Association of CYP2C19 genotypes with postoperative atrial fibrillation after coronary artery bypass surgery.

This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.

Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function.

Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder cells expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons of mbIL15 to mbIL21 for NK expansion lack comparisons of key attributes of the resulting NK cells, including their high-dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL15- and mbIL21-based feeder cells are absent. We addressed these gaps and found that using mbIL15- versus mbIL21-based feeder cells drove distinct phenotypic and functional profiles. Feeder cells expressing mbIL15 alone drove superior functionality by nearly all measures, whereas those expressing mbIL21 alone drove superior yield. In combination, most attributes resembled those imparted by mbIL21, whereas in sequence, NK yield approximated that imparted by the first cytokine, and the phenotype, transcriptome, and function resembled that driven by the second cytokine, highlighting the plasticity of NK cell differentiation. The sequence mbIL21 followed by mbIL15 was advantageous in achieving significant yields of highly functional NK cells that demonstrated equivalent in vivo activity to those expanded by mbIL15 alone in two of three xenograft models. Our findings define the impact of mbIL15 versus mbIL21 during NK expansion and reveal a previously underappreciated tradeoff between NK yield and function for which sequential use of mbIL21-based followed by mbIL15-based feeder cells may be the optimal approach in many settings.

Intergenerational toxic effects of parental exposure to [Cn mim]NO3 (n = 2,4,6) on nervous and skeletal development in zebrafish offspring.

Ionic liquids (ILs) are thought to have negative effects on human health. Researchers have explored the effects of ILs on zebrafish development during the early stages, but the intergenerational toxicity of ILs on zebrafish development has rarely been reported. Herein, parental zebrafish were exposed to different concentrations (0, 12.5, 25, and 50 mg/L) of [Cn mim]NO3 (n = 2, 4, 6) for 1 week. Subsequently, the F1 offspring were cultured in clean water for 96 h. [Cn mim]NO3 (n = 2, 4, 6) exposure inhibited spermatogenesis and oogenesis in F0 adults, even causing obvious lacunae in the testis and atretic follicle oocytes in ovary. After parental exposure to [Cn mim]NO3 (n = 2, 4, 6), the body length and locomotor behavior were measured in F1 larvae at 96 hours post-fertilization (hpf). The results showed that the higher the concentration of [Cn mim]NO3 (n = 2, 4, 6), the shorter the body length and swimming distance, and the longer the immobility time. Besides, a longer alkyl chain length of [Cn mim]NO3 had a more negative effect on body length and locomotor behavior. RNA-seq analysis revealed several downregulated differentially expressed genes (DEGs)-grin1b, prss1, gria3a, and gria4a-enriched in neurodevelopment-related pathways, particularly the pathway for neuroactive ligand-receptor interaction. Moreover, several upregulated DEGs, namely col1a1a, col1a1b, and acta2, were mainly associated with skeletal development. Expression of DEGs was tested by RT-qPCR, and the outcomes were consistent with those obtained from RNA-Seq. We provide evidence showing the effects of parental exposure to ILs on the regulation of nervous and skeletal development in F1 offspring, demonstrating intergenerational effects.

MicroRNA-29a-3p Prevents Drug-Induced Acute Liver Failure through Inflammation-Related Pyroptosis Inhibition.

OBJECTIVE: Little is known about the role of microRNA-29a-3p (miR-29a-3p) in inflammation-related pyroptosis, especially in drug-induced acute liver failure (DIALF). This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms. METHODS: Thioacetamide (TAA)- and acetaminophen (APAP)-induced ALF mouse models were established, and human samples were collected. The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, or immunochemical staining in miR-29a-3p knock-in transgenic mouse (MIR29A(KI/KI)) DIALF models. In addition, RNA sequencing was conducted to explore the mechanisms. RESULTS: MiR-29a-3p levels were decreased in TAA- and APAP-induced DIALF models. MiR-29a-3p prevented DIALF caused by TAA and APAP. RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis, and the inhibition was dependent on activation of the PI3K/AKT pathway. In addition, miR-29a-3p levels were reduced, and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients. CONCLUSION: The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF. MiR-29a-3p may be a promising therapeutic target for DIALF.

