Laparoscopic Hepatectomy for the Patient with Hemophilia A with High Titer Factor VIII Inhibitor

We present the first case of laparoscopic left lateral segmentectomy for hepatocellular carcinoma (HCC) in a patient with hemophilia A, acquired hepatitis C, and high-titer factor VIII inhibitor, which was confirmed by preoperative diagnosis. He underwent laparoscopic left lateral segmentectomy with the administration of recombinant activated factor VII. Surgery could be performed with reduced intraoperative hemorrhage. He experienced postoperative intra-abdominal wall hemorrhage, which was successfully managed with red cell concentrates transfusion and administration of recombinant activated factor VII. Laparoscopic hepatectomy can be applied for hemophilia patients with high titer inhibitors

Genome organization of the vg1 and nodal3 gene clusters in the allotetraploid frog Xenopus laevis.

Extracellular factors belonging to the TGF-β family play pivotal roles in the formation and patterning of germ layers during early Xenopus embryogenesis. Here, we show that the vg1 and nodal3 genes of Xenopus laevis are present in gene clusters on chromosomes XLA1L and XLA3L, respectively, and that both gene clusters have been completely lost from the syntenic S chromosome regions. The presence of gene clusters and chromosome-specific gene loss were confirmed by cDNA FISH analyses. Sequence and expression analyses revealed that paralogous genes in the vg1 and nodal3 clusters on the L chromosomes were also altered compared to their Xenopus tropicalis orthologs. X. laevis vg1 and nodal3 paralogs have potentially become pseudogenes or sub-functionalized genes and are expressed at different levels. As X. tropicalis has a single vg1 gene on chromosome XTR1, the ancestral vg1 gene in X. laevis appears to have been expanded on XLA1L. Of note, two reported vg1 genes, vg1(S20) and vg1(P20), reside in the cluster on XLA1L. The nodal3 gene cluster is also present on X. tropicalis chromosome XTR3, but phylogenetic analysis indicates that nodal3 genes in X. laevis and X. tropicalis were independently expanded and/or evolved in concert within each cluster by gene conversion. These findings provide insights into the function and molecular evolution of TGF-β family genes in response to allotetraploidization

Chromosomal localization of the 18S-28S and 5S rRNA genes and (TTAGGG)n sequences of butterfly lizards (Leiolepis belliana belliana and Leiolepis boehmei, Agamidae, Squamata)

Chromosomal mapping of the butterfly lizards Leiolepis belliana belliana and L. boehmei was done using the 18S-28S and 5S rRNA genes and telomeric (TTAGGG)n sequences. The karyotype of L. b. belliana was 2n = 36, whereas that of L. boehmei was 2n = 34. The 18S-28S rRNA genes were located at the secondary constriction of the long arm of chromosome 1, while the 5S rRNA genes were found in the pericentromeric region of chromosome 6 in both species. Hybridization signals for the (TTAGGG)n sequence were observed at the telomeric ends of all chromosomes, as well as interstitially at the same position as the 18S-28S rRNA genes in L. boehmei. This finding suggests that in L. boehmei telomere-to-telomere fusion probably occurred between chromosome 1 and a microchromosome where the 18S-28S rRNA genes were located or, alternatively, at the secondary constriction of chromosome 1. The absence of telomeric sequence signals in chromosome 1 of L. b. belliana suggested that its chromosomes may have only a few copies of the (TTAGGG)n sequence or that there may have been a gradual loss of the repeat sequences during chromosomal evolution

Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 32–79 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4–89.4%] and 61.0% (95%CI: 44.5–75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95%CI: 36.4–67.5%) and 73.2% (95%CI: 56.8–84.1%), respectively. The younger patients (≤ 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade ≥ 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes

Genome evolution in the allotetraploid frog Xenopus laevis

To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of ???fossil??? transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.ope

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

Measurements of the branching fractions for B→K∗γB \to K^{*}\gamma decays at Belle II

This paper reports a study of $B \to K^{*}\gamma$ decays using $62.8\pm 0.6$ fb$^{-1}$ of data collected during 2019--2020 by the Belle II experiment at the SuperKEKB $e^{+}e^{-}$ asymmetric-energy collider, corresponding to $(68.2 \pm 0.8) \times 10^6$ $B\overline{B}$ events. We find $454 \pm 28$, $50 \pm 10$, $169 \pm 18$, and $160 \pm 17$ signal events in the decay modes $B^{0} \to K^{*0}[K^{+}\pi^{-}]\gamma$, $B^{0} \to K^{*0}[K^0_{\rm S}\pi^{0}]\gamma$, $B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma$, and $B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma$, respectively. The uncertainties quoted for the signal yield are statistical only. We report the branching fractions of these decays: $$\mathcal{B} [B^{0} \to K^{*0}[K^{+}\pi^{-}]\gamma] = (4.5 \pm 0.3 \pm 0.2) \times 10^{-5},$$ $$\mathcal{B} [B^{0} \to K^{*0}[K^0_{\rm S}\pi^{0}]\gamma] = (4.4 \pm 0.9 \pm 0.6) \times 10^{-5},$$ $$\mathcal{B} [B^{+} \to K^{*+}[K^{+}\pi^{0}]\gamma] = (5.0 \pm 0.5 \pm 0.4)\times 10^{-5},\text{ and}$$ $$\mathcal{B} [B^{+} \to K^{*+}[K^0_{\rm S}\pi^{+}]\gamma] = (5.4 \pm 0.6 \pm 0.4) \times 10^{-5},$$ where the first uncertainty is statistical, and the second is systematic. The results are consistent with world-average values

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

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

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