tbuckley/cabot-search huggingface dataset:
Abstract 3525: The BET inhibitor INCB054329 is efficacious as a single agent or in combination with targeted agents in colorectal cancer models
Authors: Xuesong Liu, Jun Li, Xin He, Matthew Stubbs, Margaret Favata, Xiaoming Wen, Hong Chang, Beth R. Rumberger, Yanlong Li, Thomas Maduskuie, Richard Sparks, Nikoo Falahatpisheh, Padmaja Polam, Andrew P. Combs, Reid Huber, Gregory Hollis, Peggy Scherle, Phillip C. Liu
Journal: Cancer Research (2015)

Abstract The Bromodomain and extra-terminal (BET) family of proteins consists of BRD2, BRD3, BRD4 and BRDT. Each BET protein contains two bromodomains (BD1 and BD2) that recognize acetylated histones at enhancer and promoter regions of a select number of genes. BET proteins function as transcriptional regulators that are critical for the expression of oncogenes such as c-Myc; thus, BET proteins are important for cancer cell proliferation and survival. We have identified INCB054329, a potent and selective BET protein inhibitor that targets BD1 and BD2 of BRD2, BRD3 and BRD4. In this study, we characterized the pharmacology of INCB054329 in solid tumor cell lines. In a panel of colon cancer cell lines, more than 50% are sensitive to INCB054329 treatment with IC50 values below 500 nM in cell proliferation assays. INCB054329 down-regulated c-Myc expression, and induced cell cycle arrest and apoptosis in sensitive colon cancer cell lines. Moreover, INCB54329 was efficacious in the RKO colon cancer xenograft model. To understand whether BRD inhibition would synergize with other signaling pathway inhibitors and standard of care agents for colon cancer, we employed a high throughput combination screening strategy. Several combinations were active in a panel of colon cancer cell lines and demonstrated synergistic interactions based on combination index values. As an example, strong synergy was observed between INCB054329 and MEK inhibitors. The combination of INCB054329 and MEK inhibitors synergistically blocked expression of c-Myc protein and inhibited the MEK/ERK signaling pathway. Our data suggest the potential utilization of INCB054329 as a single agent or in combination with other targeted therapies for the treatment of colon cancer. Citation Format: Xuesong Liu, Jun Li, Xin He, Matthew Stubbs, Margaret Favata, Xiaoming Wen, Hong Chang, Beth R. Rumberger, Yanlong Li, Thomas Maduskuie, Richard Sparks, Nikoo Falahatpisheh, Padmaja Polam, Andrew P. Combs, Reid Huber, Gregory Hollis, Peggy Scherle, Phillip C. Liu. The BET inhibitor INCB054329 is efficacious as a single agent or in combination with targeted agents in colorectal cancer models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3525. doi:10.1158/1538-7445.AM2015-3525
Elevated Plasma Lipoprotein(a) Is Associated With Coronary Artery Disease in Patients With Chronic Stable Angina Pectoris 11Dr. Cox is supported by a Fellowship Grant from the British Heart Foundation, London.
Authors: Raúl A Schwartzman, Ian D Cox, Jan Poloniecki, Robert Crook, Carol A Seymour, Juan Carlos Kaski
Journal: Journal of the American College of Cardiology (1998)
Abstract 553: In Vivo Cardioprotection by Postconditioning is Mediated by Endogenous PAR2 Activation
Authors: Rong Jiang, Jeremiah Deneve, Shady Eldaif, Ning-Ping Wang, Zhi-Qing Zhao, Jacob Vinten-Johansen
Journal: Circulation (2007)

