Wavelength-Conversion-Material-Mediated Semiconductor Wafer Bonding for Smart Optoelectronic Interconnects

A new concept of semiconductor wafer bonding, mediated by optical wavelength conversion materials, is proposed and demonstrated. The fabrication scheme provides simultaneous bond formation and interfacial function generation, leading to efficient device production. Wavelength-converting functionalized semiconductor interfacial engineering is realized by utilizing an adhesive viscous organic matrix with embedded fluorescent particles. The bonding is carried out in ambient air at room temperature and therefore provides a cost advantage with regard to device manufacturing. Distinct wavelength conversion, from ultraviolet into visible, and high mechanical stabilities and electrical conductivities in the bonded interfaces are verified, demonstrating their versatility for practical applications. This bonding and interfacial scheme can improve the performance and structural flexibility of optoelectronic devices, such as solar cells, by allowing the spectral light incidence suitable for each photovoltaic material, and photonic integrated circuits, by delivering the respective preferred frequencies to the optical amplifier, modulator, waveguide, and detector materials

Expression of SARS‐CoV‐2 entry factors in human oral tissue

The distribution of cells expressing SARS‐CoV‐2 entry factor angiotensin‐converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested. The investigation was conducted with normal flesh tissue and paraffin‐embedded specimens. The ACE2 and TMPRSS2 expression was detected with all subjects in the normal mucosa of the keratinized stratified squamous epithelia of the tongue and non‐keratinized stratified squamous epithelia of the lip and cheek. It was found that ACE2 is expressed in the cytoplasm and on the cell membrane mainly in the stratum granulosum of the epithelia while the TMPRSS2 is strongly expressed on the cell membrane mainly in the stratum granulosum and stratum spinosum, but not in the stratum basale. Antibodies’ reactions for ACE2 and TMPRSS2 were not observed in the nuclei or keratin layer. The expression of ACE2 and TMPRSS2 in the oral epithelia appears to be general, and the expression was also observed in the mucous and serous acini of the labial glands. The SARS‐CoV‐2 may transiently attach to the oral mucosa and the minor salivary glands which are present under all of the oral mucosa. The oral cavity can be considered an important organ for SARS‐CoV‐2 attachment and may provide a preventive medical avenue to guard against COVID‐19 by preventing saliva from scattering

L type Ca2+ channel blockers prevent oxaliplatin-induced cold hyperalgesia and TRPM8 overexpression in rats

<p>Abstract</p> <p>Background</p> <p>Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the cold hyperalgesia. In the present study, we examined the effects of Ca²⁺channel blockers on oxaliplatin-induced cold hyperalgesia in rats.</p> <p>Methods</p> <p>Cold hyperalgesia was assessed by the acetone test. Oxaliplatin (4 mg/kg), sodium oxalate (1.3 mg/kg) or vehicle was injected i.p. on days 1 and 2. Ca²⁺(diltiazem, nifedipine and ethosuximide) and Na⁺(mexiletine) channel blockers were administered p.o. simultaneously with oxaliplatin or oxalate on days 1 and 2.</p> <p>Results</p> <p>Oxaliplatin (4 mg/kg) induced cold hyperalgesia and increased in the transient receptor potential melastatin 8 (TRPM8) mRNA levels in the dorsal root ganglia (DRG). Furthermore, oxalate (1.3 mg/kg) significantly induced the increase in TRPM8 protein in the DRG. Treatment with oxaliplatin and oxalate (500 μM for each) also increased the TRPM8 mRNA levels and induced Ca²⁺influx and nuclear factor of activated T-cell (NFAT) nuclear translocation in cultured DRG cells. These changes induced by oxalate were inhibited by nifedipine, diltiazem and mexiletine. Interestingly, co-administration with nifedipine, diltiazem or mexiletine prevented the oxaliplatin-induced cold hyperalgesia and increase in the TRPM8 mRNA levels in the DRG.</p> <p>Conclusions</p> <p>These data suggest that the L type Ca²⁺channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced cold hyperalgesia, and that Ca²⁺channel blockers have prophylactic potential for acute neuropathy.</p

A Case of Malignant Gastrointestinal Stromal Tumor of the Transverse Colon: Evaluation of Proliferation Activity

Here, we report a colonic gastrointestinal stromal tumor (GIST) in a middle-aged man above 40. A histologically similar second tumor was detected 2 years after initial surgery. The primary GIST, measuring 5.5 ? 6.0 cm, consisted of spindle tumor cells with a higher number of mitoses and Ki67 labeling index (about 20%) than those of the second tumor, implying a de novo GIST. These markers might be useful in evaluating malignant potential, as well as to differentiate between a de novo and a recurrent tumor in the colonic GIST

