tbuckley/cabot-search huggingface dataset:
Ocular Chlamydia trachomatis infection, anti-Pgp3 antibodies and conjunctival scarring in Vanuatu and Tarawa, Kiribati before antibiotic treatment for trachoma
Authors: Robert Butcher, Becca Handley, Mackline Garae, Raebwebwe Taoaba, Harry Pickering, Annie Bong, Oliver Sokana, Matthew J Burton, Nuno Sepúlveda, Ana Cama, Richard Le Mesurier, Anthony W. Solomon, David Mabey, Fasihah Taleo, Rabebe Tekeraoi, Chrissy h Roberts
Journal: Journal of Infection (2020)

In the peri-elimination setting, the positive predictive value of trachomatous inflammation-follicular (TF), the primary marker used to determine need for antibiotics for trachoma, is suboptimal. Here, three non-TF measures are used to compare two regions where TF prevalence exceeds the threshold for intervention, but where the Chlamydia trachomatis (Ct) prevalence is different.Population prevalence of trachoma was measured in Vanuatu (n = 3470) and Kiribati (n = 2922). Dried blood spots (DBS) and conjunctival photographs were collected from every survey participant, and conjunctival swabs were collected from those aged 1-9 years. Individuals were tested for blood anti-Pgp3 antibodies, Ct DNA at the conjunctiva and severity of conjunctival scarring.The prevalence of TF in 1-9-year-olds was 16.5% in Vanuatu and 38.2% in Tarawa. 7% of people aged ≥1 year in Vanuatu had conjunctival scarring compared to 27% in Tarawa. The prevalence of ocular Ct infection in 1-9-year-olds was 1.5% in Vanuatu and 27.4% in Tarawa. The seroconversion rate amongst 1-9-year-old children in Vanuatu and Tarawa was 0.018 and 0.197 events per child per year, respectively.Comparing Vanuatu to Tarawa demonstrates several markers that could be used to differentiate the trachoma status of populations in these (and other) locations.
Therapeutic ultrasound combined with microbubbles improves atherosclerotic plaque stability by selectively destroying the intraplaque neovasculature
Authors: Xinzhong Li, Shengcun Guo, Tong Xu, Xiang He, Yili Sun, Xiaoqiang Chen, Shiping Cao, Xiaoyun Si, Wangjun Liao, Yulin Liao, Yuan Han, Jianping Bin
Journal: Theranostics (2020)

