bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver fibrosis phenotyping and severity scoring by quantitative image analysis of biopsy slides
Authors: Watson Adam , Petitjean Louis , Petitjean Mathieu , Pavlides Michael 
Published: November 2023

AbstractBackground & AimsDigital pathology image analysis can phenotype liver fibrosis using histological traits that reflect collagen content, morphometry and architecture. Here, we aimed to calculate fibrosis severity scores to quantify these traits.MethodsLiver biopsy slides were categorised by Ishak stage and aetiology. We used a digital pathology technique to calculate four fibrosis severity scores: Architecture Composite Score (ACS), Collagen Composite Score (CCS), Morphometric Composite Score (MCS) and Phenotypic Fibrosis Composite Score (PH‐FCS). We compared how these scores varied according to disease stage and aetiology.ResultsWe included 80 patients (40% female, mean age 59.0 years, mean collagen proportionate area 17.1%) with mild (F0‐2, n = 28), moderate (F3‐4, n = 17) or severe (F5‐6, n = 35) fibrosis. All four aetiology independent scores corelated with collagen proportionate area (ACS: rp = .512, CCS: rp = .727, MCS: rp = .777, PFCS: r = .772, p < .01 for all) with significant differences between moderate and severe fibrosis (p < .05). ACS increased primarily between moderate and severe fibrosis (by 95% to 226% depending on underlying aetiology), whereas MCS and CCS accumulation was more varied. We used 28 qFTs that distinguished between autoimmune‐ and alcohol‐related liver disease to generate an MCS that significantly differed between mild and severe fibrosis for these aetiologies (p < .05).ConclusionsWe describe four aetiology‐dependent and ‐independent severity scores that quantify fibrosis architecture, collagen content and fibre morphometry. This approach provides additional insight into how progression of architectural changes and accumulation of collagen may differ depending on underlying disease aetiology.
Exercise training improves serum biomarkers of liver fibroinflammation in patients with metabolic dysfunction‐associated steatohepatitis
Authors: Harris Sara J. , Smith Nataliya , Hummer Breianna , Schreibman Ian R. , Faust Alison J. , Geyer Nathaniel R. , Chinchilli Vernon M. , Sciamanna Chris , Loomba Rohit , Stine Jonathan G. 
Published: November 2023

AbstractBackground and AimsExercise training is recommended for all patients with metabolic dysfunction‐associated steatotic liver disease and may reverse liver fibrosis. Whether exercise training improves liver fibrosis without body weight loss remains controversial. We further investigated this relationship using serum biomarkers of liver fibroinflammation in a post hoc analysis of an exercise trial where patients did not lose significant body weight.MethodsIn the NASHFit trial, patients with metabolic dysfunction‐associated steatohepatitis were randomized to receive either moderate‐intensity aerobic exercise training or standard clinical care for 20 weeks. Mediterranean‐informed dietary counselling was provided to each group. Change in serum biomarkers was measured and compared between the two groups.ResultsExercise training led to improvement in serum biomarkers of liver fibroinflammation, including (1) ≥17 IU/L reduction in alanine aminotransferase (ALT) in 53% of individuals in the exercise training group compared to 13% in the standard clinical care group (p < 0.001; mean reduction 24% vs. 10% respectively) and (2) improvement in CK18 (−61 vs. +71 ng/mL, p = 0.040). ALT improvement ≥17 IU/L was correlated with ≥30% relative reduction in magnetic resonance imaging‐measured liver fat and PNPLA3 genotype.ConclusionExercise training improves multiple serum biomarkers of liver fibroinflammation at clinically significant thresholds of response without body weight loss. This study provides further evidence that exercise training should be viewed as a weight‐neutral intervention for which response to intervention can be readily monitored with widely available non‐invasive biomarkers that can be applied at the population level.
HLA matching between donors and recipients improves clinical liver transplant graft survival
Authors: Nabulsi Sarah , Otunla Afolarin A. , Salciccioli Justin , Marshall Dominic C. , Villani Vincenzo , Shanmugarajah Kumaran , Shalhoub Joseph 
Published: November 2023

