tbuckley/cabot-search huggingface dataset:
Airway hyperresponsiveness in asthma: The role of the epithelium
Authors: Peter Bradding, Celeste Porsbjerg, Andréanne Côté, Sven-Erik Dahlén, Teal S. Hallstrand, Christopher E. Brightling
Journal: Journal of Allergy and Clinical Immunology (2024)

Airway hyperresponsiveness (AHR) is a key clinical feature of asthma. The presence of AHR in people with asthma provides the substrate for bronchoconstriction in response to numerous diverse stimuli, contributing to airflow limitation and symptoms including breathlessness, wheeze, and chest tightness. Dysfunctional airway smooth muscle significantly contributes to AHR and is displayed as increased sensitivity to direct pharmacologic bronchoconstrictor stimuli, such as inhaled histamine and methacholine (direct AHR), or to endogenous mediators released by activated airway cells such as mast cells (indirect AHR). Research in in vivo human models has shown that the disrupted airway epithelium plays an important role in driving inflammation that mediates indirect AHR in asthma through the release of cytokines such as thymic stromal lymphopoietin and IL-33. These cytokines upregulate type 2 cytokines promoting airway eosinophilia and induce the release of bronchoconstrictor mediators from mast cells such as histamine, prostaglandin D
Harnessing diversity to study Alzheimer’s disease: A new iPSC resource from the NIH CARD and ADNI
Authors: Laurel A. Screven, Caroline B. Pantazis, Katherine M. Andersh, Samantha Hong, Dan Vitale, Erika Lara, Ray Yueh Ku, Peter Heutink, Jason Meyer, Kelley Faber, Kwangsik Nho, Andrew J. Saykin, Tatiana M. Foroud, Mike A. Nalls, Cornelis Blauwendraat, Andrew Singleton, Priyanka S. Narayan
Journal: Neuron (2024)
A synergistic two-drug therapy specifically targets a DNA repair dysregulation that occurs in p53-deficient colorectal and pancreatic cancers
Authors: Mohammed M. Alruwaili, Justin Zonneville, Maricris N. Naranjo, Hannah Serio, Thomas Melendy, Robert M. Straubinger, Bryan Gillard, Barbara A. Foster, Priyanka Rajan, Kristopher Attwood, Sarah Chatley, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin
Journal: Cell Reports Medicine (2024)

The tumor-suppressor p53 is commonly inactivated in colorectal cancer and pancreatic ductal adenocarcinoma, but existing treatment options for p53-mutant (p53
Characteristics and drivers of fatigue in patients with psoriasis and psoriatic arthritis: A cross sectional study
Authors: Lea Nymand, Lars Erik Kristensen, Simon Francis Thomsen, Jacob P Thyssen, Alexander Egeberg
Journal: Journal of the American Academy of Dermatology (2024)

A multitude of factors may influence fatigue in psoriasis and psoriatic arthritis (PsA); however, their individual fatigue components have not been thoroughly examined.
Author correction to ‘Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer’ [Acta Pharm Sin B 11 (2021) 1853–1866]
Authors: Yi Qian, Meimei Zhao, Qinghua Han, Jingkang Wang, Lixi Liao, Heng Yang, Dan Liu, Pengfei Tu, Hong Liang, Kewu Zeng
Journal: Acta Pharmaceutica Sinica B (2024)

[This corrects the article DOI: 10.1016/j.apsb.2021.01.011.].
The measurement properties and feasibility of FRAIL scale in older adults: A systematic review and meta-analysis
Authors: Yu Xuan NG, Ling Jie CHENG, Yu Yi QUEK, Ruby YU, Xi Vivien WU
Journal: Ageing Research Reviews (2024)

