tbuckley/cabot-search huggingface dataset:
Nuclear translocation matters: Role of FABP7 in driving glioblastoma stemness and invasion: Reply to Mu et al.
Authors: Rong-Zong Liu, Won-Shik Choi, Roseline Godbout
Journal: Neuro-Oncology (2024)

Journal Article Nuclear translocation matters: Role of FABP7 in driving glioblastoma stemness and invasion: Reply to Mu et al. Get access Rong-Zong Liu, Rong-Zong Liu Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Won-Shik Choi, Won-Shik Choi Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Roseline Godbout Roseline Godbout Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada Corresponding Author: Roseline Godbout, PhD, Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada (rgodbout@ualberta.ca). https://orcid.org/0000-0002-4779-9265 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 26, Issue 3, March 2024, Pages 590–591, https://doi.org/10.1093/neuonc/noad239 Published: 19 January 2024 Article history Corrected and typeset: 19 January 2024 Published: 19 January 2024
Cardiometabolic disease: linking pathogenic mechanisms to therapeutic opportunities
Authors: Triantafyllos Chavakis, Francesco Cosentino, Ann Marie Schmidt
Journal: Cardiovascular Research (2023)

Cardiometabolic disease is a complex entity in which perturbations of homeostasis driven by fundamental disturbances in body mass and composition mediate dysregulation of insulin signaling, blood pressure, lipid homeostasis, energy expenditure, inflammation, immunity and the host interface with gut microbiota.Multiple cell types and tissues, such as the brain, brown and white adipose tissues, liver, skeletal muscle, intestine, bone marrow and immune cell niches, vasculature and the heart conspire to impart pathobiological consequences through cell-intrinsic and cell-cell communication mechanisms.This Compendium is an assembly of nine
Prognostic value of DNA methylation subclassification, aneuploidy, and <i>CDKN2A/B</i> homozygous deletion in predicting clinical outcome of IDH mutant astrocytomas
Authors: Kristyn Galbraith, Mekka Garcia, Siyu Wei, Anna Chen, Chanel Schroff, Jonathan Serrano, Donato Pacione, Dimitris G Placantonakis, Christopher M William, Arline Faustin, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, Mitsuaki Shirahata, David Reuss, Quynh T Tran, Zahangir Alom, Andreas von Deimling, Brent A Orr, Erik P Sulman, John G Golfinos, Daniel A Orringer, Rajan Jain, Evan Lieberman, Yang Feng, Matija Snuderl
Journal: Neuro-Oncology (2024)

Abstract Background Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. Methods We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts. Results There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534). Conclusions The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.
Recent Advances in Gut‐ and Gut–Organ‐Axis‐on‐a‐Chip Models
Authors: Raehyun Kim, Jong Hwan Sung
Journal: Advanced Healthcare Materials (2024)

The human gut extracts nutrients from the diet while forming the largest barrier against the outer environment. In addition, the gut actively maintains homeostasis through intricate interactions with the gut microbes, the immune system, the enteric nervous system, and other organs. These interactions influence digestive health and, furthermore, play crucial roles in systemic health and disease. Given its primary role in absorbing and metabolizing orally administered drugs, there is significant interest in the development of preclinical in vitro model systems that can accurately emulate the intestine in vivo. A gut-on-a-chip system holds great potential as a testing and screening platform because of its ability to emulate the physiological aspects of in vivo tissues and expandability to incorporate and combine with other organs. This review aims to identify the key physiological features of the human gut that need to be incorporated to build more accurate preclinical models and highlights the recent progress in gut-on-a-chip systems and competing technologies toward building more physiologically relevant preclinical model systems. Furthermore, various efforts to construct multi-organ systems with the gut, called gut-organ-axis-on-a-chip models, are discussed. In vitro gut models with physiological relevance can provide valuable platforms for bridging the gap between preclinical and clinical studies.
Genetically Encoded Lizard Color Divergence for Camouflage and Thermoregulation
Authors: Bao-Jun Sun, Wei-Ming Li, Peng Lv, Guan-Nan Wen, Dan-Yang Wu, Shi-Ang Tao, Ming-Ling Liao, Chang-Qing Yu, Zhong-Wen Jiang, Yang Wang, Hong-Xin Xie, Xi-Feng Wang, Zhi-Qiang Chen, Feng Liu, Wei-Guo Du
Journal: Molecular Biology and Evolution (2024)

