Well-Tempered Medical Prompt Engineering for Explainable Extubation.

This study investigated whether the large language model (LLM) utilizes sufficient domain knowledge to reason about critical medical events such as extubation. In detail, we tested whether the LLM accurately comprehends given tabular data and variable importance and whether it can be used in complement to existing ML models such as XGBoost.

Assessment of safety: In vitro reverse mutation and in vivo acute oral toxicity tests of three biomass products from amino acid-producing Corynebacterium glutamicum.

Microbial fermentation has emerged as a pivotal process for sustainable production of essential goods and chemicals. Corynebacterium glutamicum is a proficient platform organism that contributes significantly to amino acid production through microbial fermentation. Despite its recognized safety, challenges persist in efficiently biosynthesizing natural products compared with other organisms. This study evaluated the safety of biomass products from bioengineered C. glutamicum through two different toxicological studies: a bacterial reverse mutation test (AMES test) and an acute oral toxicity test in rats. Three types of dried fermentation biomass products, each engineered for the enhanced production of specific amino acids (L-lysine, L-threonine, and L-tryptophan), were examined. The tests were conducted in compliance with Organization for Economic Co-operation and Development guidelines and revealed no mutagenicity or acute toxicity at the tested doses. These findings suggest the safety of biomass products from bioengineered C. glutamicum as potential feed materials, although further toxicity studies are recommended for comprehensive evaluation. This study underscores the importance of stringent safety assessments for advancing biotechnological applications and provides valuable insights into the potential utilization of microbial fermentation products in various industries. Moreover, this study highlights the significance of regulatory compliance and adherence to international standards to ensure the safety and efficacy of novel biotechnological products.

Extracts of Phlomoides umbrosa Turczaninow alleviate allergic airway inflammation in lipopolysaccharide-stimulated RAW 264.7 cells and ovalbumin-induced hyper-responsiveness mouse model.

Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01521-3.

Worse prognosis of metaplastic breast cancer patients than other patients with triple-negative breast cancer.

The present study was designed to assess the clinical characteristics and outcomes of metaplastic breast cancer (MBC) compared to general invasive ductal carcinoma (IDC) and the triple-negative subtype (TN-IDC). The study population included 35 MBC and 2,839 IDC patients, including 473 TN-IDC diagnoses, from the National Cancer Center, Korea between 2001 and 2008. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. Mean age of patients was 47.4 years for the MBC group and 48.3 years for the IDC group. The MBC patients presented with a larger tumor size (>/=T2, 74.3% vs. 38.8%, P < 0.001), more distant metastasis at the first diagnosis (8.6% vs. 2.0%, P = 0.04), higher histologic grade (grade 3, 65.7% vs. 41.4%, P < 0.001), fewer estrogen receptor (ER), and progesterone receptor (PgR) positivity (ER+, 5.7% vs. 65.4%, P < 0.001; PgR+, 8.6% vs. 55.8%, P < 0.001), higher Ki-67 expression (35.5 +/- 26.2% vs. 20.6 +/- 19.8%, P = 0.024), and more TN subtypes (80.0% vs. 16.7%, P < 0.001) compared to the IDC group. Fifteen (46.8%) MBC patients and 260 (9.3%) IDC patients experienced disease recurrence with a median follow-up of 47.2 months (range 4.9-100.6 months). MBC was a poor prognostic factor for disease recurrence and overall survival in univariate and multivariate analysis (HR 3.89 in recurrence, 95% CI: 1.36-11.14, P = 0.01; HR 5.29 in death, 95% CI: 2.15-13.01, P < 0.001). MBC patients also experienced more disease recurrence (HR 3.99, 95% CI: 1.31-12.19, P = 0.01) and poorer overall survival (HR 3.14, 95% CI: 1.19-8.29, P = 0.02) compared to the 473 TN-IDC patients, as reflected by aggressive pathological features. Patients with MBC appeared to have inherently aggressive tumor biology with poorer clinical outcomes than those with general IDC or TN-IDC.

