tbuckley/cabot-search huggingface dataset:
Barriers for lung cancer screening in an inner city community primary care center.
Authors: Jean Gabriel Bustamante Alvarez, Konstantinos Sdrimas, Daniel Brito, Jessica Stemple
Journal: Journal of Clinical Oncology (2016)

e13037 Background: lung cancer remains the leading cause of cancer death worldwide. Recently the USPFTF launched guidelines for lung cancer screening with low dose computer tomography of the chest. However compliance with the guidelines in the community remains low. We tried to identify barriers for proper lung cancer screening in the primary care setting Methods: anonymous questioners were filled by the internal medicine residents in a community practice center with 20 questions regarding their knowledge and practices about current USPSTF guidelines on lung cancer screening. Results were analyzed per year of training. In parallel, a patient survey to assess awareness and personal preferences regarding lung cancer screening was conducted and 50 of the questionnaires were included in the analysis. Results: 36 residents were included in the survey at the community center clinic of AEMC. 15 were PGY1, 13 PGY2 and 8 PGY3. 73 % of PGY 1s were aware of proper lung cancer screening with low dose CT of the chest, compared to 84.6% and 87.5% of PGY 2 and 3 respectively. Only 31 % of the residents felt confident applying the proper screening criteria and 69% of them felt they are not doing a good job referring patients for screening. 28 % of the patient preferred not to know whether they have lung cancer and 10% raised concerns about cost and lack of insurance coverage regarding screening. Conclusions: the implementation of established lung cancer screening guidelines in the community remains problematic. Despite the non-invasiveness of the screening modality a significant percentage of the population refrains from screening due to the guarded prognosis of the diagnosis. At the same time residents even at the final year of training failed to properly screen and identify eligible candidates.
Disability Enrollment in a Community-Based Coordinated Specialty Care Program
Authors: Jennifer Humensky, Jennifer Scodes, Melanie Wall, Igor Malinovsky, Leslie Marino, Thomas Smith, Lloyd Sederer, Ilana Nossel, Iruma Bello, Lisa Dixon
Journal: American Journal of Psychiatry (2017)

safe storage of firearms.Although legislation governing firearm safety is largely a matter of state law, there is also a role for national leadership.We urge the American Psychiatric Association to work with interested national stakeholders to draft model state legislation concerning firearm safety during suicidal crises.If widely adopted, such legislation could help combat the national crisis in firearm-related suicides.A model state law would enable psychiatrists, other physicians, and other licensed mental health professionals to authorize temporary firearm transfers from suicidal individuals to other responsible adults.
Abstract 15928: Cardiovascular Stroke Nursing Best Abstract Award: Association of Posttraumatic Stress Disorder With Repolarization Heterogeneity in Veteran Twins
Authors: Amit J Shah, Zain Khan, Nino Isakadze, Emir Veledar, Jack Goldberg, James D Bremner, Rachel Lampert, Viola Vaccarino
Journal: Circulation (2016)

Introduction:  Posttraumatic stress disorder (PTSD) is a debilitating psychological condition that is prevalent amongst veterans and associated with increased risk of CHD. The elevated sympathetic nervous system activity that characterizes PTSD could affect cardiac electrophysiology and increase the risk of sudden cardiac death. We hypothesized that PTSD is associated with increased microvolt T-wave alternans (TWA), a measure of repolarization heterogeneity that is associated with increased risk of sudden cardiac death.   Methods:  We studied 186 male twins from the Vietnam Era Twin Registry. The twins wore a Holter monitor for 24 hours, and a thorough baseline assessment was performed, including a structured clinical interview for diagnosing psychiatric disorders, as well as cardiovascular assessment for traditional risk factors. The maximum T-wave alternans in 24 hours of monitoring was measured using the modified moving average method (GE Medical). Mixed models were used in analysis to assess covariance within pairs, and co-twin control modeling was performed to evaluate genetic and familial confounding.   Results:  The average (SD) age was 57 (2) years, and 28 twins had PTSD symptoms within 30 days of assessment. The twins with active PTSD had a 28% higher TWA compared to the others (p=0.03). This relationship did not change after adding heart rate to the model; further addition of CHD history and traditional CHD risk factors to the model also did not significantly influence the association. When analyzing the association within 22 pairs discordant for PTSD (to adjust for familial factors), the brother with PTSD had a 42% higher TWA compared to the brother without PTSD in fully adjusted models. An interaction with zygosity was also found (p=0.03), such that the effect was significant within the dizygotic (10 pairs), but not monozygotic twin pairs (12 pairs). Within the dizygotic twin pairs, the PTSD brother was found to have a 127% (p=0.001, adjusted) higher TWA compared to the non-PTSD brother.   Conclusion:  PTSD is associated with increased TWA in veteran twins, but this relationship is confounded by genetic factors. This suggests common genetic factors may predispose to both PTSD and repolarization heterogeneity. Further research is warranted.
Social functioning in patients with first-episode psychosis
Authors: Nikolai Albert, Jamal Uddin, Merete Nordentoft
Journal: The Lancet Psychiatry (2017)

