tbuckley/cabot-search huggingface dataset:
Racial differences in delay of treatment for localized prostate cancer (CaP): A population-based study.
Authors: William Allen Stokes, Laura H Hendrix, Trevor Joseph Royce, Ian M. Allen, Andrew Wang, Ronald C. Chen
Journal: Journal of Clinical Oncology (2012)

6037 Background: African-Americans (AA) are diagnosed with more advanced CaP than Caucasians (CA) and are more likely to die from CaP. Treatment delay is a potentially modifiable obstacle to care and clinically may be more important in AA patients because of more aggressive cancer at diagnosis. We examined time from diagnosis to curative treatment (surgery or radiation) in AA and CA patients in the Surveillance, Epidemiologic and End Results (SEER)-Medicare linked database. Methods: 21,454 CA and 2,506 AA patients who were diagnosed with non-metastatic CaP from 2004-08 and received treatment within 12 months of diagnosis were included. Linear regression was used to examine factors associated with number of days from diagnosis to treatment initiation, and logistic regression to assess odds of treatment within 6 months of diagnosis. Results: AA patients were more likely to have high-risk CaP than CA patients (39 vs. 35%), and less likely to have low-risk CaP (27 vs. 31%) (p&lt;.001). Time to treatment was significantly prolonged for AA patients in all risk groups of CaP, and the difference was most prominent for high-risk patients (median 105 days for AA vs. 96 days for CA, p=.002). Racial differences in time to treatment persisted in multivariable analysis (Table). Sensitivity analyses examining the proportion of AA and CA patients initiating treatment within 6 months of diagnosis revealed similar results. Conclusions: AA patients, especially those with high-risk CaP, experience longer treatment delays than CA patients. This is the first large-scale study to examine treatment delays in AA and CA patients with CaP. The differences found may contribute to our understanding of racial disparities in CaP treatment outcomes. [Table: see text]
Effect of injection solutions in the dispersion of syringe lubricant (silicone oil)
Authors: Bruna Mikulis Lemes, Evelyn Assis de Andrade, Luiza Stolz Cruz, Bruno Rodrigo Minozzo, Wayne D. Carey, William Damsky, Helio Amante Miot, Flávio Luís Beltrame, Carlos Gustavo Wambier
Journal: Journal of the American Academy of Dermatology (2019)
Mesenchymal Stem Cells (MSC) from Patients with Multiple Myeloma Promote Myeloid Cells to Become Granulocytic-Myeloid-Derived Suppressor Cells (G-MDSC) with Immunosuppressive, Bone Resorption and Pro-Angiogenic Activity
Authors: Cesarina Giallongo, Daniele Tibullo, Nunziatina Laura Parrinello, Piera La Cava, Giuseppina Camiolo, Nunzia Caporarello, Carmelina Daniela Anfuso, Fabrizio Puglisi, Concetta Conticello, Maria Violetta Brundo, Alessandra Romano, Francesco Di Raimondo
Journal: Blood (2016)
Performance of the systemic lupus erythematosus disease activity score (SLE-DAS) in a Latin American population.
Authors: Melissa G Rodríguez-González, Grissell A Valero-Gaona, Tania Vargas-Aguirre, Luis M Amezcua Guerra
Journal: Annals of the Rheumatic Diseases (2019)

The accurate assessment of disease activity in patients with systemic lupus erythematosus (SLE) remains a pending task. Recently, Jesus et al developed and validated a novel instrument, the SLE Disease Activity Score (SLE-DAS), in two representative cohorts of Caucasian patients.1 Through an elegant methodology, the authors demonstrated that SLE-DAS provides a more accurate identification of clinically meaningful changes over time, with higher sensitivity and similar specificity compared with the SLE Disease Activity Index 2000 (SLEDAI-2K). Although these finding have adequate methodological support, there are some points of concern that deserve further clarification. On the one hand, a clinimetric instrument must be validated in populations of different ethnic and geographical substrate before being accepted as of generalised use. On the other hand, the extent of lupus activity does not show a linear distribution in patients from a real-life scenario, so the performance of any instrument should be evaluated in individuals with quiescence or mild disease activity separately from patients with moderate to severe disease activity.

