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Objective: To examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population. Methods: We conducted a cross‐sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio‐demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self‐reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions. Result: OHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50–2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22–2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82–1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90–1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19–2.63), and dry mouth (PR, 2.79; 95% CI, 1.90–4.07) was higher among patients with RA than residents. Conclusion: Compared with the general older adult population, patients with RA have a higher prevalence of self‐reported OHF. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Dersimelagon is a novel, investigational, orally administered, selective agonist of the melanocortin‐1 receptor that has demonstrated efficacy at increasing symptom‐free light exposure and an acceptable safety profile in patients with protoporphyria. A phase 1 drug–drug interaction (DDI) study demonstrated that dersimelagon 300 mg has the potential for clinically relevant DDIs with drugs that are substrates for breast cancer resistance protein, such as atorvastatin and rosuvastatin. This study uses physiologically based pharmacokinetic (PBPK) modelling to further investigate the DDI effects at lower doses of dersimelagon with substrate drugs.The data from in silico, in vitro and in vivo studies were used to construct a PBPK model for dersimelagon to assess the DDI potential between dersimelagon and substrate drugs for cytochrome P450 3A, P‐glycoprotein, organic anion transporting polypeptide 1B1/1B3, organic anion transporter 3 and breast cancer resistance protein, including atorvastatin and rosuvastatin.The systemic exposure of atorvastatin based on the maximum plasma concentration and area under the plasma concentration–time curve was predicted to increase 1.21‐fold and 1.25‐fold, respectively, if coadministered with dersimelagon 100 mg, and 1.42‐fold and 1.45‐fold with dersimelagon 200 mg. The systemic exposure of rosuvastatin followed trends similar to atorvastatin (1.67‐fold and 1.34‐fold increase in maximum plasma concentration and area under the plasma concentration–time curve, respectively, with dersimelagon 100 mg, and 2.40‐fold and 1.69‐fold with dersimelagon 200 mg).Overall, PBPK modelling results indicate that the simulated changes in plasma exposure of atorvastatin and rosuvastatin following coadministration with dersimelagon 100 or 200 mg are not clinically significant, but caution and appropriate clinical monitoring should be recommended. [ABSTRACT FROM AUTHOR]

Polymerization‐induced phase separation takes place when a miscible component of the monomer becomes immiscible as the polymer is formed. One example is the polymerization of methyl methacrylate (MMA) in the presence of poly(ethylene glycol) (PEG). Depending on the initial conditions, microscopic structures, including porous structures, co‐continuous monolith structures, and particle aggregation structures, are obtained. In this study, the phase separation process is analyzed using an optical microscope and fluorescence microscope. The nucleation or spinodal decomposition in the initial stage, subsequent growth in the microscopic domains, and eventual fixation of the structure are observed. The observed images are analyzed using image analysis software. The particle number and the particle size as a function of reaction time are evaluated. Conversion and molecular weight distribution as a function of reaction time are also analyzed. [ABSTRACT FROM AUTHOR]

Aim: Protein‐energy wasting (PEW) is a common syndrome in patients undergoing haemodialysis (HD) and is associated with poor prognosis. Bioelectrical impedance analysis (BIA)‐derived phase angle (PA) is useful for predicting PEW, but sex and age need to be considered. We aimed to reveal sex‐specific cut‐off values of PA predicting PEW in HD patients aged ≥65. Methods: This two‐centre retrospective cohort study included patients on HD who underwent BIA. PEW was detected using the International Society of Renal Nutrition and Metabolism (ISRNM) criteria as a reference. The PA was measured using a multifrequency bioimpedance device. Sex‐specific cut‐off values of PA predicting PEW were detected by receiver‐operator characteristic analysis. We investigated the association between PEW determined using sex‐specific cut‐off values for PA and all‐cause mortality. Results: This study included 274 patients undergoing HD, with a median age of 75 (70–80) years, mean PA of 3.8 ± 1.1° and PEW of 43%. Over a median follow‐up duration of 1095 (400–1095) days, 111 patients died. Cut‐off values of PA predicting PEW were as follows: female, 3.00° (sensitivity, 87.3%; specificity, 77.5%), and male, 3.84° (sensitivity, 77.6%; specificity, 71.4%). The kappa coefficient between sex‐specific cut‐off values of the PA and ISRNM criteria had a moderate coincidence level of 0.55. PEW detected by PA was independently associated with all‐cause mortality (hazard ratio: 2.40; 95% confidence interval: 1.51–3.85; p <.001). Conclusions: Sex‐specific cut‐off values for PA in older HD patients may be useful as a screening tool for predicting PEW and mortality. [ABSTRACT FROM AUTHOR]

This article provides guidelines for qualified surgeons on endoscopic surgery procedures related to the stomach. It focuses on laparoscopic surgery for conditions such as gastroduodenal ulcer perforation, gastric gastrointestinal stromal tumor (GIST), gastric cancer, and gastric/esophagogastric junction cancer. The guidelines discuss the outcomes, benefits, and risks of these procedures, emphasizing the need for further research and skilled supervision. The article also mentions the use of laparoscopic gastric restrictive surgery for improving quality of life in Stage I gastric cancer patients and recommends laparoscopic gastric restrictive surgery and robotic gastrectomy for severe obesity and gastric cancer, respectively. It emphasizes the importance of adhering to specific criteria and requirements when performing these procedures. [Extracted from the article]

A 27‐year‐old nulliparous woman presented with a feeling of fullness in the lower abdomen and abdominal pain. A left ovarian tumor, uterus didelphys, left renal agenesis, and left vaginal atresia were observed on imaging. The ovarian tumor was presumed to have caused the abdominal pain, and an abdominal left adnexectomy was performed. After 3 months, she reported severe lower abdominal pain during menstruation. Transvaginal ultrasonography revealed uterine enlargement. After 17 days, the patient presented with abdominal pain and fever. She was diagnosed with peritonitis due to infection and left uterine hematometra. Because she did not improve with antibiotic treatment, left laparoscopic hysterectomy was performed. Subsequently, she did not experience the lower abdominal pain. Appropriate diagnosis and treatment based on the morphology of the reproductive tract and symptoms must be considered in patients with Herlyn–Werner–Wunderlich syndrome. Treatment must permit the outflow of menstrual blood. [ABSTRACT FROM AUTHOR]

