bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Rapid Relaxed-Clock Methods for Phylogenomic Dating
Authors: Barba-Montoya Jose , Tao Qiqing , Kumar Sudhir 
Published: November 2021

AbstractRapid relaxed-clock dating methods are frequently applied to analyze phylogenomic data sets containing hundreds to thousands of sequences because of their accuracy and computational efficiency. However, the relative performance of different rapid dating methods is yet to be compared on the same data sets, and, thus, the power and pitfalls of selecting among these approaches remain unclear. We compared the accuracy, bias, and coverage probabilities of RelTime, treePL, and least-squares dating time estimates by applying them to analyze computer-simulated data sets in which evolutionary rates varied extensively among branches in the phylogeny. RelTime estimates were consistently more accurate than the other two, particularly when evolutionary rates were autocorrelated or shifted convergently among lineages. The 95% confidence intervals (CIs) around RelTime dates showed appropriate coverage probabilities (95% on average), but other methods produced rather low coverage probabilities because of overly narrow CIs of time estimates. Overall, RelTime appears to be a more efficient method for estimating divergence times for large phylogenies.
A method for assaying peptide:N-glycanase/N-glycanase 1 activities in crude extracts using anN-glycosylated cyclopeptide
Authors: Hirayama Hiroto , Tachida Yuriko , Seino Junichi , Suzuki Tadashi 
Published: November 2021

AbstractCytosolic peptide: N-glycanase (PNGase; NGLY1), an enzyme responsible for de-glycosylation of N-glycans on glycoproteins, is known to play pivotal roles in a variety of biological processes. In 2012, NGLY1 deficiency, a rare genetic disorder, was reported and since then, more than 100 patients have now been identified worldwide. Patients with this disease exhibit several common symptoms that are caused by the dysfunction of NGLY1. However, correlation between the severity of patient symptoms and the extent of the reduction in NGLY1 activity in these patients remains to be clarified, mainly due to the absence of a facile quantitative assay system for this enzyme, especially in a crude extract as an enzyme source. In this study, a quantitative, non-radioisotope (RI)-based assay method for measuring recombinant NGLY1 activity was established using a BODIPY-labeled asialoglycopeptide (BODIPY-ASGP) derived from hen eggs. With this assay, the activities of 27 recombinant NGLY1 mutants that are associated with the deficiency were examined. It was found that the activities of three (R469X, R458fs and H494fs) out of the 27 recombinant mutant proteins were 30–70% of the activities of wild-type NGLY1. We further developed a method for measuring endogenous NGLY1 activity in crude extracts derived from cultured cells, patients’ fibroblasts, iPS cells or peripheral blood mononuclear cells (PBMCs), using a glycosylated cyclopeptide (GCP) that exhibited resistance to the endogenous proteases in the extract. Our methods will not only provide new insights into the molecular mechanism responsible for this disease but also promises to be applicable for its diagnosis.
Small RNAs encoded by human endogenous retrovirus K overexpressed in PBMCs may contribute to the diagnosis and evaluation of systemic lupus erythematosus as novel biomarkers
Authors: Liu Xinyi , Ding Yanjun , Zheng Xiaoqiu , Huang He , Shi Liyu , Yang Xiaolan , Wei Jing , Li Yang , Kao Wenping , Zhang Fengmin , Qian Jun 
Published: November 2021

Abstract
This study aimed to identify the genes and small RNAs (sRNAs) expressed by the human endogenous retrovirus K (HERV-K) HML2 and their associations with the immune process of systemic lupus erythematosus (SLE). RNA-Seq data including 99 SLE patients and 18 controls (GSE72420) was obtained from the Gene Expression Omnibus. Differentially expressed genes (DEGs) as well as HML2-DEGs between SLE patients and normal controls were identified. Five HML2-DEGs involved in immune-regulating function were identified using weighted gene co-expression network analysis. The associations between these genes and the proportions of immune cells were determined by CIBERSORT. Ten candidate HML2-encoded sRNAs were identified based on specific criteria, and three of them were further validated in SLE patients by qRT-PCR. The diagnostic values of these three sRNAs were evaluated in SLE and lupus nephritis (LN). This study suggested that HML2 genes and their encoded sRNAs might be involved in the immune regulation and progress of SLE. These potential sRNAs might function as regulatory molecules and diagnostic biomarkers of SLE and LN.
Why double ovarian stimulation in an in vitro fertilization cycle is potentially unsafe
Authors: Tocci Angelo 
Published: November 2021

