tbuckley/cabot-search huggingface dataset:
Triple negative breast cancer in African American women: Disparity between women in New Orleans versus Louisiana.
Authors: Michelle Marie Loch, John Estrada, Thomas Reske, Xiangrong Li, Vivien Chen, Xiao-cheng Wu
Journal: Journal of Clinical Oncology (2013)

e12501 Background: For years clinicians have made the empirical observation that there is an unusually high number of African American women (AAW) with triple-negative (Tneg) breast cancer (BC) in New Orleans (NO). Knowing the rate of Tneg BC in AAW is higher than white women (WW), we explored the hypothesis that AAW in NO have a higher rate of Tneg BC when compared to AAW in the rest of Louisiana (LA). Methods: We analyzed data from the Louisiana Tumor Registry, one of the NCI funded SEER registries, for the tumor characteristics of invasive female BC diagnosed in 2010, focusing on racial disparities; HER2 status was not available for prior to 2010 diagnosis. We explored the association of HER2 status with age, race, ER, PR, HER2, T, N, M to determine crude and adjusted odds ratios and rate distribution of subtypes using SEER*Stat and SAS programs. Results: Overall age-adjusted incidence rate of Tneg BC in AAW was 30 per 100,000 in NO, which was 24% higher than that in AAW in the rest of LA and two-fold the rate in WW of both NO and LA. The highest rate of Tneg BC was seen in AAW aged 65-69 in NO (184.97 per 100,000) compared with 81.5 per 100,000 in AAW aged 55-59 in LA. AAW with Tneg BC in NO were more likely to have more aggressive BC. Young age, black race, large tumor size, higher grade and TNM stage were significantly associated with the high risk of Tneg BC. After adjusting for age, geographic area, and other tumor characteristics, the higher risk of Tneg BC in AAW remained in NO compared with the rest of LA (OR=1.4; 95% CI: 1.01-1.87). Conclusions: AAW in NO are more likely to have poorly differentiated and Tneg BC compared to AAW in the rest of LA. This disparity remains when comparing our data to previously published literature in other parts of the US. We plan to continue our data analysis and compare NO data to the national average as the HER2 data become available in the SEER Program to better characterize the disparity. This newly identified disparity in the AAW population in NO has clinical implications and translational research potential as it enables us to broaden the understanding and treatment of this aggressive disease.
Tumor volume changes on serial imaging with megavoltage CT for non-small cell lung cancer during conformal radiotherapy
Authors: M. L. Siker, W. A. Tome, M. P. Mehta
Journal: Journal of Clinical Oncology (2006)

17041 Background: Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intra-treatment imaging capabilities on radiotherapy devices. This study assesses non-small cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage CT (MVCT) scans. Methods: MVCTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in 5 fractions) and 17 on a dose-per-fraction escalation protocol (57–80.5 Gy in 25 fractions). Four patients were treated palliatively (22–30 Gy in 8–10 fractions). Gross tumor volumes (GTVs) were contoured on serial MVCTs at weekly intervals, by individuals other than the treating physician, to minimize bias. Each patient had 3–25 scans including one at the beginning, mid-way, and one at the end of treatment. Initial GTVs ranged from 1.4 - 565.5 cm 3 (mean = 70 cm 3 ). Results: At completion of treatment, no patient demonstrated a complete response (CR). Partial response (PR) defined as a &gt;65% decrease in tumor volume occurred in 3 (12%) and marginal response (MR) defined as a 35 - 65% reduction in tumor volume was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease (SD) defined as &lt;35% reduction or &lt;40% increase in size. The minimum “scorable threshold” for volume discrepancy between scans to account for inter-scan assessment variability was set at &gt;25% volume change; 10 patients (40%) had &gt;25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Conclusions: Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, as there is no way to document histologic tumor clearance and therefore field reductions during radiotherapy cannot be recommended. [Table: see text]
Mapping of the Multiple Myeloma Transcriptional Core Regulatory Circuitry Reveals TCF3 As a Novel Dependency and an Oncogenic Collaborator of MYC
Authors: Charles Y Lin, Mariateresa Fulciniti, Michael A Lopez, Mehmet Kemal Samur, Raphael Szalat, Christopher J. Ott, Charles Epstein, Richard A. Young, James Bradner, Kenneth C Anderson, Nikhil Munshi
Journal: Blood (2017)
Characterization of the RbBP6 gene in colon cancer
Authors: Charleen Rupnarain, Zodwa Dlamini
Journal: Cancer Research (2005)

