tbuckley/cabot-search huggingface dataset:
Abstract 9046: Childhood Underweight Affects Left Ventricular Geometry and Function
Authors: Kenji Harada, Yukiko Harada
Journal: Circulation (2012)

Background: Obesity is associated with structural and functional changes in the heart. Childhood underweight is also associated with an increased risk of later cardiovascular disease. In contrast to overweight/obesity, much less is known about underweight-related changes in left ventricular (LV) geometry and function. Myocardial performance index (MPI) combines both systolic and diastolic phases of cardiac cycle and has been shown to be useful for assessing global LV function. The purpose of the study is to assess the relationships between BMI z-score and LV geometry and MPI in children. Methods: Echocardiography with tissue Doppler imaging was performed in 643 children aged 7 to 15 years (BMI z-score -2.4 to +6.8). Subjects were divided into 9 groups according to BMI z-score. Cardiac dimensions, LV end-diastolic volume, LV mass, ejection fraction, isovolumic relaxation time (IRT), and tissue Doppler-derived MPI were measured. Results: There were significant relationships between BMI z-score and LV mass, LVEDV, and mass to volume ratio (r = 0.37, 0.23, and 0.39, p &lt; 0.01, respectively). LVEF did not correlate with BMI z-score. A U-shaped association was observed between BMI z-score and MPI, and MPI at both BMI z-score &lt;-2.0 and BMI z-score ≥ +3.0 were significantly greater compared with normal weight children as shown in Figure. There was a J-shaped association between BMI z-score and IRT with a significant increase at higher BMI (z-score ≥ +2.0). Conclusions: The present study suggests that lower BMI is associated with LV hypotrophy and increased MPI. Childhood underweight as well as overweight has a negative effect on cardiovascular function. Our findings suggest that primary prevention programs should be initiated in not only overweight but also underweight children.
SAT0042 Clinical features of psoriatic arthritis with a delayed onset
Authors: MD Lopez-Montilla, A Escudero, M Romero, V Perez, C Castro, J Gonzalez, MC Muñoz-Villanueva, E Collantes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The influence of patient age at onset on the clinical expression of rheumatic diseases has been widely demonstrated in relation to pathologies such as rheumatoid arthritis and ankylosing spondylitis. Such influence, however, has only occasionally been considered in connexion with psoriatic arthritis (PsoA). <h3>Objectives</h3> To identify potential differences among the clinical manifestations of PsoA depending on patient age at the onset of the disease. <h3>Methods</h3> Ninety-six consecutive patients diagnosed with PsoA as per the criteria of Moll and Wright were split into two groups according to whether their early symptoms of the disease appeared before or after the age of 60. The clinical features of both groups were assessed. <h3>Results</h3> The following Table 1 shows the differential clinical features of the two patient groups, established according to onset age. <h3>Conclusion</h3> PsoA patients with a delayed onset of the disease exhibit clinical symptoms that differ clearly from those of the other PsoA patients.
Nano and Microparticle Emerging Strategies for Treatment of Autoimmune Diseases: Multiple Sclerosis and Type 1 Diabetes
Authors: Alexander J. Kwiatkowski, Joshua M. Stewart, Jonathan J. Cho, Dorina Avram, Benjamin G. Keselowsky
Journal: Advanced Healthcare Materials (2020)

Abstract Autoimmune diseases affect 10% of the world's population, and 1 in 200 people worldwide suffer from either multiple sclerosis (MS) or type 1 diabetes (T1D). While the targeted organ systems are different, MS and T1D share similarities in terms of autoreactive immune cells playing a critical role in pathogenesis. Both diseases can be managed only symptomatically without curative remission, and treatment options are limited and non‐specific. Most current therapies cause some degree of systemic immune suppression, leaving the patients susceptible to opportunistic infections and other complications. Thus, there is considerable interest in the development of immunotherapies not associated with generalized immune suppression for these diseases. This review presents current and preclinical strategies for MS and T1D treatment, emphasizing those aimed to modulate the immune response, including the most recent strategies for tolerance induction. A central focus is on the emerging approaches using nano‐ and microparticle platforms, their evolution as immunotherapeutic carriers, including those incorporating specific antigens to induce tolerance and reduce unwanted generalized immune suppression.
Clostridioides difficile in national food surveillance, Slovenia, 2015 to 2017
Authors: Valerija Tkalec, Urska Jamnikar-Ciglenecki, Maja Rupnik, Stanka Vadnjal, Katja Zelenik, Majda Biasizzo
Journal: Eurosurveillance (2020)

