tbuckley/cabot-search huggingface dataset:
Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies
Authors: Zhen Lu, Ioannis Verginadis, Motofumi Kumazoe, Gerardo M. Castillo, Yao Yao, Rebecca E. Guerra, Sandra Bicher, Menghao You, George McClung, Rong Qiu, Zebin Xiao, Zhen Miao, Subin S. George, Daniel P. Beiting, Takashi Nojiri, Yasutake Tanaka, Yoshinori Fujimura, Hiroaki Onda, Yui Hatakeyama, Akiko Nishimoto-Ashfield, Katrina Bykova, Wei Guo, Yi Fan, Nikolay M. Buynov, J. Alan Diehl, Ben Z. Stanger, Hirofumi Tachibana, Terence P. Gade, Ellen Puré, Constantinos Koumenis, Elijah M. Bolotin, Serge Y. Fuchs
Journal: Science Translational Medicine (2024)

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.
Uncovering Long COVID in Children
Authors: Suchitra Rao
Journal: JAMA (2024)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 journal
Stress-induced eosinophil activation contributes to postoperative morbidity and mortality after lung resection
Authors: Zhongcheng Mei, May A. Khalil, Yizhan Guo, Dongge Li, Anirban Banerjee, Mojtaba Taheri, Christina M. Kratzmeier, Kelly Chen, Christine L. Lau, Irina G. Luzina, Sergei P. Atamas, Sivaveera Kandasamy, Daniel Kreisel, Andrew E. Gelman, Elizabeth A. Jacobsen, Alexander Sasha Krupnick
Journal: Science Translational Medicine (2024)

Respiratory failure occurs more frequently after thoracic surgery than abdominal surgery. Although the etiology for this complication is frequently attributed to underlying lung disease present in patients undergoing thoracic surgery, this notion is often unfounded because many patients with normal preoperative pulmonary function often require prolonged oxygen supplementation even after minimal resection of lung tissue. Using a murine model of pulmonary resection and peripheral blood samples from patients undergoing resection of the lung or abdominal organs, we demonstrated that lung surgery initiates a proinflammatory loop that results in damage to the remaining lung tissue, noncardiogenic pulmonary edema, hypoxia, and even death. Specifically, we demonstrated that resection of murine lung tissue increased concentrations of the homeostatic cytokine interleukin-7, which led to local and systemic activation of type 2 innate lymphoid cells. This process activated lung-resident eosinophils and facilitated stress-induced eosinophil maturation in the bone marrow in a granulocyte-macrophage colony-stimulating factor–dependent manner, resulting in systemic eosinophilia in both mice and humans. Up-regulation of inducible nitric oxide synthase in lung-resident eosinophils led to tissue nitrosylation, pulmonary edema, hypoxia, and, at times, death. Disrupting this activation cascade at any stage ameliorated deleterious outcomes and improved survival after lung resection in the mouse model. Our data suggest that repurposing US Food and Drug Administration–approved eosinophil-targeting strategies may potentially offer a therapeutic intervention to improve outcomes for patients who require lung resection for benign or malignant etiology.
Smoking Cessation and Hidradenitis Suppurativa
Authors: Alexandra Charrow, Leandra A. Barnes
Journal: JAMA Dermatology (2024)

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 Dermatology 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 2024 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 Dermatology journal
Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice
Authors: Pritesh Desai, Courtney E. Karl, Baoling Ying, Chieh-Yu Liang, Tamara Garcia-Salum, Ana Carolina Santana, Felipe ten-Caten, None Joseph F. Urban Jr., Sayda M. Elbashir, Darin K. Edwards, Susan P. Ribeiro, Larissa B. Thackray, Rafick P. Sekaly, Michael S. Diamond
Journal: Science Translational Medicine (2024)

Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection–endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4 + and CD8 + T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein–specific CD8 + T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8 + T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants.
Microglia-specific <i>IL-10</i> gene delivery inhibits neuroinflammation and neurodegeneration in a mouse model of Parkinson’s disease
Authors: Simone Bido, Melania Nannoni, Sharon Muggeo, Diana Gambarè, Giorgia Ruffini, Edoardo Bellini, Laura Passeri, Silvia Iaia, Mirko Luoni, Martino Provinciali, Serena Gea Giannelli, Francesca Giannese, Dejan Lazarevic, Silvia Gregori, Vania Broccoli
Journal: Science Translational Medicine (2024)

