Japan COVID-19 Task Force: a nation-wide consortium to elucidate host genetics of COVID-19 pandemic in Japan

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Simultaneous Evaluation of Laryngopharyngeal Reflux and Swallowing Function Using Hypopharyngeal Multichannel Intraluminal Impedance Measurements in Neurologically Impaired Patients

Background/Aims@#This study aims to evaluate the presence of laryngopharyngeal reflux (LPR) and to investigate the use of hypopharyngeal baseline impedance (BI) for assessing swallowing dysfunction and gastroesophageal reflux disease (GERD) using hypopharyngeal multichannel intraluminal impedance and pH (HMII-pH) monitoring in neurologically impaired patients (NIPs). @*Methods@#The study population in this retrospective study comprised 20 NIPs (mean age, 36.1 ± 15.0 years; age range, 13-64 years) who underwent multichannel intraluminal impedance and pH (MII-pH), HMII-pH, and laryngoscopy using the Hyodo scoring method from December 2016 to April 2019. The MII-pH and HMM-pH parameters were compared in the NIPs, whereas hypopharyngeal BI values were compared between NIPs with ≥ 5 and < 5 in Hyodo scores. Correlations between the hypopharyngeal BI values and the Hyodo score were analyzed using Spearman’s correlation coefficient. A receiver operator characteristic curve was created to determine the optimum cut-off of hypopharyngeal BI value to discriminate SD. @*Results@#Three NIPs were diagnosed with pathological LPR and GERD by the HMII-pH monitoring. No significant differences in parameters were observed between MII-pH and HMII-pH monitoring. The correlation analysis demonstrated a significant negative correlation between the hypopharyngeal BI values and Hyodo scores. The optimal cutoff value for hypopharyngeal BI was 1552 Ω. @*Conclusions@#This study demonstrated the usefulness of HMII-pH monitoring in identifying NIP with pathological LPR. Considering the difficulties in performing examinations in NIPs, HMII-pH monitoring may be a potentially useful technique for the simultaneous evaluation of swallowing dysfunction, LPR, and GERD in NIP.

Simultaneous Evaluation of Laryngopharyngeal Reflux and Swallowing Function Using Hypopharyngeal Multichannel Intraluminal Impedance Measurements in Neurologically Impaired Patients

Background/Aims@#This study aims to evaluate the presence of laryngopharyngeal reflux (LPR) and to investigate the use of hypopharyngeal baseline impedance (BI) for assessing swallowing dysfunction and gastroesophageal reflux disease (GERD) using hypopharyngeal multichannel intraluminal impedance and pH (HMII-pH) monitoring in neurologically impaired patients (NIPs). @*Methods@#The study population in this retrospective study comprised 20 NIPs (mean age, 36.1 ± 15.0 years; age range, 13-64 years) who underwent multichannel intraluminal impedance and pH (MII-pH), HMII-pH, and laryngoscopy using the Hyodo scoring method from December 2016 to April 2019. The MII-pH and HMM-pH parameters were compared in the NIPs, whereas hypopharyngeal BI values were compared between NIPs with ≥ 5 and < 5 in Hyodo scores. Correlations between the hypopharyngeal BI values and the Hyodo score were analyzed using Spearman’s correlation coefficient. A receiver operator characteristic curve was created to determine the optimum cut-off of hypopharyngeal BI value to discriminate SD. @*Results@#Three NIPs were diagnosed with pathological LPR and GERD by the HMII-pH monitoring. No significant differences in parameters were observed between MII-pH and HMII-pH monitoring. The correlation analysis demonstrated a significant negative correlation between the hypopharyngeal BI values and Hyodo scores. The optimal cutoff value for hypopharyngeal BI was 1552 Ω. @*Conclusions@#This study demonstrated the usefulness of HMII-pH monitoring in identifying NIP with pathological LPR. Considering the difficulties in performing examinations in NIPs, HMII-pH monitoring may be a potentially useful technique for the simultaneous evaluation of swallowing dysfunction, LPR, and GERD in NIP.

Correction to: New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology

Unfortunately, Acknowledgements section was missing in the originally published article.

Generation and Fusion of Human Cortical and Medial Ganglionic Eminence Brain Organoids.

Three-dimensional (3D) brain organoid culture has become an essential tool for investigating human brain development and modeling neurological disorders during the past few years. Given the specific regionalization during brain development, it is important to produce distinct brain organoids that reproduce different brain regions and their interaction. The authors' laboratory recently established the platform to generate brain organoids resembling the medial ganglionic eminence (MGE), a specific brain region responsible for interneurogenesis, and found when fusing with organoid resembling the cortex, the fused organoids enabled modeling of interneuron migration in the brain. This unit describes four basic protocols that have been successfully applied in the authors' laboratory, covering the generation of embryonic body (EB) with neuroectodermal fate, the production of MGE organoids (hMGEOs) and cortical organoids (hCOs), and the fusion of the two organoids.

