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The existing literature consistently finds that emotional experiences and cortisol secretion are linked at the within-person level. Further, relationship partners tend to covary in emotional experience, and in cortisol secretion. However, we are only beginning to understand whether and how an individuals' emotions are linked to their relationship partners' cortisol secretion. In this project, we harmonized data from three intensive measurement studies originating from Canada and Germany to investigate the daily dynamics of emotions and cortisol within 321 older adult couples (age range=56-87 years). Three-level multilevel models accounted for the nested structure of the data (repeated assessments within individuals within couples). Actor-Partner Interdependence Models were used to examine the effect of own emotional experiences (actor effects) and partner emotional experiences (partner effects) on momentary and daily cortisol secretion. Adjusting for age, sex, education, comorbidities, assay version, diurnal cortisol rhythm, time spent together, medication, and time-varying behaviors that may increase cortisol secretion, results suggest that higher relationship partner's positive emotions are linked with lower momentary cortisol and total daily cortisol. Further, this association was stronger for older participants and those who reported higher relationship satisfaction. We did not find within-couple links between negative emotions and cortisol. Overall, our results suggest that one's relationship partner's positive emotional experience may be a protective factor for their physiological responding, and that these more fleeting and day-to-day fluctuations may accumulate over time, contributing to overall relationship satisfaction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aims to evaluate the prevalence of unilateral hyperaldosteronism (UHA) and its clinical characteristics in patients with primary aldosteronism (PA), diagnosed using plasma aldosterone concentration (PAC) measured by chemiluminescent enzyme immunoassay (CLEIA). We retrospectively analyzed data of 199 PA patients from the Japan Primary Aldosteronism Study II (JPAS II) dataset, including patients who underwent adrenal venous sampling (AVS) and the captopril challenge test (CCT) and/or saline infusion test (SIT), with PAC measured by CLEIA. We focused on two categories: confirmed PA, where patients exhibit clear biochemical evidence of the disorder, and borderline PA, where patients present with marginal biochemical indicators, as outlined in the Japan Endocrine Society's clinical practice guideline for the diagnosis and management of PA. In confirmed PA cases, over the half of patients was UHA, while approximately 15 to 20% of borderline cases were found to be UHA. The prevalence of hypokalemia was identified as predictor of UHA among borderline cases. Among borderline cases with no hypokalemia and adrenal nodules on CT imaging, only 6 to 8% of patients were found to have UHA. Notably, some patients exhibited UHA despite negative results on one test but confirmed result on the other, particularly those with hypokalemia or adrenal nodules on CT imaging. In conclusion, the findings validate the importance of AVS in confirmed PA cases and the need for careful assessment in borderline cases. When feasible, conducting both CCT and SIT, and interpreting their results alongside other clinical indicators, could provide a more comprehensive assessment., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Activation of the renin-angiotensin-aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels of the angiotensinogen angiotensin-converting enzyme , angiotensin type 1 receptor gene, Agtr1a , and the aldosterone synthase gene, CYP11B2, have been reported in the heart, blood vessels, and kidneys in salt-sensitive hypertension. However, the mechanism of gene regulation in each component of the RAAS in cardiovascular and renal tissues is unclear. Epigenetic mechanisms, which are important for regulating gene expression, include DNA methylation, histone post-translational modifications, and microRNA (miRNA) regulation. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. Several miRNAs influence AGT expression and are associated with cardiovascular diseases. Expression of both ACE and ACE2 genes is regulated by DNA methylation, histone modifications, and miRNAs. Expression of both angiotensinogen and CYP11B2 is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. The mineralocorticoid receptor (MR) exists in cardiovascular and renal tissues, in which many miRNAs influence expression and contribute to the pathogenesis of hypertension. Expression of the 11beta-hydroxysteroid dehydrogenase type 2 ( HSD11B2 ) gene is also regulated by methylation and miRNAs. Epigenetic regulation of renal and vascular HSD11B2 is an important pathogenetic mechanism for salt-sensitive hypertension.

