bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Dynamics Upon Immune Checkpoint Inhibition
Authors: Lin Zhongyang , Petrenko Ekaterina , Chandra Mitalee , Srinivas Nalini , Ugurel Selma , Becker Jürgen C. , Aran Dvir 
Published: July 2024

AbstractCellular dynamics in the tumor microenvironment upon immune checkpoint inhibition (ICIs) treatment remain largely known. To elucidate these dynamics and associated mechanisms of response and resistance, we analyzed a large-scale single-cell RNA-sequencing dataset of 326 samples from 163 patients across multiple cancer types, with longitudinally site-matched samples. We developed a robust, integration-free deep phenotyping framework, and annotated 1,022,526 cells into 83 granular cell states. Our analysis revealed consistent compositional changes in 19 cell subtypes during ICI treatment, including enhanced adaptive immune responses (e.g., CD8+ IL7R+ central memory T cells, GZMK+ effector memory T cells, germinal center B cells), reduced interferon-responsive immune cells, quiescent CD4+CREM- memory T cells, and angiogenesis tip cells. Co-regulatory network analysis revealed a continuum between two patterns resembling tertiary lymphoid structure maturity. Accumulation of interferon-responsive subtypes was associated with T cell expansion. We further identified a B cell- centric response-specific pattern indicating an enhanced early-phase adaptive immune response favored treatment efficacy, which was subsequently validated through supervised subgroup analysis. Our study presents a comprehensive landscape of TME cellular dynamics during ICI treatment, showcasing the importance of a systems-level understanding in improving patient stratification and advancing personalized cancer immunotherapy.
Different phylogenetic characteristics of Icterids: would they be evolutionary strategies to avoid parasitism by Molothrus spp.?
Authors: Barbosa Vinícius Munhoz , Dinis da Silva Bianca , Xavier da Silva Vinícius , Hasui Érica 
Published: July 2024

ABSTRACTSome birds exhibit the behavior of nest parasitism, which involves laying their eggs in the nests of other species to be incubated and cared for by the adoptive parents. Among all the studies conducted on this subject, there is a gap regarding the nest type of nest parasites and their hosts. Therefore, using species from the Icteridae family, this study aimed to identify if there is a tendency for more closed nests to be less parasitized than open nests and if there is a phylogenetic relationship between them. In this context, we expected open nests to be an ancestral condition to closed nests, serving as an evolutionary feature to avoid nest parasitism. We also analyzed other characteristics such as the number of eggs, nest type and parental care. As a result, we observed that open nests were more common, while closed nests were predominant in a specific clade and some isolated species. The analyses indicated a phylogenetic signal clustered within the Icteridae family concerning nest types, which may imply a selective pressure. However, we cannot assert that it is a direct response to nest parasitism, as closed nests are also parasitized, specifically byM. oryzivorus. Parental care and diet type also showed phylogenetic signal, indicating that these changes were not random. However, we did not observe associations in host selection by the parasites based on these characteristics. Furthermore, we found a progression in the number of species parasitized byMolothrusspp. along the phylogenetic lineage. We also observed a similarity in host choice betweenM. aterandM. aeneus, indicating evolutionary convergence, as they are not sister groups.
Does Emergency Department point-of-care ultrasound in the evaluation of possible small bowel obstruction lead to meaningful improvements in patient-centric milestones?
Authors: Chen Yi-Ru , Sierra Melva Morales , Nasir Rida , Mahabir Naya , Iyeke Lisa , Jordan Lindsay , Shah Trupti , Burke Kevin , Friedman Matthew , Dexeus Daniel , Mihailos Athena , Richman Mark , Guttman Joshua 
Published: July 2024

