tbuckley/cabot-search huggingface dataset:
Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Primary Results From AMEERA-5
Authors: Javier Cortés, Sara A. Hurvitz, Joyce O'Shaughnessy, Suzette Delaloge, Hiroji Iwata, Hope S. Rugo, Patrick Neven, Dheepak Kanagavel, Patrick Cohen, Gautier Paux, Sylvaine Cartot-Cotton, Maya Stefanova-Urena, Laure Deyme, Jihane Aouni, Bernard Sebastien, Aditya Bardia
Journal: Journal of Clinical Oncology (2024)

PURPOSE AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced/metastatic breast cancer (aBC). MATERIALS AND METHODS In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266 ), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2– aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.5 mg once daily + standard palbociclib dosage, stratified by de novo metastatic disease, postmenopausal women, and visceral metastasis. The primary end point was progression-free survival (PFS), compared using a stratified log-rank test with one-sided type I error rate of 2.5%. Secondary end points included overall survival (key secondary), pharmacokinetics, and safety. RESULTS Between October 14, 2020, and December 2, 2021, 1,068 patients were randomly assigned to amcenestrant + palbociclib (N = 534) or letrozole + palbociclib (N = 534). At the interim analysis (median follow-up 8.4 months), the stratified hazard ratio for PFS was 1.209 (95% CI, 0.939 to 1.557; one-sided P value = .9304); therefore, the study was stopped for futility. The 6-month PFS rate was 82.7% (95% CI, 79.0 to 85.8) with amcenestrant + palbociclib versus 86.9% (95% CI, 83.5 to 89.6) with letrozole + palbociclib. In the amcenestrant + palbociclib versus letrozole + palbociclib groups, treatment-emergent adverse events (any grade) occurred in 85.6% versus 85.4% of patients and grade ≥3 events in 46.3% versus 60.8%, respectively. CONCLUSION The AMEERA-5 study was discontinued on the basis of the recommendation of the data monitoring committee at the interim futility analysis. No new safety signals were identified.
Biomarkers Unveil Insights into Pathology of Transitional Epithelial States in Pulmonary Fibrosis
Authors: Christopher Ting, Kristine Konopka, Rachel E Benedeck, David W. H. Riches, Elizabeth F Redente, Justin M. Oldham, Rachel L Zemans
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Biomarkers Unveil Insights into Pathology of Transitional Epithelial States in Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers
Authors: Paul Brinkman, Michael Wilde, Waqar Ahmed, Ran Wang, Marc van der Schee, Shahd Abuhelal, Chad Schaber, Danen Cunoosamy, Graham W Clarke, Anke H. Maitland-van der Zee, Sven-Erik Dahlén, Salman Siddiqui, Stephen J. Fowler
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

The exhaled breath represents an ideal matrix for noninvasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review, we specifically address volatile organic compounds in the breath, with a view toward fulfilling the promise of these as actionable biomarkers, in particular, for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.
Single-Cell RNA Sequencing Shows that Circulating Monocytes Enriched in IFN Signaling Are Associated with Nontuberculous Mycobacteria Pulmonary Disease in Cystic Fibrosis
Authors: Nicola I. Lorè, Andrea Gramegna, Stefano de Pretis, Federico Di Marco, Francesca Giannese, Fabio Saliu, Caterina Oneto, Martina Contarini, Lisa Cariani, Francesco Blasi, Daniela M. Cirillo
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
Risk of Suicide in Individuals with Idiopathic Pulmonary Fibrosis: A Nationwide Cohort Study
Authors: Bo-Guen Kim, Kyungdo Han, Jin-Hyung Jung, Dong Won Park, Sang-Heon Kim, Jang Won Sohn, Ho Joo Yoon, Hyun Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Risk of Suicide in Individuals with Idiopathic Pulmonary Fibrosis: A Nationwide Cohort Study." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Air Pollution in Cardio-Oncology and Unraveling the Environmental Nexus
Authors: Wenqiang Zhu, Sadeer G. Al-Kindi, Sanjay Rajagopalan, Xiaoquan Rao
Journal: JACC CardioOncology (2024)

