tbuckley/cabot-search huggingface dataset:
Resting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation
Authors: Brian T. Gaudette, Carly J. Roman, Trini A. Ochoa, Daniela Gómez Atria, Derek D. Jones, Christian W. Siebel, Ivan Maillard, David Allman
Journal: Journal of Clinical Investigation (2021)

Little is known about how cells regulate and integrate distinct biosynthetic pathways governing differentiation and cell division. For B lineage cells it is widely accepted that activated cells must complete several rounds of mitosis before yielding antibody-secreting plasma cells. However, we report that marginal zone (MZ) B cells, innate-like naive B cells known to generate plasma cells rapidly in response to blood-borne bacteria, generate functional plasma cells despite cell-cycle arrest. Further, short-term Notch2 blockade in vivo reversed division-independent differentiation potential and decreased transcript abundance for numerous mTORC1- and Myc-regulated genes. Myc loss compromised plasma cell differentiation for MZ B cells, and reciprocally induced ectopic mTORC1 signaling in follicular B cells enabled division-independent differentiation and plasma cell–affiliated gene expression. We conclude that ongoing in situ Notch2/mTORC1 signaling in MZ B cells establishes a unique cellular state that enables rapid division-independent plasma cell differentiation.
Macrophage monocarboxylate transporter 1 promotes peripheral nerve regeneration after injury in mice
Authors: Mithilesh Kumar Jha, Joseph V. Passero, Atul Rawat, Xanthe Heifetz Ament, Fang Yang, Svetlana Vidensky, Samuel L. Collins, Maureen R. Horton, Ahmet Hoke, Guy A. Rutter, Alban Latremoliere, Jeffrey D. Rothstein, Brett M. Morrison
Journal: Journal of Clinical Investigation (2021)

Peripheral nerves have the capacity for regeneration, but the rate of regeneration is so slow that many nerve injuries lead to incomplete recovery and permanent disability for patients. Macrophages play a critical role in the peripheral nerve response to injury, contributing to both Wallerian degeneration and nerve regeneration, and their function has recently been shown to be dependent on intracellular metabolism. To date, the impact of their intracellular metabolism on peripheral nerve regeneration has not been studied. We examined conditional transgenic mice with selective ablation in macrophages of solute carrier family 16, member 1 (Slc16a1), which encodes monocarboxylate transporter 1 (MCT1), and found that MCT1 contributed to macrophage metabolism, phenotype, and function, specifically in regard to phagocytosis and peripheral nerve regeneration. Adoptive cell transfer of wild-type macrophages ameliorated the impaired nerve regeneration in macrophage-selective MCT1-null mice. We also developed a mouse model that overexpressed MCT1 in macrophages and found that peripheral nerves in these mice regenerated more rapidly than in control mice. Our study provides further evidence that MCT1 has an important biological role in macrophages and that manipulations of macrophage metabolism can enhance recovery from peripheral nerve injuries, for which there are currently no approved medical therapies.
Frequency and prognostic impact of blood-circulating tumor mast cells in mastocytosis
Authors: Ana Henriques, Javier I. Muñoz-González, Laura Sánchez-Muñoz, Almudena Matito, Lidia Torres-Rivera, María Jara-Acevedo, Carolina Caldas, Andrea Mayado, Alba Pérez-Pons, Andrés C. García-Montero, Iván Álvarez-Twose, Alberto Orfao
Journal: Blood (2021)
Abstract 14462: Long-Term Exposure to Elevated Lipoprotein(a) Levels Influences Human Longevity
Authors: Benoit Arsenault, William Pelletier, Yannick Kaiser, Nicolas Perrot, Christian Couture, Kay-Tee Khaw, Nicholas Wareham, Yohan Bosse, Philippe Pibarot, Erik S Stroes, Patrick Mathieu, Sebastien Theriault, S. Matthijs Boekholdt
Journal: Circulation (2019)

Background: Elevated Lipoprotein(a) (Lp[a]) levels are associated with a broad range of atherosclerotic cardiovascular diseases. The impact of high Lp(a) levels on human longevity is however contro...
Paradigm shift in the pathogenesis and treatment of oral cancer and other cancers focused on the oralome and antimicrobial‐based therapeutics
Authors: Allan Radaic, Sean Ganther, Pachiyappan Kamarajan, Jennifer Grandis, Sue S. Yom, Yvonne L. Kapila
Journal: Periodontology 2000 (2021)

