tbuckley/cabot-search huggingface dataset:
T(6;14)(q25;q32) involves BCL11B and is highly associated with mixed-phenotype acute leukemia, T/myeloid
Authors: Wei Wang, Hannah Beird, Caleb Jonathan Kroll, Shimin Hu, Carlos E. Bueso-Ramos, Hong Fang, Guilin Tang, Zhenya Tang, Feng Wang, Koichi Takahashi, M. James You, Joseph D. Khoury, L. Jeffrey Medeiros, P. Andrew Futreal
Journal: Leukemia (2020)
The genome of Shaw’s sea snake (Hydrophis curtus) reveals secondary adaptation to its marine environment
Authors: Changjun Peng, Jin-Long Ren, Cao Deng, Dechun Jiang, Jichao Wang, Jiangyong Qu, Jiang Chang, Chaochao Yan, Ke Jiang, Robert W Murphy, Dong-Dong Wu, Jia-Tang Li
Journal: Molecular Biology and Evolution (2020)

The transition of terrestrial snakes to marine life ∼10 Ma is ideal for exploring adaptive evolution. Sea snakes possess phenotype specializations including laterally compressed bodies, paddle-shaped tails, valvular nostrils, cutaneous respiration, elongated lungs, and salt glands, yet, knowledge on the genetic underpinnings of the transition remains limited. Herein, we report the first genome of Shaw's sea snake (Hydrophis curtus) and use it to investigate sea snake secondary marine adaptation. A hybrid assembly strategy obtains a high-quality genome. Gene family analyses date a pulsed coding-gene expansion to ∼20 Ma, and these genes associate strongly with adaptations to marine environments. Analyses of selection pressure and convergent evolution discover the rapid evolution of protein-coding genes, and some convergent features. Additionally, 108 conserved noncoding elements appear to have evolved quickly, and these may underpin the phenotypic changes. Transposon elements may contribute to adaptive specializations by inserting into genomic regions around functionally related coding genes. The integration of genomic and transcriptomic analyses indicates independent origins and different components in sea snake and terrestrial snake venom; the venom gland of the sea snake harbors the highest PLA2 (17.23%) expression in selected elapids and these genes may organize tandemly in the genome. These analyses provide insights into the genetic mechanisms that underlay the secondary adaptation to marine and venom production of this sea snake.
Result of phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small cell lung cancer.
Authors: Yan Sun, Ying Cheng, Xuezhi Hao, Jie Wang, Chengping Hu, Baohui Han, Xiaoqing Liu, Li Zhang, Huiping Wan, Zhongjun Xia, Yunpeng Liu, Wei Li, Mei Hou, Helong Zhang, Qingyu Xiu, Yunzhong Zhu, Jifeng Feng, Shukui Qin
Journal: Journal of Clinical Oncology (2013)

7507 Background: Etoposide combined with cisplatin (EP) has been the first-line chemotherapy regimen for small cell lung cancer (SCLC) for &gt;20 years; however, a more effective regimen has been recommended by many clinical oncologists. Thus, we here present our preliminary results of a phase III clinical trial of the novel drug amrubicin in combination with cisplatin (AP) in comparison to EP in patients with previously untreated extensive SCLC (ED-SCLC). Methods: A total of 299 previously untreated ED-SCLC patients were randomized (ratio, 1:1) into two treatment groups: (1) the AP group (n = 149): 4–6 cycles of amrubicin (40 mg/m 2 /day on days 1–3) and cisplatin (60 mg/m 2 /day on day 1) and (2) the EP group (n = 150): 4–6 cycles of etoposide (100 mg/m 2 /day on days 1–3) and cisplatin (80 mg/m 2 /day on day 1 every 21 days). Patients were evaluated for therapy response and electrocardiography results every 2 cycles. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and general safety. Results: Baseline characteristics were similar among the two groups. For AP and EP groups, the median OS was 11.79 and 10.28 months, the median PFS was 7.13 and 6.37 months, and ORR was 69.8% and 57.3%, respectively. The most frequent adverse events (≥grade 3) in AP and EP groups were bone marrow failure (23.5% and 21.3%, respectively), neutropenia (54.4% and 44.0%, respectively), and leukopenia (34.9% and 19.3%, respectively). Conclusions: Our phase III trial demonstrated that for previously untreated ED-SCLC patients, AP therapy was not inferior to EP therapy in terms of OS and offered predictable and manageable toxicities. Clinical trial information: NCT00660504.
Do men want to perform testicular self-examination?
Authors: Shawn Dason, Sarah Beebe, Alicia Scimeca, Tasha Posid
Journal: Journal of Clinical Oncology (2020)

