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A Ka-band three-stage monolithic microwave integrated circuit (MMIC) low-noise amplifier using source inductors with different values for each stage has been developed for use in active phased-array receiver modules. The three-stage MMIC low-noise amplifier with 0.15×120 μm2 AlGaAs-InGaAs pHEMTs has achieved a noise figure of 1.6 dB, a gain of 22.8 dB, an input return loss of 29 dB, and an output return loss of 24 dB at 28 GHz by optimizing the values of source inductors for each stage. The minimum noise figure was 1.3 dB at 30 GHz [ABSTRACT FROM PUBLISHER]

Objective: To examine the relationship of fear of fear and broad dimensions of psychopathology in panic disorder with agoraphobia over the course of cognitive behavioural therapy in Japan. Methods: A total of 177 Japanese patients with panic disorder with agoraphobia were treated with group cognitive behavioural therapy between 2001 and 2015. We examined associations between the change scores in Agoraphobic Cognitions Questionnaire or Body Sensations Questionnaire and the changes in subscales of Symptom Checklist-90 Revised during cognitive behavioural therapy controlling the change in panic disorder severity using multiple regression analysis. Results: Reduction in Agoraphobic Cognitions Questionnaire score was related to a decrease in all Symptom Checklist-90 Revised (SCL-90-R) subscale scores. Reduction in Body Sensations Questionnaire score was associated with a decrease in anxiety. Reduction in Panic Disorder Severity Scale score was not related to any SCL-90-R subscale changes. Conclusions: Changes in fear of fear, especially maladaptive cognitions, may predict broad dimensions of psychopathology reductions in patients of panic disorder with agoraphobia over the course of cognitive behavioural therapy. For the sake of improving a broader range of psychiatric symptoms in patients of panic disorder with agoraphobia, more attention to maladaptive cognition changes during cognitive behavioural therapy is warranted. [ABSTRACT FROM AUTHOR]

Background and Purpose: No guidelines exist for the clinical target volume (CTV) and radiotherapy dose in sinonasal mucosal melanoma (SNMM). Thus, we aimed to determine the carbon-ion radiotherapy (CIRT) CTV and dose for SNMM., Materials and Methods: In total, 135 patients with SNMM who received CIRT were reviewed. The relative biological effectiveness-weighted dose was 57.6 or 64 Gy in 16 fractions. CTV was classified into small CTV, which included the gross tumor and visible melanosis with a certain margin, and extended CTV, which included the tumor site and adjacent anatomical structures. Local recurrence (LR) patterns were pattern I, II, and III, defined as recurrence over the gross tumor, visible melanosis and subclinical area, which would be covered if extended CTV was applied, and outside the extended CTV, respectively., Results: The 5-year LR rate was 35.3 %. The prescribed dose was not a significant risk factor for pattern I LR; however, 57.6 Gy for a large tumor was insufficient for local control. Using an extended CTV was significantly associated with a lower risk of pattern II LR, and these recurrences did not occur in regions that received > 40 Gy. The 5-year pattern III LR rate was 6.4 %., Conclusion: Utilizing an extended CTV in CIRT for SNMM is appropriate even for small tumors. Using a smaller CTV after an extended CTV of at least 40 Gy is recommended to reduce adverse events. Although the optimal dose for gross tumors remains unclear, the latest technology with 64 Gy showed good outcomes., 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 B.V. All rights reserved.)

The rates of appearance of new mutations play a central role in evolution. However, mutational processes in natural environments and their relationship with growth rates are largely unknown, particular in tropical ecosystems with high biodiversity. Here, we examined the somatic mutation landscapes of two tropical trees, Shorea laevis (slow-growing) and S. leprosula (fast-growing), in central Borneo, Indonesia. Using newly constructed genomes, we identified a greater number of somatic mutations in tropical trees than in temperate trees. In both species, we observed a linear increase in the number of somatic mutations with physical distance between branches. However, we found that the rate of somatic mutation accumulation per meter of growth was 3.7-fold higher in S. laevis than in S. leprosula . This difference in the somatic mutation rate was scaled with the slower growth rate of S. laevis compared to S. leprosula, resulting in a constant somatic mutation rate per year between the two species. We also found that somatic mutations are neutral within an individual, but those mutations transmitted to the next generation are subject to purifying selection. These findings suggest that somatic mutations accumulate with absolute time and older trees have a greater contribution towards generating genetic variation., Competing Interests: AS, RI, TF, ST, KO, MN, SI, WW, SP, AM, VN, NT, YS, ES, MK No competing interests declared, (© 2023, Satake, Imai et al.)

