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.

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.

Isolation, Identification, and Biological Activities of a New Chlorin e6 Derivative.

Chlorin e6 is a well-known photosensitizer used in photodynamic diagnosis and therapy. A method for identifying and purifying a novel process-related impurity during the synthesis of chlorin e6 has been developed. Its structure was elucidated using NMR and HRMS. This new impurity is formed from chlorophyll b rather than chlorophyll a, which is the source of chlorin e6. The intermediates formed during chlorin e6 synthesis were monitored using HPLC-mass spectrometry. This new impurity was identified as rhodin g7 71-ethyl ester, the structure of which remains unknown to date. The cytotoxic effects of this novel compound in both dark and light conditions were studied against five cancer cell lines (HT29, MIA-PaCa-2, PANC-1, AsPC-1, and B16F10) and a normal cell line (RAW264.7) and compared to those of chlorin e6. Upon irradiation using a laser at 0.5 J/cm2, rhodin g7 71-ethyl ester demonstrated higher cytotoxicity (2-fold) compared to chlorin e6 in the majority of the cancer cell lines. Furthermore, this new compound exhibited higher dark cytotoxicity compared to chlorin e6. Studies on singlet oxygen generation, the accumulation in highly vascular liver tissue, and the production of reactive oxygen species in MIA-PaCa-2 cancer cells via rhodin g7 71-ethyl ester correspond to its higher cytotoxicity as a newly developed photosensitizer. Therefore, rhodin g7 71-ethyl ester could be employed as an alternative or complementary agent to chlorin e6 in the photodynamic therapy for treating cancer cells.

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.

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.

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.

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.

The first report of single nucleotide polymorphisms in the open reading frame of the prion-like protein gene in rabbits.

Background: Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics. Methods: Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2. Results: We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects. Conclusion: In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Robot-Assisted Gait Training in Individuals With Spinal Cord Injury: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Spinal cord injury (SCI) rehabilitation emphasizes locomotion. Robotic-assisted gait training (RAGT) is widely used in clinical settings because of its benefits; however, its efficacy remains controversial. We conducted a systematic review and meta-analysis to investigate the efficacy of RAGT in patients with SCI. We searched international and domestic databases for articles published until April 18, 2024. The meta-analysis employed a random effects model to determine the effect size as either mean difference (MD) or standardized MD (SMD). Evidence quality was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty-three studies with a total of 690 participants were included in the final analysis. The overall pooled effect size for improvement in activities of daily living was 0.24, with SMD (95% confidence interval [95% CI], 0.04-0.43; GRADE: high) favoring RAGT over conventional rehabilitation. Muscular strength (MD, 0.23; 95% CI, 0.02-0.44; GRADE: high), walking index for SCI (MD, 0.31; 95% CI, 0.07-0.55; GRADE: moderate) and 6 min walk test distance (MD, 0.38; 95% CI, 0.14-0.63; GRADE: moderate) showed significant improvement in the robot group. Subgroup analysis revealed that subacute patients and intervention periods >2 months were more effective. This meta-analysis revealed that RAGT significantly improved activities of daily living, muscular strength, and walking abilities. Additional studies are needed to identify the optimal treatment protocol and specific patient groups for which the protocol is most effective.

Comparison of digital and analog [68Ga]Ga-PSMA-11 PET/CT for detecting post-prostatectomy biochemical recurrence in prostate cancer patients: a prospective study.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

2023 Korean Society of Echocardiography position paper for the diagnosis and management of valvular heart disease, part II: mitral and tricuspid valve disease.

This manuscript represents the official position of the Korean Society of Echocardiography on valvular heart diseases. This position paper focuses on the diagnosis and management of valvular heart diseases with referring to the guidelines recently published by the American College of Cardiology/American Heart Association and the European Society of Cardiology. The committee sought to reflect national data on the topic of valvular heart diseases published to date through a systematic literature search based on validity and relevance. In the part II of this article, we intend to present recommendations for diagnosis and treatment of mitral valve disease and tricuspid valve disease.

Paramixta manurensis gen. nov., sp. nov., a novel member of the family Erwiniaceae producing indole-3-acetic acid isolated from mushroom compost.

There are numerous species in the Erwiniaceae family that are important for agricultural and clinical purposes. Here we described the Erwiniaceae bacterium PD-1 isolated from mushroom (Pleurotus eryngii) compost. Comparative genomic and phylogenetic analyses showed that the strain PD-1 was assigned to a new genus and species, Paramixta manurensis gen. nov., sp. nov. in the family Erwiniaceae. From the average amino acid index, we identified the five AroBEKAC proteins in the shikimate pathway as a minimal set of molecular markers to reconstruct the phylogenetic tree of the Erwiniaceae species. The strain PD-1 containing annotated genes for ubiquinone and menaquinone produced a higher level of ubiquinone (Q8) than demethylmenaquinone (DMK8) and menaquinone (MK8) in anaerobic condition compared to aerobic condition, as similarly did the reference strains from the genera Mixta and Erwinia. Results from fatty acid methyl ester and numerical analyses of strain PD-1 showed a similarity to species of the genera Mixta and Winslowiella. This study revealed that the strain's ability to utilize polyols, such as glycerol, erythritol, and D-arabitol, distinguished the strain PD-1 from the nearest relative and other type strains. The analyzed genetic markers and biochemical properties of the strain PD-1 suggest its potential role in the process of mushroom compost through the degradation of carbohydrates and polysaccharides derived from fungi and plants. Additionally, it can produce a high concentration of indole-3-acetic acid as a plant growth-promoting agent.

scMultiome analysis identifies a single caudal hindbrain compartment in the developing zebrafish nervous system.

BACKGROUND: A key step in nervous system development involves the coordinated control of neural progenitor specification and positioning. A long-standing model for the vertebrate CNS postulates that transient anatomical compartments - known as neuromeres - function to position neural progenitors along the embryonic anteroposterior neuraxis. Such neuromeres are apparent in the embryonic hindbrain - that contains six rhombomeres with morphologically apparent boundaries - but other neuromeres lack clear morphological boundaries and have instead been defined by different criteria, such as differences in gene expression patterns and the outcomes of transplantation experiments. Accordingly, the caudal hindbrain (CHB) posterior to rhombomere (r) 6 has been variably proposed to contain from two to five 'pseudo-rhombomeres', but the lack of comprehensive molecular data has precluded a detailed definition of such structures. METHODS: We used single-cell Multiome analysis, which allows simultaneous characterization of gene expression and chromatin state of individual cell nuclei, to identify and characterize CHB progenitors in the developing zebrafish CNS. RESULTS: We identified CHB progenitors as a transcriptionally distinct population, that also possesses a unique profile of accessible transcription factor binding motifs, relative to both r6 and the spinal cord. This CHB population can be subdivided along its dorsoventral axis based on molecular characteristics, but we do not find any molecular evidence that it contains multiple pseudo-rhombomeres. We further observe that the CHB is closely related to r6 at the earliest embryonic stages, but becomes more divergent over time, and that it is defined by a unique gene regulatory network. CONCLUSIONS: We conclude that the early CHB represents a single neuromere compartment that cannot be molecularly subdivided into pseudo-rhombomeres and that it may share an embryonic origin with r6.

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.

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.

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.