Neuroinflammation plays a key role in exacerbating dopaminergic neuron (DAN) loss in Parkinson’s disease (PD). However, it remains unresolved how to effectively normalize this immune response given the complex interplay between the innate and adaptive immune responses occurring within a scarcely accessible organ like the brain. In this study, we uncovered a consistent correlation between neuroinflammation, brain parenchymal lymphocytes, and DAN loss among several commonly used mouse models of PD generated by a variety of pathological triggers. We validated a viral therapeutic approach for the microglia-specific expression of interleukin 10 (IL-10) to selectively mitigate the excessive inflammatory response. We found that this approach induced a local nigral IL-10 release that alleviated DAN loss in mice overexpressing the human SNCA gene in the substantia nigra. Single-cell transcriptomics revealed that IL-10 induced the emergence of a molecularly distinct microglial cell state, enriched in markers of cell activation with enhanced expression of prophagocytic pathways. IL-10 promoted microglial phagocytotic and clearance activities in vitro and reduced αSYN aggregate burden in the nigral area in mice overexpressing SNCA . Furthermore, IL-10 stimulated the differentiation of CD4 + T lymphocytes into active T regulatory cells and promoted inhibitory characteristics in CD8 + T cells. In summary, our results show that local and microglia-specific IL-10 transduction elicited strong immunomodulation in the nigral tissue with enhanced suppression of lymphocyte toxicity that was associated with DAN survival. These results offer insights into the therapeutic benefits of IL-10 and showcase a promising gene delivery approach that could minimize undesired side effects.
Repeated Omicron exposures redirect SARS-CoV-2–specific memory B cell evolution toward the latest variants
Authors: Ryutaro Kotaki, Saya Moriyama, Shintaro Oishi, Taishi Onodera, Yu Adachi, Eita Sasaki, Kota Ishino, Miwa Morikawa, Hiroaki Takei, Hidenori Takahashi, Tomohiro Takano, Ayae Nishiyama, Kohei Yumoto, Kazutaka Terahara, Masanori Isogawa, Takayuki Matsumura, Masaharu Shinkai, Yoshimasa Takahashi
Journal: Science Translational Medicine (2024)

Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B mem ) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain–based mRNA vaccines. After a second BA.5 exposure, B mem cells with BA.5 spike protein–skewed reactivity were promptly elicited, correlating with preexisting antibody titers. Clonal lineage analysis identified BA.5-skewed B mem cells that had redirected their specificity from the ancestral strain to BA.5 through somatic hypermutations. Moreover, B mem cells with redirected BA.5 specificity exhibited accelerated development compared with de novo B mem cells derived from naïve repertoires. This redirected BA.5 specificity demonstrated greater resilience to viral point mutation and adaptation to recent Omicron variants HK.3 and JN.1, months after the second BA.5 exposure, suggesting that existing B mem cells elicited by older vaccines can redirect their specificity toward newly evolving variants.
KIR2DL2/DL3+NKs and Helios+Tregs in peripheral blood predict nivolumab response in patients with metastatic renal cell cancer
Authors: Sara Santagata, Anna Maria Trotta, Crescenzo D’Alterio, Maria Napolitano, Giuseppina Rea, Marilena Di Napoli, Luigi Portella, Caterina Ieranò, Giuseppe Guardascione, Elisabetta Coppola, Christophe Caux, Bertrand Dubois, Helen J. Boyle, Joan Carles, Sabrina Rossetti, Rosa Azzaro, Florinda Feroce, Sisto Perdonà, Mario Fordellone, Anna Maria Bello, Daniela Califano, Paolo Chiodini, Sandro Pignata, Stefania Scala
Journal: Clinical Cancer Research (2024)

