tbuckley/cabot-search huggingface dataset:
The glycosaminoglycans of the human artery and their changes in atherosclerosis.
Authors: R L Stevens, M Colombo, J J Gonzales, W Hollander, K Schmid
Journal: Journal of Clinical Investigation (1976)

The changes in levels of glycosaminoglycans (GAGs) of the intima and media of the human artery in atherosclerosis were determined by a recently introduced two-dimensional electrophoresis technique that permits direct measurments of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE-Sephadex A-25 column, and the resulting three fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestability by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies we concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, we demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N-acetylgalactosamine-6-sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentrations. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.
Effects of a Single Bout of Interval Hypoxia on Cardiorespiratory Control and Blood Glucose in Patients With Type 2 Diabetes
Authors: Tobias Duennwald, Hannes Gatterer, Per-Henrik Groop, Martin Burtscher, Luciano Bernardi
Journal: Diabetes Care (2013)

Hypoxia may cause functional autonomic imbalance in diabetes. Intermittent hypoxia (IH), a technique improving the adaptation to hypoxia, might improve cardiorespiratory reflexes and, ultimately, blood glucose concentrations in patients with type 2 diabetes. We tested whether a single bout of IH could initiate a long-lasting response potentially leading to better adaptation to hypoxia.In 14 patients with type 2 diabetes without autonomic complications, we measured blood pressure, heart rate, oxygen saturation, chemoreflex (hypoxic and hypercapnic ventilatory responses, ventilatory recruitment threshold), and baroreflex sensitivity before, immediately after, and 3 and 6 h after a 1-h single bout of IH (6-min breathing of 13% oxygen mixture 5 times each separated by 6-min recovery). The measurements were repeated on a placebo day (at least 1 week apart, in random sequence) when subjects were only breathing room air (single-blind protocol).IH significantly increased hypercapnic ventilatory responses and reduced ventilatory recruitment threshold, and increased oxygen saturation and blood pressures, whereas increases in heart rate variability and baroreflex sensitivity were not significant. Blood glucose significantly decreased after IH. No such changes were observed during the placebo day, except an increase in oxygen saturation. Some of the effects lasted 3 h after IH, and some even persisted until 6 h after IH.A single bout of IH induced an initial adaptation to hypoxia, with improvement in cardiorespiratory reflexes and reduction in blood glucose. Patients with type 2 diabetes could potentially benefit from the application of a full (>2 weeks) IH intervention.
High cancer risk and increased mortality in patients with Peutz-Jeghers syndrome
Authors: M. G. F. van Lier, A. M. Westerman, A. Wagner, C. W. N. Looman, J. H. P. Wilson, F. W. M. de Rooij, V. E. P. P. Lemmens, E. J. Kuipers, E. M. H. Mathus-Vliegen, M. E. van Leerdam
Journal: Gut (2011)

<h3>Background</h3> Peutz–Jeghers syndrome (PJS) is associated with an increased cancer risk. As the determination of optimal surveillance strategies is hampered by wide ranges in cancer risk estimates and lack of data on cancer-related mortality, we assessed cancer risks and mortality in a large cohort of patients with PJS. <h3>Methods</h3> Dutch PJS patients were included in this cohort study. Patients were followed prospectively between January 1995 and July 2009, and clinical data from the period before 1995 were collected retrospectively. Data were obtained by interview and chart review. Cumulative cancer risks were calculated by Kaplan–Meier analysis and relative cancer and mortality risks by Poisson regression analysis. <h3>Results</h3> We included 133 PJS patients (48% males) from 54 families, contributing 5004 person-years of follow-up. 49 cancers were diagnosed in 42 patients (32%), including 25 gastrointestinal (GI) cancers. The median age at first cancer diagnosis was 45 years. The cumulative cancer risk was 20% at age 40 (GI cancer 12%), increasing to 76% at age 70 (GI cancer 51%). Cumulative cancer risks were higher for females than for males (p=0.005). The relative cancer risk was higher in PJS patients than in the general population (HR 8.96; 95% CI 6.46 to 12.42), and higher among female (HR 20.40; 95% CI 13.43 to 30.99) than among male patients (HR 4.76; 95% CI 2.82 to 8.04). 42 patients had died at a median age of 45 years, including 28 cancer-related deaths (67%). Mortality was increased in our cohort compared to the general population (HR 3.50; 95% CI 2.57 to 4.75). <h3>Conclusions</h3> PJS patients carry high cancer risks, leading to increased mortality. The malignancies occur particularly in the GI tract and develop at young age. These results justify surveillance in order to detect malignancies in an early phase to improve outcome.
Focused Ultrasound Delivers Targeted Immune Cells to Metastatic Brain Tumors
Authors: Ryan Alkins, Alison Burgess, Milan Ganguly, Giulio Francia, Robert Kerbel, Winfried S. Wels, Kullervo Hynynen
Journal: Cancer Research (2013)

