tbuckley/cabot-search huggingface dataset:
Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study
Authors: Ibrahim A Khalil, Christopher Troeger, Puja C Rao, Brigette F Blacker, Alexandria Brown, Thomas G Brewer, Danny V Colombara, Eugenio L De Hostos, Cyril Engmann, Richard L Guerrant, Rashidul Haque, Eric R Houpt, Gagandeep Kang, Poonum S Korpe, Karen L Kotloff, Aldo A M Lima, William A Petri, James A Platts-Mills, David A Shoultz, Mohammed H Forouzanfar, Simon I Hay, Robert C Reiner, Ali H Mokdad
Journal: The Lancet Global Health (2018)

BackgroundThe protozoan Cryptosporidium is a leading cause of diarrhoea morbidity and mortality in children younger than 5 years. However, the true global burden of Cryptosporidium infection in children younger than 5 years might have been underestimated in previous quantifications because it only took account of the acute effects of diarrhoea. We aimed to demonstrate whether there is a causal relation between Cryptosporidium and childhood growth and, if so, to quantify the associated additional burden.MethodsThe Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2016 was a systematic and scientific effort to quantify the morbidity and mortality associated with more than 300 causes of death and disability, including diarrhoea caused by Cryptosporidium infection. We supplemented estimates on the burden of Cryptosporidium in GBD 2016 with findings from a systematic review of published and unpublished cohort studies and a meta-analysis of the effect of childhood diarrhoea caused by Cryptosporidium infection on physical growth.FindingsIn 2016, Cryptosporidium infection was the fifth leading diarrhoeal aetiology in children younger than 5 years, and acute infection caused more than 48 000 deaths (95% uncertainty interval [UI] 24 600–81 900) and more than 4·2 million disability-adjusted life-years lost (95% UI 2·2 million–7·2 million). We identified seven data sources from the scientific literature and six individual-level data sources describing the relation between Cryptosporidium and childhood growth. Each episode of diarrhoea caused by Cryptosporidium infection was associated with a decrease in height-for-age Z score (0·049, 95% CI 0·014–0·080), weight-for-age Z score (0·095, 0·055–0·134), and weight-for-height Z score (0·126, 0·057–0·194). We estimated that diarrhoea from Cryptosporidium infection caused an additional 7·85 million disability-adjusted life-years (95% UI 5·42 million–10·11 million) after we accounted for its effect on growth faltering—153% more than that estimated from acute effects alone.InterpretationOur findings show that the substantial short-term burden of diarrhoea from Cryptosporidium infection on childhood growth and wellbeing is an underestimate of the true burden. Interventions designed to prevent and effectively treat infection in children younger than 5 years will have enormous public health and social development impacts.FundingThe Bill & Melinda Gates Foundation.
Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study
Authors: K.K.W. To, C.C.Y. Yip, C.Y.W. Lai, C.K.H. Wong, D.T.Y. Ho, P.K.P. Pang, A.C.K. Ng, K.-H. Leung, R.W.S. Poon, K.-H. Chan, V.C.C. Cheng, I.F.N. Hung, K.-Y. Yuen
Journal: Clinical Microbiology and Infection (2018)
AB1275 Research contribution to the journal of annals of the rheumatic diseases from 2012 to 2016: a bibliometric analysis
Authors: Y. Tetik-Aydogdu, O. Aydogdu, Z. Sarı
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatology, a subspecialty of medicine, is devoted to diagnosis and therapy of rheumatic diseases, including clinical problems in joints, soft tissues, and autoimmune diseases. "Annals of the Rheumatic Diseases" is one of the most read and prestigious journals in the field of rheumatology. Bibliometric studies concerning the quantity and quality of articles published in rheumatology journals are scarce. The scientific production in the field of rheumatology from 1996 to 2010 was compared by Cheng.<sup>1</sup> On the other hand, as to our knowledge, there is no study investigating research contribution to Annals of the Rheumatic Diseases since 2012. <h3>Objectives</h3> This study aims to investigate countries' research contribution in the field of rheumatology by classifying scientific papers according to their countries between 2012 and 2016 in Annals of the Rheumatic Diseases, official journal of EULAR. <h3>Methods</h3> All scientific papers which were published from 2012 to 2016 in Annals of the Rheumatic Diseases were screened. Some scientific papers such as editorial, viewpoint notes, or letters were excluded. In addition, supplementary issues were excluded as well. Rest of the papers were separated in two different part: "<i>clinical and epidemiological research</i>" and "<i>basic and translational research</i>". The papers were investigated one-by-one to determine their countries. All papers were classified according to their corresponding author. <h3>Results</h3> A total of 1616 scientific papers were investigated. Totally 1092 papers were included. While <i>clinical and epidemiological research</i> included 753 articles, <i>basic and translational research</i> contained 339 articles. There are 211, 188, 260, 235, 198 published articles in 2012, 2013, 2014, 2015, 2016, respectively. ,<sup>In 2012</sup> ,<sup>2014 and 2015</sup> the top countries to publish articles in Annals of the Rheumatic Diseases are England, Netherlands and USA. In 2013 and 2016, France is in the list of top countries instead of Netherlands. While, 46, 37 and 37 articles were published from England, Netherlands and USA, respectively in 2012, 53, 35 and 18 articles were published from England, USA and France, respectively in 2016. <h3>Conclusions</h3> According to our results, Western Europe and USA clearly dominate the production of scientific papers in Annals of the Rheumatic Diseases, official journal of EULAR. Our results are in accordance with the literature. We conclude that research resources, financial and other some issues may contribute the publishing process. <h3>Reference</h3> [1] Cheng T, Zhang G. Worldwide research productivity in the field of rheumatology from 1996 to 2010: a bibliometric analysis. Rheumatology (Oxford). 2013Sep;52(9):1630–4. <h3>Disclosure of Interest</h3> None declared
Scotland identifies public health priorities
Authors: Bryan Christie
Journal: BMJ (2018)

