Automated abdominal organ segmentation algorithms for non-enhanced CT for volumetry and 3D radiomics analysis.

PURPOSE: To develop fully-automated abdominal organ segmentation algorithms from non-enhanced abdominal CT and low-dose chest CT and assess their feasibility for automated CT volumetry and 3D radiomics analysis of abdominal solid organs. METHODS: Fully-automated nnU-Net-based models were developed to segment the liver, spleen, and both kidneys in non-enhanced abdominal CT, and the liver and spleen in low-dose chest CT. 105 abdominal CTs and 60 low-dose chest CTs were used for model development, and 55 abdominal CTs and 10 low-dose chest CTs for external testing. The segmentation performance for each organ was assessed using the Dice similarity coefficients, with manual segmentation results serving as the ground truth. Agreements between ground-truth measurements and model estimates of organ volume and 3D radiomics features were assessed using the Bland-Altman analysis and intraclass correlation coefficients (ICC). RESULTS: The models accurately segmented the liver, spleen, right kidney, and left kidney in abdominal CT and the liver and spleen in low-dose chest CT, showing mean Dice similarity coefficients in the external dataset of 0.968, 0.960, 0.952, and 0.958, respectively, in abdominal CT, and 0.969 and 0.960, respectively, in low-dose chest CT. The model-estimated and ground truth volumes of these organs exhibited mean differences between - 0.7% and 2.2%, with excellent agreements. The automatically extracted mean and median Hounsfield units (ICCs, 0.970-0.999 and 0.994-0.999, respectively), uniformity (ICCs, 0.985-0.998), entropy (ICCs, 0.931-0.993), elongation (ICCs, 0.978-0.992), and flatness (ICCs, 0.973-0.997) showed excellent agreement with ground truth measurements for each organ; however, skewness (ICCs, 0.210-0.831), kurtosis (ICCs, 0.053-0.933), and sphericity (ICCs, 0.368-0.819) displayed relatively low and inconsistent agreement. CONCLUSION: Our nnU-Net-based models accurately segmented abdominal solid organs in non-enhanced abdominal and low-dose chest CT, enabling reliable automated measurements of organ volume and specific 3D radiomics features.

The role of 2'-5'-oligoadenylate synthase-like protein (OASL1) in biliary and hepatotoxin-induced liver injury in mice.

Following an injury, the liver embarks on a process that drives the accumulation and reformation of the extracellular matrix, leading to hepatic fibrosis. Type I interferons (IFNs), including IFN-α and IFN-ß, play a crucial role in averting chronic liver injury through the activation of IFN-stimulated genes (ISGs), which are instrumental in sculpting adaptive immunity. The role of 2'-5'-oligoadenylate synthase-like protein 1 (OASL1), an antiviral ISG, in the context of liver fibrosis remains to be elucidated. To elicit liver fibrosis, a diet containing 0.1% diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4) were employed to induce cholestatic- and hepatotoxin-mediated liver fibrosis, respectively. Histological analyses of both models revealed that OASL1-/- mice exhibited reduced liver damage and, consequently, expressed lower levels of fibrotic mediators, notably α-smooth muscle actin. OASL1-/- mice demonstrated significantly elevated IFN-α and IFN-ß mRNA levels, regulated by the IFN regulatory factor 7 (IRF7). Additionally, OASL1-/- ameliorated chronic liver fibrosis through the modulation of nuclear factor-κB (NF-κB) signaling. The effect of OASL1 on type I IFN production in acute liver damage was further explored and OASL1-/- mice consistently showed lower alanine transaminase levels and pro-inflammatory cytokines, but IFN-α and IFN-ß mRNA levels were upregulated, leading to amelioration of acute liver injury. Additionally, the study discovered that F4/80-positive cells were observed more frequently in OASL1-/- CCl4 acutely treated mice. This implies that there is a significant synergy in the function of macrophages and OASL1 deficiency. These results demonstrate that in instances of liver injury, OASL1 inhibits the production of type I IFN by modulating the NF-κB signaling pathway, thereby worsening disease.

Paulownin elicits anti-tumor effects by enhancing NK cell cytotoxicity through JNK pathway activation.

