tbuckley/cabot-search huggingface dataset:
Response to single-agent (SA) chemotherapy (CTx) after immunotherapy exposure in non-small cell lung cancer (NSCLC).
Authors: Gustavo Schvartsman, S. Andrew Peng, Giorgios Bis, J. Jack Lee, Marcelo Felipe Kuperman Benveniste, Jianjun Zhang, Waree Rinsurongkawong, Jeff Lewis, Emily Roarty, Lara Lacerda, Jack A. Roth, Stephen Swisher, John Heymach, Frank V. Fossella, William Nassib William
Journal: Journal of Clinical Oncology (2017)

9083 Background: Overall response rates (ORR) to 2 nd -line SACTx in NSCLC have consistently not exceeded 15%. Exploratory analysis of clinical trials in various tumor types have demonstrated potential improvements in ORR to CTx after exposure to vaccine-based immunotherapy. The objective of this retrospective study was to determine if SACTx (3 rd -line or beyond) would yield improved ORR when given after exposure to programmed-death-(ligand)1 inhibitors (PD1i) in metastatic NSCLC. Methods: Eligibility criteria - patients registered in the Thoracic GEMINI database of MD Anderson treated between 06/12 and 11/16 who received at least one SACTx as 3 rd -line or beyond, following progression after platinum-based CTx and PD1i. We computed efficacy outcomes to each therapy, including ORR by RECIST v1.1, progression-free survival (PFS) and overall survival (OS). Results: Of 306 PD1i-treated patients registered in the database, 28 met eligibility criteria - 54% were male, median age 66 years, 82% adenocarcinoma, 29% never smokers. The PD1i and SACTx most commonly used were nivolumab (82%) and docetaxel (54%). ORR to SACTx after exposure to PD1i was 39% (11/28 patients, 8 confirmed). In contrast, ORR to 1 st -line CTx in this cohort was 30% (Table). Liver metastasis and pembrolizumab as the PD1i of choice were the only factors associated with response to SACTx on univariate analysis (p &lt; 0.05). Conclusions: In NSCLC patients, ORR to SACTx after immunotherapy exposure was higher compared to historical data from the pre-PD1i era, and approached ORR to 1 st -line platinum-based CTx. Further investigation of a possible chemosensitization effect by immunotherapy is warranted. [Table: see text]
Outcomes of Patients with Pre-Existing Invasive Fungal Disease Undergoing Allogeneic Haematopoietic Stem Cell Transplantation — 5 Years Single Centre Experience
Authors: Varun Mehra, Eleanor Barnwell, Ute Boczek, Stefanie Widya, Kavita Raj, Hugues De Lavallade, Donal McLornan, Victoria Potter, Carmel Rice, Christina Lim, Michelle Kenyon, Alessandra Bisquera, Judith Marsh, M. Mansour Ceesay, Antonio Pagliuca, Ghulam Mufti
Journal: Blood (2017)
Pregnancy in Patients With Chronic Myeloid Leukemia
Authors: Ellin Berman
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">Estimates suggest that nearly 30% of patients diagnosed with chronic myeloid leukemia (CML) are aged &lt;49 years, with approximately half being women. For many of these women, childbearing concerns are a major factor as they initiate treatment with tyrosine kinase inhibitors, which are known to be teratogenic. During her presentation at the NCCN 23rd Annual Conference, Dr. Berman identified the challenges in helping women undergoing treatment for CML who want to have children, and emphasized the importance of an individualized and multidisciplinary approach to management. In addition, she encouraged NCCN to create a pregnancy registry of this patient population to enable clinicians to collect firm data to guide clinical decision-making. </section>
AB0079 Cyclophosphamide exposure during pregnancy: two cases
Authors: Ý Ertenli, V Cobankara, S Apras, S Kiraz, MA Oztürk, M Çalgüneri
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Lupus nephritis is a severe clinical entity that should be treated with cytotoxic drugs. Cyclophospamide is an effective cytotoxic agent against lupus nephritis. Cyclophosphamide is probably a potent teratogen. Severe birth defects reported in several cases after cyclophosphamide given as little as 200 mg during pregnancy. Some authorities, however, recommend the use of cyclophosphamide in life-threatening lupus during pregnancy. <h3>Objectives</h3> In this report, we present two cases that used cyclophosphamide during unpredicted pregnancy. <h3>Methods</h3> <h3>Results</h3> Case-I: A 20-year-old female was diagnosed as SLE with arthritis, photosensitivity, haemolytic anaemia, leukopenia, proteinuria