Prediction of individual mortality risk among patients with chronic obstructive pulmonary disease: a convenient, online, individualized, predictive mortality risk tool based on a retrospective cohort study
Background Chronic obstructive pulmonary disease (COPD) is a serious condition with a poor prognosis. No clinical study has reported an individual-level mortality risk curve for patients with COPD. As such, the present study aimed to construct a prognostic model for predicting individual mortality risk among patients with COPD, and to provide an online predictive tool to more easily predict individual mortality risk in this patient population. Patients and methods The current study retrospectively included data from 1,255 patients with COPD. Random survival forest plots and Cox proportional hazards regression were used to screen for independent risk factors in patients with COPD. A prognostic model for predicting mortality risk was constructed using eight risk factors. Results Cox proportional hazards regression analysis identified eight independent risk factors among COPD patients: B-type natriuretic peptide (hazard ratio [HR] 1.248 [95% confidence interval (CI) 1.155–1.348]); albumin (HR 0.952 [95% CI 0.931–0.974); age (HR 1.033 [95% CI 1.022–1.044]); globulin (HR 1.057 [95% CI 1.038–1.077]); smoking years (HR 1.011 [95% CI 1.006–1.015]); partial pressure of arterial carbon dioxide (HR 1.012 [95% CI 1.007–1.017]); granulocyte ratio (HR 1.018 [95% CI 1.010–1.026]); and blood urea nitrogen (HR 1.041 [95% CI 1.017–1.066]). A prognostic model for predicting risk for death was constructed using these eight risk factors. The areas under the time-dependent receiver operating characteristic curves for 1, 3, and 5 years were 0.784, 0.801, and 0.806 in the model cohort, respectively. Furthermore, an online predictive tool, the “Survival Curve Prediction System for COPD patients”, was developed, providing an individual mortality risk predictive curve, and predicted mortality rate and 95% CI at a specific time. Conclusion The current study constructed a prognostic model for predicting an individual mortality risk curve for COPD patients after discharge and provides a convenient online predictive tool for this patient population. This predictive tool may provide valuable prognostic information for clinical treatment decision making during hospitalization and health management after discharge (https://zhangzhiqiao15.shinyapps.io/Smart_survival_predictive_system_for_COPD/).
Lu et al. (2022) Prediction of individual mortality risk among patients with chronic obstructive pulmonary disease: a convenient, online, individualized, predictive mortality risk tool based on a retrospective cohort study. PeerJ 10:e14457 https://doi.org/10.7717/peerj.14457
LncRNA RP11-551L14.4 suppresses breast cancer development by inhibiting the expression of miR-4472
Background Previous studies have been reported that long non-coding RNA (lncRNA) can regulate the expression of genes which are involved in many important cellular processes The potential role of lncRNA RP11-551L14.4 in the development of breast cancer and the possible regulatory mechanisms was investigated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze RP11-551L14.4 expression in 36 paired breast cancer tissues and adjacent tissues. The expression of RP11-551L14.4 in multiple breast cancer cell lines was detected by qRT-PCR. Meanwhile, overexpression of RP11-551L14.4 models was established using lentivirus in BT474 and T47D breast cancer cells. Cell counting kit-8 (CCK-8), cell colony formation and cell cycle assays were performed to detect the effects of RP11-551L14.4 on the biological function of breast cancer cells. Besides, bioinformatics techniques, dual luciferase reporter gene assay and rescue experiments were used to investigate the potential mechanisms. Results RP11-551L14.4 expression was negatively associated with the advanced tumor stage. Breast cancer patients with low RP11-551L14.4 expression manifested a poorer prognosis. The results of qRT-PCR showed that RP11-551L14.4 expression in breast cancer tissues was significantly lower than in adjacent tissues. Meanwhile, overexpression of RP11-551L14.4 significantly decreased the cell proliferation and cell cycle. Bioinformatics technology showed that RP11-551L14.4 could complementarily bind to miR-4472. qRT-PCR results indicated that the expression levels of miR-4472 and RP11-551L14.4 in breast cancer were negatively correlated. Luciferase reporter gene assay showed that miR-4472 remarkably decreased the relative luciferase activity of the wild-type RP11-551L14.4 vector. miR-4472 is a direct target gene of RP11-551L14.4. miR-4472 levels were reduced, and repulsive guidance molecule A (RGMA) mRNA or protein levels were increased after overexpression of RP11-551L14.4 in the breast cancer cells. miR-4472 reversed the effects caused by RP11-551L14.4 in breast cancer cells. Conclusion RP11-551L14.4 expression was remarkably decreased in breast cancer tissues and cells. RP11-551L14.4 may inhibit the malignant progression of breast cancer by regulating miR-4472 expression.