Dissemination of early intervention facilities in many developed countries has led to an improved outcome for patients with first-episode psychosis.1–3 However, this improvement does not necessarily mean that the illness trajectory is radically shifted or that the overall outcome of the illness can be described as positive. Studies have shown that, although most patients have remission of their psychotic symptoms, a higher proportion have continuous negative symptoms that are severely debilitating for their long-term functional outcome.
Monocytes enhance neutrophil‐induced blister formation in an ex vivo model of bullous pemphigoid
Authors: E. de Graauw, C. Sitaru, M. P. Horn, L. Borradori, S. Yousefi, D. Simon, H.‐U. Simon
Journal: Allergy (2017)

Abstract Background Lesions of bullous pemphigoid ( BP ), an autoimmune subepidermal blistering disease characterized by the presence of tissue‐bound and circulating autoantibodies to hemidesmosomal antigens, harbor a mixed inflammatory cellular infiltrate. In various models, neutrophils, eosinophils, mast cells, monocytes as well as B and T cells have been shown to be involved in the pathogenesis of BP . However, their interactions with and effective role in blister formation remain uncertain. This study was aimed at investigating the effect of monocyte/neutrophil interaction on blister formation in an ex vivo BP model. Methods Skin cryosections were incubated with purified human neutrophils and monocytes, in the presence or absence of BP autoantibodies. Production of reactive oxygen species ( ROS ), degranulation, mediator release (neutrophil elastase [ NE ], myeloperoxidase [ MPO ], matrix metalloproteinase‐9 [ MMP ‐9]), binding of Fcγ receptor ( CD 16, CD 32, CD 64), and cell adhesion ( CD 18, ICAM ‐1) was investigated using appropriate inhibitors. Dermal‐epidermal separation ( DES ) was assessed by light microscopy and quantified by Fiji software. Results Monocytes and neutrophils synergistically interact resulting in a significantly higher DES compared to either monocytes or neutrophils separately ( P &lt; .0001). Monocyte/neutrophil‐induced DES was associated with increased ROS production and was dependent on adhesion and Fcγ RIII binding. Upon stimulation by the granule‐poor fraction of monocyte supernatants, neutrophils increased their release of MMP ‐9, thereby also DES at the dermal‐epidermal junction of skin cryosections. Conclusion Our observations suggest that the interaction of cells, as shown here for monocytes and neutrophils, enhances mediator release resulting in an increased subepidermal blister formation. Thus, blocking intercellular cross talk promises a new therapeutic approach for blocking tissue damage in BP .
The identification of genes associated with the metastatic LNCaP-LN3 prostate cancer cell line.
Authors: Loleta Harris, Renduo Song, Curtis Pettaway
Journal: Cancer Research (2008)

