bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicidal thoughts and behaviours among student nurses and midwives: A systematic review
Authors: Groves Samantha , Lascelles Karen , Hawton Keith
Published: November 2023

Aim

To synthesize research investigating suicide, suicide attempts, self‐harm and suicide ideation in nursing and midwifery students, a group of interest due to high rates of suicide among qualified nurses. Specific areas of interest for this review included prevalence, factors which may contribute to or mitigate risk and suicide prevention interventions.

Design

A systematic review was conducted, and Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines were followed.

Data Sources

Three electronic databases were searched, and additional articles identified using hand‐searching. Studies were included if they examined suicide, suicide attempts, self‐harm or suicide ideation in nursing or midwifery students.

Review Methods

Studies were deduplicated and assessed for inclusion. Data from included studies were extracted, quality of studies assessed and data synthesized, informed by study focus, design and assessed quality.

Results

About 46 studies of largely moderate to low quality were identified. A high‐quality study demonstrated increased risk of suicide in Swedish female nursing students, and increased risk of self‐harm in nursing students of both sexes. Prevalence of suicide ideation did not appear to differ across course year, or between nursing students and students on other programmes. Psychiatric conditions, particularly depression, were associated with suicide ideation. Three studies related to suicide prevention interventions were identified. Integration of wellness initiatives into the curriculum and peer support were preferred interventions among nursing students and teaching staff.

Conclusions

To understand the extent of suicide and self‐harm among nursing and midwifery students there is a need for further epidemiological research stratified by programme of study. To develop prevention interventions and initiatives for nursing students, high‐quality longitudinal studies should examine characteristics associated with suicide and self‐harm.

Impact

Current findings suggest interventions could include support for students experiencing mental health difficulties, foster peer support, and help develop wellness.

No patient or public contribution.
Assessment of runs of homozygosity, heterozygosity‐rich regions and genomic inbreeding estimates in a subpopulation of Guzerá (Bos indicus) dual‐purpose cattle
Authors: Carrara E. R. , Lopes P. S. , Veroneze R. , Pereira R. J. , Zadra L. E. F. , Peixoto M. G. C. D.
Published: November 2023

For decades, inbreeding in cattle has been evaluated using pedigree information. Nowadays, inbreeding coefficients can be obtained using genomic information such as runs of homozygosity (ROH). The aims of this study were to quantify ROH and heterozygosity‐rich regions (HRR) in a subpopulation of Guzerá dual‐purpose cattle, to examine ROH and HRR islands, and to compare inbreeding coefficients obtained by ROH with alternative genomic inbreeding coefficients. A subpopulation of 1733 Guzerá animals genotyped for 50k SNPs was used to obtain the ROH and HRR segments. Inbreeding coefficients by ROH (FROH), by genomic relationship matrix based on VanRaden's method 1 using reference allele frequency in the population (FGRM), by genomic relationship matrix based on VanRaden's method 1 using allele frequency fixed in 0.5 (FGRM_0.5), and by the proportion of homozygous loci (FHOM) were calculated. A total of 15,660 ROH were identified, and the chromosome with the highest number of ROH was BTA6. A total of 4843 HRRs were identified, and the chromosome with the highest number of HRRs was BTA23. No ROH and HRR islands were identified according to established criteria, but the regions closest to the definition of an island were examined from 64 to 67 Mb of BTA6, from 36 to 37 Mb of BTA2 and from 0.50 to 1.25 Mb of BTA23. The genes identified in ROH islands have previously been associated with dairy and beef traits, while genes identified on HRR islands have previously been associated with reproductive traits and disease resistance. FROH was equal to 0.095 ± 0.084, and its Spearman correlation with FGRM was low (0.44) and moderate‐high with FHOM (0.79) and with FGRM_0.5 (0.80). The inbreeding coefficients determined by ROH were higher than other cattle breeds' and higher than pedigree‐based inbreeding in the Guzerá breed obtained in previous studies. It is recommended that future studies investigate the effects of inbreeding determined by ROH on the traits under selection in the subpopulation studied.
Identification of hypoxia‐related gene signatures based on multi‐omics analysis in lung adenocarcinoma
Authors: Luo Qineng , Li Xing , Meng Zixing , Rong Hao , Li Yanguo , Zhao Guofang , Zhu Huangkai , Cen Lvjun , Liao Qi
Published: November 2023

