tbuckley/cabot-search huggingface dataset:
Epigenetic underpinnings of tumor-immune dynamics in prostate cancer immune suppression
Authors: Duminduni Hewa Angappulige, Nupam P. Mahajan, Kiran Mahajan
Journal: Trends in cancer (2024)

Prostate cancer (PC) is immunosuppressive and refractory to immunotherapy. Infiltration of myeloid-derived suppressor cells (MDSCs) and senescent-like neutrophils and T cell exhaustion are observed in the tumor microenvironment (TME) following androgen receptor (AR) antagonism with antiandrogens or androgen ablation. De novo post-translational acetylation of the AR, HOXB13, and H2A at K609, K13, and K130, respectively, and phosphorylation of H4 at Y88 have emerged as key epigenetic modifications associated with castration-resistant PC (CRPC). The resulting chromatin changes are integrated into cellular processes via phosphorylation of the AR, ACK1, ATPF1A, and SREBP1 at Y267, Y284, Y243/Y246, and Y673/Y951, respectively. In this review, we discuss how these de novo epigenetic alterations drive resistance and how efforts aimed at targeting these regulators may overcome immune suppression observed in PC.
Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage
Authors: Kevin N. Sheth, Nicole Solomon, Brooke Alhanti, Steven R. Messe, Ying Xian, Deepak L. Bhatt, J. Claude Hemphill, Jennifer A. Frontera, Raymond C. Chang, Ilya M. Danelich, Joanna Huang, Lee Schwamm, Eric E. Smith, Joshua N. Goldstein, Brian Mac Grory, Gregg C. Fonarow, Jeffrey L. Saver
Journal: JAMA Neurology (2024)

Intracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice.
Rationality, preferences, and emotions with biological constraints: it all starts from our senses
Authors: Rafael Polanía, Denis Burdakov, Todd A. Hare
Journal: Trends in Cognitive Sciences (2024)

Is the role of our sensory systems to represent the physical world as accurately as possible? If so, are our preferences and emotions, often deemed irrational, decoupled from these 'ground-truth' sensory experiences? We show why the answer to both questions is 'no'. Brain function is metabolically costly, and the brain loses some fraction of the information that it encodes and transmits. Therefore, if brains maximize objective functions that increase the fitness of their species, they should adapt to the objective-maximizing rules of the environment at the earliest stages of sensory processing. Consequently, observed 'irrationalities', preferences, and emotions stem from the necessity for our early sensory systems to adapt and process information while considering the metabolic costs and internal states of the organism.
Extracellular vesicles are key players in mesenchymal stem cells’ dual potential to regenerate and modulate the immune system
Authors: Martijn van Griensven, Elizabeth R. Balmayor
Journal: Advanced Drug Delivery Reviews (2024)

MSCs are used for treatment of inflammatory conditions or for regenerative purposes. MSCs are complete cells and allogenic transplantation is in principle possible, but mostly autologous use is preferred. In recent years, it was discovered that cells secrete extracellular vesicles. These are active budded off vesicles that carry a cargo. The cargo can be miRNA, protein, lipids etc. The extracellular vesicles can be transported through the body and fuse with target cells. Thereby, they influence the phenotype and modulate the disease. The extracellular vesicles have, like the MSCs, immunomodulatory or regenerative capacities. This review will focus on those features of extracellular vesicles and discuss their dual role. Besides the immunomodulation, the regeneration will concentrate on bone, cartilage, tendon, vessels and nerves. Current clinical trials with extracellular vesicles for immunomodulation and regeneration that started in the last five years are highlighted as well. In summary, extracellular vesicles have a great potential as disease modulating entity and treatment. Their dual characteristics need to be taken into account and often are both important for having the best effect.
Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations
Authors: Márta Korbonits, Joanne C. Blair, Anna Boguslawska, John Ayuk, Justin H. Davies, Maralyn R. Druce, Jane Evanson, Daniel Flanagan, Nigel Glynn, Claire E. Higham, Thomas S. Jacques, Saurabh Sinha, Ian Simmons, Nicky Thorp, Francesca M. Swords, Helen L. Storr, Helen A. Spoudeas
Journal: Nature Reviews Endocrinology (2024)

