bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of drug‐induced liver injury: Current knowledge and future prospects
Authors: Daly Ann K. 
Published: October 2022

AbstractIdiosyncratic drug‐induced liver injury (DILI) remains an important clinical problem, both during drug development and the prescription of a range of licensed drugs. Although rare, the consequences are serious. Ongoing studies on genetic risk factors for DILI, especially genomewide association studies, have resulted in the identification of a number of genetic risk factors, including particular HLA alleles and a few non‐HLA genes, both immune‐related and metabolic. Some non‐HLA associations, such as N‐acetyltransferase 2 in isoniazid DILI and interferon regulatory factor 6 in interferon‐beta DILI are likely to be drug‐specific due to the role of the associated gene, but there is also evidence for polygenic susceptibility involving pathways such as oxidative and endoplasmic reticulum stress and mitochondrial function for DILI induced by multiple drugs. Increased knowledge of genetic risk factors should assist in better understanding underlying DILI mechanisms and help improve methods for identifying hepatotoxic drugs early in development. HLA allele‐specific T cell proliferation together with in silico prediction of drug binding to specific HLA proteins have confirmed genetic findings for certain common causes of DILI. However, studies in hepatocytes exposed to high drug concentrations suggest toxicity that is not dependent on genotype also occurs. It seems likely that susceptibility to DILI involves several genetic risk factors combining with other factors that affect drug levels. Despite recent progress in detecting genetic risk factors for DILI, low positive predictive values mean that general implementation of genotyping prior to prescription of potentially hepatotoxic drugs is not useful currently.
Reactive infectious mucocutaneous eruption due to COVID‐19 with erythema‐multiforme‐like lesions and myeloid cells
Authors: Ortiz Eduardo G. , Junkins‐Hopkins Jacqueline M. 
Published: October 2022

AbstractReactive infectious mucocutaneous eruption (RIME) is a recently described entity in which there is prominent mucositis, most commonly involving the oral and urogenital mucosa, secondary to a variety of pathogens. There is typically minimal cutaneous involvement in RIME. This contrasts with erythema multiforme (EM) in which characteristic targetoid lesions predominate, usually in isolation (EM minor), but in a subset of cases, with severe mucositis (EM major). While the histopathologic features of RIME have not been as well defined, those of EM are characterized by epidermal apoptosis and interface dermatitis with lymphocytes making up the predominant cell type. We report a unique case of RIME in a 16‐year‐old male with COVID‐19 characterized by significant mucositis involving the oral and genital mucosa, as well as numerous targetoid lesions on the trunk and extremities. Histopathologically, there was an inflammatory infiltrate obscuring and disrupting the epidermal interface, associated with epidermal necrosis, and blister formation. The infiltrate was composed of cells with irregular, non‐segmented and elongate nuclei, with myeloid and histiocytoid cytomorphology. The cells were positive for myeloperoxidase, CD68, and CD163 (subset) suggesting myeloid lineage. RIME is a rarely reported COVID‐19‐related eruption, and targetoid lesions and myeloid interface reactions have not been described with RIME.
Beliefs and attitudes of drug and alcohol clinicians when considering referral of Aboriginal clients to involuntary drug and alcohol treatment: A qualitative study
Authors: Lee K. S. Kylie , Bullen Lynette M. , Zheng Catherine , Dawson Angela , Munro Alice , Conigrave Katherine M. 
Published: October 2022

AbstractIntroductionInvoluntary drug and alcohol treatment occurs in many countries and its role is often controversial. This can be a particular concern in relation to First Nations or other culturally distinct populations. This study explores beliefs and attitudes of drug and alcohol clinicians when considering referral of Aboriginal Australians to involuntary drug and alcohol treatment in New South Wales (NSW), Australia.MethodsThe Involuntary Drug and Alcohol Treatment program (IDAT) is legislated by the NSW Drug and Alcohol Treatment Act 2007. There are two IDAT units—in urban (Sydney, four beds) and regional NSW (Orange, eight beds). NSW Health drug and alcohol clinicians who had referred clients to IDAT between 2016 and 2018 were invited to participate in a semi‐structured 1:1 interview. Eleven clinicians (n = 2, male) from six local health districts (urban through to remote) agreed to participate. A descriptive qualitative analysis of responses was conducted.ResultsTwo key themes summarised the beliefs and attitudes that clinicians reported influencing them when considering referral of Aboriginal Australians to involuntary drug and alcohol treatment in NSW: (i) dilemma between saving someone's life and being culturally safe; and (ii) need for holistic wrap‐around care.Discussion and ConclusionsAlmost all clinicians were worried that being in IDAT would further erode their Aboriginal client's autonomy and be retraumatising. Strategies are needed to support the involvement of Aboriginal‐specific services in IDAT processes and ensure local support options for clients on discharge. Future research should examine the effectiveness, acceptability and feasibility of involuntary drug and alcohol treatment programs.
Differential response to climate change and human activities in three lineages of Sichuan snub‐nosed monkeys (Rhinopithecus roxellana)
Authors: Zhao Xumao , Li Xinrui , Zhang Zhixin , Garber Paul A. , Yu Min , Qiao Huijie , Li Ming 
Published: October 2022

