title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1002 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Adaptive evolution at mRNA editing sites in soft-bodied cephalopods link: https://peerj.com/articles/10456 last-modified: 2020-11-27 description: BackgroundThe bulk of variability in mRNA sequence arises due to mutation—change in DNA sequence which is heritable if it occurs in the germline. However, variation in mRNA can also be achieved by post-transcriptional modification including mRNA editing, changes in mRNA nucleotide sequence that mimic the effect of mutations. Such modifications are not inherited directly; however, as the processes affecting them are encoded in the genome, they have a heritable component, and therefore can be shaped by selection. In soft-bodied cephalopods, adenine-to-inosine RNA editing is very frequent, and much of it occurs at nonsynonymous sites, affecting the sequence of the encoded protein.MethodsWe study selection regimes at coleoid A-to-I editing sites, estimate the prevalence of positive selection, and analyze interdependencies between the editing level and contextual characteristics of editing site.ResultsHere, we show that mRNA editing of individual nonsynonymous sites in cephalopods originates in evolution through substitutions at regions adjacent to these sites. As such substitutions mimic the effect of the substitution at the edited site itself, we hypothesize that they are favored by selection if the inosine is selectively advantageous to adenine at the edited position. Consistent with this hypothesis, we show that edited adenines are more frequently substituted with guanine, an informational analog of inosine, in the course of evolution than their unedited counterparts, and for heavily edited adenines, these transitions are favored by positive selection. Our study shows that coleoid editing sites may enhance adaptation, which, together with recent observations on Drosophila and human editing sites, points at a general role of RNA editing in the molecular evolution of metazoans. creator: Mikhail Moldovan creator: Zoe Chervontseva creator: Georgii Bazykin creator: Mikhail S. Gelfand uri: https://doi.org/10.7717/peerj.10456 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Moldovan et al. title: Invasion history of Harmonia axyridis (Pallas, 1773) (Coleoptera: Coccinellidae) in Ecuador link: https://peerj.com/articles/10461 last-modified: 2020-11-27 description: Harmonia axyridis is a ladybird extensively used around the world for biological control of agricultural pests. However, it has become invasive in several countries, producing negative ecological and socio-economic impacts. Herein, we review the invasion history of the Harlequin Ladybird Harmonia axyridis (Pallas, 1773) in Ecuador. Although first reported in Ecuador in 2012, museum specimens date back to 2004 and it is currently established across the country, especially along the Andean region. Due to its invasive nature, further studies are urgently needed to evaluate possible impacts of H. axyridis on the Ecuadorian biodiversity and agroindustry. creator: Diego F. Cisneros-Heredia creator: Emilia Peñaherrera-Romero uri: https://doi.org/10.7717/peerj.10461 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Cisneros-Heredia and Peñaherrera-Romero title: Cumulative oxygen deficit is a novel predictor for the timing of invasive mechanical ventilation in COVID-19 patients with respiratory distress link: https://peerj.com/articles/10497 last-modified: 2020-11-27 description: Background and objectivesThe timing of invasive mechanical ventilation (IMV) is controversial in COVID-19 patients with acute respiratory hypoxemia. The study aimed to develop a novel predictor called cumulative oxygen deficit (COD) for the risk stratification.MethodsThe study was conducted in four designated hospitals for treating COVID-19 patients in Jingmen, Wuhan, from January to March 2020. COD was defined to account for both the magnitude and duration of hypoxemia. A higher value of COD indicated more oxygen deficit. The predictive performance of COD was calculated in multivariable Cox regression models.ResultsA number of 111 patients including 80 in the non-IMV group and 31 in the IMV group were included. Patients with IMV had substantially lower PaO2 (62 (49, 89) vs. 90.5 (68, 125.25) mmHg; p < 0.001), and higher COD (−6.87 (−29.36, 52.38) vs. −231.68 (−1040.78, 119.83) mmHg·day) than patients without IMV. As compared to patients with COD < 0, patients with COD > 30 mmHg·day had higher risk of fatality (HR: 3.79, 95% CI [2.57–16.93]; p = 0.037), and those with COD > 50 mmHg·day were 10 times more likely to die (HR: 10.45, 95% CI [1.28–85.37]; p = 0.029).ConclusionsThe study developed a novel predictor COD which considered both magnitude and duration of hypoxemia, to assist risk stratification of COVID-19 patients with acute respiratory distress. creator: Huiqing Ge creator: Jian-cang Zhou creator: FangFang Lv creator: Junli Zhang creator: Jun Yi creator: Changming Yang creator: Lingwei Zhang creator: Yuhan Zhou creator: Binbin Ren