bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Single‐Cell Immune Characteristics Contribute to the Diagnosis of Alzheimer's Disease and Dementia With Lewy Bodies
Authors: Qiu Conglong , Zhang Danhua , Wang Majie , Mei Xi , Chen Wei , Yu Haihang , Yin Weiwei , Peng Guoping , Hu Shaohua 
Published: January 2025

ABSTRACTObjectiveAlzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD.MethodsWe utilized time‐of‐flight mass cytometry (CyTOF) with single‐cell resolution to quantitatively analyze peripheral PBMCs, identifying 1228 immune characteristics. Based on the top‐selected immune features, we constructed immunological elastic net (iEN) models.ResultsThese models demonstrated high diagnostic efficacy in distinguishing diseased samples from healthy donors as well as distinguishing AD and DLB cases. The selected features reveal that the primary peripheral immune characteristic of AD is a decrease in total T cells, while DLB is characterized by low expression of I‐kappa‐B‐alpha (IKBα) in the classical monocyte subset.ConclusionsThese findings suggest that peripheral immune characteristics could serve as potential biomarkers, facilitating the diagnosis of neurodegenerative diseases.
A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases
Authors: Cheng Lin , Liu Ziying , Shen Chunxiao , Xiong Yinyi , Shin Sang Yol , Hwang Yong , Yang Seung‐Bum , Chen Zhiying , Zhang Xiaorong 
Published: January 2025

ABSTRACTBackgroundAdenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double‐stranded RNA (dsRNA) molecules into inosine in a process known as A‐to‐I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.ResultsIn recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed. It is worth noting that recent studies have shown ADAR1 has great potential in the treatment of neurodegenerative diseases, but the mechanisms are still unclear. Therefore, it is necessary to elaborate on the role of ADAR1 in CNS diseases.ConclusionsHere, we focus on the effects and mechanisms of ADAR1 on CNS diseases such as Aicardi–AicardiGoutières syndrome, Alzheimer's disease, Parkinson's disease, glioblastoma, epilepsy, amyotrophic lateral sclerosis, and autism. We also evaluate the impact of ADAR1‐based treatment strategies on these diseases, with a particular focus on the development and treatment strategies of new technologies such as microRNAs, nanotechnology, gene editing, and stem cell therapy. We hope to provide new directions and insights for the future development of ADAR1 gene editing technology in brain science and the treatment of CNS diseases.
Reasons for Thinking About Suicide Among Individuals With First‐Episode Psychosis: An Ecological Momentary Assessment Study
Authors: Wastler Heather M. , Manges Margaret , Thompson Elizabeth , Bornheimer Lindsay A. 
Published: January 2025

ABSTRACTAimThis study aimed to examine patient perceived reasons for thinking about suicide among individuals with first‐episode psychosis (FEP).MethodsParticipants completed a baseline assessment followed by 28 days of ecological momentary assessment (EMA). Baseline measures assessed lifetime suicidal ideation and reasons for thinking about suicide. EMA items assessed real‐time suicidal ideation and reasons for thinking about suicide.ResultsThe average number of lifetime reasons for thinking about suicide was 11.47 ± 5.99, with the most commonly endorsed reasons being to get away or escape (81.6%), to stop bad feelings (71.1%), and to relieve feelings of aloneness, emptiness or isolation (57.9%). Only 31.6% of participants endorsed positive symptoms as a lifetime reason for thinking about suicide. EMA results were consistent with lifetime data. Participants typically endorsed multiple reasons (2.15 ± 0.71), with the desire to escape and to stop bad feelings being the most commonly endorsed items. Psychosis was endorsed as a reason for thinking about suicide during 16.3% of instances of ideation during EMA.ConclusionThese findings highlight the multi‐faceted nature of suicide risk in psychosis. Interestingly, positive symptoms were not frequently endorsed as reasons for thinking about suicide from the patient's perspective. Further research is needed to identify when and for whom positive symptoms contribute to suicide risk. Additionally, our results identify important risk factors for further study, namely the desire to escape and/or stop bad feelings.
When patients with Creutzfeldt–Jakob disease are misdiagnosed as having nonconvulsive status epilepticus
Authors: Gélisse Philippe , Crespel Arielle 
Published: January 2025