Abstract Natural killer (NK) cells are cytotoxic lymphocytes involved in innate immunity. NK-92, a human NK cell line, may be targeted to tumor-associated antigens in solid malignancies where it exhibits antitumor efficacy, but its clinical utility for treating brain tumors is limited by an inability to cross the blood–brain barrier (BBB). We investigated the potential for focused ultrasound (FUS) to deliver targeted NK-92 cells to the brain using a model of metastatic breast cancer. HER2-expressing human breast tumor cells were implanted into the brain of nude rats. The NK-92-scFv(FRP5)-zeta cell line expressing a chimeric HER2 antigen receptor was transfected with superparamagnetic iron oxide nanoparticles before intravenous injection, before and following BBB disruption using focused ultrasound (551.5 kHz focused transducer, 0.33 MPa average peak rarefaction pressure) in the presence of a microbubble contrast agent. Baseline and posttreatment 1.5T and 7T MR imaging was done, and histology used to identify NK-92 cells post-mortem. Contrast-enhanced MRI showed reproducible and consistent BBB disruption. 7T MR images obtained at 16 hours posttreatment revealed a significant reduction in signal indicating the presence of iron-loaded NK-92 cells at the tumor site. The average ratio of NK-92 to tumor cells was 1:100 when NK cells were present in the vasculature at the time of sonication, versus 2:1,000 and 1:1,000 when delivered after sonication and without BBB disruption, respectively. Our results offer a preclinical proof-of-concept that FUS can improve the targeting of immune cell therapy of brain metastases. Cancer Res; 73(6); 1892–9. ©2012 AACR.
Children worldwide can grow to the same height, says WHO
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

New growth charts for infants and young children can be applied globally, says the World Health Organization. The charts will enable doctors and others to detect and tackle growth related conditions, such as undernutrition, overweight, and obesity, at an early stage.

The new child growth standards confirm that children given healthy growth conditions born anywhere in the world—be it India, Brazil, or Norway—have the potential to develop to within the same range of height and weight. They prove that differences in children's growth to the age of 5 are influenced more by nutrition, feeding practices, environment, and health care than by …
Investigation of optimal aminolaevulinic acid concentration applied in topical aminolaevulinic acid-photodynamic therapy for treatment of moderate to severe acne: a pilot study in Chinese subjects
Authors: R. Yin, F. Hao, J. Deng, X.C. Yang, H. Yan
Journal: British Journal of Dermatology (2010)

