tbuckley/cabot-search huggingface dataset:
Axonal organization defects in the hippocampus of adult conditional BACE1 knockout mice
Authors: Ming-Hsuan Ou-Yang, Jonathan E. Kurz, Toshihiro Nomura, Jelena Popovic, Tharinda W. Rajapaksha, Hongxin Dong, Anis Contractor, Dane M. Chetkovich, Warren G. Tourtellotte, Robert Vassar
Journal: Science Translational Medicine (2018)

Conditional loss of BACE1 in adult mouse brain results in abnormalities in the hippocampal mossy fiber pathway, which is important for learning and memory.
Depression and anxiety in oncology nurses.
Authors: Özge Keskin, Esin Oktay, Merve Turan, Neyran Kertmen, Ozgur Tanriverdi, Goksen Inanc Imamoglu, Deniz Yuce, Banu Ozturk, Ozlem Ata
Journal: Journal of Clinical Oncology (2018)

e18552 Background: To examine the rates of depression and anxiety among nurses working in oncology units and the situations in which these ratios may be related. Methods: A descriptive study. Nurses working at outpatient and / or inpatient oncology units filled out a form for demographic information. And HAD scale was applied. Results: There are 73 nurses from 7 medical centers in the study. The median age was found to be 34.8 ± 8.6 years old. The majority of nurses (89%) are female and only 8 (11%) nurses are male. Of the nurses 38.4% were single and the remaining 61.6% were married. Among the nurses the rate of drug use prescribed by the psychiatric department for any reason was 27.4%; and the remaining (72.6%) did not use any psychiatric medication. In the entire study group; when the total time spent as a nurse in oncology and / or other branches was examined, the median was 14.02 ± 8.81 years. When only in an oncology department working period were examined, 69.08 ± 61.9 months were determined. HAD scales were used to score depression and anxiety among the nurses. Depressive mood was defined as a score of 7 and above according to the depression scale, and 60.3% of the nurses were found to have depressive mood. Depression was more frequently observed in married and female nurses (p < 0.05). A score of 10 and over support the presence of common anxiety disorder according to the anxiety scale. This was also found in 31.5% of all nurses. Anxiety was more evident in married nurses working at inpatient oncology service (p < 0,05). According to the Maslach and Minnesota scales, each of the two scales was found to be effective at following the depression process (p < 0,05). But, there was no significant relationship between Minnesota scale and anxiety (p > 0,05). Conclusions: Along with the increasing number of patients, the workload of the oncology nurses is also increasing. Burnout caused by this workload and perhaps even less experienced occupational satisfaction are also increasing. Both of the situations can be causes of depression and anxiety. Perhaps the application of these tests periodically to healthcare staff working in oncology units may give us preliminary information about depression and / or anxiety.
Reactive oxygen species modulator 1 (Romo1) to predict poor outcomes in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.
Authors: Seung Hyeun Lee, Sue In Choi, Ji Sung Lee, Chul Hwan Kim, Won Jai Jung, Eun Joo Lee, Kyung Hoon Min, Gyu Young Hur, Seung Heon Lee, Sung Yong Lee, Je Hyeong Kim, Sang Yeub Lee, Chol Shin, Jae Jeong Shim, Kyung Ho Kang, Kwang Ho In
Journal: Journal of Clinical Oncology (2016)