Aims Methods and Results Conclusion The PEComa family of tumours is defined by spindle/epithelioid cells with myomelanocytic differentiation. A small subset harbours TFE3 fusion; however, YAP1::TEE3 has not been reported. Clear cell stromal tumour of the lung (CCST‐L) is an emerging entity characterized by spindle to epithelioid cells with focal cytoplasmic clearing, inflammatory infiltrates, no myomelanocytic differentiation, and YAP1::TFE3 fusion. Herein, we report two cases of lung tumours with myomelanocytic differentiation that showed inflammatory spindle cell histology, focal epithelioid clear cells, as well as YAP1::TFE3 fusion.The patients were both men, aged 61 and 68 years. The tumours in both cases presented as well‐circumscribed solid masses involving the lung hilum. After lobectomy, no recurrence was observed at 7 and 32 months. Both tumours shared storiform to short fascicular growth of long spindle cells, with a minor component of epithelioid cells showing clear cytoplasm in the background of substantial intratumoral chronic inflammation and dilated blood vessels. One tumour showed focal melanin deposition. Both tumours were immunohistochemically positive for HMB45, Melan A, and h‐caldesmon. Fluorescence in situ hybridization assays indicated the presence of YAP1::TFE3 fusions, which was confirmed by RNA sequencing in one case tested, and by immunohistochemical TFE3 expression and loss of YAP1 C‐terminus staining.We present two cases of inflammatory spindle to epithelioid cell tumours of the lungs with myomelanocytic differentiation and YAP1::TFE3 fusion. This unique morphology and gene fusion suggest that these tumours may constitute a distinct subset of lung PEComa. Furthermore, morphological and molecular overlap with CCST‐L gives rise to a hypothesis of a potential inherent relationship between PEComa and CCST‐L. [ABSTRACT FROM AUTHOR]

Understanding the mechanism by which non‐native fish species integrate into native communities is crucial for evaluating the possibility of their establishment success. The genus Pangasianodon, comprising Pangasianodon gigas and Pangasianodon hypophthalmus, has been introduced into reservoirs, which are non‐native habitats, for fishery stock enhancement. P. gigas and P. hypophthalmus often successfully establish and co‐occur in several Thai reservoirs, but there is little information on differences in food resource use between the two species. To investigate the trophic niche width of P. gigas and P. hypophthalmus in a Thai reservoir, we conducted stable carbon and nitrogen ratio (δ13C and δ15N) analyses. We examined the degree of individual specialization in both species using the δ13C and δ15N values of muscle and liver tissues, which provides long‐ and short‐term diet information. The isotopic niches did not overlap between P. gigas and P. hypophthalmus. The δ15N value of P. gigas was significantly higher than that of P. hypophthalmus, whereas the δ13C value did not significantly differ between the two species. The isotopic niche sizes were larger in P. hypophthalmus than in P. gigas. Individual specialization was observed in P. hypophthalmus but not in P. gigas, indicating that intraspecific variation in food resource use was larger in P. hypophthalmus compared to P. gigas. These findings suggest that trophic niche partitioning was one of the factors facilitating the establishment success of P. gigas and P. hypophthalmus in a reservoir, but the establishment process may differ between the two species. [ABSTRACT FROM AUTHOR]

Aim: In March 2021, the Japanese Ministry of Health, Labour and Welfare revised the optimal gestational weight gain standards. In this study, we examined whether this revision affected gestational weight gain and low birth weight rates. Methods: We analyzed the records of singleton pregnant women who underwent checkups from their 1st trimester and delivered at our institute after 37 weeks between 2020 and 2021 (before the revision) and between 2022 and 2023 (after the revision). Pregnancy outcomes were assessed in the following four groups stratified by pre‐pregnancy body mass index (BMI): underweight (BMI: <18.5 kg/m2), normal‐weight (BMI: 18.5–24.9 kg/m2), overweight (BMI: 25–29.9 kg/m2), and obese (BMI: ≥30 kg/m2). Leaflets on the optimal gestational weight gain standards for each group were distributed to all pregnant women at the first prenatal checkup. Results: In each group, gestational weight gain did not change before and after the revision, with the corresponding values of 10.8 kg and 11.1 kg in the underweight (p = 0.94), 10.7 kg and 10.4 kg in the normal weight (p = 0.14), 9.7 kg and 9.2 kg in the overweight (p = 0.32), and 7.4 kg and 6.7 kg in the obese (p = 0.44) groups. Furthermore, the prevalence of low birth weight did not decrease in all groups. Conclusions: No significant differences in gestational weight gain or low birth weight were observed after the revision of the 2021 gestational weight gain recommendations. Merely distributing leaflets to pregnant women may not be sufficient to improve gestational weight gain or reduce low birth weight rates. [ABSTRACT FROM AUTHOR]

Austocystin D is a natural compound that induces cytochrome P450 (CYP) monooxygenase‐dependent DNA damage and growth inhibition in certain cancer cell lines. Cancer cells exhibiting higher sensitivity to austocystin D often display elevated CYP2J2 expression. However, the essentiality and the role of CYP2J2 for the cytotoxicity of this compound remain unclear. In this study, we demonstrate that CYP2J2 depletion alleviates austocystin D sensitivity and DNA damage induction, while CYP2J2 overexpression enhances them. Moreover, the investigation into genes involved in austocystin D cytotoxicity identified POR and PGRMC1, positive regulators for CYP activity, and KAT7, a histone acetyltransferase. Through genetic manipulation and analysis of multiomics data, we elucidated a role for KAT7 in CYP2J2 transcriptional regulation. These findings strongly suggest that CYP2J2 is crucial for austocystin D metabolism and its subsequent cytotoxic effects. The potential use of austocystin D as a therapeutic prodrug is underscored, particularly in cancers where elevated CYP2J2 expression serves as a biomarker. [ABSTRACT FROM AUTHOR]

