tbuckley/cabot-search huggingface dataset:
Estimation of Cancer Deaths Averted From Prevention, Screening, and Treatment Efforts, 1975-2020
Authors: Katrina A. B. Goddard, Eric J. Feuer, Jeanne S. Mandelblatt, Rafael Meza, Theodore R. Holford, Jihyoun Jeon, Iris Lansdorp-Vogelaar, Roman Gulati, Natasha K. Stout, Nadia Howlader, Amy B. Knudsen, Daniel Miller, Jennifer L. Caswell-Jin, Clyde B. Schechter, Ruth Etzioni, Amy Trentham-Dietz, Allison W. Kurian, Sylvia K. Plevritis, John M. Hampton, Sarah Stein, Liyang P. Sun, Asad Umar, Philip E. Castle
Journal: JAMA Oncology (2024)

Cancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites. To quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers. In this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020. Model inputs were based on national data on risk factors, cancer incidence, cancer survival, and mortality due to other causes, and dissemination and effects of prevention, screening (for interception and early detection), and treatment. Simulated or modeled data using parameters derived from multiple birth cohorts of the US population were used. Primary prevention via smoking reduction (lung), screening for interception (cervix and colorectal) or early detection (breast, cervix, colorectal, and prostate), and therapy (breast, colorectal, lung, and prostate). The estimated cumulative number of cancer deaths averted with interventions vs no advances. An estimated 5.94 million cancer deaths were averted for breast, cervical, colorectal, lung, and prostate cancers combined. Cancer prevention and screening efforts averted 8 of 10 of these deaths (4.75 million averted deaths). The contribution of each intervention varied by cancer site. Screening accounted for 25% of breast cancer deaths averted. Averted cervical cancer deaths were nearly completely averted through screening and removal of cancer precursors as treatment advances were modest during the study period. Averted colorectal cancer deaths were averted because of screening and removal of precancerous polyps or early detection in 79% and treatment advances in 21%. Most lung cancer deaths were avoided by smoking reduction (98%) because screening uptake was low and treatment largely palliative before 2014. Screening contributed to 56% of averted prostate cancer deaths. Over the past 45 years, cancer prevention and screening accounted for most cancer deaths averted for these causes; however, their contribution varied by cancer site according to these models using population-level cancer mortality data. Despite progress, efforts to reduce the US cancer burden will require increased dissemination of effective interventions and new technologies and discoveries.
Extracorporeal Photopheresis for the prevention of rejection after lung transplantation – a prospective randomized controlled trial
Authors: Alberto Benazzo, Ara Cho, Sophia Auner, Stefan Schwarz, Zsofia Kovacs, Dariga Ramazanova, Vera Kolovratova, Manuela Branka, Gabriela Muraközy, Elisabeth Hielle-Wittmann, Clemens Aigner, Konrad Hoetzenecker, Thomas Wekerle, Nina Worel, Robert Knobler, Peter Jaksch
Journal: European Respiratory Journal (2024)

Rationale Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD). Objective To investigate the efficacy of ECP as a prophylactic treatment to prevent acute cellular rejection (ACR), CMV infections and reduce the risk of CLAD. Methods Single-center prospective randomized controlled trial conducted at Medical University of Vienna between 2018 and 2020. It included 31 COPD recipients per group. Treatment group underwent extracorporeal photopheresis in addition to standard triple-drug immunosuppression protocol after lung transplantation. Control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation. Results In the control group, 19 patients (61.3%) achieved the primary combined endpoint, compared with only 6 patients (19.4%) in the treatment group (p&lt;0.001). Freedom from high-grade ACR was significantly greater in the ECP group (p=0.045). Cumulative A scores were significantly lower in the ECP group than in the control group at 3 months (0.18±0.44 versus 0.56±0.94, p&lt;0.05) and at 12 months (0.25±0.48 versus 1.0±1.45, p=0.002). The rate of infections was lower in the ECP group with 5 cases and 67 cumulative hospital days compared to 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at three years was significantly greater in the ECP group (p=0.015). Conclusion Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.
Are Cardiovascular Complications the Achilles’ Heel of Osimertinib?
Authors: Nicholas S. Wilcox, Michael G. Fradley
Journal: JAMA Network Open (2024)

