title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=805 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Risk factors associated with prolonged viral clearance in patients with a refractory course of COVID-19: a retrospective study link: https://peerj.com/articles/12535 last-modified: 2021-11-23 description: BackgroundThis study aimed to characterize a cohort of patients with a refractory course of COVID-19, and to investigate factors associated with the duration of viral clearance (DoVC).Materials & MethodsA total of 65 patients with refractory COVID-19 were retrospectively enrolled from Huoshenshan Hospital. Univariate analysis and multivariate analysis were performed to examine the potential association between clinicopathologic characteristics and the DoVC.ResultsThe median DoVC in the overall study cohort was 48 days (ranged from 21 to 104 days). Multivariate analysis indicated that fever at illness onset (Hazard ratio (HR) = 4.897, 95% CI [1.809–13.260], p = 0.002), serum level of aspartate aminotransferase (AST) > 21.8 IU/L (HR = 3.010, 95% CI [1.195–7.578], p = 0.019), and titer of SARS-CoV-2 IgG > 142.09 AU/ml (HR = 3.061, 95% CI [1.263–7.415], p = 0.013) were the three independent risk factors associated with delayed viral clearance.ConclusionThe current study suggested that clinical characteristics such as fever at illness onset, a high serum level of AST or SARS-CoV-2 IgG were associated with delayed viral clearance. Patients with these characteristics might need a more individualized treatment strategy to accelerate their recovery from the refractory COVID-19. creator: Weitao Zhuang creator: Shujie Huang creator: Dongya Wang creator: Lulu Zha creator: Wei Xu creator: Guibin Qiao uri: https://doi.org/10.7717/peerj.12535 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Zhuang et al. title: Which environmental factors control extreme thermal events in rivers? A multi-scale approach (Wallonia, Belgium) link: https://peerj.com/articles/12494 last-modified: 2021-11-22 description: Managers need to know how to mitigate rising stream water temperature (WT) due to climate change. This requires identifying the environmental drivers that influence thermal regime and determining the spatial area where interventions are most effective. We hypothesized that (i) extreme thermal events can be influenced by a set of environmental factors that reduce thermal sensitivity and (ii) the role played by those factors varies spatially. To test these hypotheses, we (i) determined which of the environmental variables reported to be the most influential affected WT and (ii)identified the spatial scales over which those environmental variables influenced WT. To this end, the influence of multi-scale environmental variables, namely land cover, topography (channel slope, elevation), hydromorphology (channel sinuosity, water level, watershed area, baseflow index) and shade conditions, was analyzed on the three model variables (day thermal sensitivity, night thermal sensitivity, and non-convective thermal flux) in the model developed by Georges et al. (2021) of the temporal thermal dynamics of daily maximum WT during extreme events. Values were calculated on six spatial scales (the entire upstream catchment and the associated 1 km and 2 km circular buffer, and 50 m wide corridors on each side of the stream with the associated 1 km and 2 km circular buffer). The period considered was 17 extreme days during the summer identified by Georges et al. (2021) based on WT data measured every 10 min for 7 years (2012–2018) at 92 measurement sites. Sites were located evenly throughout the Wallonia (southern Belgium) hydrological network. Results showed that shade, baseflow index (a proxy of the influence of groundwater), water level and watershed area were the most significant variables influencing thermal sensitivity. Since managers with finite financial and human resources can act on only a few environmental variables, we advocate restoring and preserving the vegetation cover that limits solar radiation on the watercourse as a cost-effective solution to reduce thermal sensitivity. Moreover, management at small spatial scale (50 m riparian buffer) should be strategically promoted (for finance and staffing) as our results show that a larger management scale is not more effective in reducing thermal sensitivity to extreme events. creator: Blandine Georges creator: Adrien Michez creator: Hervé Piegay creator: Leo Huylenbroeck creator: Philippe Lejeune creator: Yves Brostaux uri: https://doi.org/10.7717/peerj.12494 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Georges et al. title: Applications of the indole-alkaloid gramine modulate the assembly of individual members of the barley rhizosphere microbiota link: https://peerj.com/articles/12498 last-modified: 2021-11-22 description: Microbial communities