Prognostic Impact of [18F] FDG-PET in operable breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: This study aimed to evaluate the usefulness of serial [(18)F] 2-fluoro-2-deoxy-D: -glucose-positron emission tomography ([(18)F] FDG-PET) in potentially operable breast cancer with neoadjuvant chemotherapy. METHODS: Serial positron emission tomography was undertaken in 66 breast cancer patients who comprised a subset of the population in a phase III randomized neoadjuvant trial at National Cancer Center, Korea. We assessed the peak standardized uptake value (SUVp) in the primary tumor and axillary nodes before and after neoadjuvant chemotherapy and calculated the reduction rate (RR) of the SUVp. By means of a receiver operating characteristic curve, we identified an optimal cutoff value for the RR for predicting the pathologic response and evaluated the prognostic power of this cutoff value. RESULTS: Ten patients (15.2%) experienced a pathologic complete response (pCR) in the primary tumor, and 19 patients (28.8%) experienced a pCR in the axillary nodes. The mean RR of the SUVp in primary tumors was 70.3% +/- 28.7%, and this value was significantly different by the pathological response (89.2% +/- 11.1% in pCR vs. 66.9% +/- 29.6% in non-pCR, P < .001). When 84.8% of the RR was used as a cutoff value for the pCR, sensitivity and specificity was 70.0% and 69.6%, respectively. Ten patients (15.2%) developed recurrent disease at a median follow-up period of 61.5 (range, 13.5-71.8) months. In a univariate analysis, the 5-year disease-free survival (DFS) was correlated with the clinical T stage (91.1% in T1/2 vs. 71.4% in T3/4, P = .02), HER-2 status (77.8% in positive vs. 96.9% in negative, P = .03), and the 84.8% RR of the SUVp in the primary tumor (95.8% vs. 78.5%, P = .04). HER-2 positivity was a significant independent prognosticator in the multivariate analysis (hazard ratio 8.73, 95% confidence interval 1.03-73.84, P = .04). The presence of a pCR in the primary tumor or nodes was not a prognostic factor in this subset of patients. The RR of the SUVp in the axillary nodes was not correlated with the nodal pCR and DFS. CONCLUSIONS: The RR of the SUVp in the primary tumor was correlated with the pathologic response and DFS. This study suggests the possible prognostic value of the RR in positron emission tomography by neoadjuvant chemotherapy.

Anti-Fatigue Activity of a Mixture of Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. Fruit Extract.

Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. are commonly used in traditional herbal medicine and food and both exhibit antioxidant and anti-inflammatory effects. Herein, hot-water extracts of Stauntonia hexaphylla (Thunb.) Decaisne and Vaccinium bracteatum Thunb. fruits (1:1 mixture) were used to produce a complex extract NET-1601. The anti-fatigue activity of NET-1601 was evaluated in an in vitro oxidative stress model induced by treating C2C12 myotubes with H2O2. An exhaustive swimming test (EST) in vivo model was established using ICR mice. NET-1601-treated C2C12 myotubes (50, 100, and 200 mg/mL) with H2O2-induced oxidative stress displayed significantly increased cell viability and ATP content, but significantly decreased levels of reactive oxygen species. All NET-1601-treated EST models demonstrated significantly higher maximum swimming rates than control mice. Furthermore, serum lactate, lactate dehydrogenase activity, non-esterified fatty acid, and intramuscular glycogen levels were higher in NET-1601-treated mice than in control mice. In addition, mRNA levels of regulatory factors involved in muscle mitochondrial fatty acid ß-oxidation increased upon NET-1601 treatment. Moreover, catalase, superoxide dismutase, glutathione-S-transferase, and liver glutathione content, and antioxidant activity were higher in NET-1601-treated mice than in control mice. Reduced malondialdehyde levels indicated that NET-1601 treatment inhibited exercise-induced lipid peroxidation. Together, these results suggest that NET-1601 retains antioxidant enzyme activity during oxidative stress, simultaneously enhancing both muscle function via glycogen and fatty acid oxidation, thereby exerting a positive effect on recovery from fatigue.

Osteopontin levels in patients with papillary thyroid cancer according to the presence of Hashimoto's thyroiditis.

BACKGROUND: Human papillary thyroid carcinoma (PTC) is often associated with Hashimoto's thyroiditis (HT); their coexistence improves PTC prognosis. Osteopontin, a secreted glycoprotein, plays a role in cell survival, immunity, and tumor progression, its expression being associated with a poor prognosis and metastasis in several malignancies. Osteopontin overexpression correlates with aggressive clinicopathological features in PTC. Lymph node metastases and large tumor size positively correlate with osteopontin positivity. This study aimed to: (1) confirm osteopontin overexpression in human PTC samples; (2) compare osteopontin expression levels in PTC cases with and without HT; and (3) identify correlations between tumor aggressiveness and osteopontin expression levels. MATERIALS AND METHODS: Plasma osteopontin was assessed in 45 patients with PTC, 22 patients with PTC and HT, and 24 healthy controls by enzyme-linked immunosorbent assay. Thyroid tissue osteopontin mRNA and protein levels were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively. RESULTS: Plasma osteopontin levels were significantly higher in PTC patients than in healthy controls. Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone. In advanced disease stage cases, osteopontin mRNA and protein expression levels were lower in patients with PTC and HT than in those with PTC alone. However, the osteopontin expression level was not significantly associated with the TNM stage. CONCLUSIONS: Plasma osteopontin, tissue osteopontin mRNA, and tissue osteopontin protein levels were significantly lower in patients with PTC and HT than in those with PTC alone, suggesting that HT attenuates PTC aggressiveness through negative regulation of osteopontin expression.

Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats.

Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes.

A case of constrictive pericarditis associated with huge epicardial fat volume.

Massive deposits of fat around heart are seen in overweight persons and are associated with coronary artery disease. Investigators have focused on the clinical significance of epicardial fat with respect to metabolic effects such as insulin resistance and inflammation, but the mechanical effects, such as constriction, have been largely ignored. We present an unusual case of a 59-year-old woman with obesity and diabetes mellitus who had been undergoing peritoneal dialysis due to end-stage renal disease, and who developed constrictive pericarditis, possibly secondary to extensive epicardial fatty accumulation.