tbuckley/cabot-search huggingface dataset:
Challenges and research opportunities for lung cancer screening in China
Authors: Zixing Wang, Yuyan Wang, Yao Huang, Fang Xue, Wei Han, Yaoda Hu, Lei Wang, Wei Song, Jingmei Jiang
Journal: Cancer Communications (2018)

Abstract Following publication of the results of the National Lung Screening Trial in the United States, a randomized controlled trial in Italy (ITALUNG) and two simulation studies in China reported similar findings in 2017 favoring lung cancer screening with low‐dose computed tomography among smokers. With such advances in lung cancer screening, worldwide interest has gradually shifted from evaluating whether refining lung cancer screening protocols is effective in preventing deaths. However, there are several practical problems to be resolved, including the balance of enrollment criteria and cost effectiveness, precise measurements to reduce false positive findings, risk‐based optimization of screening frequency, challenges associated with cancer heterogeneity, strategies to combine image screening with novel biomarkers, dynamic monitoring of the natural history of cancer, accurate identification and diagnosis of cases among huge populations, and the impact of tobacco control policy and environment protection. As one in three individuals with lung cancer worldwide resides in China, these questions pose great challenges as well as research opportunities for population screening programs in China.
The new primary chemotherapy with S-1 and docetaxel for advanced breast cancer: A first report of N-1 trial.
Authors: Misako Nakagawa, Masami Morimoto, Hirokazu Takechi, Yukikiyo Kawakami, Akira Tangoku
Journal: Journal of Clinical Oncology (2012)

e11560 Background: We reported the result of the efficacy and toxicity of S-1 combined with docetaxel (S-1+DOC) in ASCO 2011 (abstract No.1075). It showed good objective response rate (ORR) and some cases showed of complete response (CR) before middle of 8 cycles regimen. But this regimen was difficult to keep compliance of per oral S-1 intake. To improve pathological CR (pCR) rate, we planned a new protocol of primary chemotherapy with S-1+DOC (N-1 trial). Methods: Patients with advanced breast cancer (stage II-IV) were treated with i.v. docetaxel (40mg/m 2 ) on day1 and oral S-1 (80mg as FT/m 2 /day) on day1 to 14 every 3 weeks for 4 cycles. According to the RECIST criteria, patients with CR were underwent operation, partial response were continued more 4cycles of S-1+DOC. Stable disease or progressive disease cases were changed regimen for EC or Trastuzumab and Paclitaxel (HT) according to their HER2 status. Adequate supportive therapy was provided for typical adverse events. Primary endpoint is a pCR rate. Secondary endpoints are ORR, breast conservation rate and safety. Results: Between 2009 and 2011, Forty-two patients were originally entered. After 4 cycles of S-1+DOC, CR was noted in 6 cases, and PR in 20 cases. 8 cases of SD and 1 case of PD were underwent EC, 4 cases of SD were underwent HT. Among 36 patients who had completed the whole regimen, 30.7% achieved pCR. ORR was 79.4% and breast conservation rate was 97.4%. Patients could keep an intake more than 80% dose of S-1 was 87%. Adverse events over grade3 were peripheral sensory neuropathy, nausea, nail change and neutropenia. Grade 3, 4 of neutropenia was noted in 62%. Conclusions: The new primary chemotherapy with S-1 and Docetaxel is expected to exhibit satisfactory efficacy and showed the possibility of shortened the term of primary chemotherapy. In order to establish this treatment, it is important to proper response assessment.
Expression of MT4-MMP, EGFR, and RB in Triple-Negative Breast Cancer Strongly Sensitizes Tumors to Erlotinib and Palbociclib Combination Therapy
Authors: Pierre Foidart, Cassandre Yip, Jean Radermacher, Silvia Blacher, Mehdi Lienard, Laetitia Montero-Ruiz, Erik Maquoi, Elodie Montaudon, Sophie Château-Joubert, Joëlle Collignon, Michel Coibion, Véronique Jossa, Elisabetta Marangoni, Agnès Noël, Nor Eddine Sounni, Guy Jerusalem
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Here, we investigated the clinical relevance of an unprecedented combination of three biomarkers in triple-negative breast cancer (TNBC), both in human samples and in patient-derived xenografts of TNBC (PDX-TNBC): EGFR, its recently identified partner (MT4-MMP), and retinoblastoma protein (RB). Experimental Design: IHC analyses were conducted on human and PDX-TNBC samples to evaluate the production of the three biomarkers. The sensitivity of cancer cells expressing or not MT4-MMP to anti-EGFR (erlotinib) or anti-CDK4/6 inhibitor (palbociclib) was evaluated in vitro in 2D and 3D proliferation assays and in vivo using xenografts and PDX-TNBC displaying different RB, MT4-MMP, and EGFR status after single (erlotinib or palbociclib) or combined (erlotinib + palbociclib) treatments. Results: EGFR and MT4-MMP were coexpressed in &amp;gt;70% of TNBC samples and PDX-TNBC, among which approximately 60% maintained RB expression. Notably, approximately 50% of all TNBC and PDX-TNBC expressed the three biomarkers. Single erlotinib and palbociclib treatments drastically reduced the in vitro proliferation of cells expressing EGFR and MT4-MMP when compared with control cells. Both TNBC xenografts and PDX expressing MT4-MMP, EGFR, and RB, but not PDX-TNBC with RB loss, were sensitive to erlotinib and palbociclib with an additive effect of combination therapy. Moreover, this combination was efficient in another PDX-TNBC expressing the three biomarkers and resistant to erlotinib alone. Conclusions: We defined a new association of three biomarkers (MT4-MMP/EGFR/RB) expressed together in 50% of TNBC and demonstrated its usefulness to predict the TNBC response to anti-EGFR and anti-CDK4/6 drugs used in single or combined therapy.
Идиопатическая нецирротическая портальная гипертензия и ее причины
Authors: O.M. Vlasova
Journal: GASTROENTEROLOGY (2018)