Abstract Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.
Dynamic Phytomeric Growth Contributes to Local Adaptation in Barley
Authors: Yongyu Huang, Andreas Maurer, Ricardo F H Giehl, Shuangshuang Zhao, Guy Golan, Venkatasubbu Thirulogachandar, Guoliang Li, Yusheng Zhao, Corinna Trautewig, Axel Himmelbach, Andreas Börner, Murukarthick Jayakodi, Nils Stein, Martin Mascher, Klaus Pillen, Thorsten Schnurbusch
Journal: Molecular Biology and Evolution (2024)

Abstract Vascular plants have segmented body axes with iterative nodes and internodes. Appropriate node initiation and internode elongation are fundamental to plant fitness and crop yield; however, how these events are spatiotemporally coordinated remains elusive. We show that in barley (Hordeum vulgare L.), selections during domestication have extended the apical meristematic phase to promote node initiation, but constrained subsequent internode elongation. In both vegetative and reproductive phases, internode elongation displays a dynamic proximal—distal gradient, and among subpopulations of domesticated barleys worldwide, node initiation and proximal internode elongation are associated with latitudinal and longitudinal gradients, respectively. Genetic and functional analyses suggest that, in addition to their converging roles in node initiation, flowering-time genes have been repurposed to specify the timing and duration of internode elongation. Our study provides an integrated view of barley node initiation and internode elongation and suggests that plant architecture should be recognized as a collection of dynamic phytomeric units in the context of crop adaptive evolution.
Poly (Betulinic Acid) Nanoparticles Loaded with bFGF Improve Functional Recovery After Spinal Cord Injury
Authors: Xianghang Chen, Beini Wang, Yongxiu Zhou, Xuejuan Wu, Anyu Du, Abdullah Al Mamun, Yitie Xu, Shuangshuang Wang, Chang Jiang, Ling Xie, Kailiang Zhou, Siwang Hu, Jian Xiao
Journal: Advanced Healthcare Materials (2024)