AbstractAimDetermining the mechanisms by which climate change and human activities affect patterns of ecological specialization in different genetic units of the same species is crucial for developing local or regionally‐based conservation solutions. This study uses species distribution models and genetic analysis to (1) identify the evidence of intraspecific differences in the population size and distribution of the three extant lineages (Sichuan/Gansu (SG), Qinling (QL) and Shennongjia (SNJ)) of Sichuan snub‐nosed monkeys and (2) determine why some lineages have lower population numbers, a smaller geographical distribution, and are more threatened with extinction.LocationChina.MethodsWe used n‐dimensional hypervolume modelling and genotype‐environment association (GEA) models to compare the climatic niches of three snub‐nosed monkey lineages, SDMs to reconstruct the historical, current and future distributions of each lineage and SMC++ to calculate their effective population sizes.ResultsWe found evidence of: (1) climatic niche differentiation among the SG, QL and SNJ lineages of Sichuan snub‐nosed monkeys; (2) geographical isolation combined with a decrease in population size during the LGM resulted in ecological specialization among these three lineages; and (3) a decline in climatic suitability and anthropogenically driven land conversion, combined with small population size and a narrow distributional range, indicates that the SNJ lineage is at a greater risk of extinction than the SG and QL lineages.Main conclusionsWe demonstrate that during the LGM a reduction in habitat suitability driven by climate change, in concert with decreasing population size, resulted in the geographical isolation of the three Sichuan snub‐nosed monkey subpopulations, leading to lineage differences in ecological specialization. GEA models and hypervolume models demonstrated that the three lineages occupy different ecological niches. Based on lineage‐level models, the SNJ and QL lineages should be the immediate focus of conservation efforts due to their small effective population size and expected future reductions in available suitable habitats. The modelling approach used here is robust and can be applied effectively to examine the biogeography, recent evolutionary history and effective population size of other endangered animal taxa.
Factors associated with successful weight loss after liraglutide treatment for obesity
Authors: Sannaa Wassel , Dilmaghani Saam , BouSaba Joelle , Maselli Daniel , Atieh Jessica , Eckert Deborah , Taylor Ann L. , Harmsen W. Scott , Acosta Andres , Camilleri Michael 
Published: October 2022

AbstractAimTo identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once‐daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity.MethodsOne hundred and thirty‐six obese adults (87% female) were randomized in a placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET1/2); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model.ResultsWeight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide‐ and 16% of placebo‐treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4‐kg weight loss were GET1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57‐3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602‐0.864) per 100 kcal. Among only the 60 liraglutide‐treated subjects, kcal intake at 16 weeks was associated with 4‐kg weight loss (AUROC = 0.757).ConclusionsSlower GET1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide‐treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.
Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon‐like peptide‐1 receptor agonist use
Authors: Rossing Peter , Agarwal Rajiv , Anker Stefan D. , Filippatos Gerasimos , Pitt Bertram , Ruilope Luis M. , Fonseca Vivian , Umpierrez Guillermo E. , Caramori Maria Luiza , Joseph Amer , Lambelet Marc , Lawatscheck Robert , Bakris George L. ,   the FIDELIO‐DKD and FIGARO‐DKD Investigators
Published: October 2022

AbstractAimsTo explore the modifying effect of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO‐DKD and FIGARO‐DKD.Materials and methodsPatients with T2D and CKD treated with optimized renin‐angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin‐to‐creatinine ratio (UACR), and safety were analysed by GLP‐1RA use.ResultsOf 13 026 patients, 944 (7.2%) used GLP‐1RAs at baseline. Finerenone reduced the risk of the cardiovascular composite outcome (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.52–1.11 with GLP‐1RA; HR 0.87, 95% CI 0.79–0.96 without GLP‐1RA; P‐interaction = 0.63) and the kidney composite outcome (HR 0.82, 95% CI 0.45–1.48 with GLP‐1RA; HR 0.77, 95% CI 0.67–0.89 without GLP‐1RA; P‐interaction = 0.79) irrespective of baseline GLP‐1RA use. Reduction in UACR with finerenone at Month 4 was –38% in patients with baseline GLP‐1RA use compared with –31% in those without GLP‐1RA use (P‐interaction = 0.03). Overall safety and incidence of hyperkalaemia were similar, irrespective of GLP‐1RA use.ConclusionsThe cardiorenal benefits of finerenone on composite cardiovascular and kidney outcomes and UACR reduction in patients with CKD and T2D appear to be maintained, regardless of GLP‐1RA use. Subsequent studies are needed to investigate any potential benefit of this combination.
Seeing credit and property rights from below: The experience of Catalan smallholders in the eighteenth century
Authors: Congost Rosa , Garcia‐Orallo Ricard , Saguer Enric 
Published: October 2022

