bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term physicochemical stability of acyclovir 5 mg/mL solution stored in polypropylene bags as a simulated hospital stock preparation
Authors: Legeron Rachel , Bougueon Guillaume , Berroneau Aude , De-Germay Sybille , Bernadou Jean-Marc , Djabarouti Sarah , Crauste-Manciet Sylvie , Xuereb Fabien
Published: February 2021

Purpose

To investigate the long-term chemical and physical stability of 5-mg/mL acyclovir solution in polypropylene bags stored at 5°C ± 3°C for 2 months in order to determine the feasibility of batch production by a centralized intravenous additive service.

Methods

Eight empty 100-mL polypropylene bags (bags A) and 8 empty 250-mL bags (bags B) were respectively filled with 60 mL and 200 mL of 5-mg/mL acyclovir and 0.9% sodium chloride injection (NaCl) under aseptic conditions through a semiautomated manufacturing process and vacuum packed before storage at 5°C ± 3°C. Four bags A and 4 bags B were tested for chemical stability via a stability-indicating high-performance liquid chromatography (HPLC) method immediately after preparation (time 0) and after 7, 14, 21, 28, 35, 42, and 63 days. Samples for microbiological assay were collected on days 0 and 63 from 4 bags A and 4 bags B immediately after breaking the vacuum. Osmolality, pH, and physical stability were assessed by visual examination, Subvisible particle counting was performed on 6 additional bags (3 each of bags A and B).

Results

Mean percentage loss of acyclovir relative to the mean experimental concentration at time 0 was below 5% over the 63-day study period.. No significant differences of pH, no change in color and no precipitate were observed during the study. Subvisible particle counts were compliant with European Pharmacopoeia requirements. Acyclovir solutions remained sterile over the 63 days of the study.

Conclusion

Extemporaneously prepared acyclovir 5 mg/mL solutions in 0.9% NaCl stored in polypropylene bags were chemically and physically stable over 63 days when stored at 5°C ± 3°C.
Moral worth and accidentally right actions
Authors: Coates Allen
Published: February 2021

The reasons view holds that morally worthy actions are right actions motivated by the reasons that make them right. Opponents object that such actions are only accidentally right, and it is widely held that morally worthy actions cannot be accidentally right. My aim here is to defend the reasons view from this objection by considering conditional reasons. Once these reasons are in view, actions motivated by the reasons that make them right will no longer appear accidentally right.

Keywords: Moral worth; Moral reasons; Conditional reasons
Three founding ancestral genomes involved in the origin of sugarcane
Authors: Pompidor Nicolas , Charron Carine , Hervouet Catherine , Bocs Stéphanie , Droc Gaëtan , Rivallan Ronan , Manez Aurore , Mitros Therese , Swaminathan Kankshita , Glaszmann Jean-Christophe , Garsmeur Olivier , D’Hont Angélique
Published: February 2021

Background and Aims

Modern sugarcane cultivars (Saccharum spp.) are high polyploids, aneuploids (2n = ~12x = ~120) derived from interspecific hybridizations between the domesticated sweet species Saccharum officinarum and the wild species S. spontaneum.

Methods

To analyse the architecture and origin of such a complex genome, we analysed the sequences of all 12 hom(oe)ologous haplotypes (BAC clones) from two distinct genomic regions of a typical modern cultivar, as well as the corresponding sequence in Miscanthus sinense and Sorghum bicolor, and monitored their distribution among representatives of the Saccharum genus.

Key Results

The diversity observed among haplotypes suggested the existence of three founding genomes (A, B, C) in modern cultivars, which diverged between 0.8 and 1.3 Mya. Two genomes (A, B) were contributed by S. officinarum; these were also found in its wild presumed ancestor S. robustum, and one genome (C) was contributed by S. spontaneum. These results suggest that S. officinarum and S. robustum are derived from interspecific hybridization between two unknown ancestors (A and B genomes). The A genome contributed most haplotypes (nine or ten) while the B and C genomes contributed one or two haplotypes in the regions analysed of this typical modern cultivar. Interspecific hybridizations likely involved accessions or gametes with distinct ploidy levels and/or were followed by a series of backcrosses with the A genome. The three founding genomes were found in all S. barberi, S. sinense and modern cultivars analysed. None of the analysed accessions contained only the A genome or the B genome, suggesting that representatives of these founding genomes remain to be discovered.

Conclusions

This evolutionary model, which combines interspecificity and high polyploidy, can explain the variable chromosome pairing affinity observed in Saccharum. It represents a major revision of the understanding of Saccharum diversity.
Blinking statistics and molecular counting in direct stochastic reconstruction microscopy (dSTORM)
Authors: Patel Lekha , Williamson David , Owen Dylan M. , Cohen Edward A. K.
Published: February 2021

Motivation

Many recent advancements in single-molecule localization microscopy exploit the stochastic photoswitching of fluorophores to reveal complex cellular structures beyond the classical diffraction limit. However, this same stochasticity makes counting the number of molecules to high precision extremely challenging, preventing key insight into the cellular structures and processes under observation.

