tbuckley/cabot-search huggingface dataset:
Abstract A011: Modeling the coevolution of native and CAR T-cells in large B cell lymphoma reveals a potential biomarker for response to therapy
Authors: Chandler D. Gatenbee, Mark Robertson-Tessi, Maximilian Strobl, Ryan O. Schenck, Bachisio Ziccheddu, Francesco Maura, Frederick Locke, Alexander R.A. Anderson
Journal: Cancer Research (2024)

Abstract Application of CD19 targeted Chimeric Antigen Receptor (CAR) T-cell therapy to large B cell lymphoma (LBCL) has yielded unprecedented clinical outcomes in a cancer largely resistant to conventional chemotherapy. This is highlighted in the recent ZUMA-7 trial, where axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy, yielded a complete response (CR) rate in 65% of patients, an improvement over the 32% CR rate when using standard chemotherapy. The ZUMA-7 trial highlights the potential of CAR T-cell therapy to treat traditionally resistant cancers, but work remains to be done to identify biomarkers predictive of response. Operating under the assumption that CAR T not only directly targets CD19+ tumor cells, but also enhances tumor kill by amplifying the native T-cell populations, we hypothesized that neoantigen burden (NAB) may serve as a useful biomarker to make predictions of response to CAR T. We explore this hypothesis by building upon traditional predator-prey mathematical models to simulate the evolution of LBCL under immune predation and treatment with CAR T-cell therapy. More specifically, in our model native T-cells prey upon tumor cells that carry their cognate neoantigen, and each T-cell has variable search rate proportional to the cognate neoantigen’s recognition potential, modeled using a type III functional response. Tumor cells may mutate during division, always gaining a neoantigen, but possibly also losing HLA function, paving the way for immune escape. In addition to modeling the direct killing of tumor by CAR T, we also explore the synergistic effect of CAR T on native T-cells by modeling increased amplification of, and killing by, native T-cells based on interactions with the CAR T-cell population. Preliminary simulations suggest a high NAB can indeed be predictive of CAR T response, although only if the tumor has not evolved an escape mechanism. Indeed, simulations suggest that high NAB can also be a signature of an immune escaped tumor, as neoantigens become neutral traits once the immune system is removed as a selective force. These results suggest that knowledge of a patients’ NAB and immune competency can be used to guide CAR T treatment decisions. Citation Format: Chandler D. Gatenbee, Mark Robertson-Tessi, Maximilian Strobl, Ryan O. Schenck, Bachisio Ziccheddu, Francesco Maura, Frederick Locke, Alexander R.A. Anderson. Modeling the coevolution of native and CAR T-cells in large B cell lymphoma reveals a potential biomarker for response to therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A011.
Abstract IA014: Detecting epistatic effects among somatic cancer mutations across oncogenesis
Authors: Jorge A. Alfaro-Murillo, Krishna Dasari, Jeffrey P. Townsend
Journal: Cancer Research (2024)

Abstract The somatic evolution of cancer depends on the rate at which new mutations are acquired, as well as the selective pressure acting on them. Further, mutual exclusivity or co-occurrence of somatic variants suggests that current somatic variants can exert antagonistic or synergistic epistatic effects on the selection of new mutations, contributing to a complex landscape of evolutionary trajectories. However, quantifying these epistatic effects—which are essential to estimation of the trajectory of likely cancer genotoypes—has been a challenge, especially for higher-order epistatic effects. To estimate these epistatic effects, we have developed a continuous-time Markov chain model that enables the estimation of mutation origination and fixation, dependent on somatic cancer genotype. Coupling the continuous-time Markov chain model with a mutation-rate deconvolution approach, we have estimated the underlying mutation rates and selection intensities across trajectories of oncogenesis. Specifically, we report the mutation rates, selection intensities, and consequent variant fluxes for lung adenocarcinoma, informed by a compilation of samples from multiple data sets including The Cancer Genome Atlas and the AACR Project GENIE. Furthermore, we compare smoker and nonsmoker tumor cohorts describing the distinct evolutionary trajectories jointly, influenced by differential mutation and also by the differential physiological effects that smoking can have on the selective regime of lung tissue. Our approach enables inference of the most likely routes of site-specific variant evolution, as well as estimation of the selection strength operating on each step along the route—a key component of what we need to know to prioritize, develop, and implement personalized cancer therapies. Citation Format: Jorge A. Alfaro-Murillo, Krishna Dasari, Jeffrey P. Townsend. Detecting epistatic effects among somatic cancer mutations across oncogenesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr IA014.
Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease
Authors: Greta Viebahn, Phillipp Hartmann, Sonja Lang, Münevver Demir, Xinlian Zhang, Derrick E. Fouts, Peter Stärkel, Bernd Schnabl
Journal: Gut Microbes (2024)

