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InSb thin film was deposited on glass by r.f. sputtering using the InSb (atomic ratio of 1:1) target. The film was capped by SiO2 film to prevent the effusion of Sb of low melting point. After that, blue laser beam at 445 nm of controlled power density was irradiated using CW scanning mode. The film was crystalized successfully with keeping the ratio of In and Sb as (1:1). High electron Hall mobility of 1,050 cm2/(Vs) was obtained without degrading under glass. New device applications such as magnetic or infrared sensor system with poly Si TFTs are expected not only on glass but also on flexible panel such as on plastic sheet.

Perpendicular CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) prepared from (Co25Fe75)1−xBx alloys are found to have better annealing stability when made with 30at% boron relative to a more typical 20at% boron. A comparison of film-level properties shows that perpendicular magnetic anisotropy (PMA) increases significantly for 30at%B, while the range of electrode thicknesses that maintain a perpendicular easy axis also increases. Because capping layer interdiffusion has been previously suggested to play a role in the breakdown of PMA with annealing temperature, we have isolated its effect by studying the annealing process of thin Ta/CoFeB(2nm)/Ta trilayers. Through analysis of the decrease in Curie temperature during annealing, we can infer that higher boron content indeed suppresses growth of the intermixed CoFeB-Ta dead layer. For device structures and processing conditions where interdiffusion is a limiting factor, increasing boron content is shown to result in substantially improved tunneling magnetoresistance (TMR).

Using a genome-wide CRISPR screen, the authors here identify Toxoplasma genes that counteract the anti-parasitic activity of interferon gamma in murine macrophages. One of these genes, dense granule protein GRA45, is critical for the trafficking of GRA effectors and affects virulence in mice.

A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016–2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposure in utero, which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS), Listeria monocytogenes, Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV, L. monocytogenes, Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates.

Flat low-temperature two-stage flames were established on a Powling burner using rich diethyl-ether/ air or n-heptane/air mixtures, and nitrogen monoxide NO was added into the fuel-air mixtures with a concentration of 240 ppm. The temperature development and chemical-species histories, especially of NO, nitrogen dioxide NO2 and hydrogen cyanide HCN were examined associated with an emission-spectrum measurement from the low-temperature flames. Nitrogen monoxide was consumed in the cool-flame region, where NO was converted to the NO2. The NO2 generated, however, fell suddenly in the cool-flame degenerate region, in which the HCN superseded. In the blue-flame region the NO came out again and developed accompanied with remained HCN in the post blue-flame region. The NO seeding into the mixture intensified the blue-flame luminescence probably due to the cyanide increase.

Locoregional recurrence of non-small-cell lung cancer (NSCLC) after complete resection lacks standard treatment. Durvalumab after chemoradiotherapy (CRT) or CRT alone is often selected in daily clinical practice for patients with locoregional recurrence; however, the therapeutic efficacy of these treatments remains unclear, and we aimed to assess this. This retrospective observational study used data from patients with NSCLC diagnosed with locoregional recurrence after complete resection who subsequently underwent concurrent CRT followed by durvalumab (CRT-D group) or CRT alone (CRT group). We employed propensity score analysis with inverse probability treatment weighting (IPTW) to adjust for various confounders and evaluate efficacy in the CRT-D group. After IPTW adjustment, the CRT-D group contained 119 patients (64.7% male; 69.7% adenocarcinoma), and the CRT group contained 111 patients (60.5% male; 73.4% adenocarcinoma). Their mean ages were 66 and 65 years, respectively. The IPTW-adjusted median progression-free survival was 25.4 and 11.5 months for the CRT-D and CRT groups, respectively (hazard ratio, 0.44; 95% confidence interval, 0.30-0.64); the median overall survival was not reached in either group favoring CRT-D (hazard ratio, 0.49; 95% confidence interval, 0.24-0.99). Grade 3 or 4 adverse events were observed in 48.8% of patients during CRT, 10.7% after initiating durvalumab maintenance therapy in the CRT-D group, and 57.3% in the CRT group. Overall, the sequential approach of CRT followed by durvalumab is a promising treatment strategy for locoregional recurrence of NSCLC after complete resection., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Pembrolizumab is a major treatment for recurrent or advanced non-small-cell lung cancer (NSCLC). However, data on its use and pharmacokinetics (PK) in older patients are limited. This open-label, multicenter, observational study evaluated real-world data on the safety, efficacy, and PK of pembrolizumab in older patients with NSCLC. In 99 patients aged ≥75 years, PK was determined by liquid chromatography-mass spectrometry on pretreatment samples. Performance status (PS), geriatric assessment (GA), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The median age was 78 (75-87) years. PS was 2-3 in 14 patients. The median ORR, PFS, and OS were 47.5%, 8.0, and 20.5 months, respectively. Although PK and ORR were not significantly associated, patients with the lowest Cycle 1-trough quartile (Q1) experienced poorer PFS (Q1 vs. Q2-4; 3.4 vs. 11.8 months, P = 0.006) and OS (Q1 vs. Q2-4; 9.9 vs. 21.7 months, P = 0.005) than in other quartiles overall, and even in the PD-L1 ≥50% subset (PFS, Q1 vs. Q2-4; 4.1 vs. 14.7 months, P = 0.005; OS, Q1 vs. Q2-4; 9.4 vs. 22.1 months, P = 0.010). The Q1 subgroup was characterized by poor PS and lower albumin, and more frequent "weight loss ≥ 10%" on the GA. Pembrolizumab therapy had similar PK and efficaciousness in older as well as younger patients. In patients with PS ≥2, low albumin, and vulnerable GA, early increases in PK levels are less likely, potentially diminishing efficacy even when PD-L1 ≥50%., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