To identify predictive factors of nivolumab sensitivity, peripheral blood NKs and regulatory T-cell (Treg) were evaluated in patients with metastatic renal cell carcinoma (mRCC) enrolled in the REVOLUTION trial.
Pembrolizumab and cabozantinib in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC): long-term survival update with a biomarker analysis
Authors: Nabil F. Saba, Ritu Chaudhary, Kedar Kirtane, Angelo Marra, Asari Ekpenyong, Ashley McCook-Veal, Nicole C. Schmitt, Jennifer H. Gross, Mihir R. Patel, Jill Remick, James E. Bates, Mark W. McDonald, Soumon F. Rudra, William A. Stokes, Maria Biernacki, Xiaofei Song, Robbert J.C. Slebos, Yuan Liu, Conor E. Steuer, Dong M. Shin, Yong Teng, Christine H. Chung
Journal: Clinical Cancer Research (2024)

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) have immunomodulatory properties and improve clinical outcomes in combination with anti-PD-1 therapy in different malignancies. We report the long-term efficacy and safety of pembrolizumab and cabozantinib in patients with RMHNSCC and include a correlative biomarker analysis.
A PHASE 1 FIRST-IN-HUMAN STUDY OF THE MCL-1 INHIBITOR AZD5991 IN PATIENTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES
Authors: Pinkal Desai, Sagar Lonial, Amanda Cashen, Manali Kamdar, Ian Flinn, Susan O’Brien, Jacqueline S. Garcia, Neha Korde, Javid Moslehi, Margaret Wey, Patricia Cheung, Shringi Sharma, Damilola Olabode, Hong Chen, Firasath Ali Syed, Mary Liu, Jamal Saeh, Marcio Andrade-Campos, Tapan M. Kadia, James S. Blachly
Journal: Clinical Cancer Research (2024)

AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.
Sensors and Devices Guided by AI for Personalized Pain Medicine
Authors: Yantao Xing, Kaiyuan Yang, Albert Lu, Ken Mackie, Feng Guo
Journal: Cyborg and Bionic Systems (2024)

Personalized pain medicine aims to tailor pain treatment strategies for the specific needs and characteristics of an individual patient, holding the potential for improving treatment outcomes, reducing side effects, and enhancing patient satisfaction. Despite existing pain markers and treatments, challenges remain in understanding, detecting, and treating complex pain conditions. Here, we review recent engineering efforts in developing various sensors and devices for addressing challenges in the personalized treatment of pain. We summarize the basics of pain pathology and introduce various sensors and devices for pain monitoring, assessment, and relief. We also discuss advancements taking advantage of rapidly developing medical artificial intelligence (AI), such as AI-based analgesia devices, wearable sensors, and healthcare systems. We believe that these innovative technologies may lead to more precise and responsive personalized medicine, greatly improved patient quality of life, increased efficiency of medical systems, and reducing the incidence of addiction and substance use disorders.
Limited predictive value of the gut microbiome and metabolome for response to biological therapy in inflammatory bowel disease
Authors: Femke M. Prins, Iwan J. Hidding, Marjolein A.Y. Klaassen, Valerie Collij, Johannes P.D. Schultheiss, Werna T.C. Uniken Venema, Amber Bangma, Jurne B. Aardema, Bernadien H. Jansen, Wout G.N. Mares, Ben J.M. Witteman, Eleonora A.M. Festen, Gerard Dijkstra, Marijn C. Visschedijk, Herma H. Fidder, Arnau Vich Vila, Bas Oldenburg, Ranko Gacesa, Rinse K. Weersma
Journal: Gut Microbes (2024)

Emerging evidence suggests the gut microbiome's potential in predicting response to biologic treatments in patients with inflammatory bowel disease (IBD). In this prospective study, we aimed to predict treatment response to vedolizumab and ustekinumab, integrating clinical data, gut microbiome profiles based on metagenomic sequencing, and untargeted fecal metabolomics. We aimed to identify predictive biomarkers and attempted to replicate microbiome-based signals from previous studies. We found that the predictive utility of the gut microbiome and fecal metabolites for treatment response was marginal compared to clinical features alone. Testing our identified microbial ratios in an external cohort reinforced the lack of predictive power of the microbiome. Additionally, we could not confirm previously published predictive signals observed in similar sized cohorts. Overall, these findings highlight the importance of external validation and larger sample sizes, to better understand the microbiome's impact on therapy outcomes in the setting of biologicals in IBD before potential clinical implementation.
Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis
Authors: Jihyun An, Young Eun Chon, Gunho Kim, Mi Na Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Miyoung Choi, Dae Won Jun, Seung Up Kim, Ji Won Han, Young-Joo Jin
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease.Methods: Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, according to liver biopsy.Results: Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87, 0.89, and 0.99 for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88, 0.88, and 0.92, respectively, while in PSC, they were 0.88, 0.95, and 0.92, respectively. The cutoff values for AF were 7.5–17.9 kPa in PBC, 8.18–12.1 kPa in AIH, and 9.6 kPa in PSC.Conclusions: VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases. This non-invasive method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.
Morgellons disease shows a lower quality of life than psoriasis, atopic dermatitis, and prurigo nodularis
Authors: Mackenzie O Gipple, Ramneek K Dhami, Emile Latour, Jesse J Keller
Journal: British Journal of Dermatology (2024)