In an attempt to answer these unsolved questions, we conducted a study in our lupus cohort, which is based on a general practice of rheumatology in a …
Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus
Authors: Karin Rådholm, Gemma Figtree, Vlado Perkovic, Scott D. Solomon, Kenneth W. Mahaffey, Dick de Zeeuw, Greg Fulcher, Terrance D. Barrett, Wayne Shaw, Mehul Desai, David R. Matthews, Bruce Neal
Journal: Circulation (2018)

Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups.
Switching chemotherapy in adult osteosarcoma patients with poor necrosis rates post neoadjuvant methotrexate, cisplatin, and doxorubicin (MAP).
Authors: Grainne O'Kane, Karen Anne Cadoo, Elaine Walsh, Conor O'Keane, Gary O'Toole, Sean Dudney, Desmond Carney
Journal: Journal of Clinical Oncology (2013)

10530 Background: Chemotherapy in the treatment of osteosarcoma has improved 5 year overall survival (OS) from 20% with surgery alone to 60-70%. However, poor tumor necrosis following neoadjuvant chemotherapy (NAC) is associated with decreased survival, therefore strategies to improve outcomes are required for these patients. Methods: Records from all adult patients diagnosed with osteosarcoma between 1986 and 2012 were retrospectively reviewed. Patients were stratified according to age at diagnosis (&lt;40yrs and &gt;40yrs), stage (localised or metastatic) and tumor necrosis post NAC (&lt;90% and &gt;90%). All patients received 2 cycles of methotrexate alternating with cisplatin/doxorubicin (MAP) preoperatively. Following surgery, patients with &gt;90% tumor necrosis continued MAP whilst those with &lt;90% necrosis switched to 4 cycles of ifosfamide and etoposide (IE). Results: 105 patients were identified and 98 who received systemic chemotherapy were included. Median age was 23yrs (Range 15-75yrs); 68% of patients were male. Limb sparing surgery was performed in 76% of applicable patients. Of the patients with localised disease (N=85), 5 year OS, with a median follow up of 8 years (1-26 yrs) was 68% (p=0.002). Patients &lt;40 yrs with localised disease had a 5yr OS of 71% (N=73) compared to 40% in those &gt;40 yrs (N=12) (p=0.05). 2/13 patients with metastatic disease at diagnosis are disease free &gt;10 years post diagnosis. 65 of 73 patients with localised disease &lt; 40 yrs had histology reviewed post neoadjuvant MAP. 34/65 (52%) had &gt;90% tumor necrosis and continued on MAP, 5 yr OS 79%, 31 patients (48%) had &lt;90% necrosis and received adjuvant IE, 5 yr OS 68% (P=0.10). Conclusions: Age and stage are important prognostic factors in patients with osteosarcoma treated with chemotherapy and surgery. Historically, patients with &lt;90% tumor necrosis post NAC are considered to have a poorer prognosis. Switching from MAP to IE is an appropriate salvage regimen in such patients and appears to improve long term survival.
Abstract 17521: Improved Evaluation of Mitral Valve Pathophysiology for Better Prediction of Repair Success
Authors: Yonghoon Rim, Susan T Laing, Patrick Kee, David D McPherson, Hyunggun Kim
Journal: Circulation (2012)

Background: Computational simulation in combination with 3D echocardiography can provide detailed biomechanical information of mitral valve (MV) function with better pathophysiologic evaluation. Of...
Genetic Aberrations in the CDK4 Pathway Are Associated with Innate Resistance to PD-1 Blockade in Chinese Patients with Non-Cutaneous Melanoma
Authors: Jiayi Yu, Junya Yan, Qian Guo, Zhihong Chi, Bixia Tang, Bin Zheng, Jinyu Yu, Ting Yin, Zhiyuan Cheng, Xiaowen Wu, Huan Yu, Jie Dai, Xinan Sheng, Lu Si, Chuanliang Cui, Xue Bai, Lili Mao, Bin Lian, Xuan Wang, Xieqia Yan, Siming Li, Li Zhou, Keith T. Flaherty, Jun Guo, Yan Kong
Journal: Clinical Cancer Research (2019)