Here, we report a smart genome editing system for soybean (Glycine max) using the in planta bombardment-ribonucleoprotein (iPB-RNP) method without introducing foreign DNA or requiring traditional tissue culture processes such as embryogenesis and organogenesis. Shoot apical meristem (SAM) of embryonic axes was used as the target tissue for genome editing because the SAM in soybean mature seeds has stem cells and specific cell layers that develop germ cells during the reproductive growth stage. In the iPB-RNP method, the RNP complex of the CRISPR/Cas9 system was directly delivered into SAM stem cells via particle bombardment, and genome-edited plants were generated from these SAMs. Soybean allergenic gene Gly m Bd 30K was targeted in this study. Many E0 (the first generation of genome-edited) plants in this experiment harbored mutant alleles at the targeted locus. Editing frequency of inducing mutations transmissible to the E1 generation was approximately 0.4 to 4.6 % of all E0 plants utilized in various soybean varieties. Furthermore, simultaneous mutagenesis by iPB-RNP method was also successfully performed at other loci. Our results offer a practical approach for both plant regeneration and DNA-free genome editing achieved by delivering RNP into the SAM of dicotyledonous plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Pancreatic neuroendocrine tumors (PanNETs) are generally hypervascular and readily detectable on imaging tests. However, hypovascular PanNETs are clinically problematic, requiring multiple imaging tests and tissue analyses to differentiate them from pancreatic ductal cancers. A 41 year-old man presented with Whipple's triad; 72 h fasting test followed by glucagon challenge test suggested insulinoma. However, contrast-enhanced computed tomography image showed a 17 mm tumor with poor enhancement and unclear borders in the tail of the pancreas . Abdominal magnetic resonance imaging and contrast-enhanced endoscopic ultrasonography (EUS) indicated cystic degeneration and necrosis at the same site; EUS-guided fine-needle aspiration cytology indicated a PanNET Grade 1 tumor. Although the imaging was inconclusive, diazoxide treatment ameliorated the hypoglycemia-related symptoms and insulinoma was deemed likely; following tail pancreatectomy and splenectomy, the symptoms disappeared. Pathological examination revealed a tumor positive for insulin and classed as PanNET Grade 1 according to the 2019 WHO classification. The microvessel density (MVD) of the tumor was found to be as low as 3.9%, which may partly account for the inconclusive images. The present case was difficult to diagnose preoperatively due to hypovascularity on imaging because of reduced MVD. It is clinically important to evaluate MVD in cases of hypovascular PanNETs by multiple preoperative imaging studies to differentiate them from pancreatic cancers and to validate the findings by postoperative pathological analysis., Competing Interests: Conflicts of interestDY has received consulting/lecture fees from Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim, Eli Lilly Japan K.K., and Kyowa Kirin Co., Ltd. DY also received grants from Arkray Inc., Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim, Taisho Pharmaceutical Co. Ltd., and Terumo Corporation. YH has received lecture fees from Sumitomo Pharma Co. Ltd. RI, MS, TK, SO, SK, YL, YT, KT, MM, TH, TM, TK, TK, and TM declare that they have no conflict of interest. All authors declare that they have no competing interests relevant to this study., (© The Japan Diabetes Society 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.)