[Simultaneous determination of seven quaternary ammonium compounds in frozen food by ultra performance liquid chromatography-tandem mass spectrometry combined with modified QuEChERS method].

Quaternary ammonium compounds (QACs) are a class of cationic surfactants that can be used as the main active ingredient of disinfectants. The increased use of QACs is concerning as exposure from inhalation or ingestion to these compounds that has been associated with adverse effects on the reproductive and respiratory systems. Humans are exposed to QACs primarily by food consumption and inhalation of air. QAC residues pose significant threats to public health. Given the importance of assessing potential residue levels for QACs in food, therefore, a method was developed for the simultaneous detection of six common QACs and one emerging QAC (Ephemora) in frozen food by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with the modified QuEChERS method. The main factors governing the response, recovery, and sensitivity of the method, including extraction solvents, types and dosages of adsorbents, apparatus conditions, and mobile phases, were optimized in the course of sample pretreatment and instrument analysis. QAC residues in frozen food were extracted using 20 mL methanol-water (90∶10, containing 0.5% formic acid) for 20 min by the vortex shock method. The mixture was ultrasonicated for 10 min and centrifuged at 10000 r/min for 10 min. A 1-mL aliquot of the supernatant was transferred to a new tube and purified using 100 mg of PSA adsorbents. After mixing and centrifugation at 10000 r/min for 5 min, the purified solution was analyzed. Target analytes were separated on an ACQUITY UPLC BEH C8 chromatographic column (50 mm×2.1 mm, 1.7 µm) at a column temperature of 40 ℃ and a flow rate of 0.3 mL/min. The injection volume was 1 µL. Gradient elution was performed using methanol and 5 mmol/L ammonium acetate solution as the mobile phases. Multiple reaction monitoring (MRM) was conducted in the positive electrospray ionization (ESI+) mode. The matrix-matched external standard method was used to quantify seven QACs. The optimized chromatography-based method completely separated the seven analytes. Good linear relationships were obtained for the seven QACs in the range of 0.1-100.0 ng/mL. The correlation coefficient (r2) ranged from 0.9971 to 0.9983. The limits of detection and limits of quantification ranged from 0.5 to 1.0 µg/kg and 1.5 to 3.0 µg/kg, respectively. Accuracy and precision were determined by spiking salmon and chicken samples with 3.0, 10.0, and 100.0 µg/kg of analytes, in compliance with the current legislation, with six replicates per determination. The average recoveries of the seven QACs ranged from 65.4% to 101%. The relative standard deviations (RSDs) were between 0.64% and 16.8%. Matrix effects of the analytes were between -27.5% and 33.4% in salmon and chicken samples after purifying using PSA. The developed method was applied to the determination of seven QACs in rural samples. QACs were detected in only one sample; the level did not exceed European Food Safety Authority specified residue limit standards. The detection method has high sensitivity, good selectivity and stability, and the results are accurate and reliable. It is suitable for the simultaneous rapid determination of seven QAC residues in frozen food. The results provide valuable information for future risk assessment studies targeting this class of compounds.

Simultaneous Measurement of Group Refractive Index Dispersion and Thickness of Fused Silica Using a Scanning White Light Interferometer.

In this study, we simultaneously measured the group refractive index dispersion and thickness of fused silica using a scanning white light interferometer on a spectral range from 800 to 1050 nm. A delay error correction was performed using a He-Ne laser. The accuracy of the measured group refractive index dispersion of fused silica, when compared to the temperature-dependent Sellmeier equation, is within 4 × 10-5.

Thermal suppression of high-repetition rate SBS pulse compression in liquid media.

Thermal problems of high-repetition-rate stimulated Brillouin scattering (SBS) pulse compression in liquid media are theoretically and experimentally analyzed in detail. A wedge lens with less coma-aberration was designed using the ray tracing method and the thermally induced beam-pattern distortion was compensated by inhibiting thermal convection. The heat transfer form and fluid state were quantitatively analyzed for different SBS liquid media. For a 74-W pump power, 3-kHz pulse-compressed phase-conjugation mirror with an energy efficiency of 36.2% is achieved. A potential optimization method of continuously adjusting SBS output characteristics using a mixed medium is proposed and theoretically demonstrated, to improve energy efficiency.

Clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: results from the China Cardiovascular Association Database-Heart Failure Center Registry.

AIM: We aimed to evaluate clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) from China. Factors associated with outcomes (hospitalization for HF [HHF] and cardiovascular [CV] death) were assessed. METHOD AND RESULTS: Data were from the China Cardiovascular Association (CCA) Database-HF Center Registry. Between January 2017 and June 2021, 41 708 hospitalized HFpEF patients with 1-year follow-up from 481 CCA Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China were included in this study. Of study participants (mean age 72.2 years, 49.3% female), 18.2% had HHF in prior 1 year and 55.8% had New York Heart Association class III/IV. Median left ventricular ejection fraction was 59%. Ischaemia (26.6%), infection (14.4%) and arrhythmia (10.5%) were the three most common precipitating factors for index HHF. Nearly 67.4% had ≥3 comorbidities. Hypertension (65.2%), coronary heart disease (60.3%) and atrial fibrillation (41.2%) were the three most common comorbidities. Device and medication therapy non-compliance with current HF guideline recommendation was observed. The 1-year rate of clinical outcomes was 16.4%, the 1-year rate of HHF was 13.6% and CV death was 3.1%. Factors associated with clinical outcomes included HHF in prior 1 year, serum level of sodium <135 mmol/L and N-terminal pro-B-type natriuretic peptide >1800 pg/ml. CONCLUSION: Patients with HFpEF from China were characterized by high comorbid burden and high 1-year risk of HHF and CV death. Immediate efforts are needed to improve HFpEF management in China.

Prevalence of Cirrhosis/Advanced Fibrosis Among HBsAg-Negative and HBcAb-Positive US Adults: A Nationwide Population-Based Study.

INTRODUCTION: Evaluation of cirrhosis appears to be easily overlooked in the clinic for the HBsAg-negative (hepatitis B surface antigen-negative) and HBcAb-positive (hepatitis B core antibody-positive) population. Herein, we determine the prevalence of cirrhosis/advanced fibrosis among HBsAg-negative/HBcAb-positive US adults. METHODS: Data came from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. A total of 3115 HBsAg-negative/HBcAb-positive US adults were enrolled in this study. We assessed cirrhosis by using the Fibrosis-4 (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) score. RESULTS: Out of 50,201 NHANES adults, 45,087 were tested for HBcAb/HBsAg, of whom 3115 met the inclusion criteria (HBsAg-negative/HBcAb-positive with available data for FIB-4/APRI). The weighted proportion of HBsAg-negative/HBcAb-positive among US adults was 4.46% (95% CI 4.17-4.75%), affecting 9.87 million US adults. According to the results of the FIB-4, the weighted prevalence of cirrhosis/advanced fibrosis among HBsAg-negative/HBcAb-positive US adults was 3.76% (95% CI 2.80-4.72%), which corresponds to 371,112 (95% CI 276,360-465,864) HBsAg-negative/HBcAb-positive American adults who had already developed cirrhosis. Among those, cirrhosis/advanced fibrosis in the HBsAb-negative (hepatitis B surface antibody) group (6.28%, 95% CI 4.10-8.45%) was significantly higher than in the HBsAb-positive group (3.08%, 95% CI 2.07-4.08%). Results were similar when APRI was used. CONCLUSION: According to the FIB-4, 3.76% of HBsAg-negative and HBcAb-positive US adults had cirrhosis/advanced fibrosis, much higher than in the general population of the USA. Our data highlight the importance of cirrhosis screening in the HBsAg-negative/HBcAb-positive population to prevent advanced liver disease, especially in those who are HBsAb-negative.

Quantitative immunopeptidomics reveals a tumor stroma-specific target for T cell therapy.