Идиопатическая нецирротическая портальная гипертензия представляет собой плохо диагностируемое заболевание неясной этиологии. Заболевание прогрессирует медленно, является доброкачественным, прогноз более оптимистичный, чем при лечении осложнений портальной гипертензии. Данное заболевание фиксируют в различных странах мира и в разнообразных этнических группах с различными факторами риска, чем обусловлены существование разнообразной терминологии и отсутствие стандартизированных критериев диагностики, хотя для постановки диагноза «идиопатическая нецир­ротическая портальная гипертензия» требуется клинически и гистологически исключить другую патологию.
Systematic evaluation of CRISPR-Cas systems reveals design principles for genome editing in human cells
Authors: Yuanming Wang, Kaiwen Ivy Liu, Norfala-Aliah Binte Sutrisnoh, Harini Srinivasan, Junyi Zhang, Jia Li, Fan Zhang, Charles Richard John Lalith, Heyun Xing, Raghuvaran Shanmugam, Jia Nee Foo, Hwee Ting Yeo, Kean Hean Ooi, Tore Bleckwehl, Yi Yun Rachel Par, Shi Mun Lee, Nur Nadiah Binte Ismail, Nur Aidah Binti Sanwari, Si Ting Vanessa Lee, Jan Lew, Meng How Tan
Journal: Genome biology (2018)

While CRISPR-Cas systems hold tremendous potential for engineering the human genome, it is unclear how well each system performs against one another in both non-homologous end joining (NHEJ)-mediated and homology-directed repair (HDR)-mediated genome editing.
Maximizing Aggregation of Organic Fluorophores to Prolong Fluorescence Lifetime for Two‐Photon Fluorescence Lifetime Imaging
Authors: Wenbo Hu, Lihong Guo, Lei Bai, Xiaofei Miao, Yun Ni, Qi Wang, Hui Zhao, Meng Xie, Lin Li, Xiaomei Lu, Wei Huang, Quli Fan
Journal: Advanced Healthcare Materials (2018)

Two-photon fluorescence lifetime imaging (TP-FLIM) not only permits imaging deep inside the tissues with precise spatial manipulation but also circumvents tissue autofluorescence, holding tremendous promise in molecular imaging. However, the serious lack of suitable contrast agents with long fluorescence lifetime and efficient two-photon absorption (TPA) greatly limits the advance of TP-FLIM. This study reports a simple approach to fabricate water-soluble organic semiconducting nanoparticles [thioxanthone (TXO) NPs] with ultralong fluorescence lifetime and efficient TPA for in vivo TP-FLIM. The approach utilizes the aggregation of a specifically selected thermally activated delayed fluorescence (TADF) fluorophore to prolong its fluorescence lifetime. Encapsulating the TADF fluorophore within an amphiphilic copolymer not only maximizes its aggregation but also obtains TXO NPs with efficient TPA. Importantly, as-prepared TXO NPs exhibit a considerably long fluorescence lifetime at a magnitude of 4.2 µs, which is almost 1000 times larger than that of existing organic contrast agents. Moreover, such long fluorescence lifetime is almost oxygen-inert, readily realizing both in vitro and in vivo TP-FLIM. This work may set valuable guidance for designing organic semiconducting materials with ultralong fluorescence lifetimes to fulfill the potential of FLIM.
Increasing physical activity in cancer survivors using eHealth: A focus group study.
Authors: Ciaran Haberlin, Jonathan Moran, Julie M Broderick, Dearbhaile M. O'Donnell
Journal: Journal of Clinical Oncology (2018)

