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LINKED CONTENT: This article is linked to Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16633 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Thiele et al papers. To view these articles, visit https://doi.org/10.1111/apt.16567 and https://doi.org/10.1111/apt.16672 [ABSTRACT FROM AUTHOR]

Purpose: Liver is one of the organs with a high incidence of tumors in the human body. Malignant liver tumors seriously threaten human life and health. The difficulties of liver tumor segmentation from computed tomography (CT) image are: (a) The contrast between the liver tumors and healthy tissues in CT images is low and the boundary is blurred; (b) The image of liver tumor is complex and diversified in size, shape, and location. Methods: To solve the above problems, this paper focused on the human liver and liver tumor segmentation algorithm based on convolutional neural network (CNN), and specially designed a three‐dimensional dual path multiscale convolutional neural network (TDP‐CNN). To balance the performance of segmentation and requirement of computational resources, the dual path was used in the network, then the feature maps from both paths were fused at the end of the paths. To refine the segmentation results, we used conditional random fields (CRF) to eliminate the false segmentation points in the segmentation results to improve the accuracy. Results: In the experiment, we used the public dataset liver tumor segmentation (LiTS) to analyze the segmentation results qualitatively and quantitatively. Ground truth segmentation of liver and liver tumor was manually labeled by an experienced radiologist. Quantitative metrics were Dice, Hausdorff distance, and average distance. For the segmentation results of liver tumor, Dice was 0.689, Hausdorff distance was 7.69, and the average distance was 1.07; for the segmentation results of the liver, Dice was 0.965, Hausdorff distance was 29.162, and the average distance was 0.197. Compared with other liver and liver tumor segmentation algorithms in Medical Image Computing and Intervention (MICCAI) 2017 competition, our method of liver segmentation ranked first, and liver tumor segmentation ranked second. Conclusions: The experimental results showed that the proposed algorithm had good performance in both liver and liver tumor segmentation. [ABSTRACT FROM AUTHOR]

Aim. The aim of this paper is to investigate the effects of ethyl pyruvate (EP) on experimental liver fibrosis induced by bile duct ligation (BDL) and explore the underlying molecular mechanisms. Material and Method. Rats were randomly divided into three groups: the sham group, the BDL group, and the BDL+EP group. Liver fibrosis was induced by common bile duct ligation and was evaluated by serum biochemical parameter levels, Masson's trichrome staining, α-SMA expression, and collagen I deposition. The levels of Nrf2 signaling pathway-related antioxidant genes (Nrf2, SOD2, NQO1, and GSH-Px) in liver tissues were also measured. Meanwhile, the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27 were analyzed. In BDL-induced liver fibrosis rats, the successfully established model was confirmed by the significant increase of serum ALT and AST levels, the high liver fibrosis score, α-SMA expression, and collagen deposition. Results. Compared with the BDL group, EP administration could diminish fibrosis level and substantially increase the expression of Nrf2 signaling pathway-related antioxidant genes. Furthermore, EP significantly suppressed the mRNA expression levels of HMGB1, IL-1β, TNF-α, and HSP27. Conclusions. The results suggested that EP administration could effectively inhibit the liver fibrosis induced by BDL in rat, which may be associated with the enhanced activity of Nrf2 to mediate antioxidant enzyme system and downregulate the inflammatory genes. [ABSTRACT FROM AUTHOR]

For several years, research has been carried out on the effectiveness of solutions for perfusion and preservation of organs, including the liver. There is a search for an optimal pharmacological composition of these solutions, allowing to preserve or improve vital functions of the organ for as long as possible until it is transplanted into a recipient. Hormones due to their properties, often resulting from their pleiotropic effects, may be a valuable component for optimizing the composition of liver perfusion and preservation solutions. The paper presents the current state of knowledge on liver perfusion and preservation solutions modified with hormones. It also shows the characteristics of the hormones evaluated, taking into account their physiological functions in the body. [ABSTRACT FROM AUTHOR]

Summary: Background: Direct‐acting anti‐viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear. Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC. Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross‐sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan‐Meier estimation. Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow‐up from start of DAA therapy was 32.4 months. Twenty‐eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64‐5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients. Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate. Linked Content This article is linked to Hollande and Pol paper. To view this article, visit https://doi.org/10.1111/apt.15328. [ABSTRACT FROM AUTHOR]

Background: Initial treatment of autoimmune hepatitis (AIH) with prednisolone ± azathioprine is based on randomised controlled trials. Many patients receive long‐term immunosuppressive treatment to prevent disease relapse; this strategy has a weaker evidence base. Aim: To consider whether immunosuppressive treatment (IST) withdrawal in AIH is justified and to develop a rationale for patient selection. Methods: We reviewed published papers between 1972 and 2018, which addressed the outcomes of IST withdrawal and/or complications of IST in AIH. Results: (1) AIH relapse rates after withdrawal of IST vary between 25% and 100%. There is heterogeneity in these studies regarding relapse definition, IST duration prior to withdrawal and criteria for biochemical and histological remission prior to withdrawal. (2) Factors associated with relapse following IST withdrawal include: (a) absence of an identifiable initial disease trigger, (b) presence of other autoimmune diseases, (c) longer time to biochemical remission and (d) elevated serum transaminases on treatment withdrawal. Reports of associations between relapse and age, IST duration and failure of histological remission have been inconsistent. (3) Continued IST reduces risk of AIH relapse over at least 5 years. However, there is no evidence that routine (as opposed to selective) long‐term IST improves disease outcome. (4) Patients with AIH have an increased risk of extrahepatic cancer, notably non‐melanoma skin cancer, to which long‐term IST may contribute. Long‐term corticosteroid therapy is associated with weight gain, low‐trauma fractures, diabetes and possibly vascular disease. Conclusions: While further studies are needed, evidence supports a strategy of IST withdrawal in some patients with AIH who have achieved remission. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tan et al paper. To view this article, visit https://doi.org/10.1111/apt.17914 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Hey et al paper. To view this article, visit https://doi.org/10.1111/apt.17917 [ABSTRACT FROM AUTHOR]