Researchers have attempted to identify the factors involved in lymph node recurrence in cT1‐2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1‐2, N0 (cT1‐2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information. A dataset from 148 patients with cT1‐2N0 tongue SCC was divided into training and test sets. The prediction models were constructed using AI‐extracted information from whole slide images (WSIs), human‐assessed clinicopathological information, and both combined. Weakly supervised learning and machine learning algorithms were used for WSIs and clinicopathological information, respectively. The combination model utilised both algorithms. Highly predictive patches from the model were analysed for histopathological features. In the test set, the areas under the receiver operating characteristic (ROC) curve for the model using WSI, clinicopathological information, and both combined were 0.826, 0.835, and 0.991, respectively. The highest area under the ROC curve was achieved with the model combining WSI and clinicopathological factors. Histopathological feature analysis showed that highly predicted patches extracted from recurrence cases exhibited significantly more tumour cells, inflammatory cells, and muscle content compared with non‐recurrence cases. Moreover, patches with mixed inflammatory cells, tumour cells, and muscle were significantly more prevalent in recurrence versus non‐recurrence cases. The model integrating AI‐extracted histopathological and human‐assessed clinicopathological information demonstrated high accuracy in predicting lymph node recurrence in patients with cT1‐2N0 tongue SCC. [ABSTRACT FROM AUTHOR]

Certain guidelines recommend a second‐generation H1‐antihistamine (AH) as first‐line treatment for patients with chronic urticaria (CU). However, some patients show insufficient response to a standard dose of this therapy and might benefit from adding leukotriene receptor antagonists (LTA). Therefore, we aimed to perform a systematic review and meta‐analysis comparing LTA plus antihistamines with antihistamines alone. We performed a systematic review and meta‐analysis, searching PubMed, EMBASE, and Cochrane Central for randomized clinical trial (RCT) data comparing LTA plus AH treatment to AH alone in patients with CU. Statistical analysis was performed using R Studio 4.3.2. Heterogeneity was assessed with I2 statistics. Three studies comprising 234 patients with urticaria were included. The mean age was 37.23 years in the leukotriene antagonist + antihistamines (LTA + AH) group and 39.14 years in the antihistamines (AH) group. Follow‐up ranged from 2 to 18 months between studies. There was no statistically significant difference between groups in terms of TSS level (SMD: −74.82; 95% CI: −222.66 to 73.02; P = 0.32; I2 = 98%), neither in terms of pruritus (MD: −0.07; 95% CI: −0.42 to 0.28; P = 0.70; I2 = 74%). After sensitivity analysis, with the systematic exclusion of each study from the grouped estimates, the result for TSS level did not change. These findings suggest that leukotriene receptor antagonists with antihistamines do not have better outcomes than antihistamines alone regarding TSS and pruritus in patients with CU. [ABSTRACT FROM AUTHOR]

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo‐electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population. [ABSTRACT FROM AUTHOR]

Aim: To assess the impact of perioperative prognostic nutritional index (PNI) changes on prognosis and recurrence after colorectal cancer surgery. Methods: A total of 475 patients who underwent curative resection for primary colorectal adenocarcinoma and were diagnosed with pathological stage (pStage) II/III were retrospectively reviewed. The patients were divided into two groups: the high group (preoperative PNI ≤ postoperative PNI, n = 290) and the low group (preoperative PNI > postoperative PNI, n = 185). Results: The low group exhibited significantly higher recurrence and mortality rates (all p < 0.001). Kaplan–Meier analysis showed worse overall and recurrence‐free survival in the low group (all p < 0.001). Perioperative PNI changes predicted prognosis and recurrence independent of preoperative nutritional conditions. Subgroup analyses showed better overall survival and recurrence‐free survival in the high group across various parameters, such as patient background, surgical outcomes, adjuvant chemotherapy, and pathological characteristics. Multivariate analysis revealed that the low group based on perioperative PNI changes (hazard ratio [HR]: 5.809, 95% confidence interval [CI]: 3.451–9.779, p < 0.001), pathological T stage (HR: 1.962, 95% CI: 1.184–3.253, p = 0.009), and pathological N stage (HR: 3.434, 95% CI: 1.964–6.004, p < 0.001) were identified as independent predictors of worse overall survival. Conclusions: Patients with pStage II/III colorectal cancer who demonstrate a lower postoperative PNI levels compared to preoperative had poorer overall survival and recurrence‐free survival. Perioperative PNI changes can serve as useful biomarkers for predicting survival and recurrence. [ABSTRACT FROM AUTHOR]

Most elements of filamentous fungi seen in human tissue by pathologists are hyphae, and encountering other elements may interfere with diagnosis. Sporangia and chlamydospores are such elements that have been described in only a few case reports. We present an autopsy case with the extremely rare coexistence of Mucorales sporangia and chlamydospores in the lung. These fungal elements must be recognized and identified accurately because they can easily be mistaken for other fungi, microorganisms, or degenerated tissue structures. [ABSTRACT FROM AUTHOR]

This work investigated in‐situ synthesis of porous silica‐nickel‐ruthenium composite catalysts for hydrolysis of ammonia borane. The precursors were prepared with an anionic surfactant, sodium dodecyl sulfate (SDS), to form porous structure in the precursor particles, and the precursors was treated in aqueous solution including sodium borohydride and ammonia borane for in‐situ process to parallelly activate and use the catalysts for hydrolysis of ammonia borane. The result of TEM and nitrogen sorption measurements suggested that the primary particle size of the in‐situ synthesized catalysts decrease with increasing the amount of SDS and sodium chloride as the additive for controlling the primary particle size probably because of the effect of sodium ions to inhibit nuclei growth of the primary particles. From the EDS analyses, the composition of active nickel and ruthenium contents increased with increasing the amount of SDS and sodium chloride except for the highest amount of SDS probably because of adsorption of the metal cations with the excess amount of the surfactant anion to decrease the amount of the metal cations including the catalyst. The in‐situ synthesized catalyst including small size primary particles and high nickel and ruthenium content tended to exhibit high activity for hydrolysis of ammonia borane. [ABSTRACT FROM AUTHOR]