AbstractIntroductionPoint-of-care ultrasound (POCUS) has 90-95% sensitivity and specificity for small bowel obstruction (SBO) compared with computed tomography (CT). ED clinicians might reasonably use a positive POCUS to progress to patient-centric milestones (eg, nasogastric tube (NGT) placement, general surgery consult, and disposition). Awaiting CT performance and interpretation before moving to such milestones may delay care. Literature is limited concerning the effects of POCUS vs. CT alone on such patient-centric milestones for patients with SBO. This study compared time to patient-centric milestones (NGT, general surgery consult, and disposition) among ED patients suspected of having SBO who underwent POCUS vs. CT only in their SBO diagnostic process.MethodsData from 11,801 SBO patients seen among 14 EDs between 2017-2022 was queried. Patients were categorized into two groups according to diagnostic method (POCUS + CT vs. CT alone). Patients were included if they had a POCUS positive for SBO and an ED diagnosis of SBO; they were excluded from analysis of any specific/particular milestone (NGT, general surgery consult, or disposition) if they had that milestone prior to POCUS. Median time from ED arrival to each milestone was calculated for both groups (POCUS + CT vs. CT alone).ResultsCompared to CT-only patients, patients with POCUS plus CT had a non-statistically-significant longer wait time from ED arrival to NGT (414 vs. 390, p=0.7) and from ED arrival to general surgery consult (487.5 vs. 442 minutes, p = 0.07). They had statistically-significantly longer time to from ED arrival to disposition (475.5 vs. 377 minutes, p=0.009). Among cases in which POCUS was performed, 80% of the time the NGT was placed, 77% of the time the general surgery consult was performed, and 100% of time disposition was made only after CT result rather than after POCUS but before CT result.ConclusionUse of POCUS was not associated with earlier achievement of patient-centric milestones (NGT or general surgery consult) and was associated with longer time to disposition. This is most-likely because, despite POCUS suggesting SBO, clinicians waited for CT results prior to placing the NGT, consulting general surgery, and entering the disposition. Such results suggest that, despite POCUS’s high sensitivity and specificity, ED and/or general surgery clinicians rely on CT scan results to confirm SBO, delaying patient-centric milestones.
Plasmodium falciparum multidrug resistance 1gene polymorphisms associated with outcomes after antimalarial treatment
Authors: Laird Veronika R. , Plucinski Mateusz M. , Venkatesan Meera , Rondini Kelsey A. , Randrianarivelojosia Milijaona , Andriamananjara Mauricette N. , Moonga Hawela , Ishengoma Deus S. , Chidimatembue Arlindo , Dimbu Pedro Rafael , Adeothy Adicatou-Laï , Beavogui Abdoul Habib , Kariuki Simon , Nsobya Sam L. , Uwimana Aline , Kahunu Gauthier Mesia , Assefa Ashenafi , Koita Ousmane A. , Lucchi Naomi W. , Souza Samaly S. Svigel , Zhou Zhiyong , Moriarty Leah F. , Halsey Eric S. 
Published: July 2024

Article summaryThis study suggests that: 1) patients given AL infected with parasites carrying N86 were statistically more likely to experience a recurrent infection; 2) patients given ASAQ infected with parasites carrying 86Y were statistically more likely to experience a recurrent infection.BackgroundPlasmodium falciparum multidrug resistance transporter 1(Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapies (ACTs), particularly those containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies ofPfmdr1single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ.MethodsTo determine whether infection with parasites carrying specificPfmdr1SNPs leads to increased risk of recurrent parasitemia (recrudescent or new infection), data from 4,129 samples from 16 therapeutic efficacy studies from 13 African countries between 2013–2019 were analyzed.ResultsPatients treated with AL and infected with parasites carryingPfmdr1N86 were at greater risk of treatment failure than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carriedPfmdr186Y were more likely to experience a recurrent infection.ConclusionsOur results support prior studies that suggested: 1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; 2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience recurrent infection. These findings suggest that ACT andPfmdr1genotype may influence outcome afterP. falciparuminfection.
Trajectories of physical activity after ischemic stroke: exploring prediction of change
Authors: Damsbo Andreas Gammelgaard , Blauenfeldt Rolf Ankerlund , Andersen Grethe , Johnsen Søren P. , Mortensen Janne Kaergaard 
Published: July 2024

AbstractBackground and aimsPhysical activity (PA) is associated with lower risk of stroke and better functional outcome. However, sedentary behavior after stroke is prevalent. We aimed to identify predictors for PA after first-time ischemic stroke and to develop prediction models to assess change in PA after stroke.MethodsWe used the Physical Activity Scale for the Elderly (PASE) to quantify PA prior to stroke and six months after stroke. Demographic and clinical data were enriched with registry data on socioeconomic status (SES). Associations with post-stroke PA were analyzed using linear regression. Elastic net regression models were used to predict decrease from higher PASE quartile to the lowest and increase from lowest to higher.ResultsA total of 523 patients, from The Efficacy of Citalopram Treatment in Acute Ischemic Stroke (TALOS) trial, had complete PASE data. Median [IQR] age was 69 years [59, 77], 181 (35%) were female and median [IQR] National Institute of Health Stroke Scale score was 3 [2, 5]. Overall, median PASE score did not change, but 20 % of patients decreased to the lowest PASE quartile whereas 48% from the lowest PASE quartile increased to a higher level. The prediction model performance, as represented by the area under receiver operating curve, was 0.679 for predicting a decrease and 0.619 for predicting an increase in PA. SES was the most consistent predictor for both decrease and for a lack of increase in PA.ConclusionsAlmost 1/2 of the least active patients increased their PA after stroke whereas 1/5 decreased to the least active level with socioeconomic factors being the most consistent predictors for change. Despite including comprehensive data, the PA prediction models had a modest predictive performance. Efforts to optimize PA should include all stroke survivors to improve PA for previously inactive patients and prevent PA decrease.
Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies
Authors: Wei Yuandan , Zhen Jianxin , Hu Liang , Gu Yuqin , Liu Yanhong , Guo Xinxin , Yang Zijing , Zheng Hao , Cheng Shiyao , Wei Fengxiang , Xiong Likuan , Liu Siyang 
Published: July 2024

AbstractMaintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide novel insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.
A transphyletic study of metazoan β-catenin protein complexes
Authors: Mbogo Ivan , Kawano Chihiro , Nakamura Ryotaro , Tsuchiya Yuko , Villar-Briones Alejandro , Hirao Yoshitoshi , Yasuoka Yuuri , Hayakawa Eisuke , Tomii Kentaro , Watanabe Hiroshi 
Published: July 2024

Abstractβ-catenin is essential for various biological processes, such as body axis determination and cell differentiation, during embryonic development in metazoans. β-catenin functions are thought to be exerted through complexes formed with various types of proteins. Although β-catenin complex proteins have been identified in several bilaterians, little is known about the structural and functional properties of β-catenin complexes in early metazoan evolution. In this study, we performed a comparative analysis of β-catenin sequences in nonbilaterian lineages that diverged early in metazoan evolution. We also carried out transphyletic function experiments with β-catenin from nonbilaterian metazoans using developingXenopusembryos, which included secondary axis induction in embryos and proteomic analysis of β-catenin protein complexes. Comparative functional analysis of nonbilaterian β-catenins demonstrated sequence characteristics important for β-catenin functions, and the deep origin and evolutionary conservation of the cadherin-catenin complex. Proteins co-immunoprecipitated with β-catenin included several proteins conserved among metazoans. These data provide new insights into the conserved repertoire of β-catenin complexes.
Unravelling the progression of the zebrafish primary body axis with reconstructed spatiotemporal transcriptomics
Authors: Dong Yang , Cheng Tao , Liu Xiang , Fu Xin-Xin , Hu Yang , Yang Xian-Fa , Yang Ling-En , Li Hao-Ran , Bian Zhi-Wen , Jing Naihe , Liao Jie , Fan Xiaohui , Xu Peng-Fei 
Published: July 2024

AbstractElucidating the spatiotemporal dynamics of gene expression is essential for understanding complex physiological and pathological processes. Traditional technologies likein situhybridization (ISH) and immunostaining have been restricted to analyzing expression patterns of a limited number of genes. Spatial transcriptomics (ST) has emerged as a robust alternative, enabling the investigation of spatial patterns of thousands of genes simultaneously. However, current ST methods are hindered by low read depths and limited gene detection capabilities. Here, we introduce Palette, a pipeline that infers detailed spatial gene expression patterns from bulk RNA-seq data, utilizing existing ST data as only reference. This method identifies more precise expression patterns by smoothing, imputing and adjusting gene expressions. We applied Palette to construct theDaniorerioSpatioTemporalExpressionProfiles (DreSTEP)by integrating 53-slice serial bulk RNA-seq data from three developmental stages with existing ST references and 3D zebrafish embryo images.DreSTEP provides a comprehensive cartographic resource for examining gene expression and spatial cell-cell interactions within zebrafish embryos. Utilizing machine learning-based screening, we identified key morphogens and transcription factors (TFs) essential for anteroposterior (AP) axis development and characterized their dynamic distribution throughout embryogenesis. In addition, among these TFs, Hox family genes were found to be pivotal in AP axis refinement. Their expression was closely correlated with cellular AP identities, andhoxbgenes may act as central regulators in this process.
The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4
Authors: Feringa Femke M. , Koppes-den Hertog Sascha J. , Wang Lian , Derks Rico J.E. , Kruijff Iris , Erlebach Lena , Heijneman Jorin , Miramontes Ricardo , Pömpner Nadine , Blomberg Niek , Olivier-Jimenez Damien , Johansen Lill Eva , Cammack Alexander J. , Giblin Ashling , Toomey Christina E , Rose Indigo V.L. , Yuan Hebao , Ward Michael , Isaacs Adrian M. , Kampmann Martin , Kronenberg-Versteeg Deborah , Lashley Tammaryn , Thompson Leslie M. , Ori Alessandro , Mohammed Yassene , Giera Martin , van der Kant Rik 
Published: July 2024