Abstract Oxidative stress (OS) is one of the crucial molecular events of secondary spinal cord injury (SCI). Basic fibroblast growth factor (bFGF) is a multipotent cell growth factor with an anti‐oxidant effect. However, bFGF has a short half‐life in vivo, which limits its therapeutic application. Biodegradable polymers with excellent biocompatibility have been recently applied in SCI. The negative aspect is that polymers cannot provide a significant therapeutic effect. Betulinic acid (BA), a natural anti‐inflammatory compound, has been polymerized into poly (betulinic acid) (PBA) to serve as a drug carrier for bFGF. This study explores the therapeutic effects and underlying molecular mechanisms of PBA nanoparticles (NPs) loaded with bFGF (PBA‐bFGF NPs) in SCI. Results show that PBA‐bFGF NPs produce remarkable biocompatibility in vivo and in vitro. The results also demonstrate that local delivery of PBA‐bFGF NPs enhances motor function recovery, inhibits OS, mitigates neuroinflammation, and alleviates neuronal apoptosis following SCI. Furthermore, the results indicate that local delivery of PBA‐bFGF NPs activates the nuclear factor erythroid 2‐related factor 2 (Nrf‐2) signaling pathway following SCI. In summary, results suggest that local delivery of PBA‐bFGF NPs delivers potential therapeutic advantages in the treatment and management of SCI.
Correlation between tumor size change and outcome in a rare cancer immunotherapy basket trial
Authors: Megan Othus, Sandip P Patel, Young K Chae, Eliana Dietrich, Howard Streicher, Elad Sharon, Razelle Kurzrock
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background RECIST criteria for progressive disease, partial response, and complete response, reflecting +20%, −30%, and −100% tumor size changes, respectively, are critical outcome variables in oncology clinical trials. Herein, we evaluated post-immunotherapy tumor size change correlation with outcomes. Methods We used a unique clinical trial data resource, a multicenter basket trial in patients with rare solid tumors treated with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) between 2017 and 2023 (National Cancer Institute/Southwest Oncology Group-sponsored DART trial [NCT02834013]) (open at 1083 sites at its peak). Outcome associations were evaluated by survival analysis techniques including Martingale residuals. Results In 638 evaluable patients, we found strong linear relationships between percent change in tumor measurement up to a 40%-50% increase and progression-free (PFS) and overall survival (OS) (both Cox regression P &amp;lt; .001; landmark analyses based on day 65). Pearson R correlation between survival estimates and tumor change category were −0.94, −0.89, and −0.89 (PFS) and −0.84, −0.90, and −0.90 (OS) for median, 6-month (PFS), and 1-year (OS) and for 1-year (PFS) and 2-year (OS) estimates. Conclusions Percent change in tumor measurement per RECISTv1.1 (the sum of longest dimensions of target lesions) has a linear association with PFS and OS up to a 40% to 50% increase in tumor measurement in this cohort of patients with rare cancers who received combination immune checkpoint blockade. Quantitative first scan tumor measurement changes include important information to evaluate the potential efficacy of a therapy beyond the proportion of patients who achieve an objective response.
Biological processes and factors involved in soft and hard tissue healing
Authors: Mark Bartold, Saso Ivanovski
Journal: Periodontology 2000 (2024)

Abstract Wound healing is a complex and iterative process involving myriad cellular and biologic processes that are highly regulated to allow satisfactory repair and regeneration of damaged tissues. This review is intended to be an introductory chapter in a volume focusing on the use of platelet concentrates for tissue regeneration. In order to fully appreciate the clinical utility of these preparations, a sound understanding of the processes and factors involved in soft and hard tissue healing. This encompasses an appreciation of the cellular and biological mediators of both soft and hard tissues in general as well as specific consideration of the periodontal tissues. In light of good advances in this basic knowledge, there have been improvements in clinical strategies and therapeutic management of wound repair and regeneration. The use of platelet concentrates for tissue regeneration offers one such strategy and is based on the principles of cellular and biologic principles of wound repair discussed in this review.
Real-world analysis of teclistamab in 123 RRMM patients from Germany
Authors: C. Riedhammer, F. Bassermann, B. Besemer, M. Bewarder, F. Brunner, A. Carpinteiro, H. Einsele, J. Faltin, J. Frenking, D. Gezer, S. Goldman-Mazur, M. Hänel, M. Hoegner, K. M. Kortuem, J. Krönke, M. Kull, T. Leitner, C. Mann, R. Mecklenbrauck, M. Merz, A. Morgner, A. Nogai, M. S. Raab, R. Teipel, R. Wäsch, L. Rasche
Journal: Leukemia (2024)
Huge pseudoaneurysm of the left ventricular outflow tract developed a few years after surgery for subvalvular mitral aneurysm: to plug or not to plug it is the question
Authors: Humberto Morais, Elsa Fernandes, Mauer A A Gonçalves
Journal:  (2024)

A 36-year-old male patient presented with dyspnea, fatigue, and pre-syncope episodes 1 during moderate exertion.Relevant history included surgery for a subvalvular mitral 2 aneurysm (SMA) performed 14 years earlier.Although surgery was done suspecting 3 a type A aortic aneurysm, the diagnosis wasn't confirmed intraoperatively.Detailed 4
Issue Information
Journal: American Journal of Hematology (2024)