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and one of the malignancies with the highest incidence rate and mortality worldwide. Hypoxia is a typical feature of tumour microenvironment (TME), which affects the progression of LUAD from multiple molecular levels. However, the underlying molecular mechanisms behind LUAD hypoxia are not fully understood. In this study, we estimated the level of hypoxia by calculating a score based on 15 hypoxia genes. The hypoxia scores were relatively high in LUAD patients with poor prognosis and were bound up with tumour node metastasis (TNM) stage, tumour size, lymph node, age and gender. By comparison of high hypoxia score group and low hypoxia score group, 1820 differentially expressed genes were identified, among which up‐regulated genes were mainly about cell division and proliferation while down‐regulated genes were primarily involved in cilium‐related biological processes. Besides, LUAD patients with high hypoxia scores had higher frequencies of gene mutations, among which TP53, TTN and MUC16 had the highest mutation rates. As for DNA methylation, 1015 differentially methylated probes‐related genes were found and may play potential roles in tumour‐related neurobiological processes and cell signal transduction. Finally, a prognostic model with 25 multi‐omics features was constructed and showed good predictive performance. The area under curve (AUC) values of 1‐, 3‐ and 5‐year survival reached 0.863, 0.826 and 0.846, respectively. Above all, our findings are helpful in understanding the impact and molecular mechanisms of hypoxia in LUAD.
Editorial: Innovation in child and adolescent mental health interventions
Authors: Ramchandani Paul , Dalgleish Tim , Luby Joan , Peterson Bradley , Sonuga‐Barke Edmund
Published: November 2023

We are living in a time when children and adolescents are showing higher levels of mental health problems in many countries, and when Child and Adolescent Mental Health Services (CAMHS) in most areas (where they exist at all) are struggling with delivering services to all the young people and families who need them. Many treatment centers respond by restricting the scope of their service, some by excluding younger children, some by focusing on narrower diagnostic groupings, and some by providing online information as a holding strategy.
Retrospective study of the mortality of the Vieira's titi monkey (Plecturocebus vieirai) at the Sorocaba Zoo, Brazil
Authors: Silva Maraya Lincoln , Caiaffa Mayara Grego , da Costa André Luiz Mota , Ferreira‐Machado Eduardo , Ervedosa Ticiana Brasil , Navas‐Suárez Pedro Enrique , Guerra Juliana Mariotti , Matos Flora Nogueira , Gonzaga Cássia Regina Ramos , de Azevedo Fernandes Natália Coelho Couto , Teixeira Rodrigo Hidalgo Friciello
Published: November 2023

Background

The Vieira's titi monkey (Plecturocebus vieirai) was recently described and characterized as endemic to Brazil. According to the IUCN red list, this species is classified as critically endangered (CR). At the date of the publication of this manuscript, there are no published data on the health aspects of this species.

Methods

For this study, the necropsy, and histopathological data of the mortality of P. vieirai at Sorocaba Zoo (São Paulo, Brazil) were collected and analyzed.

Results

Causes of death diagnosed included disorders of the urinary, gastrointestinal, immune, and circulatory systems.

Conclusions

This study provides information regarding the pathological conditions of P. vieirai and points to urinary and gastrointestinal diseases as the main causes of death in this species at Sorocaba Zoo. These results can help veterinarians who have this species under their care diagnose and deal with it more quickly, increasing the probability of survival.
Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke
Authors: Hood Rebecca J. , Sanchez‐Bezanilla Sonia , Beard Daniel J. , Rust Ruslan , Turner Renée J. , Stuckey Shannon M. , Collins‐Praino Lyndsey E. , Walker Frederick R. , Nilsson Michael , Ong Lin Kooi
Published: November 2023

