tbuckley/cabot-search huggingface dataset:
AB1013 CHILDREN IN RISK OF LOW BONE MASS HAVE MORE THAN 2 RISK FACTORS
Authors: Berta Paula Magallares López, Dacia Cerda, Jocelyn Betancourt, Gloria Fraga, Estefanía Quesada-Masachs, Mireia López- Corbetó, Montserrat Torrent, Ana María Marín, Silvia Herrera, Jordi Casademont, Hector Corominas, Jorge Malouf
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Low Bone Mass (LBM)/Infantile Osteoporosis (IOP) require an active evaluation for its diagnosis and prevention. Therefore, its incidence is unknown and could be undertreated. The systematic collection of risk factors associated with LBM/IOP could help identify the population at risk of presenting it <h3>Objectives</h3> To assess the prevalence and number of risk factors (RF) in the pediatric population at risk of developing LBM/IOP. Assess its influence on Bone Mineral Density <h3>Methods</h3> Demographic and clinical data were prospectively collected from patients from 2 to 20 years of age, who had at least one risk factor for LBM/IOP, among them: chronic diseases, treatment with immunosuppressants and/or corticosteroids and insufficient calcium intake. Calcemia, calciuria, and vitamin D were determined in blood samples, and whole body and lumbar DXA were performed. The calcium intake, the number of previous fractures and other RF were collected <h3>Results</h3> Data were collected from 103 patients, with an average age of 9'8 years, 52'4% women, and 80%Caucasians. Of these, 9 were preschoolers (2-3 years old), 33 schoolchildren (4-9y), 55 teenagers (10-17th) and 6 young people (18-20th) The most frequent diagnoses were: Malabsorption/Food allergies: 46.6%, JIA: 17.5%, Nephropathies: 17.8%, Hematological diseases: 6.8%, and Vasculitis and connective tissue diseases: 3.9% each The frequency of RFs can be observed inTable 1 The average dose of current corticoids was 0.21 mg/kg/day of prednisone with a total cumulative average dose of: 7 gr, with an exposure of 1 to 144 months 4'3% of the sample had an isolated RF, 38% had 2 RF, 31% 3, 15% 4, and 12% 5 or more 8'7% of the sample presented a LBM and 4.8% met criteria for Opi for vertebral fractures, 3 of them asymptomatic and discovered by morphometry In the multiple linear regression analysis: age, latin ethnicity, gender, and hypovitaminosis D were the main RFs related to lumbar BMD. Likewise, age, latin ethnicity and sedentary lifestyle were the RF related to the BMD of the whole body without head (BMDwbwh) In lumbar BMD, these 4 FR explained up to 85% of the BMD variation, where the age adds 0'032 per year gained, the male sex subtracts 0'061, the hypovitaminosis D sum 0'077 and the latin ethnicity subtracts 0'070 Up to a 90'8% variation of BMDwbwh is explained by these 3 RF: age adds 0'036 per year gained, sedentary life subtracts 0'084 and latin ethnicity subtracts 0'055. <h3>Conclusion</h3> The child population at risk of LBM/IOp associates 2 or more risk factors 8.7% of children with risk factors have LBM and 4.8% IOP The RFs related to changes in BMD are: age, sex, sedentary lifestyle and ethnicity. Hypovitaminosis D correlated positively with lumbar BMD <h3>Disclosure of Interests</h3> None declared
Functional characterization of enhancer evolution in the primate lineage
Authors: Jason C. Klein, Aidan Keith, Vikram Agarwal, Timothy Durham, Jay Shendure
Journal: Genome biology (2018)

Enhancers play an important role in morphological evolution and speciation by controlling the spatiotemporal expression of genes. Previous efforts to understand the evolution of enhancers in primates have typically studied many enhancers at low resolution, or single enhancers at high resolution. Although comparative genomic studies reveal large-scale turnover of enhancers, a specific understanding of the molecular steps by which mammalian or primate enhancers evolve remains elusive.We identified candidate hominoid-specific liver enhancers from H3K27ac ChIP-seq data. After locating orthologs in 11 primates spanning around 40 million years, we synthesized all orthologs as well as computational reconstructions of 9 ancestral sequences for 348 active tiles of 233 putative enhancers. We concurrently tested all sequences for regulatory activity with STARR-seq in HepG2 cells. We observe groups of enhancer tiles with coherent trajectories, most of which can be potentially explained by a single gain or loss-of-activity event per tile. We quantify the correlation between the number of mutations along a branch and the magnitude of change in functional activity. Finally, we identify 84 mutations that correlate with functional changes; these are enriched for cytosine deamination events within CpGs.We characterized the evolutionary-functional trajectories of hundreds of liver enhancers throughout the primate phylogeny. We observe subsets of regulatory sequences that appear to have gained or lost activity. We use these data to quantify the relationship between sequence and functional divergence, and to identify CpG deamination as a potentially important force in driving changes in enhancer activity during primate evolution.
