tbuckley/cabot-search huggingface dataset:
Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function
Authors: Torri D. Metz, Amanda A. Allshouse, Gwendolyn A. McMillin, Tom Greene, Judith H. Chung, William A. Grobman, David M. Haas, Brian M. Mercer, Samuel Parry, Uma M. Reddy, George R. Saade, Hyagriv N. Simhan, Robert M. Silver
Journal: JAMA (2023)

Importance Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score–weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.
Abstract 16230: Genetically Confirmed Hypertrophic Cardiomyopathy, Initially Misdiagnosed as Cardiac Amyloidosis by Cardiac Biopsy
Authors: yeo reum kim, Sang Hoon Shin, Chang Yong Shin, junghyuck lee, Do Young Kim, YONGHEE KIM, Jaeho Seung, Moon Kyung Jung, Hyun Ki Lee, Kyung Hoon Roh, Mi-Hyang Jung, Byung-Hee Hwang, Kiyuk Chang
Journal: Circulation (2023)

A 72-year-old male was admitted with worsening dyspnea. 5 years ago, echocardiography demonstrated biventricular hypertrophy with highly reflective myocardium. Cardiac MRI demonstrated epicardial and mesocardial late gadolinium enhancement suggesting possibility of infiltrative cardiomyopathy. Endomyocardial biopsy revealed the deposition of eosinophilic amorphous material, consistent with amyloidosis. Congo red stain was also compatible with cardiac amyloidosis. There was no evidence of monoclonal gammopathy in the serum and urine immunofixation and electrophoresis. He was diagnosed with cardiac amyloidosis of unknown etiology. 2 years later, he complained dyspnea on exertion. Echocardiography revealed decreased LV systolic function (LVEF 53 -&gt; 38%). Single gene mutation test for TTR and a-galactosidase level turned out to be negative. Recently, echocardiography seems to be more stiff and accompanied by slight wall thinning locally. Cardiac MRI demonstrated wall thickening has been slightly decreased and enhancement of interventricular septum appeared to be more prominent. We performed DPD bone scan and it showed no cardiac uptake, suggesting low probability of ATTR cardiac amyloidosis. We performed genetic test (whole exome sequencing based on next generation sequencing) and it showed MYBPC3 (myosin binding protein C3) gene mutation, which suggestive of hypertrophic cardiomyopathy. He was discharged with heart failure medications and familial screening is in progress. HCMP can be presented with many faces which often hampers the true diagnosis. We often think of pathological findings as a golden diagnosis, and try to match everything to the pathological findings, but cardiac pathology is a relatively unfamiliar area for most pathologists. Cardiologists need to closely review clinical and imaging findings along with pathological findings. And additional testing, such as genetic testing, may be helpful in making a diagnosis.
Abstract 14923: Induced Pluripotent Stem Cell Derived Endothelial Progenitor Cells Attenuate Pulmonary Arterial Hypertension
Authors: Wei-Chun Huang, Mei-Tzu Wang, Kun-Chang LIN
Journal: Circulation (2023)

