tbuckley/cabot-search huggingface dataset:
New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation
Authors: Milton Packer, Paul A. Grayburn
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Traditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus. <h3>Observations</h3> A novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair. <h3>Conclusions and Relevance</h3> The characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.
Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction
Authors: Yashu Kuang, Xiaolin Li, Xiuxiang Liu, Lu Wei, Xiaoli Chen, Jie Liu, Tao Zhuang, Jingjiang Pi, Yanfang Wang, Chenying Zhu, Xin Gong, Hao Hu, Zuoren Yu, Jiming Li, Ping Yu, Huimin Fan, Yuzhen Zhang, Zhongmin Liu, Lin Zhang
Journal: Cardiovascular Research (2020)

Endothelial cell (EC) homoeostasis plays an important role in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodelling after myocardial infarction (MI). It has been shown that the sphingosine 1-phosphate receptor 1 (S1pr1) was highly expressed in ECs and played an important role in maintaining endothelial functions. We thus hypothesized that the endothelial S1pr1 might be involved in post-MI cardiac remodelling.
Abstract 12912: Reduction of 5-Lipoxygenase Derived Docosahexaenoic Acid Metabolites Under Social Mental Stress: Their Function for Maintenance of Heme Oxygenase-1 Expression in Macrophage
Authors: Makoto Nishimori, Masakazu Shinohara, Kouichi Watanabe, Mitsumasa Okano, Toshihiko Oshita, Kenta Mori, Tetsuya Hara, Yasuhiro Irino, Seimi Kobayashi, Ryuji Toh, Tatsuro Ishida, Ken-ichi Hirata
Journal: Circulation (2018)

Epidemiological studies reveal an association between social mental stresses and incidence of cardiovascular disease. Although hyperactivation of sympathetic nerve system is reported to induce syst...
Chronic Cough in America: Characteristics of Chronic Cough Patients with Allergies
Authors: John Oppenheimer, Eli Meltzer, Jonathan Bernstein, Michael Schatz, Robert Zeiger, Peter Dicpinigaitis, Nate Way, Vicky Li, Eileen Fonseca, Robert Boggs, Jonathan Schelfhout
Journal: Journal of Allergy and Clinical Immunology (2020)
Effect of Traditional Chinese Medicine (TCM) in moderate-to-severe eczema in clinic and animal model: beyond corticosteroids
Authors: Kamal Srivastava, Nan Yang, Serife Uzun, Erin Thanik, Paul Ehrlich, Danna Chung, Qian Yuan, Anna Nowak-Wegrzyn, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2020)
Poor Infection Control Led to Child HIV Outbreak in Pakistan
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors
Authors: William Hankey, Zhong Chen, Qianben Wang
Journal: Cancer Research (2020)

Abstract The androgen receptor (AR) is a critical therapeutic target in prostate cancer that responds to antagonists in primary disease, but inevitably becomes reactivated, signaling onset of the lethal castration-resistant prostate cancer (CRPC) stage. Epigenomic investigation of the chromatin environment and interacting partners required for AR transcriptional activity has uncovered three pioneer factors that open up chromatin and facilitate AR-driven transcriptional programs. FOXA1, HOXB13, and GATA2 are required for normal AR transcription in prostate epithelial development and for oncogenic AR transcription during prostate carcinogenesis. AR signaling is dependent upon these three pioneer factors both before and after the clinical transition from treatable androgen-dependent disease to untreatable CRPC. Agents targeting their respective DNA binding or downstream chromatin-remodeling events have shown promise in preclinical studies of CRPC. AR-independent functions of FOXA1, HOXB13, and GATA2 are emerging as well. While all three pioneer factors exert effects that promote carcinogenesis, some of their functions may inhibit certain stages of prostate cancer progression. In all, these pioneer factors represent some of the most promising potential therapeutic targets to emerge thus far from the study of the prostate cancer epigenome.
A study of the rare disease pachyonychia congenita (PC)
Authors: A.G. Zieman, P.A. Coulombe
Journal: British Journal of Dermatology (2020)

