Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Successful open surgical treatment for persistent type II endoleak following thoracic endovascular aortic repair: a case report.

BACKGROUND: The occurrence of type II endoleaks after endovascular repair of aortic aneurysm has gradually gained increasing attention. We present a case of a patient with an expanding aneurysm after thoracic endovascular aortic repair (TEVAR) for a type II endoleak, in which successful direct ligations of the intercostal artery were performed using a sac incision without cardiopulmonary bypass (CPB) or graft replacement. CASE PRESENTATION: A 62-year-old male patient, previously treated with TEVAR for a descending thoracic aortic aneurysm, presented with ongoing chest discomfort. Based on the diagnosis of a growing aneurysm and type II endoleak, the patient was prepared for CPB and aortic cross-clamping, as a precautions against the possibility of a type I endoleak. A longitudinal opening of the thoracic aortic aneurysm sac was performed following left thoracotomy. Visual confirmation identified the T5 level intercostal artery as the source of the endoleak, and after confirming the absence of a type I endoleak, multiple ligations were applied to the intercostal artery. Follow-up computed tomography confirmed the absence of endoleaks or sac growth. CONCLUSION: In a case involving TEVAR for a thoracic aortic aneurysm, open suture ligations were used to treat type II endoleaks without having to resort to CPB, resulting in successful outcomes.

Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Gas and particle emissions from rifle and pistol firing.

Emissions were sampled from firing an M4 carbine rifle and a M9 (military issue of Beretta 75 FS 9 mm pistol) to develop sampling methods and assess potential exposures and range contamination issues. Breech and muzzle emissions were sampled from the rifle when firing M855A1 ammunition (lead (Pb)-free slugs) in single- and triple-shot burst mode and from single pistol shots when firing 9 mm XM1152 ammunition (not Pb-free). Emissions were sampled for carbon monoxide (CO), carbon dioxide (CO2), methane, hydrogen cyanide, ammonia, particulate matter by size, polycylic aromatic hydrocarbons, and volatile organics. Analyses on the particles included elemental composition, size distribution, carbon composition (black, total, organic, and elemental carbon), and particle composition and morphology. Emission concentrations from both the rifle and pistol were characterized by CO/CO2 ratios between, approximately, 1/1 and 2/1, respectfully, indicating incomplete carbon oxidation. The initial particle size distribution was dominated in number by particles smaller than 40 nm but the high particle concentrations led to rapid agglomeration. The abundance of CO and metals of inhalable particle size are noteworthy and indicate that further assessment of exposure would determine potential inhalation health hazards, particularly in indoor firing ranges.

The significant impact of MPs in the industrial/municipal effluents on the MPs abundance in the Nakdong River, South Korea.

Owing to extensive plastic consumption, wastewater from households, business establishments, and industrial activities has been recognised as a significant contributor to microplastics (MPs) in aquatic environments. This case study represents the first investigation of MPs in the Nakdong River, Republic of Korea, that traverses through the largest industrial complex midstream and densely populated cities of Daegu and Busan downstream before flowing into the sea. Monitoring of MP abundance in effluents discharged from three municipal, two industrial, and one livestock wastewater treatment plant (WWTP) into the Nakdong River was conducted over four seasons from August 2022 to April 2023. Identification and quantification of MPs were performed using micro-Fourier transform infrared spectrometry. Seasonal variation in MPs in the Nakdong River was found to be strongly influenced by the nearest upstream WWTPs and rivers, exhibiting a linear relationship that decreased gradually with increasing distance from the WWTPs. The average concentrations of MPs in the six effluent sources ranged from 101±13 to 490±240 particles/L during the yearly monitoring period, while MP concentrations in the river ranged between 90±41 and 120±43 particles/L. Industrial effluents contained higher amounts of discharged MPs (314±78 particles/L) than did municipal sources (201±61 particles/L). Notably, two municipal WWTPs, located in the highly densely populated city, discharged the highest total MP amounts per day and released the greatest volumes of effluents. This study provides valuable insights into the monitoring and impact of effluents on MPs in rivers, which could inform MP treatment and management strategies for in river and marine environments.

CD39 delineates chimeric antigen receptor regulatory T cell subsets with distinct cytotoxic & regulatory functions against human islets.

Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human ß cell line and human islet ß cells in vitro. Targeting of HLA-A2-CAR (A2-CAR) bulk Tregs to HLA-A2+ cells resulted in dichotomous cytotoxic killing of human monocytes and islet ß cells. In exploring subsets and mechanisms that may explain this pattern, we found that CD39 expression segregated CAR Treg cytotoxicity. CAR Tregs from individuals with more CD39low/- Tregs and from individuals with genetic polymorphism associated with lower CD39 expression (rs10748643) had more cytotoxicity. Isolated CD39- CAR Tregs had elevated granzyme B expression and cytotoxicity compared to the CD39+ CAR Treg subset. Genetic overexpression of CD39 in CD39low CAR Tregs reduced their cytotoxicity. Importantly, ß cells upregulated protein surface expression of PD-L1 and PD-L2 in response to A2-CAR Tregs. Blockade of PD-L1/PD-L2 increased ß cell death in A2-CAR Treg co-cultures suggesting that the PD-1/PD-L1 pathway is important in protecting islet ß cells in the setting of CAR immunotherapy. In summary, introduction of CAR can enhance biological differences in subsets of Tregs. CD39+ Tregs represent a safer choice for CAR Treg therapies targeting tissues for tolerance induction.

Epsti1 Regulates the Inflammatory Stage of Early Muscle Regeneration through STAT1-VCP Interaction.

During muscle regeneration, interferon-gamma (IFN-γ) coordinates inflammatory responses critical for activation of quiescent muscle stem cells upon injury via the Janus kinase (JAK) - signal transducer and activator of transcription 1 (STAT1) pathway. Dysregulation of JAK-STAT1 signaling results in impaired muscle regeneration, leading to muscle dysfunction or muscle atrophy. Until now, the underlying molecular mechanism of how JAK-STAT1 signaling resolves during muscle regeneration remains largely elusive. Here, we demonstrate that epithelial-stromal interaction 1 (Epsti1), an interferon response gene, has a crucial role in regulating the IFN-γ-JAK-STAT1 signaling at early stage of muscle regeneration. Epsti1-deficient mice exhibit impaired muscle regeneration with elevated inflammation response. In addition, Epsti1-deficient myoblasts display aberrant interferon responses. Epsti1 interacts with valosin-containing protein (VCP) and mediates the proteasomal degradation of IFN-γ-activated STAT1, likely contributing to dampening STAT1-mediated inflammation. In line with the notion, mice lacking Epsti1 exhibit exacerbated muscle atrophy accompanied by increased inflammatory response in cancer cachexia model. Our study suggests a crucial function of Epsti1 in the resolution of IFN-γ-JAK-STAT1 signaling through interaction with VCP which provides insights into the unexplored mechanism of crosstalk between inflammatory response and muscle regeneration.

Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14).

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for Adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). The recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with 5 of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in 5 patients (5.4%) and 4 cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in 2 patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and local recurrence mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.

Prediction Model for Chronological Weight Loss After Bariatric Surgery in Korean Patients.

Purpose: This study aimed to develop a predictive model for monitoring chronological weight loss during the early postoperative period following bariatric surgery in Korean patients with morbid obesity. Materials and Methods: The baseline characteristics and postoperative weight loss outcomes were collected for up to 24 months after surgery in patients who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). The factors influencing weight loss outcomes were analyzed, and longitudinal percentile charts were plotted using quantile regression models adjusted for the identified independent factors. Results: The analysis included 491 and 274 patients who underwent SG and RYGB, respectively, of whom 225 (29.4%) were men. A positive association was found between the maximum percentage of total weight loss (%TWL) and female sex, body mass index (BMI) ≥40, and age <40 years. Among patients who reached nadir BMI or had at least 12 months of follow-up data (n=304), 7.6% exhibited inadequate weight loss (TWL <20%). The predictors of insufficient weight loss were older age (>40 years), male sex, and psychological problems. Centile charts were generated for the entire cohort, incorporating age, sex, and the type of procedure as covariates. Conclusion: The percentile charts proposed in the present study can assist surgeons and healthcare providers in gauging patients' progress toward their weight loss goals and determining the timing of adjunctive intervention in poor responders during early postoperative follow-up.

Effects of diets for three growing stages by rumen inocula donors on in vitro rumen fermentation and microbiome.