VINITI (All-Russian Institute of Science & Technological Information) • Web of Science ® (Thomson ISI).For submission instructions, subscription and all other information visit: www.wileyonlinelibrary.com/ajh.ESG (Environmental, Social, Governance) is essential to Wiley's mission of unlocking human potential.For over two centuries, Wiley has a history of helping the world's researchers, learners, innovators, and leaders achieve their goals and solve the world's most important challenges.We take our role as a corporate citizen seriously and are guided by transparency, accountability, and industry best practices.Through intentional climate action and strategic social impact, ESG advances Wiley's commitment to sustainability, positive impact, and leading global change.Follow our progress at https://www.
Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution
Authors: Araks Martirosyan, Rizwan Ansari, Francisco Pestana, Katja Hebestreit, Hayk Gasparyan, Razmik Aleksanyan, Silvia Hnatova, Suresh Poovathingal, Catherine Marneffe, Dietmar R. Thal, Andrew Kottick, Victor J. Hanson-Smith, Sebastian Guelfi, William Plumbly, T. Grant Belgard, Emmanouil Metzakopian, Matthew G. Holt
Journal: Molecular Neurodegeneration (2024)

Abstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD is loss of dopaminergic neurons and the presence of aggregated α-synuclein, primarily in the substantia nigra pars compacta (SNpc) of the midbrain. However, the molecular mechanisms that underlie the pathology in different cell types is not currently understood. Here, we present a single nucleus transcriptome analysis of human post-mortem SNpc obtained from 15 sporadic Parkinson’s Disease (PD) cases and 14 Controls. Our dataset comprises ∼84K nuclei, representing all major cell types of the brain, allowing us to obtain a transcriptome-level characterization of these cell types. Importantly, we identify multiple subpopulations for each cell type and describe specific gene sets that provide insights into the differing roles of these subpopulations. Our findings reveal a significant decrease in neuronal cells in PD samples, accompanied by an increase in glial cells and T cells. Subpopulation analyses demonstrate a significant depletion of tyrosine hydroxylase ( TH ) enriched astrocyte, microglia and oligodendrocyte populations in PD samples, as well as TH enriched neurons, which are also depleted. Moreover, marker gene analysis of the depleted subpopulations identified 28 overlapping genes, including those associated with dopamine metabolism (e.g., ALDH1A1, SLC6A3 &amp; SLC18A2 ). Overall, our study provides a valuable resource for understanding the molecular mechanisms involved in dopaminergic neuron degeneration and glial responses in PD, highlighting the existence of novel subpopulations and cell type-specific gene sets.
Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target
Authors: Xiaoliang Huang, Weiming Zhang, Na Yang, Yujie Zhang, Tianyu Qin, Hanyi Ruan, Yan Zhang, Chao Tian, Xianwei Mo, Weizhong Tang, Jungang Liu, Beibei Zhang
Journal: Molecular Cancer (2024)
Bispecific antibody drug conjugates: Making 1+1&gt;2
Authors: Yilin Gu, Zhijia Wang, Yuxi Wang
Journal: Acta Pharmaceutica Sinica B (2024)

Bispecific antibody‒drug conjugates (BsADCs) represent an innovative therapeutic category amalgamating the merits of antibody‒drug conjugates (ADCs) and bispecific antibodies (BsAbs). Positioned as the next-generation ADC approach, BsADCs hold promise for ameliorating extant clinical challenges associated with ADCs, particularly pertaining to issues such as poor internalization, off-target toxicity, and drug resistance. Presently, ten BsADCs are undergoing clinical trials, and initial findings underscore the imperative for ongoing refinement. This review initially delves into specific design considerations for BsADCs, encompassing target selection, antibody formats, and the linker-payload complex. Subsequent sections delineate the extant progress and challenges encountered by BsADCs, illustrated through pertinent case studies. The amalgamation of BsAbs with ADCs offers a prospective solution to prevailing clinical limitations of ADCs. Nevertheless, the symbiotic interplay among BsAb, linker, and payload necessitates further optimizations and coordination beyond a simplistic "1 + 1" to effectively surmount the extant challenges facing the BsADC domain.
Macrophage senescence in health and diseases
Authors: Longling Wang, Wenxiang Hong, Hong Zhu, Qiaojun He, Bo Yang, Jiajia Wang, Qinjie Weng
Journal: Acta Pharmaceutica Sinica B (2024)