proliferating at the root-soil interface, collectively referred to as the rhizosphere microbiota, represent an untapped beneficial resource for plant growth, development and health. Integral to a rational manipulation of the microbiota for sustainable agriculture is the identification of the molecular determinants of these communities. In plants, biosynthesis of allelochemicals is centre stage in defining inter-organismal relationships in the environment. Intriguingly, this process has been moulded by domestication and breeding selection. The indole-alkaloid gramine, whose occurrence in barley (Hordeum vulgare L.) is widespread among wild genotypes but has been counter selected in several modern varieties, is a paradigmatic example of this phenomenon. This prompted us to investigate how exogenous applications of gramine impacted on the rhizosphere microbiota of two, gramine-free, elite barley varieties grown in a reference agricultural soil. High throughput 16S rRNA gene amplicon sequencing revealed that applications of gramine interfere with the proliferation of a subset of soil microbes with a relatively broad phylogenetic assignment. Strikingly, growth of these bacteria appeared to be rescued by barley plants in a genotype- and dosage-independent manner. In parallel, we discovered that host recruitment cues can interfere with the impact of gramine application in a host genotype-dependent manner. Interestingly, this latter effect displayed a bias for members of the phyla Proteobacteria. These initial observations indicate that gramine can act as a determinant of the prokaryotic communities inhabiting the root-soil interface. creator: Mauro Maver creator: Carmen Escudero-Martinez creator: James Abbott creator: Jenny Morris creator: Pete E. Hedley creator: Tanja Mimmo creator: Davide Bulgarelli uri: https://doi.org/10.7717/peerj.12498 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Maver et al. title: Atypical functioning of female genitalia explains monandry in a butterfly link: https://peerj.com/articles/12499 last-modified: 2021-11-22 description: Monandrous species are rare in nature, especially in animals where males transfer nutrients to females in the ejaculate. The proximate mechanisms responsible for monandry are poorly studied. In butterflies and moths, the male transfers a nutritious spermatophore into the corpus bursae (CB) of the female. The CB is a multifunctional organ that digests the spermatophore and has partial control of the post-mating sexual receptivity of the female. The spermatophore distends the CB and the post-mating sexual receptivity of the female is inversely proportional to the degree of distension. The CB of many butterfly species has a muscular sheath whose contractions mechanically contribute to digest the spermatophore. As the contents of the CB are absorbed, the degree of distension decreases and the female recovers receptivity. We studied the monandrous butterfly Leptophobia aripa (Boisduval, 1836) (Pieridae) and found that females do not digest the spermatophores. We investigated the structure of the CB and found that a muscular sheath is absent, indicating that in this butterfly females lack the necessary “apparatus” for the mechanical digestion of the spermatophore. We propose that female monandry in this species is result of its incapability to mechanically digest the spermatophore, which results in a constant degree of CB distension after mating and, thus, in the maintenance of the sexually unreceptive state of females. Hypotheses on the evolution of this mechanism are discussed. creator: David Xochipiltecatl creator: Joaquín Baixeras creator: Carlos R. Cordero uri: https://doi.org/10.7717/peerj.12499 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Xochipiltecatl et al. title: Association of endothelial dysfunction with sarcopenia and muscle function in a relatively young cohort of kidney transplant recipients link: https://peerj.com/articles/12521 last-modified: 2021-11-22 description: BackgroundSarcopenia and endothelial dysfunction are both common among kidney transplant (KT) recipients. We aimed to evaluate the association between endothelial dysfunction and sarcopenia, as well as its individual components.MethodsVascular reactivity index (VRI), skeletal muscle index (SMI = skeletal muscle mass/height2), handgrip strength (HGS), and 6-meter usual gait speed (GS) were measured in 95 KT recipients. Low SMI was defined as SMI less than 10% of the sex-specific reference values from Chinese adults; low HGS as HGS < 28 kg for men and < 18 kg for women; slow GS as GS below 1.0 m/s. Sarcopenia was diagnosed based on the presence of low SMI as an essential criterion, accompanied by either low HGS or slow GS. Vascular reactivity was classified as being indicative of poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), or good (VRI ≥ 2.0) vascular