(+)-Plakevulin A (1), an oxylipin isolated from an Okinawan sponge Plakortis sp. inhibits enzymatic inhibition of DNA polymerases (pols) α and δ and exhibits cytotoxicity against murine leukemia (L1210) and human cervix carcinoma (KB) cell lines. However, the half-maximal inhibitory concentration (IC 50 ) value for cytotoxicity significantly differed from those observed for the enzymatic inhibition of pols α and β, indicating the presence of target protein(s) other than pols. This study demonstrated cytotoxicity against human promyelocytic leukemia (HL60), human cervix epithelioid carcinoma (HeLa), mouse calvaria-derived pre-osteoblast (MC3T3-E1), and human normal lung fibroblast (MRC-5) cell lines. This compound had selectivity to cancer cells over normal ones. Among these cell lines, HL60 exhibited the highest sensitivity to (+)-plakevulin A. (+)-Plakevulin A induced DNA fragmentation and caspase-3 activation in HL60 cells, indicating its role in apoptosis induction. Additionally, hydroxysteroid 17-β dehydrogenase 4 (HSD17B4) was isolated from the HL60 lysate as one of its binding proteins through pull-down experiments using its biotinylated derivative and neutravidin-coated beads. Moreover, (+)-plakevulin A suppressed the activation of interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3). Because the knockdown or inhibition of STAT3 induces apoptosis and HSD17B4 regulates STAT3 activation, (+)-plakevulin A may induce apoptosis in HL60 cell lines by suppressing STAT3 activation, potentially by binding to HSD17B4. The present findings provide valuable information for the mechanism of its action., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Oligometastasis and oligoprogression (OP) has not been adequately defined in extensive-stage SCLC (ES-SCLC) and may be a good indication for adding local treatment. Therefore, this multicenter study aimed to investigate the prognostic impact of oligometastasis and OP in ES-SCLC., Methods: We enrolled patients who received chemoimmunotherapy between September 2019 and June 2022. Patients were classified into oligometastasis and non-oligometastasis groups by determining the number of original tumor lesions and distant metastases (worsening or newly appearing lesions) at the time of initial diagnosis and disease progression after first-line treatment., Results: We retrospectively analyzed 265 consecutive patients with ES-SCLC. Synchronous oligometastasis (SOM) and OP was defined as less than or equal to five lesions in less than or equal to two organs, including lungs; 21.0% and 53.2% of patients had SOM and OP, respectively. Median progression-free survival was 5.8 months and 4.9 months in patients with and without SOM, respectively (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.51-1.02, p  = 0.065). Median overall survival was 20.5 months and 15.0 months in patients with and without SOM (HR = 0.58, 95% CI: 0.37-0.95, p  = 0.027) from the initiation of first-line treatment. The OP group revealed a better progression-free survival of 5.2 months (versus 3.2 mo, HR = 0.69, 95% CI: 0.50-0.96, p  = 0.026) and overall survival of 15.1 months (versus 7.5 mo, HR = 0.44, 95% CI: 0.29-0.66, p  = 0.027) from the initiation of second-line treatment compared with the non-OP group. The Lung Immune Prognostic Index score was significantly lower in the SOM and OP group., Conclusions: ES-SCLC in patients with SOM and OP may be more indolent than that of the nonoligometastasis group, therefore, new treatment strategies, including the addition of local treatment, should be explored., Clinical Trial Registration: This study was registered at UMIN-CTR (UMIN000053402)., Competing Interests: Dr. Asahina reported receiving grants from 10.13039/100004325AstraZeneca, receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Chugai Pharmaceutical, Merck Sharp & Dohme, Bristol-Myers Squib, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Merck, KyowaHakko-Kirin and reported participation on a data safety monitoring board or advisory board of AstraZeneca. Dr. Yokouchi reported receiving grants from Chugai Pharmaceuticals Co., Ltd., AstraZeneca, AbbVie, Daiichi Sankyo, Bristol-Myers Squibb Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sanofi, and personal fees from Chugai Pharmaceutical Co., Ltd. and AstraZeneca during the conduct of the study. Dr. Megumi Furuta reported receiving honoraria from AstraZeneca K.K., Daiichi Sankyo Co, Ltd., Nippon Kayaku Co, Ltd., and Chugai Pharmaceutical Co. during the conduct of the study. Dr. Konno reported receiving grants from 10.13039/100010795Chugai Pharmaceutical. Dr. Hosomi reported receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, and educational events from AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Nippon Kayaku, Takeda, Eisai, Novartis, Pfizer, Merck Sharp & Dohme during the conduct of the study. Dr. Oizumi reports receiving grants from 10.13039/100006483AbbVie, 10.13039/100002429Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Merck Sharp & Dohme, Pfizer, Sanofi, Taiho Pharmaceutical, and Takeda Pharmaceutical; honoraria from AstraZeneca, Chugai Pharmaceutical, Merck Sharp & Dohme. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Aims: This study investigates the cell physiology of thermally injured bacterial cells, with a specific focus on oxidative stress and the repair mechanisms associated with oxidative secondary stress., Methods and Results: We explored the effect of heat treatment on the activity of two protective enzymes, levels of intracellular reactive oxygen species, and redox potential. The findings reveal that enzyme activity slightly increased after heat treatment, gradually returning to baseline levels during subculture. The response of Escherichia coli cells to heat treatment, as assessed by the level of superoxide radicals generated and redox potential, varied based on growth conditions, namely minimal and rich media. Notably, the viability of injured cells improved when antioxidants were added to agar media, even in the presence of metabolic inhibitors., Conclusions: These results suggest a complex system involved in repairing damage in heat-treated cells, particularly in rich media. While repairing membrane damage is crucial for cell regrowth and the electron transport system plays a critical role in the recovery process of injured cells under both tested conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Fungi compose a minority but a common component of normal oral microbiota and contribute to oral and systemic health by interacting with bacterial inhabitants. This study investigated the relationship of oral fungal profiles to health status and bacterial profiles of 159 elderly adults receiving community support and home care services. Fungal and bacterial densities and compositions were determined based on the fungal ribosomal internal transcribed spacer region and bacterial 16S rRNA gene amplicon analyses, respectively. The total fungal density of 87 individuals exceeded 5,000 copies, and their microbiota was characterized by significantly less dense bacterial populations and lower relative abundances of oral health-associated taxa, such as Neisseria perflava and Porphyromonas pasteri , compared with those with less than 5,000 copies of fungi. These individuals were significantly older, had fewer teeth, had lower physical function, and comprised more denture users and individuals with cognitive decline. Fungal compositions were classified into three profiles ( Candida albicans -dominant, non- albicans Candida -dominant, and non- Candida -dominant), and individuals with a non- albicans Candida -dominant profile exhibited significantly lower physical and cognitive function than those with the Candida albicans -dominant profile. These results demonstrate that a high-density fungal population co-occurs with poor oral and systemic health status of the host and dysbiosis of the bacterial community, and particularly, the overgrowth of non- albicans Candida species may be implicated in worsening systemic conditions., Importance: The interaction between fungal and bacterial components involved in the virulence of oral microbiota has received attention. This study demonstrates that an increase in fungal components is associated with a dysbiotic bacterial community and poor health status in elderly adults. Among individuals with a high-density fungal population, particularly, those with a non- albicans Candida -dominant profile had lower physical and cognitive functions than those with a C. albicans -dominant profile. These findings indicate that the evaluation of fungal components, in addition to the bacterial components, is important to understand the involvement of oral microbiota in oral and systemic diseases in elderly adults., Competing Interests: The authors declare no conflict of interest.

