tbuckley/cabot-search huggingface dataset:
Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS‐STING Pathway
Authors: Kaiyuan Liu, Pengfei Zan, Zihua Li, Hengli Lu, Peng Liu, Li Zhang, Hongsheng Wang, Xiaojun Ma, Feng Chen, Jing Zhao, Wei Sun
Journal: Advanced Healthcare Materials (2024)

Abstract The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti‐tumor immunity through the induction of immunogenic cell death and activation of the cGAS‐STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol‐based nanoplatform (Mn/Fe‐Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS‐STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage‐associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.
Early Mortality in Clinical Trials of Acute Respiratory Distress Syndrome
Authors: Vassilis G. Giannakoulis, Edward J. Schenck, Eleni Papoutsi, David R Price, Jesús Villar, Hina Sarwath, Frank Schmidt, B. Taylor Thompson, Augustine M.K. Choi, Ilias I. Siempos
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons
Authors: Yi Liu, Anthony Flamier, George W Bell, Annette Jun Diao, Troy W Whitfield, Hao-Che Wang, Yizhe Wu, Fabian Schulte, Max Friesen, Ruisi Guo, Maisam Mitalipova, X Shawn Liu, Seychelle M Vos, Richard A Young, Rudolf Jaenisch
Journal: Neuron (2024)
Development and Standardization of an Osteoradionecrosis Classification System in Head and Neck Cancer: Implementation of a Risk-Based Model
Authors: Erin E. Watson, Katrina Hueniken, Junhyung Lee, Shao Hui Huang, Amr El Maghrabi, Wei Xu, Amy C. Moreno, C. Jillian Tsai, Ezra Hahn, Andrew J. McPartlin, Christopher M.K.L. Yao, David P. Goldstein, John R. De Almeida, John N. Waldon, Clifton D. Fuller, Andrew J. Hope, Salvatore L. Ruggiero, Michael Glogauer, Ali A. Hosni
Journal: Journal of Clinical Oncology (2024)

PURPOSE Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN. METHODS Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared with 15 existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection). RESULTS ORN was identified in 219 of 2,732 (8%) consecutive patients with HNC. Factors associated with high risk of ORN were oral cavity or oropharyngeal primaries, received IMRT dose ≥60 Gy, current/ex-smokers, and/or stage III to IV periodontal condition. The ORN rate for high-risk versus low-risk patients was 12.7% versus 3.1% ( P &lt; .001) with an AUC of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, ClinRad, was proposed on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems. CONCLUSION We identified risk factors for ORN and proposed a novel ORN classification system on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN and may facilitate clinical care and clinical trials.
Watching an Evolution in Progress, Cutting-Edge Research Transforming Outcomes in Interstitial Lung Disease: Introduction to an <i>AJRCCM</i> Special Issue
Authors: Toby M. Maher, Anna J. Podolanczuk, Wonder P. Drake, Patricia J. Sime, Oliver Eickelberg, Dawn L. DeMeo, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV
Authors: Annegret Pelchen-Matthews, Amanda Mocroft, Lene Ryom, Michael J. Ross, Shweta Sharma, Steven Coca, Amit Achhra, Elaine Cornell, Russell Tracy, Andrew Phillips, Marta Montero Alonso, Giota Toulomi, Brian K. Agan, Nicholas Medland, Christina M. Wyatt
Journal: Kidney International (2024)

People with human immunodeficiency virus (HIV) are at risk for chronic kidney disease (CKD) due to HIV and antiretroviral therapy (ART) nephrotoxicity. Immediate ART initiation reduces mortality and is now the standard of care, but the long-term impact of prolonged ART exposure on CKD is unknown. To evaluate this, the Strategic Timing of Antiretroviral Treatment (START) trial randomized 4,684 ART-naïve adults with CD4 cell count under 500 cells/mm<sup>3</sup> to immediate versus deferred ART. We previously reported a small but statistically significantly greater decline in estimated glomerular filtration rate (eGFR) over a median of 2.1 years in participants randomized to deferred versus immediate ART. Here, we compare the incidence of CKD events and changes in eGFR and urine albumin/creatinine ratio (UACR) in participants randomized to immediate versus deferred ART during extended follow-up. Over a median of 9.3 years, eight participants experienced kidney failure or kidney-related death, three in the immediate and five in the deferred ART arms, respectively. Over a median of five years of more comprehensive follow-up, the annual rate of eGFR decline was 1.19 mL/min/1.73m<sup>2</sup>/year, with no significant difference between treatment arms (difference deferred – immediate arm 0.055; 95% confidence interval -0.106, 0.217 mL/min/1.73m<sup>2</sup>). Results were similar in models adjusted for baseline covariates associated with CKD, including UACR and APOL1 genotype. Similarly, there was no significant difference between treatment arms in incidence of confirmed UACR 30 mg/g or more (odds ratio 1.13; 95% confidence interval 0.85, 1.51). Thus, our findings provide the most definitive evidence to date in support of the long-term safety of early ART with respect to kidney health.
Housing: an overlooked social determinant of health
Authors: None The Lancet
Journal: The Lancet (2024)