BackgroundClostridioides difficile is an important human and animal intestinal pathogen. Because of increasing indications of an association between C. difficile and food, in 2015, the Administration of the Republic of Slovenia for Food Safety, Veterinary Sector and Plant Protection (UVHVVR) included C. difficile in its national food surveillance.AimWe aim to report the results and experience with a nationwide and long-term testing of food for C. difficile as a part of a regular national food surveillance programme.MethodsRetail minced meat and meat preparations (beef, pork and poultry) were sampled within a three-year period, 2015 to 2017. Selected raw retail vegetables, leaf salads and root vegetables, and ready-to-eat salads were only sampled during 2016 and 2017. Seafood was only sampled in 2017.ResultsAltogether, 434 samples were tested, with 12 of 336 (3.6%) meat samples and 6 of 98 (6.1%) raw vegetables contaminated with C. difficile. Twelve of 18 recovered food isolates were toxigenic (toxinotypes 0, III, V, XII). The isolates belonged to 13 different PCR ribotypes, 001 being most common (5 isolates). Several food types with an increased potential of being contaminated with C. difficile were detected by surveillance.ConclusionThe three-year C. difficile testing within the national food surveillance revealed a low proportion of C. difficile-contaminated food and high genotype variability. Because the risk of C. difficile infection associated with C. difficile-contaminated food is unknown, no measures were recommended in the case of positive results.
Air Pollutant Exposure and Stove Use Assessment Methods for the Household Air Pollution Intervention Network (HAPIN) Trial
Authors: Michael A. Johnson, Kyle Steenland, Ricardo Piedrahita, Maggie L. Clark, Ajay Pillarisetti, Kalpana Balakrishnan, Jennifer L. Peel, Luke P. Naeher, Jiawen Liao, Daniel Wilson, Jeremy Sarnat, Lindsay J. Underhill, Vanessa Burrowes, John P. McCracken, Ghislaine Rosa, Joshua Rosenthal, Sankar Sambandam, Oscar de Leon, Miles A. Kirby, Katherine Kearns, William Checkley, Thomas Clasen
Journal: Environmental Health Perspectives (2020)

BACKGROUND: High quality personal exposure data is fundamental to understanding the health implications of household energy interventions, interpreting analyses across assigned study arms, and characterizing exposure-response relationships for household air pollution.This paper describes the exposure data collection for the Household Air Pollution Intervention Network (HAPIN), a multicountry randomized controlled trial of liquefied petroleum gas stoves and fuel among 3,200 households in India, Rwanda, Guatemala, and Peru.OBJECTIVES: The primary objectives of the exposure assessment are to estimate the exposure contrast achieved following a clean fuel intervention and to provide data for analyses of exposure-response relationships across a range of personal exposures.METHODS: Exposure measurements are being conducted over the 3-y time frame of the field study.We are measuring fine particulate matter [PM < 2:5 lm in aerodynamic diameter (PM 2:5 )] with the Enhanced Children's MicroPEM™ (RTI International), carbon monoxide (CO) with the USB-EL-CO (Lascar Electronics), and black carbon with the OT21 transmissometer (Magee Scientific) in pregnant women, adult women, and children <1 year of age, primarily via multiple 24-h personal assessments (three, six, and three measurements, respectively) over the course of the 18month follow-up period using lightweight monitors.For children we are using an indirect measurement approach, combining data from area monitors and locator devices worn by the child.For a subsample (up to 10%) of the study population, we are doubling the frequency of measurements in order to estimate the accuracy of subject-specific typical exposure estimates.In addition, we are conducting ambient air monitoring to help characterize potential contributions of PM 2:5 exposure from background concentration.Stove use monitors (Geocene) are being used to assess compliance with the intervention, given that stove stacking (use of traditional stoves in addition to the intervention gas stove) may occur.CONCLUSIONS: The tools and approaches being used for HAPIN to estimate personal exposures build on previous efforts and take advantage of new technologies.In addition to providing key personal exposure data for this study, we hope the application and learnings from our exposure assessment will help inform future efforts to characterize exposure to household air pollution and for other contexts.
Cardio-Oncology Care in the Time of COVID-19 and the Role of Telehealth
Authors: Amar Parikh, Anupam A. Kumar, Eiman Jahangir
Journal: JACC CardioOncology (2020)