Abstract The oral microbiome is a community of microorganisms, comprised of bacteria, fungi, viruses, archaea, and protozoa, that form a complex ecosystem within the oral cavity. Although minor perturbations in the environment are frequent and compensable, major shifts in the oral microbiome can promote an unbalanced state, known as dysbiosis. Dysbiosis can promote oral diseases, including periodontitis. In addition, oral dysbiosis has been associated with other systemic diseases, including cancer. The objective of this review is to evaluate the epidemiologic evidence linking periodontitis to oral, gastrointestinal, lung, breast, prostate, and uterine cancers, as well as describe new evidence and insights into the role of oral dysbiosis in the etiology and pathogenesis of the cancer types discussed. Finally, we discuss how antimicrobials, antimicrobial peptides, and probiotics may be promising tools to prevent and treat these cancers, targeting both the microbes and associated carcinogenesis processes. These findings represent a novel paradigm in the pathogenesis and treatment of cancer focused on the oral microbiome and antimicrobial‐based therapies.
Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Clinical Outcomes in COVID-19
Authors: M. Pan, T. Azam, H. Shadid, H. Berlin, C. Meloche, R. Feroze, J. Leya, P. O'Hayer, E. Anderson, R. Kaakati, A. Bitar, K. Padalia, D. Perry, P. Blakely, P. Y. Zhao, L. L. Zhao, S. Hayek
Journal: Circulation (2020)
Privacy-first health research with federated learning
Authors: Adam Sadilek, Luyang Liu, Dung Nguyen, Methun Kamruzzaman, Stylianos Serghiou, Benjamin Rader, Alex Ingerman, Stefan Mellem, Peter Kairouz, Elaine O. Nsoesie, Jamie MacFarlane, Anil Vullikanti, Madhav Marathe, Paul Eastham, John S. Brownstein, Blaise Aguera y. Arcas, Michael D. Howell, John Hernandez
Journal: npj Digital Medicine (2021)

Abstract Privacy protection is paramount in conducting health research. However, studies often rely on data stored in a centralized repository, where analysis is done with full access to the sensitive underlying content. Recent advances in federated learning enable building complex machine-learned models that are trained in a distributed fashion. These techniques facilitate the calculation of research study endpoints such that private data never leaves a given device or healthcare system. We show—on a diverse set of single and multi-site health studies—that federated models can achieve similar accuracy, precision, and generalizability, and lead to the same interpretation as standard centralized statistical models while achieving considerably stronger privacy protections and without significantly raising computational costs. This work is the first to apply modern and general federated learning methods that explicitly incorporate differential privacy to clinical and epidemiological research—across a spectrum of units of federation, model architectures, complexity of learning tasks and diseases. As a result, it enables health research participants to remain in control of their data and still contribute to advancing science—aspects that used to be at odds with each other.
Elucidating the anticancer activities of guanidinium-functionalized amphiphilic random copolymers by varying the structure and composition in the hydrophobic monomer
Authors: Joyce Tay, Yanli Zhao, James L. Hedrick, Yi Yan Yang
Journal: Theranostics (2021)