Results

Modelling the photoswitching behaviour of a fluorophore as an unobserved continuous time Markov process transitioning between a single fluorescent and multiple dark states, and fully mitigating for missed blinks and false positives, we present a method for computing the exact probability distribution for the number of observed localizations from a single photoswitching fluorophore. This is then extended to provide the probability distribution for the number of localizations in a direct stochastic optical reconstruction microscopy experiment involving an arbitrary number of molecules. We demonstrate that when training data are available to estimate photoswitching rates, the unknown number of molecules can be accurately recovered from the posterior mode of the number of molecules given the number of localizations. Finally, we demonstrate the method on experimental data by quantifying the number of adapter protein linker for activation of T cells on the cell surface of the T-cell immunological synapse.

Availability and implementation

Software and data available at https://github.com/lp1611/mol_count_dstorm.

Supplementary information

Supplementary data are available at Bioinformatics online.
CCmed: cross-condition mediation analysis for identifying replicable trans-associations mediated by cis-gene expression
Authors: Yang Fan , Gleason Kevin J. , Wang Jiebiao , Duan Jubao , He Xin , Pierce Brandon L. , Chen Lin S.
Published: February 2021

Motivation

Trans-acting expression quantitative trait loci (eQTLs) collectively explain a substantial proportion of expression variation, yet are challenging to detect and replicate since their effects are often individually weak. A large proportion of genetic effects on distal genes are mediated through cis-gene expression. Cis-association (between SNP and cis-gene) and gene-gene correlation conditional on SNP genotype could establish trans-association (between SNP and trans-gene). Both cis-association and gene-gene conditional correlation have effects shared across relevant tissues and conditions, and trans-associations mediated by cis-gene expression also have effects shared across relevant conditions.

Results

We proposed a Cross-Condition Mediation analysis method (CCmed) for detecting cis-mediated trans-associations with replicable effects in relevant conditions/studies. CCmed integrates cis-association and gene-gene conditional correlation statistics from multiple tissues/studies. Motivated by the bimodal effect-sharing patterns of eQTLs, we proposed two variations of CCmed, CCmedmost and CCmedspec for detecting cross-tissue and tissue-specific trans-associations, respectively. We analyzed data of 13 brain tissues from the Genotype-Tissue Expression (GTEx) project, and identified trios with cis-mediated trans-associations across brain tissues, many of which showed evidence of trans-association in two replication studies. We also identified trans-genes associated with schizophrenia loci in at least two brain tissues.

Availability and implementation

CCmed software is available at http://github.com/kjgleason/CCmed.

Supplementary information

Supplementary data are available at Bioinformatics online.
Trading Animal Lives: Ten Tricky Issues on the Road to Protecting Commodified Wild Animals
Authors: Macdonald David W , Harrington Lauren A , Moorhouse Tom P , D'Cruze Neil
Published: February 2021

Wildlife commodification can generate benefits for biodiversity conservation, but it also has negative impacts; overexploitation of wildlife is currently one of the biggest drivers of vertebrate extinction risk. In the present article, we highlight 10 issues that in our experience impede sustainable and humane wildlife trade. Given humanity's increasing demands on the natural world we question whether many aspects of wildlife trade can be compatible with appropriate standards for biodiversity conservation and animal welfare, and suggest that too many elements of wildlife trade as it currently stands are not sustainable for wildlife or for the livelihoods that it supports. We suggest that the onus should be on traders to demonstrate that wildlife use is sustainable, humane, and safe (with respect to disease and invasion risk), rather than on conservationists to demonstrate it is not, that there is a need for a broad acceptance of responsibility and, ultimately, widespread behavior change. We urge conservationists, practitioners, and others to take bold, progressive steps to reach consensus and action.
Impact of neoadjuvant chemotherapy on thrombus viability in patients with Wilms tumour and caval extension: systematic review with meta-analysis
Authors: Boam T D , Gabriel M , Shukla R , Losty P D
Published: February 2021

Background

Inferior vena cava (IVC) tumour thrombus in children with Wilms tumour is typically managed with neoadjuvant chemotherapy with the intention of achieving thrombus regression in order to minimize the risks associated with complex vascular surgery.

Methods

A systematic review of Medline and Embase databases was undertaken to identify all eligible studies with reference to thrombus viability in Wilms tumour index cases with caval/cardiac extension. A meta-analysis of proportions was utilized for pooled thrombus viability data across studies. Logistic regression was used to analyse the relationship between thrombus viability and duration of chemotherapy.

Results

Thirty-five eligible observational studies and case reports met inclusion criteria describing a total of 236 patients with thrombus viability data. The pooled proportion of patients with viable tumour thrombus after neoadjuvant chemotherapy was 0.53 (0.43–0.63). Logistic regression analysis of 54 patients receiving either a standard (4–6 weeks) or extended (more than 6 weeks) course of neoadjuvant chemotherapy resulted in an odds ratio of 3.14 (95 per cent c.i. 0.97 to 10.16), P = 0.056, with extended course therapy trending towards viable tumour thrombus.

