tbuckley/cabot-search huggingface dataset:
Discovery of <i>Salmonella</i> trehalose phospholipids reveals functional convergence with mycobacteria
Authors: Peter Reinink, Jeffrey Buter, Vivek K. Mishra, Eri Ishikawa, Tan-Yun Cheng, Peter T.J. Willemsen, Steffen Porwollik, Patrick J. Brennan, Eva Heinz, Jacob A. Mayfield, Gordon Dougan, Cécile A. van Els, Vincenzo Cerundolo, Giorgio Napolitani, Sho Yamasaki, Adriaan J. Minnaard, Michael McClelland, D. Branch Moody, Ildiko Van Rhijn
Journal: The Journal of Experimental Medicine (2019)

Salmonella species are among the world’s most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6′-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6′-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.
Activated CLL B Cells Variably Modulate microRNA-155 Levels in Naïve CD4+ T Cells, and the Direction and Magnitude of microRNA-155 Change Correlates with Th17 Levels and Clinical Course
Authors: Byeongho Jung, Gerardo Ferrer, Pui Yan Chiu, Rukhsana Aslam, Florencia Palacios, Barbara Sherry, Nicholas Chiorazzi
Journal: Blood (2018)
Sex Differences in the Prevalence of, and Trends in, Cardiovascular Risk Factors, Treatment, and Control in the United States, 2001 to 2016
Authors: Sanne A.E. Peters, Paul Muntner, Mark Woodward
Journal: Circulation (2019)

Background: Improvements have been made in the treatment and control of some but not all major cardiovascular risk factors in the United States. It remains unclear whether women and men have benefited equally. Methods: Data from the 2001 to 2002 through the 2015 to 2016 US National Health and Nutrition Examination Survey on adults aged 20 to 79 years were used. We assessed sex differences in temporal trends in the levels of systolic blood pressure, body mass index, smoking status, high-density lipoprotein and total cholesterol, and hemoglobin A 1c . Trends in treatment and control rates of hypertension, diabetes mellitus, and dyslipidemia were also assessed. Results: Overall, 35 416 participants (51% women) were included. Trends in systolic blood pressure, smoking status, high-density lipoprotein cholesterol, and hemoglobin A 1c were similar between the sexes. Body mass index increased more in women than men ( P =0.006). Mean levels were 28.1 and 29.6 kg/m 2 in women and 27.9 and 29.0 kg/m 2 in men in 2001 to 2004 and 2013 to 2016, respectively. Total cholesterol decreased more in men than women ( P =0.002): mean levels in 2001 to 2004 and 2013 to 2016, respectively, were 203 and 194 mg/dL in women and 201 and 188 mg/dL in men. Improvements in the control of hypertension, diabetes mellitus, and dyslipidemia were similar between the sexes; however, sex differences persisted. In 2013 to 2016, control rates in women versus men were 30% versus 22% for hypertension, 30% versus 20% for diabetes mellitus, and 51% versus 63% for dyslipidemia. Conclusions: Temporal trends in cardiovascular risk factor levels were broadly similar between the sexes, except for total cholesterol and body mass index. Sex differences in the control of hypertension, diabetes mellitus, and dyslipidemia persist, and further efforts are required to reduce this differential.
Efficacy and Safety Profile of Novel Alkylators in Combination Regimens for Patients with Multiple Myeloma: A Review of Literature
Authors: Shehroz Aslam, Rida Riaz, Abdul Rafae, Mustafa Nadeem Malik, Jemin Aby Jose, Zunairah Shah, Muhammad Abu Zar, Anum Qureshi, Ahmad Kamal, Awais Ijaz, Ali Younas Khan, Saad Ullah Malik, Faiz Anwer
Journal: Blood (2018)
551. Enhanced Cell Killing Effect of E1 Modified Adenoviruses Expressing HSV-TK Suicide Gene
Journal: Molecular Therapy (2005)