The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera Saccharomyces, Kluyveromyces, Scopulariopsis, and the species Candida albicans (C. albicans), Malassezia restricta (M. restricta), Scopulariopsis cordiae (S. cordiae) were significantly increased in patients with ALD, whereas the genera Kazachstania and Mucor were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of Scopulariopsis, Kluyveromyces, M. restricta, and Mucor to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised Scopulariopsis, Kluyveromyces, Mucor, M. restricta, and Kazachstania. For more advanced fibrosis stages (F2-F4), the fungal signature composed of Scopulariopsis, Kluyveromyces, Mucor, and M. restricta achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.
Staring us in the face: resumption of CPAP therapy
Authors: Simon A. Joosten, Pedro R. Genta
Journal: European Respiratory Journal (2024)

Continuous positive airway pressure (CPAP) treatment is the mainstay treatment of obstructive sleep apnoea (OSA). The treatment offers significant benefits, including improvements in cognition, mood [1] and metabolic outcomes [2]. However, CPAP prescription is vexed by the issue of poor compliance, with approximately 34% of patients no longer using the treatment effectively after 6 months [3] and up to 50% off CPAP at 3 years [4]. In this context, the paper by Pépin et al. [4] offers a potential solution to the problem of CPAP treatment failure: a re-trial of CPAP. Re-initiation of CPAP treatment can lead to a significant cohort of long-term CPAP users <https://bit.ly/48nOzbQ>
Reconciling the past and considering the future of pulmonary function test interpretation
Authors: Anh Tuan Dinh-Xuan, Brian L. Graham, Bruce Thompson, Martin R. Miller, Sanja Stanojevic
Journal: European Respiratory Journal (2024)

<h3>Tweetable abstract</h3> <b>Pulmonary function testing, however useful for clinicians, is an evolving tool, and its interpretation is a difficult exercise that requires precision, open-mindedness and modesty</b> https://bit.ly/3S7eiQL
Gut microbiota-derived indole compounds attenuate metabolic dysfunction-associated steatotic liver disease by improving fat metabolism and inflammation
Authors: Byeong Hyun Min, Shivani Devi, Goo Hyun Kwon, Haripriya Gupta, Jin-Ju Jeong, Satya Priya Sharma, Sung-Min Won, Ki-Kwang Oh, Sang Jun Yoon, Hee Jin Park, Jung A Eom, Min Kyo Jeong, Ji Ye Hyun, Nattan Stalin, Tae-Sik Park, Jieun Choi, Do Yup Lee, Sang Hak Han, Dong Joon Kim, Ki Tae Suk
Journal: Gut Microbes (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and its prevalence has increased worldwide in recent years. Additionally, there is a close relationship between MASLD and gut microbiota-derived metabolites. However, the mechanisms of MASLD and its metabolites are still unclear. We demonstrated decreased indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA) in the feces of patients with hepatic steatosis compared to healthy controls. Here, IPA and IAA administration ameliorated hepatic steatosis and inflammation in an animal model of WD-induced MASLD by suppressing the NF-κB signaling pathway through a reduction in endotoxin levels and inactivation of macrophages. Bifidobacterium bifidum metabolizes tryptophan to produce IAA, and B. bifidum effectively prevents hepatic steatosis and inflammation through the production of IAA. Our study demonstrates that IPA and IAA derived from the gut microbiota have novel preventive or therapeutic potential for MASLD treatment.
ERS/ATS spirometry interpretation standards: a gap in grading severity of airflow obstruction
Authors: Surya P. Bhatt, Sandeep Bodduluri, Arie Nakhmani
Journal: European Respiratory Journal (2024)