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation. [ABSTRACT FROM AUTHOR]

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis. Synopsis: Besides inflammation, metabolic dysregulation also contributes to sepsis lethality, offering therapeutic potential. This study shows that loss of hepatic HNF4α activity in sepsis disrupts PPARα-regulated lipid metabolism and the acute phase response, both of which can be restored by the agonist NCT. Hepatic HNF4α loses its function during sepsis due to alterations in its chromatin binding. These changes in HNF4α chromatin binding during sepsis mainly affect H3K27 acetylation, thereby modulating enhancer activity, with little effect on chromatin accessibility. Hepatocyte-specific HNF4α knockout mice show reduced PPARα expression and activity, decreased IL6-induced acute phase response, and increased lipid accumulation during sepsis, all of these contributing to sepsis lethality. The HNF4α agonist NCT protects against sepsis by preventing lipid metabolic dysregulation caused by HNF4α and PPARα loss-of-function and enhancing the hepatic acute phase response. The HNF4α loss-of-function in sepsis could be translated to pigs and a humanized liver mouse model, emphasizing the relevance of the findings. Besides inflammation, metabolic dysregulation also contributes to sepsis lethality, offering therapeutic potential. This study shows that loss of hepatic HNF4α activity in sepsis disrupts PPARα-regulated lipid metabolism and the acute phase response, both of which can be restored by the agonist NCT. [ABSTRACT FROM AUTHOR]

Eimeria stiedae is one of the few eukaryotic pathogens that exclusively infect the liver and serves as a good model to study the host–pathogen interactions in this vital organ. In this study, we show that rabbits infected with E. stiedae develop severe but self‐healing cholangitis. RNA‐seq analysis of the liver gene expression landscapes over the long course of E. stiedae infection identified 912 differentially expressed genes (DEGs) in the prepatent period (794 up‐ and 118 downregulated genes), 2889 DEGs in the early oocyst shedding period (1870 up‐ and 1019 downregulated genes), 2859 DEGs in the peak oocyst shedding period (1923 up‐ and 936 downregulated genes), and 327 DEGs in the recovery period (164 up‐ and 163 downregulated genes). Combined with pathological observations, we identified dynamic changes in host–parasite interactions involving multiple pathways. They showed that E. stiedae infection induced full‐blown inflammatory, Th1 and Th17 immune responses at all time points. This was associated with the strong innate immune responses during the prepatent period, including increased Toll‐like and NOD‐like receptor signaling. Despite mounting several damage control and repair responses, such as PI3K‐Akt signaling, Ras signaling, and extracellular matrix‐receptor interactions, the liver underwent severe metabolic dysfunction, oxidative damage, and coagulopathy after patency and at peak infection, possibly as a result of suppressed peroxisome activities and downregulated PPAR signaling. These responses largely disappeared during late infection, suggesting that the liver self‐heals after severe cholangitis. These data provide new insights into host–pathogen interactions during Eimeria infection and improve our understanding of the pathogenesis of parasitic cholangitis. [ABSTRACT FROM AUTHOR]

The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long‐term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis‐related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis‐related complications and discuss key challenges for wide application of long‐term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9‐11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long‐term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature. [ABSTRACT FROM AUTHOR]

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age‐related diseases. Here, we show that hepatic phospho‐active ACLY correlates with overweight and Model for End‐stage Liver Disease score in humans. Wild‐type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB‐204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy‐fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy‐fed mice, and improved locomotion in mice exposed to cardiotoxin‐induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration. [ABSTRACT FROM AUTHOR]

Background: In this study, we comprehensively profiled the T‐cell receptor (TCR) repertoire of the tumor and adjacent normal tissue in patients with HBV‐associated hepatocellular carcinoma (HCC) and determined the baseline characteristics and clinical significance of TCR. Methods: High‐throughput sequencing was used to determine the profile of complementarity‐determining region 3 (CDR3) of the TCR‐β chain variable (TRBV) in the tumor and normal tissue samples of 14 HCC patients. At the same time, TRBV diversity and differences in expression between tumor and normal tissues were investigated. The cumulative frequency of top 100 CDR3 (CF100), clonality, and Shannon entropy as indices to evaluate diversity, Results: The diversity of TRBV CDR3 showed no significant difference between tumor and normal tissues. Of the 58 V gene segments in TRBV, TRBV16 and TRBV7‐6 had a significantly higher frequency in the tumor group than in the normal group (p < 0.05). The frequency of 14 J gene segments showed no significant difference between tumor and normal tissues. In contrast, the frequency of 22 TRBVx/BJx combinations was significantly higher in the tumor than in the normal tissue. In addition, the length and type of TRBV CDR3 were similar in tumor and normal tissues, and a Gaussian distribution was observed in both groups. Conclusion: This study provided a large amount of information about the TCR lineage in HBV‐associated HCC, laying the foundation for further research. In addition, the fact that the immune repertoire (TRBV CDR3) hardly differs between tumor and adjacent normal tissue provides a new clue for exploring the mechanism of the liver as an organ with immune privileges. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17320 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Tong et al papers. To view these articles, visit https://doi.org/10.1111/apt.17263 and https://doi.org/10.1111/apt.17319 [ABSTRACT FROM AUTHOR]