Objective: The current antiangiogenic therapy for atherosclerotic plaques was mainly achieved by the use of antiangiogenic drugs, but serious side effects have limited the clinical application. The present study investigated whether therapeutic ultrasound (TUS) treatment with appropriate pressure could selectively deplete the neovasculature in vulnerable plaques to improve its stability with no side effects on the body; the underlying mechanisms were also explored. Methods and Results: A mouse model of advanced atherosclerosis was generated by maintaining apolipoprotein E-deficient (ApoE-/-) mice on a hypercholesterolemic diet (HCD). Plaque, skeletal muscle, mesentery and skin tissue from 114 atheroma-bearing mice were subjected to sham therapy, an ultrasound application combined with microbubbles at four different ultrasound pressures (1.0, 2.0, 3.0, 5.0 MPa), or ultrasound at 5.0 MPa alone. Microvessel density (MVD) was assessed by immunofluorescence and immunohistochemical methods. The plaque necrotic center/fiber cap (NC/FC) ratio and vulnerability index were calculated to evaluate plaque vulnerability. Twenty-four hours after TUS treatment at 3.0 MPa, the MVD in the plaque was substantially decreased by 84% (p < 0.05), while there was almost no change in MVD and neovessel density (NVD) in normal tissues, including skeletal muscle, mesentery and skin. Additionally, a marked reduction in the number of immature vessels was observed in the plaques (reduced by 90%, p < 0.05), whereas the number of mature vessels was not significantly decreased. Furthermore, TUS treatment at 3.0 MPa significantly improved plaque stability, as reflected by the NC/FC ratio and vulnerability index, which may be due to the selective destruction of intraplaque neovascularization by TUS treatment, thereby decreasing the extravasation of erythrocytes and leading to vascular inflammation alleviation and thin-cap fibroatheroma reduction. Conclusions: TUS treatment at 3.0 MPa selectively depleted plaque neovessels and improved the stability of vulnerable plaques through a reduction in erythrocyte extravasation and inflammatory mediator influx, with no significant effect on normal tissue.
Endoscopic ultrasound-guided drainage of pancreatic walled-off necrosis using 20-mm versus 15-mm lumen-apposing metal stents: an international, multicenter, case-matched study
Authors: Nasim Parsa, Jose M. Nieto, Patrick Powers, Shuji Mitsuhashi, Abdelhai Abdelqader, George Hadzinakos, Andrea A. Anderloni, Alessandro Fugazza, Theodore W. James, Alexander Arlt, Mark Ellrichmann, Jose Ramon Aparicio, Arvind J. Trindade, Tyler K. Stevens, Prabhleen Chahal, Shawn L. Shah, Ahmed A. Messallam, Gabriel Lang, M. Phillip Fejleh, Petros C. Benias, Divyesh V. Sejpal, Jason Jones, Fahad Faisal Mir, Mohamad Aghaie Meybodi, Yervant Ichkhanian, Kia Vosoughi, Aleksey A. Novikov, Shayan S. Irani, Rishi Pawa, Ali M. Ahmed, Alireza Sedarat, William Hsueh, Jochen Hampe, Reem Z. Sharaiha, Tyler M. Berzin, Field F. Willingham, Vladimir M. Kushnir, Olaya I. Brewer Gutierrez, Saowanee Ngamruengphong, Matthew T. Huggett, Todd H. Baron, Alessandro Repici, Douglas G. Adler, John T. Nasr, Thomas E. Kowalski, Vivek Kumbhari, Vikesh K. Singh, Mouen A. Khashab
Journal: Endoscopy (2020)

Abstract Backgrounds Endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMSs) has gained popularity for the treatment of pancreatic walled-off necrosis (WON). We compared the 20-mm and 15-mm LAMSs for the treatment of symptomatic WON in terms of clinical success and adverse events. Methods We conducted a retrospective, case-matched study of 306 adults at 22 tertiary centers from 04/2014 to 10/2018. A total of 102 patients with symptomatic WON who underwent drainage with 20-mm LAMS (cases) and 204 patients who underwent drainage with 15-mm LAMS (controls) were matched by age, sex, and drainage approach. Conditional logistic regression analysis was performed to compare clinical success (resolution of WON on follow-up imaging without reintervention) and adverse events (according to American Society for Gastrointestinal Endoscopy criteria). Results Clinical success was achieved in 92.2 % of patients with 20-mm LAMS and 91.7 % of patients with 15-mm LAMS (odds ratio 0.92; P = 0.91). Patients with 20-mm LAMS underwent fewer direct endoscopic necrosectomy (DEN) sessions (mean 1.3 vs. 2.1; P &lt; 0.001), despite having larger WON collections (transverse axis 118.2 vs. 101.9 mm, P = 0.003; anteroposterior axis 95.9 vs. 80.1 mm, P = 0.01). There was no difference in overall adverse events (21.6 % vs. 15.2 %; P = 0.72) and bleeding events (4.9 % vs. 3.4 %; P = 0.54) between the 20-mm and 15-mm LAMS groups, respectively. Conclusions The 20-mm LAMS showed comparable clinical success and safety profile to the 15-mm LAMS, with the need for fewer DEN sessions for WON resolution.
Survival impact of post-progression chemotherapy (post-Cx) in advanced gastric cancer (AGC): Systematic review and meta-analysis.
Authors: Sakura Iizumi, Atsuo Takashima, Kentaro Sakamaki, Satoshi Morita, Narikazu Boku
Journal: Journal of Clinical Oncology (2018)