Introduction: Although transplantation of adult endothelial progenitor cells (EPCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the low number and weakened functions of human primary EPCs are serious problems for autologous transplantation for patients and limited their therapeutic efficiency. Hypothesis: Te aim of this study is to investigate the efficiency of induced pluripotent stem cell derived EPCs on attenuating PAH. Methods: This study differentiated induced pluripotent stem cells from healthy people into vascular endothelial precursor cells (iPSC-EPC), whose specific protein expressed CD133 accounted for 95.4% and KDR accounted for 75.7%, and further confirmed that iPSC-EPC have the ability to differentiate vascular endothelial cells (iPSC-EC) with similar EC cobblestone morphology, acetylated LDL uptake, and UEA-1 lectin binding. IPSC-EC-specific protein expression CD144 accounts for 99.0% and CD31 accounts for 75.1%. Results: This study explored the efficacy of healthy iPSC-EPC in the treatment of PAH in an animal model. Both prophylactic and therapeutic treatments of iPSC-EPC were effective in rescuing monocrotaline (MCT)-induced right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary artery wall thickening in PAH. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-EPC derived culture medium (EPC-CM) treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by EPC-CM with suppression of PCNA, cyclin D1, MMP-1, and MMP-9. This study also found that iPSC-EPC treatment reduced MCT-PASMC senescence and senescence-associated secretory phenotype (SASP) in MCT-treated rats. Conclusions: This study found that ctrl iPSC-EPC restored miRNA levels in the lung tissue of MCT-treated rats. IPSC-EPC is effective at preventing and reversing pulmonary hypertension by regulating the expression of miRNAs, and reducing pulmonary vascular remodelling.
Abstract 14914: Vascular Remodelling Can Be Alleviated by Stem Cell Exosomes in Pulmonary Arterial Hypertension via HIF-1α and Runx2 Signalling Pathway
Authors: Mei-Tzu Wang, Kun-Chang LIN, Wei-Chun Huang
Journal: Circulation (2023)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared to the induced pluripotent stem cells (iPSCs). Hypothesis: In this study, we determined the efficacy and mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Methods: Both prophylactic and therapeutic iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Results: Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and PAK1/AKT/Runx2 pathways. Conclusions: IPSC-Exo are effective at preventing and reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.
Disease as an Aftermath of War
Journal: JAMA (2023)

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
iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer
Authors: Yoshiki Furukawa, Midori Ishii, Jun Ando, Kazuya Ikeda, Kyomi J. Igarashi, Shintaro Kinoshita, Yoko Azusawa, Tokuko Toyota, Tadahiro Honda, Mahito Nakanishi, Koichi Ohshima, Ayako Masuda, Emiko Yoshida, Mari Kitade, Matthew Porteus, Yasuhisa Terao, Hiromitsu Nakauchi, Miki Ando
Journal: Cell Reports Medicine (2023)

Functionally rejuvenated human papilloma virus-specific cytotoxic T lymphocytes (HPV-rejTs) generated from induced pluripotent stem cells robustly suppress cervical cancer. However, autologous rejT generation is time consuming, leading to difficulty in treating patients with advanced cancer. Although use of allogeneic HPV-rejTs can obviate this, the major obstacle is rejection by the patient immune system. To overcome this, we develop HLA-A24&-E dual integrated HPV-rejTs after erasing HLA class I antigens. These rejTs effectively suppress recipient immune rejection while maintaining more robust cytotoxicity than original cytotoxic T lymphocytes. Single-cell RNA sequencing performed to gain deeper insights reveal that HPV-rejTs are highly enriched with tissue resident memory T cells, which enhance cytotoxicity against cervical cancer through TGFβR signaling, with increased CD103 expression. Genes associated with the immunological synapse also are upregulated, suggesting that these features promote stronger activation of T cell receptor (TCR) and increased TCR-mediated target cell death. We believe that our work will contribute to feasible "off-the-shelf" T cell therapy with robust anti-cervical cancer effects.
Itaconate suppresses atherosclerosis by activating a Nrf2-dependent antiinflammatory response in macrophages in mice
Authors: Jianrui Song, Yanling Zhang, Ryan A. Frieler, Anthony Andren, Sherri Wood, Daniel J. Tyrrell, Peter Sajjakulnukit, Jane C. Deng, Costas A. Lyssiotis, Richard M. Mortensen, Morgan Salmon, Daniel R. Goldstein
Journal: Journal of Clinical Investigation (2023)

Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as "immune-responsive gene 1"/IRG1) are upregulated during atherogenesis in mice. Deletion of Acod1 in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4-ocytyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, Nuclear factor erythroid-2 Related Factor 2 (Nrf2) was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis.
Metformin for Diabetes in Pregnancy
Authors: Denice S. Feig
Journal: JAMA (2023)