Chien-Yu Lin, MD; Wei-Ting Chang, MD; Po-Lan Su, MD, PhD; Chin-Wei Kuo, MD; Jen Yang, MD; Chien-Chung Lin, MD, PhD; Sheng-Hsiang Lin, PhD
Continuous Positive Airway Pressure and Mandibular Advancement Splints: The CHOICE Multi-center Open-Label Randomized Clinical Trial
Authors: Mona M Hamoda, Nelly Hyunh, Najib T. Ayas, Pierre Rompre, Nick Bansback, Jean-François Masse, Patrick Arcache, Gilles Lavigne, Frederic Series, John A Fleetham, Fernanda R. Almeida
Journal: European Respiratory Journal (2024)

RATIONALE Adherence to Continuous Positive Airway Pressure (CPAP) for Obstructive Sleep Apnoea (OSA) continues to be low with high termination rates. Alternative therapies to CPAP are needed. OBJECTIVES To compare objective adherence to CPAP and Mandibular Advancement Splints (MAS) and to evaluate their effectiveness. Additionally, to identify treatment usage patterns and the clinical effectiveness of having both therapies. METHODS This multi-center, double-randomized, three-phase trial (titration/cross-over/observation) was conducted at three Canadian universities. Eligible participants were treatment-naïve with mild to severe OSA. MEASUREMENTS AND MAIN RESULTS Primary outcome was objectively measured adherence (hours/night) during cross-over phase. Secondary outcomes included efficacy during cross-over phase; adherence during observational phase; patient-centered outcomes, blood pressure and side-effects during cross-over and observational phases. Duration of cross-over and observational phases were 2.5 and 6 months respectively. Eighty-one participants were enrolled in the first randomization. Seventy-nine entered the adaptation/titration phase [mean age ( sd ); 52·3 (10·8) years, 58 males], 73 entered the cross-over phase (included in the intention-to-treat analysis) and 64 completed the observation phase. Mean objective adherence over 1-month, MAS showed higher adherence than CPAP, 6·0 versus 5·3 h/night (difference= 0·7 h/night, 95% CI: 0·3–1·2 h, p&lt;0·001). Mean CPAP-MAS difference (95% CI) in efficacy of 10·4 (7·8–13) events/hour, p&lt;0·001. During the observation phase 55% (35/64) of participants chose to alternate therapies. All treatments led to substantial improvement in patient-centered outcomes. CONCLUSIONS Despite the higher efficacy of CPAP and higher adherence to MAS, both demonstrate comparable clinical effectiveness on patient-centered outcomes. Having both CPAP and MAS can improve long-term management of OSA.
Alteration of the Tumor Microenvironment With Intratumoral Dendritic Cells Before Chemotherapy in <i>ERBB2</i> Breast Cancer
Authors: Hyo S. Han, Amy L. Aldrich, Saurabh K. Garg, R. Jared Weinfurtner, Jonathan V. Nguyen, Qianxing Mo, Junmin Whiting, Jennifer Childress, Hatem Soliman, Ricardo Costa, Avan Armaghani, Aixa Soyano, John Kiluk, Susan Hoover, Marie C. Lee, Nazanin Khakpour, Nithin Shenoi, Zena Jameel, Gary K. Koski, Brian J. Czerniecki
Journal: JAMA Oncology (2024)

