Management of follicular thyroid carcinoma.

Follicular thyroid carcinoma (FTC) is the second most common histological type of thyroid carcinoma. This review aims to summarize the available evidence and guidelines and provide an updated consensus regarding the management of FTC. The cytoarchitectural features of FTC are similar to those of follicular adenoma (FA), and it is difficult to preoperatively distinguish between FA and FTC. For nodules with Bethesda class III-V cytology, molecular test results (if available) should be considered before the operation. However, it should be noted that molecular tests are not available in all countries. The goals of initial surgical therapy for patients with FTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification while minimizing treatment-related morbidity and unnecessary therapy. Previous studies have reported some prognostic factors such as distant metastasis, age, tumor size, vascular invasion, TERT promoter mutation, and histological subtype. In particular, the degree of vascular invasion is becoming increasingly important. Evaluating these prognostic factors is essential for prognostic prediction and precise management of patients with FTC. Recurrence and distant metastasis of FTC are treated with radioactive iodine (RAI). However, some FTCs become refractory to RAI. Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin-angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

Image quality improvement in single plane-wave imaging using deep learning.

In ultrasound image diagnosis, single plane-wave imaging (SPWI), which can acquire ultrasound images at more than 1000 fps, has been used to observe detailed tissue and evaluate blood flow. SPWI achieves high temporal resolution by sacrificing the spatial resolution and contrast of ultrasound images. To improve spatial resolution and contrast in SPWI, coherent plane-wave compounding (CPWC) is used to obtain high-quality ultrasound images, i.e., compound images, by coherent addition of radio frequency (RF) signals acquired by transmitting plane waves in different directions. Although CPWC produces high-quality ultrasound images, their temporal resolution is lower than that of SPWI. To address this problem, some methods have been proposed to reconstruct a ultrasound image comparable to a compound image from RF signals obtained by transmitting a small number of plane waves in different directions. These methods do not fully consider the properties of RF signals, resulting in lower image quality compared to a compound image. In this paper, we propose methods to reconstruct high-quality ultrasound images in SPWI by considering the characteristics of RF signal of a single plane wave to obtain ultrasound images with image quality comparable to CPWC. The proposed methods employ encoder-decoder models of 1D U-Net, 2D U-Net, and their combination to generate the high-quality ultrasound images by minimizing the loss that considers the point spread effect of plane waves and frequency spectrum of RF signals in training. We also create a public large-scale SPWI/CPWC dataset for developing and evaluating deep-learning methods. Through a set of experiments using the public dataset and our dataset, we demonstrate that the proposed methods can reconstruct higher-quality ultrasound images from RF signals in SPWI than conventional method.

A case of situs inversus totalis with hemosuccus pancreaticus due to intrapancreatic pseudocyst perforation of the common hepatic artery treated with a vascular stent graft.

Hemosuccus pancreaticus (HP) is characterized by gastrointestinal bleeding from the papilla of Vater via the pancreatic duct. In this report, we describe a case of HP due to arterial perforation in a pancreatic pseudocyst and discuss the computed tomography (CT) findings and efficacy of stent graft placement. A 64-year-old man with a history of heavy alcohol use, situs inversus totalis, and total gastrectomy was hospitalized with hematochezia. Enhanced CT revealed a pseudoaneurysm in the common hepatic artery (CHA) with mildly high density in the main pancreatic duct. Subsequent CT revealed an enlarged cystic lesion with inflow of contrast medium. Angiography confirmed blood flow from the CHA into the pancreatic pseudocyst, and the patient was diagnosed with HP due to intrapancreatic pseudocyst perforation of the CHA pseudoaneurysm. Coil packing into the pseudocyst failed to block the blood flow, and a covered stent graft was placed into the CHA. The patient had an uneventful clinical course. The identification of a pseudoaneurysm and a high-density area in the main pancreatic duct on enhanced CT and changes in the pancreatic cyst diameter may indicate the acute phase of HP, and stent grafting is an effective treatment for intracystic arterial perforation.

Incidence of the postpartum diagnosis of thyroid eye disease in relation to thyroid function in Graves' disease.

