tbuckley/cabot-search huggingface dataset:
EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care
Authors: Peter W. Hellings, Isam Alobid, Wilma T. Anselmo‐Lima, Manuel Bernal‐Sprekelsen, Leif Bjermer, Lisa Caulley, Adam Chaker, Jannis Constantinidis, Diego M. Conti, Eugenio De Corso, Martin Desrosiers, Zuzana Diamant, Philippe Gevaert, Joseph K. Han, Enrico Heffler, Claire Hopkins, Basile N. Landis, Olga Lourenco, Valerie Lund, Amber U. Luong, Joaquim Mullol, Anju Peters, Carl Philpott, Sietze Reitsma, Dermot Ryan, Glenis Scadding, Brent Senior, Peter Valentin Tomazic, Elina Toskala, Thibaut Van Zele, An‐Sofie Viskens, Martin Wagenmann, W. J. Fokkens
Journal: Allergy (2023)

Abstract Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.
Diagnostic capabilities, clinical features, and longitudinal <scp><i>UBA1</i></scp> clonal dynamics of a nationwide <scp>VEXAS</scp> cohort
Authors: Carmelo Gurnari, Maria Rosaria Pascale, Antonio Vitale, Elisa Diral, Alessandro Tomelleri, Elisa Galossi, Giulia Falconi, Alessandro Bruno, Francesca Crisafulli, Micol Frassi, Chiara Cattaneo, Diego Bertoli, Massimo Bernardi, Annalisa Condorelli, Erika Morsia, Antonella Poloni, Elena Crisà, Daniela Caravelli, Paola Triggianese, Luisa Brussino, Giorgia Battipaglia, Sara Bindoli, Paolo Sfriso, Federico Caroni, Matteo Dragani, Flavia Mallegni, Federica Pilo, Davide Firinu, Antonio Curti, Cristina Papayannidis, Attilio Olivieri, Sharham Kordasti, Francesco Albano, Fabrizio Pane, Pellegrino Musto, Monica Bocchia, Elisabetta Lugli, Massimo Breccia, Marco Frigeni, Lorenzo Dagna, Raffaella Greco, Franco Franceschini, Corrado Campochiaro, Luca Cantarini, Maria Teresa Voso
Journal: American Journal of Hematology (2023)

Abstract VEXAS is a prototypic hemato‐inflammatory disease combining rheumatologic and hematologic disorders in a molecularly defined nosological entity. In this nationwide study, we aimed at screenshotting the current diagnostic capabilities and clinical‐genomic features of VEXAS, and tracked UBA1 longitudinal clonal dynamics upon different therapeutics, including allogeneic hematopoietic cell transplant. We leveraged a collaboration between the Italian Society of Experimental Hematology and of Rheumatology and disseminated a national survey to collect clinical and molecular patient information. Overall, 13/29 centers performed UBA1 genomic testing locally, including Sanger sequencing (46%), next‐generation sequencing (23%), droplet digital polymerase chain reaction (8%), or combination (23%). A total of 41 male patients were identified, majority (51%) with threonine substitutions at Met41 hotspot, followed by valine and leucine (27% and 8%). Median age at VEXAS diagnosis was 67 years. All patients displayed anemia (median hemoglobin 9.1 g/dL), with macrocytosis. Bone marrow vacuoles were observed in most cases (89%). The most common rheumatologic association was polychondritis (49%). A concomitant myelodysplastic neoplasm/syndrome (MDS) was diagnosed in 71% of patients ( n = 28), chiefly exhibiting lower Revised International Prognostic Scoring System risk profiles. Karyotype was normal in all patients, except three MDS cases showing ‐Y, t(12;16)(q13;q24), and +8. The most frequently mutated gene was DNMT3A ( n = 10), followed by TET2 ( n = 3). At last follow‐up, five patients died and two patients progressed to acute leukemia. Longitudinal UBA1 clonal dynamics demonstrated mutational clearance following transplant. We collected a nationwide interdisciplinary VEXAS patient cohort, characterized by heterogeneous rheumatologic manifestations and treatments used. MDS was diagnosed in 71% of cases. Patients exhibited various longitudinal UBA1 clonal dynamics.
Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology
Authors: F. Roth‐Walter, I. M. Adcock, C. Benito‐Villalvilla, R. Bianchini, L. Bjermer, G. Caramori, L. Cari, K. F. Chung, Z. Diamant, I. Eguiluz‐Gracia, E. F. Knol, M. Jesenak, F. Levi‐Schaffer, G. Nocentini, L. O'Mahony, O. Palomares, F. Redegeld, M. Sokolowska, B. C. A. M. Van Esch, C. Stellato
Journal: Allergy (2023)