Wang et al. (2022) LncRNA RP11-551L14.4 suppresses breast cancer development by inhibiting the expression of miR-4472. PeerJ 10:e14482 https://doi.org/10.7717/peerj.14482
A pipeline for assembling low copy nuclear markers from plant genome skimming data for phylogenetic use
Background Genome skimming is a popular method in plant phylogenomics that do not include a biased enrichment step, relying on random shallow sequencing of total genomic DNA. From these data the plastome is usually readily assembled and constitutes the bulk of phylogenetic information generated in these studies. Despite a few attempts to use genome skims to recover low copy nuclear loci for direct phylogenetic use, such endeavor remains neglected. Causes might include the trade-off between libraries with few reads and species with large genomes (i.e., missing data caused by low coverage), but also might relate to the lack of pipelines for data assembling. Methods A pipeline and its companion R package designed to automate the recovery of low copy nuclear markers from genome skimming libraries are presented. Additionally, a series of analyses aiming to evaluate the impact of key assembling parameters, reference selection and missing data are presented. Results A substantial amount of putative low copy nuclear loci was assembled and proved useful to base phylogenetic inference across the libraries tested (4 to 11 times more data than previously assembled plastomes from the same libraries). Discussion Critical aspects of assembling low copy nuclear markers from genome skims include the minimum coverage and depth of a sequence to be used. More stringent values of these parameters reduces the amount of assembled data and increases the relative amount of missing data, which can compromise phylogenetic inference, in turn relaxing the same parameters might increase sequence error. These issues are discussed in the text, and parameter tuning through multiple comparisons tracking their effects on support and congruence is highly recommended when using this pipeline. The skimmingLoci pipeline (https://github.com/mreginato/skimmingLoci) might stimulate the use of genome skims to recover nuclear loci for direct phylogenetic use, increasing the power of genome skimming data to resolve phylogenetic relationships, while reducing the amount of sequenced DNA that is commonly wasted.
Reginato (2022) A pipeline for assembling low copy nuclear markers from plant genome skimming data for phylogenetic use. PeerJ 10:e14525 https://doi.org/10.7717/peerj.14525
Cryptic population structure at the northern range margin of the service tree Sorbus domestica
Climate change has aroused interest in planting warm- and drought-adapted trees in managed forests and urban areas. An option is to focus on tree species that occur naturally, but have centers of distribution in warmer and drier areas. However, in order to protect the species pool of genetic diversity, efforts of planting and promotion should be informed by knowledge on the local genetic diversity. Here, we studied the macro- and micro-scale population genetic structure of the rare European fruit tree Sorbus domestica at its northern range margin, in western Switzerland. New microsatellite data were combined with published data from across the European distribution of the species. Analyses revealed the presence of mainly one of two species-wide ancestral clusters, i.e., the western European cluster, with evidence that it consists of two cryptic sub-clusters. Average pairwise FST of 0.118 was low across the range, and only allelic richness was reduced in the northern margin compared to more southern and southeastern areas of Europe. Based on our finding of considerable genetic diversity of the species in western and northern Switzerland, we suggest that a national propagation program should focus on collecting seeds from natural, high-density tree stands and propagate locally. More generally, our study shows that rare tree species in marginal areas of their distributions do not necessarily have low genetic diversity or heightened levels of inbreeding, and in those cases probably need no assisted migration in efforts to propagate them.