The European Respiratory Society/American Thoracic Society (ERS/ATS) technical standard on interpretive strategies for routine lung function tests made several major changes in how to interpret spirometry [1]. For the classification of severity, the recommendation is to use z-scores based on age, height and sex. The recommended three-level system would deem a z-score >−1.645 as normal, z-scores between −1.65 and −2.5 as mild impairment, z-scores between −2.5 and −4 as moderate impairment, and z-scores <−4 as severe impairment. There is a gap in the classification scheme recommended by ERS/ATS for staging severity of airflow obstruction <https://bit.ly/3Gop9Pv>
<i>Citrobacter rodentium</i> possesses a functional type II secretion system necessary for successful host infection
Authors: Z Krekhno, SE Woodward, A Serapio-Palacios, J Peña-Díaz, KM Moon, LJ Foster, BB Finlay
Journal: Gut Microbes (2024)

Infectious diarrheal diseases are the third leading cause of mortality in young children, many of which are driven by Gram-negative bacterial pathogens. To establish successful host infections these pathogens employ a plethora of virulence factors necessary to compete with the resident microbiota, and evade and subvert the host defenses. The type II secretion system (T2SS) is one such conserved molecular machine that allows for the delivery of effector proteins into the extracellular milieu. To explore the role of the T2SS during natural host infection, we used Citrobacter rodentium, a murine enteric pathogen, as a model of human intestinal disease caused by pathogenic Escherichia coli such as Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC). In this study, we determined that the C. rodentium genome encodes one T2SS and 22 potential T2SS-secreted protein effectors, as predicted via sequence homology. We demonstrated that this system was functional in vitro, identifying a role in intestinal mucin degradation allowing for its utilization as a carbon source, and promoting C. rodentium attachment to a mucus-producing colon cell line. During host infection, loss of the T2SS or associated effectors led to a significant colonization defect and lack of systemic spread. In mice susceptible to lethal infection, T2SS-deficient C. rodentium was strongly attenuated, resulting in reduced morbidity and mortality in infected hosts. Together these data highlight the important role of the T2SS and its effector repertoire during C. rodentium pathogenesis, aiding in successful host mucosal colonization.
Direct evidence of host-mediated glycosylation of NleA and its dependence on interaction with the COPII complex
Authors: Lindsay Burns, François Le Mauff, Samantha Gruenheid
Journal: Gut Microbes (2024)

Non-LEE-encoded Effector A (NleA) is a type III secreted effector protein of enterohaemorrhagic and enteropathogenic Escherichia coli as well as the related mouse pathogen Citrobacter rodentium. NleA translocation into host cells is essential for virulence. We previously published several lines of evidence indicating that NleA is modified by host-mediated mucin-type O-linked glycosylation, the first example of a bacterial effector protein modified in this way. In this study, we use lectins to provide direct evidence for the modification of NleA by O-linked glycosylation and determine that the interaction of NleA with the COPII complex is necessary for this modification to occur.
TARGETing the utility of CT-guided pleural biopsy facilitated by PET-CT imaging
Authors: Uffe Bodtger, José M. Porcel
Journal: European Respiratory Journal (2024)