Background: The post-insertion clinical course of esophageal self-expandable metal stents (SEMS) in initially frail patients with esophageal carcinoma (EC) with dysphagia remains unclear. This study aimed to assess dysphagia improvement and evaluate prognosis in initially frail patients with advanced EC following SEMS insertion., Methods: We retrospectively reviewed EC patients with EC who underwent esophageal SEMS insertion at our institution between January 2014 and March 2023. Inclusion criteria comprised Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3 or ECOG PS 2 for individuals aged ≥ 75 years and recommendation for best supportive care by a multidisciplinary team., Results: Forty-six patients met the inclusion criteria. Among them, 37 patients (80.4%) were ≥ 75 years old, and 21 patients (45.7%) exhibited ECOG PS 3 or 4. Dysphagia score (DS) ≥ 3 was observed in 27 patients (58.7%). All esophageal SEMS insertions were successfully completed. Post-procedure, there were two fatal cases of aspiration pneumonia and one perforation incident. DS improved to ≤ 1 in 25 patients (54.3%), with multivariate analysis indicating DS 3-4 and Glasgow Prognostic Score (GPS) 1-2 as negative predictive factors. The median overall survival was 4.1 months (95% confidence interval 1.8-6.5)., Conclusions: Esophageal SEMS insertion effectively alleviated dysphagia in initially frail EC patients, yet prognosis remained poor, with occurrences of some fatal adverse events. Careful selection of candidates for esophageal SEMS insertions is crucial in this demographic, particularly considering the challenges in improving dysphagia for patients with DS 3-4 and GPS 1-2., (© 2024. The Author(s).)

Transparent oxide semiconductors (TOSs) based thin-film transistors (TFTs) that exhibit higher field effect mobility (µ FE ) are highly required toward the realization of next-generation displays. Among numerous types of TOS-TFTs, In 2 O 3 -based TFTs are the front-running candidate because they exhibit the highest µ FE ≈100 cm 2  V -1  s -1 . However, the device operation of In 2 O 3 TFTs is unreliable; a large voltage shift occurs especially when negative gate bias is applied due to adsorption/desorption of gas molecules. Although passivation of the TFTs is used to overcome such instability, previously proposed passivation materials do not improve the reliability. Here, it is shown that the In 2 O 3 TFTs passivated with Y 2 O 3 and Er 2 O 3 films are highly reliable and do not show threshold voltage shifts when applying gate bias. Positive and negative gate bias is applied to the In 2 O 3 TFTs passivated with various insulating oxides and found that only the In 2 O 3 TFTs passivated with Y 2 O 3 and Er 2 O 3 films do not exhibit threshold voltage shifts. It is observed that only the Y 2 O 3 grew heteroepitaxially on the In 2 O 3 crystal. This is the origin of the high reliability of the In 2 O 3 TFTs passivated with Y 2 O 3 and Er 2 O 3 films. This finding accelerates the development of next-generation displays using high-mobility In 2 O 3 TFTs., (© 2024 Wiley‐VCH GmbH.)

Background: Left ventricular pseudoaneurysm (LVPA) is an infrequent but highly lethal complication of myocardial infarction. Early surgical repair with a resection of pseudoaneurysm is often performed, given that medical therapy alone is associated with a high risk of mortality. This report describes a case of a giant LVPA on the lateral wall post-infarction and mitral valve regurgitation that was successfully treated by surgical transatrial closure and mitral valve replacement., Case Summary: A 77-year-old man with chronic kidney disease and a history of percutaneous coronary interventions for acute myocardial infarction was referred to the cardiac surgeons because of a spontaneous finding of an abnormal mass adjacent to the heart on imaging studies, which was missed on a chest radiograph obtained 3 months earlier. Cardiac studies revealed LVPA and severe mitral regurgitation with poor ejection fraction. Early repair of LVPA and concurrent mitral valve surgery were recommended. Transatrial patch closure and mitral valve replacement were performed using an interatrial approach via median sternotomy. Although the patient's post-operative course was complicated by congestive heart failure and irreversible renal failure, he was discharged with good functional status after 1 month of intermittent renal replacement therapy with haemodialysis., Discussion: Transatrial repair of LVPA and concurrent mitral valve replacement can be a treatment of choice for reducing surgical trauma to the left ventricle and protecting the sealing structure from rupture., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The nucleic acids found in food play a crucial role in maintaining various bodily functions. This study investigated the potential anticancer effects of dietary nucleic acids, an area that is still not fully understood. By utilizing an in vivo mouse model and an in vitro cell model, we discovered an anti-proliferative impact of RNA in both systems. DNA exhibited anti-proliferative effects in the mouse model, while this phenomenon wasn't observed in the in vitro cell model using Ehrlich ascites tumor (EAT) cells. Conversely, DNA hydrolysate demonstrated distinct anti-proliferative effects in EAT cells, suggesting that nucleotides or nucleosides generated during nucleic acid digestion act as active constituents. Furthermore, we examined various nucleosides and two sodium-independent equilibrative nucleoside transporter inhibitors (ENTs), identifying guanosine and 2'-deoxyguanosine as pivotal in the anti-proliferative effect. We also found that the anti-proliferation activity with both nucleosides was suppressed by the treatment of dipyridamole, a non-selective inhibitor for ENT1 and ENT2, but not nitrobenzylthioinosine, a low inhibitor for ENT2. The uptake of these compounds into cells is likely facilitated by ENT2. These nucleotides impeded the progression of cancer cells from the G1 phase to the S phase in the cell cycle. Another significant finding is the increased expression of CCAAT/enhancer-binding protein (C/EBPβ) induced by guanosine and 2'-deoxyguanosine. Furthermore, immunostaining revealed that C/EBPβ diffuses into the nucleus, indicating its presence. This suggests that guanosine or 2-deoxyguanosine induces G1 arrest in cancer cells via the activation of C/EBPβ. Encouraged by these promising results, guanosine and 2'-deoxyguanosine show potential applications in cancer prevention., Competing Interests: A part of the research grant and DNA, hydrolyzed DNA and RNA materials were provided by Fordays Co., Ltd. We declare that these relationships do not affect the results and conclusions of this study. This does not alter on adherence to PLOS ONE politics on sharing data and materials., (Copyright: © 2024 Shiomi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Identifying host genetic factors modulating immune checkpoint inhibitor (ICI) efficacy has been experimentally challenging because of variations in both host and tumor genomes, differences in the microbiome, and patient life exposures. Utilizing the Collaborative Cross (CC) multi-parent mouse genetic resource population, we developed an approach that fixes the tumor genomic configuration while varying host genetics. With this approach, we discovered that response to anti-PD-1 (aPD1) immunotherapy was significantly heritable in four distinct murine tumor models ( H 2 between 0.18-0.40). For the MC38 colorectal carcinoma system ( H 2 = 0.40), we mapped four significant ICI response quantitative trait loci (QTL) localized to mouse chromosomes (mChr) 5, 9, 15 and 17, and identified significant epistatic interactions between specific QTL pairs. Differentially expressed genes within these QTL were highly enriched for immune genes and pathways mediating allograft rejection and graft vs host disease. Using a cross species analytical approach, we found a core network of 48 genes within the four QTLs that showed significant prognostic value for overall survival in aPD1 treated human cohorts that outperformed all other existing validated immunotherapy biomarkers, especially in human tumors of the previously defined immune subtype 4. Functional blockade of two top candidate immune targets within the 48 gene network, GM-CSF and high affinity IL-2/IL-15 signaling, completely abrogated the MC38 tumor transcriptional response to aPD1 therapy in vivo . Thus, we have established a powerful cross species in vivo platform capable of uncovering host genetic factors that establish the tumor immune microenvironment configuration propitious for ICI response.