4496  Introduction and Objective: To investigate the biology of prostate cancer progression our lab establishedanorthotopic model of human prostate cancer. Two distinct subpopulations of the parental LNCaP cell line were selected. The LNCaP-Pro5 cell line is tumorigenic within the prostate while the LNCaP-LN3 cell line is metastatic (Pettaway et.al Clin.Can.Res.). To identify candidate genes and signaling pathways associated with the metastatic phenotype of prostate cancer we examined the differential expression between the LNCaP-Pro5 and LNCaP-LN3 cell lines.  Materials and Methods: RNA was extracted from LNCaP-Pro5 and LNCaP-LN3 cell lines and used for DNA microarray and real time PCR analysis. The U133A plus 2.0 Affymetrix chips were used. Gene expression was detected and analyzed using GCOS software (Affymetrix). Differential expression was determined significant using the criteria FC   2.00, where FC was computed as the ratio of expression in the geometric means in LNCaP-LN3 to LNCaP-Pro5. Genes meeting the FC criteria for change in the LNCaP-Pro5 and LNCaP-LN3 cell lines were loaded into Ingenuity Systems, and explored for pathway and functional enrichment.  Results: Sixty percent of the genes tested by real time PCR analysis correlated with DNA microarray data. Of these genes BCL2, ERBB4, NFKBIA, SEMA3F, SNAI1, TWIST1 and VEGF were validated. Overall microarray analysis identified fifty-five genes differentially expressed between LNCaP-Pro5 and LNCaP-LN3 involved in metastasis and angiogenesis. These data implicate established genes (i.e. BCL2, CXCR4, TWIST1, and VEGF) as well as genes novel to prostate cancer progression (i.e. AHSG, F2R, RET, and ZAP70) . In addition, significant changes observed in AHSG, CD44, CXCR4, ERBB2, ERBB4, F2R, FGF2, FYN, ITGB3, ITGB4, MAPK1, MMP14, MMP3, MMP9, NFKBIA, NRG1, NRP1, PTK2, RHOC, SERPINA1, SOCS1, and STAT3, implicate the actin cytoskeleton, acute phase response, axonal guidance, ephrin receptor, integrin, leukocyte extravasation, and neuregulin signaling pathways in prostate cancer metastasis.  Conclusion: Gene expression analysis of the LNCAP-Pro5 and LNCAP-LN3 cell lines identified fifty-five genes significantly associated with the metastatic phenotype of LNCaP-LN3. The differential expression between LNCAP-Pro5 and LNCAP-LN3 involve alterations in the actin cytoskeleton, acute phase response, axonal guidance, ephrin receptor, integrin, leukocyte extravasation, and neuregulin signaling pathways.
Abstract B17: Targeting the oncogenic TBX3 and its co-factors in anti-cancer drug development
Authors: Tarryn Willmer, Shannon Smyly, Danica Smuts, Sharon Prince
Journal: Cancer Research (2017)

Abstract Sarcomas are heterogeneous neoplasms of mesenchymal origin whose clinical management is compromised due to inadequate diagnostic markers and limited therapeutic options. While the incidence rates for sarcomas in Africa remain uncertain, there is a widely held view that they are common in black African children and adolescents. Indeed, according to a Nigerian study, soft tissue sarcomas make up as much as 11.3% of all childhood cancers. We recently reported that the transcription factor, TBX3, is overexpressed in a diverse range of sarcoma subtypes where it plays a direct oncogenic role and it has been proposed as a novel target for their treatments. Direct targeting of transcription factors for therapies however continues to represent a serious challenge and therefore the molecular mechanisms that mediate its biological activity may be more amenable as anti-cancer drug targets. To address this, affinity purifications coupled with mass spectrometry was performed to identify TBX3 protein co-factors that regulate its oncogenic activity in sarcomas. Here we describe the validation of nucleolin as TBX3 co-factor by co-immunoprecipitation assays and confocal microscopy/co-localization analysis. The effect of nucleolin on TBX3 function was determined using RNAi rescue experiments coupled with growth curve and scratch motility assays to assess cell proliferation and migration respectively. Finally, the effect of the nucleolin targeting aptamer, AS1411, on the cell viability of a range of sarcoma subtypes was tested. Results show that the overexpression of TBX3 and nucleolin are common in a number of sarcoma subtypes. We provide compelling evidence that nucleolin interacts with and co-operates with TBX3 to promote proliferation and migration of chondrosarcoma, liposarcoma and rhabdomyosarcoma cells. Furthermore, AS1411 exhibits potent anti-cancer activity in these sarcomas whilst it has no effect on normal cells. In conclusion, we propose that TBX3 and nucleolin can be used in combination as biomarkers for the diagnosis and targeted therapy of a diverse range of sarcomas which are highly aggressive and treatment resistant cancers. Citation Format: Tarryn Willmer, Shannon Smyly, Danica Smuts, Sharon Prince. Targeting the oncogenic TBX3 and its co-factors in anti-cancer drug development [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B17.
Helicobacter pylori CagA expression is closely associated with tumor PD-L1 expression and the better prognosis of gastric cancer patients
Authors: S-H Kuo, M-S Wu, J-M Liou, C-T Shun, M-F Wei, Y-S Zeng, P-N Hsu, A-L Cheng
Journal: Annals of Oncology (2017)
Quality and Outcomes Framework could be a unique new national information resource
Authors: John Robson, Kambiz Boomla
Journal: BMJ (2017)