e20514 Background: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. Several in vitro studies have suggested that Romo1 may be involved in many steps in carcinogenesis, including tumor progression and invasion. Recently, we have showed that Romo1 overexpression is related to early recurrence and shorter survival in non-small cell lung cancer (NSCLC) patients who undergo surgery. However, there is still a dearth of studies concerning the clinical implications of Romo1 in advanced NSCLC. We investigated whether Romo1 expression is associated with clinical outcomes in NSCLC patients treated with platinum-based doublet as first-line therapy. Methods: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by a semiquantitative histologic score (H score). We performed survival analyses according to Romo1 expression and evaluated the association between Romo1 expression and clinical parameters. Results: A total of 88 tumor specimens were analyzed. The median progression-free survival (PFS) of the high Romo1 group was significantly shorter than that of the low Romo1 group (4.5 vs 9.8 months, p < 0.001). The median overall survival (OS) of high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 vs 15.5 months, p < 0.001). Multivariate analyses showed that high Romo1 expression was significantly associated with both poor PFS (hazard ratio [HR] = 2.75, 95% confidence interval [CI]: 1.71–4.44) and poor OS (HR = 3.99, 95% CI: 2.36–6.74). In subgroup analysis, the association was similar regardless of tumor histology. Romo1 expression was not associated with any clinical parameters including age, gender, smoking status, stage, differentiation, or tumor histology. Conclusions: Romo1 overexpression was independently associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive and prognostic marker in this setting.
A Long Noncoding RNA Regulates Hepatitis C Virus Infection Through Interferon Alpha–Inducible Protein 6
Authors: Xiao Liu, Xiaoqiong Duan, Jacinta A. Holmes, Wenting Li, Sae Hwan Lee, Zeng Tu, Chuanlong Zhu, Shadi Salloum, Anna Lidofsky, Esperance A. Schaefer, Dachuan Cai, Shilin Li, Haoju Wang, Yongfu Huang, Yongju Zhao, Ming‐Lung Yu, Zhiwen Xu, Limin Chen, Jian Hong, Wenyu Lin, Raymond T. Chung
Journal: Hepatology (2018)

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of many important cellular processes. However, the mechanisms by which lncRNAs regulate viral infection and host immune responses are not well understood. We sought to explore lncRNA regulation of hepatitis C virus (HCV) infection and interferon response. We performed RNA sequencing (RNAseq) in Huh7.5.1 cells with or without interferon alpha (IFNα) treatment. Clustered regularly interspaced short palindromic repeats/Cas9 guide RNA (gRNA) was used to knock out selected genes. The promoter clones were constructed, and the activity of related interferon‐stimulated genes (ISGs) were detected by the secrete‐pair dual luminescence assay. We constructed the full‐length and four deletion mutants of an interferon‐induced lncRNA RP11‐288L9.4 (lncRNA‐IFI6) based on predicted secondary structure. Selected gene mRNAs and their proteins, together with HCV infection, in Huh7.5.1 cells and primary human hepatocytes (PHHs) were monitored by quantitative real‐time PCR (qRT‐PCR) and western blot. We obtained 7,901 lncRNAs from RNAseq. A total of 1,062 host‐encoded lncRNAs were significantly differentially regulated by IFNα treatment. We found that lncRNA‐IFI6 gRNA significantly inhibited HCV infection compared with negative gRNA control. The expression of the antiviral ISG IFI6 was significantly increased following lncRNA‐IFI6 gRNA editing compared with negative gRNA control in Japanese fulminant hepatitis 1 (JFH1)–infected Huh7.5.1 cells and PHHs. We observed that lncRNA‐IFI6 regulation of HCV was independent of Janus kinase‐signal transducer and activator of transcription (JAK‐STAT) signaling. lncRNA‐IFI6 negatively regulated IFI6 promoter function through histone modification. Overexpression of the truncated spatial domain or full‐length lncRNA‐IFI6 inhibited IFI6 expression and increased HCV replication. Conclusion: A lncRNA, lncRNA‐IFI6, regulates antiviral innate immunity in the JFH1 HCV infection model. lncRNA‐IFI6 regulates HCV infection independently of the JAK‐STAT pathway. lncRNA‐IFI6 exerts its regulatory function via promoter activation and histone modification of IFI6 through its spatial domain.
Variations in incidence, overall survival, and cytogenetic risk in patients of white and Korean ethnicity with acute myeloid leukemia in the United States.
Authors: Peter G Kim, Tao Zou, Andrew Mark Brunner, Ashley M. Perry, Kristin L McGregor, Amir Tahmasb Fathi
Journal: Journal of Clinical Oncology (2016)