Hanwoo and Jeju Black cattle (Jeju Black) are native breeds of Korean cattle. Jeju Black cattle are recognized as natural monuments and are known to exhibit slower growth rates compared to Hanwoo. While several studies have analyzed the genetic characteristics of these cattle, there has been limited research on the differences in their microbiome. In this study, rumen fluid was obtained from three Hanwoo steers and three Jeju Black steers, and three different diets (total mixed rations [TMRs] for growing, early fattening, and late fattening periods) were used as substrates for in vitro fermentation. The in vitro incubation was conducted for 3 h and 24 h following a 2 × 3 factorial arrangement. After both incubation periods, fermentation characteristics were analyzed, and ruminal microbiome analysis was performed using 16S rRNA gene sequencing, employing both QIIME2 and PICRUSt2. The results revealed significant differences in the ruminal microbiota due to the inoculum effect. At the phylum level, Patescibacteria and Synergistota were found to be enriched in the Jeju Black inoculum-treated group. Additionally, using different inocula also affected the relative abundance of major taxa, including Ruminococcus, Pseudoramibacter, Ruminococcaceae CAG-352, and the [Eubacterium] ruminantium group. These microbial differences induced by the inoculum may have originated from varying levels of domestication between the two subspecies of donor animals, which mainly influenced the fermentation and microbiome features in the early incubation stages, although this was only partially offset afterward. Furthermore, predicted commission numbers of microbial enzymes, some of which are involved in the biosynthesis of secondary metabolites, fatty acids, and alpha amylase, differed based on the inoculum effect. However, these differences may account for only a small proportion of the overall metabolic pathway. Conversely, diets were found to affect protein biosynthesis and its related metabolism, which showed differential abundance in the growing diet and were potentially linked to the growth-promoting effects in beef cattle during the growing period. In conclusion, this study demonstrated that using different inocula significantly affected in vitro fermentation characteristics and microbiome features, mainly in the early stages of incubation, with some effects persisting up to 24 h of incubation.

Correlation between reproductive performance and sow body weight change during gestation.

This study investigated the correlation between piglet performance and sow body weight change (BWC) during two gestational periods: 35-70, 70-105, and 35-105 days. A cohort of 70 sows was evaluated for BWC, backfat thickness change (BFC), caliper score change (CALC), feed intake, and weaning-to-estrus interval (WEI). The collected data were then analyzed according to the two specified periods. Our findings highlighted that piglet birth weight, weaning weight, and average daily weight gain (ADG) correlated with sow body characteristics, including BFC and CALC. The strongest correlation was observed with BWC. Piglet mortality was intimately associated with BFC. Piglet birth weight, weaning weight, and ADG showed a positive correlation with sow BWC, particularly during the 35-70 day period. Furthermore, sows displaying a higher BWC during the 70-105 day period, and also exhibiting a higher BW gain from 35-70 days, registered greater piglet weight gains and higher weaning weights. These trends became more apparent as the sow's BWC increased during the 70-105 day period. Piglet mortality increased when the sow exhibited a lower BWC during both the 35-70 and 70-105 day periods. No significant observations were found concerning the number of stillborn piglets, live-born piglets, or weaned piglets, and no interaction effects were detected between these periods. In conclusion, our findings underscore the significance of sow BWC during the early stages of gestation (d 35-70) for enhancing piglet performance from birth to weaning.

Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial-Stromal Interplay in Cancer Development.

Epithelial-stromal interplay through chemomechanical cues from cells and matrix propels cancer progression. Elevated tissue stiffness in potentially malignant tissues suggests a link between matrix stiffness and enhanced tumor growth. In this study, employing chronic oral/esophageal injury and cancer models, it is demonstrated that epithelial-stromal interplay through matrix stiffness and Hedgehog (Hh) signaling is key in compounding cancer development. Epithelial cells actively interact with fibroblasts, exchanging mechanoresponsive signals during the precancerous stage. Specifically, epithelial cells release Sonic Hh, activating fibroblasts to produce matrix proteins and remodeling enzymes, resulting in tissue stiffening. Subsequently, basal epithelial cells adjacent to the stiffened tissue become proliferative and undergo epithelial-to-mesenchymal transition, acquiring migratory and invasive properties, thereby promoting invasive tumor growth. Notably, transcriptomic programs of oncogenic GLI2, mechano-activated by actin cytoskeletal tension, govern this process, elucidating the crucial role of non-canonical GLI2 activation in orchestrating the proliferation and mesenchymal transition of epithelial cells. Furthermore, pharmacological intervention targeting tissue stiffening proves highly effective in slowing cancer progression. These findings underscore the impact of epithelial-stromal interplay through chemo-mechanical (Hh-stiffness) signaling in cancer development, and suggest that targeting tissue stiffness holds promise as a strategy to disrupt chemo-mechanical feedback, enabling effective cancer treatment.

Real-world incidence of incident noninfectious uveitis in patients treated with BRAF inhibitors: a nationwide clinical cohort study.

