tbuckley/cabot-search huggingface dataset:
Single-cell RNA landscape of the osteoimmunology microenvironment in periodontitis
Authors: Yue Chen, Hua Wang, Qiudong Yang, Wenhua Zhao, Yuyi Chen, Qiaoqi Ni, Wenlei Li, Jiali Shi, Wei Zhang, Lu Li, Yan Xu, Hengwei Zhang, Dengshun Miao, Lianping Xing, Wen Sun
Journal: Theranostics (2022)

Single-cell RNA sequencing (scRNA-seq) enables specific profiling of cell populations at single-cell resolution.The osteoimmunology microenvironment in the occurrence and development of periodontitis remains poorly understood at the single-cell level.In this study, we used single-cell transcriptomics to comprehensively reveal the complexities of the molecular components and differences with counterparts residing in periodontal tissues.Methods: We performed scRNA-seq to identify 51248 single cells from healthy controls (n=4), patients with severe chronic periodontitis (n=5), and patients with severe chronic periodontitis after initial periodontal therapy within 1 month (n=3).Uniform manifold approximation and projection (UMAP) were further conducted to explore the cellular composition of periodontal tissues.Pseudotime cell trajectory and RNA velocity analysis, combined with gene enrichment analysis were used to reveal the molecular pathways underlying cell fate decisions.CellPhoneDB were performed to identify ligand-receptor pairs among the major cell types in the osteoimmunology microenvironment of periodontal tissues.Results: A cell atlas of the osteoimmunology microenvironment in periodontal tissues was characterized and included ten major cell types, such as fibroblasts, monocytic cells, endothelial cells, and T and B cells.The enrichment of TNFRSF21 + fibroblasts with high expression of CXCL1, CXCL2, CXCL5, CXCL6, CXCL13, and IL24 was detected in patients with periodontitis compared to healthy individuals.The fractions of CD55 + mesenchymal stem cells (MSCs), APOE + pre-osteoblasts (pre-OBs), and IBSP + osteoblasts decreased significantly in response to initial periodontal therapy.In addition, CXCL12 + MSC-like pericytes could convert their identity into a pre-OB state during inflammatory responses even after initial periodontal therapy confirmed by single-cell trajectory.Moreover, we portrayed the distinct subtypes of monocytic cells and abundant endothelial cells significantly involved in the immune response.The heterogeneity of T and B cells in periodontal tissues was characterized.Finally, we mapped osteoblast/ osteoclast differentiation mediators to their source cell populations by identifying ligand-receptor pairs and highlighted the effects of Ephrin-Eph signaling on bone regeneration after initial periodontal therapy.Conclusions: Our analyses uncovered striking spatiotemporal dynamics in gene expression, population composition, and cell-cell interactions during periodontitis progression.These findings provide insights into the cellular and molecular underpinning of periodontal bone regeneration.
2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary
Authors: Rick A. Nishimura, Catherine M. Otto, Robert O. Bonow, Blase A. Carabello, John P. Erwin, Robert A. Guyton, Patrick T. O'Gara, Carlos E. Ruiz, Nikolaos J. Skubas, Paul Sorajja, Thoralf M. Sundt, James D. Thomas
Journal: Journal of the American College of Cardiology (2014)
Role of Fcγ receptors in HER2-targeted breast cancer therapy
Authors: Antonino Musolino, William J Gradishar, Hope S Rugo, Jeffrey L Nordstrom, Edwin P Rock, Fernanda Arnaldez, Mark D Pegram
Journal: Journal for ImmunoTherapy of Cancer (2022)