and positive antinuclear and anti-ds-DNA antibodies. Anti-phospholipid antibodies were negative. The disease remained under control with corticosteroids, hydroxychloroquine and cyclophosphamide. In June 1999, it was noticed that she had been pregnant for 24 weeks and she had received five cycles of intravenous pulse cyclophosphamide (500 mg for each cycle, 2500 mg total dose). Until the end of pregnancy, the treatment was continued with corticosteroids. The baby is now 16 months-old and in good health. Case-II: A 21-year-old female patient presented with arthritis, carditis, and proteinuria. She had positive antinuclear, anti-ds-DNA, and negative anti-phospholipid antibodies, and the diagnosis of SLE was made. She was treated with oral corticosteroids and intravenous cyclophosphamide. In September 1999, while she was in remission, it was noticed that she had been pregnant for 12 weeks. Since that time, she had been given intravenous 500 mg pulse cyclophosphamide twice (1000 mg totally). During pregnancy, only corticosteroids and salicylic acid were given. In March 2000, she delivered a healthy male baby. The baby is now 9 month old and healthy. <h3>Conclusion</h3> Although fertility is decreased in SLE due to lupus nephritis and cyclophosphamide treatment, some pregnancies may occur. The pregnancies of SLE patients with anti-phospholipid syndrome have poorer prognosis. The absence of anticardiolipin antibodies in these two patients might have protected from poor outcome. Some authors believe that cyclophosphamide should not be used due to its teratogenic effect. Reported abnormalities due to cyclophosphamide during pregnancy include absent thumbs, absence of the great toes or all toes, palatal abnormalities, and a single coronary artery. However there are also reports of normal infants born from cyclophosphamide-treated mothers, and cyclophosphamide was proposed in life-threatening lupus. Experiences of cases like the present two may help the physician to make decisions on cyclophosphamide therapy during pregnancy in life-threating cases.
Risk of subsequent myeloid neoplasms after radiotherapy treatment for a solid cancer among adults in the United States, 2000–2014
Authors: Jop C. Teepen, Rochelle E. Curtis, Graça M. Dores, Amy Berrington de Gonzalez, Marry M. van den Heuvel-Eibrink, Leontien C. M. Kremer, Ethel S. Gilbert, Flora E. van Leeuwen, Cécile M. Ronckers, Lindsay M. Morton
Journal: Leukemia (2018)
Extracellular α-synuclein levels are regulated by neuronal activity
Authors: Kaoru Yamada, Takeshi Iwatsubo
Journal: Molecular Neurodegeneration (2018)

α-Synuclein is a presynaptic protein abundant in the cytoplasmic compartment of neurons, whereas its presence in the extracellular space has also been observed under physiological conditions. Extracellular α-synuclein has pathological significance, exhibiting cellular toxicity and impairment of synaptic transmission. Notably, misfolded α-synuclein drives the cell-to-cell propagation of pathology via the extracellular space. However, the primary mechanism that regulates the extracellular levels of α-synuclein remains to be determined. Using several mechanistically distinct methods to modulate neuronal/synaptic activities in primary neuronal culture and in vivo microdialysis, we examined the involvement of neuronal/synaptic activities on α-synuclein release. We demonstrate here that physiological release of endogenous α-synuclein highly depends on intrinsic neuronal activities. Elevating neuronal activity rapidly increased, while blocking activity decreased, α-synuclein release. In vivo microdialysis experiments in freely moving mice revealed that ~ 70% of extracellular α-synuclein arises from neuronal activity-dependent pathway. Selective modulation of glutamatergic neurotransmission altered extracellular α-synuclein levels, implicating this specific neuronal network in the mechanism of activity-dependent release of α-synuclein. While neuronal activity tightly regulated α-synuclein release, elevated synaptic vesicle exocytosis per se was capable to elicit α-synuclein release. We also found that extracellular α-synuclein exists as high molecular weight species. The present study uncovers a novel regulatory pathway associated with α-synuclein release, whose dysregulation might affect various pathological actions of extracellular α-synuclein including its trans-synaptic propagation.