Randomized Controlled Trial Comparing the Usefulness of Endoscopic Ultrasound Processor

[Background] Although endoscopic ultrasonography (EUS) is a useful tool for diagnosing pancreatobiliary diseases, not many facilities perform this technique as it is difficult to master. Currently, two new EUS systems exist: EU-ME2/GF-UCT260, manufactured by Olympus, and SU-1/EG-580UT, manufactured by Fujifilm. Some reports have compared new EUS models to older versions, but the operability and image quality of these two latest systems have not been compared. Our study aimed to compare the usefulness of these two types of EUS. [Methods] Forty consecutive patients were recruited and randomized in a two-arm clinical trial; Arm 1: EU-ME2/GF-UCT260 was used only for observation and SU-1/EG-580UT for EUS-fine needle aspiration (FNA); Arm 2: SU-1/EG-580UT was used only for observation and EU-ME2/GF-UCT260 for EUS-FNA. Using a crossover design, we evaluated image findings, ease of scope insertion, and visibility of the gastrointestinal (GI) tract. Each procedure was scored using a 5-point scale (Clinical Trial ID: UMIN000031373). [Results] SU-1/EG-580UT was significantly better in terms of lesion-delineating capacity: lesion border (P < 0.001), internal echo (P < 0.001). Significantly easier scope insertion was observed with SU-1/EG-580UT with respect to any insertion into the piriform recess (P = 0.018), the pylorus ring (P < 0.001), and the superior duodenal angle (P < 0.001). Visibility during gastrointestinal observation was also significantly better with the SU-1/EG-580UT (P < 0.001) than with the EU-ME2/GF-UCT260. [Conclusion] SU-1/EG-580UT EUS demonstrated superior performance during ultrasonic endoscopic GI observation, operability, and ultrasonic image quality. The result of the superior ultrasound imaging quality of SU-1/EG-580UT EUS will aid in the identification of small pancreatic malignancies with unclear borders and prove useful in evaluating mural nodules of IPMN in detail. These findings could result in an increased use of EUS and improve identification and prognosis of patients with pancreatobiliary diseases

Effects of 6-month eicosapentaenoic acid treatment on postprandial hyperglycemia, hyperlipidemia, insulin secretion ability, and concomitant endothelial dysfunction among newly-diagnosed impaired glucose metabolism patients with coronary artery disease. An open label, single blinded, prospective randomized controlled trial

Additional file 2: Table S2. Comparison of cookie meal test data between baseline and 6 months, and comparison of absolute change from baseline among patients with baseline plasma glucose <110 mg/dL

Topographic variability of the left atrium and pulmonary veins assessed by 3D-CT predicts the recurrence of atrial fibrillation after catheter ablation

AbstractBackgroundCatheter ablation (CA) is an established therapy for atrial fibrillation (AF). However, the assessment of anatomical information and predictors of AF recurrence remain unclear. We investigated the relationship between anatomical information on the left atrium (LA) and pulmonary veins (PVs) from three-dimensional computed tomography images and the recurrence of AF after CA.MethodsSixty-seven consecutive AF patients (mean age: 62±10 years, median AF history: 42 (12; 60) months, mean LA size: 41±7mm, paroxysmal: 56%) underwent CA and were followed for 19±10 months. The segmented surface areas (antral, posterior, septal, and lateral) and dimensions (between the anterior and posterior walls, the right inferior PV and mitral annulus [MA], the right superior PV and MA, the left superior PV and MA, and the mitral isthmus) of the LA were evaluated three dimensionally using the NavX system. The cross-sectional areas of the PVs were also evaluated.ResultsAfter the follow-up period, 49 patients (73%) remained free from AF. A multivariate analysis showed that the diameter of the mitral isthmus and cross-sectional area of the right upper PV were associated with AF recurrence (odds ratio: 1.070, CI: 1.02–1.12, p=0.001; odds ratio: 0.41, CI: 0.21–0.77, p=0.006).ConclusionEnlargement of the mitral isthmus and a smaller right superior PV cross-sectional area were associated with AF recurrence

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T-and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30 min of left ascending coronary I/R. Benidipine was administered orally at 3 mg kg -1daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2′ deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels. © 2012 The Japanese Society of Hypertension All rights reserved

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