Tumours of the anterior part of the pituitary gland represent just 1% of all childhood (aged <15 years) intracranial neoplasms, yet they can confer high morbidity and little evidence and guidance is in place for their management. Between 2014 and 2022, a multidisciplinary expert group systematically developed the first comprehensive clinical practice consensus guideline for children and young people under the age 19 years (hereafter referred to as CYP) presenting with a suspected pituitary adenoma to inform specialist care and improve health outcomes. Through robust literature searches and a Delphi consensus exercise with an international Delphi consensus panel of experts, the available scientific evidence and expert opinions were consolidated into 74 recommendations. Part 1 of this consensus guideline includes 17 pragmatic management recommendations related to clinical care, neuroimaging, visual assessment, histopathology, genetics, pituitary surgery and radiotherapy. While in many aspects the care for CYP is similar to that of adults, key differences exist, particularly in aetiology and presentation. CYP with suspected pituitary adenomas require careful clinical examination, appropriate hormonal work-up, dedicated pituitary imaging and visual assessment. Consideration should be given to the potential for syndromic disease and genetic assessment. Multidisciplinary discussion at both the local and national levels can be key for management. Surgery should be performed in specialist centres. The collection of outcome data on novel modalities of medical treatment, surgical intervention and radiotherapy is essential for optimal future treatment. Evidence and guidance for the care of pituitary adenomas in children and adolescents is currently lacking. Part 1 of this two-part consensus guideline presents 17 general recommendations for diagnosis and management of pituitary adenomas in children and young people under 19 years of age.
Cell Membrane‐Targeting Type I/II Photodynamic Therapy Combination with FSP1 Inhibition for Ferroptosis‐Enhanced Photodynamic Immunotherapy
Authors: Jian Chen, Zeyu Duan, Lidong Deng, Lie Li, Qiyan Li, Jinqing Qu, Xiang Li, Ruiyuan Liu
Journal: Advanced Healthcare Materials (2024)

Abstract An imbalance in reactive oxygen species (ROS) levels in tumor cells can result in the accumulation of lipid peroxide (LPO) which can induce ferroptosis. Moreover, elevated ROS levels in tumors present a chance to develop ROS‐based cancer therapeutics including photodynamic therapy (PDT) and ferroptosis. However, their anticancer efficacies are compromised by insufficient oxygen levels and inherent cellular ROS regulatory mechanism. Herein, a cell membrane‐targeting photosensitizer, TBzT‐CNQi, which can generate 1 O 2 , •OH, and O 2 •− via type I/II process to induce a high level of LPO for potent ferroptosis and photodynamic therapy is developed. The FSP1 inhibitor (iFSP1) is incorporated with TBzT‐CNQi to downregulate FSP1 expression, lower the intracellular CoQ10 content, induce a high level of LPO, and activate initial tumor immunogenic ferroptosis. In vitro and in vivo experiments demonstrate that the cell membrane‐targeting type I/II PDT combination with FSP1 inhibition can evoke strong ICD and activate the immune response, which subsequently promotes the invasion of CD8+ T cells infiltration, facilitates the dendritic cell maturation, and decreases the tumor infiltration of tumor‐associated macrophages. The study indicates that the combination of cell membrane‐targeting type I/II PDT and FSP1 inhibition holds promise as a potential strategy for ferroptosis‐enhanced photodynamic immunotherapy of hypoxia tumors.
ONC201 (Dordaviprone) in Recurrent H3 K27M–Mutant Diffuse Midline Glioma
Authors: Isabel Arrillaga-Romany, Sharon L. Gardner, Yazmin Odia, Dolly Aguilera, Joshua E. Allen, Tracy Batchelor, Nicholas Butowski, Clark Chen, Timothy Cloughesy, Andrew Cluster, John de Groot, Karan S. Dixit, Jerome J. Graber, Aya M. Haggiagi, Rebecca A. Harrison, Albert Kheradpour, Lindsay B. Kilburn, Sylvia C. Kurz, Guangrong Lu, Tobey J. MacDonald, Minesh Mehta, Allen S. Melemed, Phioanh Leia Nghiemphu, Samuel C. Ramage, Nicole Shonka, Ashley Sumrall, Rohinton S. Tarapore, Lynne Taylor, Yoshie Umemura, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2024)

Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG.
When I use a word . . . Medicines regulation—diethylene glycol
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