Recent clinical trials with Herpes Simplex Virus Thymidine Kinase (HSV-TK) gene therapy using E1-deleted replication-incompetent adenovirus have shown encouraging results, but with limited efficacy. We have previously demonstrated that the cytolytic potency of replication-competent adenoviruses with different combination of E1B genes differed significantly depending on the presence or deletion of E1B 55kDa and E1B 19kDa function (Kim JS. et al. Cancer Gene Therapy). To combine the advantages of the suicide gene approach with that of replicating adenoviruses, we have developed replicating adenoviral vectors harboring HSV-TK, generating Ad-|[Delta]|E1B19/55-TK, Ad-|[Delta]|E1B19-TK, and Ad-|[Delta]|E1B55-TK adenoviruses. The cytotoxicity of the combination therapy with replicating adenoviruses (Ad-|[Delta]|E1B55-TK or Ad-|[Delta]|E1B19/55-TK) and GCV was dramatically increased compared with replicating adenoviruses alone or replication-incompetent adenovirus expressing HSV-TK (Ad-|[Delta]|E1-TK) with GCV. In contrast, the cytotoxicity of the combination therapy with Ad-|[Delta]|E1B19-TK and GCV was significantly reduced when compared to the treatment with Ad-|[Delta]|E1B19-TK alone. In addition, the total viral production of Ad-|[Delta]|E1B19-TK in the presence of GCV was significantly reduced. Taken together, these results suggest that the inhibition of viral replication by the HSV-TK/GCV system counterbalance the cytotoxicity of Ad-|[Delta]|E1B19-TK. The human cervical cancer (C33A) and lung cancer (A549) xenograft models treated with replication-competent adenoviruses with GCV had more significant reduction in tumor growth compared to animals that were injected with PBS or Ad-|[Delta]|E1-TK with GCV. In summary, these data indicate that the suicide gene approach with replicating adenoviruses elicits more enhanced anti-tumor effect than that with replication-incompetent adenovirus.
NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis
Authors: Stephen A. Harrison, Stephen J. Rossi, Angelo H. Paredes, James F. Trotter, Mustafa R. Bashir, Cynthia D. Guy, Rajarshi Banerjee, Mark J. Jaros, Sandra Owers, Bryan A. Baxter, Lei Ling, Alex M. DePaoli
Journal: Hepatology (2019)

NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double-blind, placebo-controlled study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement. In this open-label study, we assessed the histological efficacy of NGM282 in patients with biopsy-confirmed nonalcoholic steatohepatitis. Paired liver biopsies from 43 patients who received subcutaneous NGM282 (1 mg, n = 24; 3 mg, n = 19) once daily for 12 weeks were evaluated blinded to time point, subject, and clinical information. At week 12, NGM282 significantly reduced nonalcoholic fatty liver disease activity score (NAS; -1.9; 95% confidence interval, -2.6 to -1.2; P < 0.001 in the 1 mg group; -2.2, -3.1 to -1.3; P < 0.001 in the 3 mg group) and fibrosis (-0.5; -0.9 to 0; P = 0.035 in the 3 mg group) scores. Overall, 50% and 63% of the patients receiving NGM282 1 mg or 3 mg, respectively, improved NAS by 2 or more points without fibrosis worsening. Of the patients receiving NGM282 1 mg or 3 mg, 25% and 42%, respectively, improved liver fibrosis by one stage or more without worsening of steatohepatitis. Treatment with NGM282 led to relative reductions in liver fat content (-58% and -67% in the 1 mg and 3 mg groups, respectively), corrected T1 (cT1; -8% and -9%), alanine aminotransferase (ALT) (-67% and -60%), aspartate aminotransferase (-57% and -52%), and fibrogenesis biomarkers neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3; -22% and -33%) and enhanced liver fibrosis score (ELF; -3% and -6%) at week 12. Greater reductions in Pro-C3, ELF, and cT1, but not in liver fat content, 7alpha-hydroxy-4-cholesten-3-one, or ALT, were observed in histological responders than in nonresponders. Conclusion: In this open-label study, NGM282 improved the histological features of NASH in 12 weeks with significant reductions in NAS and fibrosis scores, accompanied by improvements in noninvasive imaging and serum markers.
P128 An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis – a proof of concept trial
Authors: H De Jong, G Buijze, M Kox, M van de Sande, DJ van Schaardenburg, R van Vugt, C Popa, P Picckers, D Baeten
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Previous research in healthy individuals showed that the innate immune response can be voluntarily modulated by a training program involving breathing exercises, exposure to cold and meditation<sup>1</sup>. It is unknown whether the same intervention could potentially lead to suppression of inflammation and whether it can safely be applied in patients with chronic inflammatory diseases. <h3>Objectives</h3> The objective of this study was to assess safety and anti-inflammatory effects of an add-on training program comprising breathing exercises, cold exposure and meditation in patients with axial spondyloarthritis. <h3>Methods</h3> This was an open-label randomised one-way crossover proof-of-concept trial. Participants were randomised to either the early or late intervention group. The intervention consisted of an 8 weeks training program comprising cold exposure, meditation and breathing exercises. <h3>Results</h3> There was no significant difference in adverse events between groups, with one serious adverse event occurring 8 weeks after end of the intervention and judged 'unrelated'. After 8 weeks there was a significant decline of the hs-CRP in the intervention group (median [interquartile range] from 10.2 [6.5–17.1] to 6.0 [3.9–15.6] mg/L; p=0.02), but not in the control group (from 8.7 [5.2–17.2] to 13.2 [7.9–20.1] mg/L; p=0.70). A similar trend was seen for serum calprotectin (p=0.07 in intervention versus p=0.31 in control), but not for ESR. In addition, ASDAS-CRP (p=0.02), BASDAI (p=0.04), SF-36 physical component score (p=0.01), EQ-5D (p=0.049), and EQ-5D VAS (p=0.02) decreased significantly in the intervention group, but not the control group. <h3>Conclusions</h3> In the present trial we show that the add-on training program involving breathing exercises, cold exposure, and meditation can safely be applied in patients with axial spondyloarthritis, a prototype chronic inflammatory disease. Furthermore, it attenuated inflammation and improved disease activity, function, and quality of life. <h3>Reference</h3> Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, Pickkers P. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. <i>Proc Natl Acad Sci USA</i> 2014 May 20;111(20):7379–84. <h3>Acknowledgements</h3> Professor Piet van Riel, Lisa van Maanen, Sanne Pons, Wim Hof, Isa Hof, Henk van den Berg, Marianne Peper, Linda Hochstenbach, and Iris Premssler. <h3>Disclosure of Interest</h3> None declared.
Constructing care cascades for active tuberculosis: A strategy for program monitoring and identifying gaps in quality of care
Authors: Ramnath Subbaraman, Ruvandhi R. Nathavitharana, Kenneth H. Mayer, Srinath Satyanarayana, Vineet K. Chadha, Nimalan Arinaminpathy, Madhukar Pai
Journal: PLoS Medicine (2019)

The cascade of care is a model for evaluating patient retention across sequential stages of care required to achieve a successful treatment outcome. This approach was first used to evaluate HIV care and has since been applied to other diseases. The tuberculosis (TB) community has only recently started using care cascade analyses to quantify gaps in quality of care. In this article, we describe methods for estimating gaps (patient losses) and steps (patients retained) in the care cascade for active TB disease. We highlight approaches for overcoming challenges in constructing the TB care cascade, which include difficulties in estimating the population-level burden of disease and the diagnostic gap due to the limited sensitivity of TB diagnostic tests. We also describe potential uses of this model for evaluating the impact of interventions to improve case finding, diagnosis, linkage to care, retention in care, and post-treatment monitoring of TB patients.
Brexit could spell trouble for unsung heroes of UK biomedical research
Authors: Richard Hurley
Journal: BMJ (2019)

Fiona Hanson

The work of technicians may go unseen but is pivotal to keeping the wheels of laboratory research turning. An exhibition dedicated to these crucial specialists at London’s Francis Crick Institute shows their typical laboratory benches and showcases films, interviews, photographs, and interactive items.

