A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Physicochemical Properties of Mixed Gelatin Gels with Soy and Whey Proteins.

The physicochemical properties of the mixed gelatin gels with soy and whey proteins were investigated to develop the gel base with a soft texture and abundant essential amino acids for the elderly. Gelatin-only gel (control) was prepared at 6% (w/v), and mixed gelatin gels were formulated by replacing gelatin with soy protein isolate and whey protein concentrate at different mixing ratios [gelatin (G):soy protein isolate (S):whey protein concentrate (W)]. Results showed that replacing gelatin with the globular proteins in gelatin gels increased the pH value and processing yield (p < 0.05). Moreover, the mixed gelatin gels, particularly the G2:S1:W3 treatment, showed significantly higher essential amino acids than the gelatin-only control. The partial replacement of gelatin with the globular proteins could decrease the hardness of gelatin gel (p < 0.05), but there was no difference in hardness between the G2:G3:W1, G2:S2:W2, and G2:S1:W3 treatments (p > 0.05). The results of protein pattern, x-ray diffraction, and microstructure had no clear evidence for specific protein-protein interaction in the mixed gelatin gels. Therefore, this study indicates that mixed gelatin gels with the globular proteins at specific mixing ratios could be a practical approach to providing a soft texture and high-level essential amino acids to the elderly.

Chemometric approach for an application of Atlantic salmons (Oncorhynchus keta) by-product for potential food sources.

This study identified the aroma profile of salmon by-product for high utilization of by-products, including hydrolysates of head, frame, and skin were treated with reducing sugars and thermal processing. Electronic nose (E-nose) and gas chromatography-mass spectrometry (GC-MS) coupled with gas chromatography-olfactometry (GC-O) were used to analyzed the aroma profile. A total of 140 and 90 volatile compounds were detected through E-nose and GC-MS respectively, and the main volatile compounds were aldehydes. A total of 23 odor active compounds were recognized using GC-O, and 3-methyl-butanal, heptanal, benzaldehyde, octanal, furfural, and methoxy-phenyl-oxime were identified as the aroma of salmon. Using multivariate analysis, the pattern between the pretreated samples and aroma profiles was confirmed, and there were clear separations among the samples. The results of this study provide the aroma profile of salmon by-products and are expected salmon by-products to be used as a potential food source.

Proteolytic Activity of Silkworm Thorn (Cudrania tricuspidata) Fruit for Enzymatic Hydrolysis of Food Proteins.

This study aimed to isolate the proteolytic fraction from the silkworm thorn fruit (Cudrania tricuspidata) through ethanol precipitation at different ratios, and to determine its proteolytic activity and optimal activity conditions. Furthermore, the hydrolysis characteristics and antioxidant activity of soy protein isolate (SPI) and whey protein concentrate (WPC) hydrolyzates obtained through the enzymatic hydrolysis of freeze-dried silkworm thorn fruit powder (SF) were evaluated. For isolation and partial purification of proteolytic fraction, the water-solubilized fraction of the silkworm thorn fruit was purified through ethanol precipitation at four different ratios of 1:1, 1:2, 1:4, and 1:6 (v/v). The protein recovery rate, caseinolytic activity, protein pattern, and optimal activity (pH, temperature, and inhibitors) of fractional ethanol precipitate obtained from the silkworm thorn fruit (ESF) were evaluated. The proteolytic fraction obtained from silkworm thorn fruit exhibited a major protein band around 65-70 kDa and showed the highest proteolytic activity at a 1:4 ratio of ethanol precipitation (p < 0.05). The optimal activity of the measured enzyme fraction was determined to be at pH 9.0 and 50 °C, and the proteolytic activity of ESF was almost inhibited by phenyl methyl sulphonyl fluoride (PMSF, 2 mM), a serine protease inhibitor. Compared to Alcalase and papain, extensively used as commercial enzymes, the silkworm thorn fruit powder was less effective in hydrolyzing SPI and WPC. Nevertheless, SPI and WPC hydrolyzates mediated with silkworm thorn fruit powder showed even better antioxidant activities than those mediated with Alcalase and papain. Thus, our results show the potential application of silkworm thorn fruit as a novel source of plant protease for producing human-grade protein hydrolyzates.