Abstract The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune‐driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence‐related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.
A horizon scan of global biological conservation issues for 2024
Authors: William J. Sutherland, Craig Bennett, Peter N.M. Brotherton, Stuart H.M. Butchart, Holly M. Butterworth, Stewart J. Clarke, Nafeesa Esmail, Erica Fleishman, Kevin J. Gaston, James E. Herbert-Read, Alice C. Hughes, Jennifer James, Hermanni Kaartokallio, Xavier Le Roux, Fiona A. Lickorish, Sarah Newport, James E. Palardy, James W. Pearce-Higgins, Lloyd S. Peck, Nathalie Pettorelli, Richard B. Primack, Willow E. Primack, Irene R. Schloss, Mark D. Spalding, Dirk ten Brink, Eleanor Tew, Anastasiya Timoshyna, Nicolas Tubbs, James E.M. Watson, Jonathan Wentworth, Jeremy D. Wilson, Ann Thornton
Journal: Trends in Ecology & Evolution (2023)

We present the results of our 15th horizon scan of novel issues that could influence biological conservation in the future. From an initial list of 96 issues, our international panel of scientists and practitioners identified 15 that we consider important for societies worldwide to track and potentially respond to. Issues are novel within conservation or represent a substantial positive or negative step-change with global or regional extents. For example, new sources of hydrogen fuel and changes in deep-sea currents may have profound impacts on marine and terrestrial ecosystems. Technological advances that may be positive include benchtop DNA printers and the industrialisation of approaches that can create high-protein food from air, potentially reducing the pressure on land for food production.
scNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles
Authors: Biqing Zhu, Yuge Wang, Li-Ting Ku, David van Dijk, Le Zhang, David A. Hafler, Hongyu Zhao
Journal: Genome biology (2023)

Abstract Many deep learning-based methods have been proposed to handle complex single-cell data. Deep learning approaches may also prove useful to jointly analyze single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) data for novel discoveries. We developed scNAT, a deep learning method that integrates paired scRNA-seq and scTCR-seq data to represent data in a unified latent space for downstream analysis. We demonstrate that scNAT is capable of removing batch effects, and identifying cell clusters and a T cell migration trajectory from blood to cerebrospinal fluid in multiple sclerosis.
Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women
Authors: Aoxing Liu, Evelina T. Akimova, Xuejie Ding, Sakari Jukarainen, Pekka Vartiainen, Tuomo Kiiskinen, Sara Koskelainen, Aki S. Havulinna, Mika Gissler, Stefano Lombardi, Tove Fall, Melinda C. Mills, Andrea Ganna
Journal: Nature Human Behaviour (2023)