Background : Protease activated receptor 2 (PAR2) is a member of the seven transmembrane G-protein coupled receptor (GPCR) family. Activation of PAR2 is cardioprotective in ex vivo and in vivo myocardial ischemia reperfusion model, potentially by cognate ligands released at reperfusion (R). Postconditioning (postcon), defined as alternating brief (seconds) episodes of R and ischemia applied at the onset of R , is also cardioprotective. This cardioprotection involves activation of GPCR by adenosine, bradykinin and opioids. However, the role of the GPCR PAR2 in cardioprotection by postcon has not been investigated. Hypothesis : This study tested the hypothesis that cardioprotection by postcon is mediated in part by endogenous PAR2 activation. Methods : Rats were randomly assigned to one of 5 groups with 30 min left coronary artery (LCA) occlusion followed by 3 h reperfusion: Control: no intervention was applied either before or after LCA occlusion (n =8); Postcon alone: 3 cycles of 10-s full reperfusion and 10-s re-occlusion were initiated at the onset of R (n=8); PAR2 antagonist alone: the selective PAR2 antagonist (FSLLRY-NH2, 1 mg/Kg) was injected 5 min before R (n=8); PAR2 antagonist + Postcon: PAR2 antagonist (1 mg/Kg) was administered 5 min before Postcon (n=8); Delayed PAR2 antagonist: PAR2 antagonist (1 mg/Kg) was given 5 min after the postcon protocol (n=8). Results: Area at risk (AAR) was comparable in all groups (35–38%). Compared to control, infarct size (TTC, area of necrosis/AAR, %) was significantly reduced by postcon alone (39.0% ± 1.3% vs 53.7% ± 1.5%, P&lt;0.05). The PAR2 antagonist alone administered just before R had no effect on infarct size (57.4% ± 2.4% vs 53.7% ± 1.5%). Interestingly, the infarct sparing effect of postcon was completely reversed by PAR2 antagonist administered before postcon to control values ( 56.7% ± 2.7% *). Furthermore, the infarct sparing effect of postcon was also blocked by PAR2 antagonist given after postcon (50.3% ± 3.3% *). These results suggest that endogenous PAR2 activation induced by postcon during the early moments of R is cardioprotective. Conclusions : Cardioprotection by postcon is mediated, in part, by activation of endogenous PAR2, and suggests a general activation of GPCR. *P&lt;0.05 vs Postcon.
Bone SPECT/CT of Femoral Head Subchondral Insufficiency Fracture
Authors: Goro Motomura, Takuaki Yamamoto, Kazuyuki Karasuyama, Yukihide Iwamoto
Journal: Clinical Nuclear Medicine (2015)

Subchondral insufficiency fracture of the femoral head may be confused with osteonecrosis, mainly because of radiological overlap. SPECT/CT with Tc-99 m hydroxymethylene diphosphonate images in 7 patients with subchondral insufficiency fracture were retrospectively reviewed and compared with those from 11 patients with symptomatic early osteonecrosis. In all of the hips with subchondral insufficiency fracture, SPECT/CT showed increased uptake at the subchondral lesions of the femoral head. On the other hand, in all of the hips with osteonecrosis, absence of uptake was confirmed at the subchondral lesions. SPECT/CT may assist in differentiating subchondral insufficiency fracture from osteonecrosis.
Abstract 14840: Regional changes in Left Ventricular function and geometry - Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement.
Authors: Timothy A Fairbairn, Christopher D Steadman, Adam N Mather, Manish Motwani, Daniel J Blackman, Gerry P McCann, Sven Plein, John P Greenwood
Journal: Circulation (2011)

Introduction Aortic Stenosis (AS) produces a pressure overloaded left ventricle (LV). Initial hypertrophy leads to eventual diastolic and systolic dysfunction. Transcatheter Aortic Valve Implantati...
Clinical predictors of recurrence in depression
Authors: D. E. Giles, R. B. Jarrett, M. M. Biggs, D. S. Guzick, A. J. Rush
Journal: American Journal of Psychiatry (1989)

In a longitudinal study of 30 successfully treated unipolar depressed patients, the authors evaluated number of depressive episodes, early onset of depression, and lifetime prevalence of affective disorders other than major depression as risk factors for recurrence. Early onset of depression (before age 20) and a history of affective disorders other than major depression were each significantly associated with recurrence. Number of episodes was not as powerful in predicting recurrence as either early onset or lifetime prevalence of other affective disorders.
Endometrial Histology and Biochemistry in Climacteric Women during Oestrogen and Oestrogen/Progestogen Therapy
Authors: M I Whitehead, J McQueen, R J B King, S Campbell
Journal: Journal of the Royal Society of Medicine (1979)

