tbuckley/cabot-search huggingface dataset:
Comparative DNA cytometry of primary and recurrent soft tissue sarcomas.
Authors: Irina Dashkova, Larisa N. Vashchenko, Oleg Ivanovich Kit, Inna A. Novikova, Ekaterina Komarova, Tatiana V. Ausheva, Elena A. Andreyko, Elizaveta Komarova, Emma Kechedzhieva
Journal: Journal of Clinical Oncology (2019)

e22516 Background: Soft tissue sarcomas (STS) are aggressive tumors with a high degree of recurrence. Radical resection within healthy tissues allows to reduce the recurrence percentage to 25-30% without subsequent therapy. The literary analysis has shown that the study of various biological properties of primary and recurrentsoft tissue tumorsis being conducted. However, currently there is a lack of information to understand the reasons for STS recurrence. The goal of investigation was to reveal the distinctive features of the DNA content and cell distribution in the phases of the cell cycle of recurrent STS. Methods: DNA cytometry in the tumor tissue of 30 primary soft tissue sarcomas and 30 STS recurrences was carried out using the method of flow cytofluorometry. The tumor ploidy and cell distribution in the cell cycle phases were analyzed. Results: A number of differences in the DNA cytometric parameters of primary and recurrent STS have been revealed, they include: an increase in the proportion of aneuploid tumors in case of recurrence, the number of tumors with DNA index within the mitotic cycle, an increase in the proportion of cells in G2+M- phase of diploid and aneuploid tumors and a decrease in S- phase of aneuploid ones. It has been shown that with a G2 differentiation degree, the proportion of cells in G2+M, S- and proliferation index of recurrent STS is significantly lower than the primary parameters. An increase in the proportion of cells in G2+M- phase and a decrease in the rate of proliferation of recurrent STS, depending on the stage, are shown only in case of stage III. Conclusions: The revealed features of DNA content and cell cycle of tumor cells of soft tissue sarcomas will allow to approach to understanding of biological bases of recurrence of this malignant disease.
Sequenced circulating tumor (ct) DNA to detect the molecular landscape in advanced GIST.
Authors: Ciara Marie Kelly, Sandra P. D'Angelo, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, Samantha Wheeler, Maysun Hasan, Michael F. Berger, Cristina R. Antonescu, William D. Tap, Ping Chi
Journal: Journal of Clinical Oncology (2019)

11036 Background: Molecular (mol) characteristics-guided precision therapy has well-established utility in GIST management. The GIST mol landscape is poorly represented by selective tumor biopsy (bx) material, especially in metastatic and treatment-refractory GIST. ctDNA can overcome some of the limitations of selective tissue bx specimens and provide comparable or greater mol information. ctDNA represents an emerging mol biomarker in advanced (adv) GIST. Methods: Next generation sequencing analyses (MSK-IMPACT or custom-capture GIST specific panel) were performed on ctDNA prospectively collected from patients (pts) with adv GIST. MSK-IMPACT was performed on tumor material (archival tissue or paired tissue bx specimens taken in parallel with ctDNA collection from clinical trial participants). The primary objective was to determine the concordance between the mol landscape of GIST identified by sequenced tumor tissue versus ctDNA. Secondary objective was to correlate characteristics of sequenced ctDNA with standard measurements of response assessment. Results: 47 ctDNA samples collected from 25 pts with adv GIST were sequenced using MSK-IMPACT ( &gt; 400 genes). MSK-IMPACT was performed on archival tumor material. Sequenced ctDNA detected the mutational spectrum of tumor tissue in 48% of cases. In 50% of these cases, ctDNA identified novel treatment-resistance mutations not previously identified in the archival tissues. To optimize sensitivity of detection, a custom-designed GIST specific ctDNA sequencing panel was developed incorporating 19 of the most commonly altered genes observed from MSK-IMPACT analysis performed on &gt; 75 imatinib-refractory adv GIST tumor samples. 52 ctDNA samples collected from 30 pts with paired tumor bx samples have been sequenced using the custom-capture GIST panel. The tumor bx samples have been sequenced using MSK-IMPACT. Results are pending and will be presented. A separate cohort of ctDNA samples serially collected in the setting of a prospective clinical trial are being sequenced. The mol results with correlated treatment response by RECIST will also be presented. Conclusions: ctDNA could detect a broad spectrum of mol heterogeneity and potentially be used as a biomarker to guide precision therapy in adv GIST. Further research is necessary to determine the optimal ctDNA sequencing assay and the appropriate clinical setting to utilize in GIST.
Thalidomide, lenalidomide and pomalidomide reduce the metastatic capability of cancer cells in vivo and in vitro
Authors: Wai Liu, Jake Henry, Brendan Meyer, Marie-Christine Labarthe, J Bartlett, Angus Dalgleish, Christine Galustian
Journal: Cancer Research (2008)