Primary aldosteronism (PA) is a subtype of secondary hypertension categorized as either unilateral PA (eg, aldosterone-producing adenoma [APA]) or bilateral PA. CYP11B2, an aldosterone synthase, is highly expressed in APA. Recent studies have revealed a high prevalence of pathogenic variants in KCNJ5 and the role of DNA methylation on CYP11B2 in APA. We present a case of unilateral PA with pathogenic variants in KCNJ5 and suppressed CYP11B2 expression. A 55-year-old woman with hypertension was referred to our hospital. A high aldosterone-renin ratio was observed; PA was confirmed using the captopril challenge test and the furosemide upright test. Although computed tomography showed no evident tumors in either adrenal gland, adrenal vein sampling revealed left gland dominance. Postoperatively, the aldosterone-renin ratio decreased and captopril challenge test showed negative findings. Pathogenic variants in the KCNJ5 were detected in the adenoma. Although immunohistochemistry for CYP11B2 was negative in adenoma, an aldosterone-producing cell cluster was confirmed in the adjacent left adrenal gland. Furthermore, DNA methylation analysis of the adenoma indicated hypermethylation in the CYP11B2 promoter region. The pathogenic variant in KCNJ5 , specific to APA, induces CYP11B2 overexpression, resulting in excess aldosterone. However, these effects can be suppressed by DNA methylation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The clinical importance of nutrition and inflammation in patients with end-stage renal disease is well established. In this study, we investigated the role of nutritional and inflammatory indicators in the patient outcomes of living donor kidney transplant recipients., Methods: We included 204 consecutive patients who underwent kidney transplantation at our institute between 2003 and 2022. We retrospectively reviewed medical charts to obtain clinical information. Six nutritional indicators and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored., Results: The median patient age and follow-up period were 48 years and 99 months, respectively. The cohort included patients with preoperative malnutrition and microinflammation. No significant differences in graft survival were identified according to nutritional and inflammatory indicators, whereas the survival index, controlled nutritional status, and C-reactive protein levels were associated with patient survival. The survival index was an independent indicator of survival and death in patients with functioning grafts (P = 0.047 and P = 0.013, respectively). Furthermore, the C-reactive protein level could distinguish between low and high mortality risks in patients with good nutrition (P = 0.019)., Conclusions: Our findings suggest that nutrition and inflammation indicators play important roles in predicting outcomes in living donor kidney transplantation recipients. Further research is warranted to establish optimal management strategies., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background/aim: This study investigated the follow-up rate of living kidney donors and explored the factors related to continuous follow-up and remnant renal function, enabling the optimal management of living kidney donors., Patients and Methods: We retrospectively evaluated 180 living kidney donors who underwent donor nephrectomies at our institute. Clinical information was obtained from medical charts, and remnant renal function was defined as the estimated glomerular filtration rate 12 months after donor nephrectomy., Results: Overall, 6/180 donors (3.3%) were lost to follow-up within a year, and the follow-up rate gradually declined yearly. Independent risk factors for loss to follow-up included a follow-up period <60 months and graft survival of the recipient (p=0.002 and p=0.043, respectively). Recipient survival was correlated with loss to follow-up; however, this was not significant (p=0.051). Regarding remnant renal function, age ≥60 years, preoperative estimated glomerular filtration rate <74 ml/min/1.73 m 2 , and a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73m 2 were independent risk factors for poorly preserved remnant renal function (p=0.036, p<0.0001, and p<0.0001, respectively). Using propensity score matching to adjust for preoperative factors, a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73 m 2 was the only significant postoperative factor for poorly preserved remnant renal function (p=0.023)., Conclusion: An increased 5-year follow-up rate could lead to an increase in long-term follow-up, and recipient prognosis may be correlated with the living kidney donor follow-up status. Furthermore, Δsingle-kidney estimated glomerular filtration rate was identified as a factor for establishing the optimal precision follow-up management of living kidney donors., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Loneliness is a pervasive experience with adverse impacts on health and well-being. Despite its significance, notable gaps impede a full understanding of how loneliness changes across the adult life span and what factors influence these changes. To address this, we conducted a coordinated data analysis of nine longitudinal studies encompassing 128,118 participants ages 13 to 103 from over 20 countries. Using harmonized variables and models, we examined loneliness trajectories and predictors. Analyses revealed that loneliness follows a U -shaped curve, decreasing from young adulthood to midlife and increasing in older adulthood. These patterns were consistent across studies. Several baseline factors (i.e., sex, marital status, physical function, education) were linked to loneliness levels, but few moderated the loneliness trajectories. These findings highlight the dynamic nature of loneliness and underscore the need for targeted interventions to reduce social disparities throughout adulthood.