AbstractContemporary studies report nonconvulsive status epilepticus (NCSE) in Creutzfeldt–Jakob disease (CJD), based on benzodiazepine (BZP)‐responsive epileptiform discharges on the electroencephalogram (EEG), with the following false syllogism: (1) intravenous (IV) administration of BZPs usually suppress ictal activity in NCSE; (2) in CJD, periodic sharp wave complexes (PSWCs) are suppressed by IV BZPs; (3) therefore, these patients have NCSE. This is a simplistic and invalid conclusion, because authors of 20th‐century science reports have clearly shown that IV BZPs, short‐acting barbiturates, and drugs with no antiseizure effects, such as chloral hydrate and IV naloxone, suppress PSWCs, but patients fall asleep with no clinical improvement. In contrast, IV methylphenidate transiently improves both the EEG and clinical states. Unlike NCSE, which is unlikely to be stopped by external stimuli, PSWCs can be transiently stopped by sensory or painful stimulation. Since the end of the 1970s, the effect of spontaneous sleep on the disappearance of PSWCs has been well documented, with a description of a cycling alternating pattern. Phase A features periodic discharges and is associated with increased arousal, whereas phase B exhibits a reduction or suppression of the PSWCs and is associated with a reduction in the arousal level and hypotonia (non‐rapid eye movement sleep). When considering the use of IV BZP administration during EEG as a diagnostic test, the sequence of disappearance of PSWCs at sleep onset and reappearance after each stimulation or sleep apnea episode is compelling evidence against NCSE, as is the observation of a pattern of stimulus‐induced wakefulness with transient improvement of the EEG. The cycling alternating pattern during sleep and reactivity to sensory or painful stimulation disappear with increasing disease severity; however, this occurs in the later stages of the disease, where there is no diagnostic doubt.
Spatiotemporal Synchrony of Climate and Fire Occurrence Across North American Forests (1750–1880)
Authors: Margolis Ellis , Wion Andreas , Abatzoglou John , Daniels Lori , Falk Donald , Guiterman Chris , Johnston James , Kipfmueller Kurt , Lafon Charles , Loehman Rachel , Lonergan Maggie , Naficy Cameron , Parisien Marc‐André , Parks Sean , Portier Jeanne , Stambaugh Michael , Whitman Ellen , Williams A. Park , Yocom Larissa 
Published: January 2025

ABSTRACTAimIncreasing aridity has driven widespread synchronous fire occurrence in recent decades across North America. The lack of historical (pre‐1880) fire records limits our ability to understand long‐term continental fire‐climate dynamics. The goal of this study is to use tree‐ring reconstructions to determine the relationships between spatiotemporal patterns in historical climate and widespread fire occurrence in North American forests, and whether they are stable through time. This information will address a major knowledge gap required to inform projections of future fire.LocationNorth American Forests.Time Period1750–1880 CE.Major Taxa StudiedTrees.MethodsWe applied regionalisation methods to tree‐ring reconstructions of historical summer soil moisture and annual fire occurrence to independently identify broad‐ and fine‐scale climate and fire regions based on common inter‐annual variability. We then tested whether the regions were stable through time and for spatial correspondence between the climate and fire regions. Last, we used correlation analysis to quantify the strength of the fire‐climate associations through time.ResultsWe found that broad‐scale historical patterns in climate and fire have strong spatial coherence. Although climate and fire regions vary over time, large core areas of the regions were stable. The association between climate and fire varied through time and was strongest in western North America, likely due to a combination of factors, such as the magnitude of drought frequency and severity, as well as varying use of fire by human communities.Main ConclusionsThe historical perspective gained through tree‐ring reconstructions of climate and fire patterns and their association suggests that climate‐driven synchrony of fire across large areas of the continent in recent decades is not unprecedented, will likely continue into the future, and may exhibit similar spatial patterns.
How Do Cognitive Proximity and Knowledge Space Position Affect Firms' Innovation? Evidence From Micro and Small Manufacturing Firms in South Africa
Authors: Galetti Jefferson R. B. , Tregenna Fiona 
Published: January 2025

