tbuckley/cabot-search huggingface dataset:
Is asthma remission an important clinical outcome in asthma management?
Authors: Marcia M.M. Pizzichini, Emílio Pizzichini
Journal: European Respiratory Journal (2024)

<title>Extract</title> In recent years, with the introduction of biologic therapies for the treatment of severe asthma, there has been a shift in the goals of asthma management, from control to remission; although remission is not a cure, it is a meaningful, relevant patient-oriented outcome [1]. However, the definition of asthma remission is evolving [2] and varies across studies [3–5]. In addition, the associated factors and determinants of asthma remission are not yet completely understood. Nevertheless, there is no doubt that remission (irrespective of its definition) can be achieved in a proportion of patients with severe asthma under treatment with biologics [3–5], something until recently deemed unattainable.
Glycerolipids disrupt regulatory T-cells in asthma
Authors: Fatma Betul Oktelik, Mehdi Benamar
Journal: European Respiratory Journal (2024)

<title>Extract</title> Asthma is a chronic inflammatory disease that arises due to an exacerbated immune response causing narrowing and hypersensitivity of the airways [1]. The full aetiology of asthma is not fully understood; however, several studies have shown the role of genetic, immunological and environmental factors in its development or severity. Asthma remains a significant health challenge, contributing to substantial morbidity and, in some instances, mortality. Therefore, it is crucial to enhance our understanding of this condition and to identify new biomarkers. From an immunological point of view, different cell types, such as T-cells, mast cells and eosinophils, play a crucial role in disease induction or exacerbation [2]. T-cells, in particular Th2 and Th17 cells, have been shown to be involved in promoting asthma severity by promoting the recruitment of immune cells, such as eosinophils and neutrophils, respectively [3, 4].
Comment on the European Respiratory Society pulmonary alveolar proteinosis guidelines
Authors: Ali Ataya, Elinor Lee
Journal: European Respiratory Journal (2024)

<title>Extract</title> We read with great interest the European Respiratory Society (ERS) guidelines for pulmonary alveolar proteinosis (PAP) by M<sc>c</sc>C<sc>arthy</sc> <italic>et al</italic>. [1], which were recently published in the <italic>European Respiratory Journal</italic>. The task force's recommendations addressed many important questions on the role and hierarchical steps in diagnostic testing and treatment of patients with suspected and diagnosed PAP. We would like to commend the authors on this collaborative and important work, while highlighting some of the challenges that remain in the management of this rare and often life-threatening syndrome.
Identification of an emphysema-specific ATII cell: a step towards understanding impaired lung regeneration in COPD?
Authors: Yiling Guo, Louise E. Donnelly
Journal: European Respiratory Journal (2024)

<title>Extract</title> The ability to rejuvenate lung tissue and restore function is currently an ideal goal for those working in respiratory science. Understanding the mechanisms involved in lung remodelling and repair are paramount for the development of new treatments for several lung diseases and in particular for emphysema, a major component of COPD. Despite many studies investigating the underlying pathophysiologies of COPD, to date there are no disease-modifying treatments for this disease. Repair of damaged lung tissue is complex and many chronic lung diseases, such as COPD or idiopathic pulmonary fibrosis, might arise from dysregulated repair mechanisms. Nevertheless, replenishment of the gas exchange units in the lung remains an enticing target. In the alveoli, alveolar type I (ATI) cells form ∼90% of the area, providing a surface for gas exchange due to their large, flattened surface [1, 2]. ATII cells account for the remainder of the surface area and are much smaller cuboidal cells that have a role in production and secretion of surfactant proteins, including surfactant protein C (SFTPC) [3].
Aberrantly Expressed Mitochondrial Lipid Kinase, AGK Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy
Authors: Murali K. Mamidi, Sutapa Sinha, Mariana T. Mendez, Tapojyoti Sanyal, Hasan Mahmud, Neil E. Kay, Mamta Gupta, Chao Xu, Sara K. Vesely, Priyabrata Mukherjee, Jennifer Holter Chakrabarty, Asish K. Ghosh
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Although the B-cell receptor (BCR) signal plays a critical role in CLL cell survival and a target of current therapies (ibrutinib targets Bruton’s tyrosine kinase; idelalisib targets PI3Kδ), contribution of the cytokine-driven JAK2 pathway to the “CLL cell-survival signaling network” is largely undefined. Experimental Design: CLL patients were enrolled to investigate expression/activation of JAK2 and acylglycerol kinase (AGK), and their functional implication in primary CLL cell survival. A series of biochemical and molecular biology assays were employed to uncover the underlying mechanism. Results: We detected that compared to normal B-cells, CLL cells aberrantly express constitutively active JAK2. Mechanistically, HSP90 forms a chaperoning complex with JAK2, resulting in its aberrant accumulation in CLL cells. We also discovered aberrant upregulation of a novel mitochondrial lipid kinase, AGK, which remains complexed with HSP90 in CLL cells activating JAK2. Although AGK is typically mitochondrial, we detected its nuclear localization in association with JAK2 in some CLL cells. Functionally, JAK2 phosphorylates its non-canonical substrate, histone H3(Y41), but not STAT3, activating transcription of diverse sets of genes in a patient-specific manner. Additionally, JAK2 activates the BCR-signal in CLL cells via LYN/BTK axis. Targeted inhibition of JAK2 as monotherapy, or in combination with the BCR-inhibitors or venetoclax (a BCL2-inhibitor) induced apoptosis synergistically in CLL cells. Conclusions: These findings suggest that aberrantly expressed AGK activates JAK2, independent of cytokine, leading to activation of diverse sets of gene transcription in CLL cells. Combined targeting of JAK2 and BCR signals or BCL2 may be effective in some CLL patients.
A breath of the future: a novel human model for COPD and beyond
Authors: Maja C. Funk, Janna Nawroth, Mareike Lehmann
Journal: European Respiratory Journal (2024)