In 1937, when diethylene glycol was used as a solvent in the preparation of a medicinal product, an elixir of sulfanilamide, resulting in deaths, public outcry hastened the promulgation of an act that had been in preparation in the USA for several years, but which had met with opposition from pharmaceutical companies. The 1938 Food, Drug, and Cosmetics Act, as it was known, gave greater powers to the then recently formed Food and Drug Administration (FDA) in regulating the contents of medicinal formulations. Nevertheless, although similar regulatory systems have since been established around the world, episodes of poisoning with diethylene glycol in pharmaceutical formulations, whether deliberately included adulteration or as a contaminant, continue to be reported, generally in developing countries, usually affecting children, and often causing deaths.
Women in science: inspiring future generations
Authors: None The Lancet Diabetes & Endocrinology
Journal: The Lancet Diabetes & Endocrinology (2024)

Feb 11 marks International Day of Women and Girls in Science, an annual observance established by the UN General Assembly on Dec 22, 2015, to promote gender equality in the fields of science, technology, engineering, and mathematics (STEM). This year, the theme is Women and Girls in Science Leadership, a New Era for Sustainability, with a focus on increasing the number of women researchers working on some of the utmost challenges of our time (as outlined in the 2030 Agenda for Sustainable Development), from improving health to combating climate change.
Adding New Dimensions to 3D Cancer Models
Authors: Kevan Chu, Lukas E. Dow
Journal: Cancer Research (2024)