AbstractBackground and AimsThe importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large‐scale multi‐centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status.MethodsThis retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0–3 mismatches vs. 4–6 mismatches) and then subcategorized by indication and donor status. Risk‐adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan–Meier survival curves.ResultsAllograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4–6 HLA mismatch group, whereas no significant difference was found in the 0–3 HLA mismatch group.ConclusionHLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.
Dual alcohol and metabolic‐related liver disease: Results from a population of liver transplant patients
Authors: Erard Domitille , Villeret François , Chouik Yasmina , Guillaud Olivier , Scoazec Jean‐Yves , Caussy Cyrielle , Disse Emmanuel , Boillot Olivier , Hervieu Valérie , Dumortier Jérôme 
Published: November 2023

AbstractBackground & AimsIf alcohol‐related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are now the two main indications for liver transplantation (LT), it has been recognized that both conditions can coexist in varying degrees and the concept of dual‐aetiology fatty liver disease (DAFLD) has been proposed. This retrospective study aimed to evaluate, in a cohort of patients transplanted for ALD and NAFLD, the prevalence of DAFLD before LT and the impact on liver graft outcome.MethodsFrom 1990 to 2010, all patients who underwent LT for the so‐called ALD or NAFLD in our centre were included. Before LT, DAFLD was defined as patients with a history of excessive alcohol consumption and obesity associated with either diabetes or hypertension. Before LT, patients were separated into three groups: DAFLD, ALD, and NAFLD. Fatty liver graft disease was classified according to the FLIP algorithm.ResultsOut of 907, adult LT recipients were identified: 33 DAFLD patients, 333 ALD patients, and 24 NAFLD patients. After LT, ALD patients experienced significantly more alcohol relapse than DAFLD patients, who had twice more post‐LT metabolic syndrome. Out of 926, post‐LT biopsies, DAFLD patients had significantly more fatty liver graft disease due to metabolic syndrome features than ALD patients.ConclusionOur results support that DAFLD recently emerged as an indication of LT. In the future, this particular population needs to be identified as a specific entity since post‐LT outcome on the graft is different from ALD and more similar to NAFLD patients.
Impact of socio‐economic environment on incidence of primary liver cancer in France between 2006 and 2016
Authors: Comoz Bertille , Ollivier‐Hourmand Isabelle , Bouvier Anne‐Marie , Nousbaum Jean‐Baptiste , Nguyen Thi Thu Nga , Launoy Guy , Bouvier Véronique , Bryere Joséphine 
Published: November 2023

AbstractBackground and AimsTo measure the impact of socio‐economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA).MethodThe study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio‐economic environment was assessed by the European Deprivation Index (EDI). Sex‐ and age‐standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation.ResultsWe included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person‐years for HCC and iCCA, respectively. There was an over‐incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9–10.66] per 100 000 person‐years, Q2 11.43 [10.48–12.47] (p < .0001), Q3 11.81 [10.82–12.89] (p < .0001), Q4 12.26 [11.25–13.37] (p < .001) and Q5 11.53 [10.57–12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407).ConclusionThe incidence of HCC is related to socio‐economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies.
Endogenous sex hormones and nonalcoholic fatty liver disease in US adults
Authors: Kim Donghee , Manikat Richie , Cholankeril George , Ahmed Aijaz 
Published: November 2023

AbstractBackground and AimsSex steroid hormones and sex hormone‐binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone‐to‐estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults.MethodsA cross‐sectional analysis using the 2013–2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease.ResultsOut of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose‐dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women.ConclusionThe T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD.
Liver disease mortality and hospitalisations among people with type 2 diabetes mellitus: A population‐based study
Authors: Tomic Dunya , Salim Agus , George Jacob , Magliano Dianna J. , Shaw Jonathan E. 
Published: November 2023

AbstractBackground and AimsThe burden of liver disease among people with diabetes at a population level is unknown. We explored the burden and trends of liver disease mortality and hospitalisations among Australians with diabetes.MethodsWe linked Australians with type 2 diabetes on the National Diabetes Services Scheme to the National Death Index for 2002–2019 to determine trends in the proportion of deaths due to liver disease, overall and by subcategory. We also determined the leading reasons and risk factors for liver disease hospitalisations in those with diabetes over this period. Finally, we compared the burden of liver disease hospitalisations among those with diabetes to the general population using excess hospitalisations per 100 000 person‐years.ResultsAmong Australians with type 2 diabetes (n = 1 122 431) liver diseases accounted for between 1.5% and 1.9% of deaths between 2002 and 2019, roughly one‐third of the proportion of deaths caused by kidney disease. The proportion of deaths due to inflammatory liver diseases among those with diabetes increased from .08% in 2002 to .27% in 2019. Alcohol‐related liver disease accounted for the greatest share (22.7%) of liver disease hospitalisation in those with diabetes, but the number of hospitalisations for this condition declined over time. Compared to the general population, men (RR 3.63, 95% CI 3.44–3.84) and women (RR 4.49, 4.21–4.78) with diabetes were at higher risk of hospitalisation for fibrosis and cirrhosis; however, this did not translate to a substantial excess risk per 100 000 population.ConclusionsBetter screening methods for liver disease among people with diabetes should be developed and implemented into practice.
From complement to complosome in non‐alcoholic fatty liver disease: When location matters
Authors: Nguyen Van‐Dien , Hughes Timothy R. , Zhou You 
Published: November 2023