ABSTRACTCognitive proximity between firms, and their position in relation to other firms in a knowledge space, can influence firms' innovation performance. While some studies have begun analysing this in developing countries, there is a dearth of evidence in Africa, and more generally for small and especially micro enterprises as well as for informal enterprises. To fill this gap, we utilise rich new survey data covering 711 micro and small manufacturing firms in Johannesburg, South Africa. We develop and apply a novel multidimensional measure of cognitive proximity, using information on the skills most needed in firms' activities, firms' proximity in an industrial space, and the types of external co‐operation in which they engage. We find that cognitive proximity is positively associated with innovation outcomes. Although this relationship is increasing for most of the sample, there is evidence of an inverted‐U relationship for firms located at higher percentiles, suggesting that too much proximity may lead to a cognitive lock‐in. Firms' knowledge space position is also associated with differential innovation outcomes. In extensions of the model, we find interesting differences in how both cognitive proximity and knowledge space positions are associated with the degree of innovation novelty and also vary according to whether the firm is formal or informal.
Newly Found Rat CD103− Dendritic Cells Represent a Highly Immunogenic Subpopulation of Type‐2 Conventional Dendritic Cells, Corresponding to Known Dendritic Cell Subsets in Mice and Humans
Authors: Sawanobori Yasushi , Ogawa Tadayuki , Ueta Hisashi , Kitazawa Yusuke , Tokuda Nobuko 
Published: January 2025

ABSTRACTDendritic cells (DCs), the primary antigen‐presenting cells, have traditionally been identified by CD103 molecules in rats, whereas mouse and human DCs are identified by CD11c molecules. However, this history does not preclude the existence of CD103− DCs in rats. To explore this possibility, we examined MHCII+ cells in rat spleen and thymus, identifying a novel population of CD103−MHCII+CD45R−CD172a+ cells. These cells are negative for CD103 and B cell marker CD45R, but positive for the type‐2 conventional DC (cDC2) marker CD172a. Transcriptomic analyses revealed that they represent a subpopulation of cDC2. Additionally, gene set enrichment analysis predicted enhanced immunogenic activities for this novel population compared to known rat cDC2s. Mixed leukocyte reaction assays confirmed that the rat CD103− cDC2s induce T cell proliferation more effectively than other DC subsets, suggesting enhanced immunogenic potential. In reaggregated thymic organ culture assays, both the rat CD103− and CD103+ cDC2 subsets suppressed the total number of generated thymocytes and skewed the differentiation toward CD8 single‐positive cells. Comparisons with previously published single‐cell RNA‐sequencing datasets showed that the rat CD103− cDC2 subset shares markers and GO terms of known mouse and human cDC2 subpopulations: cDC2a, cDC2b, inf‐cDC2, and moDC. In contrast, the classic rat CD103+ cDC2 subset expresses only cDC2a markers. These findings provide new insights into DC subpopulations, particularly in species other than mice and humans, where much remains to be uncovered.
Allosteric Changes Underlie the Outside‐In Transmission of Activatory Signals in the TCR
Authors: Alarcon Balbino , Schamel Wolfgang W. 
Published: January 2025

ABSTRACTRather than being contained in a single polypeptide, and unlike receptor tyrosine kinases, the T cell receptor (TCR) divides its signaling functions among its subunits: TCRα/β bind the extracellular ligand, an antigenic peptide–MHC complex (pMHC), and the CD3 subunits (CD3γ, CD3δ, CD3ε, and CD3ζ) transmit this information to the cytoplasm. How information about the quality of pMHC binding outside is transmitted to the cytoplasm remains a matter of debate. In this review, we compile data generated using a wide variety of experimental systems indicating that TCR engagement by an appropriate pMHC triggers allosteric changes transmitted from the ligand‐binding loops in the TCRα and TCRβ subunits to the cytoplasmic tails of the CD3 subunits. We summarize how pMHC and stimulatory antibody binding to TCR ectodomains induces the exposure of a polyproline sequence in the CD3ε cytoplasmic tail for binding to the Nck adapter, the exposure of the RK motif in CD3ε for recruiting the Lck tyrosine kinase, and the induced exposure and phosphorylation of tyrosine residues in all the CD3 cytoplasmic tails. We also review the yet incipient data that help elucidate the structural basis of the Active and Resting conformations of the TCR.
Labour Market Integration of Former Clients of Czech and Polish Rehabilitation Centres: A Case Study
Authors: Zavadzki Matyáš , Vokoun Marek , Neugebauer Jan 
Published: January 2025

