Optimal LZ-End Parsing Is Hard

LZ-End is a variant of the well-known Lempel-Ziv parsing family such that each phrase of the parsing has a previous occurrence, with the additional constraint that the previous occurrence must end at the end of a previous phrase. LZ-End was initially proposed as a greedy parsing, where each phrase is determined greedily from left to right, as the longest factor that satisfies the above constraint [Kreft & Navarro, 2010]. In this work, we consider an optimal LZ-End parsing that has the minimum number of phrases in such parsings. We show that a decision version of computing the optimal LZ-End parsing is NP-complete by showing a reduction from the vertex cover problem. Moreover, we give a MAX-SAT formulation for the optimal LZ-End parsing adapting an approach for computing various NP-hard repetitiveness measures recently presented by [Bannai et al., 2022]. We also consider the approximation ratio of the size of greedy LZ-End parsing to the size of the optimal LZ-End parsing, and give a lower bound of the ratio which asymptotically approaches 2

Cutaneous T-cell-attracting chemokine as a novel biomarker for predicting prognosis of idiopathic pulmonary fibrosis: a prospective observational study

[Background] Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease that leads to respiratory failure and death. Although there is a greater understanding of the etiology of this disease, accurately predicting the disease course in individual patients is still not possible. This study aimed to evaluate serum cytokines/chemokines as potential biomarkers that can predict outcomes in IPF patients. [Methods] A multi-institutional prospective two-stage discovery and validation design using two independent cohorts was adopted. For the discovery analysis, serum samples from 100 IPF patients and 32 healthy controls were examined using an unbiased, multiplex immunoassay of 48 cytokines/chemokines. The serum cytokine/chemokine values were compared between IPF patients and controls; the association between multiplex measurements and survival time was evaluated in IPF patients. In the validation analysis, the cytokines/chemokines identified in the discovery analysis were examined in serum samples from another 81 IPF patients to verify the ability of these cytokines/chemokines to predict survival. Immunohistochemical assessment of IPF-derived lung samples was also performed to determine where this novel biomarker is expressed. [Results] In the discovery cohort, 18 cytokines/chemokines were significantly elevated in sera from IPF patients compared with those from controls. Interleukin-1 receptor alpha (IL-1Rα), interleukin-8 (IL-8), macrophage inflammatory protein 1 alpha (MIP-1α), and cutaneous T-cell-attracting chemokine (CTACK) were associated with survival: IL-1Rα, hazard ratio (HR) = 1.04 per 10 units, 95% confidence interval (95% CI) 1.01–1.07; IL-8, HR = 1.04, 95% CI 1.01–1.08; MIP-1α, HR = 1.19, 95% CI 1.00–1.36; and CTACK, HR = 1.12 per 100 units, 95% CI 1.02–1.21. A replication analysis was performed only for CTACK because others were previously reported to be potential biomarkers of interstitial lung diseases. In the validation cohort, CTACK was associated with survival: HR = 1.14 per 100 units, 95% CI 1.01–1.28. Immunohistochemistry revealed the expression of CTACK and CC chemokine receptor 10 (a ligand of CTACK) in airway and type II alveolar epithelial cells of IPF patients but not in those of controls. [Conclusions] CTACK is a novel prognostic biomarker of IPF

頭頸部領域および食道領域の各種症状に対する食道運動機能の関与について : High Resolution Manometry を用いた検討

頭頸部領域および食道領域における各種症状に対する食道運動機能の関与を検討した.2007年9月から2012年6月までに,咽喉頭異常感などの頭頸部領域の症状および嚥下困難感,胸痛,胸やけなどの食道領域に関連した症状を主訴に,当科を受診した261例(男性138例,女性123例,平均年齢56.8±17.1才)を対象とし,健康関連QOL(Health Related Quality of Life: HRQL)の測定と食道内圧検査を施行した.健康関連QOLの検討では,咽喉頭違和感,嚥下困難感,胸やけ等の各症状を訴えた患者で,身体的QOL,精神的QOL を表すPCS(physical component summary)あるいはMCS(mental component summary)が低下し,健常者と比較して有意にQOLの低下を認めた.食道内圧検査による食道運動機能異常は,全対象患者中62.0%に認めた.各症状別に食道運動機能障害の内訳を見ると,咽喉頭違和感ではIEM(ineffective esophageal motility)(31.8%),嚥下困難感は食道アカラシア(56.6%),喉のつかえ感は食道アカラシア(35.5%),胸やけはIEM(39.4%),胸痛は食道アカラシア(50.0%),噫気はIEM(50.0%)を最も多く認めた.咽喉頭違和感,嚥下困難感,喉のつかえ感,胸やけ,胸痛などの頭頚部および食道症状を有するものの,器質的疾患を認めない患者のQOLは障害されており,その病態の一つとして食道運動機能異常の存在を念頭に置き,診療にあたることが重要である.There are many cases of patients presenting at the hospital complaining of dysphagia or chest pain. At that time organic diseases are not always detected in these patients;previously several studies showed esophageal motility dysfunction was one of the important factors in the development of these symptoms. However, there have been few reports investigating the relationship between esophageal motility dysfunction and these symptoms. Between September 2007 and June 2012, 216 patients (138 men,123 women;mean age 56.8±17.1 years old) were admitted complaining of the following symptoms:dysphagia, globus sensation, or heart burn and non-cardiac chest pain,but without any organic diseases related symptoms. They all underwent high-resolution esophageal manometry (HRM) and completed a questionnaire regarding their health-related quality of life (HRQOL). The aim of this study was to evaluate the relationship between these symptoms and esophageal motility dysfunction and QOL. In our series, 62% of patients with non-obstructive dysphagia, globus sensation, heartburn and unexplained (non-cardiac) chest pain have an esophageal motility disorder (Achalasia 31.5%, IEM 26.4%, Diffuse esophageal spasm 4.6%;nutcracker esophagus 2.8% and Impaired ECJ relaxation 0.5%). SF-8 score of PCS(Physical Component Summary) in all of the symptoms were significantly lower in comparison with the matched healthy control. SF-8 score of MCS(Mental Component Summary) with globus sensation and esophageal dysphagia were significantly lower in comparison with the matched healthy control. The patients complaining of several symptoms located in the pharynx or esophagus have impaired quality of life and esophageal motility dysfunctions.It is important to consider these issues while examining these patients

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

Public health leadership education in North America

Hideo Uno, Kenneth ZakariasenDepartment of Public Health Sciences, School of Public Health, University of Alberta, Edmonton, AB, CanadaAbstract: Public health leadership is one of the priority disciplines public health professionals need to learn well if they are to deal with demanding public health issues effectively and efficiently. This article looks at the trends in public health leadership education by reviewing the literature and using the Internet to explore the public health leadership programs offered in various parts of the world, and suggests several principles to be taken into account for the development of public health leadership education in the future. A variety of educational programs in public health leadership are classified into several types in terms of their formats: degree programs offered by schools of public health or other programs of public health, those offered in partnership with public health agencies, and so on. All of these programs have important implications for the overall effectiveness of public health leadership education. For public health leadership education to be effective, the partnership between academia and public health agencies is vitally important. Programs should provide opportunities to learn on the basis of practical public health experience, a commitment to life-long learning, flexibility in design, and recognition of the diverse needs of individuals and communities. The application of distance learning methods is one of the options to make this possible.Keywords: public health leadership, public health professionals, school of public healt