We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal‐dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid‐β accumulation in the hippocampus, a region remote from the primary infarct. Interestingly, there is emerging evidence suggesting that deposition of amyloid‐β around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood–brain barrier integrity. However, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the current study, we aimed to characterise the spatiotemporal cerebrovascular changes after cortical stroke. This was done using the photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Cerebrovascular morphology as well as the co‐localisation of amyloid‐β with vasculature and blood–brain barrier integrity were assessed in the cortex and hippocampal regions at 7, 28 and 84 days post‐stroke. Our findings showed transient cerebrovascular remodelling in the peri‐infarct area up to 28 days post‐stroke. Importantly, the cerebrovascular changes were extended beyond the peri‐infarct region to the ipsilateral hippocampus and were sustained out to 84 days post‐stroke. When investigating vessel diameter, we showed a decrease at 84 days in the peri‐infarct and CA1 regions that were exacerbated in vessels with amyloid‐β deposition. Lastly, we showed sustained vascular leakage in the peri‐infarct and ipsilateral hippocampus, indicative of a compromised blood–brain‐barrier. Our findings indicate that hippocampal vasculature may represent an important therapeutic target to mitigate the progression of post‐stroke cognitive impairment.
Morphofunctional characterisation of axonal damage in different rat models of chemotherapy‐induced peripheral neurotoxicity: The role of nerve excitability testing
Authors: Chiorazzi Alessia , Canta Annalisa , Carozzi Valentina Alda , Meregalli Cristina , Pozzi Eleonora , Ballarini Elisa , Rodriguez‐Menendez Virginia , Marmiroli Paola , Cavaletti Guido , Alberti Paola
Published: November 2023

Background and Aims

Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a common and long‐lasting adverse event of several anticancer compounds, for which treatment has not yet been developed. To fill this gap, preclinical studies are warranted, exploiting highly translational outcome measure(s) to transfer data from bench to bedside. Nerve excitability testing (NET) enables to test in vivo axonal properties and can be used to monitor early changes leading to axonal damage.

Methods

We tested NET use in two different CIPN rat models: oxaliplatin (OHP) and paclitaxel (PTX). Animals (female) were chronically treated with either PTX or OHP and compared to respective control animals. NET was performed as soon as the first injection was administered. At the end of the treatment, CIPN onset was verified via a multimodal and robust approach: nerve conduction studies, nerve morphometry, behavioural tests and intraepidermal nerve fibre density.

Results

NET showed the typical pattern of axonal hyperexcitability in the 72 h following the first OHP administration, whereas it showed precocious signs of axonal damage in PTX animals. At the end of the month of treatment, OHP animals showed a pattern compatible with a mild axonal sensory polyneuropathy. Instead, PTX cohort was characterised by a rather severe sensory axonal polyneuropathy with minor signs of motor involvement.

Interpretation

NET after the first administration demonstrated the ongoing OHP‐related channelopathy, whereas in PTX cohort it showed precocious signs of axonal damage. Therefore, NET could be suggested as an early surrogate marker in clinical trials, to detect precocious changes leading to axonal damage.
Political economy of input–output markets of groundnut: A case from the groundnut value chain of Turkey
Authors: Özalp Burhan , Ören M. Necat
Published: November 2023

Mainstream economics argues that value chains provide farmers better prices and incomes, thus aiding development. However, this study contradicts this consensus, revealing that the value chain generates the status of petty commodity producers for farmers. Furthermore, it demonstrates that the value chain keeps downstream actors, such as merchants, processors, wholesalers, and retailers, in a powerful position against farmers. The study delves into these phenomena by considering the historical relationship between the market, the commodification of agriculture, the state, the interconnection of markets, the value chain, and neoliberalism. This research focuses on the political economy of groundnut input–output markets in Turkey through value chain analysis. Based on thorough primary field research, the paper demonstrates that the functioning of the value chain strengthens the position of downstream actors against farmers. Additionally, it shows that the value chain creates interlinking between farmers and merchants and makes small farmers the most disadvantaged actor. Moreover, the study highlights that groundnut production costs have risen at a higher rate than incomes under neoliberal policies. Finally, the article demonstrates that mechanization in groundnut farming, while increasing productivity by meeting the chain demands, fails to significantly improve farmers' incomes and profits due to the impact of neoliberal policies on other input costs.
Treatment of periorbital aging with negative pressure fractional microneedle radiofrequency: A self‐controlled clinical trial
Authors: Gao Yulian , Che Qilei , He Qiang , Wang Wenju , Luo Wangsha , Tong Yao , Liu Lufeng , Tang Qiuyue , Xie Yuhong , Zhou Zixuan , Wa Qingbiao
Published: November 2023