Conclusion

Preoperative chemotherapy is successful in achieving non-viability of caval and cardiac thrombi in around 50 per cent of children, without added benefit from extended cycles of neoadjuvant chemotherapy. Risks versus benefits of extirpative vascular surgery must be considered, therefore, for these high-risk patients.
MALAT1 Maintains the Intestinal Mucosal Homeostasis in Crohn’s Disease via the miR-146b-5p-CLDN11/NUMB Pathway
Authors: Li Ying , Zhu Liguo , Chen Peng , Wang Ying , Yang Guang , Zhou Gaoshi , Li Li , Feng Rui , Qiu Yun , Han Jing , Chen Baili , He Yao , Zeng Zhirong , Chen Minhu , Zhang Shenghong
Published: February 2021

Background and Aims

Intestinal homeostasis disorder is critical for developing Crohn’s disease [CD]. Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs [lncRNAs] in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 [MALAT1] modulated CD and consequent disruption of intestinal homeostasis.

Methods

Microarray analyses on intestinal mucosa of CD patients and controls were performed to identify dysregulated lncRNAs. MALAT1 expression was investigated via qRT-PCR and its distribution in intestinal tissues was detected using BaseScope. Intestines from MALAT1 knockout mice with colitis were investigated using histological, molecular, and biochemical approaches. Effects of intestinal epithelial cells, transfected with MALAT1 lentiviruses and Smart Silencer, on monolayer permeability and apical junction complex [AJC] proteins were analysed. MiR-146b-5p was confirmed as a critical MALAT1 mediator in cells transfected with miR-146b-5p mimic/inhibitor and in colitis mice administered agomir-146b-5p/antagomir-146b-5p. Interaction between MALAT1 and miR-146b-5p was predicted via bioinformatics and validated using Dual-luciferase reporter assay and Ago2-RIP.

Results

MALAT1 was aberrantly downregulated in the intestine mucosa of CD patients and mice with experimental colitis. MALAT1 knockout mice were hypersensitive to DSS-induced experimental colitis. MALAT1 regulated the intestinal mucosal barrier and regained intestinal homeostasis by sequestering miR-146b-5p and maintaining the expression of the AJC proteins NUMB and CLDN11.

Conclusions

Downregulation of MALAT1 contributed to the pathogenesis of CD by disrupting AJC. Thus, a specific MALAT1-miR-146b-5p-NUMB/CLDN11 pathway that plays a vital role in maintaining intestinal mucosal homeostasis may serve as a novel target for CD treatment.
Early cardiac involvement in patients with acute COVID-19 infection identified by multiparametric cardiovascular magnetic resonance imaging
Authors: Chen Bing-Hua , Shi Nan-Nan , Wu Chong-Wen , An Dong-Aolei , Shi Yu-Xin , Wesemann Luke D , Hu Jiani , Xu Jian-Rong , Shan Fei , Wu Lian-Ming
Published: February 2021

Aims

In order to determine acute cardiac involvement in patients with COVID-19, we quantitatively evaluated tissue characteristics and mechanics by non-invasive cardiac magnetic resonance (CMR) in a cohort of patients within the first 10 days of the onset of COVID symptoms.

Methods and results

Twenty-five patients with reverse transcription polymerase chain reaction confirmed COVID-19 and at least one marker of cardiac involvement [cardiac symptoms, abnormal electrocardiograph (ECG), or abnormal cardiac biomarkers] and 25 healthy age- and gender-matched control subjects were recruited to the study. Patients were divided into those with elevated (n = 8) or normal TnI (n = 17). There were significant differences in global longitudinal strain among patients who were positive and negative for hs-TnI, and controls [−12.3 (−13.3, −11.5)%, −13.1 (−14.2, −9.8)%, and −15.7 (−18.3, −12.7)%, P = 0.004]. Native myocardial T1 relaxation times in patients with positive and negative hs-TnI manifestation (1169.8 ± 12.9 and 1113.2 ± 31.2 ms) were significantly higher than the normal (1065 ± 57 ms) subjects, respectively (P < 0.001). The extracellular volume (ECV) of patients who were positive and negative for hs-TnI was higher than that of the normal controls [32 (31, 33)%, 29 (27, 30)%, and 26 (24, 27.5)%, P < 0.001]. In our study, quantitative T2 mapping in patients who were positive and negative for hs-TnI [51 (47.9, 52.8) and 48 (47, 49.4) ms] was significantly higher than the normal [42 (41, 45.2) ms] subjects (P < 0.001).

Conclusion

In patients with early-stage COVID-19, myocardial oedema, and functional abnormalities are a frequent finding, while irreversible regional injury such as necrosis may be infrequent.
Diagnostic uncertainty in primary care: what is known about its communication, and what are the associated ethical issues?
Authors: Cox Caitríona L , Miller Benjamin M , Kuhn Isla , Fritz Zoë
Published: February 2021

Background

Diagnostic uncertainty (DU) in primary care is ubiquitous, yet no review has specifically examined its communication, or the associated ethical issues.

Objectives

To identify what is known about the communication of DU in primary care and the associated ethical issues.

Methods

Systematic review, critical interpretive synthesis and ethical analysis of primary research published worldwide. Medline, Embase, Web of Science and SCOPUS were searched for papers from 1988 to 2020 relating to primary care AND diagnostic uncertainty AND [ethics OR behaviours OR communication]. Critical interpretive synthesis and ethical analysis were applied to data extracted.