It has been reported that Graves' disease (GD) sometimes improves spontaneously during pregnancy, although exacerbation of GD during postpartum period or relapse of hyperthyroidism caused by GD might occur. This study aimed to investigate the incidence of postpartum diagnosis of thyroid eye disease (TED) in relation to thyroid dysfunction. This retrospective cross-sectional study enrolled 11,104 deliveries from the patients with GD between January 2004 and August 2022. Within the 12-month postpartum period, 72 patients (0.65%) were diagnosed with TED. The thyroid function of the 72 patients comprised 9 remission, 13 continued antithyroid medicine, and 50 thyroid dysfunction; 30 newly diagnosed GD, 1 hypothyroidism, and 19 relapse/recurrence of GD. In the 49 patients with thyroid dysfunction, no difference was observed in the median values of thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and TSH receptor stimulating antibody between the TED diagnosis and the development of hyperthyroidism. However, when the patients were classified into the newly developed GD and relapse/recurrence of GD groups, the difference became significant and the TRAb level was high in the newly developed GD (16.1 vs. 5.0 IU/L, p < 0.0001, and 15.0 vs. 6.0 IU/L, p = 0.0003). Thyroid dysfunction preceded TED diagnosis in more than half of the patients and the median time for each event was 6.5 vs. 8.1 months. The active phase TED was observed in 8 of the 72 patients. Of the 72 patients newly diagnosed with TED in postpartum, two-thirds were accompanied by thyroid dysfunction and 8 of them were in active phase.

Exacerbation of Thyroid Eye Disease and Dysthyroid Optic Neuropathy During Pregnancy: A Case Report.

A 37-year-old, never-smoker, pregnant woman diagnosed with Graves' disease who had stable thyroid eye disease (TED) before pregnancy presented with aggravated proptosis and eyelid swelling at 13 weeks of pregnancy. Despite the administration of local triamcinolone and 3 cycles of corticosteroid pulse therapy from 25 to 28 weeks, the patient's visual acuity decline necessitated postpartum orbital decompression surgery. Although TSH receptor antibody (TRAb) levels decreased during the mid- to late term of pregnancy, the TED worsened. This finding suggests that factors other than anti-TSH receptor antibodies may have a significant effect on disease severity.

Real world data of cabozantinib in patients with hepatocellular carcinoma: Focusing on dose setting and modification.

AIM: To investigate the outcomes of cabozantinib in patients with unresectable hepatocellular carcinoma (uHCC), focusing on dose setting and modification. METHODS: We retrospectively analyzed 34 Japanese patients who received cabozantinib for uHCC. Trough concentrations (Ctrough) of cabozantinib were also measured weekly for 6 weeks in the 18 patients. RESULTS: Sixteen patients received ≥40 mg (high-dose group), and 18 patients received 20 mg (low-dose group). Dose escalations were performed in 27.8% of the patients in the low-dose group. Although median duration of the first dose reduction or interruption in the low-dose group was twice that in the high-dose group (28 vs. 14 days, p < 0.001), there were no significant differences in the relative dose intensity (RDI) during 6 weeks, progression free survival (PFS), and overall survival (p = 0.162, p = 0.950, p = 0.817, respectively) between the two groups. Patients who received RDI during 6 weeks ≥33.4% showed a trend toward longer median PFS (p = 0.054). Each serum aldolase value during the 6 weeks was significantly correlated with the Ctrough at any point (r = 0.500, p < 0.001). In multivariate analyses, aldolase ≥8.7 U/L within 2 weeks was significantly associated with the very early dose reduction or interruption (odds ratio 20.0, p = 0.002). CONCLUSIONS: An initial dose of 20 mg cabozantinib could be a safe option in Japanese patients. The serum aldolase value could be useful for making appropriate dose modifications of cabozantinib.

Subacute thyroiditis during pregnancy: clinical characteristics of seven cases.

