bluuebunny/crossref_metadata_2025_split huggingface dataset:
Freshwater megafauna shape ecosystems and facilitate restoration
Authors: He Fengzhi , Svenning Jens‐Christian , Chen Xing , Tockner Klement , Kuemmerle Tobias , le Roux Elizabeth , Moleón Marcos , Gessner Jörn , Jähnig Sonja C. 
Published: February 2024

ABSTRACTFreshwater megafauna, such as sturgeons, giant catfishes, river dolphins, hippopotami, crocodylians, large turtles, and giant salamanders, have experienced severe population declines and range contractions worldwide. Although there is an increasing number of studies investigating the causes of megafauna losses in fresh waters, little attention has been paid to synthesising the impacts of megafauna on the abiotic environment and other organisms in freshwater ecosystems, and hence the consequences of losing these species. This limited understanding may impede the development of policies and actions for their conservation and restoration. In this review, we synthesise how megafauna shape ecological processes in freshwater ecosystems and discuss their potential for enhancing ecosystem restoration. Through activities such as movement, burrowing, and dam and nest building, megafauna have a profound influence on the extent of water bodies, flow dynamics, and the physical structure of shorelines and substrata, increasing habitat heterogeneity. They enhance nutrient cycling within fresh waters, and cross‐ecosystem flows of material, through foraging and reproduction activities. Freshwater megafauna are highly connected to other freshwater organisms via direct consumption of species at different trophic levels, indirect trophic cascades, and through their influence on habitat structure. The literature documenting the ecological impacts of freshwater megafauna is not evenly distributed among species, regions, and types of ecological impacts, with a lack of quantitative evidence for large fish, crocodylians, and turtles in the Global South and their impacts on nutrient flows and food‐web structure. In addition, population decline, range contraction, and the loss of large individuals have reduced the extent and magnitude of megafaunal impacts in freshwater ecosystems, rendering a posteriori evaluation more difficult. We propose that reinstating freshwater megafauna populations holds the potential for restoring key ecological processes such as disturbances, trophic cascades, and species dispersal, which will, in turn, promote overall biodiversity and enhance nature's contributions to people. Challenges for restoration actions include the shifting baseline syndrome, potential human–megafauna competition for habitats and resources, damage to property, and risk to human life. The current lack of historical baselines for natural distributions and population sizes of freshwater megafauna, their life history, trophic interactions with other freshwater species, and interactions with humans necessitates further investigation. Addressing these knowledge gaps will improve our understanding of the ecological roles of freshwater megafauna and support their full potential for facilitating the development of effective conservation and restoration strategies to achieve the coexistence of humans and megafauna.
Demographic and evolutionary consequences of hunting of wild birds
Authors: Grzegorczyk Emilienne , Caizergues Alain , Eraud Cyril , Francesiaz Charlotte , Le Rest Kévin , Guillemain Matthieu 
Published: February 2024

ABSTRACTHunting has a long tradition in human evolutionary history and remains a common leisure activity or an important source of food. Herein, we first briefly review the literature on the demographic consequences of hunting and associated analytical methods. We then address the question of potential selective hunting and its possible genetic/evolutionary consequences. Birds have historically been popular models for demographic studies, and the huge amount of census and ringing data accumulated over the last century has paved the way for research about the demographic effects of harvesting. By contrast, the literature on the evolutionary consequences of harvesting is dominated by studies on mammals (especially ungulates) and fish. In these taxa, individuals selected for harvest often have particular traits such as large body size or extravagant secondary sexual characters (e.g. antlers, horns, etc.). Our review shows that targeting individuals according to such genetically heritable traits can exert strong selective pressures and alter the evolutionary trajectory of populations for these or correlated traits. Studies focusing on the evolutionary consequences of hunting in birds are extremely rare, likely because birds within populations appear much more similar, and do not display individual differences to the same extent as many mammals and fishes. Nevertheless, even without conscious choice by hunters, there remains the potential for selection through hunting in birds, for example by genetically inherited traits such as personality or pace‐of‐life. We emphasise that because so many bird species experience high hunting pressure, the possible selective effect of harvest in birds and its evolutionary consequences deserves far more attention, and that hunting may be one major driver of bird evolutionary trajectories that should be carefully considered in wildlife management schemes.
Scoring system for diagnosis and pretreatment risk assessment of neuroblastoma using urinary biomarker combinations
Authors: Amano Hizuru , Uchida Hiroo , Harada Kazuharu , Narita Atsushi , Fumino Shigehisa , Yamada Yuji , Kumano Shun , Abe Mayumi , Ishigaki Takashi , Sakairi Minoru , Shirota Chiyoe , Tainaka Takahisa , Sumida Wataru , Yokota Kazuki , Makita Satoshi , Karakawa Shuhei , Mitani Yuichi , Matsumoto Shojiro , Tomioka Yutaka , Muramatsu Hideki , Nishio Nobuhiro , Osawa Tsuyoshi , Taguri Masataka , Koh Katsuyoshi , Tajiri Tatsuro , Kato Motohiro , Matsumoto Kimikazu , Takahashi Yoshiyuki , Hinoki Akinari 
Published: February 2024