130 Background: We conducted a systematic review and meta-analysis to assess the survival impact of post-Cx after first-line chemotherapy (1st-line Cx) and second-line chemotherapy (2nd-line Cx) for AGC. Methods: Phase III trials published in English between 2005 and 2015 or presented at annual meetings of ASCO or ESMO between 2013 and 2015 were searched. No. of patients, types of chemotherapy, and patient characteristics, proportion of post-Cx use (post-Cx%), median progression free survival (mPFS), and median overall survival (mOS) of each treatment arm were surveyed; trials not reporting these were excluded from the study. Median post-progression survival (mPPS) was calculated as difference between mOS and mPFS. Weighted Spearman's correlation coefficients between post-Cx% and survival outcomes (mOS and mPPS) were calculated. The effect of post-Cx% on survival outcomes adjusted for the types of chemotherapy and patient characteristics was evaluated by meta-regressions. Results: Overall, 25 trials were selected: 15 with 31 arms for 1st-line Cx, and 10 with 16 arms for 2nd-line Cx. Weighted Spearman's correlation coefficients between post-Cx% and mOS/mPPS were 0.520/0.739 for 1st-line Cx, and 0.767/0.823 for 2nd-line Cx, respectively. Meta-regression analysis adjusting for types of chemotherapy, age and PS, showed that 10% increase in post-Cx% was associated with prolongation of mOS by 1.033 months for 1st-line Cx and 0.34 months for 2nd-line Cx. Conclusions: Post-Cx% after 2nd-line Cx are correlated with mPPS and mOS as well as 1st-line Cx, suggesting a survival benefit of 3rd-line Cx. [Table: see text]
Hypoxia-Inducible Factor 1 is required for hypoxia-induced resistance to doxorubicin in breast carcinoma cells
Authors: Richard Sullivan, Lisa J. Frederiksen, Genevieve C. Pare, Charles H. Graham
Journal: Cancer Research (2006)

1711  Background: The Hedgehog (HH) pathway signals via Patched (PTCH) and Smoothened (SMO) at the cell surface to GLI in the nucleus. It is known to be required for cell differentiation and organ formation during embryogenesis. Deregulation of HH signaling due to mutations in PTCH or SMO is seen in medulloblastomas and basal cell carcinomas. In a previous microarray-based comparison of expression profiles of 46 synovial sarcoma (SS) samples and 137 samples of 4 other translocation-associated sarcomas (Ewing sarcoma, alveolar rhabdomyosarcoma, desmoplastic small round cell tumor, alveolar soft part sarcoma), we observed features of HH pathway activation in SS, specifically GLI and SMO were significantly overexpressed, as were some downstream targets of GLI such as WIF1 and PDGFRA. We therefore performed a mutational and functional analysis of the HH signaling pathway in SS. Design: Mutational analysis was performed on all coding exons of PTCH and SMO in 40 SS samples and 3 SS cell lines (FUJI, HS-SY-II, SYO-1) by direct sequencing. We also examined the changes in cell growth and in expression of HH target genes and of SUFU, a member of intracellular GLI complex, upon blockade of HH signaling by cyclopamine, a specific inhibitor of SMO, in the 3 SS cell lines. . Result: The mutational analysis revealed no somatic mutations in PTCH and SMO in the 40 SS samples and the 3 SS cell lines. By RT-PCR, all three cell lines expressed GLI, GLI2, GLI3, SUFU, SMO and PTCH. There was a wide range of sensitivity to cyclopamine among 3 cell lines: FUJI cells were most sensitive, with an IC50 (50% reduction in cell counts relative to untreated cells) between 1 uM and 5 uM whereas SYO-1 cells were less sensitive (IC50: 10 uM), and HS-SY-II cells were resistant (IC50>10 uM). We also examined the effect of cyclopamine on genes reported to be transcriptionally up-regulated by HH signaling in other cell types (GLI, PTCH, BCL2, PDGFRA, BMP4, BMP7, CRLF1, SOX9, WIF1, WNT5A). Quantitative RT-PCR assays showed decreases of 80%, 60%, and 30% in the expression levels of GLI, PTCH and BMP4, respectively, relative to untreated cells in the FUJI cell line (p
Associations between early-life screen viewing and 24 hour movement behaviours: findings from a longitudinal birth cohort study
Authors: Bozhi Chen, Jonathan Y Bernard, Natarajan Padmapriya, Yilin Ning, Shirong Cai, Carla Lança, Kok Hian Tan, Fabian Yap, Yap-Seng Chong, Lynette Shek, Keith M Godfrey, Seang Mei Saw, Shiao-Yng Chan, Johan G Eriksson, Chuen Seng Tan, Falk Müller-Riemenschneider
Journal: The Lancet Child & Adolescent Health (2020)
Hope for diabetes: five minutes with David Unwin
Authors: Jane Feinmann
Journal: BMJ (2020)