Objective: There are few reports of subacute thyroiditis (SAT) during pregnancy. This study aimed to clarify the clinical characteristics of SAT in pregnant patients. Methods and results: Seven patients diagnosed with SAT during pregnancy at our institution from January 2004 to December 2021 were identified, and their clinical findings were retrospectively examined. At SAT diagnosis, the median age was 34 (range: 31-42) years, the median duration of pregnancy was 5 (4-24) weeks, and all patients had neck pain but no fever. On laboratory examination, median (range) free thyroxine, free triiodothyronine, and C-reactive protein levels were 2.66 (1.14-7.77) ng/dL, 7.1 (3.3-16.1) pg/mL, and 2.22 (0.42-5.79) mg/dL, respectively, and all patients had a hypoechoic lesion of the thyroid gland. Three patients (43%) were treated with steroids, and three patients (43%) received replacement therapy with levothyroxine for hypothyroidism following destructive thyroiditis. There were no pregnancy complications in any of the cases. These seven patients (pregnancy group) were compared with 217 non-pregnant female patients (non-pregnancy group) aged 31 to 42 years who were diagnosed with SAT at our institution from 2016 to 2019. The frequency of body temperatures above 37°C was lower in the pregnancy group than in the non-pregnancy group (0% vs 65%). Conclusion: Patients who develop SAT during pregnancy may have less fever than non-pregnant patients with SAT. There were no pregnancy complications in the pregnancy group in this study. This suggests that adverse pregnancy outcomes may be avoided by the appropriate management of SAT, including hypothyroidism after destructive thyroiditis.

Active surveillance vs. surgery in low-risk papillary thyroid microcarcinoma patients and the risk of loss to follow-up.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) management has evolved, with active surveillance (AS) gaining prominence as a management option. However, a key concern for both clinicians and patients is the potential for patient loss to follow-up during AS. AIMS: This study aimed to determine adherence and loss-to-follow-up rates in low-risk PTMC patients undergoing AS versus surgical intervention, in order to gain insights into clinical pathways and safety profiles. MATERIALS AND METHODS: This cohort study analyzed the 2016 data from a single registered institution of Japan's public National Cancer Registry. RESULTS: We identified and retrospectively analyzed the cases of 327 patients diagnosed with low-risk PTMC; 227 patients chose to undergo AS while the other 100 underwent PTMC surgery. Main outcomes were the adherence rate and loss-to-follow-up rate of each group, factors influencing discontinuation, and safety considerations. The rate of AS adoption was substantial in the complete series of 327 low-risk PTMC patients (69.4%). There was a significantly higher loss-to-follow-up rate at 5 years in the AS group (28.6%) compared to the Surgery group (17.8%) (HR 1.62, 95% CI: 1.01-2.61; p = 0.046). Both univariate and multivariate analyses confirmed the significantly higher loss-to-follow-up rate in the AS group as well as in older patients. No deaths due to PTMC progression were observed in the cases lost to follow-up. CONCLUSION: Despite concerns about loss to follow-up, active surveillance remains a safe option for low-risk PTMCs. Consistent follow-up strategies are crucial, and further research is needed to enhance patient counseling and care for the management of patients with PTMC.

Metabolic Effects of Short-Term High-Fat Intake Vary Depending on Dietary Amino Acid Composition.

Background: It is generally accepted that excessive fat intake has undesirable effects on the energy metabolism of our body. Dietary amino acid composition is also critical to the regulation of lipid metabolism. Objectives: This study aimed to investigate whether high-fat diets (HFDs) with different amino acid deficiencies lead to different metabolic outcomes. Methods: Six-wk-old male Wistar rats were fed either a control diet (CN; 3.7 kcal/g, 12% calories from fat) or HFDs (5.1 kcal/g, 60% calories from fat) with 7 different amino acid compositions [control or methionine, arginine, histidine, lysine, threonine, or branched-chain amino acids (BCAAs) deficient], for 7 d. Tissue weights and lipid accumulation in the liver, skeletal muscle, and adipose tissue were measured, and serum biochemical parameters were analyzed. Results: Although the food intake of the HFD groups was a little less than that of the CN group, the total calorie intakes were comparable among the groups, except for histidine-deficient and BCAA-deficient groups. In rats fed am HFD with a control amino acid composition (HFCN), dramatic increase in triglyceride (TG) accumulation in the liver and serum LDL cholesterol concentration were observed compared with the CN group. However, when the arginine content in the diet was reduced, liver TG accumulation was completely inhibited, with no apparent effects on serum lipoprotein-cholesterol concentrations. Meanwhile, deficiency of the other amino acids, such as threonine, reversed HFD-induced upregulation of serum LDL cholesterol. Conclusions: It is observed that although the rats ingested an excessive amount of fat, neither ectopic fat accumulation nor dyslipidemia were always induced at least in the short term; hence, the consequent metabolic change was dependent on the dietary amino acid composition. These findings introduce an important perspective regarding HFD regimens in both scientific and clinical contexts.

