tbuckley/cabot-search huggingface dataset:
Abstract P3-05-11: Immune and basal signature correlation to targeted therapies and race in QNBC patients
Authors: RW Hughley, WD Colomb, T Shweta, C Yates
Journal: Cancer Research (2018)

Abstract Background: African American women have worse prognosis and poor survival rates due to lack of Androgen Receptor expression. These subtypes, the Quadruple Negative Breast Cancers (QNBC), currently have no treatments. Previously, we found that AA TNBC have 28% more chance of being QNBC and have 25% higher rate of progression vs the Caucasian Americans (CA). Also, these QNBC patients have a unique immune and basal signature. Here, we explore individual genes and their correlation to race and immune therapies. Methods: We analyzed AR mRNA expression in 925 tumors from CA or AA women from The Cancer Genome Atlas and independently validated AR protein levels by immunohistochemistry in 197 primary tumors. Samples were dichotomized as AR positive or negative using mean gene expression cutoff. Gene expression comparisons among groups were determined using standard t-tests, ANOVA, and odds ratios with a significance threshold alpha of 0.05. a of 0.05. Therapy targets were selected from the list of significantly differentiated genes. Boxplots and heatmaps were made using R packages. Cumulative Incidence plots for time to progression were constructed using XLStats and Grays test for significance. Results: QNBC CA have higher expression of PDCD4 (p &amp;lt;.001), CD46 (p &amp;lt;.001), CD3EAP (p =.04) and CD84 (p =.07) compared to QNBC AA. CD47 (p = .63) and PD1 (p =.96) express no significant differences in race[CY1]. QNBC AA show higher expression of NFKB (p &amp;lt;.001), CCL2 (p &amp;lt;.001), and IL12 (p &amp;lt;.001) compared to QNBC CAs. Interestingly, QNBCs with high expressions of CD47 (p = .04) have poor prognosis[L2]. Thus, QNBC patients with low expression of CD46 (p =.025), PDCD4 (p &amp;lt; .001), and CD3EAP (p &amp;lt; .001) have poor prognosis and overall survival. Conclusions: Current immune targeted therapies like CD47 and PD1 looks favorable for treatment in some QNBC patients. Race appears to effect other major therapy target gene expressions in the QNBC immune basal signature as well. This may imply that QNBC AA and CA have different immune response which may explain racial progression differences. Assessment of immune markers may contribute to more accurate prognosis. Citation Format: Hughley RW, Colomb WD, Shweta T, Yates C. Immune and basal signature correlation to targeted therapies and race in QNBC patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-11.
Long-term outcomes of magnetic resonance image-guided partial prostate brachytherapy for favorable-risk prostate cancer.
Authors: Martin T. King, Paul L. Nguyen, Ninjiin Boldbaatar, Clare Mary Tempany, Robert A. Cormack, Clair Beard, Mark Hurwitz, Warren Suh, Anthony Victor D'Amico, Peter F Orio
Journal: Journal of Clinical Oncology (2018)

138 Background: To report long-term outcomes of magnetic resonance image-guided partial prostate brachytherapy of the peripheral zone. Methods: We conducted an institutional-board approved retrospective review of all men who underwent 0.5 Tesla GE Signa SP MRI-guided partial prostate brachytherapy to the peripheral zone. We estimated actuarial rates of biochemical progression (nadir +2 definition), as well as cumulative incidences of biopsy proven local recurrence, distant metastasis, and prostate cancer specific mortality. Fine and Gray’s competing risk regression was utilized in order to evaluate clinical factors associated with times to metastasis and prostate cancer specific mortality. Results: Between 1997 and 2008, 354 men underwent MRI-guided partial prostate brachytherapy. The numbers of patients with low and intermediate risk disease were 295 (83%) and 59 (17%), respectively. Sixty-seven (19%) patients received supplemental external beam radiotherapy. The median follow-up was 8.6 years. For National Cancer Center Network (NCCN) low risk-disease, 8-year estimates of biochemical progression, local recurrence, metastasis, and prostate cancer specific mortality were 23.5% (17.4-29.1), 6.4% (3.6-10.2), 2.0% (0.6-4.8), and 0%. Corresponding estimates for intermediate risk disease were 51.2% (31.3-65.4), 21.2% (10.2-34.9), 6.6% (1.7-16.3), and 5.4% (0.9-16.2). Twenty of 45 biopsy proven local recurrences occurred outside of the implanted peripheral zone. Of the 22 patients who developed distant metastases, 14 events occurred more than 10 years from therapy. On multivariate analyses, biopsy proven local recurrence was the only factor to demonstrate a significant association with metastasis (hazard ratio 2.50; p = 0.05) and a trend with prostate cancer specific mortality (5.02; p = 0.09). Conclusions: MRI-guided partial prostate brachytherapy to the peripheral zone in men with favorable risk prostate cancer is suboptimal with respect to long term cancer control outcomes. Additional studies using contemporary MRI techniques including 3 Tesla based multi-parametric imaging and fusion biopsy may lead to improved outcomes.
U-SMART: (UCSD-small mass alt renal score tumor diameter) a novel scoring system of preoperative predictors to stratify oncologic risk of small renal mass.
Authors: Kendrick Yim, Ahmet Bindayi, Stephen Ryan, Madhumitha Reddy, Ryan Nasseri, Fang Wan, Christopher Long, Zachary Hamilton, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2018)