<title>Extract</title> We have cured chronic lung diseases, including COPD, in mice many times. However, translation to clinical application has failed in most cases. Why is this the case and what can we do about it? One of the reasons for this is that mice are simply not small humans. Developing novel human lung models will help us in identifying more promising novel therapeutic strategies, thereby hopefully leading to therapeutic options that translate to the clinic.
<i>Notes from the Field:</i> Rollout of Nirsevimab to Protect Infants and Young Children During the Respiratory Syncytial Virus Season — New York City, 2023–2024
Authors: Melanie S. Askari, Kristin Oliver, Denise Benkel, Melissa Mickle-Hope, Vincent Tam, Marisa Langdon-Embry, Georgia Elysee, Bindy Crouch
Journal: MMWR Morbidity and Mortality Weekly Report (2024)
Detection of Illegally Manufactured Fentanyls and Carfentanil in Drug Overdose Deaths — United States, 2021–2024
Authors: Lauren J. Tanz, Andrea Stewart, R. Matt Gladden, Jean Y. Ko, Lauren Owens, Julie O’Donnell
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

During 2023, approximately 72,000, or nearly seven in 10, drug overdose deaths in the United States were estimated to involve illegally manufactured fentanyls (IMFs). Carfentanil, a fentanyl analog 100 times more potent than fentanyl, has reemerged in the U.S. drug supply. Using CDC's State Unintentional Drug Overdose Reporting System data, this report describes trends in overdose deaths during January 2021-June 2024, overall and with IMFs detected, by U.S. Census Bureau region, and in deaths with carfentanil detected, in 45 states and the District of Columbia (DC). Numbers of deaths with carfentanil detected by state during January 2023-June 2024 in 49 states and DC are also reported. The number of overdose deaths with IMFs detected declined from 2022 to 2023 in the Northeast (3.2% decline), Midwest (7.8%), and South (2.8%) regions; deaths in the West increased 33.9%. The percentage of deaths with IMFs detected was steady at approximately 70%-80% in the Northeast, Midwest, and South. In contrast, the percentage of deaths with IMFs detected in the West increased from 48.5% during January-March 2021 to 66.5% during April-June 2024. Overdose deaths with carfentanil detected increased approximately sevenfold, from 29 during January-June 2023 to 238 during January-June 2024; during January 2023-June 2024, overdose deaths with carfentanil detected were reported in 37 states. Overdose prevention efforts that address the widespread presence of IMFs, including carfentanil, and can rapidly adapt to other potent opioids in the drug supply might result in lasting reductions in overdose deaths across the entire United States.
Updated Recommendation for Universal Hepatitis B Vaccination in Adults Aged 19–59 Years — United States, 2024
Authors: Amy L. Sandul, Karina Rapposelli, Melissa Nyendak, Min Kim
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). The Advisory Committee on Immunization Practices recommends universal HepB vaccination for adults aged 19-59 years, including pregnant persons, and adults aged ≥60 years with risk factors for hepatitis B. Adults aged ≥60 years without known risk factors for hepatitis B may also receive HepB vaccines (2).