Several therapeutic monoclonal antibodies (mAbs), including those targeting epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), and CD20, mediate fragment crystallizable gamma receptor (FcγR)–dependent activities as part of their mechanism of action. These activities include induction of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which are innate immune mechanisms of cancer cell elimination. FcγRs are distinguished by their affinity for the Fc fragment, cell distribution, and type of immune response they induce. Activating FcγRIIIa (CD16A) on natural killer cells plays a crucial role in mediating ADCC, and activating FcγRIIa (CD32A) and FcγRIIIa on macrophages are important for mediating ADCP. Polymorphisms in FcγRIIIa and FcγRIIa generate variants that bind to the Fc portion of antibodies with different affinities. This results in differential FcγR-mediated activities associated with differential therapeutic outcomes across multiple clinical settings, from early stage to metastatic disease, in patients with HER2+ breast cancer treated with the anti-HER2 mAb trastuzumab. Trastuzumab has, nonetheless, revolutionized HER2+ breast cancer treatment, and several HER2-directed mAbs have been developed using Fc glyco-engineering or Fc protein-engineering to enhance FcγR-mediated functions. An example of an approved anti-HER2 Fc-engineered chimeric mAb is margetuximab, which targets the same epitope as trastuzumab, but features five amino acid substitutions in the IgG 1 Fc domain that were deliberately introduced to increase binding to activating FcγRIIIa and decrease binding to inhibitory FcγRIIb (CD32B). Margetuximab enhances Fc-dependent ADCC in vitro more potently than the combination of pertuzumab (another approved mAb directed against an alternate HER2 epitope) and trastuzumab. Margetuximab administration also enhances HER2-specific B cell and T cell–mediated responses ex vivo in samples from patients treated with prior lines of HER2 antibody-based therapies. Stemming from these observations, a worthwhile future goal in the treatment of HER2+ breast cancer is to promote combinatorial approaches that better eradicate HER2+ cancer cells via enhanced immunological mechanisms.
Research round-up
Authors: Seema Kang
Journal: The Lancet Psychiatry (2020)

Using data from a Danish population-based cohort, Natalie Momen and colleagues estimated the risk of developing subsequent medical conditions in people with a mental disorder. The cohort included 5 940 299 people (n=698 874 with a mental disorder), followed up for 83·9 million person-years. Analysis showed that there was an overall increased risk for developing a medical condition in people with a mental disorder (median hazard ratio [HR] 1·37 [IQR 1·20–1·55]). The greatest risk noted was for developing a urogenital condition in people with an eating disorder (HR 3·62 [3·11–4·22]).
Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction
Authors: Kieran F. Docherty, Ross T. Campbell, Katriona J.M. Brooksbank, John G. Dreisbach, Paul Forsyth, Rosemary L. Godeseth, Tracey Hopkins, Alice M. Jackson, Matthew M.Y. Lee, Alex McConnachie, Giles Roditi, Iain B. Squire, Bethany Stanley, Paul Welsh, Pardeep S. Jhund, Mark C. Petrie, John J.V. McMurray
Journal: Circulation (2021)

Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects.We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril/valsartan 97/103 mg twice daily with valsartan 160 mg twice daily in patients ≥3 months after myocardial infarction with a LV ejection fraction ≤40% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril ≥2.5 mg twice daily) and a β-blocker unless contraindicated or intolerant. Patients in New York Heart Association class ≥II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire.From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7±10.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2-7.2); mean LV ejection fraction, 36.8%±7.1%; and median NT-proBNP, 230 pg/mL (interquartile range, 124-404). Sacubitril/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, -1.9 mL/m2 (95% CI, -4.9 to 1.0); P=0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change.In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril/valsartan did not have a significant reverse remodeling effect compared with valsartan. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03552575.
Estimated Prevalence of Risk Factors for Preeclampsia Among Individuals Giving Birth in the US in 2019
Authors: Sarahn M. Wheeler, Sabrena O. Myers, Geeta K. Swamy, Evan R. Myers
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Low-dose aspirin (LDA) is one of the few evidence-based interventions for preventing preeclampsia, which is a leading cause of maternal or fetal morbidity and mortality. Current guidelines recommend LDA based on the presence of risk factors for preeclampsia, but the population-based prevalence of these factors is unknown. <h3>Objective</h3> To estimate population-level prevalence of preeclampsia risk factors used in prophylactic LDA guidelines for pregnant patients and the association of these risk factors with reported rates of pregnancy-related hypertension. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted using National Center for Health Statistics birth certificate data to describe the frequency of pregnant individuals with moderate to high-risk factors for preeclampsia and pregnancy-related hypertension rates. The study used all birth records in the United States for the 2019 calendar year. <h3>Exposures</h3> Documentation of preeclampsia risk factors: multifetal gestation, pregestational diabetes, chronic hypertension (high-risk factors) and nulliparity, a body mass index greater than 30, African American race, a maternal age 35 years or older, an interval of more than 10-years since last birth, and having low socioeconomic status (moderate risk factors). <h3>Main Outcomes and Measures</h3> Prevalence of each risk factor alone and in combinations leading to a recommendation for LDA; incidence of pregnancy-related hypertension by risk factor and combinations of risk factors. <h3>Results</h3> There were 3 695 019 pregnancies in 2019, including 528 778 with no risk factors, 169 540 with 1 or more high-risk factors, and 2 996 701 with 1 or more moderate-risk factors. The mean (SD) of the cohort was 29.1 (5.8) years. Multifetal gestation was the most common high-risk factor and found in 123 995 pregnancies (3.4%), and low socioeconomic status was the most common moderate-risk factor and present in 1 732 729 pregnancies (46.9%). Based on 2021 criteria (a single high- or moderate-risk factors for preeclampsia), 3 166 241 pregnant patients (85.7%) were eligible for LDA. The incidence of pregnancy-related hypertension increased with the number of moderate-risk factors. The 2021 guidelines suggest considering or recommend LDA in 92.3% of pregnancies diagnosed with pregnancy-related hypertension. <h3>Conclusions and Relevance</h3> These data support the recently published guidelines and suggest further simplified guidelines recommending LDA to patients with any single moderate-risk factors.
Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems Ralf Sodian Matthias Loebe, Christoph Schmitt, Evgenij Potapov, Henryk Siniawski, Johannes M�ller, Harald Hausmann, Heinz R. Zurbr�gg, Yuguo Weng, Roland Hetzer. Deutsches Herzzentrum Berlin, Berlin, Germany
Journal: Journal of the American College of Cardiology (2001)
Impact of local therapy on survival among patients with metastatic anal squamous cell carcinoma.
Authors: Olatunji B. Alese, Yining Zhang, Katerina Mary Zakka, Renjian Jiang, Rami Atallah, Maria Diab, Walid Labib Shaib, Mehmet Akce, Christina Wu, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2022)

4 Background: About 10-20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease, and are usually treated with systemic chemotherapy. The role of local therapy to control the primary tumor is controversial in this setting. We evaluated survival impact of local therapy in metastatic anal SCCa. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. We excluded patients who did not receive palliative systemic chemotherapy. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: 1,160 patients were identified over 12 years. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with a significant improvement in OS on MVA (HR 0.66; 0.55-0.79; p &lt; 0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24-1.67; p &lt; 0.001), age &gt; 70 years (HR 1.28; 1.02-1.62; p = 0.034), lack of health insurance (HR 1.32; 1.02-1.71; p = 0.034), and cloacogenic zone location (HR 4.02; 1.43-11.30; p = 0.008). There was no benefit from abdominoperineal resection (mOS = 19.7mos; HR 1.05; 0.48-2.29; p = 0.909), but both local resection of the primary (mOS = 24.8mos, HR 0.48; 0.29-0.80; p = 0.005) and palliative radiation (mOS = 22.6 mos; HR 0.66; 0.55-0.79; p &lt; 0.001) were associated with improved OS. Conclusions: This is the largest reported study on management of de novo stage IV SCCa. The data suggest that local control of the primary tumor through resection or radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local therapy include age over 70 years, male, lack of health insurance and cloacogenic carcinoma.
Impairment of coronary vasodilator capacity is predictive of unfavorable outcome in patients with hypertrophic cardiomyopathy Franco Cecchi, Roberto Gistri, Iacopo Olivotto, Roberto Lorenzoni, Giampaolo Chiriatti, Francesco Mazzuoli, Alberto Dolara, Paolo G. Camici. Cardiologia San Luca Ospedale Careggi, Firenze, Italy
Journal: Journal of the American College of Cardiology (2001)
Is right ventricular septal pacing superior to conventional right ventricular apical pacing in chronically implanted patients? A prospective randomized crossover comparison Fr�d�ric Victor, Sr., Hassan Mansour, Sr., Dominique Pavin, Sr., Christine Alonso, Sr., Christophe Leclercq, Sr., Phillippe Mabo, Sr., Claude Daubert, Sr.. Departement de Cardiologie CHU, Rennes, France
Journal: Journal of the American College of Cardiology (2001)
WASHINGTON NEWS
Journal: JAMA (1966)

