tbuckley/cabot-search huggingface dataset:
Transdermal drug delivery systems in diabetes management: A review
Authors: Li Ching Ng, Manish Gupta
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Diabetes mellitus is a chronic disease in which there is an insufficient production of insulin by the pancreas, or the insulin produced is unable to be utilized effectively by the body. Diabetes affects more than 415 million people globally and is estimated to strike about 642 million people in 2040. The WHO reported that diabetes will become the seventh biggest cause of mortality in 2030. Insulin injection and oral hypoglycemic agents remain the primary treatments in diabetes management. These often present with poor patient compliance. However, over the last decade, transdermal systems in diabetes management have gained increasing attention and emerged as a potential hope in diabetes management owing to the advantages that they offer as compared to invasive injection and oral dosage forms. This review presents the recent advances and developments in transdermal research to achieve better diabetes management. Different technologies and approaches have been explored and applied to the transdermal systems to optimize diabetes management. Studies have shown that these transdermal systems demonstrate higher bioavailability compared to oral administration due to the avoidance of first-pass hepatic metabolism and a sustained drug release pattern. Besides that, transdermal systems have the advantage of reducing dosing frequency as drugs are released at a predetermined rate and control blood glucose level over a prolonged time, contributing to better patient compliance. In summary, the transdermal system is a field worth exploring due to its significant advantages over oral route in administration of antidiabetic drugs and biosensing of blood glucose level to ensure better clinical outcomes in diabetes management.
Abstract 12091: Higher Chadsvasc Scores but Similar Complication and Mortality Rates in Women With Atrial Fibrillation Over 1 Year in an Outpatient Cardiology Setting
Authors: Tiffany Foltz, Narendra Singh, Sandeep Chandra, David Song, Linda Yan, David Suh
Journal: Circulation (2016)

Background: Gender differences in atrial fibrillation are recognized with women having a higher stroke risk and therefore having an extra point attributed within the CHADSVasc score. We evaluate if a higher score affects oral anticoagulant use (OAC) and outcomes over 1 year. Methods: Retrospective chart review of all pts being treated for atrial fibrillation in a single, multi-site suburban, outpatient cardiology practice for the calendar year 2014. Results: Of the 1366 pts being followed 645 (47.2%) were females. Females had a higher CHADSVasc score (4.0± 1.6 vs 2.7± 1.6, p=0.001). This difference was driven by the CHADSVasc components of age &gt; 75 (47% vs 31%, p=0.001) and cerebrovascular accidents (16% vs 12.5%, p=0.05). Other components were similar-heart failure (26 vs 26%), hypertension (82 vs 81%), diabetes (31 vs 31%) vascular disease (12 vs 13%). The % of females vs males having a CHADSVasc score of 1-3 was (32 vs 68%, p&lt;0.00001) 4-6 (66 vs 34%, p&lt;0.00001) and 7-9 (80 vs 20%, p=0.000001). Females had a higher ejection fraction (56 vs 53%, p=0.6) and more valvular heart disease (32 vs 24%, p=0.0002) but similar BMI (29 vs 29). Paroxysmal AF was similar (72% vs 70%) Females were more likely to have Medicare coverage vs private insurance (64% vs 29%, p=0.000054) and more often of black ethnicity (35 vs 23%, p=0.000001). Females were equally likely to be prescribed warfarin vs a NOAC (48 vs 45.1%, p=0.3) and time in therapeutic range was similar at 50%. There was no difference in the number of pts not receiving an OAC (49.7 vs 50.3%, p=0.3) Stroke and bleeding complication rates over 1 year were similar (9.1% vs 8.5%, p=0.6) as was mortality (3.7 vs 3.9%, p=0.8). Conclusions: Our findings confirm that women with atrial fibrillation tend to be older which results in a higher CHADSVasc score. This however did not appear to translate into a higher utilization of OAC compared to men but also did not worsen 1 year outcomes. If validated in other datasets then it may be necessary to revisit if females warrant an extra point on the CHADSVasc scale in the contemporary AF population.
A Genome-Wide Association Study Identifies Blood Disorder–Related Variants Influencing Hemoglobin A1c With Implications for Glycemic Status in U.S. Hispanics/Latinos
Authors: Jee-Young Moon, Tin L. Louie, Deepti Jain, Tamar Sofer, Claudia Schurmann, Jennifer E. Below, Chao-Qiang Lai, M. Larissa Aviles-Santa, Gregory A. Talavera, Caren E. Smith, Lauren E. Petty, Erwin P. Bottinger, Yii-Der Ida Chen, Kent D. Taylor, Martha L. Daviglus, Jianwen Cai, Tao Wang, Katherine L. Tucker, José M. Ordovás, Craig L. Hanis, Ruth J.F. Loos, Neil Schneiderman, Jerome I. Rotter, Robert C. Kaplan, Qibin Qi
Journal: Diabetes Care (2019)