PD-1 checkpoint blockade immunotherapy induces long and durable response in patients with advanced melanoma. However, only a subset of patients with melanoma benefit from this approach. The mechanism triggering the innate resistance of anti-PD-1 therapy remains unclear.Experimental Design: Whole-exome sequencing (WES) and RNA sequencing (RNA-Seq) analyses were performed in a training cohort (n = 31) using baseline tumor biopsies of patients with advanced melanoma treated with the anti-PD-1 antibody. Copy-number variations (CNVs) for the genes CDK4, CCND1, and CDKN2A were assayed using a TaqMan copy-number assay in a validation cohort (n = 85). The effect of CDK4/6 inhibitors combined with anti-PD-1 antibody monotherapy was evaluated in PD-1-humanized mouse (C57BL/6-hPD-1) and humanized immune system (HIS) patient-derived xenograft (PDX) models.WES revealed several significant gene copy-number gains in the patients of no clinical benefit cohort, such as 12q14.1 loci, which harbor CDK4. The association between CDK4 gain and innate resistance to anti-PD-1 therapy was validated in 85 patients with melanoma (P < 0.05). RNA-Seq analysis of CDK4-normal cell lines and CDK4-normal tumors showed altered transcriptional output in TNFα signaling via NF-κB, inflammatory response, and IFNγ response gene set. In addition, CDK4/6 inhibitor (palbociclib) treatment increased PD-L1 protein levels and enhanced efficacy (P < 0.05) in the C57BL/6-hPD-1 melanoma cell and the HIS PDX model.In summary, we discovered that genetic aberrations in the CDK4 pathway are associated with innate resistance to anti-PD-1 therapy in patients with advanced melanoma. Moreover, our study provides a strong rationale for combining CDK4/6 inhibitors with anti-PD-1 antibody for the treatment of advanced melanomas.
Does HE4 have a role in the recurrence of ovarian cancer?
Authors: Roberto Montera, Francesco Plotti, Ludovico Muzii, Corrado Terranova, Michela Angelucci, Irma Oronzi, Patrizio Damiani, Nella Dugo, Federica Guzzo, Maria Antonietta De Oronzo, Roberto Ricciardi, Alessia Aloisi, Daniela Luvero, Rosa Alba Valentina Portuesi, Giuseppe Scaletta, Stella Capriglione, Francesca Linciano, Paolo Gennari, Pierluigi Benedetti Panici, Roberto Angioli
Journal: Journal of Clinical Oncology (2012)

e15550 Background: Human epididymis protein 4 (HE4) has been recently described as a new marker for early ovarian cancer, with higher sensitivity (76.9%) compared to CA125. This is the third study in literature on the role of HE4 in recurrence of ovarian cancer and the first evaluating the sensitivity of HE4 and CA125 in these patients Methods: Plasma was obtained 24 hours before secondary cytoreductive surgery from consecutive patients with suspicious recurrence ovarian cancer operated from November 2010 to April 2011 at University Campus Bio-Medico of Rome. CA125 levels were evaluated by a one-step "sandwich" radioimmunoassay. HE4 levels were determined using the HE4 enzymatic immune assay. The CA125 cut-off was less than 35 U/mL. Two cut-off were considered for HE4: less than 150 pmol/L (according to the manufacturer's indications) and less than 70 pmol/L. Results: Fourteen patients were histologically confirmed as recurrence ovarian cancer. Mean Ca125 plasma concentration was 31.95 ± 22.09 U/mL (range 1.1 – 64.3). Mean HE4 plasma concentration was 225.83± 286.82 pmol/L (range 21.61- 633.6). The sensitivity of CA125 was 35.7 %. The sensitivity of HE4 was 71.4% and 28.6% above the cut-off of 70 pmol/L and 150 pmol/L, respectively. The dual marker combination of CA125 and HE4 at 70 pmol/L cut-off yielded the highest sensitivity (85.7%) to detect recurrence ovarian cancer. Conclusions: Even if a standard cut-off point has not been determined, this study suggested that HE4 may potentially be a more sensible marker for recurrence ovarian cancer than CA125 and the association between CA125 and HE4 at cut-off of 70 pmol/L seems to yield the highest sensitivity.
Immunomodulation: Immunostimulatory Effects Triggered by Self‐Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands (Adv. Healthcare Mater. 4/2019)
Authors: Dajeong Kim, Hyejin Kim, Sangwoo Han, Marta Scatena, Deok‐Ho Kim, Jong Bum Lee
Journal: Advanced Healthcare Materials (2019)