Introduction: Campylobacter spp. are a public health concern, yet there is still no effective vaccine or medicine available., Methods: Here, we developed a Campylobacter jejuni -specific antibody and found that it targeted a menaquinol cytochrome c reductase complex QcrC., Results: The antibody was specifically reactive to multiple C. jejuni strains including clinical isolates from patients with acute enteritis and was found to inhibit the energy metabolism and growth of C. jejuni . Different culture conditions produced different expression levels of QcrC in C. jejuni , and these levels were closely related not only to the energy metabolism of C. jejuni but also its pathogenicity. Furthermore, immunization of mice with recombinant QcrC induced protective immunity against C. jejuni infection., Discussion: Taken together, our present findings highlight a possible antibody- or vaccination-based strategy to prevent or control Campylobacter infection by targeting the QcrC-mediated metabolic pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hosomi, Hatanaka, Hinenoya, Adachi, Tojima, Furuta, Uchiyama, Morita, Nagatake, Saika, Kawai, Yoshii, Kondo, Yamasaki and Kunisawa.)

Background: Recent studies have reported the therapeutic use of endoscopic submucosal dissection (ESD) using an ultrathin endoscope for targeting pharyngeal and distal side lesions in the stenosis or as a less invasive treatment via the nasal route. However, the effectiveness and safety of these treatments remain undetermined. Therefore, this study aimed to review treatment outcomes and discuss the advantages and precautions of the treatments based on our experience., Methods: This study included 13 patients with 14 lesions who underwent 14 sessions of upper gastrointestinal ESD using an ultrathin endoscope between December 2021 and August 2023. The outcome measures included lesion background, en bloc resection rate, en bloc complete resection rates, and incidence of adverse events (including post-operative bleeding, intraoperative perforation, and delayed perforation)., Results: The lesions in the esophagus, stomach, and duodenum were eight, three, and three, respectively, and the median length (range) of each located lesion was 16.5 (6-26), 17 (9-36), and 10 (4-16) mm, respectively. En bloc resection and en bloc complete resection rates were 100 and 92.9%, respectively. The only adverse event was an intraoperative perforation observed during duodenal ESD, resulting from the assistant's inadvertent expansion of the SOUTEN at the final dissection stage., Conclusion: Our results demonstrate that ESD with an ultrathin endoscope effectively reaches lesions in difficult locations and enables treatment within a small working space. Therefore, ESD using an ultrathin endoscope is a treatment option for lesions located distally to gastrointestinal stenosis, highly fibrotic lesions, and duodenal tumors., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aberrant aggregates of amyloid-β (Aβ) and tau protein (tau), called amyloid, are related to the etiology of Alzheimer disease (AD). Reducing amyloid levels in AD patients is a potentially effective approach to the treatment of AD. The selective degradation of amyloids via small molecule-catalyzed photooxygenation in vivo is a leading approach; however, moderate catalyst activity and the side effects of scalp injury are problematic in prior studies using AD model mice. Here, leuco ethyl violet (LEV) is identified as a highly active, amyloid-selective, and blood-brain barrier (BBB)-permeable photooxygenation catalyst that circumvents all of these problems. LEV is a redox-sensitive, self-activating prodrug catalyst; self-oxidation of LEV through a hydrogen atom transfer process under photoirradiation produces catalytically active ethyl violet (EV) in the presence of amyloid. LEV effectively oxygenates human Aβ and tau, suggesting the feasibility for applications in humans. Furthermore, a concept of using a hydrogen atom as a caging group of a reactive catalyst functional in vivo is postulated. The minimal size of the hydrogen caging group is especially useful for catalyst delivery to the brain through BBB., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Metal-organic frameworks (MOFs) exhibit high adsorption and catalytic activities for various gas species. Because gas adsorption can cause a temperature increase in the MOF, which decreases the capacity and adsorption rate, a strict evaluation of its effect on the thermal conductivity of MOFs is essential. In this study, the thermal conductivity measurement of the MOF under water vapor adsorption was performed using an oriented film of copper tetrakis(4-carboxyphenyl)porphyrin (Cu-TCPP) MOF. A recently developed bidirectional 3ω method enabled the anisotropic thermal conductivity measurement of layered Cu-TCPP while maintaining its ordered structure. The water adsorption was found to increase the thermal conductivity in both in-plane and cross-plane directions with different trends and magnitudes, owing to the structural anisotropy. Molecular dynamics simulations suggest that additional vibrational modes provided by the adsorbed water molecules were the reason for the thermal conductivity enhancement.

Huntington's disease (HD) is a dominantly inherited neurological disorder characterized by chorea, psychiatric symptoms, and cognitive decline but typically lacks muscular atrophy and weakness. We herein report a case of genetically confirmed HD showing progressive systemic weakness with findings of upper and lower motor neuron involvement due to amyotrophic lateral sclerosis (ALS). The current patient and the previously reported cases with complications of HD and ALS indicate that cytosine-adenine-guanine (CAG) repeat expansion in the huntingtin gene might have a pathogenic role in causing the two neurological disorders.

