tbuckley/cabot-search huggingface dataset:
THERAPEUTIC APPROACHES FOR MYOCARDIAL INJURY: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Jose M. Gonzalez-Rayas, Jose A Hernandez-Hernandez, Rosa C. Lopez-Sanchez, Jose Gonzalez-Yanez, Ana Lilia Rayas Gomez, Tecnologico de Monterrey
Journal: Journal of the American College of Cardiology (2022)
Higher-Dose Primaquine to Prevent Relapse of <i>Plasmodium vivax</i> Malaria
Authors: Nathália N. Chamma-Siqueira, Suiane C. Negreiros, Sarah-Blythe Ballard, Sâmela Farias, Sandro P. Silva, Stella M. Chenet, Eduardo J.M. Santos, Luann W. Pereira de Sena, Flávia Póvoa da Costa, Amanda G.N. Cardoso-Mello, Paola B. Marchesini, Cássio R.L. Peterka, Giselle M.R. Viana, Alexandre Macedo de Oliveira
Journal: New England Journal of Medicine (2022)

In most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy.In this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days.We enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3.The administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).
A developmentally prometastatic niche to hepatoblastoma in neonatal liver mediated by the Cxcl1/Cxcr2 axis
Authors: Li Fan, Qingfei Pan, Wentao Yang, Selene C. Koo, Cheng Tian, Liyuan Li, Meifen Lu, Anthony Brown, Bensheng Ju, John Easton, Sarangarajan Ranganathan, Soona Shin, Alexander Bondoc, Jun J. Yang, Jiyang Yu, Liqin Zhu
Journal: Hepatology (2022)

Hepatoblastoma (HB) is the most common pediatric liver cancer. Its predominant occurrence in very young children led us to investigate whether the neonatal liver provides a protumorigenic niche to HB development.HB development was compared between orthotopic transplantation models established in postnatal day 5 (P5) and 60 (P60) mice (P5Tx and P60Tx models). Single-cell RNA-sequencing (sc-RNAseq) was performed using tumor and liver tissues from both models and the top candidate cell types and genes identified are investigated for their roles in HB cell growth, migration, and survival.We found that various HB cell lines including HepG2 cells were consistently and considerably more tumorigenic and metastatic in the P5Tx model than in the P60Tx models. Sc-RNAseq of the P5Tx and P60Tx HepG2 models revealed that the P5Tx tumor was more hypoxic and had a larger number of activated hepatic stellate cells (aHSCs) in the tumor-surrounding liver that express significantly higher levels of Cxcl1 than those from the P60Tx model. We found these differences were developmentally present in normal P5 and P60 liver. We showed that the Cxcl1/Cxcr2 axis mediated HB cell migration and was critical to HB cell survival under hypoxia. Treating HepG2 P60Tx model with recombinant CXCL1 protein induced intrahepatic and pulmonary metastasis and CXCR2 knockout (KO) in HepG2 cells abolished their metastatic potential in the P5Tx model. Lastly, we showed that in tumors from patients with metastatic HB, there was a similar larger population of aHSCs in the tumor-surrounding liver than in localized tumors, and tumor hypoxia was uniquely associated with prognosis of patients with HB among pediatric cancers. We demonstrated that the neonatal liver provides a prometastatic niche to HB development through the Cxcl1/Cxcr2 axis.
Abstract P2-14-15: Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients
Authors: Issam Makhoul, Saddam M Ibrahim, Muhammad Abu-Rmaileh, Fariba Jousheghany, Eric Siegel, Lora J Rogers, John J Lee, Sergio Pina-Oviedo, Ginell R Post, Thaddeus Beck, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi
Journal: Cancer Research (2022)

