tbuckley/cabot-search huggingface dataset:
Decoding the healing dialogues for tissue repair
Authors: Subhadip Ghatak
Journal: Molecular Therapy (2024)

Extracellular vesicles (EVs), once identified as "platelet dust," have catapulted from the realm of cellular curiosities to the forefront of innovative clinical research, heralding a new era in precision medicine. This substantial paradigm shift is attributed primarily to the intrinsic stability of EVs, their minimal immunogenicity, and their potential for precise, targeted delivery of therapeutic agents.1 Within a complex cutaneous wound microenvironment, much of the paracrine signaling between the resident cells, such as fibroblasts and blood-borne macrophages, relies on EVs. To that end, in this issue of Molecular Therapy, Park et al. explore the crosstalk between myeloid cells and fibroblasts in diabetic wounds.2
Impact of Prior Chemotherapy on Response to Second-line Pembrolizumab in Urothelial Cancer: Exploratory Analysis of the Phase 3 KEYNOTE-045 Trial
Authors: Ronald de Wit, David J Vaughn, Yves Fradet, Lawrence Fong, Miguel A Climent, Andrea Necchi, Daniel P Petrylak, Winald R Gerritsen, Howard Gurney, David I Quinn, Stéphane Culine, Cora N Sternberg, Dean F Bajorin, Toni K Choueiri, Jin Xu, Kentaro Imai, Blanca Homet Moreno, Joaquim Bellmunt, Jae-Lyun Lee
Journal: European Urology (2024)
Presentation of chronic myeloid leukemia in basophilic blast crisis
Authors: Biswadip Hazarika, Barbara J. Bain
Journal: American Journal of Hematology (2024)

Basophilia with mature and dysplastic basophils is a common phenomenon in CML. However, a basophilic blast crisis is a very rare form of acute transformation. A review of 410 patients with disease in transformation revealed only two cases (0.5%) of basophilic blast crisis.1 The dominance of basophil blast cells with fewer or no other myeloblasts or lymphoblasts confirms the diagnosis. Clonal evolution is likely to be evident with additional chromosomal abnormalities, often including i(17q) or other abnormality of chromosome 17.1-4 Diagnosis is straightforward when a patient is known to have CML but is more problematic if a patient presents already in blast crisis. The authors declare no conflict of interest.
MA-SAM: Modality-agnostic SAM adaptation for 3D medical image segmentation
Authors: Cheng Chen, Juzheng Miao, Dufan Wu, Aoxiao Zhong, Zhiling Yan, Sekeun Kim, Jiang Hu, Zhengliang Liu, Lichao Sun, Xiang Li, Tianming Liu, Pheng-Ann Heng, Quanzheng Li
Journal: Medical Image Analysis (2024)
Early detection and treatment of obstructive sleep apnoea in infants with Down syndrome: a prospective, non-randomised, controlled, interventional study
Authors: Brigitte Fauroux, Silvia Sacco, Vincent Couloigner, Alessandro Amaddeo, Aimé Ravel, Emmanuelle Prioux, Jeanne Toulas, Cécile Cieuta-Walti, Hervé Walti, Romain Luscan, Ségolène Falquero, Manon Clert, Marie-Anne Caillaud, Livio De Sanctis, Sonia Khirani, Isabelle Marey, Clotilde Mircher
Journal: The Lancet Regional Health - Europe (2024)

Infants with Down syndrome (DS) are at high risk of obstructive sleep apnoea (OSA) which is associated with neurocognitive dysfunction and behaviour problems. The aim of our study was to evaluate the effect of early OSA treatment in infants with DS on neurocognitive development and behaviour.
The molecular conversations of sarcomas: exosomal non-coding RNAs in tumor’s biology and their translational prospects
Authors: Margherita Luongo, Pasqualina Laurenziello, Giuseppe Cesta, Anna Maria Bochicchio, Ludmila Carmen Omer, Geppino Falco, Maria Rita Milone, Francesca Cibarelli, Sabino Russi, Simona Laurino
Journal: Molecular Cancer (2024)