107 Background: Physical activity (PA) is beneficial in reducing disease and treatment related side‐effects of cancer. However, insufficient PA levels are common among cancer survivors. eHealth may offer an innovative delivery platform to support cancer survivors to increase PA. Few qualitative studies have explored the views of cancer survivors towards eHealth based PA interventions. Our aim was to use cancer survivors’ input to inform the design of a feasibility study of eHealth for PA promotion. Methods: A ten-item scoping questionnaire-based cross-sectional study was administered to 102 cancer survivors. It evaluated their knowledge of PA guidelines, their access to smartphones and interest in eHealth interventions designed to increase PA levels. Questions were refined and evaluated in a follow-up focus group study (7 groups, n=23). Focus groups were audio recorded and transcribed. Transcripts were coded using NVivo software and themes identified by thematic content analysis. Results: In the questionnaire study, only 17.6% (n=18) of participants correctly identified PA guidelines. Sixty-two (60.8%) participants reported having access to a smartphone. Interest in participating in an eHealth intervention was expressed by 56.9% of all participants (n=58) and by 75.8% (n=47) of those with access to a smartphone. Emergent themes from the focus groups included: the physical barriers to PA, the need for PA goals, the importance of both information from healthcare professionals about PA and of a support network (e.g. peer support), the need for technological support and a motivation to improve general health. Conclusions: Very few cancer survivors were aware of the correct PA guidelines. However, over half of our sample was interested in participating in an eHealth intervention for PA, demonstrating that the cancer survivor population is responsive to a PA program delivered using technology. The focus groups have given us insights about the key elements of an effective PA intervention for cancer survivors using eHealth. We are conducting a feasibility study (The IMPETUS study; NCT03036436) of an eHealth intervention targeting PA in cancer survivors; its design was informed by those insights.
Biomanufacturing for clinically advanced cell therapies
Authors: Ayesha Aijaz, Matthew Li, David Smith, Danika Khong, Courtney LeBlon, Owen S. Fenton, Ronke M. Olabisi, Steven Libutti, Jay Tischfield, Marcela V. Maus, Robert Deans, Rita N. Barcia, Daniel G. Anderson, Jerome Ritz, Robert Preti, Biju Parekkadan
Journal: Nature Biomedical Engineering (2018)
Abstract 18847: Impact of Coronary Artery Aneurysms in Myocardial Deformation of Convalescent Kawasaki Disease Patients
Authors: Aura Sanchez Mejia, Kristen Sexson Tejtel, Myriam Almeida-Jones, Douglas Feagin, Carolyn Altman, Ricardo Pignatelli
Journal: Circulation (2015)

Background: Abnormal strain, independent of coronary involvement, has been reported in the acute phase of KD. However, there is limited data about the impact of coronary aneurysms in myocardial deformation during the convalescent phase of KD. Objective: To perform a comprehensive assessment of myocardial deformation in patients with KD during the convalescent phase and assess for the effect of coronary artery aneurysms. Methods: KD patients with echocardiograms performed during the convalescent phase (&gt;42 days from fever onset to study date) between 8/2013 -11/2014, and with adequate images for analysis with two-dimensional speckle tracking echocardiography (2DSTE) were included. Demographic, clinical, 2D and 2DSTE parameters were measured, including left ventricular global longitudinal strain (GLS), global circumferential strain (GCS) and strain rate (SR), torsion and right ventricular longitudinal strain (RLS) and SR. The patients with and without aneurysms were compared using Chi-square and T-test. Linear regression was used to assess association between variables. Results: A total of 67 patients were included. Table 1 shows the demographic, clinical and echocardiographic data. The groups differ in heart rate (HR) and body surface area (BSA). Treatment resistance and coronary involvement at presentation were more frequent in the aneurysms group. The myocardial deformation values were within normal limits for age. However, the aneurysms group had significantly lower GLSR and GCSR relative to the group without aneurysms. GLSR was associated with BSA and HR and GCSR with age, p&lt;0.05 for all. Conclusions: Convalescent KD patients with aneurysms have subtle decrease in LV longitudinal and circumferential myocardial deformation. This data suggests potential impact of chronic coronary involvement in the myocardial function of KD patients that warrants follow-up. BSA, HR and age should be considered when evaluating GLSR and GCSR.
Which way does the axis tip? IBD increases the risk of Parkinson’s disease
Authors: Susan Hutfless, Gregor K Wenning
Journal: Gut (2018)