This article discusses the development and advancements of magnetic resonance imaging (MRI) in the field of medicine. It highlights the contributions of Paul C. Lauterbur and Raymond Damadian in the invention of MRI and their impact on the field. The article also mentions various MRI techniques and contrast mechanisms that have been introduced over the years, including T1ρ MRI. The focus of the paper by Qian and colleagues is on using dynamic glucose-enhanced T1ρ imaging to study glucose metabolism in the liver of patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The study demonstrates the potential of this technique in detecting and quantifying changes in liver metabolism. The article concludes by discussing the advantages of this novel application, including real-time functional and metabolic information, non-invasiveness, and improved image quality. However, it acknowledges the limitations of the study and suggests further research in this area. [Extracted from the article]

With the recent Food and Drug Administration approval of Lumason (sulfur hexafluoride lipid‐type A microsphere, Bracco Diagnostics Inc, Monroe Township, NJ) for contrast‐enhanced ultrasound (CEUS) to characterize focal liver lesions in both adult and pediatric patients, widespread use of CEUS is expected in the United States. This paper provides guidance in setting up a CEUS program, and reviews the practical details that will need to be instituted in a standard ultrasound department to provide both safe and efficient use of CEUS. A review of the indications, contraindications, adverse events, instructions for performing the exam, and image interpretation are discussed. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Wong and Coenen et al and Hooymans papers. To view these articles visit https://doi.org/10.1111/apt.13879 and https://doi.org/10.1111/apt.13955. [ABSTRACT FROM AUTHOR]

Imaging demonstrated an American Association for the Surgery of Trauma (AAST) grade 4 liver laceration, predominantly of the left lobe of liver, with moderate volume hemoperitoneum without contrast extravasation (Fig. The AAST Grade IV liver injury sustained in this case was considered avoidable. [Extracted from the article]

Liver ultrasound is a cost‐effective, non‐invasive, and sufficient technique to diagnose most of the liver disorders. The recent advancements in research in image processing have led to the development of image‐based liver disorder classification systems. In spite of being popular in the diagnostic imaging of liver, ultrasound images, owing to their poor quality, render the conventional and state of the art segmentation and feature extraction techniques incapable, to accurately classify a large mixed group of liver disorders; due to the similarities and differences in appearances among the different and same disorders, respectively. Classification of liver disorders using ultrasound images poses various challenges at each phase, from segmentation to classification. There is a need for better segmentation, powerful features, and optimal classification parameter combinations to obtain decent classification accuracy, when a large sub‐set of liver disorders is considered. In this work, the region of interest is extracted using iso‐contour technique. Feature extraction is performed using multi‐level fractal features and multi‐domain wavelet‐texture features for better discrimination capability. Then, an optimization problem is formulated, for minimizing the five fold cross validation error to classify 10 types of disorders, both focal and diffused, by selecting the best features, suitable classifier, and its parameters using the particle swarm optimization technique for obtaining better classification. An overall accuracy of 91% is obtained using the proposed features in addition to 50% reduction in multi‐level fractal feature set which justifies the efficacy of the proposed technique. [ABSTRACT FROM AUTHOR]

Background. Patients with β‐thalassemia major depend on lifelong transfusion, resulting in tissue iron overload. This longitudinal retrospective observational study aims to assess myocardial and liver iron overload using magnetic resonance imaging (MRI) and investigate the lag between myocardial and liver iron unloading in β‐thalassemia patients undergoing chelation therapy. Methods. Beta‐thalassemia major patients with at least two MRI studies between 2016 and 2020 were enrolled. Myocardial and liver iron overload were defined as T2∗ less than 20 and 2.1, respectively. Outcomes included mortality, myocardial and liver T2∗ changes, and systolic dysfunction assessed by cardiac MRI. Results. Fifty‐five patients with a mean age of 24.62 ± 7.94 years, a mean follow‐up duration of 24.3 ± 12.9 months, and a mean ferritin level of 1475.75 ± 771.12 ng/mL were enrolled. All of the abovementioned patients only took deferoxamine as the iron‐chelating medication. Mortality occurred in three patients (5.5%) during follow‐up. Liver T2∗ significantly increased (p value <0.05), while myocardial T2∗ showed a nonsignificant increase. Iron unloading of the myocardium was not significantly different from that of the liver and did not result in a significant lag (56% vs. 44%; p value = 0.419). Baseline myocardial T2∗ correlated with extramedullary hematopoiesis, weekly number of deferoxamine injections (p value <0.01), timing between the transfusions, and serum ferritin (p value <0.05). Conclusion. Liver T2∗ reduced during deferoxamine chelation therapy, while myocardial T2∗ remained unchanged. No significant lag was observed between myocardial and liver iron unloading. Further studies are required to elucidate these findings. [ABSTRACT FROM AUTHOR]

