tbuckley/cabot-search huggingface dataset:
A feasibility study of interventions to improve intraoperative lymph node (LN) collection and pathologic examination of lung cancer resection specimens.
Authors: Robert A. Ramirez, Laura Elizabeth Miller, Christopher Gene Wang, Thomas O'Brien, Alim Khandekar, Glenn P Schoettle, Samuel G Robbins, Edward T Robbins, Jeffrey B Gibson, Raymond U Osarogiagbon
Journal: Journal of Clinical Oncology (2012)

e17531^ Background: The number of LNs examined following lung cancer resection has prognostic value. The International Association for the Study of Lung Cancer (IASCLC) recommends a minimum of 6 LNs and other series have recommended greater than 11. Most resections in the United States fail to meet these recommendations. We hypothesized that simple interventions could improve on the number of LNs examined. Methods: We used a pre-labeled specimen collection kit to aid in collection of N2 LNs and developed a re-dissection protocol to retrieve discarded N1 LNs. We performed a 3 era case control study: Era 1, routine surgical examination (RSE) + routine pathology examination. Era 2, RSE + special pathology examination (SPE). Era 3, SPE + special surgical examination. The Chi-Square, Fishers Exact, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests were used where appropriate for comparisons. Results: Patient demographic and tumor characteristics were similar across three groups. Significantly more N1 and total LNs were examined in eras 2 and 3 compared to era 1 (Table). Significantly more N2 LNs were examined in era 3 compared to eras 1 and 2. There was a non-significant trend toward detection of metastatic LNs. More cases met both IASLC recommendations and had at least 11 LNs examined LNs in eras 2 and 3 compared to era 1. Conclusions: The interventions were feasible and effective in improving LN examination. The number of LNs examined using these interventions exceeded consensus recommendations. A phase III trial incorporating these interventions is being designed. [Table: see text]
A phase II trial of a cremophor-free, polymeric micelle formulation of paclitaxel and gemcitabine in patients with advanced non-small cell lung cancer.
Authors: Hee Kyung Ahn, Junsik Hong, Shin Myung Kang, Sun Jin Sym, Jinny Park, Dong Bok Shin, Jae Hoon Lee, Eun Kyung Cho
Journal: Journal of Clinical Oncology (2013)

e19129 Background: Non-platinum doublet paclitaxel and gemcitabine has shown efficacy on par with platinum-based doublet regimens as first-line chemotherapy in advanced non-small cell lung cancer patients. Genexol-PM is a Cremorphor EL(CrEL)-free polymeric micelle formulation of paclitaxel. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients. Methods: This is a single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230mg/m 2 on day 1 and gemcitabine 1000mg/m 2 on day 1 and day 8 of a 3-week cycle as first-line chemotherapy. Six cycles of chemotherapy were administered unless there is a disease progression. The primary endpoint was response rate. Results: Forty-three patients received the study drugs with median of 4 cycles per patient (range, 1-6). Among 35 patients who received more than one cycle, mean dose intensity of CrEL-free paclitaxel and gemcitabine was 209 mg/m 2 /3-week and 1,853 mg/m 2 /3-week respectively. Overall response rate was 46.5%. The median progression free survival was 4.0 months (95% CI 2.0-6.0 months) and median overall survival was 14.8 months (95% CI 9.1-20.5 months). 18 patients (51%) experienced grade 3/4 adverse events, including neutropenia or febrile neutropenia (n=7), pneumonia (n=3), asthenia (n=3), peripheral neuropathy (n=2), diarrhea (n=1), skin rash (n=1), myalgia (n=1), pulmonary thromboembolism (n=1), LV dysfunction (n=1), and dyspnea with sudden death (n=1). Adverse events leading to drug discontinuation were occurred in 9 patients, among which 2 patients were died of adverse events (pneumonia, dyspnea with sudden death). Conclusions: CrEL-free paclitaxel in combination with gemcitabine demonstrated comparable antitumor activity with less emetogenicities in non-small cell lung cancer patients. Clinical trial information: NCT01770795.
Development of a Theranostic Convergence Bioradiopharmaceutical for Immuno-PET Based Radioimmunotherapy of L1CAM in Cholangiocarcinoma Model
Authors: In Ho Song, Mun Sik Jeong, Hyo Jeong Hong, Jong Il Shin, Yong Serk Park, Sang-Keun Woo, Byung Seok Moon, Kwang Il Kim, Yong Jin Lee, Joo Hyun Kang, Tae Sup Lee
Journal: Clinical Cancer Research (2019)

Cholangiocarcinoma is a malignancy of bile duct with a poor prognosis. Conventional chemotherapy and radiotherapy are generally ineffective, and surgical resection is the only curative treatment for cholangiocarcinoma. L1-cell adhesion molecule (L1CAM) has been known as a novel prognostic marker and therapeutic target for cholangiocarcinoma. This study aimed to evaluate the feasibility of immuno-PET imaging-based radioimmunotherapy using radiolabeled anti-L1CAM antibody in cholangiocarcinoma xenograft model.We prepared a theranostic convergence bioradiopharmaceutical using chimeric anti-L1CAM antibody (cA10-A3) conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator and labeled with 64Cu or 177Lu and evaluated the immuno-PET or SPECT/CT imaging and biodistribution with 64Cu-/177Lu-cA10-A3 in various cholangiocarcinoma xenograft models. Therapeutic efficacy and response monitoring were performed by 177Lu-cA10-A3 and 18F-FDG-PET, respectively, and immunohistochemistry was done by TUNEL and Ki-67.Radiolabeled cA10-A3 antibodies specifically recognized L1CAM in vitro, clearly visualized cholangiocarcinoma tumors in immuno-PET and SPECT/CT imaging, and differentiated the L1CAM expression level in cholangiocarcinoma xenograft models. 177Lu-cA10-A3 (12.95 MBq/100 μg) showed statistically significant reduction in tumor volumes (P < 0.05) and decreased glucose metabolism (P < 0.01). IHC analysis revealed 177Lu-cA10-A3 treatment increased TUNEL-positive and decreased Ki-67-positive cells, compared with saline, cA10-A3, or 177Lu-isotype.Anti-L1CAM immuno-PET imaging using 64Cu-cA10-A3 could be translated into the clinic for characterizing the pharmacokinetics and selecting appropriate patients for radioimmunotherapy. Radioimmunotherapy using 177Lu-cA10-A3 may provide survival benefit in L1CAM-expressing cholangiocarcinoma tumor. Theranostic convergence bioradiopharmaceutical strategy would be applied as imaging biomarker-based personalized medicine in L1CAM-expressing patients with cholangiocarcinoma.
Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Authors: Monique E. van Leerdam, Victorine H. Roos, Jeanin E. van Hooft, Evelien Dekker, Rodrigo Jover, Michal F. Kaminski, Andrew Latchford, Helmut Neumann, Maria Pellisé, Jean-Christophe Saurin, Pieter J. Tanis, Anja Wagner, Francesc Balaguer, Luigi Ricciardiello
Journal: Endoscopy (2019)

Main Recommendations ESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and endoscopic performance measures. Strong recommendation, moderate quality of evidence, level of agreement 90 %. ESGE recommends performing esophagogastroduodenoscopy, small-bowel examination, and/or colonoscopy earlier than the planned surveillance procedure if a patient is symptomatic. Strong recommendation, low quality of evidence, level of agreement 100 %.
Abstract 18539: Molecular Imaging of Factor XIII for Early Diagnosis of Coronary Microvascular Disease in Mice
Authors: Zhen W Zhuang, Yan Huang, Rong Ju, Yongming Ren, John Hwa
Journal: Circulation (2015)