AbstractThe urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3‐methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography–mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2‐penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high‐risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.
Harnessing the potential of reverse‐phase protein array technology: Advancing precision oncology strategies
Authors: Masuda Mari , Nakagawa Riko , Kondo Tadashi 
Published: February 2024

AbstractThe last few decades have seen remarkable strides in the field of cancer therapy. Precision oncology coupled with comprehensive genomic profiling has become routine clinical practice for solid tumors, the advent of immune checkpoint inhibitors has transformed the landscape of oncology treatment, and the number of cancer drug approvals has continued to increase. Nevertheless, the application of genomics‐driven precision oncology has thus far benefited only 10%–20% of cancer patients, leaving the majority without matched treatment options. This limitation underscores the need to explore alternative avenues with regard to selecting patients for targeted therapies. In contrast with genomics‐based approaches, proteomics‐based strategies offer a more precise understanding of the intricate biological processes driving cancer pathogenesis. This perspective underscores the importance of integrating complementary proteomic analyses into the next phase of precision oncology to establish robust biomarker‐drug associations and surmount challenges related to drug resistance. One promising technology in this regard is the reverse‐phase protein array (RPPA), which excels in quantitatively detecting protein modifications, even with limited amounts of sample. Its cost–effectiveness and rapid turnaround time further bolster its appeal for application in clinical settings. Here, we review the current status of genomics‐driven precision oncology, as well as its limitations, with an emphasis on drug resistance. Subsequently, we explore the application of RPPA technology as a catalyst for advancing precision oncology. Through illustrative examples drawn from clinical trials, we demonstrate its utility for unraveling the molecular mechanisms underlying drug responses and resistance.
Machine learning identifies fatigue as a key symptom of fibromyalgia reflected in tyrosine, purine, pyrimidine, and glutaminergic metabolism
Authors: Zetterman Teemu , Nieminen Anni I. , Markkula Ritva , Kalso Eija , Lötsch Jörn 
Published: February 2024

AbstractFibromyalgia patients vary in clinical phenotype and treatment can be challenging. The pathophysiology of fibromyalgia is incompletely understood but appears to involve metabolic changes at rest or in response to stress. We enrolled 54 fibromyalgia patients and 31 healthy controls to this prospective study. Symptoms were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and blood samples were collected for metabolomics analysis at baseline and after an oral glucose tolerance test and a cardiopulmonary exercise test. We identified key symptoms of fibromyalgia and related them to changes in metabolic pathways with supervised and unsupervised machine learning methods. Algorithms trained with the FIQ information assigned the fibromyalgia diagnosis in new data with balanced accuracy of 88% while fatigue alone already provided the diagnosis with 86% accuracy. Supervised analyses reduced the metabolomic information from 77 to 13 key markers. With these metabolites, fibromyalgia could be identified in new cases with 79% accuracy. In addition, 5‐hydroxyindole‐3‐acetic acid and glutamine levels correlated with the severity of fatigue. Patients differed from controls at baseline in tyrosine and purine pathways, and in the pyrimidine pathway after the stress challenges. Several key markers are involved in glutaminergic neurotransmission. This data‐driven analysis highlights fatigue as a key symptom of fibromyalgia. Fibromyalgia is associated with metabolic changes which also reflect the degree of fatigue. Responses to metabolic and physical stresses result in a metabolic pattern that allows discrimination of fibromyalgia patients from controls and narrows the focus on key pathophysiological processes in fibromyalgia as treatment targets.
Hume and the fiction of the self
Authors: Parrott Matthew 
Published: February 2024