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
The safety and efficacy of transarterial chemoembolization (TACE) + lenvatinib + programmed cell death protein 1 (PD-1) antibody of advanced unresectable hepatocellular carcinoma.
Authors: Xiaoyun Zhang, Xinrui Zhu, Chang Liu, Wusheng Lu, Qiu Li, Weixia Chen, Zhiping Li, Qiang Lu, Wei Peng, Chuan Li, Lvnan Yan, Jiayin Yang, Tianfu Wen
Journal: Journal of Clinical Oncology (2022)

453 Background: More than 70% of hepatocellular carcinoma (HCC) patients are in the intermediate or advanced stages at the time of diagnosis. TACE, TKI and PD-1 antibody are all recommended for patients with unresectable HCC (uHCC) according to Chinese HCC guidelines. There are few scientific trials to back up the safety and effecacy of TACE+TKI+PD-1 antibody for the treatment of uHCC and conversion resection. In this study, we explored the safety and efficacy of the TACE+TKI+PD-1 antibody in uHCC. Methods: This is a prospective, multicenter, cohort study (NCT04997850). Key Eligibility Criteria:18 years old ≤ age ≤ 70 years old; HCC confirmed by histopathology or cytology; No systemic treatment history. ECOG PS score 0-1; Child-Pugh A/B; BCLC stage B/C.Experience group: TACE + Lenvatinib (12mg when≥ 60kg/8mg when &lt; 60kg QD) + Camrelizumab/ Sintilimab (200 mg ivgtt Q3W);Control group: TACE. Results: From Sep 2020 to May 2021, 38 patients were enrolled in experimental group (Table). At the cutoff date (Sep 10 2021), the median follow-up was of 33.34 weeks (Table). The conversion resection rate was 50% (19/38), and the conversion success rate was 52.6% (20/38). Among the 19 patients, 5 cases achieved complete pathological response and 1 case achieved major pathological response. The 48 weeks’ OS rate and PFS were 96.4% (95%CI 92.9% to 99.9%) and 91.7%(95%CI 85.8% to 97.4%).22 patients had level 3 treatment related adverse events (TRAE), there were no level 4 and 5 TRAEs. At the last follow-up, the ORR rate based on mRECIST was 84.2%, and the DCR rate was 94.7% (Table). Conclusions: TACE + Lenvatinib + PD-1 antibody is safe and effective, and conversion resection after the triple-treatment is feasible for uHCC. Clinical trial information: 04997850.[Table: see text]
Response to Comment on Hamblin et al. Capillary Ketone Concentrations at the Time of Colonoscopy: A Cross-Sectional Study With Implications for SGLT2 Inhibitor–Treated Type 2 Diabetes. Diabetes Care 2021;44:e124–e126
Authors: Peter S. Hamblin, Rosemary Wong, Elif I. Ekinci, Shoshana Sztal-Mazer, Shananthan Balachandran, Aviva Frydman, Timothy P. Hanrahan, Raymond Hu, Shara N. Ket, Alan Moss, Mark Ng, Sashikala Ragunathan, Leon A. Bach
Journal: Diabetes Care (2021)
Non invasive assessment of serial changes in left ventricular diastolic function during myocardial ischemia reperfusion Marta Sitges, Takahiro Shiota, Jian Xin Qin, Yong Jin Kim, Fabrice Bauer, Kai Wang, Zhongmin Zhou, Xiaorong Zhou, Niel L. Greenberg, Mario J. Garcia, James D. Thomas. The Cleveland Clinic Foundation, Cleveland, OH
Journal: Journal of the American College of Cardiology (2001)
Varicella-Zoster Immune Globulin for the Prevention of Chickenpox
Journal: Annals of Internal Medicine (1984)

