tbuckley/cabot-search huggingface dataset:
Biomarkers and Outcomes in Omalizumab-Treated Patients with Allergic Asthma: A Real-World Study in a Large Allergy Practice in the United States (US)
Authors: Benjamin Ortiz, Abhishek Kavati, Maryia Zhdanava, Jason Lecocq, Bradd Schiffman, Dominic Pilon, Harriet Ho, Brian D. Stone
Journal: Journal of Allergy and Clinical Immunology (2019)
Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study
Authors: Barbara H. Braffett, Samuel Dagogo-Jack, Ionut Bebu, William I. Sivitz, Mary Larkin, Orville Kolterman, John M. Lachin
Journal: Diabetes Care (2019)

The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes.
Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9
Authors: Hong-Xia Zhang, Ying Zhang, Hao Yin
Journal: Molecular Therapy (2019)

Genome-editing technologies based on programmable nucleases have significantly broadened our ability to make precise and direct changes in the genomic DNA of various species, including human cells. Delivery of programmable nucleases into the target tissue or cell is one of the pressing challenges in transforming the technology into medicine. In vitro-transcribed (IVT) mRNA-mediated delivery of nucleases has several advantages, such as transient expression with efficient in vivo and in vitro delivery, no genomic integration, a potentially low off-target rate, and high editing efficiency. This review focuses on key barriers related to IVT mRNA delivery, on developed modes of delivery, and on the application and future prospects of mRNA encoding nuclease-mediated genome editing in research and clinical trials.
Constitutive activation of NF-kB is present in malignant gliomas and may serve as a therapeutic target
Authors: Yulong Han, Tao Lu, Jennifer Nelms, Chunbiao Li, Michael A. Vogelbaum
Journal: Cancer Research (2004)

4208  Malignant gliomas remain one of the deadliest forms of cancer in humans and are often poorly responsive to chemotherapy and/or radiation therapy. Recent studies reveal that aberrant constitutive activation of NF-kB, a latent transcription factor which acts as a suppressor of apoptosis, contributes to carcinogenesis and confers resistance to chemotherapy in a number of cancers. We have found, by gel-shift assay and by use of an NF-kB sensitive promoter-reporter construct, that constitutive NF-kB activation is present in all glioma cell lines and primary tumor cultures tested. This activation was not serum dependent and was associated with elevated levels of NF-kB dependent gene transactivation in these cell lines. Furthermore, nuclear localization of p65, an indicator of NF-kB activation, was demonstrated in pathological specimens of surgically resected glioblastoma multiform (GBM) tumors. Overexpression of the IkB super-repressor (IkB SR) completely blocks constitutive NF-kB activation, nuclear translocation of p65 and gene transcription, indicating that activation of NF-kB signaling in gliomas involves the IkB-mediated pathway. However, overexpression of IkB SR does not affect bcl-xL expression at transcriptional level, implying that anti-apoptotic effect of NF-kB in gliomas is not through bcl-xL-mediated signaling. Furthermore, we demonstrate that persistent activation of NF-kB may involve, at least in part, an autocrine mechanism. Our data taken in the context of the chemoresistance role that constitutive activation of NFkB may play in other cancers suggests that NF-kB signaling may contribute to the chemoresistance of malignant gliomas. Pharmacologic interruption of NF-kB signaling by may provide novel therapeutic strategies for malignant brain tumors.
The preventive effect of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal squamous cell carcinoma: A retrospective cohort study.
Authors: Masashi Takeuchi, Hirofumi Kawakubo, Shuhei Mayanagi, Tomoyuki Irino, Kazumasa Fukuda, Rieko Nakamura, Norihito Wada, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2019)