No standard treatment has been established for gastric neuroendocrine carcinoma (G-NEC). We present the case of a patient with recurrent G-NEC who achieved a complete response (CR) with nivolumab. A woman in her 70 s, with no significant medical or family history of illness, underwent an upper gastrointestinal endoscopy, which revealed a Borrmann type 2 tumor in the gastric antrum. Malignant tumor cells were not detected in the endoscopic biopsy samples; however, a malignant gastric tumor was strongly suspected. Therefore, surgical resection was performed, and the tumor was pathologically diagnosed as a G-NEC with liver metastases. Adjuvant etoposide plus carboplatin was administered for four cycles, but recurrence in the liver was observed 5 months after the completion of adjuvant chemotherapy. Ramucirumab plus paclitaxel and irinotecan were introduced as second and third-line treatments. After these treatments, the mesenteric lymph node metastases expanded. Tumor mutation burden (TMB) was low (five mutations/megabase), and microsatellite instability remained stable. However, programmed death-ligand 1 Combined Positive Score (CPS) was ≥ 5 in the resected sample. Therefore, nivolumab monotherapy was introduced as a fourth-line treatment. The mesenteric lymph node metastases exhibited swelling 3 weeks after the initiation of nivolumab; however, they rapidly shrank, and CR was later achieved. Treatment with nivolumab is currently ongoing for 12 months. This is the first report of nivolumab monotherapy in a patient with G-NEC who showed pseudo-progression. Even in TMB-low and microsatellite stable cases, nivolumab may be a viable option for patients with G-NEC., Competing Interests: Conflict of interestNozomu Machida received honoraria from Bristol Myers Squibb, Ono Pharmaceutical, and Eli Lilly. Junji Furuse received honoraria from Ono Pharmaceutical and Eli Lilly and research funding from Ono Pharmaceutical. Shin Maeda received research funding from Eli Lilly., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: The purpose of this study was to determine the utility of compressed sensing (CS) with deep learning reconstruction (DLR) for improving spatial resolution, image quality and focal liver lesion detection on high-resolution contrast-enhanced T1-weighted imaging (HR-CE-T1WI) obtained by CS with DLR as compared with conventional CE-T1WI with parallel imaging (PI)., Methods: Seventy-seven participants with focal liver lesions underwent conventional CE-T1WI with PI and HR-CE-T1WI, surgical resection, transarterial chemoembolization, and radiofrequency ablation, followed by histopathological or >2-year follow-up examinations in our hospital. Signal-to-noise ratios (SNRs) of liver, spleen and kidney were calculated for each patient, after which each SNR was compared by means of paired t-test. To compare focal lesion detection capabilities of the two methods, a 5-point visual scoring system was adopted for a per lesion basis analysis. Jackknife free-response receiver operating characteristic (JAFROC) analysis was then performed, while sensitivity and false positive rates (/data set) for consensus assessment of the two methods were also compared by using McNemar's test or the signed rank test., Results: Each SNR of HR-CE-T1WI was significantly higher than that of conventional CE-T1WI with PI (p < 0.05). Sensitivities for consensus assessment showed that HR-CE-MRI had significantly higher sensitivity than conventional CE-T1WI with PI (p = 0.004). Moreover, there were significantly fewer FP/cases for HR-CE-T1WI than for conventional CE-T1WI with PI (p = 0.04)., Conclusion: CS with DLR are useful for improving spatial resolution, image quality and focal liver lesion detection capability of Gd-EOB-DTPA enhanced 3D T1WI without any need for longer breath-holding time., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The enrichment of oral taxa in the gut has recently been reported as a notable alteration in the microbial balance in patients with intestinal disorders. However, translocation in populations without such diseases remains controversial. In this study, we examined 49 pairs of tongue and rectal samples collected from orthopedic patients without a history of intestinal disorders to verify the presence of oral taxa in the rectal microbiota. The bacterial composition of each sample was determined using 16S rRNA gene sequencing and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of the tongue and rectal microbiota were distinctly different, tongue ASVs were detected in 67.3% of the participants and accounted for 0.0%-9.37% of the rectal microbiota. Particularly, Streptococcus salivarius , Fusobacterium nucleatum , and Streptococcus parasanguinis were abundant in the rectal microbiota. According to the network analysis, tongue taxa, such as S. salivarius and S. parasanguinis , formed a cohabiting group with Klebsiella pneumoniae and Alistipes finegoldii in the rectal microbiota. The total abundance of tongue ASVs in the rectal microbiota was significantly higher in participants with older age, hypertension, and proton pump inhibitor (PPI) use. Our study presents an extensive translocation of oral taxa to the rectum of a population without intestinal disorders and suggests that aging, hypertension, and PPI use are associated with an increased abundance of oral taxa and potential pathogenic bacteria in the rectal microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Kageyama, Maeda, Sakamoto, Ma, Asakawa, Furuta, Yamashita and Takeshita.)

This study aimed to evaluate the association between the oral health status and appetite in community-dwelling older adults. We enrolled 100 people aged ≥65 years who had participated in long-term care prevention projects between December 2018 and January 2019. Appetite was assessed using the Council on Nutrition Appetite Questionnaire score. The oral health status was assessed based on the number of teeth, occlusal condition, swallowing function, tongue coating, and the Oral Health Assessment Tool. A multiple linear regression analysis was performed with appetite as the dependent variable and each variable related to oral health status as an independent variable. The analysis was adjusted for sex, age, activities of daily living, cognitive function, smoking habit, and alcohol consumption. Dental pain was associated with poor appetite in community-dwelling older adults. No other oral health status parameter was associated with appetite. Thus, controlling dental pain is critical to prevent appetite loss while considering other factors., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Local anaesthetic systemic toxicity (LAST) is a rare but life-threatening complication that can occur after local anaesthetic administration. Various clinical guidelines recommend an intravenous lipid emulsion as a treatment for local anaesthetic-induced cardiac arrest. However, its therapeutic application in pregnant patients has not yet been established. This scoping review aims to systematically identify and map the evidence on the efficacy and safety of intravenous lipid emulsion for treating LAST during pregnancy., Method: We searched electronic databases (Medline, Embase and Cochrane Central Register Controlled Trials) and a clinical registry (lipidrescue.org) from inception to Sep 30, 2022. No restriction was placed on the year of publication or the language. We included any study design containing primary data on obstetric patients with signs and symptoms of LAST., Results: After eliminating duplicates, we screened 8,370 titles and abstracts, retrieving 41 full-text articles. We identified 22 women who developed LAST during pregnancy and childbirth, all presented as case reports or series. The most frequent causes of LAST were drug overdose and intravascular migration of the epidural catheter followed by wrong-route drug errors (i.e. intravenous anaesthetic administration). Of the 15 women who received lipid emulsions, all survived and none sustained lasting neurological or cardiovascular damage related to LAST. No adverse events or side effects following intravenous lipid emulsion administration were reported in mothers or neonates. Five of the seven women who did not receive lipid emulsions survived; however, the other two died., Conclusion: Studies on the efficacy and safety of lipids in pregnancy are scarce. Further studies with appropriate comparison groups are needed to provide more robust evidence. It will also be necessary to accumulate data-including adverse events-to enable clinicians to conduct risk-benefit analyses of lipids and to facilitate evidence-based decision-making for clinical practice., (© 2024. The Author(s).)

