tbuckley/cabot-search huggingface dataset:
Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation
Authors: Nandini Raghuraman, Lorene A. Temming, Michelle M. Doering, Carolyn R. Stoll, Arvind Palanisamy, Molly J. Stout, Graham A. Colditz, Alison G. Cahill, Methodius G. Tuuli
Journal: JAMA Pediatrics (2021)

Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice.To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes.Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance.Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded.Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models.The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission.The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11).This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.
Insulinemic and Inflammatory Dietary Patterns Show Enhanced Predictive Potential for Type 2 Diabetes Risk in Postmenopausal Women
Authors: Qi Jin, Ni Shi, Desmond Aroke, Dong Hoon Lee, Joshua J. Joseph, Macarius Donneyong, Darwin L. Conwell, Phil A. Hart, Xuehong Zhang, Steven K. Clinton, Zobeida Cruz-Monserrate, Theodore M. Brasky, Rebecca Jackson, Lesley F. Tinker, Simin Liu, Lawrence S. Phillips, Aladdin H. Shadyab, Rami Nassir, Wei Bao, Fred K. Tabung
Journal: Diabetes Care (2021)

The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk. We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 73,495 postmenopausal women in the Women's Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes. During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32-1.68; P trend < 0.0001) and EDIP 1.45 (1.29-1.63; P trend < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88-1.12; P trend = 0.46) and GL 1.01 (0.89-1.16; P trend = 0.30). Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.
SP0094 Rheumatology development: how to reach the equally and high standard educated and trained health professional throughout europe
Authors: AD Woolf
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> The health-related outcome for all with musculoskeletal conditions (MSC) in Europe should be equal which requires similarities in their care. This is dependent on financial and human resources, a key one being the competency of the health professional which will be determined by their training and CME. The integrated multidisciplinary team need suitable training which must be harmonised throughout Europe to ensure the outcome of care is similar for all. Learning objectives must be established for all the professional groups relevant to their contribution to the management of MSC which may vary between countries. From this a curriculum can be developed. Different methods of teaching may be used but the tendency is towards problem-based learning integrating basic with clinical knowledge and linking all those involved in the management of similar problems. The assessment should be based on the curriculum. Standards for rheumatology have been developed in Europe for undergraduates, specialist training and CME. Similar standards need to be developed for other health professionals in rheumatology. These must reflect the educational needs which will depend on their roles in clinical practice in different countries. The ultimate measure of the quality of training of all HPs in rheumatology is the clinical outcomes achieved within the constraints of financial resources and priority given to their care.
Venetoclax induces deep hematologic remissions in t(11;14) relapsed/refractory AL amyloidosis
Authors: Vikram J. Premkumar, Suzanne Lentzsch, Samuel Pan, Divaya Bhutani, Joshua Richter, Sundar Jagannath, Michaela Liedtke, Arnaud Jaccard, Ashutosh D. Wechalekar, Raymond Comenzo, Vaishali Sanchorawala, Bruno Royer, Michael Rosenzweig, Jason Valent, Stefan Schönland, Rafael Fonseca, Sandy Wong, Prashant Kapoor
Journal: Blood Cancer Journal (2021)

Abstract Venetoclax is efficacious in relapsed/refractory t(11;14) multiple myeloma, thus warranting investigation in light-chain amyloidosis (AL). This retrospective cohort includes 43 patients with previously treated AL, from 14 centers in the US and Europe. Thirty-one patients harbored t(11;14), 11 did not, and one t(11;14) status was unknown. Patients received a venetoclax-containing regimen for at least one 21- or 28-day cycle; the median prior treatments was three. The hematologic response rate for all patients was 68%; 63% achieved VGPR/CR. t(11;14) patients had higher hematologic response (81% vs. 40%) and higher VGPR/CR rate (78% vs. 30%, odds ratio: 0.12, 95% CI 0.02–0.62) than non-t(11;14) patients. For the unsegregated cohort, median progression-free survival (PFS) was 31.0 months and median OS was not reached (NR). For t(11;14), median PFS was NR and for non-t(11;14) median PFS was 6.7 months (HR: 0.14, 95% CI 0.04–0.53). Multivariate analysis incorporating age, sex, prior lines of therapy, and disease stage suggested a risk reduction for progression or death in t(11;14) patients. Median OS was NR for either subgroup. The organ response rate was 38%; most responders harbored t(11;14). Grade 3 or higher adverse events occurred in 19% with 7% due to infections. These promising results require confirmation in a randomized clinical trial.
Abstract 11295: Diagnostic Accuracy of Dobutamine Stress Echocardiography in the Detection of Cardiac Allograft Vasculopathy in Heart Transplant Recipients: A Systematic Review and Meta-Analysis Study
Authors: Ahmed Elkaryoni, Ahmed M Altibi, Adil Hassan, Ahmed Elgebaly, Eman M Elsabbagh, Navin C Nanda
Journal: Circulation (2018)

Introduction: Cardiac allograft vasculopathy (CAV) is an important cause of death after the first year following cardiac transplantation. The absence of classic signs of myocardial ischemia because...
Does the COMPare approach lead to scientific progress? : Letter to the editor in response to: Drysdale HM, Goldacre B. Reponse to the authors: Outcomes consist of time-points and methods of measurement, as stated in CONSORT. BMJ. 2015 Nov 23;351:h6127.
Authors: Rma van Nispen, Hpa van der Aa, Ghmb van Rens
Journal: BMJ (2015)
PTEN deficiency leads to proteasome addiction: a novel vulnerability in glioblastoma
Authors: Jorge A Benitez, Darren Finlay, Anthony Castanza, Alison D Parisian, Jianhui Ma, Ciro Longobardi, Alex Campos, Raghavendra Vadla, Alejandro Izurieta, Gianluca Scerra, Tomoyuki Koga, Tao Long, Lukas Chavez, Jill P Mesirov, Kristiina Vuori, Frank Furnari
Journal: Neuro-Oncology (2021)

Glioblastoma (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months; therefore, more effective treatment options for GBM are required. To identify new drugs targeting GBMs, we performed a high-throughput drug screen using patient-derived neurospheres cultured to preferentially retain their glioblastoma stem cell (GSC) phenotype.High-throughput drug screening was performed on GSCs followed by a dose-response assay of the 5 identified original "hits." A PI3K/mTOR dependency to a proteasome inhibitor (carfilzomib), was confirmed by genetic and pharmacologic experiments. Proteasome Inhibition Response Signatures were derived from proteomic and bioinformatic analysis. Molecular mechanism of action was determined using three-dimensional (3D) GBM-organoids and preclinical orthotopic models.We found that GSCs were highly sensitive to proteasome inhibition due to an underlying dependency on an increased protein synthesis rate, and loss of autophagy, associated with PTEN loss and activation of the PI3K/mTOR pathway. In contrast, combinatory inhibition of autophagy and the proteasome resulted in enhanced cytotoxicity specifically in GSCs that did express PTEN. Finally, proteasome inhibition specifically increased cell death markers in 3D GBM-organoids, suppressed tumor growth, and increased survival of mice orthotopically engrafted with GSCs. As perturbations of the PI3K/mTOR pathway occur in nearly 50% of GBMs, these findings suggest that a significant fraction of these tumors could be vulnerable to proteasome inhibition.Proteasome inhibition is a potential synthetic lethal therapeutic strategy for GBM with proteasome addiction due to a high protein synthesis rate and autophagy deficiency.
A Transcriptional Regulatory Loop of Master Regulator Transcription Factors, PPARG, and Fatty Acid Synthesis Promotes Esophageal Adenocarcinoma
Authors: Sai Ma, Bo Zhou, Qian Yang, Yunzhi Pan, Wei Yang, Stephen J. Freedland, Ling-Wen Ding, Michael R. Freeman, Joshua J. Breunig, Neil A. Bhowmick, Jian Pan, H. Phillip Koeffler, De-Chen Lin
Journal: Cancer Research (2021)