Journal Article Investigation of optimal aminolaevulinic acid concentration applied in topical aminolaevulinic acid–photodynamic therapy for treatment of moderate to severe acne: a pilot study in Chinese subjects Get access R. Yin, R. Yin Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Search for other works by this author on: Oxford Academic Google Scholar F. Hao, F. Hao Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Correspondence: Fei Hao. E‐mail: swyinrui@163.com Search for other works by this author on: Oxford Academic Google Scholar J. Deng, J. Deng Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Search for other works by this author on: Oxford Academic Google Scholar X.C. Yang, X.C. Yang Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Search for other works by this author on: Oxford Academic Google Scholar H. Yan H. Yan Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 5, 1 November 2010, Pages 1064–1071, https://doi.org/10.1111/j.1365-2133.2010.09860.x Published: 01 November 2010
Mesenchymal stem cells participate in the loop leading to amplification of inflammation through secretion of interleukin (IL)6, IL1 and IL8
Authors: A Eljaafari, M-L Tartelin, P Miossec
Journal: Annals of the Rheumatic Diseases (2010)

Background Mesenchymal cells and subsets of T cells interact in the rheumatoid arthritis (RA) synovium leading to the local production of infl ammatory cytokines.These high levels suggest a defect in the regulation of cytokine secretion, but the respective contribution of Th1 and Th17 cells remains to be clarifi ed.Objectives Mesenchymal stem cells (MSC) are known to play a role in the regulation of the immune response and are present in the synovium.The authors investigated the effects of exogenous Th1 and Th17 cytokines on their functions.The impact on RA synoviocytes (fi broblast-like synoviocytes (FLS)) was investigated in parallel because FLS derive from MSC and are the most abundant cells in synovium.Methods MSC were isolated from the bone marrow of healthy controls and were developed by culture of adherent cells in α-MEM+10%FCS.RA FLS were obtained from hip surgery and were cultured in DMEM+10%FCS.Cells were treated for 24 h with interleukin (IL)7A (50 ng/ml), tumour necrosis factor (TNF)α (1 or 10 ng/ml) or interferon (IFN)γ (50 ng/ml), alone or in combination.mRNA levels of infl ammatory cytokines (IL6, IL1β, IL8) were measured by Q-RT-PCR.Results Culture of MSC with IL17A or TNFα for 24 h resulted in increased expression of IL6, IL1β and IL8 mRNA, with a synergistic effect when IL17α and TNFα were combined.In contrast, IFNγ induced a weak increase in IL6 mRNA expression, with on August 19,
Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations
Authors: Julia U Holle, Christin Dubrau, Karen Herlyn, Martin Heller, Petra Ambrosch, Bernhard Noelle, Eva Reinhold-Keller, Wolfgang L Gross
Journal: Annals of the Rheumatic Diseases (2011)

First, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA.This study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010. Patients were assessed by a standardised interdisciplinary diagnostic procedure (including ear, nose and throat and ophthalmology assessment, MRI, immunodiagnostics, B-cell levels and Birmingham Vasculitis Activity Score) and were treated by standardised therapeutic regimens according to available evidence.59 patients received 75 cycles of RTX. 9.3% achieved complete remission. A response was documented in 61.3% (improvement in 52%, unchanged disease activity in 9.3%), 26.7% had refractory disease. Birmingham Vasculitis Activity Score, disease extent index, erythrocyte sedimentation rate, C-reactive protein and prednisolone demand decreased significantly. All patients achieved B-cell depletion. Granulomatous manifestations such as orbital granuloma and pachymeningitis were more frequently refractory to RTX than vasculitis or other granulomatous manifestations. Thus, for example, complete remission/improvement was found in 89.2% of patients with renal disease and in only 44.4% of those with orbital masses (p=0.003). The relapse rate was 44.4% after a median period of 13.5 months. Adverse events occurred in 29%, pneumonia in 15% and death in 3%.The overall response rate of refractory GPA to RTX was high (61.3% complete remission or improvement). Response rates of vasculitic manifestations were excellent; failure of response/progress was mostly due to granulomatous manifestations, especially orbital masses. Relapse rates were high (40%) despite maintenance treatment.
Anti-tissue transglutaminase antibodies from coeliac patients inhibit transglutaminase activity both in vitro and in situ
Authors: C Esposito, F Paparo, I Caputo, M Rossi, M Maglio, D Sblattero, T Not, R Porta, S Auricchio, R Marzari, R Troncone
Journal: Gut (2002)