“My wife Jen and I were on a run in 2012 when we first got the idea of Hope for T2D (type 2 diabetes). I had been inspired by a patient who had put her diabetes into drug free remission by cutting sugar and starchy carbs. I wanted to see if what that patient had done could be replicated, but the practice was overstretched and understaffed. Jen, a clinical psychologist, thought that hope for a better future would be a better motivator than fear and suggested we try a hope based approach, including group consultations. In this way we …
CDAI and DAS28 in the management of rheumatoid arthritis in clinical practice
Authors: Satoshi Takanashi, Yuko Kaneko, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2020)

The primary therapeutic target for rheumatoid arthritis is remission, assessed using validated composited measures.1 Currently, index-based remission frequently used in clinical practice are disease activity (CDAI) and Disease Activity Score for 28 joints (DAS28). Generally, it has been reported that CDAI is more stringent than DAS28 in assessing clinical remission.1 2 However, this confirmation was mainly derived from trial results. Hence, this study aimed to investigate the real-world performance of CDAI and DAS28-erythrocyte sedimentation rate (ESR).

In total, 1585 consecutive patients with rheumatoid arthritis (mean age: 64 years, sex: 84% were women, mean disease duration: 12.0 years) in Keio University Hospital were reviewed cross-sectionally. Current treatments were conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone, tumour necrosis factor inhibitors (TNFi), interleukin 6 receptor inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen (CTLA)-4Ig and janus kinase inhibitors (JAKi) in 39.2%, 29.0%, 22.8%, 7.1% and 1.8% patients, respectively. Definition of cut-offs of each composite scores was following; remission, CDAI ≤2.8, DAS28-ESR  22, DAS28-ESR >5.1.

First, we focused on the patients in CDAI remission (62.7% in all, 66.4% treated with csDMARDs, 65.8% treated with TNFi, 58.6% treated with IL-6i, …
The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function
Authors: Helen L Spencer, Rachel Sanders, Mounia Boulberdaa, Marco Meloni, Amy Cochrane, Ana-Mishel Spiroski, Joanne Mountford, Costanza Emanueli, Andrea Caporali, Mairi Brittan, Julie Rodor, Andrew H Baker
Journal: Cardiovascular Research (2020)