T cell receptor (TCR)-based immunotherapy has emerged as a promising therapeutic approach for the treatment of patients with solid cancers. Identifying peptide-human leukocyte antigen (pHLA) complexes highly presented on tumors and rarely expressed on healthy tissue in combination with high-affinity TCRs that when introduced into T cells can redirect T cells to eliminate tumor but not healthy tissue is a key requirement for safe and efficacious TCR-based therapies. To discover promising shared tumor antigens that could be targeted via TCR-based adoptive T cell therapy, we employed population-scale immunopeptidomics using quantitative mass spectrometry across ~1500 tumor and normal tissue samples. We identified an HLA-A*02:01-restricted pan-cancer epitope within the collagen type VI α-3 (COL6A3) gene that is highly presented on tumor stroma across multiple solid cancers due to a tumor-specific alternative splicing event that rarely occurs outside the tumor microenvironment. T cells expressing natural COL6A3-specific TCRs demonstrated only modest activity against cells presenting high copy numbers of COL6A3 pHLAs. One of these TCRs was affinity-enhanced, enabling transduced T cells to specifically eliminate tumors in vivo that expressed similar copy numbers of pHLAs as primary tumor specimens. The enhanced TCR variants exhibited a favorable safety profile with no detectable off-target reactivity, paving the way to initiate clinical trials using COL6A3-specific TCRs to target an array of solid tumors.

ARNI or ARB Treats Residual Left Ventricular Remodelling after Surgery for Valvular Regurgitation: ReReRe study protocol.

AIMS: Patients with persistent or de novo left ventricular (LV) dilation and/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline-directed medical therapy after successful aetiology-reversing surgery. We aim to (i) compare the effectiveness of sacubitril/valsartan vs. valsartan in promoting LV reverse remodelling and (ii) explore the safety of medication withdrawal after LV recovery. METHODS AND RESULTS: The ReReRe study is a multicentre, randomized, open-label, parallel trial that consists of two consecutive parts. A total of 371 patients with an LV end-diastolic diameter (LVEDD) > 60 mm or LVEF < 50%, assessed by transthoracic echocardiography (TTE) 7-14 days after valve surgery for significant AR or primary MR will be enrolled. The 1st randomization into the sacubitril/valsartan or valsartan groups and structured follow-up (1, 3, 6, 9, and 12 months after randomization) will be conducted to observe the primary objective as the rate of complete recovery of LV remodelling (i.e. LVEDD < 55 mm and LVEF ≥ 60% by TTE at two consecutive visits). Those who have complete recovery of LV remodelling will be enrolled in Study Part 2; consequently, they will receive the 2nd randomization into the medication withdrawal or maintenance group and 6-monthly visits for the observation of the primary objective as the rate of LV remodelling relapse (LVEDD > 60 mm or LVEF < 50%). The secondary objectives include the rate of composite clinical outcomes and the degree of change in 6-min walk distance and Kansas City Cardiomyopathy Questionnaire scores. CONCLUSIONS: The ReReRe study will provide new evidence for the treatment of patients with residual LV remodelling after curable unloaded surgery, as well as the duration of treatment. The study results will fill the gap in identifying an appropriate medical therapy regimen for this group of patients and perhaps for those with reversible aetiologies of heart failure.

Paeoniflorin Inhibits ASK1-TF Axis by Up-Regulating SOCS3 to Alleviate Radiation Enteritis.

Radiation enteritis is one of the main adverse effects of radiotherapy, presenting with a poorly understood etiology and limited options for therapy. Intestinal inflammation and ischemia are the core mechanisms of radiation enteritis. Suppressor of cytokine signaling 3 (SOCS3) is an endogenous "inflammation brake." We hypothesized that paeoniflorin, a pinane monoterpene bitter glycoside, could increase SOCS3 expression to reduce inflammation and ischemia and improve enteritis in mice. Laser Doppler flowmetry was used to detect changes in intestinal blood flow. RAW264.7 and human umbilical vein endothelial cells were used to investigate the mechanism of action of paeoniflorin. It was observed that radiation caused high mortality, intestinal inflammatory responses, and low blood flow in mice. Paeoniflorin effectively alleviated intestinal atrophy, prevented thrombosis, improved radiation enteritis, and reduced mortality in mice undergoing radiotherapy. In addition, paeoniflorin increased the release of growth arrest-specific gene 6 (Gas6) and phosphorylation of the Axl receptor, subsequently inducing the expression of SOCS3 and inhibiting the expression of p-apoptosis signal-regulating kinase 1 and tissue factor in vivo and in vitro. Based on our findings, we suggest that paeoniflorin is potentially effective in alleviating radiation enteritis via the activation of the Gas6/Axl/SOCS3 axis and subsequent reduction in intestinal inflammation and ischemia.

