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Context HNF4A–maturity-onset diabetes of the young (MODY1) is a relatively rare subtype of monogenic diabetes caused by loss of function of the HNF4A gene, which encodes the transcription factor HNF4α. HNF4α is known to form heterodimers, and the various combinations of isoforms that make up these heterodimers have been reported to result in a diversity of targeted genes. However, the function of individual HNF4α variant isoforms and the heterodimers comprising both wild-type (WT) and variant HNF4α have not yet been assessed. Objective In this study, we analyzed the functional consequence of the HNF4A D248Y variant in vitro. Methods We investigated the case of a 12-year-old Japanese girl who developed diabetes at age 11 years. Genetic sequencing detected a novel heterozygous missense HNF4A variant (c.742G > T, p.Asp248Tyr; referred as "D248Y") in the patient and her relatives who presented with diabetes. Results Although the WT HNF4α isoforms (HNF4α2, HNF4α3, HNF4α8, HNF4α9) enhanced the INS gene promoter activity in HepG2 cells, the promoter activity of D248Y was consistently low across all isoforms. The presence of D248Y in homodimers and heterodimers, comprising either HNF4α8 or HNF4α3 or a combination of both isoforms, also reduced the INS promoter activity in Panc-1 cells. Conclusion We report the clinical course of a patient with HNF4A-MODY and the functional analysis of novel HNF4A variants, with a focus on the isoforms and heterodimers they form. Our results serve to improve the understanding of the dominant-negative effects of pathogenic HNF4A variants. [ABSTRACT FROM AUTHOR]

Non-Intrusive Load Monitoring (NILM), which provides sufficient load for the energy consumption of an entire building, has become crucial in improving the operation of energy systems. Although NILM can decompose overall energy consumption into individual electrical sub-loads, it struggles to estimate thermal-driven sub-loads such as occupants. Previous studies proposed Non-Intrusive Thermal Load Monitoring (NITLM), which disaggregates the overall thermal load into sub-loads; however, these studies evaluated only a single building. The results change for other buildings due to individual building factors, such as floor area, location, and occupancy patterns; thus, it is necessary to analyze how these factors affect the accuracy of disaggregation for accurate monitoring. In this paper, we conduct a fundamental evaluation of NITLM in various realistic office buildings to accurately disaggregate the overall thermal load into sub-loads, focusing on occupant thermal load. Through experiments, we introduce NITLM with deep learning models and evaluate these models using thermal load datasets. These thermal load datasets are generated by a building energy simulation, and its inputs for the simulation were derived from realistic data like HVAC on/off data. Such fundamental evaluation has not been done before, but insights obtained from the comparison of learning models are necessary and useful for improving learning models. Our experimental results shed light on the deep learning-based NITLM models for building-level efficient energy management systems. [ABSTRACT FROM AUTHOR]

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long‐term ACTH therapy (LT‐ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT‐ACTH. We evaluated the effectiveness of LT‐ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin‐releasing hormone (CRH) stimulation test during LT‐ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life‐threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT‐ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT‐ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely. [ABSTRACT FROM AUTHOR]

This paper reports results from an experimental auction conducted in Japan. The auction experiment featured simultaneous bidding for the non-GM and GM products, combined with a stated choice question. We first estimated separately the hypothetical and nonhypothetical discounts on GM food for respondents to accept them. We then jointly estimated nonhypothetical and hypothetical GM discount functions to find little evidence of hypothetical bias for a common food product. We found that Japanese consumers required about 40% discount on the GM foods. [ABSTRACT FROM AUTHOR]

This paper reports results from a pilot U.S. national telephone survey on genetically modified foods (vegetable oil, cornflake cereal, and salmon). The survey featured contingent valuation in which respondents chose between the GM and non-GM alternatives. The binary and multinomial logit models yield estimated willingness to pay to avoid the GM alternatives. Perceived risk of GM food is an important determinant of GM choice along with the price. Respondents are willing to pay 41.2%, 31.4%, 40.9%, and 52.5% of the base prices to avoid GM vegetable oil, GM cornflakes, GM-fed salmon, and GM salmon, respectively. [ABSTRACT FROM AUTHOR]

Adipsic hypernatremia is typically caused by congenital dysplasia of the hypothalamus and pituitary or brain tumors. However, cases of adipsic hypernatremia without underlying organic abnormalities are rare, and some cases have been reported to be complicated by hypothalamic-pituitary dysfunction. The patient in this case was a 9-yr-old boy who was referred to our hospital because of hypernatremia. His growth chart revealed that he had rapidly become obese since infancy, with growth retardation since the age of seven. His hands and feet were very cold, and he had erythema on his abdomen, indicating possible autonomic dysregulation due to hypothalamic dysfunction. Several hormone load tests showed severe GH deficiency (GHD) and marked hyperprolactinemia (peak: 302.8 ng/mL). Magnetic resonance imaging revealed no organic abnormalities in the hypothalamus and pituitary gland. GH replacement therapy was initiated. Although his growth rate improved, obesity persisted. To the best of our knowledge, this is the first report of adipsic hypernatremia without organic intracranial abnormalities that was treated with GH. Moreover, the patient's prolactin levels were higher than those reported in previous studies. In conclusion, adipsic hypernatremia requires the evaluation of pituitary function and appropriate therapeutic interventions., Competing Interests: The authors indicate no potential conflicts of interest., (2024©The Japanese Society for Pediatric Endocrinology.)

A 62-year-old male patient was referred to our hospital for jaundice and bloody feces. He had hyper-IgG4-emia. Computed tomography (CT) showed diffuse pancreatic enlargement, pancreatic pseudocyst, and hematoma of the splenic flexure of the colon. Magnetic resonance imaging (MRI) showed a fistula in the pancreatic pseudocyst and splenic flexure of the colon. Moreover, lower gastrointestinal endoscopy showed a fistula in the same region. Endoscopic retrograde cholangiopancreatography (ERCP) showed narrowing of the main pancreatic duct and stenosis of the lower bile duct. Following this, the patient was diagnosed with autoimmune pancreatitis-induced pancreatic pseudocyst and colonic perforation-induced gastrointestinal bleeding. The pancreatic pseudocyst and fistula were resolved through steroid treatment.

We herein report a rare case of a 66-year-old woman who had synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome with marked sternal osteitis and bilateral pleural effusions. SAPHO syndrome was diagnosed based on the characteristic features of a hyperostotic sternum and thoracic spine. The inflammatory changes of sternal osteitis and involvement of the adjacent soft tissue were assumed to be the cause of the pleural effusions. The effusions decreased during the natural course of the disease and resolved after methotrexate therapy. The pain dramatically decreased with oral tramadol. Physicians should consider the possibility of SAPHO syndrome in patients with anterior chest pain and pleural effusions.

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

We report a novel sensing technique that uses an evanescent terahertz (THz) wave, without detecting the THz wave directly. When a THz wave generated by Cherenkov phase matching via difference frequency generation undergoes total internal reflection, the evanescent THz wave is subject to a phase change and an amplitude decrease. The reflected THz wave, under the influence of the sample, interferes with the propagating THz wave and the changing electric field of the THz wave interacts with the electric field of the pump waves. We demonstrate a sensing technique for detecting changes in the electric field of near-infrared light, transcribed from changes in the electric field of a THz wave.