177 patients were recruited between 1973 and 1977 to participate in a study to determine the endometrial response to exogenous estrogens and the modifying effect of progestogens on this response; hence, the endometrial proliferation during cyclical estrogen therapy and sequential estrogen/progestogen therapy was studied longitudinally. The patients were peri-or postmenopausal. Cyclical thereapy ranged from 2-47 months (mean, 15.1 months). With high-dose estrogen, cystic glandular hyperplasia was diagnosed in 16 (23%) patients, and atypical hyperplasia in 6 (9%); with low-dose regimens, cystic glandular hyperplasia was diagnosed in 4 (12%) and atypical hyperplasia in 2 (6%) patients. Sequentia therapy ranged from 2-50 months (mean, 16.2 months). With high dose regimens, 1 (2%) was found to have cystic glandular hyperplasia and 1 atient (2%) atypical hyperplasia; with low doses atypical hyperplasi was diagnosed in 1 patient (3%). these data therefore suggested that progestogens protected the endometrium against estrogen-induced stimulation, although complete protection was not afforded. Progestogens also depressed cytoplasmic progesterone receptor levels and induced the formation of estradiol 17-beta-dehydrogenase, as shown by the following findings: in all samples from Weeks 2 and 3, no activity of the enzyme was detectable. During norethisterone administration (Week 4), however, the activity rose to the premenopausal secretory range and was significantly higher than that in Weeks 2 and 3 (P .001 and P .001, respectively). Measurement of cytoplasmic progesterone receptor confirmed that the estrogenic stimulus being applied to the endometrium was potent.
Abstract 1112: Loss-of-function genetic screening with shRNA and CRISPR libraries
Authors: Donato Tedesco, Mikhail Makhanov, Sylvain Baron, Dmitry Suchkov, Alex Chenchik
Journal: Cancer Research (2015)

Abstract Genome-wide loss-of-function screens provide a direct approach to identify the genes regulating biological responses and find new therapeutic targets. While RNAi screens have proven an effective tool for these screens, CRISPR/CAS9 provides an alternative approach to implement these screens. To complement our established shRNA screening platform, we have developed pooled format genome-wide modular sgRNA libraries for cost-effective functional CRISPR knockout screens. Pooled sgRNA and shRNA libraries were then run to identify lethal interactions in isogenic PDX-derived cell line pairs. Citation Format: Donato Tedesco, Mikhail Makhanov, Sylvain Baron, Dmitry Suchkov, Alex Chenchik. Loss-of-function genetic screening with shRNA and CRISPR libraries. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1112. doi:10.1158/1538-7445.AM2015-1112
Emerging Salmonella Enteritidis anaerogenic phage type 14b: Outbreak in Norwegian, Swedish and Finnish travellers returning from Greece
Authors: P J Guérin, K Nygård, A Siitonen, L Vold, M Kuusi, B de Jong, J A Rottingen, O Alvseike, A Olsson, J Lassen, Y Andersson, P Aavitsland
Journal: Eurosurveillance (2006)

In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet, FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in Norwegian travellers returning from Greece. An increase in the same uncommon phage type was also registered in Sweden and Finland at the same time. Cases of S. Enteritidis PT 14b in patients returning from Greece were reported in these three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199 cases). Case-control studies performed in 2001 in Norway and Sweden indicated that consumption of chicken was associated with illness. In 2002 and 2003, continuing case reports indicated that this uncommon phage type had probably become established in the Greek food chain. Tour operators were informed and contacts were made with Greek public health authorities. Because place of infection is not systematically included in most Salmonella notification systems, the S. Enteritidis phage type 14b outbreak reported here may represent only part of a larger outbreak among travellers visiting Greece. Infections are often reported only in the tourists’ home countries and public health authorities in the tourist destinations may not be aware of the problem. Further collaboration between national institutes of public health in Europe is needed to detect outbreaks occurring among tourists.
Abstract 13729: Surgical Myectomy Results in Significantly Improved Long-term Event Rate in Hypertrophic Cardiomyopathy Patients With Severe Left Ventricular Outflow Tract Obstruction
Authors: Milind Y Desai, Nicholas G Smedira, Aditya Bhonsale, Nitesh Ainani, Maran THamilarasan, Bruce Lytle, Harry Lever
Journal: Circulation (2014)