Aspirin eugenol ester affects ileal barrier function, inflammatory response and microbiota in broilers under lipopolysaccharide-induced immune stress conditions.

Aims: The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune stress. Methods: Two hundred and forty one-day-old male Arbor Acres chicks were randomly divided into four groups (saline, LPS, saline + AEE and LPS + AEE) with six replicates of ten broilers each. The saline group and LPS group were fed the normal diet, while the other two groups received normal diet plus 0.1 g/kg AEE. Broilers in the LPS and LPS + AEE groups were injected intraperitoneally with 0.5 mg/kg B.W LPS in saline for seven consecutive days beginning at 14 days of age, while broilers in the saline and saline + AEE groups were injected with saline only. Results: The results showed that AEE improved the ileal morphology and increased the ratio of villus height to crypt depth of immune-stressed broilers. LPS-induced immune stress significantly reduced the expression of the genes for the tight junction proteins occludin, zonula occludens-1 (ZO-1), claudin-1 and claudin-2, in the ileum, while AEE significantly up-regulated the expression of these genes. Compared with the saline group, the LPS-treated chickens showed significantly increased mRNA expression of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), cyclooxygenase-2 (COX-2), and microsomal Prostaglandin E Synthesase-1 (mPGES-1) in the ileum, while they were significantly decreased by AEE supplementation. In addition, analysis of the ileal bacterial composition showed that compared with saline and LPS + AEE groups, the proportion of Firmicutes and Lactobacillus in the LPS group was lower, while the proportion of Proteobacteria and Escherichia-Shigella was higher. Similarly, Line Discriminant Analysis Effect Size (LEfSe) analysis showed that compared with the LPS group, Brevibacillus was dominant in the saline group, while the LPS + AEE group was rich in Rhizobium, Lachnoclostridium, Ruminococcaceae, Faecalibacterium, Negativibacillus, Oscillospiraceae, and Flavonifractor. Conclusion: These results indicate that dietary supplementation with 0.1 g/kg AEE could protect the intestinal health by improving the intestinal villus morphology, enhancing the expression of tight junction genes and alleviating inflammation to resist the immune stress caused by LPS stimulation in broilers, and the mechanism may involve COX-2-related signal transduction and improved intestinal microbiota composition.

Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

Effect of dietary aspirin eugenol ester on the growth performance, antioxidant capacity, intestinal inflammation, and cecal microbiota of broilers under high stocking density.

This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal microbiota of broilers raised under stressful high density (HD) stocking conditions compared with normal density broilers (ND). A total of 432 one-day-old AA+ male broilers were randomly divided into 4 groups: normal density (ND, 14 broilers /m2), high density (HD, 22 broilers /m2), ND + AEE, and HD + AEE. The results of the study revealed a significant decrease in the growth performance of broiler chickens as a result of HD stress (P < 0.05). The total antioxidant capacity (T-AOC) in serum demonstrated a significant decrease (P < 0.05) at both 28 and 35 d. Conversely, the serum level of malondialdehyde (MDA) exhibited a significant increase (P < 0.05). Dietary supplementation of AEE resulted in a significant elevation (P < 0.05) of serum GSH-PX, SOD and T-AOC activity at both 28 and 35 d. Moreover, exposure to HD stress resulted in a considerable reduction in the height of intestinal villi and mRNA expression of tight junction proteins in the jejunum, along with, a significant elevation in the mRNA expression of inflammatory cytokines (P < 0.05). However, the administration of AEE reversed the adverse effects of HD-induced stress on villus height and suppressed the mRNA expression of the pro-inflammatory genes, COX-2 and mPGES-1. Additionally, the exposure to HD stress resulted in a substantial reduction in the α-diversity of cecal microbiota and disruption in the equilibrium of intestinal microbial composition, with a notable decrease in the relative abundance of Bacteroides and Faecalibacterium (P < 0.05). In contrast, the addition of AEE to the feed resulted in a notable increase in the relative abundance of Phascolarctobacterium and enhanced microbial diversity (P < 0.05). The inclusion of AEE in the diet has been demonstrated to enhance intestinal integrity and growth performance of broilers by effectively mitigating disruptions in gut microbiota induced by HD stress.