AbstractThe Catalan case in south‐western Europe offers us the opportunity to take a detailed look at the impact a lowering of the interest rate may have had on the poor of a specific area. It is vital to examine how property rights operated in specific contexts, given the close relationship between land and credit markets. Our working hypothesis is that, in some instances where property rights were redefined, as happened in eighteenth‐century Catalonia, the reduction of the interest rate in secured loans benefitted the poorer social groups. The findings of this research, in line with those of some development economists, suggest that only an empirical and bottom‐up perspective allows for a proper analysis of the eradication of poverty by placing it within the real picture of social change.
Long‐term progression‐free survival in patients with chronic lymphocytic leukemia treated with novel agents: An analysis based on indirect comparisons
Authors: Messori Andrea 
Published: October 2022

AbstractObjectiveIn chronic lymphocytic leukemia, growing evidence has accumulated about long‐term outcomes of first‐line treatments. Our objective was to perform indirect comparisons across first‐line treatments.MethodsWe applied the Shiny method, an artificial intelligence technique that analyses Kaplan–Meier curves and reconstructs patient‐level data. Reconstructed patient data were then evaluated through standard survival statistics and indirect head‐to‐head comparisons. The endpoint was progression‐free survival (PFS).ResultsSeven first‐line treatments were studied (1983 patients). Three treatments based on either ibrutinib or venetoclax (i.e., ibrutinib monotherapy, ibrutinib+ rituximab/obinutuzumab, and venetoclax+obinutuzumab) showed a very similar survival pattern. The PFS for these three treatments was significantly better than that of the remaining four treatments (fludarabine+cyclophosphamide+rituximab, chlorambucil+obinutuzumab, bendamustine+rituximab, and chlorambucil monotherapy). Regarding chlorambucil+ obinutuzumab, a significant between‐trial variability was found.ConclusionsLong‐term results are particularly favorable to ibrutinib (alone or in combination) and discourage further use of chlorambucil. As in other studies based on the Shiny method, the multi‐treatment Kaplan–Meier graph summarized the available evidence in comparative terms. The evidence generated this way contributes to define the place in therapy of individual agents.
Screening for occult cancer after unprovoked venous thromboembolism: Assessing the current literature and future directions
Authors: Patel Sarah S. , Tao Derrick , McMurry Hannah S. , Shatzel Joseph J. 
Published: October 2022

AbstractWhile significant evidence has established an increased rate of thrombosis in patients with cancer, the risk of occult malignancy in the setting of an unprovoked thrombosis is less clear. Despite continued interest in developing an effective screening system for occult malignancy following unprovoked venous thromboembolism (VTE), discrepancies in the literature and guideline recommendations leave providers uncertain whether to screen or perform further diagnostics for this patient population. Evidence suggests that screening for malignancy can detect cancer sooner in patients with unprovoked VTE, but there is a lack of high‐quality evidence demonstrating improvements in survival who receive early detection. In the following manuscript, we summarize VTE in relation to cancer epidemiology and pathophysiology. Our literature review summarizes the spectrum of testing strategies for occult malignancy following unprovoked VTE, including biomarker detection methods and various imaging approaches. We evaluate the benefit of additional diagnostic strategies, review current guidelines on the issue, and provide guidance to the reader on the best practice for investigating undiagnosed malignancy in patients with unprovoked VTE.
Effect of stress wave propagation phenomenon on the determination of strain energy density theory parameters and dynamic J‐integral
Authors: Saribay Murat 
Published: October 2022