In Gut , Villumsen et al 1 report a statistically significant association between UC and the risk of parkinsonism in a Danish nested case–control study. Patients with Crohn’s disease and UC with at least one inpatient or outpatient encounter for IBD between 1977 and 2014 were compared with age-matched and sex-matched controls (76 477 IBD; 7 548 259 controls). Follow-up started at the time of the first IBD encounter (or the corresponding date for the controls) until the first diagnosis of Parkinson’s disease or multiple system atrophy. Parkinsonism was increased among patients with UC (HR 1.35 (95% CI 1.20 to 1.52)), but not Crohn’s disease (HR 1.12 (95% CI 0.89 to 1.40)). Parkinson’s disease and multiple system atrophy were rare both in patients …
Single center long term results from the randomized phase-3 TARGIT-A trial comparing intraoperative (IORT) and whole-breast radiation therapy (WBRT) for early breast cancer.
Authors: Yasser Abo-Madyan, Grit Welzel, Elena Sperk, Christian Neumaier, Anke Keller, Sven Clausen, Frank Schneider, Michael Ehmann, Marc Sütterlin, Frederik K. Wenz
Journal: Journal of Clinical Oncology (2018)

e12616 Background: Partial breast irradiation using IORT after breast conserving surgery is non-inferior to WBRT for a selected group of breast cancer patients. We report the results of patients treated in our center as a part of the TARGIT-A trial. Methods: Patients (≥45y) with cT1 cN0 cM0 and invasive ductal histology on biopsy were randomized between immediate post-resection IORT (Arm-A) or post-operative WBRT (Arm-B). IORT was delivered using a 50kV x-ray generator (Intrabeam®) up to 20 Gy. WBRT was delivered up to 50-56 Gy in 2 Gy fractions. Post-operatively, patients in Arm-A with extensive intraductal component, invasive lobular carcinoma, multifocality, lymph vessel invasion or small resection margins ( < 1cm) received post-operative WBRT up to 46 Gy and those with lymphnode metastases with 46-50 Gy to the breast and lymphatics. Results: Between 2002 and 2012, 184 patients were randomized, 91 in Arm-A and 93 in Arm-B. One patient in Arm-A and three in Arm-B never showed for follow up and were not further analyzed. Median follow up was 8.5 years (Arm-A: 8.3 years, Arm-B: 8.5 years). The median age at randomization was 64 years. According to intention to treat analysis, the 5 year overall survival was 94.4% in Arm-A and 93.3% in Arm-B (p = 0.73). Two local recurrences were observed; one recurrence at 70.3 months in an Arm-A patient that received IORT+WBRT and one recurrence at 4.5 months in an Arm-B patient that refused all forms of adjuvant treatments making the 5 year local recurrence free survival 100% in Arm-A and 98.9% in Arm-B. The 5 year in-breast-recurrence/second primary free survival (out of index quadrant) was 100% in Arm-A and 98.9% in Arm-B with one recurrence in each study arm at 86.5/43.9 months after surgery. Both patients had received WBRT and anti-hormone therapy as part of their adjuvant treatment. Salvage mastectomy was performed successfully in all recurring patients. Conclusions: Long term follow-up of this single center cohort consolidates the earlier reports of extremely low local recurrence rate after single dose IORT. Our results fall in line with non-inferiority of risk adapted IORT for selected patients with early breast cancer. Clinical trial information: NCT00983684.
Experimental models of murine atherosclerosis: does perception match reality?
Authors: Jessica M Johnston, Sheila E Francis, Endre Kiss-Toth
Journal: Cardiovascular Research (2018)

