Neuropathic Bladder Caused by Caudal Regression Syndrome without Any Other Neurogenic Symptoms

Caudal regression syndrome (CRS) is a rare congenital vertebral anomaly, which occurs most often in combination with spinal cord malformations and morphologic dysfunctions of the lower extremities; these signs are useful for both patients and clinicians in the diagnosis of this syndrome. However, in certain cases, clinicians have failed to identify the syndrome due to the lack of apparent anomalies, resulting in the progression of renal dysfunction caused by neuropathic bladder when CRS is eventually identified. Here, we report a case of a 2-year-old girl who was referred to our hospital for vesicoureteral reflux. At examination, she presented no neurological symptoms; however, on cystourethrography and CT scanning we found that the sacral bone was absent, through which CRS was diagnosed. A urodynamic study indicated detrusor-sphincter dyssynergia, and clean intermittent catheterization was initiated. In the present report, we describe a case of CRS with no neurologic symptoms other than a neuropathic bladder. The lack of outward signs can result in delayed diagnosis. Thus, urological examinations, including a urodynamic study, might be the only clue for identifying an underlying neurologic injury involving the lower spinal cord

SNP- and haplotype-based genome-wide association studies for growth, carcass, and meat quality traits in a Duroc multigenerational population

Average linkage disequilibrium coefficient (r2) values plotted against intermarker distance for all autosomal chromosomes. (PDF 407 kb

Exploring indicators of genetic selection using the sniffer method to reduce methane emissions from Holstein cows

Objective This study aimed to evaluate whether the methane (CH4) to carbon dioxide (CO2) ratio (CH4/CO2) and methane-related traits obtained by the sniffer method can be used as indicators for genetic selection of Holstein cows with lower CH4 emissions. Methods The sniffer method was used to simultaneously measure the concentrations of CH4 and CO2 during milking in each milking box of the automatic milking system to obtain CH4/CO2. Methane-related traits, which included CH4 emissions, CH4 per energy-corrected milk, methane conversion factor (MCF), and residual CH4, were calculated. First, we investigated the impact of the model with and without body weight (BW) on the lactation stage and parity for predicting methane-related traits using a first on-farm dataset (Farm 1; 400 records for 74 Holstein cows). Second, we estimated the genetic parameters for CH4/CO2 and methane-related traits using a second on-farm dataset (Farm 2; 520 records for 182 Holstein cows). Third, we compared the repeatability and environmental effects on these traits in both farm datasets. Results The data from Farm 1 revealed that MCF can be reliably evaluated during the lactation stage and parity, even when BW is excluded from the model. Farm 2 data revealed low heritability and moderate repeatability for CH4/CO2 (0.12 and 0.46, respectively) and MCF (0.13 and 0.38, respectively). In addition, the estimated genetic correlation of milk yield with CH4/CO2 was low (0.07) and that with MCF was moderate (−0.53). The on-farm data indicated that CH4/CO2 and MCF could be evaluated consistently during the lactation stage and parity with moderate repeatability on both farms. Conclusion This study demonstrated the on-farm applicability of the sniffer method for selecting cows with low CH4 emissions

Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis

Kumazaki S., Hikita H., Tahata Y., et al. Serum growth differentiation factor 15 is a novel biomarker with high predictive capability for liver cancer occurrence in patients with MASLD regardless of liver fibrosis. Alimentary Pharmacology and Therapeutics , (2024); https://doi.org/10.1111/apt.18063.Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) patients with a Fib-4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high-risk populations requiring follow-up is needed. We explored the utility of serum levels of growth differentiation factor-15 (GDF15), a cell stress-responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy-performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy-MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib-4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high-GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib-4 index 1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high-GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low-GDF15 patients, whether limited to high-Fib-4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib-4 index >1.3, 2.7% had a Fib-4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Angular analysis of B+→ρ+ρ0B^+ \to \rho^+\rho^0 decays reconstructed in 2019, 2020, and 2021 Belle II data