Guidelines on Diabetic Eye Care
Authors: Tien Y. Wong, Jennifer Sun, Ryo Kawasaki, Paisan Ruamviboonsuk, Neeru Gupta, Van Charles Lansingh, Mauricio Maia, Wanjiku Mathenge, Sunil Moreker, Mahi M.K. Muqit, Serge Resnikoff, Juan Verdaguer, Peiquan Zhao, Frederick Ferris, Lloyd P. Aiello, Hugh R. Taylor
Journal: Ophthalmology (2018)
Abstract 19417: Change in Cardiovascular Health Score Predicts Incident Cardiovascular Disease and Total Mortality
Authors: Shouling Wu, Shasha An, Weijuan Li, Alice H Lichtenstein, Jingsheng Gao, Penny Kris-Etherton, Yuntao Wu, Cheng Jin, Frank B Hu, Xiang Gao
Journal: Circulation (2017)

Introduction:  The AHA 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health in all Americans with the use of 4 health behaviors (smoking, body weight, physical activity and diet) and 3 health factors (plasma glucose, plasma cholesterol and blood pressure) metrics. The cardiovascular health score (CHS), which is based on all the 7 ideal health metrics, has been shown to be inversely associated with cardiovascular disease (CVD) risk. However, how the changes in the CHS over time impact risk of CVD and mortality has not been examined in a large population.   Methods:  Our study included 63,905 Chinese adults (50,081 men and 13,824 women) free of CVD and cancer in 2008. Information on the cardiovascular health metrics in 2006 and 2008 was collected. We calculated the change in CHS (ΔCHS), which was defined as the CHS in 2008 minus the CHS in 2006. We used Cox regression model to calculate HRs and the 95% CIs for risk of CVD and total mortality in 2008-2014, respectively, according to ΔCHS from 2006 to 2008.   Results:  During median 6 years of follow-up, we identified 1,838 incident CVD events and 2,162 deaths. Improvement in CHS from 2006 to 2008 was associated with lower risk of developing CVD (P-trend  = 0.001, Figure 1B). Each unit of improvement in CHS was associated with 13% lower subsequent risk of CVD (adjusted HR=0.87; 95% CI: 0.84-0.91) and 4% lower risk of total mortality (adjusted HR =0.96; 95% CI: 0.94-0.98), respectively, after adjusting for age, sex, educational level, income, occupation, alcohol intake, serum high-sensitivity C-reactive protein concentrations, and CHS in 2006. The associations were not modified by age, sex, baseline CHS, and C-reactive protein concentrations (P-interaction>0.1 for all).   Conclusions:  Improving the overall cardiovascular health status by optimizing cardiovascular health behaviors and factors was associated with lower incidence of CVD and total mortality.
Extracorporeal Photochemotherapy Drives Monocyte-to-Dendritic Cell Maturation to Induce Anticancer Immunity
Authors: Alessandra Ventura, Aaron Vassall, Eve Robinson, Renata Filler, Douglas Hanlon, Katrina Meeth, Harib Ezaldein, Michael Girardi, Olga Sobolev, Marcus W. Bosenberg, Richard L. Edelson
Journal: Cancer Research (2018)

Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T-cell lymphoma (CTCL) operative in more than 350 centers worldwide. Although its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anticancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size. Second, we used that miniaturized device to produce a cellular vaccine that regularly initiated therapeutic antimelanoma immunity. Third, we individually subtracted key factors from either the immunizing inoculum or the treated animal to ascertain their contribution to the in vivo antimelanoma response. Platelet-signaled monocyte-to-dendritic cell (DC) differentiation followed by sorting/processing/presentation of tumor antigens derived from internalized apoptotic tumor cells were absolute requirements. As in clinical ECP, immunogenic cell death of tumor cells was finely titrated by DNA cross-linkage mediated by photoactivated 8-methoxypsoralen (8-MOPA). ECP-induced tumor-loaded DC were effective immunotherapeutic agents only if they were spared exposure to 8-MOPA, indicating that healthy DC are required for ECP. Infusion of responder T cells into naïve tumor-challenged mice established the protective role of stimulated T-cell antitumor immunity. Collectively, these results reveal that selective antitumor effects of ECP are initiated by tumor antigen-loaded, ECP-induced DC, which promote potent collaboration between CD4 and CD8 tumor-specific T cells. These mechanistic insights suggest potential therapeutic applicability of ECP to solid tumors in addition to CTCL.Significance: These findings identify principal cellular contributors to the anticancer immunotherapeutic impact of ECP and suggest this treatment may be applicable to a broad spectrum of immunogenic malignancies. Cancer Res; 78(14); 4045-58. ©2018 AACR.