Abstract The percentage of people without children over their lifetime is approximately 25% in men and 20% in women. Individual diseases have been linked to childlessness, mostly in women, yet we lack a comprehensive picture of the effect of early-life diseases on lifetime childlessness. We examined all individuals born in 1956–1968 (men) and 1956–1973 (women) in Finland ( n = 1,035,928) and Sweden ( n = 1,509,092) to the completion of their reproductive lifespan in 2018. Leveraging nationwide registers, we associated sociodemographic and reproductive information with 414 diseases across 16 categories, using a population and matched-pair case–control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers). The strongest associations were mental–behavioural disorders (particularly among men), congenital anomalies and endocrine–nutritional–metabolic disorders (strongest among women). We identified new associations for inflammatory and autoimmune diseases. Associations were dependent on age at onset and mediated by singlehood and education. This evidence can be used to understand how disease contributes to involuntary childlessness.
Smoother: a unified and modular framework for incorporating structural dependency in spatial omics data
Authors: Jiayu Su, Jean-Baptiste Reynier, Xi Fu, Guojie Zhong, Jiahao Jiang, Rydberg Supo Escalante, Yiping Wang, Luis Aparicio, Benjamin Izar, David A. Knowles, Raul Rabadan
Journal: Genome biology (2023)

Spatial omics technologies can help identify spatially organized biological processes, but existing computational approaches often overlook structural dependencies in the data. Here, we introduce Smoother, a unified framework that integrates positional information into non-spatial models via modular priors and losses. In simulated and real datasets, Smoother enables accurate data imputation, cell-type deconvolution, and dimensionality reduction with remarkable efficiency. In colorectal cancer, Smoother-guided deconvolution reveals plasma cell and fibroblast subtype localizations linked to tumor microenvironment restructuring. Additionally, joint modeling of spatial and single-cell human prostate data with Smoother allows for spatial mapping of reference populations with significantly reduced ambiguity.
Phase separations in oncogenesis, tumor progressions and metastasis: a glance from hallmarks of cancer
Authors: Le-Wei Zheng, Cui-Cui Liu, Ke-Da Yu
Journal: Journal of Hematology & Oncology (2023)

Abstract Liquid–liquid phase separation (LLPS) is a novel principle for interpreting precise spatiotemporal coordination in living cells through biomolecular condensate (BMC) formation via dynamic aggregation. LLPS changes individual molecules into membrane-free, droplet-like BMCs with specific functions, which coordinate various cellular activities. The formation and regulation of LLPS are closely associated with oncogenesis, tumor progressions and metastasis, the specific roles and mechanisms of LLPS in tumors still need to be further investigated at present. In this review, we comprehensively summarize the conditions of LLPS and identify mechanisms involved in abnormal LLPS in cancer processes, including tumor growth, metastasis, and angiogenesis from the perspective of cancer hallmarks. We have also reviewed the clinical applications of LLPS in oncologic areas. This systematic summary of dysregulated LLPS from the different dimensions of cancer hallmarks will build a bridge for determining its specific functions to further guide basic research, finding strategies to intervene in LLPS, and developing relevant therapeutic approaches.
2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Sarah M. Perman, Jonathan Elmer, Carolina B. Maciel, Anezi Uzendu, Teresa May, Bryn E. Mumma, Jason A. Bartos, Amber J. Rodriguez, Michael C. Kurz, Ashish R. Panchal, Jon C. Rittenberger
Journal: Circulation (2023)

Cardiac arrest is common and deadly, affecting up to 700 000 people in the United States annually. Advanced cardiac life support measures are commonly used to improve outcomes. This "2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support" summarizes the most recent published evidence for and recommendations on the use of medications, temperature management, percutaneous coronary angiography, extracorporeal cardiopulmonary resuscitation, and seizure management in this population. We discuss the lack of data in recent cardiac arrest literature that limits our ability to evaluate diversity, equity, and inclusion in this population. Last, we consider how the cardiac arrest population may make up an important pool of organ donors for those awaiting organ transplantation.
Targeting CRAF kinase in anti-cancer therapy: progress and opportunities
Authors: Penglei Wang, Kyle Laster, Xuechao Jia, Zigang Dong, Kangdong Liu
Journal: Molecular Cancer (2023)

Abstract The RAS/mitogen-activated protein kinase (MAPK) signaling cascade is commonly dysregulated in human malignancies by processes driven by RAS or RAF oncogenes. Among the members of the RAF kinase family, CRAF plays an important role in the RAS-MAPK signaling pathway, as well as in the progression of cancer. Recent research has provided evidence implicating the role of CRAF in the physiological regulation and the resistance to BRAF inhibitors through MAPK-dependent and MAPK-independent mechanisms. Nevertheless, the effectiveness of solely targeting CRAF kinase activity remains controversial. Moreover, the kinase-independent function of CRAF may be essential for lung cancers with KRAS mutations. It is imperative to develop strategies to enhance efficacy and minimize toxicity in tumors driven by RAS or RAF oncogenes. The review investigates CRAF alterations observed in cancers and unravels the distinct roles of CRAF in cancers propelled by diverse oncogenes. This review also seeks to summarize CRAF-interacting proteins and delineate CRAF's regulation across various cancer hallmarks. Additionally, we discuss recent advances in pan-RAF inhibitors and their combination with other therapeutic approaches to improve treatment outcomes and minimize adverse effects in patients with RAF/RAS -mutant tumors. By providing a comprehensive understanding of the multifaceted role of CRAF in cancers and highlighting the latest developments in RAF inhibitor therapies, we endeavor to identify synergistic targets and elucidate resistance pathways, setting the stage for more robust and safer combination strategies for cancer treatment.
Co-option of an Astacin Metalloprotease Is Associated with an Evolutionarily Novel Feeding Morphology in a Predatory Nematode
Authors: Yuuki Ishita, Ageha Onodera, Taisuke Ekino, Takahiro Chihara, Misako Okumura
Journal: Molecular Biology and Evolution (2023)

Abstract Animals consume a wide variety of food sources to adapt to different environments. However, the genetic mechanisms underlying the acquisition of evolutionarily novel feeding morphology remain largely unknown. While the nematode Caenorhabditis elegans feeds on bacteria, the satellite species Pristionchus pacificus exhibits predatory feeding behavior toward other nematodes, which is an evolutionarily novel feeding habit. Here, we found that the astacin metalloprotease Ppa-NAS-6 is required for the predatory killing by P. pacificus. Ppa-nas-6 mutants were defective in predation-associated characteristics, specifically the tooth morphogenesis and tooth movement during predation. Comparison of expression patterns and rescue experiments of nas-6 in P. pacificus and C. elegans suggested that alteration of the spatial expression patterns of NAS-6 may be vital for acquiring predation-related traits. Reporter analysis of the Ppa-nas-6 promoter in C. elegans revealed that the alteration in expression patterns was caused by evolutionary changes in cis- and trans-regulatory elements. This study suggests that the co-option of a metalloprotease is involved in an evolutionarily novel feeding morphology.
Incidence of Colorectal Cancer in Patients Diagnosed With Pyogenic Liver Abscess
Authors: Hiroyuki Suzuki, Ian Kidder, Tomohiro Tanaka, Michihiko Goto
Journal: JAMA Network Open (2023)