Rationale: Use of traditional anticancer chemotherapeutics has been hindered by the multifactorial nature of multi-drug resistance (MDR) development and metastasis.Recently, cationic polycarbonates were reported as novel unconventional anticancer agents that mitigated MDR and inhibited metastasis.The aim of this study is to explore structure-anticancer activity relationship.Specifically, a series of cationic guanidinium-based random copolymers of varying hydrophobicity was synthesized with a narrow polydispersity (Ð = 1.12-1.27)via organocatalytic ring-opening polymerization (OROP) of functional cyclic carbonate monomers, and evaluated for anticancer activity, killing kinetics, degradability and functional mechanism.Methods: Linear, branched and aromatic hydrophobic side chain units, such as ethyl, benzyl, butyl, isobutyl and hexyl moieties were explored as comonomer units for modulating anticancer activity.As hydrophobicity/hydrophilicity balance of the polymers determines their anticancer efficacy, the feed ratio between the two monomers was varied to tune their hydrophobicity.Results: Notably, incorporating the hexyl moiety greatly enhanced anticancer efficiency and killing kinetics on cancer cells.Degradation studies showed that the polymers degraded completely within 4-6 days.Flow cytometry and lactate dehydrogenase (LDH) release analyses demonstrated that anticancer mechanism of the copolymers containing a hydrophobic co-monomer was concentration dependent, apoptosis at IC50, and both apoptosis and necrosis at 2 × IC50.In contrast, the homopolymer without a hydrophobic comonomer killed cancer cells predominantly via apoptotic mechanism. Conclusion:The hydrophobicity of the polymers played an important role in anticancer efficacy, killing kinetics and anticancer mechanism.This study provides valuable insights into designing novel anticancer agents utilizing polymers.
Genome of the Giant Panda Roundworm Illuminates Its Host Shift and Parasitic Adaptation
Authors: Yue Xie, Sen Wang, Shuangyang Wu, Shenghan Gao, Qingshu Meng, Chengdong Wang, Jingchao Lan, Li Luo, Xuan Zhou, Jing Xu, Xiaobin Gu, Ran He, Zijiang Yang, Xuerong Peng, Songnian Hu, Guangyou Yang
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Baylisascaris schroederi, a roundworm (ascaridoid) parasite specific to the bamboo-feeding giant panda (Ailuropoda melanoleuca), represents a leading cause of mortality in wild giant panda populations. Here, we present a 293-megabase chromosome-level genome assembly of B. schroederi to infer its biology, including host adaptations. Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations, suggesting their potential for transmission and rapid adaptation to new hosts. Genomic and anatomical lines of evidence, including expansion and positive selection of genes related to the cuticle and basal metabolisms, indicate that B. schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism. Additionally, we characterized the secretome of B. schroederi and predicted potential drug and vaccine targets for new control strategies. Overall, this genome resource provides new insights into the host adaptation of B. schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages. Our findings on the unique biology of B. schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.
Pancreatic Cancer
Authors: Wungki Park, Akhil Chawla, Eileen M. O’Reilly
Journal: JAMA (2021)

<h3>Importance</h3> Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030. <h3>Observations</h3> Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86];<i>P</i> = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control. For patients with advanced (locally advanced and metastatic) PDAC, multiagent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil, all have a survival benefit of 2 to 6 months compared with a single-agent gemcitabine. For the 5% to 7% of patients with a<i>BRCA</i>pathogenic germline variant and metastatic PDAC, olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, is a maintenance option that improves progression-free survival following initial platinum-based therapy. <h3>Conclusions and Relevance</h3> Approximately 60 000 new cases of PDAC are diagnosed per year, and approximately 50% of patients have advanced disease at diagnosis. The incidence of PDAC is increasing. Currently available cytotoxic therapies for advanced disease are modestly effective. For all patients, multidisciplinary management, comprehensive germline testing, and integrated supportive care are recommended.
Underuse of Electronic Health Record Features—The Case for CancelRx
Authors: Scott D. Nelson, Yaa Kumah-Crystal
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
Acuity Circles—Higher Cost for Fewer Transplants?
Authors: Seth J. Karp
Journal: JAMA Surgery (2021)

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 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 Surgery journal
Performance of the 2017 European Alliance of Associations for Rheumatology/American College of Rheumatology Classification Criteria for Idiopathic Inflammatory Myopathies in Patients With <scp>Myositis‐Specific</scp> Autoantibodies
Authors: Maria Casal‐Dominguez, Iago Pinal‐Fernandez, Katherine Pak, Wilson Huang, Albert Selva‐O'Callaghan, Jemima Albayda, Livia Casciola‐Rosen, Julie J. Paik, Eleni Tiniakou, Christopher A. Mecoli, Thomas E. Lloyd, Sonye K. Danoff, Lisa Christopher‐Stine, Andrew L. Mammen
Journal: Arthritis & Rheumatology (2021)