The fact that our homes are inextricably linked to our health is not new. "One might have imagined that science and common sense would by now have appreciated the importance of such considerations" reads a letter on housing and health, published in The Lancet in 1922. Access to adequate housing is recognised as a fundamental human right under law. Why then do we continue to allow so many people to live in unhealthy housing conditions? The UN Statistics Division estimated that in 2022, more than 1 billion people lived in urban slums or slum-like conditions, with this figure expected to triple by 2050.
Offline: One life
Authors: Richard Horton
Journal: The Lancet (2024)

St Margaret's Church, Westminster Abbey. A service of thanksgiving for the life and work of Professor Roger Greenhalgh. Amid the hymns and bible readings, family and former colleagues remembered the life of this unusual vascular surgeon—a man who cared about whether the techniques he was applying to patients had any evidence to support them at all. As I say, unusual. The Reverend Canon presiding over the event, Ralph Godsall, called Greenhalgh's work "pioneering". It was. The Lancet had the privilege of publishing some of his most important randomised trials (eg, EVAR 1).
Digital governance needed to tackle commercial determinants of health
Authors: Ilona Kickbusch, Louise Holly
Journal: The Lancet (2024)

In the Lancet Series on the commercial determinants of health, authors warn that policy inertia is enabling the products and practices of some commercial actors to cause substantial harms to health.1Gilmore AB Fabbri A Baum F et al.Defining and conceptualising the commercial determinants of health.Lancet. 2023; 401: 1194-1213Summary Full Text Full Text PDF PubMed Scopus (120) Google Scholar In the digital environment, the actions of commercial actors (including those involved in social media, information and communications technology, and digital health solutions, to name just a few) are contributing both directly and indirectly to health and wellbeing.2Holly L Wong BLH van Kessel R Awah I Agrawal A Ndili N Optimising adolescent wellbeing in a digital age.BMJ. 2023; 380e068279PubMed Google Scholar Digital platforms are increasingly the main channel through which one accesses products and services and receives messages from commercial actors. Data are constantly being collected by companies and used to shape online experiences. An individual's level of digital connectivity and literacy will determine not only what products and information they can access, but whether digital interactions with commercial actors improve or undermine their health and wellbeing. In The Lancet and Financial Times Commission on Governing Health Futures 2030, we highlight the close relationship between digital determinants and other commercial, social, and environmental determinants of health.3Kickbusch I Piselli D Agrawal A et al.The Lancet and Financial Times Commission on governing health futures 2030: growing up in a digital world.Lancet. 2021; 398: 1727-1776Summary Full Text Full Text PDF PubMed Scopus (107) Google Scholar We argue that identifying the intersections of digital transformations and other determinants of health can help policy makers develop more effective governance responses to the positive and negative effects of digital transformations on health and wellbeing. Calls for stronger governance mechanisms that prioritise public health over commercial interest4Friel S Collin J Daube M et al.Commercial determinants of health: future directions.Lancet. 2023; 401: 1229-1240Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar echo this Commission's recommendations. As we transition into the Digital Transformations for Health Lab, we will be taking these recommendations forward by working with governments, technology companies, youth organisations, and other key actors to address the digital determinants of health and build more trusted digital ecosystems. We declare no competing interests.
Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization
Authors: Andrew J Shattock, Helen C Johnson, So Yoon Sim, Austin Carter, Philipp Lambach, Raymond C W Hutubessy, Kimberly M Thompson, Kamran Badizadegan, Brian Lambert, Matthew J Ferrari, Mark Jit, Han Fu, Sheetal P Silal, Rachel A Hounsell, Richard G White, Jonathan F Mosser, Katy A M Gaythorpe, Caroline L Trotter, Ann Lindstrand, Katherine L O'Brien, Naor Bar-Zeev
Journal: The Lancet (2024)