Abstract Background: We have developed P10s-PADRE, a carbohydrate-mimetic-based peptide, cancer vaccine and demonstrated its safety and immunogenicity in a Phase I clinical trial performed in stage IV breast cancer patients. HR+/HER2- breast cancer is the most common form of breast cancer diagnosed in the United States. These patients face a persistent risk of distant recurrence long after completion of their treatment and new strategies to activate anti-tumor immune responses can improve outcomes of standard therapies. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Methods: Five combination schedules were designed based on the timing of immunizations relative to a standard-of-care neoadjuvant chemotherapy regimen. Induction of on-treatment antibody and cellular responses, including T-cells, natural killer (NK) cells, and cytokines was determined. Tumor-infiltrating lymphocytes were quantified in core and surgical biopsies. The data were used to define the treatment effect in general and the vaccine contribution in particular. Results: Combination of P10s-PADRE with chemotherapy was safe and immunogenic. Antibody response was superior in a particular combination schedule, called schedule C, where 3 weekly immunizations preceded the first dose of chemotherapy. We observed that the schedule C, relative to other schedules, displayed an increase in CD16 expression on NK cells, a drop in serum IFN-γ, and an increase in quantity of stromal TILs in residual tumors. Subjects demonstrated a significant reduction in the size of their primary tumor and three subjects achieved pCR. Conclusions: The timing of the immunization relative to the chemotherapy seems to define the type and strength of the immune responses elicited. A particular combination schedule, schedule C, appears promising and the results warrant the conduct of randomized phase II trials. Citation Format: Issam Makhoul, Saddam M Ibrahim, Muhammad Abu-Rmaileh, Fariba Jousheghany, Eric Siegel, Lora J Rogers, John J Lee, Sergio Pina-Oviedo, Ginell R Post, Thaddeus Beck, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-15.
PERCUTANEOUS TRANSVENOUS MITRAL COMMISSUROTOMY IN PREGNANT WOMEN WITH SEVERE RHEUMATIC MITRAL STENOSIS: MATERNAL AND FOETAL OUTCOME
Authors: Justin Paul Gnanaraj, Gnanavelu Ganesan, N. Swaminathan, Ravishankar G, Manohar G, Nageswaran M, Rajasekar Ramesh, Elangovan C, Pratap Kumar G, Tamilselvan K, Elavarasi E, Ravindran R, Dharmarajan G, Thiagarajan K, Venkatesan S, Vinila N, Anju S
Journal: Journal of the American College of Cardiology (2022)
SAFETY AND EFFICACY OF RADIOFREQUENCY ABLATION VS. MEDICAL THERAPY AS FIRST-LINE TREATMENT FOR PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Drew M. Johnson, Waqas Ullah, Sean J. Dikdan, Eitan Frankel, Wajahat Humayun, Behzad B. Pavri, Daniel R. Frisch
Journal: Journal of the American College of Cardiology (2022)
Loci for prediction of penicillin and tetracycline susceptibility in Neisseria gonorrhoeae: a genome-wide association study
Authors: Tatum D Mortimer, Jessica J Zhang, Kevin C Ma, Yonatan H Grad
Journal: The Lancet Microbe (2022)

Neisseria gonorrhoeae poses an urgent public health threat because of increasing antimicrobial resistance; however, much of the circulating population remains susceptible to historical treatment regimens. Point-of-care diagnostics that report susceptibility could allow for reintroduction of these regimens, but development of such diagnostics has been restricted to ciprofloxacin, for which susceptibility can be predicted from a single locus. We aimed to define genetic variants associated with susceptibility to penicillin and tetracycline.
Improving Enrollment of Underrepresented Racial and Ethnic Populations in Heart Failure Trials
Authors: Ersilia M. DeFilippis, Melvin Echols, Philip B. Adamson, Wayne B. Batchelor, Lauren B. Cooper, Lawton S. Cooper, Patrice Desvigne-Nickens, Richard T. George, Nasrien E. Ibrahim, Mariell Jessup, Dalane W. Kitzman, Eric S. Leifer, Martin Mendoza, Ileana L. Piña, Mitchell Psotka, Fortunato Fred Senatore, Kenneth M. Stein, John R. Teerlink, Clyde W. Yancy, JoAnn Lindenfeld, Mona Fiuzat, Christopher M. O’Connor, Orly Vardeny, Muthiah Vaduganathan
Journal: JAMA Cardiology (2022)

