tbuckley/cabot-search huggingface dataset:
Cancer Mortality Patterns by Birthplace and Generation Status of Mexican Latinos: The Multiethnic Cohort
Authors: Hongjie Chen, Anna H Wu, Songren Wang, Arthur Bookstein, Loïc Le Marchand, Lynne R Wilkens, Christopher A Haiman, Iona Cheng, Kristine R Monroe, Veronica Wendy Setiawan
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Latinos are the largest minority group in the United States. We assessed cancer mortality by birthplace and generation status of Mexican Latinos in the Multiethnic Cohort. Methods We included 26 751 Latinos of Mexican origin and 6093 non-Latino Whites aged 45-74 years at cohort entry (1993-1996) from the California Multiethnic Cohort component. The Mexican Latinos comprised 42% first-generation Mexico-born immigrants, 42% second-generation (28% US-born with both parents Mexico-born and 14% US-born with 1 parent US-born and 1 parent Mexico-born), and 16% third-generation or more who were US-born with both parents US-born. Multivariable Cox models were used to calculate covariate adjusted hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality by birthplace and generation status. All statistical tests were 2-sided. Results Cancer death rate was highest among the US-born with 1 parent US-born and 1 parent Mexico-born (age-adjusted rate = 471.0 per 100 000 person-years) and US-born with both parents US-born (age-adjusted rate = 469.0 per 100 000 person-years) groups. The US-born with both parents Mexico-born group had a 30% (hazard ratio = 1.30, 95% confidence interval = 1.18 to 1.44) higher risk of cancer death than the first-generation Mexico-born immigrants group, showing US birthplace was associated with an elevated cancer mortality. For cancer-specific mortality, US birthplace was positively associated with colorectal, liver and lung, and ovarian cancer (P values ranged from .04 to .005). Among US-born Mexican Latinos, generation status was not statistically significantly associated with overall cancer or site-specific cancer mortality. Conclusions Our findings suggest that US birthplace is a risk factor for cancer death in Mexican Americans. Identification of the contributing factors is important to curtail patterns of increasing cancer mortality in US-born Mexican Latinos.
A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk
Authors: Stephen A. Williams, Rachel Ostroff, Michael A. Hinterberg, Josef Coresh, Christie M. Ballantyne, Kunihiro Matsushita, Christian E. Mueller, Joan Walter, Christian Jonasson, Rury R. Holman, Svati H. Shah, Naveed Sattar, Roy Taylor, Michael E. Lean, Shintaro Kato, Hiroaki Shimokawa, Yasuhiko Sakata, Kotaro Nochioka, Chirag R. Parikh, Steven G. Coca, Torbjørn Omland, Jessica Chadwick, David Astling, Yolanda Hagar, Natasha Kureshi, Kelsey Loupy, Clare Paterson, Jeremy Primus, Missy Simpson, Nelson P. Trujillo, Peter Ganz
Journal: Science Translational Medicine (2022)

A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about 5000 proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death. The 27 proteins encompassed 10 biologic systems, and 12 were associated with relevant causal genetic traits. We independently validated results in 11,609 participants. Compared to a clinical model, the ratio of observed events in quintile 5 to quintile 1 was 6.7 for proteins versus 2.9 for the clinical model, AUCs (95% CI) were 0.73 (0.72 to 0.74) versus 0.64 (0.62 to 0.65), c -statistics were 0.71 (0.69 to 0.72) versus 0.62 (0.60 to 0.63), and the net reclassification index was +0.43. Adding the clinical model to the proteins only improved discrimination metrics by 0.01 to 0.02. Event rates in four predefined protein risk categories were 5.6, 11.2, 20.0, and 43.4% within 4 years; median time to event was 1.71 years. Protein predictions were directionally concordant with changed outcomes. Adverse risks were predicted for aging, approaching an event, anthracycline chemotherapy, diabetes, smoking, rheumatoid arthritis, cancer history, cardiovascular disease, high systolic blood pressure, and lipids. Reduced risks were predicted for weight loss and exenatide. The 27-protein model has potential as a “universal” surrogate end point for cardiovascular risk.
