title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=777 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Development of a T-cell activation-related module with predictive value for the prognosis and immune checkpoint blockade therapy response in glioblastoma link: https://peerj.com/articles/12547 last-modified: 2021-12-22 description: BackgroundDespite the rise in the use of immune checkpoint blockade drugs (ICBs) in recent years, there are no ICB drugs that are currently approved or under large-scale clinical trials for glioblastoma (GBM). T-cells, which mainly mediate adaptive immunity, are an important part of the tumor immune microenvironment. The activation of T-cells in tumors plays a key role in evaluating the sensitivity of patients to immunotherapy. Therefore, we applied bioinformatics approaches to construct a T-cell activation related risk score to study the effect of the activation of T-cells on the prognosis and ICB response of patients with GBM.Materials and MethodsThis study collected TCGA, CGGA, and GSE16011 glioma cohorts, as well as the IMvigor210 immunotherapy dataset, with complete mRNA expression profiles and clinical information. GraphPad Prism 8 and R 3.6.3 were used for bioinformatics analysis and plotting.ResultsThe activation of T-cells in patients with GBM is characterized by obvious heterogeneity. We established a T-cell activation-related risk score based on five univariate Cox regression prognostic genes (CD276, IL15, SLC11A1, TNFSF4, and TREML2) in GBM. The risk score was an independent risk factor for poor prognosis. The overall survival time of patients in the high-risk group was significantly lower than in the low-risk group. Moreover, the high-risk score was accompanied by a stronger immune response and a more complex tumor immune microenvironment. “Hot tumors” were mainly enriched in the high-risk group, and high-risk group patients highly expressed inhibitory immune checkpoints (PD1, PD-L1, TIM3 etc.). By combining the risk and priming scores we obtained the immunotherapy score, which was shown to be a good evaluation index for sensitivity to GBM immunotherapy.ConclusionsAs an independent risk factor for poor prognosis, the T-cell activation-related risk score, combined with other clinical characteristics, could efficiently evaluate the survival of patients with GBM. The immunotherapy score obtained by combining the risk and priming scores could evaluate the ICB response of patients with GBM, providing treatment opportunities. creator: Zihao Yan creator: Siwen Chu creator: Chen Zhu creator: Yunhe Han creator: Qingyu Liang creator: Shuai Shen creator: Wen Cheng creator: Anhua Wu uri: https://doi.org/10.7717/peerj.12547 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Yan et al. title: The metabolism and role of free fatty acids in key physiological processes in insects of medical, veterinary and forensic importance link: https://peerj.com/articles/12563 last-modified: 2021-12-22 description: Insects are the most widespread group of organisms and more than one million species have been described. These animals have significant ecological functions, for example they are pollinators of many types of plants. However, they also have direct influence on human life in different manners. They have high medical and veterinary significance, stemming from their role as vectors of disease and infection of wounds and necrotic tissue; they are also plant pests, parasitoids and predators whose activities can influence agriculture. In addition, their use in medical treatments, such as maggot therapy of gangrene and wounds, has grown considerably. They also have many uses in forensic science to determine the minimum post-mortem interval and provide valuable information about the movement of the body, cause of the death, drug use, or poisoning. It has also been proposed that they may be used as model organisms to replace mammal systems in research. The present review describes the role of free fatty acids (FFAs) in key physiological processes in insects. By focusing on insects of medical, veterinary significance, we have limited our description of the physiological processes to those most important from the point of view of insect control; the study examines their effects on insect reproduction and resistance to the adverse effects of abiotic (low temperature) and biotic (pathogens) factors. creator: Agata Kaczmarek creator: Mieczysława Boguś uri: https://doi.org/10.7717/peerj.12563 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Kaczmarek and Boguś title: Wearable technology to inform the prediction and diagnosis of cardiorespiratory events: a scoping review link: https://peerj.com/articles/12598 last-modified: 2021-12-22 description: BackgroundThe need for health systems that