tbuckley/cabot-search huggingface dataset:
Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles
Authors: Niusha Nikravesh, Owen G. Davies, Ioannis Azoidis, Richard J. A. Moakes, Lucia Marani, Mark Turner, Cathal J. Kearney, Neil M. Eisenstein, Liam M. Grover, Sophie C. Cox
Journal: Advanced Healthcare Materials (2019)

Abstract Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell‐therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet‐like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs.
Risk Factors and Manageability of the Mainly Mild Mucocutaneous Bleeding Profile Observed in Attp Patients Treated with Caplacizumab during the Phase III Hercules Study
Authors: Spero R Cataland, Marie Scully, Flora Peyvandi, Paul Coppo, Paul Knöbl, Johanna A. Kremer Hovinga, Ara Metjian, Javier De La Rubia, Katerina Pavenski, Jessica Minkue, Rui Passos Sousa, Filip Callewaert, Hilde De Winter
Journal: Blood (2018)
Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers
Authors: Deepak L. Bhatt, Charles V. Pollack, Jeffrey I. Weitz, Lisa K. Jennings, Sherry Xu, Susan E. Arnold, Bret R. Umstead, Michael C. Mays, John S. Lee
Journal: New England Journal of Medicine (2019)

Ticagrelor is an oral P2Y12 inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful.
Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes, NRG Oncology/RTOG 9501-0234.
Authors: Vasu Divi, Jonathan Harris, Paul M. Harari, Jay Scott Cooper, Jonathan B. McHugh, Diana Bell, Erich M. Sturgis, Anthony Cmelak, Mohan Suntharalingam, David Raben, Harold E. Kim, Sharon Spencer, George E Laramore, Andy Trotti, Robert Leonard Foote, Christopher J. Schultz, Wade L. Thorstad, Qiang Zhang, Quynh-Thu Le, F. Christopher Holsinger
Journal: Journal of Clinical Oncology (2015)

6011 Background: Quality of head and neck surgery has thus far focused on adherence to clinical national guidelines and margin status. For other solid tumors, an association has been found between lymph node counts from regional nodal dissection and overall survival; as such, lymph node counts have been proposed as measure of quality. Yet, for neck dissection, no prospective metrics for surgical quality have been established for mucosal squamous cell carcinoma. The purpose of this study is to investigate the association between lymph node counts from primary neck dissection, local-regional recurrence, and overall survival (OS). Methods: Secondary analysis of patients in RTOG trials 9501 and 0234 was performed. The number of lymph nodes counted from regional nodal dissection was evaluated for its prognostic impact on overall survival using a multivariate Cox model adjusted for demographic, tumor, and lymph node data, and stratified by postoperative treatment group: (1) radiation or (2) chemoradiation on RTOG 9501 or (3) chemoradiation and cetuximab on RTOG 0234. Models were compared by Akaike Information Criterion (AIC). Results: Five hundred and seventy-two patients were analyzed. Median follow-up for surviving patients was eight years. Median number of lymph nodes recorded on the left and right sides were 24 and 25. Fewer than 18 nodes was associated with significantly worse OS relative to ≥ 18 nodes (hazard ratio 1.38, 95%CI 1.09-1.74, p = 0.007). The model with this cut point had minimum AIC of all possible models. The difference appears to be driven by local-regional failure (HR 1.46, 95%CI 1.02-2.08, p = 0.04) but not distant metastasis (HR 1.08, 95%CI 0.77-1.53, p = 0.65). Limited to RTOG 0234, adding p16 status to the model does not affect the hazard ratio for sampled nodes and the effect of nodes is not different by p16 status (p-value for interaction 0.99). Conclusions: Identifying 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure. The benefit is seen in both p16-positive and p16-negative patients. The removal and identification of at least 18 lymph nodes should be considered as a measure of quality in neck dissections for mucosal squamous cell carcinoma.
Relationships between anticancer effects and serum gemcitabine levels, human antigen-R expression, and their combination in advanced urothelial cancer treated with gemcitabine and platinum agents.
Authors: Yuji Sagara, Yasuyoshi Miyata, Tsutomu Yuno, Kyohei Araki, Yuichiro Nakamura, Tomohiro Matsuo, Kojiro Ohba, Hideki Sakai
Journal: Journal of Clinical Oncology (2019)

