Objective: Research and development for drug discovery is time-consuming and expensive. Artificial intelligence (AI) technologies, such as machine learning are attracting the attention of researchers as tools for efficiently advancing drug discovery. However, the use of AI technology requires a high amount of data, and the scope of application and accuracy of prediction depend on data quality. Therefore, the development of technology for efficiently collecting drug information data is required. The present examined an interactive AI system for extracting absorption, distribution, metabolism, and excretion (ADME) data from clinical practice documents. Methods: Attachments for five drugs were collected from the Pharmaceuticals and Medical Devices Agency (PMDA) for properties influencing pharmacokinetics, including dosage, maximum concentration (Cmax), half-life (T1/2), time to peak drug concentration (Tmax), area under the curve (AUC), and clearance (CL). Data were collected directly from PDFs using ChatGPT Plus, SciSpace, and ChatPDF as interactive AI systems capable of performing this task, and variations in these properties were compared. In addition, we compared the variations in the prompting outputs. Results: ChatGPT Plus was able to retrieve some pharmacokinetic properties including the values in the tables, whereas SciSpace and ChatPDF were unable to retrieve pharmacokinetic information. In addition, the ChatGPT Plus output changed depending on the prompt, whereas the results obtained using SciSpace and ChatPDF did not change significantly based on the prompt. Therefore, ChatGPT Plus was the most appropriate system for collecting ADME data. Conclusion: Based on the results of collection of ADME characteristics from documents using the three interactive AI systems, ChatGPT Plus is the most effective method for obtaining the desired characteristics, although several issues need to be addressed. Interactive AI will be an indispensable technology for data collection in drug research, and could contribute significantly to drug discovery in the future.

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*

Nutritional status tends to be poor in patients undergoing chemotherapy. We investigated anorexia caused by olfactory dysfunction by examining olfactory sense in chemotherapy patients and healthy volunteers. We used the Open Essence® olfactometry test, which assesses the accuracy of identifying 12 different odors. Twenty-seven patients (mean age 69.8 years) who received chemotherapy for lung cancer from March 2016 to September 2017 participated in multiple olfactometry examinations from the start of their chemotherapy. We also examined 284 healthy volunteers (mean age 41.9 years), and performed an additional subgroup analysis with 35 volunteers aged 60 years or older (mean age 73.2 years) to more closely align with the mean age of the patients. The mean accuracy rate was 44.4% for the patients, although this rate varied from odor to odor. In contrast, the mean accuracy rate of the healthy volunteers was 76.8%. There were significant differences according to sex and smoking history. For the subgroup of healthy volunteers aged 60 years and older, the mean accuracy rate was 54.5%; accuracy rate decreased as age increased. There was no significant difference in the accuracy rate according to type of chemotherapy, but the overall rate for patients was lower than that for healthy volunteers. Our results show that olfactory sense in lung cancer patients undergoing chemotherapy is altered compared with that in healthy individuals. Smoking habit was shown to have the greatest effect and most of the lung cancer patients in this study were smokers. A change in olfactory sense caused by smoking was also noted in the healthy volunteer group. We intend to conduct a similar investigation of patients with diseases other than lung cancer in the future as well as utilize the findings to investigate nutritional status.

Purpose: This study investigated the current state of critical hemorrhage during home palliative care for terminally ill cancer patients. Methods: We conducted a retrospective medical chart review of 7 cancer patients (1.4%) who received home palliative care from our clinic and died of critical hemorrhage at home from October 2007 to December 2014. Results: Four patients were male, the mean age was 70±11 years, and underlying diseases were different. None of the patients were accompanied by medical staff at the onset of bleeding. Six patients died at home and one patient was admitted to hospital for hemostasis. Six patients had a pre-hemorrhage episode more than 24 hours before critical hemorrhage occurred from the same site. One patient was administered a hemostatic agent, hemostasis was attempted in one, and one was given sedation. Six patients wanted to die at home, and did die at home. Discussion: If terminally ill cancer patients have critical hemorrhage at home, our options are limited. The results of this study suggest the importance of hemorrhage risk assessment and advance care planning.

　　Epidermal growth factor receptor (EGFR) gene mutation examination is now performed in most medical institutions in order to select the molecular targeted medicine for lung cancer. It became clear that the positive rate of the biopsy material was lower than that of the surgical sample in this hospital. The cause was attributed to false negatives due to low tumor cell content in biopsy specimens. We investigated the presence of the mutation using surgical samples and preoperative biopsy specimens from the same patients in 13 cases. Furthermore, we investigated the tumor cell content of the biopsy specimens by cell counting. Results showed that 3 of 6 biopsy specimens that were associated with positive surgical samples were judged to be negative. The tumor cell content was less than 5% in all negative cases. Regarding EGFR gene mutation examination, we should carefully determine tumor cell content when using biopsy specimens.

　　We report a case of spindle cell type medullary carcinoma of the thyroid in a 77-year-old man. Fine needle aspiration cytology showed numerous spindle cells without inflammation and hemorrhage. The spindle cells were uniform and exhibited no malignant features. Immunocytochemistry was positive for carcinoembryonic antigen and calcitonin, and the tumor was diagnosed as spindle cell type medullary carcinoma. There are various histological subtypes of medullary carcinoma, and diagnosis by cytomorphology alone is difficult. Preservation with LBC fixative was helpful for diagnosis by immunocytochemistry in this case.

Streptococcus pneumoniae (the pneumococcus) causes a major upper respiratory tract infection often leading to severe illness and death in the elderly. Thus, it is important to induce safe and effective mucosal immunity against this pathogen in order to prevent pnuemocaccal infection. However, this is a very difficult task to elicit protective mucosal IgA antibody responses in older individuals. A combind nasal adjuvant consisting of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligonucleotide (CpG ODN) successfully enhanced S. pneumoniae-specific mucosal immunity in aged mice. In particular, a pneumococcal surface protein A-based nasal vaccine given with pFL and CpG ODN induced complete protection from S. pneumoniae infection. These results show that nasal delivery of a combined DNA adjuvant offers an attractive potential for protection against the pneumococcus in the elderly.
Aged* ; Aging ; Animals ; Antibody Formation ; Bacterial Infections ; DNA ; DNA, Complementary ; Humans ; Immunity, Mucosal ; Immunoglobulin A ; Mice ; Mucous Membrane ; Plasmids ; Pneumococcal Infections* ; Pneumonia ; Respiratory Tract Infections ; Streptococcus pneumoniae ; Vaccination

Twister orthoses are used to correct in-toeing and out-toeing, and consist of a pelvic band, a twister cable, and an ankle-foot orthosis (AFO). The twister cable is made of spiral coiled springs and connects the pelvic band with the AFO. Twister orthoses are used for children with lower limb paralysis who in many cases present with a rotation deformity of the hip joint ; however, their use in adults has not yet been reported. We report our experience treating two cases of adult poststroke hemiplegic patients whose gate ability was improved by using twister orthoses.

　　It is known that uterine cervical cancer is caused by persistent infection with high-risk type of HPV (human papilloma virus). We have run HPV genotyping tests on patients since November, 2011. In 111 cases so far examined, HPV types 16, 52 and 58 were detected with high frequency, but type 18 was with low frequency. This trend was comparable to nationwide tendency. Type 52, 56 and 58 were detected from the patients of advanced age frequently. There weredifferences in HPV infection rate between cytology-negative cases and positive cases, but there was not the difference in HPV typing by cytology-negative and positive patients. Furthermore, it was made clear that the superinfection of HPV who significantly related to the development of tumor. In the cytology negative patients who were followed up because of dysplasia, there are many who are negative for high risk HPV. Therefore, HPV genotyping examination may help physicians determine the relative priority for treatment.

　　We investigated the detection situation of the HER-2 examination that was performed to investigate the adaptation of the molecular targeted medicine trastuzumab for mammary and gastric cancers. The HER-2 positive rate was higher in biopsy specimens than in surgical specimen. In gastric cancer, the positive rate was significantly high when it was of the papillary type, histologically. In comparison with mammary cancer, the percentage of FISH positive was high in 2＋ cases. In addition, as the results of trial investigation showed, HER-2 positive cases ware few in colon cancer.