The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi‐timepoint drug administration strategies across a wide range of drugs. Here, droplet‐engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici‐plate as an in vitro high‐throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time‐dependent variations are demonstrated in toxicity on the Chronotoxici‐plate, highlighting the importance of considering time‐dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are major contributors to immunological responses following solid organ transplantation. Donor derived EVs are best known for their role in transplant rejection through transferring donor major histocompatibility complex proteins to recipient antigen presenting cells, a phenomenon known as ‛cross‐decoration'. In contrast, donor liver‐derived EVs are associated with organ tolerance in small animal models. Therefore, the cellular source of EVs and their cargo could influence their downstream immunological effects. To investigate the immunological effects of EVs released by the liver in a physiological and transplant‐relevant model, we isolated EVs being produced during normothermic ex vivo liver perfusion (NEVLP), a novel method of liver storage prior to transplantation. We found EVs were produced by the liver during NEVLP, and these EVs contained multiple anti‐inflammatory miRNA species. In terms of function, liver‐derived EVs were able to cross‐decorate allogeneic cells and suppress the immune response in allogeneic mixed lymphocyte reactions in a concentration‐dependent fashion. In terms of cytokine response, the addition of 1 × 109 EVs to the mixed lymphocyte reactions significantly decreased the production of the inflammatory cytokines TNF‐α, IL‐10 and IFN‐γ. In conclusion, we determined physiologically produced liver‐derived EVs are immunologically regulatory, which has implications for their role and potential modification in solid organ transplantation. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute liver injury (ALI) often follows biliary acute pancreatitis (BAP), but the exact cause and effective treatment are unknown. The aim of this study was to investigate the role of the gut microflora–bile acids–liver axis in BAP‐ALI in mice and to assess the potential therapeutic effects of Yinchenhao decoction (YCHD), a traditional Chinese herbal medicine formula, on BAP‐ALI. Methods: Male C57BL/6 mice were allocated into three groups: negative control (NC), BAP model, and YCHD treatment groups. The severity of BAP‐ALI, intrahepatic bile acid levels, and the gut microbiota were assessed 24 h after BAP‐ALI induction in mice. Results: Our findings demonstrated that treatment with YCHD significantly ameliorated the severity of BAP‐ALI, as evidenced by the mitigation of hepatic histopathological changes and a reduction in liver serum enzyme levels. Moreover, YCHD alleviated intrahepatic cholestasis and modified the composition of bile acids, as indicated by a notable increase in conjugated bile acids. Additionally, 16S rDNA sequencing analysis of the gut microbiome revealed distinct alterations in the richness and composition of the microbiome in BAP‐ALI mice compared to those in control mice. YCHD treatment effectively improved the intestinal flora disorders induced by BAP‐ALI. Spearman's correlation analysis revealed a significant association between the distinct compositional characteristics of the intestinal microbiota and the intrahepatic bile acid concentration. Conclusions: These findings imply a potential link between gut microbiota dysbiosis and intrahepatic cholestasis in BAP‐ALI mice and suggest that YCHD treatment may confer protection against BAP‐ALI via the gut microflora–bile acids–liver axis. [ABSTRACT FROM AUTHOR]

Statins are used to reduce liver cholesterol levels but also carry a dose‐related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity. To bridge this gap, we used physiologically based pharmacokinetic (PBPK) modeling to predict intracellular concentrations of statins. Quantitative data on transporter clearance were scaled from in vitro to in vivo conditions by integrating targeted proteomics and transporter kinetics data. The developed PBPK models, informed by proteomics, suggested that organic anion–transporting polypeptide 2B1 (OATP2B1) and multidrug resistance–associated protein 1 (MRP1) play a pivotal role in the distribution of statins in muscle. Using these PBPK models, we were able to predict the impact of alterations in transporter function due to genotype or drug–drug interactions on statin systemic concentrations and exposure in liver and muscle. These results underscore the potential of proteomics‐guided PBPK modeling to scale transporter clearance from in vitro data to real‐world implications. It is important to evaluate the role of drug transporters when predicting tissue exposure associated with on‐ and off‐target effects. [ABSTRACT FROM AUTHOR]

Globally, large quantity of animal byproducts is generated from the slaughter of food animals, but there is lack of research articles related to drying of these byproducts and its use as pet food. Therefore, this study was conducted with the aim of utilization of intact whole buffalo liver by drying for pet treat, evaluating its shelf life and palatability. The intact liver surface was superficially sliced, and the surface was pierced. Thereafter, the livers were pretreated in 3% sugar and 4% salt solution (1 : 3 w / v) for 3 h followed by microwaving for 4 min and hot air drying at 60°C for 40 h (designated as T2L). The livers which were dried the same as T2L except surface piercing were referred as T1L, whereas the livers dried only using hot air oven were referred as control (CL). The moisture and protein contents of the dried CL and T2L were found to be 28.46% and 14.29% and 43.85% and 52.76%, respectively. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) image of T2L revealed the presence of few low as well as high molecular weight protein bands which were absent in CL and T1L indicating a comparatively lower level of protein degradation in T2L. The shelf life of T1L and T2L samples based on microbiological and lipid oxidation analyses was found to be more than 60 days at 25 and 4°C. Palatability studies using dogs showed that all dried samples were highly palatable. Thus, it could be concluded that intact buffalo liver could be dried using surface slicing, with/without piercing followed by salt and sugar pretreatment, 4 min microwaving, and hot air drying at 60°C for 40 h. Future study should focus on the sensory properties such as aroma, texture, and flavor and sensory analysis of the dried liver by human. [ABSTRACT FROM AUTHOR]