Abstract Understanding patient-specific responses to anticancer therapies and how individual tumors interact with their tumor microenvironment (TME) is a challenging task. To measure the impact of the TME on diverse and clinically relevant treatments, Ramos Zapatero and colleagues coupled patient-derived organoid (PDO) and cancer-associated fibroblast (CAF) cocultures with high-throughput mass cytometry–based assessment of cell state. Using a newly developed “Trellis” algorithm enabled integration and analysis of highly complex, multidimensional treatment response data. This work showed that tumor cell response to chemotherapy was associated with both intrinsic and nonintrinsic signaling states, whereby proliferative rate, growth factor signaling, and CAFs interaction influenced chemoprotection. Furthermore, the work suggests a potential role for the TME in promoting lineage plasticity associated with drug resistance. In all, the pipeline described provides a blueprint for exploring the intricate interplay of factors influencing cancer treatment response.
Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM
Authors: Christina C Chang, Thomas S Harrison, Tihana A Bicanic, Methee Chayakulkeeree, Tania C Sorrell, Adilia Warris, Ferry Hagen, Andrej Spec, Rita Oladele, Nelesh P Govender, Sharon C Chen, Christopher H Mody, Andreas H Groll, Yee-Chun Chen, Michail S Lionakis, Alexandre Alanio, Elizabeth Castañeda, Jairo Lizarazo, José E Vidal, Takahiro Takazono, Martin Hoenigl, Jan-Willem Alffenaar, Jean-Pierre Gangneux, Rajeev Soman, Li-Ping Zhu, Alexandro Bonifaz, Joseph N Jarvis, Jeremy N Day, Nikolai Klimko, Jon Salmanton-García, Grégory Jouvion, David B Meya, David Lawrence, Sebastian Rahn, Felix Bongomin, Brendan J McMullan, Rosanne Sprute, Tinashe K Nyazika, Justin Beardsley, Fabianne Carlesse, Christopher H Heath, Olusola O Ayanlowo, Olga M Mashedi, Flavio Queiroz-Telles Filho, Mina C Hosseinipour, Atul K Patel, Elvis Temfack, Nina Singh, Oliver A Cornely, David R Boulware, Olivier Lortholary, Peter G Pappas, John R Perfect
Journal: The Lancet Infectious Diseases (2024)
Geriatric assessment and quality of life for 2 years in older patients with head and neck cancer
Authors: Charlotte Lafont, Elena Paillaud, Chloe Bertolus, Melany Baron, Philippe Caillet, Eric Bouvard, Marie Laurent, Didier Salvan, Laurence Chaumette, Laure de Decker, Benoit Piot, Beatrix Barry, Agathe Raynaud-Simon, Elisabeth Sauvaget, Aurélien Minard, Amélie Anota, Henri Panjo, Lydia Brugel, Florence Canouï-Poitrine
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Due to the location and toxicity of treatments, head and neck cancer (HNC) has a major impact on quality of life (QoL). Objective: to assess the effects of geriatric-assessment (GA)-driven interventions on QoL over 2 years in older adults with HNC. EGeSOR was a randomized study of HNC patients aged ≥65, receiving a pretreatment GA, a geriatric intervention and follow-up (intervention) or standard of care (control). The primary endpoint was QoL score using the European Organisation for Research and Treatment of Cancer’s (EORTC QLQ-C30) and HNC (QLQ-HN35) QoL questionnaires over 24 months. In total, 475 patients were included (median age: 75.3; women: 31%; oral cancer: 44%). QoL scores improved over 24 months with various trajectories, without significant differences between the groups. A total of 74% of patients (interventional group) did not receive the complete intervention. Cancer characteristics, functional status, and risk of frailty were associated with change in the Global Health Status QoL score. There is a need to develop an alternative model of implementation such as patient-centered health-care pathways. Trial registration NCT02025062.
Burden of intracerebral haemorrhage in Europe: forecasting incidence and mortality between 2019 and 2050
Authors: Hatem A. Wafa, Iain Marshall, Charles D.A. Wolfe, Wanqing Xie, Catherine O. Johnson, Roland Veltkamp, Yanzhong Wang, Roland Veltkamp, Kirsten H. Harvey, Eleni Korompoki, Lucio D’Anna, Omid Halse, Emily R. Harvey, Klemens Hügen, Uwe Malzahn, Sabine Ullmann, Carolin Schuhmann, Gabriele Putz Todd, Hannes Brinz, Cornelia Fiessler, Peter U. Heuschmann, Kirsten Haas, Viktoria Rücker, Christian Enzinger, Stefan Ropele, Daniela Pinter, Melanie Haidegger, Thomas Gattringer, Simon Fandler-Höfler, Charles D.A. Wolfe, Yanzhong Wang, Hatem A. Wafa, Joan Montaner, Elena Palà, Anna Penalba, Marcel Lamana Vallverdu, Daisy Guaman Pilco, Stéphanie Debette, Igor Sibon, Pauline Renou, Morgane Lachaize, Léa Milan, Nathalie Heyvang, Sylvain Ledure, Pascale Michel, Johanna Conhoc, Léa Donnadieu, Kelly Hyves, Valeria Caso, Maria Giulia Mosconi, Mara Graziani, Virginia Cancelloni, Laura Marchini, Bianca Emanuela Koehler, Peter Brønnum Nielsen, Torben Bjerregaard Larsen, Gregory Y.H. Lip, Solveigh Horstmann, Jan Purrucker, Peter Ringleb, Mariam Haffa, Sabrina Klein, Lenka Taylor, Torsten Hoppe-Tichy, Walter E. Haefeli, Hanna M. Seidling, Jürgen Burhenne, Kathrin I. Foerster, Viktoria Wurmbach, Claudia Marquart, Deirdre A. Lane, Gregory Y.H. Lip, Elena Ivany, Robyn Lotto
Journal: The Lancet Regional Health - Europe (2024)

Anticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050.
The impact of psychiatric comorbidity on Parkinson's disease outcomes: a systematic review and meta-analysis
Authors: Ella Burchill, Cameron James Watson, Jack B. Fanshawe, James Brunton Badenoch, Emma Rengasamy, Dory Anthony Ghanem, Constantine Holle, Isabella Conti, Mohammed Ahmed Sadeq, Aman Saini, Abdelilah Lahmar, Ben Cross, Gareth McGuigan, Amar Nandrha, Edward J. Kane, Julia Wozniak, Reem Mohamed Farouk Ghorab, Jia Song, Andrew Sommerlad, Andrew Lees, Michael S. Zandi, Anthony S. David, Glyn Lewis, Ben Carter, Jonathan P. Rogers
Journal: The Lancet Regional Health - Europe (2024)

The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission.
BCL6 is required for the thymic development of TCRαβ <sup>+</sup> CD8αα <sup>+</sup> intraepithelial lymphocyte lineage
Authors: Qi Xing, Dehui Chang, Shiyuan Xie, Xiaohong Zhao, Hao Zhang, Xiaohu Wang, Xue Bai, Chen Dong
Journal: Science Immunology (2024)