Background: In hypertrophic cardiomyopathy (HCM) with severe left ventricular outflow tract obstruction (LVOTO), surgical myectomy (SM) performed for relief of intractable symptoms is safe and associated with excellent long-term symptom-free survival. In such patients, we sought to determine if SM also results in improvement of long-term outcomes. Methods: We studied 1530 HCM patients with severe LVOTO (50±13 years, 63% men) that were evaluated at our center [excluding &lt;18 years of age, LV ejection fraction (LVEF) &lt;50%, LVOT gradient &lt;30 mm Hg). Clinical, echocardiographic and surgical data were recorded. A composite endpoint of death and/or implantable defibrillator (ICD) discharge was recorded. Results: Hypertension, coronary artery disease (CAD), family history of HCM and syncope were present in 41%, 15%, 17% and 18%, while 73% patients were in Functional Class (FC) ≥ II. Mean LVEF, basal septal thickness, LVOT gradient (resting or provocable) and indexed left atrial dimensions were 62±5%, 2.2±1 cm, 101±39 mm Hg, 2.2±0.4 cm/m2. During 8±6 years of follow-up, 990 (65%) patients underwent SM (of which 65% were isolated SM), while 540 (35%) did not. 94 (6%) patients had alcohol septal ablation (66 in the non myectomy group), while 18% developed atrial fibrillation (AF), and 18% had ICD. There were 169 (11%) events (151 deaths), with 0% 30-day mortality in the SM group. On stepwise multivariable Cox Proportional Hazard analysis, increasing age (Hazard Ratio or HR 1.22 [1.06-1.40]), CAD (HR 1.57 [1.06-2.33]), worsening FC (HR 1.34 [1.05-1.71]) and AF (HR 1.73 [1.23-2.43]) predicted higher events, while SM as a time-dependent covariate (HR 0.58 [0.41-0.81]) was associated with improved event-free survival (all p&lt;0.01). Kaplan-Meier curve showing impact of SM on outcomes is shown in Figure. Conclusion: In HCM patients with severe LVOTO, SM is associated with significant improvement in long-term outcomes when compared to watchful waiting.
Predictors of Response and Outcome to Terlipressin in Patients With Hepatorenal Syndrome
Authors: S. Vinit, A. Kumar, P. Sharma, R. Bansal, P. Tyagi, N. Bansal, V. Singla, M. Kumar, P. Ranjan, M. Sachdeva, A. Arora
Journal: Clinical Gastroenterology and Hepatology (2015)
Magnetic resonance imaging of schizophrenia-like psychoses associated with cerebral trauma: clinicopathological correlates
Authors: P Buckley, J P Stack, C Madigan, E O'Callaghan, C Larkin, O Redmond, J T Ennis, J L Waddington
Journal: American Journal of Psychiatry (1993)

Three patients with schizophrenia-like psychosis and two with schizoaffective-like psychosis who experienced cerebral trauma before the onset of their illness underwent clinical and magnetic resonance imaging evaluation. Each patient with a schizophrenia-like psychosis, but neither of those with a schizoaffective-like psychosis, showed abnormalities confined to or including the left temporal lobe. These observations complement recent findings in schizophrenia.
Gynecomastia
Authors: Glenn D. Braunstein
Journal: New England Journal of Medicine (2007)