AbstractNon‐alcoholic fatty liver disease (NAFLD) is a growing public health threat and becoming the leading cause of liver transplantation. Nevertheless, no approved specific treatment is currently available for NAFLD. The pathogenesis of NAFLD is multifaceted and not yet fully understood. Accumulating evidence suggests a significant role of the complement system in the development and progression of NAFLD. Here, we provide an overview of the complement system, incorporating the novel concept of complosome, and summarise the up‐to‐date evidence elucidating the association between complement dysregulation and the pathogenesis of NAFLD. In this process, the extracellular complement system is activated through various pathways, thereby directly contributing to, or working together with other immune cells in the disease development and progression. We also introduce the complosome and assess the evidence that implicates its potential influence in NAFLD through its direct impact on hepatocytes or non‐parenchymal liver cells. Additionally, we expound upon how complement system and the complosome may exert their effects in relation with hepatic zonation in NAFLD. Furthermore, we discuss the potential therapeutic implications of targeting the complement system, extracellularly and intracellularly, for NAFLD treatment. Finally, we present future perspectives towards a better understanding of the complement system's contribution to NAFLD.
Molecular signatures of alternative reproductive strategies in a facultatively social hover wasp
Authors: Taylor Benjamin A. , Taylor Daisy , Bodrug‐Schepers Alexandrina , Câmara Ferreira Francisco , Stralis‐Pavese Nancy , Himmelbauer Heinz , Guigó Roderic , Reuter Max , Sumner Seirian 
Published: November 2023

AbstractSocial insect reproductives and non‐reproductives represent ideal models with which to understand the expression and regulation of alternative phenotypes. Most research in this area has focused on the developmental regulation of reproductive phenotypes in obligately social taxa such as honey bees, while relatively few studies have addressed the molecular correlates of reproductive differentiation in species in which the division of reproductive labour is established only in plastic dominance hierarchies. To address this knowledge gap, we generate the first genome for any stenogastrine wasp and analyse brain transcriptomic data for non‐reproductives and reproductives of the facultatively social species Liostenogaster flavolineata, a representative of one of the simplest forms of social living. By experimentally manipulating the reproductive ‘queues’ exhibited by social colonies of this species, we show that reproductive division of labour in this species is associated with transcriptomic signatures that are more subtle and variable than those observed in social taxa in which colony living has become obligate; that variation in gene expression among non‐reproductives reflects their investment into foraging effort more than their social rank; and that genes associated with reproductive division of labour overlap to some extent with those underlying division of labour in the separate polistine origin of wasp sociality but only explain a small portion of overall variation in this trait. These results indicate that broad patterns of within‐colony transcriptomic differentiation in this species are similar to those in Polistinae but offer little support for the existence of a strongly conserved ‘toolkit’ for sociality.
Heterogeneous patterns of heterozygosity loss in isolated populations of the threatened eastern barred bandicoot (Perameles gunnii)
Authors: Black John G. , van Rooyen Anthony R. J. , Heinze Dean , Gaffney Robbie , Hoffmann Ary A. , Schmidt Thomas L. , Weeks Andrew R. 
Published: November 2023