120 Background: Postoperative complications have a negative impact on overall survival after esophagectomy because systemic inflammation may induce residual cancer cell growth. A solution that could suppress micrometastasis is neoadjuvant therapy; however, to date, no study has shown that neoadjuvant therapy suppresses the proliferation of cancer cells due to postoperative complications after esophagectomy. To investigate the preventive effect of neoadjuvant therapy on poor long-term outcomes of postoperative complications in patients with esophageal squamous cell carcinoma. Methods: In total, 509 patients who underwent esophagectomy for primary esophageal squamous cell carcinoma were included in this retrospective cohort study. We investigated the relationship between complications, such as pneumonia, and long-term oncologic outcomes with and without neoadjuvant therapy. Results: Among all the patients, the 3-year overall survival (OS) rate was 68.4% and the disease-free survival (DFS) rate was 58.1%. The patients were categorized into two groups: the neoadjuvant therapy (+) group (n = 227) and the neoadjuvant therapy (−) group (n = 282). Among patients not undergoing neoadjuvant therapy, the patients with pneumonia, atrial fibrillation, pyothorax, or chylothorax had significantly poorer OS and DFS than patients without these complications. However, among patients undergoing neoadjuvant therapy, there were no significant differences in long-term outcomes, regardless of the presence of complications. In multivariate analyses, pneumonia (p = 0.014) and chylothorax (p = 0.006) were identified as predictors of death in the neoadjuvant therapy (−) group. Conclusions: In patients with esophageal squamous cell carcinoma, the negative impact of postoperative complications can be reduced by performing neoadjuvant therapy.
Abstract 80: Correlation of N-terminal pro-BNP Release with Myocardial Involvement in Acute Kawasaki Disease
Authors: Anne Fournier, Laurent Desjardins, Nagib Dahdah
Journal: Circulation (2015)

N-terminal pro-BNP (NT-proBNP) is elevated at the onset of Kawasaki Disease (KD). This is based on the hypothesis of immune myocardial inflammation. We sought to study the relationship between NT-proBNP and cardiac function in KD. Parameters of myocardial involvement determined by ECG (PR and QTc intervals, QT dispersion, R-T axis) and by echocardiogram (systole and diastole) were correlated with levels of NT-proBNP in the acute (1 week), sub-acute (2-3 months) and chronic (6 months to 1 year) phases of KD. KD patients were compared to a febrile group. KD patients were further subdivided into 2 groups according to the levels of NT-proBNP; normal NT-proBNP (NT-proBNP Z-score &lt; 2), or elevated NT-proBNP (Z-score ≥ 2). There were 56 subjects (14 controls, 19 KD-1 and 23 KD-2 patients), with similar age at assessment (3.8±4.3 vs. 3.3±2.3 years-old, p=0.609). Myocardial contractility was significantly lower in KD patients in the acute phase with an ejection fraction of 57.4±7.5% compared to CTL 61.9±6.5%; p=0.049). Myocardial dysfunction was more significant in KD with high NT-proBNP compared to those with normal NT-proBNP, (shortening fraction Z-score of-1.6±1.5 versus -0.5±1.5; p=0.025) QTc interval was longer in KD compared to febrile CTL (412.3±21.0 mS vs. 390.6±14.6 mS, respectively; p=0.009). In contrast, there were no significant differences for left ventricular mass index (p=0.935) or LV end-diastolic diameter (p=0.565). Likewise, there were no significant differences for the PR interval (p=0.344), QT dispersion (p=0.288) or R-T axis (p=0.577). Otherwise, there was a significant correlation between coronary artery involvement (CA z-score ≥ 2.5) and the likelihood of lower LV ejection fraction (p=0.049) and higher NT-proBNP z-score (p=0.043), but no correlation with normalized LV shortening fraction (p=0.16) or QTc (p=0.14). The anomalous findings disappear in the sub-acute phase. On the other hand, a lengthening of QTc interval in the acute phase, irrespective of NT-proBNP status, resolves after 2-3 months. In acute KD, there is a reduction in myocardial function, to a higher extent in cases with elevated NT-proBNP. This correlates with coronary artery involvement. KD patients with elevated NT-proBNP z-score may warrant careful follow-up.
Omalizumab in Patients with Severe Asthma and Persistent Sputum Eosinophilia
Authors: Manali Mukherjee, Melanie Kjarsgaard, Katherine Radford, Chynna Huang, Richard Leigh, Del Dorscheid, Catherine Lemiere, Louis-Philippe Boulet, Susan Waserman, James G. Martin, Parameswaran K. Nair
Journal: Journal of Allergy and Clinical Immunology (2019)
Neoadjuvant chemotherapy followed by surgery versus upfront surgery in patients with borderline resectable and locally advanced unresectable pancreatic adenocarcinoma.
Authors: Junho Kang, Changhoon Yoo, Sang Hyun Shin, Kyu-Pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Baek-Yeol Ryoo, Song Cheol Kim
Journal: Journal of Clinical Oncology (2019)