Paulownin, a natural compound derived from Paulownia tomentosa wood, exhibits various physiological functions, including anti-bacterial and anti-fungal effects. However, the impact of paulownin on natural killer (NK) cell immune activity remains largely unknown. In this study, we investigated the effect of paulownin on NK cell activity both in vitro and in vivo, and explored its potential mechanisms. NK-92 cells were used for in vitro experiments and a BALB/c mouse model with B16F10 cells injected subcutaneously were used for in vivo anti-tumor analysis. We found that paulownin enhanced the cytolytic activity of NK-92 cells against leukemia, human colon, and human lung cancer cell lines. Paulownin treatment increased the expression of the degranulation marker protein CD107a and cytolytic granules, including granzyme B and perforin in NK-92 cells. Moreover, these enhancements of cytotoxicity and the expression of cytolytic granules induced by paulownin were also observed in human primary NK cells. Signaling studies showed that paulownin promoted the phosphorylation of JNK. The increased perforin expression and elevated cytotoxic activity induced by paulownin were effectively inhibited by pre-treatment with a JNK inhibitor. In vivo studies demonstrated that the administration of paulownin suppressed the growth of B16F10 melanoma cells allografted into mice. Paulownin administration promoted the activation of NK cells in the spleen of mice, resulting in enhanced cytotoxicity against YAC-1 cells. Moreover, the anti-tumor effects of paulownin were reduced upon the depletion of NK cells. Therefore, these results suggest that paulownin enhances NK cell cytotoxicity by activating the JNK signaling pathway and provide significant implications for developing new strategies for cancer immunotherapy.

Accelerometer-Based Physical Activity and Health-Related Quality of Life in Korean Adults: Observational Study Using the Korea National Health and Nutrition Examination Survey.

BACKGROUND: Health-related quality of life (HRQoL) reflects an individual's perception of their physical and mental health over time. Despite numerous studies linking physical activity to improved HRQoL, most rely on self-reported data, limiting the accuracy and generalizability of findings. This study leverages objective accelerometer data to explore the association between physical activity and HRQoL in Korean adults. OBJECTIVE: The objective of this study is to analyze the relationship between objectively measured physical activity using accelerometers and HRQoL among Korean adults, aiming to inform targeted interventions for enhancing HRQoL through physical activity. METHODS: This observational study included 1298 participants aged 19-64 years from the Korea National Health and Nutrition Examination Survey (KNHANES) VI, who wore an accelerometer for 7 consecutive days. HRQoL was assessed using the EQ-5D questionnaire, and physical activity was quantified as moderate-to-vigorous physical activity accelerometer-total (MVPA-AT) and accelerometer-bout (MVPA-AB). Data were analyzed using logistic regression to determine the odds ratio (ORs) for low HRQoL, adjusting for socioeconomic variables and mental health factors. RESULTS: Participants with higher HRQoL were younger, more likely to be male, single, highly educated, employed in white-collar jobs, and had higher household incomes. They also reported less stress and better subjective health status. The high HRQoL group had significantly more participants meeting MVPA-AB ≥600 metabolic equivalents (P<.01). Logistic regression showed that participants meeting MVPA-AB ≥600 metabolic equivalents had higher odds of high HRQoL (OR 1.55, 95% CI 1.11-2.17). Adjusted models showed consistent results, although the association weakened when adjusting for mental health factors (OR 1.45, 95% CI 1.01-2.09). CONCLUSIONS: The study demonstrates a significant association between HRQoL and moderate to vigorous physical activity sustained for at least 10 minutes, as measured by accelerometer. These findings support promoting physical activity, particularly sustained moderate to vigorous activity, to enhance HRQoL. Further interventional studies focusing on specific physical activity domains such as occupational, leisure-time, and commuting activities are warranted.

C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 promotes flowering with TAF15b by repressing the floral repressor gene FLOWERING LOCUS C.

Arabidopsis TBP-ASSOCIATED FACTOR15b (TAF15b) is a plant-specific component of the transcription factor IID (TFIID) complex. TAF15b is involved in the autonomous pathway for flowering and represses the transcription of FLOWERING LOCUS C (FLC), a major floral repressor in Arabidopsis. While components of the autonomous flowering pathway have been extensively studied, scant attention has been directed towards elucidating the direct transcriptional regulators responsible for repressing FLC transcription. Here, we demonstrate that C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 (CPL1) is a physical and functional partner of TAF15b, playing a role for FLC repression. CPL1 is a protein phosphatase that dephosphorylates the C-terminal domain (CTD) of RNA polymerase II (Pol II). Through the immunoprecipitation and mass spectrometry technique, we identified CPL1 as an interacting partner of TAF15b. Similar to taf15b, the cpl1 mutant showed a late-flowering phenotype caused by an increase in FLC levels. Additionally, the increase in cpl1 was correlated with the enrichment of phosphorylated Pol II in the FLC chromatin, as expected. We also discovered that CPL1 and TAF15b share additional common target genes through transcriptome analysis. These results suggest that TAF15b and CPL1 cooperatively repress transcription through the dephosphorylation of Pol II, especially at the FLC locus.