Permeability transition pore (PTP) opening dissipates ion and electron gradients across the internal mitochondrial membrane (IMM), including excess Ca2+ in the mitochondrial matrix. After opening, immediate PTP closure must follow to prevent outer membrane disruption, loss of cytochrome c, and eventual apoptosis. Flickering, defined as the rapid alternative opening/closing of PTP, has been reported in heart, which undergoes frequent, large variations in Ca2+. In contrast, in tissues that undergo depolarization events less often, such as the liver, PTP would not need to be as dynamic and thus these tissues would not be as resistant to stress. To evaluate this idea, it was decided to follow the reversibility of the permeability transition (PT) in isolated murine mitochondria from two different tissues: the very dynamic heart, and the liver, which suffers depolarizations less frequently. It was observed that in heart mitochondria PT remained reversible for longer periods and at higher Ca2+ loads than in liver mitochondria. In all cases, Ca2+ uptake was inhibited by ruthenium red and PT was delayed by Cyclosporine A. Characterization of this phenomenon included measuring the rate of oxygen consumption, organelle swelling and Ca2+ uptake and retention. Results strongly suggest that there are tissue‐specific differences in PTP physiology, as it resists many more Ca2+ additions before opening in a highly active organ such as the heart than in an organ that seldom suffers Ca2+ loading, such as the liver. [ABSTRACT FROM AUTHOR]

This paper describes the fragments obtained by digestion with RNAase T1 from rat liver serine-tRNA1 as well as from a mixture of very lipophilic serine-tRNAs. From the data obtained by these digest as well as from the digestion with pancreatic RNAase the nucleotide sequence of the anticodon of serine-tRNA1 can be constructed. Evidence from different nucleotide sequences in other serine-tRNAs is presented [ABSTRACT FROM AUTHOR]

1. Tryptic digest, s of the [14C]carboxymethylated derivatives of the t, hree isoenzymes EE, ES and SS of horse liver alcohol dehydrogenase have been compared in "fingerprint" experiments. 2. Eight peptide spots present in the digest of the carboxymethylated EE enzyme were not detected in the digest of the carboxymethylated SS enzyme; and seven spots found in the latter were not discovered in the former. No other differences were noticed. The ES derivative yielded both types of spots but in reduced amounts, It is concluded that the E- and S-types of subunits are very similar and that the ES isoenzyme is a hybrid molecule. 3. From the carboxymethylated SS and ES isoenzymes the S-chain peptides that, differ from their counterparts in the E-chain were prepared and their structures analysed. They were compared to the known structures [ 1 — 3] of the corresponding E-chain peptides. It is concluded that all the differences between the two sets of peptides are accounted for by amino acid changes at only six positions along the protein chains of the E- and S-types of subunits, and an ancestral geneduplication is suggested. The differences at five positions (17, 94, 101, 110 and 366) are amino acid exchanges compatible with one-base mutations, while the nature of the sixth difference (position 115) is not fully established. 4. The six differences make the S-chain more hydrophobic and three units of charge more positive than the E-chain. These properties fit the solubilities and electrophoretic mobilities of the three isoenzymes. The difference in substrate specificity between the E- and S-chains might be explained by a direct participation in the substrate binding site of some of the residues exchanged, but, other explanations cannot be excluded. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Tsung et al paper. To view this article, visit https://doi.org/10.1111/apt.15413. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Shen et al and Kim and Kim papers. To view these articles, visit https://doi.org/10.1111/apt.15298 and https://doi.org/10.1111/apt.15364. [ABSTRACT FROM AUTHOR]

Purpose: To develop a novel probability-based sorting method capable of generating multiple breathing cycles of 4D-MRI images and to evaluate performance of this new method by comparing with conventional phase-based methods in terms of image quality and tumor motion measurement. Methods: Based on previous findings that breathing motion probability density function (PDF) of a single breathing cycle is dramatically different from true stabilized PDF that resulted from many breathing cycles, it is expected that a probability-based sorting method capable of generating multiple breathing cycles of 4D images may capture breathing variation information missing from conventional single-cycle sorting methods. The overall idea is to identify a few main breathing cycles (and their corresponding weightings) that can best represent the main breathing patterns of the patient and then reconstruct a set of 4D images for each of the identified main breathing cycles. This method is implemented in three steps: (1) The breathing signal is decomposed into individual breathing cycles, characterized by amplitude, and period; (2) individual breathing cycles are grouped based on amplitude and period to determine the main breathing cycles. If a group contains more than 10% of all breathing cycles in a breathing signal, it is determined as a main breathing pattern group and is represented by the average of individual breathing cycles in the group; (3) for each main breathing cycle, a set of 4D images is reconstructed using a result-driven sorting method adapted from our previous study. The probability-based sorting method was first tested on 26 patients' breathing signals to evaluate its feasibility of improving target motion PDF. The new method was subsequently tested for a sequential image acquisition scheme on the 4D digital extended cardiac torso (XCAT) phantom. Performance of the probability-based and conventional sorting methods was evaluated in terms of target volume precision and accuracy as measured by the 4D images, and also the accuracy of average intensity projection (AIP) of 4D images. Results: Probability-based sorting showed improved similarity of breathing motion PDF from 4D images to reference PDF compared to single cycle sorting, indicated by the significant increase in Dice similarity coefficient (DSC) (probability-based sorting, DSC = 0.89±0.03, and single cycle sorting, DSC = 0.83±0.05, p-value <0.001). Based on the simulation study on XCAT, the probability-based method outperforms the conventional phase-based methods in qualitative evaluation on motion artifacts and quantitative evaluation on tumor volume precision and accuracy and accuracy of AIP of the 4D images. Conclusions: In this paper the authors demonstrated the feasibility of a novel probability-based multicycle 4D image sorting method. The authors' preliminary results showed that the new method can improve the accuracy of tumor motion PDF and the AIP of 4D images, presenting potential advantages over the conventional phase-based sorting method for radiation therapy motion management. [ABSTRACT FROM AUTHOR]