During an evaluation for low back pain, a 67-year-old man is found to have gynecomastia on the right side that is nontender on palpation. Other than a body-mass index of 32, the findings on physical examination are normal. His medical history is notable only for hyperlipidemia; his only medication is a statin. How should his gynecomastia be evaluated and managed?
A Phase Ib/II Study of the Novel Anti-CXCR4 Antibody Ulocuplumab (BMS-936564) in Combination with Lenalidomide Plus Low-Dose Dexamethasone, or with Bortezomib Plus Dexamethasone in Subjects with Relapsed or Refractory Multiple Myeloma
Authors: Irene M. Ghobrial, Chia-Jen Liu, Raymond P. Perez, Paul Richardson, Kenneth C. Anderson, Jacob Laubach, Patrick Henrick, Alexandra Savell, Kaitlen Reyes, Kalvis Hornburg, Stacey Chuma, Peter Sabbatini, Pamela S. Becker
Journal: Blood (2018)
Abstract 3351: The Coronary Suction Wave in Humans Is Not Diminished by Ischemia Induced Left Ventricular Diastolic Dysfunction.
Authors: Stephen P Hoole, Paul A White, Patrick M Heck, Sadia N Khan, Michael O’Sullivan, Sarah C Clarke, Leonard M Shapiro, Peter M Schofield, David P Dutka
Journal: Circulation (2007)

Background: A dominant suction wave due to ventricular relaxation has been postulated to contribute to normal coronary artery flow. We hypothesised that this wave would: be present in diseased coronary arteries, occur at the appropriate time in the cardiac cycle and be diminished following coronary artery balloon occlusion due to ischemia induced diastolic LV dysfunction. Methods: Simultaneous coronary pressure - velocity and LV pressure - volume were invasively recorded at baseline and after 1 minute coronary balloon occlusion, in 10 patients with single vessel coronary disease and normal LV function. Net coronary wave intensity (WI) = (dP/dt).(dU/dt) was calculated using MatLab software. Results: A dominant forward pushing wave and a backward suction wave (figure - shaded wave) were demonstrated in diseased coronary arteries. The suction wave occurred early in diastole, during active ventricular relaxation. Ischemia induced LV diastolic dysfunction was demonstrated after coronary artery occlusion (mean % Δ from baseline (SD): LV dP/dt min = −14.8 (13.8), p=0.008, LV Tau = +19.1(14.9), p = 0.011) but there was no significant change in suction WI (mean (SD): baseline = −1.35 (0.20) m −2 s −2 x10 5 , post-balloon occlusion −1.49(0.59) m −2 s −2 x10 5 , p =0.67). Conclusion: The coronary suction wave occurs in diseased coronary arteries at the appropriate time in the cardiac cycle but is not diminished by ischemia induced diastolic left ventricular dysfunction.
Cortical Function in Asymptomatic Carriers and Patients With<i>C9orf72</i>Amyotrophic Lateral Sclerosis
Authors: Nimeshan Geevasinga, Parvathi Menon, Garth A. Nicholson, Karl Ng, James Howells, Jillian J. Kril, Con Yiannikas, Matthew C. Kiernan, Steve Vucic
Journal: JAMA Neurology (2015)

IMPORTANCEThe identification of the chromosome 9 open reading frame 72 (c9orf72) gene hexanucleotide repeat expansion represents a major advance in the understanding of amyotrophic lateral sclerosis (ALS) pathogenesis.The pathophysiological mechanism by which the c9orf72 gene expansion leads to neurodegeneration is not yet elucidated.Cortical hyperexcitability is potentially an important pathophysiological process in sporadic ALS and familial ALS (FALS).OBJECTIVE To investigate whether cortical hyperexcitability forms the pathophysiological basis of c9orf72 FALS using the threshold-tracking transcranial magnetic stimulation technique. DESIGN, SETTING, AND PARTICIPANTSProspective case-control single-center study that took place at hospitals and outpatient clinics from January 1, 2013, to January 1, 2015.Clinical and functional assessments along with transcranial magnetic stimulation studies were taken on 15 patients with c9orf72 FALS and 11 asymptomatic expansion carriers of c9orf72 who were longitudinally followed up for 3 years.Results were compared with 73 patients with sporadic ALS and 74 healthy control participants. MAIN OUTCOMES AND MEASURESCortical excitability variables, including short-interval intracortical inhibition, were measured in patients with c9orf72 FALS and results were compared with asymptomatic c9orf72 carriers, patients with sporadic ALS, and healthy control participants.RESULTS Mean (SD) short-interval intracortical inhibition was significantly reduced in patients with c9orf72 FALS (1.2% [1.8%]) and sporadic ALS (1.6% [1.2%]) compared with asymptomatic c9orf72 expansion carriers (10.2% [1.8%]; F = 16.1;P < .001)and healthy control participants (11.8% [1.0%]; F = 16.1;P < .001).The reduction of short-interval intracortical inhibition was accompanied by an increase in intracortical facilitation (P < .01)and motor-evoked potential amplitude (P < .05)as well as a reduction in the resting motor threshold (P < .05)and cortical silent period duration (P < .001). CONCLUSIONS AND RELEVANCEThis study establishes cortical hyperexcitability as an intrinsic feature of symptomatic c9orf72 expansion-related ALS but not asymptomatic expansion carriers.
Abstract 9262: Clinical Implication of ST-Segment Elevation in Lead aVR in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Kengo Tsukahara, Nobuhiko Maejima, Noriaki Iwahashi, Yoshio Tahara, Masaaki Konishi, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2013)

