tbuckley/cabot-search huggingface dataset:
Corrigendum to ‘IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications’
Authors: M. Burotto, Z. Zvirbule, A. Mochalova, Y. Runglodvatana, L. Herraez-Baranda, S.N. Liu, P. Chan, E. Shearer-Kang, X. Liu, N. Tosti, J.A. Zanghi, B. Leutgeb, E. Felip
Journal: Annals of Oncology (2024)

The authors regret that there was an error to the Results section, page 697, of the published manuscript. The corrected sentence is shown below: Serious AEs occurred in 15.4% (n ¼ 38) of patients receiving atezolizumab SC and 17.7% (n ¼ 22) of patients receiving atezolizumab IV (Table 2). The authors would like to apologise for any inconvenience caused. IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indicationsAnnals of OncologyVol. 34Issue 8PreviewAtezolizumab intravenous (IV) is approved for the treatment of various solid tumours. To improve treatment convenience and health care efficiencies, a coformulation of atezolizumab and recombinant human hyaluronidase PH20 was developed for subcutaneous (SC) use. Part 2 of IMscin001 (NCT03735121) was a randomised phase III, open-label, multicentre, noninferiority study comparing the drug exposure of atezolizumab SC with atezolizumab IV. Full-Text PDF Open Access
Baseline 12-Lead Electrocardiographic Characteristics in Genetically Modified Porcine Cardiac Xenotransplant
Authors: Timm Dickfeld, Calvin Kagan, Richard Amara, Susie Hong-Zohlman, Manjula Ananthram, Charles C. Hong, John Sorkin, Vincent See, Stephen Shorofsky, Bart Griffith, Muhammad Mohiuddin
Journal: Circulation (2024)
Comparison of Direct Oral Anticoagulants vs Vitamin K Antagonists After Transcatheter Mitral Valve Replacement
Authors: Nathan El Bèze, Dominique Himbert, Gaspard Suc, Eric Brochet, Nadine Ajzenberg, Audrey Cailliau, John Kikoïne, Clemence Delhomme, Jose Luis Carrasco, Phalla Ou, Bernard Iung, Marina Urena
Journal: Journal of the American College of Cardiology (2024)
Prevalence, Dynamics, and Prognostic Role of Clonal Hematopoiesis of Indeterminate Potential in Patients With Breast Cancer
Authors: Stefania Morganti, Christopher J. Gibson, Qingchun Jin, Katheryn Santos, Ashka Patel, Alex Wilson, Margaret Merrill, Julie Vincuilla, Samantha Stokes, Marla Lipsyc-Sharf, Tonia Parker, Tari A. King, Elizabeth A. Mittendorf, Giuseppe Curigliano, Melissa E. Hughes, Daniel G. Stover, Sara M. Tolaney, Lachelle D. Weeks, Nabihah Tayob, Nancy U. Lin, Judy E. Garber, Peter G. Miller, Heather A. Parsons
Journal: Journal of Clinical Oncology (2024)