Background: The severity of coronavirus disease 2019 (COVID-19) is known to be high in kidney transplant recipients; however, the risk factors for COVID-19 infection in these patients has not been studied extensively. Therefore, we explored the predictors of COVID-19 infection and severity in kidney transplant recipients in Japan., Methods: This study included kidney transplant recipients who were regularly followed-up at our hospital from February 2021 to March 2023. We retrospectively reviewed the patients' medical charts; obtained their clinical information, including comorbidities, immunosuppressant usage, and presence of COVID-19 infection; and assessed the risk of COVID-19 infection and severity. Severe illness was defined as a decrease in oxygen saturation., Results: Among the 155 patients, 50 (32.3%) were infected with COVID-19. Multivariate analysis revealed that recipients taking >5 mg of prednisolone or taking tacrolimus instead of cyclosporine were at higher risk of infection (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.01-5.40; OR 2.29, 95% CI 1.03-5.07, respectively). Furthermore, of the 50 infected recipients, 42 had minor illness and eight had severe illness. Multivariate analysis revealed that recipients taking >5 mg of prednisolone were at a higher risk of severity (OR, 11.60, 95% CI 1.19-113.00)., Conclusion: In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking >5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Plasticity during the critical period is important for the functional maturation of cortical neurons. While characteristics of plasticity are diverse among cortical layers, it is unknown whether critical period timing is controlled by a common or unique molecular mechanism among them. We here clarified layer-specific regulation of the critical period timing of ocular dominance plasticity in the primary visual cortex. Mice lacking the endocannabinoid synthesis enzyme diacylglycerol lipase-α exhibited precocious critical period timing, earlier maturation of inhibitory synaptic function in layers 2/3 and 4, and impaired development of the binocular matching of orientation selectivity exclusively in layer 2/3. Activation of cannabinoid receptor restored ocular dominance plasticity at the normal critical period in layer 2/3. Suppression of GABA A receptor rescued precocious ocular dominance plasticity in layer 4. Therefore, endocannabinoids regulate critical period timing and maturation of visual function partly through the development of inhibitory synaptic functions in a layer-dependent manner., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Aldosterone secretion in primary aldosteronism (PA) is often regulated by adrenocorticotropic hormone (ACTH) in addition to its autonomous secretion. However, the clinical characteristics and risk of cardiovascular and cerebrovascular (CCV) events in PA patients with aldosterone responsiveness to ACTH stimulation remain unclear. This study aimed to investigate the prevalence of CCV events in PA patients with high aldosterone responsiveness to ACTH stimulation. A retrospective cross-sectional study was conducted as part of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Disease project. PA patients with adrenal venous sampling (AVS) between January 2006 and March 2019 were enrolled. The ACTH-stimulated plasma aldosterone concentration (PAC) of the inferior vena cava during AVS was used to evaluate aldosterone responsiveness to ACTH. We analyzed the relationship between responsiveness and previous CCV events. Logistic regression analysis demonstrated that the ΔPAC (the difference between the PAC measurements before and after ACTH stimulation) significantly increased the odds of previous CCV events in PA patients after adjusting for classical CCV event risk factors, baseline PAC and duration of hypertension (relative PAC: odds ratio [OR], 2.896; 95% confidence interval [CI], 0.989-8.482; ΔPAC: OR, 2.344; 95% CI, 1.149-4.780; ACTH-stimulated PAC: OR, 2.098; 95% CI, 0.694-6.339). This study clearly demonstrated that aldosterone responsiveness to ACTH is closely related to previous CCV events. The responsiveness of the PAC to ACTH could be useful in predicting CCV event risk.Registration Number in UMIN-CTR is UMIN000032525.