We aimed to identify hemoglobin A
Abstract 15708: Cardiovascular Event Rates According to Low-density Lipoprotein Cholesterol Level Among Statin-treated Patients With Existing Cardiovascular Disease
Authors: Alanna M Chamberlain, Sarah S Cohen, Susan A Weston, Kathleen M Fox, Pin Xiang, Jill M Killian, Yi Qian
Journal: Circulation (2017)

Purpose: To describe subsequent cardiovascular disease burden by low-density lipoprotein cholesterol (LDL-C) level among patients with atherosclerotic cardiovascular disease (ASCVD) receiving moder...
Prevention of Firearm Injuries Among Children and Adolescents
Authors: Rebecca M. Cunningham, Patrick M. Carter, Megan L. Ranney, Maureen Walton, April M. Zeoli, Elizabeth R. Alpern, Charles Branas, Rinad S. Beidas, Peter F. Ehrlich, Monika K. Goyal, Jason E. Goldstick, David Hemenway, Stephen W. Hargarten, Cheryl A. King, Lynn Massey, Quyen Ngo, Jesenia Pizarro, Lisa Prosser, Ali Rowhani-Rahbar, Fredrick Rivara, Laney A. Rupp, Eric Sigel, Jukka Savolainen, Marc A. Zimmerman
Journal: JAMA Pediatrics (2019)

<h3>Importance</h3> Firearm injuries are the second leading cause of death among US children and adolescents. Because of the lack of resources allocated to firearm injury prevention during the past 25 years, research has lagged behind other areas of injury prevention. Identifying timely and important research questions regarding firearm injury prevention is a critical step for reducing pediatric mortality. <h3>Objective</h3> The Firearm Safety Among Children and Teens (FACTS) Consortium, a National Institute for Child Health and Human Development–funded group of scientists and stakeholders, was formed in 2017 to develop research resources for the field, including a pediatric-specific research agenda for firearm injury prevention to assist future researchers and funders, as well as to inform cross-disciplinary evidence-based research on this critical injury prevention topic. <h3>Evidence Review</h3> A nominal group technique process was used, including 4 key steps (idea generation, round-robin, clarification, and voting and consensus). During idea generation, stakeholders and workgroups generated initial research agenda topics after conducting scoping reviews of the literature to identify existing gaps in knowledge. Agenda topics were refined through 6 rounds of discussion and survey feedback (ie, round-robin, and clarification steps). Final voting (using a 5-point Likert scale) was conducted to achieve consensus (≥70% of consortium ranking items at 4 or 5 priority for inclusion) around key research priorities for the next 5 years of research in this field. Final agenda questions were reviewed by both the stakeholder group and an external panel of research experts not affiliated with the FACTS Consortium. Feedback was integrated and the final set of agenda items was ratified by the entire FACTS Consortium. <h3>Findings</h3> Overall, 26 priority agenda items with examples of specific research questions were identified across 5 major thematic areas, including epidemiology and risk and protective factors, primary prevention, secondary prevention and sequelae, cross-cutting prevention factors, policy, and data enhancement. <h3>Conclusions and Relevance</h3> These priority agenda items, when taken together, define a comprehensive pediatric-specific firearm injury prevention research agenda that will guide research resource allocation within this field during the next 5 years.
Abstract 2934: The Effects of Anti-α1-adrenoceptor Autoantibody on Vasoconstriction
Authors: Li Yan, Long-Gang Niu, Yan-Wu Xu, Xiao-Liang Wang, Ye Wu, Hui-Rong Liu
Journal: Circulation (2007)