Introduction: An investigation of the suitability of reagents for measuring FVIII products in a one‐stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII‐deficient plasma (F8DP), even though the APTT‐based OSA is comprised of APTT reagents and factor‐deficient plasma. Aim: A single‐centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. Methods: FVIII:C in nine types of FVIII product‐spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. Results: F8DP‐dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP‐3). This lower TR was not observed with alternative manufacturing lots of F8DP‐3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP‐3. Conclusion: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur. [ABSTRACT FROM AUTHOR]

Background and Aim: Neutrophil gelatinase‐associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. Methods: This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. Results: Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child–Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. Conclusion: Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Although metabolic dysfunction‐associated steatotic liver disease (MASLD) patients with a Fib‐4 index >1.3 are recommended for fibrosis evaluation via elastography or biopsy, a more convenient method identifying high‐risk populations requiring follow‐up is needed. We explored the utility of serum levels of growth differentiation factor‐15 (GDF15), a cell stress‐responsive cytokine related to metabolic syndrome, for stratifying the risk of clinical events in MASLD patients. Methods: Serum GDF15 levels were measured in 518 biopsy‐performed MASLD patients, 216 MASLD patients for validation, and 361 health checkup recipients with MASLD. Results: In the biopsy‐MASLD cohort, multivariate analysis indicated that the serum GDF15 level was a risk factor for liver cancer, independent of the fibrosis stage or Fib‐4 index. Using a GDF15 cutoff of 1.75 ng/mL based on the Youden index, high‐GDF15 patients, regardless of fibrosis status, had a higher liver cancer incidence rate. While patients with a Fib‐4 index <1.3 or low‐GDF15 rarely developed liver cancer, high‐GDF15 patients with a Fib‐4 index >1.3 developed liver cancer and decompensated liver events at significantly higher rates and had poorer prognoses. In the validation cohort, high‐GDF15 patients had significantly higher incidences of liver cancer and decompensated liver events and poorer prognoses than low‐GDF15 patients, whether limited to high‐Fib‐4 patients. Among health checkup recipients with MASLD, 23.0% had a Fib‐4 index >1.3, 2.7% had a Fib‐4 index >1.3 and >1.75 ng/mL GDF15. Conclusions: Serum GDF15 is a biomarker for liver cancer with high predictive capability and is useful for identifying MASLD patients requiring regular surveillance. [ABSTRACT FROM AUTHOR]

Background: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. Methods: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. Results: Two‐hundred and thirty‐two patients were included. Comparing patients with and without adjuvant radiotherapy, 3‐year regional recurrence‐free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3‐year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). Conclusions: In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow‐up is necessary if the primary lesion is T2 or greater. [ABSTRACT FROM AUTHOR]

Aims: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission. Methods and results: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all‐cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non‐fatal myocardial infarction, or non‐fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow‐up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m2, a history of malignancy, and non‐use of angiotensin‐converting enzyme inhibitors at discharge. The cumulative incidence of all‐cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all‐cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33–4.39, P = 0.004). Conclusions: Utilizing real‐world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all‐cause mortality rates. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the significance of background noise in machine learning models assessing the GRBAS scale for voice disorders. Methods: A dataset of 1406 voice samples was collected from retrospective data, and a 5‐layer 1D convolutional neural network (CNN) model was constructed using TensorFlow. The dataset was divided into training, validation, and test data. Gaussian noise was added to test samples at various intensities to assess the model's noise resilience. The model's performance was evaluated using accuracy, F1 score, and quadratic weighted Cohen's kappa score. Results: The model's performance on the GRBAS scale generally declined with increasing noise intensities. For the G scale, accuracy dropped from 70.9% (original) to 8.5% (at the highest noise), F1 score from 69.2% to 1.3%, and Cohen's kappa from 0.679 to 0.0. Similar declines were observed for the remaining RBAS components. Conclusion: The model's performance was affected by background noise, with substantial decreases in evaluation metrics as noise levels intensified. Future research should explore noise‐tolerant techniques, such as data augmentation, to improve the model's noise resilience in real‐world settings. Level of Evidence: This study evaluates a machine learning model using a single dataset without comparative controls. Given its non‐comparative design and specific focus, it aligns with Level 4 evidence (Case‐series) under the 2011 OCEBM guidelines Laryngoscope, 134:3537–3541, 2024 [ABSTRACT FROM AUTHOR]

Multi‐family therapy for children and adolescents with anorexia nervosa (MFT‐AN) draws on the same principles as family therapy for AN (FT‐AN), but is delivered in a more intensive format to help families overcome a sense of isolation and stigmatisation and to maximise their own resources. In Japan, the main treatment for AN is inpatient care, and family‐based treatment that is based on the practice at the Maudsley Hospital in the 1980s has started to be introduced at an inpatient level in Japan. MFT‐AN could offer more opportunities to practice managing AN symptoms and reduce the family's anxiety. It may also act as a step‐down intervention during transition from inpatient to outpatient care or a step‐up in intensity if outpatient treatment is stalling. This article reports on MFT‐AN's theoretical underpinnings, the current Japanese eating disorder treatment context, and the way MFT‐AN may be adapted for the unique Japanese socio‐cultural context. [ABSTRACT FROM AUTHOR]

