tbuckley/cabot-search huggingface dataset:
IL-33 acts as a costimulatory signal to generate alloreactive Th1 cells in graft-versus-host disease
Authors: Gaelen K. Dwyer, Lisa R. Mathews, José A. Villegas, Anna Lucas, Anne Gonzalez de Peredo, Bruce R. Blazar, Jean-Philippe Girard, Amanda C. Poholek, Sanjiv A. Luther, Warren Shlomchik, Hēth R. Turnquist
Journal: Journal of Clinical Investigation (2022)

Antigen-presenting cells (APCs) integrate signals emanating from local pathology and program appropriate T cell responses. In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory APCs that secrete IL-12, which is a driver of donor Th1 responses, causing graft-versus-host disease (GVHD). Nevertheless, other mechanisms exist to initiate alloreactive T cell responses, as recipients with disrupted DAMP signaling or lacking IL-12 develop GVHD. We established that tissue damage signals are perceived directly by donor CD4+ T cells and promoted T cell expansion and differentiation. Specifically, the fibroblastic reticular cell-derived DAMP IL-33 is increased by recipient conditioning and is critical for the initial activation, proliferation, and differentiation of alloreactive Th1 cells. IL-33 stimulation of CD4+ T cells was not required for lymphopenia-induced expansion, however. IL-33 promoted IL-12-independent expression of Tbet and generation of Th1 cells that infiltrated GVHD target tissues. Mechanistically, IL-33 augmented CD4+ T cell TCR-associated signaling pathways in response to alloantigen. This enhanced T cell expansion and Th1 polarization, but inhibited the expression of regulatory molecules such as IL-10 and Foxp3. These data establish an unappreciated role for IL-33 as a costimulatory signal for donor Th1 generation after alloHCT.
Reply
Authors: Antonio D’Alessio, Claudia Angela Maria Fulgenzi, David J. Pinato
Journal: Hepatology (2022)

AD received educational support for congress attendance and consultancy fees from Roche. DJP received lecture fees from ViiV Healthcare, EISAI, IPSEN and Bayer Healthcare and travel expenses from Bristol Myers Squibb and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, IPSEN, DaVolterra, Mursla and Astra Zeneca; received research funding (to institution) from Merck Sharp & Dome and Bristol Myers Squibb.
Surgeon Volume and Outcomes in Primary Hyperparathyroidism—What Is Old Is New Again
Authors: Timothy M. Ullmann, Mohamed Abdelgadir Adam, Julie Ann Sosa
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Albumin nanoparticle containing a PI3Kγ inhibitor and paclitaxel in combination with α-PD1 induces tumor remission of breast cancer in mice
Authors: Yudong Song, Luke Bugada, Ruiting Li, Hongxiang Hu, Luchen Zhang, Chengyi Li, Hebao Yuan, Krishani Kumari Rajanayake, Nathan A. Truchan, Fei Wen, Wei Gao, Duxin Sun
Journal: Science Translational Medicine (2022)

Immunomodulators that remodel the tumor immunosuppressive microenvironment have been combined with anti–programmed death 1 (α-PD1) or anti–programmed death ligand 1 (α-PDL1) immunotherapy but have shown limited success in clinical trials. However, therapeutic strategies to modulate the immunosuppressive microenvironment of lymph nodes have been largely overlooked. Here, we designed an albumin nanoparticle, Nano-PI, containing the immunomodulators PI3Kγ inhibitor (IPI-549) and paclitaxel (PTX). We treated two breast cancer mouse models with Nano-PI in combination with α-PD1, which remodeled the tumor microenvironment in both lymph nodes and tumors. This combination achieved long-term tumor remission in mouse models and eliminated lung metastases. PTX combined with IPI-549 enabled the formation of a stable nanoparticle and enhanced the repolarization of M2 to M1 macrophages. Nano-PI not only enhanced the delivery of both immunomodulators to lymph nodes and tumors but also improved the drug accumulation in the macrophages of these two tissues. Immune cell profiling revealed that the combination of Nano-PI with α-PD1 remodeled the immune microenvironment by polarizing M2 to M1 macrophages, increasing CD4 + and CD8 + T cells, B cells, and dendritic cells, decreasing regulatory T cells, and preventing T cell exhaustion. Our data suggest that Nano-PI in combination with α-PD1 modulates the immune microenvironment in both lymph nodes and tumors to achieve long-term remission in mice with metastatic breast cancer, and represents a promising candidate for future clinical trials.
化脓性汗腺炎可能的新口服治疗
Journal: British Journal of Dermatology (2022)

