ALBERT

Description: Background Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities. Whole genome sequencing (WGS) better captures genetic variation but remains prohibitively expensive. Thus, we explored WGS at “mid-pass” 1-7x coverage. Results Here, we developed and benchmarked methods for mid-pass sequencing. When applied to a population without an existing genomic reference panel, 4x mid-pass performed consistently well across ethnicities, with high recall (98%) and precision (97.5%). Conclusion Compared to array data imputed into 1000 Genomes, mid-pass performed better across all metrics and identified novel population-specific variants with potential disease relevance. We hope our work will reduce financial barriers for geneticists from underrepresented populations to characterize their genomes prior to biomedical genetic applications.

Description: Background The proper identification of feather grasses in nature is often limited due to phenotypic variability and high morphological similarity between many species. Among plausible factors influencing this issue are hybridisation and introgression recently detected in the genus. Nonetheless, to date, only a bounded set of taxa have been investigated using integrative taxonomy combining morphological and molecular data. Here, we report the first large-scale study on five feather grass species across several hybrid zones in Russia and Central Asia. In total, 302 specimens were sampled in the field and classified based on the current descriptions of these taxa. They were then genotyped with high density genome-wide markers and measured based on a set of morphological characters to delimitate species and assess levels of hybridisation and introgression. Moreover, we tested species for past introgression and estimated divergence times between them. Results Our findings demonstrated that 250 specimens represent five distinct species: S. baicalensis, S. capillata, S. glareosa, S. grandis and S. krylovii. The remaining 52 individuals provided evidence for extensive hybridisation between S. capillata and S. baicalensis, S. capillata and S. krylovii, S. baicalensis and S. krylovii, as well as to a lesser extent between S. grandis and S. krylovii, S. grandis and S. baicalensis. We detected past reticulation events between S. baicalensis, S. krylovii, S. grandis and inferred that diversification within species S. capillata, S. baicalensis, S. krylovii and S. grandis started ca. 130–96 kya. In addition, the assessment of genetic population structure revealed signs of contemporary gene flow between populations across species from the section Leiostipa, despite significant geographical distances between some of them. Lastly, we concluded that only 5 out of 52 hybrid taxa were properly identified solely based on morphology. Conclusions Our results support the hypothesis that hybridisation is an important mechanism driving evolution in Stipa. As an outcome, this phenomenon complicates identification of hybrid taxa in the field using morphological characters alone. Thus, integrative taxonomy seems to be the only reliable way to properly resolve the phylogenetic issue of Stipa. Moreover, we believe that feather grasses may be a suitable genus to study hybridisation and introgression events in nature.

Description: Background Self-care and participation of patients in improving health and increasing awareness about the risk factors that affect the development of disease in patients with urinary tract stones are influential factors in controlling and improving the quality of life in these patients. In this regard, the availability and capability of smartphones increase patients’ self-care ability. The present study aimed to develop and evaluate a self-care application based on smartphones for patients with urinary tract stones. Methods The present study is a developmental and applied study that was conducted in three phases. First, the information needs and functionalities of the self-care application were determined by surveying 101 patients, 32 urologists and nephrologists, 11 nurses, and six other specialists. In the second phase, the initial sample of the smartphone-based application was created, and in the third phase, the designed application was evaluated by 15 experts using the standard Post-Study System Usability Questionnaire (PSSUQ 18.3) and Nielsen’s Attributes of Usability (NAU) questionnaire. Results of the questionnaires were entered into SPSS-23 software for analysis using descriptive statistics. Results In the first phase, 21 information elements and nine critical functionalities for the self-care application were identified, and then this application was designed by Java programming language. The evaluation of experts showed that two aspects of the quality of system user interface from the user's point of view and the overall performance of the application together obtained the highest score (6.43 from 7), which was equal to 91.85%. Then according to the experts, aspects of the degree of convenience and user-friendliness of the application received the highest score (6.10 from 7), which was equal to 87.14%, and also all aspects of the application were evaluated at an acceptable level. In general, results of the evaluation of application's usability by experts showed that the usability of the application for patients with urinary tract stones was at an acceptable level. Conclusion According to the results obtained from evaluating the smartphone-based application for patients with urinary tract stones, this self-care application can be used to prevent and control urinary tract stones and facilitate self-care and active patient participation in care.