PURPOSE Clonal hematopoiesis of indeterminate potential (CHIP) is frequent in patients with solid tumors. Prospective data about CHIP prevalence at breast cancer diagnosis and its dynamic evolution under treatment selective pressure are limited. PATIENTS AND METHODS We performed targeted error-corrected sequencing on 614 samples from 380 patients with breast cancer. We investigated the dynamics of CHIP on prospectively collected paired samples from patients with early breast cancer (eBC) receiving chemotherapy (CT) or endocrine therapy (ET). We assessed the correlation of CHIP with survival in patients with metastatic triple-negative breast cancer (mTNBC). We estimated the risk of progression to treatment-related myeloid neoplasms (t-MN) according to the clonal hematopoiesis risk score (CHRS). In exploratory analyses, we considered clonal hematopoiesis (CH) with variant allele fraction (VAF) ≥0.005. RESULTS CHIP was identified in 15% of patients before treatment. Few CHIP emerged after treatment, and the risk of developing new mutations was similar for patients receiving CT versus ET (odds ratio [OR], 1.16; P = .820). However, CT increased the risk of developing new CH with VAF ≥0.005 (OR, 3.45; P = .002). Five TP53- mutant CH with VAF ≥0.005 emerged among patients receiving CT. Most patients had low risk of t-MN according to the CHRS score. CHIP did not correlate with survival in mTNBC. CONCLUSION CHIP is frequent in patients with breast cancer. In this study, CT did not lead to emergence of new CHIP, and most patients had low risk of developing t-MN. This finding is reassuring, given long life expectancy of patients with eBC and the association of CHIP with morbidity and mortality. However, TP53 -mutant CH with VAF ≥0.005 emerged with CT, which carries high risk of t-MN. Evolution of these small clones and their clinical significance warrant further investigation.
Higher Molecular Injury at Diagnosis of Acute Cellular Rejection Increases the Risk of Lung Allograft Failure: A Clinical Trial
Authors: Michael B. Keller, Xin Tian, Moon Kyoo Jang, Rohan Meda, Ananth Charya, Gerald J. Berry, Charles C. Marboe, Hyesik Kong, Ileana L. Ponor, Shambhu Aryal, Jonathan B. Orens, Pali D. Shah, Steven D. Nathan, Sean Agbor-Enoh
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: The association of acute cellular rejection (ACR) with chronic lung allograft dysfunction (CLAD) in lung transplant recipients has primarily been described before consensus recommendations incorporating restrictive phenotypes. Furthermore, the association of the degree of molecular allograft injury during ACR with CLAD or death remains undefined. Objectives: To investigate the association of ACR with the risk of CLAD or death and to further investigate if this risk depends on the degree of molecular allograft injury. Methods: This multicenter, prospective cohort study included 188 lung transplant recipients. Subjects underwent serial plasma collections for donor-derived cell-free DNA (dd-cfDNA) at prespecified time points and bronchoscopy. Multivariable Cox proportional-hazards analysis was conducted to analyze the association of ACR with subsequent CLAD or death as well as the association of dd-cfDNA during ACR with risk of CLAD or death. Additional outcomes analyses were performed with episodes of ACR categorized as "high risk" (dd-cfDNA ⩾ 1%) and "low risk" (dd-cfDNA < 1%). Measurements and Main Results: In multivariable analysis, ACR was associated with the composite outcome of CLAD or death (hazard ratio [HR], 2.07 [95% confidence interval (CI), 1.05–4.10]; P = 0.036). Elevated dd-cfDNA ⩾ 1% at ACR diagnosis was independently associated with increased risk of CLAD or death (HR, 3.32; 95% CI, 1.31–8.40; P = 0.012). Patients with high-risk ACR were at increased risk of CLAD or death (HR, 3.13; 95% CI, 1.41–6.93; P = 0.005), whereas patients with low–risk status ACR were not. Conclusions: Patients with ACR are at higher risk of CLAD or death, but this may depend on the degree of underlying allograft injury at the molecular level. Clinical trial registered with www.clinicaltrials.gov (NCT 02423070).
Dissecting mechanisms of fecal microbiota transplantation efficacy in disease
Authors: Catherine M. Andary, Kait F. Al, John A. Chmiel, Shaeley Gibbons, Brendan A. Daisley, Seema Nair Parvathy, Saman Maleki Vareki, Dawn M.E. Bowdish, Michael S. Silverman, Jeremy P. Burton
Journal: Trends in Molecular Medicine (2024)
Body Weight Correlates with Molecular Variances in Cancer Patients
Authors: Fengyuan Huang, Peng Xu, Zongliang Yue, Yuwei Song, Kaili Hu, Xinyang Zhao, Min Gao, Zechen Chong
Journal: Cancer Research (2024)