Background

Several treatment modalities are used for the treatment of periorbital rejuvenation with variable results. Recent studies showed that fractional radiofrequency may be an effective treatment modality for periorbital aging. This study aims to determine the efficacy and safety of negative pressure fractional microneedle radiofrequency (NPFMR) as a treatment for periorbital aging.

Methods

Twenty‐five patients with periorbital aging were involved in this study. They were treated two times with an interval of 1 month. The patients were evaluated before treatment and 1, 3, and 6 months after the final treatment.

Results

The research findings suggest that periorbital wrinkles of the patients were significantly improved by VISIA system (p < 0.05). Physiological indicators detected by MPA10 system showed that compared with before treatment, the hydration increased (p < 0.05) and trans epidermal water loss (TEWL) decreased (p < 0.05) at 3 and 6 months after treatment. The glossiness increased at 1 month after treatment compared to pre‐treatment (p < 0.05) and returned to the baseline level at 3 and 6 months after treatment. There was no significant change in melanin content (p > 0.05). Periorbital dermal thickness of the patients significantly increased at 1, 3, and 6 months after treatment according to skin ultrasound (p < 0.05). A periorbital skin biopsy revealed that the collagen fibers in the dermis were significantly thicker and more orderly after treatment, and the expression of type I collagen fibers and elastic fibers was increased compared with that before treatment. One patient developed post‐inflammatory hyperpigmentation (PIH) at 1 month after the first treatment, which improved after active treatment. No other adverse reactions were observed.

Conclusions

NPMFR could be an effective and safe treatment modality for the treatment of periorbital aging.
Firm Competition and Cooperation with Norm‐Based Preferences for Sustainability
Authors: Inderst Roman , Sartzetakis Eftichios S. , Xepapadeas Anastasios
Published: November 2023

We analyze firms' incentives to coordinate on the introduction of a sustainable product variant when consumers' preferences for sustainability depend on the perceived social norm, which in turn is shaped by average consumption behavior. We show that such preferences could lead to multiple equilibria. If the level of competition among potential adopters is very low and adoption of the sustainable variant allows them to sufficiently expand their aggregate market share, they will coordinate on introducing the sustainable variant when a lenient legal regime makes this feasible. If competition among them is intense and market expansion under the sustainable variant is very limited, coordination can forestall the adoption of the sustainable variant. Our analysis thus both confirms and qualifies the notion of a sustainability “first‐mover disadvantage” as a justification for an agreement between competitors, which has gained traction in antitrust. We also provide empirical evidence for norm‐based sustainability preferences.
Circulating extracellular choline acetyltransferase regulates inflammation
Authors: Gabalski Arielle H. , Tynan Aisling , Tsaava Tea , Li Jian Hua , Lee Diana , Hepler Tyler D. , Hide Daniel , George Sam , Bravo Iñiguez Carlos E. , Thompson Dane A , Zhu Cassie , Wang Haichao , Brines Michael , Tracey Kevin J. , Chavan Sangeeta S.
Published: November 2023

Background

Choline acetyltransferase (ChAT) is required for the biosynthesis of acetylcholine, the molecular mediator that inhibits cytokine production in the cholinergic anti‐inflammatory pathway of the vagus nerve inflammatory reflex. Abundant work has established the biology of cytoplasmic ChAT in neurons, but much less is known about the potential presence and function of ChAT in the extracellular milieu.

Objectives

We evaluated the hypothesis that extracellular ChAT activity responds to inflammation and serves to inhibit cytokine release and attenuate inflammation.

Methods

After developing novel methods for quantification of ChAT activity in plasma, we determined whether ChAT activity changes in response to inflammatory challenges.

