Abstract
The current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human ...assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.
An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This ...case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Chronic kidney disease (CKD) is associated with bone and mineral metabolism. In this study we evaluated the comparative efficacies and safety of osteoporosis medications in patients with CKD or a ...history of kidney transplantation, and make recommendations for the best choice of osteoporosis treatment among patients with CKD or a history of kidney transplantation.
We systemically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases up to June 2020. Network-meta analysis was used to compare the relative effectiveness of different treatments. A random-effects model was used when heterogeneity was expected. The safety of different treatments was also evaluated in terms of reported major adverse events.
A total of 17 studies with data from 10,214 patients who had stage 2-5 CKD, were receiving dialysis, or had a history of kidney transplantation were included in the network meta-analysis. Treatment with teriparatide, denosumab, alendronate, and raloxifene were all associated with a significantly reduced risk of fractures compared to treatment with placebos teriparatide: odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.10-0.35; denosumab: OR = 0.40, 95% CI: 0.27-0.58; alendronate: OR = 0.61, 95% CI: 0.40-0.92; raloxifene: OR = 0.52, 95% CI: 0.41-0.67. The rank probability and the surface under the cumulative ranking (SUCRA) values suggested that teriparatide ranked the highest for improvement in vertebral bone mineral density (BMD) (SUCRA = 97.8%), whereas denosumab ranked the highest for improvement in femoral neck BMD (SUCRA = 88.3%).
Teriparatide and denosumab seem to be the most effective treatments for preventing bone loss and reducing the risk of fracture in our network comparison. However, because of the limitations and potential biases in the reviewed studies, there is still some uncertainty about the best treatment options for osteoporosis in patients with CKD or a history of kidney transplantation.
: PROSPERO, identifier CRD42020209830.
Early detection is important for improving the survival rate of patients with gastric cancer (GC). Serum tumor markers have been widely used for detecting GC. However, their clinical values remain ...controversial. This study aims to investigate the role of serum cancer antigen 72-4 (CA72-4) in the diagnosis of GC in a healthy population. A total of 7757 adults who underwent upper gastrointestinal endoscopy and serum CA72-4 level measurement in multicenters in Taiwan from January 2006 to August 2016 were recruited in this retrospective study. Risk factors for GC, serum tumor markers, and esophagogastroduodenoscopy (EGD) findings were evaluated. High serum levels of CA72-4 were found in 7.2% of healthy adults. CA72-4 level showed lower sensitivity (33.3%) but higher specificity (92.8%); however, the positive predictive value was quite low (0.18%). After adjustment of clinical risk factors for GC using EGD findings, gastric ulcer (adjusted odds ratio (aOR) = 2.11), gastric polyps (aOR = 1.42), and atrophic gastritis (aOR = 1.27) were significantly associated with high serum CA72-4 levels. Furthermore, both age (OR = 1.01) and
infection (OR = 1.44) exhibited a significant association with high serum CA72-4 levels. These results indicate that routine screening of CA72-4 levels for diagnosing GC in asymptomatic patients may be ineffective due to low sensitivity and low positive predictive value. The clinical utility of EGD findings along with serum CA72-4 level for screening healthy individuals with GC is warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cancer is a dangerous and sometimes life-threatening disease that can have several negative consequences for the body, is a leading cause of mortality, and is becoming increasingly difficult to ...detect. Each form of cancer has its own set of traits, symptoms, and therapies, and early identification and management are important for a positive prognosis. Doctors utilize a variety of approaches to detect cancer, depending on the kind and location of the tumor. Imaging tests such as X-rays, Computed Tomography scans, Magnetic Resonance Imaging scans, and Positron Emission Tomography (PET) scans, which may provide precise pictures of the body's interior structures to spot any abnormalities, are some of the tools that doctors use to diagnose cancer. This article evaluates computational-intelligence approaches and provides a means to impact future work by focusing on the relevance of machine learning and deep learning models such as K Nearest Neighbour (KNN), Support Vector Machine (SVM), Naïve Bayes, Decision Tree, Deep Neural Network, Deep Boltzmann machine, and so on. It evaluates information from 114 studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). This article explores the advantages and disadvantages of each model and provides an outline of how they are used in cancer diagnosis. In conclusion, artificial intelligence shows significant potential to enhance cancer imaging and diagnosis, despite the fact that there are a number of clinical issues that need to be addressed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) ...modalities render objective assessment of survival benefits a greater challenge.
Data were retrieved from Taiwan's National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities.
For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 95% confidence interval (CI) 0.89-1.02 in the propensity score study design and 1.06 (95% CI 1.01-1.12) in the time-varying study design. For all-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05-1.13) in the propensity score study design and 1.13 (95% CI 1.09-1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15-1.28), patients ≥65 years old (1.30, 95% CI 1.24-1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22-1.34).
The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.
Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome ...signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis.