Purpose: Decidualization is an important event for embryo implantation and successful pregnancy. Impaired decidualization leads to implantation failure and miscarriage. However, it is unclear how often decidualization failure occurs in infertile women. By analyzing the endometrium at late-secretory phase, we investigated the incidence and pathogenesis of decidualization failure among infertile women., Methods: Endometrial dating was performed on the endometria obtained in the late-secretory phase from 33 infertile women. Endometrial dating of more than 2 days delay was taken as an indication of decidualization failure. The expression of essential transcription factors for decidualization (FOXO1, WT1, and C/EBPβ) was examined by immunohistochemistry., Results: Among 32 cases, 20 cases (62.5%) showed decidualization failure. These patients tended to have a history of more frequent miscarriages than those without decidualization failure. The percentage of cells that immunostained positive for the expression of three transcription factors was significantly lower in the patients with decidualization failure than in those without decidualization failure. Serum progesterone levels measured in the mid- and late-secretory phase were not significantly different between the cases with and without decidualization failure., Conclusions: The incidence of decidualization failure is high in infertile women., Competing Interests: The authors declare no conflict of interest. Isao Tamura and Norihiro Sugino are Editorial Board members of Reproductive Medicine and Biology and co‐authors of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication., (© 2024 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Cardiovascular and cerebrovascular diseases (CCVD) are prominent mortality causes in Japan, necessitating effective preventative measures, early diagnosis, and treatment to mitigate their impact. A diagnostic model was developed to identify patients with ischemic heart disease (IHD), stroke, or both, using specific health examination data. Lifestyle habits affecting CCVD development were analyzed using five causal inference methods. This study included 473,734 patients aged ≥ 40 years who underwent specific health examinations in Kanazawa, Japan between 2009 and 2018 to collect data on basic physical information, lifestyle habits, and laboratory parameters such as diabetes, lipid metabolism, renal function, and liver function. Four machine learning algorithms were used: Random Forest, Logistic regression, Light Gradient Boosting Machine, and eXtreme-Gradient-Boosting (XGBoost). The XGBoost model exhibited superior area under the curve (AUC), with mean values of 0.770 (± 0.003), 0.758 (± 0.003), and 0.845 (± 0.005) for stroke, IHD, and CCVD, respectively. The results of the five causal inference analyses were summarized, and lifestyle behavior changes were observed after the onset of CCVD. A causal relationship from 'reduced mastication' to 'weight gain' was found for all causal species theory methods. This prediction algorithm can screen for asymptomatic myocardial ischemia and stroke. By selecting high-risk patients suspected of having CCVD, resources can be used more efficiently for secondary testing., (© 2024. The Author(s).)

Background: The clinical significance of nutrition and inflammation in dialysis patients is well established. This study aimed to evaluate the association between prognosis and indicators of nutrition and inflammation., Methods: A total of 253 consecutive patients who underwent peritoneal dialysis (PD) as primary renal replacement therapy at our institute between 2006 and 2021 were included. We retrospectively reviewed the patient's medical charts and obtained their clinical information. Nine nutritional and two inflammatory indicators were assessed. Patient outcomes were investigated, and predictive factors were explored., Results: The median age and follow-up period were 65 years and 54 months, respectively. Most nutritional indicators and C-reactive protein (CRP) levels showed a significant correlation with residual renal function. Multivariate analysis revealed that the survival index, nutritional risk index for Japanese hemodialysis patients, and CRP levels were independent indicators of patient survival (P < 0.001, P = 0.034, and P = 0.005, respectively) and cardiovascular disease-free survival (P = 0.009, P = 0.04, and P = 0.017, respectively). Patients with a survival index < 19 and CRP ≥ 0.5 had a high risk of mortality and cardiovascular death (P < 0.0001 and P = 0.0002, respectively)., Conclusions: Our findings suggest that indicators of nutrition and inflammation play important roles in predicting patient outcomes. Further research is warranted to establish optimal management strategies for patients on PD., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

11Beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) is a key enzyme involved in metabolic syndrome. Transcript-specific epigenetic regulation of the gene encoding 11β-HSD1 (HSD11B1) has been reported. We examined the mRNA level and methylation status of the HSD11B1 promoter region in the adipose tissue of patients with primary aldosteronism (PA). We compared 10 tissue specimens from patients with PA caused by aldosterone-producing adenoma (APA) with 8 adipose tissue specimens from patients with subclinical Cushing's syndrome (SCS) caused by cortisol-producing adenomas, 4 tissue specimens from patients with Cushing's adenoma (Cu), or 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). PA, SCS, and Cu were diagnosed according to the guideline of the Japan Endocrine Society. The mRNA level of HSD11B1 was quantified using real-time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific to the human HSD11B1 promoter region. The glycohemoglobin level was significantly higher in patients with APA, SCS, or Cu than in those with NFA (p < 0.05). Blood pressure was significantly higher in patients with APA than in those with SCS, Cu, or NFA (p < 0.01). The HSD11B1 mRNA level was significantly increased in the adipose tissues of APA or SCS patients compared with Cu or NFA patients (p < 0.05). The methylation ratio was significantly lower in SCS patients than in APA, Cu, or NFA patients (p < 0.05). HSD11B1 expression is partly controlled by an epigenetic mechanism in human tissues. The pathophysiological role of epigenetic regulation of HSD11B1 expression in adipose tissue requires further study.