In the last few months, the world has been swept by coronavirus disease-19 (COVID-19), a disease caused by the severe acute respiratory syndrome coronavirus-2 that can lead to fatal acute respiratory distress syndrome, cardiomyopathy, and arrhythmias. We have quickly learned that patients with pre-
Microbiota Metabolites in Health and Disease
Authors: Justin L. McCarville, Grischa Y. Chen, Víctor D. Cuevas, Katia Troha, Janelle S. Ayres
Journal: Annual Review of Immunology (2020)

Metabolism is one of the strongest drivers of interkingdom interactions—including those between microorganisms and their multicellular hosts. Traditionally thought to fuel energy requirements and provide building blocks for biosynthetic pathways, metabolism is now appreciated for its role in providing metabolites, small-molecule intermediates generated from metabolic processes, to perform various regulatory functions to mediate symbiotic relationships between microbes and their hosts. Here, we review recent advances in our mechanistic understanding of how microbiota-derived metabolites orchestrate and support physiological responses in the host, including immunity, inflammation, defense against infections, and metabolism. Understanding how microbes metabolically communicate with their hosts will provide us an opportunity to better describe how a host interacts with all microbes—beneficial, pathogenic, and commensal—and an opportunity to discover new ways to treat microbial-driven diseases.
Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy
Authors: Jiang Yu, Yingli Wang, Shuang Zhou, Jinbo Li, Jiamei Wang, Dongxu Chi, Xue Wang, Guimei Lin, Zhonggui He, Yongjun Wang
Journal: Acta Pharmaceutica Sinica B (2020)

The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX-S-DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu2+) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
p27 as a Transcriptional Regulator: New Roles in Development and Cancer
Authors: Seyedeh Fatemeh Razavipour, Kuzhuvelil B. Harikumar, Joyce M. Slingerland
Journal: Cancer Research (2020)