reactivity.ResultsOf the 95 patients, aged 45.2 ± 10.9 years, 11.6% had sarcopenia and 13.7% had poor vascular reactivity. Patients with sarcopenia were lower in body mass index (p = 0.001) and VRI (p = 0.041), and have a higher proportion of low muscle mass (p < 0.001), low HGS (p < 0.001), and slow GS (p = 0.001). Patients with poor vascular reactivity have a higher proportion of sarcopenia (p = 0.005), low HGS (p = 0.006), and slow GS (p = 0.029). Multivariate logistic regression analysis showed that patients in the poor VRI group were significantly associated with sarcopenia (odds ratio, OR = 6.17; 95% confidence interval [1.06–36.04]; p = 0.043), comparing to those with good VRI. We further analysed the effects of VRI on individual components of sarcopenia and found that VRI predicted slow GS significantly (OR = 0.41; 95% CI = [0.21–0.79]; p = 0.007), but not low SMI (OR = 1.15; 95% CI [0.53–2.49]; p = 0.718) and HGS (OR = 0.59; 95% CI [0.31–1.16]; p = 0.125).ConclusionsWe concluded that endothelial dysfunction is a key determinant of sarcopenia in KT recipients. Furthermore, endothelial dysfunction is more closely related to gait speed than muscle mass and strength. creator: Siok-Bin Khoo creator: Yu-Li Lin creator: Guan-Jin Ho creator: Ming-Che Lee creator: Bang-Gee Hsu uri: https://doi.org/10.7717/peerj.12521 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Khoo et al. title: Climate change favours connectivity between virus-bearing pest and rice cultivations in sub-Saharan Africa, depressing local economies link: https://peerj.com/articles/12387 last-modified: 2021-11-19 description: AimsRice is a staple food for many countries, being fundamental for a large part of the worlds’ population. In sub-Saharan Africa, its importance is currently high and is likely to become even more relevant, considering that the number of people and the per-capita consumption are both predicted to increase. The flea beetles belonging to the Chaetocnema pulla species group (pulla group), a harmful rice pest, are an important vector of the Rice Yellow Mottle Virus, a disease which leads even to 80–100% yield losses in rice production. We present a continental-scale study aiming at: (1) locating current and future suitable territories for both pulla group and rice; (2) identifying areas where rice cultivations may occur without suffering the presence of pulla group using an Ecological Niche Modelling (ENM) approach; (3) estimating current and future connectivity among pulla group populations and areas predicted to host rice cultivations, based on the most recent land-use estimates for future agricultural trends; (4) proposing a new connectivity index called “Pest Aggression Index” (PAI) to measure the agricultural susceptibility to the potential future invasions of pests and disease; (5) quantifying losses in terms of production when rice cultivations co‐occur with the pulla group and identifying the SSA countries which, in the future inferred scenarios, will potentially suffer the greatest losses.LocationSub-Saharan Africa.MethodsSince the ongoing climate and land-use changes affect species’ distributions, we first assess the impact of these changes through a spatially-jackknifed Maxent-based Ecological Niche Modelling in GIS environment, for both the pulla group and rice, in two climatic/socioeconomic future scenarios (SSP_2.45 and 3.70). We then assess the connectivity potential of the pulla group populations towards rice cultivations, for both current and future predictions, through a circuit theory-based approach (Circuitscape implemented in Julia language). We finally measure the rice production and GPD loss per country through the spatial index named “Pest Aggression Index”, based on the inferred connectivity magnitude.ResultsThe most considerable losses in rice production are observed for Liberia, Sierra Leone and Madagascar in all future scenarios (2030, 2050, 2070). The future economic cost, calculated as USD lost from rice losses/country’s GDP results are high for Central African Republic (−0.6% in SSP_2.45 and −3.0% in SSP_3.70) and Guinea–Bissau (−0.4% in SSP_2.45 and −0.68% in SSP_3.70), with relevant losses also obtained for other countries.Main conclusionsSince our results are spatially explicit and focused on each country, we encourage careful land-use planning. Our findings could support best practices to avoid the future settlement of new cultivations in territories where rice would be attacked by pulla group and the virus, bringing economic and biodiversity losses. creator: Mattia Iannella creator: Walter De Simone creator: Paola D’Alessandro creator: Maurizio Biondi uri: https://doi.org/10.7717/peerj.12387 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Iannella et al. title: Commercial utilities and future perspective of nanomedicines link: https://peerj.com/articles/12392 last-modified: 