Morgellons disease (MD) greatly affects a patient’s quality of life (QoL). Therefore, we aimed to measure the disease burden of MD on QoL and compare it with well-funded dermatological conditions, including prurigo nodularis (PN), atopic dermatitis (AD) and psoriasis. This qualitative cross-sectional survey, comprising Dermatology Life Quality Index (DLQI), Pittsburgh Sleep Quality Index (PSQI) and 5-D itch scale questionnaires, was distributed to patients with untreated MD seen at the Oregon Health and Science University Dermatology clinic from July 2022 to July 2023. When comparing mean scores across dermatological conditions, MD had significantly higher DLQI scores than PN, AD and psoriasis, and significantly higher PSQI scores than AD and psoriasis.
Academic Readiness among Young Children Treated for Brain Tumors: A Multisite, Prospective, Longitudinal Trial
Authors: Melanie R Somekh, Jason M Ashford, Michelle A Swain, Lana L Harder, Bonnie L Carlson-Green, Joanna Wallace, Ryan J Kaner, Catherine A Billups, Arzu Onar-Thomas, Jeanelle S Ali, Jennifer L Harman, Thomas E Merchant, Amar Gajjar, Heather M Conklin
Journal: JNCI Journal of the National Cancer Institute (2024)

Young children treated for central nervous system (CNS) malignancies are at high risk for difficulties with academic functioning due to increased vulnerability of the developing brain and missed early developmental opportunities. Extant literature examining academics in this population is limited. We investigated academic readiness, its clinical and demographic predictors, and its relationship with distal academic outcomes among patients treated for CNS tumors during early childhood.
Integrated Approach in Evaluating the Results of Cosmetic Procedures Using Ultrasonography and Magnetic Resonance Tomography (Clinical Study)
Authors: I. N. Bondarenko, I. F. Dzhubueva, S. A. Magomedova, A. Yu. Vasil'ev
Journal: Radiology - Practice (2024)

Aim. To investigate the capabilities of comprehensive assessment using ultrasound and magnetic resonance imaging (MRI) of the results of cosmetic procedures. Materials and Methods . A study of the soft tissues of the anterior abdominal wall of a 43-year-old woman complaining of skin atony and postpartum stretch marks using highresolution ultrasound and MRI. Results . At ultrasonography in the projection of injection of polylactic acid and calcium hydroxyapatite preparations and radiofrequency treatment, an increase in echogenicity of hypodermis with the presence of acoustic shadow was noted. On MRI at the level of derma and hypoderma of periumbilical region in the projection of radiofrequency treatment, injections of preparations based on polylactic acid on the left, calcium hydroxyapatite on the right in 3 months after subdermal injection, areas of hyperintense MR-signal in T2 weight image (WI) and STIR programs, hypointense in T1 WI, without diffusion limitation on DWI b=1000 were determined. In SWI mode, the focus of hypointense MR signal of rounded shape with clear and smooth contours was visualized on the right side of the image. Conclusion . The clinical study demonstrates the possibilities of an integrated approach in evaluating the results of cosmetic procedures using ultrasonography and MRI.
Examining racial and ethnic disparities in diagnosis and access to care in infantile atopic dermatitis in the USA: a retrospective cohort study
Authors: Sarah E Servattalab, Michelle Lee, Madeline Hlobik, Hannah Song, Jennifer T Huang
Journal: British Journal of Dermatology (2024)

Atopic dermatitis (AD) is an inflammatory skin disorder that is common in children and associated with medical and psychosocial comorbidities. Previous studies have shown that there exist significant racial disparities in healthcare utilization in children with AD; however, literature on disparities in dermatology access is limited.