Results

Sixteen papers met inclusion criteria. Although DU is inherent in primary care, its communication is often limited. Evidence on the effects of communicating DU to patients is mixed; research on patient perspectives of DU is lacking. The empirical literature is significantly limited by inconsistencies in how DU is defined and measured. No primary ethical analysis was identified; secondary analysis of the included papers identified ethical issues relating to maintaining patient autonomy in the face of clinical uncertainty, a gap in considering the direct effects of (not) communicating DU on patients, and considerations regarding over-investigation and justice.

Conclusions

This review highlights significant gaps in the literature: there is a need for explicit ethical and patient-centred empirical analyses on the effects of communicating DU, and research directly examining patient preferences for this communication. Consensus on how DU should be defined, and greater research into tools for its measurement, would help to strengthen the empirical evidence base.
Supply-side factors influencing informal payment for healthcare services in Tanzania
Authors: Binyaruka Peter , Balabanova Dina , McKee Martin , Hutchinson Eleanor , Andreoni Antonio , Ramesh Mary , Angell Blake , Kapologwe Ntuli A , Mamdani Masuma
Published: February 2021

Informal payments for healthcare are widespread in sub-Saharan Africa. They are often regressive, potentially limiting access to quality healthcare, particularly for the most vulnerable, and can have catastrophic consequences for households. Yet there is little empirical research that uses theory-driven hypotheses to explore what influences informal payments and, especially, from health workers’ perspectives. Consequently, we have explored the characteristics of health workers and facilities influencing informal payments in Tanzania, examining two hypotheses: health workers with power and position in the system are more likely to receive informal payments, and transparency and accountability measures can be bypassed by those who can game the system. We conducted a cross-sectional survey of 432 health workers from 42 public health facilities (hospitals and health centres) in 12 district councils from Pwani and Dar es Salam regions in Tanzania. Our dependent variable was whether the health worker has ever asked for or been given informal payments or bribes, while explanatory variables were measured at the individual and facility level. Given the hierarchical structure of the data, we used a multilevel mixed-effect logistic regression to explore the determinants. Twenty-seven percent of 432 health workers ever engaged in informal payment. This was more common amongst younger (<35 years) health workers and those higher in the hierarchy (specialists and heads of departments). Those receiving entitlements and benefits in a timely manner and who were subject to continued supervision were significantly less likely to receive informal payments. The likelihood of engaging in informal payments varied among health workers, consistent with our first hypothesis, but evidence on the second hypothesis remains mixed. Thus, policy responses should address both individual and system-level factors, including ensuring adequate and progressive health sector financing, better and timely remuneration of frontline public health providers, and enhanced governance and supervision.
How many modes can a mixture of Gaussians with uniformly bounded means have?
Authors: Kashyap Navin , Krishnapur Manjunath
Published: February 2021

We show, by an explicit construction, that a mixture of univariate Gaussian densities with variance $1$ and means in $[-A,A]$ can have $\varOmega (A^2)$ modes. This disproves a recent conjecture of Dytso et al. (2020, IEEE Trans. Inf. Theory, 66, 2006–2022) who showed that such a mixture can have at most $O(A^{2})$ modes and surmised that the upper bound could be improved to $O(A)$. Our result holds even if an additional variance constraint is imposed on the mixing distribution. Extending the result to higher dimensions, we exhibit a mixture of Gaussians in ${\mathbb{R}}^{d}$, with identity covariances and means inside ${[-A,A]}^{d}$, that has $\varOmega (A^{2d})$ modes.
Paediatric Common Infections Pathways: improving antimicrobial stewardship and promoting ambulation for children presenting with common infections to hospitals in the UK and Ireland
Authors: Horner Carolyne , Cunney Robert , Demirjian Alicia , Doherty Conor , Green Helen , Mathai Mathew , McMaster Paddy , Munro Alasdair , Paulus Stéphane , Roland Damian , Patel Sanjay
Published: February 2021

Paediatric common infection pathways have been developed in collaboration between the BSAC and national paediatric groups, addressing the management of cellulitis, lymphadenitis/lymph node abscess, pneumonia/pleural empyema, pyelonephritis, tonsillitis/peritonsillar abscess, otitis media/mastoiditis, pre-septal/post-septal (orbital) cellulitis, and meningitis. Guidance for the management of a child presenting with a petechial/purpuric rash and the infant under 3 months of age with fever is also provided. The aim of these pathways is to support the delivery of high-quality infection management in children presenting to a hospital. The pathways focus on diagnostic approaches, including the recognition of red flags suggesting complex or severe infection requiring urgent intervention, approaches to antimicrobial stewardship (AMS) principles and guidance on safe and timely ambulation aligned with good practice of outpatient parenteral antimicrobial therapy (OPAT).
Practical applications of whey protein in supporting skeletal muscle maintenance, recovery, and reconditioning
Authors: Arentson-Lantz Emily J , Kilroe Sean
Published: February 2021