FNIP1 regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics
Authors: Yujing Yin, Dengqiu Xu, Yan Mao, Liwei Xiao, Zongchao Sun, Jing Liu, Danxia Zhou, Zhisheng Xu, Lin Liu, Tingting Fu, Chenyun Ding, Qiqi Guo, Wanping Sun, Zheng Zhou, Likun Yang, Yuhuan Jia, Xinyi Chen, Zhenji Gan
Journal: The Journal of Experimental Medicine (2022)

Metabolically beneficial beige adipocytes offer tremendous potential to combat metabolic diseases. The folliculin interacting protein 1 (FNIP1) is implicated in controlling cellular metabolism via AMPK and mTORC1. However, whether and how FNIP1 regulates adipocyte browning is unclear. Here, we demonstrate that FNIP1 plays a critical role in controlling adipocyte browning and systemic glucose homeostasis. Adipocyte-specific ablation of FNIP1 promotes a broad thermogenic remodeling of adipocytes, including increased UCP1 levels, high mitochondrial content, and augmented capacity for mitochondrial respiration. Mechanistically, FNIP1 binds to and promotes the activity of SERCA, a main Ca2+ pump responsible for cytosolic Ca2+ removal. Loss of FNIP1 resulted in enhanced intracellular Ca2+ signals and consequential activation of Ca2+-dependent thermogenic program in adipocytes. Furthermore, mice lacking adipocyte FNIP1 were protected against high-fat diet–induced insulin resistance and liver steatosis. Thus, these findings reveal a pivotal role of FNIP1 as a negative regulator of beige adipocyte thermogenesis and unravel an intriguing functional link between intracellular Ca2+ dynamics and adipocyte browning.
Adolescents Are Still Waiting on a Digital Health Revolution
Authors: Alexandra M. Psihogios, Meghan B. Lane-Fall, Andrea K. Graham
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 Pediatrics journal
Changes in Life Expectancy Between 2019 and 2020 in the US and 21 Peer Countries
Authors: Steven H. Woolf, Ryan K. Masters, Laudan Y. Aron
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Prior studies reported that US life expectancy decreased considerably in 2020 because of the COVID-19 pandemic, with estimates suggesting that the decreases were much larger among Hispanic and non-Hispanic Black populations than non-Hispanic White populations. Studies based on provisional data suggested that other high-income countries did not experience the large decrease in life expectancy observed in the US; this study sought to confirm these findings according to official death counts and to broaden the pool of comparison countries. <h3>Objective</h3> To calculate changes in US life expectancy between 2019 and 2020 by sex, race, and ethnicity and to compare those outcomes with changes in other high-income countries. <h3>Design, Setting, and Participants</h3> This cross-sectional study involved a simulation of life tables based on national death and population counts for the US and 21 other high-income countries in 2019 and 2020, by sex, including an analysis of US outcomes by race and ethnicity. Data were analyzed in January 2022. <h3>Exposures</h3> Official death counts from the US and 21 peer countries. <h3>Main Outcomes and Measures</h3> Life expectancy at birth and credible range (CR) based on 10% uncertainty. <h3>Results</h3> Between 2019 and 2020, US life expectancy decreased by a mean of 1.87 years (CR, 1.70-2.03 years), with much larger decreases occurring in the Hispanic (3.70 years; CR, 3.53-3.87 years) and non-Hispanic Black (3.22 years; CR, 3.03-3.40 years) populations than in the non-Hispanic White population (1.38 years; CR, 1.21-1.54 years). The mean decrease in life expectancy among peer countries was 0.58 years (CR, 0.42-0.73 year) across all 21 countries. No peer country experienced decreases as large as those seen in the US. <h3>Conclusions and Relevance</h3> Official death counts confirm that US life expectancy decreased between 2019 and 2020 on a scale not seen in 21 peer countries, substantially widening the preexisting gap in life expectancy between the US and peer countries. The decrease in US life expectancy was experienced disproportionately by Hispanic and non-Hispanic Black populations, consistent with a larger history of racial and ethnic health inequities resulting from policies of exclusion and systemic racism. Policies to address the systemic causes of the US health disadvantage relative to peer countries and persistent racial and ethnic inequities are essential.