AbstractIdentifying and analysing isolated populations is critical for conservation. Isolation can make populations vulnerable to local extinction due to increased genetic drift and inbreeding, both of which should leave imprints of decreased genome‐wide heterozygosity. While decreases in heterozygosity among populations are frequently investigated, fewer studies have analysed how heterozygosity varies among individuals, including whether heterozygosity varies geographically along lines of discrete population structure or with continuous patterns analogous to isolation by distance. Here we explore geographical patterns of differentiation and individual heterozygosity in the threatened eastern barred bandicoot (Perameles gunnii) in Tasmania, Australia, using genomic data from 85 samples collected between 2008 and 2011. Our analyses identified two isolated demes undergoing significant genetic drift, and several areas of fine‐scale differentiation across Tasmania. We observed discrete genetic structures across geographical barriers and continuous patterns of isolation by distance, with little evidence of recent or historical migration. Using a recently developed analytical pipeline for estimating autosomal heterozygosity, we found individual heterozygosities varied within demes by up to a factor of two, and demes with low‐heterozygosity individuals also still contained those with high heterozygosity. Spatial interpolation of heterozygosity scores clarified these patterns and identified the isolated Tasman Peninsula as a location where low‐heterozygosity individuals were more common than elsewhere. Our results provide novel insights into the relationship between isolation‐driven genetic structure and local heterozygosity patterns. These may help improve translocation efforts, by identifying populations in need of assistance, and by providing an individualised metric for identifying source animals for translocation.
The role of intensive care unit diaries in the grieving process: A monocentric qualitative study
Authors: Bazzano Giacomo , Buccoliero Francesco , Villa Marta , Pegoraro Flavia , Iannuzzi Luigi , Rona Roberto , Fumagalli Roberto , Giani Marco , Lucchini Alberto 
Published: November 2023

AbstractBackgroundThe growing importance of psychological recovery for patients and their families following intensive care unit (ICU) experiences in recent years cannot be overemphasized. The ICU diary is used to aid patients in reducing the prevalence of post‐traumatic stress disorder, anxiety, and depression. The usefulness of maintaining a diary during the grieving process has not yet been thoroughly investigated.AimTo investigate the role of ICU diaries in the grief process experienced by family members of a person who died in the intensive care unit.Study DesignNine family members of seven deceased ICU patients with an ICU diary were contacted and interviewed by phone using a semi‐structured interview. A qualitative data analysis was performed using thematic synthesis.SettingItalian general intensive care unit.FindingsInterviewed family members felt that the diary helped them during the grieving process. The return of diaries was desired by family members for support and to remember one's loved one. The diary helped them process their losses in various ways, including signs of evidence of care, emotional involvement, consideration, and coping with grief. Four main themes emerged from the analysis: writing the diary, reading the diary, talking about the diary, and the diary during the grieving process.ConclusionsThe overall perception of the ICU diary was positive. The diary mostly helped relatives to “give back something of what we lost”. This study also affirms the positive link between ICU diaries and bereavement in Italian ICU. Further studies are required to confirm the usefulness of this tool in the grieving process.Relevance to Clinical PracticeThe ICU diary can help patients' family members understand what happened to their loved one and play an important role in the grieving process. The diary served as a valuable source of information that aided in providing bereavement support to the family by helping them to gain a rational and emotional understanding of the patient's death.
Coordinated phosphate uptake by extracellular alkaline phosphatase and solute carrier transporters in marine diatoms
Authors: Matsui Hiroaki , Harada Hisashi , Maeda Kanako , Sugiyama Toshiki , Fukuchi Yohei , Kimura Nanae , Nawaly Hermanus , Tsuji Yoshinori , Matsuda Yusuke 
Published: November 2023

Summary

Marine diatoms express genes encoding potential phosphate transporter and alkaline phosphatase (APase) under phosphate‐limited (−P) condition. This indicates that diatoms use high‐affinity phosphate uptake system with organic phosphate hydration. The function of molecules playing roles for Pi uptake was determined in this study.

Pi uptake and APase activity of two marine diatoms, Phaeodactylum tricornutum and Thalassiosira pseudonana, were monitored during acclimation to −P condition. The transcript levels of Pi transporter were analyzed, and Pi transporters were localized with GFP tagging in diatom cells. KO mutants of plasma membrane solute carrier proteins (SLC34s) or APase were established, and their phenotype was evaluated.

Some Na+/Pi transporter candidates, SLC34s in P. tricornutum and T. pseudonana, increased transcript under −P condition. Whole‐cell Pi transport was specifically stimulated by sodium ion but independent of potassium, lithium, or proton. Genome‐editing KO of PtSLC34‐5 and APase (Pt49678) in P. tricornutum was highly inhibitory for Pi uptake, and KO of TpSLC34‐2 was also highly inhibitory for Pi uptake in T. pseudonana.

SLC34s and APase were co‐expressed under −P conditions in marine diatoms. SLC34s play a major role in the initial acclimation stage of diatom cells to −P condition and APase plays an increasing role in the prolonged Pi‐starved condition.