tbuckley/cabot-search huggingface dataset:
A population-based study of COVID-19 mortality risk in US cancer patients
Authors: Kyle A Mani, Xue Wu, Daniel E Spratt, Ming Wang, Nicholas G Zaorsky
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. Methods A total of 4 020 669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database were abstracted. We investigated prognostic factors for death due to COVID-19 using a Cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios were calculated using observed mortality counts from Surveillance, Epidemiology, and End Results and expected mortality based on US mortality rates. Results A total of 291 323 patients died, with 14 821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10 000-persons years, and the standardized mortality ratio of COVID-19 was 2.30 (95% confidence interval [CI] = 2.26 to 2.34; P &amp;lt; .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 noncancer causes of death. Patients who are older (80 years and older vs 49 years and younger: HR = 21.47, 95% CI = 19.34 to 23.83), male (vs female: HR = 1.46, 95% CI = 1.40 to 1.51), unmarried (vs married: HR = 1.47, 95% CI = 1.42 to 1.53), and Hispanic or non-Hispanic African American (vs non-Hispanic White: HR = 2.04, 95% CI = 1.94 to 2.14 and HR = 2.03, 95% CI = 1.94 to 2.14, respectively) were at greatest risk of COVID-19 mortality. Conclusions We observed that people living with cancer are at 2 times greater risk of dying from COVID-19 compared with the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.
Use of a large patient database to analyse disease burden and treatment patterns among patients with vitiligo
Authors: Valeria Brazzelli, Andrea Michelerio
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript Use of a large patient database to analyze disease burden and treatment patterns among patients with vitiligo Get access Valeria Brazzelli, Valeria Brazzelli Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, ItalyDermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Corresponding Author: Valeria Brazzelli, MD Email:v.brazzelli@smatteo.pv.it Search for other works by this author on: Oxford Academic Google Scholar Andrea Michelerio Andrea Michelerio Dermatology Unit, Ospedale Cardinal Massaia, Asti, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae166, https://doi.org/10.1093/bjd/ljae166 Published: 16 April 2024 Article history Received: 07 April 2024 Accepted: 14 April 2024 Published: 16 April 2024
Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning
Authors: Fei Tian, Dong Liu, Na Wei, Qianqian Fu, Lin Sun, Wei Liu, Xiaolong Sui, Kathryn Tian, Genevieve Nemeth, Jingyu Feng, Jingjing Xu, Lin Xiao, Junya Han, Jingjie Fu, Yinhua Shi, Yichen Yang, Jia Liu, Chunhong Hu, Bin Feng, Yan Sun, Yunjun Wang, Guohua Yu, Dalu Kong, Meiyun Wang, Wencai Li, Kexin Chen, Xiangchun Li
Journal: Nature Medicine (2024)

Abstract Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal ( n = 12,799) and two external ( n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P &lt; 0.001), enhancing junior pathologists’ diagnostic scores significantly (1.326 versus 1.101, P &lt; 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.
Alternative routes into clinical research: a guide for early career doctors
Authors: Phillip LR Nicolson, Martha Belete, Rebecca Hawes, Nicole Fowler, Cheng Hock Toh
Journal: BMJ (2024)

Working in clinical research alongside clinical practice can make for a rewarding and worthwhile career.123 Building research into a clinical career starts with research training for early and mid-career doctors. Traditional research training typically involves a dedicated period within an integrated clinical academic training programme or as part of an externally funded MD or PhD degree. Informal training opportunities, such as journal clubs and principal investigator (PI)-mentorship are available (box 1), but in recent years several other initiatives have launched in the UK, meaning there are more ways to obtain research experience and embark on a career in clinical research. Box 1 ### Examples of in-person and online research training opportunities These are available either informally or formally, free of charge or paid, and via local employing hospital trusts, allied health organisations, royal colleges, or universities #### Acute medicine #### Anaesthesia #### Cardiology #### Cardiothoracic surgery #### Emergency medicine #### Ear, nose, and throat #### Gastroenterology #### General practice #### General surgery #### Geriatrics #### Haematology (non-malignant) #### Haematology (malignant) #### Hepatology #### Histopathology #### Intensive care medicine #### Internal medicine #### Interventional radiology #### Maxillofacial surgery #### Nephrology #### NeurologyRETURN TO TEXT
Refocusing the World Health Organization’s Model List of Essential Medicines on the needs of low and middle income countries
Authors: Veronika J Wirtz, Andrew L Gray, Sangeeta Sharma, Jing Sun, Hans V Hogerzeil
Journal: BMJ (2024)