Like humans, many companion animals experience a gradual decline in skeletal muscle mass and function during later years of life. This process, analogous to sarcopenia in humans, increases risk for morbidity and mortality. Periods of reduced activity due to injury or illness, followed by an incomplete recovery, can accelerate the loss of muscle mass and function. Emerging research from human studies suggests that moderate amounts of high-quality protein may attenuate the loss of muscle, while preventing accumulation of fat during periods of disuse. Whey protein is a consumer-friendly and readily available source of high-quality protein. It supports skeletal muscle maintenance during normal aging and may also provide anabolic support during periods of illness, injury, and recovery. Ongoing research efforts continue to refine our understanding of how protein quality, quantity, and meal timing can be optimized to support retention of muscle mass and function during aging. Priority research areas include supplementation with high-quality protein during illness/injury to stimulate anabolism by targeting molecular mechanisms that regulate skeletal muscle metabolism.
A Hybrid Artificial Intelligence Model forAeneolamia varia(Hemiptera: Cercopidae) Populations in Sugarcane Crops
Authors: Figueredo Luis , Villa-Murillo Adriana , Colmenarez Yelitza , Vásquez Carlos
Published: February 2021

Sugarcane spittlebugs are considered important pests in sugarcane crops ranging from the southeastern United States to northern Argentina. To evaluate the effects of climate variables on adult populations of Aeneolamia varia (Fabricius) (Hemiptera: Cercopidae), a 3-yr monitoring study was carried out in sugarcane fields at week-long intervals during the rainy season (May to November 2005–2007). The resulting data were analyzed using the univariate Forest-Genetic method. The best predictive model explained 75.8% variability in physiological damage threshold. It predicted that the main climatic factors influencing the adult population would be, in order of importance, evaporation; evapotranspiration by 0.5; evapotranspiration, cloudiness at 2:00 p.m.; average sunshine and relative humidity at 8:00 a.m. The optimization of the predictive model established that the lower and upper limits of the climatic variables produced a threshold in the population development rate of 184 to 267 adult insects under the agroecological conditions of the study area. These results provide a new perspective on decision-making in the preventive management of A. varia adults in sugarcane crops.
Relative Roles of Blow Flies (Diptera: Calliphoridae) and Invasive Fire Ants (Hymenoptera: Formicidae:Solenopsisspp.) in Carrion Decomposition
Authors: De Jong Grant D , Meyer Florencia , Goddard Jerome
Published: February 2021

Fire ants (Solenopsis spp.) have increasingly been reported from carrion in the southeastern United States and are now a part of the normal succession community. There have been previous observations of these ants altering carrion and preying on other carrion-attendant fauna; however, the overall effects of these activities on carrion decomposition rates, community composition, and blow fly larval development are poorly understood. Alteration of these ecological processes by fire ants could affect the forensic interpretation of entomological data. We conducted a study in Mississippi and Florida whereby portions of the succession fauna were excluded from access to pig carrion to study the relative effects of fire ants and blow flies on carrion decomposition and succession: a control with all fauna having access, a second treatment where fire ants and other geophilic taxa were excluded, and a third treatment in which blow flies and other large organisms were excluded. Fire ants inflicted lesions in the carrion, buried portions that touched the ground, and preyed on some members of the succession fauna. Their exclusion did not affect carrion decomposition rates that were measured but slightly affected the overall carrion community, and strongly affected the oviposition and development of blow flies. Despite the presence of fire ants early in the control, blow flies were eventually able to overcome predation of eggs and larvae, continue colonization, and complete development; however, the delay in the colonization of blow flies on carrion could affect the determination of postmortem intervals when development rates of blow flies are considered in the calculation.
Sterile Insect Technique: Lessons From the Past
Authors: Benedict Mark Q
Published: February 2021

When E.F. Knipling conceived of the release of sexually sterile insects to suppress wild populations, he laid down several fundamental qualities that characterized suitable target species—some of which mosquitoes generally violate—including high reproductive rates and large population numbers. Regardless of this, their global importance in public health has led numerous research teams to attempt to use the mosquito sterile insect technique against several species. Because of the degree of financial commitment required for suppression programs, most releases have consisted of preliminary investigations of male performance, population characteristics, and production methods. Those that have accomplished suppression provide important insights regarding the challenges of production, dispersal, and immigration. Insights gained from these studies remain relevant today, regardless of the genetic control technology being applied. In this article, I highlight studies that were notable for the insights that were gained, the intrinsic difficulties that mosquitoes present, and synthesize these into recommendations for successful applications of the sterile insect technique and newer technologies to mosquitoes.
Kimura disease: a rare cause of a recurrent cheek mass in a Jamaican man
Authors: Williams Geoffrey , Neblett Carlos , Arscott Jade , McLean Sheena , Warren Shereika , Blake Garfield
Published: February 2021

Kimura disease (KD) is a chronic, inflammatory, benign disorder endemic to Asia that typically manifests as a triad of painless masses in the head and neck region, elevated eosinophils and serum immunoglobulin. It usually affects young men in their second and third decades of life and is rarely seen outside of the orient. This is a report of a case of KD in a young man of African descent who presented with a cheek mass. KD was not included in our differential diagnosis, and this report highlights the need to consider this entity, which can be easily missed due to its rarity in the Western world. There is no cure for the disease, and management includes medical and surgical modalities, but local recurrence or relapse is not uncommon.
Distinct genetic basis for root responses to lipo-chitooligosaccharide signal molecules from different microbial origins
Authors: Bonhomme Maxime , Bensmihen Sandra , André Olivier , Amblard Emilie , Garcia Magali , Maillet Fabienne , Puech-Pagès Virginie , Gough Clare , Fort Sébastien , Cottaz Sylvain , Bécard Guillaume , Jacquet Christophe
Published: February 2021