Potential prognostic value of rheumatoid factor in anti-aquaporin 4-immunoglobin G-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies. METHODS: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD. RESULTS: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001). CONCLUSION: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR.

Impact of the life-sustaining treatment decision act on organ donation in out-of-hospital cardiac arrests in South Korea: a multi-centre retrospective study.

BACKGROUND: The demand for organ transplants, both globally and in South Korea, substantially exceeds the supply, a situation that might have been aggravated by the enactment of the Life-Sustaining Treatment Decision Act (LSTDA) in February 2018. This legislation may influence emergency medical procedures and the availability of organs from brain-dead donors. This study aimed to assess LSTDA's impact, introduced in February 2018, on organ donation status in out-of-hospital cardiac arrest (OHCA) patients in a metropolitan city and identified related factors. METHODS: We conducted a retrospective analysis of a regional cardiac arrest registry. This study included patients aged 16 or older with cardiac arrest and a cerebral performance category (CPC) score of 5 from January 2015 to December 2022. The exclusion criteria were CPC scores of 1-4, patients under 16 years, and patients declared dead or transferred from emergency departments. Logistic regression analysis was used to analyse factors affecting organ donation. RESULTS: Of the 751 patients included in this study, 47 were organ donors, with a median age of 47 years. Before the LSTDA, there were 30 organ donations, which declined to 17 after its implementation. In the organ donation group, the causes of cardiac arrest included medical (34%), hanging (46.8%), and trauma (19.2%). The adjusted odds ratio for organ donation before the LSTDA implementation was 6.12 (95% CI 3.09-12.12), with non-medical aetiology as associated factors. CONCLUSION: The enactment of the LSTDA in 2018 in South Korea may be linked to reduced organ donations among patients with OHCA, underscoring the need to re-evaluate the medical and legal aspects of organ donation, especially considering end-of-life care decisions.

Tuning the Properties of Halide Nanocomposite Solid Electrolytes with Diverse Oxides for All-Solid-State Batteries.

Herein, we report halide nanocomposite solid electrolytes (HNSEs) that integrate diverse oxides with alterations that allow tuning of their ionic conductivity, (electro)chemical stability, and specific density. A two-step mechanochemical process enabled the synthesis of multimetal (or nonmetal) HNSEs, MO2-2Li2ZrCl6, as verified by pair distribution function and X-ray diffraction analyses. The multimetal (or nonmetal) HNSE strategy increases the ionic conductivity of Li2ZrCl6 from 0.40 to 0.82 mS cm-1. Additionally, cyclic voltammetry test findings corroborated the enhanced passivating properties of the HNSEs. Notably, incorporating SiO2 into HNSEs leads to a substantial reduction in the specific density of HNSEs, demonstrating their strong potential for achieving a high energy density and lowering costs. Fluorinated SiO2-2Li2ZrCl5F HNSEs exhibited enhanced interfacial compatibility with Li6PS5Cl and LiCoO2 electrodes. Cells employing SiO2-2Li2ZrCl5F with LiCoO2 exhibit superior electrochemical performance delivering the initial discharge capacity of 162 mA h g-1 with 93.7% capacity retention at the 100th cycle at 60 °C.

Risk factors and chlorhexidine dressings in external ventricular drainage: a retrospective analysis on infection rates.