<h3>Introduction</h3> Despite climate change being recognised as the greatest health threat of the 21st century, current medical education curricula do not reflect the urgency of the climate crisis. Preparing for climate-related health repercussions requires educational institutions to disseminate planetary health knowledge in a systematic way. We sought to evaluate the extent of the literature on the inclusion of planetary health in undergraduate and postgraduate medical education to guide curricular development. <h3>Methods and analysis</h3> A scoping review is being undertaken with a search strategy developed with a health sciences librarian. The search strategy was run on the following databases from inception to 22 June 2021: Medline, Embase, APA PsycINFO, CINAHL, Global Health, Scopus. This scoping review is being conducted as per methodology that has been previously outlined. Studies that discuss the implementation of planetary health education within undergraduate and postgraduate medical education will be included, whether they discuss formal inclusion or supplemental courses. To supplement our database search, data from the Health and Environment Adaptive Task Force's National Report on Planetary Health Education, the Planetary Health Report Card and the Association for Medical Education in Europe Consensus Statement on Planetary Health and Education for Sustainable Healthcare will be included. As we anticipate varying methodologies, the data analysis will consist of both a quantitative and a qualitative component. Outcomes will be categorised within the domains of the Planetary Health Education Framework, which incorporates concepts of systems thinking, social justice and interconnection within nature as they apply to education for planetary health. <h3>Ethics and dissemination</h3> As no intervention or patient recruitment will be required, research ethics board approval is not applicable. We plan to disseminate our results via publication in a peer-reviewed journal or conference presentation. <h3>Trial registration number</h3> This protocol has been registered in Open Science Framework (10.17605/OSF.IO/7M6GZ).
25-Hydroxyvitamin D in Obese Youth Across the Spectrum of Glucose Tolerance From Normal to Prediabetes to Type 2 Diabetes
Authors: Javier de las Heras, Kumaravel Rajakumar, SoJung Lee, Fida Bacha, Michael F. Holick, Silva A. Arslanian
Journal: Diabetes Care (2013)

OBJECTIVE To 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and β-cell function in this cohort. RESEARCH DESIGN AND METHODS Plasma 25(OH)D concentrations were examined in banked specimens in 9- to 20-year-old obese youth (n = 175; male 42.3%, black 46.3%) (NGT, n = 105; impaired glucose tolerance [IGT], n = 43; type 2 diabetes, n = 27) who had in vivo insulin sensitivity and secretion measured by hyperinsulinemic-euglycemic and hyperglycemic clamp techniques and had an assessment of total body composition and abdominal adiposity. RESULTS The mean age and BMI of the subjects were 14.3 ± 2.1 years and 35.7 ± 5.6 kg/m2, respectively. BMI, plasma 25(OH)D, and the proportion of vitamin D–deficient and –insufficient children did not differ across the three groups. Furthermore, there was no association between 25(OH)D and in vivo insulin sensitivity or β-cell function relative to insulin sensitivity (disposition index) in all groups combined or in each group separately. CONCLUSIONS Our data in obese youth show 1) no differences in plasma 25(OH)D concentrations across the glucose tolerance groups and 2) no relationship between 25(OH)D and in vivo insulin sensitivity and β-cell function relative to insulin sensitivity in any of the groups. It remains uncertain if enhancement of the vitamin D status could improve pathophysiological mechanisms of prediabetes and type 2 diabetes in obese youth.
Sacro-iliac Joint in Adult Rheumatoid Arthritis and Psoriatic Arthropathy
Authors: A. St. J. Dixon, E. Lience
Journal: Annals of the Rheumatic Diseases (1961)