e18516 Background: Cancer outcomes, including in acute myeloid leukemia (AML) may vary by ethnic background. Korean AML patients have been reported to have a lower incidence of certain mutations, such as FLT3-ITD (J Korean Med Sci. 2008; 23:833). We examined AML incidence, overall survival (OS) and cytogenetic risk among Whites and Koreans with AML in the US. Methods: We utilized the 1990-2010 Surveillance, Epidemiology, and End Results Program (SEER) Asian/Pacific Islander database to identify AML patients, including acute promyelocytic leukemia patients, diagnosed between 2000-2010 with documented ethnicity and age at diagnosis. Age-adjusted incidence was standardized to the US Census. The primary outcome was OS according to ethnicity. We performed a stratified analysis of patients age 15-64 and patients over 65. OS was estimated by the Kaplan-Meier method. Results: Age-adjusted AML incidence was significantly lower in Koreans than Whites in patients above 55 years old (Table 1). Median survival was 5 and 2 months for Koreans and Whites, respectively. Korean ethnicity was associated with improved OS for ages 65 or older (5-year OS Koreans 14.5%, Whites 8.1%, p = 0.0007), but not for ages 15-64 (p = 0.3). In multivariable analysis of ages 65 or older, there was worse OS with increased age (HR 1.05 per year, p < 0.0001) and undocumented insurance status (HR 1.11, p < 0.0001) but improved OS with Korean ethnicity (HR 0.67, p = 0.004), core-binding factor AML (HR 0.56, p = 0.0002). Korean ethnicity was also associated with 2.2-fold increased incidence of favorable cytogenetics based on accepted definitions. Conclusions: In the SEER population, AML patients of Korean ethnicity had improved OS, particularly above age 65. This appears to relate to an increased incidence of favorable cytogenetics in this population, and merits further investigation into underlying differences in AML pathogenesis in this population. Age-adjusted Incidence Per 100,000 Age Group White Korean 0-4 1.1 0.9 5-19 0.7 0.8 20-24 1 0.7 25-34 1.1 0.9 35-44 1.7 1.5 45-54 3.1 2.6 55-64 6.6 3.6 65-74 14.5 8.2 75+ 23.4 11.6
Crizotinib in children and adolescents with advanced ROS1, MET, or ALK-rearranged cancer: Results of the AcSé phase II trial.
Authors: Gilles Vassal, Laura Faivre, Birgit Geoerger, Dominique Plantaz, Anne Auvrignon, Carole Coze, Nathalie Aladjidi, Arnauld Verschuur, Celine Icher, Minckes Odile, Nicolas Sirvent, Gudrun Schleiermacher, Nathalie Auger, Etienne Lonchamp, Celine Mahier - Ait Oukhatar, Marie-Cecile Le Deley, Marta Jimenez, Natalie Hoog Labouret
Journal: Journal of Clinical Oncology (2016)

11509 Background: Alterations of crizotinib (crz) molecular targets ALK, MET, ROS1 are found in a wide range of adult and pediatric (ped) cancers. Crz is approved for the treatment of adult patients (pts) with ALK+ advanced NSCLC but not developed and licenced in Europe for children. To avoid off-label use and allow for a nationwide safe access to crz for pts with ALK, MET or ROS1+ tumor, the French National Cancer Institute (INCa) launched the AcSé program, funding both access to tumor molecular diagnosis and an exploratory multi tumor phase II trial. We report the results of 11 ped cases out of 159 pts. Methods: Molecular diagnosis was performed in 28 regional INCa molecular genetic centers by break-apart FISH assays or sequencing. Rearrangements identified through pangenomic tumor profiling were eligible as well. Pts with ROS1, ALK or MET+ in treatment failure received crz 280 mg/m2 BID (except Anaplastic Large Cell Lymphoma [ALCL] pts who received crz 165 mg/m2BID) in capsules or oral solution. Responses were assessed every-8 weeks using RECIST v1.1. Results: From Aug. 2013 to Aug. 2015, 107 ped tumors were analyzed. Altered targets were found in 18 tumors (see table). 11 pts were enrolled, median age 9 yrs (range 3–16), 64% boys. 7 pts were still on treatment at the cut-off date, 2 for >12 months; 4 have stopped crz (2 PD, 1 doctor's decision, 1 patient's decision). Among the 8 evaluable pts (3 assessments pending), best responses were 1 CR (ALCL ALK trans), 3 PR (ALCL ALK trans, IMT ROS1 trans, meningioma ROS1 trans), 1 SD (mesothelioma ALK trans), and 3 PD (2 Nb ALK mut, glioma MET trans). Crz was well tolerated with 4 grade ≥3 AEs (QTc prolongation, nausea, loss of appetite, anemia). Mainly AEs were grade 1, were elevated transaminases (60% of pts), vomiting (50%), visual disorders (40%), fatigue (40%). Conclusions: Alterations of all crz targets were found in ped tumors and children can benefit from crz therapy. Clinical trial information: NCT02034981. Neuroblastoma (Nb) N=49 Rhabdomyosarcoma N=10 Inflammatory Myofibroblastic Tumor (IMT) N=3 Malignant Glioma N=14 Other cancers N=29 Miscellaneous with pangenomic profiling N=2 ALK Mutated 5 ALK Amplified (Amp) (>6 copies) 2 0 ALK Translocated (Trans) 1* 0 1 3 ROS1 Trans 1 1 MET Amp (>6 copies) 1 1 1 MET Trans 1 *: + ALK mutated.
Two distinct clinical phenotypes of pulmonary arterial hypertension secondary to systemic lupus erythematosus
Authors: Fangfang Sun, Yunxia Lei, Wanlong Wu, Li Guo, Kaiwen Wang, Zhiwei Chen, Wenwen Xu, Xiaodong Wang, Ting Li, Xiao Zhang, Shuang Ye
Journal: Annals of the Rheumatic Diseases (2018)

Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE), and SLE-PAH is the most common connective tissue disease (CTD)-associated PAH in Chinese patients.1 The prognosis of SLE-PAH is poor, with 3-year survival rates varying from 45% to 88%.2 3 Due to the complexity and heterogeneity of the underlying disease, it is necessary to further differentiate among SLE-PAH patterns to better understand the disease and optimise its management.

Between 2011 and 2016, a derivation cohort (Shanghai Ren Ji Hospital, n=108) and a validation cohort (Guangdong General Hospital, n=87) of patients with SLE-PAH from two medical centres were included. Patients with SLE-PAH were diagnosed based on right heart catheterisation or echocardiography (peak tricuspid regurgitation velocity >3.4 m/s), and those with left heart disease, pulmonary thrombosis and lung diseases were excluded.4 Based on the baseline clinical manifestations and laboratory findings at the time of the diagnosis of PAH, two distinct clusters were identified and validated by multiple correspondence analysis and k-means clustering. …
P04.59 Modeling the safety of topical agents for skin toxicity associated with tumor treating fields therapy in glioblastoma
Authors: M Lacouture, H Hershkovich, M Giladi, R Blat, Z Bomzon, E Kirson, U Weinberg, Y Palti
Journal: Neuro-Oncology (2018)

Tumor Treating Fields are low intensity, intermediate frequency, alternating electric fields that are approved for the treatment of patients with glioblastoma (GBM). TTFields are applied continuously using a set of four transducer arrays placed on the skin. The main TTFields-related adverse event is mild-moderate dermatitis occurring under the arrays, which is primarily caused by long-term exposure to irritants and may be exacerbated by local hyperhidrosis and occlusion. Strategies that mitigate skin irritation may improve patients’ quality of life and compliance with TTFields. Four product groups (antiperspirants, moisturizing creams, antibiotics, and skin barriers) have been anecdotally reported to alleviate factors related to TTFields-related skin irritation. Nonetheless, not all of the aforementioned products are compatible with TTFields as some may increase electrical impedance, which may lead to increased temperatures beneath the arrays. This study investigated the effect of applying 40 commercially available skin care products on electrical impedance during TTFields application, using a rat model. In these experiments, 200 kHz TTFields were applied using ceramic disks and hydrogels identical to those used with human arrays. Changes in impedance caused by applying each product on the rat skin were measured using the Optune device and an LCR meter system. The review identified a set of skin care products from all 4 groups that did not lead to a significant change in the impedance. Preliminary tests in the clinical setting with these products were promising in a few patient case studies. These results suggest that local application of TTFields-compatible skin care products could maintain normal electrical resistance of the scalp-array interface, thereby allowing optimal delivery of TTFields to the brain. These products should be prospectively investigated for their potential role in minimizing TTFields-related skin irritation.
TCT-667 Causes and Clinical Outcomes of Patients with Mitral Regurgitation Who are ineligible for Transcatheter Mitral Valve Replacement
Authors: Hiroki Niikura, Mario Goessl, Vibhu Kshettry, Sara Olson, Benjamin Sun, Judah Askew, John Lesser, Richard Bae, Kevin Harris, Paul Sorajja
Journal: Journal of the American College of Cardiology (2018)
Sustained long-term benefits of a psycho-educational intervention targeting fear of cancer recurrence in people at high risk of developing another melanoma: A randomised controlled trial.
Authors: Mbathio Dieng, Rachael L Morton, Daniel SJ Costa, Phyllis Butow, Scott Menzies, Serigne Lo, Graham J Mann, Anne E. Cust, Nadine Kasparian
Journal: Journal of Clinical Oncology (2018)