Although recent advancements in cancer therapies have extended the lifespan of patients with cancer, they have also introduced new challenges, including chronic health issues such as cardiovascular disease arising from pre-existing risk factors or cancer therapies. Consequently, cardiovascular disease has become a leading cause of non–cancer-related death among cancer patients, driving the rapid evolution of the cardio-oncology field. Environmental factors, particularly air pollution, significantly contribute to deaths associated with cardiovascular disease and specific cancers, such as lung cancer. Despite these statistics, the health impact of air pollution in the context of cardio-oncology has been largely overlooked in patient care and research. Notably, the impact of air pollution varies widely across geographic areas and among individuals, leading to diverse exposure consequences. This review aims to consolidate epidemiologic and preclinical evidence linking air pollution to cardio-oncology while also exploring associated health disparities and environmental justice issues.
Neighborhood Archetypes and Cardiovascular Health in Black Breast Cancer Survivors
Authors: Carola T. Sánchez-Díaz, Riddhi A. Babel, Hari S. Iyer, Noreen Goldman, Nur Zeinomar, Andrew G. Rundle, Coral O. Omene, Karen S. Pawlish, Christine B. Ambrosone, Kitaw Demissie, Chi-Chen Hong, Gina S. Lovasi, Elisa V. Bandera, Bo Qin
Journal: JACC CardioOncology (2024)

Maintaining cardiovascular health (CVH) is critical for breast cancer (BC) survivors, particularly given the potential cardiotoxic effects of cancer treatments. Poor CVH among Black BC survivors may be influenced by various area-level social determinants of health, yet the impact of neighborhood archetypes in CVH among this population remains understudied. This study aimed to characterize the neighborhood archetypes where Black BC survivors resided at diagnosis and evaluate their associations with CVH. We assessed CVH 24 months post-diagnosis in 713 participants diagnosed between 2012 and 2017 in the Women's Circle of Health Follow-Up Study, a population-based study of Black BC survivors in New Jersey. Neighborhood archetypes, identified via latent class analysis based on 16 social and built environment features, were categorized into tertiles. Associations between neighborhood archetypes and CVH scores were estimated using polytomous logistic regression. CVH scores were assessed categorically (low, moderate, and optimal) and as continuous variables. On average, Black BC survivors achieved only half of the recommended score for optimal CVH. Among the 4 identified archetypes, women in the Mostly Culturally Black and Hispanic/Mixed Land Use archetype showed the lowest CVH scores. Compared to this archetype, Black BC survivors in the Culturally Diverse/Mixed Land Use archetype were nearly 3 times as likely to have optimal CVH (relative risk ratio: 2.92; 95% CI: 1.58-5.40), with a stronger association observed in younger or premenopausal women. No significant CVH differences were noted for the other 2 archetypes with fewer built environment features. Neighborhood archetypes, integrating social and built environment factors, may represent crucial targets for promoting CVH among BC survivors.
Social Determinants of Health Mediate Racial Disparities in Cardiovascular Disease in Men With Prostate Cancer
Authors: Biniyam G. Demissei, Kyunga Ko, Anran Huang, Daniel J. Lee, Abigail G. Doucette, Amanda M. Smith, Nicholas S. Wilcox, Jacob Reibel, Lova Sun, Manuj Agarwal, Naomi B. Haas, Genevieve Hollis, Jason E. Shpilsky, Samuel U. Takvorian, David J. Vaughn, Jinbo Chen, Rebecca A. Hubbard, Tiffany Powell-Wiley, Clyde Yancy, Vivek Narayan, Bonnie Ky
Journal: JACC CardioOncology (2024)

Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in men with prostate cancer; however, data on racial disparities in CVD outcomes are limited. We quantified the disparities in CVD according to self-identified race and the role of the structural social determinants of health in mediating disparities in prostate cancer patients. A retrospective cohort study of 3,543 prostate cancer patients treated with systemic androgen deprivation therapy (ADT) between 2008 and 2021 at a quaternary, multisite health care system was performed. The multivariable adjusted association between self-reported race (Black vs White) and incident major adverse cardiovascular events (MACE) after ADT initiation was evaluated using cause-specific proportional hazards. Mediation analysis determined the role of theme-specific and overall social vulnerability index (SVI) in explaining the racial disparities in CVD outcomes. Black race was associated with an increased hazard of MACE (HR: 1.38; 95% CI: 1.16-1.65; P < 0.001). The association with Black race was strongest for incident heart failure (HR: 1.79; 95% CI: 1.32-2.43), cerebrovascular disease (HR: 1.98; 95% CI: 1.37-2.87), and peripheral artery disease (HR: 1.76; 95% CI: 1.26-2.45) (P < 0.001). SVI, specifically the socioeconomic status theme, mediated 98% of the disparity in MACE risk between Black and White patients. Black patients are significantly more likely to experience adverse CVD outcomes after systemic ADT compared with their White counterparts. These disparities are mediated by socioeconomic status and other structural determinants of health as captured by census tract SVI. Our findings motivate multilevel interventions focused on addressing socioeconomic vulnerability.
Race and Socioeconomic Status Impact Diagnosis and Clinical Outcomes in Transthyretin Cardiac Amyloidosis
Authors: Bairavi Shankar, Lisa Yanek, Artrish Jefferson, Vivek Jani, Emily Brown, Daniel Tsottles, Jennifer Barranco, Serena Zampino, Mark Ranek, Kavita Sharma, Michael Polydefkis, Joban Vaishnav
Journal: JACC CardioOncology (2024)

Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with significant mortality. The Val122Ile variant, highly prevalent in Black patients, portends poorer survival compared with other ATTR-CM subtypes. Although Val122Ile is biologically more aggressive, the contribution of race and socioeconomic status (SES) to disease outcomes in patients with ATTR-CM is undefined. The aim of this study was to evaluate the impact of race and SES on clinical outcomes in patients with ATTR-CM. Patients with ATTR-CM who received care at Johns Hopkins Hospital between 2006 and 2022 were included. SES was assessed using area deprivation index (ADI). Associations of race and ADI with heart failure (HF) hospitalization and/or death were measured using multivariable logistic or Cox proportional hazards models. Of 282 patients, 225 (80%) were men, and 129 (46%) were Black. Black vs White patients disproportionately constituted the highest ADI (most deprived) category (66% vs 28%; P = 0.004), and Black patients were more likely to have HF hospitalization or death over 5 years compared with White patients (log-rank P < 0.001). Among those with ADI >25, Black patients had a significantly greater hazard of HF hospitalization or death compared with White patients, independent of disease stage at diagnosis (HR: 2.77; 95% CI: 1.45-5.32; P = 0.002). Black patients with low SES may be at greater risk for underdiagnosis and adverse outcomes compared with White patients. Ongoing efforts are needed to improve outcomes in this subset of patients with ATTR-CM.
Black-White Disparities in Submaximal Exercise Capacity Reductions in Breast Cancer Survivors
Authors: Kerryn W. Reding, Warren Szewczyk, Ralph B. D’Agostino, Nathaniel S. O’Connell, Alexi Vasbinder, Moriah P. Bellissimo, Alexander R. Lucas, Vanessa B. Sheppard, Arnethea L. Sutton, Bonnie Ky, Glenn J. Lesser, W. Gregory Hundley
Journal: JACC CardioOncology (2024)
Community Engagement to Advance Equitable Cardio-Oncology Care
Authors: Vanessa B. Sheppard, Arnethea L. Sutton, Shiva Salehian, Anika L. Hines, Karen Patricia Williams, Megan C. Edmonds, Alisa Brewer, Marcie S. Wright, Avirup Guha
Journal: JACC CardioOncology (2024)

• Situating engagement within the experience and priorities of survivors will enhance translational research and health equity. • The TRUST framework provides a guide to expand opportunities for community engagement in cardio-oncology for multiple constituents and across the care continuum. • Training community members as cardio-oncology champions may promote stakeholder representation. • Community connectors can support bidirectional engagement and support for survivors as they transition from active treatment.
Diversity in Cardio-Oncology Clinical Trials
Authors: Yehoda M. Martei, Henrietta A. Afari, Carmen E. Guerra
Journal: JACC CardioOncology (2024)

• Intersectionality of health inequities in CVD and cancer may compound inequities in cardio-oncology. • Equitable access to clinical trials is 1 of many key strategies to mitigate these health disparities. • Cardio-oncology trials should collect and report the race and ethnicity of participants, including disaggregate data on smaller minority groups. • Successful interventions consist of multilevel strategies targeting structural-, clinical-, provider-, and patient-level barriers.
In-situ-formed immunotherapeutic and hemostatic dual drug-loaded nanohydrogel for preventing postoperative recurrence of hepatocellular carcinoma
Authors: Jianji Ke, Yahui Liu, Feiqi Liu, Hongqiao Cai, Xiaocheng Li, Zhiyuan Zhang, Ning Wang, Bingru Shao, Zhihua Wang, Mingda Han, Bai Ji
Journal: Journal of Controlled Release (2024)
Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality
Authors: Koki Hattori, Yusuke Sakaguchi, Tatsufumi Oka, Yuta Asahina, Takayuki Kawaoka, Yohei Doi, Nobuhiro Hashimoto, Yasuo Kusunoki, Satoko Yamamoto, Masafumi Yamato, Ryohei Yamamoto, Isao Matsui, Masayuki Mizui, Jun-Ya Kaimori, Yoshitaka Isaka
Journal: Journal of the American Society of Nephrology (2024)

