Endlessly single-mode holey fibers: the influence of core design

In this paper we evaluate the cut-off properties of holey fibers (HFs) with a triangular lattice of air holes and the core formed by the removal of a single (HF1) or more air holes (HF3 and HF7). With the aid of finite-element simulations we determine the single-mode and multi-mode phases and also find the air hole diameters limiting the endlessly single-mode regime. From calculations of V and W parameters we find that in general HF1 is less susceptible to longitudinal non-uniformities compared to the other designs for equivalent effective areas. As an example we illustrate this general property for the particular case of a macro-bending induced loss.Comment: 7 pages including 4 figures. Accepted for Opt. Expres

Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma

Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease

Ultrafiltration attenuates cardiopulmonary bypass–induced acute lung injury in a canine model of single-lung transplantation

ObjectiveThe purpose of this study was to investigate the effects of cardiopulmonary bypass and ultrafiltration on graft function in a canine single-lung transplantation model.MethodsFifteen left single-lung transplantations were done in weight-mismatched canine pairs. The animals were divided into 3 groups: group 1, in which transplantation was done without cardiopulmonary bypass; group 2, in which transplantation was done with cardiopulmonary bypass and in which the cardiopulmonary bypass flow was decreased slowly with controlled pulmonary artery pressure; and group 3, in which transplantation was done with cardiopulmonary bypass and ultrafiltration. Hemodynamic parameters and lung function were monitored for 6 hours after reperfusion. The grafts were harvested for histologic studies, myeloperoxidase assay, and real-time quantitive reverse transcription–polymerase chain reaction of mRNA encoding interleukin 6.ResultsThe hemodynamic parameters were similar among the 3 groups. In group 1 Pao2 and alveolar to arterial gradient for O2 levels were excellent throughout the 6-hour observation period, but in group 2 they progressively deteriorated. However, ultrafiltration significantly (P = .02) improved the Pao2 level in group 3. On histology, interstitial edema and polynuclear cell infiltration were most marked in group 2 and significantly worse than in groups 1 and 3. Myeloperoxidase assay and real-time quantitative reverse transcription–polymerase chain reaction showed increased myeloperoxidase activity and interleukin 6 gene expression in group 2 grafts compared with group 1 grafts. Myeloperoxidase activity and interleukin 6 gene expression were suppressed with ultrafiltration.ConclusionsCardiopulmonary bypass had negative effects on the graft, but ultrafiltration attenuated acute lung dysfunction by reducing the inflammatory response

Oxaliplatin for Metastatic Colon Cancer in a Patient with Renal Failure

The efficacy, safety, pharmacokinetics, and dialysability of oxaliplatin were assessed in a hemodialysis patient with recurrent cecal cancer

Molecular Phylogeny of the Genus Nipponnemertes (Nemertea: Monostilifera: Cratenemertidae) and Descriptions of 10 New Species, With Notes on Small Body Size in a Newly Discovered Clade

Nemerteans, or ribbon worms, have been reported from intertidal to hadal depths, often showing bathymetrically wide distribution in genus levels. Although current nemertean systematics practices require to provide DNA sequences and infer phylogenetic relationships with suitable molecular markers, previous molecular systematics on nemerteans are mostly biased toward shallow-water species. Members in the genus Nipponnemertes occur worldwide, from tropical to polar waters and intertidal to bathyal waters. Molecular phylogenetic studies are scarce for the genus; only six shallow-water species of 18 species in the genus were subject to molecular phylogeny. Thus, Nipponnemertes is one candidate that needs to be assessed by genetic approaches. In this study, we performed molecular phylogenetic analyses using 59 specimens in 23 species based on partial sequences of two mitochondrial (16S rRNA and cytochrome c oxidase subunit I) and three nuclear gene markers (18S rRNA, 28S rRNA, and histone H3). Our extensive sampling from intertidal to bathyal waters in the Northwest Pacific significantly updated the fauna of Nipponnemertes in this region from four to 17 species. We herein establish 10 new species and provide an updated species list concisely summarizing all the congeners known from the world. Our phylogenetic tree indicated three major lineages within the genus (herein referred to as “Clade A, B, and C”), each presumably characterized by the combination of morphological characters in the head region. Members in Clade A are: Nipponnemertes pulchra (Johnston, 1837), Nipponnemertes ogumai (Yamaoka, 1947), and several unidentified congeners, characterized by having demarcated head without cephalic patches; members in Clade B are: Nipponnemertes crypta sp. nov., Nipponnemertes jambio sp. nov., Nipponnemertes neonilae sp. nov., and Nipponnemertes ojimaorum sp. nov., species having demarcated head with cephalic patches; members in Clade C are: Nipponnemertes ganahai sp. nov., Nipponnemertes kozaensis sp. nov., Nipponnemertes lactea sp. nov., Nipponnemertes notoensis sp. nov., Nipponnemertes ornata sp. nov., Nipponnemertes sugashimaensis sp. nov., and two unidentified forms collected off Jogashima (Japan) and Guam (USA), species with non-demarcated head lacking cephalic patches. Furthermore, we discuss the evolution of remarkably small body size retained among Clade C

Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus : A randomized, crossover trial

Aims: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. Methods: This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). Results: The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). Conclusions: The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM

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

Design of effectively single-mode leakage channel fibers with large mode area and low bending loss

Novel design of large-mode-area leakage channel fibers (LCFs) with a single air-hole ring surrounding a multi-unit-cell solid core is investigated for realizing robust single-mode and low bending loss characteristics. We perform detailed numerical simulations using a finite element method, and we show that the proposed LCFs with a solid core formed by multiple missing neighboring air-holes can achieve much lower bending losses compared with the reported LCF with six large air-holes