Armbruster et al. (2022) Cryptic population structure at the northern range margin of the service tree Sorbus domestica. PeerJ 10:e14397 https://doi.org/10.7717/peerj.14397
Combined use of karyotyping and copy number variation sequencing technology in prenatal diagnosis
Background Karyotyping and genome copy number variation sequencing (CNV-seq) are two techniques frequently used in prenatal diagnosis. This study aimed to explore the diagnostic potential of using a combination of these two methods in order to provide a more accurate clinical basis for prenatal diagnosis. Methods We selected 822 pregnant women undergoing amniocentesis and separated them into six groups according to different risk indicators. Karyotyping and CNV-seq were performed simultaneously to compare the diagnostic performance of the two methods. Results Among the different amniocentesis indicators, abnormal fetal ultrasounds accounted for 39.29% of the total number of examinees and made up the largest group. The abnormal detection rate of non-invasive prenatal testing (NIPT) high risk was 37.93% and significantly higher than the other five groups (P < 0.05). The abnormal detection rate of mixed indicators was significantly higher than the history of the adverse reproductive outcomes group (P = 0.0151). The two methods combined found a total of 119 abnormal cases (14.48%). Karyotyping detected 57 cases (6.93%) of abnormal karyotypes, 30 numerical aberrations, and 27 structural aberrations. CNV-seq identified 99 cases (12.04%) with altered CNVs, 30 cases of chromosome aneuploidies, and 69 structural aberrations (28 pathogenic, eight that were likely pathogenic, and 33 microdeletion/duplication variants of uncertain significance (VUS)). Thirty-seven cases were found abnormal by both methods, 20 cases were detected abnormally by karyotyping (mainly mutual translocation and mostly balanced), and 62 cases of microdeletion/duplication were detected by CNV-seq. Steroid sulfatase gene (STS) deletion was identified at chromosome Xp22.31 in three cases. Postnatal follow-up confirmed that babies manifested skin abnormalities one week after birth. Six fetuses had Xp22.31 duplications ranging from 1.5 Kb to 1.7 Mb that were detected by CNV-seq. Follow-up showed that five babies presented no abnormalities during follow-up, except for one terminated pregnancy due to a history of adverse reproductive outcomes. Conclusion The combination of using CNV-seq and karyotyping significantly improved the detection rate of fetal pathogenic chromosomal abnormalities. CNV-seq is an effective complement to karyotyping and improves the accuracy of prenatal diagnosis.
Zhang et al. (2022) Combined use of karyotyping and copy number variation sequencing technology in prenatal diagnosis. PeerJ 10:e14400 https://doi.org/10.7717/peerj.14400
Upregulated TUBG1 expression is correlated with poor prognosis in hepatocellular carcinoma
Background Hepatocellular carcinoma (HCC) development is a complex pathological process. Tubulin gamma 1 (TUBG1) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Methods Herein we first evaluated the gene expression levels of TUBG1 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases. We then elucidated the association between TUBG1 gene expression levels and survival rates of patients with HCC. Cell cycle, proliferation, transwell migration, and matrigel invasion assays were used to study the effects of TUBG1 on the malignant phenotypes of HCC cells. Results Based on the data obtained from the aforementioned databases and our in vitro experiments, TUBG1 was found to be overexpressed in HCC and patients with high TUBG1 expression levels showed a remarkably poor overall survival rate. In addition, the expression of TUBG1 significantly promoted the malignant phenotypes of HCC cells in vitro. Gene ontology term enrichment analysis revealed that co-regulated genes were enriched in biological processes mainly involved in chromosome segregation, chromosomal region, and chromatin binding; moreover, Kyoto Encyclopedia of Genes and Genome pathway analysis showed that they were mainly involved in cell cycle, oocyte meiosis, platinum drug resistance, and the p53 signaling pathway. Conclusions We report that TUBG1 is an important oncogene in HCC. It promotes HCC progression and may serve as a potential prognostic biomarker for HCC. Future studies are warranted to unveil molecular biological mechanisms underlying TUBG1 carcinogenesis.
Zhang et al. (2022) Upregulated TUBG1 expression is correlated with poor prognosis in hepatocellular carcinoma. PeerJ 10:e14415 https://doi.org/10.7717/peerj.14415
Effects of saddle tilt and stirrup length on the kinetics of horseback riders
Background How the modification of saddle fitting parameters in horse riding affects rider’s kinetics is very uncertain. The aim of this study is to describe how manipulating the two main adjustments that an end-user is likely to perform (saddle tilt and stirrup length) affects the biomechanics of a horse rider on a living horse. Methods Eleven showjumpers volunteered to take part in this study. Each participant performed a 120-strides standardization trial at trot and canter, with 0° saddle tilt and stirrup length that would position the rider’s knee at 90°. Following the standardization trial, four interventions were performed, which consisted of 60 strides with 60 mm shorter stirrups, 60 mm longer stirrups, 4° forward tilted saddle and 4° backward tilted saddle. Stirrup and rein tension forces were measured with tension loadcells. A symmetry index was calculated. Acceleration was measured with inertial measuring units at the helmet and back of the rider and shock attenuation was calculated. Results Shortening the stirrups and adjusting saddle tilt significantly enhanced shock attenuation at canter and increased force on the stirrups at trot and canter (p < 0.05). Lowering the stirrups reduced rein tension forces (p = 0.01). At trot, adjusting saddle tilt and stirrup length enhanced symmetry index on the bit (p < 0.05). These results allowed for general guidelines to be proposed, although individualization became an evident part of any saddle setup design due to a high inter-subject variability.