Exosomes mediate cell-to-cell crosstalk involving a variety of biomolecules through an intricate signaling network. In recent years, the pivotal role of exosomes and their non-coding RNAs cargo in the development and progression of several cancer types clearly emerged. In particular, tumor bulk and its microenvironment co-evolve through cellular communications where these nanosized extracellular vesicles are among the most relevant actors. Knowledge about the cellular, and molecular mechanisms involved in these communications will pave the way for novel exosome-based delivery of therapeutic RNAs as well as innovative prognostic/diagnostic tools. Despite the valuable therapeutic potential and clinical relevance of exosomes, their role on sarcoma has been vaguely reported because the rarity and high heterogeneity of this type of cancer. Here, we dissected the scientific literature to unravel the multifaceted role of exosomal non-coding RNAs as mediator of cell-to-cell communications in the sarcoma subtypes.
SGLT2 inhibitors for patients with type 2 diabetes mellitus after myocardial infarction: a nationwide observation registry study from SWEDEHEART
Authors: Hans Christian Rosén, Moman A. Mohammad, Tomas Jernberg, Stefan James, Jonas Oldgren, David Erlinge
Journal: The Lancet Regional Health - Europe (2024)

SummaryBackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisations and cardiovascular death in patients with type 2 diabetes and prior cardiovascular disease. We hypothesised that SGLT2 inhibitors could provide cardiovascular benefits in the post-myocardial infarction setting. We aimed to investigate cardiovascular outcomes of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus after myocardial infarction in a Swedish nationwide registry.MethodsWe included all patients with type 2 diabetes surviving a type 1 acute myocardial infarction from January 1, 2018 to December 31, 2021. Patients were included if they were discharged with an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 in the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. We identified all patients discharged with or without an SGLT2 inhibitor prescription 120 days before or within three days after discharge from the cardiac care unit. The primary outcome measure was a composite of death and first hospitalisation for heart failure after one year analysed using an adjusted Cox regression.FindingsA total of 11,271 patients were included. Of these, 2498 (22.2%) received SGLT2 inhibitor treatment. Patients who were prescribed SGLT2 inhibitors were younger, more often presented with a STEMI and had worse left ventricular ejection fraction at index hospitalisation. SGLT2 inhibitor use was associated with lower rates of the composite outcome (hazard ratio (HR) of 0.70 (95% confidence interval (CI) 0.59–0.82).InterpretationTreatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower rate of cardiovascular events.FundingThis work was supported by Hjärt-Lungfonden, Vetenskapsrådet, Knut and Alice Wallenberg Foundation, ALF, the Bundy Academy, and Skåne University Hospital funds.
Enhancement of Bone Repair in Diabetic Rats with Metformin‐Modified Silicified Collagen Scaffolds
Authors: Yi‐Rong Wang, Xiao‐Xia Zhang, Xu‐Xu Chen, Xin‐Hua Yin, Ming Yang, Kuo Jiang, Shi‐Chang Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin‐modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio‐factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio‐factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.
Early childcare arrangements and children's internalizing and externalizing symptoms: an individual participant data meta-analysis of six prospective birth cohorts in Europe
Authors: Katharine M Barry, Demetris Avraam, Tim Cadman, Ahmed Elhakeem, Hanan El Marroun, Pauline W Jansen, Anne-Marie Nybo-Andersen, Katrine Strandberg-Larsen, Llúcia González Safont, Raquel Soler-Blasco, Florencia Barreto-Zarza, Jordi Julvez, Martine Vrijheid, Barbara Heude, Marie-Aline Charles, Alexandre Ramchandar Gomajee, Maria Melchior
Journal: The Lancet Regional Health - Europe (2024)

Early childcare attendance may be related to children's internalizing and externalizing symptoms throughout childhood and young adolescence, however evidence from Europe is limited. We aimed to assess this association across multiple population-based birth cohorts of children recruited in different European countries.
Pan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020: a prospective cohort study
Authors: Harry A Thorpe, Maiju Pesonen, Marta Corbella, Henri Pesonen, Stefano Gaiarsa, Christine J Boinett, Gerry Tonkin-Hill, Tommi Mäklin, Anna K Pöntinen, Neil MacAlasdair, Rebecca A Gladstone, Sergio Arredondo-Alonso, Teemu Kallonen, Dorota Jamrozy, Stephanie W Lo, Chrispin Chaguza, Grace A Blackwell, Antti Honkela, Anita C Schürch, Rob J L Willems, Cristina Merla, Greta Petazzoni, Edward J Feil, Patrizia Cambieri, Nicholas R Thomson, Stephen D Bentley, Davide Sassera, Jukka Corander
Journal: The Lancet Microbe (2024)