Frailty is a prevalent condition amongst older adults, significantly affecting their quality of life. The FRAIL tool has been purposefully designed for clinical application by assisting healthcare professionals in identifying and managing frailty-related issues in older adults, making it a preferred choice for assessing frailty across diverse older populations. This review aimed to synthesize the measurement properties and feasibility of FRAIL. Guided by COSMIN guidelines, seven databases were searched from inception to 31 Mar 2023. The measurement properties were extracted for quality appraisal of the populations in the studied samples. Where possible, random-effects meta-analysis and meta-regression were used for quantitative synthesis. Eighteen articles containing 273 tests were drawn from 14 different populations. We found that populations testing for criterion validity had high-quality ratings, while construct validity ratings varied based on health status and geographical region. Test-retest reliability had sufficient quality ratings, while scale agreement had sufficient ratings in only four out of 14 populations tested. Responsiveness ratings were insufficient in seven out of eight populations, with inconsistent ratings in one population. Our analysis of missing data across three articles showed a 16.3% rate, indicating good feasibility of the FRAIL. FRAIL is a feasible tool for assessing frailty of older adults in community settings, with good criterion validity and test-retest reliability. However, more research is needed on construct validity and responsiveness.
Effectiveness of pyriproxyfen-pyrethroid and chlorfenapyr-pyrethroid long-lasting insecticidal nets (LLINs) compared with pyrethroid-only LLINs for malaria control in the third year post-distribution: a secondary analysis of a cluster-randomised controlled trial in Benin
Authors: Manfred Accrombessi, Jackie Cook, Edouard Dangbenon, Arthur Sovi, Boulais Yovogan, Landry Assongba, Constantin J Adoha, Bruno Akinro, Cyriaque Affoukou, Germain Gil Padonou, Immo Kleinschmidt, Louisa A Messenger, Mark Rowland, Corine Ngufor, Martin C Akogbeto, Natacha Protopopoff
Journal: The Lancet Infectious Diseases (2024)

Malaria continues to kill approximately 650 000 people each year. There is evidence that some second-generation insecticide-treated nets, which combine insecticide formulations with different modes of action, are protective against malaria while the nets are new; however, evidence for their impact over 3 years is scarce. In this study, we report the third-year results of a cluster-randomised controlled trial assessing the long-term effectiveness of dual-active ingredient long-lasting insecticidal nets (LLINs).
NIR-enhanced Pt single atom/g-C3N4 nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression
Authors: Jianhui Xiang, Xin Yang, Manli Tan, Jianfeng Guo, Yuting Ye, Jiejia Deng, Zhangrui Huang, Hanjie Wang, Wei Su, Jianwen Cheng, Li Zheng, Sijia Liu, Jingping Zhong, Jinmin Zhao
Journal: Bioactive Materials (2024)

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt
Lipid-mediated protein corona regulation with increased apolipoprotein A-I recruitment for glioma targeting
Authors: Yiwei Zhang, Wei Xiao, Siqin He, Xue Xia, Wenqin Yang, Zhihang Yang, Haili Hu, Yushan Wang, Xiaorong Wang, Hanmei Li, Yuan Huang, Huile Gao
Journal: Journal of Controlled Release (2024)
Multi-material 3D printed eutectogel microneedle patches integrated with fast customization and tunable drug delivery
Authors: Huan Liu, Xinmeng Zhou, Aminov Nail, Hao Yu, Zilian Yu, Yue Sun, Kun Wang, Nanbin Bao, Decheng Meng, Liran Zhu, Huanjun Li
Journal: Journal of Controlled Release (2024)
Controlling the function of bioactive worm micelles by enzyme-cleavable non-covalent inter-assembly cross-linking
Authors: Alina Romanovska, Martin Schmidt, Volker Brandt, Jonas Tophoven, Joerg C. Tiller
Journal: Journal of Controlled Release (2024)