Results

Active ChAT circulates within the plasma compartment of mice and responds to immunological perturbations. Following the administration of bacterial endotoxin, plasma ChAT activity increases for 12–48 h, a time period that coincides with declining tumor necrosis factor (TNF) levels. Further, a direct activation of the cholinergic anti‐inflammatory pathway by vagus nerve stimulation significantly increases plasma ChAT activity, whereas the administration of bioactive recombinant ChAT (r‐ChAT) inhibits endotoxin‐stimulated TNF production and anti‐ChAT antibodies exacerbate endotoxin‐induced TNF levels, results of which suggest that ChAT activity regulates endogenous TNF production. Administration of r‐ChAT significantly attenuates pro‐inflammatory cytokine production and disease activity in the dextran sodium sulfate preclinical model of inflammatory bowel disease. Finally, plasma ChAT levels are also elevated in humans with sepsis, with the highest levels observed in a patient who succumbed to infection.

Conclusion

As a group, these results support further investigation of ChAT as a counter‐regulator of inflammation and potential therapeutic agent.
What is the moral person like? An examination of the shared and unique perspectives on moral character
Authors: Pringle Victoria , Sun Jessie , Carlson Erika N.
Published: November 2023

Objective

The psychological profile of the moral person might depend on whose perspective is being used. Here, we decompose moral impressions into three components: (a) Shared Moral Character (shared variance across self‐ and informant reports), (b) Moral Identity (how a person uniquely views their morality), and (c) Moral Reputation (how others uniquely view that person's morality).

Method

In two samples (total N  = 458), we used an extended version of the Trait‐Reputation‐Identity model to examine the extent to which each perspective accounts for the overall variance in moral impressions and the degree to which social and personal outcomes were associated with each perspective, controlling for method variance (i.e., positivity and acquiescence bias).

Results

Results suggest that moral character impressions are strongly influenced by positivity and largely idiosyncratic. All components were related to higher levels of agreeableness. For the most part, however, the three components had unique correlates: people higher in Shared Moral Character tended to have higher standings on conscientiousness and honesty‐humility, were more respected, and donated more during an in‐lab game; people higher in Moral Identity endorsed various moral foundations to a greater extent; and people higher in Moral Reputation valued the loyalty foundation less.

Conclusion

These results demonstrate the value of considering multiple perspectives when measuring moral character.
Methodological approaches to assess tactile sensitivity in the food context—A scoping review
Authors: Galler Martina , Varela Paula
Published: November 2023

In contrast to taste sensitivity, the assessment of texture or tactile sensitivity has received relatively little attention in the food context. Texture plays an important role in food preferences and food intake, and individual differences make it important to understand physiological drivers of perception as tactile sensitivity. The multi‐dimensional and dynamic aspects of texture perception suggest there is not one single method that can explain individual differences. This scoping review aims to systematically map methods assessing tactile sensitivity, in the context of food, highlighting differences in approach and implementation. Eligibility criteria included papers describing methods to assess individual differences in tactile sensitivity, that involved human participants and the context was relevant to food behavior. Sources are peer‐reviewed publications of original research in English. In mapping the methods, we assessed how they relate to food texture parameters (mechanical, geometrical, and surface) and the dynamics of breaking down (touch with hand, first bite/sip, oral processing, residual or after‐swallowing sensations). We also review other parameters associated (oral processing, preference, diet and food intake behavior). The literature in this relatively young area is still very fragmented and it is difficult to have a clear picture regarding best practices or recommendations for the measurement of tactile sensitivity in the food context. Future studies should aim to methodological harmonization for application in the food behavior area, with a design of experiment combining different aspects of tactile sensitivity to food, focusing on the thresholds and perceived intensity of textural parameters as well as affective and behavioral responses, and covering the whole spectrum of tactile texture perception (mechanical, geometrics, and surface), including the dynamics of perception.
Effects of the interaction between tank color and type of feed pellets on biological and physiological indicators in red hybrid tilapia (Oreochromis mossambicus × Oreochromis niloticus) juveniles reared in brackish water
Authors: El‐Dakar Ashraf Y. , Shalaby Shymaa M. , El Basuini Mohammed F. , Atiya Mayada N. , Yakop Al‐Shaimaa M. , Younis Elsayed M. , Abdelwarith Abdelwahab A. , Davies Simon J. , Abdel‐Aziz Mohamed F.
Published: November 2023