312 Background: Although neoadjuvant chemotherapy (NACT) has been widely investigated, the magnitude of the clinical benefit and the potential risk of NACT followed by surgery compared with upfront surgery remains unclear for patients with locally advanced pancreatic cancer (LAPC). Methods: This retrospective, prospective cohort-based analysis included 135 patients who underwent NACT followed by surgery and 359 patients who received upfront surgery for LAPC between October 2005 and April 2017. Disease-free survival (DFS) and overall survival (OS) from surgery were compared between the two groups. Results: There were no significant differences in gender (male, 53% vs 56%) and age (median 60 vs 61 years) between the NACT followed by surgery group and upfront surgery group. As NACT, gemcitabine-based regimens and FOLFIRINOX were used in 69 (51%) and 66 (49%) patients, respectively. The NACT followed by surgery group showed significantly less advanced T stage (T3–4, 93% vs 99%, p = 0.001) and N stage (N+, 49% vs 71%, p &lt; 0.001) than the upfront surgery group. NACT followed by surgery was significantly associated with better OS (median, 25.4 [18.6–32.2] vs 17.1 [15.5–18.7] months, p = 0.001) and DFS (median, 9.0 [95% CI, 6.8–11.2] vs 7.1 [6.4–7.8] months, p = 0.005) than upfront surgery. These results were consistent in the multivariate analysis for OS (adjusted hazard ratio [aHR], 0.73 [95% CI, 0.56–0.96], p = 0.02) and DFS (aHR, 0.72 [95% CI, 0.56–0.93], p = 0.01). There was no difference in length of hospital stay (median 13 vs 17 days, p = 0.14) for surgery between the two groups, and the NACT followed by surgery group showed a significantly lower incidence of postoperative complication than the upfront surgery group (38% vs 27%, p = 0.03). Conclusions: The present study revealed that NACT followed by surgery may provide survival benefit compared with upfront surgery in LAPC without causing significant safety issues.
GW25-e5238 Lycopene protects endoplasmic reticulum stress induced apoptosis against neonatal mouse cardiomyocytes hypoxia/reoxygenation injury
Authors: Jiqian Xu, Houxiang Hu, Bin Chen, Zhou Zhou, Lei Xu, Shuang Zhang, Zhengping Yu
Journal: Journal of the American College of Cardiology (2014)
Revalidation of the Hypoglycemia Risk Stratification Tool Using ICD-10 Codes
Authors: Andrew J. Karter, E. Margaret Warton, Howard H. Moffet, James D. Ralston, Elbert S. Huang, Donald R. Miller, Kasia J. Lipska
Journal: Diabetes Care (2019)

We previously developed and validated a hypoglycemia risk stratification tool (1) and made available the computer source code for implementation (online-only supplemental eTable 2 [1]). This tool classifies 12-month risk of hypoglycemia-related utilization (HRU) of emergency department (ED) or in-patient services among type 2 diabetes (T2D) patients as high (>5%), intermediate (1–5%), or low (<1%). Since its publication, health care delivery systems in the U.S. (including Kaiser Permanente and Mayo Clinic) have adopted this tool to identify higher-risk patients for targeted population management interventions designed to reduce hypoglycemia risk. Among the six inputs required to calculate HRU risk (prior HRU, insulin use, sulfonylurea use, any ED visits, chronic kidney disease stage, and age), only prior HRU relied on diagnostic coding and was based on an algorithm (2) comprising International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes. Since 1 October 2015, the Centers for Medicare & Medicaid Services has required use of the 10th revision (ICD-10-CM), necessitating an updated HRU case identification algorithm that includes ICD-10-CM codes for hypoglycemia.

We identified ICD-10-CM codes for hypoglycemia to complement the existing ICD-9-CM–based algorithm (any of the following: 251.0, 251.1, 251.2, 962.3, or 250.8, without concurrent 259.8, 272.7, 681.XX, 682.XX, 686.9X, 707.1–707.9, 709.3, 730.0–730.2, or 731.8). The ICD-10-CM codes for hypoglycemia (any of the …
Platelet-Derived Microvesicles Reverse the Lupus Anticoagulant Effect and Are More Potent then Synthetic Phospholipids in Supporting Thrombin Generation in Antiphospholipid Syndrome
Authors: Cuicui Bai, Saartje Bloemen, Xiao Xuan Wu, Ruchika Goel, Sheshadri Narayanan, Bas De Laat, Jacob H. Rand, Ljiljana V. Vasovic
Journal: Blood (2018)
Phase I results from the phase 1/3 FIGHT study evaluating bemarituzumab and mFOLFOX6 in advanced gastric/GEJ cancer (GC).
Authors: Mohamedtaki Abdulaziz Tejani, Eric Cheung, Peter D. Eisenberg, Aaron James Scott, Anteneh A. Tesfaye, Lyndah Dreiling, Clarence Eng, Neyssa Marina, Siddhartha Mitra, Hong Xiang, Xiaohong Yan, Daniel V.T. Catenacci
Journal: Journal of Clinical Oncology (2019)