The institute is home to over 1200 scientists working to understand the fundamental biology that underlies health and disease. The Craft & Graft exhibition tells the stories of some of its 577 technical specialists. Their work, without which the science would stop, includes feeding the …
Minimizing the burden of cancer in the United States: Goals for a high‐performing health care system
Authors: K. Robin Yabroff, Ted Gansler, Richard C. Wender, Kevin J. Cullen, Otis W. Brawley
Journal: CA A Cancer Journal for Clinicians (2019)

Between 1991 and 2015, the cancer mortality rate declined dramatically in the United States, reflecting improvements in cancer prevention, screening, treatment, and survivorship care. However, cancer outcomes in the United States vary substantially between populations defined by race/ethnicity, socioeconomic status, health insurance coverage, and geographic area of residence. Many potentially preventable cancer deaths occur in individuals who did not receive effective cancer prevention, screening, treatment, or survivorship care. At the same time, cancer care spending is large and growing, straining national, state, health insurance plans, and family budgets. Indeed, one of the most pressing issues in American medicine is how to ensure that all populations, in every community, derive the benefit from scientific research that has already been completed. Addressing these questions from the perspective of health care delivery is necessary to accelerate the decline in cancer mortality that began in the early 1990s. This article, part of the Cancer Control Blueprint series, describes challenges with the provision of care across the cancer control continuum in the United States. It also identifies goals for a high-performing health system that could reduce disparities and the burden of cancer by promoting the adoption of healthy lifestyles; access to a regular source of primary care; timely access to evidence-based care; patient-centeredness, including effective patient-provider communication; enhanced coordination and communication between providers, including primary care and specialty care providers; and affordability for patients, payers, and society.
Let the “A” in WASH Stand for Air: Integrating Research and Interventions to Improve Household Air Pollution (HAP) and Water, Sanitation and Hygiene (WaSH) in Low-Income Settings
Authors: Thomas Clasen, Kirk R. Smith
Journal: Environmental Health Perspectives (2019)

Research often suffers from overspecialization, a practice nurtured in academia and reinforced by funders. Indeed, investigators in household air pollution (HAP) and water, sanitation and hygiene (WaSH), working in poor parts of the world, rarely interact despite having similar training and using similar methods to evaluate interventions in the same vulnerable populations. Disappointing results from recent trials of improved cookstoves and traditional approaches to WaSH suggest the need for alternative approaches.We argue that bringing these two areas together would improve the effectiveness and efficiency of interventions to reduce the massive disease burden associated with HAP and poor WaSH, including pneumonia and diarrhea, the leading killers of young children in low-income countries.HAP and WaSH face similar challenges in designing, implementing, and securing the sustained and exclusive use of scalable interventions such as clean fuel and water.Research can advance greater coordination of these areas by demonstrating their interactions and wider impacts on well-being as well as the potential for programmatic synergies. Integrated solutions to clean households and communities can benefit from the contribution in multiple disciplines, including economics and policy analysis; business and finance; engineering and technology; lab sciences, environmental health, and biomedical sciences; and behavioral and implementation sciences.There are compelling reasons to overcome the artificial and unproductive segregation of HAP and WaSH. Researchers should encourage integration by expanding the scope of their collaborations and projects. Policy makers, funders, and implementers can help by supporting comprehensive solutions, encouraging innovation, and requiring rigorous evaluations of their effects. https://doi.org/10.1289/EHP4752.
SP0091 Data visualisation: tables and graphs for publication and presentation
Authors: M Boers
Journal: Annals of the Rheumatic Diseases (2017)

This workshop (held both on Thursday and on Friday) is an introduction to the principles of good graph and table design as pioneered by Cleveland<sup>1</sup> and Tufte<sup>2</sup> and updated by Few<sup>3</sup> so that the participant can better answer the following questions: <i>Which of the messages in my research results requires a graph or table?</i> Recognizing how graphs improve on simple statistics and convey much more information. Knowing when a table is better, or keeping the data in the body text. <i>How can I best convey the message?</i> Striving for clear vision by choice of graph, scaling, discrimination of data series, minimizing non-data ink, avoiding chart junk. Striving for clear understanding through a balance between data and explanation. Using order, subheadings, formatting and rules to guide your reader through your table data. <i>Is my graph/table truthful?</i> Creating a direct proportion between graph and data quantities, avoiding forms prone to misinterpretation, labels to prevent ambiguity; keeping data in context, avoiding more dimensions in the graph than in the data. This year9s course will extend introductory material available via YouTube clips on the ARD website (ard.com)! Direct link: https://www.youtube.com/playlist?list=PLXU14EQbU_V9JpmolAKsaCC0VjJzbxzAN Note that you can also sign up for a special lecture followed by a poster tour after the session, devoted to poster design! <h3>References</h3> Cleveland WS. The elements of graphing data: Hobart Press, Summit, NJ, USA; 1994. Tufte E. The visual display of quantitative information. 2nd ed: Graphics Press, Cheshire, CT, USA; 2001. Few S. Show me the numbers. Designing tables and graphs to enlighten. 2nd ed: Analytics Press, Oakland, CA, USA; 2012. <h3>Disclosure of Interest</h3> M. Boers Consultant for: Director of Epiconsult BV that offers training in data visualization
MPs call for “revolution” in early years health
Authors: Jacqui Thornton
Journal: BMJ (2019)

