tbuckley/cabot-search huggingface dataset:
Management Algorithm for Interrupting Mother-to-Child Transmission of Hepatitis B Virus
Authors: Jinlin Hou, Fuqiang Cui, Yang Ding, Xiaoguang Dou, Zhongping Duan, Guorong Han, Jidong Jia, Qing Mao, Jie Li, Zengde Li, Zhihua Liu, Lai Wei, Qing Xie, Xizhong Yang, Hua Zhang, Hui Zhuang
Journal: Clinical Gastroenterology and Hepatology (2018)

In areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Four aspects (screening, antiviral intervention during pregnancy, immunoprophylaxis, and postvaccination serologic testing) are the core components of preventing MTCT. Although the combination of passive and active immunization in newborns of hepatitis B surface antigen-positive mothers reduces MTCT of HBV, this immunoprophylaxis cannot completely eradicate MTCT. In the past decade, administration of antiviral agents to pregnant women has been shown to be safe and effective in reducing MTCT of HBV in combination with immunoprophylaxis. Aiming to achieve zero MTCT, this algorithm recommends the use of antivirals during pregnancy by women with high viral loads. Preventing MTCT is key to achieving the goal of eliminating HBV as a public health threat by 2030. Implementation and enhancement of the standardized algorithm for pregnant women with chronic HBV infection and their infants is urgently needed to prevent MTCT.
Statistical challenges posed by uncontrolled master protocols: sensitivity analysis of the vemurafenib study
Authors: B.P. Hobbs, M.J. Kane, D.S. Hong, R. Landin
Journal: Annals of Oncology (2018)

Within the evidentiary hierarchy of experimental inquiry, randomized trials are the gold standard. Oncology patients enter clinical studies with diverse lifestyles, treatment pathways, host tissue environments, and competing comorbidities. Randomization attempts to balance prognostic characteristics among study arms, thereby enabling statistical inference of 'average benefit' and attribution to the studied therapies. In contrast, interpretations of uncontrolled trials require additional scrutiny to attempt to place the findings in the context of external evidence. Counter-factual reasoning and speculation across trials may be obscured by the disproportionate enrollment of prognostic subpopulations which may be unknown from publications of trial reports. Recent modifications to the regulatory environment (Food and Drug Administration Safety and Innovation Act) have elevated the importance of non-comparative trials. Moreover, the emergence of recent innovations in precision medicine have yielded trial designs that partition potentially heterogeneous subpopulations into 'statistically exchangeable' cohorts by histologies, or genetic alterations, further elevating the importance of single-cohort analyses. As patient cohorts become ever more refined into smaller targeted subsets, consumers of reports of uncontrolled trials should be further empowered with improvements in reporting practices that better describe the enrolled prognostic subpopulations and importantly their association with study end points. This article demonstrates the issue with a sensitivity analysis of the findings reported in a recent trial that was devised to evaluate the preliminary clinical efficacy of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers.
GW29-e0111 Hypertrophic Cardiomyopathy Is an Unneglectable Cause of Chronic Aortic Regurgitation: An Echocardiography and Cardiac Magnetic Resonance Imaging Study
Authors: Zixian Chen, Chen Cui, Gang Yin, Junqiang Lei, Shunlin Guo, Zheng Zhang, Sirajuddin Arlene, Andrew E. Arai, Shihua Zhao, Minjie Lu
Journal: Journal of the American College of Cardiology (2018)
P3.12-03 Targeting DLL3 with AMG 757, a BiTE® Antibody Construct, and AMG 119, a CAR-T, for the Treatment of SCLC
Authors: M. Giffin, K. Cooke, E. Lobenhofer, M. Friedrich, T. Raum, A. Coxon
Journal: Journal of Thoracic Oncology (2018)
PolyTran™ RNAi nanoplex (PT-NPX) carrying siRNAs against VEGF; VEGFR2; or EGFR achieves successful systemic delivery and significant anti-tumor activity in multiple xenograft tumor models
Authors: Qing Zhou, Ying Liu, Flora Tang, Linda Zhang, Li Wang, Frank Xie, Xiaodong Yang
Journal: Cancer Research (2008)