Intimate Partner Violence and Pregnancy and Infant Health Outcomes — Pregnancy Risk Assessment Monitoring System, Nine U.S. Jurisdictions, 2016–2022
Authors: Megan Steele-Baser, Alyssa L. Brown, Denise V. D’Angelo, Kathleen C. Basile, Rosalyn D. Lee, Antoinette T. Nguyen, Cynthia H. Cassell
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Intimate partner violence (IPV) can include emotional, physical, or sexual violence. IPV during pregnancy is a preventable cause of injury and death with negative short- and long-term impacts for pregnant women, infants, and families. Using data from the 2016-2022 Pregnancy Risk Assessment Monitoring System in nine U.S. jurisdictions, CDC examined associations between IPV during pregnancy among women with a recent live birth and the following outcomes: prenatal care initiation, health conditions during pregnancy (gestational diabetes, pregnancy-related hypertension, and depression), substance use during pregnancy, and infant birth outcomes. Overall, 5.4% of women reported IPV during pregnancy. Emotional IPV was most prevalent (5.2%), followed by physical (1.5%) and sexual (1.0%) IPV. All types were associated with delayed or no prenatal care; depression during pregnancy; cigarette smoking, alcohol use, marijuana or illicit substance use during pregnancy; and having an infant with low birth weight. Physical, sexual, and any IPV were associated with having a preterm birth. Physical IPV was associated with pregnancy-related hypertension. Evidence-based prevention and intervention strategies that address multiple types of IPV are important for supporting healthy parents and families because they might reduce pregnancy complications, depression and substance use during pregnancy, and adverse infant outcomes.
Development and validation of artificial intelligence models for early detection of postoperative infections (PERISCOPE): a multicentre study using electronic health record data
Authors: Siri L van der Meijden, Anna M van Boekel, Laurens J Schinkelshoek, Harry van Goor, Ewout W Steyerberg, Rob G H H Nelissen, Dieter Mesotten, Bart F Geerts, Mark G J de Boer, M Sesmu Arbous
Journal: The Lancet Regional Health - Europe (2024)
Lung Cancer in Mozambique
Authors: Assucena Guisseve, Albertino Mualinque, Matchecane Cossa, Ariel Durañones Jerez, Satish Tulsidás, Vania Cabrá, Edília Botão, Narciso Sitoe, Adriano Tivane, Anilsa Daniel, Alberto Gudo Morais, Atílio Morais, Fabíola Fernandes, Cesaltina Lorenzoni, Fátima Carneiro, Elizabete Nunes, Rita Barros, Carla Carrilho
Journal: Journal of Thoracic Oncology (2024)
Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment
Authors: Alex C. Soupir, Mitchell T. Hayes, Taylor C. Peak, Oscar Ospina, Nicholas H. Chakiryan, Anders E. Berglund, Paul A. Stewart, Jonathan Nguyen, Carlos Moran Segura, Natasha L. Francis, Paola M. Ramos Echevarria, Jad Chahoud, Roger Li, Kenneth Y. Tsai, Jodi A. Balasi, Yamila Caraballo Peres, Jasreman Dhillon, Lindsey A. Martinez, Warren E. Gloria, Nathan Schurman, Sean Kim, Mark Gregory, James Mulé, Brooke L. Fridley, Brandon J. Manley
Journal: Genome biology (2024)