allow for continuous monitoring and early adverse event detection in individuals outside of the acute care setting has been highlighted by the global rise in chronic cardiorespiratory diseases and the recent COVID-19 pandemic. Currently, it is unclear what type of evidence exists concerning the use of physiological data collected from commercially available wrist and textile wearables to assist in clinical decision making. The aim of this review was therefore to systematically map and summarize the scientific literature surrounding the use of these wearables in clinical decision making as well as identify knowledge gaps to inform further research.MethodologySix electronic bibliographic databases were systematically searched (Ovid MEDLINE, EMBASE, CINAHL, PubMed, Scopus, and SportsDiscus). Publications from database inception to May 6, 2020 were reviewed for inclusion. Non-indexed literature relevant to this review was also searched systematically. Results were then collated, summarized and reported.ResultsA total of 107 citations were retrieved and assessed for eligibility with 31 citations included in the final analysis. A review of the 31 papers revealed three major study designs which included (1) observational studies (n = 19), (2) case control series and reports (n = 8), and (3) reviews (n = 2). All papers examined the use of wearable monitoring devices for clinical decisions in the cardiovascular domain, with cardiac arrhythmias being the most studied. When compared to electrocardiogram (ECG) the performance of the wearables in facilitating clinical decisions varied depending upon the type of wearable, user’s activity levels and setting in which they were employed. Observational studies collecting data in the inpatient and outpatient settings were equally represented. Eight case control series and reports were identified which reported on the use of wrist wearables in patients presenting to an emergency department or clinic to aid in the clinical diagnosis of a cardiovascular event. Two narrative reviews were identified which examined the impact of wearable devices in monitoring cardiovascular disease as well as potential challenges they may pose in the future.ConclusionsTo date, studies employing wearables to facilitate clinical decisions have largely focused upon the cardiovascular domain. Despite the ability of some wearables to collect physiological data accurately, there remains a need for a specialist physician to retrospectively review the raw data to make a definitive diagnosis. Analysis of the results has also highlighted gaps in the literature such as the absence of studies employing wearables to facilitate clinical decisions in the respiratory domain. The disproportionate study of wearables in atrial fibrillation detection in comparison to other cardiac arrhythmias and conditions, as well as the lack of diversity in the sample populations used prevents the generalizability of results. creator: Hamzeh Khundaqji creator: Wayne Hing creator: James Furness creator: Mike Climstein uri: https://doi.org/10.7717/peerj.12598 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Khundaqji et al. title: Effects of short-term nitrogen and phosphorus addition on leaf stoichiometry of a dominant alpine grass link: https://peerj.com/articles/12611 last-modified: 2021-12-22 description: The effects of increasing nitrogen (N) and phosphorus (P) deposition on the nutrient stoichiometry of soil and plant are gaining improving recognition. However, whether and how the responses of N cycle coupled with P of the soil–plant system to external N and P deposition in alpine grassland is still unclear. A short-term external N and P addition experiment was conducted in an alpine grazing grassland in the KunLun Mountain to explore the effects of short-term N and P addition on the nutrient stoichiometry in soil and plant. Different rates of N addition (ranging from 0.5 g N m−2 yr−1 to 24 g N m−2 yr−1) and P addition (ranging from 0.05 g N m−2 yr−1 to 3.2 g P m−2 yr−1) were supplied, and the soil available N, P, leaf N and P stoichiometry of Seriphidium rhodanthum which dominant in the alpine ecosystem were measured. Results showed that N addition increased soil inorganic N, leaf C, leaf N, and leaf N:P ratio but decreased soil available P and leaf C:P. Furthermore, P addition increased soil available P, leaf P, soil inorganic N, leaf N, and leaf C and reduced leaf C:N, C:P, and N:P ratios. Leaf N:P was positively related to N addition gradient. Leaf C:P and leaf N:P were significantly negatively related to P addition gradient. Although external N and P addition changed the value of leaf N:P, the ratio was always lower than 16 in all treatments. The influences of P addition on soil and plant mainly caused the increase in soil available