Purpose: There are no definitive prognostic factors for patients with pathological Grade Group 5 (pGG 5) prostate cancer (PCa) undergoing robot-associated radical prostatectomy (RARP). This study aimed to explore the prognostic factors among patients with pGG 5 PCa in a large Japanese cohort (MSUG94)., Methods: This retrospective, multi-institutional cohort study was conducted between 2012 and 2021 at ten centers in Japan and included 3195 patients. Patients with clinically metastatic PCa (cN1 or cM1) and those receiving neoadjuvant and/or adjuvant therapy were excluded. Finally, 217 patients with pGG5 PCa were analyzed., Results: The median follow-up period was 28.0 months. The 3- and 5-year biochemical recurrence-free survival (BCRFS) rates of the overall population were 66.1% and 57.7%, respectively. The optimal threshold value (47.2%) for the percentage of positive cancer cores (PPCC) with any GG by systematic biopsy was chosen based on receiver operating characteristic curve analysis. Univariate analysis revealed that the prostate-specific antigen level at diagnosis, pT, pN, positive surgical margins (PSMs), lymphovascular invasion, and PPCC were independent prognostic factors for BCRFS. A multivariate analysis revealed that PSMs and PPCC were independent prognostic factors for BCRFS. Using these two predictors, we stratified BCRFS, metastasis-free survival (MFS), and castration-resistant PCa-free survival (CRPC-FS) among patients with pGG 5 PCa., Conclusion: The combination of PSMs and PPCC may be an important predictor of BCRFS, MFS, and CRPC-FS in patients with pGG 5 PCa undergoing RARP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV.

Competing Interests: Competing interests: None declared.

Objective: This study aimed to investigate whether lymphovascular invasion (LVI) was associated with oncological outcomes in patients with prostate cancer (PCa) undergoing robotic-assisted radical prostatectomy (RARP)., Methods: This retrospective multicenter cohort study was conducted on 3195 patients with PCa who underwent RARP in nine institutions in Japan. The primary endpoints were the associations between biochemical recurrence (BCR) and LVI and between BCR and clinicopathological covariates, while the secondary endpoints were the association between LVI and the site of clinical recurrence and metastasis-free survival (MFS)., Results: In total, 2608 patients met the inclusion criteria. At the end of the follow-up period, 311 patients (11.9%) were diagnosed with BCR and none died of PCa. In patients with pathological stage T2 (pT2) + negative resection margins (RM-), and pT3+ positive RM (RM+), LVI significantly worsened BCR-free survival (BRFS). For patients with PCa who had pT3 and RM+, the 2-year BRFS rate in those with LVI was significantly worse than in those without LVI. Patients with LVI had significantly worse MFS than those without LVI with respect to pT3, RM+, and pathological Gleason grade (pGG). In multivariate analysis, LVI was significantly associated with BRFS in patients with pT3 PCa, and with worse MFS in PCa patients with pT3, RM+, and pGG ≥ 4., Conclusions: LVI was an independent prognostic factor for recurrence and metastasis after RARP, particularly in patients with pT3 and RM+ PCa. Locally advanced PCa with positive LVI and RM+ requires careful follow-up because of the high likelihood of recurrence., (© 2024. Society of Surgical Oncology.)

