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

Measurement of metallic contaminants in food with a high-Tc SQUID

We have proposed and demonstrated a high-Tc SQUID system for detecting metallic contaminants in foodstuffs. There is a demand for the development of systems for detecting not only magnetic materials but also non-magnetic materials such as Cu and aluminium in foodstuffs to ensure food safety. The system consists of a SQUID magnetometer, an excitation coil and a permanent magnet. For a non-magnetic sample, an AC magnetic field is applied during detection to induce an eddy current in the sample. For a magnetizable sample, a strong magnetic field is applied to the sample prior to the detection attempt. We were able to detect a stainless steel ball with a diameter of 0.1 mm and a Cu ball less than 1 mm in diameter, for example

Robotic‐assisted colectomy for right‐sided colon cancer: Short‐term surgical outcomes of a multi‐institutional prospective cohort study in Japan

Abstract Background In Japan, there are no substantial reports on robotic‐assisted colectomy because few institutions performed the procedure, as it was not covered by national insurance until March 2022. Aim This study aimed to evaluate the safety and feasibility of robotic‐assisted colectomy for patients with curatively resectable colon cancer in Japan. Methods This multi‐institutional, prospective, single‐arm, observational study enrolled patients diagnosed with curatively resectable clinical stage I–IIIC colon adenocarcinoma with D2 or D3 lymph node dissection and treated with robotic‐assisted colectomy. The primary endpoint was the conversion rate to laparotomy. The non‐inferiority of outcomes for robotic‐assisted colectomy versus laparoscopic colectomy, which was determined from historical data, was verified. Results One hundred patients were registered between July 2019 and March 2022 and underwent robotic‐assisted colectomy performed by seven expert surgeons at six institutions. Thirteen patients were excluded because their surgeons had insufficient experience performing robotic‐assisted colectomy; therefore, 87 patients were eligible for the primary endpoint analysis. There was no conversion in these 87 patients, and robotic‐assisted colectomy was non‐inferior to laparoscopic colectomy in terms of conversion rate (90% confidence interval 0–3.38, p = 0.0006). No intraoperative adverse events occurred, and no mortality was observed in a total of 100 patients. The rate of patients with Clavien–Dindo complications grade III or higher was 4%. Conclusion This study showed the non‐inferiority of the conversion rates between robotic‐assisted colectomy and laparoscopic colectomy. Favorable perioperative outcomes also suggest the safety and feasibility of robotic‐assisted colectomy

Influence of Proton Activity Gaps between Electrodes on Open-Circuit Potential of H2/H2 and H2/Air Cells

Polymer -electrolyte-fuel-cell open-circuit voltages (OCVs) are exactly defined by equation (1), where cathode and anode proton activities [(aH+)cathode and (aH+)anode, respectively] usually are identical, so the third term in the right-hand side of equation (2) is ignored. OCV=E0+RT/2F*ln(a1/2 O2*(a2 H+)cathode/aH2O)-RT/2F*ln((a2 H+)anode/aH2) (1) =E0+RT/2F*ln(a1/2 O2*aH2/aH2O)+RT/2F*ln((a2 H+)cathode/(a2 H+)anode) (2) Water vapor pressure is a colligative property that fundamentally correlates to electrolyte concentrations in aqueous solutions. Proton activity is a function of acid concentration, such as pH, when electrolytes are acids. In polymer-electrolyte membranes, water vapor pressure and acid concentration are understood as relative humidity (RH) and water uptake (λ), respectively, where λ represents number of water molecules per sulfonic acid molecule. Several investigations have reported the relationship between RH and λ, meaning that proton activities and associated water uptakes are intimately related to RH. In actual fuel cell operation, cathode RH is determined by ambient-atmosphere and/or humidifier RH(s), and anode RH depends on hydrogen-circulator RH. Therefore, RH is not always identical at both electrodes, and the difference between electrode RHs is considerable during dry operation of polymer electrolyte fuel cells. Therefore, the third term in the right-hand side of equation (2) may be significant for dry operation. We measured OCVs when hydrogen was supplied to both electrodes at 80°C. One electrode (A) was fixed at 30% RH, while RH at the other electrode (B) was varied (0, 5, 10, 20, and 30%). Measured OCVs varied from 0 to 75 mV. For fuel cell tests, electrode A was supplied with hydrogen at 30% RH; electrode B, oxygen at 0, 5, 10, 20, and 30% RH. OCVs deviated from that measured when RH at electrode B was 30%, increasing from 0 to 60 mV with decreasing RH at electrode B. Results are also shown in Figure 1. Proton activities of both electrodes were thermodynamically calculated. The Gibbs–Duhem relation was applied to obtain molar Gibbs free energies of water and sulfonic acid, and proton activity coefficient was calculated using the Gibbs free energy of sulfonic acid and the relationship between RH and λ1–4, assuming that protons and sulfonic anions show identical ionic-activity coefficients. OCVs were estimated using the third term in the right-hand side of equation (2). Results are shown in Figure 1. Fuel-cell current–voltage performance was poor when RHs at the anode and cathode were 30 and 20%, respectively. To determine kinetic current, we measured the oxygen-reduction reaction (ORR) using a rotating-disk electrode (RDE) in concentrated-acid aqueous solutions, which modeled catalyst-layer ionomers. Kinetic currents decreased with acid concentrations. References T. A. Zawodzinski, Jr., C. Derouin, S. Radzinski, R. J. Sherman, V. T. Smith, T. E. Springer and S. Gottesfeld , J. Electrochem. Soc., 140,1041 (1993) P. K. Das and A. Z. Weber, Proceedings of the ASME 2013 11th Fuel Cell Science, Engineering and Technology Conference, Fuel Cell 18010 (2013) V. A. Sethuraman, J. W. Weidner, A. T. Haug, S. Motupally,b and L. V. Protsailo, J. Electrochem. Soc., 155, B50 (2008) A. Kusoglu and A. Z. Weber, Chem. Rev., 117, 987 (2017) Figure

Additional file 1: Table S1. of Risk of low bone mineral density in patients with rheumatoid arthritis treated with biologics

Univariate analysis of factors potentially associated with low bone mineral density in patients with rheumatoid arthritis treated with biologics. (DOCX 14 kb