Dedicated Echoendoscope for Interventional Endoscopic Ultrasound: Comparison with a Conventional Echoendoscope.

Background/Objective: Interventional endoscopic ultrasound (I-EUS) is technically difficult and has risks of severe adverse events due to the scarcity of dedicated endoscopes and tools. A new EUS scope was developed for I-EUS and was modified to increase the puncture range, reduce the blind area, and overcome guidewire difficulties. We evaluated the usefulness and safety of a new EUS scope compared to a conventional EUS scope. Methods: All I-EUS procedures were performed at Juntendo University Hospital from April 2020 to April 2022. The primary outcomes included the procedure time and fluoroscopy time. The secondary outcomes included the technical success rate and the rates of procedure-related adverse events. Clinical data were retrospectively reviewed and statistically analyzed between the new and conventional EUS scopes. Results: In total, 143 procedures in 120 patients were analyzed. The procedure time was significantly shorter with the new EUS scope, but the fluoroscopy time was not different. Among the patients only undergoing EUS-guided biliary drainage (EUS-BD), 79 procedures in 74 patients were analyzed. Both the procedure time and fluoroscopy time were significantly shorter with the new EUS scope. Multivariate analysis revealed that a new EUS scope and use of covered metal stents could reduce the fluoroscopy time. The technical success rate and the adverse event rate were not significantly different between the total I-EUS and the EUS-BD only groups. However, the conventional scope showed stent deviation during stent placement, which did not happen with the new scope. Conclusions: The new EUS scope reduced procedure time for total I-EUS and fluoroscopy time for EUS-BD compared to a conventional EUS scope because of the improvement suitable for I-EUS.

Efficacy of antiviral therapy for the prevention of mother-to-child transmission of hepatitis B virus and the risk of postpartum hepatitis flare after discontinuation of antiviral therapy.

The use of nucleos(t)ide analogs (NAs) is recommended for mothers with a high viral load of hepatitis B virus (HBV) during the second or third trimester of pregnancy. However, postpartum hepatitis flares can occur in some cases. We examined the efficacy of NA administration for the prevention of mother-to-child transmission of hepatitis B virus, and evaluated the risk of postpartum hepatitis flares in mothers after NA discontinuation. Nine pregnant women with a high viral load (HBV DNA ≥5.3 log IU/mL) received tenofovir disoproxil fumarate (TDF) at approximately 28 weeks of gestation, and TDF was discontinued at 4-10 weeks after delivery. We evaluated the virological and biochemical parameters in mothers after TDF discontinuation. Hepatitis flares in mothers were defined as alanine transaminase level ≥60 U/L. None of the infants developed any congenital anomaly or acquired HBV infection during infancy. Hepatitis flares occurred within 6 months after TDF discontinuation in five of seven cases, whereas two cases were lost to follow-up. Furthermore, three cases required the resumption of NA use. NA administration was highly effective against mother-to-child-transmission of HBV in pregnant women with high HBV DNA levels. However, hepatitis flares were commonly observed after NA discontinuation in the postpartum period. Patients should be followed up carefully after NA discontinuation, and NA resumption should be considered based on a comprehensive assessment of virological and biochemical parameters.

Human movement avoidance decisions during Coronavirus disease 2019 in Japan.