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. Persistent senescence of macrophages may lead to maladaptation, immune dysfunction, and finally the development of age-related diseases, infections, autoimmune diseases, and malignancies. However, it is a ubiquitous, multi-factorial, and dynamic complex phenomenon that also plays roles in remodeled processes, including wound repair and embryogenesis. In this review, we summarize some general molecular changes and several specific biomarkers during macrophage senescence, which may bring new sight to recognize senescent macrophages in different conditions. Also, we take an in-depth look at the functional changes in senescent macrophages, including metabolism, autophagy, polarization, phagocytosis, antigen presentation, and infiltration or recruitment. Furthermore, some degenerations and diseases associated with senescent macrophages as well as the mechanisms or relevant genetic regulations of senescent macrophages are integrated, not only emphasizing the possibility of regulating macrophage senescence to benefit age-associated diseases but also has an implication on the finding of potential targets or drugs clinically.
Inhaled nanoparticles for treating idiopathic pulmonary fibrosis by inhibiting honeycomb cyst and alveoli interstitium remodeling
Authors: Meng-Meng Han, Ling Tang, Bin Huang, Xue-Na Li, Yue-Fei Fang, Liang Qi, Bo-Wen Duan, Ya-Ting Yao, Yu-Jing He, Lei Xing, Hu-Lin Jiang
Journal: Journal of Controlled Release (2024)
Accelerated corrosion of 316L stainless steel in a simulated oral environment via extracellular electron transfer and acid metabolites of subgingival microbiota
Authors: Ying Zheng, Yi Yang, Xianbo Liu, Pan Liu, Xiangyu Li, Mingxing Zhang, Enze Zhou, Zhenjin Zhao, Xue Wang, Yuanyuan Zhang, Bowen Zheng, Yuwen Yan, Yi Liu, Dake Xu, Liu Cao
Journal: Bioactive Materials (2024)
Mixed Patterns of Intergenerational DNA Methylation Inheritance in <i>Acropora</i>
Authors: Christopher R Peterson, Carly B Scott, Rashin Ghaffari, Groves B Dixon, Mikhail V Matz
Journal: Molecular Biology and Evolution (2024)

Abstract For sessile organisms at high risk from climate change, phenotypic plasticity can be critical to rapid acclimation. Epigenetic markers like DNA methylation are hypothesized as mediators of plasticity; methylation is associated with the regulation of gene expression, can change in response to ecological cues, and is a proposed basis for the inheritance of acquired traits. Within reef-building corals, gene-body methylation (gbM) can change in response to ecological stressors. If coral DNA methylation is transmissible across generations, this could potentially facilitate rapid acclimation to environmental change. We investigated methylation heritability in Acropora, a stony reef-building coral. Two Acropora millepora and two Acropora selago adults were crossed, producing eight offspring crosses (four hybrid, two of each species). We used whole-genome bisulfite sequencing to identify methylated loci and allele-specific alignments to quantify per-locus inheritance. If methylation is heritable, differential methylation (DM) between the parents should equal DM between paired offspring alleles at a given locus. We found a mixture of heritable and nonheritable loci, with heritable portions ranging from 44% to 90% among crosses. gBM was more heritable than intergenic methylation, and most loci had a consistent degree of heritability between crosses (i.e. the deviation between parental and offspring DM were of similar magnitude and direction). Our results provide evidence that coral methylation can be inherited but that heritability is heterogenous throughout the genome. Future investigations into this heterogeneity and its phenotypic implications will be important to understanding the potential capability of intergenerational environmental acclimation in reef building corals.