creator: Qing Pan creator: Zhongheng Zhang uri: https://doi.org/10.7717/peerj.10497 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Ge et al. title: Early abolition of cough reflex predicts mortality in deeply sedated brain-injured patients link: https://peerj.com/articles/10326 last-modified: 2020-11-26 description: BackgroundDeep sedation may hamper the detection of neurological deterioration in brain-injured patients. Impaired brainstem reflexes within the first 24 h of deep sedation are associated with increased mortality in non-brain-injured patients. Our objective was to confirm this association in brain-injured patients.MethodsThis was an observational prospective multicenter cohort study involving four neuro-intensive care units. We included acute brain-injured patients requiring deep sedation, defined by a Richmond Assessment Sedation Scale (RASS) < −3. Neurological assessment was performed at day 1 and included pupillary diameter, pupillary light, corneal and cough reflexes, and grimace and motor response to noxious stimuli. Pre-sedation Glasgow Coma Scale (GCS) and Simplified Acute Physiology Score (SAPS-II) were collected, as well as the cause of death in the Intensive Care Unit (ICU).ResultsA total of 137 brain-injured patients were recruited, including 70 (51%) traumatic brain-injured patients, 40 (29%) vascular (subarachnoid hemorrhage or intracerebral hemorrhage). Thirty patients (22%) died in the ICU. At day 1, the corneal (OR 2.69, p = 0.034) and cough reflexes (OR 5.12, p = 0.0003) were more frequently abolished in patients that died in the ICU. In a multivariate analysis, abolished cough reflex was associated with ICU mortality after adjustment to pre-sedation GCS, SAPS-II, RASS (OR: 5.19, 95% CI [1.92–14.1], p = 0.001) or dose of sedatives (OR: 8.89, 95% CI [2.64–30.0], p = 0.0004).ConclusionEarly (day 1) cough reflex abolition is an independent predictor of mortality in deeply sedated brain-injured patients. Abolished cough reflex likely reflects a brainstem dysfunction that might result from the combination of primary and secondary neuro-inflammatory cerebral insults revealed and/or worsened by sedation. creator: Stanislas Kandelman creator: Jérémy Allary creator: Raphael Porcher creator: Cássia Righy creator: Clarissa Francisca Valdez creator: Frank Rasulo creator: Nicholas Heming creator: Guy Moneger creator: Eric Azabou creator: Guillaume Savary creator: Djillali Annane creator: Fabrice Chretien creator: Nicola Latronico creator: Fernando Augusto Bozza creator: Benjamin Rohaut creator: Tarek Sharshar uri: https://doi.org/10.7717/peerj.10326 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Kandelman et al. title: Spatial and temporal activity patterns of Golden takin (Budorcas taxicolor bedfordi) recorded by camera trapping link: https://peerj.com/articles/10353 last-modified: 2020-11-26 description: Understanding animals’ migration, distribution and activity patterns is vital for the development of effective conservation action plans; however, such data for many species are lacking. In this study, we used camera trapping to document the spatial and temporal activity patterns of golden takins (Budorcas taxicolor bedfordi) in Changqing National Nature Reserve in the Qinling mountains, China, from April 2014 to October 2017. Our study obtained 3,323 independent detections (from a total of 12,351 detections) during a total camera trapping effort of 93,606 effective camera trap days at 573 sites. Results showed that: (1) the golden takin’s utilization distributions showed seasonal variation, with larger utilization distributions during spring and autumn compared to summer and winter; (2) the species was recorded at the highest elevations in July, and lowest elevations in December, with the species moving to higher-elevations in summer, lower-elevations in spring and autumn; (3) during all four seasons, golden takins showed bimodal activity peaks at dawn and dusk, with activity intensity higher in the second peak than the first, and overall low levels of activity recorded from 20:00–06:00; and (4) there were two annual activity peaks, the first being in April and the second in November, with camera capture rate during these two months higher than in other months, and activity levels in spring and autumn higher than in summer and winter. This study is the first application of camera traps to assess the spatial and temporal activity patterns of golden takins at a population level. Our findings suggest that the proposed national park should be designed to include golden takin habitat and that ongoing consistent monitoring efforts will be crucial to mitigating novel and ongoing threats to the species. creator: Jia Li creator: Yadong Xue creator: Yu Zhang creator: Wei Dong creator: Guoyu Shan creator: Ruiqian Sun creator: Charlotte Hacker creator: Bo Wu creator: Diqiang Li uri: https://doi.org/10.7717/peerj.10353 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Li et al. title: The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma link: https://peerj.com/articles/10385 last-modified: 