Ministers must produce a long term, cross government strategy for the “critical” first 1000 days of life to improve support and services for children and families, a select committee has recommended.

The report by the House of Commons Health and Social Care Committee called for demanding goals to be set to reduce adverse childhood experiences, improve readiness for school, and reduce infant mortality and child poverty.1

It said that an “early years revolution” was needed, led by the minister for the Cabinet Office, with the support of a small centralised delivery team. The report said, “Improving support for children, parents and families during this vulnerable period requires a …
Estimates of case-fatality ratios of measles in low-income and middle-income countries: a systematic review and modelling analysis
Authors: Allison Portnoy, Mark Jit, Matthew Ferrari, Matthew Hanson, Logan Brenzel, Stéphane Verguet
Journal: The Lancet Global Health (2019)

In the 21st century, increases in immunisation coverage and decreases in under-5 mortality have substantially reduced the global burden of measles mortality. However, the assessment of measles mortality burden is highly dependent on estimates of case-fatality ratios for measles, which can vary according to geography, health systems infrastructure, prevalence of underlying risk factors, and measles endemicity. With imprecise case-fatality ratios, there is continued uncertainty about the burden of measles mortality and the effect of measles vaccination. In this study, we aimed to update the estimations of case-fatality ratios for measles, to develop a prediction model to estimate case-fatality ratios across heterogeneous groupings, and to project future case-fatality ratios for measles up to 2030.We did a review of the literature to identify studies examining measles cases and deaths in low-income and middle-income countries in all age groups from 1980 to 2016. We extracted data on case-fatality ratios for measles overall and by age, where possible. We developed and examined several types of generalised linear models and determined the best-fit model according to the Akaike information criterion. We then selected a best-fit model to estimate measles case-fatality ratios from 1990 to 2015 and projected future case-fatality ratios for measles up to 2030.We selected 124 peer-reviewed journal articles published between Jan 1, 1980, and Dec 31, 2016, for inclusion in the final review-85 community-based studies and 39 hospital-based studies. We selected a log-linear prediction model, resulting in a mean case-fatality ratio of 2·2% (95% CI 0·7-4·5) in 1990-2015. In community-based settings, the mean case-fatality ratio was 1·5% (0·5-3·1) compared with 2·9% (0·9-6·0) in hospital-based settings. The mean projected case-fatality ratio in 2016-2030 was 1·3% (0·4-3·7).Case-fatality ratios for measles have seen substantial declines since the 1990s. Our study provides an updated estimation of case-fatality ratios that could help to refine assessment of the effect on mortality of measles control and elimination programmes.Bill & Melinda Gates Foundation.
Abstract 11196: Dental Caries is Associated With Out-of hospital Cardiac Arrest of Cardiac Origin, but not Noncardiac Origin: From the All-Japan Utstein Registry
Authors: Yasunori Suematsu, Shin-ichiro Miura, Yoshinari Uehara, Bo Zhang, Naohiro Yonemoto, Hiroshi Nonogi, Ken Nagao, Takeshi Kimura, Keijiro Saku
Journal: Circulation (2013)

Background: Dental caries and periodontal disease are the two top problems in the oral cavity, and both contribute to the progression of atherosclerosis and coronary artery disease. However, there ...