PURPOSE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy. DESIGN: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration. RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < 0.001 and 95% CI 2.81-11.47, P < 0.001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = 0.001 and 95% CI 1.76-141.00, P = 0.014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = 0.046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis. CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

Generating 3D images of VMAT plans for predictive models and activation maps associated with plan deliverability.

BACKGROUND: Intensity modulation with dynamic multi-leaf collimator (MLC) and monitor unit (MU) changes across control points (CPs) characterizes volumetric modulated arc therapy (VMAT). The increased uncertainty in plan deliverability required patient-specific quality assurance (PSQA), which remained inefficient upon Quality Assurance (QA) failure. To prevent waste before QA, plan complexity metrics (PCMs) and machine learning models with the metrics were generated, which were lack of providing CP-specific information upon QA failures. PURPOSE: By generating 3D images from digital imaging and comminications in medicine in radiation therapy (DICOM RT) plan, we proposed a predictive model that can estimate the deliverability of VMAT plans and visualize CP-specific regions associated with plan deliverability. METHODS: The patient cohort consisted of 259 and 190 cases for left- and right-breast VMAT treatments, which were split into 235 and 166 cases for training and 24 cases from each treatment for testing the networks. Three-channel 3D images generated from DICOM RT plans were fed into a DenseNet-based deep learning network. To reflect VMAT plan complexity as an image, the first two channels described MLC and MU variations between two consecutive CPs, while the last channel assigned the beam field size. The network output was defined as binary classified PSQA results, indicating deliverability. The predictive performance was assessed by accuracy, sensitivity, specificity, F1-score, and area under the curve (AUC). The gradient-weighted class activation map (Grad-CAM) highlighted the regions of CPs in VMAT plans associated with deliverability, compared against PCMs by Spearman correlation. RESULTS: The DenseNet-based predictive model yielded AUCs of 92.2% and 93.8%, F1-scores of 97.0% and 93.8% and accuracies of 95.8% and 91.7% for the left- and right-breast VMAT cases. Additionally, the specificity of 87.5% for both cases indicated that the predictive model accurately detected QA failing cases. The activation maps significantly differentiated QA failing-labeled from passing-labeled classes for the non-deliverable cases. The PCM with the highest correlation to the Grad-CAM varied from patient cases, implying that plan deliverability would be considered patient-specific. CONCLUSION: This work demonstrated that the deep learning-based network based on visualization of dynamic VMAT plan information successfully predicted plan deliverability, which also provided control-point specific planning parameter information associated with plan deliverability in a patient-specific manner.

Development of AI-generated medical responses using the ChatGPT for cancer patients.

BACKGROUND AND OBJECTIVE: To develop a healthcare chatbot service (AI-guided bot) that conducts real-time conversations using large language models to provide accurate health information to patients. METHODS: To provide accurate and specialized medical responses, we integrated several cancer practice guidelines. The size of the integrated meta-dataset was 1.17 million tokens. The integrated and classified metadata were extracted, transformed into text, segmented to specific character lengths, and vectorized using the embedding model. The AI-guide bot was implemented using Python 3.9. To enhance the scalability and incorporate the integrated dataset, we combined the AI-guide bot with OpenAI and the LangChain framework. To generate user-friendly conversations, a language model was developed based on Chat-Generative Pretrained Transformer (ChatGPT), an interactive conversational chatbot powered by GPT-3.5. The AI-guide bot was implemented using ChatGPT3.5 from Sep. 2023 to Jan. 2024. RESULTS: The AI-guide bot allowed users to select their desired cancer type and language for conversational interactions. The AI-guided bot was designed to expand its capabilities to encompass multiple major cancer types. The performance of the AI-guide bot responses was 90.98 ± 4.02 (obtained by summing up the Likert scores). CONCLUSIONS: The AI-guide bot can provide medical information quickly and accurately to patients with cancer who are concerned about their health.

Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis.

BACKGROUND: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

Junctionless Structure Indium-Tin Oxide Thin-Film Transistors Enabling Enhanced Mechanical and Contact Stability.

