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A startup optimization control system for a gas and steam turbine combined cycle power plant is developed. The system can minimize startup time of the plant through cooperative fuzzy reasoning and a neural network autonomously adapting to varying process dynamics due to varying operational conditions, i.e. the ambient temperature and humidity. The operational conditions are taken into consideration by the neural network with a learning mechanism to optimize the schedule. The system is applied to a simulation for a plant with a three pressure staged reheat type 235.7 MW rated capacity, and the following points are seen. (1) The system can harmonize machines operations making good use of the operational margins, i.e. machine thermal stress and NOx emission. (2) Startup time and energy loss are reduced by 35.6% and 26.3%, respectively, compared with the conventional off-line startup scheduling method.

We determined the clinical utility of the direct Coombs’ test in the absence of hemolytic anemia as an indicator of disease activity and therapeutic response in systemic lupus erythematosus (SLE). SLE patients without hemolytic anemia who visited our hospital from January 2016 to November 2016 were retrospectively evaluated with a direct Coombs’ test. Clinical features, including SLE disease activity index (SLEDAI), treatment and laboratory findings were analyzed. For patients with lupus nephritis, we additionally evaluated the cumulative complete renal response rate over one year after induction therapy. Among 182 patients evaluated, 10 (5.8%) patients had a positive direct Coombs’ test in the absence of hemolytic anemia. They had a higher SLEDAI (p < 0.01), higher circulating immune complex levels (p = 0.01), higher anti-DNA titers (p < 0.01) and a lower complete renal response rate (p = 0.03) compared with those who were negative. Multivariate analysis indicated that SLEDAI was an independent factor correlated with the direct Coombs’ test without hemolytic anemia (odds ratio 2.4, 95% confidence interval 1.66–4.98, p < 0.01). A positive direct Coombs’ test in the absence of hemolytic anemia may therefore represent a useful biomarker for assessing disease activity and therapeutic response. [ABSTRACT FROM AUTHOR]

Objectives: To clarify the prevalence of anti-signal recognition particle (anti-SRP) antibody in connective tissue diseases (CTDs) and investigate the clinical characteristics of patients without inflammatory myopathy.Method: Sera from 6180 patients with CTD were examined by immunoprecipitation (IPP) assays, and the records of patients positive for anti-SRP antibody were reviewed retrospectively. The antibody against the 54-kDa protein of SRP (SRP54) was quantified by enzyme-linked immunosorbent assay (ELISA) in patients with anti-SRP antibody.Results: Of the 28 patients positive for anti-SRP antibody, nine (32.1%) did not have inflammatory myopathy. The clinical diagnoses and characteristics of those patients varied considerably. In patients with inflammatory myopathy, the index of anti-SRP54 was much higher than in those without myopathy (1.15 vs. 0.46; p = 0.036).Conclusions: The prevalence of anti-SRP antibody was 0.5% in a cohort of Japanese patients with CTD, and one-third of them did not have inflammatory myopathy. Sera from patients with inflammatory myopathy recognized SRP54 more strongly than in those without myopathy. [ABSTRACT FROM AUTHOR]

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p < 0.001). Circulating anti-dsDNA antibody-secreting cells are a useful biomarker for assessing disease activity in SLE patients. [ABSTRACT FROM PUBLISHER]

Objective: L-3-[¹⁸F]-fluoro-α-methyl tyrosine (FAMT) is transported into cancer cells by L: -type amino acid transporter 1 (LAT1). The purpose of the present study is to correlate the uptake of FAMT and FDG with the cellular proliferative activity measured by the Ki-67 labeling index (Ki-67 LI) in oral squamous cell carcinoma (OSCC). Methods: Twenty-five patients with OSCC were enrolled in this study. Both FAMT-PET and FDG-PET were performed within 4 weeks before surgery in all cases. The uptake of FAMT and FDG was compared by semiquantitative analysis with maximal standardized uptake values (SUVmax) of the primary tumors. Ki-67 LI of the tumors was analyzed by immunohistochemical staining and correlated with the clinicopathologic variables and the uptake of PET tracers. Results: For primary tumor detection, FAMT-PET exhibited a sensitivity of 84%, whereas that of FDG-PET was 88%. In all visible lesions, mean FDG uptake determined by average SUVmax was 9.7 (range 4.2-15.9) and mean FAMT uptake was 3.5 (range 1.3-8.5). The SUVmax of FAMT tended to show a better correlation with Ki-67 LI (r = 0.878) than that of FDG (r = 0.643). Conclusions: Uptake of FAMT correlated with cellular proliferation of OSCC. FAMT-PET may be a useful procedure to evaluate tumor proliferation of OSCC. [ABSTRACT FROM AUTHOR]

Objective: In-111 ((111)In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ((64)Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a (64)Cu-labeled octreotide analog, (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D: -Phe(1)-Tyr(3)-octreotide ((64)Cu-DOTA-TOC). Methods: (64)Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 degrees C. The stability of (64)Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of (64)Cu-DOTA-TOC and (111)In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of (64)Cu-DOTA-TOC or (64)Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ((64)Cu-TETA-OC). The tumor was imaged using (64)Cu-DOTA-TOC, (64)Cu-TETA-OC, and FDG with an animal PET scanner. Results: (64)Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. (64)Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of (64)Cu was higher than that of (111)In in all organs except kidney. In tumor-bearing mice, (64)Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 +/- 1.17 at 6 h after administration. (64)Cu-DOTA-TOC showed significantly higher accumulation in the tumor than (64)Cu-TETA-OC. (64)Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of (18)F-FDG PET and very similar to that of (64)Cu-TETA-OC. Conclusions: (64)Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase. [ABSTRACT FROM AUTHOR]

Copper-64 was produced by the 64Ni(p, n)64Cu reaction using enriched 64NiO target. We investigated and compared the production yield of 64Cu for proton beams of various energies by using a thick target. Enriched 64Ni was recovered with high yield by simple procedures. Imaging studies using positron emission tomography (PET) and positron emitting tracer imaging system (PETIS) were performed. We obtained clear images in PET and PETIS studies. The results of this study indicate that 64Cu can be utilized as a biomedical tracer for the molecular imaging both in animals and plants. [ABSTRACT FROM AUTHOR]

The radionuclide 67Cu was produced via the 68Zn(p,2p)67Cu reaction by irradiating enriched 68Zn targets with 70 MeV proton beam. Copper-67 was chemically separated from the zinc target by ion-exchange chromatography using Chelex-100 chelating ion-exchange resin. Procedure for recovery of the enriched 68Zn was developed. The target recovery yield of this method was evaluated to be more than 97%. [ABSTRACT FROM AUTHOR]

The purpose of this study was to conduct group reminiscence therapy by using cooking activities among elderly dementia patients and to assess its efficacy. We conducted reminiscence therapy for 11 patients in a total of 9 sessions, once a week, 60 minutes each. Evaluations were performed on three occasions: one week before the start of the intervention and one week and four weeks after completion of the intervention. No particular adverse events were noted during the conduct of the study. There were significant improvements in the patients' scores for cognitive function and in their behavior, and the improvement in cognitive function continued until four weeks after the intervention. Based on these results, it will be necessary to verify the efficacy by means of a randomized controlled study in a larger number of patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the prevalence of depression among residents of a health care institution for the elderly and to identify factors associated with it. The subjects were 44 elderly persons who had resided in a health care institution for the elderly for 3 months or more. The Cornell Scale for Depression in Dementia was used to evaluate depression. The results showed that 50% of the residents exhibited mild to moderate depression and that visual impairment, hypochondriac symptoms, grooming ability, and social cognition ability were significantly associated with it. These results suggested that rehabilitative interventions focused on grooming and social cognition may prevent or mitigate the depression of residents of health care institutions for the elderly. However, a longitudinal study is necessary to elucidate case-effect relationships. [ABSTRACT FROM AUTHOR]

Neurinomas are relatively common benign tumors thought to arise from nerve sheath cells. Although intraosseous neurinomas may destroy the bone, extraosseous neurinomas with extensive destruction and invasion of bone are considered rare. We present two unusual cases of a benign extraosseous neurinoma that extensively invaded the vertebral body through the nutrient canal. [ABSTRACT FROM AUTHOR]

Recent advancements in the development of positron emission tomography (PET) tracers have significantly enhanced our ability to image neuroinflammatory processes and neurotransmitter systems, which are vital for understanding and treating neurodegenerative and psychiatric disorders. Similarly, innovative tracers in oncology provide detailed images of the metabolic and molecular characteristics of tumors, which are crucial for tailoring targeted therapies and monitoring responses, including radiotherapy. Notable advancements include programmed death ligand 1 (PD-L1)-targeting agents for lung cancer, prostate-specific membrane antigen-based tracers for prostate cancer, chemokine receptor-targeting agents for hematological malignancies, human epidermal growth factor receptor 2 (HER2)-targeting tracers for various cancers, Claudin 18 based tracers for epithelial tumors, glutamine tracers for colorectal cancer, and ascorbic acid analogs for assessing cancer metabolism and therapy efficacy. Additionally, novel tracers have been developed for non-neurological and non-oncological applications, including adrenal imaging, amyloidosis, and human immunodeficiency virus (HIV) infection. This overview focuses on the newly developed tracers, particularly those used in neurology and oncology., (© 2024. The Author(s).)

Background: Persons with dementia in nursing homes often experience cognitive decline (e.g., memory and visuospatial/construction problems), behavioural and psychological symptoms of dementia (BPSD), and impaired activities of daily living. Therefore, comprehensive interventions for this population are needed. We assessed whether a multimodal non-pharmacological intervention improved cognitive functions, BPSD, and activities of daily living in persons with dementia in nursing homes., Methods: This was a multicentre randomised controlled trial. Participants were 40 persons with dementia (38 women) living in four nursing homes (intervention group = 21; control group = 19). The intervention was conducted for 8 weeks, followed by an 8-week follow-up. Outcome measures were scores on the Japanese version of the Neurobehavioral Cognitive Status Examination Five and the ABC Dementia Scale. In the analysis, parameters were estimated using Bayesian statistics and a mixed-effects linear regression model for the change in each outcome measure., Results: There were significant between-group differences in changes in ABC Dementia Scale BPSD scores (8-week: posteriori median = 1.66, 95% Bayesian confidence interval 0.36-3.01; 16-week: median = 2.37, 95% Bayesian confidence interval 0.05-4.65). There was also a significant between-group difference in changes in Neurobehavioral Cognitive Status Examination Five constructional ability scores (16-week: median = 0.93, 95% Bayesian confidence interval 0.35-1.50)., Conclusion: This intervention may have a maintenance and improvement effect on BPSD in persons with dementia in nursing homes, and a sustained effect on constructional ability post-intervention. The intervention may be useful and easy to apply in practice., (© 2024 Japanese Psychogeriatric Society.)

Sjögren's syndrome (SS) can present with extraglandular organs, such as interstitial lung disease (ILD). Anti-SS-A antibody is frequently found in SS cases, whereas anti-centromere antibody (ACA) is detected in some SS cases. Notably, the anti-SS-A and ACA double-positive cases exhibited distinct features with a higher prevalence of ILD. However, there have so far been no reports on the treatment of ILD in anti-SS-A and ACA double-positive cases. We herein present a case of ILD with anti-SS-A and ACA double-positive SS that was successfully treated with immunosuppressive therapy. Our case suggests the potential efficacy of immunosuppressive therapy for this poorly understood condition.

Objective: To elucidate the effectiveness of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor, on renal function in patients with rheumatic musculoskeletal diseases complicated by chronic kidney disease (CKD) and identify factors associated with the response to dapagliflozin., Methods: We conducted a retrospective analysis of patients with rheumatic musculoskeletal disease and CKD who were treated with dapagliflozin for more than a year. The good response was defined as an improvement in the estimated glomerular filtration rate (eGFR) slope per year after dapagliflozin treatment compared to that before treatment. Additionally, we investigated the response rate and its predictive factors., Results: In this analysis, 43 patients were included. The average eGFR slope demonstrated a significant improvement after dapagliflozin treatment compared to that before the treatment (0.04 vs -0.55 mL/min/1.73m²/year, p=0.001). A good response rate was 69.8% and was associated with low average levels of C-reactive protein, a high frequency of angiotensin II receptor blocker (ARB) use, and a low frequency of tacrolimus use compared to non-response (0.08 ± 0.18 vs 0.25 ± 0.29 mg/dL, p=0.03; 80.0% vs 38.4%, p=0.01; 10.0% vs 76.9%, p<0.01)., Conclusion: Dapagliflozin is effective for rheumatic musculoskeletal diseases patients with CKD for preventing deterioration of renal function. Antihypertensive treatment with ARBs and inflammation control without tacrolimus was associated with a high likelihood of favorable response to dapagliflozin., (© Japan College of Rheumatology 2024. Published by Oxford University Press. 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.)

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease (CD), not only causes significant intestinal inflammation but also leads to extra-intestinal manifestations such as spondyloarthritis (SpA). Although the efficacy of tumor necrosis factor (TNF) inhibitors has been reported for IBD-related SpA, some cases still encounter treatment failure, highlighting the need for novel therapeutic alternatives. Recently, Janus kinase inhibitors have demonstrated their efficacy in IBD and SpA, yet their impact on CD-related SpA remains unexplored. Here we present the first two cases of CD-related peripheral SpA successfully treated with upadacitinib. Additionally, our literature review identified a reported case of CD-related peripheral SpA treated with tofacitinib. All cases achieved clinical remission of both CD and peripheral SpA with Janus kinase inhibitors, and no adverse events or disease relapses were reported during the observation period. Our cases and literature review highlight the promising potential of Janus kinase inhibitors as a novel treatment not only for intestinal inflammation of CD, but also for CD-related peripheral SpA., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: There is a pressing need to understand the pathogenesis of histological findings and identify the biomarkers for predicting the histological severity in lupus nephritis (LN). This study aimed to identify the pathogenic signal pathway and elucidate urinary biomarkers for predicting the presence or severity of histological findings in LN., Methods: Urine samples from patients with biopsy-proven active LN were screened for 1305 proteins using an aptamer-based proteomic assay. The diversity and expansion of individual renal histological features in LN were quantified to identify the urinary proteins associated with the histological findings found in each score. Candidate urinary proteins were validated in a validation cohort. Immunohistochemical staining of the renal tissues was performed to clarify the localisation of the candidate proteins., Results: Cluster analysis extracted five histological subgroups according to their correlations with each histological finding in LN. Protein groups which correlated with each histological subgroup revealed a distinct pathogenesis in LN using pathway analyses. Enzyme-linked immunosorbent assay validation revealed that urinary calgranulin B (S100A9), MCP-1, and IGFBP-5 levels could specifically predict the presence and severity of active glomerular lesions, interstitial inflammation, and interstitial fibrosis, respectively. Immunohistochemical staining revealed the localisation of these proteins in each lesion., Conclusions: Renal histological findings may reflect the different pathogeneses involved in each lesion, and estimating the urinary calgranulin B, MCP-1, and IGFBP-5 levels may be useful in predicting the presence and severity of histological findings in LN., (© 2024 American College of Rheumatology.)

Eosinophilic granulomatosis with polyangiitis (EGPA) poses a significant diagnostic challenge due to its varied clinical presentation. Here, we present a case of a 59-year-old female with a history of asthma and sinusitis, who manifested with an extremely rare presentation of drastic tense blisters and hemorrhagic bullae alongside purpuric lesions and peripheral neuropathy. Examinations revealed eosinophilia, positive anti-neutrophil cytoplasmic antibody, and characteristic pathological findings with small vessel vasculitis in the purpura. Treatment with glucocorticoids and cyclophosphamide led to rapid improvement in peripheral eosinophilia, skin manifestations and motor neuron deficits. Although rare, our case underscores that bullous skin lesions should be recognized as a potential cutaneous hallmark of EGPA to aid timely diagnosis, since prompt treatment initiation is crucial given the potential irreversible organ damage and poor prognosis of EGPA., (© Japan College of Rheumatology 2024. Published by Oxford University Press. 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.)

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections., (© 2024 UICC.)

Osteosarcoma is the most common bone tumor, and it possesses high metastatic propensity. Although systemic chemotherapy has improved its prognosis, improvements in survival rates have stalled in recent years. Moreover, the prognosis of patients with metastatic osteosarcoma remains poor. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer therapy that induces immunogenic cell death (ICD), and the therapeutic effects spread to distant metastatic sites. Therefore, NIR-PIT could be useful in both primary and metastatic osteosarcoma treatment. In this study, we investigated the efficacy of NIR-PIT targeting epidermal growth factor receptor (EGFR) in osteosarcoma. The cytotoxic effects of NIR-PIT in osteosarcoma cell lines with different EGFR expression levels (MG63; high, Saos-2; low) were evaluated. NIR-PIT-induced cell death was dependent on the EGFR expression level. After NIR-PIT, swelling and bleb formation, the characteristic morphological changes induced by NIR-PIT associated with necrosis caused by the influx of extracellular fluid, were observed. In addition, the release of the ICD markers lactate dehydrogenase and ATP was detected after NIT-PIT. NIR-PIT significantly suppressed tumor growth in tumor-bearing mice. This study revealed that NIR-PIT targeting EGFR has therapeutic effects and induces ICD in osteosarcoma; thus, it is potentially a novel therapeutic strategy for primary and metastatic osteosarcoma., 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. Published by Elsevier Inc.)

Watanabe T, Hirowatari H, Tokura Y, Takeda K, Hanaoka H. A 30-day kendama program for community-dwelling elderly: Effects on participants' physical and cognitive functions and the practicality of the program. Jpn J Compr Rehabil Sci 2024; 15: 34-41., Purpose: This study examined the effects of a 30-day kendama program on physical and cognitive functions and the practicality of the program for community-dwelling elderly individuals to reduce the risk of dementia and musculoskeletal disorders., Method: Seventeen community-dwelling elderly persons aged ≥65 years participated in a 30-day kendama program wherein they practiced kendama in groups once a week for a total of four times and individually for at least 20 minutes a day for 30 days. The frequency and duration of the group and individual practices were surveyed to assess the practicality of the program., Results: The physical function assessment revealed that knee extension muscle strength increased significantly by 18.8% after the intervention ( p < 0.01). Further, the cognitive function assessment showed that the time required to perform the Stroop test decreased by 10.1%, the number of Symbol Digit Modalities Tests (SDMTs) performed increased by 5.6%, and the number of correct answers in the word memory test increased by 17.8% after the intervention, with each showing a significant change ( p < 0.05). The results of the questionnaire on the participants' 30-day kendama program showed that approximately 30% answered that the frequency of individual practice was "a little too much," indicating that the program needed to be modified., Conclusion: The results of this study suggested that kendama can be enjoyed easily and is expected to be practiced continuously with friends. Therefore, kendama can serve as an exercise program for reducing the risk of dementia and musculoskeletal disorders. In the future, it will be necessary to reconsider the frequency of individual kendama practice., Competing Interests: Conflict of Interest: The author declares no conflict of interest., (©Kaifukuki Rehabilitation Ward Association 2024.)

Near-infrared photoimmunotherapy (NIR-PIT) is a new cancer therapy that uses NIR light and conjugates of a tumor-targeting monoclonal antibody and phthalocyanine dye. In clinical practice, frontal and cylindrical diffusers are the only options for NIR illumination. However, illumination in a narrow space is technically difficult with such diffusers. Therefore, we evaluated a lateral illumination system using a lateral emitting laser (LEL) fiber. The LEL fiber illuminated a certain area in a lateral direction. NIR-PIT with an LEL fiber reduced luciferase activity in a light-dose-dependent manner in A431-GFP-luc cells in vitro and significantly suppressed tumor proliferation in a xenograft mouse model. To evaluate the usefulness of the LEL fiber in the illumination of a narrow space, a tumor was illuminated from the inside of a cylinder, mimicking a narrow space, and the fluorescence intensity in the tumor was monitored. In the frontal diffuser, NIR light was unevenly delivered and little light reached a distal tumor area from the illuminated side. By contrast, the LEL fiber allowed a uniform illumination of the entire tumor, and a loss of fluorescence was observed even in distal areas. These findings suggested that the LEL fiber can be used for NIR-PIT and is suitable for NIR light illumination in a narrow space.

Lupus protein-losing enteropathy (LUPLE) is a rare condition in patients with systemic lupus erythematosus (SLE). Since the causes and exact pathological mechanism have not been elucidated, appropriate treatment has not been determined. Here, we report the case of a 69-year-old woman with systemic lupus erythematosus who developed LUPLE which was successfully treated with belimumab without an increase in glucocorticoid dose. This case suggests that belimumab monotherapy may be a treatment option for LUPLE., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

We examined the development strategies of new molecular entities approved during a 10-year period (fiscal years of 2012-2021) in Japan to determine the differences in drug lag between Japan and foreign companies. The results demonstrated a clear difference in development strategies. For example, products were usually developed through a "only-Japan" strategy by Japan companies (51.1% of products), compared to a "MRCT (multi-regional clinical trials)" strategy by foreign companies (54.9% of products). Regarding types of licenses, for Japan companies, the percentage of original products was higher in the category of less drug lag, such as "no approval in the US and EU" (59.1%), whereas the percentage of "license-in" products was markedly higher in the "drug lag ≥ 5 years" category (52.5%). Such differences were not observed for products developed by foreign companies. Of 64 license-in products developed by Japan companies with a drug lag > 5 years, 51 (79.7%) had already been approved in the US or EU at initiation of clinical development in Japan. The origin of approximately half (34) of the products was from the emerging companies (non-member foreign companies of the Japan Pharmaceutical Manufacture Association). These results suggest that more global cooperation of Japan companies, particularly with emerging foreign companies, is necessary in terms of the earlier timing of license-in and development strategies of products to promote drug development without drug lag or drug loss in Japan., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Introduction: Insomnia is a common health problem and cognitive-behavioural therapy (CBT) is recommended as a treatment. As there is a critical shortage of CBT-trained therapists, we developed a digital CBT application (IIIP MED: Sleepy Med) as Software as a Medical Device for insomnia. This paper describes the study protocol for an exploratory randomised controlled trial (RCT) to evaluate effectiveness and safety of our developed digital CBT (dCBT) for 5 weeks compared with zolpidem tartrate for patients with insomnia disorder., Methods and Analysis: This proposed multicentre exploratory RCT will be conducted at the outpatient clinic of Chiba University Hospital, Akita University Hospital and Yoyogi Sleep Disorder Center, Japan. The study population comprises two parallel groups (dCBT and zolpidem) consisting of 15 participants each (n=30 in total) diagnosed with insomnia disorder who remain symptomatic at 4 weeks after sleep hygiene education. We will evaluate the effectiveness at baseline, week 5 (post-intervention) and week 10 (follow-up). The primary outcome will be the change of subjective sleep onset latency at week 5 from baseline. Secondary outcomes include sleep-related outcomes, such as objective sleep onset latency measured by mobile electroencephalography, functional improvement during the daytime and quality of life., Ethics and Dissemination: Ethics approval was granted by the Institutional Review Board of Chiba University Hospital (K2023001). All participants will be required to provide written informed consent. Results will be published in international journals., Trial Registration Number: jRCT2032230353., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Therapy-induced senescent cancer and stromal cells secrete cytokines and growth factors to promote tumor progression. Therefore, senescent cells may be novel targets for tumor treatment. Near-infrared photoimmunotherapy (NIR-PIT) is a highly tumor-selective therapy that employs conjugates of a molecular-targeting antibody and photoabsorber. Thus, NIR-PIT has the potential to be applied as a novel senolytic therapy. This study aims to investigate the efficacy of NIR-PIT treatment on senescent cancer and stromal cells., Methods: Two cancer cell lines (human lung adenocarcinoma A549 cells and human pancreatic cancer MIA PaCa-2 cells) and two normal cell lines (mouse fibroblast transfected with human epidermal growth factor receptor 2 [HER2] cells and human fibroblast WI38 cells) were used. The cytotoxicity of NIR-PIT was evaluated using anti-epidermal growth factor receptor (EGFR) antibody panitumumab and anti-HER2 antibody transtuzumab., Results: Cellular senescence was induced in A549 and MIA PaCa-2 cells by 10 Gy γ-irradiation. The up-regulation of cellular senescence markers and characteristic morphological changes in senescent cells, including enlargement, flattening, and multinucleation, were observed in cancer cells after 5 days of γ-irradiation. Then, NIR-PIT targeting EGFR was performed on these senescent cancer cells. The NIR-PIT induced morphological changes, including bleb formation, swelling, and the inflow of extracellular fluid, and induced a significant decrease in cellular viability. These results suggested that NIR-PIT may induce cytotoxicity using the same mechanism in senescent cancer cells. In addition, similar morphological changes were also induced in radiation-induced senescent 3T3-HER2 fibroblasts by NIR-PIT targeting human epidermal growth factor receptor 2., Conclusion: NIR-PIT eliminates both senescent cancer and stromal cells in vitro suggesting it may be a novel strategy for tumor treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

This cross-sectional study investigated staff's attitudes towards the use of mobile telepresence robots in long-term care (LTC) homes in western Canada. We drew on a Health Technology Assessment Core Model 3.0 to design a survey examining attitudes towards nine domains of mobile telepresence robots. Staff, including nurses, care staff, and managers, from two LTC homes were invited to participate. Statistical analysis of survey data from 181 participants revealed that overall, participants showed positive attitudes towards features and characteristics, self-efficacy on technology use, organizational aspects, clinical effectiveness, and residents and social aspects; neutral attitudes towards residents' ability to use technology, and costs; and negative attitudes towards safety and privacy. Participants who disclosed their demographic backgrounds tended to exhibit more positive attitudes than participants who did not. Content analysis of textual data identified specific concerns and benefits of using the robots. We discuss options for implementing mobile telepresence robots in LTC.