Purpose: The purpose of this in vivo study was to determine the effect of reverse encoding direction (RDC) on apparent diffusion coefficient (ADC) measurements and its efficacy for improving image quality and diagnostic performance for differentiating malignant from benign tumors on head and neck diffusion-weighted imaging (DWI)., Methods: Forty-eight patients with head and neck tumors underwent DWI with and without RDC and pathological examinations. Their tumors were then divided into two groups: malignant (n = 21) and benign (n = 27). To determine the utility of RDC for DWI, the difference in the deformation ratio (DR) between DWI and T2-weighted images of each tumor was determined for each tumor area. To compare ADC measurement accuracy of DWIs with and without RDC for each patient, ADC values for tumors and spinal cord were determined by using ROI measurements. To compare DR and ADC between two methods, Student's t-tests were performed. Then, ADC values were compared between malignant and benign tumors by Student's t-test on each DWI. Finally, sensitivity, specificity and accuracy were compared by means of McNemar's test., Results: DR of DWI with RDC was significantly smaller than that without RDC (p < 0.0001). There were significant differences in ADC between malignant and benign lesions on each DWI (p < 0.05). However, there were no significant difference of diagnostic accuracy between the two DWIs (p > 0.05)., Conclusion: RDC can improve image quality and distortion of DWI and may have potential for more accurate ADC evaluation and differentiation of malignant from benign head and neck tumors., Competing Interests: Declaration of competing interest This work was financially and technically supported by Canon Medical Systems Corporation, Japan. Drs. Nagata, Toyama and Ohno received research grants from Canon Medical Systems, Japan. Four of the authors (Ms. Kaori Yamamoto, Ms. Maiko Shinohara, Mr. Masato Ikedo and Mr. Masao Yui) are employees of Canon Medical Systems, Japan but did not have control over any of the data and information submitted for publication or which data and information were to be included in this study. None of the patients enrolled in this study were also entered in previous studies. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we evaluated the effects of gamma irradiation on the germination of Aspergillus conidia and mycelial growth using microscopy and predictive microbiological modeling methods. A dose of 0.4 kGy reduced the germination rate by 20% compared to the untreated control, indicating interphase death due to the high radiation dose. The number of colonies formed (5.5%) was lower than the germination rate (69%), suggesting that most colonies died after germination. Microscopic observations revealed that mycelial elongation ceased completely in the middle of the growth phase, indicating reproductive death. The growth curves of irradiated conidia exhibited a delayed change in the growth pattern, and a decrease in slope during the early stages of germination and growth at low densities. A modified logistic model, which is a general purpose growth model that allows for the evaluation of subpopulations, was used to fit the experimental growth curves. Dose-dependent waveform changes may reflect the dynamics of the subpopulations during germination and growth. These methods revealed the occurrence of two cell death populations resulting from gamma irradiation of fungal conidia and contribute to the understanding of irradiation-induced cell death in fungi., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: While a basic understanding of pelvic size and typology is still important for obstetricians, pelvic measurement data for Japanese women are very scarce. To our best knowledge, no large-scale pelvimetry studies of Japanese women have been made for the past 50 years. This study aimed to investigate the accurate size, particularly the obstetric conjugate (OC) and transverse diameter of the pelvic inlet (TD), of modern Japanese women, using three-dimensional (3D) computed tomography (CT), and to obtain their reference values., Methods: This retrospective, single-center observational study enrolled Japanese non-pregnant women aged between 20 and 40 years, who underwent pelvic CT examination from 2016 to 2021. CT was performed for various reasons, including acute abdomen, search for cancer metastases, and follow-up of existing disease. However, no cases were taken for pelvic measurements. Pelvimetry was performed retrospectively using a 3D workstation. The OC was measured on a strict lateral view and the TD was measured on an axial-oblique view. Other clinical data, such as age, height, and weight, were also extracted from the medical charts and analyzed., Results: A total of 1,263 patients were enrolled, with the mean age of 32.7 years (standard deviation [SD] 6.2). The mean height, weight, and body mass index were 158.8 cm (SD 5.8), 54.8 kg (SD 11.7), and 21.7 kg/m 2 (SD 4.4), respectively. The mean OC length was 127.0 mm (SD 9.5, 95% confidence interval [CI] 126.5-127.5), while the mean TD length was 126.8 mm (SD 7.5, 95% CI 126.4-127.2). Both values were normally distributed. Height was significantly associated with OC (regression coefficient = 0.75 [95% CI 0.66-0.84], p  < .001) and TD (regression coefficient = 0.63 [95% CI 0.56-0.70], p  < .001). Age showed a weak but statistically significant positive association with TD (regression coefficient = 0.14 [95% CI 0.07-0.20], p  < .001) and OC (regression coefficient = -0.10 [95% CI -0.18 to -0.01], p  = .026)., Conclusion: The 3D CT pelvimetry in 1,263 non-pregnant Japanese women of childbearing age revealed the mean OC and TD of 127.0 mm, and 126.8 mm, which were 11.8 mm and 4.3 mm larger, respectively, than those in the survey in 1972. Our data will be referred to in clinical practice as the standard pelvic measurement values for the Japanese population.

We herein report a case of anti-gamma aminobutyric acid type A receptor antibody-associated encephalitis (anti-GABA A -RE) with progressive aphasia and generalized tonic-clonic seizures. Cerebral magnetic resonance imaging (MRI) showed cortical brain lesions coupled with hypermetabolism on fluorodeoxyglucose-positron emission tomography. After two courses of methylprednisolone pulse therapy, improvements in neurological symptoms without sequelae and the total disappearance of MRI lesions were observed. Upon encountering patients with refractory status epilepticus, multifocal cerebral MRI lesions, and suspected autoimmune encephalitis, especially in cases with thymoma, it would be prudent to suspect anti-GABA A -RE and consider the evaluation of anti-GABA A receptor antibody and methylprednisolone pulse therapy.

Importance: Understanding the development of oral microbiota early in life and the factors that influence it is important for preventing the establishment of dysbiotic oral microbiota later in life. This study demonstrates that the tongue microbiota undergoes early development from 4 to 18 months of age and converges into two types of microbiota showing indications of adult characteristics, with either S. salivarius or Neisseria -dominance. Interestingly, their divergence was strongly determined by their weaning status and the dietary frequencies of sweetened beverages, snacks, and fruits, suggesting that dietary habits during this period might influence the establishment of the oral microbiota. These findings may contribute to the development of novel preventive strategies against oral microbiota-related diseases., Competing Interests: The authors declare no conflict of interest.