Understanding host behavioral change in response to epidemics is important to forecast the disease dynamics. To predict the behavioral change relevant to the epidemic situation (e.g., the number of reported cases), we need to know the epidemic situation at the moment of decision, which is difficult to identify from the records of actually performed human mobility. In this study, the largest travel accommodation reservation data covering half of the existed accommodations in Japan was analyzed to observe decision-making timings and how it responded to the changing epidemic situation during Japan's Coronavirus Disease 2019 until February 2023. To this end, we measured mobility avoidance index proposed in Ito et al., 2022 to indicate people's decision of mobility avoidance and quantified it using the time-series of the accommodation booking/cancellation data. We observed matches of the peak dates of the mobility avoidance and the number of reported cases, and mobility avoidance changed proportional to the logarithmic number of reported cases. We also found that the slope of mobility avoidance against the change of the logarithmic number of reported cases were similar among the epidemic waves, while the intercept of that was much reduced as the first epidemic wave passed by. People measure the intensity of epidemic by logarithm of the number of reported cases. The sensitivity of their response is established during the first wave and the people's response became weakened after the first experience, as if the number of reported cases were multiplied by a constant small factor.

Effects of Aspirin Eugenol Ester on Liver Oxidative Damage and Energy Metabolism in Immune-Stressed Broilers.

The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on liver oxidative damage and energy metabolism in immune-stressed broilers. In total, 312 broilers were divided into 4 groups (saline, LPS, SAEE, and LAEE). Broilers in the saline and LPS groups were fed a basal diet; the SAEE and LAEE groups had an added 0.01% AEE in their diet. Broilers in the LPS and LAEE groups were injected with lipopolysaccharides, while the saline and SAEE groups were injected with saline. Results showed that AEE increased the body weight, average daily gain, and average daily feed intake, as well as decreasing the feed conversion ratio of immune-stressed broilers. AEE protects against oxidative damage in immune-stressed broiler livers by elevating the total antioxidant capacity, superoxide dismutase activity, and glutathione S-transferase alpha 3 (GSTA3) and glutaredoxin 2 (GLRX2) expression, while decreasing malondialdehyde content. AEE lessened inflammation by reducing prostaglandin-F2α production and prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-1beta (IL-1ß) expression. AEE decreased oxidative phosphorylation rates by increasing succinic acid levels and lowering both adenosine diphosphate (ADP) levels and ceroid lipofuscinosis neuronal 5 (CLN5) expression. AEE modulated the metabolism of phenylalanine, tyrosine, lipids, and cholesterol by reducing the phenyllactate and L-arogenate levels, lowering dopachrome tautomerase (DCT) and apolipoprotein A4 (APOA4) expression, and increasing phenylpyruvic acid and dopa decarboxylase (DDC) expression. In summary, AEE can effectively alleviate liver oxidative damage and energy metabolism disorders in immune-stressed broilers.

Effects of dietary chlorogenic acid on cecal microbiota and metabolites in broilers during lipopolysaccharide-induced immune stress.