Abstract p27 binds and inhibits cyclin-CDK to arrest the cell cycle. p27 also regulates other processes including cell migration and development independent of its cyclin-dependent kinase (CDK) inhibitory action. p27 is an atypical tumor suppressor–deletion or mutational inactivation of the gene encoding p27, CDKN1B, is rare in human cancers. p27 is rarely fully lost in cancers because it can play both tumor suppressive and oncogenic roles. Until recently, the paradigm was that oncogenic deregulation results from either loss of growth restraint due to excess p27 proteolysis or from an oncogenic gain of function through PI3K-mediated C-terminal p27 phosphorylation, which disrupts the cytoskeleton to increase cell motility and metastasis. In cancers, C-terminal phosphorylation alters p27 protein–protein interactions and shifts p27 from CDK inhibitor to oncogene. Recent data indicate p27 regulates transcription and acts as a transcriptional coregulator of cJun. C-terminal p27 phosphorylation increases p27-cJun recruitment to and action on target genes to drive oncogenic pathways and repress differentiation programs. This review focuses on noncanonical, CDK-independent functions of p27 in migration, invasion, development, and gene expression, with emphasis on how transcriptional regulation by p27 illuminates its actions in cancer. A better understanding of how p27-associated transcriptional complexes are regulated might identify new therapeutic targets at the interface between differentiation and growth control.
Urolithiasis Practice Patterns Following the COVID-19 Pandemic: Overview from the EULIS Collaborative Research Working Group
Authors: Tzevat Tefik, Selcuk Guven, Luca Villa, Mehmet Ilker Gokce, Panagiotis Kallidonis, Kremena Petkova, Murat Can Kiremit, Mehmet Giray Sonmez, Elisa de Lorenzis, Bilal Eryildirim, Kemal Sarica
Journal: European Urology (2020)
Accuracy of Biomarker Testing for Neuropathologically Defined Alzheimer Disease in Older Adults With Dementia
Authors: Howard A. Fink, Eric J. Linskens, Pombie C. Silverman, J. Riley McCarten, Laura S. Hemmy, Jeannine M. Ouellette, Nancy L. Greer, Timothy J. Wilt, Mary Butler
Journal: Annals of Internal Medicine (2020)

Biomarker accuracy for Alzheimer disease (AD) is uncertain.To summarize evidence on biomarker accuracy for classifying AD in older adults with dementia.Electronic bibliographic databases (searched from January 2012 to November 2019 for brain imaging and cerebrospinal fluid [CSF] tests and from inception to November 2019 for blood tests), ClinicalTrials.gov (to November 2019), and systematic review bibliographies.English-language studies evaluating the accuracy of brain imaging, CSF testing, or blood tests for distinguishing neuropathologically defined AD from non-AD among older adults with dementia. Studies with low or medium risk of bias were analyzed.Two reviewers rated risk of bias. One extracted data; the other verified accuracy.Fifteen brain imaging studies and 9 CSF studies met analysis criteria. Median sensitivity and specificity, respectively, were 0.91 and 0.92 for amyloid positron emission tomography (PET), 0.89 and 0.74 for 18F-labeled fluorodeoxyglucose (18F-FDG) PET, 0.64 and 0.83 for single-photon emission computed tomography, and 0.91 and 0.89 for medial temporal lobe atrophy on magnetic resonance imaging (MRI). Individual CSF biomarkers and ratios had moderate sensitivity (range, 0.62 to 0.83) and specificity (range, 0.53 to 0.69); in the few direct comparisons, β-amyloid 42 (Aβ42)/phosphorylated tau (p-tau) ratio, total tau (t-tau)/Aβ42 ratio, and p-tau appeared more accurate than Aβ42 and t-tau alone. Single studies suggested that amyloid PET, 18F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation.Studies were small, biomarker cut points and neuropathologic AD were inconsistently defined, and methods with uncertain applicability to typical clinical settings were used. Few studies directly compared biomarkers, assessed test combinations, evaluated whether biomarkers improved classification accuracy when added to clinical evaluation, or reported harms.In methodologically heterogeneous studies of uncertain applicability to typical clinical settings, amyloid PET, 18F-FDG PET, and MRI were highly sensitive for neuropathologic AD. Amyloid PET, 18F-FDG PET, and CSF test combinations may add accuracy to clinical evaluation.Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).
Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020
Authors: Ranawaka APM Perera, Chris KP Mok, Owen TY Tsang, Huibin Lv, Ronald LW Ko, Nicholas C Wu, Meng Yuan, Wai Shing Leung, Jacky MC Chan, Thomas SH Chik, Chris YC Choi, Kathy Leung, Kin Ho Chan, Karl CK Chan, Ka-Chi Li, Joseph T Wu, Ian A Wilson, Arnold S Monto, Leo LM Poon, Malik Peiris
Journal: Eurosurveillance (2020)