Nosocomial infections pose a considerable risk to patients who are susceptible, and this is particularly acute in intensive care units when hospital-associated bacteria are endemic. During the first wave of the COVID-19 pandemic, the surge of patients presented a significant obstacle to the effectiveness of infection control measures. We aimed to assess the risks and extent of nosocomial pathogen transmission under a high patient burden by designing a novel bacterial pan-pathogen deep-sequencing approach that could be integrated with standard clinical surveillance and diagnostics workflows.
Manganese‐Modified Aluminum Adjuvant Enhances both Humoral and Cellular Immune Responses
Authors: Yaxin Li, Chenya Wang, Haoyuan Lv, Jingting Li, Xupei Zhang, Shiyuan Zhang, Qing Shen, Qianqian Wu, Yong Liu, Rui Peng, Zhuang Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Aluminum adjuvants remain the most commonly used vaccine adjuvants. Being rather effective in triggering humoral immunity, however, aluminum adjuvants usually show limited abilities in activating cellular immunities. Herein, by adding manganese ions during the preparation of aluminum adjuvant, a manganese‐modified aluminum (Mn‐Al) adjuvant is obtained, which can effectively stimulate both humoral and cellular immune responses. Such Mn‐Al adjuvant can enhance antigen adsorption and promote antigen internalization by dendritic cells (DCs). Subsequently, the released Mn 2+ can activate the cyclic guanosine monophosphate–adenosine monophosphate synthase‐stimulator of interferon genes pathway to further promote DC activation. When combines with the model antigen ovalbumin (OVA), the Mn‐Al‐adjuvantes vaccine can induce high levels of antigen‐specific antibody titers and high proportions of antigen‐specific cytotoxic T cells in vivo. Moreover, the Mn‐Al‐adjuvanted vaccine elicited stronger antigen‐specific humoral and cellular immune responses than high‐dose of the aluminum‐based adjuvant. Additionally, immunization of mice with OVA in the presence of the Mn‐Al adjuvant significantly inhibited the growth of B16‐OVA tumors. Furthermore, when formulated with human papillomavirus antigens, Mn‐Al‐adjuvanted vaccines show better in vivo vaccination performance than aluminum‐adjuvanted vaccines. Therefore, the manganese‐modified aluminum adjuvant may thus become a new vaccine adjuvant with the potential to replace conventional aluminum adjuvants.
TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function
Authors: Muhammad S Alam, Matthias M Gaida, Hagen R Witzel, Shizuka Otsuka, Aamna Abbasi, Theresa Guerin, Abdalla Abdelmaksoud, Nathan Wong, Margaret C Cam, Serguei Kozlov, Jonathan D Ashwell
Journal: Cell Reports Medicine (2024)
Advanced glycation end products mediate biomineralization disorder in diabetic bone disease
Authors: Qianmin Gao, Yingying Jiang, Dongyang Zhou, Guangfeng Li, Yafei Han, Jingzhi Yang, Ke Xu, Yingying Jing, Long Bai, Zhen Geng, Hao Zhang, Guangyin Zhou, Mengru Zhu, Ning Ji, Ruina Han, Yuanwei Zhang, Zuhao Li, Chuandong Wang, Yan Hu, Hao Shen, Guangchao Wang, Zhongmin Shi, Qinglin Han, Xiao Chen, Jiacan Su
Journal: Cell Reports Medicine (2024)
A future role for health applications of large language models depends on regulators enforcing safety standards
Authors: Oscar Freyer, Isabella Catharina Wiest, Jakob Nikolas Kather, Stephen Gilbert
Journal: The Lancet Digital Health (2024)

Among the rapid integration of artificial intelligence in clinical settings, large language models (LLMs), such as Generative Pre-trained Transformer-4, have emerged as multifaceted tools that have potential for health-care delivery, diagnosis, and patient care. However, deployment of LLMs raises substantial regulatory and safety concerns. Due to their high output variability, poor inherent explainability, and the risk of so-called AI hallucinations, LLM-based health-care applications that serve a medical purpose face regulatory challenges for approval as medical devices under US and EU laws, including the recently passed EU Artificial Intelligence Act. Despite unaddressed risks for patients, including misdiagnosis and unverified medical advice, such applications are available on the market. The regulatory ambiguity surrounding these tools creates an urgent need for frameworks that accommodate their unique capabilities and limitations. Alongside the development of these frameworks, existing regulations should be enforced. If regulators fear enforcing the regulations in a market dominated by supply or development by large technology companies, the consequences of layperson harm will force belated action, damaging the potentiality of LLM-based applications for layperson medical advice.
Temperature-related mortality burden and projected change in 1368 European regions: a modelling study
Authors: David García-León, Pierre Masselot, Malcolm N Mistry, Antonio Gasparrini, Corrado Motta, Luc Feyen, Juan-Carlos Ciscar
Journal: The Lancet Public Health (2024)