1498   The discovery of RNA interference (RNAi) using small interfering RNA (siRNA) molecules has generated significant attention for its potential application as a new therapeutic class. This potential is still unrealized due to lack of effective systemic delivery methods for siRNAs in vivo. In this study, we demonstrated the in vivo efficacy of systemic delivery of siRNA against human VEGF, mouse VEGFR2, and human EGFR using PolyTran™ Technology. PolyTran™ is a synthetic biodegradable cationic polypeptide which serves as a condenser for negatively charged siRNA and forms nanoparticle when mixed together with siRNA at appropriate charge ratios. PolyTran™ nanoparticles (PT-NPX) formed in different formulations are stable and can protect siRNA from nuclease-mediated degradation. We have shown that PT-NPX carrying VEGF-siRNA can be internalized by tumor cells and are capable of silencing VEGF expression in vitro. To test the in vivo efficacy and safety of this delivery method, nude mice bearing human epidermoid carcinoma A431 were treated intravenously (i.v.) with PT-NPX carrying siRNAs against either human VEGF; mouse VEGFR2; or human EGFR at 2mg/kg dose every other day for three weeks and compared with positive control using bevacizumab for VEGF and Erlotinib for EGFR. All cohorts treated with PT-NPX carrying active siRNAs demonstrated significant tumor growth inhibition similar to the positive control treated animals. In the same A431 xenograft model, the efficacy resulting from daily or every other day treatment regimen was superior to that of twice weekly or other regimens. Significant anti-tumor efficacy was also observed in human non-small cell lung cancer A549, and rhabdomyosarcoma A673 xenograft tumor models. No apparent toxicity or significant body weight loss were seen in the animals treated with PT-NPX suggesting that PolyTran siRNA NPX is safe in mice. Systemic tissue distribution was confirmed using fluorescent-labeled siRNA PT-NPX. These results provided the preclinical validation of PolyTran™ technology as an option for systemic delivery of potential therapeutic siRNAs for cancer treatment. We concluded that the PolyTran™ RNAi Nanoplex is an effective method of systemic delivery of siRNA and is a promising delivery system for the development of novel RNAi-based cancer therapeutics in humans.
Real-Time Molecular Diagnosis of Tumors Using Water-Assisted Laser Desorption/Ionization Mass Spectrometry Technology
Authors: Philippe Saudemont, Jusal Quanico, Yves-Marie Robin, Anna Baud, Julia Balog, Benoit Fatou, Dominique Tierny, Quentin Pascal, Kevin Minier, Mélissa Pottier, Cristian Focsa, Michael Ziskind, Zoltan Takats, Michel Salzet, Isabelle Fournier
Journal: Cancer Cell (2018)
新的第 8 版皮肤癌 TNM 分期和影响
Authors: S.G. Keohane, C.M. Proby, C. Newlands, R.J. Motley, I. Nasr, M.F. Mohd Mustapa, D.N. Slater
Journal: British Journal of Dermatology (2018)

准确分期皮肤癌对于正确规划其管理至关重要。分期考虑到肿瘤本身 (T)、是否已扩散至淋巴腺(淋巴结 ‐ N)以及是否已扩散至远处器官(转移灶 ‐ M)。TNM 分类系统根据新的研究不断进行修订。最新版的皮肤癌 (TNM8) 于 2016 年由国际癌症控制联盟发布, 现已被英国相关机构采用。TNM8 相比于 TNM7 在皮肤癌分期中表现出显著变化, 包括常见的基底细胞癌和鳞状细胞癌(非黑色素瘤皮肤癌, NMSC)、黑色素瘤以及罕见的皮肤肿瘤。这些变化对治疗患者的临床医生施加了额外的责任。这些措施包括测量每个潜在 NMSC 的最大直径, 并将其写在表格上, 以便随切除的肿瘤一起带到实验室。此外, 表格必须说明是否可以用手感觉到扩大的腺体或在扫描时肉眼可见。黑色素瘤小于 0.8mm, 且淋巴结在称为前哨淋巴结活检的技术中显示无癌症的患者现在具有更低的 TNM 分期。他们的医院随访时间从 5 年减少到 1 年, 这是一个重要的进步。一些以前被认为表明肿瘤侵袭性的显微镜特征已从 TNM8 分类中删除。例如, 鳞状癌的分化(偏离正常组织外观)和黑素瘤中可见分裂细胞的数量不再被认为是重要的。
Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen‐Week Results From a Phase <scp>III</scp> Randomized, Double‐Blind, Placebo‐Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors
Authors: Atul Deodhar, Denis Poddubnyy, Cesar Pacheco‐Tena, Carlo Salvarani, Eric Lespessailles, Proton Rahman, Pentti Järvinen, Juan Sanchez‐Burson, Karl Gaffney, Eun Bong Lee, Eswar Krishnan, Silvia Santisteban, Xiaoqi Li, Fangyi Zhao, Hilde Carlier, John D. Reveille
Journal: Arthritis & Rheumatology (2018)