91 Background: GC with FGFR2b overexpression or FGFR2 amplification is associated with a poor prognosis. Bemarituzumab (bema, FPA144) is a first-in-class humanized monoclonal IgG1 antibody that selectively blocks FGFR2b and triggers antibody-dependent cell-mediated cytotoxicity. With favorable safety and activity as a single agent in 2L+ patients with FGFR2b+ GC, the global, randomized, double-blind, placebo-controlled FIGHT study (NCT03343301) is evaluating the front-line combination of bema with mFOLFOX6. We report here the results from the phase I evaluation of the combination. Methods: Patients (pts) with unresectable, locally advanced or metastatic gastrointestinal malignancy (irrespective of FGFR2b status) for whom mFOLFOX6 would be appropriate were eligible for enrollment in the phase I. Her2+ disease or prior treatment with FGF-FGFR inhibitors was not allowed. All pts in the Phase 1 received mFOLFOX6 combined with bema in Q2W cycles. Cohort 1 (3+3) began with bema 6 mg/kg and cohort 2 (Rolling-6) bema 15 mg/kg with one dose of 7.5 mg/kg on C1D8. A dose-limiting toxicity (DLT) evaluation window of 28 days was used for both cohorts. Results: Cohorts 1 and 2 treated 3 pts and 9 pts respectively with a median of 4 and 2 prior lines of therapy. As of the iDMC data-cut on July 24, 2018, the median duration of treatment was 15 wks for cohort 1 and 4 wks for cohort 2; 6/9 pts in cohort 2 continue on treatment. No DLTs were identified. No adverse events (AEs) led to treatment discontinuation. There were no newly identified bema-related toxicities and the only ≥ Gr 2 AE attributable to bema in cohort 2 was fatigue (1 pt/Gr 2). The most common AEs overall were fatigue (6 pts/50%), nausea, vomiting and diarrhea (5 pts/42% each) and were generally attributed to FOLFOX or underlying disease. The ≥ Gr 3 AEs present in ≥ 1 pt were fatigue and neutropenia (2 pts/Gr 3 each). mFOLFOX6 did not affect bema exposure and all evaluable pts in cohort 2 achieved the target ≥ 60 µg/mL trough concentration by day 15. 2/7 pts at the data-cut had FGFR2b+ GC. Conclusions: Bema in combination with mFOLFOX6 has acceptable safety to proceed with the cohort 2 dose to the phase III portion of the FIGHT trial in previously untreated patients with FGFR2b+ GC. Clinical trial information: NCT03343301.
Dupilumab Suppresses Type 2 Biomarkers in Asthma Patients With and Without Comorbid Chronic Rhinosinusitis With or Without Nasal Polyposis (CRS/NP): Post Hoc Analysis of LIBERTY ASTHMA QUEST
Authors: Jorge F. Maspero, Jonathan Corren, Linda B. Ford, Lawrence Sher, Bradley E. Chipps, Anju T. Peters, Megan Rice, Paul Rowe, Yufang Lu, Sivan Harel, Heribert Staudinger, Nikhil Amin, Marcella Ruddy, Neil M.H. Graham, Ariel Teper
Journal: Journal of Allergy and Clinical Immunology (2019)
Prevention of Gonococcal Eye Infection in Newborns
Authors: Jill Jin
Journal: JAMA (2019)

US Preventive Services Task Force; Susan J. Curry, PhD; Alex H. Krist, MD, MPH; Douglas K. Owens, MD, MS; Michael J. Barry, MD; Aaron B. Caughey, MD, PhD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Martha Kubik, PhD, RN; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Revisiting the issue of how to assess pneumococcal vaccine immunogenicity: a post hoc analysis of antipneumococcal antibody responses among adult patients with systemic lupus erythematosus previously immunised with 23-valent pneumococcal polysaccharide vaccine
Authors: Rodrigo Poubel Rezende, Luís Eduardo Coelho Andrade, Evandro Mendes Klumb
Journal: Annals of the Rheumatic Diseases (2019)