395 Background: Early detection of testicular cancer (TC) may reduce the required burden of therapy. The long-term adverse effects of therapy in TC survivors are becoming increasingly recognized. The U.S. Preventive Services Task Force (USPSTF) currently recommends against testicular self-examinations (TSE) for TC screening due to a low incidence and lack of data to support a benefit. Our objective was to better understand the baseline knowledge and practices of men in the general population regarding TC/TSE in an effort to understand whether current screening guidelines reflect their viewpoint. Methods: This was a prospective survey study (51 questions). Participants (N=250; MAge=33 years, IQR: 28-39) were recruited via Amazon Mechanical Turk, a crowdsourcing platform used recruit minimally compensated participants. This platform has been extensively validated in US populations as being concordant with surveys conducted by other methods. Results: Most respondents were white (65.6%), had a college degree (76.4%), and did not work in a medical field (89.6%). Men rated themselves as “somewhat unknowledgeable” about testicular cancer, with no respondents considering themselves “very knowledgeable”. Only 26.4% of men knew that testicular cancer was curable most of the time. Despite 90.8% of men feeling that their doctor had at least some role in discussing TC/TSE, only 17.2% had actually discussed these topics with their doctor. Even after being informed of the rationale behind USPSTF recommendations, only 8% of men thought that potential false positives of TSE would be more important than the rare chance of finding early testicular cancer. Conclusions: Based on the largest survey of American men regarding testicular self-examination since the 2009 USPSTF recommendations, men don’t feel knowledgeable about testicular cancer, have a favorable attitude towards testicular self-examination, and want their doctor to discuss these topics. Shared decision making regarding testicular cancer screening is warranted given the low risk of harm and patient interest.
Pembrolizumab with chemoradiotherapy as treatment for muscle invasive bladder cancer: A planned interim analysis of safety and efficacy of the PCR-MIB phase II clinical trial (ANZUP 1502).
Authors: Andrew James Weickhardt, Farshad Foroudi, Nathan Lawrentschuk, Laura Galleta, Amanda Seegum, Alan Herschtal, Emma Link, Margaret Mary McJannett, Elizabeth Chien Hern Liow, Peter S. Grimison, Alison Yan Zhang, NItya Patanjali, Siobhan Ng, Robert Goodwin, Colin Tang, Colin Chen, Elizabeth J. Hovey, George Hruby, Alexander David Guminski, Ian D. Davis
Journal: Journal of Clinical Oncology (2020)

485 Background: In patients (pts) with muscle invasive bladder (MIBC) suitable for curative definitive chemoradiotherapy (CRT), we hypothesise that the addition of pembrolizumab may be safe and improve efficacy. A pre-planned safety analysis was performed after the first 10 of planned 30 pts were enrolled and completed treatment. Methods: Patients with maximally resected non-metastatic MIBC and ECOG 0-1, who desire bladder preservation or are ineligible for cystectomy were treated with 64Gy in 32 daily radiation fractions to the whole bladder alone over 6.5 weeks in combination with 6 concurrent doses of weekly cisplatin at 35mg/m2 IV. Pembrolizumab was commenced concurrently with radiation and given flat-dose 200mg IV q21 days for 7 doses. Surveillance cystoscopy, urine cytology and CT chest-abdomen-pelvis were performed 12 &amp; 24 weeks post CRT. The primary endpoint is feasibility, defined by a satisfactory low rate of unacceptable toxicity of a) G3-4 non-urinary adverse events (AE) or b) failure of completion of planned CRT according to defined parameters. Secondary endpoints include complete cystoscopic response without metastatic disease at 12 &amp; 24 weeks, loco-regional PFS, metastatic DFS, and overall survival. A 2-stage design was planned, with accrual to be halted if &gt;5 of the first 10 pts experienced unacceptable toxicity up to 12 weeks post treatment. Results: All 10 pts completed the course of CRT and pembrolizumab without alteration in radiation dose or schedule. 1 patient had a dose of cisplatin withheld. 4/10 pts experienced G3-4 non-urinary adverse events within 12 weeks of completing treatment. One immune related AE interrupted pembrolizumab delivery (G2 nephritis). By week 24, 9/10 pts achieved a complete cystoscopic response to treatment post CRT and were free of distant metastatic disease. Conclusions: Interim results indicate that pembrolizumab and CRT shows satisfactory safety, and promising efficacy. There were no unexpected safety signals. Follow up of these and additional pts will better define the efficacy and safety of the combination. Enrolment is ongoing with 20 pts recruited out of a planned total of 30. Clinical trial information: NCT02662062.
Predicting the Landscape of Recombination Using Deep Learning
Authors: Jeffrey R Adrion, Jared G Galloway, Andrew D Kern
Journal: Molecular Biology and Evolution (2020)