The gut microbiota begins to colonize the host body following birth, develops during the suckling period and changes to the adult type after weaning. The early gut microbiota during the suckling period is thought to have profound effects on the host physiology throughout life but it is still unclear whether early dysbiosis is retained lifelong. Our previous study indicated that chronic nasal inflammation induces dysbiosis of gut microbiota in adult mice. In the present study, we addressed the question as to whether early exposure to chronic nasal inflammation induces dysbiosis, and if so, whether the dysbiosis is retained until adulthood and the sex differences in this effect. Male and female mice received repeated intranasal administration of lipopolysaccharide (LPS) or saline twice a week from P7 to P24 and were weaned at P24. The cecal contents were obtained for 16S rRNA analysis at 2 time points: at 4 weeks (wks), just after weaning, and at maturation to adulthood at 10 wks. The body weight did not differ between saline- and LPS-treated mice till around weaning, suggesting that the mothers' milk was given similarly to all mice. At 4 wks, the beta diversity was significantly different between saline- and LPS-treated male and female mice and the composition of the gut microbiota changed in LPS-treated mice. The abundance of phylum Bacteroidota tended to decrease and that of Firmicutes increased in LPS-treated male mice, while the abundance of Deferribacterota increased in LPS-treated female mice. At 10 wks, the beta diversity was not different between saline- and LPS-treated mice, but the abundance of family Lachnospiraceae significantly decreased in LPS-treated male and female mice by LEfSe analysis. Together, chronic nasal inflammation early in life caused transient and long-term dysbiosis of gut microbiota, which may contribute to the onset and progress of metabolic and neuropsychiatric disorders., Competing Interests: None., (© 2024 The Authors. Published by Elsevier Inc.)

Excessive muscle co-contraction is one of the factors related to the progression of knee osteoarthritis (OA). A previous study demonstrated that pain, joint instability, lateral thrust, weight, and lower extremity alignment were listed as factors affecting excessive co-contraction in knee OA. However, this study aimed to assess the association between fear-avoidance beliefs and muscle co-contraction during gait and stair climbing in people with knee OA. Twenty-four participants with knee OA participated in this cross-sectional study. Co-contraction ratios (CCRs) were used to calculate muscle co-contraction during walking and stair climbing, using surface electromyography. Fear-avoidance beliefs were assessed by the Tampa Scale for Kinesiophobia-11 (TSK-11) for kinesiophobia and the Pain Catastrophizing Scale (PCS) for pain catastrophizing. Secondary parameters that may influence co-contraction, such as degree of pain, lateral thrust, weight, and lower extremity alignment, were measured. The relationships between the CCR during each movement, TSK-11, and PSC were evaluated using Spearman's rank correlation coefficient and partial correlation analysis, adjusted by weight and lower extremity alignment. Partial correlation analysis showed a significant correlation only between medial muscles CCR and TSK-11 during stair descent (r = 0.54, p < 0.05). Our study revealed that kinesiophobia could be associated with co-contraction during stair descent in people with knee OA.

Pulmonary sclerosing pneumocytoma (PSP) is a rare, benign tumor. Given the challenges of a bronchoscopic diagnosis, surgery is performed during the early stages of the disease. Therefore, little is known about the growth pattern of PSP. This case of PSP was not diagnosed despite bronchoscopy, resulting in lung resection eight years after the anomaly was first identified on computed tomography (CT). This report compares the long-term follow-up of CT and pathological findings and discusses the difficulty in making a diagnosis using a bronchoscopic forceps biopsy to aid in future PSP diagnoses and treatment planning.