Abstract
The occurrence of two antral follicle recruitment waves in a single inter-ovulatory interval has been detected in ovaries of normal women. This data supports the claim that a double ovarian stimulation in the same cycle may benefit poor responder patients with an increased recovery of mature oocytes and good quality embryos per single cycle. The double stimulation protocol was the object of several published studies in which, surprisingly, the mechanism and the safety of the double stimulation in the same cycle were poorly addressed. We propose that in the double stimulation protocol, the first stimulation impacts more committed oocytes progenitors ready to differentiate into mature oocytes. Conversely, the protracted exposure of developmentally earlier less-committed ovarian stem cells to FSH, which occurs in the double stimulation protocol, impacts the less differentiated stem cells which take longer to differentiate into oocytes. The proposed mechanism has broad implications for the safety of the double stimulation strategy.
Analysis of a model of a natural gas pipeline—a transfer function approach
Authors: Baker Luke , Armbruster Dieter , Scaglione Anna , Platte Rodrigo B 
Published: November 2021

Abstract
A framework for natural gas pipelines is developed in a context similar to the theory of electric transmission lines. The system of semi-linear partial differential equations describing the time-dependent flow of natural gas is linearized around the steady-state flow. Additional approximations lead to a constant coefficient linear system that is equivalent to an electrical circuit that is analytically solvable and admits an ABCD matrix representation of input and output. The sinusoidal steady-state operation of natural gas pipelines is analysed including the distortion of waves. It is shown that the timing of the propagation of phases and other events is accurately represented in the approximation. The quantitative accuracy for flux and gas density of the approximation depending on different operating scenarios and depending on the frequency of the disturbances is documented.
Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Combination Therapy in Patients With Coronavirus Disease 2019 and Primary Antibody Deficiency
Authors: Pulvirenti Federica , Milito Cinzia , Cinetto Francesco , Fernandez Salinas Ane , Terreri Sara , Piano Mortari Eva , Auria Stefania , Soccodato Valentina , Miriam Lichtner , Nicastri Emanuele , Vincenzi Laura , Carsetti Rita , D’Offizi Gianpiero , Quinti Isabella 
Published: November 2021

Abstract

Background
Previous reports highlighted the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs) against coronavirus disease 2019.

Methods
We conducted a prospective study on the clinical outcome and antiviral effects of mAbs added to standard of care therapy in SARS-CoV-2-infected patients with primary antibody defects.

Results
Median time of SARS-CoV-2 quantitative polymerase chain reaction (qPCR) positivity was shorter in 8 patients treated with mAbs (22 days) than in 10 patients treated with standard of care therapy only (37 days, P=.026). Median time of SARS-CoV-2 qPCR positivity from mAb administration was 10 days.

Conclusions
The SARS-CoV-2 mAbs treatment was effective and well tolerated in patients with primary antibody defects.
Simulating grass phenotypic plasticity as an emergent property of growth zone responses to carbon and nitrogen metabolites
Authors: Gauthier Marion , Barillot Romain , Andrieu Bruno 
Published: November 2021

Abstract
Phenotypic plasticity—the ability of one genotype to produce different phenotypes depending on growth conditions—is a core aspect of the interactions between plants and the environment. The model CN-Wheat simulates the functioning of a grass culm and the construction of traits as properties emerging from the feedback loops between morphogenesis, the environmental factors and source–sink activities. The plant is seen as a self-regulated system where leaf growth is driven by carbon and nitrogen metabolism within each leaf and by coordination rules between successive leaves. Here, we investigated the ability of this approach to simulate realistic grass phenotypic plasticity and explored plant behaviour in a wide range of growth conditions. The growth of grass monoculms, with traits similar to a wheat stem, was simulated for highly contrasting conditions of soil nitrogen concentration, incident light and planting density. The monoculms were kept vegetative and produced ~15 mature leaves at the end of the simulations. The model simulated highly contrasting phenotypes. Overall, the simulated trends and the magnitude of responses of leaf and plant traits to growth conditions were consistent with the literature on grass species. These results demonstrate that integrating plant functioning at organ scale can simulate, as an emergent property, the phenotypic plasticity of plants in contrasting light and nitrogen conditions. Besides, simulations of the internal variables of plants gave access to plant trophic status across plant ontogeny and plant environments. In conclusion, this framework is a significant step towards better integration of the genotype–environment interactions.
BSAC Vanguard Series: AMR diagnostics in light of evolving technologies and access in low- and middle-income countries
Authors: Berman Daniel , Neale Ruth 
Published: November 2021

