tbuckley/cabot-search huggingface dataset:
Small Left Ventricle in Patients With Atrial Fibrillation Is Associated With Increased Cardiovascular Risk
Authors: Mingxiao Li, Lan Ren, Liu He, Yiwei Lai, Jue Wang, Sitong Li, Xiaodong Peng, Manlin Zhao, Qifan Li, Zixu Zhao, Le Zhou, Chao Jiang, Song Zuo, Xueyuan Guo, Songnan Li, Nian Liu, Chenxi Jiang, Ribo Tang, Deyong Long, Xin Du, Caihua Sang, Jianzeng Dong, Changsheng Ma
Journal: Journal of the American College of Cardiology (2024)
Lanreotide versus placebo for tumour reduction in patients with a 68Ga-DOTATATE PET-positive, clinically non-functioning pituitary macroadenoma (GALANT study): a randomised, multicentre, phase 3 trial with blinded outcome assessment
Authors: Tessel M. Boertien, Madeleine L. Drent, Jan Booij, Charles B.L.M. Majoie, Marcel P.M. Stokkel, Jantien Hoogmoed, Alberto M. Pereira, Nienke R. Biermasz, Suat Simsek, Ronald Groote Veldman, Annick J. Weterings, Juan M. Vink, Michael W.T. Tanck, Eric Fliers, Peter H. Bisschop
Journal: The Lancet Regional Health - Europe (2024)

No established medical treatment options currently exist for patients with non-functioning pituitary macroadenoma (NFPMA). Somatostatin analogues may prevent tumour growth, but randomised controlled trials are lacking.
Managing Implanted Cardiac Electronic Devices in Patients With Severe Tricuspid Regurgitation
Authors: Rebecca T Hahn, Bruce Larry Wilkoff, Susheel Kodali, Ulrika Maria Birgersdotter-Green, Gorav Ailawadi, Karima Addetia, Martin Andreas, Angelo Auricchio, Frederick Ehlert, Isaac George, Aakriti Gupta, Rachel Harrison, Edwin C Ho, Fred Kusumoto, Azeem Latib, Patrick O'Gara, Kristen K Patton, Sean Pinney, Emily P Zeitler, Michael J Mack, Martin B Leon, Laurence M Epstein
Journal: Journal of the American College of Cardiology (2024)
Teleonomy, legibility, and diversity: Do we need more “proxynomics”?
Authors: Oliver Braganza, Yohan J. John, Leigh Caldwell, Dakota E. McCoy
Journal: Behavioral and Brain Sciences (2024)

Abstract When a measure becomes a target, it ceases to be a good measure. (Strathern, 1997) Our target article set out with an ambitious goal: To provide a unified account of the disparate descriptions of proxy failure across not only social and natural sciences but also engineering and artificial intelligence research. Clearly such a task could only truly be achieved by a broad transdisciplinary community. The wide range of commentaries from a remarkable array of disciplines has not only confirmed our main proposition – that the disparate cases do reflect the same core phenomenon of “proxy failure” – but suggests the viability of a new interdisciplinary undertaking that we might call “proxynomics.” Several comments highlighted key issues and extensions, others provided novel illuminating examples and, perhaps most importantly, quite a few proposed viable solutions or at least mitigation strategies.
Cost-effectiveness of the children and young People's health partnership (CYPHP) model of integrated care versus enhanced usual care: analysis of a pragmatic cluster randomised controlled trial in South London
Authors: Marina Soley-Bori, Julia R. Forman, Elizabeth Cecil, James Newham, Raghu Lingam, Ingrid Wolfe, Julia Fox-Rushby
Journal: The Lancet Regional Health - Europe (2024)