Abstract Aims Long non-coding RNAs (lncRNAs) play functional roles in physiology and disease, yet understanding of their contribution to endothelial cell (EC) function is incomplete. We identified lncRNAs regulated during EC differentiation and investigated the role of LINC00961 and its encoded micropeptide, small regulatory polypeptide of amino acid response (SPAAR), in EC function. Methods and results Deep sequencing of human embryonic stem cell differentiation to ECs was combined with Encyclopedia of DNA Elements (ENCODE) RNA-seq data from vascular cells, identifying 278 endothelial enriched genes, including 6 lncRNAs. Expression of LINC00961, first annotated as an lncRNA but reassigned as a protein-coding gene for the SPAAR micropeptide, was increased during the differentiation and was EC enriched. LINC00961 transcript depletion significantly reduced EC adhesion, tube formation, migration, proliferation, and barrier integrity in primary ECs. Overexpression of the SPAAR open reading frame increased tubule formation; however, overexpression of the full-length transcript did not, despite production of SPAAR. Furthermore, overexpression of an ATG mutant of the full-length transcript reduced network formation, suggesting a bona fide non-coding RNA function of the transcript with opposing effects to SPAAR. As the LINC00961 locus is conserved in mouse, we generated an LINC00961 locus knockout (KO) mouse that underwent hind limb ischaemia (HLI) to investigate the angiogenic role of this locus in vivo. In agreement with in vitro data, KO animals had a reduced capillary density in the ischaemic adductor muscle after 7 days. Finally, to characterize LINC00961 and SPAAR independent functions in ECs, we performed pull-downs of both molecules and identified protein-binding partners. LINC00961 RNA binds the G-actin sequestering protein thymosin beta-4x (Tβ4) and Tβ4 depletion phenocopied the overexpression of the ATG mutant. SPAAR binding partners included the actin-binding protein, SYNE1. Conclusion The LINC00961 locus regulates EC function in vitro and in vivo. The gene produces two molecules with opposing effects on angiogenesis: SPAAR and LINC00961.
Mutant Calreticulin in the Myeloproliferative Neoplasms
Authors: Daniel Prins, Carlos González Arias, Thorsten Klampfl, Jacob Grinfeld, Anthony R. Green
Journal: HemaSphere (2020)

Abstract Mutations in the gene for calreticulin ( CALR ) were identified in the myeloproliferative neoplasms (MPNs) essential thrombocythaemia (ET) and primary myelofibrosis (MF) in 2013; in combination with previously described mutations in JAK2 and MPL , driver mutations have now been described for the majority of MPN patients. In subsequent years, researchers have begun to unravel the mechanisms by which mutant CALR drives transformation and to understand their clinical implications. Mutant CALR activates the thrombopoietin receptor (MPL), causing constitutive activation of Janus kinase 2 (JAK2) signaling and cytokine independent growth in vitro. Mouse models show increased numbers of hematopoietic stem cells (HSCs) and overproduction of megakaryocytic lineage cells with associated thrombocytosis. In the clinic, detection of CALR mutations has been embedded in World Health Organization and other international diagnostic guidelines. Distinct clinical and laboratory associations of CALR mutations have been identified together with their prognostic significance, with CALR mutant patients showing increased overall survival. The discovery and subsequent study of CALR mutations have illuminated novel aspects of megakaryopoiesis and raised the possibility of new therapeutic approaches.
Mortality Reduction with Low-Dose CT Screening for Lung Cancer
Authors: Stephen W. Duffy, John K. Field
Journal: New England Journal of Medicine (2020)

Since the publication of the first mortality results from the National Lung Screening Trial (NLST), which showed a 20% reduction in lung-cancer mortality with low-dose computed tomographic (CT) screening,1 the intervention has been adopted as policy in the United States, and there has been considerable discussion of the possibilities for its adoption in Europe.2,3 Policy decisions are still awaited in many countries, despite the unequivocal nature of the original NLST results.1 This is likely to be partly due to doubts fostered by the early publication of inconclusive results of a number of smaller trials in Europe.4,5 These doubts should be . . .
Coordination-induced exfoliation to monolayer Bi-anchored MnB<sub>2</sub> nanosheets for multimodal imaging-guided photothermal therapy of cancer
Authors: Zhaokui Jin, Danyang Chen, Penghe Zhao, Yanyuan Wen, Mingjian Fan, Gaoxin Zhou, Yingshuai Wang, Qianjun He
Journal: Theranostics (2020)

Background: Rapid advance in biomedicine has recently vitalized the development of multifunctional two-dimensional (2D) nanomaterials for cancer theranostics.However, it is still challenging to develop new strategy to produce new types of 2D nanomaterials with flexible structure and function for enhanced disease theranostics.Method: We explore the monolayer Bi-anchored manganese boride nanosheets (MBBN) as a new type of MBene (metal boride), and discover their unique near infrared (NIR)-photothermal and photoacoustic effects, X-ray absorption and MRI imaging properties, and develop them as a new nanotheranostic agent for multimodal imaging-guided photothermal therapy of cancer.A microwave-assisted chemical etching route was utilized to exfoliate the manganese boride bulk into the nanosheets-constructed flower-like manganese boride nanoparticle (MBN), and a coordination-induced exfoliation strategy was further developed to separate the MBN into the dispersive monolayer MBBN by the coordination between Bi and B on the surface, and the B-OH group on the surface of MBBN enabled facile surface modification with hyaluronic acid (HA) by the borate esterification reaction in favor of enhanced monodispersion and active tumor targeting. Result:The constructed MBBN displays superior NIR-photothermal conversion efficiency (η=59.4%)as well as high photothermal stability, and possesses versatile imaging functionality including photoacoustic, photothermal, CT and T1-wighted MRI imagings.In vitro and in vivo evaluations indicate that MBBN had high photothermal ablation and multimodal imaging performances, realizing high efficacy of imaging-guided cancer therapy. Conclusion:We have proposed new MBene concept and exfloliation strategy to impart the integration of structural modification and functional enhancement for cancer theranostics, which would open an avenue to facile fabrication and extended application of multifunctional 2D nanomaterials.
二重活性リゾホスファチジン酸受容体汎アンタゴニスト/自動タキシン抑制薬は,in vitroで乳癌細胞遊走を低下させて,in vivoで腫瘍退縮を生じる | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Zhang Honglu, XU Xiaoyu, Gajewiak Joanna, Tsukahara Ryoko, Fujiwara Yuko, Liu Jianxiong, I Fells James, Perygin Donna, L Parrill Abby, Tigyi Gabor, D Prestwich Glenn
Journal: Cancer Research (2009)
Total adenosine deaminase highly correlated with adenosine deaminase 2 activity in serum
Authors: Zhao-Wei Gao, Xi Wang, Fang Lin, Ke Dong
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article published by Lee and colleagues1 presenting the potential diagnostic value of adenosine deaminase 2 (ADA2) in systemic juvenile idiopathic arthritis (sJIA) with macrophage activation syndrome (MAS). Their study examined ADA2 activity in children with inflammatory and immune-mediated diseases. By comparing normal ranges of ADA2 in healthy individuals, their finding identified the utility of plasma ADA2 activity as a biomarker of MAS. ADA2 activity were measures by a spectrophotometric assay in the presence of a selective inhibitor of ADA1, erytro-9-amino-β-hexyl-α-methyl-9-ethanol hydrochloride (EHNA). We support the views expressed by the authors that ADA2 detection could be helpful in the diagnosis of MAS in sJIA. Here, we would like to share with the authors our data of ADA activity detection.

As we know, ADA contains …
Omics and Cardiometabolic Disease Risk Prediction
Authors: Usman A. Tahir, Robert E. Gerszten
Journal: Annual Review of Medicine (2020)

Risk assessments are integral for the prevention and management of cardiometabolic disease (CMD). However, individuals may develop CMD without traditional risk factors, necessitating the development of novel biomarkers to aid risk prediction. The emergence of omic technologies, including genomics, proteomics, and metabolomics, has allowed for assessment of orthogonal measures of cardiometabolic risk, potentially improving the ability for novel biomarkers to refine disease risk assessments. While omics has shed light on novel mechanisms for the development of CMD, its adoption in clinical practice faces significant challenges. We review select omic technologies and cardiometabolic investigations for risk prediction, while highlighting challenges and opportunities for translating findings to clinical practice.