To improve the dielectric strength in vacuum, spark conditioning through repetitive breakdowns by AC or impulse voltage is an effective method. AC conditioning at commercial power frequencies has been widely used due to its cost‐effectiveness, but the breakdown voltage after AC conditioning is generally lower compared to impulse conditioning. We have confirmed that multiple breakdowns occur successively in a half cycle of AC voltage application. It is considered that the multiple breakdowns are harmful for conditioning and triggered due to the previous breakdown in the same half cycle. In this paper, we discuss dielectric strength improvement by high frequency AC conditioning and how the multiple breakdowns are induced. We experimentally confirmed that the AC conditioning effect is improved by increasing the frequency of AC voltage for different applied AC conditioning voltages in a sphere‐plane electrode system. We focused on the breakdown position from the light emission images during AC conditioning to investigate whether the multiple breakdowns were induced or affected by the previous breakdown. We found that the multiple breakdowns occurred close to the previous breakdown position. The multiple breakdowns would be induced by the collision of metal particles due to the previous breakdown with the counter electrode. These breakdowns do not contribute to removing protrusion and would lead to damage to the electrode surface. The increasing frequency of AC conditioning would suppress the multiple breakdowns and improve the dielectric strength in vacuum. © 2024 The Author(s). IEEJ Transactions on Electrical and Electronic Engineering published by Institute of Electrical Engineers of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Objectives: To examine the prognosis of lower urinary tract symptoms and function after robot‐assisted radical prostatectomy (RARP) in patients with low preoperative bladder contractility. Methods: A total of 115 patients who underwent RARP were enrolled and divided into two groups by preoperative urodynamic findings: normal (patients with bladder contractility index [BCI] ≥ 100; n = 70) and low contractility (patients with BCI < 100; n = 45) groups. Lower urinary tract symptoms and function parameters were prospectively evaluated at 1, 3, 6, 9, and 12 months after RARP in both groups. Results: International Prostatic Symptom Score voiding scores 1, 3, 6, 9, and 12 months after RARP were significantly higher (p < 0.05), and the maximum flow rate (Qmax) values before and 1, 3, 9, and 12 months after RARP were significantly lower in the low contractility group (p < 0.05). Comparing preoperative and postoperative parameters, IPSS voiding scores in the normal contractility group were significantly improved from 6 months after RARP, whereas those in the low contractility group were almost unchanged. Qmax and the 1‐h pad test in both groups temporarily deteriorated 1 month after RARP, whereas voided volume and postvoiding residual volume significantly decreased from 1 to 12 months after RARP. Conclusions: This observational study showed that patients with low preoperative bladder contractility might have a weak improvement in voiding symptoms and function after RARP. [ABSTRACT FROM AUTHOR]

Background: Veno‐arterial extracorporeal membrane oxygenation (V‐A ECMO) is increasingly utilized in pediatric patients. Failure to recognize membrane oxygenator failure can lead to critical complications due to rapid deterioration of membrane oxygenator function. Therefore, identifying the predictors for membrane oxygenator exchange is crucial. However, risk factors for membrane oxygenator exchange in pediatric V‐A ECMO remain unclear; therefore, this study aimed to evaluate these risk factors. Methods: This retrospective cohort study enrolled all pediatric patients aged <18 years who received V‐A ECMO between August 2018 and July 2023 at a tertiary‐care pediatric hospital in Japan. The Cox proportional hazards model was used to evaluate the predictors of membrane oxygenator failure within 72 h after initiation. Results: During the study period, membrane oxygenator failure occurred in 18/55 (32.7%) children within 72 h; membrane oxygenator failure within 72 h occurred in 4/29 (13.8%) and 14/26 (53.8%) in the groups with ratio of blood flow divided by the blood flow limit of the membrane oxygenator (B/L) of <0.5 and ≥0.5, respectively (adjusted hazards ratio, 4.97 [95% confidence interval, 1.33–18.5]; p = 0.017). After adjusting for delta pressure of the oxygenator, an increase in body weight and aspartate aminotransferase levels were associated with an increase in early membrane oxygenator failure. Conclusions: This retrospective study demonstrated that a B/L ratio >0.5, an increase in body weight, and elevated aspartate aminotransferase were independent risk factors for early membrane oxygenator failure in pediatric V‐A ECMO. However, a prospective multicenter study with an appropriate sample size is warranted to mitigate potential bias, and enhance generalizability for further investigation of the association between a B/L ratio and early membrane oxygenator failure. [ABSTRACT FROM AUTHOR]

We proposed a current‐biased kinetic inductance detector (CB‐KID) as a novel superconducting detector to construct a neutron transmission imager. The characteristics of a superconducting neutron detector have been systematically studied to improve a spatial resolution down to 10μm$$ \upmu \mathrm{m} $$ in transmission imaging. In this study, we report the application of the energy‐resolving neutron imaging to investigate major components of materials by analyzing neutron transmission spectra from 1 meV to 500 keV. We succeeded in identifying that copper (Cu) and iron (Fe) are major components respectively in commercial nuts and screws as test samples with the aid of Rietveld imaging of transmission spectra (RITS) program in analyzing transmission spectra in longer wavelengths. The Ti screw was also confirmed by comparing the nuclear resonance absorption measurements and simulations in high‐energy regions. We demonstrated that our superconducting neutron detector is applicable to reveal the transmission spectra in the wide range from cold‐neutron energies ∼meV$$ \sim \mathrm{meV} $$ to higher neutron energies even up to 500 keV. By selecting distinctive energy regions of pulsed neutrons, we succeeded in mapping the distribution of SmSn3 compound using the strong neutron absorption in samarium (Sm) and the selective nuclear‐resonance dips in Sm. By taking advantage of using CB‐KID in conducting neutron imaging, the CB‐KID method is extensively useful for various purposes in material sciences through energy‐selective neutron spectroscopy from 1 meV to 500 keV. © 2024 Institute of Electrical Engineers of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Polar 2D macromolecular structures have attracted significant attention because of their ferroelectricity and ferro‐magnetism. However, it is challenging to synthesize them experimentally because dipoles or spins of these macromolecules tend to cancel each other. So far, there has been no successful strategy for assembling macromolecules in a unidirectional manner, achieving stereoregular polymerization on metal surfaces, and creating polar 2D polymer crystals. Recent progress in molecular assembly, on‐surface polymer synthesis, and direct control of molecules using electric field applications provides an opportunity to develop such strategies. In this regard, we first review past studies on chiral and achiral molecular assembly, on‐surface polymer synthesis, and orientation control of polar molecules. Then, we discuss our newly developed approach called "vectorial on‐surface synthesis", which is based on "dynamic chirality" of compass precursors, stereoselective polymerization, and favorable interchain interactions originating from CH‐π interactions. Finally, we conclude with a prospective outlook. [ABSTRACT FROM AUTHOR]