Background WHO, as requested by its member states, launched the Expanded Programme on Immunization (EPI) in 1974 to make life-saving vaccines available to all globally.To mark the 50-year anniversary of EPI, we sought to quantify the public health impact of vaccination globally since the programme's inception. MethodsIn this modelling study, we used a suite of mathematical and statistical models to estimate the global and regional public health impact of 50 years of vaccination against 14 pathogens in EPI.For the modelled pathogens, we considered coverage of all routine and supplementary vaccines delivered since 1974 and estimated the mortality and morbidity averted for each age cohort relative to a hypothetical scenario of no historical vaccination.We then used these modelled outcomes to estimate the contribution of vaccination to globally declining infant and child mortality rates over this period.Findings Since 1974, vaccination has averted 154 million deaths, including 146 million among children younger than 5 years of whom 101 million were infants younger than 1 year.For every death averted, 66 years of full health were gained on average, translating to 10•2 billion years of full health gained.We estimate that vaccination has accounted for 40% of the observed decline in global infant mortality, 52% in the African region.In 2024, a child younger than 10 years is 40% more likely to survive to their next birthday relative to a hypothetical scenario of no historical vaccination.Increased survival probability is observed even well into late adulthood.Interpretation Since 1974 substantial gains in childhood survival have occurred in every global region.We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50 years.In the context of strengthening primary health care, our results show that equitable universal access to immunisation remains crucial to sustain health gains and continue to save future lives from preventable infectious mortality.
Social health and subsequent cognitive functioning in people aged 50 years and older: examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies
Authors: Jean Stafford, Serhiy Dekhtyar, Anna-Karin Welmer, Davide L Vetrano, Giulia Grande, Erika J Laukka, Anna Marseglia, Vanessa Moulton, Rosie Mansfield, Yiwen Liu, Ke Ning, Karin Wolf-Ostermann, Henry Brodaty, Suraj Samtani, Mohammad Arfan Ikram, René Melis, Joanna Rymaszewska, Dorota Szcześniak, Giorgio Di Gessa, Marcus Richards, Daniel Davis, Praveetha Patalay, Jane Maddock
Journal: The Lancet Healthy Longevity (2024)

Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition.
Social health and cognition: the mediating role of depression and inflammation
Authors: Shian Ming Tan, Iris Rawtaer
Journal: The Lancet Healthy Longevity (2024)

In The Lancet Healthy Longevity, Jean Stafford and colleagues1 investigated whether depressive symptoms and inflammatory markers mediated the pathway between social health and cognitive decline. Remarkably, the use of rich datasets from two large cohort studies, the English Longitudinal Study of Ageing (ELSA) and the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), allowed for initial assessment and subsequent replication of associations between a vast set of social health exposures and cognitive trajectories.
Age-specific mortality trends in heart failure over 25 years: a retrospective Danish nationwide cohort study
Authors: Caroline Hartwell Garred, Morten Malmborg, Mariam Elmegaard Malik, Deewa Zahir, Daniel Mølager Christensen, Anojhaan Arulmurugananthavadivel, Emil L Fosbøl, Gunnar Gislason, John J V McMurray, Mark C Petrie, Charlotte Andersson, Lars Køber, Morten Schou
Journal: The Lancet Healthy Longevity (2024)

Despite advances in heart failure care reducing mortality in clinical trials, it remains unclear whether real-life cohorts have had similar improvements in life expectancy across the age spectrum. We aimed to investigate how mortality trends changed in patients with heart failure over the past 25 years, stratified by age groups.
Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial
Authors: Robert P Frantz, Vallerie V McLaughlin, Sandeep Sahay, Pilar Escribano Subías, Ronald L Zolty, Raymond L Benza, Richard N Channick, Kelly M Chin, Anna R Hemnes, Luke S Howard, Olivier Sitbon, Jean-Luc Vachiéry, Roham T Zamanian, Matt Cravets, Robert F Roscigno, David Mottola, Robin Osterhout, Jean-Marie Bruey, Erin Elman, Cindy-ann Tompkins, Ed Parsley, Richard Aranda, Lawrence S Zisman, Hossein-Ardeschir Ghofrani, Yochai Adir, Timothy Baillie, David Baratz, Charles Burger, Murali M. Chakinala, Jose Manual Cifrián Martínez, Marion Delcroix, Nathan Dwyer, Jean M. Elwing, Micah Fisher, Veronica Franco, Ekkehard Grünig, Kristin Highland, Nicholas Hill, Naushad Hirani, Marius Hoeper, Pavel Jansa, Anne Keogh, John Kingrey, Manuel Lopez-Meseguer, John W. McConnell, Sanjay Mehta, Lana Melendres-Groves, Christian Opitz, Joanna Pepke-Zaba, Priya Pillutla, Franck Rahaghi, Amresh Raina, Yael Raviv, Jeffrey Robinson, John Ryan, Jeffrey Sager, Shelley Shapiro, Marc Simon, Kerri Smith, Irina R. Sobol, Namita Sood, Leslie A. Spikes, Stefan Stadler, Wendy Stevens, Roxana Sulica, R. James White
Journal: The Lancet Respiratory Medicine (2024)
Targeting HIF‐1α with Specific DNA Yokes for Effective Anticancer Therapy
Authors: Ying Zhang, Bing Wu, Danqing Liu, Yue Chen, Yanfang Xu, Lengxi Fu, Zhenyu Lin, Gui Wu, Fei Huang
Journal: Advanced Healthcare Materials (2024)