Objective To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors ( TNF i). Methods In this phase III randomized, double‐blind, placebo‐controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNF i and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ ASAS ] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80‐mg subcutaneous ixekizumab every 2 weeks ( IXE Q2W) or 4 weeks ( IXEQ4W ), with an 80‐mg or 160‐mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria ( ASAS 40) at week 16. Secondary outcomes and safety were also assessed. Results A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS 40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment‐emergent adverse events ( AE s) with ixekizumab treatment were more frequent than with placebo. Serious AE s were similar across treatment arms. One death was reported ( IXEQ2W group). Conclusion Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNF i yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.
Atopic diseases and type I sensitization from adolescence to adulthood in an unselected population (<scp>TOACS</scp>) with focus on predictors for allergic rhinitis
Authors: Charlotte G. Mortz, Klaus E. Andersen, Lars K. Poulsen, Henrik F. Kjaer, Sigurd Broesby‐Olsen, Carsten Bindslev‐Jensen
Journal: Allergy (2018)

While much is known on childhood atopic diseases, knowledge about persistence of atopic diseases from childhood to adulthood is limited. We therefore aimed to study the clinical course of atopic diseases and type I sensitization prospectively in an unselected cohort of adolescents followed into adulthood.A cohort of unselected 8th-grade school children (mean age 14 years) established in 1995 and followed up in 2010 were evaluated with questionnaire, clinical examination, skin prick tests and measurements of specific IgE.The lifetime prevalence of atopic diseases was high and increased significantly from adolescence (31%) to adulthood (57%); particularly allergic rhinitis increased with an incidence rate of 17.5/1000 person-years. Childhood predictors for adult allergic rhinitis were atopic dermatitis, asthma and asymptomatic sensitization to pollen and house dust mite. Among those with asymptomatic sensitization in adolescence, 53%-78% developed allergic rhinitis in adulthood. Furthermore, type I sensitization increased significantly from adolescence to adulthood mostly due to increased sensitization to pollen. Type I sensitization was found mainly in those with allergic rhinitis. A high number of adults had oral allergy symptoms due to the high number of birch pollen allergic individuals.Persistence of atopic diseases in adulthood is common, and a high proportion of the adult population is sensitized giving a high prevalence of allergic rhinitis. Many with asymptomatic sensitization in adolescence will develop allergic rhinitis in adult life. The focus should be on prevention of atopic diseases and sensitization already in childhood.
Child health in England is set to fall further behind other European countries, report warns
Authors: Susan Mayor
Journal: BMJ (2018)

The health of children in England will continue to fall behind other European countries if current trends continue, with infant mortality 140% higher than in comparable countries by 2030, a report has warned.

The report,1 from the Royal College of Paediatrics and Child Health, found that key risk factors for infant mortality were higher in England than in comparable countries, with a higher proportion of young mothers, higher rates of smoking during pregnancy, and lower breastfeeding rates than in many other countries.

It analysed long term historical data to project key health outcomes in young people in England in 2030 in comparison …
Streamlining multi-omic and artificial intelligence analysis through interrogative biology and baicis for translational precision medicine applications in clinical oncology
Authors: L. Rodrigues, M.A. Kiebish, G. Miller, L. Zhang, V. Vemulapalli, V.K. Vishnudas, R. Sarangarajan, N.R. Narain, V.R. Akmaev
Journal: Annals of Oncology (2018)
Antimicrobial resistance of major clinical pathogens in South Korea, May 2016 to April 2017: first one-year report from Kor-GLASS
Authors: Hyukmin Lee, Eun-Jeong Yoon, Dokyun Kim, Seok Hoon Jeong, Eun Jeong Won, Jong Hee Shin, Si Hyun Kim, Jeong Hwan Shin, Kyeong Seob Shin, Young Ah Kim, Young Uh, Ji Woo Yang, Il Hwan Kim, Chan Park, Kwang Jun Lee
Journal: Eurosurveillance (2018)