P concentration. In addition, the N and P cycles in the soil–plant system were tightly coupled in P addition but decoupled in N addition condition. The nutrient stoichiometry of soil and leaf responded differently to continuous N and P addition gradients. These data suggested that the alpine grazing grassland was limited by P rather than N due to long-term N deposition and uniform fertilization. Moreover, increasing P addition alleviated P limitation. Therefore, the imbalanced N and P input could change the strategy of nutrient use of the grass and then change the rates of nutrient cycling in the alpine grassland ecosystem in the future. creator: YaLan Liu creator: Bo Liu creator: Zewei Yue creator: Fanjiang Zeng creator: Xiangyi Li creator: Lei Li uri: https://doi.org/10.7717/peerj.12611 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Liu et al. title: Identification of HMMR as a prognostic biomarker for patients with lung adenocarcinoma via integrated bioinformatics analysis link: https://peerj.com/articles/12624 last-modified: 2021-12-22 description: BackgroundLung adenocarcinoma (LUAD) is the most prevalent tumor in lung carcinoma cases and threatens human life seriously worldwide. Here we attempt to identify a prognostic biomarker and potential therapeutic target for LUAD patients.MethodsDifferentially expressed genes (DEGs) shared by GSE18842, GSE75037, GSE101929 and GSE19188 profiles were determined and used for protein-protein interaction analysis, enrichment analysis and clinical correlation analysis to search for the core gene, whose expression was further validated in multiple databases and LUAD cells (A549 and PC-9) by quantitative real-time PCR (qRT-PCR) and western blot analyses. Its prognostic value was estimated using the Kaplan-Meier method, meta-analysis and Cox regression analysis based on the Cancer Genome Atlas (TCGA) dataset and co-expression analysis was conducted using the Oncomine database. Gene Set Enrichment Analysis (GSEA) was performed to illuminate the potential functions of the core gene.ResultsA total of 115 shared DEGs were found, of which 24 DEGs were identified as candidate hub genes with potential functions associated with cell cycle and FOXM1 transcription factor network. Among these candidates, HMMR was identified as the core gene, which was highly expressed in LUAD as verified by multiple datasets and cell samples. Besides, high HMMR expression was found to independently predict poor survival in patients with LUAD. Co-expression analysis showed that HMMR was closely related to FOXM1 and was mainly involved in cell cycle as suggested by GSEA.ConclusionHMMR might be served as an independent prognostic biomarker for LUAD patients, which needs further validation in subsequent studies. creator: Zhaodong Li creator: Hongtian Fei creator: Siyu Lei creator: Fengtong Hao creator: Lijie Yang creator: Wanze Li creator: Laney Zhang creator: Rui Fei uri: https://doi.org/10.7717/peerj.12624 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Li et al. title: 3D reconstruction identifies loci linked to variation in angle of individual sorghum leaves link: https://peerj.com/articles/12628 last-modified: 2021-12-22 description: Selection for yield at high planting density has reshaped the leaf canopy of maize, improving photosynthetic productivity in high density settings. Further optimization of canopy architecture may be possible. However, measuring leaf angles, the widely studied component trait of leaf canopy architecture, by hand is a labor and time intensive process. Here, we use multiple, calibrated, 2D images to reconstruct the 3D geometry of individual sorghum plants using a voxel carving based algorithm. Automatic skeletonization and segmentation of these 3D geometries enable quantification of the angle of each leaf for each plant. The resulting measurements are both heritable and correlated with manually collected leaf angles. This automated and scaleable reconstruction approach was employed to measure leaf-by-leaf angles for a population of 366 sorghum plants at multiple time points, resulting in 971 successful reconstructions and 3,376 leaf angle measurements from individual leaves. A genome wide association study conducted using aggregated leaf angle data identified a known large effect leaf angle gene, several previously identified leaf angle QTL from a sorghum NAM population, and novel signals. Genome wide association studies conducted separately for three individual sorghum leaves identified a number of the same signals, a previously unreported signal shared across multiple leaves, and signals near the sorghum orthologs of two maize genes known to influence leaf angle. Automated measurement of individual leaves and mapping variants associated with leaf angle reduce the