Sacro-iliitis is held to be an early and constant sign of ankylosing spondylitis (AS), a frequent sign of Reiter's disease, and one by which it is possible to distinguish these diseases radiologically from rheumatoid arthritis (RA).Recently Cohen, McNeil, Sharp, Schubart, Calabro, and Calkins (1959), in a combined clinical and radiological study of AS and RA, briefly noted that "the sacro-iliac joints were involved in fifteen (27 per cent.) of 55 patients judged clinically to have only peripheral joint disease", a finding which might impair the validity of sacro-iliitis as a differen- tiating sign and might suggest that the two diseases, RA and AS, were part of the same pathological process.
Open-Source Science Makes Headway
Authors: M. Patlak
Journal: JNCI Journal of the National Cancer Institute (2010)

Open-source science is gaining ground as scientists explore the benefits of working together without copyright and patent constraints in virtual forums. Like Wikipedia, these “wiki-style” forums enable them to reuse, build on, and extend the work and resources of fellow researchers. In the past 5–10 years, more than a dozen websites have emerged that are dedicated to creating open access to many of the necessary ingredients for drug discovery, including data, information technology and analytic tools, biospecimens, and disease models (see sidebar).

Many advocates for open-source science claim that it can counter investigative redundancy and the squandering of biomedical research resources. They also say it will create a productive synergy that will speed up our understanding and treatment of complex diseases such as cancer.

But both advocates and critics point out challenges to this approach, such as countering the cultural and economic norms that limit sharing, creating compatible datasets, ensuring high-quality data, and finding sustained financial backing.

Despite those challenges, open-source science is making substantial headway in the biomedical arena. The amount and quality of information available in the public domain has grown dramatically, according to Thinh Nguyen, counsel for Science Commons, a nonprofit organization whose mission is to make sharing scientific data and materials among scientists easier. “These changes mean that what is available in the commons is starting to be almost as good as what companies can develop themselves internally—it's starting to get a place at the table when you are doing serious drug development research,” Nguyen said at a presentation at an Institute of Medicine (IOM) conference on precompetitive collaboration last February.

The participation of big-name players—such as the National Cancer Institute, Merck, Pfizer, Eli Lilly, several universities and foundations, and patient advocacy groups—is boosting the reputation of open-source science. So are some websites’ impressive gains. The Open-Source Drug Discovery (OSDD), which is dedicated to discovering treatments for diseases that plague the developing world, surprised many when more than 400 of its volunteer researchers reannotated the tuberculosis bacterium genome, wiki style, in just 4 months—record time for such an endeavor, according to Eli Lilly's Bernard Munos.
Promoter features related to tissue specificity as measured by Shannon entropy
Authors: Jonathan Schug, Winfried-Paul Schuller, Claudia Kappen, J Michael Salbaum, Maja Bucan, Christian J Stoeckert
Journal: Genome biology (2005)

Abstract Background The regulatory mechanisms underlying tissue specificity are a crucial part of the development and maintenance of multicellular organisms. A genome-wide analysis of promoters in the context of gene-expression patterns in tissue surveys provides a means of identifying the general principles for these mechanisms. Results We introduce a definition of tissue specificity based on Shannon entropy to rank human genes according to their overall tissue specificity and by their specificity to particular tissues. We apply our definition to microarray-based and expressed sequence tag (EST)-based expression data for human genes and use similar data for mouse genes to validate our results. We show that most genes show statistically significant tissue-dependent variations in expression level. We find that the most tissue-specific genes typically have a TATA box, no CpG island, and often code for extracellular proteins. As expected, CpG islands are found in most of the least tissue-specific genes, which often code for proteins located in the nucleus or mitochondrion. The class of genes with no CpG island or TATA box are the most common mid-specificity genes and commonly code for proteins located in a membrane. Sp1 was found to be a weak indicator of less-specific expression. YY1 binding sites, either as initiators or as downstream sites, were strongly associated with the least-specific genes. Conclusions We have begun to understand the components of promoters that distinguish tissue-specific from ubiquitous genes, to identify associations that can predict the broad class of gene expression from sequence data alone.