Next-Generation CAR T-cell Therapies
Authors: Regina M. Young, Nils W. Engel, Ugur Uslu, Nils Wellhausen, Carl H. June
Journal: Cancer Discovery (2022)

Summary: CD19- and B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T cells have enabled unprecedented responses in a subset of refractory patients with B-cell and plasma cell malignancies, leading to their approval by the FDA for the treatment of leukemia, lymphoma, and myeloma. These “living drugs” can become part of a synthetic immune system, persisting at least a decade in some patients. However, despite this tremendous impact, significant unmet treatment needs remain for patients with hematologic malignancies and solid cancers. In this perspective, we highlight recent innovations that advance the field toward production of a more potent and universal cellular immunotherapy of the future. Next-generation CAR T cells will incorporate advances in gene engineering and synthetic biology to enhance functionality and persistence, and reduce treatment-associated toxicities. The combination of autologous CAR T cells with various allogeneic cell treatment strategies designed to target the immunosuppressive tumor microenvironment will broaden the impact of future CAR T-cell therapies.
TCTAP A-074 Quantifying Coronary Arterial Stenosis and Measuring the Arterial Phase by Artificial Intelligence Program
Authors: Tri Loc Vu, Thai Dien Pham, Tri Tai Truyen, Quang Minh Mai, Thuan Huynh, Trung Thong Hoang, My Linh Phan Khanh, Cam Tu Tran Thi, Dung Ho Dung Ho, Thach Nguyen
Journal: Journal of the American College of Cardiology (2022)
UBTF::ATXN7L3 gene fusion defines novel B cell precursor ALL subtype with CDX2 expression and need for intensified treatment
Authors: Lorenz Bastian, Alina M. Hartmann, Thomas Beder, Sonja Hänzelmann, Jan Kässens, Miriam Bultmann, Marc P. Hoeppner, Sören Franzenburg, Michael Wittig, Andre Franke, Inga Nagel, Malte Spielmann, Niklas Reimer, Hauke Busch, Stefan Schwartz, Björn Steffen, Andreas Viardot, Konstanze Döhner, Mustafa Kondakci, Gerald Wulf, Knut Wendelin, Andrea Renzelmann, Alexander Kiani, Heiko Trautmann, Martin Neumann, Nicola Gökbuget, Monika Brüggemann, Claudia D. Baldus
Journal: Leukemia (2022)
Integrating Additive Manufacturing Techniques to Improve Cell‐Based Implants for the Treatment of Type 1 Diabetes
Authors: Robert P. Accolla, Amberlyn M. Simmons, Cherie L. Stabler
Journal: Advanced Healthcare Materials (2022)

The increasing global prevalence of endocrine diseases like type 1 diabetes mellitus (T1DM) elevates the need for cellular replacement approaches, which can potentially enhance therapeutic durability and outcomes. Central to any cell therapy is the design of delivery systems that support cell survival and integration. In T1DM, well-established fabrication methods have created a wide range of implants, ranging from 3D macro-scale scaffolds to nano-scale coatings. These traditional methods, however, are often challenged by their inherent limitations in reproducible and discrete fabrication, particularly when scaling to the clinic. Additive manufacturing (AM) techniques provide a means to address these challenges by delivering improved control over construct geometry and microscale component placement. While still early in development in the context of T1DM cellular transplantation, the integration of AM approaches serves to improve nutrient material transport, vascularization efficiency, and the accuracy of cell, matrix, and local therapeutic placement. This review highlights current methods in T1DM cellular transplantation and the potential of AM approaches to overcome these limitations. In addition, emerging AM technologies and their broader application to cell-based therapy are discussed.