barriers to engineering ideal canopy architectures in sorghum and other grain crops. creator: Michael C. Tross creator: Mathieu Gaillard creator: Mackenzie Zwiener creator: Chenyong Miao creator: Ryleigh J. Grove creator: Bosheng Li creator: Bedrich Benes creator: James C. Schnable uri: https://doi.org/10.7717/peerj.12628 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Tross et al. title: Small herbivores and abiotic heterogeneity promote trait variation of a saltmarsh plant in local communities link: https://peerj.com/articles/12633 last-modified: 2021-12-22 description: Intraspecific trait variation (ITV) enables plants to respond to global changes. However, causes for ITV, especially from biotic components such as herbivory, are not well understood. We explored whether small vertebrate herbivores (hares and geese) impact ITV of a dominant clonal plant (Elytrigia atherica) in local communities. Moreover, we looked at the relative importance of their direct (e.g., selective grazing) and indirect effects (altering genotypic richness/diversity and abiotic environment) on ITV. We used exclosures at two successional stages in a Dutch saltmarsh, where grazing pressure at the early successional stage was ca. 1.5 times higher than that of the intermediate successional stage. We measured key functional traits of E. atherica including height, aboveground biomass, flowering (flower or not), specific leaf area, and leaf dry matter content in local communities (1 m × 1 m plots) inside and outside the exclosures. We determined genotypic richness and diversity of each plant using molecular markers. We further measured abiotic variations in topography and clay thickness (a proxy for soil total nitrogen). Structural equation models revealed that small herbivores significantly promoted ITV in height and flowering at the early successional stage, while they marginally promoted ITV in height at the intermediate successional stage. Moreover, the direct effects of herbivores played a major role in promoting ITV. Small herbivores decreased genotypic diversity at the intermediate successional stage, but genotypic richness and diversity did not impact ITV. Small herbivores did not alter topographic variation and variation in clay thickness, but these variations increased ITV in all traits at the early successional stage. Small herbivores may not only impact trait means in plants as studies have shown but also their ITV. creator: Qingqing Chen creator: Christian Smit creator: Ido Pen creator: Han Olff uri: https://doi.org/10.7717/peerj.12633 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Chen et al. title: Ferric citrate is a safe and digestible source of iron in broilers and piglets link: https://peerj.com/articles/12636 last-modified: 2021-12-22 description: BackgroundIron (Fe) is traditionally supplemented in poultry and swine diets using inorganic forms (e.g. sulfates, oxides). However, research suggests that organic sources are more beneficial due to greater bioavailability. In this paper, we present results from four studies aimed at assessing ferric citrate (CI-FER™, Akeso Biomedical Inc., Burlington, MA, USA) as a safe and effective source of Fe for broilers and piglets.MethodsA total of four studies were performed in Germany following standard farming practices for each species. One study in day-old broiler chicks and one study in weaned piglets were designed as target animal safety studies where animals were randomly allocated to one of three treatment groups: a negative control group, the proposed dose group and a multifold dose group. Broilers and pigs were fed the experimental diets for 35 and 42 days, respectively. In each study, average daily feed intake, average daily weight gain and feed conversion ratio were measured, and blood samples were taken at study end for routine biochemistry and haematology. The other two studies were designed to evaluate different sources of dietary Fe for weaned piglets bred and managed under standard farm conditions. All piglets received routine Fe injections (200 mg Fe dextran, intramuscular) on day 3 of age, as well as the experimental diets for 42 days. In both studies, performance parameters were measured. In one study, Fe digestibility and serum Fe, superoxide dismutase and haptoglobin were also measured. In all studies, the general health status of the animals was monitored daily and all culls and mortality recorded. Each study followed a complete randomised block design.ResultsIn broilers, ferric citrate was well tolerated up to 2,000 mg/kg feed (×10 the recommended inclusion rate) and no adverse effects on growth, blood parameters or mortality were observed. In piglets, ferric citrate was well tolerated up to 5,000 mg/kg feed (×10 the recommended inclusion rate) with no adverse