2020-11-26 description: Background Increasing evidence has shown that N6-methyladenosine (m6A) RNA methylation regulators have important biological functions in human cancers. However, there are few studies on the value of m6A reader protein YTHDC2 in the diagnosis and tumor-infiltrating of head and neck squamous cell carcinoma (HNSCC). Therefore, it is important to understand the potential clinical value of YTHDC2 in the prognosis and immune infiltration of HNSCC.MethodsIn this study, gene expression profiles and the corresponding clinical information of 270 HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database. The gene co-expression network was established to verify whether YTHDC2 was related to the prognosis of HNSCC and verified again in the public database. The correlations between YTHDC2 and immune infiltration was investigated via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe results showed that YTHDC2 appeared in the blue module related to survival time and survival state and had a close correlation with the prognosis and immune infiltration level of HNSCC in public database. Patients with low expression of YTHDC2 had poor overall survival (OS) and recurrence-free survival (RFS) than those with high expression. In addition, the expression of YTHDC2 was positively correlated with the level of CD4+ T cell subpopulations infiltration in HNSCC.ConclusionsThrough this study, we found that YTHDC2 is a tumor suppressor gene with high expression in normal tissues and low expression in tumor tissues. In addition, YTHDC2 is correlated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells in HNSCC, which may become a potential marker for prognosis and immune infiltration of HNSCC. creator: Yang Li creator: Ji-Na Zheng creator: En-Hao Wang creator: Chan-Juan Gong creator: Keng-Fu Lan creator: XiaoJun Ding uri: https://doi.org/10.7717/peerj.10385 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Li et al. title: A signature of tumor DNA repair genes associated with the prognosis of surgically-resected lung adenocarcinoma link: https://peerj.com/articles/10418 last-modified: 2020-11-26 description: BackgroundLung cancer has the highest morbidity and mortality of cancers worldwide. Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer and surgery is its most common treatment. The dysregulated expression of DNA repair genes is found in a variety of cancers and has been shown to affect the origin and progression of these diseases. However, the function of DNA repair genes in surgically-treated LUAD is unclear.MethodsWe sought to determine the association between the signature of DNA repair genes for patients with surgical LUAD and their overall prognosis. We obtained gene expression data and corresponding clinical information of LUAD from The Cancer Genome Atlas (TCGA) database. The differently expressed DNA repair genes of surgically-treated LUAD and normal tissues were identified using the Wilcoxon rank-sum test. We used uni- and multivariate Cox regression analyses to shrink the aberrantly expressed genes, which were then used to construct the prognostic signature and the risk score formula associated with the independent prognosis of surgically-treated LUAD. We used Kaplan–Meier and Cox hazard ratio analyses to confirm the diagnostic and prognostic roles. Two validation sets (GSE31210 and GSE37745) were downloaded from the Gene Expression Omnibus (GEO) and were used to externally verify the prognostic value of the signature. OSluca online database verifies the hazard ratio for the DNA repair genes by which the signature was constructed. We investigated the correlation between the signature of the DNA repair genes and the clinical parameters. The potential molecular mechanisms and pathways of the prognostic signature were explored using Gene Set Enrichment Analysis (GSEA).ResultsWe determined the prognostic signature based on six DNA repair genes (PLK1, FOXM1, PTTG1, CCNO, HIST3H2A, and BLM) and calculated the risk score based on this formula. Patients with surgically-treated LUAD were divided into high-risk and low-risk groups according to the median risk score. The high-risk group showed poorer overall survival than the low-risk group; the signature was used as an independent prognostic indicator and had a greater prognostic value in surgically-treated LUAD. The prognostic value was replicated in GSE31210 and GSE37745. OSluca online database analysis shows that six DNA repair genes were associated with poor prognosis in most lung cancer datasets. The prognostic signature risk score correlated with the pathological stage and smoking status in surgically-treated LUAD. The GSEA of the risk signature in high-risk patients showed pathways associated with the cell cycle, oocyte meiosis, mismatch repair, homologous recombination, and nucleotide excision repair.ConclusionsA six-DNA repair gene signature was determined using TCGA data mining and GEO data verification. The gene signature may serve as a novel prognostic biomarker and therapeutic target for surgically-treated LUAD. creator: Xiongtao Yang creator: Guohui Wang creator: Runchuan Gu creator: Xiaohong Xu creator: Guangying Zhu uri: https://doi.org/10.7717/peerj.10418 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2020 Yang et al. title: Evolutionary dynamics and geographic dispersal of beta coronaviruses in African bats link: https://peerj.com/articles/10434 last-modified: 2020-11-26 description: Bats have been shown to serve as reservoir host of various viral agents including coronaviruses. They have also been associated with the novel coronavirus SARS-CoV-2. This has made them an all important agent for CoV evolution and transmission. Our objective in this study was to investigate the dispersal, phylogenomics and evolution of betacoronavirus (βCoV) among African bats. We retrieved sequence data from established databases such as GenBank and Virus Pathogen Resource, covering the partial RNA dependent RNA polymerase (RdRP) gene of bat coronaviruses from eight African, three Asian, five European, two South American countries and Australia. We analyzed for phylogeographic information relating to genetic diversity and evolutionary dynamics. Our study revealed that majority of the African strains fell within Norbecovirus subgenera, with an evolutionary rate of 1.301 × 10−3, HPD (1.064 × 10−3–1.434 × 10−3) subs/site/year. The African strains diversified into three main subgenera, Norbecovirus, Hibecovirus and Merbecovirus. The time to most common recent ancestor for Norbecovirus strains was 1973, and 2007, for the African Merbecovirus strains. There was evidence of inter species transmission of Norbecovirus among bats in Cameroun and DRC. Phlylogeography showed that there were inter-continental spread of Bt-CoV from Europe, China and Hong Kong into Central and Southern Africa, highlighting the possibility of long distance transmission. Our study has elucidated the possible evolutionary origins of βCoV among African bats; we therefore advocate for broader studies of whole genome sequences of BtCoV to further understand the drivers for their emergence and zoonotic spillovers into human population. creator: Babatunde O. Motayo creator: Olukunle Oluwapamilerin Oluwasemowo creator: Paul A. Akinduti uri: https://doi.org/10.7717/peerj.10434 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Motayo et al. title: Partial restoration of normal intestinal microbiota in morbidly obese women six months after bariatric surgery link: https://peerj.com/articles/10442 last-modified: 2020-11-26 description: We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery. creator: Jukka Koffert creator: Leo Lahti creator: Lotta Nylund creator: Seppo Salminen creator: Jarna C. Hannukainen creator: Paulina Salminen creator: Willem M. de Vos creator: Pirjo Nuutila uri: https://doi.org/10.7717/peerj.10442 license: https://creativecommons.org/licenses/by-nc/4.0 rights: ©2020 Koffert et al. title: Characteristics and outcomes of hemodialysis patients with COVID-19: a retrospective single center study link: https://peerj.com/articles/10459 last-modified: 2020-11-26 description: BackgroundThe coronavirus 19 (COVID-19) pandemic has heightened the threat to the health and lives of patients with comorbid diseases. Infection by COVID-19 is especially detrimental to patients on hemodialysis. In this study, we evaluated the clinical characteristics, laboratory findings, treatments and prognoses of hemodialysis patients with COVID-19.MethodsA total of 16 hemodialysis patients with COVID-19 were recruited from Wuhan Fourth Hospital from 5 February to 20 March 2020 for a retrospective, single-center study. A total of 62 non-dialysis patients with COVID-19 were the control group. We collected data on the clinical characteristics, laboratory findings, treatments, and clinical outcomes of patients affected by the virus.ResultsHemodialysis patients with COVID-19 had a lower incidence of fever (P = 0.001) and relatively higher incidence of pre-admission comorbidities and shortness of breath than non-dialysis patients with COVID-19 (75% vs. 61%, P = 0.467 50% vs. 33.87%, P = 0.248 ). Hemodialysis patients had lower levels of hemoglobin (P < 0.001), white blood cell counts (P = 0.015), neutrophils (P = 0.016), AST (P = 0.037), ALT (P < 0.001) and procalcitonin (P < 0.001), and higher levels of D-dimer (P < 0.001) and thrombin time (P < 0.001). Hemodialysis patients had a higher incidence of pulmonary effusion, cord-like high-density shadows, pleural thickening, and atelectasis (P < 0.05). Hemodialysis patients also had relatively higher rates of mortality and prolonged hospital stays compared with the control group.ConclusionsHemodialysis patients typically present with multiple comorbidities and are considered to be a high-risk group for COVID-19 infections. Hemodialysis patients with COVID-19 may have prolonged hospital stays and unfavorable prognoses and should be closely monitored. creator: Yongwen Luo creator: Junli Li creator: Zhifen Liu creator: Heping Yu creator: Xiang Peng creator: Cheng’an Cao uri: https://doi.org/10.7717/peerj.10459 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2020 Luo et al.