Background: In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), ST-segment depression (STD) has been shown to be associated with poor outcomes; however, lead aVR is not considered. Lead aVR is referred to as a “cavity lead,” and ST-segment elevation in this lead (STE-aVR) might reflect global subendocardial ischemia. Methods: We studied 818 patients with NSTE-ACS who underwent coronary angiography during hospitalization. ST-segment deviation was measured on admission ECG, and it was considered present if ≥ 0.5 mm. Troponin T (TnT), hemoglobin (Hb), estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hsCRP), brain natriuretic peptide (BNP), and TIMI risk score were also measured on admission. Results: STD in 11 leads except aVR was observed in 568 patients. Among these patients, 225 patients had STE-aVR. In patients with no STD (n=250), isolated STD (n=343), and STD plus STE-aVR (n=225), age was 63±10, 67±11, and 70±11 years; the rates of diabetes mellitus were 25%, 32%, and 50%; Killip class ≥2 was 2%, 6%, and 27%; positive TnT was 22%, 34%, and 49%; the levels of Hb were 13.8±1.7, 13.9±1.9, and 12.7±2.2 g/dl; eGFR was 69.1±22.8, 65.8±24.7, and 56.8±27.5 ml/min/1.73m 2 ; hsCRP was 0.310±1.480, 0.499±1.249, and 0.899±1.820 mg/dl; BNP was 90±203, 200±359, and 431±575 pg/ml; TIMI risk core was 1.9±1.2, 3.1±1.3, and 3.6±1.2; the frequencies of left main/3-vessel disease were 4.0%, 8.5%, and 56.9%; and in-hospital adverse events (death, [re]infarction, or urgent revascularization) were 5.2%, 8.7%, and 31.6%, respectively (all p&lt;0.01). Multivariate analysis showed that STD plus STE-aVR (OR 3.56, 95%CI 1.13-7.99, p&lt;0.01) was the strongest predictor of in-hospital adverse events, followed by positive TnT (OR 1.33, 95%CI 1.03-2.99, p=0.048), but isolated STD was not. Conclusions: In patients with NSTE-ACS, STE-aVR in addition to STD on admission ECG was strongly associated with left main/3-vessel disease and in-hospital adverse outcomes, but isolated STD was not. Our findings suggest the importance of evaluation of ST-segment deviation in 12 leads including aVR in early risk stratification.
Cantor coding and chaotic itinerancy: Relevance for episodic memory, amnesia, and the hippocampus?
Authors: Jonathan K. Foster
Journal: Behavioral and Brain Sciences (2001)

This commentary provides a critique of Tsuda's target article, focusing on the hippocampus and episodic long-term memory. More specifically, the relevance of Cantor coding and chaotic itinerancy for long-term memory functioning is considered, given what we know about the involvement of the hippocampus in the mediation of long-term episodic memory (based on empirical neuroimaging studies and investigations of brain-damaged amnesic patients).