Background: The risk and survival of patients with non-small cell lung cancer (NSCLC) with pre-existing autoimmune disorders (AIDs) receiving immune checkpoint blockade (ICB) therapy have not been clearly established., Patients and Methods: This multi-institutional, retrospective cohort study was conducted in collaboration with 20 centers in Japan., Results: In total, 229 patients with advanced or recurrent NSCLC and pre-existing AID, with or without ICB treatment from January 2010-February 2020, were included and analyzed. Among 69 patients who received ICB, 2 received two lines of ICBs with a total of 71 ICB treatments; 57 (80.3 %) and 14 (19.7 %) patients received ICB monotherapy and combination therapy, respectively. AID flares were observed in 18 patients (25.4 %, 95 % confidence interval [CI], 15.8-37.1 %) receiving ICB. AID exacerbations were more likely when NSCLC was diagnosed less than 1 year after the AID diagnosis (odds ratio 5.26 [95 % CI, 1.40-21.61]; P = 0.016). Immune-related adverse events were observed in 32 patients (45.1 %, 95 % CI, 33.2-57.3 %); 17 had grade 3 or higher. The safety profile of combination immunotherapy was not significantly different from that of the monotherapy. After inverse probability weighting, the use of ICB prolonged survival (hazard ratio 0.43 [95 % CI, 0.26-0.70]; P = 0.0006)., Conclusions: These findings revealed a novel risk factor for AID flares following ICB treatment, that is the diagnosis of NSCLC within 1 year of AID diagnosis, and showed that ICBs may improve survival in this population. These results support the utilization of ICB in patients with NSCLC and pre-existing AID., 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. Dr. Asao reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Biopharma, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Dr. Shukuya reported receiving grants from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, MSD, and Novartis, outside the submitted work; and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, outside the submitted work. Dr. Mouri reported receiving personal fees from Chugai Pharmaceutical and Eli Lilly, outside the submitted work. Dr. Tsukita reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Eli Lilly, MSD, and Taiho Pharmaceutical, outside the submitted work. Dr. Watanabe reported receiving grants from Nippon Kayaku outside the submitted work, personal fees from AstraZeneca, Bristol-Meyers Squibb, Celltrion, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly, Kyowa Kirin, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, outside the submitted work. Dr. Morita reported receiving personal fees from Amgen, AstraZeneca, Bristol-Meyers Squibb, Chugai Pharmaceutical, Daiichi-Sankyo, Eli Lilly, MSD, Nippon Kayaku, Novartis, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical, and ThermoFisher Scientific, outside the submitted work. Dr. Yoshioka reported receiving grants from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Delta Fly Pharma, Janssen Pharmaceutical, MSD, and Novartis, outside the submitted work; and personal fees from AstraZeneca, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kyowa Kirin, MSD, Nippon Kayaku, Nipro Pharma, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Taiho Pharmaceutical, outside the submitted work. Dr. Namba reported receiving personal fees from Chugai Pharmaceutical, Kyowa Kirin, MSD, and Taiho Pharmaceutical, outside the submitted work. Dr. Nakagawa reported receiving personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Japan Blood Products Organization, MSD, Nippon Kayaku, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, and Taiho Pharmaceutical, outside the submitted work. Dr. Watanabe reported receiving grants from MSD, outside the submitted work. Dr. Kobayashi reported receiving personal fees from AstraZeneca and Takeda Pharmaceutical, outside the submitted work. Dr. Takahashi reports grant support from Asahi Kasei Pharma, Bayer, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli-Lilly, Kyorin Pharmaceutical, Kyowa Kirin, Nippon Kayaku, Nippon Shinyaku, Nipro Pharma, Novartis, Ono Pharmaceutical, Pfizer, Sanofi, Shionogi, Takeda Pharmaceutical, Taiho Pharmaceutical, Teijin Pharma, and Tsumura, outside the submitted work; personal fees from Abbott Japan, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, Merck Biopharma, MSD, Kyorin Pharmaceutical, Nippon Kayaku, Novartis, Ono Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Taiho Pharmaceutical, Takeda Pharmaceutical, ThermoFisher Scientific and Viatris, outside the submitted work.; and serving as a board member of director of the Japan Lung Cancer Society and The Japanese Respiratory Society. No other disclosures were reported., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Aromatase inhibitor (AI)-induced musculoskeletal symptoms (AIMSS) can decrease health-related quality of life and lead to discontinuation of AI therapy for postmenopausal women with breast cancer (BC). Although central sensitization (CS) may contribute to AIMSS, the relevance of CS-related symptoms to AIMSS has not been fully clarified. This study aimed to investigate the relationship between AIMSS and CS-related symptoms in women with BC who received AI therapy., Methods: This cross-sectional study recruited women who underwent BC surgery before at least 1 year and were taking AI for at least 6 months. Participants were assessed for joint pain and CS-related symptoms using the central sensitization inventory (CSI). The severity of CS-related symptoms was classified into three groups, and the prevalence of AIMSS was calculated. Multiple logistic regression analysis was used to assess the relationship between AIMSS and factors of possible relevance to AIMSS, including CSI severity., Results: Of the 73 women who were included in this study, 31 (42.4%) were categorized into the AIMSS group and 42 (57.6%) into the non-AIMSS group. Participants with a history of chemotherapy and higher CSI score were significantly more likely to have AIMSS. Multiple logistic regression analysis showed that a history of chemotherapy (odds ratio = 4.21) and higher CSI severity (odds ratio = 13.43) had significantly associated with AIMSS., Conclusion: CS-related symptoms assessed using CSI may be strongly associated with AIMSS. Further longitudinal studies to investigate the causal relationship and effectiveness of CS-targeted interventions are needed to prevent and treat AIMSS effectively., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