Key Points Restarting renin-angiotensin system inhibitor after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to hyperkalemia. Our findings support a proactive approach to restarting renin-angiotensin system inhibitor among patients with CKD. Background While renin-angiotensin system inhibitors (RASi) have been the mainstream treatment for patients with CKD, they are often discontinued because of adverse effects such as hyperkalemia and AKI. It is unknown whether restarting RASi after discontinuation improves clinical outcomes. Methods Using the Osaka Consortium for Kidney disease Research database, we performed a target trial emulation study including 6065 patients with an eGFR of 10–60 ml/min per 1.73 m 2 who were followed up by nephrologists and discontinued RASi between 2005 and 2021. With a clone-censor-weight approach, we compared a treatment strategy for restarting RASi within a year after discontinuation with that for not restarting RASi. Patients were followed up for 5 years at maximum after RASi discontinuation. The primary outcome was a composite kidney outcome (initiation of KRT, a ≥50% decline in eGFR, or kidney failure [eGFR &lt;5 ml/min per 1.73 m 2 ]). Secondary outcomes were all-cause death and incidence of hyperkalemia (serum potassium levels ≥5.5 mEq/L). Results Among those who discontinued RASi (mean [SD] age 66 [15] years, 62% male, mean [SD] eGFR 40 [26] ml/min per 1.73 m 2 ), 2262 (37%) restarted RASi within a year. Restarting RASi was associated with a lower hazard of the composite kidney outcome (hazard ratio [HR], 0.85; 95% confidence intervals [CIs], 0.78 to 0.93]) and all-cause death (HR, 0.70; 95% CI, 0.61 to 0.80) compared with not restarting RASi. The incidence of hyperkalemia did not differ significantly between the two strategies (HR, 1.11; 95% CI, 0.96 to 1.27). Conclusions Restarting RASi after discontinuation was associated with a lower risk of kidney outcomes and mortality but not related to the incidence of hyperkalemia.
Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes
Authors: Elaine Ku, Hocine Tighiouart, Charles E. McCulloch, Lesley A. Inker, Ogechi M. Adingwupu, Tom Greene, Raymond O. Estacio, Mark Woodward, Dick de Zeeuw, Julia B. Lewis, Thierry Hannedouche, Fan Fan Hou, Tazeen H. Jafar, Enyu Imai, Giuseppe Remuzzi, Hiddo J.L. Heerspink, Robert D. Toto, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2024)

Key Points Renin-angiotensin system inhibition was favorable for risk of kidney failure (compared with 0% decline with use of placebo or other agents) up to declines in eGFR of 13% over a 3-month period. Relation between eGFR decline after renin-angiotensin system inhibitor initiation and risk of outcomes was stronger in the first 2 years of follow-up and waned over time. Background Declines in GFR occur commonly when renin-angiotensin system (RAS) inhibitors are started. Our objective was to determine the relation between declines in eGFR during trials of RAS inhibition and kidney outcomes. Methods We included participants with CKD (eGFR &lt;60 ml/min per 1.73 m 2 ) from 17 trials of RAS inhibition. The exposure was subacute declines in eGFR expressed as % change between randomization and month 3, and in the subset of trials with data available, we also examined % change in eGFR between randomization and month 1. The primary outcome was kidney failure with replacement therapy. Cox proportional hazards models were used to examine the association between subacute declines in eGFR and risk of kidney failure. We used spline models to identify the threshold of change in eGFR below which RAS inhibition was favorable (conservatively comparing a given decline in eGFR with RAS inhibition to no decline in the comparator). Results A total of 11,800 individuals with mean eGFR 43 (SD 11) ml/min per 1.73 m 2 and median urine albumin-to-creatinine ratio of 362 mg/g (interquartile range, 50–1367) were included, and 1162 (10%) developed kidney failure. The threshold of decline in eGFR that favored the use of RAS inhibitors for kidney failure was estimated to be up to 13% (95% confidence interval, 8% to 17%) over a 3-month interval and up to 21% (95% confidence interval, 15% to 27%) over a 1-month interval after starting RAS inhibitors. Conclusions In patients treated with RAS inhibitors, ≤13% decline in eGFR over a 3-month period or ≤21% decline over a 1-month period was associated with lower risk of kidney failure compared with no decline in those assigned to placebo or other agents.
Human CD127 negative ILC2s show immunological memory
Authors: Laura Mathä, Lisette Krabbendam, Sergio Martinez Høyer, Balthasar A. Heesters, Korneliusz Golebski, Chantal Kradolfer, Maryam Ghaedi, Junjie Ma, Ralph Stadhouders, Claus Bachert, Lars-Olaf Cardell, Nan Zhang, Gabriele Holtappels, Sietze Reitsma, Leanne Carijn Helgers, Teunis B.H. Geijtenbeek, Jonathan M. Coquet, Fumio Takei, Hergen Spits, Itziar Martinez-Gonzalez
Journal: The Journal of Experimental Medicine (2024)

ILC2s are key players in type 2 immunity and contribute to maintaining homeostasis. ILC2s are also implicated in the development of type 2 inflammation–mediated chronic disorders like asthma. While memory ILC2s have been identified in mouse, it is unknown whether human ILC2s can acquire immunological memory. Here, we demonstrate the persistence of CD45RO, a marker previously linked to inflammatory ILC2s, in resting ILC2s that have undergone prior activation. A high proportion of these cells concurrently reduce the expression of the canonical ILC marker CD127 in a tissue-specific manner. Upon isolation and in vitro stimulation of CD127−CD45RO+ ILC2s, we observed an augmented ability to proliferate and produce cytokines. CD127−CD45RO+ ILC2s are found in both healthy and inflamed tissues and display a gene signature of cell activation. Similarly, mouse memory ILC2s show reduced expression of CD127. Our findings suggest that human ILC2s can acquire innate immune memory and warrant a revision of the current strategies to identify human ILC2s.
Genomic reconstruction of the successful establishment of a feralized bovine population on the subantarctic island of Amsterdam
Authors: Mathieu Gautier, Thierry Micol, Louise Camus, Katayoun Moazami-Goudarzi, Michel Naves, Elise Guéret, Stefan Engelen, Arnaud Lemainque, François Colas, Laurence Flori, Tom Druet
Journal: Molecular Biology and Evolution (2024)

The feral cattle of the subantarctic island of Amsterdam provide an outstanding case study of a large mammalian population that was established by a handful of founders and thrived within a few generations in a seemingly inhospitable environment. Here, we investigated the genetic history and composition of this population using genotyping and sequencing data. Our inference showed an intense but brief founding bottleneck around the late 19th century and revealed contributions from European taurine and Indian Ocean Zebu in the founder ancestry. Comparative analysis of whole-genome sequences further revealed a moderate reduction in genetic diversity despite high levels of inbreeding. The brief and intense bottleneck was associated with high levels of drift, a flattening of the site frequency spectrum and a slight relaxation of purifying selection on mildly deleterious variants. Unlike some populations that have experienced prolonged reductions in effective population size, we did not observe any significant purging of highly deleterious variants. Interestingly, the population's success in the harsh environment can be attributed to preadaptation from their European taurine ancestry, suggesting no strong bioclimatic challenge, and also contradicting evidence for insular dwarfism. Genome scan for footprints of selection uncovered a majority of candidate genes related to nervous system function, likely reflecting rapid feralization driven by behavioral changes and complex social restructuring. The Amsterdam Island cattle offers valuable insights into rapid population establishment, feralization, and genetic adaptation in challenging environments. It also sheds light on the unique genetic legacies of feral populations, raising ethical questions according to conservation efforts.
Exploring the role of macrophages in the pathogenesis of Alcohol-associated liver disease
Authors: Prakash Ramachandran, Frank Tacke
Journal: Hepatology (2024)

1Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom 2Department of Hepatology and Gastroenterology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany Correspondence Prakash Ramachandran, Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, 4 Little France Drive, Edinburgh, EH16 4UU, United Kingdom. Email: [email protected]