A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium.
Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the western North Pacific subtropical ocean, the Anatahan volcano of the Mariana Islands erupted on 10 May 2003 for the first time in recorded history. Based on nine different types of remote ...sensing data provided by NASA, laboratory experiment of the Anatahan samples, and a 3‐D ocean circulation model developed by the U.S. Naval Research Laboratory, the postvolcanic ocean biogeochemical response to the Anatahan eruption was explored. It was observed that soon after the eruption, the aerosol optical depth abruptly increased from the pre‐eruption loading of ∼0.1 to ∼2. In the week following the eruption, a “bloom‐like” patch was observed by NASA's Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) ocean color sensor. Based on the chlorophyll a, fluorescence line height (FLH), at‐sensor total radiance, and normalized water‐leaving radiance data obtained by MODIS, the cause of the bloom‐like patch was diagnosed. The results suggest that the patch was most likely a mixture of suspended volcanic particles and a phytoplankton bloom. FLH was found to be ∼9–17 × 10−3 mW cm−2μm−1 sr−1 in the patch and ∼3–5 × 10−3 mW cm−2μm−1 sr−1 in the ambient water, indicating that a 2–5‐fold increase in biological activity occurred during the week following the eruption. Satellite altimetry indicated that the bloom took place in the presence of downwelling and was not a result of upwelled nutrients in this oligotrophic ocean. Analysis of satellite ocean color spectra of the bloom region found similar spectra as the reference Trichodesmium spectra. Laboratory experiments further substantiate the satellite observations which show elevated concentrations of limiting nutrients provided by the Anatahan samples, and the averaged soluble nitrate, phosphate, and Fe were 42, 3.1, and 2.0 nM, respectively. Though it was not possible to obtain in situ observations of the ocean biogeochemical responses that followed the Anatahan eruption, this study provided evidence based on remote sensing data and laboratory experiment that fertilization of volcanic aerosols occurred following this eruption in one of the most oligotrophic low‐nutrient low‐chlorophyll ocean deserts on Earth.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Direct-acting antiviral agents achieve sustained virological response in most chronic hepatitis C patients. However, histological responses are not consistent among all patients. We conducted an ...observational study to analyze the histological changes after direct-acting antiviral agent therapy.
We recruited 220 patients who achieved sustained virological response after direct-acting antiviral agent. Histology was assessed by liver biopsy and laboratory indices including fibrosis-4 and aspartate aminotransferase to platelet ratio index. Primary outcomes were change in the dynamic laboratory results. Secondary outcomes were histological changes on liver biopsy. We analyzed the factors predictive of histological regression.
The mean fibrosis-4 index decreased from 4.78 at baseline to 3.30, 3.31, 3.65, and 3.66 at week 4, 8, end of treatment, and 12 weeks after treatment, respectively (all p < 0.01). Mean aspartate aminotransferase to platelet ratio index decreased from 1.62 at baseline to 0.61, 0.66, 0.64, and 0.82 at week 4, 8, end of treatment, and 12 weeks after treatment, respectively (all p < 0.01). Mean Histological Activity Index at baseline and post-treatment was 6.9 ± 1.9 and 5.0 ± 2.3. The METAVIR fibrosis scores improved in 61.9% of the patients. We compared patients who achieved fibrosis-regression with the non-regression group. There was no significant difference in the baseline host/virological factors between the groups.
Reversal of liver inflammation and fibrosis was achieved in a significant number of patients who received direct-acting antiviral agent. No baseline host or virological factor was predictive of histological regression after antiviral treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There are many laboratory indices to assess liver fibrosis. Aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index have been used as well-known serum markers of liver ...fibrosis. With the increasing use of non-invasive fibrosis assessment, it is important to recognize the limitations of these tests. The factors influencing the diagnostic accuracy to evaluate liver fibrosis are not well-established. This study aimed to perform a subgroup analysis of the predictive ability of laboratory indices.
Overall, 113 patients with chronic hepatitis C infection who underwent liver biopsy were retrospectively examined. The histological assessment of liver fibrosis was performed using the METAVIR scoring system, and the values of several laboratory tests were also evaluated on the same day. We categorized our study population by treatment status, body mass index (BMI), and age.
The two laboratory indices APRI and FIB-4 index could predict advanced (F3-4) liver fibrosis and cirrhosis (F4), with the area under the receiver operating characteristic curve (AUROC) > 0.8 and accuracy >70%. The AUROCs and accuracies were higher among patients with sustained virological response (SVR) than among those without SVR. A higher predictive ability was also observed among patients with BMI <25 kg/m2. Age did not appear to affect liver fibrosis predictability.
The laboratory indices APRI and FIB-4 index exhibit good diagnostic performance for determining advanced fibrosis and cirrhosis among patients with hepatitis C infection. The diagnostic accuracy appears better among patients with SVR and those with BMI <25 kg/m2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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