Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Terahertz spectroscopy of antiferromagnetic resonances in YFe1-xMnxO3(0 ≤ x ≤ 0:4) across a spin reorientation transition

© 2022 AIP Publishing LLC. We have conducted a terahertz spectroscopic study of antiferromagnetic resonances in bulk orthoferrite YFe1-xMnxO3 0 ≤ x ≤ 0.4. Both the quasi-ferromagnetic resonance mode and the quasi-antiferromagnetic resonance mode in the weak ferromagnetic Γ4 phase disappear near the spin reorientation temperature, TSR, for the onset of the collinear antiferromagnetic Γ1 phase (x ≥ 0.1). Below TSR, an antiferromagnetic resonance mode emerges and exhibits a large blueshift with decreasing temperature. However, below 50 K, this mode softens considerably, and this tendency becomes stronger with Mn doping. We provide a deeper understanding of such behaviors of the antiferromagnetic resonance modes in terms of the influence of the Mn3+ ions on the magnetocrystalline anisotropy. Our results show that terahertz time-domain spectroscopy is a useful, complementary tool in tracking magnetic transitions and probing the interaction between disparate magnetic subsystems in antiferromagnetic materials with multiple ionic species.11Nsciescopu

Nutcracker syndrome in children with gross haematuria: Doppler sonographic evaluation of the left renal vein

BACKGROUND: Nutcracker syndrome is characterized by gross haematuria caused by left renal vein (LRV) entrapment. OBJECTIVE: To assess the role of LRV ultrasonography in the diagnosis of the nutcracker syndrome in children. MATERIALS AND METHODS: Twelve children (eight male, four female; mean age 12.8 years) with venographically confirmed nutcracker syndrome (LRV-IVC pressure gradient > or = 3 mm Hg) underwent LRV sonography including Doppler spectral analysis (n=7). The diameter and peak velocity (PV) were measured at two sites of the LRV (renal hilum and aortomesenteric portion). The US findings of nutcracker syndrome were compared with those of 20 control subjects using the t-test. We identified the optimal cut-off value of the US parameters for the diagnosis of the nutcracker syndrome using ROC analysis. RESULTS: The PV at the aortomesenteric portion and the ratio of the PV between the two measured points showed significant differences between the two groups (P<0.0001). The optimum cut-off values were found to be 4.7 for the PV ratio (sensitivity 100%, specificity 90%, accuracy 93%), and 93 cm/s for the PV at the aortomesenteric portion (sensitivity 100%, specificity 85%, accuracy 89%). CONCLUSION: LRV sonography, including Doppler spectral analysis, can demonstrate LRV entrapment haemodynamically

Prevalence, clinical significance, and persistence of autoantibodies in COVID-19

Abstract Background Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. Methods We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. Results A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. Conclusion A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation

Anti-Inflammatory and Antimicrobial Effects of a Novel Herbal Formulation (WSY-1075) in a Chronic Bacterial Prostatitis Rat Model

Purpose: The aim of this study was to investigate the anti-inflammatory and anti-oxidative effects of a multi-herbal formula known as WSY-1075 in the treatment of chronic bacterial prostatitis in a rat model. Materials and Methods: Experimental chronic bacterial prostatitis was induced in 32 Wistar rats by instillation of a bacterial suspension (Escherichia coli, 108 colony-forming units [CFU]/mL) into the prostatic urethra. After the induction of prostatitis, the rats were randomly divided into one of 4 treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg)+ciprofloxacin (n=8). After 4 weeks of treatment, microbiological data from prostate tissue cultures, level of prostatic pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-8), anti-oxidant effects (superoxide dismutase [SOD]), and histological findings were noted. Results: The WSY-1075, ciprofloxacin, and WSY-1075+ciprofloxacin groups showed fewer CFUs in prostate tissue cultures than the control group. The WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups showed statistically significantly lower levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 than the control group. SOD levels in the WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups were significantly higher than in the control group. Conclusions: This study found that WSY-1075 had anti-microbial effects, anti-inflammatory effects, and anti-oxidative effects in a chronic bacterial prostatitis rat model. We expect the WSY-1075 may be useful for the clinical treatment of chronic bacterial prostatitis

Anti-Inflammatory and Antimicrobial Effects of a Novel Herbal Formulation (WSY-1075) in a Chronic Bacterial Prostatitis Rat Model

Purpose: The aim of this study was to investigate the anti-inflammatory and anti-oxidative effects of a multi-herbal formula known as WSY-1075 in the treatment of chronic bacterial prostatitis in a rat model. Materials and Methods: Experimental chronic bacterial prostatitis was induced in 32 Wistar rats by instillation of a bacterial suspension (Escherichia coli, 108 colony-forming units [CFU]/mL) into the prostatic urethra. After the induction of prostatitis, the rats were randomly divided into one of 4 treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg)+ciprofloxacin (n=8). After 4 weeks of treatment, microbiological data from prostate tissue cultures, level of prostatic pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-8), anti-oxidant effects (superoxide dismutase [SOD]), and histological findings were noted. Results: The WSY-1075, ciprofloxacin, and WSY-1075+ciprofloxacin groups showed fewer CFUs in prostate tissue cultures than the control group. The WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups showed statistically significantly lower levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 than the control group. SOD levels in the WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups were significantly higher than in the control group. Conclusions: This study found that WSY-1075 had anti-microbial effects, anti-inflammatory effects, and anti-oxidative effects in a chronic bacterial prostatitis rat model. We expect the WSY-1075 may be useful for the clinical treatment of chronic bacterial prostatitis

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research