This retrospective study endeavors to scrutinize risk factors associated with infections resulting from external ventricular drainage (EVD) and to assess the effectiveness of chlorhexidine dressing in mitigating infection rates. Conducted from January 2018 to July 2023, this single-center study encompassed 108 EVD patients. Comprehensive data on demographics, comorbidities, surgical procedures, and the utilization of chlorhexidine dressing were meticulously compiled. The primary endpoint was the incidence of EVD-associated infections based on CDC criteria. Infection rates attributable to EVD were 24.32% without and 20.59% with chlorhexidine dressing. Notably, diabetes mellitus emerged as the solitary significant infection risk factor (p < 0.01). Although the application of chlorhexidine dressing suggested a propensity for diminishing infection rates, statistical significance remained elusive. No notable disparities were discerned in variables such as catheter type, procedural location, and underlying diseases. Diabetes mellitus has been identified as a significant risk factor for EVD-associated infections. While the utilization of chlorhexidine dressing exhibited a potential reduction in infection rates, the lack of statistical significance underscores the imperative for further research, encompassing more expansive randomized trials, to comprehensively evaluate the safety and efficacy of chlorhexidine dressings in preventing EVD-associated infections.

Comparison of Clinical Outcomes Using Left and Right Liver Grafts in Adult-to-adult Living-donor Liver Transplantation: A Retrospective Cohort Study Using the Korean Organ Transplantation Registry.

BACKGROUND: Living-donor liver transplantation has been widely performed as an alternative to the scarce liver grafts from deceased donors. More studies are reporting favorable outcomes of left liver graft (LLG). This study compared the clinical outcomes between living-donor liver transplantation using LLG and right liver graft (RLG) with similar graft-to-recipient body weight ratios. METHODS: This study analyzed 4601 patients from a multicenter observational cohort using the Korean Organ Transplantation Registry between 2014 and 2021. After matching the Model for End-stage Liver Disease score and graft-to-recipient body weight ratios because of the extremely different number in each group, the LLG and RLG groups comprised 142 (25.1%) and 423 (74.9%) patients, respectively. RESULTS: For donors, the median age was higher in the LLG group than in the RLG group (34 y [range, 16-62 y] versus 30 y [16-66 y] ; P = 0.002). For recipients, the LLG group showed higher 90-d mortality than the RLG group (11 [7.7%] versus 9 [2.1%]; P = 0.004). The long-term graft survival was significantly worse in the LLG group (P = 0.011). In multivariate Cox proportional hazards regression analysis for graft survival, LLG was not a significant risk factor (hazard ratio, 1.01 [0.54-1.87]; P = 0.980). Otherwise, donor age (≥40 y; 2.18 y [1.35-3.52 y]; P = 0.001) and recipients' body mass index (<18.5 kg/m2; 2.98 kg/m2 [1.52-5.84 kg/m2]; P = 0.002) were independent risk factors for graft survival. CONCLUSIONS: Although the short-term and long-term graft survival was worse in the LLG group, LLG was not an independent risk factor for graft survival in multivariate analysis. LLGs are still worth considering for selected donors and recipients regarding risk factors for graft survival.

Enhanced Colorimetric Detection of Volatile Organic Compounds Using a Dye-Incorporated Photonic Crystal-Based Sensor Array.

Chemoresponsive dyes offer the potential to selectively detect volatile organic compounds (VOCs) unique to certain disease states. Among different VOC sensing techniques, colorimetric sensing offers the advantage of facile recognition. However, it is often challenging to discern the color changes by the naked eye. Here, highly sensitive colorimetric VOC sensor arrays from dye-incorporated colloidal photonic crystals (dye-cPhCs) are reported. cPhCs are scalably fabricated on a 4-inch wafer by spin-coating of silica nanoparticles (NPs) dispersed in a photo-cross-linkable monomer, where the gradient shear flow along the film thickness creates densely-packed square arrays of NPs in the top layers, whereas the bulk is quasi-amorphous with larger periodicities. The broadened reflection peak allows for augmented dye absorption originating from the overlap between the photonic bandgap edge of the cPhC and the dye absorption peak, leading to a more noticeable color change upon exposure to VOCs. The sensor array generates distinct color difference maps for acetaldehyde, acetone, and acetic acid, respectively, without any data amplification. The limit of detection for acetaldehyde, acetone, and acetic acid is 1, 0.1, and 0.02 ppm, respectively. Moreover, VOC can be diagonalized by visually intuitive pattern recognition, and principal component analysis at reduced dimensionality is demonstrated.

Ruptured triple hormone-secreting adrenal cortical carcinoma with hyperaldosteronism, hypercortisolism, and elevated normetanephrine: a case report.