The present work aimed to investigate the impacts of tank color (transparent, light blue, and red), feed pellet types (floating and sinking), and their interaction on the performance and welfare of red hybrid tilapia juveniles with an initial average weight of 19.59 g for a 50 day trial period following a 3 × 2 factorial design. Fish were cultured randomly at a stoking rate of 10 juveniles/100‐L tank. Fish were fed 6 days per week at a rate of 4% biomass twice daily. Three replicates were performed for each measurement. A two‐way analysis of variance showed that using tanks of different colors (transparent, light blue, and red) has no impact on the growth, feed efficacy, survival rate, and blood composition (except for red blood cells, hematocrit, and triglycerides) of tilapia. Also, pellet types (floating and sinking) showed no significant alterations for the above variables except for glucose and hematocrit levels. Interestingly, the interaction between tank color and pellet type exhibited significant impacts on growth parameters, feed utilization, blood variables, and intestinal enzymes of red hybrid tilapia. Moreover, fish reared in transparent or light blue tanks and fed with floating diets performed the best for all evaluated parameters. Additionally, sinking pellets had better effects when combined with red (dark)‐colored tanks.
Policy integration of climate change adaptation in Central America: A review for development, land‐use planning, and risk management
Authors: Segura Ramírez Luis Diego , van Zeijl‐Rozema Annemarie , Martens Pim
Published: November 2023

Central American countries have been described as highly exposed to the negative effects of climate change (CC). Policies dedicated to CC and climate policy integration—mainstreaming—into sectoral policies have been considered key strategies. Previous research has documented the progress made in this region regarding dedicated policies, but regarding policy integration, information is limited or nonexistent. This article aims to address this gap by studying the level of integration of climate‐change adaptation considerations into three prioritized sectors—general development planning, risk management, and land‐use planning—by applying three criteria for policy integration—inclusion, consistency, and weighting. The results show a progressive trend to integrate adaptation into the policy outputs of the three sectors in all countries. Still, the operational level of instruments in some cases fails to fulfill the mandates to mainstream climate adaptation, and consistency is limited. These failures are indicators of lower levels of organizational maturity, which has also been detected in other developing countries and is connected to conflict and tradeoff avoidance behaviors as a filtering strategy to ensure progress at the cost of leaving key issues outside the mainstreaming process.
Unknown Vocabulary Density and Reading Comprehension: Replicating Hu and Nation (2000)
Authors: Kremmel Benjamin , Indrarathne Bimali , Kormos Judit , Suzuki Shungo
Published: November 2023

Hu and Nation's (2000) study, which stipulated that second language (L2) readers need to be familiar with 98% of lexical items for adequate text comprehension, has become highly influential in L2 vocabulary research and pedagogy. However, the 98% critical threshold figure is based on findings from a research project in which a regression analysis was conducted with only 66 university students in New Zealand. The present study replicated Hu and Nation's research in a context different from a typical Western, educated, industrialized, rich, and democratic context with a sample of 104 Sri Lankan adult L2 learners in a nonacademic context. They each took a Vocabulary Levels Test and read one of five versions of two reading texts at different levels of density of unknown words before answering comprehension questions. The results of the original study could not be fully replicated.
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

Background & Aims

Digital 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.

Methods

Liver 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.

Results

We 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).

Conclusions

We 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

Background and Aims

Exercise 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.

Methods

In 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.

Results

Exercise 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.

Conclusion

Exercise 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

Background and Aims

The 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.

Methods

This 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.

Results

Allograft 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.

Conclusion

HLA 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

Background & Aims

If 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.

Methods

From 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.

Results

Out 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.

Conclusion

Our 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

Background and Aims

To measure the impact of socio‐economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA).

Method

The 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.

Results

We 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).

Conclusion

The 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

Background and Aims

Sex 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.

Methods

A 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.

Results

Out 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.

Conclusion

The 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

Background and Aims

The 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.

Methods

We 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.

Results

Among 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.

Conclusions

Better 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

Non‐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

Social 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

Identifying 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.