AbstractLipid changes in the brain have been implicated in many neurodegenerative diseases including Alzheimer’s Disease (AD), Parkinson’s disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named the Neurolipid Atlas, that we have pre-populated with novel human, mouse and isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. We show that iPSC-derived neurons, microglia and astrocytes display distinct lipid profiles that recapitulatein vivolipotypes. Leveraging multiple datasets, we show that the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation in human astrocytes recapitulating CE accumulation measured in the human AD brain. Multi-omic interrogation of iPSC-derived astrocytes revealed that cholesterol plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex (MHC) class I antigen presentation. We show that through enhanced cholesterol esterification ApoE4 suppresses immune activation of astrocytes. Our novel data commons, available at neurolipidatlas.com, provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.
A novel behavioral paradigm using mice to study predictive postural control
Authors: Doi Yurika , Asaka Meiko , Born Richard T. , Yanagihara Dai , Uchida Naoshige 
Published: July 2024

AbstractPostural control circuitry performs the essential function of maintaining balance and body position in response to perturbations that are either self-generated (e.g. reaching to pick up an object) or externally delivered (e.g. being pushed by another person). Human studies have shown that anticipation of predictable postural disturbances can modulate such responses. This indicates that postural control could involve higher-level neural structures associated with predictive functions, rather than being purely reactive. However, the underlying neural circuitry remains largely unknown. To enable studies of predictive postural control circuits, we developed a novel experimental paradigm formice. In this paradigm, modeled after human studies, a dynamic platform generated reproducible translational perturbations. While mice stood bipedally atop a perch to receive water rewards, they experienced backward translations that were either unpredictable or preceded by an auditory cue. To validate the paradigm, we investigated the effect of the auditory cue on postural responses to perturbations across multiple days in three mice. These preliminary results serve to validate a new postural control experimental paradigm, opening the door to the types of neural recordings and circuit manipulations that are currently possible in mice.Significance StatementThe ability to anticipate disturbances and adjust one’s posture accordingly—known as “predictive postural control”—is crucial for preventing falls and for advancing robotics. While human balance is often assessed via floor perturbations, rodent studies typically use rotarod tests. Here, we developed a postural perturbation task for freely moving mice, modeled after those used in human studies. Using a dynamic platform, we delivered reproducible perturbations with or without preceding auditory cues and quantified how the auditory cue affects postural responses to perturbations. Our work provides validation of a new postural control experimental paradigm, which opens the door to the types of neural population recordings and circuit manipulation that are currently possible in mice.
Early ctDNA kinetics as a dynamic biomarker of cancer treatment response
Authors: Li Aaron , Lou Emil , Leder Kevin , Foo Jasmine 
Published: July 2024

AbstractCirculating tumor DNA assays are promising tools for the prediction of cancer treatment response. Here, we build a framework for the design of ctDNA biomarkers of therapy response that incorporate variations in ctDNA dynamics driven by specific treatment mechanisms. We develop mathematical models of ctDNA kinetics driven by tumor response to several therapy classes, and utilize them to simulate randomized virtual patient cohorts to test candidate biomarkers. Using this approach, we propose specific biomarkers, based on ctDNA longitudinal features, for targeted therapy, chemotherapy and radiation therapy. We evaluate and demonstrate the efficacy of these biomarkers in predicting treatment response within a randomized virtual patient cohort dataset. These biomarkers are based on novel proposals for ctDNA sampling protocols, consisting of frequent sampling within a compact time window surrounding therapy initiation – which we hypothesize to hold valuable prognostic information on longer-term treatment response. This study highlights a need for tailoring ctDNA sampling protocols and interpretation methodology to specific biological mechanisms of therapy response, and it provides a novel modeling and simulation framework for doing so. In addition, it highlights the potential of ctDNA assays for making early, rapid predictions of treatment response within the first days or weeks of treatment, and generates hypotheses for further clinical testing.
Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline
Authors: Gao Fangyuan , Tom Emily , Rydz Cezary , Cho William , Kolesnikov Alexander V. , Sha Yutong , Papadam Anastasios , Jafari Samantha , Joseph Andrew , Ahanchi Ava , Saraei Nika Balalaei Someh , Lyon David , Foik Andrzej , Nie Qing , Grassmann Felix , Kefalov Vladimir J. , Skowronska-Krawczyk Dorota 
Published: July 2024

ABSTRACTThe retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD).ELOVL2(Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently the best predictor of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE, HTRA1 and complement proteins in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of several variants in the humanELOVL2locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.