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
trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing
Authors: Amitabha Mukhopadhyay, Yoshikazu Tsukasaki, Wan Ching Chan, Jonathan P. Le, Man Long Kwok, Jian Zhou, Viswanathan Natarajan, Nima Mostafazadeh, Mark Maienschein-Cline, Ian Papautsky, Chinnaswamy Tiruppathi, Zhangli Peng, Jalees Rehman, Balaji Ganesh, Yulia Komarova, Asrar B. Malik
Journal: Immunity (2023)

The regulation of polymorphonuclear leukocyte (PMN) function by mechanical forces encountered during their migration across restrictive endothelial cell junctions is not well understood. Using genetic, imaging, microfluidic, and in vivo approaches, we demonstrated that the mechanosensor Piezo1 in PMN plasmalemma induced spike-like Ca2+ signals during trans-endothelial migration. Mechanosensing increased the bactericidal function of PMN entering tissue. Mice in which Piezo1 in PMNs was genetically deleted were defective in clearing bacteria, and their lungs were predisposed to severe infection. Adoptive transfer of Piezo1-activated PMNs into the lungs of Pseudomonas aeruginosa-infected mice or exposing PMNs to defined mechanical forces in microfluidic systems improved bacterial clearance phenotype of PMNs. Piezo1 transduced the mechanical signals activated during transmigration to upregulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4, crucial for the increased PMN bactericidal activity. Thus, Piezo1 mechanosensing of increased PMN tension, while traversing the narrow endothelial adherens junctions, is a central mechanism activating the host-defense function of transmigrating PMNs.
Immunomodulatory leptin receptor+ sympathetic perineurial barrier cells protect against obesity by facilitating brown adipose tissue thermogenesis
Authors: Emma R. Haberman, Gitalee Sarker, Bernardo A. Arús, Karin A. Ziegler, Sandro Meunier, Noelia Martínez-Sánchez, Eliška Freibergerová, Sinem Yilmaz-Özcan, Iara Fernández-González, Chloe Zentai, Conan J.O. O’Brien, David E. Grainger, Davi Sidarta-Oliveira, Svetoslav Chakarov, Andrea Raimondi, Matteo Iannacone, Stefan Engelhardt, Miguel López, Florent Ginhoux, Ana I. Domingos
Journal: Immunity (2023)
Abstract 14908: The Impact of Virtual Reality on Early Rehabilitation in Cardiac Intensive Care Units
Authors: Mei-Tzu Wang, Wei-Chun Huang
Journal: Circulation (2023)

Introduction: The early mobilization of patients in the intensive care unit (ICU) was shown to be important in patients’ recovery. Hypothesis: The aim of this study in to investigate the impact of virtual reality (VR) on early rehabilitation in cardiac intensive care units. Methods: The consecutive patients in adult cardiac intensive care units were enrolled. The patients were divided into two groups VR rehabilitation group and control group. The patients in VR rehabilitation group received respiratory, functional training with virtual reality (VR). Maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), SF-36, ICU stay and intubation days were collected. Results: After VR training, the maximal inspiratory pressure (MIP) showed significant improvement ( p =0.0088) and maximal expiratory pressure (MEP) also improved significantly ( p =0.0203). Further, VR rehabilitation group also had better Barthel index ( p &lt;0.0001), intensive mobility scale ( p &lt;0.0001), shorter ICU stay ( p =0.0063), and intubation days ( p =0.006). Conclusions: This study demonstrate VR rehabilitation in cardiac intensive care units improved exercise capacity, Barthel index, intensive mobility scale, ICU stay and intubation days.
Integrated omics landscape of hepatocellular carcinoma suggests proteomic subtypes for precision therapy
Authors: Xiaohua Xing, En Hu, Jiahe Ouyang, Xianyu Zhong, Fei Wang, Kaixin Liu, Linsheng Cai, Yang Zhou, Yingchao Wang, Geng Chen, Zhenli Li, Liming Wu, Xiaolong Liu
Journal: Cell Reports Medicine (2023)