Synthetic Data Improve Survival Status Prediction Models in Early-Onset Colorectal Cancer.

PURPOSE: In artificial intelligence-based modeling, working with a limited number of patient groups is challenging. This retrospective study aimed to evaluate whether applying synthetic data generation methods to the clinical data of small patient groups can enhance the performance of prediction models. MATERIALS AND METHODS: A data set collected by the Cancer Registry Library Project from the Yonsei Cancer Center (YCC), Severance Hospital, between January 2008 and October 2020 was reviewed. Patients with colorectal cancer younger than 50 years who started their initial treatment at YCC were included. A Bayesian network-based synthesizing model was used to generate a synthetic data set, combined with the differential privacy (DP) method. RESULTS: A synthetic population of 5,005 was generated from a data set of 1,253 patients with 93 clinical features. The Hellinger distance and correlation difference metric were below 0.3 and 0.5, respectively, indicating no statistical difference. The overall survival by disease stage did not differ between the synthetic and original populations. Training with the synthetic data and validating with the original data showed the highest performances of 0.850, 0.836, and 0.790 for the Decision Tree, Random Forest, and XGBoost models, respectively. Comparison of synthetic data sets with different epsilon parameters from the original data sets showed improved performance >0.1%. For extremely small data sets, models using synthetic data outperformed those using only original data sets. The reidentification risk measures demonstrated that the epsilons between 0.1 and 100 fell below the baseline, indicating a preserved privacy state. CONCLUSION: The synthetic data generation approach enhances predictive modeling performance by maintaining statistical and clinical integrity, and simultaneously reduces privacy risks through the application of DP techniques.

Effect of coating with combined chitosan and gallic acid on shelf-life stability of Jeju black cattle beef.

OBJECTIVE: Beef of Jeju black cattle (JBC) is considered as a healthy meat type due to its significantly higher unsaturated fatty acids (UFA). Lipid (e.g., UFA) is highly susceptible to oxidizing agents, which results in the quality deterioration and economic value loss of meat products. Therefore, development and application of novel preservative techniques is necessary to improve the shelf-life stability of high-UFA beef. The objective of this study was to assess the applicability of chitosan-based coatings in preservation of JBC beef. METHODS: Different coating solutions: 2% chitosan alone, and 2% chitosan containing 0.1% or 0.3% gallic acid were prepared to investigate their applicability in preservation of fresh beef during storage. Jeju black cattle beef (2-cm thick steaks) were non-coated (control) or coated with the above coating solutions, placed on trays, over-wrapped with plastic film and stored at 4°C. The microbiological indices, color, total volatile basic nitrogen (TVBN) and lipid oxidation of the beef were investigated after 1, 10, and 21 days of storage. RESULTS: Coating with 2% chitosan alone reduced the spoilage bacteria count, TVBN and thiobarbituric acid reactive substances levels in the beef compared with control during storage (p<0.05). Noticeably, coating with 2% chitosan containing 0.1% or 0.3% gallic acid was more effective on retardation of spoilage bacteria growth, lipid oxidation and discoloration in the beef compared to the chitosan coating alone over the storage period (21 days) (p<0.05). CONCLUSION: Taken together, the combined chitosan and gallic acid coating could be used as a bio-preservative technique in the meat industry.

Effects of Poly-L-Lactic Acid on Adipogenesis and Collagen Gene Expression in Cultured Adipocytes Irradiated with Ultraviolet B Rays.