Abstract Background Immunotherapy has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with immunotherapy naïve and exposed primary ccRCC tumors to better understand immunotherapy resistance. Results Spatial molecular imaging of tumor and adjacent stroma samples from 21 tumors suggests that viable tumors following immunotherapy harbor more stromal CD8 + T cells and neutrophils than immunotherapy naïve tumors. YES1 is significantly upregulated in immunotherapy exposed tumor cells. Spatial GSEA shows that the epithelial-mesenchymal transition pathway is spatially enriched and the associated ligand-receptor transcript pair COL4A1 - ITGAV has significantly higher autocorrelation in the stroma after exposure to immunotherapy. More integrin αV + cells are observed in immunotherapy exposed stroma on multiplex immunofluorescence validation. Compared to other cancers in TCGA, ccRCC tumors have the highest expression of both COL4A1 and ITGAV . Assessing bulk RNA expression and proteomic correlates in CPTAC databases reveals that collagen IV protein is more abundant in advanced stages of disease. Conclusions Spatial transcriptomics of samples of 3 patient cohorts with cRCC tumors indicates that COL4A1 and ITGAV are more autocorrelated in immunotherapy-exposed stroma compared to immunotherapy-naïve tumors, with high expression among fibroblasts, tumor cells, and endothelium. Further research is needed to understand changes in the ccRCC tumor immune microenvironment and explore potential therapeutic role of integrin after immunotherapy treatment.
Advances in CAR-T cell therapy for hematologic and solid malignancies: latest updates from 2024 ESMO Congress
Authors: Huageng Huang, Le Yu, Huawei Weng, Wei Zhang, Zhao Wang, Lin Wang, He Huang
Journal: Journal of Hematology & Oncology (2024)

Chimeric antigen receptor (CAR)-T cell therapy has emerged as one of the most rapidly evolving modalities of immunotherapy, with substantial success in the treatment of hematological malignancies and encouraging outcomes in solid tumors. Yet, the efficacy of CAR-T therapy is hindered by challenges such as suboptimal expansion and persistence, adverse events, a scarcity of ideal targets, high immunosuppression, and insufficient infiltration due to the intricate tumor microenvironment, all of which limit its application. The 2024 European Society for Medical Oncology (ESMO) Congress presented novel CAR-T cell therapies for hematologic and solid malignancies, focusing on strategies such as cytokine modulation, innovative targets, allogeneic development, mRNA vaccine synergy, in vivo delivery and conditional activation to surmount these challenges.
A Solid Pseudopapillary Tumor of the Pancreas Incidentally Detected by 68Ga-Pentixafor PET/CT in a Patient With Primary Aldosteronism
Authors: Xiang Chen, Yan Xing, Changcun Liu, Rui Zhang, Jinhua Zhao
Journal: Clinical Nuclear Medicine (2024)

Abstract A 27-year-old woman underwent 68 Ga-pentixafor PET/CT for primary aldosteronism localization and characterization. No functional adrenal nodules were detected by 68 Ga-pentixafor PET/CT, whereas a hypodense nodule with focal pentixafor uptake was incidentally discovered in the head of pancreas. Retrospective analysis of contrast-enhanced CT scan revealed a subtly enhancing nodule devoid of calcification in the pancreatic head. Pancreatic cancer cannot be excluded. 18 F-FDG PET/CT was suggested, and the scan showed an FDG-avid lesion in the same region. Needle biopsy was performed, and the pathological result is solid pseudopapillary tumor, a rare pancreatic tumor of low malignant potential.
Candida tropicalis Liver Abscess in an Immunocompromised Patient With Pancreatic Head Cancer on 68Ga-FAPI PET/CT
Authors: Jahae Kim, Seong Eun Kim, Eunae Cho, Kang-Ho Choi
Journal: Clinical Nuclear Medicine (2024)

Abstract Candida infections have become a growing concern to the immunocompromised patients with cancer. We report a case of liver abscess causing Candida tropicalis candidemia in an immunocompromised patient with pancreatic head cancer on 68 Ga-FAPI PET/CT. A 77-year-old man had a history of 10-year duration of uncontrolled diabetes, the presence of neutropenia, immunocompromised condition, and the progression of pancreatic cancer despite the 14 cycles of chemotherapy and palliative radiotherapy. After 3 weeks of radiotherapy, he presented with fever and elevated CRP level. 68 Ga-FAPI PET/CT scan showed new intense uptake in the liver, and 2 pairs of blood culture revealed C. tropicalis.
Commentary on “Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC”
Authors: Robert B Cameron, Jacobi B Hines, Valter Torri, Marina C Garassino
Journal: Journal of Thoracic Oncology (2024)
Tuberous Sclerosis Complex Demonstrated on 18F-FDG PET/CT
Authors: Selin Kesim, Nuh Filizoglu
Journal: Clinical Nuclear Medicine (2024)