Importance Current chemotherapy regimens for patients with ERBB2 (formerly HER 2)–positive breast cancer are associated with considerable morbidity. These patients may benefit from more effective and less toxic therapies. Objective To evaluate the safety, immunogenicity, and preliminary efficacy of intratumoral (IT) delivery of conventional type 1 dendritic cells (cDC1) in combination with ERBB2 -targeted therapies. Design, Setting, and Participants This phase 1 (lead-in phase of a single-center phase 2 trial) nonrandomized clinical trial was conducted at Moffitt Cancer Center (Tampa, Florida). Patients were enrolled from October 2021 to October 2022. Data were analyzed in 2023 Patients with early-stage ERBB2 -positive breast cancer with tumors 1 cm or larger were eligible. Interventions Treatment included IT delivery of cDC1, 6 times weekly, followed by paclitaxel, 80 mg/m 2 , intravenously, 12 times weekly. Trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) were administered intravenously every 3 weeks for 6 cycles starting from day 1 of cDC1 injections. Two dose levels (DLs) of IT cDC1 (DL1 = 50 million and DL2 = 100 million cells) were evaluated, including 6 patients in each DL. Main Outcomes and Measures The primary outcomes were the safety and immune response, and the secondary outcomes were the antitumor efficacy as measured by breast magnetic resonance imaging and residual cancer burden at surgery following neoadjuvant therapy. Results Twelve ERBB2 -positive patients were enrolled and received treatment (DL1 = 6 and DL2 = 6). Nine patients had hormone receptor–positive disease and 3 had hormone receptor–negative disease, with clinical stage I (n = 5), II (n = 4), and III (n = 3). The most frequently observed adverse events with cDC1 were grade 1 to 2 chills (50%), fatigue (41.7%), headache (33%), and injection site reactions (33%). DL2 was associated with a diminished anti- ERBB2 CD4 T-helper 1 blood response with a concomitant increase in innate and adaptive responses within the tumor. Preimmunotherapy and postimmunotherapy breast magnetic resonance imaging results showed 9 objective responses, 6 partial responses, 3 complete responses, and 3 stable diseases. Following surgery, 7 patients had a pathologic complete response. Conclusions and Relevance In this nonrandomized clinical trial, the addition of IT cDC1 and trastuzumab/pertuzumab before neoadjuvant chemotherapy was well tolerated with manageable adverse effects. Based on safety and immunogenicity, DL2 was selected for the phase 2 dose. Trial Registration ClinicalTrials.gov Identifier: NCT05325632
Treating Sleep-Disordered Breathing for Cardiovascular Outcomes: Observational and Randomised Trial Evidence
Authors: T. Douglas Bradley, Alexander G. Logan, John S. Floras
Journal: European Respiratory Journal (2024)