This is the first statement by the Immunization Practices Advisory Committee on the use of varicella-zoster immune globulin ( VZIG ). Prior recommendations have been made by the manufacturer in cooperation with the Centers for Disease Control and approved by the Office of Biologics, National Center for Drugs and Biologics, U.S. Food and Drug Administration. Because of exceedingly limited supplies, VZIG use has been restricted to proven high-risk individuals--for prophylaxis against chickenpox in immunocompromised children and prevention of postnatal chickenpox following intrauterine exposure. With increasing supplies, some of these restrictions can be lifted. This statement includes use of VZIG for immunocompromised persons of any age, normal adults, pregnant women, and premature and full-term infants. However, because the supply of VZIG is still limited, it continues to be recommended primarily for immunocompromised children and certain neonates exposed in utero. It should not be used indiscriminately.
Impact of hydrogen peroxide on human and canine atrial calcium current and action potentials: Implications for postoperative atrial fibrillation David R. Van Wagoner, Michelle Lamorgese, Laurie Castel, John A. Bauer, Cynthia A. Carnes, Mina K. Chung, Patrick M. McCarthy. Cleveland Clinic Foundation, Cleveland, OH, Ohio State University College of Pharmacy, Columbus, OH
Journal: Journal of the American College of Cardiology (2001)
Early Q waves are clinical predictors of no-reflow after succesful recanalization of the infarct related artery Leonarda Galiuto, Antonella Lombardo, Antonio G. Rebuzzi, Luca Santoro, Domenico Cianflone, Filippo Crea, Attilio Maseri. Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy
Journal: Journal of the American College of Cardiology (2001)
A randomized controlled feasibility trial of online compassion‐focused self‐help for psoriasis*
Authors: Zina Muftin, Paul Gilbert, Andrew R. Thompson
Journal: British Journal of Dermatology (2022)

People with psoriasis can experience psychological distress that might be amenable to psychosocial self-help.This study tested the feasibility and acceptability of two theoretically developed self-help interventions designed to reduce feelings of shame and improve quality of life.A randomized controlled feasibility trial was conducted comprising 130 participants with psoriasis who were randomly allocated to receive either compassion-based self-help (n = 65) or mindfulness-based self-help (n = 65), over a 4-week period. Both interventions were provided online.The interventions were found to be acceptable, with over 70% of study completers reporting that they found the materials helpful. Of the 130 participants, 92 completed the study, with attrition at 29%. Both interventions showed modest yet statistically significant reductions in shame (Cohen's d = 0.20) and improvements in quality of life (Cohen's d = 0.40).Self-help based on compassion and mindfulness is acceptable to users, and can reduce feelings of shame and improve quality of life for people living with psoriasis. What is already known about this topic? Psoriasis can be associated with psychological distress. Various forms of psychological intervention have been tested; however, few compassion based interventions have been developed or trialled. What does this study add? This study demonstrates that compassion-based self-help is acceptable to people with psoriasis. This study provides provisional evidence of effectiveness of compassion based self-help in reducing feelings of shame and improving quality of life for people living with psoriasis.