Abstract Tuberous sclerosis complex is a rare neurocutaneous genetic disorder that can affect multiple organ systems including the skin, eyes, brain, kidneys, heart, and lungs. Herein, we report 18 F-FDG PET/CT findings of brain and skin lesions, bilateral renal angiomyolipomas, and pulmonary lymphangioleiomyomatosis in a patient with tuberous sclerosis complex.
Gut microbiota CLA and IL-35 induction in macrophages through Gαq/11-mediated STAT1/4 pathway: an animal-based study
Authors: Xiaomin Su, Yazheng Yang, Yunhuan Gao, Juanjuan Wang, Yang Hao, Yuan Zhang, Rongcun Yang
Journal: Gut Microbes (2024)

Gut microbiota/metabolites not only participate in the food and energy metabolism but also contribute to the host immune response and homeostasis. The alternation of gut microbiota/metabolites has been widely related to intestinal and extra-intestinal disorders such as intestinal bowel diseases (IBDs). Bactericidal substances from gut epithelial cells can regulate the composition of gut microbiota. However, the effects of regenerating protein 4 (REG4) (human)/(Reg4) (mice), a potentially bactericidal substance from gut epithelial cells, on the gut immune homeostasis maintain elusive. Here, we found that REG4/Reg4 is essential in maintaining gut immune homeostasis through REG4/Reg4 associated gut microbiota. Reg4 knockout (KO) mice were highly sensitive to DSS-mediated colitis, whereas human REG4 intestine epithelial cell transgenic (huREG4IECtg) mice exhibited more resistance to DSS-mediated colitis. Mechanistically, sequencing of gut microbiota and liquid chromatography-mass spectrometry showed that REG4/Reg4 could affect the composition of gut microbiota. REG4/Reg4 associated gut microbiota such as Lactobacillus could metabolize linoleic acid (LA) into conjugated linoleic acid (CLA). Immunoprecipitation and immunoblot showed that CLA could effectively promote the expression of IL-35 in macrophages through Gαq/11 mediated activation STAT1/4. Thus, our results demonstrate that REG4/Reg4 plays a critical role in maintaining gut immune homeostasis through CLA-mediated IL-35+ macrophages.
The real-world association between digital markers of circadian disruption and mental health risks
Authors: Minki P. Lee, Dae Wook Kim, Yu Fang, Ruby Kim, Amy S. B. Bohnert, Srijan Sen, Daniel B. Forger
Journal: npj Digital Medicine (2024)

While circadian disruption is recognized as a potential driver of depression, its real-world impact is poorly understood. A critical step to addressing this is the noninvasive collection of physiological time-series data outside laboratory settings in large populations. Digital tools offer promise in this endeavor. Here, using wearable data, we first quantify the degrees of circadian disruption, both between different internal rhythms and between each internal rhythm and the sleep-wake cycle. Our analysis, based on over 50,000 days of data from over 800 first-year training physicians, reveals bidirectional links between digital markers of circadian disruption and mood both before and after they began shift work, while accounting for confounders such as demographic and geographic variables. We further validate this by finding clinically relevant changes in the 9-item Patient Health Questionnaire score. Our findings validate a scalable digital measure of circadian disruption that could serve as a marker for psychiatric intervention.
Predicting future fallers in Parkinson’s disease using kinematic data over a period of 5 years
Authors: Charalampos Sotirakis, Maksymilian A. Brzezicki, Salil Patel, Niall Conway, James J. FitzGerald, Chrystalina A. Antoniades
Journal: npj Digital Medicine (2024)

Abstract Parkinson’s disease (PD) increases fall risk, leading to injuries and reduced quality of life. Accurate fall risk assessment is crucial for effective care planning. Traditional assessments are subjective and time-consuming, while recent assessment methods based on wearable sensors have been limited to 1-year follow-ups. This study investigated whether a short sensor-based assessment could predict falls over up to 5 years. Data from 104 people with PD without prior falls were collected using six wearable sensors during a 2-min walk and a 30-s postural sway task. Five machine learning classifiers analysed the data. The Random Forest classifier performed best, achieving 78% accuracy (AUC = 0.85) at 60 months. Most models showed excellent performance at 24 months (AUC &gt; 0.90, accuracy 84–92%). Walking and postural variability measures were key predictors. Adding clinicodemographic data, particularly age, improved model performance. Wearable sensors combined with machine learning can effectively predict fall risk, enhancing PD management and prevention strategies.