Elmeua González et al. (2022) Effects of saddle tilt and stirrup length on the kinetics of horseback riders. PeerJ 10:e14438 https://doi.org/10.7717/peerj.14438
Prevalence, classification and dental treatment requirements of dens invaginatus by cone-beam computed tomography
Background This study aimed the evaluation of the prevalence, characteristics, types of dens invaginatus (DI) and co-observed dental anomalies to understand dental treatment requirements in anterior teeth that are susceptible to developmental anomalies by using cone-beam computed tomography (CBCT). Methods In this retrospective study, the anterior teeth of 958 patients were evaluated by using CBCT for the presence of DI. The demographic features, types of DI and treatment requirements were also recorded. The association between sex and the presence of DI was evaluated using chi-squared test. Results Seventy-three DI anomalies were detected in the anterior teeth of 49 patients (18 females, 31 males). The frequency of DI was 5.11% and the most frequently involved teeth were lateral (57.53%). Forty-six teeth were classified as Type I (63.01%), 24 as Type II (32.87%), and three as Type III (4.10%). Apical pathosis was found to be 20.54% in all DIs detected and accounted for all Type III and one-third of Type II. Conclusions CBCT imaging can be effective in the detection of dental anomalies such as DI and planning for root canal therapy and surgical treatments. Prophylactic interventions might be possible to prevent apical pathosis with the data obtained from CBCT images.
Yalcin et al. (2022) Prevalence, classification and dental treatment requirements of dens invaginatus by cone-beam computed tomography. PeerJ 10:e14450 https://doi.org/10.7717/peerj.14450
Genome-wide identification and expression pattern analysis of quinoa BBX family
BBX is a transcription factor encoding zinc finger protein that plays a key role in plant growth and development as well as in responding to abiotic stresses. However, in quinoa, which is known as a “super grain” and has extremely high nutritional value, this gene family has not yet been thoroughly studied. In this study, in order to fully understand the family function of the BBX in quinoa, a total of 31 BBX members were identified by bioinformatics methods. These BBX members were mainly acidic proteins, and most of their secondary structures were random coil s, 31 CqBBX members were unevenly distributed on 17 chromosomes, and the analysis of replication events found that quinoa BBX genes produced a total of 14 pairs of gene replication. The BBX genes were divided into five subfamilies according to phylogenetics, and its gene structure and conserved motif were basically consistent with the classification of its phylogenetic tree. In addition, a total of 43 light response elements, hormone response elements, tissue-specific expression response elements, and abiotic stress response elements were found in the promoter region, involving stress elements such as drought and low temperature. Finally, the expression patterns of CqBBX genes in different tissues and abiotic stresses were studied by combining transcriptome data and qRT-PCR , and all 13 genes responded to drought, salt, and low-temperature stress to varying degrees. This study is the first comprehensive study of the BBX family of quinoa, and its results provide important clues for further analysis of the function of the abiotic stress response.
Xuefen et al. (2022) Genome-wide identification and expression pattern analysis of quinoa BBX family. PeerJ 10:e14463 https://doi.org/10.7717/peerj.14463
Identification, classification, and expression profile analysis of heat shock transcription factor gene family in Salvia miltiorrhiza
In response to abiotic stresses, transcription factors are essential. Heat shock transcription factors (HSFs), which control gene expression, serve as essential regulators of plant growth, development, and stress response. As a model medicinal plant, Salvia miltiorrhiza is a crucial component in the treatment of cardiovascular illnesses. But throughout its growth cycle, S.miltiorrhiza is exposed to a series of abiotic challenges, including heat and drought. In this study, 35 HSF genes were identified based on genome sequencing of Salvia miltiorrhiza utilizing bioinformatics techniques. Additionally, 35 genes were classified into three groups by phylogeny and gene structural analysis, comprising 22 HSFA, 11 HSFB, and two HSFC. The distribution and sequence analysis of motif showed that SmHSFs were relatively conservative. In SmHSF genes, analysis of the promoter region revealed the presence of many cis-acting elements linked to stress, hormones, and growth and development, suggesting that these factors have regulatory roles. The majority of SmHSFs were expressed in response to heat and drought stress, according to combined transcriptome and real-time quantitative PCR (qRT-PCR) analyses. In conclusion, this study looked at the SmHSF gene family using genome-wide identification, evolutionary analysis, sequence characterization, and expression analysis. This research serves as a foundation for further investigations into the role of HSF genes and their molecular mechanisms in plant stress responses.
Liu et al. (2022) Identification, classification, and expression profile analysis of heat shock transcription factor gene family in Salvia miltiorrhiza. PeerJ 10:e14464 https://doi.org/10.7717/peerj.14464