ABSTRACTThis study investigates the determinants influencing the labour market integration of former clients of rehabilitation centres, with a focus on past clients of Europe Teen Challenge (ETC). The research aims to examine the impact of economic, social and personal factors on the likelihood of successful labour market integration and the motivation to maintain employment among former ETC rehab clients. The study utilizes a questionnaire encompassing sections on employment, demographics, work experience, societal and personal elements related to motivation theories and substance usage. The results indicate that poor relations with superiors significantly reduce the duration of job retention. Experience exhibits a beneficial impact on labour market involvement, and previous users of hallucinogens demonstrate higher job retention rates. Salary, commute to work, prior alcohol addiction, workplace discrimination due to past substance abuse and limited opportunities for education or certification also play crucial roles in labour market integration. The study emphasizes the importance of supportive work environments and tailored strategies to enhance labour market outcomes for individuals with a history of substance abuse. These findings contribute to a better understanding of the complexities surrounding labour market integration for former rehab clients and offer implications for policy and practice in the field of rehabilitation and workforce integration.
Single‐Step Genome‐Wide Association Study of Factors for Evaluated and Linearly Scored Traits in Swedish Warmblood Horses
Authors: Nazari‐Ghadikolaei Anahit , Fikse W. Freddy , Viklund Åsa Gelinder , Mikko Sofia , Eriksson Susanne 
Published: January 2025

ABSTRACTSwedish Warmblood horses (SWB) are bred for show jumping and/or dressage with young horse test scores as indicator traits. This study aimed to investigate possible candidate genes and regions of importance for evaluated and linearly scored young horse test traits. A single‐step genome‐wide association study (ssGWAS) was done using the BLUPF90 suite of programs for factors scores from factor analysis of traits assessed at young horse tests together with height at withers. The ssGWAS included 20,814 SWB with factors scores for four factors for evaluated traits. A total of 6436 of these horses also had factor scores for 13 factors for linearly scored traits. Genotypes from a 670K SNP array were available for 380 of the horses in this study. All genotyped horses had factor scores for evaluated traits, and 379 also had factors scores for linearly scored traits. Significant SNPs associated with three factors related to size were located on ECA3 within or nearby a well‐known region, including the genes ligand dependent nuclear receptor corepressor like (LCORL), non‐SMC condensin I complex subunit G (NCAPG), DDB1 and CUL4 Associated Factor 16 (DCAF16), and the Family with Sequence Similarity 184 Member B (FAM184B). Significant SNPs were also detected for two factors for evaluated traits representing conformation and jumping, and four factors for linearly scored traits related to body length, neck conformation, walk and trot (hindleg position and activity), respectively. Among nearby genes, calcium/calmodulin‐dependent protein kinase type 1D (CAMK1D) for the factor for linearly scored traits related to neck conformation and GLI Family Zinc Finger 2 (GLI2) for the factor for evaluated jumping traits, were most promising. For these, top associated SNPs were detected within the genes, and the known gene functions seems to be related to the phenotypes. In conclusion, ssGWAS is beneficial to detect plausible candidate genes/regions for desired traits in warmblood horses.
Upshot of Some Bioactive Compounds on Angiogenesis in Retinal Pigment Epithelial Cells
Authors: Sen Serkan , Kasikci Murat 
Published: January 2025