Abstract Overweight and obesity are identified by a high body mass index (BMI) and carry significant health risks due to associated comorbidities. Although epidemiologic data connect overweight/obesity with 13 cancer types, a better understanding of the molecular mechanisms underlying this correlation is needed to improve prevention and treatment strategies. In this study, we conducted a comprehensive analysis of molecular differences between overweight or obese patients and normal weight patients across 14 different cancer types from The Cancer Genome Atlas. Using the propensity score weighting algorithm to control for confounding factors, obesity-specific mutational features were identified, such as higher mutation burden in rectal cancer and biased mutational signatures in other cancers. Differentially expressed genes (DEG) in tumors from patients with overweight/obesity were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of elevated body fat on gene expression profiles and clinical outcomes in patients with cancer. Interestingly, while high BMI seemed to have a negative impact on most cancer types, the normal weight–biased mutational and gene expression patterns indicated overweight/obesity may be beneficial in endometrial cancer, suggesting the presence of an “obesity paradox” in this context. Body fat also significantly impacted the tumor microenvironment by modulating immune cell infiltration, underscoring the importance of understanding the interplay between weight and immune response in cancer progression. Together, this study systematically elucidates the molecular differences corresponding to body weight in multiple cancer types, offering potentially critical insights for developing precision therapy for patients with cancer. Significance: Elucidation of the complex interplay between body weight and the molecular landscape of cancer could potentially guide tailored therapies and improve patient management amid the global obesity crisis.
Host and Microbe Blood Metagenomics Reveals Key Pathways Characterizing Critical Illness Phenotypes
Authors: Lucile P. A. Neyton, Pratik Sinha, Aartik Sarma, Eran Mick, Katrina Kalantar, Stephanie Chen, Nelson Wu, Kevin Delucchi, Hanjing Zhuo, Lieuwe D. J. Bos, Alejandra Jauregui, Antonio Gomez, Carolyn M. Hendrickson, Kirsten N. Kangelaris, Aleksandra Leligdowicz, Kathleen D. Liu, Michael A. Matthay, Charles R. Langelier, Carolyn S. Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Two molecular phenotypes of sepsis and acute respiratory distress syndrome, termed hyperinflammatory and hypoinflammatory, have been consistently identified by latent class analysis in numerous cohorts, with widely divergent clinical outcomes and differential responses to some treatments; however, the key biological differences between these phenotypes remain poorly understood.
Diaphragm Activity during Expiration in Ventilated Critically Ill Patients
Authors: Heder J. de Vries, Annemijn H. Jonkman, Minke C. Holleboom, Harm J. de Grooth, Zhonghua Shi, Coen A. Ottenheijm, Angelique M. de Man, Pieter R. Tuinman, Leo Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Diaphragm Activity During Expiration in Ventilated Critically Ill Patients." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Adjustments of Ventilator Parameters during Operating Room–to–ICU Transition and 28-Day Mortality
Authors: Dario von Wedel, Simone Redaelli, Aiman Suleiman, Luca J. Wachtendorf, Maxime Fosset, Peter Santer, Denys Shay, Ricardo Munoz-Acuna, Guanqing Chen, Daniel Talmor, Boris Jung, Elias N. Baedorf-Kassis, Maximilian S. Schaefer
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Lung-protective mechanical ventilation strategies have been proven beneficial in the operating room (OR) and the ICU. However, differential practices in ventilator management persist, often resulting in adjustments of ventilator parameters when transitioning patients from the OR to the ICU.
Rethinking False Positive Exercise Electrocardiographic Stress Tests by Assessing Coronary Microvascular Function
Authors: Aish Sinha, Utkarsh Dutta, Ozan M. Demir, Kalpa De Silva, Howard Ellis, Samuel Belford, Mark Ogden, Matthew Li Kam Wa, Holly P. Morgan, Ajay M. Shah, Amedeo Chiribiri, Andrew J. Webb, Michael Marber, Haseeb Rahman, Divaka Perera
Journal: Journal of the American College of Cardiology (2024)