New thinking and innovative solutions will be needed to improve public health in Scotland, says an official report that sets out priorities for action over the next decade.1

It identifies six areas for action to help people lead healthier lives and acknowledges that success will require activity across all sectors because “wellbeing cannot be created and sustained by the NHS alone.”

The report, produced by the Scottish government and the organisation representing Scotland’s local authorities, says: …
Identification and Characterization of Failures in Infectious Agent Transmission Precaution Practices in Hospitals
Authors: Sarah L. Krein, Jeanmarie Mayer, Molly Harrod, Lauren E. Weston, Lynn Gregory, Laura Petersen, Matthew H. Samore, Frank A. Drews
Journal: JAMA Internal Medicine (2018)

Using personal protective equipment (PPE) and transmission-based precautions are primary strategies for reducing the transmission of infectious agents.
Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome
Authors: Franz Schaefer, Gianluigi Ardissino, Gema Ariceta, Fadi Fakhouri, Marie Scully, Nicole Isbel, Åsa Lommelé, Varant Kupelian, Christoph Gasteyger, Larry A. Greenbaum, Sally Johnson, Masayo Ogawa, Christoph Licht, Johan Vande Walle, Véronique Frémeaux-Bacchi, Miquel Blasco, Donata Cresseri, Galina Generolova, Nicholas Webb, Patricia Hirt-Minkowski, Natalya Lvovna Kozlovskaya, Danny Landau, Anne-Laure Lapeyraque, Chantal Loirat, Christoph Mache, Michal Malina, Leena Martola, Annick Massart, Eric Rondeau, Andrew Siedlecki, Lisa Sartz
Journal: Kidney International (2018)
Pharmacodynamics of regulatory T cells in mice and humans treated with low-dose IL-2
Authors: Guillaume Churlaud, Chadi Abbara, Pierre-Axel Vinot, Gwladys Fourcade, Paul-Gydeon Ritvo, Roberta Lorenzon, Michelle Rosenzwajg, Bertrand Diquet, David Klatzmann
Journal: Journal of Allergy and Clinical Immunology (2018)
AB0644 Pregnancy outcomes of planned pregnancy in patients with systemic lupus erythematosus: a retrospective multicenter study
Authors: Z. Zhan, D. Chen, M. Lao, X. Cai, J. Zhang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Compared with the general population, patients with SLE are still at high risk of adverse pregnancy outcomes (APOs). A number of studies have shown that patients with SLE are more likely to develop fetal complications, including fetal loss, preterm birth and IUGR, compared to healthy women. <h3>Objectives</h3> To investigate the fetal and maternal outcomes, as well as predictors for APOs in women with SLE who conceived when disease was stable, the so called "planned pregnancy". <h3>Methods</h3> A retrospective multicenter study of 243 patients with SLE who underwent planned pregnancy was performed. APOs in fetus and mothers were recorded. <h3>Results</h3> The average age at conception was 28.9±3.9 years. Duration of SLE prior to pregnancy was 4.4±4.3 years. Fetal APOs occurred in 86 (86/243, 35.4%) patients. Preterm births, intrauterine growth retardation (IUGR), fetal distress, and fetal loss accounted for 22.2%, 14.8%, 11.1%, and 4.9%, respectively. Forty-two preterm infants (42/54, 77.8%) were delivered after the 34th week of gestation. All the preterm infants were viable. Fifty-two patients (52/243, 21.4%) had disease flares, among which 45 (45/52, 86.5%) cases were mild, 6 (6/52, 11.5%) were moderate and 1 (1/52, 1.9%) was severe. Fifty-two disease flares (21.4%) occurred, among which 8 disease flares occurred during the first-trimester, 15 during the second-trimester, and 29 during the third-trimester. Disease activity was mild in 45 (45/52, 86.5%) patients, moderate in 6 (6/52, 11.5%), and high in 1 (1/52, 1.9%). Disease flares were mainly presented as active lupus nephritis (41/52, 78.8%), thrombocytopenia (10/52, 19.2%), and skin/mucosa lesions (9/52, 17.3%). Pregnancy-induced hypertension (PIH) occurred in 29 patients, among which 3 were gestational hypertension and 26 were preeclampsia. Multiple analysis showed that disease flares (OR 8.1, 95% CI 3.8–17.2, p&lt;0.001) and anticardiolipin antibodies positivity (OR 7.4, 95% CI 2.5–21.8, p&lt;0.001) were associated with composite fetal APOs. <h3>Conclusions</h3> Planned pregnancy improved fetal and maternal outcomes, presenting as lower rate of fetal loss, more favourable outcomes for preterm infants as well as less severe disease flares during pregnancy. Our research reinforced the importance of planned pregnancy, which allowed women with SLE to conceive in a proper time monitored by multidisciplinary experts. <h3>Disclosure of Interest</h3> None declared
AB0206 Expression of inflammatory genes and the il1b gene association with the severity of rheumatoid arthritis in tamil nadu population
Authors: B. Vellingiri, A. V, A. I, V. B, D. V, S. C
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a multifactorial complex and chronic inflammatory disease associated with progressive joint destruction, disabling and systemic complications. The prevalence is about 0.5%–1% worldwide and 0.9% in India. Genetic factors are recognised to have substantial effect on the susceptibility to RA. <h3>Objectives</h3> The present study aims to investigate the inflammatory caspase genes (<i>CASP5</i> and <i>CASP8</i>) as well as proinflammatory cytokine interleukin-1beta (IL-1β) in RA patients. Hence the study was designed to explore the possible association of inflammatory genes in Tamil Nadu population. <h3>Methods</h3> We conducted a study involving 55 RA patients and equal number of normal healthy controls and performed gene expression analysis in <i>CASP5</i> and <i>CASP8</i> genes. We also carried out genotyping of IL-1β gene using PCR-RFLP. For gene expression study, the mRNA levels of inflammatory genes were assessed using qPCR and the inflammatory marker levels (IL-1β) were estimated by ELISA. <h3>Results</h3> The gene expression analysis of RA patients showed activation of <i>CASP5</i> and <i>CASP8</i> compared to the healthy individuals. The inflammatory marker levels in the serum showed significantly higher levels (23.35±2.12 pg/mL) p&lt;0.05) in RA patients compared to the control subjects. The homozygous and heterozygous mutant variants of <i>IL1B</i> were observed to be higher in the RA patients (OR=2.1, p&lt;0.01). <h3>Conclusions</h3> Thus the results of our study suggests that, the mutant alleles of <i>IL1B</i> was associated with RA susceptibility which in turn has direct association with the increased levels of serum IL-1β in RA patients. In addition, the activation of inflammatory genes supports the role of inflammasome in the development of RA in Tamil Nadu population. <h3>References</h3> [1] Parle M, Kaura, S. How to live with rheumatoid arthritis. Int. Res. J. Pharm2012;3:115–12. [2] Huan R, Ting Y, Zhiyong H, Ruiping L, Liqun W. The association between caspase-5 gene polymorphisms and rheumatoid arthritis in a Chinese population. Gene2018;642:307–312. [3] Ben Hamad M, Cornelis F, Marzouk S, et al. (2012) Association study of CARD8 (p.C10X) and NLRP3 (p.Q705K) variants with rheumatoid arthritis in French and Tunisian populations. Int J Immunogenet. 39(2): 131–6. <h3>Disclosure of Interest</h3> None declared
An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma
Authors: Viktor Grünwald, Berit Eberhardt, Axel Bex, Anne Flörcken, Thomas Gauler, Thorsten Derlin, Martin Panzica, Hans Roland Dürr, Knut Achim Grötz, Rachel H. Giles, Christian von Falck, Anno Graser, Alexander Muacevic, Michael Staehler
Journal: Nature Reviews Urology (2018)

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.
Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements
Authors: Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri
Journal: Cancer Research (2018)

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, that is dynamics. Expression of ubiquitination-defective SNPH mutant Lys111→Arg or Lys153→Arg increased the speed and distance traveled by mitochondria, repositioned mitochondria to the cortical cytoskeleton, and supported heightened tumor chemotaxis, invasion, and metastasis in vivo Interference with SNPH ubiquitination activated mitochondrial dynamics, resulting in increased recruitment of the fission regulator dynamin-related protein-1 (Drp1) to mitochondria and Drp1-dependent tumor cell motility. These data uncover nondegradative ubiquitination of SNPH as a key regulator of mitochondrial trafficking and tumor cell motility and invasion. In this way, SNPH may function as a unique, ubiquitination-regulated suppressor of metastasis.Significance: These findings reveal a new mechanism of metastasis suppression by establishing the role of SNPH ubiquitination in inhibiting mitochondrial dynamics, chemotaxis, and metastasis. Cancer Res; 78(15); 4215-28. ©2018 AACR.
Bile-duct obstruction model imaged at the single-cell level
Authors: Kazuhiko Tsuji, Kensuki Yamauchi, Meng Yang, Ping Jiang, H. Endo, Y. Kanai, K. Yamashita, A. R. Moossa, Robert M. Hoffman
Journal: Cancer Research (2005)

5660   Bile duct obstruction often occurs in pancreatic cancer and other tumors. We have developed a new model to visualize tumor cell obstruction of the bile duct as well as the nuclear cytoplasmic dynamics of the invading cancer cells. The cancer cells were genetically double-labeled with green fluorescent protein (GFP) linked to histone H2B in the nucleus and with retroviral red fluorescent protein (RFP) in the cytoplasm. The doubly-labeled fluorescent tumor cells were injected into the head portion of the pancreas. The tumor cells were followed intravitally in the live animal by dual-color fluorescence. Dual-labeled cancer cells spread rapidly in the pancreas, and by three days were visualized to invade the bile duct. The tumor cells rapidly divided within the bile duct. Duodenal obstruction and resulting jaundice in the mice resulted 20 days after cell injection. Most of the mice were dead by 40 days. It was possible to visualize single cells invading the bile duct and to determine the nuclear and cellular dynamics including apoptosis of the invading cells. This dual-fluorescent model should prove to be useful for understanding the cell biology of bile duct invasion in cancer. The ability to visualize bile duct invasion by cancer cells should also enable the selective targeting of this process by new agents.
<scp>RAGE</scp>‐dependent <scp>VCAM</scp>‐1 expression in the lung endothelium mediates <scp>IL</scp>‐33‐induced allergic airway inflammation
Authors: T. N. Perkins, E. A. Oczypok, P. S. Milutinovic, R. E. Dutz, T. D. Oury
Journal: Allergy (2018)

The receptor for advanced glycation endproducts (RAGE) has been implicated as a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation (AAI). It has been previously shown that RAGE acts both upstream of interleukin-33 (IL-33) release and downstream of IL-33 release via RAGE-dependent IL-33-induced accumulation of type 2 innate lymphoid cells (ILC2s) in the lungs, which perpetuate type 2 inflammation and mucus metaplasia. However, the mechanism by which RAGE mediates downstream IL-33-induced type 2 inflammatory responses is unknown.This study tested the hypothesis that ILC2s are recruited to the lungs via RAGE-dependent vascular cell adhesion molecule 1 (VCAM-1) expression on lung endothelial cells.House dust mite extract, Alternaria alternata extract, or rIL-33 was used to induce AAI/VCAM-1 expression in wild-type (WT) and RAGE-knockout (RAGE-KO) mice. Intravenous (i.v.) anti-VCAM-1 or intraperitoneal (i.p.) β7 blocking antibody administration was used to determine the role of VCAM-1 in IL-33-induced AAI.Enhanced VCAM-1 expression in the lungs by HDM, AA, or rIL-33 exposure was found to be RAGE-dependent. In addition, stimulation of primary mouse lung endothelial cells with IL-33 induced VCAM-1 expression in WT, but not RAGE-KO cells. Administration of VCAM-1 and β7-integrin blocking antibodies reduced IL-33-induced eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses.This study demonstrates that allergen- and cytokine-induced VCAM-1 expression is RAGE-dependent and contributes to lung ILC2 accumulation and downstream eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses.
Overall survival in COLUMBUS: A phase 3 trial of encorafenib (ENCO) plus binimetinib (BINI) vs vemurafenib (VEM) or enco in <i>BRAF</i>-mutant melanoma.
Authors: Reinhard Dummer, Paolo Antonio Ascierto, Helen Gogas, Ana M. Arance, Mario Mandalà, Gabriella Liszkay, Claus Garbe, Dirk Schadendorf, Ivana Krajsova, Ralf Gutzmer, Vanna Chiarion-Sileni, Caroline Dutriaux, Jan Willem de Groot, Naoya Yamazaki, Carmen Loquai, Laure A. De Parseval, Michael D Pickard, Victor Sandor, Caroline Robert, Keith Flaherty
Journal: Journal of Clinical Oncology (2018)

9504 Background: Combined BRAF/MEK inhibitor therapy is standard of care in advanced BRAFV600-mutant melanoma. COLUMBUS Part 1 evaluated ENCO 450 mg once daily (QD) + BINI 45 mg twice daily (BID;COMBO450) vs VEM 960 mg BID or ENCO 300 mg QD (ENCO300) in patients (pts) with advanced BRAFV600-mutant melanoma. The primary study endpoint was progression-free survival (PFS); median PFS was 14.9 vs 7.3 mo for COMBO450 vs VEM; hazard ratio (HR): 0.54 (2-sided P< 0.001). Here we report a planned analysis of overall survival (OS), a secondary endpoint of the study. Methods: Pts with advanced/metastatic BRAFV600-mutant melanoma, untreated or progressed on/after first-line immunotherapy, were stratified by disease stage, Eastern Cooperative Oncology Group Performance Status and prior first-line immunotherapy. Pts in Part 1 were randomized 1:1:1 to COMBO450 (n = 192), ENCO300 (n = 194), or VEM (n = 191). Tumor responses and progression were assessed by blinded independent central review. An analysis of OS was planned after 232 events in the COMBO450 and VEM arms combined. Results: As of data cutoff,105, 106, and 127 events contributed to the OS analysis in the COMBO450, ENCO300, and VEM arms, respectively; median follow-up across arms was 21.5 mo. Median OS was 33.6 mo (95% CI, 24.4-39.2) with COMBO450, 23.5 mo (95% CI, 19.6-33.6) with ENCO300, and 16.9 mo (95% CI, 14.0-24.5) with VEM. Risk of death was reduced with COMBO450 vs VEM (HR, 0.61 [95% CI, 0.47-0.79]; nominal 2-sided P< 0.001). Updated median PFS was 14.9 mo (95% CI, 11.0–20.2) with COMBO450, 9.6 mo (95% CI, 7.4–14.8) with ENCO300, and 7.3 mo (95% CI, 5.6–7.9) with VEM. PFS was longer with COMBO450 vs VEM (HR, 0.51 [95% CI, 0.39–0.67]). Updated response rates, safety data, and information on 2nd-line therapy will be presented at the meeting. Conclusions: The best-in-class median PFS of 14.9 and median OS of 33.6 mo suggest that COMBO450 is a promising new regimen for treatment of BRAF-mutant melanoma. SPONSOR: Array BioPharma Inc. Clinical trial information: NCT01909453.