AbstractIn the Treatise, Hume attempts to explain why we all believe that the self is a single unified entity that persists over time, a belief which Hume calls a fiction. In this paper, I demonstrate how Hume uses a type of functional explanation to account for this belief. After explicating Hume's view, I shall argue that it faces two related problems, which constitute a sort of dilemma. In the final section, I show how one of the horns of this dilemma is plausibly what troubles Hume in the famous Appendix passage where he retracts his positive account of personal identity.
Fuzzy logic‐based trusted routing protocol using vehicular cloud networks for smart cities
Authors: Kait Ramesh , Kaur Sarbjit , Sharma Purushottam , Ankita Chhikara , Kumar Tajinder , Cheng Xiaochun 
Published: February 2024

AbstractDue to the characteristics of vehicular ad hoc networks, the increased mobility of nodes and the inconsistency of wireless communication connections pose significant challenges for routing. As a result, researchers find it to be a fascinating topic to study. Furthermore, since these networks are vulnerable to various assaults, providing an authentication method between the source and destination nodes is crucial. How to route in such networks more efficiently, taking into account node mobility characteristics and accompanying massive historical data, is still a matter of discussion. Fuzzy logic‐based Trusted Routing Protocol for vehicular cloud networks (FTRP) is proposed in this study that determines the secure path for data dissemination. Fuzzy Logic determines the node candidacy value and selects or rejects a path accordingly. The cloud assigns a confidence score to each vehicle based on the data it collects from nodes after each interaction. Our study identifies the secure path on the basis of trust along with factors such as speed, closeness to other nodes, signal strength and distance from the neighbouring nodes. Simulations of the novel protocol demonstrate that it can keep the packet delivery ratio high with little overhead and low delay. FTRP has significant implications for deploying Vehicular Cloud Networks using electric vehicle technologies in smart cities. The routing data is collected with the help of Internet of Technology (IOT) sensors. The information is transmitted between vehicles using IOT gateways.
Children's behavioural and emotional reactions towards living with congenital heart disease in Saudi Arabia: A grounded theory study
Authors: Dahlawi Nada , Milnes Linda , Swallow Veronica 
Published: February 2024

AbstractBackgroundA high incidence of children with congenital heart disease (CHD) was found in Saudi Arabia (SA). International literature reports that children with CHD exhibit behavioural and emotional issues due to experiencing hospitalisation and clinical treatments combined with a dearth of qualitative understanding of the experiences of younger children with CHD. Therefore, the aim was to explore the behaviour and emotions of 4–10‐year‐olds with CHD in SA through children's accounts of their own experiences and parental proxy reports of children's behaviour and emotions.MethodsCharmaz's constructivist grounded theory (GT) approach was used. Twenty single semi‐structured interviews of 10 child/parent dyads were undertaken at a hospital clinic in SA. Children's interviews were combined with an arts‐based approach using drawings, pictures and faces of emotions (emojis). Constant comparison analysis was undertaken. Consolidated Criteria for Reporting Qualitative Research guidelines was followed in reporting this study.FindingsA substantive GT: children's behavioural and emotional reactions towards stressors related to living with CHD was developed and provides new insights into children's and parents' perceptions of the children's behavioural and emotional reactions to living with CHD in SA. The theory proposes that children's reactions to living with CHD relate to medical treatment stressors, sociocultural stressors and physical change stressors. Several further factors influenced children's responses to these stressors.ConclusionChildren and parents in SA contributed to a new understanding of the relationship between CHD and children's behavioural and emotional reactions. In addition, findings support the need for early assessment of behaviour and emotions among children with CHD and the application of preventative and supportive measures for the children and their families in SA.Patient or Public ContributionBefore the research commenced, the developmental appropriateness of the proposed arts‐based data collection tools was tested with three healthy children aged 6–9 years old; the tools were then revised accordingly before the interviews were undertaken.
Whole‐exome sequencing has revealed novel genetic characteristics in intracranial germ cell tumours in the Chinese
Authors: Huang Xiang , Huang Jianhan , Zhou Xiaoyu , Zhang Chao , Ding Xinghua , Wong Peter Jih Cheng , Wang Yang , Zhang Rong 
Published: February 2024

AimsIntracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown.Methods and ResultsIn this study, 47 patients were enrolled and their tumour specimens were analysed by whole‐exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression‐free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance.ConclusionThis study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.
Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations
Authors: Collins Katrina , Galea Laurence A , Foroughi Forough , Siegmund Stephanie E , Anderson William J , Appu Sree , Idrees Muhammad T , Ulbright Thomas M , Acosta Andres M 
Published: February 2024

BackgroundCarcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored.DesignIn this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes).ResultsThe tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian‐type clear cell phenotype, two mucinous tumours resembling low‐grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post‐radiation mucinous adenocarcinoma had genomic findings consistent with bi‐allelic inactivation of TP53, as well as multiple copy‐number changes with regional and chromosomal arm‐level copy‐number losses. The Müllerian‐type clear cell carcinoma exhibited a complex copy‐number profile with numerous regional and arm‐level copy‐number changes, as well as focal amplification events, including copy‐number gain of 8q and amplification of a region within 20q13. Both low‐grade mucinous tumours resembling LAMN harboured hot‐spot gain‐of‐function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma.ConclusionOur results suggest that primary low‐grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain‐of‐function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.
STING inhibition alleviates bone resorption in apical periodontitis
Authors: Mao Han‐Qing , Zhou Lu , Li Jia‐Qi , Wen Yuan‐Hao , Chen Zhi , Zhang Lu 
Published: February 2024

AbstractAimThe goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis.MethodologyWe established an apical periodontitis mouse model in Sting−/− and WT mice in vivo. The progression of apical periodontitis was analysed by micro‐CT analysis and H&E staining. The expression level and localization of STING in F4/80+ cells were identified by IHC and immunofluorescence staining. RANKL in periapical tissues was tested by IHC staining. TRAP staining was used to detect osteoclasts. To clarify the effect of STING inhibitor C‐176 as an immunotherapeutic drug, mice with apical periodontitis were treated with C‐176 and the bone loss was identified by H&E, TRAP, RANKL staining and micro‐CT. Bone marrow‐derived macrophages (BMMs) were isolated from Sting−/− and WT mice and induced to osteoclasts in a lipopolysaccharide (LPS)‐induced inflammatory environment in vitro. Moreover, WT BMMs were treated with C‐176 to determine the effect on osteoclast differentiation by TRAP staining. The expression levels of osteoclast‐related genes were tested using qRT‐PCR.ResultsCompared to WT mice, the bone resorption and inflammatory cell infiltration were reduced in exposed Sting−/− mice. In the exposed WT group, STING was activated mainly in F4/80+ macrophages. Histological staining revealed the less osteoclasts and lower expression of osteoclast‐related factor RANKL in Sting−/− mice. The treatment of the STING inhibitor C‐176 in an apical periodontitis mice model alleviated inflammation progression and bone loss, similar to the effect observed in Sting−/− mice. Expression of RANKL and osteoclast number in periapical tissues were also decreased after C‐176 administration. In vitro, TRAP staining showed fewer positive cells and qRT‐PCR reflected decreased expression of osteoclastic marker, Src and Acp5 were detected during osteoclastic differentiation in Sting−/− and C‐176 treated BMMs.ConclusionsSTING was activated and was proven to be a positive factor in bone loss and osteoclastogenesis in apical periodontitis. The STING inhibitor C‐176 administration could alleviate the bone loss via modulating local immune response, which provided immunotherapy to the treatment of apical periodontitis.