Background: Data regarding treatment sequence for vulnerable patients with metastatic colorectal cancer (mCRC) in a real-world setting are lacking., Objective: We aimed to assess treatment outcomes in second-line or later chemotherapy for vulnerable patients with mCRC in a real-world setting., Patients and Methods: Vulnerable patients with mCRC who received less intensive treatment ('vulnerable') regimens, i.e. fluoropyrimidines with or without biologics (FP), reduced-dose doublet regimens with or without biologics (Doublet), and anti-epidermal growth factor receptor monotherapy (Anti-EGFR), as first-line therapy between June 2015 and December 2018 were retrospectively reviewed., Results: A total of 210 patients from 15 hospitals were analyzed. The median age was 78 years (range 28-90), and 44 patients (21%) had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 2. In the entire population, the median time to treatment failure (TTF) and overall survival (OS) were 7.6 and 21.4 months, respectively. Following the failure of first-line therapy in 195 patients, 74 (38%), 24 (12%), and 13 (7%) patients received vulnerable regimens, full-dose doublet regimens with or without biologics, and other regimens, respectively, whereas 84 (43%) received best supportive care (BSC). In patients receiving vulnerable regimens as second-line therapy, the median TTF and OS were 4.4 and 13.7 months, respectively, while response rate and disease control rate were 18% and 62%, respectively. In 84 patients who received BSC, the median OS was 3.5 months., Conclusions: Second-line chemotherapy for vulnerable patients with mCRC showed clinically meaningful outcomes; however, few patients received second-line therapy, and survival among patients who received BSC was dismal., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Catalytic photo-oxygenation of tau amyloid is a potential therapeutic approach to tauopathies, including Alzheimer disease (AD). However, tau is a complex target containing great molecular size and heterogeneous isoforms/proteoforms. Although catalytic photo-oxygenation has been confirmed when using catalyst 1 and recombinant tau pretreated with heparin, its effects on tau from human patients have not yet been clarified. In this study, focusing on the histidine residues being oxygenated, we have constructed two assay systems capable of quantitatively evaluating the catalytic activity when used on human patient tau: (1) fluorescence labeling at oxygenated histidine sites and (2) LC-MS/MS analysis of histidine-containing fragments. Using these assays, we identified 2 as a promising catalyst for oxygenation of human tau. In addition, our results suggest that aggregated tau induced by heparin is different from actual AD patient tau in developing effective photo-oxygenation catalysts.

Aim: To investigate the existence of a bidirectional temporal relationship between periodontal condition and glycaemic status., Materials and Methods: This longitudinal study included 2198 participants with mean age 43.4 ± 7.7 years, who underwent dental examinations in Yokohama, Japan, at two time points, 2003-2004 and 2008-2009, at an interval of 5 years. Periodontal condition was assessed by the mean value of probing pocket depth (PPD) and clinical attachment level (CAL). Glycaemic status was assessed by fasting glucose and glycated haemoglobin (HbA1c)., Results: The cross-lagged panel models showed the effect of HbA1c at baseline on mean PPD at follow-up (β = 0.044, p = .039). There was a marginal effect of fasting glucose on the mean PPD (β = 0.037, p = .059). It was similar to the effect of fasting glucose or HbAlc on mean CAL. However, in the opposite direction, no effect of mean PPD or CAL at baseline on fasting glucose or HbAlc at follow-up was identified., Conclusions: This study demonstrated a unidirectional relationship between glycaemic status and periodontal condition. The study population, however, had mostly mild periodontitis. Future studies are needed to investigate the effect of periodontal condition on glycaemic status in patients with severe periodontitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Most multigene mutation tests require tissue specimens. However, cytological specimens are easily obtained in the clinical practice and provide high-quality DNA and RNA. We aimed to establish a test that utilizes cytological specimens and performed a multi-institutional study to investigate the performance of MINtS, a test based on next-generation sequencing. A standard procedure for specimen isolation was defined. The specimens were considered suitable for the test if >100 ng DNA and >50 ng RNA could be extracted from them. In total, 500 specimens from 19 institutions were investigated. MINtS detected druggable mutations in 63% (136 of 222) of adenocarcinomas. Discordant results between MINtS and the companion diagnostics were observed in 14 of 310 specimens for the EGFR gene, and 6 of 339 specimens for the ALK fusion genes. Confirmation by other companion diagnostics for the EGFR mutations or the clinical response to an ALK inhibitor all supported the results obtained by MINtS. MINtS along with the isolation procedure presented in the current study will be a platform to establish multigene mutation tests that utilize cytological specimens. UMIN000040415., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: This study aimed to determine if hamstring-strain-injury risk factors related to muscle structure and morphology differed between rugby union players and controls., Methods: The biceps femoris long head (BFlh) fascicle length and passive muscle stiffness and relative and absolute muscle volume of knee flexors (KF) and extensors (KE) were measured in 21 male subelite rugby players and 21 male physically active nonathletes., Results: BFlh fascicle length was significantly longer (mean difference [MD] = 1.6 [1.7] cm) and BFlh passive muscle stiffness was significantly higher in rugby players (MD = 7.8 [14.8] kPa). The absolute BFlh (MD = 71.9 [73.3] cm3), KF (MD = 332.3 [337.2] cm3), and KE (MD = 956.3 [557.4] cm3) muscle volumes were also significantly higher in rugby players. There were no significant differences in the relative BFlh and KF muscle volumes. The relative KE muscle volumes were significantly higher in rugby players (MD = 2.3 [3.7] cm3/kg). However, the percentage BFlh fascicle length:KE (MD = -0.1% [0.1%]), BFlh/KE (MD = -0.9% [1.9%]), and KF:KE (MD = -4.9% [5.9%]) muscle volume ratios were significantly lower in the rugby players. BFlh muscle volume significantly correlated with BFlh fascicle length (r = .59, r2 = .35) and passive muscle stiffness (r = .46, r2 = .21)., Conclusion: Future prospective studies should examine whether there are threshold values in BFlh passive muscle stiffness and BFlh fascicle length:KE, BFlh:KE, and KF:KE muscle volume ratios for predicting hamstring strain injuries.