Background:Recent studies demonstrated that autoantibody against α1-adrenergic receptor (α1-AR) could be detected in the serum of patients with primary hypertension, and accumulating evidences indi...
SP0169 COMPLEMENT AND LUPUS IN THE YOUNG AND THE OLD
Authors: Marina Botto
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Complement component C1q is known to play an important recognition role in adaptive and innate immunity. More recently evidence has emerged that C1q may have roles outside the complement system and the relevance of these functions may change with ageing. Homozygous deficiency of the first component of the complement system, C1q, is one of the most powerful susceptibility genetic factors for the development of systemic lupus erythematosus (SLE). The vast majority of patients with C1q deficiency develop a syndrome closely related to SLE. The disease is typically of early onset and is often very severe. Although the phenotype of disease varies between patients, the fact that C1q deficiency is sufficient to cause SLE in almost all humans identifies a pivotal role for this molecule. The challenge is to identify the relevant physiological activity that can explain this strong association. On the other hand, C1q seems to play a different role in old people. The concentration of C1q rises with aging and can be modulated by exercises. Of note, increased levels of C1q have been reported in the central nervous systemof old people, with the highest levels being seen in close proximity to synapses and central regions of the brainsuggesting that C1q may play a role in the development of problems associated with aging. Consistent with this hypothesis aged C1q-deficient mice showed less cognitive and memory decline in hippocampus-dependent behaviour tests compared to their wild-type litter mates. In summary,the traditional view of the role of C1q as just initiator of the classical complement pathway needs revision. Evidence is emerging that C1q has roles outside the complement system and these will be discussed. <h3>Disclosure of Interests:</h3> None declared
SAT0112 NO DIFFERENCE IN TREATMENT CONTINUATION OF DIFFERENT BIOLOGICS IN ELDERLY PATIENTS &gt; 70 YEARS COMPARED TO YOUNGER PATIENTS ≤ 65 YEARS
Authors: Anja Strangfeld, Klaus Krueger, Bernhard Manger, Christian Kneitz, Angela Zink, Martin Schaefer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Due to demographic changes an increasing number of persons reach an age above 70 years. Therefore, the adequate therapy of elderly patients with rheumatoid arthritis (RA) is an increasingly important topic. <h3>Objectives:</h3> To compare treatment continuation of several biologic DMARDs in patients ≤ 65 with elderly patients &gt; 70 years, stratified by onset of disease (young onset (&lt;65 years) and late onset (≥65 years)) and by seropositivity. <h3>Methods:</h3> The German register RABBIT is a prospective longitudinally followed cohort of RA patients enrolled with a new start of a DMARD after at least one csDMARD failure. For the current analysis patients who were enrolled with a biologic DMARD between 01/2007 and 04/2018 were included. Kaplan Meier methods were applied to analyse treatment continuation. <h3>Results:</h3> Among the 9,819 RA patients included in the analysis, 7,972 were ≤ 65 years old and 1,847 were older than 70 years (among them 180 patients above 80 years). Among the patients ≤ 65 years, 28% received a csDMARDs and 72% a bDMARD, while among the patients above 70 years, 35% received a csDMARDs and 65% a biological. Elderly patients with a young disease onset (YORA) were more frequently women and more frequently seropositive, on average had a higher number of prior treatment failures, a worse physical function and were more likely to have joint erosions than elderly patients with late onset (LORA) (Table 1). On all bDMARD treatments investigated, elderly RA patients showed the same treatment continuation as seen in younger patients. While neither the age of the patients nor the age at disease onset changed the continuation of biologics, patients being seronegative had a significantly lower continuation with rituximab and abatacept treatment, irrespective of age (Figure 1). <h3>Conclusion:</h3> These results suggest that bDMARD treatment may be used for elderly patients with the same effectiveness as in younger patients. <h3>Acknowledgement:</h3> RABBIT is supported by a joint, unconditional grant from AbbVie, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, MSD Sharp &amp; Dohme, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCB. <h3>Disclosure of Interests:</h3> Anja Strangfeld Speakers bureau: Speakers fees from Bristol-Myers Squibb, MSD, Pfizer, Roche, Klaus Krueger: None declared, Bernhard Manger: None declared, Christian Kneitz: None declared, Angela Zink Speakers bureau: Speakers fees from AbbVie, Janssen, Pfizer, Roche, Sanofi, Martin Schaefer: None declared
Targeting the SUMO Pathway Primes All-<i>trans</i> Retinoic Acid–Induced Differentiation of Nonpromyelocytic Acute Myeloid Leukemias
Authors: Hayeon Baik, Mathias Boulanger, Mohsen Hosseini, Julie Kowalczyk, Sonia Zaghdoudi, Tamara Salem, Jean-Emmanuel Sarry, Yosr Hicheri, Guillaume Cartron, Marc Piechaczyk, Guillaume Bossis
Journal: Cancer Research (2018)

Differentiation therapies using all-trans retinoic acid (ATRA) are highly efficient at treating acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). However, their efficacy, if any, is limited in the case of non-APL AML. We report here that inhibition of SUMOylation, a posttranslational modification related to ubiquitination, restores the prodifferentiation and antiproliferative activities of retinoids in non-APL AML. Controlled inhibition of SUMOylation with the pharmacologic inhibitors 2-D08 or anacardic acid, or via overexpression of SENP deSUMOylases, enhanced the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis in non-APL AML cells. This activated ATRA-induced terminal myeloid differentiation and reduced cell proliferation and viability, including in AML cells resistant to chemotherapeutic drugs. Conversely, enhancement of SUMOylation via overexpression of the SUMO-conjugating enzyme Ubc9 dampened expression of ATRA-responsive genes and prevented differentiation. Thus, inhibition of the SUMO pathway is a promising strategy to sensitize patients with non-APL AML to retinoids and improve the treatment of this poor-prognosis cancer.Significance: SUMOylation silences key ATRA-responsive genes in nonpromyelocytic acute myeloid leukemias. Cancer Res; 78(10); 2601-13. ©2018 AACR.
PS1429 LIVING ALONE WITH MULTIPLE MYELOMA: THE NEXT‐GENERATION CHALLENGE
Authors: R. Ríos‐Tamayo, D. Sánchez Rodríguez, P. Garrido Collado, Y.L. Chang Chan, J. Sainz Perez, P.A. González Sierra, A. Romero Aguilar, A. García Ruiz, G. Salas, J. Muñoz Ballester, M.J. Sánchez Pérez
Journal: HemaSphere (2019)

Background: According with the Spanish National Institute of Statistics (2017), 25.4% of Spanish households are formed by a single person and this trend is increasing in recent years. The outcome of patients with newly diagnosed multiple myeloma (NDMM) who live alone is not well known. Aims: To assess the impact in terms of overall survival (OS) and early mortality (EM) of NDMM patients who live alone, either voluntarily or not. Methods: All consecutive patients with the variable of interest available on clinical records and included in the population‐based Granada Myeloma Registry (Ríos‐Tamayo et al, 2015) until the end of 2018 are reported. Comparisons for categorical variables among different groups were made with the x 2 ‐test. Comparisons of means of quantitative continuous variables between two groups were made with the t‐test. OS curves were estimated using the Kaplan‐Meier method, and comparisons among groups were carried out with the log‐rank test. Results: 200 patients were evaluated, 117 men (58.5%) and 83 women. 35 patients (17.5%) lived alone at diagnosis, 19 men and 16 women. There was a trend to better OS for patients with some caregiver available with respect to patients who live alone (p = 0.074) (Figure 1). Median age for patients living alone was 68.74 vs 62.1 years (p = 0.006). Weight loss was documented in 18/35 (51.4%) vs 53/163 (32.5%) (p = 0.077). No statistical differences were shown between groups for other variables (body mass index, number of comorbidities, sex, ECOG, ISS, Light‐chain only MM and High‐Risk FISH). There were not statistically significant differences in EM at 6 months (6.8% vs 11.8%; p = 0.3). Summary/Conclusion: Patients with NDMM who live alone represent approximately 17.5% and have to face a huge challenge, showing a trend to poorer OS in comparison with patients who have a caregiver. This poor outcome may be due in part to a more advanced age. However, we cannot rule out other factors such as a poor adherence to the treatment. image
Tumor vasodilation by N-Heterocyclic carbene-based nitric oxide delivery triggered by high-intensity focused ultrasound and enhanced drug homing to tumor sites for anti-cancer therapy
Authors: Youngnam Kang, Jeesu Kim, Junbeom Park, Yeong Mi Lee, Gurusamy Saravanakumar, Kyeng Min Park, Wonseok Choi, Kimoon Kim, Eunsung Lee, Chulhong Kim, Won Jong Kim
Journal: Biomaterials (2019)
Adaptive Landscape of Protein Variation in Human Exomes
Authors: Ravi Patel, Laura B Scheinfeldt, Maxwell D Sanderford, Tamera R Lanham, Koichiro Tamura, Alexander Platt, Benjamin S Glicksberg, Ke Xu, Joel T Dudley, Sudhir Kumar
Journal: Molecular Biology and Evolution (2018)

The human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles experienced a reversal of fortune in the human lineage. We explored nonadaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Many nonadaptive hypotheses were tested, but failed to explain the data, which suggests that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This suggestion is supported by the fact that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and hundreds of CAP alleles are protective in genotype-phenotype association data. Our integrated phylogenomic and population genetic EPA approach predicts the existence of thousands of nonneutral candidate variants in the human proteome. We expect this collection to be enriched in beneficial variation. The EPA approach can be applied to discover candidate adaptive variation in any protein, population, or species for which allele frequency data and reliable multispecies alignments are available.
Abstract 13944: J Relationship of Body Mass Index of 22-year Cardiovascular Disease Mortality versus Body Mass Index
Authors: William J Kostis, Javier Cabrera, Fei Wang, Sara J Guterl, Dhammika Amaratunga, John S Pantazopolous, John B Kostis
Journal: Circulation (2015)

Introduction: J relationships of body mass index (BMI) with mortality have been described. However, little data are available on long-term follow-up in controlled clinical trials with respect to cardiovascular (CV) and all cause mortality. Hypothesis: We tested whether there is a J shape relationship between BMI with CV and all cause mortality at 22 years in the Systolic Hypertension in the Elderly Program (SHEP). Methods: SHEP was a placebo controlled, randomized clinical trial of antihypertensive therapy in patients with isolated systolic hypertension aged 60 and older. The relationship between CV and all cause mortality with baseline BMI was examined in 4,211 SHEP participants. Results: In unadjusted analyses, a J relationship was observed for all-cause mortality (linear term p=0.0318, quadratic term p=0.3217 and tricubic term p=0.0046) and for CV mortality (linear term p=0.0962, quadratic term p=0.6866 and tricubic term p=0.0908, left figure). The lowest risk was at a BMI of 25.9 for all-cause and 25.5 for CV mortality. The J shaped relationship between BMI and mortality was attenuated after adjustment for age, gender, comorbidities (e.g. diabetes, heart failure) and risk factors for CV disease (e.g. smoking and dyslipidemia, right figure). Age and gender were significant predictors of both all- cause and CV mortality: age p&lt;0.0001, female gender p=0.0063 for all-cause mortality and p&lt;0.0001 for age and p=0.0004 for female gender for CV mortality. &lt;br/Conclusions: This study indicates that both very low and very high BMI are markers of high risk. The J relationship between BMI and mortality is mediated by age, female gender, comorbidities and risk factors for CV disease.
De Novo Mutations Resolve Disease Transmission Pathways in Clonal Malaria
Authors: Seth N Redmond, Bronwyn M MacInnis, Selina Bopp, Amy K Bei, Daouda Ndiaye, Daniel L Hartl, Dyann F Wirth, Sarah K Volkman, Daniel E Neafsey
Journal: Molecular Biology and Evolution (2018)

Detecting de novo mutations in viral and bacterial pathogens enables researchers to reconstruct detailed networks of disease transmission and is a key technique in genomic epidemiology. However, these techniques have not yet been applied to the malaria parasite, Plasmodium falciparum, in which a larger genome, slower generation times, and a complex life cycle make them difficult to implement. Here, we demonstrate the viability of de novo mutation studies in P. falciparum for the first time. Using a combination of sequencing, library preparation, and genotyping methods that have been optimized for accuracy in low-complexity genomic regions, we have detected de novo mutations that distinguish nominally identical parasites from clonal lineages. Despite its slower evolutionary rate compared with bacterial or viral species, de novo mutation can be detected in P. falciparum across timescales of just 1-2 years and evolutionary rates in low-complexity regions of the genome can be up to twice that detected in the rest of the genome. The increased mutation rate allows the identification of separate clade expansions that cannot be found using previous genomic epidemiology approaches and could be a crucial tool for mapping residual transmission patterns in disease elimination campaigns and reintroduction scenarios.
Abstract 16153: Interval Between QRS Onset to End of the R-Wave in Left Chest Leads Reflects the Left Ventricular Activation Delay -Evaluations of 12-Lead Electrocardiogram and Coronary Sinus Bipolar Electrogram-
Authors: Hideyuki Hara, Masami Murakami, Tamami Fujiishi, Toyoji Kaida, Kumie Ito, Hiroshi Ito, Masahiro Karakawa, Shinichi Niwano
Journal: Circulation (2013)

Background: Delayed activation of the left ventricle (LV) is thought to be an important factor relating with response to cardiac resynchronization therapy. Our objective was to test the hypothesis ...