TCTAP C-157 Coronary Physiology Assessment in a Patient With Triple Vessel Disease and Chronic Total Occlusion
Authors: Koon Wee Koay, Chong Aik Goh, Shahul Hamid Bin K A Ahmadsah, Poi Keong Kong, Muhamad Ali SK Abdul Kader
Journal: Journal of the American College of Cardiology (2022)
Immune Checkpoint Inhibitor Use in Solid Organ Transplant Recipients: A Systematic Review
Authors: Andrew J. Portuguese, Scott S. Tykodi, Christopher D. Blosser, Ted A. Gooley, John A. Thompson, Evan T. Hall
Journal: Journal of the National Comprehensive Cancer Network (2022)

Chronic immunosuppression in solid organ transplant recipients (SOTRs) leads to an increased risk of a wide variety of cancers. Immune checkpoint inhibitor (ICI) therapy is indicated for many of these; however, the risks and benefits of ICI use in the SOTR population have not been well characterized. We performed a systematic literature review identifying 119 reported cases of ICI use among SOTRs. Treatments used included PD-1 inhibition (75.6%), CTLA-4 inhibition (12.6%), PD-L1 inhibition (1.7%), and combination and/or sequential ICI therapy (10.1%). The most common cancers included cutaneous melanoma (35.3%), hepatocellular carcinoma (22.7%), and cutaneous squamous cell carcinoma (18.5%). The overall objective response rate (ORR) was 34.5%, with a median duration of response of 8.0 months. Ongoing response was seen in 21.0%. Cutaneous squamous cell carcinoma had significantly better ORR compared with other cancer types (68.2% vs 26.8%; odds ratio [OR], 5.85; P =.0006). Factors associated with improved ORR included increasing time from transplant to ICI (OR, 1.09; P =.008) and preemptive reduction in intensity of the graft maintenance immunosuppressive regimen (50.0% vs 18.5%; OR, 4.40; P =.0088). Rejection occurred in 41.2%, graft failure in 23.5%, and immune-related adverse events in 18.5%. Factors significantly associated with allograft rejection included allograft PD-L1 positivity (100% vs 0%; P &lt;.0001) and absence of tacrolimus in the immunosuppressive regimen (48.7% vs 25.6%; OR, 0.36; P =.019). The most common cause of death was progressive malignancy (64.0%), followed by graft failure (24.0%). Our analysis provides current benchmark data to help inform management of SOTRs with advanced cancers that are reflected by our patient cohort. Biomarker development, more robust datasets, and prospective study of concomitant immunosuppression management may help refine decision-making in this complex scenario in the future. Close coordination of care between the medical oncologist and transplant specialist is encouraged to help optimize treatment outcomes.
Effectiveness of a serogroup B outer membrane vesicle meningococcal vaccine against gonorrhoea: a retrospective observational study
Authors: Winston E Abara, Kyle T Bernstein, Felicia M T Lewis, Julia A Schillinger, Kristen Feemster, Preeti Pathela, Susan Hariri, Aras Islam, Michael Eberhart, Iris Cheng, Alexandra Ternier, Jennifer Sanderson Slutsker, Sarah Mbaeyi, Robbie Madera, Robert D Kirkcaldy
Journal: The Lancet Infectious Diseases (2022)
Intranasal administration of a virus like particles‐based vaccine induces neutralizing antibodies against SARS‐CoV‐2 and variants of concern
Authors: Dominik A. Rothen, Pascal S. Krenger, Aleksandra Nonic, Ina Balke, Anne‐Cathrine S. Vogt, Xinyue Chang, Alessandro Manenti, Fabio Vedovi, Gunta Resevica, Senta M. Walton, Andris Zeltins, Emanuele Montomoli, Monique Vogel, Martin F. Bachmann, Mona O. Mohsen
Journal: Allergy (2022)

The highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of a vaccine against COVID-19.In the current study, we evaluated the immunogenicity of a traditional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal administration in a murine model. The candidate vaccine platform, CuMVTT -RBD, has been optimized to incorporate a universal T helper cell epitope derived from tetanus-toxin and is self-adjuvanted with TLR7/8 ligands.CuMVTT -RBD vaccine elicited a strong systemic RBD- and spike-IgG and IgA antibodies of high avidity. Local immune response was assessed, and our results demonstrate a strong mucosal antibody and plasma cell production in lung tissue. Furthermore, the induced systemic antibodies could efficiently recognize and neutralize different variants of concern (VOCs).Our data demonstrate that intranasal administration of CuMVTT -RBD induces a protective systemic and local specific antibody response against SARS-CoV-2 and its VOCs.
