tbuckley/cabot-search huggingface dataset:
AB0867 Axial spondyloarthritis posture assessment using inertial sensors
Authors: J.L. Garrido-Castro, I.C. Concha-Aranda, P. Gardiner, P.M. Machado, J. Williams, E. Collantes-Estevez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Axial Spondyloarthritis (axSpA) often causes spinal deformity in patients, most commonly a flexed kyphotic posture. In the early stages a flattening of the lumbar spine or reduced lordosis may become apparent. Kyphosis of the thoracic and cervical spine is also common in severe cases, resulting in an increased ‘tragus to wall distance’ as clinically assessed in the BASMI score. No other measurement related to posture is routinely recorded in clinical practice. Inertial Measurement Units (IMU) is a new technology that can measure angles of anatomical regions where the sensor is located. <h3>Objectives</h3> To compare the spinal curvature of axSpA and healthy individuals to analyse if there are any significant differences between them and to correlate these with conventional assessment variables. <h3>Methods</h3> 20 axSpa patients and 20 healthy age, BMI and sex matched controls, were recruited. An IMUs system (ViMove©) was used to obtain angles at key points along the spine. Sensors were located at Pelvis, L1, T3 and occiput (figure 1). Calibrated angles for all the participants where obtained with the subject in quiet standing position looking to a point in front of her/him. PRO questionnaires (only patients) and metrology for axSpA (both groups) were also assessed. ROM for cervical and lumbar spine was also measured using IMUs. <h3>Results</h3> Greater values of posture angles were obtained in healthy controls. Despite this, differences where significant (p&lt;0.05) only for Lordosis and Cervical Posture. Lordosis angle shown a good correlation with mobility measured by Schöber and by IMU system, especially for flexion movements. Pelvis angle correlates better than L1 angle with all mobility variables. For cervical angles, occiput angle appears to be the best indicator for functional assessment. Thoracic angle is very similar between patients and healthy subjects. Figure represents the location of sensors with mean angles obtained by healthy group and the worst patient of axSpA group. <h3>Conclusions</h3> IMU based sensors are a useful new tool for the assessment of axSpA patients. This is the first formal evaluation of posture in axSpA and seems to be a promising tool in the functional evaluation of axSpA patients. More studies (reliability, feasibility, sensitivity to change, etc.) are needed for validating these measures. <h3>Acknowledgements</h3> This study has been funded by FOREUM, University of Cordoba Research Program and Junta de Andalucía (CS-S0029/2016). <h3>Disclosure of Interest</h3> None declared
Type 2 diabetes: sweetened drinks pose greater risk than other sugary foods
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

Sweetened drinks pose a greater risk of type 2 diabetes than most other foods containing fructose because of their effect on blood glucose levels, an evidence review in The BMJ has found.1 Fruit and other foods containing fructose seemed to have no harmful effects.

“These findings might help guide recommendations on important food sources of fructose in the prevention and management of diabetes,” said John Sievenpiper, the study’s lead author and a researcher at the Clinical Nutrition and Risk Factor Modification Centre of St Michael’s Hospital in Toronto, Canada. “But the level of evidence is low, and more high quality studies are needed.” …
Contributions of diseases and injuries to widening life expectancy inequalities in England from 2001 to 2016: a population-based analysis of vital registration data
Authors: James E Bennett, Jonathan Pearson-Stuttard, Vasilis Kontis, Simon Capewell, Ingrid Wolfe, Majid Ezzati
Journal: The Lancet Public Health (2018)

Life expectancy inequalities in England have increased steadily since the 1980s. Our aim was to investigate how much deaths from different diseases and injuries and at different ages have contributed to this rise to inform policies that aim to reduce health inequalities.
Results of Pivotal Phase 2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Naveen Pemmaraju, Andrew A. Lane, Kendra L. Sweet, Anthony S. Stein, Sumithira Vasu, William Blum, David A. Rizzieri, Eunice S. Wang, Madeleine Duvic, Sharon Spence, Shay Shemesh, Christopher Brooks, Ivan Bergstein, Janice Chen, Vanessa Dunn, Peter McDonald, John Mark Sloan, Jeffrey E. Lancet, Hagop M. Kantarjian, Marina Y. Konopleva
Journal: Blood (2018)
Arterial Embolization During Programmed Death-1 Inhibitor Treatment: An Unexpected Finding
Authors: Filippo Gustavo Dall’Olio, Francesca Sperandi, Karim Rihawi, Mauro Gargiulo, Barbara Melotti, Stefano Brocchi, Francesco Gelsomino, Andrea Ardizzoni
Journal: Journal of Thoracic Oncology (2018)
Targeted expression of cyclin D2 ameliorates late stage anthracycline cardiotoxicity
Authors: Wuqiang Zhu, Sean Reuter, Loren J Field
Journal: Cardiovascular Research (2018)

Doxorubicin (DOX) is a widely used and effective anti-cancer therapeutic. DOX treatment is associated with both acute and late onset cardiotoxicity, limiting its overall efficacy. Here, the impact of cardiomyocyte cell cycle activation was examined in a juvenile model featuring aspects of acute and late onset DOX cardiotoxicity.Two-week old MHC-cycD2 transgenic mice (which express cyclin D2 in postnatal cardiomyocytes and exhibit sustained cardiomyocyte cell cycle activity; D2 mice) and their wild type (WT) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), cardiac function was suppressed in both groups. Acute DOX cardiotoxicity in D2 and WT mice was associated with similar increases in the levels of cardiomyocyte apoptosis and Ku70/Ku80 expression (markers of DNA damage and oxidative stress), as well as similar reductions in hypertrophic cardiomyocyte growth. Cardiac dysfunction persisted in WT mice for 13 weeks following the last DOX treatment (late stage) and was accompanied by increased levels of cardiomyocyte apoptosis, Ku expression, and myocardial fibrosis. In contrast, D2 mice exhibited a progressive recovery in cardiac function, which was indistinguishable from saline-treated animals by 9 weeks following the last DOX treatment. Improved cardiac function was accompanied by reductions in the levels of late stage cardiomyocyte apoptosis, Ku expression, and myocardial fibrosis.These data suggest that cardiomyocyte cell cycle activity can promote recovery of cardiac function and preserve cardiac structure following DOX treatment.
Prognostic factors for post-progression survival after trabectedin treatment in patients with advanced soft tissue sarcoma
Authors: S. Iwata, K. Yonemori, A. Arakawa, A. Maejima, F. Nakatani, E. Kobayashi, T. Mori, K. Sudo, E. Noguchi, T. Hirose, S. Komatsubara, H. Fujimoto, C. Ogawa, K. Tamura, A. Kawai
Journal: Annals of Oncology (2018)
African Clinicians’ Prioritization of Needs in International Breast Cancer Partnerships
Authors: Kofi Gyan, Ishmael Kyei, Laura L. Susick, Yalei Chen, Melissa B. Davis, Barbara Salem, Lisa A. Newman
Journal: JAMA Surgery (2018)

This study analyzes a survey conducted at a gathering of clinicians who specialize in breast cancer in sub-Saharan Africa to better understand what they need from international collaborators.
AB1041 Occurrence of major cardiovascular events in patients with gout treated with febuxostat
Authors: N. Quilis, M. Andrés
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Controversy persists regarding the use of febuxostat (FBX) in patients with gout and the development of cardiovascular (CV) events. In both APEX<sup>1</sup> and FACT<sup>2</sup> trials a higher risk was identified in those on the FBX arm compared to those on allopurinol, but this was later not confirmed in CONFIRMS trial<sup>3</sup> and the extension phases. Recently, the FDA has published a warning on the risk of CV death in relation to FBX, based on preliminary data of a safety study enrolling 6000 participants.<sup>4</sup> <h3>Objectives</h3> To assess the occurrence of CV events in patients with gout after been prescribed with FBX in clinical practice. <h3>Methods</h3> Retrospective review of patients with crystal-proven gout enrolled in an inception cohort since January 2014. Epidemiological (age, gender), clinical (CV risk factors, CV disease background), and laboratory variables (serum urate – SU -, glomerular filtration rate – GFR) were registered. The primary endpoint was the occurrence of CV events (death, coronary heart disease (CHD), congestive heart failure (CHF), stroke, peripheral artery disease (PAP)) developed during treatment with FBX. A comparison on secondary study variables regarding the development of CV events was performed by Mann-Whitney's U, chi-square and Fisher's exact tests. <h3>Results</h3> In the cohort, 43 patients were treated with FBX, but three were excluded (two early stopped FBX because of rash, and one was lost of follow-up), so finally 40 patients were analysed. Their median age was 76 years (p25-p75 70–79), being 24 of them men (60%). CV risk factors were prevalent, especially hypertension (87.5%), and 20 of them (50%) had established CV disease. Median time since first gout attack was 1.5 years (p25–75 0.0–9.5) and 14 patients (35.0%) were tophaceous. After initiating FBX, 7 cases (17.5%, 95% CI 5%–30%) of CV events were identified: three of CHF (7.5%), two of CHD (5.0%) and one stroke (2.5%), with no PAP events. Five CV-related deaths (12.5%) were noted. The occurrence of CV events significantly associated with an older age and background of established CV disease (table 1). <h3>Conclusions</h3> In our cohort, about one on six patients treated with FBX suffered from a CV event, some being fatal. The development associated with older age and CV disease background, so it merits a cautious use in this setting, although whether these CV events are directly related to FBX needs further clarification. <h3>References</h3> [1] Arthritis Rheum2008; 59 (11):1540. [2] N Engl J Med2005; 353 (23):2450. [3] Arthritis Res Ther. 2010;12(2):R63. [4] US Food and Drug Administration. Febuxostat (Brand Name Uloric): Drug safety Communication – FDA to Evaluate Increased Risk of Heart-related Death. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm585281.htm [accessed at 2018, 29January]. <h3>Disclosure of Interest</h3> None declared
Association of Focused Medication Review With Optimization of Psychotropic Drug Prescribing
Authors: Rory Sheehan, André Strydom, Emma Brown, Louise Marston, Angela Hassiotis
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Medication review has been proposed to achieve improved use of psychotropic drugs, but benefits have not been confirmed. <h3>Objective</h3> To synthesize evidence for focused psychotropic medication review in medication optimization. <h3>Data Sources</h3> Medline, PsycINFO, EMBASE, and CINAHL Plus were searched from inception to February 2018 using the index terms "drug utilization review" and "psychotropic drugs" and synonyms. Additional articles were retrieved using citation tracking and reference checking. <h3>Study Selection</h3> Full-length, peer-reviewed articles that reported focused psychotropic medication review were included. Inclusion was determined against prespecified criteria and assessed independently. <h3>Data Extraction and Synthesis</h3> Study quality was assessed using National Institutes for Health appraisal tools and informed a structured synthesis of results. Meta-analysis using a random effects model was conducted. <h3>Main Outcomes and Measures</h3> Change in the number or dosage of psychotropic medications, change in clinical parameters, change in patient-reported outcomes, and economic data were collected. <h3>Results</h3> A total of 26 studies met the inclusion criteria. Four studies were randomized clinical trials (n = 712 participants), while the remainder were before-after studies (n = 7844 participants). Most studies were conducted in elderly individuals, people with dementia, and adults with intellectual disability. Focused psychotropic medication review is a complex intervention; the professional(s) involved, target drug, degree of integration with usual care, and participant involvement varied greatly among the studies. Meta-analysis included 3 studies (n = 652 participants). Psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs compared with control (pooled odds ratio, 0.24; 95% CI, 0.14-0.39) in elderly participants with cognitive impairment living in nursing homes. Before-after studies consistently reported a change in psychotropic drug prescribing after medication review, regardless of the population. Studies that reported the effects of psychotropic medication review on clinical outcomes failed to demonstrate benefit. Economic implications of focused psychotropic medication review were not adequately assessed. The quality of evidence is poor and studies are at risk of bias. <h3>Conclusions and Relevance</h3> Focused psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs, but has not been shown to improve clinical outcomes or to provide economic benefit. More robust evidence is needed before programs of focused psychotropic medication review can be recommended as part of routine care for any patient group.
Efficacy of ramucirumab in combination with second-line or salvage-line FOLFIRI in patients with metastatic colorectal cancer
Authors: Y. Katata, T. Nagasaka, H. Tanioka, A. Nyuya, T. Toshima, Y. Mori, K. Shigeyasu, M. Okawaki, M. Yamamura, A. Tsuruta, T. Ueno, Y. Yamaguchi
Journal: Annals of Oncology (2018)
Hyperpolarized MRI Visualizes Warburg Effects and Predicts Treatment Response to mTOR Inhibitors in Patient-Derived ccRCC Xenograft Models
Authors: Yiyu Dong, Roozbeh Eskandari, Chelsea Ray, Kristin L. Granlund, Lidia Dos Santos-Cunha, Vesselin Z. Miloushev, Sui Seng Tee, Sangmoo Jeong, Omer Aras, Ying-Bei Chen, Emily H. Cheng, James J. Hsieh, Kayvan R. Keshari
Journal: Cancer Research (2018)

The ever-changing tumor microenvironment constantly challenges individual cancer cells to balance supply and demand, presenting tumor vulnerabilities and therapeutic opportunities. Everolimus and temsirolimus are inhibitors of mTOR (mTORi) approved for treating metastatic renal cell carcinoma (mRCC). However, treatment outcome varies greatly among patients. Accordingly, administration of mTORi in mRCC is diminishing, which could potentially result in missing timely delivery of effective treatment for select patients. Here, we implemented a clinically applicable, integrated platform encompassing a single dose of [1-13C] pyruvate to visualize the in vivo effect of mTORi on the conversion of pyruvate to lactate using hyperpolarized MRI. A striking difference that predicts treatment benefit was demonstrated using two preclinical models derived from patients with clear cell RCC (ccRCC) who exhibited primary resistance to VEGFRi and quickly succumbed to their diseases within 6 months after the diagnosis of metastasis without receiving mTORi. Our findings suggest that hyperpolarized MRI could be further developed to personalize kidney cancer treatment. SIGNIFICANCE: These findings demonstrate hyperpolarized [1-13C]pyruvate MRI as a tool for accurately assessing the clinical success of mTOR inhibition in patients with ccRCC.
High expression of Tob1 indicates poor survival outcome and promotes tumour progression via a Wnt positive feedback loop in colon cancer
Authors: Dandan Li, Li Xiao, Yuetan Ge, Yu Fu, Wenqing Zhang, Hanwei Cao, Binbin Chen, Haibin Wang, Yan-yan Zhan, Tianhui Hu
Journal: Molecular Cancer (2018)

Tob1, a Tob/BTG anti-proliferative protein family member, functions as a tumour suppressor in many cancers. Here, we reveal a unique oncogenic role of Tob1 in colon cancer. Tob1 expression was upregulated during colon cancer progression, was significantly correlated with tumour size and tumour differentiation, and was a prognostic indicator of colon cancer. Unlike in other cancers, where nuclear Tob1 performs anticancer activity, Tob1 is predominantly localized in the cytosol of colon cancer cells, where this protein binds and stabilizes β-catenin to activate Wnt/β-catenin signalling, which in turn enhances Tob1 expression, thus forming a positive feedback loop to promote cell proliferation. Moreover, Tob1 deficiency led to reduced tumourigenesis in AOM/DSS-treated and ApcMin/+ mice. Our findings provide important insights into a previously unrecognized oncogenic role of Tob1 in colon cancer and suggest that Tob1 is an adverse prognostic factor and therapeutic target for colon cancer.
Hypoglycemia and Incident Cognitive Dysfunction: A Post Hoc Analysis From the ORIGIN Trial
Authors: Tali Cukierman-Yaffe, Jackie Bosch, Hyejung Jung, Zubin Punthakee, Hertzel C. Gerstein
Journal: Diabetes Care (2018)

OBJECTIVE Epidemiological studies have reported a relationship between severe hypoglycemia, cognitive dysfunction, and dementia in middle-aged and older people with type 2 diabetes. However, whether severe or nonsevere hypoglycemia precedes cognitive dysfunction is unclear. Thus, the aim of this study was to analyze the relationship between hypoglycemia and incident cognitive dysfunction in a group of carefully followed patients using prospectively collected data in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial. RESEARCH DESIGN AND METHODS This prospective cohort analysis of data from a randomized controlled trial included individuals with dysglycemia who had additional cardiovascular risk factors and a Mini-Mental State Examination (MMSE) score ≥24 (N = 11,495). Severe and nonsevere hypoglycemic events were collected prospectively during a median follow-up time of 6.2 years. Incident cognitive dysfunction was defined as either reported dementia or an MMSE score of &amp;lt;24. The hazard of at least one episode of severe or nonsevere hypoglycemia for incident cognitive dysfunction (i.e., the dependent variable) from the time of randomization was estimated using a Cox proportional hazards model after adjusting for baseline cardiovascular disease, diabetes status, treatment allocation, and a propensity score for either form of hypoglycemia. RESULTS This analysis did not demonstrate an association between severe hypoglycemia and incident cognitive impairment either before (hazard ratio [HR] 1.16; 95% CI 0.89, 1.52) or after (HR 1.00; 95% CI 0.76, 1.31) adjusting for the severe hypoglycemia propensities. Conversely, nonsevere hypoglycemia was inversely related to incident cognitive impairment both before (HR 0.59; 95% CI 0.52, 0.68) and after (HR 0.58; 95% CI 0.51, 0.67) adjustment. CONCLUSIONS Hypoglycemia did not increase the risk of incident cognitive dysfunction in 11,495 middle-aged individuals with dysglycemia.
Clinical outcomes in non–small cell lung cancer patients with ultra-high expression of programmed death ligand-1 treated with pembrolizumab as first-line therapy: A retrospective multicenter cohort study
Authors: H. Kurebe, R. Edahiro, M. Kanazu, D. Fujimoto, M. Tamiya, A. Tamiya, H. Suzuki, K. Hirano, T. Yokoyama, M. Morita, Y. Fukuda, J. Uchida, T. Makio
Journal: Annals of Oncology (2018)
Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial
Authors: Stephen N. Davis, William Duckworth, Nicholas Emanuele, Rodney A. Hayward, Wyndy L. Wiitala, Lizy Thottapurathu, Domenic J. Reda, Peter D. Reaven
Journal: Diabetes Care (2018)

To determine the risk factors for severe hypoglycemia and the association between severe hypoglycemia and serious cardiovascular adverse events and cardiovascular and all-cause mortality in the Veterans Affairs Diabetes Trial (VADT).This post hoc analysis of data from the VADT included 1,791 military veterans (age 60.5 ± 9.0 years) with suboptimally controlled type 2 diabetes (HbA1c 9.4 ± 2.0%) of 11.5 ± 7.5 years disease duration with or without known cardiovascular disease and additional cardiovascular risk factors. Participants were randomized to intensive (HbA1c <7.0%) versus standard (HbA1c <8.5%) glucose control.The rate of severe hypoglycemia in the intensive treatment group was 10.3 per 100 patient-years compared with 3.7 per 100 patient-years in the standard treatment group (P < 0.001). In multivariable analysis, insulin use at baseline (P = 0.02), proteinuria (P = 0.009), and autonomic neuropathy (P = 0.01) were independent risk factors for severe hypoglycemia, and higher BMI was protective (P = 0.017). Severe hypoglycemia within the past 3 months was associated with an increased risk of serious cardiovascular events (P = 0.032), cardiovascular mortality (P = 0.012), and total mortality (P = 0.024). However, there was a relatively greater increased risk for total mortality in the standard group compared with the intensive group (P = 0.019). The association between severe hypoglycemia and cardiovascular events increased significantly as overall cardiovascular risk increased (P = 0.012).Severe hypoglycemic episodes within the previous 3 months were associated with increased risk for major cardiovascular events and cardiovascular and all-cause mortality regardless of glycemic treatment group assignment. Standard therapy further increased the risk for all-cause mortality after severe hypoglycemia.
Nanocarriers and Their Loading Strategies
Authors: Neng Wang, Xuejun Cheng, Nan Li, Hong Wang, Hongyu Chen
Journal: Advanced Healthcare Materials (2018)

Abstract Nanocarriers are of paramount significance for drug delivery and nanomedicine technology. Given the imperfect systems and nonideal therapeutic effects, there are works to be done in synthesis as much as in biological studies, if not more so. Building the foundation of synthesis would offer more tools and deeper insights for exploring the biological systems with extreme complexity. This review aims at a broad‐scope summary and classification of nanocarriers for drug delivery, with focus on the synthetic strategy and structural implications. The nanocarriers are divided into four categories according to the loading principle: molecular‐level loading, surface loading, matrix loading, and cavity loading systems. Making comparisons across diverse nanocarrier systems would make it easier to see the fundamental characteristics, from where the weakness can be addressed and the strengths combined. The systematic comparisons may also inspire new ideas and methods.
Social Injustice and the Cycle of Traumatic Childhood Experiences and Multiple Problems in Adulthood
Authors: Marc Gelkopf
Journal: JAMA Network Open (2018)

William E. Copeland, PhD; Lilly Shanahan, PhD; Jennifer Hinesley, PsyD; Robin F. Chan, PhD; Karolina A. Aberg, PhD; John A. Fairbank, PhD; Edwin J. C. G. van den Oord, PhD; E. Jane Costello, PhD