The disease pachyonychia congenita (PC) is a rare skin condition affecting approximately 900 people worldwide, according to the International PC Research Registry. PC is caused by inherited mutations (abnormalities) in a subset of genes called keratin intermediate filament genes (keratin 6A, keratin 6B, keratin 6C, keratin 16, and keratin 17), which are normally found in skin structures like hair follicles, the nail bed, and sweat glands. PC has many symptoms, but the most common and devastating symptom is palmoplantar keratoderma (PPK), which are painful, thick, callus-like sores that form on the palms of hands and/or soles of feet. There is no cure or effective treatment for PC or PC-associated PPK. The reasons for this are complex but include the fact that the condition is dominantly inherited, the calluses are difficult to penetrate, and the underlying lesions (affected patches of skin) are molecularly complex and evolving. This article, written by researchers from the University of Michigan in the U.S.A., aimed to review what is currently known about the pathophysiology (meaning the processes and changes in the body) of PC-associated PPK and suggest new strategies for the development of potentially effective therapies. There are at least three stages of PPK progression. Each of these stages has distinct molecular characteristics that can be targeted. The authors suggest ways to target each of these stages of PPK progression to develop an effective treatment for PC-associated PPK. Much can be learned from continued effort to understand this condition. This summary relates to the study: Pathophysiology of pachyonychia congenita-associated palmoplantar keratoderma: new insights into skin epithelial homeostasis and avenues for treatment
AKAP1 genetic deletion during hyperoxia causes mitochondrial damage
Authors: Sahebgowda Patil, Matthew Alleyn, Jutaro Fukumoto, Muling Lin, Helena Hernandez-Cuervo, Ramani Soundararajan, Venkat Narala Ramireddy, Richard Lockey, Narasaiah Kolliputi, Lakshmi Galam
Journal: Journal of Allergy and Clinical Immunology (2020)
Dupilumab Treatment Results in Rapid Improvement in Itch in Adult and Adolescent Patients With Moderate-to-Severe Atopic Dermatitis (LIBERTY AD SOLO 1 &amp; 2, and ADOL trials)
Authors: Gil Yosipovitch, Chih-ho Hong, Eric Simpson, Laurent Eckert, Zhen Chen, Paola Mina-Osorio, Abhijit Gadkari
Journal: Journal of Allergy and Clinical Immunology (2020)
Do Polygenic Risk Scores Improve Patient Selection for Prevention of Coronary Artery Disease?
Authors: Sadiya S. Khan, Richard Cooper, Philip Greenland
Journal: JAMA (2020)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Serial evaluation of CD19 surface expression in pediatric B-cell malignancies following CD19-targeted therapy
Authors: Diane Libert, Constance M. Yuan, Katherine E. Masih, Pallavi Galera, Dalia Salem, Haneen Shalabi, Bonnie Yates, Cindy Delbrook, Jack F. Shern, Terry J. Fry, Javed Khan, Maryalice Stetler-Stevenson, Nirali N. Shah
Journal: Leukemia (2020)
Effects of Combined Treatment with Cat Allergen Immunotherapy and Tezepelumab on Nasal Allergen Challenge
Authors: Jonathan Corren, Lisa Wheatley, Srinath Sanda, David Larson, Tielin Qin, Pedro Avila, Fuad Baroody, Paul Greenberger, Iftikhar Hussain, Mark Moss, Harold Nelson, Sarbjit Saini, Stephen Tilles, Joy Laurienzo, Michelle Sever, Don Whitehouse, Rachel Yan, Gerald Nepom
Journal: Journal of Allergy and Clinical Immunology (2020)
Minimally invasive implantation and decreased inflammation reduce osteoinduction of biomaterial
Authors: Zifan Zhao, Qin Zhao, Bin Gu, Chengcheng Yin, Kailun Shen, Hua Tang, Haibin Xia, Xiaoxin Zhang, Yanbing Zhao, Xiangliang Yang, Yufeng Zhang
Journal: Theranostics (2020)

Surgical trauma of biomaterial implantation significantly influences the immune system and the biological effects of biomaterials. Minimally invasive surgery has become a trend of clinical development but violating the concept of osteoimmunomodulation will hinder the biological effects of materials. Our study focused on biphasic calcium phosphate (BCP), the ectopia osteoinductive materials, filling the research blank of the significance of adaptive immunity crosstalk with bone biomaterials, and improving the interaction mechanism between bone biomaterials and immune response. Methods: The BCP bioceramics were implanted by conventional and minimally invasive methods in the gastrocnemius wild-type or T cells depleted mice to test the effect of ectopia osteoinduction. Moreover, flow cytometry was used to detect immune responses, T cell sorting and Western Blot molecular biology experiments, and transwell assays migration of mesenchymal stem cells (MSCs). Results: We found that BCP, an implantable osteoinductive material, could not activate the adaptive immune response mediated by T cells after minimally invasive surgery. Further studies revealed that under the conventional non-minimally invasive BCP implantation, a positive correlation existed between T cell recruitment and the infiltration and osteogenic differentiation of MSCs. Interestingly, after BCP was implanted by minimally invasive surgery or implanted in T cell depleted mice, MSCs infiltration and osteogenic differentiation were significantly reduced, and BCP could not achieve the biological effects of ectopia ossification. Finally, we confirmed that a certain extent inflammatory stimulation activated the adaptive immune response mediated by T cells, up-regulated the nuclear factor-κB (NF-κB) signal in T cells, released a large amount of chemokine C-C motif chemokine ligand 5(CCL5) to recruit MSCs to the surrounding material, and finally achieved the ideal effect of osteoinduction. Conclusion: From experimental research and clinical surgery, this study discovered that the T cells are indispensable in the ectopia ossification mediated by osteoinductive materials, put forward and confirmed the surgery method as a key variable factor restricting the application effect of biological materials, enriched the key mechanism of adaptive immunity in osteoimmunomodulation, and laid a theoretical foundation for the development of osteoinductive materials and bone tissue regeneration.
Surgeon who acted as expert witness must pay £88 000 in costs, says judge
Authors: Clare Dyer
Journal: BMJ (2020)