Despite bearing a disproportionate burden of heart failure (HF), Black and Hispanic individuals have been poorly represented in HF clinical trials. Underrepresentation in clinical trials limits the generalizability of the findings to these populations and may even introduce uncertainties and hesitancy when translating trial data to the care of people from underrepresented groups. The Heart Failure Collaboratory, a consortium of stakeholders convened to enhance HF therapeutic development, has been dedicated to improving recruitment strategies for patients from diverse and historically underrepresented groups.Despite federal policies from the US Food and Drug Administration and National Institutes of Health aimed at improving trial representation, gaps in trial enrollment proportionate to the racial and ethnic composition of the HF population have persisted. Increasing trial globalization with limited US enrollment is a major driver of these patterns. Additional barriers to representative enrollment include inequities in care access, logistical issues in participation, restrictive enrollment criteria, and English language requirements.Strategies for improving diverse trial enrollment include methodical study design and site selection, diversification of research leadership and staff, broadening of eligibility criteria, community and patient engagement, and broad stakeholder commitment. In contemporary HF trials, diverse trial enrollment is not only feasible but can be efficiently achieved to improve the generalizability and translation of trial knowledge to clinical practice.
THE RELATIONSHIP BETWEEN DONOR-TRANSMITTED LIPID BURDEN AND PLAQUE PROGRESSION IN PATIENTS AFTER HEART TRANSPLANTATION
Authors: Tatsuya Shiraki, Daisuke Nakamura, Tomohito Ohtani, Isamu Mizote, Hidetaka Kioka, Yasuhiro Akazawa, Kei Nakamoto, Seiko Ide, Yasuharu Takeda, Shungo Hikoso, Shigeru Miaygawa, Yasushi Sakata
Journal: Journal of the American College of Cardiology (2022)
Abstract OT1-12-02: Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab
Authors: Kathy Miller, Leisha A. Emens, Sara M. Tolaney, Sara A. Hurvitz, Erika Hamilton, Virginia Paton, Alison Hannah, Valentina Boni
Journal: Cancer Research (2022)

Abstract Background: Probody® therapeutic candidates (Pb-Tx) are masked antibodies designed to be conditionally activated in the tumor microenvironment by tumor-associated proteases. This allows Pb-Tx to address previously undruggable targets that are highly expressed in both tumor and normal tissues. Praluzatamab ravtansine is a masked antibody-drug conjugate targeting CD166 with a DM4 payload. A phase 1 monotherapy study showed safety and durable clinical activity (clinical benefit rate at 24 weeks [CBR24] 28%) in patients (pts) with metastatic HR-positive/HER2 non–amplified breast cancer (mHR+/HER2− BC) or metastatic triple-negative breast cancer (mTNBC). Pacmilimab, a masked PD-L1 inhibitor, demonstrated monotherapy activity in pts with TNBC with an acceptable tolerability profile.Trial design: This phase 2, open-label study with 3 parallel arms (~40 evaluable/arm) will evaluate praluzatamab ravtansine monotherapy (7 mg/kg Q3W) in pts with mHR+/HER2− BC or mTNBC, and praluzatamab ravtansine (7 mg/kg Q3W) combined with pacmilimab (1200 mg Q3W) in pts with mTNBC. Adult pts with an ECOG PS 0–1, measurable disease, and willingness to receive ocular prophylaxis for DM4-related toxicities will be enrolled. Key eligibility criteria for the mHR+/HER2− BC cohort include 2–4 prior regimens in the metastatic setting (excluding single-agent endocrine therapy). No CD166 screening required for HR+/HER2− BC but mTNBC must be CD166+. Pts with mTNBC must have received 1–3 prior metastatic regimens. For mTNBC pts who receive the doublet, key exclusion criteria include known PDL1 negative tumor, history of autoimmune disease, and progression within 120 days of 1st dose of an immuno-oncology agent. Pts with corneal disorders will be excluded. Primary endpoint is overall response rate (ORR) assessed by an independent radiology committee per RECIST v1.1. Secondary endpoints include ORR by investigator, duration of response, CBR16 &amp; 24, progression-free survival, and overall survival. This study will also evaluate safety and tolerability, pharmacokinetics, and antidrug antibodies with praluzatamab ravtansine as monotherapy and in combination with pacmilimab. This trial is enrolling (NCT04596150). Citation Format: Kathy Miller, Leisha A. Emens, Sara M. Tolaney, Sara A. Hurvitz, Erika Hamilton, Virginia Paton, Alison Hannah, Valentina Boni. Trial in progress: Phase 2, open-label study to evaluate the safety and efficacy of praluzatamab ravtansine in metastatic HER2 non-amplified breast cancer as monotherapy and combination with pacmilimab [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-02.
Can Systemic Control Be Achieved in the Treatment of Oligometastatic Hepatocellular Cancer With Hepatic Artery Infusion Fluorouracil, Leucovorin, and Oxaliplatin Treatment?
Authors: Osman Sütcüoğlu, Burcu Ulaş Kahya, Nuriye Özdemir, Ozan Yazıcı
Journal: Journal of Clinical Oncology (2022)
Gender Differences in Experiences of Leadership Emergence Among Emergency Medicine Department Chairs
Authors: Cherri Hobgood, Claire Draucker
Journal: JAMA Network Open (2022)