Patients with hepatocellular carcinoma (HCC) at the same clinical stage can have extremely different prognoses, and molecular subtyping provides an opportunity for individualized precision treatment. In this study, genomic, transcriptomic, proteomic, and phosphoproteomic profiling of primary tumor tissues and paired para-tumor tissues from HCC patients (N = 160) are integrated. Proteomic profiling identifies three HCC subtypes with different clinical prognosis, which are validated in three publicly available external validation sets. A simplified panel of nine proteins associated with metabolic reprogramming is further identified as a potential subtype-specific biomarker for clinical application. Multi-omics analysis further reveals that three proteomic subtypes have significant differences in genetic alterations, microenvironment dysregulation, kinase-substrate regulatory networks, and therapeutic responses. Patient-derived cell-based drug tests (N = 26) show personalized responses for sorafenib in three proteomic subtypes, which can be predicted by a machine-learning response prediction model. Overall, this study provides a valuable resource for better understanding of HCC subtypes for precision clinical therapy.
An Analysis of Dosing-Related Postmarketing Requirements for Novel Oncology Drugs Approved by the U.S. Food and Drug Administration, 2012–2022
Authors: Grace Collins, Brittany McKelvey, Hillary S. Andrews, Jeff D. Allen, Mark D. Stewart
Journal: Clinical Cancer Research (2023)

Abstract The FDA's Oncology Center of Excellence's (OCE) launch of Project Optimus signals increased focus on dose optimization approaches in oncology drug development, particularly toward optimization in the premarket setting. Although sponsors continue to adapt premarket study designs and approaches to align with FDA's expectations for dose optimization, including consideration of the optimal dosage(s), there are still instances where questions remain at the time of approval about whether the approved doses or schedules are optimal. In these cases, FDA can exercise regulatory flexibility by issuing postmarketing requirements (PMR) and avoid delaying patient access to promising therapies. This landscape analysis demonstrates that over the past decade (2012–2022), FDA frequently used PMRs to answer additional questions about dosing for novel oncology approvals. We found more than half of drugs (78/132, 59.1%) had a dosing PMR and observed a recent increase in PMRs intended to evaluate whether a lower dose could be more optimal. These results suggest there are opportunities to adapt premarket dose optimization strategies and leverage innovative development tools to ensure timely identification of the optimal dose.
Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers
Authors: Olli Dufva, Sara Gandolfi, Jani Huuhtanen, Olga Dashevsky, Hanna Duàn, Khalid Saeed, Jay Klievink, Petra Nygren, Jonas Bouhlal, Jenni Lahtela, Anna Näätänen, Bishwa R. Ghimire, Tiina Hannunen, Pekka Ellonen, Hanna Lähteenmäki, Pauliina Rumm, Jason Theodoropoulos, Essi Laajala, Jouni Härkönen, Petri Pölönen, Merja Heinäniemi, Maija Hollmén, Shizuka Yamano, Ryosuke Shirasaki, David A. Barbie, Jennifer A. Roth, Rizwan Romee, Michal Sheffer, Harri Lähdesmäki, Dean A. Lee, Ricardo De Matos Simoes, Matti Kankainen, Constantine S. Mitsiades, Satu Mustjoki
Journal: Immunity (2023)

Cancer cells can evade natural killer (NK) cell activity, thereby limiting anti-tumor immunity. To reveal genetic determinants of susceptibility to NK cell activity, we examined interacting NK cells and blood cancer cells using single-cell and genome-scale functional genomics screens. Interaction of NK and cancer cells induced distinct activation and type I interferon (IFN) states in both cell types depending on the cancer cell lineage and molecular phenotype, ranging from more sensitive myeloid to less sensitive B-lymphoid cancers. CRISPR screens in cancer cells uncovered genes regulating sensitivity and resistance to NK cell-mediated killing, including adhesion-related glycoproteins, protein fucosylation genes, and transcriptional regulators, in addition to confirming the importance of antigen presentation and death receptor signaling pathways. CRISPR screens with a single-cell transcriptomic readout provided insight into underlying mechanisms, including regulation of IFN-γ signaling in cancer cells and NK cell activation states. Our findings highlight the diversity of mechanisms influencing NK cell susceptibility across different cancers and provide a resource for NK cell-based therapies.