Background: Previous studies have highlighted a decline in the mental health of older adults over the course of the coronavirus disease 2019 (COVID‐19) pandemic. Few studies have determined the possible causes of behavioural and psychological symptoms of dementia during COVID‐19 in a comprehensive manner. We aimed to identify the challenges faced by older adults with dementia during the COVID‐19 pandemic. Methods: This study adopted a qualitative approach to understanding the perceptions of healthcare professionals, such as regarding the negative effects of COVID‐19 on the mental health of people with dementia. Between January and March 2022, the authors conducted individual in‐depth interviews on how COVID‐19 affected the stress levels, care, and self‐determination of people with dementia. Qualitative data from the individual interviews were data cleansed to ensure the clarity and readability of the transcripts. The qualitative data were then analyzed by inductive manual coding using a qualitative content analysis approach. The grouping process involved reading and comparing individual labels to cluster similar labels into categories and inductively formulate themes. Results: Qualitative analysis extracted 61 different semantic units that were duplicated. Seven categories were inductively extracted using a grouping process. These were further integrated to extract the following four themes: fear of personal protective equipment (PPE), loneliness, dissatisfaction with behavioural restrictions and limitations of video calls, and family interference with service use. Discussion: People with dementia often faced mental distress during the pandemic owing to preventive measures against COVID‐19, and a lack of awareness and understanding of such preventive measures worsened their distress. They experienced a severe sense of social isolation and loneliness. Findings also indicated that families tended to ignore the needs of people with dementia and their decisions and opinions regarding healthcare service use. [ABSTRACT FROM AUTHOR]

Backgrounds: Pancreatojejunostomy is a technically demanding procedure during robotic pancreaticoduodenectomy (RPD). Modified Blumgart anastomosis (mBA) is a common method for the pancreatojejunostomy; however, the technical details for robotic mBA are not well established. During RPD, we performed a mBA for the pancreatojejunostomy using thread manipulation with gauze and an additional assist port. Methods: Patients who underwent robotic pancreatoduodenectomy at Fujita Health University from November 2009 to May 2023 were retrospectively investigated, and technical details for the robotic‐modified Blumgart anastomosis were demonstrated. Results: Among 78 patients who underwent RPD during the study period, 33 underwent robotic mBA. Postoperative pancreatic fistula (POPF) occurred in six patients (18%). None of the patients suffered POPF Grade C according to the international study group of pancreatic surgery definition. The anastomotic time for mBA was 80 min (54–125 min). Conclusion: Robotic mBA resulted in reasonable outcomes. We propose that mBA could be used as one of the standard methods for robotic pancreatojejunosotomy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To detect early cognitive impairment in community‐dwelling older adults, this study explored the viability of artificial intelligence (AI)‐assisted linear acceleration and angular velocity analysis during walking. METHODS: This cross‐sectional study included 879 participants without dementia (female, 60.6%; mean age, 73.5 years) from the 2011 Comprehensive Gerontology Survey. Sensors attached to the pelvis and left ankle recorded the triaxial linear acceleration and angular velocity while the participants walked at a comfortable speed. Cognitive impairment was determined using Mini‐Mental State Examination scores. Deep learning models were used to discern the linear acceleration and angular velocity data of 12,302 walking strides. RESULTS: The models' average sensitivity, specificity, and area under the curve were 0.961, 0.643, and 0.833, respectively, across 30 testing datasets. DISCUSSION: AI‐enabled gait analysis can be used to detect signs of cognitive impairment. Integrating this AI model into smartphones may help detect dementia early, facilitating better prevention. Highlights: Artificial intelligence (AI)‐enabled gait analysis can be used to detect the early signs of cognitive decline.This AI model was constructed using data from a community‐dwelling cohort.AI‐assisted linear acceleration and angular velocity analysis during gait was used.The model may help in early detection of dementia. [ABSTRACT FROM AUTHOR]

Situs inversus complicates diagnosis and treatment due to the mirrored organ placement in relation to normal anatomy. This report describes a 78‐year‐old female patient with situs inversus totalis who underwent laparoscopic cholecystectomy and laparoscopic common bile duct exploration for cholecystolithiasis and choledocholithiasis. Utilizing the "French mirror technique" for port placement, the surgeon adeptly mirrored standard maneuvers with a 2‐mm needle forceps in the left hand and a 5‐mm forceps in the right in a reversed anatomical setting. This technique maintained familiar hand movements, despite the patient's unique anatomy. The surgeon applied transcystic ductal bile duct exploration, using choledochoscopy for duct exploration and a basket catheter for stone removal. Laparoscopic cholecystectomy and common bile duct exploration through the transcystic ductal route are viable and effective for patients with situs inversus. [ABSTRACT FROM AUTHOR]

A synthetic method for preparation of optically active trifluoromethylthio (SCF3) compounds by a copper‐catalyzed regio‐ and enantioselective hydroboration of 1‐trifluoromethylthioalkenes with H‐Bpin has been developed. The enantioselective hydrocupration of an in situ generated CuH species and subsequent boration reaction generate a chiral SCF3‐containing alkylboronate, of which Bpin moiety can be further transformed to deliver various optically active SCF3 molecules. Computational studies suggest that the SCF3 group successfully controls the regioselectivity in the reaction. [ABSTRACT FROM AUTHOR]