Description: Background Bletilla striata is one of the important species belonging to the Bletilla genus of Orchidaceae. Since its extracts have an astringent effect on human tissues, B. striata is widely used for hemostasis and healing. Recently, some other beneficial effects have also been uncovered, such as antioxidation, antiinflammation, antifibrotic, and immunomodulatory activities. As a key step towards a thorough understanding on the medicinal ingredient production in B. striata, deciphering the regulatory codes of the metabolic pathways becomes a major task. Results In this study, three organs (roots, tubers and leaves) of B. striata were analyzed by integrating transcriptome sequencing and untargeted metabolic profiling data. Five different metabolic pathways, involved in polysaccharide, sterol, flavonoid, terpenoid and alkaloid biosynthesis, were investigated respectively. For each pathway, the expression patterns of the enzyme-coding genes and the accumulation levels of the metabolic intermediates were presented in an organ-specific way. Furthermore, the relationships between enzyme activities and the levels of the related metabolites were partially inferred. Within the biosynthetic pathways of polysaccharides and flavonoids, long-range phytochemical transportation was proposed for certain metabolic intermediates and/or the enzymes. Conclusions The data presented by this work could strengthen the molecular basis for further studies on breeding and medicinal uses of B. striata.

Description: Background The FASTA file format, used to store polymeric sequence data, has become a bioinformatics file standard used for decades. The relatively large files require additional files, beyond the scope of the original format, to identify sequences and to provide random access. Multiple compressors have been developed to archive FASTA files back and forth, but these lack direct access to targeted content or metadata of the archive. Moreover, these solutions are not directly backwards compatible to FASTA files, resulting in limited software integration. Results We designed a linux based toolkit that virtualises the content of DNA, RNA and protein FASTA archives into the filesystem by using filesystem in userspace. This guarantees in-sync virtualised metadata files and offers fast random-access decompression using bit encodings plus Zstandard (zstd). The toolkit, FASTAFS, can track all its system-wide running instances, allows file integrity verification and can provide, instantly, scriptable access to sequence files and is easy to use and deploy. The file compression ratios were comparable but not superior to other state of the art archival tools, despite the innovative random access feature implemented in FASTAFS. Conclusions FASTAFS is a user-friendly and easy to deploy backwards compatible generic purpose solution to store and access compressed FASTA files, since it offers file system access to FASTA files as well as in-sync metadata files through file virtualisation. Using virtual filesystems as in-between layer offers format conversion without the need to rewrite code into different programming languages while preserving compatibility.

Description: Background Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor prognosis. The immune-related genes (IRGs) are crucial to immunocytes tumor infiltration. This study aimed to construct a IRG-related prediction signature in EAC. Methods The related data of EAC patients and IRGs were obtained from the TCGA and ImmPort database, respectively. The cox regression analysis constructed the prediction signature and explored the transcription factors regulatory network through the Cistrome database. TIMER database and CIBERSORT analytical tool were utilized to explore the immunocytes infiltration analysis. Results The prediction signature with 12 IRGs (ADRM1, CXCL1, SEMG1, CCL26, CCL24, AREG, IL23A, UCN2, FGFR4, IL17RB, TNFRSF11A, and TNFRSF21) was constructed. Overall survival (OS) curves indicate that the survival rate of the high-risk group is significantly shorter than the low-risk group (P = 7.26e−07), and the AUC of 1-, 3- and 5- year survival prediction rates is 0.871, 0.924, and 0.961, respectively. Compared with traditional features, the ROC curve of the risk score in the EAC patients (0.967) is significant than T (0.57), N (0.738), M (0.568), and Stage (0.768). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are accurate by the combined analysis of the risk score, Sex, M stage, and Stage (The AUC of 1- and 3-years are 0.911, and 0.853). Conclusion The 12 prognosis-related IRGs might be promising therapeutic targets for EAC.

Description: Background To assess the accuracy and reproducibility of right ventricular (RV) and left ventricular (LV) function and flow measurements in children with repaired tetralogy of Fallot (rTOF) using four-dimensional (4D) flow, compared with conventional two-dimensional (2D) magnetic resonance imaging (MRI) sequences. Methods Thirty pediatric patients with rTOF were retrospectively enrolled to undergo 2D balanced steady-state free precession cine (2D b-SSFP cine), 2D phase contrast (PC), and 4D flow cardiac MRI. LV and RV volumes and flow in the ascending aorta (AAO) and main pulmonary artery (MPA) were quantified. Pearson’s or Spearman’s correlation tests, paired t-tests, the Wilcoxon signed-rank test, Bland–Altman analysis, and intraclass correlation coefficients (ICC) were performed. Results The 4D flow scan time was shorter compared with 2D sequences (P  0.05), and showed strong correlations (r 〉 0.90, P  0.60, P  0.85). Conclusions RV and LV function and flow quantification in pediatric patients with rTOF using 4D flow MRI can be measured accurately and reproducibly compared to those with conventional 2D sequences.