700 Background: Small renal masses (SRMs, &lt; 4 cm in diameter) are heterogeneous, with significant proportions of benign as well as high-grade malignancy. We developed a scoring system incorporating patient factors, serum markers, and morphometric characteristics to elucidate benign and high grade pathology and guide decision making. Methods: Single institution retrospective analysis of surgically treated SRMs from 2003-2017. Demographic and clinical factors, including RENAL score, were analyzed. Patients were categorized into 3 groups: benign (BNGN), low grade (LG), or high grade (HG) disease and uni- and multivariable logistic regression were used to screen for association between potential parameters and the 3 groups. Each significant variable was analyzed by risk group and broken into quartiles. The 75 th percentile of the HG group was assigned a value of 3. Below the 75 th percentile of the BNGN group was assigned a value of 1; values that fell between these cutoffs were assigned 2 points. Tumor diameter was weighted twice that of other factors. Receiver-operating-characteristic (ROC) analysis was used to assess for predictive capability. Results: 312 patients were analyzed (65 BNGN, 204 LG, 43 HG). Factors associated with increased risk of HG were male sex (OR 1.868, p = 0.045), higher ALT (OR 1.036, p = 0.022), higher RENAL score (OR 1.318, p = 0.002), and larger tumor diameter (OR 2.415, p &lt; 0.001). Patients with low (5-8), intermediate (9-11) and high (12-14) scores had 32.8%, 5.2%, and 0% frequency of BNGN pathology. Patients with low, intermediate, and high scores had 7.7%, 18.6%, and 34.9% frequency of HG pathology. ROC analysis revealed AUC of 0.767. Conclusions: Preoperative clinical parameters were incorporated into a model that significantly predicts benign and aggressive pathology for SRMs. This risk stratification may provide a non-invasive method to aid in clinical decision making. External validation is requisite.[Table: see text]
Abstract P317: An Activity Space Approach to Assessing the Food Environments of Food Secure and Insecure Women
Authors: Ilana G Raskind, Michelle C Kegler, Michael R Kramer
Journal: Circulation (2018)