A proposal to change the conserved type of Ipomoea was published in December 2020, and recommended by the Nomenclature Committee in 2023. This was done in the light of the possible negative consequences for a name change in the crop sweetpotato, which risk our proposal would significantly minimize. Recently, Muñoz‐Rodríguez & al. have published a rebuttal to this proposal, which we respond to here. The objections raised by these authors focus as much on the expertise and credibility of our group of authors as on the merits of our arguments. In this "rebuttal to the rebuttal", we respond to the scientific questions raised, highlight demonstrated misinterpretation of the specialised literature relevant to this discussion and counter the assertion that a reclassification of Ipomoeeae is impossible given existing evidence. While the currently recognised genera of Ipomoeeae are not all monophyletic, the proposal to change the conserved type of Ipomoea is a necessary step that will allow exploring an improved classification for the tribe Ipomoeeae, either in the form of a better recircumscription of the genera or an efficient infrageneric classification for Ipomoea. Previously published literature has not advocated for the integration of all genera into a single genus, as Muñoz‐Rodríguez and co‐authors have incorrectly suggested, and instead have recommended a reanalysis of the high morphological diversity of the group in the context of expanded phylogenetic studies, with the possible maintenance of some of the existing genera. We believe that, in a concerted collaborative approach and with the contribution of experts from different regions and scientific backgrounds, an improved classification of Ipomoeeae that integrates the principles of monophyly and diagnosability may soon be achieved, and until when some uncertainty may need to be accommodated, with the added reassurance that, regardless of the direction of future systematic rearrangements, the stability of the scientific name of sweetpotato would be preserved. [ABSTRACT FROM AUTHOR]

Daphnia magna is a test organism used for ecological risk assessments of pesticides, but little is known about the expression levels of cytochrome P450s (CYP)s and their changes after pesticide exposure in the less than 24‐h‐olds used for ecotoxicity tests. In this study, D. magna juveniles were exposed to 0.2 μg/L of chlorpyrifos under the conditions for acute immobilization test as specified by the OECD test guideline for 24 h, and then the gene expression was compared between the control and chlorpyrifos‐exposure groups by RNA‐sequencing analysis, with a focus on CYP genes. Among 38 CYP genes expressed in the control group, seven were significantly up‐regulated while two were significantly down‐regulated in the chlorpyrifos‐exposure group. Although the sublethal concentration of chlorpyrifos did not change their expression levels so drastically (0.8 < fold change < 2.6), CY360A8 of D. magna (DmCYP360A8), which had been proposed to be responsible for metabolism of xenobiotics, was abundantly expressed in controls yet up‐regulated by chlorpyrifos. Therefore, homology modeling of DmCYP360A8 was performed based on the amino acid sequence, and then molecular docking simulations with the insecticides that were indicated to be metabolized by CYPs in D. magna were conducted. The results indicated that DmCYP360A8 could contribute to the metabolism of diazinon and chlorfenapyr but not chlorpyrifos. These findings suggest that chlorpyrifos is probably detoxified by other CYP(s) including up‐regulated and/or constitutively expressed one(s). [ABSTRACT FROM AUTHOR]

Background and Aim: The use of a hood at the tip of a colonoscope enables aspiration, inversion of the diverticulum, and observation of the inside of the diverticulum. In most previous studies, a short hood was used; however, observation of the diverticulum is often inadequate. Long food is promising by previous research, but it was a retrospective study using propensity matching and has some limitations. We compared the identification rate of stigmata of recent hemorrhage (SRH) between the long and standard hoods in cases of suspected colonic diverticular hemorrhage (CDH) to confirm the usefulness of long hood by prospective randomized controlled trial. Methods: Eighty patients (42 in the long hood group [L group] and 38 in the short hood group [S group]) who visited the Saitama Medical University Hospital and Tokai University Hachioji Hospital between December 2018 and July 2021 with a chief complaint of bloody stool and suspected CDH, based on the clinical course and imaging studies, were included. Patients were randomly assigned to the L or S group. Results: Regarding patient background, age was significantly higher in the L group; however, no significant differences were found in medical history or history of antithrombotic medication or nonsteroidal anti‐inflammatory drug use. Identification rate of SRH was significantly higher in the L group (58.5%, 24/42 patients) than in the S group (26.3%, 10/38 patients) (P < 0.05). All patients were treated using the clip method, and the rate of rebleeding within 1 month was not significantly different between the two groups. Conclusion: A long hood was more useful compared with a short hood in identifying SRH of CDH (UMIN000034603). [ABSTRACT FROM AUTHOR]

A recent meta‐analysis found no benefit of uric acid‐lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65–74 years and ≥ 75 years. Patients were randomized into febuxostat and non‐febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non‐fatal cerebral and cardiovascular events and all‐cause death. Patients aged ≥ 75 years exhibited more pre‐existing factors associated with cerebral and cardiorenovascular events than those aged 65–74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65–74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use. [ABSTRACT FROM AUTHOR]