Abstract Accurately inferring the genome-wide landscape of recombination rates in natural populations is a central aim in genomics, as patterns of linkage influence everything from genetic mapping to understanding evolutionary history. Here, we describe recombination landscape estimation using recurrent neural networks (ReLERNN), a deep learning method for estimating a genome-wide recombination map that is accurate even with small numbers of pooled or individually sequenced genomes. Rather than use summaries of linkage disequilibrium as its input, ReLERNN takes columns from a genotype alignment, which are then modeled as a sequence across the genome using a recurrent neural network. We demonstrate that ReLERNN improves accuracy and reduces bias relative to existing methods and maintains high accuracy in the face of demographic model misspecification, missing genotype calls, and genome inaccessibility. We apply ReLERNN to natural populations of African Drosophila melanogaster and show that genome-wide recombination landscapes, although largely correlated among populations, exhibit important population-specific differences. Lastly, we connect the inferred patterns of recombination with the frequencies of major inversions segregating in natural Drosophila populations.
Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists.
Authors: Eugene Blanchard Cone, Maya Marchese, Stephen Reese, Junaid Nabi, Kerry L. Kilbridge, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2020)

34 Background: Gonadotropic releasing hormone (GnRH) agonists and antagonists are first-line for advanced prostate cancer, but may be associated with cardiac toxicity. Observational studies show a relatively lower risk for GnRH antagonists, but a randomized trial found no difference. We compared the reporting of cardiac events for GnRH agonists and antagonists. Methods: We used VigiBase, the World Health Organization global database of case safety reports, which collects data from more than 130 countries to extract drug-adverse event (AE) pairs. Using Medical Dictionary for Regulatory Activities terminology, we identified AEs related to GnRH antagonist (degarelix) or agonist (leuprolide, goserelin, triptorelin, histrelin) therapy for prostate cancer, including myocardial infarction, heart failure, cardiomyopathies, new-onset valvular dysfunction, and other major cardiac events. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR &gt; 1 reflects a disproportionality signal that more AEs are observed than expected. Results: We found 10,504 AEs for GnRH agonists, and 1,606 for GnRH antagonists; 805 (7.7%) were cardiac for agonists, and 102 for antagonists (6.4%). We found no signal for overall cardiac events or any subgrouping for GnRH antagonists, but identified a signal both for overall cardiac events (ROR 1.20, 95% CI 1.12-1.29) and myocardial infarction (1.76, 1.57-1.97) for GnRH agonists. Conclusions: Using validated pharmacovigilance methodology, we found a signal for myocardial infarction for GnRH agonists, but did not detect one for GnRH antagonists. As cardiovascular disease is the most common cause of non-cancer death in prostate cancer patients, this finding is of specific relevance in the current era of novel second-line anti-androgen therapies which may compound toxicity when added to first-line therapy. The relative cardiac toxicity of GnRH agonist therapy compared to GnRH antagonists merits renewed attention.
Abstract 16013: The Role of Poldip2/NOX4 in Redox Regulation of Actin During Integrin-Mediated Cell Adhesion
Authors: Qian Xu, Sasha Vukelic, Elizabeth Faidley, Bernard Lassegue, Kathy Griendling
Journal: Circulation (2017)