445 Background: Combination therapy of gemcitabine (GEM) and platinum agents and immune-checkpoint inhibitors are standard regimens for advanced urothelial carcinoma (UC), and optimum selection is important to improve the prognosis. Human antigen R (HuR) increases the protein expression of the enzyme deoxycytidine kinase, which is involved in metabolizing the prodrug GEM into its active metabolites. HuR expression is a predictor for the response to gemcitabine-based chemotherapy in a variety of cancers. This study evaluated the relationship between combination pattern of serum GEM level and HuR expression in cancer cells and anti-cancer effects of GEM-based regimens in patients advanced UC. Methods: Twenty-seven advanced UC patients (bladder = 8 and upper urinary tract = 19) were treated with a combination of GEM and platinum agents (cisplatin = 15 and carboplatin = 12) as first-line chemotherapy in Nagasaki University Hospital. Serum samples were collected 30 min after GEM injection. HuR expression was examined by immunohistochemical methods. Results: Positive expression of HuR was detected in 17 (63.0%) patients, and the mean/SD of serum GEM level was 14.9/5.1 μg/mL. C-HuR expression was not associated with anti-cancer effect (P = 0.066). Serum GEM level in the progressive disease (PD) group (10.4/4.7 μg/mL) was lower than that in groups with CR + PR (16.2/3.7) or SD (16.3/6.1); however, these differences were not significant. For the anti-cancer effect of the combination of serum GEM level and HuR expression, all 3 patients with low GEM levels (under median) and negative HuR expression showed PD. In contrast, among 7 patients with high GEM levels and positive C-HuR expression, no patients showed PD, and relationship between their combination pattern and anti-cancer effect was significant (P = 0.010). Conclusions: Serum GEM level or HuR expression was not associated with anti-cancer effects; however, their combination pattern was significantly associated. Although we examined a small number of patients, our results are useful for determining treatment strategies in patients with advanced UC.
Abstract P195: Systolic Blood Pressure and 8-Year Mortality in Community-Dwelling Older Adults. Does Frailty Modify This Effect?
Authors: Kaj Kremer, Ulrike Braisch, Dietrich Rothenbacher, Michael Denkinger, Dhayana Dallmeier
Journal: Circulation (2019)

Introduction: The current literature does not provide sufficient evidence to support different treatment targets for hypertension in older adults. Hypothesis: The effect of systolic blood pressure (SBP) on 8-years mortality may vary by frailty status in community-dwelling older adults. Methods: A frailty index (FI) was constructed according to the model of deficit accumulation with 38 items from the baseline exam at the Activity and Function in the Elderly Study. Each item had a score from 0 (no deficit) to 1 (deficit). FI represents the sum of all scores divided by 38. Cox-proportional hazards models adjusted for age, sex, education, smoking, diastolic blood pressure (DBP) and antihypertensive medications analyzed the association between SBP and 8-year mortality, evaluating the presence of effect modification by frailty. Results: A total of 940 participants were included in the analysis [median age 74, interquartile range (IQR 70.1, 81.0), 42.4% women]. The prevalence of hypertension was 54%, with median SBP 144.5 mmHg (IQR 135.0, 150.0), and median DBP 78.5 mmHg (IQR 71.0, 86.5). Median follow-up time was 8.1 years. A total of 201 deaths were observed. The median FI was 0.113 (IQR 0.069, 0.113), with 19.9% (n=187, 79 deaths) being identified as frail (FI 0.2). We detected effect modification by frailty (p-value interaction term &lt;0.05). Table 1 summarizes the hazard ratios for the multivariable adjusted models stratified by frailty. Conclusions: Our results suggest the presence of effect modification by frailty with a possible protective effect of elevated SBP in frail subjects with respect to 8-year mortality even after adjustment for DBP and antihypertensive treatment.
Adiponectin-AdipoR1 axis in renal cell carcinoma plays a pivotal role in tumor progression and drug resistance.
Authors: Guangxi Sun
Journal: Journal of Clinical Oncology (2019)

634 Background: It is well established that renal cell carcinoma (RCC) is an obesity-associated cancer. Adiponectin, a major adipocyte-secreted adipokine, plays anti-tumor properties in many malignancies, but exerted paradoxical actions on RCC. Herein, we investigated the effects of adiponectin on RCC progression and resistance to sunitinib, and to exploit this molecular mechanism. Methods: Tissues were collected from 126 patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitor (TKI) therapy. Tumor Adiponectine receptor 1 (AdipoR1) and Adiponectine receptor 2 (AdipoR2) were detected by immunohistochemistry. Assays with RCC cell lines were used to examine the signal transduction pathways of adiponectin in RCC. Results: AdipoR2 was generally lower expressed than AdipoR1 in mRCC tumor (15.6% vs 89.1%, p &lt; 0.001). AdipoR1 expression, but not AdipoR2, was a significant independent predictor of favorable responding to TKI and good survival outcomes. In cultured RCC cells adiponectin inhibited migration and invasion of RCC cells and sensitized cells to killing by sunitinib. Mechanistic investigations of ligand–receptor interactions revealed that AdipoR1 could hinder migration and invasion of RCC cells by blocking GSK3β and β-Catenin pathway and increase cells sensitivity to sunitinib through inhibiting AKT and NF-κB pathway. However, AdipoR2 was not associated with the tumor-limiting properties of adiponectin. Conclusions: These results show that AdipoR1 is a potential prognostic marker for favorable outcomes of mRCC patients. Adiponectin-AdipoR1 axis could be a plausible target to impede tumor progression and sensitize tumors to TKI therapy.
Active surveillance and watchful waiting for low-risk prostate cancer in black patients: A population-based analysis.
Authors: Santino Butler, Vinayak Muralidhar, Anthony Victor D'Amico, Paul L. Nguyen, Timothy Rebbeck, Brandon Arvin Virgil Mahal
Journal: Journal of Clinical Oncology (2019)