Abstract Although obesity is one of the strongest risk factors for esophageal adenocarcinoma, the molecular mechanisms underlying this association remain unclear. We recently identified four esophageal adenocarcinoma–specific master regulator transcription factors (MRTF) ELF3, KLF5, GATA6, and EHF. In this study, gene-set enrichment analysis of both esophageal adenocarcinoma patient samples and cell line models unbiasedly underscores fatty acid synthesis as the central pathway downstream of three MRTFs (ELF3, KLF5, GATA6). Further characterizations unexpectedly identified a transcriptional feedback loop between MRTF and fatty acid synthesis, which mutually activated each other through the nuclear receptor, PPARG. MRTFs cooperatively promoted PPARG transcription by directly regulating its promoter and a distal esophageal adenocarcinoma–specific enhancer, leading to PPARG overexpression in esophageal adenocarcinoma. PPARG was also elevated in Barrett’s esophagus, a recognized precursor to esophageal adenocarcinoma, implying that PPARG might play a role in the intestinal metaplasia of esophageal squamous epithelium. Upregulation of PPARG increased de novo synthesis of fatty acids, phospholipids, and sphingolipids as revealed by mass spectrometry–based lipidomics. Moreover, ChIP-seq, 4C-seq, and a high-fat diet murine model together characterized a novel, noncanonical, and cancer-specific function of PPARG in esophageal adenocarcinoma. PPARG directly regulated the ELF3 super-enhancer, subsequently activating the transcription of other MRTFs through an interconnected regulatory circuitry. Together, elucidation of this novel transcriptional feedback loop of MRTF/PPARG/fatty acid synthesis advances our understanding of the mechanistic foundation for epigenomic dysregulation and metabolic alterations in esophageal adenocarcinoma. More importantly, this work identifies a potential avenue for prevention and early intervention of esophageal adenocarcinoma by blocking this feedback loop. Significance: These findings elucidate a transcriptional feedback loop linking epigenomic dysregulation and metabolic alterations in esophageal adenocarcinoma, indicating that blocking this feedback loop could be a potential therapeutic strategy in high-risk individuals.
Minimal transmission of SARS-CoV-2 from paediatric COVID-19 cases in primary schools, Norway, August to November 2020
Authors: Lin T Brandal, Trine S Ofitserova, Hinta Meijerink, Rikard Rykkvin, Hilde M Lund, Olav Hungnes, Margrethe Greve-Isdahl, Karoline Bragstad, Karin Nygård, Brita A Winje
Journal: Eurosurveillance (2021)

An intense debate on school closures to control the COVID-19 pandemic is ongoing in Europe. We prospectively examined transmission of SARS-CoV-2 from confirmed paediatric cases in Norwegian primary schools between August and November 2020. All in-school contacts were systematically tested twice during their quarantine period. With preventive measures implemented in schools, we found minimal child-to-child (0.9%, 2/234) and child-to-adult (1.7%, 1/58) transmission, supporting that under 14 year olds are not the drivers of SARS-CoV-2 transmission.
RNA Sequencing Reveals Mechanisms Underlying Modulation of Hodgkin Lymphoma Cells and Tumor Microenvironment By the PI3K δ/γ Inhibitor, RP6530
Authors: Silvia Laura Locatelli, Francesca Maria Consonni, Giuseppa Careddu, Simone Serio, Srikant Viswanadha, Swaroop Kumar Vs Vakkalanka, Lucia Morello, Massimo Magagnoli, Luca Castagna, Armando Santoro, Antonio Sica, Carmelo Carlo-Stella
Journal: Blood (2017)
Quantitative and Qualitative Analysis of Blood-based Liquid Biopsies to Inform Clinical Decision-making in Prostate Cancer
Authors: Irene Casanova-Salas, Alejandro Athie, Paul C. Boutros, Marzia Del Re, David T. Miyamoto, Kenneth J. Pienta, Edwin M. Posadas, Adam G. Sowalsky, Arnulf Stenzl, Alexander W. Wyatt, Joaquin Mateo
Journal: European Urology (2021)

Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative. To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine. A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC. Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers). Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation. Traces of tumors can be isolated from blood samples from patients with prostate cancer either as whole cells or as DNA fragments. These traces provide information on tumor features. These minimally invasive tests can guide diagnosis and treatment selection.
Management of pelvic abscess complicating a rectoanal fistula using endoscopic ultrasound-guided drainage with an electrocautery-enhanced lumen-apposing metal stent
Authors: Laurent Monino, Hubert Piessevaux, Marie-Armelle Denis, Tom G. Moreels
Journal: Endoscopy (2021)