Sleep-disordered breathing (SDB) is considered a risk factor for cardiovascular disease. Obstructive sleep apnea (OSA) can be treated with continuous positive airway pressure and central sleep apnea (CSA), in patients with heart failure and reduced ejection fraction (HFrEF), by peak-flow-triggered adaptive servo-ventilation (ASV PF ). Presently, there is equipoise as to whether treating SDB prevents cardiovascular events. Some propose treatment for this indication, based on observational data, while others argue against because of the lack of randomised trial evidence. This review evaluates literature concerning the cardiovascular effects of treating SDB with positive airway pressure devices in individuals with and without cardiovascular diseases. Nine observational studies report significantly lower cardiovascular event rates in those treated, than in those not treated, for SDB. Conversely, 12 randomised trials in which excessive daytime sleepiness was generally an exclusion criterion showed no reduction in cardiovascular event rates. The SERVE-HF trial showed an increase in mortality with use of minute ventilation triggered ASV for CSA in patients with HFrEF. In the ADVENT-HF trial, treating HFrEF patients with co-existing OSA or CSA using ASV PF was safe and improved sleep structure and heart failure-related quality of life but did not reduce all-cause mortality or cardiovascular events. More evidence is required to determine whether treating CSA in patients with HRrEF prevents cardiovascular events and improves survival. Presently, the rationale for treating SDB with PAP remains improving sleep structure and quality of life, as well as relieving excessive daytime sleepiness, but not reducing cardiovascular events.
Childhood interstitial lung disease survivors in adulthood: a European collaborative study
Authors: Effrosyni D. Manali, Matthias Griese, Nadia Nathan, Yurdagül Uzunhan, Raphael Borie, Katarzyna Michel, Nicolaus Schwerk, Justyna Fijolek, Elżbieta Radzikowska, Felix Chua, Rishi Pabary, Nesrin Mogulkoc, Cormac McCarthy, Maria Kallieri, Andriana I Papaioannou, Nural Kiper, Martina Koziar Vasakova, Ladislav Lacina, Maria Molina-Molina, Alba Torrent-Vernetta, Theofanis Tsiligiannis, Bulent Karadag, Maria Kokosi, Elisabetta A Renzoni, Coline HM van Moorsel, Ilaria Campo, Elisabeth Bendstrup, Thomas Skovhus Prior, Antje Prasse, Francesco Bonella, Vincent Cottin, Rémi Diesler, Antoine Froidure, Lykourgos Kolilekas, Lampros Fotis, Konstantinos Douros, Athanasios G. Kaditis, Florence Jeny, Simon Chauveau, Hilario Nunes, Azrine Dahbia, Francesca Mariani, Joanne J van der Vis, Karlijn Groen, Ela Erdem Eralp, Yasemin Gokdemir, Derya Kocakaya, Sehnaz Olgun Yildizeli, Ebru Yalçın, Nagehan Emiralioğlu, Halime Nayir Buyuksahin, Helen O'Brien, Oguz Karcıoglu, Demet Can, Alper Ezircan, Gokcen Kartal Ozturk, Nesrin Ocal, Hasan Yuksel, Sedef Narin Tongal, Martina Safrankova, Katerina Kourtesi, Camille Louvrier, Caroline Kannengiesser, Aurelie Fabre, Marie Legendre, Bruno Crestani, Petr Pohunek, Andrew Bush, Spyros A. Papiris
Journal: European Respiratory Journal (2024)

Background Interstitial lung disease (ILD) is rarer in children (chILD) than adults, but with increasing diagnostic awareness, more cases are being discovered. chILD prognosis is often poor, but increasing numbers are now surviving into adulthood. Aim To characterize chILD-survivors and identify their impact on adult-ILD centers. Methods European study (34 adult-ILD and chILD centers) reporting incident/prevalent cases of chILD-survivors from January to July 2023. Epidemiological, clinical, physiological and genetic data were collected. Results 244 patients were identified with median (years) (IQR) age at diagnosis 12.5 (6–16), age at study inclusion 25 (22–33), 51% male, 86% non-smokers, median %-predicted FVC and DLCO 70 (47–89) and 48 (32–75) respectively; 32% were prescribed long-term oxygen; 227 (93%) were followed-up in adult centers whereas 17 (7%) never transitioned. Commonest diagnoses (82%) were chILD category B1, 35% (sarcoidosis, hemosiderosis, connective tissue disorders, vasculitis); A4, 21% (surfactant-related); B2, 14% (bronchiolitis obliterans, hypersensitivity pneumonitis); Bz, 13% (unclassified-ILD). Bz patients had the worst functional status. 60% of all patients were still being prescribed corticosteroids. Re-specification of diagnosis and treatment were made after transition for 9.8% and 16% of patients respectively. Not all chILD diagnoses were recognized in adult-ILD classifications. Conclusion chILD survivors are seen in most adult-ILD centers and only a minority continue follow-up in pediatric centers. Survivors have a significant loss of lung function. The heterogeneity of their etiologies and therapeutic requirements has a real impact on adult-ILD centers. Re-specification of diagnosis and treatment may contribute to precision and personalization of management.
GOLD Science Committee recommendations for the use of pre- and post-bronchodilator spirometry for the diagnosis of COPD
Authors: Dave Singh, Robert Stockley, Antonio Anzueto, Alvar Agusti, Jean Bourbeau, Bartolome R. Celli, Gerard J. Criner, MeiLan K. Han, Fernando J. Martinez, Maria Montes de Oca, Obianuju B. Ozoh, Alberto Papi, Ian Pavord, Nicolas Roche, Sandeep Salvi, Don D. Sin, Thierry Troosters, Jadwiga Wedzicha, Jinping Zheng, Claus Volgelmeier, David Halpin
Journal: European Respiratory Journal (2024)