Purpose: Neuroinflammation, which occurs in knee osteoarthritis and sarcopenia, has attracted attention as a mechanism of central sensitization, but the relationship between central sensitization and these conditions has not been widely studied. This study investigates differences in self-reported signs of central sensitization and pressure pain threshold in individuals with knee osteoarthritis and sarcopenia., Methods: We examined 340 patients (mean age ± standard deviation: 76 ± 5.9, women were 86.9%) with knee osteoarthritis scheduled to undergo total knee arthroplasty. For comparison, 129 community-dwelling older people (mean age ± standard deviation: 76 ± 5.5, women were 68.9%) individuals without a history of knee osteoarthritis or any other diagnosed illnesses were matched for age and sex. We assessed central sensitization inventory-9, pressure pain threshold, pain-related factors, skeletal muscle mass index, and hand grip strength. ANCOVA using 2 (patients with knee osteoarthritis and community older people without knee osteoarthritis) × 2 (sarcopenia and robust) was performed to assess outcome measurements., Results: The prevalence of sarcopenia among patients with knee osteoarthritis was 50.3%. ANCOVA revealed an interaction effect for the central sensitization inventory-9. For the main effect of knee osteoarthritis, there was a significant difference in central sensitization inventory-9, and for the main effect of sarcopenia, there was a significant difference in pressure pain threshold., Conclusions: Discrepancies in the evaluation of central sensitization were identified between knee osteoarthritis and sarcopenia. Individuals with knee osteoarthritis had elevated score of self-reported indications of central sensitization, whereas sarcopenic patients had reduced pressure pain thresholds., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer., Methods: This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates., Results: Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18-1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39-2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63-3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01-1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP., Conclusion: Our results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones., (© 2024. The Author(s).)

Streptolysin O (SLO), a bacterial toxin produced by common hemolytic streptococci, including Streptococcus pyogenes and resident microbiota, may be associated with inflammation in the cardiovascular system. We previously reported that short-term treatment with SLO at relatively high concentrations (10-1000 ng/mL) diminished acetylcholine-induced, endothelial-dependent relaxation in a concentration-dependent manner. However, the vascular function effects of long-term exposure to SLO at lower concentrations are poorly understood. In this study, treatment of rat aorta with endothelium with SLO (0.1-10 ng/mL) for 72 h inhibited contractions in response to norepinephrine and phenylephrine in a concentration-dependent manner, and this effect was abolished by endothelium denudation. We also observed decreased endothelium-dependent relaxation in aorta treated with a lower concentration of SLO (10 ng/mL) for 72 h. Long-term treatment with SLO (10 ng/mL) increased the expression of iNOS in aorta with endothelium but not aorta without endothelium, and the SLO-induced decrease in contraction was restored by treatment with NOS inhibitors. Pharmacologic and gene-mutant analyses further indicated that SLO-induced vascular dysfunction and iNOS upregulation are mediated through the TLR4/NOX2/ROS/p38 MAPK pathways. In vivo SLO treatment (46.8 pg/kg/min) for 7 days also diminished vascular contraction and relaxation activity in aorta with endothelium. We concluded that long-term treatment with SLO inhibits vascular contractile responses, primarily due to increased iNOS expression in the endothelium through TLR4-mediated pathways. Our present results, together with those of our previous study, suggest that endothelial cells play a key role in the pathophysiologic changes in cardiovascular function associated with long-term exposure to SLO. Significance Statement In the present study, we showed that long-term exposure to streptococcal exotoxin SLO inhibits agonist-induced contraction in rat aorta with endothelium, driven primarily by elevated iNOS production via NOX2-mediated ROS production through TLR4 activation on endothelial cells. In vivo treatment with SLO for 7 days also diminished vascular contraction and relaxation, providing evidence of possible pathophysiologic roles of SLO in endothelium-dependent vascular homeostasis., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy.