The management of pelvic abscess is mainly radiological or surgical [1]. The use of electrocautery-enhanced lumen-apposing metal stents (LAMS) allows efficient drainage of intra-abdominal collections [2]. A few retrospective studies and case series have demonstrated the feasibility and safety of EUS-guided drainage of pelvic abscesses [3] [4] [5]. We present a case of a large pelvic abscess complicating a rectoanal fistula that was successfully drained without recurrence using an electrocautery-enhanced LAMS.
Trends in Pediatric Hospitalizations for Coronavirus Disease 2019
Authors: Zachary Levin, Kimberly Choyke, Archelle Georgiou, Soumya Sen, Pinar Karaca-Mandic
Journal: JAMA Pediatrics (2021)

While early evidence and experience with coronavirus disease 2019 (COVID-19) suggests that children are less susceptible to infection and have a lower risk for symptomatic and severe disease, pediatric patients are not immune from the virus.We examined pediatric COVID-19 hospitalization trends in 22 states for indications of both severity among this population and spread of the virus.
Large Multi-Ethnic Genome Wide Association Study Reveals Novel Genetic Associations with Childhood Acute Lymphoblastic Leukemia at Chromosomes 8q24 and 17q12
Authors: Adam J. de Smith, Kyle M. Walsh, Stephen S. Francis, Semira Gonseth, Helen M. Hansen, Ivan Smirnov, Lisa Barcellos, Rong Wang, Andrew T. DeWan, Catherine Metayer, Xiaomei Ma, Joseph L. Wiemels
Journal: Blood (2017)
Abstract 12065: The Impact of Arterial Stiffness Assessed by Cardio-ankle Vascular Index on Long-term Outcome in Patients With Acute Coronary Syndrome
Authors: Jin Kirigaya, Noriaki Iwahashi, Masaomi Gohbara, Eiichi Akiyama, Kozo Okada, Yasushi Matsuzawa, Nobuhiko Maejima, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Kouichi Tamura, Kazuo Kimura
Journal: Circulation (2019)

Background: The clinical effect of arterial stiffness on long-term outcome in patients with acute coronary syndrome (ACS) remains unclear. In this study, the clinical significance of this parameter...
Development of nanoparticle-delivery systems for antiviral agents: A review
Authors: Rana Delshadi, Akbar Bahrami, David Julian McClements, Matthew D. Moore, Leonard Williams
Journal: Journal of Controlled Release (2021)

The COVID-19 pandemic has resulted in unprecedented increases in sickness, death, economic disruption, and social disturbances globally. However, the virus (SARS-CoV-2) that caused this pandemic is only one of many viruses threatening public health. Consequently, it is important to have effective means of preventing viral transmission and reducing its devastating effects on human and animal health. Although many antivirals are already available, their efficacy is often limited because of factors such as poor solubility, low permeability, poor bioavailability, un-targeted release, adverse side effects, and antiviral resistance. Many of these problems can be overcome using advanced antiviral delivery systems constructed using nanotechnology principles. These delivery systems consist of antivirals loaded into nanoparticles, which may be fabricated from either synthetic or natural materials. Nevertheless, there is increasing emphasis on the development of antiviral delivery systems from natural substances, such as lipids, phospholipids, surfactants, proteins, and polysaccharides, due to health and environmental issues. The composition, morphology, dimensions, and interfacial characteristics of nanoparticles can be manipulated to improve the handling, stability, and potency of antivirals. This article outlines the major classes of antivirals, summarizes the challenges currently limiting their efficacy, and highlights how nanoparticles can be used to overcome these challenges. Recent studies on the application of antiviral nanoparticle-based delivery systems are reviewed and future directions are described.
MO01.17 Real-World Characteristics and Outcomes of Advanced NSCLC Patients with Exon 19 or 21 EGFR Mutations
Authors: K. Winfree, C. Molife, P. Peterson, Y. Chen, C. Visseren, J. Beyrer, M. Leusch, A. Dimou
Journal: Journal of Thoracic Oncology (2021)