2677  The novel RbBP6 gene was identified in Chinese Hamster Ovary cell lines, where knockouts of the gene showed a high resistance to staurosporine-induced apoptosis. As irregularities in the apoptotic system aid in the progression of a wide range of medical conditions, including cancer, it is very beneficial to characterise promoters and inhibitors of this system, with the potential for improving therapies. Colon cancer is ranked as the third most common cancer worldwide, and is primarily a genetic disease, the progression of which can be efficiently studied. The RbBP6 gene is transcribed into two mRNAs, the 1.1kb and 6.1kb. Alternative splicing of the 6.1kb mRNA at exon 16 produces two variable proteins of 200kD, while the 1.1kb mRNA is expressed as a 13kD protein. The 1.1kb and 6.1kb mRNA consists of the DWNN region which is highly conserved throughout the eukaryotes. In addition, the 6.1kb mRNA contains a zinc finger, RING finger, Rb-binding and p53-binding region. Using Digoxigenin-labelled RNA probes, colorimetric and fluorescent in situ hybridisation studies localised each mRNA in the adenomatous glands, adenocarcinomas and in surrounding dysplastic tissues, with a clear upregulation in the diseased state compared to normal colon tissue. Immunocytochemistry using antibodies against the RbBP6 protein confirmed the upregulation of the protein in these structures and in lymphocytes. When correlated with TUNEL results which indicated sites of apoptosis, RbBP6 upregulation was shown to be directly proportional to increased levels of apoptosis. Ki-67 proliferation assay showed that there was indirect relationship between cell proliferation and RbBP6 localisation, while Bcl-2 assay showed RbBP6 to be upregulated in areas where this apoptosis suppressor was downregulated, and vice versa. These results suggest that RbBP6 is a pro-apoptotic gene as it is implied that it acts in the same direction as apoptosis. Localisation studies for the Helicobacter pylori protein was also performed as a significant relationship between this bacteria and colon cancer incidence has previously been reported. Immunocytochemistry showed high levels of the protein in the adenocarcinomas but not in the adenomatous glands, suggesting that H. pylori aids in the progression of colon cancer from the non-invasive to the invasive state but is not involved in the initiation of the cancer. No relationship could be ascertained between H. pylori and RbBP6.
Rectifying Disparities in Funding of Asian American, Native Hawaiian, and Pacific Islander Research by the US National Institutes of Health
Authors: Moon S. Chen
Journal: JAMA Network Open (2019)

Asian American, Native Hawaiian, and Pacific Islander (AA/NHPI) is an artificial category for US citizens whose ancestry ranges across the vast continent of Asia, including the world's most populous countries such as China and India, and people descended from indigenous island populations scattered across the world's largest ocean, the Pacific.For example, the distance between Honolulu, Hawaii, and Guam requires 7 hours of air travel, compared with 5 hours of air travel between Washington, DC, and San Francisco, California.The heterogeneity of the AA/NHPI population defies simplistic characterization, as they speak hundreds of languages and dialects in their homes, reflect multiple cultures, and are further differentiated by their degrees of assimilation into mainstream American life.Consequently, while research to elucidate their health challenges should ideally be based on disaggregating AA/NHPI populations, investigators frequently must aggregate their data to derive findings that allow for comparison with other major US racial/ethnic populations.Đoàn et al 1 attempt to determine the level of investment by the US National Institutes of Health (NIH) to fund clinical research focused on AA/NHPI participants for fiscal years 1992 to 2018.Their findings were that the overall funding amounted to less than 0.2% of the NIH budget for 529 projects.These projects consisted of those that either addressed exclusively AA/NHPI individuals or AA/NHPI individuals with participants of other races and ethnicities.These findings are important and reflect both good news and bad news.
Quality Is Not the Only Part of the Emergency Department–Based Intensive Care Unit Value Equation
Authors: Michael C. Kurz, Erik P. Hess
Journal: JAMA Network Open (2019)