Description: Cell surface biochemical changes, notably excessive increase in outer leaflet sphingomyelin (SM) content, are important in cancer initiation, growth, and immune evasion. Innumerable reports describe methods to initiate, promote, or enhance immunotherapy of clinically detected cancer, notwithstanding the challenges, if not impossibility, of identification of tumor-specific, or associated antigens, the lack of tumor cell surface membrane expression of major histocompatibility complex (MHC) class I alpha and β2 microglobulin chains, and lack of expression or accessibility of Fas and other natural killer cell immune checkpoint molecules. Conversely, SM synthesis and hydrolysis are increasingly implicated in initiation of carcinogenesis and promotion of metastasis. Surface membrane SM readily forms inter- and intra- molecular hydrogen bond network, which excessive tightness would impair cell-cell contact inhibition, inter- and intra-cellular signals, metabolic pathways, and susceptibility to host immune cells and mediators. The present review aims at clarifying the tumor immune escape mechanisms, which face common immunotherapeutic approaches, and attracting attention to an entirely different, neglected, key aspect of tumorigenesis associated with biochemical changes in the cell surface that lead to failure of contact inhibition, an instrumental tumorigenesis mechanism. Additionally, the review aims to provide evidence for surface membrane SM levels and roles in cells resistance to death, failure to respond to growth suppressor signals, and immune escape, and to suggest possible novel approaches to cancer control and cure.

Description: Background The gut microbiome is a diverse network of bacteria which inhabit our digestive tract and is crucial for efficient cellular metabolism, nutrient absorption, and immune system development. Spinal cord injury (SCI) disrupts autonomic function below the level of injury and can alter the composition of the gut microbiome. Studies in rodent models have shown that SCI-induced bacterial imbalances in the gut can exacerbate the spinal cord damage and impair recovery. In this study we, for the first time, characterized the composition of the gut microbiome in a Yucatan minipig SCI model. We compared the relative abundance of the most dominant bacterial phyla in control samples to those collected from animals who underwent a contusion-compression SCI at the 2nd or 10th Thoracic level. Results We identify specific bacterial fluctuations that are unique to SCI animals, which were not found in uninjured animals given the same dietary regimen or antibiotic administration. Further, we identified a specific time-frame, “SCI-acute stage”, during which many of these bacterial fluctuations occur before returning to “baseline” levels. Conclusion This work presents a dynamic view of the microbiome changes that accompany SCI, establishes a resource for future studies and to understand the changes that occur to gut microbiota after spinal cord injury and may point to a potential therapeutic target for future treatment.

Description: Background Lipid levels in blood have decreased considerably during the past decades in the general population partly due to use of statins. This study aims to investigate the trends in lipid levels between 2001 and 2018 in a statin-free population from primary health care, overall and by sex and age. Methods In a cohort of 634,119 patients from general practice with no diagnoses or medical treatments that affected lipid levels of total cholesterol (TC; n = 1,574,339) between 2001 and 2018 were identified. Similarly, measurements of low-density lipoprotein cholesterol (LDL-C; n = 1,302,440), high-density lipoprotein cholesterol (HDL-C; n = 1,417,857) and triglycerides (TG; n = 1,329,477) were identified. Results Mean TC decreased from 5.64 mmol/L (95% CI: 5.63–5.65) in 2001 to 5.17 mmol/L (95% CI: 5.16–5.17) in 2018 while LDL-C decreased from 3.67 mmol/L (95% CI: 3.66–3.68) to 3.04 mmol/L (95% CI: 3.03–3.04). Women aged 70–74 years experienced the largest decreases in TC levels corresponding to a decrease of 0.7 mmol/L. The decrease in LDL-C levels was most pronounced in men ≥85 years with a decrease of 0.9 mmol/L. For both genders, TC and LDL-C levels increased with advancing age until around age 50. After menopause the women had higher TC and LDL-C levels than the men. The median (geometric mean) TG level decreased by 0.4 mmol/L from 2001 to 2008, after which it increased slightly by 0.1 mmol/L until 2018. During life the TG levels of the men were markedly higher than the women’s until around age 65–70. HDL-C levels showed no trend during the study period. Conclusions The levels of TC and LDL-C decreased considerably in a statin-free population from primary health care from 2001 to 2018. These decreases were most pronounced in the elderly population and this trend is not decelerating. For TG, levels have started to increase, after an initial decrease.