BackgroundIntegration of paediatric health services across primary and secondary care holds great promise for the management of chronic conditions, yet limited evidence exists on its cost-effectiveness. This paper reports the results of the economic evaluation of the Children and Young People's Health Partnership (CYPHP) aimed at integrating care for children with common chronic conditions (asthma, eczema, and constipation).MethodsCost-effectiveness, cost-utility and cost-benefit analyses were conducted alongside a pragmatic cluster randomised controlled trial involving 97,970 children in 70 general practices in South London, including 1,731 participants with asthma, eczema and or constipation with self-reported health-related quality of life measures. Analyses considered the National Health Service (NHS)/Personal Social Service (PSS) and societal perspectives, and time horizons of 6 and 12-months. Costs included intervention delivery, health service use (primary and secondary care), referrals to social services, and time lost from work and school. Health outcomes were measured through the Paediatric Quality of Life Inventory, the Child Health Utility 9-Dimensions, and monetarised benefit combining Quality-Adjusted Life Years (QALYs) for children and parental mental well-being. Results present incremental cost-effectiveness ratios (ICERs), compared to a willingness to pay threshold (WTP) of £20,000–30,000/QALY, and net monetary benefit (NMB), with deterministic sensitivity analyses.FindingsAt 6 months, from the NHS/PSS perspective, CYPHP is not cost-effective (ICER = £721,000/QALY), and this result holds at 12 months (ICER = £45,586/QALY). However, under the societal perspective CYPHP falls within WTP thresholds (ICER = £22,966/QALY), with a probability of being cost-effective between 0.4 and 0.6 at £20,000/QALY and £30,000/QALY, respectively. The cost-benefit analysis yields a positive NMB of CYPHP at 12 months £109 under the societal perspective, with similar probabilistic results.InterpretationCYPHP was not cost-effective at 6 months or under the NHS/PSS perspective. Trends towards cost-effectiveness are observed once a longer time horizon and a more inclusive perspective on effects is considered. Further research beyond 12 months is needed as the model becomes firmly embedded into the paediatric healthcare delivery system.FundingThis research was funded by Guy's and St Thomas' Charity, Lambeth and Southwark Clinical Commissioning Groups. The funders had no role in the writing of the manuscript, decision to submit it for publication, or any other process involved in the research.
Enhanced pyroptosis induction with pore-forming gene delivery for osteosarcoma microenvironment reshaping
Authors: Jing-Jun Nie, Bowen Zhang, Peng Luo, Maoguo Luo, Yuwen Luo, Jingjing Cao, Honggang Wang, Jianping Mao, Yonggang Xing, Weifeng Liu, Yuning Cheng, Renxian Wang, Yajun Liu, Xinbao Wu, Xieyuan Jiang, Xiaoguang Cheng, Chi Zhang, Da-Fu Chen
Journal: Bioactive Materials (2024)

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
Commonly used software tools produce conflicting and overly-optimistic AUPRC values
Authors: Wenyu Chen, Chen Miao, Zhenghao Zhang, Cathy Sin-Hang Fung, Ran Wang, Yizhen Chen, Yan Qian, Lixin Cheng, Kevin Y Yip, Stephen Kwok-Wing Tsui, Qin Cao
Journal: Genome biology (2024)

Abstract The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.
A Living Microecological Hydrogel with Microbiota Remodelling and Immune Reinstatement for Diabetic Wound Healing
Authors: Xiaopeng Yang, Tingting Che, Shasha Tian, Yuanyuan Zhang, Yin Zheng, Yufei Zhang, Xinge Zhang, Zhongming Wu
Journal: Advanced Healthcare Materials (2024)