Purpose: Percutaneous ablation under MRI-guidance allows treating otherwise inoperable liver tumors locally using a catheter probe. However, manually placing the probe is an error-prone and time consuming task that requires a considerable amount of training. The aim of this paper was to present a pneumatically actuated robotic instrument that can assist clinicians in MRI-guided percutaneous intervention of the liver and to assess its functionality in a clinical setting. The robot positions a needle-guide inside the MRI scanner bore and assists manual needle insertions outside the bore. Methods: The robot supports double oblique insertions that are particularly challenging for less experienced clinicians. Additionally, the system employs only standard imaging sequences and can therefore be used on different MRI scanners without requiring prior integration. The repeatability and the accuracy of the robot were evaluated with an optical tracking system. The functionality of the robot was assessed in an initial pilot study on two patients that underwent MRI-guided laser ablation of the liver. Results: The robot positioned the needle-guide in a repeatable manner with a mean error of 0.35 mm and a standard deviation of 0.32 mm. The mean position error corresponding to the needle tip, measured for an equivalent needle length of 195 mm over 25 fixed points, was 2.5 mm with a standard deviation of 1.2 mm. The pilot study confirmed that the robot does not interfere with the equipment used for MRI-guided laser ablation and does not visibly affect the MR images. The robot setup integrated seamlessly within the established clinical workflow. The robot-assisted procedure was successfully completed on two patients, one of which required a complex double oblique insertion. For both patients, the insertion depth and the tumor size were within the range reported for previous MRI-guided percutaneous interventions. A third patient initially enrolled in the pilot study and was considerably heavier than the others, preventing the use of the robot and requiring several freehand insertion attempts. Conclusions: The robot repeatability and accuracy are appropriate for liver tumors normally treated with MRI-guided ablation. The results of the pilot study endorse the clinical use of the robot in its current form: the robot is fully functional and MRI-compatible in a clinical setting and is suitable for double-oblique needle insertions. [ABSTRACT FROM AUTHOR]

There is long-standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes ( HEP), Kupffer cells ( KC) and hepatic stellate cells ( HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co-localisation of these cell types. Immunohistochemistry and design-based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ. [ABSTRACT FROM AUTHOR]

Aims Primary sclerosing cholangitis ( PSC) is characterized histologically by portal inflammation, bile duct injury and regeneration and concentric periductal fibrosis. Although seen commonly in our experience, the significance of histological thickening of the bile duct basement membrane on periodic acid Schiff ( PAS)-positive, diastase-resistant ( DPAS) staining has never been analysed formally. In this paper we provide an evidence-based assessment of basement membrane thickening ( BMT) reproducibility and diagnostic accuracy. Methods and results A total of 128 archived medical liver core biopsies were retrieved and blinded for review by two independent histopathologists. BMT was assessed and designated as absent or present with a grade (G) of G1-G3. The sensitivity of any BMT for PSC was good at 77%, with moderate specificity at 61%. When only G3 BMT was considered positive, the specificity was high at 95% but the sensitivity was poor at 16%. The interobserver agreement (0.69) and consistency (0.72) were good. Conclusions Basement membrane thickening is a reproducible predictor for PSC with good sensitivity and specificity. The presence of G2 and especially G3 BMT showed high specificity and could be regarded as highly predictive of PSC. The presence of more than G1 BMT should be reported and the possibility of PSC should be raised in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: In this paper, the authors proposed a new 3D registration algorithm, 3D-scale invariant feature transform (SIFT)-Flow, for multiatlas-based liver segmentation in computed tomography (CT) images. Methods: In the registration work, the authors developed a new registration method that takes advantage of dense correspondence using the informative and robust SIFT feature. The authors computed the dense SIFT features for the source image and the target image and designed an objective function to obtain the correspondence between these two images. Labeling of the source image was then mapped to the target image according to the former correspondence, resulting in accurate segmentation. In the fusion work, the 2D-based nonparametric label transfer method was extended to 3D for fusing the registered 3D atlases. Results: Compared with existing registration algorithms, 3D-SIFT-Flow has its particular advantage in matching anatomical structures (such as the liver) that observe large variation/deformation. The authors observed consistent improvement over widely adopted state-of-the-art registration methods such as ELASTIX, ANTS, and multiatlas fusion methods such as joint label fusion. Experimental results of liver segmentation on the MICCAI 2007 Grand Challenge are encouraging, e.g., Dice overlap ratio 96.27%±0.96% by our method compared with the previous state-of-the-art result of 94.90%±2.86%. Conclusions: Experimental results show that 3D-SIFT-Flow is robust for segmenting the liver from CT images, which has large tissue deformation and blurry boundary, and 3D label transfer is effective and efficient for improving the registration accuracy. [ABSTRACT FROM AUTHOR]

Platelets contain not only proteins needed for hemostasis but also many growth factors that are required for organ development, tissue regeneration, and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, is due to various causes, such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in CLD are poorly understood. Thus, in this paper, the experimental evidence for platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. Platelets improve liver fibrosis by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cAMP is increased by adenosine through its receptors on hepatic stellate cells, thereby resulting in inactivation of these cells. Adenosine is produced by degradation of adenine nucleotides, which are stored in abundance within the dense granules of platelets. The regenerative effect of platelets in the liver consists of three mechanisms: a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these experiments, a clinical trial suggested that the increase in platelets induced by platelet transfusion improved liver function in patients with CLD in a clinical setting.We highlight the current knowledge concerning the role of platelets in CLD and expect to open a novel avenue for application of these clinical therapies to treat liver disease. [ABSTRACT FROM AUTHOR]