Background: Murine models of atherosclerosis have been invaluable to gain mechanistic understanding of this chronic disease. Induction of atherosclerosis with relative ease in ApoE-/- and Ldlr-/-  fed a Western-type  to cause  has provided researchers with popular tools to manipulate and characterise the action of genes that affect atherogenesis. Seminal studies and reviews have discussed key phenotypic differences between different models and target levels of hyperlipidaemia have also been published. However, despite widespread use of these models and firm beliefs about differences in severity between them, there has been no meta-analysis and critical appraisal of published literature reporting phenotypes of murine  focusing on the degree of  and aortic atheroma burden. Methods and Results: A systematic search in PubMed and Web of Knowledge with the key words: atherosclerosis, western diet and mice identified 483 studies between 2006-2018. These reports used ApoE-/-, Ldlr-/- or proprotein convertase subtilisin/kexin type 9 overexpressing- adeno-associated virus (PCSK9-AAV8) models of experimental atherosclerosis (including bone marrow transplants, BMT), induced by western-diet (WD) feeding. We chose to assess standard WD (0.2% cholesterol) as it is the most widely used  in atherosclerosis studies 1. These publications were filtered based on the content of their abstracts; those that described experiments of experimental atherosclerosis (204 papers) were considered for further assessment. Of these, articles that reported at least two of the following measures were included in the main analysis to allow for correlative comparisons; lesion area in the aortic root (numerical values and not %), % en face Oil-Red O staining in the whole aorta, total plasma cholesterol and triglyceride (mg/dL) levels. These criteria yielded 144 research articles (22 used BMT of either model, 75 used ApoE-/-, 27 used Ldlr-/-, 10 used both BMT and single ApoE-/- or Ldlr-/-, 2 used PCSK9, the remaining 8 studies used mixed models BMT) where the  were fed a  for 4-28 weeks.
The association of early toxicity and outcomes for patients treated with abemaciclib.
Authors: Hope S. Rugo, George W. Sledge, Stephen R. D. Johnston, Matthew P. Goetz, Miguel Martin, Masakazu Toi, Tammy D Forrester, Martin Frenzel, Joanne Cox, Susana Barriga, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2018)

1053 Background: Abemaciclib is a CDK4 & 6 inhibitor dosed on a continuous schedule and has demonstrated efficacy with an acceptable safety profile in patients (pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer as monotherapy and in combination with endocrine therapy in the MONARCH 1, 2, and 3 trials. Early onset, low grade diarrhea was the most common toxicity and was typically manageable and reversible with antidiarrheal medication and/or dose reduction. Neutropenia was the most frequent grade 3/4 toxicity in the abemaciclib arms, typically occurring in the first 2 cycles. Here we provide an assessment of the association between these early toxicities, dose adjustment, and progression-free survival (PFS). Methods: Enrollment criteria, study designs, and endpoints were previously reported (Dickler et al. 2017; Sledge et al. 2017; Goetz et al. 2017). To examine the impact of dose reductions on efficacy, a time-dependent covariate analysis of dose level versus PFS was performed. A landmark analysis was performed for pts with/without toxicity occurring early in treatment (diarrhea: 7 days; neutropenia: 56 days) by comparing PFS for each of these arms to the placebo arm using a Cox model. Results: Discontinuation of abemaciclib due to diarrhea or neutropenia were each < 3% in the abemaciclib arms. Management of toxicity included dose adjustment as necessary. An exploratory time-dependent covariate analysis showed no difference in PFS for pts who dose-reduced compared to those who did not. Compared to placebo, pts in the abemaciclib arms received benefit whether or not diarrhea or neutropenia was observed early in treatment. Conclusions: The dose adjustment strategy used in the MONARCH trials appeared to be an effective way to manage toxicity without compromising efficacy. Clinical trial information: NCT02102490, NCT02107703, NCT02246621. HR 95% CI MONARCH 1 150 vs 200 mg 1.45 .90, 2.33 100 vs 200 mg 1.24 .59, 2.62 MONARCH 2 / 3 100 vs 150 mg 1.03 / .76 (.68, 1.57) / (.47, 1.25) 50 vs 150 mg .92 / .99 (.50, 1.71) / (.51, 1.90) MONARCH 2* / 3* With diarrhea .50 / .49 (.39, .64) / (.35, .67) Without diarrhea .61 / .58 (.48, .77) / (.43, .78) With neutropenia .58 / .54 (.45, .74) / (.39, .75) Without neutropenia .56 / .52 (.43, .73) / (.38, .70) *HR is compared to placebo arm