BACKGROUND: Poly-L-lactic acid (PLLA), a synthetic, biocompatible, and biodegradable polymer, has been safely used in several clinical applications. Recently, PLLA has been widely used in the field of dermatology to treat wrinkles in aging skin. Reportedly, PLLA directly acts on dermal fibroblasts causing a significant increase in the expression of type I collagen. However, little is known about the effect of PLLA on adipocytes. OBJECTIVE: This study aimed to analyze the effect of PLLA on adipocytes and examine its potential in treating deep wrinkles engendered by the loss of subcutaneous fat because of aging and photoaging. METHODS: To elucidate the effect of PLLA on skin photoaging, cultured 3T3-L1 adipocytes were irradiated with ultraviolet B (UVB) rays. Oil red O staining was used to detect lipid accumulation in the adipocytes. Real-time quantitative polymerase chain reaction and Western blotting were performed to detect types IV and VI collagen mRNA and protein levels, respectively, under different conditions. RESULTS: The differentiation of 3T3-L1 cells enhanced adipogenesis and the expression of types IV and VI collagens, both of which were inhibited by UVB irradiation. Following this irradiation, PLLA stimulated adipogenesis and the expression of types IV and VI collagens. CONCLUSION: PLLA may provide the beneficial effect on adipocytes from the aspect of adipogenesis and collagen expression in the subcutaneous adipose tissues.

Cases of Pernio-Like Lesions after mRNA-1273 Vaccination with Clinical and Pathological Features: A Single-Center Experience.

The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen®) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna®) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.

Organic Mixed Ionic-Electronic Conductors for Bioelectronic Sensors: Materials and Operation Mechanisms.

The field of organic mixed ionic-electronic conductors (OMIECs) has gained significant attention due to their ability to transport both electrons and ions, making them promising candidates for various applications. Initially focused on inorganic materials, the exploration of mixed conduction has expanded to organic materials, especially polymers, owing to their advantages such as solution processability, flexibility, and property tunability. OMIECs, particularly in the form of polymers, possess both electronic and ionic transport functionalities. This review provides an overview of OMIECs in various aspects covering mechanisms of charge transport including electronic transport, ionic transport, and ionic-electronic coupling, as well as conducting/semiconducting conjugated polymers and their applications in organic bioelectronics, including (multi)sensors, neuromorphic devices, and electrochromic devices. OMIECs show promise in organic bioelectronics due to their compatibility with biological systems and the ability to modulate electronic conduction and ionic transport, resembling the principles of biological systems. Organic electrochemical transistors (OECTs) based on OMIECs offer significant potential for bioelectronic applications, responding to external stimuli through modulation of ionic transport. An in-depth review of recent research achievements in organic bioelectronic applications using OMIECs, categorized based on physical and chemical stimuli as well as neuromorphic devices and circuit applications, is presented.

Impact of Coronavirus Disease 2019 on Gastric Cancer Diagnosis and Stage: A Single-Institute Study in South Korea.

PURPOSE: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. MATERIALS AND METHODS: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period. RESULTS: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. CONCLUSIONS: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

Prior antibiotic administration disrupts anti-PD-1 responses in advanced gastric cancer by altering the gut microbiome and systemic immune response.

Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.

Early-Onset Generalized Pustular Psoriasis of Pregnancy Following Hydroxychloroquine Use.

Generalized pustular psoriasis of pregnancy (GPPP), characterized by widespread sterile pustules and erythematous patches with systemic symptoms such as fever, is a rare form of pustular psoriasis. GPPP typically occurs in the third trimester of pregnancy and can be triggered by various factors such as infections, hypocalcemia, and drugs including N-butyl-scopolammonium bromide. We report a rare case of new-onset GPPP in a 33-year-old multigravida female at 17 weeks' gestation, which occurred earlier than usual, after taking hydroxychloroquine for 3 weeks to treat systemic lupus erythematosus. She stopped her medications and was treated with systemic corticosteroid, but without improvement. Her medication was changed to systemic cyclosporine; her skin lesions improved, which completely resolved after delivery. This is the first case of GPPP developed following hydroxychloroquine use for systemic lupus erythematosus, which occurred earlier than usual and completely resolved after delivery. This case demonstrates that hydroxychloroquine can induce GPPP before the third trimester of pregnancy.

Randomized comparison of in vivo performance of TearLab® and I-PEN® osmometry in normal dogs.