In article number 1801395, Deok-Ho Kim, Jong Bum Lee, and co-workers demonstrate immunostimulatory effects of RNA microspheres (RMSs), which are generated with single or double strands by rolling circle transcripton. Unlike the nature of RNA fragments, RMSs induce only basal-level expression of inflammatory cytokines as well as type I interferon from macrophages, suggesting that RMSs are immunocompatible in the therapeutic dose range, while a systematic release increasing RNA fragments from RMSs could provide self-assembled RNA-based structures with a great potential for immunomodulation.
Skin cancer and dermatoses in a majority-Hispanic population of solid organ transplant recipients
Authors: Brandon L. Adler, Jan Smogorzewski, Tiffany Sierro, Orr Shauly, Daria Osipchuk, Melanie Miller, Melissa Mert, Michael W. Fong, Sivagini Ganesh, Hyosun Han, Gino K. In, Thin Thin Maw, Miroslaw Smogorzewski, Jenny Hu, Binh Ngo, David Lee, Iris Ahronowitz
Journal: Journal of the American Academy of Dermatology (2019)
Contribution of High-Density Neutrophils to Multiple Myeloma Microenvironment Dysregulation
Authors: Alessandra Romano, Cesarina Giallongo, Nunziatina L Parrinello, Daniele Tibullo, Fabrizio Puglisi, Giusy Camiolo, Piera La Cava, Marina Parisi, maria Letizia Consoli, Concetta Conticello, Francesco Di Raimondo, Vanella Luca
Journal: Blood (2016)
Trends in modes of death in heart failure over the last two decades: less sudden death but cancer deaths on the rise
Authors: Pedro Moliner, Josep Lupón, Marta de Antonio, Mar Domingo, Evelyn Santiago‐Vacas, Elisabet Zamora, Germán Cediel, Javier Santesmases, Crisanto Díez‐Quevedo, Maria Isabel Troya, Maria Boldó, Salvador Altmir, Nuria Alonso, Beatriz González, Julio Núñez, Antoni Bayes‐Genis
Journal: European Journal of Heart Failure (2019)
The effect on detection rate of second cancers after the addition of MRI to conventional screening mammography in patients with a history of breast cancer.
Authors: Chana Weinstock, Cristina Campassi, Olga G. Goloubeva, Saranya Chumsri, Ting Bao, Susan Kesmodel, Steven J. Feigenberg, Kathleen Wooten, Olga B. Ioffe, Katherine Hanna Tkaczuk
Journal: Journal of Clinical Oncology (2012)

10572 Background: Mammography is currently used in the surveillance of breast cancer survivors, who are at increased risk of developing ipsilateral and contralateral breast cancers regardless of age at diagnosis or time since diagnosis. Several prospective studies have shown the utility of breast MRI in other high risk populations; however, little data exists on the use of MRI for surveillance of breast cancer survivors. We aimed to compare the outcome of surveillance breast MRI vs. mammography in this population. Methods: We identified women &lt;65 with non-metastatic breast cancer or DCIS with at least one MRI performed at our center &gt;11 months after initial diagnosis, along with a mammogram done within 6 months of the MRI. We compared the outcome of MRI and mammography in terms of biopsies performed as well as in detection of new cancers. Results: Of 512 consecutive charts reviewed, 204 patients met inclusion criteria, 105 (51.4%) of whom were African-American. The average number of MRIs per patient was 2.3 (range 2-7), with a total of 474 MRIs performed between 2005 and 2011. MRI resulted in BIRADS scores of 1 or 2 in 73.5% of studies vs. 84.4% for mammography. There were 19 biopsies performed due to MRI findings alone, 7 done due to mammographic findings alone, and 6 biopsies done based on abnormalities seen on both MRI and mammography. There were 7 malignancies identified based on an abnormal MRI, 3 seen on both MRI and mammography, and none identified via mammography alone. The malignancies identified via MRI alone included 1 patient with DCIS, 5 with stage I disease, and 1 with isolated lung metastases. Of the 10 recurrences detected, 5 (50%) were in African Americans. Two patients developed interval cancers within 6 months of normal screening MRI and mammography. Sensitivity and specificity for MRI were 83.3% (95% CI 0.51-0.97) and 92.2% (95% CI 0.87-0.95), vs. 25% (95% CI 0.05-0.57) and 94.8% (95% CI 0.90-0.97) for mammography. Positive and negative predictive values were 40% and 98.9% for MRI vs. 25% and 95.2% for mammography. Conclusions: Gadolinium-enhanced breast MRI is a useful surveillance modality in breast cancer survivors &lt; age 65. Prospective studies are needed in this population.
Cross-cultural disparities of subjective sleep parameters and their age-related trends over the first three years of human life: A systematic review and meta-analysis
Authors: Qing-Min Lin, Karen Spruyt, Yue Leng, Yan-Rui Jiang, Guang-Hai Wang, Shu-Mei Dong, Hao Mei, Fan Jiang
Journal: Sleep Medicine Reviews (2019)
Results of G004, a phase IIb study in recurrent glioblastoma patients with the TGF-b2 targeted compound AP 12009
Authors: U. Bogdahn, V. E. Oliushine, V. E. Parfenov, M. Kunst, A. Mahapatra, K. V. Sastry, K. N. Venkataramana, P. Jachimczak, P. Hau, K. Schlingensiepen
Journal: Journal of Clinical Oncology (2006)