The number of women entering medicine continues to increase, but women remain underrepresented at all tiers of academic rank and chair leadership in EM. The proportion of female chairs in EM has not exceeded 12% in 2 decades.To compare how male and female EM chairs experience leadership emergence, with attention to factors associated with support of the emergence of female chairs.This qualitative descriptive study was conducted between April 2020 and February 2021 at 36 US academic EM departments. Eligible participants were all current and emeritus female EM academic department chairs (with a possible cohort of 20 individuals) and an equal number of randomly selected male chairs.Semistructured interviews were conducted via teleconferencing with an 11-item interview guide.Qualitative findings identifying similarities and gender differences in leadership emergence were collected.Among 20 female chairs in EM, 19 women (mean [SD] age, 56.2 [7.1] years) participated in the study (95.0% response rate). There were 13 active chairs, and 6 women were within 5 years of chair leadership. Among 77 male chairs in EM identified and randomized, 37 men were invited to participate, among whom 19 individuals (51.4%) agreed to participate; 18 men (mean [SD] age, 52.2 [7.5] years) completed their interviews. Reflecting upon their experiences of leadership emergence, male chairs saw leadership as their destiny, were motivated to be chairs to gain influence, were dismissive of risks associated with chairing a department, and were sponsored by senior male leaders to advance in leadership. Female chairs saw leadership as something they had long prepared for, were motivated to be chairs to make a difference, were cautious of risks associated with chairing a department that could derail their careers, and relied on their own efforts to advance in leadership.This study found that experiences of leadership emergence differed by gender. These results suggest that leadership development strategies tailored to women should promote early internalization of leadership identity, tightly link leadership to purpose, cultivate active sponsorship, and encourage women's risk tolerance through leadership validation to support women's development as leaders and demonstrate a commitment to gender equity in EM leadership.
IMPROVING UTILIZATION OF SGLT2 INHIBITORS VIA EDUCATION AT A SINGLE-CENTER ACADEMIC SAFETY-NET HOSPITAL
Authors: Preeti Singhal, Grace Liu, Pradeep Nadeswaran, Sophie Miller, Meghna Motiani, Maria Latz, Choo Phei Wee, Helga Van Herle
Journal: Journal of the American College of Cardiology (2022)
Selected recent advances in understanding the role of human mast cells in health and disease
Authors: Francesca Levi-Schaffer, Bernhard F. Gibbs, Jenny Hallgren, Carlo Pucillo, Frank Redegeld, Frank Siebenhaar, Joana Vitte, Soraya Mezouar, Moïse Michel, Pier Giorgio Puzzovio, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2022)
ELEVATED URINE NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) PREDICTS DEVELOPMENT OF ACUTE KIDNEY INJURY FOLLOWING INITIATION OF MECHANICAL CIRCULATORY SUPPORT
Authors: Rachel Harris, Andrew Yates, Deipanjan Nandi, Brett Klamer, Catherine D. Krawczeski, Diana Zepeda-Orozco
Journal: Journal of the American College of Cardiology (2022)
A Phase 1a/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors
Authors: Niharika B. Mettu, Susanna V. Ulahannan, Johanna C. Bendell, Ignacio Garrido-Laguna, John H. Strickler, Kathleen N. Moore, Robert Stagg, Ann M. Kapoun, Leonardo Faoro, Sunil Sharma
Journal: Clinical Cancer Research (2021)