Abstract Hypoxia, a ubiquitous hallmark in cancer, underscores the significance of targeting HIF‐1α, the principal transcriptional factor of hypoxic responses, for effective cancer therapy. Herein, DNA yokes, a novel class of DNA nanomaterials harboring specific HIF‐1α binding sequences (hypoxia response elements, HREs), are introduced as nanopharmaceuticals for cancer treatment. Comprising a basal tetrahedral DNA nanostructure and four HRE‐bearing overhanging chains, DNA yokes exhibit exceptional stability and prolonged intracellular retention. The investigation reveals their capacity to bind HIF‐1α, thereby disrupting its interaction with the downstream genomic DNAs and impeding transcriptional activity. Moreover, DNA yokes facilitate HIF‐1α degradation via the ubiquitination pathway, thereby sequestering it from downstream targets and ultimately promoting its degradation. In addition, DNA yokes attenuate cancer cell proliferation, migration, and invasion under hypoxic conditions, while also displaying preferential accumulation within tumors, thereby inhibiting tumor growth and metastasis in vivo. This study pioneers a novel approach to cancer therapy through the development of DNA‐based drugs characterized by high stability and low toxicity to normal cells, positioning DNA yokes as promising candidates for cancer treatment.
A Chance to Grow and Excel as an Associate Editor of<i>Pharmacological Reviews</i>—Editorial
Authors: Ali H. Eid
Journal: Pharmacological Reviews (2024)

Like many scientists, my first experience with Pharmacological Reviews began when I was a senior undergraduate student. An extensive review in such a highly reputable journal is a gold mine for a student working on a term paper or a presentation. As I continued toward graduate school, when I worked
Robust language-based mental health assessments in time and space through social media
Authors: Siddharth Mangalik, Johannes C Eichstaedt, Salvatore Giorgi, Jihu Mun, Farhan Ahmed, Gilvir Gill, Adithya V Ganesan, Shashanka Subrahmanya, Nikita Soni, Sean A P Clouston, H Andrew Schwartz
Journal: npj Digital Medicine (2024)

Abstract In the most comprehensive population surveys, mental health is only broadly captured through questionnaires asking about “mentally unhealthy days” or feelings of “sadness.” Further, population mental health estimates are predominantly consolidated to yearly estimates at the state level, which is considerably coarser than the best estimates of physical health. Through the large-scale analysis of social media, robust estimation of population mental health is feasible at finer resolutions. In this study, we created a pipeline that used ~1 billion Tweets from 2 million geo-located users to estimate mental health levels and changes for depression and anxiety, the two leading mental health conditions. Language-based mental health assessments (LBMHAs) had substantially higher levels of reliability across space and time than available survey measures. This work presents reliable assessments of depression and anxiety down to the county-weeks level. Where surveys were available, we found moderate to strong associations between the LBMHAs and survey scores for multiple levels of granularity, from the national level down to weekly county measurements (fixed effects β = 0.34 to 1.82 ; p &lt; 0.001). LBMHAs demonstrated temporal validity, showing clear absolute increases after a list of major societal events (+23% absolute change for depression assessments). LBMHAs showed improved external validity, evidenced by stronger correlations with measures of health and socioeconomic status than population surveys. This study shows that the careful aggregation of social media data yields spatiotemporal estimates of population mental health that exceed the granularity achievable by existing population surveys, and does so with generally greater reliability and validity.
Constructing personalized characterizations of structural brain aberrations in patients with dementia using explainable artificial intelligence
Authors: Esten H Leonardsen, Karin Persson, Edvard Grødem, Nicola Dinsdale, Till Schellhorn, James M Roe, Didac Vidal-Piñeiro, Øystein Sørensen, Tobias Kaufmann, Eric Westman, Andre Marquand, Geir Selbæk, Ole A Andreassen, Thomas Wolfers, Lars T Westlye, Yunpeng Wang
Journal: npj Digital Medicine (2024)

Deep learning approaches for clinical predictions based on magnetic resonance imaging data have shown great promise as a translational technology for diagnosis and prognosis in neurological disorders, but its clinical impact has been limited. This is partially attributed to the opaqueness of deep learning models, causing insufficient understanding of what underlies their decisions. To overcome this, we trained convolutional neural networks on structural brain scans to differentiate dementia patients from healthy controls, and applied layerwise relevance propagation to procure individual-level explanations of the model predictions. Through extensive validations we demonstrate that deviations recognized by the model corroborate existing knowledge of structural brain aberrations in dementia. By employing the explainable dementia classifier in a longitudinal dataset of patients with mild cognitive impairment, we show that the spatially rich explanations complement the model prediction when forecasting transition to dementia and help characterize the biological manifestation of disease in the individual brain. Overall, our work exemplifies the clinical potential of explainable artificial intelligence in precision medicine.