Aims: The aim of this study was to investigate the effects of chlorogenic acid (CGA) on the intestinal microorganisms and metabolites in broilers during lipopolysaccharide (LPS)-induced immune stress. Methods: A total of 312 one-day-old Arbor Acres (AA) broilers were randomly allocated to four groups with six replicates per group and 13 broilers per replicate: (1) MS group (injected with saline and fed the basal diet); (2) ML group (injected with 0.5 mg LPS/kg and fed the basal diet); (3) MA group (injected with 0.5 mg LPS/kg and fed the basal diet supplemented with 1,000 mg/kg CGA); and (4) MB group (injected with saline and fed the basal diet supplemented with 1,000 mg/kg CGA). Results: The results showed that the abundance of beneficial bacteria such as Bacteroidetes in the MB group was significantly higher than that in MS group, while the abundance of pathogenic bacteria such as Streptococcaceae was significantly decreased in the MB group. The addition of CGA significantly inhibited the increase of the abundance of harmful bacteria such as Streptococcaceae, Proteobacteria and Pseudomonas caused by LPS stress. The population of butyric acid-producing bacteria such as Lachnospiraceae and Coprococcus and beneficial bacteria such as Coriobacteriaceae in the MA group increased significantly. Non-targeted metabonomic analysis showed that LPS stress significantly upregulated the 12-keto-tetrahydroleukotriene B4, riboflavin and mannitol. Indole-3-acetate, xanthurenic acid, L-formylkynurenine, pyrrole-2-carboxylic acid and L-glutamic acid were significantly down-regulated, indicating that LPS activated inflammation and oxidation in broilers, resulting in intestinal barrier damage. The addition of CGA to the diet of LPS-stimulated broilers significantly decreased 12-keto-tetrahydro-leukotriene B4 and leukotriene F4 in arachidonic acid metabolism and riboflavin and mannitol in ABC transporters, and significantly increased N-acetyl-L-glutamate 5-semialdehyde in the biosynthesis of amino acids and arginine, The presence of pyrrole-2-carboxylic acid in D-amino acid metabolism and the cecal metabolites, indolelactic acid, xanthurenic acid and L-kynurenine, indicated that CGA could reduce the inflammatory response induced by immune stress, enhance intestinal barrier function, and boost antioxidant capacity. Conclusion: We conclude that CGA can have a beneficial effect on broilers by positively altering the balance of intestinal microorganisms and their metabolites to inhibit intestinal inflammation and barrier damage caused by immune stress.

Neural Radiance Field-Inspired Depth Map Refinement for Accurate Multi-View Stereo.

In this paper, we propose a method to refine the depth maps obtained by Multi-View Stereo (MVS) through iterative optimization of the Neural Radiance Field (NeRF). MVS accurately estimates the depths on object surfaces, and NeRF accurately estimates the depths at object boundaries. The key ideas of the proposed method are to combine MVS and NeRF to utilize the advantages of both in depth map estimation and to use NeRF for depth map refinement. We also introduce a Huber loss into the NeRF optimization to improve the accuracy of the depth map refinement, where the Huber loss reduces the estimation error in the radiance fields by placing constraints on errors larger than a threshold. Through a set of experiments using the Redwood-3dscan dataset and the DTU dataset, which are public datasets consisting of multi-view images, we demonstrate the effectiveness of the proposed method compared to conventional methods: COLMAP, NeRF, and DS-NeRF.

MARCH2, a Novel Oncogene-regulated SNAIL E3 Ligase, Suppresses Triple-negative Breast Cancer Metastases.

Epithelial-mesenchymal transition (EMT) in cancer promotes metastasis and chemotherapy resistance. A subset of triple-negative breast cancer (TNBC) exhibits a mesenchymal gene signature that is associated with poor patient outcomes. We previously identified PTK6 tyrosine kinase as an oncogenic driver of EMT in a subset of TNBC. PTK6 induces EMT by stabilizing SNAIL, a key EMT-initiating transcriptional factor. Inhibition of PTK6 activity reverses mesenchymal features of TNBC cells and suppresses their metastases by promoting SNAIL degradation via a novel mechanism. In the current study, we identify membrane-associated RING-CH2 (MARCH2) as a novel PTK6-regulated E3 ligase that promotes the ubiquitination and degradation of SNAIL protein. The MARCH2 RING domain is critical for SNAIL ubiquitination and subsequent degradation. PTK6 inhibition promotes the interaction of MARCH2 with SNAIL. Overexpression of MARCH2 exhibits tumor suppressive properties and phenocopies the effects of SNAIL downregulation and PTK6 inhibition in TNBC cells, such as inhibition of migration, anoikis resistance, and metastasis. Consistent with this, higher levels of MARCH2 expression in breast and other cancers are associated with better prognosis. We have identified MARCH2 as a novel SNAIL E3 ligase that regulates EMT and metastases of mesenchymal TNBC. SIGNIFICANCE: EMT is a process directly linked to drug resistance and metastasis of cancer cells. We identified MARCH2 as a novel regulator of SNAIL, a key EMT driver, that promotes SNAIL ubiquitination and degradation in TNBC cells. MARCH2 is oncogene regulated and inhibits growth and metastasis of TNBC. These insights could contribute to novel strategies to therapeutically target TNBC.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.