Drugs that form self-assembled supramolecular structures to be most-active is a promising way of creating new highly specific and active pharmaceuticals. Controlling the activity of bioactive supramolecular structures such as drug-loaded micelles is possible by both core/shell and inter-assembly cross-linking. However, if the flexibility of the assembly is mandatory for the activity cross-linking is not feasible. Thus, such structures cannot be manipulated in their activity. The present study demonstrates a novel concept to control the activity of not drug-releasing, non-cross-linked bioactive superstructures. This is achieved by formation of nanostructured nanoparticles derived by non-covalent inter-assembly cross-linking of the superstructures. This is shown on the example of amphiphilic diblock-copolymers conjugated with the antibiotic ciprofloxacin (CIP). These polymer-antibiotic conjugates form worm micelles, which greatly activate the conjugated antibiotic without releasing it. Non-covalent inter-assembly cross-linking of these CIP-worm-micelles with amphiphilic triblock copolymers terminated with lipase-cleavable esters leads to nanostructured nanoparticles that resemble cross-linked worm micelles and show an up to 135-fold lower activity than the free worm micelles. The activity of the worm-micelles can be fully recovered by cleaving the end groups of the polymeric cross-linker with lipase.
Comparison of eight prehospital early warning scores in life-threatening acute respiratory distress: a prospective, observational, multicentre, ambulance-based, external validation study
Authors: Miguel A Castro Villamor, María Alonso-Sanz, Raúl López-Izquierdo, Juan F Delgado Benito, Carlos Del Pozo Vegas, Santiago López Torres, Joan B Soriano, José L Martín-Conty, Ancor Sanz-García, Francisco Martín-Rodríguez
Journal: The Lancet Digital Health (2024)
Normative modelling of brain morphometry across the lifespan with CentileBrain: algorithm benchmarking and model optimisation
Authors: Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou
Journal: The Lancet Digital Health (2024)
A computer-aided polyp detection system in screening and surveillance colonoscopy: an international, multicentre, randomised, tandem trial
Authors: Michiel H J Maas, Helmut Neumann, Haim Shirin, Lior H Katz, Ariel A Benson, Arslan Kahloon, Elsa Soons, Rawi Hazzan, Marc J Landsman, Benjamin Lebwohl, Suzanne K Lewis, Visvakanth Sivanathan, Saowanee Ngamruengphong, Harold Jacob, Peter D Siersema
Journal: The Lancet Digital Health (2024)

Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population.
Reducing HIV incidence among young people identifying as sexual and gender minorities
Authors: Ethan Moitra, Laura B Whiteley
Journal: The Lancet Digital Health (2024)

Young people aged 13–24 years accounted for 19% of new HIV diagnoses in 2021 in the USA,1 and a disproportionate number of HIV seroconversions continue to occur among young people who identify as sexual and gender minorities and Black or African American and Hispanic or Latinx young people.2 Empirically supported HIV prevention interventions are crucial to prevent the spread of HIV in young people and vulnerable populations. Moreover, these interventions will need to be scalable and appealing to a diverse spectrum of young people as the field works towards ending the HIV epidemic in the USA.
Modifiable Cardiometabolic Risk Factors in Survivors of Childhood Cancer
Authors: Rawan A Hammoud, Daniel A Mulrooney, Isaac B Rhea, Christine Yu, Jason N Johnson, Eric J Chow, Matthew J Ehrhardt, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Stephanie B Dixon
Journal: JACC CardioOncology (2024)

The growing community of childhood cancer survivors faces a heavy burden of late onset morbidities and mortality, with cardiovascular diseases being the leading noncancer cause. In addition to demographics and cancer treatment exposures, which cannot be altered, cardiometabolic risk factors (obesity, hypertension, diabetes, and dyslipidemia) and frailty potentiate the risk of morbidity and mortality associated with chronic health conditions. Important opportunities exist to target these risk factors and improve late health outcomes for survivors. Unfortunately, limited evidence exists on the optimal methods to prevent, screen, and treat cardiometabolic risk factors among survivors, resulting in significant underdiagnosis and undertreatment. In this review, we discuss the prevalence of, risk factors for, current survivor-specific recommendations, and gaps in knowledge to mitigate potentially modifiable cardiometabolic risk factors and frailty among survivors of childhood cancer.
Towards trustworthy seizure onset detection using workflow notes
Authors: Khaled Saab, Siyi Tang, Mohamed Taha, Christopher Lee-Messer, Christopher Ré, Daniel L. Rubin
Journal: npj Digital Medicine (2024)