Kyle J. Gunnerson, MD; Benjamin S. Bassin, MD; Renee A. Havey, MS, RN; Nathan L. Haas, MD; Cemal B. Sozener, MD, MEng; Richard P. Medlin Jr, MD, MSIS; Jennifer A. Gegenheimer-Holmes, RN, MSHA; Stephanie L. Laurinec, BS; Caryn Boyd, BS; James A. Cranford, PhD; Sage P. Whitmore, MD; Cindy H. Hsu, MD, PhD; Reham Khan, MHI; Neha N. Vazirani, BDS, MPH; Stephen G. Maxwell, MS; Robert W. Neumar, MD, PhD
Rapid and Ultrasensitive Quantification of Multiplex Respiratory Tract Infection Pathogen via Lateral Flow Microarray based on SERS Nanotags
Authors: Di Zhang, Li Huang, Bing Liu, Qinyu Ge, Jian Dong, Xiangwei Zhao
Journal: Theranostics (2019)

Respiratory tract infections (RTIs) are severe acute infectious diseases, which require the timely and accurate identification of the pathogens involved so that the individual treatment plan can be selected, including optimized use of antibiotics.However, high throughput and ultrasensitive quantification of multiple nucleic acids is a challenge in a point of care testing (POCT) device.Methods: Herein, we developed a 2×3 microarray on a lateral flow strip with surface enhanced Raman scattering (SERS) nanotags encoding the nucleic acids of 11 common RTI pathogens.On account of the signal magnification of encoded SERS nanotags in addition to the high surface area to volume ratio of the nitrocellulose (NC) membrane, rapid quantification of the 11 pathogens with a broad linear dynamic range (LDR) and ultra-high sensitivity was achieved on one lateral flow microarray. Results:The limit of detection (LOD) for influenza A, parainfluenza 1, parainfluenza 3, respiratory syncytial virus, coxiella burnetii, legionella pneumophila, influenza B, parainfluenza 2, adenovirus, chlamydophila pneumoniae, and mycoplasma pneumoniae were calculated to be 0.031 pM, 0.030 pM, 0.038 pM, 0.038 pM, 0.040 pM, 0.039 pM, 0.035 pM, 0.032 pM, 0.040 pM, 0.039 pM, and 0.041 pM, respectively.The LDR of measurement of the target nucleic acids of the eleven RTI pathogens were 1 pM-50 nM, which span 5 orders of magnitude.Conclusions: We anticipate this novel approach could be widely adopted in the early and precise diagnosis of RTI and other diseases.
Prognostic implications of caspase-3 expression in patients with diffuse large B-cell lymphoma (DLBCL)
Authors: W. H. Elsawy, M. Abdel Kader, A. Elfar, A. Gharib, S. Eltrhony, Y. Dorgham
Journal: Journal of Clinical Oncology (2006)