Exercise electrocardiographic stress testing (EST) has historically been validated against the demonstration of obstructive coronary artery disease. However, myocardial ischemia can occur because of coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease. The aim of this study was to assess the specificity of EST to detect an ischemic substrate against the reference standard of coronary endothelium-independent and endothelium-dependent microvascular function in patients with angina with nonobstructive coronary arteries (ANOCA). Patients with ANOCA underwent invasive coronary physiological assessment using adenosine and acetylcholine. CMD was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol, with ischemia defined as the appearance of ≥0.1-mV ST-segment depression 80 ms from the J-point on electrocardiography. The study was powered to detect specificity of ≥91%. A total of 102 patients were enrolled (65% women, mean age 60 ± 8 years). Thirty-two patients developed ischemia (ischemic group) during EST, whereas 70 patients did not (nonischemic group); both groups were phenotypically similar. Ischemia during EST was 100% specific for CMD. Acetylcholine flow reserve was the strongest predictor of ischemia during exercise. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of EST dropped to 0%. In patients with ANOCA, ischemia on EST was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.
JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis
Authors: Li Xie, Hui Chen, Li Zhang, Yue Ma, Yuan Zhou, Yong-Yu Yang, Chang Liu, Yu-Li Wang, Ya-Jun Yan, Jia Ding, Xiao Teng, Qiang Yang, Xiu-Ping Liu, Jian Wu
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet.Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. &lt;i&gt;In situ&lt;/i&gt;-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation.Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated &lt;i&gt;in situ&lt;/i&gt; HSC activation and reduced expression of fibrotic genes after BDL.Conclusions: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.
Towards a more integrated research framework for heat-related health risks and adaptation
Authors: Veruska Muccione, Robbert Biesbroek, Sherilee Harper, Marjolijn Haasnoot
Journal: The Lancet Planetary Health (2024)

Advances in research on current and projected heat-related risks from climate change and the associated responses have rapidly developed over the past decade. Modelling architectures of climate impacts and heat-related health risks have become increasingly sophisticated alongside a growing number of experiments and socioeconomic studies, and possible options for heat-related health adaptation are increasingly being catalogued and assessed. However, despite this progress, these efforts often remain isolated streams of research, substantially hampering our ability to contribute to evidence-informed decision making on responding to heat-related health risks. We argue that the integration of scientific efforts towards more holistic research is urgently needed to tackle fragmented evidence and identify crucial knowledge gaps, so that health research can better anticipate and respond to heat-related health risks in the context of a changing climate. In this Personal View, we outline six building blocks, each constituting a research stream, but each needed as part of a more integrated research framework—namely, projected heat-related health risks; adaptation options; the feasibility and effectiveness of adaptation; synergies, trade-offs, and co-benefits of adaptation; adaptation limits and residual risks; and adaptation pathways. We outline their respective importance and discuss their benefits for health-related research and policy.
Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial
Authors: Lei Fan, Zhong-Hua Wang, Lin-Xiaoxi Ma, Song-Yang Wu, Jiong Wu, Ke-Da Yu, Xin-Yi Sui, Ying Xu, Xi-Yu Liu, Li Chen, Wen-Juan Zhang, Xi Jin, Qin Xiao, Ruo-Hong Shui, Yi Xiao, Han Wang, Yun-Song Yang, Xiao-Yan Huang, A-Yong Cao, Jun-Jie Li, Gen-Hong Di, Guang-Yu Liu, Wen-Tao Yang, Xin Hu, Yan Xia, Qian-Nan Liang, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: The Lancet Oncology (2024)
Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
Authors: Carlo Di Lorenzo, Julie Khlevner, Gerardo Rodriguez-Araujo, Wangang Xie, Susanna Y Huh, Masakazu Ando, Jeffrey S Hyams, Samuel Nurko, Marc A Benninga, Michael Simon, Marcella E Hewson, Miguel Saps
Journal: The Lancet. Gastroenterology & hepatology (2024)
Ethnic and socioeconomic inequalities in air pollution exposure: a cross-sectional analysis of nationwide individual-level data from the Netherlands
Authors: Lieke van den Brekel, Virissa Lenters, Joreintje D Mackenbach, Gerard Hoek, Alfred Wagtendonk, Jeroen Lakerveld, Diederick E Grobbee, Ilonca Vaartjes
Journal: The Lancet Planetary Health (2024)

BackgroundAir pollution contributes to a large disease burden and some populations are disproportionately exposed. We aimed to evaluate ethnic and socioeconomic differences in exposure to air pollution in the Netherlands.MethodsWe did a nationwide, cross-sectional analysis of all residents of the Netherlands on Jan 1, 2019. Sociodemographic information was centralised by Statistics Netherlands and mainly originated from the National Population Register, the tax register, and education registers. Concentrations of NO2, PM2·5, PM10, and elemental carbon, modelled by the National Institute for Public Health and the Environment, were linked to the individual-level demographic data. We assessed differences in air pollution exposures across the 40 largest minority ethnic groups. Evaluation of how ethnicity intersected with socioeconomic position in relation to exposures was done for the ten largest ethnic groups, plus Chinese and Indian groups, in both urban and rural areas using multivariable linear regression analyses.FindingsThe total study population consisted of 17 251 511 individuals. Minority ethnic groups were consistently exposed to higher levels of air pollution than the ethnic Dutch population. The magnitude of inequalities varied between the minority ethnic groups, with 3–44% higher exposures to NO2 and 1–9% higher exposures to PM2·5 compared with the ethnic Dutch group. Average exposures were highest for the lowest socioeconomic group. Ethnic inequalities in exposure remained after adjustment for socioeconomic position and were of similar magnitude in urban and rural areas.InterpretationThe variability in air pollution exposure across ethnic and socioeconomic subgroups in the Netherlands indicates environmental injustice at the intersection of social characteristics. The health consequences of the observed inequalities and the underlying processes driving them warrant further investigation.FundingThe Gravitation programme of the Dutch Ministry of Education, Culture, and Science, the Netherlands Organization for Scientific Research, the Netherlands Organisation for Health Research and Development, and Amsterdam University Medical Center.
Long-Acting Reversible Contraception Initiation Among Adolescents After an American Academy of Pediatrics Policy Statement
Authors: Bianca A. Allison, Victor Ritter, Feng-Chang Lin, Kori B. Flower, Martha F. Perry
Journal: JAMA Pediatrics (2024)

This cross-sectional study compares monthly rates of long-acting reversible contraception (LARC) insertions among adolescents before and after an American Academy of Pediatrics (AAP) policy statement recommending LARC for this age group.
Comments on Sports Participation and Transgender Youths—Reply
Authors: Alexander Sin, Katherine Rizzone, Gilbert Gonzales
Journal: JAMA Pediatrics (2024)

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Ultrasound-responsive microbubbles and nanodroplets: A pathway to targeted drug delivery
Authors: Gazendra Shakya, Marco Cattaneo, Giulia Guerriero, Anunay Prasanna, Samuele Fiorini, Outi Supponen
Journal: Advanced Drug Delivery Reviews (2024)

Ultrasound-responsive agents have shown great potential as targeted drug delivery agents, effectively augmenting cell permeability and facilitating drug absorption. This review focuses on two specific agents, microbubbles and nanodroplets, and provides a sequential overview of their drug delivery process. Particular emphasis is given to the mechanical response of the agents under ultrasound, and the subsequent physical and biological effects on the cells. Finally, the state-of-the-art in their pre-clinical and clinical implementation are discussed. Throughout the review, major challenges that need to be overcome in order to accelerate their clinical translation are highlighted.