Abstract 18706: Multi-Sequence Non-Contrast MRI Characterisation of Experimental Venous Thrombi Predicts Susceptibility to Lysis and is Feasible in Man
Authors: Prakash Saha, Alkystis Phinikaridou, Marcelo E Andia, Ashish S Patel, Steven P Grover, Adnan Bajwa, Bijan Modarai, Rene Botnar, Alberto Smith
Journal: Circulation (2014)

Introduction: We have previously demonstrated that non-contrast MRI using magnetisation transfer rate (MTR), apparent diffusion coefficient (ADC) and T1 mapping can characterise different aspects of organisation in a resolving venous thrombus. We now investigate whether the combination of these non-contrast agent MRI sequences can be used to identify thrombi suitable for lysis in an experimental model, and whether multi-sequence thrombus imaging (MSTI) can be translated to man. Methods: Magnetisation transfer, diffusion weighted images and T1 relaxation times were measured at days 2, 4, 7, 10, 14, 21 and 28 after venous thrombus induction in 8-10wk old male BALB/C mice (n=8/gp). Tissue plasminogen activator (10mg/kg) was administered through tail vein injection immediately after imaging at each time point and mice scanned 24hrs later to evaluate the effect of lysis. This was considered successful if more than 50% of the vein recanalised. Murine imaging sequences were combined and optimised to image the pelvic veins in man using healthy volunteers in order to produce a clinically useable imaging card. MSTI sequences were validated using phantoms before application to patients with iliofemoral deep vein thrombosis (DVT) undergoing lysis. Results: ROC curve analysis shows that the combination of MTR smaller than 2,900(%/cm3), ADC larger than 0.93(x10-3 mm2/s) and T1 shorter than 784ms has a sensitivity of 88% and specificity of 97% to identify experimental thrombi amenable to lysis. MSTI is feasible in man, with optimisation leading to successful characterisation of iliofemoral DVT in under 25mins (Figure 1). Conclusions: Non-contrast MR imaging, using a combination of MTR, ADC and T1 mapping, accurately identifies experimental venous thrombi susceptible to lysis. These MSTI sequences can also be readily translated to man where may find utility in characterising the age and structure of thrombus, and to stratify patients undergoing thrombolysis.
Human Leukocyte Antigen F Locus Adjacent Transcript 10 Overexpression Disturbs WISP1 Protein and mRNA Expression to Promote Hepatocellular Carcinoma Progression
Authors: Jinlong Yan, Jun Lei, Leifeng Chen, Huan Deng, Dingxiang Dong, Tao Jin, Xiuxia Liu, Rongfa Yuan, Yumin Qiu, Jin Ge, Xiaogang Peng, Jianghua Shao
Journal: Hepatology (2018)

Recently, studies on transcriptome–proteome relationships have revealed mRNA/protein expression discordance for certain genes and speculated that protein posttranslational modification (PTM) may be involved. However, there is currently no evidence to support this hypothesis. Wnt‐induced secreted protein‐1 (WISP1) is the downstream target gene of β‐catenin and plays an important role in tumorigenesis and progression, but the expression and role of WISP1 in different tumor types are controversial. Here, we first confirmed that WISP1 protein expression was significantly down‐regulated in hepatocellular carcinoma (HCC) tissue and could be an independent predictor of poor prognosis for patients with HCC. In vivo and in vitro evidence was provided that WISP1 can suppress HCC cell proliferation. Further studies have found that low WISP1 protein expression was related to expression of human leukocyte antigen F locus adjacent transcript 10 (FAT10), a specific ubiquitin‐like protein with both degradation and stabilization functions, which plays an important role in PTM. FAT10 overexpression facilitated WISP1 degradation by FAT10ylation to decrease WISP1 protein expression, thus promoting HCC proliferation. Interestingly, we found and demonstrated that FAT10 overexpression could result in WISP1 protein/mRNA expression discordance, with protein expression decreasing while mRNA expression increased. The underlying mechanism is that FAT10 exerts substrate stabilization and degradation functions simultaneously, while FAT10 overexpression promotes WISP1 mRNA expression by stabilizing β‐catenin and directly degrades WISP1 protein. Conclusion : Our study demonstrated that overexpression of FAT10 results in expression discordance between WISP1 protein and mRNA, thereby promoting HCC progression by down‐regulating WISP1 protein expression.