Actin cytoskeleton assembly and organization, as a result of focal adhesion formation during cell adhesion, has been demonstrated to be highly related to reactive oxygen species (ROS) and cellular ...
Geographic and Ethnic Heterogeneity of Germline <i>BRCA1</i> or <i>BRCA2</i> Mutation Prevalence Among Patients With Metastatic Pancreatic Cancer Screened for Entry Into the POLO Trial
Authors: Talia Golan, Hedy L. Kindler, Joon Oh Park, Michele Reni, Teresa Macarulla, Pascal Hammel, Eric Van Cutsem, Dirk Arnold, Daniel Hochhauser, David McGuinness, Gershon Y. Locker, Teodora Goranova, Philipp Schatz, Yu-Zhen Liu, Michael J. Hall
Journal: Journal of Clinical Oncology (2020)

Germline BRCA1 and/or BRCA2 mutations (gBRCAms) are risk factors for pancreatic cancer. The extent to which demographic and geographic factors affect the uptake of gBRCAm testing in pancreatic cancer (PC) is unknown.We conducted a retrospective, descriptive analysis of demographic/geographic data from the first 2,206 patients with metastatic PC (mPC) screened for eligibility to enter the phase III POLO trial of maintenance olaparib. No formal statistical tests were performed.Of 2,167 patients with previously unknown gBRCAm status, 128 (5.9%) had a newly identified gBRCAm; rates were highest in the United States, France, and Israel (9.5%, 7.6%, and 7.4%, respectively). When including patients with a previously known gBRCAm, prevalence rose to 7.2% (or 5.8% after excluding populations enriched in Ashkenazi Jews, who are known to have a high rate of BRCA1 and BRCA2 founder mutations). Patients with a gBRCAm were slightly younger (57.9 v 61.1 years) and more likely to have early-onset mPC than those without. Higher newly identified gBRCAm prevalence was observed among African American (n = 28) versus white (n = 1,808), Asian (n = 218), and other (n = 61) patients (10.7% v 6.1%, 5.0%, and 1.6%, respectively). Of 139 white patients with a gBRCAm, 110 were newly identified during screening; the majority of gBRCAms in African American, Asian, and Hispanic patients (n = 3, n = 11, and n = 5, respectively) were newly identified.We identified substantial geographic and some racial variability in gBRCAm prevalence among patients with mPC, an important consideration given the increased use of familial screening and possible future use of targeted therapies in this setting. Although our study included small numbers of nonwhite patients, prior knowledge of their gBRCAm status was limited compared with their white counterparts, which suggests disparities in genetic testing uptake.
Re: Van Asten et al.: No CFH/ARMS2 interaction with omega-3 fatty acids, low vs high zinc, or β-carotene versus Lutein and Zeaxanthin on progression of age-related macular degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18 (Ophthalmology. 2019;126:1541-1548)
Authors: Brent Zanke, Rafal Kustra
Journal: Ophthalmology (2020)
Sputum ILC2s are increased in COPD subjects with eosinophils
Authors: Cameron Flayer, Angela Linderholm, Lisa Franzi, Maya Juarez, Tina Tham, Willis Bowman, Imre Redai, Alyssa Bowlsby, Michael Schivo, Brooks Kuhn, Amir Zeki, Angela Haczku
Journal: Journal of Allergy and Clinical Immunology (2020)
GEMINI: An open-label, single-arm, phase II trial of intraoperative gemcitabine intravesical instillation in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma.
Authors: Vignesh T. Packiam, Bradley C. Leibovich, R. Houston Thompson, Aaron M. Potretzke, George K. Chow, Matthew K. Tollefson, Phillip J. Schulte, Mark Tyson, Timothy D. Lyon, Stephen A. Boorjian
Journal: Journal of Clinical Oncology (2020)