Background The ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making. Aim Our objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies. Methods We developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT 90 ) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls. Results IgG and IgM RBD ELISA, MN and PRNT 90 were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT 90 tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test. Conclusion Using IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT 90 , is a valid approach for large-scale sero-epidemiology studies.
Face masks for the public during the covid-19 crisis
Authors: Trisha Greenhalgh, Manuel B Schmid, Thomas Czypionka, Dirk Bassler, Laurence Gruer
Journal: BMJ (2020)

Trisha Greenhalgh and colleagues argue that it is time to apply the precautionary principle The precautionary principle is, according to Wikipedia, "a strategy for approaching issues of potential harm when extensive scientific knowledge on the matter is lacking." The evidence base on the efficacy and acceptability of the different types of face mask in preventing respiratory infections during epidemics is sparse and contested.12 But covid-19 is a serious illness that currently has no known treatment or vaccine and is spreading in an immune naive population. Deaths are rising steeply, and health systems are under strain. This raises an ethical question: should policy makers apply the precautionary principle now and encourage people to wear face masks on the grounds that we have little to lose and potentially something to gain from this measure?3 We believe they should. Evidence based medicine tends to focus predominantly on internal validity—whether primary research studies were "done right"—using tools to assess risk of bias and adequacy of statistical analysis. External validity relates to a different question: whether findings of primary studies done in a different population with a different disease or risk state are relevant to the current policy question. We argue that there should be a greater focus on external validity in evaluation of masks. A rapid search of the literature on the wearing of masks by the general public during epidemics or pandemics by a team at the University of Galway (E Toomey, personal communication, 29 March 2020) found five peer reviewed systematic reviews:
Distinct Expression and Methylation Patterns for Genes with Different Fates following a Single Whole-Genome Duplication in Flowering Plants
Authors: Tao Shi, Razgar Seyed Rahmani, Paul F Gugger, Muhua Wang, Hui Li, Yue Zhang, Zhizhong Li, Qingfeng Wang, Yves Van de Peer, Kathleen Marchal, Jinming Chen
Journal: Molecular Biology and Evolution (2020)

Abstract For most sequenced flowering plants, multiple whole-genome duplications (WGDs) are found. Duplicated genes following WGD often have different fates that can quickly disappear again, be retained for long(er) periods, or subsequently undergo small-scale duplications. However, how different expression, epigenetic regulation, and functional constraints are associated with these different gene fates following a WGD still requires further investigation due to successive WGDs in angiosperms complicating the gene trajectories. In this study, we investigate lotus (Nelumbo nucifera), an angiosperm with a single WGD during the K–pg boundary. Based on improved intraspecific-synteny identification by a chromosome-level assembly, transcriptome, and bisulfite sequencing, we explore not only the fundamental distinctions in genomic features, expression, and methylation patterns of genes with different fates after a WGD but also the factors that shape post-WGD expression divergence and expression bias between duplicates. We found that after a WGD genes that returned to single copies show the highest levels and breadth of expression, gene body methylation, and intron numbers, whereas the long-retained duplicates exhibit the highest degrees of protein–protein interactions and protein lengths and the lowest methylation in gene flanking regions. For those long-retained duplicate pairs, the degree of expression divergence correlates with their sequence divergence, degree in protein–protein interactions, and expression level, whereas their biases in expression level reflecting subgenome dominance are associated with the bias of subgenome fractionation. Overall, our study on the paleopolyploid nature of lotus highlights the impact of different functional constraints on gene fate and duplicate divergence following a single WGD in plant.
Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial
Authors: Yuichiro Yamada, Hideki Katagiri, Yoshiyuki Hamamoto, Srikanth Deenadayalan, Andrea Navarria, Keiji Nishijima, Yutaka Seino, Y Fukushima, Y Hamamoto, A Hisatomi, Y Ide, S Inoue, T Kawada, H Kim, A Kiyosue, K Matoba, O Matsuoka, H Nishimura, M Noguchi, T Osonoi, S Sawada, Y Shibasaki, K Shin, Y Yamada
Journal: The Lancet Diabetes & Endocrinology (2020)