A statistical framework for cross-tissue transcriptome-wide association analysis
Authors: Yiming Hu, Mo Li, Qiongshi Lu, Haoyi Weng, Jiawei Wang, Seyedeh M. Zekavat, Zhaolong Yu, Boyang Li, Jianlei Gu, Sydney Muchnik, Yu Shi, Brian W. Kunkle, Shubhabrata Mukherjee, Pradeep Natarajan, Adam Naj, Amanda Kuzma, Yi Zhao, Paul K. Crane, Hui Lu, Hongyu Zhao
Journal: Nature Genetics (2019)
Assessment of Use of Arteriovenous Graft vs Arteriovenous Fistula for First-time Permanent Hemodialysis Access
Authors: Caitlin W. Hicks, Peiqi Wang, Amber Kernodle, Ying W. Lum, James H. Black, Martin A. Makary
Journal: JAMA Surgery (2019)

<h3>Importance</h3> Initial hemodialysis access with arteriovenous fistula (AVF) is associated with superior clinical outcomes compared with arteriovenous graft (AVG) and should be the procedure of choice whenever possible. To address the national underuse of AVF in the United States, the Centers for Medicare &amp; Medicaid has established an AVF goal of 66% or greater in 2009. <h3>Objective</h3> To explore contemporary practice patterns and physician characteristics associated with high AVG use compared with AVF use. <h3>Design, Setting, and Participants</h3> This review of 100% Medicare Carrier claims between January 1, 2016, and December 31, 2017, includes both inpatient and outpatient Medicare claims data. All patients undergoing initial permanent hemodialysis access placement with an AVF or AVG were included. All surgeons performing more than 10 hemodialysis access procedures during the study period were analyzed. <h3>Exposures</h3> Placement of an AVF or AVG for initial permanent hemodialysis access. <h3>Main Outcomes and Measures</h3> A surgeon-level AVG (vs AVF) use rate was calculated for all included surgeons. Hierarchical logistic regression modeling was used to identify patient-level and surgeon-level factors associated with AVG use. <h3>Results</h3> A total of 85 320 patients (median age, 70 [range, 18-103] years; 47 370 men [55.5%]) underwent first-time hemodialysis access placement, of whom 66 489 (77.9%) had an AVF and 18 831 (22.1%) had an AVG. Among the 2397 surgeons who performed more than 10 procedures per year, the median surgeon level AVG use rate was 18.2% (range, 0.0%-96.4%). However, 498 surgeons (20.8%) had an AVG use rate greater than 34%. After accounting for patient characteristics, surgeon factors that were independently associated with AVG use included more than 30 years of clinical practice (vs 21-30 years; odds ratio, 0.85 [95% CI, 0.75-0.96]), metropolitan setting (odds ratio, 1.25 [95% CI, 1.02-1.54]), and vascular surgery specialty (vs general surgery; odds ratio, 0.77 [95% CI, 0.69-0.86]). Surgeons in the Northeast region had the lowest rate of AVG use (vs the South; odds ratio, 0.83 [95% CI, 0.73-0.96]). First-time hemodialysis access benchmarking reports for individual surgeons were created for potential distribution. <h3>Conclusions and Relevance</h3> In this study, one-fifth of surgeons had an AVG use rate above the recommended best practices guideline of 34%. Although some of these differences may be explained by patient referral practices, sharing benchmarked performance data with surgeons could be an actionable step in achieving more high-value care in hemodialysis access surgery.
From Many to One to Many—the Search for Causes of Psychiatric Illness
Authors: Kenneth S. Kendler
Journal: JAMA Psychiatry (2019)

The search for the causes of medical and psychiatric disorders has gone through 3 historical phases. First, up until the mid-19th century, causes of illness were anecdotally recorded from individual cases, resulting in long and diverse lists for all disorders. Second, in the latter half of the 19th century, with the use of microbiological methods, single causes were found for many infectious diseases that led to specific diagnostic tests, effective preventions, and, in some cases, treatments. Causal thinking in medicine shifted from the earlier multicausal approaches to monocausal theories of etiology. Indeed, proving monocausal etiology became a way to establish the legitimacy of a disorder. Through the writings of Kahlbaum and Hecker, psychiatry was deeply influenced by this monocausal perspective, the importance of which was substantially amplified by a twist of fate: the increasing clinical importance of general paresis of the insane throughout the 19th century and the eventual proof that it too was a monocausal condition. However, in the mid-20th century, the third phase began. With decreasing deaths from infectious diseases, epidemiology and clinical medicine shifted to a chronic disease model in which paradigmatic disorders, such as cancer and cardiovascular disease, were shown to be highly multicausal. Biostatistics evolved from deterministic to probabilistic models of disease risk factors. Paradoxically, at this time, biological psychiatry, then rising to dominance in American psychiatry, vigorously pursued monocausal theories, first of neurochemical origin and then of genetic origin. We were trying to establish the legitimacy of our field by pursuing an outmoded model-that "real" diseases are monocausal. Despite ample evidence to the contrary, monocausal thinking continues to influence our field, for example, in the popular but improbable view that we can, with a few key advances, move easily from descriptive to etiologically based diagnoses.
SP0028 WHAT SHOULD MOBILE HEALTH APPLICATIONS FOR RMD PATIENTS BE LIKE?
Authors: Aurelie Najm
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Mobile health (mhealth) connects patients, their families and physicians by creating a network with mobile and specialized devices such as wearable sensors, recording health parameters and gathering health data converted and transferred to physicians via medical application interfaces. Apps for people with chronic health conditions have an important role to play in empowering those individuals to become more active in the self- and shared-management of their health. Since rheumatic and musculoskeletal diseases (RMDs) have multi-dimensional consequences on health, the increasing availability of apps have an important role to play in enabling people with RMDs to better self-manage their health. This talk provides insights into the most important aspects to be considered for apps designed for people living with RMDs: features, use, safety, and patient"s views and preferences. <h3>Disclosure of Interests:</h3> None declared
AB0275 RHEUMATOID ARTHRITIS IN HISPANIC PATIENTS: DEMOGRAPHIC AND BASELINE CLINICAL CHARACTERISTICS IN AN EARLY REFERRAL COHORT IN MEXICO VERSUS ROUTINE CARE IN THE UNITED STATES
Authors: Elena Obreja, Virginia Dr. Pascual, Mariam Riad, Irazú Contreras-Yáñez, Isabel Castrejon
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Hispanics are the largest minority group in the United States (US) and his percentage is expected to increase (28.6% by 2060)<sup>1</sup>, being Mexicans the largest group (67.9%). RA patients from Latin-America have distinctive features from White patients. The literature highlights a younger age at presentation and a different clinical expression compared with White<sup>2</sup> but few data for Hispanic patients in US are available. <h3>Objectives</h3> We compared baseline demographic, clinical features and disease management among Hispanic RA patients from two well characterized cohorts, in the USA and Mexico city. <h3>Methods</h3> An early arthritis clinic (EAC) was established at Site 1 (Mexico City); patients with recent-onset RA (&lt;1 year of symptoms) had a standardized assessment and received "treat to target" treatment. At Site 2 (US), a "routine care" cohort was initiated in 2011, and all patients completed a multidimensional health assessment questionnaire (MDHAQ) as part of their routine care. Patients from both sites had baseline complete evaluation including sociodemographic data, patient-reported outcomes (PROs) (patient global assessment, pain-VAS, HAQ/MHAQ, RAPID3), laboratory data, and tender joint counts. Initial treatment was noted. Data from both sites were compared and appropriate statistics was used. <h3>Results</h3> 201 patients from site 1 and 179 from site 2 were included (table 1); among them, 105 (52%) and 37 (19%), respectively, were DMARDs-naïve at baseline. Patients from site 2 were older and had longer disease duration, however demographic characteristics did not differ. Naïve-DMARDs patients from site 2 scored significantly higher pain-VAS and tender joint counts, and had higher ESR values (p≤0.05, Mann Withney); a similar tendency was seen for other PROs. Time to DMARDs initiation was shorter in the EAC. <h3>Conclusion</h3> Hispanic patients with RA from different regions in America may differ in their initial presentation. Naïve DMARDs patients belonging to an early RA cohort had shorter presentation to rheumatology resulting in earlier treatment initiation, which has been associated to better outcomes. EACs facilitate the identification of patients with recent-onset disease and help provide early access to effective therapies. <h3>References</h3> [1] Public Health Reviews 2016; 37:31. [2] Best Pract Clin Rheumatol 2008; 22:621-41. <h3>Disclosure of Interests</h3> None declared
Intraspecific Variation in Microsatellite Mutation Profiles in Daphnia magna
Authors: Eddie K H Ho, Fenner Macrae, Leigh C Latta, Maia J Benner, Cheng Sun, Dieter Ebert, Sarah Schaack
Journal: Molecular Biology and Evolution (2019)

Microsatellite loci (tandem repeats of short nucleotide motifs) are highly abundant in eukaryotic genomes and often used as genetic markers because they can exhibit variation both within and between populations. Although widely recognized for their mutability and utility, the mutation rates of microsatellites have only been empirically estimated in a few species, and have rarely been compared across genotypes and populations within a species. Here, we investigate the dynamics of microsatellite mutation over long- and short-time periods by quantifying the starting abundance and mutation rates for microsatellites for six different genotypes of Daphnia magna, an aquatic microcrustacean, collected from three populations (Finland, Germany, and Israel). Using whole-genome sequences of these six starting genotypes, descendent mutation accumulation (MA) lines, and large population controls (non-MA lines), we find each genotype exhibits a distinctive initial microsatellite profile which clusters according to the population-of-origin. During the period of MA, we observe motif-specific, highly variable, and rapid microsatellite mutation rates across genotypes of D. magna, the average of which is order of magnitude greater than the recently reported rate observed in a single genotype of the congener, Daphnia pulex. In our experiment, genotypes with more microsatellites starting out exhibit greater losses and those with fewer microsatellites starting out exhibit greater gains-a context-dependent mutation bias that has not been reported previously. We discuss how genotype-specific mutation rates and spectra, in conjunction with evolutionary forces, can shape both the differential accumulation of repeat content in the genome and the evolution of mutation rates.
Development and validation of a clinical trial feasibility assessment (CTFA) tool and evaluation of the NCI clinical trial evaluation and scoring (NCI-CTES) model.
Authors: Matthias Weiss, Angela Bulgrin, Hong Liang, Kim Fuehrer, Vidhu Choudhary, Steven Yale
Journal: Journal of Clinical Oncology (2012)

e16549 Background: The ability to predict accrual success of a specific NCI sponsored clinical trial (CT) in the setting of a Community Clinical Oncology Program (CCOP) is typically based on the experience of the local principal investigator (PI) and research staff. This study was designed to develop an objective method to predict accrual success based on CT and institution specific factors. Funded by ARRA grant #3U10CA35412-26S1. Methods: 27 potential barriers to successful CT accrual were identified by Marshfield Clinic CCOP and validated by Eastern Cooperative Oncology Group (ECOG) PI and research staff (Cronbach alpha 0.922). This 27 item CTFA tool and the NCI-CTES model were prospectively applied to 32 consecutive NCI sponsored CT which opened at Marshfield Clinic CCOP (2009-11). Incorporating PI and research staff input each CT was scored (CTFA range 27-135; NCI-CTES 0-22). These scores were correlated with accrual outcome (Wilcoxon`s rank-sum test). Statistical analysis included CTFA item content validity testing via item-test correlation and CTFA/NCI-CTES internal consistency reliability testing via Cronbach alpha. Results: 28/32 CT were available for analysis; 4 CT were excluded (never opened to accrual). Duration of time open to accrual ranged from 1-27 months (mean=13.5). 21/28 CT achieved accrual ranging from 1-50 subjects (1-5 accrual=13; 5-10=4; &gt;10=4). Median time to complete the 27 item CTFA tool was 16 minutes and 8 minutes for the NCI-CTES model. After eliminating 6/27 CTFA items due to low content validity (&lt;0.2), the remaining 21 item final CTFA tool indicated very high internal consistency reliability (Cronbach alpha 0.872). Wilcoxon`s rank-sum test revealed that the differences in NCI-CTES and CTFA scores between the groups with &lt;=0.25 and &gt;0.25 subject accrual per month were significant (CTFA P-value=0.0418; NCI-CTES P-value=0.0032). Conclusions: Application of the CTFA tool and the NCI-CTES model proved to be feasible and predictive of accrual success of NCI sponsored clinical trials at Marshfield Clinic CCOP.
ZnAs@SiO<sub>2</sub> nanoparticles as a potential anti-tumor drug for targeting stemness and epithelial-mesenchymal transition in hepatocellular carcinoma via SHP-1/JAK2/STAT3 signaling
Authors: Yongquan Huang, Bin Zhou, Hui Luo, Junjie Mao, Yin Huang, Ke Zhang, Chaoming Mei, Yan Yan, Hongjun Jin, Jinhao Gao, Zhongzhen Su, Pengfei Pang, Dan Li, Hong Shan
Journal: Theranostics (2019)

Rationale: Current therapies for hepatocellular carcinoma (HCC) are hampered by treatment failure and recurrence due to the remaining treatment-resistant liver cancer stem cells (CSCs).Stemness and epithelial-mesenchymal transition (EMT) are regarded as two fundamental characteristics of liver CSCs necessary for cancer progression; thus, drugs that simultaneously target both characteristics should prove effective in eliminating HCC and impeding recurrence.In this study, we developed new arsenic trioxide (ATO)-based nanoparticles (NPs), which are expected to be more effective than the current HCC therapy, and explored their potential mechanism.Methods: A "one-pot" reverse emulsification approach was employed to prepare the ZnAs@SiO2 NPs.HCC cell lines, MHCC97L and Hep3b, were used to analyze the antitumor activity of ZnAs@SiO2 NPs in vitro and in vivo by quantifying cell growth and metastasis as well as to study the effect on stemness and EMT.SHP-1 siRNA was used to validate the role of the SHP-1/JAK2/STAT3 signaling pathway in mediating inhibition of stemness and EMT by ZnAs@SiO2.Results: Compared with the current ATO treatment, ZnAs@SiO2 NPs promoted apoptosis and significantly inhibited proliferation, migration, and invasion of both MHCC97L and Hep3b cells.In the in vivo assay, ZnAs@SiO2 NPs inhibited tumor growth by 2.2-fold and metastasis by 3.5-fold as compared to ATO.The ZnAs@SiO2 NPs also inhibited tumor spheroid formation in vitro and tumor initiation in vivo and induced significant changes in the expression of stemness markers (CD133, Sox-2, and Oct-4) and EMT markers (E-cadherin, Vimentin, and Slug) both in vitro and in vivo.These effects of ZnAs@SiO2 that correlated with prognosis of HCC were mediated by the SHP-1/JAK2/STAT3 signaling.Conclusions: ZnAs@SiO2 NPs can effectively suppress tumor initiation, growth, metastasis, and inhibit stemness and EMT through regulation of SHP-1/JAK2/STAT3 signaling pathway in liver cancer cells in vitro and in vivo.Thus, ZnAs@SiO2 NPs have immense potential for HCC treatment in the future.
Peroxisomal gene and protein expression increase in response to a high-lipid challenge in human skeletal muscle
Authors: Tai-Yu Huang, Donghai Zheng, Robert C. Hickner, Jeffrey J. Brault, Ronald N. Cortright
Journal: Metabolism (2019)

Peroxisomes are essential for lipid metabolism and disruption of liver peroxisomal function results in neonatal death. Little is known about how peroxisomal content and activity respond to changes in the lipid environment in human skeletal muscle (HSkM).