We report a case of a ruptured triple hormone-secreting adrenal mass with hyperaldosteronism, hypercortisolism, and elevated normetanephrine levels, diagnosed as adrenal cortical carcinoma (ACC) by histology. A 53-year-old male patient who initially presented with abdominal pain was referred to our hospital for angiocoagulation of an adrenal mass rupture. Abdominal computed tomography revealed a heterogeneous 19×11×15 cm right adrenal mass with invasion into the right lobe of the liver, inferior vena cava, retrocaval lymph nodes, and aortocaval lymph nodes. Angiocoagulation was performed. Laboratory evaluation revealed excess cortisol via a positive 1-mg overnight dexamethasone suppression test, primary hyperaldosteronism via a positive saline infusion test, and plasma normetanephrine levels three times higher than normal. An adrenal mass biopsy was performed for pathological confirmation to commence palliative chemotherapy because surgical management was not deemed appropriate considering the extent of the tumor. Pathological examination revealed stage T4N1M1 ACC. The patient started the first cycle of adjuvant mitotane therapy along with adjuvant treatment with doxorubicin, cisplatin, and etoposide, and was discharged. Clinical cases of dual cortisol- and aldosterone-secreting ACCs or ACCs presenting as pheochromocytomas have occasionally been reported; however, both are rare. Moreover, to the best of our knowledge, a triple hormone-secreting ACC has not yet been reported. Here, we report a rare case and its management. This case report underscores the necessity of performing comprehensive clinical and biochemical hormone evaluations in patients with adrenal masses because ACC can present with multiple hormone elevations.

Integrative Analysis of Probiotic-Mediated Remodeling in Canine Gut Microbiota and Metabolites Using a Fermenter for an Intestinal Microbiota Model.

In contemporary society, the increasing number of pet-owning households has significantly heightened interest in companion animal health, expanding the probiotics market aimed at enhancing pet well-being. Consequently, research into the gut microbiota of companion animals has gained momentum, however, ethical and societal challenges associated with experiments on intelligent and pain-sensitive animals necessitate alternative research methodologies to reduce reliance on live animal testing. To address this need, the Fermenter for Intestinal Microbiota Model (FIMM) is being investigated as an in vitro tool designed to replicate gastrointestinal conditions of living animals, offering a means to study gut microbiota while minimizing animal experimentation. The FIMM system explored interactions between intestinal microbiota and probiotics within a simulated gut environment. Two strains of commercial probiotic bacteria, Enterococcus faecium IDCC 2102 and Bifidobacterium lactis IDCC 4301, along with a newly isolated strain from domestic dogs, Lactobacillus acidophilus SLAM AK001, were introduced into the FIMM system with gut microbiota from a beagle model. Findings highlight the system's capacity to mirror and modulate the gut environment, evidenced by an increase in beneficial bacteria like Lactobacillus and Faecalibacterium and a decrease in the pathogen Clostridium. The study also verified the system's ability to facilitate accurate interactions between probiotics and commensal bacteria, demonstrated by the production of short-chain fatty acids and bacterial metabolites, including amino acids and gamma-aminobutyric acid precursors. Thus, the results advocate for FIMM as an in vitro system that authentically simulates the intestinal environment, presenting a viable alternative for examining gut microbiota and metabolites in companion animals.

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage II-III gastric cancer patients.

Objective: Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions. In this study, we evaluated the clinical feasibility of the single patient classifier (SPC) test, a new clinical-grade prognostic assay, in stage II-III gastric cancer patients. Methods: A prospective multicenter study was conducted, involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals. The SPC test was employed to stratify patients into risk groups, and its feasibility and performance were evaluated. The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment. Furthermore, 3-year disease-free survivals of risk groups were analyzed. Results: The SPC test met the primary endpoint criteria. The 99.5% of SPC tests were timely delivered to hospitals before the postoperative treatment started. In a clinical setting, the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d. Furthermore, 3-year disease-free survivals were significantly different between risk groups classified with SPC tests. Conclusions: This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies. It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Increasing concentrations of dietary threonine, tryptophan, and glycine improve growth performance and intestinal health with decreasing stress responses in broiler chickens raised under multiple stress conditions.