TIGIT (T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) is a co-inhibitory receptor of T-cell and natural killer cell activity. Targeting TIGIT with or without PD-1/PD-L1 checkpoint inhibition may enhance antitumor immunity.This Phase 1a/b trial was a first-in-human, open-label, multicenter, dose-escalation and -expansion study in patients with locally advanced or metastatic solid tumors. Using 3 + 3 design, patients underwent 14-day treatment cycles with anti-TIGIT antibody etigilimab alone (Phase 1a; 0.3, 1.0, 3.0, 10.0, 20.0 mg/kg intravenously) or in combination with anti-PD-1 antibody nivolumab (Phase 1b; 3.0, 10.0, 20.0 mg/kg etigilimab and 240 mg nivolumab). Primary objective was safety and tolerability.Thirty-three patients were enrolled (Phase 1a, n = 23; Phase 1b, n = 10). There were no dose-limiting toxicities (DLT). MTD for single and combination therapy was not determined; maximum administered dose was 20 mg/kg. The most commonly reported adverse events (AE) were rash (43.5%), nausea (34.8%), and fatigue (30.4%) in Phase 1a and decreased appetite (50.0%), nausea (50.0%), and rash (40%) in Phase 1b. Six patients experienced Grade ≥3 treatment-related AEs. In Phase 1a, 7 patients (30.0%) had stable disease. In Phase 1b, 1 patient had a partial response; 1 patient had prolonged stable disease of nearly 8 months. Median progression-free survival was 56.0 days (Phase 1a) and 57.5 days (Phase 1b). Biomarker correlative analyses demonstrated evidence of clear dose-dependent target engagement by etigilimab.Etigilimab had an acceptable safety profile with preliminary evidence of clinical benefit alone and in combination with nivolumab and warrants further investigation in clinical trials.
Role of Glutaminase 2 in Promoting CD4+ T Cell Production of Interleukin‐2 by Supporting Antioxidant Defense in Systemic Lupus Erythematosus
Authors: Ryo Hisada, Nobuya Yoshida, Seo Yeon K. Orite, Masataka Umeda, Catalina Burbano, Marc Scherlinger, Michihito Kono, Suzanne Krishfield, George C. Tsokos
Journal: Arthritis & Rheumatology (2022)

Glutaminase (GLS) isoenzymes GLS1 and GLS2 catalyze the first step of glutaminolysis. GLS1 is requisite for Th17 cell differentiation, and its inhibition suppresses autoimmune disease in animals, but the function of GLS2 is not known. The aim of this study was to investigate the role of GLS2 in CD4+ T cell function and systemic lupus erythematosus (SLE) pathogenesis.
PCI IS SAFE AND INCREASING AMONG CANCER PATIENTS: NATIONALLY REPRESENTATIVE PROPENSITY SCORE ADJUSTED AND MACHINE LEARNING AUGMENTED STUDY OF 100 MILLION HOSPITALIZATIONS
Authors: Victor liu, Dominique Monlezun, Nikhil Agrawal, Bala Pushparaji, Nicole Thomason, Nicolas L. Palaskas, Mehmet Cilingiroglu, Konstantinos Marmagkiolis, Efstratios Koutroumpakis, Juan C. Lopez-Mattei, Peter Y. Kim, Saamir Hassan, Cezar Iliescu
Journal: Journal of the American College of Cardiology (2022)
Angiocrine polyamine production regulates adiposity
Authors: Erika Monelli, Pilar Villacampa, Amaia Zabala-Letona, Anabel Martinez-Romero, Judith Llena, Daniel Beiroa, Leonor Gouveia, Iñigo Chivite, Sebastián Zagmutt, Pau Gama-Perez, Oscar Osorio-Conles, Laia Muixi, Ainara Martinez-Gonzalez, Sandra D. Castillo, Natalia Martín-Martín, Pau Castel, Lorea Valcarcel-Jimenez, Irene Garcia-Gonzalez, Josep A. Villena, Sonia Fernandez-Ruiz, Dolors Serra, Laura Herrero, Rui Benedito, Pablo Garcia-Roves, Josep Vidal, Paul Cohen, Rubén Nogueiras, Marc Claret, Arkaitz Carracedo, Mariona Graupera
Journal: Nature Metabolism (2022)
THE PROGNOSTIC VALUE OF TROPONIN IN OHCA PATIENTS WITHOUT ST-SEGMENT ELEVATION: A COACT TRIAL SUBSTUDY
Authors: Eva Marie Spoormans, Jorrit Lemkes, Gladys Janssens, Nina Willemijn van der Hoeven, L. S.D. Jewbali, Martijn Meuwissen, Hans Bosker, Gabe Bleeker, Rémon Baak, Georgios Vlachojannis, Pim van der Harst, Michiel Voskuil, Albertus Beishuizen, Cyril Camaro, José P. Henriques, Maarten Vink, Ton Heestermans, Thijs Delnoij, Pranobe Oemrawsingh, Marcel Gosselink, Koos Plomp, Michiel Magro, Paul Elbers, Peter van de Ven, Niels Van Royen
Journal: Journal of the American College of Cardiology (2022)