The purinergic P2Y14 receptor links hepatocyte death to hepatic stellate cell activation and fibrogenesis in the liver
Authors: Ingmar Mederacke, Aveline Filliol, Silvia Affo, Ajay Nair, Celine Hernandez, Qiuyan Sun, Florian Hamberger, Francesco Brundu, Yu Chen, Aashreya Ravichandra, Peter Huebener, Helena Anke, Hongxue Shi, Raquel A. Martínez García de la Torre, James R. Smith, Neil C. Henderson, Florian W. R. Vondran, Carla V. Rothlin, Heike Baehre, Ira Tabas, Pau Sancho-Bru, Robert F. Schwabe
Journal: Science Translational Medicine (2022)

Fibrosis contributes to ~45% of deaths in western countries. In chronic liver disease, fibrosis is a major factor determining outcomes, but efficient antifibrotic therapies are lacking. Although platelet-derived growth factor and transforming growth factor–β constitute key fibrogenic mediators, they do not account for the well-established link between cell death and fibrosis in the liver. Here, we hypothesized that damage-associated molecular patterns (DAMPs) may link epithelial cell death to fibrogenesis in the injured liver. DAMP receptor screening identified purinergic receptor P2Y14 among several candidates as highly enriched in hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. Conversely, P2Y14 ligands uridine 5′-diphosphate (UDP)–glucose and UDP-galactose were enriched in hepatocytes and were released upon different modes of cell death. Accordingly, ligand-receptor interaction analysis that combined proteomic and single-cell RNA sequencing data revealed P2Y14 ligands and P2Y14 receptor as a link between dying cells and HSCs, respectively. Treatment with P2Y14 ligands or coculture with dying hepatocytes promoted HSC activation in a P2Y14-dependent manner. P2Y14 ligands activated extracellular signal–regulated kinase (ERK) and Yes-associated protein (YAP) signaling in HSCs, resulting in ERK-dependent HSC activation. Global and HSC-selective P2Y14 deficiency attenuated liver fibrosis in multiple mouse models of liver injury. Functional expression of P2Y14 was confirmed in healthy and diseased human liver and human HSCs. In conclusion, P2Y14 ligands and their receptor constitute a profibrogenic DAMP pathway that directly links cell death to fibrogenesis.
Treatment With Dupilumab for Refractory Cutaneous B-Cell Pseudolymphoma
Authors: Tejas P. Joshi, Madeleine Duvic, Carlos A. Torres-Cabala, Jaime Tschen
Journal: JAMA Dermatology (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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 Dermatology journal
TCTAP C-169 Transcatheter Septal Closure of Post-Myocardial Infarction Ventricular Septal Rupture in Patient With Inferior Wall Myocardial Infarction and Cardiac Arrest on VA ECMO
Authors: Piyoros Lertsanguansinchai, Vorarit Lertsuwunseri, Pornthep Lertsapcharoen, Thitima Limjaroen, Chaisiri Wanlapakorn, Siriporn Athisakul, Suphot Srimahachota
Journal: Journal of the American College of Cardiology (2022)
Modified Glasgow prognostic score (mGPS) is correlated with sarcopenia and dominates the prognostic role of baseline body composition parameters in advanced gastric and esophagogastric junction cancer patients undergoing first-line treatment from the phase III EXPAND trial
Authors: U.T. Hacker, D. Hasenclever, R. Baber, N. Linder, H. Busse, R. Obermannova, L. Zdrazilova-Dubska, D. Valik, F. Lordick
Journal: Annals of Oncology (2022)
A risk prediction model for hepatocellular carcinoma after hepatitis B surface antigen seroclearance
Authors: Hyun Yang, Si Hyun Bae, Heechul Nam, Hae Lim Lee, Sung Won Lee, Sun Hong Yoo, Myeong Jun Song, Jung Hyun Kwon, Soon Woo Nam, Jong Young Choi, Seung Kew Yoon, Jeong Won Jang
Journal: Journal of Hepatology (2022)