<h3>Tweetable abstract</h3> <b>In patients with a suspected malignant effusion and a first non-diagnostic pleural biopsy, a prior PET-CT scan to guide a new biopsy to areas of high FDG uptake using CT visual co-registration does not improve the diagnostic yield</b> https://bit.ly/3tO0W2m
“Every beet you take”: lowering systolic blood pressure and improving vascular function/exercise capacity<i>via</i>the dietary nitrate–nitrite–NO pathway in patients with COPD
Authors: Andrew J. Webb
Journal: European Respiratory Journal (2024)

<h3>Tweetable abstract</h3> <b>Dietary nitrate as beetroot juice taken for 90 days by 81 patients with COPD significantly lowered systolic blood pressure (primary outcome) and improved vascular function and walking distance, with potential to improve cardiovascular risk</b>https://bit.ly/48F2hY6
Atrial fibrillation: stroke prevention
Authors: Tze-Fan Chao, Tatjana S. Potpara, Gregory Y.H. Lip
Journal: The Lancet Regional Health - Europe (2024)

Stroke prevention is central to the management of patients with atrial fibrillation (AF) which has moved towards a more holistic or integrative care approach. The published evidence suggests that management of AF patients following such a holistic approach based on the Atrial fibrillation Better Care (ABC) pathway is associated with a lower risk of stroke and adverse events. Risk assessment, re-assessment and use of direct oral anticoagulants (DOACs) are important for stroke prevention in AF. The stroke and bleeding risks of AF patients are not static and should be re-assessed regularly. Bleeding risk assessment is to address and mitigate modifiable bleeding risk factors, and to identify high bleeding risk patients for early review and follow-up. Well-controlled comorbidities and healthy lifestyles also play an important role to achieve a better clinical outcome. Digital health solutions are increasingly relevant in the diagnosis and management of patients with AF, with the potential to improve stroke prevention. In this review, we provide an update on stroke prevention in AF, including importance of holistic management, risk assessment/re-assessment, and stroke prevention for special AF populations. Evidence-based and structured management of AF patients would reduce the risk of stroke and other adverse events.
Atrial fibrillation: epidemiology, screening and digital health
Authors: Dominik Linz, Monika Gawalko, Konstanze Betz, Jeroen M. Hendriks, Gregory Y.H. Lip, Nicklas Vinter, Yutao Guo, Søren Johnsen
Journal: The Lancet Regional Health - Europe (2024)

Atrial fibrillation (AF) is highly prevalent with a lifetime risk of about 1 in 3–5 individuals after the age of 45 years. Between 2010 and 2019, the global prevalence of AF has risen markedly from 33.5 million to 59 million individuals living with AF. Early detection of AF and implementation of appropriate treatment could reduce the frequency of complications associated with AF. International AF management guidelines recommend opportunistic and systematic screening for AF, but additional data are needed. Digital approaches and pathways have been proposed for early detection and for the transition to early AF management. Mobile health (mHealth) devices provide an opportunity for digital screening and should be part of novel models of care delivery based on integrated AF care pathways. For a broad implementation of mHealth-based, integrated care for patients with chronic diseases as AF, further high quality evidence is necessary. In this review, we present an overview of the present data on epidemiology, screening techniques, and the contribution of digital health solutions to the integrated management of AF. We also provide a systemic review on current data of digital and integrated AF management.
Nintedanib and symptoms of fibrotic lung disease: a glimmer of hope for patients living with pulmonary fibrosis
Authors: Anna J. Podolanczuk, Kerri I. Aronson
Journal: European Respiratory Journal (2024)

<h3>Tweetable abstract</h3> <b>Treatment with nintedanib slows the worsening of dyspnoea and fatigue, stabilises the degree of impact of pulmonary fibrosis, and may actually improve cough</b>https://bit.ly/3S01WbX
Atrial fibrillation: comorbidities, lifestyle, and patient factors
Authors: Eduard Shantsila, Eue-Keun Choi, Deirdre A. Lane, Boyoung Joung, Gregory Y.H. Lip
Journal: The Lancet Regional Health - Europe (2024)