Objective We undertook this study to 1) determine the sensitivity of the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies (IIMs) to properly classify myositis‐specific autoantibody (MSA)–positive myositis patients, 2) describe the phenotype and muscle involvement over time in different MSA‐positive patients, and 3) compare MSA subgroups to EULAR/ACR criteria–defined myositis subgroups for their capacity to predict clinical phenotypes in patients with IIMs. Methods The study included 524 MSA‐positive myositis patients from the Johns Hopkins Myositis Center. Each patient was classified using the EULAR/ACR classification criteria. Patient phenotypes were summarized using factor analysis of mixed data (FAMD). We compared the ability of MSAs to that of the EULAR/ACR classification subgroups to predict the phenotype of patients by applying the Akaike information criterion (AIC) and the Bayesian information criteria (BIC) to the linear regression models. Results Overall, 91% of MSA‐positive patients met the EULAR/ACR criteria to be classified as having myositis. However, 20% of patients with anti–hydroxymethylglutaryl‐coenzyme A reductase (anti‐HMGCR) and 50% of patients with anti–PL‐7 were incorrectly classified as not having myositis. Furthermore, ~10% of patients with anti–signal recognition particle (anti‐SRP) and patients with anti‐HMGCR were misclassified as having inclusion body myositis. FAMD demonstrated that patients within each MSA‐defined subgroup had similar phenotypes. Application of both the AIC and BIC to the linear regression models revealed that MSAs were better predictors of myositis phenotypes than the subgroups defined by the EULAR/ACR criteria. Conclusion Although the EULAR/ACR criteria successfully classified 91% of MSA‐positive myositis patients, certain MSA‐defined subgroups, including those with autoantibodies against HMGCR, SRP, and PL‐7, are frequently misclassified. In myositis patients with MSAs, autoantibodies outperform the EULAR/ACR‐defined myositis subgroups in predicting the clinical phenotypes of patients. These findings underscore the need to include MSAs in a revised myositis classification scheme.
Abstract 482: Increased Subclinical Atherosclerosis is Associated With Impaired Aortic and Coronary Artery Distensibility
Authors: Naser Ahmadi, Vahid Nabavi, Jigar Kadakia, Irfan Zeb, David Shavelle, Ramin Ebrahimi, Matthew Budoff
Journal: Circulation (2009)

Introduction: Atherosclerotic changes within the aortic and coronary artery wall can affect vessel wall distensibility. This study evaluates the relationship between the aortic (ADI) and coronary d...
Coronary Heart Disease in the Western Collaborative Group Study
Authors: Ray H. Rosenman
Journal: JAMA (1975)

Clinical coronary heart disease (CHD) occurred in 257 subjects during eight to nine years of follow-up (average, 8 1/2 years) in a prospective study of 39- to 59-year-old employed men. Incidence of CHD was significantly associated with parental CHD history, reported diabetes, schooling, smoking habits, overt behavior pattern, blood pressure, and serum levels of cholesterol, triglyceride, and beta-lipoproteins. The type A behavior pattern was strongly related to the CHD incidence, and this association could not be explained by association of behavior pattern with any single predictive risk factor or with any combination of them.
Abstract 14140: Coronary Artery Calcium and the Sex-Specific Competing Risk of Cardiovascular versus Cancer Mortality: The CAC Consortium
Authors: Omar Dzaye, Mahmoud S Al Rifai, Zeina Dardari, Leslee J Shaw, Mouaz H Al-Mallah, Catherine Handy Marshall, Alan Rozanski, Martin B Mortensen, Kunihiro Matsushita, John A Rumberger, Daniel S Berman, Matthew J Budoff, Michael D Miedema, Khurram Nasir, Michael J Blaha, Seamus P Whelton
Journal: Circulation (2019)

Introduction: Coronary artery calcium (CAC) is a predictor of both cardiovascular disease (CVD) and cancer, which are the two leading causes of death worldwide. While age and sex specific CAC value...
Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation
Authors: Steffen Desch, Anne Freund, Ibrahim Akin, Michael Behnes, Michael R. Preusch, Thomas A. Zelniker, Carsten Skurk, Ulf Landmesser, Tobias Graf, Ingo Eitel, Georg Fuernau, Hendrik Haake, Peter Nordbeck, Fabian Hammer, Stephan B. Felix, Christian Hassager, Thomas Engstrøm, Stephan Fichtlscherer, Jakob Ledwoch, Karsten Lenk, Michael Joner, Stephan Steiner, Christoph Liebetrau, Ingo Voigt, Uwe Zeymer, Michael Brand, Roland Schmitz, Jan Horstkotte, Claudius Jacobshagen, Janine Pöss, Mohamed Abdel-Wahab, Philipp Lurz, Alexander Jobs, Suzanne de Waha-Thiele, Denise Olbrich, Frank Sandig, Inke R. König, Sabine Brett, Maren Vens, Kathrin Klinge, Holger Thiele
Journal: New England Journal of Medicine (2021)

Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear.In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days.A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups.Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause. (Funded by the German Center for Cardiovascular Research; TOMAHAWK ClinicalTrials.gov number, NCT02750462.).