1173  Thalidomide (Thalomid®), lenalidomide (Revlimid®, CC-5013) and pomalidomide (CC-4047), display immunomodulatory, anti-angiogenic and anti-apoptotic effects, although little is known about the primary mode of therapeutic action in patients with cancer. Thalidomide is FDA approved, in combination with dexamethasone, for the treatment of newly diagnosed multiple myeloma (MM) patients. Lenalidomide is FDA approved in combination with dexamethasone for the treatment of MM patients who have received at least one prior therapy. Pomalidomide is being investigated as an anticancer agent in clinical trials. As part of a continuing research effort, we have investigated the effects of these agents on the metastatic capacity of a murine colorectal cell line in vivo and in vitro. The effects of these agents on the metastatic capacity of CT26 cells were established using a number of models. Results indicated that all three drugs significantly inhibited the metastatic capability of CT26 cells. Anchorage-independent growth was significantly reduced, as was migratory capacity and invasive competence (Table). In addition, an in vivo metastasis model was used whereby CT26 cells were administered by IV into the tail vein of BALB/c mice (n=15) at ten-weeks of age, and allowed to develop spontaneous metastases within the lungs. Mice challenged IP with pomalidomide (50 mg/kg) presented with a significantly lower number of metastatic pulmonary nodules relative to control mice injected with DMSO (50.8% ± 6.6% vs. 100.0% ± 10.1% at day 14; p
Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders
Authors: Michael Amlung, Emma Marsden, Katherine Holshausen, Vanessa Morris, Herry Patel, Lana Vedelago, Katherine R. Naish, Derek D. Reed, Randi E. McCabe
Journal: JAMA Psychiatry (2019)

Delay discounting is a behavioral economic index of impulsive preferences for smaller-immediate or larger-delayed rewards that is argued to be a transdiagnostic process across health conditions. Studies suggest some psychiatric disorders are associated with differences in discounting compared with controls, but null findings have also been reported.To conduct a meta-analysis of the published literature on delay discounting in people with psychiatric disorders.PubMed, MEDLINE, PsycInfo, Embase, and Web of Science databases were searched through December 10, 2018. The psychiatric keywords used were based on DSM-IV or DSM-5 diagnostic categories. Collected data were analyzed from December 10, 2018, through June 1, 2019.Following a preregistered Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, 2 independent raters reviewed titles, abstracts, and full-text articles. English-language articles comparing monetary delay discounting between participants with psychiatric disorders and controls were included.Hedges g effect sizes were computed and random-effects models were used for all analyses. Heterogeneity statistics, one-study-removed analyses, and publication bias indices were also examined.Categorical comparisons of delay discounting between a psychiatric group and a control group.The sample included 57 effect sizes from 43 studies across 8 diagnostic categories. Significantly steeper discounting for individuals with a psychiatric disorder compared with controls was observed for major depressive disorder (Hedges g = 0.37; P = .002; k = 7), schizophrenia (Hedges g = 0.46; P = .004; k = 12), borderline personality disorder (Hedges g = 0.60; P < .001; k = 8), bipolar disorder (Hedges g = 0.68; P < .001; k = 4), bulimia nervosa (Hedges g = 0.41; P = .001; k = 4), and binge-eating disorder (Hedges g = 0.34; P = .001; k = 7). In contrast, anorexia nervosa exhibited statistically significantly shallower discounting (Hedges g = -0.30; P < .001; k = 10). Modest evidence of publication bias was indicated by a statistically significant Egger test for schizophrenia and at the aggregate level across studies.Results of this study appear to provide empirical support for delay discounting as a transdiagnostic process across most of the psychiatric disorders examined; the literature search also revealed limited studies in some disorders, notably posttraumatic stress disorder, which is a priority area for research.
SRSF3-Regulated RNA Alternative Splicing Promotes Glioblastoma Tumorigenicity by Affecting Multiple Cellular Processes
Authors: Xiao Song, Xuechao Wan, Tianzhi Huang, Chang Zeng, Namratha Sastry, Bingli Wu, C. David James, Craig Horbinski, Ichiro Nakano, Wei Zhang, Bo Hu, Shi-Yuan Cheng
Journal: Cancer Research (2019)