We have analyzed Electrostatic Electron Cyclotron Harmonic (ECH) waves observed using interferometry observation mode performed by the Arase satellite to estimate low‐energy electron temperatures. Interferometry can be used to calculate velocities, but the Arase satellite can only perform interferometry observations in a one‐dimensional direction. We proposed a method to estimate the wave vector of the observed ECH waves from the observed electric fields and calculated the phase velocity for each frequency. We determined the particle parameters from the particle detector and the upper hybrid resonance and estimated the unknown low‐energy electron temperature from the agreement between the observed ECH dispersion relation and the theoretical dispersion curves. We performed our analysis for six events and found that the low‐energy electron temperature in the observed region is on the order of 1 eV. Plain Language Summary: Low‐energy electrons, which are dominant in the Earth's inner magnetosphere, are difficult to observe directly with particle instruments due to satellite charging. We have successfully estimated the plasma environment by deriving the frequency‐wavenumber relations of Electrostatic Electron Cyclotron Harmonic (ECH) waves in the inner magnetosphere and comparing them with the theoretical relations. To derive the frequency‐wavenumber relationship of the ECH waves, it is necessary to obtain the phase velocity of the ECH waves by satellite observations. We proposed a method to determine the unobserved components of the ECH wave using interferometry observations by the Arase satellite and calculated the phase velocity using this method. Thus, the obtained low‐energy electron temperatures were all 1 eV, indicating that there are many low‐energy electrons of the order of 1 eV in the inner magnetosphere. Key Points: Phase velocities of electron cyclotron harmonic (ECH) waves were calculated using interferometry observations from the Arase satelliteThe low‐energy electron temperature was estimated based on the dispersion relation of the ECH waveIt is found that low‐energy electrons of the order of 1 eV account for the majority of the electron density distribution [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine‐6 (IL‐6) and insulin‐like growth factor‐1 (IGF‐1) in monocyte in pre‐frail older adults. Methods: We conducted a randomized double‐blinded placebo‐controlled clinical trial for 12 weeks, involving 120 pre‐frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention‐to‐treat analysis. The expression of VDR, IGF‐1 and IL‐6 in monocytes, as secondary outcomes, were analyzed using per‐protocol analysis. Results: After a 12‐week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL‐6 (P = 0.509), and IGF‐1 (P = 0.503) monocytes between the groups. Conclusions: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre‐frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL‐6, and IGF‐1 in monocytes. Geriatr Gerontol Int 2024; 24: 554–562. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the effects of transcutaneous auricular vagus nerve stimulation (taVNS) to the left cymba concha on the pain perception using nociceptive withdrawal reflex (NWR), which is known to be associated with chronic pain, and to investigate whether there is a relationship between taVNS‐induced suppression of the NWR and parasympathetic activation. We applied either 3.0 mA, 100 Hz taVNS for 120 s on the left cymba concha (taVNS condition) or the left earlobe (Sham condition) for 20 healthy adults. NWR threshold was measured before (Baseline), immediately after (Post 0), 10 min (Post 10) and 30 min after (Post 30) stimulation. The NWR threshold was obtained from biceps femoris muscle by applying electrical stimulation to the sural nerve. During taVNS, electrocardiogram was recorded, and changes in autonomic nervous activity measured by heart rate variability (HRV) were analyzed. We found that the NWR thresholds at Post 10 and Post 30 increased compared with baseline in the taVNS group (10 min after: p =.008, 30 min after: p =.008). In addition, increased parasympathetic activity by taVNS correlated with a greater increase in NWR threshold at Post 10 and Post 30 (Post 10: p =.003; Post 30: p =.001). The present results of this single‐blinded study demonstrate the pain‐suppressing effect of taVNS on NWR threshold and suggest that the degree of parasympathetic activation during taVNS may predict the pain‐suppressing effect of taVNS after its application. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the prognostic outcomes in mRCC patients receiving second‐line TKI following first‐line IO combination therapy. Methods: This study retrospectively included 243 mRCC patients receiving second‐line TKI after first‐line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO–IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO–TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. Results: In the IO–IO and IO–TKI groups, the objective response rates to second‐line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second‐line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non‐CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c‐indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. Conclusions: There were no significant differences in the prognostic outcomes after introducing second‐line TKI between the IO–IO and IO–TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second‐line TKI, irrespective of first‐line IO combination therapies. [ABSTRACT FROM AUTHOR]

Pudexacianinium (ASP5354) chloride is an indocyanine green derivative designed to enable enhanced ureter visualization during surgery. The objective of the present analysis was to determine appropriate doses of pudexacianinium for a phase 2, dose‐ranging study (NCT04238481). Real‐time urine pudexacianinium concentration is considered a good pharmacodynamic surrogate marker, since ureter visualization likely depends on its concentration in the ureter. Using plasma and urine concentrations of pudexacianinium from a phase 1 single‐ascending‐dose (0.1‐24.0 mg) study in healthy participants, a 3‐compartment population pharmacokinetic model with a urine output compartment was developed and effectively described the concentration‐time profiles. The individual estimated glomerular filtration rates had a significant impact on drug clearance. Simulations suggested that a 1.0 mg intravenous injection would achieve target urine concentrations over 1 μg/mL (determined from previous nonclinical studies) for 3 hours postdose, assuming a urine production rate of 1.0 mL/min. Based on this simulation, doses of 0.3, 1.0, and 3.0 mg were proposed for the phase 2 study. The observed plasma concentrations were generally consistent with model predictions. For urine, although only limited data could be obtained due to the difficulties of spot urine collection from surgical patients, intraoperative ureter visualization was successful at 1.0 and 3.0 mg. [ABSTRACT FROM AUTHOR]

We propose a novel frailty model with change points applying random effects to a Cox proportional hazard model to adjust the heterogeneity between clusters. In the specially focused eight Empowered Action Group (EAG) states in India, there are problems with different survival curves for children up to the age of five in different states. Therefore, when analyzing the survival times for the eight EAG states, we need to adjust for the effects among states (clusters). Because the frailty model includes random effects, the parameters are estimated using the expectation‐maximization (EM) algorithm. Additionally, our model needs to estimate change points; we thus propose a new algorithm extending the conventional estimation algorithm to the frailty model with change points to solve the problem. We show a practical example to demonstrate how to estimate the change point and the parameters of the distribution of random effect. Our proposed model can be easily analyzed using the existing R package. We conducted simulation studies with three scenarios to confirm the performance of our proposed model. We re‐analyzed the survival time data of the eight EAG states in India to show the difference in analysis results with and without random effect. In conclusion, we confirmed that the frailty model with change points has a higher accuracy than the model without a random effect. Our proposed model is useful when heterogeneity needs to be taken into account. Additionally, the absence of heterogeneity did not affect the estimation of the regression parameters. [ABSTRACT FROM AUTHOR]