Backgrounds/aim: Recent studies have shown that the addition of sodium-glucose co-transporter 2 (SGLT2) inhibitors gradually reduces the estimated fluid volume parameters in a broad range of patient populations, suggesting that this mediates the clinical benefits of SGLT2 inhibitors in preventing heart failure. Here, we sought to examine the long-term (24 months) effect of the SGLT2 inhibitor ipragliflozin on the estimated fluid volume parameters in patients with type 2 diabetes mellitus (T2DM)., Methods: In this prespecified sub-analysis of the PROTECT (Prevention of Atherosclerosis by SGLT2 Inhibitor: Multicenter, Randomized Controlled Study) trial, which was an investigator-initiated, multicenter, prospective, randomized, open-label, clinical trial primarily designed to evaluate the effect of ipragliflozin treatment administered for 24 months on carotid atherosclerosis in patients with T2DM, we evaluated serial changes in estimated plasma volume (ePV, %) calculated using the Straus formula and estimated extracellular volume (eEV, mL) calculated by the body surface area by 24 months following the initiation of 50-mg ipragliflozin once daily and compared them with those following standard care for T2DM (non-SGLT2 inhibitor use)., Results: This sub-analysis included 464 patients (ipragliflozin, n = 232; control, n = 232), a full analysis set of the PROTECT trial. In an analysis using mixed-effects models for repeated measures, relative to the control group, ipragliflozin significantly reduced ePV by - 10.29% (95% confidence interval [CI]  - 12.47% to - 8.11%; P < 0.001) at 12 months and - 10.76% (95% CI - 12.86% to - 8.67%; P < 0.001) at 24 months. Additionally, ipragliflozin significantly reduced eEV by - 190.44 mL (95% CI - 249.09 to - 131.79 mL; P < 0.001) at 12 months and - 176.90 mL (95% CI  - 233.36 to - 120.44 mL; P < 0.001) at 24 months. The effects of ipragliflozin on these parameters over 24 months were mostly consistent across various patient clinical characteristics., Conclusions: This prespecified sub-analysis from the PROTECT trial demonstrated that ipragliflozin treatment, compared with the standard care for T2DM, reduced two types of estimated fluid volume parameters in patients with T2DM, and the effect was maintained for 24 months. Our findings suggest that SGLT2 inhibitor treatment regulates clinical parameters incorporated into the calculating formulas analyzed and consequently fluid volume status for the long-term, and this may be at least partly associated with clinical benefits from chronic use of SGLT2 inhibitors. Trial registration Japan Registry of Clinical Trials, ID jRCT1071220089., (© 2023. The Author(s).)

We previously reported that diacylglycerol (DG) kinase (DGK) δ interacts with DG-generating sphingomyelin synthase (SMS)-related protein (SMSr), but not SMS1 or SMS2, via their sterile α motif domains (SAMDs). However, it remains unclear whether other DGK isozymes interact with SMSs. Here, we found that DGKζ, which does not contain SAMD, interacts with SMSr and SMS1, but not SMS2. Deletion mutant analyses demonstrated that SAMD in the N-terminal cytosolic region of SMSr binds to the N-terminal half catalytic domain of DGKζ. However, the C-terminal cytosolic region of SMS1 interacts with the catalytic domain of DGKζ. Taken together, these results indicate that DGKζ associates with SMSr and SMS1 in different manners and suggest that they compose new DG signaling pathways., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

New, useful microorganism resources have been generated by ionizing radiation breeding technology. However, the mutagenic effects of ionizing radiation on microorganisms have not been systematically clarified. For a deeper understanding and characterization of ionizing radiation-induced mutations in microorganisms, we investigated the lethal effects of seven different linear energy transfer (LET) radiations based on the survival fraction (SF) and whole-genome sequencing analysis of the mutagenic effects of a dose resulting in an SF of around 1% in Bacillus subtilis spores. Consequently, the lower LET radiations (gamma [surface LET: 0.2 keV/µm] and 4 He 2+ [24 keV/µm]) showed low lethality and high mutation frequency (MF), resulting in the major induction of single-base substitutions. Whereas higher LET radiations ( 12 C 5+ [156 keV/µm] and 12 C 6+ [179 keV/µm]) showed high lethality and low MF, resulting in the preferential induction of deletion mutations. In addition, 12 C 6+ (111) ion beams likely possess characteristics of both low- and high-LET radiations simultaneously. A decrease in the relative biological effectiveness and an evaluation of the inactivation cross section indicated that 20 Ne 8+ (468 keV/µm) and 40 Ar 13+ (2214 keV/µm) ion beams had overkill effects. In conclusion, in the mutation breeding of microorganisms, it should be possible to regulate the proportions, types, and frequencies of induced mutations by selecting an ionizing radiation of an appropriate LET in accordance with the intended purpose., Competing Interests: Declaration of Competing Interest We declare that we have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ectopic enrichment of oral microbes in the gut is a notable alteration in gut microbial balance. These microbes are likely delivered from the oral cavity with saliva and food; however, evidence of oral-gut microbial transmission is insufficient and needs further investigation. In this observational study, we examined 144 pairs of saliva and stool samples collected from community-dwelling adults to verify the oral-gut microbial link and identify the relevant influencing factors on the increased abundance of oral microbes within the gut. The bacterial composition of each sample was determined using PacBio single-molecule long-read sequencing of the full-length 16S ribosomal RNA gene and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of salivary and gut microbiota were distinctly different, at least 1 ASV was shared between salivary and gut microbiota in 72.9% of subjects. Shared ASVs accounted for 0.0% to 63.1% (median 0.14%) of the gut microbiota in each subject and frequently included abundant Streptococcus salivarius and Streptococcus parasanguinis . Their total relative abundance in the gut was significantly higher in older subjects or those with dental plaque accumulation. The gut microbiota with ≥5% of shared ASVs displayed a higher abundance of Streptococcus , Lactobacillus , and Klebsiella and a lower abundance of Faecalibacterium , Blautia , Megamonas , and Parabacteroides . Our study presents evidence for the translocation of oral bacteria to the gut in community-dwelling adults and suggests that aging and dental plaque accumulation contribute to an increased abundance of oral microbes in the gut, which might be relevant to the compositional shift in the gut commensals.

Background/aim: Irinotecan and trifluridine/tipiracil (FTD/TPI) are fourth-line treatment options after third-line nivolumab for advanced gastric cancer (AGC). However, the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab remains unclear. This study aimed to evaluate the efficacy and safety of irinotecan and FTD/TPI in the fourth-line setting after third-line nivolumab., Patients and Methods: We identified 137 AGC patients treated with nivolumab as third-line treatment in our institute between October 2017 and July 2021. Of these, we recruited 19 AGC patients who initiated irinotecan and 23 AGC patients who initiated FTD/TPI in the fourth-line setting until September 2021., Results: The median overall survival was 5.83 months for irinotecan and 6.31 months for FTD/TPI. Median time-to-treatment failure was 2.07 months for irinotecan and 1.64 months for FTD/TPI. While the frequency of all-grade diarrhea was higher in irinotecan (36% vs. 17%), grade ≥3 neutropenia tended to be higher in FTD/TPI (21% vs. 35%)., Conclusion: Irinotecan and FTD/TPI may be clinically useful as fourth-line treatments after nivolumab., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)