Purpose: This study was conducted to evaluate whether thin-slice 2D fat-saturated proton density-weighted images of the shoulder joint in three imaging planes combined with parallel imaging, partial Fourier technique, and denoising approach with deep learning-based reconstruction (dDLR) are more useful than 3D fat-saturated proton density multi-planar voxel images., Methods: Eighteen patients who underwent MRI of the shoulder joint at 3T were enrolled. The denoising effect of dDLR in 2D was evaluated using coefficient of variation (CV). Qualitative evaluation of anatomical structures, noise, and artifacts in 2D after dDLR and 3D was performed by two radiologists using a five-point Likert scale. All were analyzed statistically. Gwet's agreement coefficients were also calculated., Results: The CV of 2D after dDLR was significantly lower than that before dDLR (P < 0.05). Both radiologists rated 2D higher than 3D for all anatomical structures and noise (P < 0.05), except for artifacts. Both Gwet's agreement coefficients of anatomical structures, noise, and artifacts in 2D and 3D produced nearly perfect agreement between the two radiologists. The evaluation of 2D tended to be more reproducible than 3D., Conclusion: 2D with parallel imaging, partial Fourier technique, and dDLR was proved to be superior to 3D for depicting shoulder joint structures with lower noise.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45 dim CD34 + CD133 + cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group ( P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients., Competing Interests: All authors report that they have no conflict of interest to disclose.

Background: It is known that several complications are caused by local surgery after radiotherapy. Clinical reports that describe the postoperative complications associated with surgery after carbon ion radiotherapy are sparse. This study aimed to elucidate local surgery feasibility after carbon ion radiotherapy specifically for primary bone sarcomas., Methods: The medical, surgical, and irradiation records of patients who had local surgery at the area irradiated with carbon ion beams between 2004 and 2018 were reviewed retrospectively to evaluate the feasibility and indication of local surgery after CIRT., Results: There were eight patients who had 10 local surgeries at the irradiated sites among the 42 carbon ion radiotherapy patients. There were seven males and one female with a median age of 50 years (range 26-73 years). The reasons for surgery were three for skin toxicity and associated infection, five for bone collapse, and associated implant failure, and two for tumor regrowth. All surgical fields included the area of more than 60 Gy (RBE) irradiated dose. All three surgical cases caused by skin toxicity and associated infection had Grade I wound complication after surgery according to the Clavien-Dindo Classification., Conclusion: Local surgery after CIRT appeared feasible in selected patients with primary bone sarcoma, especially for the patients with bone collapse and associated implant failure. However, infection and prescribed irradiation dose at the incision site must be carefully evaluated., Competing Interests: Declaration of conflicting interests The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

This feasibility study confirmed the initial safety and efficacy of a novel carbon-ion radiotherapy (CIRT) using linear energy transfer (LET) painting for head and neck cancer. This study is the first step toward establishing CIRT with LET painting in clinical practice and making it a standard practice in the future., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interest statement. None declared.