Introduction: Community food environments (FE) are an important correlate of diet- and weight-related CV health. Conventional approaches to measuring the FE focus on residential neighborhoods, and do not assess the full extent of food sources regularly encountered and used. Further, little attention has been given to how individual diet-related experiences, like food insecurity, may interact with features of the FE to affect health. To address these limitations, we use an activity space approach, defined by the locations women routinely visit, to measure FE exposure and use, and assess differences by food security status. Hypothesis: Food-related spatial behavior and features of the FE differ between a) conventional and activity space definitions, and b) food secure and insecure women. Methods: We present initial results (n=51) from an ongoing clinic-based study of low-income African American women in Atlanta, GA. Data are collected in-person using a Google Map-powered activity space questionnaire. USDA’s 10-item adult scale is used to measure food insecurity. Retail FE data are from Dun &amp; Bradstreet. ArcGIS 10.5 was used to define three environments: residential census tract (CT), and convex hull polygons of overall and food-specific activity spaces. We tested differences, by food security status, in mean behaviors and FE features with one-way ANOVAs. Results: Eighty-eight percent of women were food insecure. Food insecure women were lower income, less often employed, and less often had access to a car. CTs contained fewer supermarkets (μ=1.2 SD =1.4) and fast food restaurants (μ=3.9 SD =3.2) than activity spaces (μ=7.9 SD =7.0; μ=55.5 SD =44.1, respectively). On average, 6.7% ( SD =13.5) of utilized food sources fell within CT bounds, while 53.4% ( SD =35.5) fell within activity spaces. Compared to food secure women, food insecure women had smaller overall (μ=329.8km 2 SD =340.4 vs. μ=548.3km 2 SD =422.4; p =0.16) and food-specific (μ=48.1km 2 SD =74.3 vs. μ=85.6km 2 SD =106.4; p =0.28) activity spaces, and a smaller proportion of their utilized supermarkets fell within their activity spaces (μ=60.9% SD =42.4 vs. μ=81.9% SD =21.4; p =0.24). FE features did not differ by food security status. Conclusions: Conventional FE definitions likely underestimate the number of food sources women encounter, and do not capture the majority of sources used. Smaller activity spaces among food insecure women suggest that routine spatial mobility may be constrained by factors like transportation access. Still, food insecure women more often traveled outside of their activity spaces to utilize supermarkets, suggesting a dual burden of constrained spatial mobility and access. Interestingly, FE features did not differ by food security status. In planned future analyses, any observed differences in diet and weight may indicate variation in how women interact with the FE, rather than differences in exposure.
A DDX31/Mutant–p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer
Authors: Kei Daizumoto, Tetsuro Yoshimaru, Yosuke Matsushita, Tomoya Fukawa, Hisanori Uehara, Masaya Ono, Masato Komatsu, Hiro-omi Kanayama, Toyomasa Katagiri
Journal: Cancer Research (2018)

Abstract The p53 and EGFR pathways are frequently altered in bladder cancer, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of muscle-invasive bladder cancer (MIBC) through its sequential interactions with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31-bound mutp53/SP1 enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin in advanced MIBC, leading to EGFR–Akt signaling activation. High expression of both cytoplasmic DDX31 and p53 proteins correlated with poor prognosis in patients with MIBC, and blocking the DDX31/NCL interaction resulted in downregulation of EGFR/Akt signaling, eliciting an in vivo antitumor effect against bladder cancer. These findings reveal that DDX31 cooperates with mutp53 and EGFR to promote progression of MIBC, and inhibition of DDX31/NCL formation may lead to potential treatment strategies for advanced MIBC. Significance: DDX31 cooperates with mutp53 and EGFR to promote progression of muscle invasive bladder cancer. Cancer Res; 78(9); 2233–47. ©2018 AACR.
Diagnosis at a Glance: Acquired Perforating Dermatosis
Authors: Hideyuki Kosumi, Hiroaki Iwata, Masumi Tsujiwaki, Hiroshi Shimizu
Journal: Diabetes Care (2018)

A 70-year-old man receiving maintenance hemodialysis presented to the dermatology department with pruritic eruptions on the trunk and limbs. The lesions first appeared 30 months before his referral and had been gradually enlarging in size and increasing in number. His chronic kidney disease due to nephrosclerosis had been first diagnosed 20 years before his visit, and he had been receiving hemodialysis for 3 years. …
Optimizing case reports and case series: guidance on how to improve quality
Authors: I. García-Doval, J. Albrecht, C. Flohr, J. Batchelor, J.R. Ingram
Journal: British Journal of Dermatology (2018)

Case reports and case series remain an important part of journals and are often first to document medical breakthroughs. This article reviews their characteristics, aims and limitations. It provides information on how to increase the validity of the bedside decision‐making process that these studies report, using tools such as validated outcomes and split‐body or n‐of‐1 trials. A section describing tools to improve writing of case reports and case series provides suggestions for detailed reporting and good evaluation of novelty, validity and relevance. It includes general and British Journal of Dermatology‐specific guidance.
Abstract 16939: Tube-assisted Feeding is Associated With Worse Longitudinal Growth in Children With Single Ventricle Cardiac Disease
Authors: Arene Butto, Laura Mercer-Rosa, Carrie Daymont, Jonathan Edelson, Erika Mejia, Meryl S Cohen
Journal: Circulation (2016)