Lipo-chitooligosaccharides (LCOs) were originally found as symbiotic signals called Nod Factors (Nod-LCOs) controlling the nodulation of legumes by rhizobia. More recently, LCOs were also found in symbiotic fungi and, more surprisingly, very widely in the kingdom Fungi, including in saprophytic and pathogenic fungi. The LCO-V(C18:1, fucosylated/methyl fucosylated), hereafter called Fung-LCOs, are the LCO structures most commonly found in fungi. This raises the question of how legume plants such as Medicago truncatula can discriminate between Nod-LCOs and Fung-LCOs. To address this question, we performed a genome-wide association study on 173 natural accessions of M. truncatula, using a root branching phenotype and a newly developed local score approach. Both Nod-LCOs and Fung-LCOs stimulated root branching in most accessions, but the root responses to these two types of LCO molecules were not correlated. In addition, the heritability of the root response was higher for Nod-LCOs than for Fung-LCOs. We identified 123 loci for Nod-LCO and 71 for Fung-LCO responses, of which only one was common. This suggests that Nod-LCOs and Fung-LCOs both control root branching but use different molecular mechanisms. The tighter genetic constraint of the root response to Fung-LCOs possibly reflects the ancestral origin of the biological activity of these molecules.
Improving crop yield and resilience through optimization of photosynthesis: panacea or pipe dream?
Authors: Araus José L , Sanchez-Bragado Ruth , Vicente Rubén
Published: February 2021

Increasing the speed of breeding to enhance crop productivity and adaptation to abiotic stresses is urgently needed. The perception that a second Green Revolution should be implemented is widely established within the scientific community and among stakeholders. In recent decades, different alternatives have been proposed for increasing crop yield through manipulation of leaf photosynthetic efficiency. However, none of these has delivered practical or relevant outputs. Indeed, the actual increases in photosynthetic rates are not expected to translate into yield increases beyond 10–15%. Furthermore, instantaneous rates of leaf photosynthesis are not necessarily the reference target for research. Yield is the result of canopy photosynthesis, understood as the contribution of laminar and non-laminar organs over time, within which concepts such as canopy architecture, stay-green, or non-laminar photosynthesis need to be taken into account. Moreover, retrospective studies show that photosynthetic improvements have been more common at the canopy level. Nevertheless, it is crucial to place canopy photosynthesis in the context of whole-plant functioning, which includes sink–source balance and transport of photoassimilates, and the availability and uptake of nutrients, such as nitrogen in particular. Overcoming this challenge will only be feasible if a multiscale crop focus combined with a multidisciplinary scientific approach is adopted.
Constraints on large-scale magnetic fields in the intergalactic medium using cross-correlation methods
Authors: Amaral A D , Vernstrom T , Gaensler B M
Published: February 2021

Large-scale coherent magnetic fields in the intergalactic medium (IGM) are presumed to play a key role in the formation and evolution of the cosmic web, and in large-scale feedback mechanisms. However, they are theorized to be extremely weak, in the nano-Gauss regime. To search for a statistical signature of these weak magnetic fields, we perform a cross-correlation between the Faraday rotation measures (RMs) of 1742 radio galaxies at z > 0.5 and large-scale structure at 0.1 < z < 0.5, as traced by 18 million optical and infrared foreground galaxies. No significant correlation signal was detected within the uncertainty limits. We are able to determine model-dependent 3σ upper limits on the parallel component of the mean magnetic field strength of filaments in the IGM of ∼30 nG for coherence scales between 1 and 2.5 Mpc, corresponding to a mean upper bound RM enhancement of ∼3.8 rad m−2 due to filaments along all probed sightlines. These upper bounds are consistent with upper bounds found previously using other techniques. Our method can be used to further constrain intergalactic magnetic fields with upcoming future radio polarization surveys.
Identifying Primate ACE2 Variants That Confer Resistance to SARS-CoV-2
Authors: Bhattacharjee Maloyjo Joyraj , Lin Jinn-Jy , Chang Chih-Yao , Chiou Yu-Ting , Li Tian-Neng , Tai Chia-Wei , Shiu Tz-Fan , Chen Chi-An , Chou Chia-Yi , Chakraborty Paromita , Tseng Yan Yuan , Wang Lily Hui-Ching , Li Wen-Hsiung
Published: February 2021