17500 Background: Caspase-3 activation is an essential step in programmed cell death (apoptosis) and cytotoxic drug-induced apoptosis is mediated by caspase-2 and caspase-3. The following study was designed to evaluate the correlation between Caspase-3 and the clinical outcome in patients with diffuse large B-cell lymphoma. Methods: Caspase-3 was determined by both immunohistochemistry and by quantitative reverse-transcription PCR in 49 previously untreated patients with diffuse large B-cell lymphoma. Results: Caspase-3 was positive in 69.4% of the patients by immunostaining and Tumor cells displayed a diffuse cytosolic expression in 51% of patients. The median value of Caspase-3mRNA within the group by quantitative PCR was 1. Caspase-3mRNA level was μ1 in 28 patients and &lt;1 in 21 patients. Caspase-3 expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.02), and the International Prognostic Index (P = 0.0001). Patients with Caspase-3-positive immunostaining had a significantly higher complete response rate to chemotherapy and a longer overall survival than Caspase-3-negative patients. Also, patients with tumor cells expressing diffuse cytosolic immunostaining for caspase-3 had a poor prognosis when compared with those expressing a punctate staining (P &gt; 0.0004 log-rank). A low caspase-3 mRNA expression by quantitative RT-PCR was also associated with a poor prognosis, although this was not statistically significant. In addition, patients with a high TUNEL positivity had a low survival probability (P &gt; 0.02). Conclusions: Our results suggest that Caspase-3 activation or its lack may be a powerful independent predictor of response and survival in previously untreated diffuse large B-cell lymphomas. No significant financial relationships to disclose.
Absence of Interferon Regulatory Factor 1 Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: Meng Du, Xiaojing Wang, Xiaoxiang Mao, Liu Yang, Kun Huang, Fengxiao Zhang, Yan Wang, Xi Luo, Cheng Wang, Jiangtong Peng, Minglu Liang, Dan Huang, Kai Huang
Journal: Theranostics (2019)

Deciphering the molecular and cellular processes involved in foam cell formation is critical to understanding the pathogenesis of atherosclerosis. Interferon regulatory factor 1 (IRF1) was first identified as a transcriptional regulator of type-I interferons (IFNs) and IFN inducible genes. Our study aims to explore the role of IRF1 in atherosclerotic foam cell formation and understand the functional diversity of IRF1 in various cell types contributing to atherosclerosis. Methods: We induced experimental atherosclerosis in ApoE-/-IRF1-/- mice and evaluated the effect of IRF1 on disease progression and foam cell formation. Results: IRF1 expression was increased in human and mouse atherosclerotic lesions. IRF1 deficiency inhibited modified lipoprotein uptake and promoted cholesterol efflux, along with altered expression of genes implicated in lipid metabolism. Gene expression analysis identified scavenger receptor (SR)-AI as a regulated target of IRF1, and SR-AI silencing completely abrogated the increased uptake of modified lipoprotein induced by IRF1. Our data also explain a mechanism underlying endotoxemia-complicated atherogenesis as follows: two likely pro-inflammatory agents, oxidized low-density lipoprotein (ox-LDL) and bacterial lipopolysaccharide (LPS), exert cooperative effects on foam cell formation, which is partly attributable to a shift of IRF1-Ubc9 complex to IRF1- myeloid differentiation primary response protein 88 (Myd88) complex and subsequent IRF1 nuclear translocation. Additionally, it seems that improved function of vascular smooth muscle cells (VSMCs) also accounts for the diminished and more stable atherosclerotic plaques observed in ApoE-/-IRF1-/- mice. Conclusions: Our findings demonstrate an unanticipated role of IRF1 in the regulation of gene expression implicated in foam cell formation and identify IRF1 activation as a new risk factor in the development, progression and instability of atherosclerotic lesions.
To be or not to be emotionally aware and socially motivated: How alexithymia impacts autism spectrum disorders
Authors: Luigi Pastore, Sara Dellantonio, Claudio Mulatti, Gianluca Esposito
Journal: Behavioral and Brain Sciences (2019)

Abstract Autism often co-occurs with alexithymia, a condition characterized by no or diminished awareness of emotions that significantly impacts an individual's social relationships. We investigate how the social motivation of autistics would be eroded by comorbidity with alexithymia and why this diminished motivation would be difficult for non-autistic people to perceive and reciprocate.
Outcomes of surgical resections for benign colon polyps: a systematic review
Authors: Michael P.M. de Neree tot Babberich, Maxime E.S. Bronzwaer, Jurr O. Andriessen, Barbara A. J. Bastiaansen, Nahid Mostafavi, Willem A. Bemelman, Paul Fockens, Pieter J. Tanis, Evelien Dekker
Journal: Endoscopy (2019)