A consultant spinal surgeon who acted as an expert witness for a patient suing an NHS trust for negligence has been ordered to pay £88 800 (€105 000; $114 000) in costs incurred by the trust in defending the case.

In a case she described as “highly unusual,” Judge Claire Evans said that Firas Jamil was unable to answer questions about the legal test for breach of duty, the key question for determining whether a doctor was negligent.1

At the time of the trial in March 2019 Jamil was experiencing mental health and cognitive problems that had led to his being on sick leave from work from November 2017 and retiring from clinical practice in 2018. He had continued with medicolegal work but should have stepped down as an expert in November 2017, Evans ruled.

Jamil, who qualified in Iraq in …
Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs
Authors: Stephanie M. Dobson, Laura García-Prat, Robert J. Vanner, Jeffrey Wintersinger, Esmé Waanders, Zhaohui Gu, Jessica McLeod, Olga I. Gan, Ildiko Grandal, Debbie Payne-Turner, Michael N. Edmonson, Xiaotu Ma, Yiping Fan, Veronique Voisin, Michelle Chan-Seng-Yue, Stephanie Z. Xie, Mohsen Hosseini, Sagi Abelson, Pankaj Gupta, Michael Rusch, Ying Shao, Scott R. Olsen, Geoffrey Neale, Steven M. Chan, Gary Bader, John Easton, Cynthia J. Guidos, Jayne S. Danska, Jinghui Zhang, Mark D. Minden, Quaid Morris, Charles G. Mullighan, John E. Dick
Journal: Cancer Discovery (2020)

Abstract Disease recurrence causes significant mortality in B-progenitor acute lymphoblastic leukemia (B-ALL). Genomic analysis of matched diagnosis and relapse samples shows relapse often arising from minor diagnosis subclones. However, why therapy eradicates some subclones while others survive and progress to relapse remains obscure. Elucidation of mechanisms underlying these differing fates requires functional analysis of isolated subclones. Here, large-scale limiting dilution xenografting of diagnosis and relapse samples, combined with targeted sequencing, identified and isolated minor diagnosis subclones that initiate an evolutionary trajectory toward relapse [termed diagnosis Relapse Initiating clones (dRI)]. Compared with other diagnosis subclones, dRIs were drug-tolerant with distinct engraftment and metabolic properties. Transcriptionally, dRIs displayed enrichment for chromatin remodeling, mitochondrial metabolism, proteostasis programs, and an increase in stemness pathways. The isolation and characterization of dRI subclones reveals new avenues for eradicating dRI cells by targeting their distinct metabolic and transcriptional pathways before further evolution renders them fully therapy-resistant. Significance: Isolation and characterization of subclones from diagnosis samples of patients with B-ALL who relapsed showed that relapse-fated subclones had increased drug tolerance and distinct metabolic and survival transcriptional programs compared with other diagnosis subclones. This study provides strategies to identify and target clinically relevant subclones before further evolution toward relapse. See related video: https://vimeo.com/442838617 See related article by E. Waanders et al .
Structure and ingredient-based biomimetic scaffolds combining with autologous bone marrow-derived mesenchymal stem cell sheets for bone-tendon healing
Authors: Yifu Tang, Can Chen, Fei Liu, Shanshan Xie, Jin Qu, Muzhi Li, Zan Li, Xiaoning Li, Qiang Shi, Shengcan Li, Xing Li, Jianzhong Hu, Hongbin Lu
Journal: Biomaterials (2020)
Missed opportunity: An intersectional approach to disparities in long-term survival in bladder cancer.
Authors: Samuel L. Washington, Stephen Gregorich, Sikai Song, Maxwell V. Meng, Anne Suskind, Sima P. Porten
Journal: Journal of Clinical Oncology (2020)