The Korean government established an antimicrobial resistance (AMR) surveillance system, compatible with the Global AMR Surveillance System (GLASS): Kor-GLASS. We describe results from the first year of operation of the Kor-GLASS from May 2016 to April 2017, comprising all non-duplicated clinical isolates of major pathogens from blood, urine, faeces and urethral and cervical swabs from six sentinel hospitals. Antimicrobial susceptibility tests were carried out by disk diffusion, Etest, broth microdilution and agar dilution methods. Among 67,803 blood cultures, 3,523 target pathogens were recovered. The predominant bacterial species were Escherichia coli (n = 1,536), Klebsiella pneumoniae (n = 597) and Staphylococcus aureus (n = 584). From 57,477 urine cultures, 6,394 E. coli and 1,097 K. pneumoniae were recovered. Bloodstream infections in inpatients per 10,000 patient-days (10TPD) were highest for cefotaxime-resistant E. coli with 2.1, followed by 1.6 for meticillin-resistant Sta. aureus, 1.1 for imipenem-resistant Acinetobacter baumannii, 0.8 for cefotaxime-resistant K. pneumoniae and 0.4 for vancomycin-resistant Enterococcus faecium. Urinary tract infections in inpatients were 7.7 and 2.1 per 10TPD for cefotaxime-resistant E. coli and K. pneumoniae, respectively. Kor-GLASS generated well-curated surveillance data devoid of collection bias or isolate duplication. A bacterial bank and a database for the collections are under development.
A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for immunotherapy of malignant melanoma
Authors: R.A. Jabulowsky, C. Loquai, E. Derhovanessian, H. Mitzel-Rink, J. Utikal, J. Hassel, R. Kaufmann, A. Pinter, M. Diken, M. Gold, L. Heesen, K.H. Schreeb, D. Schwarck-Kokarakis, S. Kreiter, M.R. Gaiser, D. Jäger, S. Grabbe, Ö Türeci, U. Sahin
Journal: Annals of Oncology (2018)
Genetic and environmental factors drive personalized medicine for Crohn’s disease
Authors: Shigeru Oshima, Mamoru Watanabe
Journal: Journal of Clinical Investigation (2018)

The introduction of anti-TNF antibody therapy has changed the course of treatment for Crohn's disease. However, the fundamental mechanism for the onset of Crohn's disease is still unknown, and the treatment strategy for this disease remains suboptimal. The assessment of the disease phenotype based on key environmental factors and genetic background may indicate options for the personalized treatment of Crohn's disease. In this issue of the JCI, Liu et al. show that consumption of tobacco and the mutation of ATG16L1T300A, a prevalent Crohn's disease susceptibility allele, drive defects in cells at the bottom of the intestinal crypt, the Paneth cells. These factors may provide novel targets for personalized medicine.
P3.16-23 Soft-Tissue Sarcoma of the Chest Wall, Surgical Resection: Analysis Our Cases Period of Time Decembre 2004-July 2017
Authors: F. Gradica, D. Argjiri, L. Lisha, A. Cani, F. Kokici, I. Avdiu, H. Nino, Y. Vata, V. Rexha, S. Gradica
Journal: Journal of Thoracic Oncology (2018)
Abstract 12873: Blood Transfusion and the Risk of Contrast-Induced Nephropathy Among Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention
Authors: Wassef Karrowni, Amit N Vora, Dadi Dai, Daniel Wojdyla, Habib Dakik, Sunil Rao
Journal: Circulation (2015)