Abstract Background Not all benign colonic polyps are suitable for endoscopic resection, although criteria for endoscopic non-resectability vary worldwide. Clinical decision-making largely depends on endoscopic treatment options, as well as postoperative risks after surgical resection. This systematic review aimed to determine postoperative outcomes and the characteristics of surgically resected benign colonic polyps. Methods MEDLINE, EMBASE, and the Cochrane Library were searched for studies investigating the outcomes of surgical resection for benign colonic polyps since 1980. Studies were considered eligible when at least one postoperative outcome (morbidity and/or mortality) was reported. Meta-analyses were conducted for the primary outcome measures (morbidity and mortality) for studies that included patients only after the year 2000. Results Of the 4210 studies retrieved, 26 studies describing 139 897 patients were included. The most common indications for surgical resection were polyp location in the right-sided colon, non-pedunculated morphology, and large polyp size. The pooled 1-month complication and mortality rates of studies that included patients after the year 2000 were 24 % (95 % confidence interval [CI] 15 % – 36 %) and 0.7 % (95 %CI 0.6 % – 0.8 %), respectively. Conclusion The postoperative morbidity and mortality after colonic resection for benign polyps are substantial. Referral to an advanced interventional endoscopist should be considered before referral for surgery to evaluate the possibilities for endoscopic treatment of large, non-pedunculated, and/or colonic polyps in difficult locations without suspicion of submucosal malignant invasion.
Hepatitis B Screening in Pregnant Women
Authors: Neil S. Silverman
Journal: JAMA (2019)

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Vismodegib, a Hedgehog pathway inhibitor (HPI), in advanced basal cell carcinoma (aBCC): STEVIE study interim analysis in 300 patients.
Authors: Jean Jacques Grob, Rainer Kunstfeld, Brigitte Dreno, Thomas Jouary, Laurent Mortier, Nicole Basset-Seguin, Paolo Antonio Ascierto, Johan Hansson, Lada Mitchell, Michal Starnawski, Axel Hauschild
Journal: Journal of Clinical Oncology (2013)

9036 Background: Therapy options are limited for locally advanced (la) and metastatic (m) BCC. Aberrant Hedgehog (Hh) signaling is the key driver in BCC pathogenesis. Vismodegib, a first-in-class HPI, is approved in the US for use in adults with aBCC. STEVIE is an ongoing study focusing on safety of vismodegib therapy in patients with aBCC. We present data from the third interim analysis (data cutoff: 19 October 2012), which also permits a preliminary assessment of efficacy of vismodegib in the largest study ever conducted in patients with aBCC. Methods: Adult patients with laBCC or mBCC received oral vismodegib 150 mg QD until progressive disease, unacceptable toxicity, or withdrawal. Safety is the primary objective of STEVIE (Common Terminology Criteria for Adverse Events 4.0). Secondary endpoints include efficacy variables. Recruitment is ongoing. Results: This analysis included 300 patients with locally advanced (n=278) or metastatic (n=22) BCC from 11 countries with potential for ≥3-month follow-up. Median treatment duration, including vismodegib interruption, was 176.5 days (range 1-455 days). Common treatment-emergent AEs (TEAEs), typically ≤ grade 2, included muscle spasm (59.3%), alopecia (49.3%), and dysgeusia (41.0%) and were comparable to prior analysis. Serious TEAEs occurred in 53 patients (17.7%). 131 (43.7%) discontinued from the study, mainly due to patient or investigator request (n=41), AEs (n=35), disease progression (n=18) or death (n=13; 7 due to AEs assessed by the investigator as unrelated to study drug, 3 due to AEs not possible to be assessed, 3 due to disease progression). Preliminary best overall response in patients with available tumor assessments (n=251) included complete response (17.5%), partial response (39.8%), stable disease (39.0%) and progressive disease (2.8%). Patient recruitment and monitoring is ongoing. Conclusions: This third interim analysis of STEVIE confirms the previously observed vismodegib safety profile but can also provide further information about the high rate of tumor control with vismodegib in a large series of patients with aBCC. Clinical trial information: 2011-000195-34.