10082 Background: People with melanoma want and need effective treatments for managing and living with fear of cancer recurrence (FCR). This study reports the long-term efficacy of a psycho-educational intervention designed to reduce FCR in people at high risk of developing another primary melanoma compared to usual care. Methods: Adults previously diagnosed with stage 0, I or II melanoma were randomly allocated to the intervention (n= 80) or control (usual care) arm (n= 84). Of 164 participants, 87% completed the 12-month assessment. Outcomes for 8 participants (5%) who completed the 6-month but not the 12-month assessment were imputed using model-based multiple imputation; thus, 151 participants are reported in the analysis. The intervention comprised a 76-page psycho-educational resource and three individually-tailored, telephone-based sessions with a psychologist, scheduled at specific time-points around participants’ dermatological appointments. The intervention effect at 12-months was estimated by intention-to-treat analysis of the mean change in FCR score using a linear mixed model and as a FCR severity sub-score ≥13 vs < 13 using logistic regression adjusted for repeated measures. Results: The intervention group had significantly lower FCR at 12 months; the between-group mean difference was −1.41 for FCR severity (95% CI −2.6 to −0.2; p= 0.02), and −1.32 for FCR triggers (95% CI −2.6 to −0.02; p= 0.04). The odds ratio for FCR severity ≥13 (54% intervention, 63% control) was 0.59 (95% CI 0.30 to 1.14, p= 0.12). There were no differences in secondary outcomes including anxiety, depression, or health-related quality of life. Conclusions: This psycho-educational intervention had a sustained effect in reducing fear of cancer recurrence over the longer-term. This novel intervention has no adverse effects and its benefits persist long after the last psychology session, supporting implementation as part of routine clinical care in melanoma. Clinical trial information: ACTRN12613000304730.
Quality and impact of eviQ Cancer Treatments Online: The medical oncologist's perspective.
Authors: Lydia PY. Loke, Tina YT Chen, Craig R. Lewis, Robyn L. Ward, Shelley A. Rushton, Jeremy David Shapiro
Journal: Journal of Clinical Oncology (2016)

e18214 Background: eviQ is a free, point-of-care online resource supporting best practice and currently has ~ 60 000 registrants globally. Over 600 Australian clinicians are involved in content development, and eviQ lists over 600 evidence-based cancer treatment protocols in medical/radiation oncology, hematology and cancer genetics. eviQ is widely used by cancer clinicians and is easily embedded in the clinical workflow. The aim of this study was to evaluate the use, effectiveness, and impact of eviQ amongst Australian medical oncologists. Methods: A web-based survey was administered to members of the Medical Oncology Group of Australia (MOGA) by email via the distribution list (includes medical oncologists and oncology trainees). Two reminders were sent to encourage participation. Results: Amongst 97 respondents (~15%), all but one, were practicing in Australia, with varying years of oncology experience ( < 2yrs: 25%, 2-10yrs: 36%, > 10 yrs: 39%). Over half (56%) of the respondents accessed the eviQ website on most days, while 32% and 9% in most weeks and months, respectively. Only 3% rarely accessed eviQ. eviQ was most frequently used as a source for providing patient information sheets on chemotherapy side effects, with 57% of respondents using eviQ for this purpose on most days. Other common uses included accessing side effect information (27%), checking drug doses (26%) and guiding dose adjustments (22%). The information quality of eviQ was deemed high, with the majority of respondents rating it as current, relevant and easy to understand (table 1). Most of the respondents considered that they provided better care with enhanced patient experience as a result of using eviQ (table). Conclusions: eviQ is highly regarded by Australian medical oncologists who responded to our survey. The results suggest that usage of eviQ has a positive impact on individual knowledge, practice and promotes better patient-centered care. Information quality Agreed or strongly agreed Up-to-date 91% Accurate 92% Relevant 98% Clear 87% Individual impact of using eviQ Agreed or strongly agreed Better informed 93 % Make better decisions 76 % Deliver treatments more safely 82 % Think their patients have a better experience 85 %