Abstract Dysregulated skin microbiota and compromised immune responses are the major etiological factors for non‐healing diabetic wounds. Current antibacterial strategies fail to orchestrate immune responses and indiscriminately eradicate bacteria at the wound site, exacerbating the imbalance of microbiota. Drawing inspiration from the beneficial impacts that probiotics possess on microbiota, a living microecological hydrogel containing Lactobacillus plantarum and fructooligosaccharide (LP/FOS@Gel) is formulated to remodel dysregulated skin microbiota and reinstate compromised immune responses, cultivating a conducive environment for optimal wound healing. LP/FOS@Gel acts as an “evocator,” skillfully integrating the skin microecology, promoting the proliferation of Lactobacillus , Ralstonia , Muribaculum , Bacillus , and Allobaculum , while eradicating colonized pathogenic bacteria. Concurrently, LP/FOS@Gel continuously generates lactic acid to elicit a reparative macrophage response and impede the activation of the nuclear factor kappa‐B pathway, effectively alleviating inflammation. As an intelligent microecological system, LP/FOS@Gel reinstates the skin's sovereignty during the healing process and effectively orchestrates the harmonious dialogue between the host immune system and microorganisms, thereby fostering the healing of diabetic infectious wounds. These remarkable attributes render LP/FOS@Gel highly advantageous for pragmatic clinical applications.
Text Messages With Financial Incentives for Men With Obesity
Authors: Pat Hoddinott, Catriona O’Dolan, Lisa Macaulay, Stephan U. Dombrowski, James Swingler, Seonaidh Cotton, Alison Avenell, Abraham M. Getaneh, Cindy Gray, Kate Hunt, Frank Kee, Alice MacLean, Michelle McKinley, Claire Torrens, Katrina Turner, Marjon van der Pol, Graeme MacLennan
Journal: JAMA (2024)

Effective weight loss interventions are needed for men with obesity.
Imageable Brachytherapy with Chelator‐Free Radiolabeling Hydrogel
Authors: Zhencun Cui, Liqin Wang, Wei Liu, Dan Xu, Taofeng Zhang, Baoliang Ma, Kai Zhang, Lingyan Yuan, Zhitong Bing, Jiangyan Liu, Bin Liu, Wangsuo Wu, Longlong Tian
Journal: Advanced Healthcare Materials (2024)

Brachytherapy stands as an essential clinical approach for combating locally advanced tumors. Here, an injectable brachytherapy hydrogel is developed for the treatment of both local and metastatic tumor. Fe-tannins nanoparticles are efficiently and stably radiolabeled with clinical used therapeutic radionuclides (such as
Pig models for translational Duchenne muscular dystrophy research
Authors: Michael Stirm, Nikolai Klymiuk, Hiroshi Nagashima, Christian Kupatt, Eckhard Wolf
Journal: Trends in Molecular Medicine (2024)

Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked DMD gene, resulting in the absence of dystrophin, progressive muscle degeneration, and heart failure. Genetically tailored pig models resembling human DMD mutations recapitulate the biochemical, clinical, and pathological hallmarks of DMD with an accelerated disease progression compared to human patients. DMD pigs have been used to evaluate therapeutic concepts such as gene editing to reframe a disrupted DMD reading frame or the delivery of artificial chromosome vectors carrying the complete DMD gene. Moreover, DMD pigs have been instrumental in validating new diagnostic modalities such as multispectral optoacoustic tomography (MSOT) for non-invasive monitoring of disease progression. DMD pigs may thus help to bridge the gap between proof-of-concept studies in cellular or rodent models and clinical studies in patients.
A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety
Authors: Seo-Hyeon Bae, Soyeon Yoo, Jisun Lee, Hyo-Jung Park, Sung Pil Kwon, Harin Jin, Sang-In Park, Yu-Sun Lee, Yoo-Jin Bang, Gahyun Roh, Seonghyun Lee, Sue Bean Youn, In Woo Kim, Ho Rim Oh, Ashraf K. El-Damasy, Gyochang Keum, Hojun Kim, Hyewon Youn, Jae-Hwan Nam, Eun-Kyoung Bang
Journal: Bioactive Materials (2024)

The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control of the COVID-19 pandemic. However, mRNA vaccines have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, and pericarditis. In this study, we investigated the potential of trehalose glycolipids-containing LNP (LNP S050L) to reduce the risks associated with ionizable lipids. Trehalose glycolipids can form hydrogen bonds with polar biomolecules, allowing the formation of a stable LNP structure by replacing half of the ionizable lipids. The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity, respectively. Furthermore, mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity, including in the heart, spleen, and liver, while sustaining gene expression and immune efficiency, compared to conventional LNPs (Con-LNPs). Our findings suggest that LNP S050L, a trehalose glycolipid-based LNP, could facilitate the development of safe mRNA vaccines with improved clinical safety.
Platelets: Orchestrators of immunity in host defense and beyond
Authors: Leo Nicolai, Kami Pekayvaz, Steffen Massberg
Journal: Immunity (2024)