In the wake of escalating medicine prices worldwide, <b>Veronika Wirtz and colleagues</b> argue for refocusing the WHO Model List of Essential Medicines on the needs of low and middle income countries, while retaining its global relevance as a model process
Chemo-free treatment of adult patients with Ph-positive acute lymphoblastic leukemia: latest updates from the 2023 ASH annual meeting
Authors: Ting Shi, Hong-Hu Zhu
Journal: Journal of Hematology & Oncology (2024)

Abstract The chemo-free concept represents a new direction for managing adult patients with Ph-positive acute lymphoblastic leukemia (Ph + ALL). The tyrosine kinase inhibitors (TKIs), blinatumomab and venetoclax serve as the backbone of chemo-free regimens; several prospective studies involving these drugs have demonstrated high remission rates and promising, albeit short, survival outcomes. This review summarizes the latest updates on chemo-free regimens in the treatment of adult patients with Ph + ALL, presented at the 2023 ASH annual meeting.
Expert consensus on pediatric orthodontic therapies of malocclusions in children
Authors: Chenchen Zhou, Peipei Duan, Hong He, Jinlin Song, Min Hu, Yuehua Liu, Yan Liu, Jie Guo, Fang Jin, Yang Cao, Lingyong Jiang, Qingsong Ye, Min Zhu, Beizhan Jiang, Wenhua Ruan, Xiao Yuan, Huang Li, Rui Zou, Yulou Tian, Li Gao, Rui Shu, Jianwei Chen, Renkai Liu, Shujuan Zou, Xiaobing Li
Journal: International Journal of Oral Science (2024)

Abstract Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.
Author Correction: Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment
Authors: Chris Greene, Ruairi Connolly, Declan Brennan, Aoife Laffan, Eoin O’Keeffe, Lilia Zaporojan, Jeffrey O’Callaghan, Bennett Thomson, Emma Connolly, Ruth Argue, James F. M. Meaney, Ignacio Martin-Loeches, Aideen Long, Cliona Ni Cheallaigh, Niall Conlon, Colin P. Doherty, Matthew Campbell
Journal: Nature Neuroscience (2024)
Recessively Inherited Deficiency of Secreted WFDC2 (HE4) Causes Nasal Polyposis and Bronchiectasis
Authors: Gerard W Dougherty, Lawrence E Ostrowski, Tabea Nöthe-Menchen, Johanna Raidt, Andre Schramm, Heike Olbrich, Weining Yin, Patrick R. Sears, Hong Dang, Amanda J. Smith, Achim G. Beule, Rim Hjeij, Niels Rutjes, Eric G Haarman, Saskia M. Maas, Thomas W. Ferkol, Peadar G Noone, Kenneth N. Olivier, Diana C. Bracht, Pascal Barbry, Laure-Emmanuelle Zaragosi, Morgane Fierville, Sabine Kliesch, Kai Wohlgemuth, Julia König, Sebastian George, Niki T. Loges, Agathe Ceppe, Matthew R Markovetz, Hong Luo, Ting Guo, Hoda Rizk, Tarek Eldesoky, Katrin Dahlke, Karsten Boldt, Marius Ueffing, David B. Hill, Yuan-Ping Pang, Michael R Knowles, Maimoona A Zariwala, Heymut Omran
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Bronchiectasis is a pathological dilatation of the bronchi in the respiratory airways associated with environmental or genetic causes (e.g., cystic fibrosis, primary ciliary dyskinesia and primary immunodeficiency disorders), but most cases remain idiopathic. Objectives: To identify novel genetic defects in unsolved cases of bronchiectasis presenting with severe rhinosinusitis, nasal polyposis, and pulmonary Pseudomonas aeruginosa infection. Methods: DNA was analyzed by next-generation or targeted Sanger sequencing. RNA was analyzed by quantitative PCR and single-cell RNA sequencing. Patient-derived, cells, cell cultures and secretions (mucus, saliva, seminal fluid) were analyzed by Western blotting and immunofluorescence microscopy, and mucociliary activity was measured. Blood serum was analyzed by electrochemiluminescence immunoassay. Protein structure and proteomic analyses were used to assess the impact of a disease-causing founder variant. Measurements and Main Results: We identified bi-allelic pathogenic variants in WFDC2 in 11 individuals from 10 unrelated families originating from the United States, Europe, Asia, and Africa. Expression of WFDC2 was detected predominantly in secretory cells of control airway epithelium and also in submucosal glands. We demonstrate that WFDC2 is below the limit of detection in blood serum and hardly detectable in samples of saliva, seminal fluid, and airway surface liquid from WFDC2-deficient individuals. Computer simulations and deglycosylation assays indicate that the disease-causing founder variant p.Cys49Arg structurally hampers glycosylation and thus secretion of mature WFDC2. Conclusions: WFDC2 dysfunction defines a novel molecular etiology of bronchiectasis characterized by the deficiency of a secreted component of the airways. A commercially available blood test combined with genetic testing allows its diagnosis. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Transcriptome-Wide Association Study of Idiopathic Pulmonary Fibrosis Survival Identifies <i>PTPN9</i> and <i>SNRPB2</i>
Authors: Xiaowei Hu, John S. Kim, Aabida Saferali, Yong Huang, Shwu-Fan Ma, Grace C. Bingham, Catherine A. Bonham, Carlos Flores, Peter Castaldi, Craig P. Hersh, Michael H Cho, Imre Noth, Ani Manichaikul
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Transcriptome-Wide Association Study of Idiopathic Pulmonary Fibrosis Survival Identifies PTPN9 and SNRPB2." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Reply: On the use of nonselective beta blockers in cirrhosis
Authors: Guadalupe Garcia-Tsao, David E. Kaplan
Journal: Hepatology (2024)