SARS-CoV-2 infects humans through the binding of viral S-protein (spike protein) to human angiotensin I converting enzyme 2 (ACE2). The structure of the ACE2-S-protein complex has been deciphered and we focused on the 27 ACE2 residues that bind to S-protein. From human sequence databases, we identified nine ACE2 variants at ACE2–S-protein binding sites. We used both experimental assays and protein structure analysis to evaluate the effect of each variant on the binding affinity of ACE2 to S-protein. We found one variant causing complete binding disruption, two and three variants, respectively, strongly and mildly reducing the binding affinity, and two variants strongly enhancing the binding affinity. We then collected the ACE2 gene sequences from 57 nonhuman primates. Among the 6 apes and 20 Old World monkeys (OWMs) studied, we found no new variants. In contrast, all 11 New World monkeys (NWMs) studied share four variants each causing a strong reduction in binding affinity, the Philippine tarsier also possesses three such variants, and 18 of the 19 prosimian species studied share one variant causing a strong reduction in binding affinity. Moreover, one OWM and three prosimian variants increased binding affinity by >50%. Based on these findings, we proposed that the common ancestor of primates was strongly resistant to and that of NWMs was completely resistant to SARS-CoV-2 and so is the Philippine tarsier, whereas apes and OWMs, like most humans, are susceptible. This study increases our understanding of the differences in susceptibility to SARS-CoV-2 infection among primates.
iLearnPlus:a comprehensive and automated machine-learning platform for nucleic acid and protein sequence analysis, prediction and visualization
Authors: Chen Zhen , Zhao Pei , Li Chen , Li Fuyi , Xiang Dongxu , Chen Yong-Zi , Akutsu Tatsuya , Daly Roger J , Webb Geoffrey I , Zhao Quanzhi , Kurgan Lukasz , Song Jiangning
Published: February 2021

Sequence-based analysis and prediction are fundamental bioinformatic tasks that facilitate understanding of the sequence(-structure)-function paradigm for DNAs, RNAs and proteins. Rapid accumulation of sequences requires equally pervasive development of new predictive models, which depends on the availability of effective tools that support these efforts. We introduce iLearnPlus, the first machine-learning platform with graphical- and web-based interfaces for the construction of machine-learning pipelines for analysis and predictions using nucleic acid and protein sequences. iLearnPlus provides a comprehensive set of algorithms and automates sequence-based feature extraction and analysis, construction and deployment of models, assessment of predictive performance, statistical analysis, and data visualization; all without programming. iLearnPlus includes a wide range of feature sets which encode information from the input sequences and over twenty machine-learning algorithms that cover several deep-learning approaches, outnumbering the current solutions by a wide margin. Our solution caters to experienced bioinformaticians, given the broad range of options, and biologists with no programming background, given the point-and-click interface and easy-to-follow design process. We showcase iLearnPlus with two case studies concerning prediction of long noncoding RNAs (lncRNAs) from RNA transcripts and prediction of crotonylation sites in protein chains. iLearnPlus is an open-source platform available at https://github.com/Superzchen/iLearnPlus/ with the webserver at http://ilearnplus.erc.monash.edu/.
Anticoagulation management in haemodialysis patients with atrial fibrillation: evidence and opinion
Authors: De Vriese An S , Heine Gunnar
Published: February 2021

In the absence of robust evidence to guide clinical decision-making, the optimal approach to prevent stroke and systemic embolism in haemodialysis (HD) patients with atrial fibrillation (AF) remains moot. In this position paper, studies on oral anticoagulation (OAC) in HD patients with AF are highlighted, followed by an evidence-based conclusion, a critical analysis to identify sources of bias and practical opinion-based suggestions on how to manage anticoagulation in this specific population. It remains unclear whether AF is a true risk factor for embolic stroke in HD. The currently employed cut-off values for the CHA2DS2-VASc score do not adequately discriminate dialysis patients deriving a net benefit from those suffering a net harm from OAC. Anticoagulation initiation should probably be more restrictive than currently advocated by official guidelines. Recent evidence reveals that the superior benefit–risk profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) observed in the general population and in moderate chronic kidney disease can be extended to the HD population. VKA may be especially harmful in dialysis patients and should therefore be avoided, in particular in patients with a high bleeding risk and labile international normalized ratio. Dose-finding studies of DOACs suggest that rivaroxaban 10 mg daily and apixaban 2.5 mg twice daily are appropriate choices in dialysis patients. Combined treatment with oral anticoagulants and antiplatelet agents should be reserved for strong indications and limited in time. Left atrial appendage occlusion is a potential attractive solution to reduce the risk of stroke without increasing bleeding propensity, but it has not been properly studied in dialysis patients.
Rice calcium/calmodulin-dependent protein kinase directly phosphorylates a mitogen-activated protein kinase kinase to regulate abscisic acid responses
Authors: Chen Min , Ni Lan , Chen Jing , Sun Manman , Qin Caihua , Zhang Gang , Zhang Aying , Jiang Mingyi
Published: February 2021

Calcium (Ca2+)/calmodulin (CaM)-dependent protein kinase (CCaMK) is an important positive regulator of abscisic acid (ABA) and abiotic stress signaling in plants and is believed to act upstream of mitogen-activated protein kinase (MAPK) in ABA signaling. However, it is unclear how CCaMK activates MAPK in ABA signaling. Here, we show that OsDMI3, a rice (Oryza sativa) CCaMK, directly interacts with and phosphorylates OsMKK1, a MAPK kinase (MKK) in rice, in vitro and in vivo. OsDMI3 was found to directly phosphorylate Thr-25 in the N-terminus of OsMKK1, and this Thr-25 phosphorylation is OsDMI3-specific in ABA signaling. The activation of OsMKK1 and its downstream kinase OsMPK1 is dependent on Thr-25 phosphorylation of OsMKK1 in ABA signaling. Moreover, ABA treatment induces phosphorylation in the activation loop of OsMKK1, and the two phosphorylations, in the N-terminus and in the activation loop, are independent. Further analyses revealed that OsDMI3-mediated phosphorylation of OsMKK1 positively regulates ABA responses in seed germination, root growth, and tolerance to both water stress and oxidative stress. Our results indicate that OsMKK1 is a direct target of OsDMI3, and OsDMI3-mediated phosphorylation of OsMKK1 plays an important role in activating the MAPK cascade and ABA signaling.
Is Positive Sentiment in Corporate Annual Reports Informative? Evidence from Deep Learning
Authors: Azimi Mehran , Agrawal Anup
Published: February 2021