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is crucial for patients with lung cancer harboring EGFR mutations. However, almost all patients experience disease progression, regardless of their response to the targeted therapy, necessitating the development of additional treatment options. Two patients with lung cancer harboring EGFR-L858R mutations in exon 21 were treated by surgical resection during successful osimertinib treatment. Because the pathological diagnosis was suspected to be pleural metastasis, osimertinib treatment was continued until disease progression. We analyzed the evolution of genomic alterations and the levels of AXL using tumor specimens obtained by repeated biopsies during the course of treatment: initial diagnosis, operation, and disease progression. Genetic alterations detected at the three time points were dramatically changed and showed reductions in numbers, while EGFR-L858R mutations were detected in all samples tested in both patients. Immunohistochemical expression of AXL remained positive from the beginning of analysis to disease progression. Clonal evolution under oncogenesis is related to gradual accumulation of genomic alterations during tumor growth. However, our case series revealed that volume reduction procedures may cause this phenomenon. Therefore, identification of intrinsic drug-resistant cells in tumors may be as important as detection of acquired genetic alterations., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Introduction: The extent to which the Big Five personality traits and subjective well-being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia-related neuropathology is unclear., Methods: Using data from eight independent studies (N total = 44,531; N dementia = 1703; baseline M age = 49 to 81 years, 26 to 61% female; M follow-up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia., Results: Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long-term dementia diagnosis. There were no consistent associations with neuropathology., Discussion: This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy., Highlights: N(+), C(-), E(-), PA(-), and NA(+) were associated with incident diagnosis. Results were consistent despite self-report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: Loneliness and social isolation are major public health concerns among older adults in Japan. Generativity, the concern for and commitment to future generations, may buffer older adults from loneliness. This study examined the cross-sectional and longitudinal associations between generativity and social asymmetry (the discrepancy between social isolation and loneliness) among older adults in Japan., Methods: Data were from 2 waves (2008 and 2012) of the Midlife in Japan survey, a nationally representative longitudinal study of 645 adults aged 30-79 residing in the Tokyo metropolitan area. Generativity was measured using the 6-item Loyola Generativity Scale. Social asymmetry was computed as the residual score from regressing loneliness onto social isolation., Results: Higher generativity levels were associated with lower social asymmetry scores (B=-0.21, SE=0.04), but generativity change across waves did not predict social asymmetry 4 years later (B=-0.04, SE=0.06)., Discussion: Generativity may play a protective role in buffering older adults from the adverse effects of social isolation on loneliness. Promoting generativity among older adults may be a potential intervention strategy to reduce loneliness and improve well-being in aging populations in Japan., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The remarkable performance of ChatGPT, launched in November 2022, has significantly impacted the field of natural language processing, inspiring the application of large language models as supportive tools in clinical practice and research worldwide. Although GPT-3.5 recently scored high on the United States Medical Licensing Examination, its performance on medical licensing examinations of other nations, especially non-English speaking nations, has not been sufficiently evaluated. This study assessed GPT's performance on the National Medical Licensing Examination (NMLE) in Japan and compared it with the actual minimal passing rate for this exam. In particular, the performances of both the GPT-3.5 and GPT-4 models were considered for the comparative analysis. We initially used the GPT models and several prompts for 290 questions without image data from the 116th NMLE (held in February 2022 in Japan) to maximize the performance for delivering correct answers and explanations of the questions. Thereafter, we tested the performance of the best GPT model (GPT-4) with optimized prompts on a dataset of 262 questions without images from the latest 117th NMLE (held in February 2023). The best model with the optimized prompts scored 82.7% for the essential questions and 77.2% for the basic and clinical questions, both of which sufficed the minimum passing scoring rates of 80.0% and 74.6%, respectively. After an exploratory analysis of 56 incorrect answers from the model, we identified the three major factors contributing to the generation of the incorrect answers-insufficient medical knowledge, information on Japan-specific medical system and guidelines, and mathematical errors. In conclusion, GPT-4 with our optimized prompts achieved a minimum passing scoring rate in the latest 117th NMLE in Japan. Beyond its original design of answering examination questions for humans, these artificial intelligence (AI) models can serve as one of the best "sidekicks" for solving problems and addressing the unmet needs in the medical and healthcare fields., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tanaka 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.)