AbstractDynamic loading for stationary cracks leads to results that are many times greater in magnitude than their static counterparts. If the dynamic loading is in the form of impact type, stress wave propagation effects become dominant. FRAC3D program comprises enriched element formulation which doesn't require excessive mesh refinement around crack tip for accuracy. Strain energy density (SED) theory parameters and dynamic J‐integral are sought in this study to simulate and understand wave propagation phenomenon in detail. Structures under the effect of wave propagations yield more reliable J‐integral values by taking the average of the results from multiple domain sizes. Governed by stress waves, space‐time variations of minimum energy density locations strongly influence fracture characterization for straight and curved crack fronts. Details given in numerical examples section of this paper make a great contribution to understanding of the response for cracked structures subjected to sudden loading.
Mammalian body size evolution was shaped by habitat transitions as an indirect effect of climate change
Authors: Huang Shan , Saarinen Juha J. , Eyres Alison , Eronen Jussi T. , Fritz Susanne A. 
Published: October 2022

AbstractAimBody size evolution has long been hypothesized to have been driven by factors linked to climate change, but the specific mechanisms are difficult to disentangle due to the wide range of functional traits that covary with body size. In this study, we investigated the impact of regional habitat changes as a potential indirect effect of climate change on body size evolution.LocationEurope and North America.Time periodThe Neogene (~23–2 million years ago).Major taxaFive orders of terrestrial mammals: Artiodactyla, Carnivora, Perissodactyla, Proboscidea and Primates.MethodsWe compared the two continental faunas, which have exceptional fossil records of terrestrial mammals and underwent different processes of habitat transition during the Neogene. Using Bayesian multilevel regression models, we assessed the variation in the temporal dynamics of body size diversity among ecographic groups, defined by their continent of occurrence and dietary preference.ResultsModel comparisons unanimously supported a combined effect of diet and continent on all metrics of body size frequency distributions, rejecting the shared energetic advantage of larger bodies in colder climates as a dominant mechanism of body size evolution. Rather, the diet‐specific dynamics on each continent pinpointed an indirect effect of climate change – change in habitat availability, and thus the resource landscape as a key driver of mammalian evolution.Main conclusionsOur study highlights dietary preference as a mechanistic link between mammalian evolution and habitat transition mediating an indirect climate‐change effect and demonstrates the complexity of climatic influence on biodiversity. Our findings suggest that the intensified habitat modification today likely poses a bigger threat than climate change in itself to living mammals, and perhaps all endotherms.
A global analysis of viviparity in squamates highlights its prevalence in cold climates
Authors: Zimin Anna , Zimin Sean V. , Shine Richard , Avila Luciano , Bauer Aaron , Böhm Monika , Brown Rafe , Barki Goni , de Oliveira Caetano Gabriel Henrique , Castro Herrera Fernando , Chapple David G. , Chirio Laurent , Colli Guarino R. , Doan Tiffany M. , Glaw Frank , Grismer L. Lee , Itescu Yuval , Kraus Fred , LeBreton Matthew , Martins Marcio , Morando Mariana , Murali Gopal , Nagy Zoltán T. , Novosolov Maria , Oliver Paul , Passos Paulo , Pauwels Olivier S. G. , Pincheira‐Donoso Daniel , Ribeiro‐Junior Marco Antonio , Shea Glenn , Tingley Reid , Torres‐Carvajal Omar , Trape Jean‐François , Uetz Peter , Wagner Philipp , Roll Uri , Meiri Shai 
Published: October 2022

AbstractAimViviparity has evolved more times in squamates than in any other vertebrate group; therefore, squamates offer an excellent model system in which to study the patterns, drivers and implications of reproductive mode evolution. Based on current species distributions, we examined three selective forces hypothesized to drive the evolution of squamate viviparity (cold climate, variable climate and hypoxic conditions) and tested whether viviparity is associated with larger body size.LocationGlobal.Time periodPresent day.TaxonSquamata.MethodsWe compiled a dataset of 9061 squamate species, including their distributions, elevation, climate, body mass and reproductive modes. We applied species‐level and assemblage‐level approaches for predicting reproductive mode, both globally and within biogeographical realms. We tested the relationships of temperature, interannual and intra‐annual climatic variation, elevation (as a proxy for hypoxic conditions) and body mass with reproductive mode, using path analyses to account for correlations among the environmental predictors.ResultsViviparity was strongly associated with cold climates at both species and assemblage levels, despite the prevalence of viviparity in some warm climates. Viviparity was not clearly correlated with climatic variability or elevation. The probability of being viviparous exhibited a weak positive correlation with body size.ConclusionsAlthough phylogenetic history is important, potentially explaining the occurrence of viviparous species in regions that are warm at present, current global squamate distribution is characterized by a higher relative abundance of viviparity in cold environments, supporting the prediction of the “cold‐climate” hypothesis. The roles of climatic variation and hypoxia are less important and not straightforward. Elevation probably exerts various selective pressures and influences the prevalence of viviparity primarily through its effect on temperature rather than on oxygen concentration.