Background Delta‐like protein 3 (DLL3) is a Notch ligand that has an important role in the tumorigenesis of small cell lung cancer (SCLC). Recently, rovalpituzumab tesirine (Rova‐T), a DLL3‐targeted antibody‐drug conjugate, has been developed for treating SCLC. DLL3 is a transcriptional target of the achaete‐scute homolog‐1 (ASCL1) transcription factor, which is involved in pulmonary neuroendocrine cell development. However, the relationship between DLL3 and/or ASCL1 expression and the clinical features of SCLC remains unknown, especially for early‐stage resected SCLC. This study aimed to investigate the expression of DLL3 and ASCL1 in resected SCLC samples using immunohistochemical analysis. Materials and Methods We collected 95 surgically resected SCLC samples, which were formalin fixed and paraffin embedded. Immunohistochemistry staining was performed to investigate the correlation between the expression of either DLL3 or ASCL1 and clinicopathological features of study patients. Results Seventy‐seven (83%) of 93 immunohistochemically evaluable samples were positive for DLL3 (expression in ≥1% of tumor cells), and DLL3‐high expression (≥75%) was observed in 44 samples (47%). Sixty‐one (64%) of 95 samples were positive for ASCL1 (expression in ≥5% of tumor cells). A positive correlation was observed between DLL3 and ASCL1 expression. DLL3 and ASCL1 expression were not associated with survival in SCLC patients. DLL3 was more prevalent in patients with advanced clinical disease. Conclusion DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of SCLC. Implications for Practice This article examines the relationship between delta‐like protein 3 (DLL3) and achaete‐scute homolog‐1 (ASCL1) protein expression with the clinical features of 95 surgically resected small cell lung cancer (SCLC). DLL3 is attracting attention because rovalpituzumab tesirine (Rova‐T), a DLL3‐targeted antibody‐drug conjugate, was developed recently. DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of early‐stage SCLC, including with Rova‐T.

An etching technique called phase-change etching was developed. In this technique, only crystalline regions in a phase-change recording film are selectively etched by an alkaline solution, and amorphous regions remain on the sample surface, which means that a phase-change recording film can be used as a resist for pattern formation. By combination of this technique and phase-change recording, fabrication of the dot pattern with a size of about 1∕10 of the fabricating spot was demonstrated. This result indicates the possibility of nanosize fabrication using the phase-change etching technique.

Some characteristics of reversible phase-change optical data storage based on an amorphouscrystalline transformation in InSbTe alloys are given. The reversible phase change was observed in a wide region of composition. The laser amorphized spot of a ternary compound In 3 SbTe z film could be crystallized using a diode laser pulse ofless than 100 ns with an incident laser power of more than 10 m W. The crystallization temperature of the amorphized spot was 280"C and the activation energy was about 1.8 eV which shows that long-term data retention at room temperature is possible. The repetition number of static write and erase using the pulse of 50 ns reached above 10 5 , These data show that the ternary compound film has potential for reversible optical data storage medi.a with high-speed erasing and long-term data retention.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. 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.

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Background There are no established biomarkers for predicting the efficacy of first‐line pembrolizumab monotherapy in patients with high programmed death‐ligand 1 (PD‐L1) expression. In this study, we investigated whether the Glasgow prognostic score (GPS), neutrophil‐to‐lymphocyte ratio (NLR), and body mass index (BMI) can be used to evaluate the effect of first‐line pembrolizumab monotherapy in patients with advanced non‐small cell lung cancer (NSCLC) who express high levels of PD‐L1. Methods We reviewed data from 142 patients with high PD‐L1 expression who underwent first‐line pembrolizumab monotherapy for NSCLC at six Japanese institutions between February 2017 and June 2019 and assessed the prognostic value of the GPS, NLR, and BMI. The Kaplan–Meier method and Cox proportional hazard models were used to examine differences in progression‐free survival (PFS) and overall survival (OS). The GPS, NLR, and BMI were calculated using C‐reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively. Results The GPS independently predicted the first‐line pembrolizumab monotherapy efficacy, as a good GPS (GPS 0–1) was associated with a significantly better PFS and OS compared to a poor GPS (GPS 2) (PFS: 11.8 vs. 2.9 months, p < 0.0001; OS: not reached vs. 8.3 months, p < 0.0001). Furthermore, BMI independently predicted efficacy, as patients with high BMI (BMI ≥21.4) exhibited significantly better OS compared to those with low BMI (BMI <21.4) (OS: not reached vs. 14.1 months, p = 0.006). Conclusions Among patients with high PD‐L1 expression undergoing first‐line pembrolizumab monotherapy for NSCLC, the GPS is significantly correlated with both PFS and OS, and BMI with OS, indicating that they could be used to predict treatment outcome in these patients. To the best of our knowledge, this is the first study to assess the relationship among the GPS, NLR, and BMI and survival among patients with high PD‐L1 expression undergoing first‐line pembrolizumab monotherapy for NSCLC.

A three-dimensional (3-D) vertical chain-cell-type phase-change memory (VCCPCM) for next-generation large-capacity storage was developed. The VCCPCM features formation of memory holes in multi-layered stacked gates by using a single mask and a memory array without a selection transistor. As a result of this configuration, the number of process steps for fabricating the VCCPCM is reduced. The excellent scalability of the VCCPCM's new phase-change material makes it possible to reduce the cell size beyond the scaling limit of flash memory. In addition, a poly-silicon selection diode makes it possible to reduce the cell factor to 4F 2 . Consequently, relative cost of the VCCPCM compared to 3-D flash memory is reduced to 0.2. IntroductionThe most important requirement for the storage-memory market is reduction of bit cost, and that requirement has been met by reducing the cell size of flash memory. However, high-voltage operation of flash memory makes it difficult to further reduce cell size. It has recently been reported that the bit-cost reduction can be continued by utilizing 3-D flash memory [1]. 3-D flash memory needs fewer process steps compared to simple stacking of flash memory, but reducing cell size is difficult for two reasons. Firstly, a 20-nm-thick ONO layer in the memory hole is needed and, secondly, a vertical poly-silicon selection MOS transistor needs a cell factor of 6F 2 [1]. In this work, a vertical chain-cell-type phase-change memory (VCCPCM), which can overcome these problems concerning 3-D flash in view of bit cost, is proposed. The key technologies of this VCCPCM are (1) a vertical chain cell for reducing the number of process steps, (2) a scalable new phase-change material for reducing cell size, and (3) a poly-Si XY-selection diode for reducing cell factor to 4F 2 . A poly-Si diode [2] and a lateral chain-cell-type PCM [3] were previously developed. Relative bit cost of both 3-D flash memory and VCCPCM is shown in Fig. 1. By virtue of technologies (1) to (3), the relative bit cost of the VCCPCM compared to 3-D flash memory is reduced to 0.2. Table 1 compares characteristics of 3-D flash memory and VCCPCM. In the present study, set, reset, and reading operations of the VCCPCM were confirmed. Moreover, off-current variation of the poly-Si diode was suppressed by short-time annealing.2. Device structure and operation method The structure of the VCCPCM is shown in Fig. 2. The poly-Si selection diode and VCCPCM are connected serially and positioned at the cross points between the bit and word lines. The structure and equivalent circuit of a VCCPCM are shown in Fig. 3. The gate oxide, channel poly-silicon, and the phase-change material are formed on the side of the holes in the stacked gates. Each memory cell consists of a poly-silicon transistor and a phase-change layer connected in parallel. The memory cells are connected serially in the vertical direction. In the set/reset operations, an off-voltage is applied to the gate at the selected cell, and a positive on-voltage is applied to the unselect...

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