We use a novel text classification approach from deep learning to more accurately measure sentiment in a large sample of 10-Ks. In contrast to most prior literature, we find that positive and negative sentiments predict abnormal returns and abnormal trading volume around the 10-K filing date and future firm fundamentals and policies. Our results suggest that the qualitative information contained in corporate annual reports is richer than previously found. Both positive and negative sentiments are informative when measured accurately, but they do not have symmetric implications, suggesting that a net sentiment measure advocated by prior studies would be less informative. (JEL C81, D83, G10, G14, G30, M41)
Credit Shocks and Equilibrium Dynamics in Consumer Durable Goods Markets
Authors: Gavazza Alessandro , Lanteri Andrea
Published: February 2021

This article studies equilibrium dynamics in consumer durable goods markets after aggregate credit shocks. We introduce two novel features into a general-equilibrium model of durable consumption with heterogeneous households facing idiosyncratic income risk and borrowing constraints: (1) indivisible durable goods are vertically differentiated in their quality and (2) trade on secondary markets at market-clearing prices, with households endogenously choosing when to trade or scrap their durables. The model highlights a new transmission mechanism for macroeconomic shocks and successfully matches several empirical patterns that we document using data on U.S. car markets around the Great Recession. After a tightening of the borrowing limit, debt-constrained households postpone the decision to scrap and upgrade their low-quality cars, which depresses mid-quality car prices. In turn, this effect reduces wealthy households’ incentives to replace their mid-quality cars with high-quality ones, thereby decreasing new-car sales. We further use our framework to evaluate targeted fiscal stimulus policies such as the Car Allowance Rebate System in 2009 (“Cash for Clunkers”).
Patients with rheumatoid arthritis have impaired long-term outcomes after myocardial infarction: a nationwide case-control registry study
Authors: Palomäki Antti , Kerola Anne M , Malmberg Markus , Rautava Päivi , Kytö Ville
Published: February 2021

Objective

To investigate the long-term outcomes of patients with RA after myocardial infarction (MI).

Methods

All-comer, real-life MI patients with RA (n = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients’ outcomes were also studied. The median follow-up was 7.3 years.

Results

RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P <0.0001]. Patients with RA were at higher risk of new MI (HR 1.22; CI: 1.09, 1.36; P =0.0001) and revascularization (HR 1.28; CI: 1.10, 1.49; P =0.002) after discharge from index MI. Cumulative stroke rate after MI did not differ between RA and non-RA patients (P =0.322). RA duration and corticosteroid usage before MI, but not use of methotrexate or biologic antirheumatic drugs, were independently associated with higher mortality (P <0.001) and new MI (P =0.009). A higher dosage of corticosteroids prior to MI was independently associated with higher long-term mortality (P =0.002) and methotrexate usage with lower stroke rate (P =0.034). Serological status of RA was not associated with outcomes.

Conclusion

RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population.
Integrative Analyses Followed by Functional Characterization Reveal TMEM180 as a Schizophrenia Risk Gene
Authors: Wang Jun-Yang , Li Xiao-Yan , Li Hui-Juan , Liu Jie-Wei , Yao Yong-Gang , Li Ming , Xiao Xiao , Luo Xiong-Jian
Published: February 2021

Recent large-scale integrative analyses (including Transcriptome-Wide Association Study [TWAS] and Summary-data-based Mendelian Randomization [SMR]) have identified multiple genes whose cis-regulated expression changes may confer risk of schizophrenia. Nevertheless, expression quantitative trait loci (eQTL) data and genome-wide associations used for integrative analyses were mainly from populations of European ancestry, resulting in potential missing of pivotal biological insights in other continental populations due to population heterogeneity. Here we conducted TWAS and SMR integrative analyses using blood eQTL (from 162 subjects) and GWAS data (22 778 cases and 35 362 controls) of schizophrenia in East Asian (EAS) populations. Both TWAS (P = 2.89 × 10–14) and SMR (P = 6.04 × 10–5) analyses showed that decreased TMEM180 mRNA expression was significantly associated with risk of schizophrenia. We further found that TMEM180 was significantly down-regulated in the peripheral blood of schizophrenia cases compared with controls (P = 8.63 × 10–4 in EAS sample), and its expression was also significantly lower in the brain tissues of schizophrenia cases compared with controls (P = 1.87 × 10–5 in European sample from PsychENCODE). Functional explorations suggested that Tmem180 knockdown affected neurodevelopment, ie, proliferation and differentiation of neural stem cells. RNA sequencing showed that pathways regulated by Tmem180 were significantly enriched in brain development and synaptic transmission. In conclusion, our study provides convergent lines of evidence for the involvement of TMEM180 in schizophrenia, and highlights the potential and importance of resource integration and sharing at this big data era in bio-medical research.