Abstract A major barrier to deploying healthcare AI is trustworthiness. One form of trustworthiness is a model’s robustness across subgroups: while models may exhibit expert-level performance on aggregate metrics, they often rely on non-causal features, leading to errors in hidden subgroups. To take a step closer towards trustworthy seizure onset detection from EEG, we propose to leverage annotations that are produced by healthcare personnel in routine clinical workflows—which we refer to as workflow notes—that include multiple event descriptions beyond seizures. Using workflow notes, we first show that by scaling training data to 68,920 EEG hours, seizure onset detection performance significantly improves by 12.3 AUROC (Area Under the Receiver Operating Characteristic) points compared to relying on smaller training sets with gold-standard labels. Second, we reveal that our binary seizure onset detection model underperforms on clinically relevant subgroups (e.g., up to a margin of 6.5 AUROC points between pediatrics and adults), while having significantly higher FPRs (False Positive Rates) on EEG clips showing non-epileptiform abnormalities (+19 FPR points). To improve model robustness to hidden subgroups, we train a multilabel model that classifies 26 attributes other than seizures (e.g., spikes and movement artifacts) and significantly improve overall performance (+5.9 AUROC points) while greatly improving performance among subgroups (up to +8.3 AUROC points) and decreasing false positives on non-epileptiform abnormalities (by 8 FPR points). Finally, we find that our multilabel model improves clinical utility (false positives per 24 EEG hours) by a factor of 2×.
Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests
Authors: Nicolas R Barthélemy, Gemma Salvadó, Suzanne E Schindler, Yingxin He, Shorena Janelidze, Lyduine E Collij, Benjamin Saef, Rachel L Henson, Charles D Chen, Brian A Gordon, Yan Li, Renaud La Joie, Tammie L S Benzinger, John C Morris, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Rik Ossenkoppele, Gil D Rabinovici, Erik Stomrud, Randall J Bateman, Oskar Hansson
Journal: Nature Medicine (2024)

With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n = 1,422) and the US Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) cohort (n = 337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using positron emission tomography (PET) imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area under the curve (AUC) for both between 0.95 and 0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired subcohorts (BioFINDER-2: n = 720; Knight ADRC: n = 50), plasma %p-tau217 had an accuracy, a positive predictive value and a negative predictive value of 89-90% for Aβ PET and 87-88% for tau PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two-cutoffs approach. Blood plasma %p-tau217 demonstrated performance that was clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high-performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.
Integrated Actuation and Sensing: Toward Intelligent Soft Robots
Authors: Shuai Zhou, Yuanhang Li, Qianqian Wang, Zhiyang Lyu
Journal: Cyborg and Bionic Systems (2024)

Soft robotics has received substantial attention due to its remarkable deformability, making it well-suited for a wide range of applications in complex environments, such as medicine, rescue operations, and exploration. Within this domain, the interaction of actuation and sensing is of utmost importance for controlling the movements and functions of soft robots. Nonetheless, current research predominantly focuses on isolated actuation and sensing capabilities, often neglecting the critical integration of these 2 domains to achieve intelligent functionality. In this review, we present a comprehensive survey of fundamental actuation strategies and multimodal actuation while also delving into advancements in proprioceptive and haptic sensing and their fusion. We emphasize the importance of integrating actuation and sensing in soft robotics, presenting 3 integration methodologies, namely, sensor surface integration, sensor internal integration, and closed-loop system integration based on sensor feedback. Furthermore, we highlight the challenges in the field and suggest compelling directions for future research. Through this comprehensive synthesis, we aim to stimulate further curiosity among researchers and contribute to the development of genuinely intelligent soft robots.
Digital transformation of ovarian cancer diagnosis and care
Authors: None The Lancet Digital Health
Journal: The Lancet Digital Health (2024)

March is Ovarian Cancer Awareness Month in the UK. It is the eighth most common cancer in women worldwide, but is often already advanced when initially diagnosed, leading to a 5-year survival rate of approximately 50% or less. Detecting ovarian cancer at an early stage is a difficult task due to the absence or non-specificity of presenting symptoms. Additionally, current diagnostic tests—namely ultrasound imaging to look for atypicalities and tests for blood-based biomarkers—are not reliable for early detection and can lead to unnecessary surgery for benign masses.
Chondrocyte membrane–coated nanoparticles promote drug retention and halt cartilage damage in rat and canine osteoarthritis
Authors: Ronghui Deng, Ruifang Zhao, Zining Zhang, Yang Chen, Meng Yang, Yixuan Lin, Jing Ye, Nan Li, Hao Qin, Xin Yan, Jian Shi, Fuzhen Yuan, Shitang Song, Zijie Xu, Yifan Song, Jiangnan Fu, Bingbing Xu, Guangjun Nie, Jia-Kuo Yu
Journal: Science Translational Medicine (2024)