TCRαβ
Progressive accumulation of hyperinflammatory NKG2D <sup>low</sup> NK cells in early childhood severe atopic dermatitis
Authors: David E. Ochayon, Stanley B. DeVore, Wan-Chi Chang, Durga Krishnamurthy, Harsha Seelamneni, Brittany Grashel, Daniel Spagna, Sandra Andorf, Lisa J. Martin, Jocelyn M. Biagini, Stephen N. Waggoner, Gurjit K. Khurana Hershey
Journal: Science Immunology (2024)

Atopic dermatitis (AD) is a chronic inflammatory skin disease that often precedes the development of food allergy, asthma, and allergic rhinitis. The prevailing paradigm holds that a reduced frequency and function of natural killer (NK) cell contributes to AD pathogenesis, yet the underlying mechanisms and contributions of NK cells to allergic comorbidities remain ill-defined. Here, analysis of circulating NK cells in a longitudinal early life cohort of children with AD revealed a progressive accumulation of NK cells with low expression of the activating receptor NKG2D, which was linked to more severe AD and sensitivity to allergens. This was most notable in children co-sensitized to food and aeroallergens, a risk factor for development of asthma. Individual-level longitudinal analysis in a subset of children revealed coincident reduction of NKG2D on NK cells with acquired or persistent sensitization, and this was associated with impaired skin barrier function assessed by transepidermal water loss. Low expression of NKG2D on NK cells was paradoxically associated with depressed cytolytic function but exaggerated release of the proinflammatory cytokine tumor necrosis factor-α. These observations provide important insights into a potential mechanism underlying the development of allergic comorbidity in early life in children with AD, which involves altered NK cell functional responses, and define an endotype of severe AD.
Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults
Authors: Helen R. Wagstaffe, Ryan S. Thwaites, Arnold Reynaldi, Jasmin K. Sidhu, Richard McKendry, Stephanie Ascough, Loukas Papargyris, Ashley M. Collins, Jiayun Xu, Nana-Marie Lemm, Matthew K. Siggins, Benny M. Chain, Ben Killingley, Mariya Kalinova, Alex Mann, Andrew Catchpole, Miles P. Davenport, Peter J. M. Openshaw, Christopher Chiu
Journal: Science Immunology (2024)

Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became infected and showed an interferon-dominated mediator response with divergent kinetics between nasal and systemic sites. Peripheral CD4
Effect of chitin-architected spatiotemporal three-dimensional culture microenvironments on human umbilical cord-derived mesenchymal stem cells
Authors: Shuoji Zhu, Junfeng Xuan, Yunchao Shentu, Katsuhiko Kida, Masaki Kobayashi, Wei Wang, Minoru Ono, Dehua Chang
Journal: Bioactive Materials (2024)

Mesenchymal stem cell (MSC) transplantation has been explored for the clinical treatment of various diseases. However, the current two-dimensional (2D) culture method lacks a natural spatial microenvironment
Structural and temporal dynamics analysis of zinc-based biomaterials: History, research hotspots and emerging trends
Authors: Kunshan Yuan, Chengchen Deng, Lili Tan, Xiangxiu Wang, Wenhua Yan, Xiaozhen Dai, Ruolin Du, Yufeng Zheng, Haijun Zhang, Guixue Wang
Journal: Bioactive Materials (2024)

To examine the 16-year developmental history, research hotspots, and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics. The literature on zinc-based biodegradable metallic materials in WoSCC was searched. Historical characteristics, the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite. Over the past 16 years, the field of zinc-based biodegradable metal materials has remained in a hotspot stage, with extensive scientific collaboration. In addition, there are 45 subject categories and 51 keywords in different research periods, and 80 papers experience citation bursts. Keyword clustering anchored 3 emerging research subfields, namely, #1 plastic deformation #4 additive manufacturing #5 surface modification. The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property, microstructure, corrosion behavior, etc., and emerging keywords are additive manufacturing, surface modification, dynamic recrystallization, etc. The most recent research on reference clustering has six subfields. Namely, #0 microstructure, #2 sem, #3 additive manufacturing, #4 laser powder bed fusion, #5 implant, and #7 Zn–1Mg. The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials, which can help researchers identify hot spots and explore new research directions in the field.