Introduction: Emerging scientific and clinical evidence suggests that blood transfusion might be risk factor for acute kidney injury. Hypothesis: Blood transfusion is independently associated with contrast-induced nephropathy (CIN) in acute coronary syndrome (ACS) patients undergoing PCI. Methods: Retrospective cohort study from the NCDR CathPCI Registry (2009-2014) (n=1,756,864). Primary outcome was CIN defined as rise in serum creatinine peak post-procedure ≥ 0.5 mg/dl or ≥ 25% above baseline. Results: CIN developed in 9.0% of the cohort; these patients were older (66.0 vs. 64.0 years; P&lt;0.01), more often female (43.2% vs. 31.9%; P&lt;0.01), and had more baseline comorbidities including DM (46.1%), hypertension (85.1%), and lower baseline GFR. Blood transfusion was utilized in 38,626 (2.2%) of patients. The adjusted OR for the risk of CIN with transfusion in the overall sample, patients with major bleeding, and patients with no bleeding were 4.87 (4.71-5.04), 2.21 (2.12-2.31), and 4.80 (4.40 - 5.24) respectively (Table). Association of CIN with transfusion was significantly increased across all pre-procedure hemoglobin (Hgb) levels and in stepwise fashion with increasing Hgb levels and regardless of post-procedure bleeding (Hgb &amp;lt=10: adjusted OR (95%CI) 2.90 (2.75-3.05); Hgb &amp;gt10 to &amp;lt=13: 5.26 (5.06-5.48); Hgb &amp;gt13 to &amp;lt=15: 6.37 (5.99-6.78); Hgb &amp;gt15 g/dl: 7.03 (6.43-7.67); Ptrend &lt;0.01). Conclusions: Blood transfusion is strongly associated with CIN in ACS patients undergoing PCI. Whether a restrictive blood transfusion strategy lowers the risk of contrast nephropathy should be investigated.
Machine learning‐based phenogrouping in heart failure to identify responders to cardiac resynchronization therapy
Authors: Maja Cikes, Sergio Sanchez‐Martinez, Brian Claggett, Nicolas Duchateau, Gemma Piella, Constantine Butakoff, Anne Catherine Pouleur, Dorit Knappe, Tor Biering‐Sørensen, Valentina Kutyifa, Arthur Moss, Kenneth Stein, Scott D. Solomon, Bart Bijnens
Journal: European Journal of Heart Failure (2018)
Abstract 10034: Digital Assessment of Peripheral Vascular Endothelial Function is Useful for the Risk Stratification in Patients With Hypertension
Authors: Eiichiro Yamamoto, Seigo Sugiyama, Yasushi Matsuzawa, Yoshihiro Hirata, Eiichi Akiyama, Koichiro Fujisue, Takanori Tokitsu, Koichi Sugamura, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2015)

Introduction: Hypertension (HT) is the major risk factor of coronary artery disease (CAD), however all HT patients were not equally predisposed to CAD. Endothelial dysfunction has been implicated in atherogenesis, and digital assessment by reactive hyperemia peripheral arterial tonometry (RH-PAT) is a novel examination to evaluate endothelial function. Methods: In 1323 stable patients with suspected CAD including 1057 HT patients, we assessed peripheral endothelial function as fingertip RH-PAT index (RHI) and examined the presence and severity of CAD by coronary angiography. Results: Ln-RHI was significantly attenuated in HT patients (n=215) compared to risk-factor-matched non-HT patients (n=215) (0.538±0.224 vs. 0.664±0.248, p&lt;0.001) after matching number of patients and coronary risk factors (CRFs). In HT patients, ln-RHI was further lower in CAD (n=786) than in non-CAD (n=271) (0.514±0.185 vs. 0.634±0.219, p&lt;0.001). By multivariate-logistic-regression analysis, ln-RHI was independently associated with the presence of CAD in HT (per 0.1; odds ratio [OR]: 6.15, 95% confidence interval [CI]: 1.87-20.3, p&lt;0.001). CAD with high-ln-RHI was significantly associated with the complication of multi-vessel disease (MVD) and B-type natriuretic peptide (both p&lt;0.001). In receiver-operating-characteristic analysis, ln-RHI was a significant determinant for the presence of CAD (area under curve [AUC]: 0.650, 95% CI: 0.646-0.721, p&lt;0.001), and adding ln-RHI to CRFs improved predictive values of CAD (AUC: 0.737, 95% CI: 0.701-0.773, p&lt;0.001). The net reclassification index was significant with the inclusion of ln-RHI (13.8%, p&lt;0.005). Furthermore, ln-RHI was significantly lower in CAD with MVD (n=464) than in those with single-vessel disease (n=322) (0.46 vs. 0.57, p&lt;0.001). Multivariate-logistic-regression analysis suggested that ln-RHI was independently associated also with the presence of MVD in CAD (per 0.1; OR: 0.66, 95% CI: 0.60-0.73, p&lt;0.001). Conclusions: Ln-RHI significantly correlated with the presence and severity of CAD in HT, and the combination with CRFs may be more powerful at predicting CAD. Identifying high-risk HT patients by RH-PAT might provide clinical benefits for risk stratification.