The Global initiative for chronic Obstructive Lung Disease (GOLD) report states that the diagnosis of chronic obstructive pulmonary disease (COPD) should be considered in individuals with chronic respiratory symptoms and / or exposure to risk factors. Forced spirometry demonstrating airflow obstruction after bronchodilation is required to confirm the diagnosis using a threshold of forced expiratory volume in 1 s (FEV 1 ) / forced vital capacity (FVC) ratio&lt;0.7. This GOLD Science Committee review weighs the evidence for using pre- or post-bronchodilator (BD) spirometry to diagnose COPD. Cohort studies have shown that pre- and post-BD spirometry give concordant diagnostic results in most cases, although the prevalence of COPD is up to 36% lower with post-BD values. Discordant results may occur in “volume” or “flow” responders. Volume responders have reduced FVC due to gas trapping causing FEV 1 / FVC ratio &gt;0.7 pre-BD, but a volume response occurs post-BD with a greater improvement in FVC relative to FEV 1 decreasing the ratio to &lt;0.7. Flow responders show a greater FEV 1 improvement relative to FVC which may increase FEV 1 / FVC from &lt;0.7 pre-BD to &gt;0.7 post-BD; these individuals have an increased likelihood of developing post-BD obstruction during follow up and require monitoring longitudinally. GOLD 2025 recommends using pre-BD spirometry to rule out COPD and post-BD measurements to confirm the diagnosis. This will reduce clinical workload. Post-BD results close to the threshold should be repeated to ensure a correct diagnosis is made. Post-BD measurements ensure that volume responders are not overlooked and limit COPD overdiagnosis.
The respiratory microbiome is linked to the severity of RSV infections and the persistence of symptoms in children
Authors: Maartje Kristensen, Wouter A A de Steenhuijsen Piters, Joanne Wildenbeest, Marlies A van Houten, Roy P Zuurbier, Raiza Hasrat, Kayleigh Arp, Mei Ling J N Chu, Marie Billard, Terho Heikkinen, Steve Cunningham, Matthew Snape, Simon B Drysdale, Ryan S Thwaites, Federico Martinon-Torres, Andrew J Pollard, Peter J M Openshaw, Jeroen Aerssen, Justyna Binkowska, Louis Bont, Debby Bogaert
Journal: Cell Reports Medicine (2024)
EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell function
Authors: Yusuke Isshiki, Xi Chen, Matt Teater, Ioannis Karagiannidis, Henna Nam, Winson Cai, Cem Meydan, Min Xia, Hao Shen, Johana Gutierrez, Vigneshwari Easwar Kumar, Sebastián E Carrasco, Madhu M Ouseph, Samuel Yamshon, Peter Martin, Ofir Griess, Efrat Shema, Patrizia Porazzi, Marco Ruella, Renier J Brentjens, Giorgio Inghirami, Roberta Zappasodi, Amy Chadburn, Ari M Melnick, Wendy Béguelin
Journal: Cancer Cell (2024)
Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis
Authors: Ruilong Liu, Xuelian Ren, Yae Eun Park, Huixu Feng, Xinlei Sheng, Xiaohan Song, Roya AminiTabrizi, Hardik Shah, Lingting Li, Yu Zhang, Kalil G Abdullah, Sarah Dubois-Coyne, Hening Lin, Philip A Cole, Ralph J DeBerardinis, Samuel K McBrayer, He Huang, Yingming Zhao
Journal: Cell Metabolism (2024)
The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice
Authors: Xinxin Yu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Valentina Pirro, Margo P Emont, Brian A Droz, Kyla Ai Collins, Chanmin Joung, Mackenzie J Pearson, Corey M James, Gopal J Babu, Vissarion Efthymiou, Ashley Vernon, Mary Elizabeth Patti, Yu A An, Evan D Rosen, Matthew P Coghlan, Ricardo J Samms, Philipp E Scherer, Christine M Kusminski
Journal: Cell Metabolism (2024)
Human DBR1 deficiency impairs stress granule–dependent PKR antiviral immunity
Authors: Shuo Ru, Sisi Tang, Hui Xu, Jiahao Yin, Yan Guo, Liuping Song, Zhenyu Jin, Danyel Lee, Yi-Hao Chan, Xingyao Chen, Luke Buerer, William Fairbrother, Weidong Jia, Jean-Laurent Casanova, Shen-Ying Zhang, Daxing Gao
Journal: The Journal of Experimental Medicine (2024)