ABSTRACTNowadays, the use of monoclonal antibodies to target angiogenic signalling pathways is common, but, unfortunately, the clinical activity of these agents is limited. Thus, the development of approaches targeting multiple pathways for anti‐angiogenic effect will lead to increase the clinical benefit. For this purpose, oleuropein, hesperidin, piperine, proanthocyanidins and retinoic acid, which have previously been proven to be bioactive components, anti‐angiogenic performances were experimentally tested in retinal pigment epithelial cells. Bioactive ingredients were applied to retinal pigment epithelial cells at varying doses for 48 h, and then IC50 doses were calculated by MTT analysis. VEGFA and VEGFR1 protein levels were measured by ELISA analysis. Using the RT‐PCR technique, the mRNA expression levels of EGF, EGFR, PDGF, PDGFR‐β and HIF1A were analysed. Among all bioactive compounds, the bevacizumab group showed the best anti‐VEGF activity, followed by the proanthocyanidins and piperine groups. Piperine group showed EGF, PDGF and HIF1A expressions; proanthocyanidins, on the other hand, reduced EGFR, PDGF and HIF1A expressions. Retinoic acid showed an angiogenic effect by increasing VEGFA protein levels and EGF and PDGFR‐β expressions. Although hesperidin increased VEGFA protein levels, it decreased EGF, PDGF, PFGFR‐β and HIF1A expression levels. Among the bioactive components stated in previous studies to have anti‐angiogenic properties, only proanthocyanidins and piperin had anti‐VEGF properties. Considering that angiogenesis does not proceed only through VEGF, this study investigated and reported for the first time the effects of relevant bioactive components on angiogenesis through different mechanisms in retinal pigment epithelial cells.
LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome‐Lysosome Fusion in Multiple Myeloma
Authors: Li Yuxiang , Bai Jing , Liu Dan , Hao Jinxia , Yan Ruyu , Guo Hongjuan , Huang Yuzhi , Yu Hongtao , Leng Hao , Zhou Kecheng , Liu Minxia 
Published: January 2025

ABSTRACTMultiple myeloma (MM) is a haematological lymphoid malignancy marked by significant morbidity due to severe complications. Despite advances in targeted therapies, including proteasome inhibitors and the BCL‐2 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome‐associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM. Using comprehensive analyses of publicly available databases and experimental validation, we demonstrated that LAPTM5 is upregulated and enhances autophagy in recurrent multiple myeloma cells, which is a key process for cell homeostasis and drug resistance. Mechanistic studies reveal that LAPTM5 facilitates autophagic flux, linking it to the cellular catabolic processes essential for survival under therapeutic stress. Our findings highlight the underexplored functions of LAPTM5 in modulating autophagy and drug resistance, we demonstrate that LAPTM5 confers resistance to venetoclax by enhancing autophagy, suggesting that targeting LAPTM5 may provide new avenues for overcoming treatment challenges. This research underscores the potential function of LAPTM5 as a therapeutic target in improving outcomes in MM treatment.
Habituation with apparatus and group testing improves assessment of fish preferences
Authors: Varracchio Chiara , Paci Francesco Pio , Bertolucci Cristiano , Bertorelle Giorgio , Lucon‐Xiccato Tyrone 
Published: January 2025

AbstractPreference tests are commonly used to assess fish behavior and cognition in several research fields. This study aimed to investigate how fish perform in a preference test involving extended habituation to the apparatus, which was expected to reduce stress. We contrasted the choice between a sector of the apparatus with natural vegetation, expected to be the preferred stimulus, and a barren sector. Initially, we demonstrated that guppies' preference for the sector with vegetation increased after a 5‐day habituation period (Experiment 1). Subsequent experiments systematically modified the testing paradigm to observe effects on the preference. Experiment 2 introduced a physical separation between sectors to facilitate discrete choices, Experiment 3 tested groups of fish, and Experiment 4 used wild guppies. Only the modification in Experiment 3 impacted preference scores: guppies tested in groups showed a higher preference for the vegetation stimulus and spent less time in the central, no‐choice sector of the testing apparatus. Overall, this study supports the importance of methodological details in preference tests and highlights the benefits of extended habituation and group testing. Researchers should consider these factors when designing experiments to evaluate cognitive abilities or behavioral preferences in fish. Tailoring testing paradigms to specific research goals can improve the reliability and comparability of results, contributing to a deeper understanding of fish behavior and welfare.