Purpose: This paper describes a method to achieve consistent clinical image quality in 18F-FDG scans accounting for patient habitus, dose regimen, image acquisition, and processing techniques. Methods: Oncological PET/CT scan data for 58 subjects were evaluated retrospectively to derive analytical curves that predict image quality. Patient noise equivalent count rate and coefficient of variation (CV) were used as metrics in their analysis. Optimized acquisition protocols were identified and prospectively applied to 179 subjects. Results: The adoption of different schemes for three body mass ranges (<60 kg, 60-90 kg, >90 kg) allows improved image quality with both point spread function and ordered-subsets expectation maximization-3D reconstruction methods. The application of this methodology showed that CV improved significantly (p < 0.0001) in clinical practice. Conclusions: Consistent oncological PET/CT image quality on a high-performance scanner was achieved from an analysis of the relations existing between dose regimen, patient habitus, acquisition, and processing techniques. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures and achieve better patient management and cost-effective operations. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Higuchi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16745 and https://doi.org/10.1111/apt.16774 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Lazarus et al papers. To view these articles, visit https://doi.org/10.1111/apt.16720 and https://doi.org/10.1111/apt.16750 [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Lazarus et al papers. To view these articles, visit https://doi.org/10.1111/apt.16720 and https://doi.org/10.1111/apt.16768 [ABSTRACT FROM AUTHOR]

Titanium dioxide nanoparticles (TiO2) were used in various fields such as food industry, cosmetics, medicine, and agriculture. Despite the many advantages of nanotechnology, the adverse effects of nanoparticles are inevitable. The present study was conducted to evaluate the protective effect of bee bread on titanium dioxide (TiO2) nanoparticle toxicity. Male rats were randomly divided into four groups: Group 1 received daily by gavage (10 mL/kg bw) of distilled water, Group 2 received bee bread ethanolic extract (100 mg/kg bw), Group 3 received TiO2 (100 mg/kg bw) and distilled water (10 mL/kg bw), and Group 4 received TiO2 (100 mg/kg bw) and bee bread ethanolic extract (100 mg/kg bw). All treatments were given daily by gavage during 30 days. At the end of the experiment period, blood samples were collected to analyze fasting blood glucose, lipid profile (TC, TG, LDL-C, HDL-C, and VLDL-C), liver enzymes (AST, ALT, and LDH), total protein, urea, albumin, creatinine, sodium, potassium, and chloride ions. In addition, histological examinations of the kidneys, liver, and brain were investigated. The results showed that the subacute administration of TiO2 alone (100 mg/kg bw) had induced hyperglycemia (309 ± 5 mg/dL) and elevation of hepatic enzyme levels, accompanied by a change in both lipid profile and renal biomarkers as well as induced congestion and dilatation in the hepatic central vein and congestion in kidney and brain tissues. However, the cotreatment with bee bread extract restored these biochemical parameters and attenuated the deleterious effects of titanium nanoparticles on brain, liver, and kidney functions which could be due to its rich content on functional molecules. The findings of this paper could make an important contribution to the field of using bee bread as a detoxifying agent against titanium dioxide nanoparticles and other xenobiotics. [ABSTRACT FROM AUTHOR]

The authors of the article by Patel et al. (2021) noticed an error in the funding information. However, the correct information should read as: Funding information: This work was supported in part by US Public Health Service Grant DK-20478 (MSP). The presently listed information in the paper is: Funding information: This work was supported in part by US Public Health Service Grant NS093264 (MSP). [Extracted from the article]

Purpose: In image-guided radio frequency ablation for liver cancer treatment, pre- and post-interventional CT images are typically used to verify the treatment success of the therapy. In current clinical practice, the tumor zone in the diagnostic, preinterventional images is mentally or manually mapped to the ablation zone in the post-interventional images to decide success of the treatment. However, liver deformation and differences in image quality as well as in texture of the ablation zone and the tumor area make the mental or manual registration a challenging task. Purpose of this paper is to develop an automatic framework to register the pre-interventional image to the post-interventional image. Methods: The authors propose a registration approach enabling a nonrigid deformation of the tumor to the ablation zone, while keeping locally rigid deformation of the tumor area. The method was evaluated on CT images of 38 patient datasets from Erasmus MC. The evaluation is based on Dice coefficients of the liver segmentation on both the pre-interventional and post-interventional images, and mean distances between the liver segmentations. Additionally, residual distances after registration between corresponding landmarks and local mean surface distance in the images were computed. Results: The results show that rigid registration gives a Dice coefficient of 87.9%, a mean distance of the liver surfaces of 5.53 mm, and a landmark error of 5.38 mm, while non-rigid registration with local rigid deformation has a Dice coefficient of 92.2%, a mean distance between the liver segmentation boundaries near the tumor area of 3.83 mm, and a landmark error of 2.91 mm, where a part of this error can be attributed to the slice spacing in the authors' CT images. Conclusions: This method is thus a promising tool to assess the success of RFA liver cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: This work is a preliminary study of a stationary cardiac SPECT system. The goal of this research is to propose a stationary cardiac SPECT system using segmented slant-hole collimators and to perform computer simulations to test the feasibility. Compared to the rotational SPECT, a stationary system has a benefit of acquiring temporally consistent projections. The most challenging issue in building a stationary system is to provide sufficient projection view-angles. Methods: A GATE (GEANT4 application for tomographic emission) Monte Carlo model was developed to simulate a two-detector stationary cardiac SPECT that uses segmented slant-hole collimators. Each detector contains seven segmented slant-hole sections that slant to a common volume at the rotation center. Consequently, 14 view-angles over 180 were acquired without any gantry rotation. The NCAT phantom was used for data generation and a tailored maximum-likelihood expectation-maximization algorithm was used for image reconstruction. Effects of limited number of view-angles and data truncation were carefully evaluated in the paper. Results: Simulation results indicated that the proposed segmented slant-hole stationary cardiac SPECT system is able to acquire sufficient data for cardiac imaging without a loss of image quality, even when the uptakes in the liver and kidneys are high. Seven views are acquired simultaneously at each detector, leading to 5-fold sensitivity gain over the conventional dual-head system at the same total acquisition time, which in turn increases the signal-to-noise ratio by 19%. The segmented slant-hole SPECT system also showed a good performance in lesion detection. In our prototype system, a short hole-length was used to reduce the dead zone between neighboring collimator segments. The measured sensitivity gain is about 17-fold over the conventional dual-head system. Conclusions: The GATE Monte Carlo simulations confirm the feasibility of the proposed stationary cardiac SPECT system with segmented slant-hole collimators. The proposed collimator consists of combined parallel and slant holes, and the image on the detector is not reduced in size. [ABSTRACT FROM AUTHOR]