The current study aimed to compare the effects of increasing concentrations of dietary threonine (Thr), tryptophan (Trp), and glycine (Gly) on growth performance, stress biomarkers, and intestinal function in broiler chickens under multiple stress conditions. Five hundred sixty broiler chickens at 21 d old were randomly allotted to 5 treatments with 8 replicates. Birds in a positive control (PC) treatment were raised under low stock density (16.9 birds/m2 per cage) with recommended environmental conditions, whereas birds in 4 treatments were subjected to multiple stress conditions: a cyclic heat stress of 30 ± 0.3 °C for 10 h and 23 ± 0.2 °C for 14 h per day with high stock density (25.3 birds/m2 per cage). A basal diet was assigned to both PC and negative control (NC) treatments. Three additional diets were individually formulated to contain double concentrations of digestible Thr, Trp, or Gly + Ser compared with their concentrations in the basal diet. The experiment lasted for 14 d. Results showed that NC treatment had less growth performance (P < 0.001), jejunal goblet cell counts (P = 0.018), and trans-epithelial electrical resistance (TEER; P < 0.001), but greater (P = 0.026) feather corticosterone (CORT) concentrations than PC treatment. Thr treatment showed the least (P < 0.001) feed conversion ratio (FCR) among treatments under multiple stress conditions. Thr, Trp, and Gly treatments had less (P = 0.026) feather CORT concentrations, but had greater (P < 0.001) TEER than NC treatment. In conclusion, increasing concentrations of dietary Thr, Trp, or Gly improve the growth performance and intestinal health in broiler chickens with decreasing stress response under multiple stress conditions.

Impact of COVID-19 Pandemic on the Clinical and Pathologic Characteristics of Colorectal Cancer: A Retrospective Multicenter Study in South Korea.

Purpose: The COVID-19 pandemic has influenced various aspects of colorectal cancer (CRC) patient care, including diagnosis, treatment, and outcomes. This study assesses the pandemic's impact on CRC patients. Methods: We performed a retrospective analysis of medical records for CRC patients who underwent surgery at five hospitals affiliated with Hallym University from January 2017 to December 2022. Patients were divided into two groups: the pre-COVID group (2017-2019) and the COVID group (2020-2022). Results: Among 2038 patients, 987 (48.4%) were in the pre-COVID group, and 1051 (51.6%) were in the COVID group. The COVID group had more patients with two or more comorbidities (P < 0.001) and a higher incidence of rectal cancer (P = 0.010). While the rates of laparoscopic surgeries were similar, the COVID group had increased emergency surgeries (P = 0.005) and diversion procedures (P = 0.002). Additionally, the COVID group faced more overall complications (P < 0.001) and severe complications (Grade III-V, P = 0.004). There was a rise in lymphovascular invasion (P < 0.001) and T4 stage tumors (P < 0.001) within the COVID group. Despite these differences, both groups had similar 2-year overall survival rates (P = 0.409). Conclusion: Although patients treated during the COVID period experienced more frequent stoma formation, complications, and adverse prognostic factors, there were no differences in short-term oncologic outcomes, which was likely due to the follow-up period being insufficient to detect differences in OS.

The anticoagulation one year after ablation of atrial fibrillation in patients with atrial fibrillation (ALONE-AF) trial: Study protocol.

Background: The ideal long-term antithrombotic strategy for patients after successful catheter-based atrial fibrillation (AF) ablation is still uncertain. Presently, practices vary, and the advantages of oral anticoagulation (OAC) for the post-ablation population are not clearly established. To date, no randomized trials have addressed this therapeutic question. This study aimed to evaluate whether no OAC therapy is superior to apixaban in reducing the risk of stroke, systemic embolism, or major bleeding among patients without apparent recurrent atrial arrhythmias for at least 1 year after their AF ablation procedure. Methods: The ALONE-AF trial is a prospective, multicenter, open-label, randomized study with blinded outcome assessment. Patients with AF who have at least one non-gender stroke risk factor (as determined by the CHA2DS2-VASc score) and no documented recurrences of atrial arrhythmia for at least 12 months post-ablation will be randomly assigned to apixaban 5 mg b.i.d. or no OAC therapy. The primary endpoint is a composite outcome of stroke, systemic embolism, and major bleeding. Key secondary outcomes include clinically relevant non-major bleeding, all-cause mortality, myocardial infarction, transient ischemic attack, quality of life, and frailty analysis. Participants will be followed for a period of 2 years. The estimated total sample size is 840 subjects, with 420 subjects in each arm. Conclusion: The ALONE-AF trial aims to provide robust evidence for the optimal anticoagulation strategy for patients with stroke risk factors following successful AF ablation.

Dual function of PHF16 in reinstating homeostasis of murine intestinal epithelium after crypt regeneration.

Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16-/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16-/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury.