tbuckley/cabot-search huggingface dataset:
Monitoring Tumor Response to Antivascular Therapy Using Non-Contrast Intravoxel Incoherent Motion Diffusion-Weighted MRI
Authors: Changzheng Shi, Dexiang Liu, Zeyu Xiao, Dong Zhang, Guanfu Liu, Guanshu Liu, Hanwei Chen, Liangping Luo
Journal: Cancer Research (2017)

Antivascular therapy is a promising approach to the treatment of non-small cell lung cancer (NSCLC), where an imaging modality capable of longitudinally monitoring treatment response could provide early prediction of the outcome. In this study, we sought to investigate the feasibility of using intravoxel incoherent motion (IVIM) diffusion MRI to quantitatively assess the efficacy of the treatments of a vascular-disrupting agent CA4P or its combination with bevacizumab on experimental NSCLC tumors. CA4P caused a strong but reversible effect on tumor vasculature; all perfusion-related parameters-D*, f, fD*, and Ktrans-initially showed a decrease of 30% to 60% at 2 hours and then fully recovered to baseline on day 2 for CA4P treatment or on days 4 to 8 for CA4P + bevacizumab treatment; the diffusion coefficient in tumors decreased initially at 2 hours and then increased from day 2 to day 8. We observed a good correlation between IVIM parameters and dynamic contrast-enhanced MRI (DCE-MRI; Ktrans). We also found that the relative change in f and fD* at 2 hours correlated well with changes in tumor volume on day 8. In conclusion, our results suggest that IVIM is a promising alternative to DCE-MRI for the assessment of the change in tumor perfusion as a result of antivascular agents and can be used to predict the efficacy of antivascular therapies without the need for contrast media injection. Cancer Res; 77(13); 3491-501. ©2017 AACR.
Effect of different substrates on functional performance and kinase activation during reperfusion after ischaemia in hearts from obese insulin resistant rats
Authors: WenJun Fan
Journal: Circulation Research (2017)

Insulin resistance decreases glucose uptake, alters lipid metabolism and impairs PKB-dependent signaling in its target tissues. In view of the myocardial dependence on glycolysis during energy deficiency, insulin resistance may exacerbate the harmful effects of ischaemia. We hypothesize that obesity-induced insulin resistance affects functional recovery and activation of PKB, JNK, ERK and PTEN during early reperfusion.   Methods:  Insulin resistance was induced by feeding rats a high calorie diet for 16 weeks. Hearts from diet rats (D) and age-matched controls (C) were subjected to (i) 15 min global ischaemia and different reperfusion times for Western blot and measurement of functional recovery, or (ii) 35 min regional ischaemia and 2 hours reperfusion for infarct size determination (IS) using tetrazolium. Substrates were glucose (G) (10mM) or glucose (10mM) plus fatty acid (FA) (1.2mM palmitate /3%BSA) (G+FA). N=4-8/group.   Results:  Regardless of the substrate, functional recovery during reperfusion of hearts from D was higher than those of C (% recovery of total work: D+G/C+G, 69.1±3.4/50.7±4.5, D+G+FA/C+G+FA: 105.4±3.6/92.7±3.9), associated with a reduction in IS (D+G/C+G 29.7±2.8/43.5±2.5, p   Conclusion:  Contrary to expectations, hearts from D rats showed an increased tolerance to ischaemia/reperfusion (I/R) injury which was further improved by fatty acids in the perfusate. The pattern of PKB, JNK, ERK and PTEN phosphorylation during reperfusion is substrate dependent and significantly higher in hearts from D rats. With glucose as substrate activation of PKB and JNK during reperfusion was higher in hearts from D rats while FA further improved activation of ERK and PKB.
High-throughput RNA sequencing unravels pathways associated with the progression of non-alcoholic liver disease
Authors: O. Govaere, S.J. Cockell, M. Vacca, M. Allison, S. Petta, J. Boursier, E. Bugianesi, R. Darlay, H.J. Cordell, F. Marra, P. Bedossa, D. Tiniakos, A. Vidal-Puig, K. Clément, J.M. Schattenberg, V. Ratziu, Q.M. Anstee, A.K. Daly
Journal: Journal of Hepatology (2017)
Prevalence, determinants of chronic hepatitis B infection and hepatitis B genotypes in multi-ethnic Suriname
Authors: M.S. Mac Donald-Ottevanger, T. van de Laar, W. Zijlmans, M. Prins, K. Brinkman, J. Roosblad, J. Codrington, J. van der Helm, S. Vreden
Journal: Journal of Hepatology (2017)
Innate resistance in EGFR mutant non-small cell lung cancer (NSCLC) patients by coactivation of receptor tyrosine kinases (RTKs)
Authors: R. Rosell, N. Karachaliou, I. Chaib, A. Drozdowskyj, A. Frías, C. Teixidó, S. Viteri, L. Santarpia, M.A. Molina-Vila, T.G. Bivona
Journal: Annals of Oncology (2017)
High-Throughput Characterization and New Insight into the Role of Tumor Associated Macrophages (TAMs) in Multiple Myeloma (MM)
Authors: Paula Arana, Aintzane Zabaleta, Marta Lasa, Patricia Maiso, Diego Alignani, Tomas Jelinek, Victor Segura, Wouter van den Bossche, Cristina Teodosio, Daniela Damasceno, Paula Rodriguez-Otero, Felipe Prosper, Maria-Victoria Mateos, Juan Jose Lahuerta, Joan Bladé, Jacques J.M. van Dongen, Jesus San Miguel, Alberto Orfao, Bruno Paiva
Journal: Blood (2016)
Heart failure is still as “malignant” as some cancers, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Survival rates in people with heart failure remain worse than those with many common cancers despite clinical advances over the past two decades, a study in the European Journal of Heart Failure shows.1

The study included 56 658 adults registered with 393 general practices in Scotland who had a diagnosis of heart …
Acquisition and Transmission of <i>Streptococcus pneumoniae</i> Are Facilitated during Rhinovirus Infection in Families with Children
Authors: Sinikka Karppinen, Johanna Teräsjärvi, Kari Auranen, Linnea Schuez-Havupalo, Lotta Siira, Qiushui He, Matti Waris, Ville Peltola
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Laboratory and clinical evidence suggests synergy between rhinoviruses and Streptococcus pneumoniae in the pathogenesis of respiratory tract infections. However, it is unclear whether rhinoviruses promote pneumococcal acquisition and transmission.Objectives: To describe the impact of rhinovirus infection on the acquisition and transmission of pneumococci within families with children.Methods: We investigated 29 families with at least two children. The follow-up started at the onset of respiratory infectious symptoms in any family member and consisted of daily symptom diary and nasal swab samples from each participant twice per week for 3 weeks. Swabs were taken by the parents and sent to a study clinic by mail. Rhinoviruses were detected by reverse transcription–polymerase chain reaction and typed by sequencing. Pneumococci were identified by an antigen test and by standard culture methods, serotyping, and whole-genome sequencing. The effect of rhinovirus infection on the rates of pneumococcal acquisition and within-family transmission was estimated from the observed acquisition events and person-times spent uncolonized, using Poisson regression.Measurements and Main Results: Rhinovirus was detected in 38 subjects (30%) at the onset and in 86 subjects (67%) during the follow-up. S. pneumoniae was detected on the first day in 9 (7%) and during follow-up in 38 (30%) subjects. Children with rhinovirus infection had a 4.3-fold rate of pneumococcal acquisition from the community (95% confidence interval, 1.1–15.4) and a 14.8-fold rate of within-family transmission (95% confidence interval, 3.1–69.6) compared with children without rhinovirus infection.Conclusions: Rhinovirus infection within families facilitates acquisition and within-family transmission of S. pneumoniae.
Computed Tomography Measure of Lung at Risk and Lung Function Decline in Chronic Obstructive Pulmonary Disease
Authors: Surya P. Bhatt, Sandeep Bodduluri, Eric A. Hoffman, John D. Newell, Jessica C. Sieren, Mark T. Dransfield, Joseph M. Reinhardt
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

The rate of decline of lung function is greater than age-related change in a substantial proportion of patients with chronic obstructive pulmonary disease, even after smoking cessation. Regions of the lung adjacent to emphysematous areas are subject to abnormal stretch during respiration, and this biomechanical stress likely influences emphysema initiation and progression.To assess whether quantifying this penumbra of lung at risk would predict FEV1 decline.We analyzed paired inspiratory-expiratory computed tomography images at baseline of 680 subjects participating in a large multicenter study (COPDGene) over approximately 5 years. By matching inspiratory and expiratory images voxel by voxel using image registration, we calculated the Jacobian determinant, a measure of local lung expansion and contraction with respiration. We measured the distance between each normal voxel to the nearest emphysematous voxel, and quantified the percentage of normal voxels within each millimeter distance from emphysematous voxels as mechanically affected lung (MAL). Multivariable regression analyses were performed to assess the relationship between the Jacobian determinant, MAL, and FEV1 decline.The mean (SD) rate of decline in FEV1 was 39.0 (58.6) ml/yr. There was a progressive decrease in the mean Jacobian determinant of both emphysematous and normal voxels with increasing disease stage (P < 0.001). On multivariable analyses, the mean Jacobian determinant of normal voxels within 2 mm of emphysematous voxels (MAL2) was significantly associated with FEV1 decline. In mild-moderate disease, for participants at or above the median MAL2 (threshold, 36.9%), the mean decline in FEV1 was 56.4 (68.0) ml/yr versus 43.2 (59.9) ml/yr for those below the median (P = 0.044).Areas of normal-appearing lung are mechanically influenced by emphysematous areas and this lung at risk is associated with lung function decline. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).
Heritability and risks associated with early onset hypertension: multigenerational, prospective analysis in the Framingham Heart Study
Authors: Teemu J Niiranen, Elizabeth L McCabe, Martin G Larson, Mir Henglin, Neal K Lakdawala, Ramachandran S Vasan, Susan Cheng
Journal: BMJ (2017)

Objective To determine the role of early onset versus late onset hypertension as a risk factor for hypertension in offspring and cardiovascular death.Design Multigenerational, prospective cohort study.Setting Framingham Heart Study.Participants Two generations of community dwelling participants with blood pressure measurements performed at serial examinations spanning six decades: 3614 first generation participants with mortality data and 1635 initially non-hypertensive second generation participants with data available on parental blood pressure.Main outcome measures The main outcome measures were relation of parental early onset hypertension (age <55 years) with incidence of hypertension in offspring, using regression analyses, and relation of age at hypertension onset with cause specific mortality using a case (cardiovascular death) versus control (non-cardiovascular death) design.Results In second generation participants, having one or both parents with late onset hypertension did not increase the risk of hypertension compared with having parents with no hypertension; by contrast, the hazard ratios of hypertension were 2.0 (95% confidence interval 1.2 to 3.5) and 3.5 (1.9 to 6.1) in participants with one and both parents with early onset hypertension, respectively. In first generation decedents, 1151 cardiovascular deaths occurred (including 630 coronary deaths). The odds of cardiovascular death increased linearly with decreasing age of hypertension onset (P<0.001 for trend). Compared with non-hypertensive participants, hypertension onset at age <45 years conferred an odds ratios of 2.2 (1.8 to 2.7) for cardiovascular death and 2.3 (1.8 to 2.9) for coronary death, whereas hypertension onset at age ≥65 years conferred a lower magnitude odds ratios of 1.5 (1.2 to 1.9) for cardiovascular death and 1.4 (0.98 to 1.9) for coronary death (P≤0.002 for differences in odds ratios between hypertension onset at age <45 and age ≥65).Conclusions Early onset and not late onset hypertension in parents was strongly associated with hypertension in offspring. In turn, early onset compared with late onset hypertension was associated with greater odds of cardiovascular, and particularly coronary, death. These findings suggest it may be important to distinguish between early onset and late onset hypertension as a familial trait when assessing an individual's risk for hypertension, and as a specific type of blood pressure trait when estimating risk for cardiovascular outcomes in adults with established hypertension.
Lentiglobin Gene Therapy for Transfusion-Dependent β-Thalassemia: Update from the Northstar Hgb-204 Phase 1/2 Clinical Study
Authors: Alexis A. Thompson, Janet Kwiatkowski, John Rasko, Suradej Hongeng, Gary J. Schiller, Usanarat Anurathapan, Marina Cavazzana, P. Joy Ho, Christof von Kalle, Morris Kletzel, Philippe Leboulch, Elliott Vichinsky, Alexandria Petrusich, Mohammed Asmal, Mark C. Walters
Journal: Blood (2016)
Disclosure of Editors' Financial Relationships
Authors: D Newport, B Charles
Journal: American Journal of Psychiatry (2016)

a performance measure rather than a symptom rating.Moreover, the impact of practice effects is typically to reduce between-group variability.Similarly, the authors' concern regarding low baseline suicidal ideation severity is counterintuitive, as this would also tend to reduce between-group variability.Zhang and Ho posit that ketamine's rapid antidepressant effects may be attributable to "amphetamine-like properties."In our report, we acknowledged that dopaminergic activity has been postulated as a mechanism for ketamine's antidepressant effects.However, the failure of stimulant therapy to produce the rapid antidepressant effects observed in ketamine trials undermines this assertion.Finally, the caution from Zhang and Ho regarding uropathic effects of chronic ketamine use is an important clinical consideration.
Glucose Peaks and the Risk of Dementia and 20-Year Cognitive Decline
Authors: Andreea M. Rawlings, A. Richey Sharrett, Thomas H. Mosley, Shoshana H. Ballew, Jennifer A. Deal, Elizabeth Selvin
Journal: Diabetes Care (2017)

OBJECTIVE Hemoglobin A1c (HbA1c), a measure of average blood glucose level, is associated with the risk of dementia and cognitive impairment. However, the role of glycemic variability or glucose excursions in this association is unclear. We examined the association of glucose peaks in midlife, as determined by the measurement of 1,5-anhydroglucitol (1,5-AG) level, with the risk of dementia and 20-year cognitive decline. RESEARCH DESIGN AND METHODS Nearly 13,000 participants from the Atherosclerosis Risk in Communities (ARIC) study were examined. Dementia was ascertained from surveillance, neuropsychological testing, telephone calls with participants or their proxies, or death certificate dementia codes. Cognitive function was assessed using three neuropsychological tests at three visits over 20 years and was summarized as z scores. We used Cox and linear mixed-effects models. 1,5-AG level was dichotomized at 10 μg/mL and examined within clinical categories of HbA1c. RESULTS Over a median time of 21 years, dementia developed in 1,105 participants. Among persons with diabetes, each 5 μg/mL decrease in 1,5-AG increased the estimated risk of dementia by 16% (hazard ratio 1.16, P = 0.032). For cognitive decline among participants with diabetes and HbA1c &amp;lt;7% (53 mmol/mol), those with glucose peaks had a 0.19 greater z score decline over 20 years (P = 0.162) compared with those without peaks. Among participants with diabetes and HbA1c ≥7% (53 mmol/mol), those with glucose peaks had a 0.38 greater z score decline compared with persons without glucose peaks (P &amp;lt; 0.001). We found no significant associations in persons without diabetes. CONCLUSIONS Among participants with diabetes, glucose peaks are a risk factor for cognitive decline and dementia. Targeting glucose peaks, in addition to average glycemia, may be an important avenue for prevention.
Genetic variation of PNPLA3 and TM6SF2 associate with hepatocellular carcinoma in patients with alcohol-related cirrhosis
Authors: F. Stickel, S. Buch, F. Janet, J. Rosendahl, M.Y. Morgan, H.-D. Nischalke, F. Lammert, M. Casper, S. Zopf, S. Marhenke, A. Vogel, P. Deltenre, F. Eyer, J.V. Felden, D. Gotthardt, C. Datz, S. Zeisig, T. Berg, J. Hampe
Journal: Journal of Hepatology (2017)
Mortality risks associated with emergency admissions during weekends and public holidays: an analysis of electronic health records
Authors: A Sarah Walker, Amy Mason, T Phuong Quan, Nicola J Fawcett, Peter Watkinson, Martin Llewelyn, Nicole Stoesser, John Finney, Jim Davies, David H Wyllie, Derrick W Crook, Tim E A Peto
Journal: The Lancet (2017)

Weekend hospital admission is associated with increased mortality, but the contributions of varying illness severity and admission time to this weekend effect remain unexplored.We analysed unselected emergency admissions to four Oxford University National Health Service hospitals in the UK from Jan 1, 2006, to Dec 31, 2014. The primary outcome was death within 30 days of admission (in or out of hospital), analysed using Cox models measuring time from admission. The primary exposure was day of the week of admission. We adjusted for multiple confounders including demographics, comorbidities, and admission characteristics, incorporating non-linearity and interactions. Models then considered the effect of adjusting for 15 common haematology and biochemistry test results or proxies for hospital workload.257 596 individuals underwent 503 938 emergency admissions. 18 313 (4·7%) patients admitted as weekday energency admissions and 6070 (5·1%) patients admitted as weekend emergency admissions died within 30 days (p<0·0001). 9347 individuals underwent 9707 emergency admissions on public holidays. 559 (5·8%) died within 30 days (p<0·0001 vs weekday). 15 routine haematology and biochemistry test results were highly prognostic for mortality. In 271 465 (53·9%) admissions with complete data, adjustment for test results explained 33% (95% CI 21 to 70) of the excess mortality associated with emergency admission on Saturdays compared with Wednesdays, 52% (lower 95% CI 34) on Sundays, and 87% (lower 95% CI 45) on public holidays after adjustment for standard patient characteristics. Excess mortality was predominantly restricted to admissions between 1100 h and 1500 h (pinteraction=0·04). No hospital workload measure was independently associated with mortality (all p values >0·06).Adjustment for routine test results substantially reduced excess mortality associated with emergency admission at weekends and public holidays. Adjustment for patient-level factors not available in our study might further reduce the residual excess mortality, particularly as this clustered around midday at weekends. Hospital workload was not associated with mortality. Together, these findings suggest that the weekend effect arises from patient-level differences at admission rather than reduced hospital staffing or services.NIHR Oxford Biomedical Research Centre.
Quality of life (QOL) and physical function in one-year adult and elderly survivors of acute myeloid leukemia (AML).
Authors: Shabbir M.H. Alibhai, Henriette Breunis, Narhari Timilshina, Mark D. Minden, Vikas Gupta, Rena Buckstein, Madeline Li, George A. Tomlinson, Joseph Brandwein
Journal: Journal of Clinical Oncology (2013)

7071 Background: The treatment of AML with intensive chemotherapy (IC) is associated with significant short-term toxicities. We previously showed similar impairments in QOL and physical function among younger (age 18-59) and older (age 60+) patients with AML at diagnosis, with similar recovery over 3 cycles of IC. We now comprehensively describe QOL and physical function recovery over 1 year from diagnosis. Methods: Younger and older AML patients undergoing IC without stem cell transplant were enrolled in a prospective, longitudinal study. Assessments were done at baseline (pre-IC) and at 7 time points over the next year. At each visit, patients completed the EORTC QLQ-C30 and the FACT-Fatigue to measure QOL and fatigue, respectively, in addition to 3 physical function tests (grip strength, 2-minute walk test (2MWT), and timed chair stands). Analyses involved multivariable linear regression analyses stratified by age group. Results: 243 patients were recruited (147 younger and 96 older, 56% male). Attrition was greater in older adults due to death or disease progression/relapse. Among patients remaining in remission after IC, global QOL and fatigue improved significantly over time (p&lt;0.001 for both); trends were similar between older and younger patients. All 5 QOL domains improved or remained stable over time; the greatest improvements were seen in social function and role function and were similar in both age groups. Grip strength increased slightly over time (p=0.04) whereas both timed chair stands (p&lt;0.001) and the 2MWT (p&lt;0.001) had moderate to large improvements, with trends toward greater improvement in younger patients (p=0.07 and 0.09, respectively). Results were similar when missing data were imputed. Conclusions: Survivors of AML after successful conventional chemotherapy achieve significant improvements in QOL, fatigue, and physical function over time. The course of recovery is remarkably similar in younger and older AML patients, although significant attrition in older adults is a noteworthy limitation. These data suggest that appropriately selected older patients do well following IC for AML.
Abstract 14904: High-Sensitivity Cardiac Troponin, Natriuretic Peptide, and Subsequent Risk of Lower-Extremity Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kunihiro Matsushita, Lucia Kwak, Chao Yang, Yuanjie Pang, Shoshana H Ballew, Yingying Sang, Ron C Hoogeveen, Bernard Jaar, Elizabeth Selvin, Christie M Ballantyne, Richey Sharrett, Aaron Folsom, Gerardo Heiss, Josef Coresh, Alan Hirsch
Journal: Circulation (2016)

Background:  Cardiac troponin T (cTnT) has been recently shown as a potential predictor of leg amputation in patients with symptomatic peripheral artery disease (PAD). However, whether cTnT predicts ischemic leg outcomes in the general population is unknown.   Methods:  Among 12,780 ARIC participants without a history of PAD, we investigated whether high-sensitivity cTnT (hs-cTnT) was associated with future risk of clinical PAD, defined as hospitalizations with PAD diagnosis or leg revascularization. PAD cases with rest pain, gangrene, ulcer, or amputation were considered critical limb ischemia (CLI). We also analyzed another cardiac marker, N-terminal pro-brain natriuretic peptide (NT-proBNP). Both cardiac markers were categorized at 50th, 71th, 86th, and 95th percentiles, corresponding to hs-cTnT concentrations of 3, 5, 9, and 14 ng/L and NT-proBNP concentrations of 51.4, 86.4, 140.3, and 257.6 pg/mL.   Results:  During a median follow-up of 21 years, 462 participants developed PAD (171 incident CLI cases). In demographically adjusted models, the hazard ratio (HR) of PAD for the highest vs. lowest category of hs-cTnT and NT-proBNP was ~8 (Model 1 for PAD in Table). The corresponding HR of CLI was ~24 for hs-cTnT and ~10 for NT-proBNP (Model 1 for CLI in Table). Additional adjustment for each cardiac marker and traditional cardiovascular risk factors attenuated the associations. In all models, a stronger association of hs-cTnT with CLI was observed compared to NT-proBNP. Both cardiac markers significantly improved PAD risk discrimination beyond traditional cardiovascular risk factors, but only hs-cTnT (but not NT-proBNP) significantly improved CLI risk discrimination (Δc-statistic 0.012 [0.001 to 0.023] vs. 0.006 [-0.009 to 0.022]).   Conclusions:  Both hs-cTnT and NT-proBNP were independently associated with future risk of clinical PAD events in a community-based cohort. The CLI risk association was particularly evident for hs-cTnT.