We report on a Belle II measurement of the branching fraction ($\mathcal{B}$), longitudinal polarization fraction ($f_L$), and CP asymmetry ($\mathcal{A}_{CP}$) of $B^+\to \rho^+\rho^0$ decays. We reconstruct $B^+\to \rho^+(\to \pi^+\pi^0(\to \gamma\gamma))\rho^0(\to \pi^+\pi^-)$ decays in a sample of SuperKEKB electron-positron collisions collected by the Belle II experiment in 2019, 2020, and 2021 at the $\Upsilon$(4S) resonance and corresponding to 190 fb$^{-1}$ of integrated luminosity. We fit the distributions of the difference between expected and observed $B$ candidate energy, continuum-suppression discriminant, dipion masses, and decay angles of the selected samples, to determine a signal yield of $345 \pm 31$ events. The signal yields are corrected for efficiencies determined from simulation and control data samples to obtain $\mathcal{B}(B^+ \to \rho^+\rho^0) = [23.2^{+\ 2.2}_{-\ 2.1} (\rm stat) \pm 2.7 (\rm syst)]\times 10^{-6}$,$f_L = 0.943 ^{+\ 0.035}_{-\ 0.033} (\rm stat)\pm 0.027(\rm syst)$, and$\mathcal{A}_{CP}=-0.069 \pm 0.068(\rm stat) \pm 0.060 (\rm syst)$. The results agree with previous measurements. This is the first measurement of$\mathcal{A}_{CP}$in$B^+\to \rho^+\rho^0$ decays reported by Belle II

Measurement of the branching fractions and CPCP asymmetries of B+→π+π0B^+ \rightarrow \pi^+ \pi^0 and B+→K+π0B^+ \rightarrow K^+ \pi^0 decays in 2019-2021 Belle II data

We determine the branching fractions ${\mathcal{B}}$ and $CP$ asymmetries ${\mathcal{A}_{{\it CP}}}$ of the decays $B^+ \rightarrow \pi^+ \pi^0$ and $B^+ \rightarrow K^+ \pi^0$. The results are based on a data set containing 198 million bottom-antibottom meson pairs corresponding to an integrated luminosity of $190\;\text{fb}^{-1}$ recorded by the Belle II detector in energy-asymmetric electron-positron collisions at the $\Upsilon (4S)$ resonance. We measure ${\mathcal{B}(B^+ \rightarrow \pi^+ \pi^0) = (6.12 \pm 0.53 \pm 0.53)\times 10^{-6}}$, ${\mathcal{B}(B^+ \rightarrow K^+ \pi^0) = (14.30 \pm 0.69 \pm 0.79)\times 10^{-6}}$, ${\mathcal{A}_{{\it CP}}(B^+ \rightarrow \pi^+ \pi^0) = -0.085 \pm 0.085 \pm 0.019}$, and ${\mathcal{A}_{{\it CP}}(B^+ \rightarrow K^+ \pi^0) = 0.014 \pm 0.047 \pm 0.010}$, where the first uncertainties are statistical and the second are systematic. These results improve a previous Belle II measurement and agree with the world averages

Determination of ∣Vub∣|V_{ub}| from untagged B0→π−ℓ+νℓB^0\to\pi^- \ell^+ \nu_{\ell} decays using 2019-2021 Belle II data

We present an analysis of the charmless semileptonic decay $B^0\to\pi^- \ell^+ \nu_{\ell}$, where $\ell = e, \mu$, from 198.0 million pairs of $B\bar{B}$ mesons recorded by the Belle II detector at the SuperKEKB electron-positron collider. The decay is reconstructed without identifying the partner $B$ meson. The partial branching fractions are measured independently for $B^0\to\pi^- e^+ \nu_{e}$ and $B^0\to\pi^- \mu^+ \nu_{\mu}$ as functions of $q^{2}$ (momentum transfer squared), using 3896 $B^0\to\pi^- e^+ \nu_{e}$ and 5466 $B^0\to\pi^- \mu^+ \nu_{\mu}$ decays. The total branching fraction is found to be $(1.426 \pm 0.056 \pm 0.125) \times 10^{-4}$ for $B^0\to\pi^- \ell^+ \nu_{\ell}$ decays, where the uncertainties are statistical and systematic, respectively. By fitting the measured partial branching fractions as functions of $q^{2}$, together with constraints on the nonperturbative hadronic contribution from lattice QCD calculations, the magnitude of the Cabibbo-Kobayashi-Maskawa matrix element $V_{ub}$, $(3.55 \pm 0.12 \pm 0.13 \pm 0.17) \times 10^{-3}$, is extracted. Here, the first uncertainty is statistical, the second is systematic and the third is theoretical