Analysis of the androgen receptor–regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression
Authors: Yajia Zhang, Sethuramasundaram Pitchiaya, Marcin Cieślik, Yashar S. Niknafs, Jean C.-Y. Tien, Yasuyuki Hosono, Matthew K. Iyer, Sahr Yazdani, Shruthi Subramaniam, Sudhanshu K. Shukla, Xia Jiang, Lisha Wang, Tzu-Ying Liu, Michael Uhl, Alexander R. Gawronski, Yuanyuan Qiao, Lanbo Xiao, Saravana M. Dhanasekaran, Kristin M. Juckette, Lakshmi P. Kunju, Xuhong Cao, Utsav Patel, Mona Batish, Girish C. Shukla, Michelle T. Paulsen, Mats Ljungman, Hui Jiang, Rohit Mehra, Rolf Backofen, Cenk S. Sahinalp, Susan M. Freier, Andrew T. Watt, Shuling Guo, John T. Wei, Felix Y. Feng, Rohit Malik, Arul M. Chinnaiyan
Journal: Nature Genetics (2018)
MEGA Software Celebrates Silver Anniversary
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2018)

MEGA Software Celebrates Silver AnniversaryIn the past 25 years, stretching from the dawn of personal computing to the social media age, the "always free" molecular evolutionary genetics analysis (MEGA) tool has been downloaded 1.6 million times worldwide.In 1993, the very first version of Molecular Evolutionary Genetics Analysis (MEGA) software was developed to meet the growing needs for nucleic acid and protein sequence analysis tools among evolutionary and molecular biologists.MEGA was developed by Sudhir Kumar and Koichiro Tamura in the laboratory of Masatoshi Nei, who guided and supported MEGA development throughout its early years.On the occasion of MEGA's silver anniversary, Kumar and Tamura reflected on the origins and refinement of the software over the years, as well as its continuing impact on the field of evolutionary biology."I began my doctoral studies in the Nei lab in January 1991," said Kumar."The Nei lab routinely pioneered new methods and implemented them in computer programs so others could use them.MEGA's development escalated that tradition to fulfill the need for a user-friendly tool that enabled molecular phylogenetic analysis using evolutionary distances."MEGA was designed from the start to be "always free" to the public, and "developed to facilitate statistical analyses of molecular evolution by using personal computers."The MEGA software was first announced to the world in a three-page publication in the journal Computer Applications in the Biosciences, or CABIOS (later changed to Bioinformatics)."Within a few years, we received over 2,500 requests for MEGA by postal mail," said Kumar."The first version was distributed on 5.25-or 3.5-in floppy diskettes, which have long since gone extinct.We also, by necessity, ended up running a small print and distribute shop in the lab to mail out the handy 140-page instruction manual we developed, which included a lot of useful information on newer statistical methods in computational evolutionary biology, including distance estimation methods, phylogenetic inference algorithms, and basic sequence statistics."MEGA 1.0 was designed to handle single gene comparisons across species.It was written in Cþþ programming language and intended to be used on market leading IBM and IBMcompatible personal computers, which were predominantly built with 486 processors and had a maximum of 640 kb RAM memory."MEGA is designed to conduct various statistical analyses in one program and to produce results in publication-quality outputs," wrote Sudhir Kumar, Koichiro Tamura, and Masatoshi Nei.An interactive user interface, they wrote, "can be used on most color and monochrome monitors, and it responds to
Abstract 15439: Right Ventricular Function at Rest Strongly Correlates With Cardiopulmonary Exercise Phenotype in Hypertrophic Cardiomyopathy
Authors: Valeria Donghi, Francesco Bandera, Greta Generati, Vincenzo Tufaro, Valentina Labate, Eleonora Alfonzetti, Marco Guazzi
Journal: Circulation (2016)

Background:  Hypertrophic cardiomyopathy (HCM) affects the right ventricle (RV) because of the anatomically hypertrophied septum and plausibly by extension of the myopathic process to the RV. The role of RV in the functional response during exercise in hypertrophic cardiomyopathy is challenging and uninvestigated.   Purpose:  To identify how and whether RV function may relate to functional capacity and especially ventilation efficiency in patients with LV hypertrophy secondary to HCM.   Methods:  24 HCM patients (mean age 60.5±14.6; male 53%; NYHA I-II-III 60-20-20%) underwent a maximal cardiopulmonary exercise testing (CPET) evaluation combined with echo-Doppler and off-line speckle tracking analysis, collecting rest and peak exercise data. We explored at the relationship between LV (left ventricle) function vs RV function at rest (detected by tricuspid annular plane systolic excursion – TASPE - and free-wall longitudinal strain) and CPET variables, using Pearson analysis to test the significance.   Results:  Our population had a preserved LV ejection fraction (LVFE: mean 63.9 ± 12%), mean left ventricle end-diastolic volumes 46.3 ± 10.6 ml/mq, enlarged left atria (vol ind 52.2 ± 26.1) and preserved RV function, assessed by TAPSE (mean 22.7 ± 4.2 mm) and by free-wall strain (mean -28.7 ± 7.6%). LVEF did not show a significant correlation with CPET variables. Conversely, TAPSE and RV free-wall strain had good correlation with pressure of end-tidal CO2 (PetCO 2 ), ventilatory efficiency (VE/VCO 2  slope) and workload, as shown in the figure.   Conclusions:  In HCM patients with preserved ejection fraction, RV function strongly correlates with main CPET variables, and it can seemingly be considered for predicting abnormalities in functional phenotype better than LVFE.