British Journal of DermatologyVolume 186, Issue 5 p. e219-e219 Plain Language Summary 化脓性汗腺炎可能的新口服治疗 First published: 02 May 2022 https://doi.org/10.1111/bjd.21272AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Alavi et al. Br J Dermatol 2022; 186:803–813. 化脓性汗腺炎(HS)是一种罕见的慢性皮肤病，伴有痛性结节(肿块)和脓肿(充满液体的病变)，可能导致形成窦道和瘢痕。目前治疗HS的方案有限，而且患者对药物的反应以及反应的持续时间各异。 本研究的作者来自美国和加拿大。在两项针对HS成年患者的临床试验中研究了一种口服药物(INCB054707)，靶向被称为“Janus激酶介导的炎症”的过程。在这两项研究中，45位患者接受了四种剂量规格的INCB054707或安慰剂(看起来与试验药物一样但不含任何药物成分)，持续8周。对他们进行了不良副作用的检查。测量HS病变数量在一段时间后的变化，评估治疗是否起到了作用。在研究期间的不同时间，请患者描述他们最严重的皮肤疼痛和生活质量。 INCB054707治疗患者的副作用总体上轻微，36位INCB054707治疗患者中只有一位出于安全性原因完全停药。 与接受安慰剂的患者相比，接受较高药物剂量的患者在8周结束时皮肤状况得到改善。与仅接受安慰剂的患者相比，有更多接受INCB054707的患者在治疗期间的皮肤疼痛较轻，并感觉生活质量有所改善。 总而言之，这可能是治疗HS的一种新方法。有更大数量受试者参加的其他研究正在进行中。 Volume186, Issue5May 2022Pages e219-e219 RelatedInformation
Comprehensive Evaluation of Machine Learning Models and Gene Expression Signatures for Prostate Cancer Prognosis Using Large Population Cohorts
Authors: Ruidong Li, Jianguo Zhu, Wei-De Zhong, Zhenyu Jia
Journal: Cancer Research (2022)

Overtreatment remains a pervasive problem in prostate cancer management due to the highly variable and often indolent course of disease. Molecular signatures derived from gene expression profiling have played critical roles in guiding prostate cancer treatment decisions. Many gene expression signatures have been developed to improve the risk stratification of prostate cancer and some of them have already been applied to clinical practice. However, no comprehensive evaluation has been performed to compare the performance of these signatures. In this study, we conducted a systematic and unbiased evaluation of 15 machine learning (ML) algorithms and 30 published prostate cancer gene expression-based prognostic signatures leveraging 10 transcriptomics datasets with 1,558 primary patients with prostate cancer from public data repositories. This analysis revealed that survival analysis models outperformed binary classification models for risk assessment, and the performance of the survival analysis methods-Cox model regularized with ridge penalty (Cox-Ridge) and partial least squares (PLS) regression for Cox model (Cox-PLS)-were generally more robust than the other methods. Based on the Cox-Ridge algorithm, several top prognostic signatures displayed comparable or even better performance than commercial panels. These findings will facilitate the identification of existing prognostic signatures that are promising for further validation in prospective studies and promote the development of robust prognostic models to guide clinical decision-making. Moreover, this study provides a valuable data resource from large primary prostate cancer cohorts, which can be used to develop, validate, and evaluate novel statistical methodologies and molecular signatures to improve prostate cancer management.This systematic evaluation of 15 machine learning algorithms and 30 published gene expression signatures for the prognosis of prostate cancer will assist clinical decision-making.
Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials
Authors: D. Rischin, H. Mehanna, R.J. Young, M. Bressel, J. Dunn, J. Corry, P. Soni, T. Fulton-Lieuw, G. Iqbal, L. Kenny, S. Porceddu, C. Wratten, M. Robinson, B.J. Solomon
Journal: Annals of Oncology (2022)
Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline
Authors: Ganesh Raghu, Martine Remy-Jardin, Luca Richeldi, Carey C. Thomson, Yoshikazu Inoue, Takeshi Johkoh, Michael Kreuter, David A. Lynch, Toby M. Maher, Fernando J. Martinez, Maria Molina-Molina, Jeffrey L. Myers, Andrew G. Nicholson, Christopher J. Ryerson, Mary E. Strek, Lauren K. Troy, Marlies Wijsenbeek, Manoj J. Mammen, Tanzib Hossain, Brittany D. Bissell, Derrick D. Herman, Stephanie M. Hon, Fayez Kheir, Yet H. Khor, Madalina Macrea, Katerina M. Antoniou, Demosthenes Bouros, Ivette Buendia-Roldan, Fabian Caro, Bruno Crestani, Lawrence Ho, Julie Morisset, Amy L. Olson, Anna Podolanczuk, Venerino Poletti, Moisés Selman, Thomas Ewing, Stephen Jones, Shandra L. Knight, Marya Ghazipura, Kevin C. Wilson
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.
Use of Machine Learning Consensus Clustering to Identify Distinct Subtypes of Black Kidney Transplant Recipients and Associated Outcomes
Authors: Charat Thongprayoon, Pradeep Vaitla, Caroline C. Jadlowiec, Napat Leeaphorn, Shennen A. Mao, Michael A. Mao, Pattharawin Pattharanitima, Jackrapong Bruminhent, Nadeen J. Khoury, Vesna D. Garovic, Matthew Cooper, Wisit Cheungpasitporn
Journal: JAMA Surgery (2022)

Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups.To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach.This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster's key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021.Machine learning consensus clustering approach.Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant.Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4.In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups.
Simultaneous Imaging of Ventilation and Gas Exchange with Hyperpolarized <sup>129</sup>Xe MRI for Monitoring Patients with Endobronchial Valve Interventions
Authors: Hooman Hamedani, Kevin Ma, David DiBardino, Ryan Baron, Stephen Kadlecek, Faraz Amzajerdian, Kai Ruppert, Ian Duncan, Rahim R. Rizi
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Simultaneous Imaging of Ventilation and Gas Exchange with Hyperpolarized 129Xe MRI for Monitoring Patients with Endobronchial Valve Interventions." American Journal of Respiratory and Critical Care Medicine, 205(9), pp. e48–e50
CAR T cell manufacturing from naive/stem memory T lymphocytes enhances antitumor responses while curtailing cytokine release syndrome
Authors: Silvia Arcangeli, Camilla Bove, Claudia Mezzanotte, Barbara Camisa, Laura Falcone, Francesco Manfredi, Eugenia Bezzecchi, Rita El Khoury, Rossana Norata, Francesca Sanvito, Maurilio Ponzoni, Beatrice Greco, Marta Angiola Moresco, Matteo G. Carrabba, Fabio Ciceri, Chiara Bonini, Attilio Bondanza, Monica Casucci
Journal: Journal of Clinical Investigation (2022)

Chimeric antigen receptor (CAR) T cell expansion and persistence represent key factors to achieve complete responses and prevent relapses. These features are typical of early memory T cells, which can be highly enriched through optimized manufacturing protocols. Here, we investigated the efficacy and safety profiles of CAR T cell products generated from preselected naive/stem memory T cells (TN/SCM), as compared with unselected T cells (TBULK). Notwithstanding their reduced effector signature in vitro, limiting CAR TN/SCM doses showed superior antitumor activity and the unique ability to counteract leukemia rechallenge in hematopoietic stem/precursor cell–humanized mice, featuring increased expansion rates and persistence together with an ameliorated exhaustion and memory phenotype. Most relevantly, CAR TN/SCM proved to be intrinsically less prone to inducing severe cytokine release syndrome, independently of the costimulatory endodomain employed. This safer profile was associated with milder T cell activation, which translated into reduced monocyte activation and cytokine release. These data suggest that CAR TN/SCM are endowed with a wider therapeutic index compared with CAR TBULK.
NAFLD/NASH
Authors: Elisabetta Bugianesi, Salvatore Petta
Journal: Journal of Hepatology (2022)

The current nomenclature of NAFLD supports a diagnosis "in negative", based on the exclusion of other causes of liver disease. An international consensus panel has recently suggested a new nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD),1 based on the identification of the associated metabolic risk factors to support active case finding. The burden of the disease is large, with an estimated prevalence of 25.2% in the general population,2 increasing to more than 50% in high-risk groups such as diabetic and obese patients.
Understanding Vaccine Safety and the Roles of the FDA and the CDC
Authors: H. Cody Meissner
Journal: New England Journal of Medicine (2022)

T hroughout human history, epidemics and pandemics have resulted in untold suffering, localized reductions in population size, and damaged economies.Often, economic harm has caused greater loss of wellbeing than the infection itself.Increasing population density and economic and social changes, such as population shifts and the requirement for increased food production, have resulted in human encroachment into less populated areas of the globe.These factors bring people into closer contact with wildlife and arthropod vectors, as well as livestock and poultry, which increases the risk that zoonotic pathogens will spill over to humans.In the past two decades, bats have been reservoirs of three betacoronaviruses that have crossed the species barrier, causing severe acute respiratory syndrome (SARS)-like disease in humans.Recent outbreaks caused by noncoronaviruses such as pandemic influenza A (H1N1), Ebola, and Zika viruses underscore the threat of future outbreaks (Table 1).In the decades ahead, diseases caused by currently unknown viruses are likely to emerge as changes in human behavior continue to increase exposure to infectious organisms in the environment.The development and widespread acceptance of vaccines will be crucial for controlling disease caused by pathogenic organisms, especially those that acquire the capability of efficient human-to-human transmission.As existing microbes evolve and new microbes emerge, nonpharmacologic interventions, including containment, isolation, and quarantine, will play a role in outbreak control, but vaccines will form the foundation for converting a viral pandemic into manageable endemic disease (Table 2).Containment of past viral pandemics has been accomplished without vaccines, but minimizing the morbidity and mortality associated with future pandemics is likely to be difficult to achieve without high rates of vaccine acceptance, especially for viruses that use the respiratory tract as a portal of entry. 1 A widespread understanding and acceptance of vaccines will be an integral aspect of public health strategies for limiting the consequences of future pandemics.This review discusses how vaccine safety and efficacy are evaluated, the pathways by which vaccines become authorized or licensed, and considerations addressed by advisory bodies in establishing vaccine recommendations.Defining Vaccine Sa fe t y
Associating Violence With Schizophrenia—Risks and Biases
Authors: Paolo Fusar-Poli, Charlene Sunkel, Vikram Patel
Journal: JAMA Psychiatry (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal