tbuckley/cabot-search huggingface dataset:
Association between the physical stability of flurbiprofen suspension and the interaction of HPMC/SDS
Authors: Hongyu Wang, Yiwei Sun, Baixue Yang, Sanming Li
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The anionic surfactant sodium dodecylsulfate (SDS) has improved the physical stability of flurbiprofen (FBP) suspension, which was suspended by 0.2% (w/v) hydroxypropylmethyl cellulose (HPMC, K4M). Therefore, the physical stability of FBP suspensions and the interaction of HPMC/SDS were studied, and a certain association between them was revealed. The anti-solvent precipitation method was used to prepare suspensions. The apparent drug concentration from different sites was evaluated to get the dispersion of drug actually. The process of flocculation and deflocculation with the addition of SDS was caught by analyzing the morphology of the suspended particles. The physical stability of the FBP suspensions was characterized mainly by measuring the re-dispersion time, the zeta potential and particle size. Meanwhile, conductivity measurements were carried out to obtain the characteristic concentrations of SDS in HPMC/SDS system. The viscosities, the abilities for improving the solubility and wettability of FBP in the separate and mixed HPMC/SDS solutions were also contrasted respectively. The suspensions prepared with HPMC/SDS possessed better physical stability. The suspensions were uniform when the concentration of SDS was between the critical adsorption concentration (CAC) and the polymer saturation point (PSP). After PSP, the uniformity became worse and worse until the SDS was enough to form a deflocculation state. Besides, the re-dispersion time of FBP suspensions was longest when the concentration of SDS around CAC and shorter by shorter after the critical micelle concentration (CMC). The article provided a new sight on the relation between the interaction of excipient matrix and pharmaceutical preparations.
Accuracy and Reproducibility in the Induction of Tumors With Ultraviolet Radiation
Authors: Harold F. Blum
Journal: JNCI Journal of the National Cancer Institute (1943)

Accuracy and Reproducibility in the Induction of Tumors With Ultraviolet Radiation Harold F. Blum Harold F. Blum formerly senior pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 1, August 1943, Pages 75–79, https://doi.org/10.1093/jnci/4.1.75 Published: 01 August 1943
An Accessible Organotypic Microvessel Model Using iPSC‐Derived Endothelium
Authors: Patrick N. Ingram, Laurel E. Hind, Jose A. Jiminez‐Torres, Anna Huttenlocher, David J. Beebe
Journal: Advanced Healthcare Materials (2017)

Abstract While organotypic approaches promise increased relevance through the inclusion of increased complexity (e.g., 3D extracellular microenvironment, structure/function relationships, presence of multiple cell types), cell source is often overlooked. Induced pluripotent stem cell (iPSC)‐derived cells are potentially more physiologically relevant than cell lines, while also being less variable than primary cells, and recent advances have made them commercially available at costs similar to cell lines. Here, the use of induced pluripotent stem cell‐derived endothelium for the generation of a functional microvessel model is demonstrated. High precision structural and microenvironmental control afforded by the design approach synergizes with the advantages of iPSC to produce microvessels for modeling endothelial biology in vitro. iPSC microvessels show endothelial characteristics, exhibit barrier function, secrete angiogenic and inflammatory mediators, and respond to changes in the extracellular microenvironment by altering vessel phenotype. Importantly, when deployed in the investigation of neutrophils during innate immune recruitment, the presence of the iPSC endothelial vessel facilitates neutrophil extravasation and migration toward a chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic models to open the way for improved and increasingly accessible in vitro tissue, disease, and patient‐specific models.
02.24 The ap-1 transcription factor c-jun promotes arthritis by regulating cyclooxygenase-2 expression in macrophages
Authors: Nicole Hannemann, Jutta Jordan, Sushmita Paul, Stephen Reid, Hanns-Wolf Baenkler, Sophia Sonnewald, Tobias Bäuerle, Julio Vera, Georg Schett, Aline Bozec
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Pro-inflammatory macrophage activation is associated with the inflammatory state of rheumatoid arthritis (RA). Their polarisation and activation are controlled by transcription factors, such as NF-κB and the AP-1 transcription factor members JunB or JunD. However, the role of the third JUN/AP-1 member, c-Jun, is still ill defined during macrophage activation in RA. <h3>Material and methods</h3> To examine the role of c-Jun during macrophage activation, c-Jun deleted peritoneal macrophages were used for microarray and quantitative real-time PCR analysis. In addition, genes found differentially expressed were analysed by chromatin immunoprecipitation (ChIP) analysis to determine directs targets of c-Jun. To address the physiological role of c-Jun in macrophages, the serum induced arthritis (K/BxN) model was applied to c-Jun<sup>ΔLysM</sup> mice. <h3>Results</h3> C-Jun mRNA and protein levels are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology (GO) and KEGG pathway enrichment cluster analyses of microarray data using wild-type and c-Jun deleted macrophages highlight the central function of c-Jun, in particular for immune response, interleukin production and hypoxia pathways. Mice deficient for c-Jun in macrophages showed an amelioration of inflammation and bone destruction in the K/BxN arthritis model. <i>In vivo</i> and <i>in vitro</i> gene profiling, together with ChIP analysis in macrophages unravelled direct activation of the pro-inflammatory factor cyclooxygenase-2 (Cox2) and indirect inhibition of the anti-inflammatory factor arginase-1 (Arg1) by c-Jun. <h3>Conclusion</h3> Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating Cox2 and Arg1 levels.
EPIDEMIOLOGY OF TRAINING INJURIES IN ELITE INDIAN JUDOKAS – A PROSPECTIVE STUDY
Authors: Jahnavi Dande, Anirban Mallick
Journal: British Journal of Sports Medicine (2017)

Background Judo has a relatively high injury risk and hence research on training injuries in judokas can identify the risk factors and help to develop specific prevention programs. Few studies have reported data on training injuries in judokas. Objective To present an epidemiological study of training injuries in elite Indian judokas. Design Prospective observational cohort study. Setting Elite Indian judokas training at National Institute of Sports, under centre of excellence scheme. Participants 45 judokas (22 male and 23 female) were followed up from June 2011 to May 2016. Assessment of Risk Factors Height, weight, age, BMI were recorded at the time of their admission. Training data were recorded as per training log. Injury data were collected using a validated assessment tool by Finch et al (2008). Competition injuries were excluded. Main Outcome Measurements Injury rate, average injury risk, re-injury risk, location, type and severity of injuries (time loss) were analyzed and compared. Results The injury rate was 0.75 (95% CI, 0.63–0.88) injuries per athlete year. The rate per 1000 exposures was 26.0 (95% CI, 6.0–46) in males and 43.1 (95% CI, 24–62) in females. Average risk or incidence proportion was 0.73 (0.82 in males and 0.65 in females). The observed re injury risk (average probability an injured athlete is at risk of repeated injury) was 0.79 of injured athletes. No significant difference was observed in terms of body parts injured between men and women (p&gt;0.05). Injuries most frequently occurred in the lower limbs (40.7% in males and 43.2% in females) followed by upper limbs, trunk, head and neck. The most common injury type was a ligament sprain (37%). Grade 3 injuries were significantly more common in women than men (p&lt;0.05). Conclusions Indian male judokas have a high average risk of training injuries. Women are more prone to re injuries and severe injuries. Further studies are needed to address the impact of training- related risk factors for injury to implement effective preventive measures.
BLIMP1 Induces Transient Metastatic Heterogeneity in Pancreatic Cancer
Authors: Shin-Heng Chiou, Viviana I. Risca, Gordon X. Wang, Dian Yang, Barbara M. Grüner, Arwa S. Kathiria, Rosanna K. Ma, Dedeepya Vaka, Pauline Chu, Margaret Kozak, Laura Castellini, Edward E. Graves, Grace E. Kim, Philippe Mourrain, Albert C. Koong, Amato J. Giaccia, Monte M. Winslow
Journal: Cancer Discovery (2017)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most metastatic and deadly cancers. Despite the clinical significance of metastatic spread, our understanding of molecular mechanisms that drive PDAC metastatic ability remains limited. By generating a genetically engineered mouse model of human PDAC, we uncover a transient subpopulation of cancer cells with exceptionally high metastatic ability. Global gene expression profiling and functional analyses uncovered the transcription factor BLIMP1 as a driver of PDAC metastasis. The highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes, and hypoxia-mediated induction of BLIMP1 contributes to the regulation of a subset of hypoxia-associated gene expression programs. These findings support a model in which upregulation of BLIMP1 links microenvironmental cues to a metastatic stem cell character. Significance: PDAC is an almost uniformly lethal cancer, largely due to its tendency for metastasis. We define a highly metastatic subpopulation of cancer cells, uncover a key transcriptional regulator of metastatic ability, and define hypoxia as an important factor within the tumor microenvironment that increases metastatic proclivity. Cancer Discov; 7(10); 1184–99. ©2017 AACR. See related commentary by Vakoc and Tuveson, p. 1067. This article is highlighted in the In This Issue feature, p. 1047
Outcome of Myelodysplastic Syndromes over Time in the US: A National Cancer Data Base Study from 2004-2013
Authors: Aref Al-Kali, Darci Zblewski, Adam C Bartley, Mrinal M Patnaik, Naseema Gangat, Kebede H. Begna, Ayalew Tefferi, Michelle Elliott, William J Hogan, Mark R. Litzow, Ronald S. Go
Journal: Blood (2016)
07.09 Influence of b-cell activating factor genetic variants in sjögren’s syndrome related atherosclerosis
Authors: Theofanis Karageorgas, Adrianos Nezos, Dimitrios Ioakeimidis, Michael Koutsilieris, Clio P Mavragani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recent data highlight the increased risk for premature atherosclerosis in primary Sjogren's syndrome (pSS) patients. Given a potential role of B cells in atherosclerotic plaque formation, we explored the potential contribution of B-cell activating factor (BAFF) in pSS-related atherosclerosis. <h3>Materials and methods</h3> 72 patients, fulfilling the ACR/EULAR criteria for pSS, with detailed clinical, laboratory and histopathological data regarding both pSS and traditional risk factors of atherosclerosis underwent carotid and femoral arteries Doppler ultrasound scan for detection of atherosclerotic plaque. Additionally, the prevalence of 5 polymorphisms (rs1224141, rs12583006, rs61756766, rs9514828, rs1041569) in the BAFF gene was examined. BAFF mRNA levels were measured by real time PCR in a subgroup of 32 patients with available peripheral blood cDNA. Univariate and multivariate statistical analyses were performed. <h3>Results</h3> In the subgroup of 32 pSS patients, BAFF mRNA levels were significantly higher in patients with plaque (17 out of 32 patients) compared to those without plaque (p=0.03). In the entire cohort of 72 pSS patients, the prevalence the T/T genotype of the rs9514828 polymorphism, which is known to reside in the promoter area of the BAFF gene, was significantly higher in pSS patients with plaque compared with those without plaque (35.6% vs 8.0%, p=0.031 respectively, OR: 6.4, CI: 1.3–30.6). The multivariate analysis also showed the rs9514828 BAFF polymorphism to be independently associated with the presence of plaque after adjustment for age, hypertension, smoking and dyslipidemia (OR=3.5, CI: 1.2–10.1). <h3>Conclusions</h3> In pSS patients the presence of atherosclerotic plaque was significantly associated both with increased BAFF mRNA levels and the T/T genotype of rs9514828 BAFF polymorphism implying a potential role of BAFF in the pathogenesis of pSS-related atherosclerosis. Further studies are warranted in order to elucidate this association. <h3>Grants/acknowledgements</h3> Dr. T.Karageorgas' work was supported by a State Scholarship Foundation (IKY) Fellowship of Excellence for Postgraduate Studies in Greece-Siemens Programme.
Neutrophil Activation of Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration and Vascular Injury
Authors: Manish Mittal, Saroj Nepal, Yoshikazu Tsukasaki, Claudie M. Hecquet, Dheeraj Soni, Jalees Rehman, Chinnaswamy Tiruppathi, Asrar B. Malik
Journal: Circulation Research (2017)

TRPM2 (transient receptor potential melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca2+ entry in response to intracellular generation of adenosine diphosphoribose-the TRPM2 ligand.Because polymorphonuclear neutrophils (PMN) interaction with ECs generates reactive oxygen species, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs.We observed defective PMN transmigration in response to lipopolysaccharide challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted (Trpm2iΔEC ). PMN interaction with ECs induced the entry of Ca2+ in ECs via the EC-expressed TRPM2. Prevention of generation of adenosine diphosphoribose in ECs significantly reduced Ca2+ entry in response to PMN activation of TRPM2 in ECs. PMNs isolated from gp91phox-/- mice significantly reduced Ca2+ entry in ECs via TRPM2 as compared with wild-type PMNs and failed to induce PMN transmigration. Overexpression of the adenosine diphosphoribose insensitive TRPM2 mutant channel (C1008→A) in ECs suppressed the Ca2+ entry response. Further, the forced expression of TRPM2 mutant channel (C1008→A) or silencing of poly ADP-ribose polymerase in ECs of mice prevented PMN transmigration.Thus, endotoxin-induced transmigration of PMNs was secondary to TRPM2-activated Ca2+ signaling and VE-cadherin phosphorylation resulting in the disassembly of adherens junctions and opening of the paracellular pathways. These results suggest blocking TRPM2 activation in ECs is a potentially important means of therapeutically modifying PMN-mediated vascular inflammation.
病巣感染の光熱アブレーションを強化するためのin situ細菌特異的凝集を引き起こす酸性度トリガcharge convertibleナノ粒子【Powered by NICT】
Authors: Korupalli Chiranjeevi, Huang Chieh-Cheng, Lin Wei-Chih, Pan Wen-Yu, Lin Po-Yen, Wan Wei-Lin, Li Meng-Ju, Chang Yen, Sung Hsing-Wen
Journal: Biomaterials (2017)
UNDERSTANDING HOW CLINICIANS AND ATHLETES MAKE RETURN TO PLAY DECISIONS – TOWARDS PREVENTING RE INJURIES
Authors: Adam Weir, Arnlaug Wangensteen, Andreas Serner, Russel J. Steele, Ian Shrier
Journal: British Journal of Sports Medicine (2017)

Background Clinicians and athletes do not always agree when return to play (RTP) is advisable. A better understanding of how RTP decisions are made could help prevent re injury. Objective To describe and compare risk assessments from sport medicine physicians, physiotherapists and athletes during routine care of injured athletes, and to elicit if there were factors that influenced their risk tolerance. Design Feasibility study to establish this method of examining the way athletes and clinicians make RTP decisions. Setting Specialized orthopedic and sports medicine hospital in Doha, Qatar. Patients We recruited the physician, the physiotherapist, and the athlete they were caring for (“triplet”) to participate. Triplets were recruited from an acute groin injury study and an acute hamstring injury study. Of the 15 athletes approached, 5 were excluded because we obtained risk estimates from only 1 stakeholder. Of the remaining 10 cases, we obtained risk estimates from 7 triplets and 3 doublets. Outcome measures Participants provided their own estimated probability distribution for risk of re-injury within the subsequent 2 months after RTP, based on the available knowledge. In addition, we asked participants about factors that influenced their risk tolerance for the particular case. Results The figure shows the risk estimations in 2 of the 10 cases, illustrating that there were clear and considerable differences in risk estimates. Figure 1 Factors that modified risk tolerance in at least three participants were “timing and season”, “pressure from athlete” and “external pressure”. Overall, risk modifiers influenced the decision in 13 of 27 possible cases. Conclusion Clinicians and athletes with access to the same information can have considerably different estimates for the risk of reinjury. Risk tolerance in the real world is sometimes modified by external factors.
THE EPIDEMIOLOGICAL STUDY OF POST-TRAUMATIC KNEE OSTEOARTHRITIS AFTER KNEE LIGAMENT OR MENISCUS INJURIES USING NATIONAL HEALTH INSURANCE SERVICE (NHIS) 514,866 COHORT DATA: RETROSPECTIVE COHORT STUDY
Authors: Sang Gyun Kim, So Young Lee, Young Hee Lee, Sae Yong Lee
Journal: British Journal of Sports Medicine (2017)

<h3>Background</h3> Various knee injuries accompanying anterior cruciate ligament (ACL) has been established as a significant risk factor for developing knee osteoarthritis (OA). However, research using big cohort sample to examine relationship between ACL and OA have not been conducted yet. <h3>Objective</h3> The purpose of this study is to examine the impact of ACL injury and other related knee joint structures on the development of OA using National Health Insurance Service (NHIS) cohort data. <h3>Design</h3> Epidemiological retrospective cohort study. <h3>Setting</h3> Epidemiological study of active adult population from National Health Insurance Service cohort database. <h3>Patients (or Participants)</h3> The subjects consist of a total of 514,866 randomly selected NHIS cohort group (age, 52.6 years; BMI, 24.0) between 2002 and 2013. Individual with an ACL injury regardless of accompany of other structural damage were prospectively followed-up until 2013. <h3>Interventions (or Assessment of Risk Factors)</h3> ACL injury with multiple knee joint ligament damage (AL); ACL injury with meniscus damage (AM); single ACL injury (AS); and group without any knee joint ligaments or meniscus injury (Control). <h3>Main Outcome Measurements</h3> Adjusted odds ratio (OR) and 95% confidential interval (CI) were estimated. <h3>Results</h3> A total of 1,175 (2.28 per 1,000 population) ACL patients were found in 2002 and followed-up until 2013. AS (OR, 1.79; CI, 1.41–2.26), AL (OR, 2.77; CI, 2.37–3.25) and AM (OR, 2.78; CI, 2.37–3.26) demonstrated 1.79, 2.77, and 2.78 times greater to develop OA than control group respectively. AL (OR, 1.55; CI, 1.17–2.06) and AM (OR, 1.56; CI, 1.17–2.07) are approximately 1.6 times greater than AS. <h3>Conclusions</h3> This study clearly provide evidence that multiple knee joint injury is as high as approximately 3 times greater risk of developing OA than control and even 1.6 times greater than AS. Therefore, clinician should consider appropriate treatment option for ACL injured patient to prevent progression to OA.
07.01 A multi-parameter response prediction model for rituximab in rheumatoid arthritis
Authors: Tamarah D. de Jong, Jérémie Sellam, Rabia Agca, Saskia Vosslamber, Birgit I Witte, Michel Tsang-a-Sjoe, Elise Mantel, Johannes W Bijlsma, Alexandre E Voskuyl, Mike T Nurmohamed, Cornelis L. Verweij, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Elevated expression of type I IFN response genes (IRGs) was previously described to be associated with a poor response to rituximab in rheumatoid arthritis (RA). In the present study, we aimed to validate this association and assessed the predictive performance upon combination of the predictive IRG gene set with clinical parameters. <h3>Materials and methods</h3> In two independent cohorts of 93 (Cohort I) and 133 (Cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight selected IRGs was determined, and averaged into an IFN score. Individual predictive performance of the IFN score and clinical parameters was assessed by logistic regression. A multivariate prediction model was developed using a forward stepwise selection procedure. Patients with a decrease in disease activity score (ΔDAS28)≥1.8 after 6 months of therapy were considered responders. <h3>Results</h3> A higher IFN score was observed in RTX non-responders compared to RTX responders from both Cohort I and II, but this difference was most pronounced in patients who did not use prednisone (PREDN<sup>-</sup>), as described before. Univariate analysis showed that baseline DAS28, IFN score and DMARD use were associated with non-response to rituximab, whereas positivity for IgM-RF and ACPA was associated with a good response to RTX. The multivariate model consisted of DAS28, IFN score and DMARD use, which showed an area under the curve (AUC) of 0.82. Validation of this multivariate model in Cohort II revealed a comparable AUC in PREDN<sup>-</sup> patients (0.78), but the AUC in PREDN<sup>+</sup> patients was significantly lower (0.63), which seemed due to effect modification of the IFN score by prednisone. Multivariate analysis of the PREDN<sup>+</sup> subgroup of Cohort II revealed a model containing DAS28 and positivity for IgM-RF and ACPA, which showed an AUC of 0.75. <h3>Conclusions</h3> The combination of predictive parameters, including IFN score, provided a promising model for the prediction of non-response to rituximab, with possibilities for optimisation via definition of the exact interfering effect of prednisone on IFN score.
Epidemiology and impact of chronic bronchitis in chronic obstructive pulmonary disease
Authors: Lies Lahousse, Leen J.M. Seys, Guy F. Joos, Oscar H. Franco, Bruno H. Stricker, Guy G. Brusselle
Journal: European Respiratory Journal (2017)

Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results. Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear. Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years. Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years. Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB − ) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB + ). CB + subjects were older, more frequently current smokers and had more pack-years than CB − subjects. During a median 6.5 years of follow-up, CB + subjects had greater decline in lung function (−38 mL·year −1 , 95% CI −61.7–−14.6; p=0.024). CB + subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7–5.9; p&lt;0.001). In females, survival was significantly worse in CB + subjects compared to CB − subjects. Regarding cause-specific mortality, CB + subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12–4.17; p=0.002). COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.