1553 Background: In high-grade glioma (HGG), TGF-β2 expression strongly correlates with tumor grade and is highly predictive of disease outcome. The compound AP 12009 inhibits TGF-β2 expression. Preclinical results revealed strong multimodal activity including reversal of TGF-β induced immunosuppression, inhibition of tumor cell migration and proliferation. In 3 preceding phase I/II dose escalation studies, 24 HGG patients had been treated with AP 12009. Methods: G004 is an international open-label, actively controlled, dose finding phase IIb study. Objective is a comparison of two doses of AP 12009 and standard chemotherapy for efficacy and safety. 145 patients with histopathologically confirmed recurrent anaplastic astrocytoma (AA, WHO grade III) or glioblastoma (GBM, WHO grade IV) were randomized into one of 3 treatment arms. 134 patients received treatment AP 12009 10μM, AP 12009 80μM or standard chemotherapy (TMZ or PCV). AP 12009 was applied locoregionally by convection-enhanced delivery during a 6-month active treatment period with 7-day-on, 7-day-off cycles. Primary endpoint is tumor response by local and central MRI reading. All patients have completed active treatment. Follow-up for survival and tumor response assessed by local and central MRI reading is ongoing. Results: Here we report on patients with recurrent GBM (AA see separate Abstract). 96 GBM patients (37% female, 63% male; median age 51 years, range 20–74; median Karnofsky performance status 90, range 70–100) have been treated. 63 GBM patients received AP 12009 (28 pt. 10 μM, 35 pt. 80 μM), 33 patients received standard chemotherapy. Data were evaluated by an independent Data and Safety Monitoring Board. Up to now, in 89 patients treated with AP 12009 (AA and GBM patients) 6 SAEs possibly related to the study drug and 37 procedure related SAEs (92% mild or moderate) were documented. Several long-term tumor responses were observed by local MRI reading. Exact response rates are being determined by central reading. Conclusions: Responses in patients treated with AP 12009 in both AA and GBM patients are long lasting with a good quality of life. Phase III clinical trials in AA and GBM patients are currently in preparation. [Table: see text]
Comorbidity and other predictors of survival in veterans with colorectal cancer (CRC).
Authors: Fengming Zhong, Trent P Wang, Tanganyika Barnes, Melanie L. Gonzalez, Victor T Chang, Jan Einhorn, Maryann Sullivan, Basil Kasimis
Journal: Journal of Clinical Oncology (2012)

e14125 Background: The role of comorbidity as a prognostic marker is an area of great interest. This study aimed to determine whether comorbidity indices predict survival in Veterans with CRC. Methods: In an IRB-approved protocol, we reviewed the records of pts diagnosed with CRC at a VA Medical Center from 1/1/2003 to 12/31/2007. Demographics, stage, grade, ECOG performance status (PS), CEA, hemoglobin (HGB), Albumin (ALB) at diagnosis, history of surgical resection (SR) were abstracted. Comorbidity was assessed with the Charlson Comorbidity Index (CCI), the Kaplan-Feinstein Index (KFI), the Cumulative Illness Rating Scale (CIRS), and VA Comorbidity Scale (VACS). We developed a survival model with stage, ECOG PS, HGB, ALB, SR, and ECOG PS. Comorbidity indices were tested by determining if they were independent predictors of survival after inclusion in this model. Cox regression analyses were performed with SAS V9.2. Results: There were 175 pts with colorectal ca with 111 colon (C) and 64 rectal ca (R) pts. The median (M) age at diagnosis was 71 (45-90). 54% of study population was deceased at the time of data collection. Median survival was 1157 days (5-3256). Results of multivariate analyses with comorbidity indices are summarized in the table. Conclusions: Charlson, CIRS 16 and CIRS 19 comorbidity indices were significant predictors for veterans with colorectal cancer and appear to be important for the subset of veterans with colon cancer. Confirmatory studies should be done in larger populatins. These indices may be used in the design of future clinical trials. This was supported by the New Jersey Commission for Cancer Research 09-1133-CCR-EO. [Table: see text]
Challenges in funding and developing genomic software: roots and remedies
Authors: Adam Siepel
Journal: Genome biology (2019)

The computer software used for genomic analysis has become a crucial component of the infrastructure for life sciences. However, genomic software is still typically developed in an ad hoc manner, with inadequate funding, and by academic researchers not trained in software development, at substantial costs to the research community. I examine the roots of the incongruity between the importance of and the degree of investment in genomic software, and I suggest several potential remedies for current problems. As genomics continues to grow, new strategies for funding and developing the software that powers the field will become increasingly essential.