10 Background: Evidence from clinical trials supports conservative management as an acceptable alternative to definitive therapy for low-risk prostate cancer (LRPC). The optimal approach for Black men, however, remains unclear given trial underrepresentation and concern about racial differences in disease aggressiveness. We therefore sought to determine U.S. conservative management utilization rates for Black men with LRPC. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database queried 50,302 LRPC patients (N = 5218 Black), diagnosed from 2010-2015. Trends in AS/WW utilization over time were determined, stratified by race (Black versus non-Black) and number of positive biopsy cores (≤2 versus ≥3). Results: From 2010 to 2015, AS/WW utilization increased from 12.6% to 36.4% among Black men (P trend &lt; 0.001) and from 14.8% to 43.3% among non-Black men (P trend &lt; 0.001). AS/WW rates reached 52.0% and 57.3% by 2015 for Black (P trend &lt; 0.001) and non-Black (P trend &lt; 0.001) men with ≤2 positive biopsy cores, respectively. Rates continually increased for all subgroups except Black men with ≥3 positive biopsy cores, where rates plateaued at 22.9% by 2013. Conclusions: In this report from the largest U.S. population of Black LRPC patients with quality assured AS/WW data, AS/WW rates have nearly tripled for Black men from 2010-2015, suggesting AS/WW is viewed as a safe management option in all races.
Is there a role for short intensive therapy without stem cell support in relapsed germ cell tumours? A single centre experience of GAMEC chemotherapy.
Authors: Helen Hockings, Peter Wilson, Danish Mazhar, Simon Chowdhury, Katherine Mutsvangwa, Jonathan Shamash
Journal: Journal of Clinical Oncology (2015)

e15563 Background: Relapsed germ cell tumours remain a continuing clinical problem. The place of high dose chemotherapy with stem cell support at first relapse remains controversial .Recently the publication of prognostic factors (International Prognostic Factors Study Group, IPFSG) has been used to help choose therapy. These depend on response to previous therapy as well as markers and sites involved at relapse. In a previous publication(Shamash et al ,British Journal of Cancer 2007), we found that age ( > 35y) and LDH ( > ULN) were significant with the absence of both being associated with a good outcome. Neither is included in the IPFSG classification. We reviewed the performance of our standard GAMEC regimen ( cisplatin 100mg/m2, high dose methotrexate 8g/m2, actinomycin1mg/m2 and etoposide 360mg/m2 every 14 days with cisplatin on day 8 of cycles 1 and 2) for 3-5 cycles ( 6-10 weeks) , as relapse therapy to see how it performed against the established prognostic factors. Methods: Retrospective review of patients referred for relapsed GCT management. Between 1997 and 2014 , 63 patients were treated with GAMEC at first relapse following failure of cisplatin-based combination chemotherapy. Results: With a median follow up of 80 months the overall 2 y PFS was 57% ( range 42-69) with a 3 y survival of 60% ( 46.2-72).There were 6 treatment related deaths. Fifty-four percent had a normal LDH and were < 35y. According to IPFSG 22% were v.low/low , 56% were intermediate and 21% were high risk . The 2y PFS were 44%, 60% and 22% respectively. Those with normal LDH and < 35y had a 2 y PFS of 79%, those with one or both of these risk factors had a 2 y PFS of 39% and 13%. There was little association between the IPFSG criteria versus age and LDH (Chi2 = 4.85 p = 0.089) Conclusions: Good outcomes are possible using GAMEC in patients < 35y and with normal LDH despite high IPFSG grouping These two factors may be more relevant is deciding whether or not to use this treatment in relapsed germ cell tumours
Abstract P160: Racial Differences in the Association of NTproBNP With Risk of Incident Heart Failure in REGARDS Participants
Authors: Nirav Patel, Mary Cushman, Orlando Gutiérrez, George Howard, Monika Safford, Paul Muntner, Raegan Durant, Sumanth Prabhu, Garima Arora, Emily Levitan, Pankaj Arora
Journal: Circulation (2019)