2021-11-19 description: The present review aims to describe the commercial utilities and future perspectives of nanomedicines. Nanomedicines are intended to increase precision medicine and decrease the adverse effects on the patient. Nanomedicines are produced, engineered, and industrialized at the cellular, chemical, and macromolecular levels. This study describes the various aspects of nanomedicine such as governing outlooks over high use of nanomedicine, regulatory advancements for nanomedicines, standards, and guidelines for nanomedicines as per Therapeutic Goods Administration (TGA). This review also focuses on the patents and clinical trials based on nanoformulation, along with nanomedicines utilization as drug therapy and their market value. The present study concludes that nanomedicines are of high importance in biomedical and pharmaceutical production and offer better therapeutic effects especially in the case of drugs that possess low aqueous solubility. The factual data presented in this study will assist the researchers and health care professionals in understanding the applications of nanomedicine for better diagnosis and effective treatment of a disease. creator: Rishabha Malviya creator: Shivkanya Fuloria creator: Swati Verma creator: Vetriselvan Subramaniyan creator: Kathiresan V. Sathasivam creator: Vinoth Kumarasamy creator: Darnal Hari Kumar creator: Shalini Vellasamy creator: Dhanalekshmi Unnikrishnan Meenakshi creator: Shikha Yadav creator: Akanksha Sharma creator: Neeraj Kumar Fuloria uri: https://doi.org/10.7717/peerj.12392 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Malviya et al. title: Genome-wide identification and expression analysis of ethylene responsive factor family transcription factors in Juglans regia link: https://peerj.com/articles/12429 last-modified: 2021-11-19 description: BackgroundWalnut is an important economic tree species with prominent economic value and ecological functions. However, in recent years, walnuts have become susceptible to drought stress, resulting in a decline in comprehensive benefits. Therefore, it is necessary to identify the regulatory molecular mechanism associated with walnut response to drought. In many plants, ethylene responsive factor (ERF) gene family plays important roles in response to biotic and abiotic stress, especial drought. Therefore, the identification and characterisation of walnut ERF genes will benefit walnut with regard to the clarification of drought response mechanism as well as the management, production, and quality of plantations.Methods‘ERF’ was compared against the walnut transcriptome, and the JrERFs with a complete open reading frame (ORF) were identified by ORF Finder. The molecular weights, amino acid residues, and theoretical isoelectric point (pI) were predicted by ExPASy. The distribution of JrERFs in chromosome locations was determined based on walnut genome data from NCBI. The intron-exon structures and conserved domains were analysed using Gene Structure Display Server 2.0 and CD-Search, accordingly. Multi-sequence alignment and a phylogenetic tree were constructed by ClustalX2.1 and MEGA7, respectively. The conserved motifs were acquired using MEME. Total RNA was isolated using the cetyltrimethylammonium ammonium bromide (CTAB) method (Yang et al., 2018). Gene expression was determined by using real-time quantitative polymerase chain reaction (qRT-PCR) analysis and calculated according to the 2−ΔΔCT method (Livak & Schmittgen, 2001).ResultsA total of 44 JrERFs were identified from the walnut transcriptome, whose ORFs were 450–1,239 bp in length. The molecular weights of the JrERF proteins (consisting 149–412 amino acids) were 16.81–43.71 kDa, with pI ranging from 4.8 (JrERF11) to 9.89 (JrERF03). The JrERFs can be divided into six groups (B1–B6), and among the groups, B6 contained the most number of members. Each JrERF contained 1–6 motifs and each motif comprised 9–50 amino acids. Among the motifs, motif1, motif2, and motif3 were the most abundant. More than 40% of JrERFs were up-regulated continuously when subjected to ethephon (ETH), PEG6000, and PEG6000+ETH treatments. Of all the JrERFs, JrERF11 showed the highest expression. Therefore, we conclude that walnut ERF genes are highly conserved and involved in the regulation of drought response in the presence of ETH. JrERFs are possibly important candidate genes for molecular breeding; hence, the findings of this study provides the theoretical basis for further investigation of ERF genes in walnut and other species. creator: Tianyu Wang creator: Xiangqian Gao creator: Sisi Chen creator: Dapei Li creator: Shuwen Chen creator: Muhong Xie creator: Zhenggang Xu creator: Guiyan Yang uri: https://doi.org/10.7717/peerj.12429 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Wang et al. title: Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores link: https://peerj.com/articles/12452 last-modified: 2021-11-19 description: BackgroundColorectal cancer (CRC) is one of the most common malignancies.An early diagnosis and an accurate prognosis are major focuses of CRC research. Tumor microenvironment cells and the extent of infiltrating immune and stromal cells contribute significantly to the tumor prognosis.MethodsImmune and stromal scores were calculated based on the ESTIMATE algorithm using the sample expression profile of the The Cancer Genome Atlas (TCGA) database. GSE102479 was used as the validation database. Differentially expressed genes whose expression was significantly associated with the prognosis of CRC patients were identified based on the immune matrix score. Survival analysis was conducted on the union of the differentially expressed genes. A protein–protein interaction (PPI) network was constructed using the STRING database to identify the closely connected modules. To conduct functional enrichment analysis of the relevant genes, GO and KEGG pathway analyses were performed with Cluster Profiler. Pivot analysis of the ncRNAs and TFs was performed by using the RAID2.0 database and TRRUST v2 database. TF-mRNA regulatory relationships were analyzed in the TRRUST V2 database. Hubgene targeting relationships were screened in the TargetScan, miRTarBase and miRDB databases. The SNV data of the hub genes were analyzed by using the R maftools package. A ROC curve was drawn based on the TCGA database. The proportion of immune cells was estimated using CIBERSORT and the LM22 feature matrix.ResultsThe results showed that the matrix score was significantly correlated with colorectal cancer stage T. A total of 789 differentially expressed genes and 121 survival-related prognostic genes were identified. The PPI network showed that 22 core genes were related to the CRC prognosis. Furthermore, four ncRNAs that regulated the core prognosis genes, 11 TFs with regulatory effects on the core prognosis genes, and two drugs, quercetin and pseudoephedrine, that have regulatory effects on colorectal cancer were also identified.ConclusionsWe obtained a list of tumor microenvironment-related genes for CRC patients. These genes could be useful for determining the prognosis of CRC patients. To confirm the function of these genes, additional experiments are necessary. creator: Yi Zhu creator: Yuan Zhou creator: HongGang Jiang creator: ZhiHeng Chen creator: BoHao Lu uri: https://doi.org/10.7717/peerj.12452 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Zhu et al. title: Both landscape heterogeneity and configuration determine Woodlarks (Lullula arborea) breeding territories link: https://peerj.com/articles/12476 last-modified: 2021-11-19 description: Farmland birds have declined in the last decades mostly due to agriculture intensification. The Woodlark Lullula arborea, a farmland species of conservation concern and protected by the European Bird Directive, occurs in a variety of habitats across its geographic range. Although habitat heterogeneity has been recognized as a key feature, the preference or avoidance of particular habitat attributes might differ across its range because different localities may have distinct conditions. Such variation would challenge conservation efforts at the local level. Our aim was to assess habitat associations of Woodlarks and determine whether the habitat attributes identified as important in other locations across its range could be generalised and applied to Austrian populations. In addition, habitat associations can be influenced by land-use change. We examined changes in land use from 2007 to 2016 in 15 municipalities surrounding areas occupied by Woodlarks. We quantified the composition and configuration of the local landscape surrounding 18 singing males’ territories and 16 non-territory sites. We found that the probability of Woodlarks territories increased with landscape heterogeneity between 50% and 70%, increased with dispersed bare soil patches, decreased with overall patch density and were away from dirt roads. Contrary to our expectation, there was no indication of land-use change. In contrast to previous studies, vegetation height, the presence and proximity to woodland were not identified as important habitat characteristics. Thus, some conservation recommendations can be derived from other localities, for example, maintaining or enhancing landscape heterogeneity. However, others should be adapted to local conditions. In Austria, conservation efforts should focus on including dispersed patches of bare soil and limiting the development of dirt roads nearby Woodlark territories, in addition to promoting a heterogeneous landscape. creator: Marlies Resch creator: Marcela Suarez-Rubio uri: https://doi.org/10.7717/peerj.12476 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Resch and Suarez-Rubio