In recent years, considerable attention has focused on high-performance and flexible crystalline metal oxide thin-film transistors (TFTs). However, achieving both high performance and flexibility in semiconductor devices is challenging due to the inherently conductive and brittle nature of crystalline metal oxide. In this study, we propose a facile way to overcome this limitation by employing a junctionless (JL) TFT structure via oxygen plasma treatment of the crystalline indium-tin oxide (ITO) films. The oxygen plasma treatment significantly reduced oxygen vacancies in the ITO films, contributing to the significant reduction in the carrier concentration from 4.67 × 1020 to 1.39 × 1016. Importantly, this reduction was achieved without inducing any noticeable structural changes in the ITO, enabling the successful realization of ITO JL TFTs with an adjustable threshold voltage. Furthermore, the ITO JL TFTs demonstrate good stability and reliability under various bias stress conditions, aging in the air atmosphere, and high-temperature processes. In addition, the ITO JL TFTs exhibit low light sensitivity due to the wide bandgap of ITO and further suppression of Vo defects, making them suitable for applications requiring stable performance under light exposure. To compare and analyze the flexibility of the JL structure and conventional structure with additional source/drain (S/D) junction in ITO TFTs with nonencapsulation, we utilized mechanical simulations and transmission line method (TLM). By employing the JL structure in ITO TFT through carefully optimized oxygen plasma treatment, we successfully mitigated stress concentration at the S/D-channel interface. This resulted in a JL ITO TFT that exhibited a change in contact resistance of less than 20% even after 20,000 bending cycles. Consequently, a stable and flexible ITO TFT with field-effect mobility (µFE) of 12.74 cm2/(V s) was realized, outperforming conventionally structured ITO TFTs with additional S/D junction, where the contact resistance nearly tripled.

Lactate promotes fatty acid oxidation by the TCA cycle and mitochondrial respiration in muscles of obese mice.

Lower oxidative capacity in skeletal muscles (SKMs) is a prevailing cause of metabolic diseases. Exercise not only enhances the fatty acid oxidation (FAO) capacity of SKMs but also increases lactate levels. Given that lactate may contribute to tricarboxylic acid cycle (TCA) flux and impact monocarboxylate transporter 1 in the SKMs, we hypothesize that lactate can influence glucose and fatty acid (FA) metabolism. To test this hypothesis, we investigated the mechanism underlying lactate-driven FAO regulation in the SKM of mice with diet-induced obesity (DIO). Lactate was administered to DIO mice immediately after exercise over three weeks. We found that increased lactate levels enhanced energy expenditure mediated by fat metabolism during exercise recovery and decreased triglyceride levels in DIO mice SKMs. To determine the lactate-specific effects without exercise, we administered lactate to mice on a high-fat diet (HFD) for eight weeks. Similar to our exercise conditions, lactate increased FAO, TCA cycle activity, and mitochondrial respiration in the SKMs of HFD-fed mice. Additionally, under sufficient FA conditions, lactate increased uncoupling protein-3 abundance via the NADH/NAD+ shuttle. Conversely ATP synthase abundance decreased in the SKMs of HFD mice. Taken together, our results suggest that lactate amplifies the adaptive increase in FAO capacity mediated by the TCA cycle and mitochondrial respiration in SKMs under sufficient FA abundance.

Management for recurrent laryngeal nerve paralysis following oesophagectomy for oesophageal cancer: thoracic surgeon perspective.

Background: Recurrent laryngeal nerve (RLN) paralysis following oesophagectomy may increase postoperative morbidity and mortality. However, clinical studies on this complication are uncommon. The aim of this study was to report the clinical course of patients with RLN paralysis following oesophageal cancer surgery. Methods: We retrospectively examined patients who underwent oesophagectomy for oesophageal carcinoma at Asan Medical Center between January 2013 and November 2018. We enrolled 189 patients with RLN paralysis confirmed using laryngoscopy in this study. Results: Of the 189 patients, 22 patients had bilateral RLN paralysis, and 167 patients had unilateral RLN paralysis. Every patient received oral feeding rehabilitation, and 145 (76.7%) patients received hyaluronic acid injection laryngoplasty. During the postoperative period, 21 (11.1%) patients experienced aspiration pneumonia and recovered. One patient died of severe pulmonary complication. Twenty-four (12.7%) patients underwent feeding jejunotomy, while 11 (5.9%) patients underwent tracheostomy. In total, 173 (91.5%) patients were discharged with oral nutrition, and the median time to begin oral diet was 9 days. Statistical analysis using logistic regression revealed that only the advanced T stage affected nerve recovery. More than 50% of the patients showed nerve recovery within 6 months, and 165 (87.9%) patients fully or partially recovered during the observation period. Conclusions: RLN paralysis following oesophagectomy in oesophageal carcinoma is a predictable complication. In patients with RLN paralysis, early detection and intervention through multidisciplinary cooperation are required, and the incidence of postoperative complications can be reduced by implementing the appropriate management.