Introduction:  Children with single ventricle cardiac disease (SVCD) have poor growth in early life. Tube-assisted feeding (TF) has increasingly been used to improve weight gain in SVCD patients, but little is known about its long-term effects on growth. We sought to compare the longitudinal growth of SVCD patients receiving TF at the time of hospital discharge after initial cardiac surgery with those fed entirely by mouth.   Methods:  We conducted a retrospective cohort study of patients who underwent initial surgical palliation for SVCD from 1999 to 2009, excluding premature infants (   Results:  A total of 135 patients met inclusion criteria; 64% were male and 50% had HLHS. There were 44 patients (33%) in the TF group. Median weight z-score was significantly lower in the TF group at each year of life from ages 2 to 6 years (p   Conclusions:  Long-term growth of children with SVCD who require TF at hospital discharge is diminished compared to that of peers who are fed entirely by mouth. TF patients with SVCD do not experience catch-up growth during early childhood.
Government changes will knock a third off value of public sector pensions
Authors: Caroline White
Journal: BMJ (2012)

The current changes to public sector pensions will cut the average benefit offered across all four of the largest schemes in the sector by more than a third, a report from the Pensions Policy Institute on the effects of the changes has found. But public sector workers will still be significantly better off than their private sector peers, it says.

The changes—which include a switch from final salary schemes to ones based on career average earnings, higher contribution rates, and a later retirement age—are equivalent …
Regulation of hnRNPA1 by microRNAs controls the miR-18a–K-RAS axis in chemotherapy-resistant ovarian cancer
Authors: C. Rodriguez-Aguayo, E. Bayraktar, C. Ivan, E. Fuentes-Mattei, B. Ozpolat, R. Mitra, A.K. Sood, G.A. Calin, G. Lopez-Berestein
Journal: Annals of Oncology (2018)
USE OF PROTEK DUO TANDEM HEART FOR PERCUTANEOUS RIGHT VENTRICULAR SUPPORT IN VARIOUS CLINICAL SETTINGS: A CASE SERIES
Authors: Charles D. Nicolais, Manish Suryapalam, Brian O’Murchu, Riyaz Bashir, Brian P. O’Neill, Rene Alvarez, Paul Forfia, Anjali Vaidya, Jesus Gomez-Abraham, Eman Hamad, Vikas Aggarwal
Journal: Journal of the American College of Cardiology (2018)
Healthcare workers are seldom prosecuted in medical manslaughter cases
Authors: Helen Jaques
Journal: BMJ (2013)

Only 5% of cases of healthcare workers who are charged for gross negligence manslaughter in medical settings result in prosecutions.

The analysis of 75 Crown Prosecution Service files by researchers at the University of Manchester found that only a small proportion of “medical manslaughter” cases in England and Wales end in charges against healthcare workers.

A …
Integrin Clustering Matters: A Review of Biomaterials Functionalized with Multivalent Integrin‐Binding Ligands to Improve Cell Adhesion, Migration, Differentiation, Angiogenesis, and Biomedical Device Integration
Authors: Fatemeh Karimi, Andrea J. O'Connor, Greg G. Qiao, Daniel E. Heath
Journal: Advanced Healthcare Materials (2018)

Abstract Material systems that exhibit tailored interactions with cells are a cornerstone of biomaterial and tissue engineering technologies. One method of achieving these tailored interactions is to biofunctionalize materials with peptide ligands that bind integrin receptors present on the cell surface. However, cell biology research has illustrated that both integrin binding and integrin clustering are required to achieve a full adhesion response. This biophysical knowledge has motivated researchers to develop material systems biofunctionalized with nanoscale clusters of ligands that promote both integrin occupancy and clustering of the receptors. These materials have improved a wide variety of biological interactions in vitro including cell adhesion, proliferation, migration speed, gene expression, and stem cell differentiation; and improved in vivo outcomes including increased angiogenesis, tissue healing, and biomedical device integration. This review first introduces the techniques that enable the fabrication of these nanopatterned materials, describes the improved biological effects that have been achieved, and lastly discusses the current limitations of the technology and where future advances may occur. Although this technology is still in its nascency, it will undoubtedly play an important role in the future development of biomaterials and tissue engineering scaffolds for both in vitro and in vivo applications.
Health department helped draft HEE letters encouraging trusts to implement junior doctor contract, shows investigation
Authors: Abi Rimmer
Journal: BMJ (2017)

The Department of Health in England helped to draft letters sent by Health Education England to NHS trusts encouraging them to implement a new contract for junior doctors, a newspaper investigation has found.