The molecular mechanism by which inborn errors of the human RNA lariat-debranching enzyme 1 (DBR1) underlie brainstem viral encephalitis is unknown. We show here that the accumulation of RNA lariats in human DBR1-deficient cells interferes with stress granule (SG) assembly, promoting the proteasome degradation of at least G3BP1 and G3BP2, two key components of SGs. In turn, impaired assembly of SGs, which normally recruit PKR, impairs PKR activation and activity against viruses, including HSV-1. Remarkably, the genetic ablation of PKR abolishes the corresponding antiviral effect of DBR1 in vitro. We also show that Dbr1Y17H/Y17H mice are susceptible to similar viral infections in vivo. Moreover, cells and brain samples from Dbr1Y17H/Y17H mice exhibit decreased G3BP1/2 expression and PKR phosphorylation. Thus, the debranching of RNA lariats by DBR1 permits G3BP1/2- and SG assembly-mediated PKR activation and cell-intrinsic antiviral immunity in mice and humans. DBR1-deficient patients are prone to viral disease because of intracellular lariat accumulation, which impairs G3BP1/2- and SG assembly-dependent PKR activation.
Relieving dyspnoea through the brain
Authors: Andreas von Leupoldt, Carine Karachi, Valentina Jelinčić
Journal: European Respiratory Journal (2024)

ExtractDyspnoea is defined as a symptom conveying an upsetting or distressing experience of breathing awareness, which can vary in quality (e.g. air hunger, increased work/effort of breathing, chest tightness) and intensity, leading to subsequent physiological and behavioural responses [1–3]. It is the cardinal symptom in widespread pulmonary and cardiac diseases, such as asthma [4], COPD [5] and heart failure [6], but is also prevalent in various other common conditions, including neuromuscular diseases, cancer and mental disorders, such as anxiety, panic and functional somatic syndromes [3, 7–10].Shareable abstract @ERSpublicationsDyspnoea is an under-recognised and under-treated major health problem and currently available treatment options are limited. Several promising non-pharmacological treatments have recently been developed that may relieve dyspnoea by treating the brain. https://bit.ly/3XQMH7YShare
Uncovering early COPD? The T-slope as a novel CT biomarker for evaluating airway narrowing
Authors: Miranda Kirby, Grace Parraga
Journal: European Respiratory Journal (2024)

<title>Extract</title> From the tracheobronchial tree structure models described by W<sc>eibel</sc> [1], H<sc>orsfield</sc> and C<sc>umming</sc> [2], and others [3, 4], we know that in the normal lung, the airways follow a branching pattern from the trachea to the distal airways, which locks in a progressive increase in cumulative cross-sectional lumen area. In fact, in the healthy lung, this increase in cross-sectional lumen area is exponential! The small airways, <2 mm in diameter, which can appear as early as the fourth generation of airway branches [5], are believed to be the major site of airflow obstruction in patients with COPD [6]. This insight was based on small airway disease features, including airway narrowing and obliteration, as well as mucus plugging. Using micro-computed tomography (CT) imaging [7], the cross-sectional lumen area of the terminal bronchioles was also shown to be reduced by 99.7% in COPD patients relative to controls. Substantial decreases in the total cross-sectional lumen area in the small airways will necessarily result in deviations from the expected exponential relationship.