OBJECTIVE: To compare tear film (TF) osmolarity measured using TearLab® and I-PEN® osmometers in the same dogs without any ocular surface disease. ANIMAL STUDIED: Fifty-two dogs (98 eyes) of different breeds were evaluated. PROCEDURES: Tear film (TF) osmolarity was evaluated at 2-min intervals. The test was randomly determined, and single measurements were performed using each osmometer. Subsequently, complete ophthalmologic examinations were performed based on Schirmer tear test-1 (STT-1) analysis, tear film breakup time (TFBUT), and slit-lamp biomicroscopy. For each osmometer, the mean ± standard deviation of the TF osmolarity was calculated, and a paired Student's t-test was used to compare the values obtained. Pearson correlation analysis was performed to assess the association between osmolarity and other values such as STT-1, TFBUT, and age. RESULTS: Tear film osmolarity determined using TearLab® (340.42 ± 15.87 mOsm/L) and I-PEN® (321.58 ± 17.39 mOsm/L) were significantly different (p < .001). However, statistical significance could not be confirmed between osmolarity and other values, such as STT-1, TFBUT, and age. CONCLUSIONS: In dogs, the TF osmolarity values obtained using TearLab® tend to be higher than those obtained using I-PEN®, contrary to that observed in humans. These findings can serve as a reference for establishing normal values for each osmometer for clinical use in measuring TF osmolarity in dogs.

Evaluation of the Chemosensoric Properties of Commercially Available Dog Foods Using Electronic Sensors and GC-MS/O Analysis.

Pet owners think of their animals as part of their family, which further promotes the growth of the pet food market, encouraging pet owners to select nutritious, palatable, and high-quality foods for pets. Therefore, the evaluation of taste and volatile compounds in pet foods is essential to improve palatability. In this study, the sensory characteristics of taste and odor compounds in 10 commercially available dry dog foods were investigated using electronic tongue (E-tongue), electronic nose (E-nose), gas chromatography-mass spectrometry (GC-MS), and gas chromatography-olfactometry (GC-O). Dry dog foods were separated based on the sensory properties of taste and volatile compounds through the multivariate analysis of integrated results of the E-tongue and E-nose. A total of 67 odor active compounds were detected through GC-MS and GC-O, and octanal, nonanal, 2-pentyl furan, heptanal, and benzaldehyde were identified as key odor compounds which may have positive effects on food intake. The multivariate analysis was used to classify samples based on key odor compounds. Volatile compounds responsible for aroma properties of samples were evaluated using GC-O and multivariate analysis in this present study for the first time. These results are expected to provide fundamental data for sensory evaluation in producing new dog foods with improved palatability.

Inhibition of Cell Proliferation and Cell Death by Apigetrin through Death Receptor-Mediated Pathway in Hepatocellular Cancer Cells.

Epidemiologic research recommends using flavonoids in the diet due to their overall health benefits. Apigetrin (Apigenin 7-O-glucoside) is a glycoside phytonutrient found in fruits and vegetables and known for different biological activities such as antioxidant and anti-inflammatory properties. Hepatocellular cancer (HCC) is a major health concern because of its adverse prognosis and side effects of chemotherapeutic agents. In the present study, we determine the impact of apigetrin on HepG2 cells and its cell death mechanism. Apigetrin reduced HepG2 cell proliferation with morphological changes and floating cells in treated cells. Colony formation and wound healing assays showed a reduced cell number in treatment groups. Further, we checked for the cell cycle through flow cytometry to understand the cell death mechanism. Apigetrin induced G2/M phase arrest in HepG2 cells by regulating Cyclin B1 and CDK1 protein levels in HepG2 cells. Annexin V and propidium iodide (PI) staining was performed to confirm the apoptotic cell population in treated groups. At the higher concentration, apigetrin showed a late apoptotic population in HepG2 cells. Chromatin condensation was also found in the treatment groups. Western blot analysis showed an increased expression of extrinsic apoptotic proteins such as FasL, Cleaved caspase 8, Cleaved caspase 3, and cleavage of PARP. In comparison, intrinsic apoptotic pathway markers showed no changes in Bax, Bcl-xL, and Cleaved caspase 9. Altogether, these findings strongly indicate that apigetrin causes cell death in HepG2 cells through the extrinsic apoptotic pathway, and that the intrinsic/mitochondrial pathway is not involved.

Physicochemical Properties of Chicken Breast and Thigh as Affected by Sous-Vide Cooking Conditions.