Abstract
Rapid point-of-care tests are needed to control antimicrobial consumption, as recognized by the Longitude Prize. However, in addition to bacterial pathogen identification, clinicians need more information, such as which antimicrobial will be effective and how severe the infection really is. This technology is beginning to emerge, but both economic and technological challenges remain before it can be delivered, especially in low- and middle-income countries. This article outlines these challenges and how we might overcome them.
In vitro activity of the orally bioavailable ceftibuten/VNRX-7145 (VNRX-5236 etzadroxil) combination against a challenge set of Enterobacterales pathogens carrying molecularly characterized β-lactamase genes
Authors: Mendes Rodrigo E , Rhomberg Paul R , Watters Amy A , Castanheira Mariana 
Published: November 2021

Abstract

Objectives
This study assessed the activity of ceftibuten, ceftibuten combined with the active form (VNRX-5236) of the β-lactamase inhibitor VNRX-7145 and comparators against a challenge set of Gram-negative pathogens.

Methods
Two hundred and five Enterobacterales carrying plasmid AmpC (53 isolates), ESBL (50), KPC (50), OXA-48-like (49) or OXA-48-like with KPC (3) encoding genes were selected. Susceptibility was determined by broth microdilution. VNRX-5236 and avibactam were tested at a fixed concentration of 4 mg/L.

Results
Ceftibuten/VNRX-5236 (MIC50/90 0.12/1 mg/L) MIC values were 256-fold lower than those of ceftibuten (MIC50/90 32/256 mg/L) for all Enterobacterales and 2- to 4-fold lower than those of ceftazidime/avibactam (MIC50/90 0.5/2 mg/L). For isolates producing a plasmid-encoded AmpC, VNRX-5236 decreased ceftibuten MIC (MIC50/90 0.12/1 mg/L) by at least 512-fold compared with ceftibuten (MIC50/90 128/&gt;256 mg/L). Ceftibuten/VNRX-5236 (MIC50/90 0.06/0.12 mg/L) and meropenem (MIC50/90 ≤0.03/0.06 mg/L; 100% susceptible) showed comparable activities against ESBL isolates and these agents had MIC90 values 4- to 8-fold lower than that of ceftazidime/avibactam (MIC50/90 0.25/0.5 mg/L; 100% susceptible). Ceftibuten/VNRX-5236 (MIC50/90 0.12/0.5 mg/L) had the lowest MIC for KPC producers, followed by ceftazidime/avibactam (MIC50/90 2/4 mg/L; 98.0% susceptible). The same MIC90 values were obtained for ceftibuten/VNRX-5236 (MIC50/90 0.25/1 mg/L) and ceftazidime/avibactam (MIC50/90 1/1 mg/L; 100.0% susceptible) for isolates carrying blaOXA-48-like. VNRX-5236 decreased the ceftibuten MIC at least 16-fold for three isolates carrying blaOXA-48-like and blaKPC.

Conclusions
VNRX-5236 rescued the in vitro activity of ceftibuten against Enterobacterales carrying common serine β-lactamases, including ESBL, AmpC and the KPC and OXA-48-like carbapenemases. Ceftibuten/VNRX-5236 may have potential as an oral treatment for infections caused by resistant Enterobacterales, while sparing carbapenems.
Comparative Evaluation of Two NGAL Automated Immunoassays in Urine and Plasma
Authors: Whitehead Simon J , Chadwick Katie , Ford Clare , Giri Ramesh , Luckraz Heyman , Gama Rousseau 
Published: November 2021

Abstract

Background
Acute kidney injury (AKI), a frequent and serious complication of hospitalized patients, is associated with increased mortality and morbidity. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for the early identification of AKI. We report a comparative laboratory verification of the Abbott Diagnostics (ARCHITECT® urine NGAL) and BioPorto Diagnostics (NGAL TestTM) assays including an assessment of the Abbott assay’s performance in EDTA plasma.

Methods
Intra-/interbatch imprecision, linearity, recovery, and limit of quantitation (LoQ) were assessed and an interassay comparison performed (n = 51). Between-laboratory agreement was assessed against other laboratories using the Abbott (n = 48) and BioPorto (n = 94) assays. Plasma NGAL (pNGAL) levels were measured in non-AKI patients with a range of estimated glomerular filtration rates (n = 80).

Results
Coefficients of variation (CVs) for intra- and interbatch imprecision were 0.7%–12.4% and 1.9%–27.5% for the BioPorto assay, respectively, and 1.4%–6.3%/3.4%–6.8%, respectively, for the Abbott assay. The BioPorto assay exhibited a higher LoQ (27.5 ng/mL vs 1.2 ng/mL). Both assays were linear over the range 5–6000 ng/mL. Recovery of recombinant NGAL was 113.1 ± 7.1% and 96.5 ± 7.8% for the Abbott and BioPorto assays, respectively. On average, the Abbott assay gave results 9.2% lower than the BioPorto assay. Mean differences of 0.2% (Abbott) and 20.2% (BioPorto) were observed in the between-laboratory comparison. In patients without AKI, pNGAL levels were inversely proportional to eGFR.

Conclusions
Performance of the Abbott and BioPorto assays was similar although the latter performed less well at lower NGAL concentrations. The Abbott assay tended to yield lower results, exhibited a lower LoQ and over-recovered NGAL. Although only Conformité Européenne-marked and marketed for use in urine, the Abbott assay demonstrated equivalent performance to the BioPorto assay with EDTA plasma.
Understanding enterprise data warehouses to support clinical and translational research: enterprise information technology relationships, data governance, workforce, and cloud computing
Authors: Knosp Boyd M , Craven Catherine K , Dorr David A , Bernstam Elmer V , Campion Thomas R 
Published: November 2021

Abstract

Objective
Among National Institutes of Health Clinical and Translational Science Award (CTSA) hubs, effective approaches for enterprise data warehouses for research (EDW4R) development, maintenance, and sustainability remain unclear. The goal of this qualitative study was to understand CTSA EDW4R operations within the broader contexts of academic medical centers and technology.

Materials and Methods
We performed a directed content analysis of transcripts generated from semistructured interviews with informatics leaders from 20 CTSA hubs.

Results
Respondents referred to services provided by health system, university, and medical school information technology (IT) organizations as “enterprise information technology (IT).” Seventy-five percent of respondents stated that the team providing EDW4R service at their hub was separate from enterprise IT; strong relationships between EDW4R teams and enterprise IT were critical for success. Managing challenges of EDW4R staffing was made easier by executive leadership support. Data governance appeared to be a work in progress, as most hubs reported complex and incomplete processes, especially for commercial data sharing. Although nearly all hubs (n = 16) described use of cloud computing for specific projects, only 2 hubs reported using a cloud-based EDW4R. Respondents described EDW4R cloud migration facilitators, barriers, and opportunities.

Discussion
Descriptions of approaches to how EDW4R teams at CTSA hubs work with enterprise IT organizations, manage workforces, make decisions about data, and approach cloud computing provide insights for institutions seeking to leverage patient data for research.

Conclusion
Identification of EDW4R best practices is challenging, and this study helps identify a breadth of viable options for CTSA hubs to consider when implementing EDW4R services.
Molecular Identification and Functional Characterization of Vitellogenin Receptor From Harmonia axyridis (Coleoptera: Coccinellidae)
Authors: Han Hui , Han ShiPeng , Qin QiuJu , Chen Jie , Wang Da , He Yunzhuan 
Published: November 2021

Abstract
Vitellogenin receptors (VgRs) have vital roles in reproduction by mediating endocytosis of the vitellogenin (Vg) in oviparous insects. Same as most insect species that possess only one VgR, in this study, a single VgR mRNA (HmVgR) was identified in an important natural enemy ladybeetle, Harmonia axyridis (Pallas). The open reading frame of HmVgR was 5,340 bases encoding a protein of 1,779 amino acids. Bioinformatic analyses showed that HmVgR had conserved domain motifs of low-density lipoprotein receptor family. Based on phylogenetic analysis, HmVgR had highly homologous within the Coleoptera. The transcriptional level of HmVgR was initially detected in the newly emerged female adults, gradually increased from day 3 to day 9, peaked on day 13, and then sharply decreased on day 15. Similar to most insects, HmVgR was expressed specifically in ovarian tissue. Moreover, RNA interference (RNAi) clearly decreased the transcription levels of HmVgR, which blocked the deposition of yolk protein in the ovaries, shortened the ovarian length, and led to negative impacts on reproductive-related parameters (i.e., prolonged preoviposition periods, reduced spawning and depressed hatchability). In sum, these results indicated that HmVgR may be critical for yolk protein deposition of oocytes and can play a key role in reproduction of female adults of H. axyridis. Our results provide conclusive proof for the important roles of HmVgR in fecundity, and establish a basis for further research on its interaction with vitellogenin.
Reproduction of Black Soldier Fly (Diptera: Stratiomyidae) Under Different Adult Densities and Light Regimes
Authors: Liu Zhongyi , Najar-Rodriguez Adriana J , Morel Patrick C H , Minor Maria A 
Published: November 2021

Abstract
The black soldier fly (BSF) Hermetia illucens (L.) (Diptera: Stratiomyidae) has been recognized as a promising insect species for sustainable management of organic waste and by-products. Indoor breeding of BSF with artificial lighting has been proved successful, but efforts are still needed to optimize BSF reproductive output. Increasing adult density seems an option to exploit space, whereas decreasing artificial lighting duration may reduce unnecessary power consumption. This study aimed at investigating the effects of adult density (10, 25, and 50 pairs per 30 × 30 × 30 cm cage; i.e., 370, 926, and 1,852 pairs/m3), light regime (8:16, 12:12, and 16:8 [L:D] h), and their possible interactions, on some BSF life history traits relevant to reproduction. The results show that the overall BSF reproductive output increased with increasing adult density but was not affected by light regimes per se. With the highest BSF adult density tested, an average of more than 20,000 neonate larvae were produced from a cage within 10 d. At this density, increasing photoperiod increased neonate production, but also decreased the number of neonates per watt used for artificial illumination. The temporal oviposition patterns, mean individual female reproductive output, mating success, egg hatching rate, and insect survival rate were not affected by adult density or light regime as simple effects. However, the interaction between adult density and light regime was significant for the first oviposition peak, mean individual female reproductive output, and insect survival rate. The possible mechanisms behind our results are discussed.
Seasonal Distribution of Halyomorpha halys (Hemiptera: Pentatomidae) Captures in Woods-to-Orchard Pheromone Trap Transects in Virginia
Authors: Hadden Whitney T , Nixon Laura J , Leskey Tracy C , Bergh J Christopher 
Published: November 2021

Abstract
The invasive brown marmorated stink bug, Halyomorpha halys (Stål), is a pest of numerous economically important crops in the USA. In the Mid-Atlantic region, it is a significant, direct pest in tree fruit orchards, many of which are bordered by woodlots containing a variety of its deciduous tree and shrub hosts. During the growing season, H. halys moves from woodland habitats into crops, but seasonal changes in its relative abundance between these adjacent habitats have not been examined. Using linear transects of six pheromone-baited pyramid traps that extended from 100 m into the interior of woodlots to 100 m into the interior of adjacent commercial apple orchards in Virginia, spatiotemporal changes in H. halys captures were measured during three growing seasons. Captures of H. halys adults and nymphs were recorded weekly from May through October, and annual data were separated into early, mid, and late-season captures. Only adults were captured during the early season, and there was no indication of a spatial trend in captures across traps in the transects among years. Beginning in mid-season and becoming increasingly apparent by late season, captures of H. halys adults and nymphs tended to become most frequent in traps at the woods and orchard edges and at 50 m into the orchard interior. These findings conform with and expand upon previous research documenting an edge effect for H. halys relative abundance and can inform and support the optimization of perimeter-based management strategies for H. halys in Mid-Atlantic apple orchards.
Long-Term Care Services and Inter-American Human Rights in Argentina
Authors: Dabove Maria Isolina 
Published: November 2021

Abstract
Currently, long-term care services are considered socially accepted alternatives that meet the need for assistance and accommodation of older persons, especially in situations of dependency. Their design and expansion are conditioned by a new phenomenon: global aging and the multi-generational society. This article looks at the current situation of long-term care services in Argentina. It identifies the new standards of Elder Law set by the Inter American Convention on the Protecting of Human Rights of Older Persons and contrasts them with the Argentinian legal system on long-term care. It then analyses the clash between the way these services are currently provided and the new human rights approach, and considers the pioneering Argentinian judicial criteria concerning long-term care facilities. Finally, it points out the main aspects that need to be considered in order to implement the necessary social change and legal reform in Argentina.