Regarding the Quality and Outcomes Framework, Marshall and Roland say that we should “move on and do better.”1

In doing so, can we find a way to build on and develop the best of the framework? Many measures are instrumental national process measures for the NHS, which are useful for practices, Clinical Commissioning Groups, …
malERA: An updated research agenda for malaria elimination and eradication
Authors: Regina N. Rabinovich, Chris Drakeley, Abdoulaye A. Djimde, B. Fenton Hall, Simon I. Hay, Janet Hemingway, David C. Kaslow, Abdisalan Noor, Fredros Okumu, Richard Steketee, Marcel Tanner, Timothy N. C. Wells, Maxine A. Whittaker, Elizabeth A. Winzeler, Dyann F. Wirth, Kate Whitfield, Pedro L. Alonso
Journal: PLoS Medicine (2017)

Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits. WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the “Global Technical Strategy” and 21 countries are aiming to eliminate malaria by 2020. The commitment to achieve these targets should be celebrated. However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever. Over 180 experts across multiple disciplines are engaged in the Malaria Eradication Research Agenda (malERA) Refresh process to address problems that need to be solved. The result is a research and development agenda to accelerate malaria elimination and, in the longer term, transform the malaria community’s ability to eradicate it globally.
Abstract IA3: The impact of premature death of women from preventable cancers, such as cervical cancer
Authors: Lynette Denny
Journal: Cancer Research (2017)

Abstract Cervical cancer is the second most common cancer among women living in sub-Saharan Africa, yet more women die from cervical cancer than women with breast cancer. Despite cervical cancer being preventable, services for prevention, early detection and treatment are rare in most poorer countries, and most women die in the 4th-5th decade, a time when their children are particularly vulnerable, especially the girl child. The global adult mortality rate per 1000 population by WHO region in 2011 was 160, with the highest rate being in Lesotho at 541/1000. The under 5 mortality rate per 1000 live births in the African WHO region was 95/1000 in 2012 and 12 in Europe. The Gender Inequality Index (GII) is a composite index that reflects women's relative social disadvantage in three dimensions - reproductive health, empowerment and the labour market. Using the GII, among a number of other indices, it was found that overall women in developing countries had two-fold higher cervical cancer incidence rates and three-fold higher mortality rates than their counterparts from developed countries. Deprivation levels or poverty rates were a strong predictor of cross-national variations in cervical cancer incidence and mortality. Losing a parent, especially a mother for young girls may be catastrophic as her health and care is likely to deteriorate significantly. This paper will explore the range of effects of premature deaths of mothers on children in poor countries. Citation Format: Lynette Denny. The impact of premature death of women from preventable cancers, such as cervical cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA3.
Associations Between Tau, β-Amyloid, and Cognition in Parkinson Disease
Authors: Joseph R. Winer, Anne Maass, Peter Pressman, Jordan Stiver, Daniel R. Schonhaut, Suzanne L. Baker, Joel Kramer, Gil D. Rabinovici, William J. Jagust
Journal: JAMA Neurology (2017)