Purpose: For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems. Methods: The optimal selection of kV and mAs was formulated as a constrained optimization problem to minimize the objective function, Dose(kV,mAs), under the constraint that the achievable detectability index d'(kV,mAs) is not lower than the prescribed value of d' for a given imaging task. Since it is difficult to analytically model the dependence of d' on kV and mAs for the highly nonlinear MBIR method, this constrained optimization problem is solved with comprehensive measurements of Dose(kV,mAs) and d'(kV,mAs) at a variety of kV-mAs combinations, after which the overlay of the dose contours and d' contours is used to graphically determine the optimal kV-mAs combination to achieve the lowest dose while maintaining the needed detectability for the given imaging task. As an example, R' for a 17 mm hypoattenuating liver lesion detection task was experimentally measured with an anthropomorphic abdominal phantom at four tube potentials (80, 100, 120, and 140 kV) and fifteen mA levels (25 and 50-700) with a sampling interval of 50 mA at a fixed rotation time of 0.5 s, which corresponded to a dose (CTDIvol) range of [0.6, 70] mGy. Using the proposed method, the optimal kV and mA that minimized dose for the prescribed detectability level of d'R = 16 were determined. As another example, the optimal kV and mA for an 8 mm hyperattenuating liver lesion detection task were also measured using the developed framework. Both an in vivo animal and human subject study were used as demonstrations of how the developed framework can be applied to the clinical work flow. Results: For the first task, the optimal kV and mAs were measured to be 100 and 500, respectively, for FBP, which corresponded to a dose level of 24 mGy. In comparison, the optimal kV and mAs for MBIR were 80 and 150, respectively, which corresponded to a dose level of 4 mGy. The topographies of the iso-d' map and the iso-CNR map were the same for FBP; thus, the use of d'- and CNR-based optimization methods generated the same results for FBP. However, the topographies of the iso-d' and iso-CNR map were significantly different in MBIR; the CNR-based method overestimated the performance of MBIR, predicting an overly aggressive dose reduction factor. For the second task, the developed framework generated the following optimization results: for FBP, kV = 140, mA= 350, dose = 37.5 mGy; for MBIR, kV = 120, mA= 250, dose = 18.8 mGy. Again, the CNR-based method overestimated the performance of MBIR. Results of the preliminary in vivo studies were consistent with those of the phantom experiments. Conclusions: A unified and task-driven kV/mAs optimization framework has been developed in this work. The framework is applicable to both linear and nonlinear CT systems such as those using the MBIR method. As expected, the developed framework can be reduced to the conventional CNR-based kV/mAs optimization frameworks if the system is linear. For MBIR-based nonlinear CT systems, however, the developed task-based kV/mAs optimization framework is needed to achieve the maximal dose reduction while maintaining the desired diagnostic performance. [ABSTRACT FROM AUTHOR]

Aim: Malnutrition is common in patients with chronic liver disease and is recognised as a prognostic factor with evidence suggesting that sufficient nutritional support can improve outcomes. However, malnutrition in this patient population continues to be underdiagnosed and managed in clinical practice. This paper outlines a study aimed to determine current practice among dietitians, compares this with best practice guidelines and identifies barriers to achieving best practice. Methods: This study aims to involved an anonymous online survey questionnaire targeted at dietitians with at least 12 months of experience working with patients with liver cirrhosis. Results: A total of 41 completed surveys were received and analysed. Results showed that the majority (85%) of respondents were using the European Society of Clinical Nutrition and Metabolism guidelines. Over 85% of surveyed dietitians reported that they were currently recommending high ‐ energy and high ‐ protein diets to their patients. Methods used to calculate dietary requirements varied, with some respondents using actual weight and others using dry weight. There was also variation in nutrition assessment tool used among surveyed respondents. Thirty ‐ six per cent of respondents reported that nasogastric feeding always or often commenced when recommended. The most commonly reported barrier to achieving best practice was patient compliance. Conclusions: From the study, it appears that most dietitians are consistently recommending high ‐ energy and protein intake. However, there is significant variation in practice for weights used in calculating nutritional requirements, assessing nutritional status and nasogastric tube use for nutrition support. [ABSTRACT FROM AUTHOR]