Sous-vide is a cooking method used to improve the tenderness and juiciness of chicken breast. However, the comparative changes in meat quality attributes of sous-vide cooked chicken breast and thigh muscles are not fully understood. The objective of this study was to investigate the effects of sous-vide cooking conditions, based on collagen denaturation temperature of intramuscular connective tissue, on the physicochemical properties of chicken breasts and thighs. Chicken breast and thigh were cooked at four sous-vide cooking conditions (55 °C for 3/6 h and 65 °C for 3/6 h) and conventional cooking at 75 °C (core temperature of 71 °C) as control. No significant differences in pH and lightness were found between the sous-vide cooking conditions. Moisture content, cooking loss, protein solubility, shear force, myofibrillar fragmentation index, and lipid oxidation were affected by sous-vide cooking conditions (p < 0.05). The decreased shear force and total collagen content of 65 °C sous-vide cooking treatment might be associated with collagen denaturation (p < 0.05). Sous-vide cooking at 55 °C could decrease cooking loss, with higher moisture than sous-vide cooking at 65 °C (p < 0.05). These tendencies on water-holding capacity and shear force at the two different temperatures were similarly observed for both chicken breast and thigh. Therefore, this study indicates that chicken breast and thigh are similarly affected by the sous-vide cooking conditions and suggests that a novel strategy to apply together two temperature ranges based on the thermal denaturation of intramuscular connective tissue would be required.

Hepatic arterial infusion in combination with systemic chemotherapy in patients with hepatic metastasis from colorectal cancer: a randomized phase II study - (NCT05103020) - study protocol.

BACKGROUND: Although 80% of patients with metastatic colorectal cancer (CRC) experience liver metastases, only 10-25% undergo resection at the time of diagnosis. Even in initially unresectable conditions, if appropriate treatment is provided, such as surgical conversion through a combination of hepatic arterial infusion (HAI) chemotherapy and systemic chemotherapy (sys-CT), better overall survival can be expected. Therefore, this study aims to evaluate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy in patients with unresectable CRC with liver-only metastasis. METHODS: This is a single-center, randomized, open-label phase II trial (NCT05103020). Patients with untreated CRC, who have liver-only metastases and for whom liver resection is potentially possible but deemed infeasible at the time of initial diagnosis by a multidisciplinary team, will be eligible. Patients will be randomly assigned in a 1:1 ratio to either the combined HAI oxaliplatin and modified systemic 5-fluorouracil, folinic acid, and irinotecan (FOLFIRI) plus targeted therapy group or the systemic FOLFIRI plus targeted therapy group. Both regimens will be repeated every 2 weeks for a total of 12 cycles. The primary objective of this study is to compare the rate of conversion to liver resection. The surgical conversion rate is expected to increase by 25% with HAI oxaliplatin in combination with sys-CT plus targeted therapy (40% in the experimental arm versus 15% in the control arm) (power, 80%; two-sided alpha-risk, 5%). The secondary objectives include overall survival, progression-free survival, and objective response rate. DISCUSSION: This is the first randomized controlled trial to investigate the efficacy of HAI oxaliplatin in combination with sys-CT plus targeted therapy as first-line treatment from the initial diagnosis in patients with unresectable CRC with liver-only metastasis, aiming to significantly increase the surgical conversion rate. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT05103020). Trial registration date: November 2, 2021.

Effect of High-Versus Low-Frequency of Abdominopelvic Computed Tomography Follow-Up Testing on Overall Survival in Patients With Stage II Or III Colon Cancer.