The Independent reported that it had seen internal emails showing that the health secretary for England, Jeremy Hunt, and his officials collaborated with HEE, an arm’s length body of the health department, to introduce the new contract.1

The new contract for junior doctors in England began phased implementation in October 2016, despite BMA members voting to oppose the deal.23 HEE is a non-departmental public body that, the Independent said, provides £3.65bn worth of funding …
New biomarkers for drug‐induced liver injury
Authors: James W. Dear
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. TO THE EDITOR: As a researcher developing biomarkers for drug‐induced liver injury (DILI), the new Hepatology paper by Church et al. was of great interest.1 This important publication presents data regarding biomarkers that were measured in healthy subjects and patients with DILI. Church et al. state in their abstract that "glutamate dehydrogenase (GLDH) appears to be more useful than microRNA‐122 (miR‐122) in identifying DILI patients." The data presented do not robustly justify such a strong statement. Indeed, studies of acetaminophen‐DILI report the opposite finding.2 The conclusion from Church et al. is derived from GLDH having a stronger correlation with ALT than miR‐122. This should be expected given that miR‐122 has different circulating kinetics to ALT and GLDH, being released before the serum ALT is increased and normalizing before ALT.3 Prospective studies, with samples collected serially, are necessary to conclusively determine the utility of miR‐122 or GLDH in identifying DILI. Church et al. express surprise at the variability in miR‐122 within and across healthy subjects. There are questions regarding their miR‐122 analysis, the answers to which will help readers interpret the significance of this variability. The investigators state that multiple samples from healthy subjects had undetectable miR‐122. This is surprising because miR‐122 is one of the highest abundance circulating microRNAs. Our MAPP/BIOPAR study included 1,187 patients.2 All these patients had miR‐122 concentrations measurable by PCR, including those without DILI. A failure to detect miR‐122 may reflect sample degradation, especially given that some of the samples used by Church et al. were stored for multiple years. In an attempt to mitigate any effect of degradation, in MAPP/BIOPAR, we measured an internal "normalizer" microRNA (let‐7d). By contrast, in the study by Church et al., only an exogenous spike‐in control was used. This strategy can only correct for differences in microRNA extraction and cannot correct for sample degradation. It would be informative to know the range of PCR Cq values from the healthy subjects and whether they correlated with sample age, sample storage, or the site of sample processing and measurement. Finally, it would be reassuring if the reported variability in miR‐122 persisted when normalized by let‐7d. MicroRNAs are a new reservoir for the discovery of circulating biomarkers. They behave differently to proteins. More information regarding important methodological issues would alleviate concerns that the variability in miR‐122 is a result of its analytical complexity.
<i>TGFβ1</i>Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy
Authors: Ye Tao, Erich M. Sturgis, Zhigang Huang, Ying Wang, Peng Wei, Jennifer Rui Wang, Qingyi Wei, Guojun Li
Journal: Clinical Cancer Research (2018)

Purpose: TGFβ1 plays a critical role in inflammation and immune responses and treatment response and survival. TGFβ1 variants may affect its expression level or functional efficiency, thus modifying tumor status and survival in human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP).Experimental Design: We determined tumor HPV16 status and genotyped three TGFβ1 polymorphisms in 564 incident SCCOP patients treated with radiotherapy or chemoradiation. Univariate and multivariable Cox models were used to evaluate the associations between the three polymorphisms and survival.Results: Overall, 85% of patients (482 of 564) had HPV16-positive SCCOP. We found that TGFβ1 rs1982073 had statistically significant associations with survival, whereas TGFβ1 rs1800469 and TGFβ1 rs1800471 did not. Patients with TGFβ1 rs1982073 CT/CC variant genotypes had significantly better overall, disease-specific, and disease-free survival compared with those with the corresponding common homozygous TT genotype (all log-rank: P < 0.001). Furthermore, these genotypes were significantly associated with an approximately 5 times reduced risk of overall death, death owing to disease, and recurrence after multivariable adjustment. Moreover, the stratified analyses by tumor HPV status indicated that the significant effects of TGFβ1 rs1982073 polymorphism on survival were found among HPV16-positive SCCOP patients only. Finally, the functional relevance of these variants was further characterized.Conclusions: Our findings support that the TGFβ1 rs1982073 polymorphism plays a significant role in the prognosis of SCCOP, especially in HPV16-positive SCCOP patients treated with chemoradiation. Prospective studies with larger sample sizes are needed to confirm these findings. Clin Cancer Res; 24(9); 2225-33. ©2018 AACR.