Genetic diversity and population structure of Mongolian regional horses with 14 microsatellite markers.

OBJECTIVE: This study aimed to identify the genetic diversity and population structure of Mongolian horse populations according to the province of residence (Khentii, KTP; Uvs, USP; Omnogovi and Dundgovi, GOP; Khovsgol, KGP) using 14 microsatellite (MS) markers. METHODS: A total of 269 whole blood samples were obtained from the four populations (KTP, USP, GOP, KGP) geographically distinct provinces. Multiplex polymerase chain reaction (PCR) was conducted using 14 MS markers (AHT4, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, and VHL20), as recommended by the International Society for Animal Genetics. Capillary electrophoresis was conducted using the amplified PCR products, alleles were determined. Alleles were used for statistical analysis of genetic variability, Nei's DA genetic distance, principal coordinate analysis (PCoA), factorial corresponding analysis (FCA), and population structure. RESULTS: On average, the number of alleles, expected heterozygosity (HExp), observed heterozygosity (HObs), and polymorphic information content among all populations were 11.43, 0.772, 0.757, and 0.737, respectively. In the PCoA and FCA, GOP, and KGP were genetically distinct from other populations, and the KTP and USP showed a close relationship. The two clusters identified using Nei's DA genetic distance analysis and population structure highlighted the presence of structurally clear genetic separation. CONCLUSION: Overall, the results of this study suggest that genetic diversity between KTP and USP was low, and that between GOP and KGP was high. It is thought that these results will help in the effective preservation and improvement of Mongolian horses through genetic diversity analysis and phylogenetic relationships.

Analysis of genetic diversity and structure of Mongolian horse using microsatellite markers.

Mongolian horses are one of the oldest horse breeds, and are very important livestock in Mongolia as they are used in various fields such as transportation, food (milk, meat), and horse racing. In addition, research and preservation on pure Mongolian breeds are being promoted under the implementation of the new Genetics of Livestock Resources' act in Mongolia. However, despite the implementation of this act, genetic research on Mongolian horses using microsatellites (MS) has not progressed enough. Therefore, this study was conducted to analyze the genetic polymorphism of five breeds (Gobi shankh, Tes, Gal shar, Darkhad, and Undurshil) using 14 MS markers recommended by International Society for Animal Genetics (ISAG). The mean number of alleles (MNA) was 8.29, expected heterozygosity frequency (HExp) was 0.767, observed heterozygosity frequency (HObs) was 0.752, and polymorphism information content (PIC) was 0.729. The Nei's genetic distance analysis showed that the genetic distance between Gobi shankh and Darkhad horses was the farthest, and the other three breeds, Tes, Gal shar, and Undurshil were found to be close to each other. Similarly, the principal coordinate analysis (PCoA) and factorial correspondence analysis (FCA) showed that the Gobi shankh and Darkhad horses were genetically distinct from other breeds. On the other hand, it appears that Tes, Gal shar, and Undurshil horses, which are genetically similar, most likely interbred with each other. Therefore, it is expected that these results will help the conservation of genetic resources in Mongolia and the establishment of policies related to Mongolian horses.

Effects of L-glutamine supplementation on degradation rate and rumen fermentation characteristics in vitro.