Multiple disease processes are associated with cognitive impairment in Parkinson disease (PD), including Lewy bodies, cerebrovascular disease, and Alzheimer disease. It remains unknown whether tau pathology relates to cognition in patients with PD without dementia.To compare tau aggregation in patients with PD who are cognitively normal (PD-CN), patients with PD with mild cognitive impairment (PD-MCI), and healthy control participants, and evaluate the relationships between β-amyloid (Aβ), tau, and cognition in patients with PD who did not have dementia.This cross-sectional study recruited 30 patients with Parkinson disease (15 with PD-CN and 15 with PD-MCI) from a tertiary care medical center and research institutions from July 2015 through October 2016. One patient with PD-MCI did not receive a magnetic resonance imaging scan and thus was excluded from all analyses; 29 patients with PD were included in the present study. Participants underwent tau positron emission tomographic (PET) scanning with fluorine 18-labeled AV-1451, Aβ PET scanning with carbon 11-labeled Pittsburgh compound B, magnetic resonance imaging, cognitive testing, and neurologic evaluation. Imaging measures were compared with 49 healthy control participants.Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. We hypothesized that tau aggregation across groups would be related to age and Aβ status.Of the 78 participants, 47 (60%) were female, and the mean (SD) age was 71.1 (6.6) years. Six patients with PD (21%) were Aβ-positive, of whom 1 was mildly cognitively impaired; 23 were Aβ-negative (79%). (Of the 49 healthy controls, 25 were Aβ-negative and 24 Aβ-positive.) Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and additionally between all patients with PD and Aβ-negative controls, did not reveal significant differences. Tau PET binding did not differ between patients with PD-MCI and PD-CN in brain regions reflecting Alzheimer disease Braak stages 1/2, 3/4, or 5/6, and did not differ from Aβ-negative healthy older adults. Mean (SD) tau PET binding was significantly elevated in Aβ-positive patients with PD relative to Aβ-negative patients with PD within brain regions reflecting Alzheimer disease Braak stage 3/4 (1.22 [0.07] vs 1.14 [0.07]; P = .03) and Braak stage 5/6 (1.20 [0.07] vs 1.11 [0.08]; P = .02).These findings suggest that patterns of cortical Aβ and tau do not differ in people with PD-CN, people with PD-MCI, and healthy older adults. Age, Aβ, and tau do not differentiate patients with PD-CN and PD-MCI. Tau deposition is related to Aβ status and age in both people with PD and healthy older adults. Cognitive deficits in people with PD without dementia do not appear to reflect measureable Alzheimer disease.
Phase I trial of an oral TORC1/TORC2 inhibitor (CC-223) in advanced solid and hematologic cancers.
Authors: Kent C. Shih, Johanna C. Bendell, Anne Reinert, Suzanne Jones, Robin Katie Kelley, Jeffrey R. Infante, Michael Korn, Kristen Hege, Rajesh Chopra, Shuichan Xu, Lilly Wong, Yong Liu, Deborah Mortensen, Pamela N. Munster
Journal: Journal of Clinical Oncology (2012)

3006^ Background: The mammalian target of rapamycin (mTOR) signaling pathway is frequently activated in cancer. The mTOR kinase exists in two multi-protein complexes, TORC1 and TORC2, which drive key cellular metabolic and proliferative functions. TORC1-selective inhibitors can induce feedback upregulation of TORC2 and treatment resistance. CC-223 is an oral, potent, selective, ATP-competitive inhibitor of both TORC1 and TORC2, selected to address this escape mechanism. Methods: Subjects with advanced solid and hematologic cancers were enrolled using an accelerated (1+5) dose escalation design. CC-223 was administered orally once daily (QD) in 28 day cycles until disease progression. Safety, pharmacokinetic, pharmacodynamic and clinical endpoints were evaluated. Results: 28 subjects were treated across 5 dose levels: 7.5 (n=1), 15 (n=2), 30 (n=9), 45 (n=7) and 60 mg (n=8). The most common (&gt; 20%) related adverse events (all grades) were fatigue (64%), nausea (50%), hyperglycemia and diarrhea (43% each), mucositis (39%), anorexia and vomiting (32% each) and rash (29%). Dose-limiting toxicity (all grade 3) occurred in 4 subjects: hyperglycemia (30 mg), rash (45 mg), fatigue (60mg), and mucositis (60 mg). The maximum tolerated dose (MTD) was 45 mg QD. Dose proportional exposure was observed with a terminal half life of 4 to 8 hrs (mean steady state C max 485 ng/mL, AUC 0-24 2371 ng x hr/mL at 45 mg). Inhibition of TORC1 (pS6, p4EBP1) and TORC2 (pAKT) biomarkers in blood cells was characterized to be exposure-dependent and described by an E max model. Near maximal inhibition of both TORC1 and TORC2 biomarkers was achieved at the peak concentrations of 30 or 45mg QD. Target inhibition was predicted to last 8 to 20 hours at 45mg QD. Tumor responses included: 1 partial response lasting 9 months (ER+ breast) and 7 subjects with stable disease (SD) lasting 8+ weeks (range 8 to 23.3). Conclusions: CC-223 was well tolerated with toxicities comparable to other drugs in this class. Evidence of TORC1/TORC2 pathway inhibition was observed as well as preliminary signals of anti-tumor activity, including one durable PR. Expansion cohorts in selected hematologic and solid tumors will evaluate CC-223 at the MTD of 45 mg QD.