Excessively high and low temperatures substantially affect human health. Climate change is expected to exacerbate heat-related morbidity and mortality, presenting unprecedented challenges to public health systems. Since localised assessments of temperature-related mortality risk are essential to formulate effective public health responses and adaptation strategies, we aimed to estimate the current and future temperature-related mortality risk under four climate change scenarios across all European regions.
Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2
Authors: Joseph A Bell, Elizabeth R Davies, Christopher J Brereton, Milica Vukmirovic, James J W Roberts, Kerry Lunn, Leanne Wickens, Franco Conforti, Robert A Ridley, Jessica Ceccato, Lucy N Sayer, David A Johnston, Andres F Vallejo, Aiman Alzetani, Sanjay Jogai, Ben G Marshall, Aurelie Fabre, Luca Richeldi, Phillip D Monk, Paul Skipp, Naftali Kaminski, Emily Offer, Yihua Wang, Donna E Davies, Mark G Jones
Journal: Cell Reports Medicine (2024)
Focus, vigilance, resilience: towards stronger infectious disease surveillance, threat detection and response in the EU/EEA
Authors: Phillip Zucs, Julien Beauté, Daniel Palm, Gianfranco Spiteri
Journal: Eurosurveillance (2024)

This perspective summarises and explains the long-term surveillance framework 2021-2027 for infectious diseases in the European Union/European Economic Area (EU/EEA) published in April 2023. It shows how shortcomings in the areas of public health focus, vigilance and resilience will be addressed through specific strategies in the coming years and how these strategies will lead to stronger surveillance systems for early detection and monitoring of public health threats as well as informing their effective prevention and control. A sharper public health focus is expected from a more targeted list of notifiable diseases, strictly public-health-objective-driven surveillance standards, and consequently, leaner surveillance systems. Vigilance should improve through mandatory event reporting, more automated epidemic intelligence processing and increased use of genomic surveillance. Finally, EU/EEA surveillance systems should become more resilient by modernising the underlying information technology infrastructure, expanding the influenza sentinel surveillance system to other respiratory viruses for better pandemic preparedness, and increasingly exploiting potentially more robust alternative data sources, such as electronic health records and wastewater surveillance. Continued close collaboration across EU/EEA countries will be key to ensuring the full implementation of this surveillance framework and more effective disease prevention and control.
Mobile vaccination units to increase COVID-19 vaccination uptake in areas with lower coverage: a within-neighbourhood analysis using national registration data, the Netherlands, September–December 2021
Authors: Mattijs S Lambooij, Joyce Pijpers, Jan van de Kassteele, Mirjam P Fransen, Susan JM Hahné, Niek Hof, Floor M Kroese, Hester de Melker, Mart van Dijk, Ellen Uiters, Marijn de Bruin
Journal: Eurosurveillance (2024)

Background Vaccine uptake differs between social groups. Mobile vaccination units (MV-units) were deployed in the Netherlands by municipal health services in neighbourhoods with low uptake of COVID-19 vaccines. Aim We aimed to evaluate the impact of MV-units on vaccine uptake in neighbourhoods with low vaccine uptake. Methods We used the Dutch national-level registry of COVID-19 vaccinations (CIMS) and MV-unit deployment registrations containing observations in 253 neighbourhoods where MV-units were deployed and 890 contiguous neighbourhoods (total observations: 88,543 neighbourhood-days). A negative binomial regression with neighbourhood-specific temporal effects using splines was used to study the effect. Results During deployment, the increase in daily vaccination rate in targeted neighbourhoods ranged from a factor 2.0 (95% confidence interval (CI): 1.8–2.2) in urbanised neighbourhoods to 14.5 (95% CI: 11.6–18.0) in rural neighbourhoods. The effects were larger in neighbourhoods with more voters for the Dutch conservative Reformed Christian party but smaller in neighbourhoods with a higher proportion of people with non-western migration backgrounds. The absolute increase in uptake over the complete intervention period ranged from 0.22 percentage points (95% CI: 0.18–0.26) in the most urbanised neighbourhoods to 0.33 percentage point (95% CI: 0.28–0.37) in rural neighbourhoods. Conclusion Deployment of MV-units increased daily vaccination rate, particularly in rural neighbourhoods, with longer travel distance to permanent vaccination locations. This public health intervention shows promise to reduce geographic and social health inequalities, but more proactive and long-term deployment is required to identify its potential to substantially contribute to overall vaccination rates at country level.
Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension
Authors: Qingqing Chu, Yujia Li, Jichao Wu, Yanjiao Gao, Xiangyun Guo, Jing Li, Hang Lv, Min Liu, Wei Tang, Peng Zhan, Tao Zhang, Huili Hu, Hong Liu, Jinpeng Sun, Xiaojie Wang, Fan Yi
Journal: Circulation Research (2024)