OBJECTIVE: Two follow-up studies (exp. 1 and 2) were conducted to determine the effects of L-glutamine (L-Gln) supplementation on degradation and rumen fermentation characteristics in vitro. METHODS: First, rumen liquor from three cannulated cows was used to test L-Gln (50 mM) degradation rate and ammonia-N production at 6, 12, 24, 36, and 48 h after incubation (exp. 1). Second, rumen liquor from two cannulated steers was used to assess the effects of five levels of L-Gln including 0% (control), 0.5%, 1%, 2%, and 3% at 0, 3, 6, 12, 24, 36, and 48 h after incubation on fermentation characteristics, gas production, and degradability of nutrients (exp. 2). RESULTS: In exp. 1, L-Gln degradation rate and ammonia-N concentrations increased over time (p<0.001). In exp. 2, pH was reduced significantly as incubation time elapsed (p<0.001). Total gas production tended to increase in all groups as incubation time increased. Acetate and propionate tended to increase by increasing glutamine (Gln) levels, whereas levels of total volatile fatty acids (VFAs) were the highest in 0.5% and 3% Gln groups (p<0.001). The branched-chain VFA showed both linear and quadratic effects showing the lowest values in the 1% Gln group particularly after 6 h incubation (p<0.001). L-Gln increased crude protein degradability (p<0.001), showing the highest degradability in the 0.5% Gln group regardless of incubation time (p<0.05). Degradability of acid detergent fiber and neutral detergent fiber showed a similar pattern showing the highest values in 0.5% Gln group (p<0.10). CONCLUSION: Although L-Gln showed no toxicity when it was supplemented at high dosages (2% to 3% of DM), 0.5% L-Gln demonstrated the positive effects on main factors including VFAs production in-vitro. The results of this study need to be verified in further in-vivo study.

Accurate prediction of acute pancreatitis severity based on genome-wide cell free DNA methylation profiles.

BACKGROUND: Patients with severe acute pancreatitis (SAP) have a high mortality, thus early diagnosis and interventions are critical for improving survival. However, conventional tests are limited in acute pancreatitis (AP) stratification. We aimed to assess AP severity by integrating the informative clinical measurements with cell free DNA (cfDNA) methylation markers. METHODS: One hundred and seventy-five blood samples were collected from 61 AP patients at multiple time points, plus 24 samples from healthy individuals. Genome-wide cfDNA methylation profiles of all samples were characterized with reduced representative bisulfite sequencing. Clinical blood tests covering 93 biomarkers were performed on AP patients within 24 h. SAP predication models were built based on cfDNA methylation and conventional blood biomarkers separately and in combination. RESULTS: We identified 565 and 59 cfDNA methylation markers informative for acute pancreatitis and its severity. These markers were used to develop prediction models for AP and SAP with area under the receiver operating characteristic of 0.92 and 0.81, respectively. Twelve blood biomarkers were systematically screened for a predictor of SAP with a sensitivity of 87.5% for SAP, and a specificity of 100% in mild acute pancreatitis, significantly higher than existing blood tests. An expanded model integrating 12 conventional blood biomarkers with 59 cfDNA methylation markers further improved the SAP prediction sensitivity to 92.2%. CONCLUSIONS: These findings have demonstrated that accurate prediction of SAP by the integration of conventional and novel blood molecular markers, paving the way for early and effective SAP intervention through a non-invasive rapid diagnostic test.

Estimation of Genetic Parameters and Correlation between Yearling Ultrasound Measurements and Carcass Traits in Hanwoo Cattle.

Genetic parameters have a significant role in designing a breeding program and are required to evaluate economically important traits. The objective of this study was to estimate heritability and genetic correlation between yearling ultrasound measurements, such as backfat thickness (UBFT), eye muscle area (UEMA), intramuscular fat content (UIMF), and carcass traits, such as backfat thickness (BFT), carcass weight (CW), eye muscle area (EMA), marbling score (MS) at approximately 24 months of age, as well as yearling weight (YW) in Hanwoo bulls (15,796) and steers (5682). The (co) variance components were estimated using a multi-trait animal model. Moderate to high heritability estimates were obtained and were 0.42, 0.50, 0.56, and 0.59 for CW, EMA, BFT, and MS, respectively. Heritability estimates for yearling measurements of YW, UEMA, UBFT, and UIMF were 0.31, 0.32, 0.30, and 0.19, respectively. Favorable and strong genetic correlations were observed between UIMF and MS (0.78), UBFT and BFT (0.63), and UEMA and EMA (0.65). Moreover, the estimated genetic correlation between YW and CW was high (0.84) and relatively moderate between YW and EMA (0.43). These results suggest that genetic improvement can be achieved for carcass traits when using yearling ultrasound measurements as selection criteria in ongoing Hanwoo breeding programs.