04, 0.06, p = 0.64) results in comparisons of normocephalic, ZIKV-exposed children to controls were not statistically significant.

Conclusion
Our results suggest that elements of previously-identified adult epigenetic markers of mortality risk are associated with ZIKV-associated microcephaly, a known contributor to pediatric mortality risk. These findings may provide insights for efforts aimed at developing pediatric mortality markers.