Background: Coronary microvascular disease (MVD) remains a major clinical challenge, involving endothelial cell (ECs) dysfunction and microthrombosis. We hypothesize that active FXIII can be a specific biomarker for MVD and its activity can be evaluated by a FXIII targeted radiolabeled probe ( 99m Tc-NC100668). We also hypothesize that a murine MVD model can be established through photodynamic therapy (PDT). Methods: To optimize the PDT parameters, primary ECs from the heart were isolated and treated with various concentrations of rose bengal, different illumination times, multiple combinations of rose bengal and illumination times (PDT), or nothing to evaluate cell viability and production of reactive oxygen species (ROS). The optimal parameters were translated for in vivo MVD model establishment. 52 female mice were assigned to one of four groups: 1) rose bengal, 2) green light, 3) combination, or 4) nothing. Microvascular injury was evaluated by fluorescent myocardial perfusion, coronary microCT angiography, and electron microscopy. To validate the efficacy of this tracer for the diagnosis of coronary MVD, an additional 124 female mice with MVD were injected either 0.1mCi 99m Tc-NC100668 or 99m Tc-AH110563 (an inactive analog), at 3 hrs, 24 hrs, 3, 7, or 14 days, for ex vivo gamma well counting (GWC, n=100) to assess regional myocardial activity as %injection dose/mg (id/mg), or in vivo microSPECT/CT (n=24) to visualize active FXIII. Results: PDT were capable of injuring primary ECs by over-producting ROS in vitro . Coronary MVD developed only in PDT mice with focal “no flow phenomena”. microCT demonstrated arteriole rarefaction and Electron Microscopy showed luminal microthrombi and loss of endothelial integrity in PDT-treated myocardium. GWC demonstrated 99m Tc-NC100668 activity within endothelial-damaged myocardium, compared to an inactive tracer at early time points (3 hours: 9.33±1.98 vs. 2.84±1.97% id/mg, p&lt;0.01; 3 days: 3.3±2.23 vs. 0.275±0.072% id/mg, p&lt;0.05). In vivo microSPECT/CT images confirmed focal myocardial uptake up to day 3. Conclusions: We successfully established a murine model of coronary MVD. Molecular imaging of the activated FXIII allowed visualization of acute and sub-acute coronary micro-thrombi, a hallmark of MVD.
Author Correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics
Authors: Mark R. Davies, Liam McIntyre, Ankur Mutreja, Jake A. Lacey, John A. Lees, Rebecca J. Towers, Sebastián Duchêne, Pierre R. Smeesters, Hannah R. Frost, David J. Price, Matthew T. G. Holden, Sophia David, Philip M. Giffard, Kate A. Worthing, Anna C. Seale, James A. Berkley, Simon R. Harris, Tania Rivera-Hernandez, Olga Berking, Amanda J. Cork, Rosângela S. L. A. Torres, Trevor Lithgow, Richard A. Strugnell, Rene Bergmann, Patric Nitsche-Schmitz, Gusharan S. Chhatwal, Stephen D. Bentley, John D. Fraser, Nicole J. Moreland, Jonathan R. Carapetis, Andrew C. Steer, Julian Parkhill, Allan Saul, Deborah A. Williamson, Bart J. Currie, Steven Y. C. Tong, Gordon Dougan, Mark J. Walker
Journal: Nature Genetics (2019)
Development and validation of a prediction model for fat mass in children and adolescents: meta-analysis using individual participant data
Authors: Mohammed T Hudda, Mary S Fewtrell, Dalia Haroun, Sooky Lum, Jane E Williams, Jonathan C K Wells, Richard D Riley, Christopher G Owen, Derek G Cook, Alicja R Rudnicka, Peter H Whincup, Claire M Nightingale
Journal: BMJ (2019)

Abstract Objectives To develop and validate a prediction model for fat mass in children aged 4-15 years using routinely available risk factors of height, weight, and demographic information without the need for more complex forms of assessment. Design Individual participant data meta-analysis. Setting Four population based cross sectional studies and a fifth study for external validation, United Kingdom. Participants A pooled derivation dataset (four studies) of 2375 children and an external validation dataset of 176 children with complete data on anthropometric measurements and deuterium dilution assessments of fat mass. Main outcome measure Multivariable linear regression analysis, using backwards selection for inclusion of predictor variables and allowing non-linear relations, was used to develop a prediction model for fat-free mass (and subsequently fat mass by subtracting resulting estimates from weight) based on the four studies. Internal validation and then internal-external cross validation were used to examine overfitting and generalisability of the model’s predictive performance within the four development studies; external validation followed using the fifth dataset. Results Model derivation was based on a multi-ethnic population of 2375 children (47.8% boys, n=1136) aged 4-15 years. The final model containing predictor variables of height, weight, age, sex, and ethnicity had extremely high predictive ability (optimism adjusted R 2 : 94.8%, 95% confidence interval 94.4% to 95.2%) with excellent calibration of observed and predicted values. The internal validation showed minimal overfitting and good model generalisability, with excellent calibration and predictive performance. External validation in 176 children aged 11-12 years showed promising generalisability of the model (R 2 : 90.0%, 95% confidence interval 87.2% to 92.8%) with good calibration of observed and predicted fat mass (slope: 1.02, 95% confidence interval 0.97 to 1.07). The mean difference between observed and predicted fat mass was −1.29 kg (95% confidence interval −1.62 to −0.96 kg). Conclusion The developed model accurately predicted levels of fat mass in children aged 4-15 years. The prediction model is based on simple anthropometric measures without the need for more complex forms of assessment and could improve the accuracy of assessments for body fatness in children (compared with those provided by body mass index) for effective surveillance, prevention, and management of clinical and public health obesity.
Consultants have responsibility to community, not just inpatients, says chair of GP partnership review
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Hospitals and hospital consultants have a responsibility to the wider community, not just their patients, and should start thinking that way, the chair of the government’s GP partnership review has said.

Nigel Watson, who was speaking on a panel at a King’s Fund event on primary care networks on 17 July, said that the new networks were an opportunity to completely rethink the health service, for example by moving certain services and the resources tied to them into the community.

At the end of June this year over 99% of general practices in England (around 70 000) had come together to form 1200 primary care networks (PCNs), meeting …
Global effort to reduce new HIV infections is stalling, UN warns
Authors: Jacqui Wise
Journal: BMJ (2019)

The global pace of progress in reducing new HIV infections and increasing access to treatment is slowing down, says a report from the Joint United Nations Programme on HIV/AIDS (UNAIDS).1

Communities at the Centre shows that, while some countries are making very good progress towards UN targets, others are seeing rises in new infections and AIDS related deaths.

Launching the report, Gunilla Carlsson, UNAIDS executive director, said, “We urgently need increased political leadership to end AIDS. This starts with investing adequately and smartly and by looking at what’s making some countries so successful.”

Around 1.7 million people became newly infected with HIV in 2018, down 16% since 2010. This decline has been driven mostly by steady progress in eastern and southern Africa. …
Pegylated E. coli Asparaginase Desensitization: An Effective and Feasible Option for Pediatric Patients with Acute Lymphoblastic Leukemia Who Have Developed Hypersensitivity to Pegaspargase in the Absence of Asparaginase Erwinia Chrysanthemi availability
Authors: Anupam Verma, Karin Chen, Jacob Johnsen, Phillip Barnette
Journal: Blood (2018)
Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors
Authors: Jennifer L Guida, Tim A Ahles, Daniel Belsky, Judith Campisi, Harvey Jay Cohen, James DeGregori, Rebecca Fuldner, Luigi Ferrucci, Lisa Gallicchio, Leonid Gavrilov, Natalia Gavrilova, Paige A Green, Chamelli Jhappan, Ronald Kohanski, Kevin Krull, Jeanne Mandelblatt, Kirsten K Ness, Ann O’Mara, Nathan Price, Jennifer Schrack, Stephanie Studenski, Olga Theou, Russell P Tracy, Arti Hurria
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled “Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.” Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.
Modeling Future Projections of Temperature-Related Excess Morbidity due to Infectious Gastroenteritis under Climate Change Conditions in Japan
Authors: Daisuke Onozuka, Antonio Gasparrini, Francesco Sera, Masahiro Hashizume, Yasushi Honda
Journal: Environmental Health Perspectives (2019)