BACKGROUND: Despite endothelial dysfunction being an initial step in the development of hypertension and associated cardiovascular/renal injuries, effective therapeutic strategies to prevent endothelial dysfunction are still lacking. GPR183 (G protein-coupled receptor 183), a recently identified G protein-coupled receptor for oxysterols and hydroxylated metabolites of cholesterol, has pleiotropic roles in lipid metabolism and immune responses. However, the role of GPR183 in the regulation of endothelial function remains unknown. METHODS: Endothelial-specific GPR183 knockout mice were generated and used to examine the role of GPR183 in endothelial senescence by establishing 2 independent hypertension models: desoxycorticosterone acetate/salt-induced and Ang II (angiotensin II)–induced hypertensive mice. Echocardiography, transmission electron microscopy, blood pressure measurement, vasorelaxation response experiments, flow cytometry analysis, and chromatin immunoprecipitation analysis were performed in this study. RESULTS: Endothelial GPR183 was significantly induced in hypertensive mice, which was further confirmed in renal biopsies from subjects with hypertensive nephropathy. Endothelial-specific deficiency of GPR183 markedly alleviated cardiovascular and renal injuries in hypertensive mice. Moreover, we found that GPR183 regulated endothelial senescence in both hypertensive mice and aged mice. Mechanistically, GPR183 disrupted circadian signaling by inhibiting PER1 (period circadian regulator 1) expression, thereby facilitating endothelial senescence and dysfunction through the cAMP (cyclic adenosine monophosphate)/PKA (protein kinase A)/CREB (cAMP-response element binding protein) signaling pathway. Importantly, pharmacological inhibition of the oxysterol-GPR183 axis by NIBR189 or clotrimazole ameliorated endothelial senescence and cardiovascular/renal injuries in hypertensive mice. CONCLUSIONS: This study discovers a previously unrecognized role of GPR183 in promoting endothelial senescence. Pharmacological targeting of GPR183 may be an innovative therapeutic strategy for hypertension and its associated complications.
Calcium Phosphates: A Key to Next‐Generation In Vitro Bone Modeling
Authors: Ashish Pandit, Abhishek Indurkar, Janis Locs, Håvard Jostein Haugen, Dagnija Loca
Journal: Advanced Healthcare Materials (2024)

Abstract The replication of bone physiology under laboratory conditions is a prime target behind the development of in vitro bone models. The model should be robust enough to elicit an unbiased response when stimulated experimentally, giving reproducible outcomes. In vitro bone tissue generation majorly requires the availability of cellular components, the presence of factors promoting cellular proliferation and differentiation, efficient nutrient supply, and a supporting matrix for the cells to anchor – gaining predefined topology. Calcium phosphates (CaP) are difficult to ignore while considering the above requirements of a bone model. Therefore, the current review focuses on the role of CaP in developing an in vitro bone model addressing the prerequisites of bone tissue generation. Special emphasis is given to the physico‐chemical properties of CaP that promote osteogenesis, angiogenesis and provide sufficient mechanical strength for load‐bearing applications. Finally, the future course of action is discussed to ensure efficient utilization of CaP in the in vitro bone model development field.
Corrigendum to“Synergistically targeting synovium STING pathway for rheumatoid arthritis treatment” [Bioact Mater 24 (2022) 37–53]
Authors: Haotian Shen, Lulu Jin, Qiangqiang Zheng, Ziqiang Ye, Linxiang Cheng, Yuxu Wu, Honghao Wu, Tae Gyong Jon, Wenduo Liu, Zongyou Pan, Zhengwei Mao, Yue Wang
Journal: Bioactive Materials (2024)

[This corrects the article DOI: 10.1016/j.bioactmat.2022.12.001.].