Background: Black individuals have lower N-terminal-pro-B-type natriuretic peptide (NTproBNP) levels than whites. Higher NTproBNP levels are associated with increased risk of incident heart failure (HF). Although, the ability of NTproBNP for risk stratification is variable in the setting of obesity and kidney disease. We studied the 1) association of NTproBNP with incident HF stratified by race and 2) tested the predictive ability across body mass index (BMI) and estimated glomerular filtration rate (eGFR) categories. Methods: Using a case-cohort design, NTproBNP levels were measured from the Reasons for Geographic And Racial Differences in Stroke study for 855 participants who subsequently developed incident HF and 3,680 randomly selected participants. Multivariable Cox proportional hazard modeling including all the factors which can affect NTproBNP levels was used to assess 1) the association of NTproBNP with incident HF; 2) interaction by race, and 3) predictive ability of NTproBNP based on percentage contribution in global Wald Chi-square score across BMI and eGFR categories. Results: The mean age of the random sub-cohort was 66.6 (12.1) years, 1,847 (50.2%) were females and 1,775 (48.2%) were blacks. The magnitude and strength of the relationship of NTproBNP with incident HF differed by race (p=0.01 for interaction). A doubling in NTproBNP levels was associated with greater risk of incident HF among whites [(hazard ratio (HR): 1.82; 95% CI: 1.62-2.04] compared with blacks (HR: 1.54; 95% CI: 1.35-1.75). NTproBNP remained a strong predictor (25%-50% Wald score) of incident HF across all BMI and eGFR categories in whites. However, among blacks with obesity (BMI ≥ 30 kg/m 2 ) and eGFR ≤60 mL/min/1.73 m 2 , NTproBNP was a weak predictor of incident HF (&lt;7% Wald score) ( Figure ). Conclusions: Higher NTproBNP was more strongly associated with incident HF among whites compared with blacks. The predictive ability of NTproBNP levels with incident HF was preserved with obesity and impaired renal function among whites, but not in blacks.
Abstract P078: Racial Differences in the Association Between Diabetes and Length of Residence Among African Migrants to the US
Authors: Debora Kamin Mukaz
Journal: Circulation (2019)

Background: In the US, length of residence has been shown to increase diabetes risk in migrants. Unfortunately, there is a dearth of research on the topic for African migrants especially as it relates racial differences. However, the prevalence of diabetes is higher in North Africa compared to sub-Saharan Africa. Thus, the goal of our study was to assess the effects of race on the association between the length of residence and diabetes among African migrants. Hypothesis: There is a positive association between length of residence and diabetes among non-Black African migrants compared to Black African migrants. Methods: Data from the 2010-2017 NHIS (National Health Interview Survey) were analyzed. The initial sample selected 1911 individuals, 18 years or older, whose birthplace was Africa and who answered questions about diabetes diagnosis. After selecting on non-missing values, the final sample included 1899 African migrants. Chi-square tests and logistic models were used to assess the association between race, length of residence divided into less than 10 years vs 10 years or more and, diabetes. Results were weighted to account for the complex sampling design. Results: The prevalence of diabetes in the selected population was 5.9 % (95% CI: 4.8%-7.1%). The prevalence was significantly higher (p=0.027) for non-Black migrants (8.2%, 95% CI: 5.7-11.6%) compared to non-Black migrants (5.1%, 95% CI: 4.1- 6.3%). Additionally, a larger proportion of non-Black migrants (74.5%, 95% CI: 69.9-78.5%) had resided in the US for 10 years or more compared to Black migrants (58.6%, 95% CI: 55.6-61.6%; p&lt;0.001). The age-and gender-adjusted regression analysis revealed there was no significant association between diabetes and length of residence (OR= 1.41, 95% CI: 0.78-2.55) in the general African migrant population. While the association remained non-significant among non-Black African migrants (OR=0.54, 95% CI: 0.15-1.92), the age-and gender-adjusted model revealed that Black Africans who had lived in the US for 10 years or more were twice more likely to be diabetic compared to those who had lived in the country for less than 10 years (OR=2.02, 95% CI: 1.09-3.77). Conclusions: In conclusion, in the US, the association between length of residence and diabetes was significant for Black Africans and non-significant for non-Black Africans. These results suggest the need for diabetes prevention programs that acknowledge the racial and cultural diversity of African migrants.