BACKGROUND: Intensive surveillance of colon cancer by using the abdominopelvic computed tomography (AP-CT) is common in real world practice; however, it is still unclear whether high-frequency surveillance using AP-CT in patients with these risk factors is superior to that in the low-frequency surveillance. PATIENTS AND METHODS: We retrospectively reviewed 1803 patients with stage II-III colon cancer receiving curative surgery between January 1, 2005 to December 31, 2015. We evaluated the average scan-to-scan intervals of postoperative AP-CT testing and assigned patients with an interval of 5 to 8 and 9 to 13 months to the high-frequency (HF) and low-frequency (LF) groups, respectively. The cutoff value of preoperative and postoperative CEA levels was 5 ng/mL. We also applied propensity score matching (PSM) and inverse probability of treatment weighting to adjust clinicopathologic differences between the 2 groups. RESULTS: We matched 1:1 for each surveillance group yielding a cohort of 776 matched patients. After PSM, Baseline demographics were overall well balanced between 2 groups. Stage III (OR, 2.00; 95% Confidence interval [CI], 1.21-3.30) and postoperative CEA elevation (OR, 2.30; 95% CI, 1.08-4.92) were independent risk factors of recurrence in multivariate analyses. Patient in the HF group had more surgery plus chemo- or radiotherapy as postrecurrence treatment than patient in the LF group (46.2% vs. 23.1%, P = .017). This trend was retained after PSM, although it is not significant (44.4% vs. 23.1%, P = .060). However, survival outcomes of high-frequency AP-CT surveillance were not superior to those of low-frequency surveillance in all subgroups, including stage III (HR 0.99, 95% CI 0.40-2.47) and postoperative CEA elevation (HR 1.36, 95% CI 0.45-4.11). CONCLUSION: High-frequency AP-CT testing is associated with a higher proportion of surgery plus chemo- or radiotherapy as postrecurrence treatment, without improvement in 5-year overall survival.

A Comparative Study on the Carcass and Meat Chemical Composition, and Lipid-Metabolism-Related Gene Expression in Korean Hanwoo and Brindle Chikso Cattle.

The objective of this study was to elucidate the effect of cattle breed on carcass and meat chemical composition, fatty acid profiles, and lipid-metabolism-related genes. For this study, same-age Hanwoo and Chikso steers (n = 6 per breed) reared under identical conditions were used. Immediately after slaughter, muscle tissues were collected for analysis of mRNA expression. At 24 h post-mortem, the carcasses were assessed for carcass traits (marbling score, meat yield, etc.), and meat quality and fatty acid profiles in the longissimus lumborum (LL) and semimembranosus (SM) muscles. The results showed that no differences in the slaughter weight, dressing rate, back-fat thickness, trimmed fat, and total meat yield occurred between the two breeds (p > 0.05). However, Hanwoo cattle had a higher marbling score, intramuscular fat (IMF) content, and expression level of lipid-metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor gamma, and fatty acid binding protein 4, compared with Chikso (p < 0.05). Contrastingly, Chikso had a higher total unsaturated fatty acid content and expression level of stearoyl CoA desaturase 1 (p < 0.05). It may be said that the difference in the expression levels of lipid-metabolism-related genes could be the molecular factors underlying IMF deposition and fatty acid profile differences in the beef from the two breeds.

Lazertinib in pretreated EGFR T790M-mutated advanced non-small cell lung cancer: A real-world multicenter study.

INTRODUCTION: Lazertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that provides a high level of selectivity for sensitizing and p.Thr790Met (T790M) EGFR mutations. We aimed to collect real-world data regarding the efficacy and safety of lazertinib. METHODS: This study included patients treated with lazertinib for T790M-mutated non-small cell lung cancer who had previously been treated with an EGFR-TKI. The primary outcome measure was progression-free survival (PFS). Additionally, this study evaluated overall survival (OS), time-to-treatment failure (TTF), duration of response (DOR), objective response rate (ORR) and disease control rate (DCR). Drug safety was also assessed. RESULTS: In a study of 103 patients, 90 received lazertinib as a second- or third-line therapy. The ORR and DCR were 62.1% and 94.2%, respectively. The median follow-up duration was 11.1 months, and the median PFS period was 13.9 (95% confidence interval [CI], 11.0-not reached [NR]) months. OS, DOR, and TTF had not yet been determined. In a subgroup of 33 patients with evaluable brain metastases, the intracranial DCR and ORR were 93.5% and 57.6%, respectively. The median intracranial PFS period was 17.1 (95% CI, 13.9-NR) months. Approximately 17.5% of patients had dose modification or discontinuation due to adverse events, with the most common being grade 1 or 2 paresthesia. CONCLUSIONS: The efficacy and safety of lazertinib were recapitulated in a real-world study reflecting routine clinical practice in Korea, showing durable disease control both systematically and intracranially, with manageable side effects.