To investigate the incidence and risk factors of inguinal hernia (IH) after robot-assisted radical prostatectomy (RARP) using a multicentric database. The present study used a multicentric database (the MSUG94) containing data on 3,195 Japanese patients undergoing RARP between 2012 and 2021. Surgical procedures utilized for IH prevention were as follows: isolation of the vas deferens, transection of the vas deferens, isolation of the spermatic vessels, and separation of the peritoneum from the internal inguinal ring. The primary and secondary endpoints were IH-free survival and any association between post-RARP IH and clinical covariates. The prophylactic effect of the above procedures were also assessed. IH prevention was attempted in 1,465 (46.4%) patients at five of the nine hospitals. During follow-up (median 24 months), post-RARP IH developed in 243 patients. The post-RARP IH-free survival rates at years 1, 2, and 3 were 94.3%, 91.7%, and 90.5%, respectively. Old age (hazard ratio [HR] 1.037; 95% confidence interval [CI] 1.014-1.061; p = 0.001), low BMI (HR 0.904; 95% CI 0.863-0.946: p < 0.001), and low hospital volume (HR 1.385; 95% CI 1.003-1.902; p = 0.048) were independently associated with IH development. None of the procedures for IH prevention were associated with IH development. Our findings may represent the current, real-world status of post-RARP IH in Japan. The prophylactic effects of the surgical procedures for IH prevention should be further investigated in well-designed, prospective studies to optimize the surgical technique., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Introduction: Individuals who have had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop post-coronavirus disease conditions, also known as long COVID. The symptoms of long COVID are nonspecific, and there are similarities between the symptoms of long COVID and those of Graves' disease (GD). Therefore, it is important to rule out GD in patients suspected of having long COVID. Telemedicine is widely used to avoid the risk of SARS-CoV-2 infection. However, owing to the lack of in-person examinations, diagnostic errors can occur., Case Description: A 27-year-old Japanese woman presented complaining of persistent fatigue, dyspnea, and low-grade fever, and after in-person examination was finally diagnosed with GD. She had been diagnosed with SARS-CoV-2 infection four months earlier and her symptoms had resolved within 5 days but then recurred. Subsequently, she had 3 telemedicine visits and had been diagnosed with long COVID., Discussion: With telemedicine there may be delayed diagnosis of GD in patients with a recent history of SARS-CoV-2 infection. Some symptoms and abnormalities cannot be confirmed in telemedicine visits performed using a simple mobile phone. Therefore it is important to know which findings obtained in telemedicine visits with a simple mobile phone are suggestive of GD. Low-grade fever and tachycardia are often observed in patients with GD, but rarely occur in patients with long COVID., Conclusion: Tachycardia and persistent low-grade fever after SARS-CoV-2 infection, which can be confirmed by telemedicine, can be clues for the diagnosis of GD. Therefore, in-person examination should be added if these symptoms are confirmed by telemedicine., Learning Points: The symptoms of Graves 'disease (GD) and long COVID may overlap.With telemedicine there may be delayed diagnosis of GD, in patients with recent history of severe acute respiratory syndrome mediated by coronavirus 2 (SARS-CoV-2) infections.In telemedicine visits, tachycardia and persistent low-grade fever could be clues for the diagnosis of GD after SARS-CoV-2 infections on telemedicine., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Background: Living kidney donors are evaluated to determine their physical and psychological suitability for transplantation and ensure their safety. During this process, we frequently encounter cases where a donor is found to be ineligible. In this study, we surveyed donors who are ineligible for transplantation at our hospital to educate patients, their families, and medical staff regarding transplantation in the future., Methods: We examined the proportion of ineligible donors among 237 potential donors who visited our hospital between January 2002 and March 2022. Data were collected retrospectively from electronic medical records and evaluated from various aspects such as age, body mass index, medical history, medications, and renal function., Results: The mean age at presentation was 55.5 years, the male-to-female ratio was 1:1.6, and no significant difference was found between the ineligible and eligible donor groups. The transplant ineligibility rate was 23.6%, and the categories were for medical, backout, immunologic, and recipient-related reasons, in descending order. Furthermore, a low glomerular filtration rate (GFR) was the most common cause of medical cases., Conclusions: Many patients were judged ineligible because of lifestyle-related diseases such as low GFR, diabetes mellitus, and obesity. Therefore, thorough patient education should be conducted using these data as a reference to reduce the number of donors ineligible because of lifestyle-related diseases., 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 © 2023 Elsevier Inc. All rights reserved.)

The development of generic pharmaceuticals involves a bioequivalence study to ensure the therapeutic equivalence of the test formulation to the original innovative product. The formulation characteristics of generic products are expected to be maintained in the long term after approval. This study analyzed the factors contributing to the changes in the dissolution profiles of approved products during their life cycles. Cumulative data on the dissolution similarity of 1675 products of 127 ingredients tested by official laboratories in Japan were assessed according to Japanese bioequivalence guidelines with slight modifications. The products showing dissimilarities in dissolution profiles were analyzed for reporting year, therapeutic category, co-development, physical properties of the active pharmaceutical ingredient (API), and suspected reasons for dissolution change. The increase in the number of dissimilar products is related to the co-development of generic products. Although the solubility of the API was not associated with the dissolution change in the analysis of the total dissolution data, control of the API particle size is suggested to be important for drugs with poorly soluble APIs. Additionally, a risk factor for dissolution changes in the test solutions at a certain pH was the presence of acidic or basic residues. These results indicate the importance of proper development through a thorough evaluation of the formulation and process factors affecting the dissolution properties throughout the product lifecycle.