Misregulated alternative RNA splicing (AS) contributes to the tumorigenesis and progression of human cancers, including glioblastoma (GBM). Here, we showed that a major splicing factor, serine and arginine rich splicing factor 3 (SRSF3), was frequently upregulated in clinical glioma specimens and that elevated SRSF3 was associated with tumor progression and a poor prognosis for patients with glioma. In patient-derived glioma stem-like cells (GSC), SRSF3 expression promoted cell proliferation, self-renewal, and tumorigenesis. Transcriptomic profiling identified more than 1,000 SRSF3-affected AS events, with a preference for exon skipping in genes involved with cell mitosis. Motif analysis identified the sequence of CA(G/C/A)CC(C/A) as a potential exonic splicing enhancer for these SRSF3-regulated exons. To evaluate the biological impact of SRSF3-affected AS events, four candidates were selected whose AS correlated with SRSF3 expression in glioma tissues, and their splicing pattern was modified using a CRISPR/Cas9 approach. Two functionally validated AS candidates were further investigated for the mechanisms underlying their isoform-specific functions. Specifically, following knockout of SRSF3, transcription factor ETS variant 1 (ETV1) gene showed exon skipping at exon 7, while nudE neurodevelopment protein 1 (NDE1) gene showed replacement of terminal exon 9 with a mutually exclusive exon 9'. SRSF3-regulated AS of these two genes markedly increased their oncogenic activity in GSCs. Taken together, our data demonstrate that SRSF3 is a key regulator of AS in GBM and that understanding mechanisms of misregulated AS could provide critical insights for developing effective therapeutic strategies against GBMs. SIGNIFICANCE: SRSF3 is a significant regulator of glioma-associated alternative splicing, implicating SRSF3 as an oncogenic factor that contributes to the tumor biology of GBM.
Pancreaticobiliary therapy (biliary): plastic stents, metal stents and … beyond
Authors: Guido Costamagna, David L. Carr-Locke
Journal: Endoscopy (2019)

When Nib Soehendra described in 1980 the technique of endoscopic placement of a stent to bypass a stricture of the common bile duct (CBD) [1], a new epoch of endotherapy was born. Soehendra’s stents were home-made from a Teflon tube, cut to the proper length and customized with hot water. Later, companies producing endoscopic accessories turned to polyethylene, a material with a smoother surface, and introduced commercially available products to the market, although Soehendra remained faithful to Teflon! The shape of the stents was also modified, from a single-pigtail configuration to a straight design, following the ideas of Kees Huibregtse in the Netherlands, and Peter Cotton and Joseph Leung who had recently moved from London and Hong Kong to the United States.
2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)
Authors: Stavros V. Konstantinides, Guy Meyer, Cecilia Becattini, Héctor Bueno, Geert-Jan Geersing, Veli-Pekka Harjola, Menno V. Huisman, Marc Humbert, Catriona Sian Jennings, David Jiménez, Nils Kucher, Irene Marthe Lang, Mareike Lankeit, Roberto Lorusso, Lucia Mazzolai, Nicolas Meneveau, Fionnuala Ní Áinle, Paolo Prandoni, Piotr Pruszczyk, Marc Righini, Adam Torbicki, Eric Van Belle, José Luis Zamorano
Journal: European Respiratory Journal (2019)

<b>New @ESCardio Guidelines for the Diagnosis and Management of Acute #PulmonaryEmbolism developed in collaboration with @EuroRespSoc now available: #cardiotwitter @erspublications</b>http://bit.ly/2HnrJaj
Analysis of Tumor Genomic Pathway Alterations Using Broad-Panel Next-Generation Sequencing in Surgically Resected Lung Adenocarcinoma
Authors: Jian Zhou, Francisco Sanchez-Vega, Raul Caso, Kay See Tan, Whitney S. Brandt, Gregory D. Jones, Shi Yan, Prasad S. Adusumilli, Matthew Bott, James Huang, James M. Isbell, Smita Sihag, Daniela Molena, Valerie W. Rusch, Walid K. Chatila, Natasha Rekhtman, Fan Yang, Marc Ladanyi, David B. Solit, Michael F. Berger, Nikolaus Schultz, David R. Jones
Journal: Clinical Cancer Research (2019)