476 Background: For individuals with muscle-invasive bladder cancer (MIBC), studies focused on racial disparities have shown black race is associated with 21% lower odds of guideline-based treatment (GBT) and differences in treatment explain 35% of observed black-white differences in survival. To characterize how the interaction between race/ethnicity and receipt of GBT drive within- and between-race differences in survival for black, white, and Latino individuals with MIBC. Methods: We identified a cohort of individuals with cT2-4 MIBC from 2004-2013 in the National Cancer Database. GBT was defined by American Urological Association guidelines. A Cox proportional hazards model of patient mortality estimated effects of patient GBT status, race/ethnicity, and the GBT-by-race/ethnicity interaction, adjusting for covariates. Results: Of 54,910 MIBC individuals with 125,821 person-years of post-treatment observation (max=11 years), 90.1% were white, 6.9% black, and 3.0% Latino. Half (50.2%) received GBT. Averaging across GBT status, Latino individuals had lower hazard of death compared to black (HR 0.81, 95% CI 0.75-0.87) and white individuals (HR 0.92, 0.86-0.98). With GBT, Latino and white individuals had similar outcomes (HR=1.00, 0.91-1.10) and both groups fared significantly better than black individuals (HR=0.88, 0.79-0.99 and HR=0.88, 0.83-0.94, respectively). Without GBT, Latino individuals fared better than white (HR=0.85, 0.77-0.93) and black individuals (HR=0.74, 0.67-0.82) while white individuals fared better than black individuals (HR=0.87, 0.83-0.92). Latino without GBT fared better than black individuals with GBT (H=0.98, 0.88-1.09), although not statistically significant. Conclusions: Our study finds that not only are GBT levels generally low, which is concerning, but there is also an apparent 'under-allocation' of GBT to a patient group who arguably needs it the most-- black individuals. Future efforts to improve the delivery of GBT, a factor directly impacted by urologic care providers, may mitigate the race-based survival differences observed in individuals with MIBC.
Association of modified Glasgow Prognostic Score (mGPS) with survival outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (CPI).
Authors: Jacqueline T Brown, Yuan Liu, Dylan J. Martini, Julie M. Shabto, Elise Hitron, Greta Russler, Sarah Caulfield, Lauren Beth Yantorni, Shreyas S. Joshi, Haydn Kissick, Kenneth Ogan, Bradley Curtis Carthon, Omer Kucuk, Wayne Harris, Viraj A. Master, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2020)

738 Background: The current risk models for mRCC were developed for patients treated with targeted therapy. The mGPS incorporates albumin and C-reactive protein and may serve as a composite prognostic biomarker in mRCC in the era of CPI. Methods: We conducted a retrospective analysis of patients with mRCC treated with CPI (anti-PD1 or PD-L1 agents) at Winship Cancer Institute between 2015-2018. Overall survival (OS) and progression-free survival (PFS) were defined as months from CPI initiation to death or clinical/radiographic progression, respectively. mGPS was defined as a summary score with one point given for CRP &gt; 10 mg/L and/or albumin &lt; 3.5 g/dL. Univariate (UVA) and multivariate (MVA) analyses were carried out for OS and PFS using Cox proportional hazard model. Results: A total of 78 eligible patients were included with a median follow up of 30.7 months. Median age was 66 years (range = 38-82), 64% were male, 78% had clear cell histology, and 76% received anti-PD-1 monotherapy. Higher mGPS at baseline was significantly associated with worse OS while at week 6 was associated with worse OS and PFS (Table). Conclusions: A higher mGPS score in the early course of CPI treatment was associated with worse survival in patients with mRCC. These results should be validated in a larger, prospective study.[Table: see text]
Comment on Segar et al. Machine Learning to Predict the Risk of Incident Heart Failure Hospitalization Among Patients With Diabetes: The WATCH-DM Risk Score. Diabetes Care 2019;42:2298–2306
Authors: Hui Shao, Lizheng Shi, Vivian Fonseca
Journal: Diabetes Care (2020)

We congratulate Segar et al. (1) on their prediction of hospitalization for heart failure (HHF) in type 2 diabetes, which confirms our previously published finding (2). Indeed, we have used a more sophisticated approach (machine learning, left truncation, time-varying risk factors, parametric proportional hazard) with a superior predictive capability (5-year c-statistic >0.80) for Action to Control Cardiovascular Risk in Diabetes (ACCORD) patients without heart failure at baseline. We have risk equations not just for HHF and other cardiovascular events, but for a wide range of complications of diabetes, including microvascular complications. …
AK002, an Anti-Siglec-8 Antibody, Suppresses Acute IL-33-induced Neutrophil Infiltration and Attenuates Tissue Damage in a Chronic Experimental COPD Model Through Mast Cell Inhibition
Authors: Julia Schanin, Emily Brock, John Leung, Philip Hansbro, Brad Youngblood
Journal: Journal of Allergy and Clinical Immunology (2020)