Modern anticoagulation therapy has dramatically reduced the risk of stroke and systemic thromboembolism in people with atrial fibrillation (AF). However, AF still impairs quality of life, increases the risk of stroke and heart failure, and is linked to cognitive impairment. There is also a recognition of the residual risk of thromboembolic complications despite anticoagulation. Hence, AF management is evolving towards a more comprehensive understanding of risk factors predisposing to the development of this arrhythmia, its' complications and interventions to mitigate the risk. This review summarises the recent advances in understanding of risk factors for incident AF and managing these risk factors. It includes a discussion of lifestyle, somatic, psychological, and socioeconomic risk factors. The available data call for a practice shift towards a more individualised approach considering an increasingly broader range of health and patient factors contributing to AF-related health burden. The review highlights the needs of people living with co-morbidities (especially with multimorbidity), polypharmacy and the role of the changing population demographics affecting the European region and globally.
ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease
Authors: J.A. Ledermann, X. Matias-Guiu, F. Amant, N. Concin, B. Davidson, C. Fotopoulou, A. González-Martin, C. Gourley, A. Leary, D. Lorusso, S. Banerjee, L. Chiva, D. Cibula, N. Colombo, S. Croce, A.G. Eriksson, C. Falandry, D. Fischerova, P. Harter, F. Joly, C. Lazaro, C. Lok, S. Mahner, F. Marmé, C. Marth, W.G. McCluggage, I.A. McNeish, P. Morice, S. Nicum, A. Oaknin, J.A. Pérez-Fidalgo, S. Pignata, P.T. Ramirez, I. Ray-Coquard, I. Romero, G. Scambia, J. Sehouli, R. Shapira-Frommer, S. Sundar, D.S.P. Tan, C. Taskiran, W.J. van Driel, I. Vergote, F. Planchamp, C. Sessa, A. Fagotti
Journal: Annals of Oncology (2024)

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.
Atrial fibrillation: better symptom control with rate and rhythm management
Authors: Dhiraj Gupta, Michiel Rienstra, Isabelle C. van Gelder, Laurent Fauchier
Journal: The Lancet Regional Health - Europe (2024)

Atrial fibrillation (AF) is often associated with limiting symptoms, and with significant impairment in quality of life. As such, treatment strategies aimed at symptom control form an important pillar of AF management. Such treatments include a wide variety of drugs and interventions, including, increasingly, catheter ablation. These strategies can be utilised either singly or in combination, to improve and restore quality of life for patients, and this review covers the current evidence base underpinning their use. In this Review, we discuss the pros and cons of rate vs. rhythm control, while offering practical tips to non-specialists on how to utilise various treatments and counsel patients about all relevant treatment options. These include antiarrhythmic and rate control medications, as well as interventions such as cardioversion, catheter ablation, and pace-and-ablate.
Publisher Correction: Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician
Authors: Zoltán Szekanecz, Maya H. Buch, Christina Charles-Schoeman, James Galloway, George A. Karpouzas, Lars Erik Kristensen, Steven R. Ytterberg, Attila Hamar, Roy Fleischmann
Journal: Nature Reviews Rheumatology (2024)
First-line sugemalimab with chemotherapy for advanced esophageal squamous cell carcinoma: a randomized phase 3 study
Authors: Jin Li, Zhendong Chen, Yuxian Bai, Bo Liu, Qingshan Li, Jingdong Zhang, Jun Zhou, Ting Deng, Fuyou Zhou, Shegan Gao, Shujun Yang, Feng Ye, Long Chen, Wei Bai, Xianli Yin, Shundong Cang, Lianke Liu, Yueyin Pan, Hui Luo, Yanxia Ji, Zhen Zhang, Jufeng Wang, Quanliang Yang, Na Li, Rong Huang, Chenglin Qu, Jing Ni, Bo Wang, Yan Xu, Jin Hu, Qingmei Shi, Jason Yang
Journal: Nature Medicine (2024)