A judicious analysis and comparison of studies on the immunogenicity of pneumococcal vaccine in patients with systemic lupus erythematosus (SLE)1–9 is hampered by wide heterogeneity in several factors, including differences in the immunoassays performed, cut-off levels used as serological correlates of protection, number of individual serotypes as well as types of capsular antigens analysed, response criteria, and SLE-related immunosuppressive treatment. In addition, how to interpret vaccine response when preimmunisation antipneumococcal antibody titres (anti-PnAbs) are already high (or protective) is not yet clear, which is of relevance given that non-immunised adults often have high antibody levels for some serotypes as a result of prior pneumococcal infections. Moreover, only a minority of individuals with high prevaccination anti-PnAbs are reportedly capable of mounting a ≥4-fold rise in …
Early treatment of HIV-1 infection
Authors: Anthony Fauci, John G Barlett, Eric Goosby
Journal: The Lancet (1998)

As representatives of the Department of Health and Human Services (DHHS) Panel on Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, we wish to comment on the viewpoint by Jay Levy (Sept 19, p 982)1Levy JA Caution: should we be treating HIV infection early?.Lancet. 1998; 352: 982-983Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar who urges caution with regard to early therapy of HIV-1 infection. We believe that Levy makes several important points, but are concerned about his rigid interpretation of the DHHS guidelines. The DHHS recommendation is to consider therapy of chronically infected patients when the CD4 cell count is below 500 cells/μL or the viral burden exceeds 10 000 copies/mL (bDNA assay) or 20 000 copies/mL (RP PCR assay). However, this recommendation is modified by the following caveat articulated in the guidelines that deserves emphasis: "The strength of this recommendation is dependent on patient acceptance, probability of adherence, and prognosis as indicated by the CD4 cell count and the viral burden." This statement provides the physician and patients with substantial flexibility in the treatment decision, a position that is emphasised by a table that lists five reasons to treat early and five reasons to delay therapy. 3 years of experience with patients has shown the complexity of the decision to initiate or change highly active antiretroviral therapy (HAART). The DHHS panel emphasised the need for an open patient-provider dialogue at all decision points. Another relevant point is that the limits suggested by Levy, a CD4 cell count below 400 cells/μL and a viral burden greater than 30000 copies/mL, are, in fact, within the range of error of the tests compared with the thresholds offered by the DHHS Panel. Levy has also underscored the potential importance of methods to improve the immune response against HIV-1. We agree, and in this regard, the development of such immune enhancing drug regimens is the subject of intensive study. Levy is right to suggest that some flexibility is needed in establishing thresholds for recommendations for treatment of HIV-1, but we emphasise the fact that guidelines from DHHS, and other sources as well, are commonly interpreted far more rigidly than intended by the authors. Flexibility in the application of these guidelines is critical to their successful use. Early treatment of HIV-1 infectionAuthor's reply Full-Text PDF
Screening programmes miss coverage targets because of complex and outdated IT systems
Authors: Ingrid Torjesen
Journal: BMJ (2019)

Screening programmes in England are missing their targets for the percentage of eligible people who should be screened, says a report by the government’s spending watchdog,1 as some patients are not invited for screening because of complex and outdated IT systems.

The National Audit Office investigated four routine health screening programmes in England—for abdominal aortic aneurysm, bowel cancer, breast cancer, and cervical cancer—and found that none hit its screening target in 2017-18. Coverage was also inconsistent around the country, and much of the lowest performance was in London.

The bowel screening programme came closest to hitting its 60% coverage target at 59.6%, but in eight clinical commissioning groups only 30-44% of eligible people were …
Prostate Cancer Genomic-risk Differences Between African-American and White Men Across Gleason Scores
Authors: Brandon A. Mahal, Mohammed Alshalalfa, Daniel E. Spratt, Elai Davicioni, Shuang G. Zhao, Felix Y. Feng, Timothy R. Rebbeck, Paul L. Nguyen, Franklin W. Huang
Journal: European Urology (2019)
Abstract 17640: An in vitro Approach to Studying Shear Stress - Induced Inflammation in Cerebral Aneurysm Progression
Authors: Kamil W Nowicki, Koji Hosaka, Yong He, Daniel P Downes, Peter S McFetridge, Ed W Scott, Brian L Hoh
Journal: Circulation (2012)

OBJECTIVE: The development of cerebral aneurysms is thought to be an inflammatory process and related to shear stress, but how shear stress causes inflammatory progression of aneurysms is not fully...