effects on growth, blood parameters or mortality. In addition, piglets fed ferric citrate performed significantly better than animals fed the negative control diet (containing only endogenous Fe) and those fed inorganic forms of Fe. Moreover, piglets fed ferric citrate demonstrated improved Fe digestibility and improved oxidative status. Altogether, these findings show that ferric citrate is a safe and easily digestible source of dietary Fe for broilers and piglets. creator: Klaus Männer creator: Hannah Lester creator: Eliana Henriquez-Rodriguez uri: https://doi.org/10.7717/peerj.12636 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Männer et al. title: Impact of climatic conditions projected at the World Cup in Qatar 2022 on repeated maximal efforts in soccer players link: https://peerj.com/articles/12658 last-modified: 2021-12-22 description: This study aimed to investigate the relationship between the climatic conditions predicted for the 2022 FIFA World Cup in Qatar and the capacity for repeated maximum effort (RSA), of soccer players. Twenty-four semi-professional soccer players participated in the study. The exercise test consisted of ten 6-second maximal efforts on a cycloergometer. A 90-second passive rest interval was used. Mechanical parameters were recorded in each repetition, and biochemical parameters at rest and even repetitions. The test was performed in a Weiss Technik WK-26 climate chamber under two different conditions: (1) thermoneutral (TNC - 20.5 °C; 58.7% humidity); (2) predicted for the 2022 World Cup in Qatar (QSC - 28.5 ± 1.92 °C; 58.7 ± 8.64% humidity). Significantly higher mean maximum power values were recorded in the second repetition under QSC conditions (1731,8 ± 214,4 W) (p = 0.025). A significantly longer time to reach maximum power was also recorded under TNC conditions compared to QSC conditions in repetition 2 (1,32 ± 0,33 s), (1,05 ± 0,29 s) (p = 0.016) and 6 (1,41 ± 0,48 s), (1,17 ± 0,25) (p = 0.036). There was a significantly higher rate of power loss, between repetition 2 (p = 0.023) and 4 (p = 0.043) under QSC conditions, compared to TNC. Considering the biochemical parameters, a significantly higher pO2 concentration was registered under QSC conditions in the 10th repetition (p = 0.006). The ambient temperature during exercise should be taken into account to determine the anaerobic exercise capacity of the athletes. At higher temperatures, there is a greater capacity for maximal effort, in terms of maximal power achieved, but with a greater decrease in performance. creator: Wiktor Chodor creator: Paweł Chmura creator: Jan Chmura creator: Marcin Andrzejewski creator: Ewa Jówko creator: Tomasz Buraczewski creator: Adrian Drożdżowski creator: Andrzej Rokita creator: Marek Konefał uri: https://doi.org/10.7717/peerj.12658 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Chodor et al. title: A taxonomic outline of the Poecilimon affinis complex (Orthoptera) using the geometric morphometric approach link: https://peerj.com/articles/12668 last-modified: 2021-12-22 description: The genus Poecilimon contains 145 species, widely distributed in the Palaearctic, among which the Poecilimon ornatus group has the greatest diversity in the Balkans. Despite several revisions of the genus, the systematics of the species group, and in particular, of the taxa associated with the species Poecilimon affinis, is still unsolved. Due to morphological similarity, P. affinis with its subspecies, P. nonveilleri and P. pseudornatus form the Poecilimon affinis complex. The aim of this study is to test the hypotheses of an outlined species complex, namely the P. affinis complex, within the P. ornatus group using morphological data. Geometric analysis was conducted to explore variation in the structure of the male tegmen, ovipositor, male cercus, and male pronotum. The number of teeth and stridulatory file measurements provided additional information on morphological variation within the complex. A phylogenetic tree based on the cytochrome c oxidase subunit I gene (COI) was used for comparison with the morphological data. Canonical variate analysis showed that male tegmen and male cercus are good morphostructures to distinguish the taxa belonging to the P. affinis complex from other species in the P. ornatus group. This may confirm our assumption for the designation of the P. affinis complex. The results of the principal component analysis of stridulatory file measurements, molecular data, and CVA of the ovipositor suggest adding two additional species to the complex: P. ornatus and P. hoelzeli. creator: Maciej Kociński creator: Beata Grzywacz creator: Georgi Hristov creator: Dragan Chobanov uri: https://doi.org/10.7717/peerj.12668 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Kociński et al.