Background: Climate change has marked implications for the burden of infectious diseases. However, no studies have estimated future projections of climate change–related excess morbidity due to diarrhea according to climate change scenarios. Objectives: We aimed to examine temperature-infectious gastroenteritis associations throughout Japan and project temperature-related morbidity concomitant with climate change for the 2090s. Methods: Weekly time series of average temperature and morbidity for infectious gastroenteritis cases in the period 2005–2015 were collated from the 47 Japanese prefectures. A two-stage time-series analysis was adopted to estimate temperature-infectious gastroenteritis relationships. Time series of present and future average daily temperature fluctuations were projected for the four climate change scenarios of representative concentration pathways (RCPs) according to five general circulation models. Excess morbidity for high and low temperatures and the net change in the period 1990–2099 were projected for each climate change scenario by assuming the absence of adaptation and population alterations. Results: In the period 2005–2015, 11,529,833 infectious gastroenteritis cases were reported. There were net reductions in temperature-induced excess morbidity under higher emission scenarios. The net change in the projection period 2090–2099 in comparison with 2010–2019 was −0.8% (95% empirical confidence interval [eCI]: −2.3, 0.5) for RCP2.6, −3.8% (95% eCI: −6.1, −1.7) for RCP4.5, −5.1% (95% eCI: −7.7, −2.8) for RCP6.0, and −9.1% (95% eCI: −15.5, −4.2) for RCP8.5, and the higher the emissions scenario, the larger the estimates reductions. Spatial heterogeneity in the temperature-morbidity relationship was observed among prefectures (Cochran Q test, p<0.001; I2=62.0%). Conclusions: Japan may experience a net reduction in temperature-related excess morbidity due to infectious gastroenteritis in higher emission scenarios. These results might be because the majority of temperature-related diarrhea cases in Japan are attributable to viral infections during the winter season. Further projections of specific pathogen-induced infectious gastroenteritis due to climate change are warranted. https://doi.org/10.1289/EHP4731
MicroRNA Biogenesis is enhanced by Liposome- Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma
Authors: Dan Sun, Shuangyan Tan, Yanli Xiong, Wenchen Pu, Jiao Li, Wei Wei, Canhua Huang, Yu-Quan Wei, Yong Peng
Journal: Theranostics (2019)

Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality.We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor.Despite its significant anti-HCC activity, the low water solubility and in vivo bioavailability of API-1 limit its clinical application.To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy.Methods: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP.Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized.The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both in vitro and in vivo.Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically.Results: API-LP had good formulation characteristics and exhibited an enhanced in vitro activity of suppressing proliferation and migration of HCC cells when compared with free API-1.The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5.Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1.Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice. Conclusion:The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.
Abstract 3639: Enhanced Contractility but Reduced Excitation-contraction Coupling Efficiency and Adrenergic Reserve in Hearts With Increased Cav1.2 Activities
Authors: Xiongwen Chen, Mingxin Tang, Xiaoying Zhang, Yingxin Li, Hiroyuki Nakayama, Hongyu Zhang, Remus Berretta, Jeffery D Molkentin, Steven R Houser
Journal: Circulation (2009)

Hypercontractility has been proposed to for hearts under stresses to maintain the perfusion of the body, which is brought about by the activation of the adrenergic system and molecular remodeling, ...