The majority of broad-panel tumor genomic profiling has used a gene-centric approach, although much of that data is unused in clinical decision making. We hypothesized that a pathway-centric approach using next-generation sequencing (NGS), combined with conventional clinicopathologic features, may better predict disease-free survival (DFS) in early stage lung adenocarcinoma.Utilizing our prospectively maintained database, we analyzed 492 patients with primary, untreated, completely surgically resected lung adenocarcinoma. Ten canonical pathways were analyzed using broad-panel NGS. The correlations of DFS and number (and type) of pathway (NPA) were analyzed using the Kaplan-Meier method and log-rank test. Associations between altered pathways and clinicopathologic variables, as well as identification of actionable therapeutic strategies were explored.Median NPA for the cohort was two (range, 0-5). Smoking status, solid morphologic appearance on preoperative CT, maximal standardized uptake value, pathologic tumor size, aggressive histologic subtype, lymphovascular invasion, visceral pleural invasion, and positive lymph nodes were significantly associated with NPA (P < 0.05). Of 543 actionable genetic alterations identified, 455 (84%) were within the RTK/RAS pathway. A total of 86 tumors had actionable therapeutic genomic alterations in >1 pathway. On multivariable analysis, higher NPA was significantly associated with worse DFS (HR, 1.31; P = 0.014).NPA and specific pathway alterations are associated with clinicopathologic features in patients with surgically resected lung adenocarcinoma. Cell cycle, Hippo, TGFβ, and p53 pathway alterations are associated with poor DFS. Finally, NPA is an independent risk factor for poor DFS in our cohort.See related commentary by Blakely, p. 7269.
Clinical outcome of treatment with pemetrexed/cisplatin in patients with EGFR-mutation negative (EGFR–) metastatic non-small cell lung cancer (NSCLC).
Authors: Anna E Storozhakova, Liubov Yu Vladimirova, Oleg Ivanovich Kit
Journal: Journal of Clinical Oncology (2013)

e19047 Background: Althogh some improvements of the treatment of NSCLC were achieved recently the results of therapy in patients with EGFR– adenocarcinoma are still poor. The purpose of the study was to evaluate the effectiveness and toxicity of the treatment in these patients. Methods: Pts with EGFR– adenocarcinoma were recruited in 2010-2011. Key elegibility criteria included measurable EGFR– adenocarcinoma, confirmed stage IV, ECOG ≤2, adequate organ function, CT-naïve pts. Pemetrexed/cisplatin was administered 500/75 mg/ m² 1 day q3w up to 6 cycles. Treatment was continued until progression or unacceptable toxicity. A total of 94 cycles were estimated. Endpoints include response rate, OS, PFS and safety. Results: 16 pts (12 male and 4 female) were recruited. Mean age was 56.6±5.6. Infiltrative EGFR– adenocarcinoma was found in 93.75%, adenocarcinoma mixed with squamous cancer – 6.25% (1pt). All the pts had ≥2 disease sites: lung 16 (100%), lymph nodes 16 (100%), bones 5 (31.25%), liver 7 (43.75%), brain 1 (6.25%). Mean number of disease sites = 2.8. Overall RR was 43.75% (7) including 2 CR (12.5%), 3 PR (18.75%) and 2 SD (12.5%). Med OS = 16.1 mo ±1.5, Med PFS = 7.4 mo ±0.8. 6 pts (37.5%) are alive till the abstract submission. Most common adverse events in 94 cycles were neutropenia 1/2 Gd. -30.85, 3/4 Gd. -6.4%, thrombocytopenia 1/2 Gd .-2.1% cycles. Nonhematological toxicity included nausea 1/2 Gd.- 74.5%, 3/4 Gd.- 12.7%, vomiting 1/2 Gd.- 43.6%, 3/4 Gd.- 6.4%, hyperthermia 2 Gd. –6.4%, fatigue 1/2 Gd.-15.95%, hiccough 2 Gd.-2.1%. No treatment-related mortality occurred. Conclusions: Pemetrexed/cisplatin combination had a satisfactory efficacy and controlled toxicity as well in patients with EGFR-mutation negative (EGFR–) metastatic NSCLC. The favorable PFS and OS allow to use it in clinical setting widely.
Prevalence of Financial Considerations Documented in Primary Care Encounters as Identified by Natural Language Processing Methods
Authors: Meliha Skaljic, Ihsaan H. Patel, Amelia M. Pellegrini, Victor M. Castro, Roy H. Perlis, Deborah D. Gordon
Journal: JAMA Network Open (2019)