Importance Colorectal cancer (CRC) can compromise the mucosal barrier and subsequently allow a route for bacterial invasion into the portal system or systemic circulation. Despite preliminary data suggesting that patients who experienced pyogenic liver abscess (PLA) have higher CRC incidence rates, data from outside the Southeast Asian population are sparse. Objective To investigate whether there is an association between PLA and the subsequent incidence of diagnosed CRC using the Veterans Health Administration (VHA) cohort. Design, Setting, and Participants A patient-level matched retrospective cohort study was conducted at 127 VHA hospitals across the US from January 1, 2003, to December 31, 2020. Patients were followed up to 10 years from PLA diagnosis. Data analysis was performed from April 14, 2002, to October 31, 2023. All patients who were admitted to VHA hospitals with a diagnosis of PLA were included. For each patient with PLA, up to 3 controls without diagnosis of PLA, matching age, sex, and health care facility, were selected. Exposure Pyogenic liver abscess. Main Outcomes and Measures The primary outcome was CRC diagnosis during the follow-up period. A multivariable Fine-Gray subdistribution regression model with time-dependent coefficient was used to estimate the time-varying hazard ratio (HR) of CRC incidence while accounting for mortality as a competing event. Results A total of 8286 patients with PLA (male, 96.5%; mean [SD] age, 65.8 [11.9] years) and 23 201 patient-level matched controls (male, 96.3%; mean age, 65.3 [11.7] years) were included. A diagnosis of CRC was found in a significantly higher proportion of patients with PLA compared with controls (1.9% [159 of 8286] vs 0.8% [196 of 23 201]; P &amp;amp;lt; .001). The incidence of CRC was significantly higher among patients with PLA during the first 3 years from PLA diagnosis (HR, 3.64; 95% CI, 2.70-4.91 at 0.5 years; HR, 2.51; 95% CI, 1.93-3.26 at 1 year; HR, 1.74; 95% CI, 1.33-2.28 at 2 years; and HR, 1.41; 95% CI, 1.05-1.89 at 3 years), but not significant after 3 years. This association was not observed among patients whose PLA was likely secondary to cholangitis or cholecystitis (HR, 1.78; 95% CI, 0.89-3.56 at 0.5 years). Conclusions and Relevance In this patient-level matched retrospective cohort study, a significantly higher incidence of CRC was observed up to 3 years from PLA diagnosis. The findings suggest that offering CRC screening for patients with cryptogenic PLA may be useful, especially patients who have not been screened according to guidelines.
RNA-based modulation of macrophage-mediated efferocytosis potentiates antitumor immunity in colorectal cancer
Authors: Xuefei Zhou, Dezhi Li, Shenglong Xia, Xixi Ma, Rong Li, Yongli Mu, Zimo Liu, Lu Zhang, Quan Zhou, Wei Zhuo, Kefeng Ding, Aifu Lin, Wei Liu, Xiangrui Liu, Tianhua Zhou
Journal: Journal of Controlled Release (2023)
Estimated Savings After Stopping Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myeloid Leukemia
Authors: Aaron N. Winn, Ehab Atallah, Jorge Cortes, Michael W. N. Deininger, Vamsi Kota, Richard A. Larson, Joseph O. Moore, Michael J. Mauro, Vivian G. Oehler, Javier Pinilla-Ibarz, Jerald P. Radich, Neil P. Shah, James E. Thompson, Kathryn E. Flynn
Journal: JAMA Network Open (2023)

Importance Patients with chronic myeloid leukemia (CML) who have a sustained deep molecular response using tyrosine kinase inhibitors (TKIs) can safely attempt to stop their use. As these medications are very costly, this change in treatment protocols may result in large savings. Objective To estimate future savings from attempting to stop TKI use among patients with CML who have deep molecular response. Design, Setting, and Participants A microsimulation model was developed for this decision analytical modeling study to estimate costs for US adults moving from using a TKI, to attempting discontinuation and then reinitiating TKI therapy, if clinically appropriate. Estimates were calculated for US patients who currently have CML and simulated newly diagnosed cohorts of patients over the next 30 years. Exposure Attempting to stop using a TKI. Main Outcomes and Measures Estimated savings after attempted discontinuation of TKI use. Results A simulated population of individuals with CML in 2018 and future populations were created using estimates from the SEER*Explorer website. The median age at diagnosis was 66 years for men and 65 years for women. Between 2022 and 2052, the savings associated with eligible patients attempting discontinuation of TKI therapy was estimated at more than $30 billion among those currently diagnosed and over $15 billion among those who will develop CML in the future, for a total savings of over $54 billion by 2052 for drug treatment and polymerase chain reaction testing. The estimate is conservative as it does not account for complications and other health care–associated costs for patients continuing TKI therapy. Conclusions and Relevance The findings of this decision analytical modeling study of patients with CML suggest that attempting discontinuation of TKI therapy could save over $54 billion during the next 30 years. Further education for patients and physicians is needed to safely increase the number of patients who can successfully attain treatment-free remission.