1Yale University, New Haven, USA; VA-CT Healthcare System, West Haven, CT, USA 2Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA US Abbreviations: None Correspondence David E. Kaplan, MD MSc, 3400 Civic Center Blvd, PCAM 708 South, Philadelphia, PA 19104; 215-360-0522. Email: [email protected]
Lung Tissue Multi-Layer Network Analysis Uncovers the Molecular Heterogeneity of COPD
Authors: Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using a novel multi-layer approach may unravel mechanisms associated with clinical characteristics. Methods. We profiled mRNA, miRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer) we built a patient network based on molecular similarity. The three networks were used to build a multi-layer network, and optimization of multiplex-modularity was employed to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features. Results. We identified five patient communities in the multi-layer network which were molecularly distinct and related to clinical characteristics, such as FEV1 and blood eosinophils. Two communities (C#3 and C#4) had both similarly low FEV1 values and emphysema, but were molecularly different: C#3, but not C#4, presented B and T cell signatures and a downregulation of secretory (SCGB1A1/SCGB3A1) and ciliated cells. A machine learning model was set up to discriminate C#3 and C#4 in our cohort, and to validate them in an independent cohort. Finally, using spatial transcriptomics we characterized the small airway differences between C#3 and C#4, identifying an upregulation of T/B cell homing chemokines, and bacterial response genes in C#3. Conclusions. A novel multi-layer network analysis is able to identify clinically relevant COPD patient communities. Patients with similarly low FEV1 and emphysema can have molecularly distinct small airways and immune response patterns, indicating that different endotypes can lead to similar clinical presentation.
Innovations in health care delivery for patients with cirrhosis
Authors: Michael L. Volk
Journal: Hepatology (2024)

Baylor Scott and White Central Texas, Internal Medicine, 2401 S 31st St,Temple, Texas 76508 Correspondence Michael L. Volk, Baylor Scott and White Central Texas, Internal Medicine, 2401 S 31st St,Temple, Texas 76508. Email: [email protected]
<i>ATP13A3</i> variants promote pulmonary arterial hypertension by disrupting polyamine transport
Authors: Bin Liu, Mujahid Azfar, Ekaterina Legchenko, James A West, Shaun Martin, Chris Van den Haute, Veerle Baekelandt, John Wharton, Luke Howard, Martin R Wilkins, Peter Vangheluwe, Nicholas W Morrell, Paul D Upton
Journal: Cardiovascular Research (2024)

Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase of undefined function, were recently identified in patients with pulmonary arterial hypertension (PAH). ATP13A3 is implicated in polyamine transport but its function has not been fully elucidated. In this study, we sought to determine the biological function of ATP13A3 in vascular endothelial cells (ECs) and how PAH-associated variants may contribute to disease pathogenesis.
Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade
Authors: Nina Wyss, Fiamma Berner, Vincent Walter, Ann-Kristin Jochum, Mette T. Purde, Marie-Therese Abdou, Tobias Sinnberg, Kathrin Hofmeister, Oltin T. Pop, Omar Hasan Ali, Jens Bauer, Hung-Wei Cheng, Mechthild Lütge, Niklas Klümper, Stefan Diem, Zeynep Kosaloglu-Yalcin, Yizheng Zhang, Laura Sellmer, Boris Macek, Julia Karbach, David König, Heinz Läubli, Lars Zender, Britta S. Meyer, Christoph Driessen, Christian M. Schürch, Wolfram Jochum, Teresa Amaral, Lucie Heinzerling, Antonio Cozzio, Ahmed N. Hegazy, Tino Schneider, Martin H. Brutsche, Alessandro Sette, Tobias L. Lenz, Juliane Walz, Hans-Georg Rammensee, Martin Früh, Elke Jäger, Burkhard Becher, Amanda Tufman, Nicolas Nuñez, Markus Joerger, Lukas Flatz
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. Objectives: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. Methods: The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T-cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with NSCLC and patients with melanoma. Measurements and Main Results: Across both cohorts, patients in whom pneumonitis developed had higher pretreatment levels of immunoglobulin G autoantibodies targeting surfactant protein (SP)-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4+ IFN-γ-positive SP-B-specific T cells and expanding T-cell clonotypes recognizing this protein, accompanied by a proinflammatory serum proteomic profile. Conclusions: Our data suggest that the cooccurrence of SP-B-specific immunoglobulin G autoantibodies and CD4+ T cells is associated with the development of pneumonitis during ICI therapy. Pretreatment levels of these antibodies may represent a potential biomarker for an increased risk of developing pneumonitis, and on-treatment levels may provide a diagnostic aid.
Language in Bioethics: Beyond the Representational View
Authors: Justin T. Clapp, Jacqueline M. Kruser, Margaret L. Schwarze, Rachel A. Hadler
Journal: The American Journal of Bioethics (2024)

Though assumptions about language underlie all bioethical work, the field has rarely partaken of theories of language. This article encourages a more linguistically engaged bioethics. We describe the tacit conception of language that is frequently upheld in bioethics—what we call the representational view, which sees language essentially as a means of description. We examine how this view has routed the field's theories and interventions down certain paths. We present an alternative model of language—the pragmatic view—and explore how it expands and clarifies traditional bioethical concerns. To lend concreteness, we apply the pragmatic view to a pervasive concept in bioethics and adjacent fields: decision making. We suggest that problems of the decision-making approach to bioethical issues are grounded in adherence to the representational view. Drawing on empirical work in surgery and critical care, we show how the pragmatic view productively reframes bioethical questions about how medical treatments are pursued.
TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods
Authors: Gary S Collins, Karel G M Moons, Paula Dhiman, Richard D Riley, Andrew L Beam, Ben Van Calster, Marzyeh Ghassemi, Xiaoxuan Liu, Johannes B Reitsma, Maarten van Smeden, Anne-Laure Boulesteix, Jennifer Catherine Camaradou, Leo Anthony Celi, Spiros Denaxas, Alastair K Denniston, Ben Glocker, Robert M Golub, Hugh Harvey, Georg Heinze, Michael M Hoffman, André Pascal Kengne, Emily Lam, Naomi Lee, Elizabeth W Loder, Lena Maier-Hein, Bilal A Mateen, Melissa D McCradden, Lauren Oakden-Rayner, Johan Ordish, Richard Parnell, Sherri Rose, Karandeep Singh, Laure Wynants, Patricia Logullo
Journal: BMJ (2024)

The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum reporting recommendations for studies developing or evaluating the performance of a prediction model. Methodological advances in the field of prediction have since included the widespread use of artificial intelligence (AI) powered by machine learning methods to develop prediction models. An update to the TRIPOD statement is thus needed. TRIPOD+AI provides harmonised guidance for reporting prediction model studies, irrespective of whether regression modelling or machine learning methods have been used. The new checklist supersedes the TRIPOD 2015 checklist, which should no longer be used. This article describes the development of TRIPOD+AI and presents the expanded 27 item checklist with more detailed explanation of each reporting recommendation, and the TRIPOD+AI for Abstracts checklist. TRIPOD+AI aims to promote the complete, accurate, and transparent reporting of studies that develop a prediction model or evaluate its performance. Complete reporting will facilitate study appraisal, model evaluation, and model implementation.