Quantifying patient-physician cost conversations is challenging but important as out-of-pocket spending by US patients increases and patients are increasingly interested in discussing costs with their physicians.To characterize the prevalence of financial considerations documented in narrative clinical records of primary care encounters and their association with patient-level features.This cohort study applied natural language processing to narrative clinical notes obtained from electronic health records for adult primary care visits. Participants included patients aged 18 years and older with at least 1 primary care visit for an annual preventive examination at outpatient clinics at a US academic health system between January 2, 2008, and July 30, 2013. Data were analyzed in March 2019.Presence of financial content documented in narrative clinical notes.The data set included 222 457 primary care visits for 46 244 individuals aged 18 years and older; 30 556 patients (60.1%) were female, 27 869 patients (60.3%) were white, and the mean (SD) age was 51.3 (17.7) years. In total, 6058 patients (13.1%) had at least 1 narrative clinical note indicating a financial conversation with their physician. In fully adjusted regression models, the odds of having a financial note were greater among patients with Medicare (odds ratio [OR], 1.27; 95% CI, 1.15-1.41; P < .001) or Medicaid (OR, 1.43; 95% CI, 1.25-1.64; P < .001) insurance, those residing in zip codes with lower median income (OR, 0.97; 95% CI, 0.96-0.98; P < .001), black individuals (OR, 1.40; 95% CI, 1.28-1.53; P < .001), Hispanic individuals (OR, 1.10; 95% CI, 1.01-1.20; P = .03), and those who were unmarried (OR, 1.23; 95% CI, 1.15-1.33; P < .001).Cost considerations were more likely to be noted in annual preventive examinations than previously observed in intensive care unit admissions, but still infrequently. Associations with particular patient subgroups may indicate differential financial burden or willingness to discuss financial concerns.
Pediatric Cancer Registry in Turkey 2009-2018 (TPOG &amp; TPHD).
Authors: M. Tezer Kutluk, Akif Yeşilipek
Journal: Journal of Clinical Oncology (2019)

e21510 Background: In Children and adolescents aged 0-14, each year more than 200.000 new cancer cases are expected at global level. For the planning and implementation of an effective pediatric cancer control program, pediatric cancer registries are essential. The long term survival rates have been improved to 85% in high income countries, however it is still less than this in LMICs. This work presents the most updated results of the pediatric cancer registry in Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the Pediatric Cancer Registry in 2002. The childhood cancer cases registered between 2009-2018 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 10 years from 2009 to 2018, 15713 cases were registered. For all cases, median age was 6.7 year (0-17; M/F 8838/6867, 3 hermaphrodite, 5 unknown). Age distribution was 0-4 yrs, 40.7%; 5-9 yrs, 24.4%; 10-14 yrs, 23.2%; 15-19 yrs, 11.7%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (4368, 27.8%, 5.4, 2519/1849); Lymphoma &amp; other RES tumors (2996, 19.1%, 9.7, 2012/979, 1 hermaphrodite &amp; 4 unknown); CNS [brain &amp; spinal] (2089, 13.3%, 7.1, 1142/947); Symphatetic system (1243, 7.9%, 2.4, 650/593); Retinoblastoma (358, 2.3%, 1.4, 204/154); Renal (788, 5.0%, 3.3, 369/419); Liver (260, 1.7%, 1.8, 143/117); Malignant bone (1030, 6.6%, 12.6, 566/464); Soft tissue sarcomas (1052, 6.7%, 7.4, 611/441); Germ cell (971, 6.2%, 8.4, 346/622, 2 hermaphrodite, 1 unknown); Carcinoma &amp; other malignant epithelial (462, 2.9%, 13.7, 226/236); Other/non-specific malignant (96, 0.5%, 7.8, 50/46). Five year survival rate was found as 70.8%. Conclusions: This registry has been used widely among health care professionals since its establishment in 2002. Survival rates for children and adolescents has been improved to 70%. This level of survival is at the acceptable level for an upper middle income country. This registry became a useful source for investigator and decision makers at national and international level.