Severe Delayed Gastric Emptying Induces Non-acid Reflux up to Proximal Esophagus in Neurologically Impaired Patients

BACKGROUND/AIMS: The aim of this study is to investigate the degree of delayed gastric emptying (DGE) and evaluate how the severity of DGE affects gastroesophageal reflux disease (GERD) in neurologically impaired (NI) patients utilizing 24-hour multichannel intraluminal impedance pH measurements (pH/MII) and ¹³C-acetate breath test (¹³C-ABT) analyses. METHODS: ¹³C-ABT and pH/MII were conducted in 26 NI patients who were referred to our institution due to suspected GERD. At first, correlation analyses were performed to investigate the correlation between the ¹³C-ABT parameters and the clinical or pH/MII parameters. Thereafter, all patients were divided into 2 groups (DGE and severe DGE [SDGE] group) according to each cut off half emptying time (t(1/2), 90–170 minutes). Each pH/MII parameter was compared between the 2 groups in each set-up cutoff t(1/2). RESULTS: The mean t(1/2) of all patients was 215.5 ± 237.2 minutes and the t(1/2) of 24 (92.3%) patients were > 100 minutes. Significant moderate positive correlations were observed between both t(1/2) and lag phase time and the non-acid reflux related parameters. Furthermore, the patients in the SDGE group demonstrated higher non-acid reflux related parameters than those of the DGE groups when the cutoff was t(1/2) ≥ 140 minutes. CONCLUSION: The present study demonstrated that GE with t(1/2) ≥ 140 minutes was related to an increase of non-acid exposure reaching up to the proximal esophagus in NI patients, and indicating that NI patients with SDGE might have a high risk of non-acid GERD.

New Advances in Human X Chromosome Status from a Developmental and Stem Cell Biology

Recent advances in stem cell biology have dramatically increased the understanding of molecular and cellular mechanism of pluripotency and cell fate determination. Additionally, pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, arose as essential resources for disease modeling and cellular therapeutics. Despite these advancements, the epigenetic dysregulation in pluripotency such as the imprinting status, and X chromosome dosage compensation, and its consequences on future utility of PSCs yet remain unresolved. In this review, we will focus on the X chromosome regulation in human PSCs (hPSCs). We will introduce the previous findings in the dosage compensation process on mouse model, and make comparison with those of human systems. Particularly, the X chromosome activation status of human preimplantation embryos, and the regulation of the active X chromosome by human specific lincRNA, X Active Coating Transcript (XACT), will be discussed. We will also discuss the recent findings on higher order X chromosome architecture, and abnormal X chromosome status in hPSCs.

Current State of Critical Hemorrhage during Home Palliative Care for Terminally Ill Cancer Patients

Purpose: This study investigated the current state of critical hemorrhage during home palliative care for terminally ill cancer patients. Methods: We conducted a retrospective medical chart review of 7 cancer patients (1.4%) who received home palliative care from our clinic and died of critical hemorrhage at home from October 2007 to December 2014. Results: Four patients were male, the mean age was 70±11 years, and underlying diseases were different. None of the patients were accompanied by medical staff at the onset of bleeding. Six patients died at home and one patient was admitted to hospital for hemostasis. Six patients had a pre-hemorrhage episode more than 24 hours before critical hemorrhage occurred from the same site. One patient was administered a hemostatic agent, hemostasis was attempted in one, and one was given sedation. Six patients wanted to die at home, and did die at home. Discussion: If terminally ill cancer patients have critical hemorrhage at home, our options are limited. The results of this study suggest the importance of hemorrhage risk assessment and advance care planning.

A reevaluation of the epimeric and anomeric relationship of glucosides and galactosides in thermotropic liquid crystal self-assemblies.

Anomers and epimers α- and ß-gluco and -galactosides are expected to behave differently. However, recent results on a series of Guerbet glycosides have indicated similar liquid crystal clearing temperatures for pure ß-glucosides and the corresponding α-galactosides. This observation has led to speculation on similarities in the self-assembly interactions between the two systems, attributed to the trans-configuration of the 4-OH group and the hydrophobic aglycon. Previous simulations on related bilayers systems support this hypothesis, by relating this clearing transition temperature to intralayer (sugar-sugar) hydrogen bonding. In order to confirm the hypothesis, the comparison was expanded to include the cis-configurated pair, that is, α-gluco/ß-galactoside. A set of α-configurated Guerbet glucosides as well as octyl α-galactoside were prepared and their thermotropic phase behavior studied. The data obtained enabled a complete comparison of the isomers of interest. While the results in general are in line with a pairing of the stereo-isomers according to the indicated cis/trans-configuration, differences within the pairs can be explained based on the direction of hydrogen bonds from a simple modeling study.

Use of a stent of shape memory alloy in angioplasty / 日本心臓血管外科学会雑誌

The surface-coated vascular stent of shape memory alloy was made for use of occlusion of pseudo-lumen of the dissecting aneurysm of the aorta, as the usage of shape memory alloy in angioplasty, and the metal flexible delivery catheter was also made for the introduction of the stent. In the present study, antithrombogenicity of the vascular stent was much improved by surface-coating with EPTFE and segmented polyurethane. The long-term usage of the stent was confirmed by radiological, macroscopic, and electron microscopic examinations. Moreover, the metal flexible delivery catheter was demonstrated to be of much benefit for the introduction of the surface-coated vascular stent of shape memory alloy.