TPS594 Background: The standard treatment for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff resection. Subsequent intravesical recurrence is common and results in patient morbidity and increased healthcare cost. Level 1 evidence has demonstrated reduction of intravesical recurrence with instillation of intravesical Mitomycin C at 10 days following RNU. However, there has been limited adoption of Mitomycin C due to concerns for toxicity and logistics of postoperative drug delivery. Meanwhile, immediate intravesical gemcitabine has been shown to reduce intravesical recurrence following transurethral resection of bladder cancers without increasing toxicity compared to placebo. Moreover, small series have suggested improved efficacy of intraoperative intravesical chemotherapy for RNU. The purpose of the GEMINI trial, therefore, is to prospectively establish the safety and efficacy of intraoperative instillation of intravesical gemcitabine in patients undergoing RNU for UTUC. Methods: GEMINI is a multi-center open-label, single-arm, Phase II study that aims to enroll 90 patients with cTa-T4N0M0 UTUC. Patients receive intraoperative intravesical instillation of gemcitabine at the beginning of RNU, to be held in the bladder for at least 1 hour. The instilled drug will be drained prior to resection of the bladder cuff. Patients will undergo standard of care postoperative surveillance, including cystoscopy at 3, 6, 12, 18, and 24 months. The primary endpoint is 1-year intravesical recurrence-free survival. The historical event rate for no treatment is 30%, and we estimated a 40% relative reduction in event rate with gemcitabine. The study is powered to provide 80% power to detect this difference based on a one-sided exact test of proportions with alpha level 0.05. Secondary endpoints include time to recurrence and stratification of recurrence free survival by tumor grade, tumor stage, neoadjuvant chemotherapy, ureteral tumor location, and history of bladder cancer. Safety and adverse event endpoints will be evaluated. Complete accrual is expected within 3 years.
Cost-effectiveness of radical cystectomy versus trimodality therapy for muscle invasive bladder cancer.
Authors: Nathan Suskovic, Ann C. Raldow, Trevor Joseph Royce, Angela Smith
Journal: Journal of Clinical Oncology (2020)

575 Background: Muscle invasive bladder cancer (MIBC) comprises 25% of all bladder cancers at the time of diagnosis. Radical Cystectomy (RC) has traditionally been the gold standard curative treatment for MIBC. Trimodality therapy (TMT) with maximal transurethral resection of bladder tumor, chemotherapy, and radiation is a treatment alternative and Category 1 recommendation by the NCCN. TMT has shown equivalent survival for carefully selected patients. However, the comparative cost effectiveness between RC and TMT is unknown. Therefore, the purpose of this study was to compare the cost-effectiveness of RC versus TMT for MIBC. Methods: We developed a Markov model using TreeAge software to simulate a 5-year outcome for one million 65-year old hypothetical patients with MIBC undergoing either RC or TMT. Hypothetical patients in the RC treatment pathway would have an adverse event, no adverse event, or immediate death after surgery. After RC, patients either would have no evidence of disease or transition to locoregional recurrence, metastatic recurrence, or death. Hypothetical patients in the TMT treatment pathway would either have an adverse event or no adverse from treatment. After TMT, patients either would have disease-free bladder intact survival or transition to locoregional failure, metastatic recurrence, or death. Patients with locoregional failure from TMT transition into non-salvageable disease or salvageable disease. Patients with salvageable disease prompted a salvage cystectomy. Model probabilities and utilities were extracted from the literature. Costs were derived from 2019 National Medicare Fee Schedule. Results: RC and TMT were associated with quality adjusted life years (QALY) of 2.88 and 3.38 respectively (incremental QALYs of 0.5 favoring TMT). The mean costs of RC and TMT were $37,107 and $23,916 respectively. TMT was less expensive with an incremental cost of $13,191. Conclusions: In patients aged 65 and older with MIBC, TMT was the dominant strategy as compared to RC, as it was both cheaper and associated with increased QALYs based upon model assumptions. The results of this study are the first to evaluate the cost effectiveness of RC and TMT.
A Low-Carbon Future Could Improve Global Health and Achieve Economic Benefits
Authors: Jonathan A. Patz, Valerie J. Stull, Vijay S. Limaye
Journal: JAMA (2020)

This Viewpoint proposes that framing climate change as a human health crisis could accelerate climate action, and reviews evidence pointing toward the health benefits of transitioning to renewable energy, plant-based diets, and a global lower carbon footprint.
Mechanisms of Allergen Capture by Skin DC Differ between naïve and sensitized individuals in a specific-IgG dependent manner
Authors: Pierre-Louis Hervé, Nathalie Oreal, Audrey Perrin, Laetitia Gaulme, Camille Plaquet, Jean-Louis Labernardière, Hugh Sampson, Fabrice Porcheray
Journal: Journal of Allergy and Clinical Immunology (2020)