Non-volatile optical phase shift in ferroelectric hafnium zirconium oxide

A non-volatile optical phase shifter is a critical component for enabling large-scale, energy-efficient programmable photonic integrated circuits (PICs) on a silicon (Si) photonics platform. While ferroelectric materials like BaTiO3 offer non-volatile optical phase shift capabilities, their compatibility with complementary metal-oxide-semiconductor (CMOS) fabs is limited. Hence, the search for a novel CMOS-compatible ferroelectric material for non-volatile optical phase shifting in Si photonics is of utmost importance. Hafnium zirconium oxide (HZO) is an emerging ferroelectric material discovered in 2011, which exhibits CMOS compatibility due to the utilization of high-k dielectric HfO2 in CMOS transistors. Although extensively studied for ferroelectric transistors and memories, its application in photonics remains relatively unexplored. Here, we show the optical phase shift induced by ferroelectric HZO deposited on a SiN optical waveguide. We observed a negative change in refractive index at a 1.55 um wavelength in the pristine device regardless of the direction of an applied electric filed. We achieved approximately pi phase shift in a 4.5-mm-long device with negligible optical loss. The non-volatile multi-level optical phase shift was confirmed with a persistence of > 10000 s. This phase shift can be attributed to the spontaneous polarization within the HZO film along the external electric field. We anticipate that our results will stimulate further research on optical nonlinear effects, such as the Pockels effect, in ferroelectric HZO. This advancement will enable the development of various devices, including high-speed optical modulators. Consequently, HZO-based programmable PICs are poised to become indispensable in diverse applications, ranging from optical fiber communication and artificial intelligence to quantum computing and sensing

Risk of Drug-Induced Accidents and Injuries in Elderly Patients Treated with Specific Drugs Rather than Polypharmacy : Analyses of the Japanese Adverse Drug Event Report Database

One of the reasons the health care system requires long-term nursing care for elderly patients is the risk of falls and fractures. In this study, we sought to identify risk factors for drug-induced falls and fractures in elderly patients in Japan. Risk factors for drug-induced falls and fractures in the elderly were analyzed by searching for the Standardised Medical Dictionary for Regulatory Activities （MedDRA） query （SMQ） “accidents/injuries” in the Japanese Adverse Drug Event Report database （JADER）, as this SMQ was the most well suited for evaluating data on falls and fractures. For elderly patients in Japan, the risk factors for drug-induced accidents/injuries include age ≥ 70 years old, female sex, and treatment with specific drugs, but not polypharmacy. Among the risk factors with the 10 highest reporting odds ratios （RORs） were treatment with: anti-osteoporosis agents such as bisphosphonates （e.g., minodronic acid）, eldecalcitol and bazedoxifene; dementia therapeutic agents such as rivastigmine and memantine; antiparkinsonian agents such as entacapone and pramipexole; and neuropathic pain relievers such as pregabalin. Although various geriatric syndromes were generally caused by polypharmacy, it has been posited that individual medications such as those mentioned above have a more significant association with drug-induced accidents and injuries in the elderly than polypharmacy. These drugs should be used cautiously while considering drug interruption, dose reductions, and switching to alternative therapies with lower risks. An association between accidents/injuries and drugs targeting the central nervous system （such as hypnotics, sedatives, anxiolytics, and antidepressants） has previously been reported. However, in the present study, no elevated risks in association with triazolam, zopiclone, flunitrazepam, diazepam, rilmazafone, estazolam, etizolam, or paroxetine were detected. Using RORs for risk detection for drugs in the JADER database is accessible and useful, and enables sensitive risk detection

Inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>It has been reported that immunoglobulin G4-related systemic disease can spread to nearly every organ, and often presents as an inflammatory mass or masses at those sites. In the kidney, this disease is often diagnosed after a radical or partial nephrectomy following the discovery of an inflammatory mass which is often suspected to be a malignant tumor. Here, we present a rare case of inflammatory pseudotumors of the kidney and the lung presenting as immunoglobulin G4-related disease, which were diagnosed by computed tomography-guided biopsies.</p> <p>Case presentation</p> <p>A 54-year-old Japanese man was referred to our hospital with suspected bilateral renal cancer, multiple lung metastases and autoimmune pancreatitis. His serum immunoglobulin G4 level was high. We used computed tomography-guided biopsies and histopathological examinations of the biopsied specimens to diagnose the tumors as immunoglobulin G4-related bilateral renal and lung inflammatory pseudotumors. Our patient was treated with oral prednisolone, and after one month of treatment, contrast-enhanced computed tomography demonstrated a general improvement, as noted by a reduction in size of the masses.</p> <p>Conclusion</p> <p>Renal masses that are formed due to immunoglobulin G4-related disease require comprehensive diagnosis to prevent unnecessary surgical resections from being performed. Further consideration should be paid to immunoglobulin G4-related diseases in the future.</p

A rare case of metastatic renal carcinoid

<p>Abstract</p> <p>Background</p> <p>Carcinoid is an endocrine cell tumor with low-grade atypia, which is generally a low-grade malignant cancer with a good prognosis. Metastatic renal carcinoid is even rarer than primary carcinoids.</p> <p>Case presentation</p> <p>We present our experience of a patient with metastatic renal carcinoid from the gastrointestinal tract.</p> <p>Conclusions</p> <p>The carcinoid tumor of the kidney in our patient, who had a history of liver metastasis from rectal carcinoid, was considered metastatic based on the pathological findings.</p

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