Platelets prevent blood loss during vascular injury and contribute to thrombus formation in cardiovascular disease. Beyond these classical roles, platelets are critical for the host immune response. They guard the vasculature against pathogens via specialized receptors, intracellular signaling cascades, and effector functions. Platelets also skew inflammatory responses by instructing innate immune cells, support adaptive immunosurveillance, and influence antibody production and T cell polarization. Concomitantly, platelets contribute to tissue reconstitution and maintain vascular function after inflammatory challenges. However, dysregulated activation of these multitalented cells exacerbates immunopathology with ensuing microvascular clotting, excessive inflammation, and elevated risk of macrovascular thrombosis. This dichotomy underscores the critical importance of precisely defining and potentially modulating platelet function in immunity.
Ghrelin deletion and conditional ghrelin cell ablation increase pancreatic islet size in mice
Authors: Deepali Gupta, Avi W. Burstein, Dana C. Schwalbe, Kripa Shankar, Salil Varshney, Omprakash Singh, Subhojit Paul, Sean B. Ogden, Sherri Osborne-Lawrence, Nathan P. Metzger, Corine P. Richard, John N. Campbell, Jeffrey M. Zigman
Journal: Journal of Clinical Investigation (2024)
Targeting arrhythmogenic macrophages: lessons learned from arrhythmogenic cardiomyopathy
Authors: Thassio Mesquita, Eugenio Cingolani
Journal: Journal of Clinical Investigation (2024)

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac condition characterized by cardiac remodeling and life-threatening ventricular arrhythmias. In this issue of the JCI, Chelko, Penna, and colleagues mechanistically addressed the intricate contribution of immune-mediated injury in ACM pathogenesis. Inhibition of nuclear factor κ-B (NF-κB) and infiltration of monocyte-derived macrophages expressing C-C motif chemokine receptor-2 (CCR2) alleviated the phenotypic ACM features (i.e., fibrofatty replacement, contractile dysfunction, and ventricular arrhythmias) in desmoglein 2-mutant (Dsg2mut/mut) mice. These findings pave the way for efficacious and targetable immune therapy for patients with ACM.
Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma
Authors: Shuhua Yi, Yuting Yan, Meiling Jin, Supriyo Bhattacharya, Yi Wang, Yiming Wu, Lu Yang, Eva Gine, Guillem Clot, Lu Chen, Ying Yu, Dehui Zou, Jun Wang, An T. Phan, Rui Cui, Fei Li, Qi Sun, Qiongli Zhai, Tingyu Wang, Zhen Yu, Lanting Liu, Wei Liu, Rui Lyv, Weiwei Sui, Wenyang Huang, Wenjie Xiong, Huijun Wang, Chengwen Li, Zhijian Xiao, Mu Hao, Jianxiang Wang, Tao Cheng, Silvia Bea, Alex F. Herrera, Alexey Danilov, Elias Campo, Vu N. Ngo, Lugui Qiu, Lili Wang
Journal: Journal of Clinical Investigation (2024)
LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes
Authors: Jingzhong Ding, Anh Tram Nguyen, Kurt Lohman, Michael T. Hensley, Daniel Parker, Li Hou, Jackson Taylor, Deepak Voora, Janet K. Sawyer, Elena Boudyguina, Michael P. Bancks, Alain Bertoni, James S. Pankow, Jerome I. Rotter, Mark O. Goodarzi, Russell P. Tracy, David M. Murdoch, Stephen S. Rich, Bruce M. Psaty, David Siscovick, Christopher Newgard, David Herrington, Ina Hoeschele, Steven Shea, James H. Stein, Manesh Patel, Wendy Post, David Jacobs, John S. Parks, Yongmei Liu
Journal: Journal of Clinical Investigation (2024)

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Authors: Heather L. Gornik, Herbert D. Aronow, Philip P. Goodney, Shipra Arya, Luke Packard Brewster, Lori Byrd, Venita Chandra, Douglas E. Drachman, Jennifer M. Eaves, Jonathan K. Ehrman, John N. Evans, Thomas S.D. Getchius, J. Antonio Gutiérrez, Beau M. Hawkins, Connie N. Hess, Karen J. Ho, W. Schuyler Jones, Esther S.H. Kim, Scott Kinlay, Lee Kirksey, Debra Kohlman-Trigoboff, Chandler A. Long, Amy West Pollak, Saher S. Sabri, Lawrence B. Sadwin, Eric A. Secemsky, Maya Serhal, Mehdi H. Shishehbor, Diane Treat-Jacobson, Luke R. Wilkins
Journal: Circulation (2024)

The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia).
Posttranslational protein modifications as gatekeepers of cancer immunogenicity
Authors: Emanuela Marchese, Shadmehr Demehri
Journal: Journal of Clinical Investigation (2024)

Triple-negative breast cancer (TNBC) presents a formidable challenge in oncology due to its aggressive phenotype and the immunosuppressive nature of its tumor microenvironment (TME). In this issue of the JCI, Zhu, Banerjee, and colleagues investigated the potential of targeting the OTU domain-containing protein 4 (OTUD4)/CD73 axis to mitigate immunosuppression in TNBC. They identified elevated CD73 expression as a hallmark of immunosuppression in TNBC. Notably, the CD73 expression was regulated by OTUD4-mediated posttranslational modifications. Using ST80, a pharmacologic inhibitor of OTUD4, the authors demonstrated the restoration of cytotoxic T cell function and enhanced efficacy of anti-PD-L1 therapy in preclinical models. These findings underscore the therapeutic potential of targeting the OTUD4/CD73 axis in TNBC.
Time to split: biomarker trajectories in pediatric acute respiratory distress syndrome hint at underlying disease
Authors: Ashley A Zurawel, Bria M Coates
Journal: Journal of Clinical Investigation (2024)

Pediatric acute respiratory distress syndrome (ARDS) is severe, noncardiac hypoxemic respiratory failure that carries a substantial risk of death. Given the complexity of this clinically defined syndrome and the repeated failure of therapeutic trials, there has been an effort to identify subphenotypes of ARDS that may share targetable mechanisms of disease. In this issue of the JCI, Yehya and colleagues measured 19 plasma biomarkers in 279 children over the first seven days of ARDS. Increases in select tissue injury makers and inflammatory cytokines in peripheral blood were associated with multiple organ dysfunction syndrome and death, but not persistent ARDS. These findings argue that splitting patients by clinical and molecular phenotype may be more informative than lumping them under the umbrella diagnosis of ARDS. However, future studies are needed to determine whether these plasma factors represent targetable pathways in lung injury or are a consequence of systemic organ dysfunction.
Anti–4-1BB×PDL1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD1 Blockade
Authors: Seung Hyuck Jeon, Gihoon You, Junsik Park, Youseung Chung, Kyungjin Park, Hyunjoo Kim, Jaehyoung Jeon, Youngkwang Kim, Woo-Chan Son, Da Som Jeong, Eui-Cheol Shin, Jung-Yun Lee, Dai Hoon Han, Jaeho Jung, Su-Hyung Park
Journal: Clinical Cancer Research (2024)

To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti-4-1BB×PDL1 bispecific antibody-ABL503 (also known as TJ-L14B)-was designed to simultaneously target PDL1 and 4-1BB and demonstrated strong antitumor T-cell responses without considerable toxicity. In this study, we investigated the mechanisms by which the combination of ABL503 and anti-PD1 blockade affected the reinvigoration of exhausted tumor-infiltrating CD8+ T cells (CD8+ TIL) and antitumor efficacy.