Osteoarthritis (OA) is a chronic joint disease characterized by progressive degeneration of articular cartilage. A challenge in the development of disease-modifying drugs is effective delivery to chondrocytes. The unique structure of the joint promotes rapid clearance of drugs through synovial fluid, and the dense and avascular cartilage extracellular matrix (ECM) limits drug penetration. Here, we show that poly(lactide- co -glycolic acid) nanoparticles coated in chondrocyte membranes (CM-NPs) were preferentially taken up by rat chondrocytes ex vivo compared with uncoated nanoparticles. Internalization of the CM-NPs was mediated primarily by E-cadherin, clathrin-mediated endocytosis, and micropinocytosis. These CM-NPs adhered to the cartilage ECM in rat knee joints in vivo and penetrated deeply into the cartilage matrix with a residence time of more than 34 days. Simulated synovial fluid clearance studies showed that CM-NPs loaded with a Wnt pathway inhibitor, adavivint (CM-NPs-Ada), delayed the catabolic metabolism of rat and human chondrocytes and cartilage explants under inflammatory conditions. In a surgical model of rat OA, drug-loaded CM-NPs effectively restored gait, attenuated periarticular bone remodeling, and provided chondroprotection against cartilage degeneration. OA progression was also mitigated by CM-NPs-Ada in a canine model of anterior cruciate ligament transection. These results demonstrate the feasibility of using chondrocyte membrane–coated nanoparticles to improve the pharmacokinetics and efficacy of anti-OA drugs.
Prophylactic underwater vessel coagulation for submucosal endoscopy
Authors: Antonio Capogreco, Cesare Hassan, Federico De Blasio, Davide Massimi, Roberto de Sire, Piera Alessia Galtieri, Edward John Despott, Asma Alkandari, Pradeep Bhandari, Antonio Facciorusso, Roberta Maselli, Alessandro Repici
Journal: Gut (2024)
Ethnoracial Risk Variation Across the Psychosis Continuum in the US
Authors: Els van der Ven, Thomas M. Olino, Katharina Diehl, Stephanie M. Nuñez, Griffin Thayer, Miranda A. Bridgwater, Sabrina Ereshefsky, Christie Musket, Sarah Hope Lincoln, R. Tyler Rogers, Mallory J. Klaunig, Emily Soohoo, Jordan E. DeVylder, Rebecca E. Grattan, Jason Schiffman, Lauren M. Ellman, Tara A. Niendam, Deidre M. Anglin
Journal: JAMA Psychiatry (2024)

Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking.
Early Longitudinal Change in Heart Failure Health Status Following Initiation of Canagliflozin
Authors: Reza Mohebi, Philip G. Jones, John A. Spertus, Ildiko Lingvay, David E. Lanfear, Kensey L. Gosch, Mary Birmingham, Mikhail N. Kosiborod, Javed Butler, James L. Januzzi
Journal: JACC Heart Failure (2024)
Prioritizing Maternal Mental Health in Addressing Morbidity and Mortality
Authors: Katherine L. Wisner, Caitlin Murphy, Megan M. Thomas
Journal: JAMA Psychiatry (2024)

The rate of maternal mortality in the United States is 2-fold to 3-fold greater than that in other high-income countries. While many national initiatives have been developed to combat maternal mortality, these efforts often fail to include mental illness.
A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis
Authors: Gideon M. Hirschfield, Christopher L. Bowlus, Marlyn J. Mayo, Andreas E. Kremer, John M. Vierling, Kris V. Kowdley, Cynthia Levy, Alejandra Villamil, Alma L. Ladrón de Guevara Cetina, Ewa Janczewska, Ehud Zigmond, Sook-Hyang Jeong, Yusuf Yilmaz, Yiannis Kallis, Christophe Corpechot, Peter Buggisch, Pietro Invernizzi, Maria Carlota Londoño Hurtado, Sandrin Bergheanu, Ke Yang, Yun-Jung Choi, Daria B. Crittenden, Charles A. McWherter
Journal: New England Journal of Medicine (2024)

Effective treatments for patients with primary biliary cholangitis are limited. Seladelpar, a peroxisome proliferator-activated receptor delta agonist, has potential benefits.