tbuckley/cabot-search huggingface dataset:
Molecular detection of inflammation in cell models using hyperpolarized <sup>13</sup>C-pyruvate
Authors: Renuka Sriram, Julia Nguyen, Justin DeLos Santos, Linda Nguyen, Jinny Sun, Seth Vigneron, Mark Van Criekinge, John Kurhanewicz, John D. MacKenzie
Journal: Theranostics (2018)

The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (13C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized 13C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized 13C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized 13C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized 13C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.
Effects of community-embedded care management model on patients, providers, and payors.
Authors: Sheryl Riley, Samantha Manns
Journal: Journal of Clinical Oncology (2018)

44 Background: Comprehensive oncology care management is commonly built on expert clinical support and coordinated services, but lacks a community focus during critical phases of the cancer journey. However, a community-embedded approach extends past practice walls by incorporating local resources and identifying barriers to care in-between office visits. The cycle of care management adheres to the following objectives: Improve health outcomes; Engage the patient, their family and healthcare team; Advance payor efficiency and cost savings; Support the treatment plan in the community. Methods: Stratification Technology Platform &amp; Levels of Care: A risk-based process is implemented through proprietary stratification software, which combines all data points of the healthcare system. A three-step risk acuity score is calculated for each patient based on claims data, diagnoses and disabilities to assure care is tailored to meet individual needs. Patients are then designated to care programs in accordance to their various risk levels. This allows for personalized care plans and staff workflows. Care Teams: Teams of a care coordinator, registered nurse and social worker provide consistent healthcare navigation, monitor patients’ treatment adherence and improve health outcomes. They act as a safety net for patients and their families at all times. Results: 31% decrease in ER visits; 51% decrease in hospital admissions; Hospice conversion at 8x national average; Improved side effects management; ROI of 3:1. Conclusions: Through community-embedded oncology care management, patients not only receive the proper level of care, but also show various improved health outcomes. Providers and patients see decreased emergency room visits, shorter hospital stays and improved quality of life, while payers experience tremendous cost savings due to smarter spending and utilization management. Practices continue to recognize community-embedded care management as a transformative standard of treatment that is central to positive health outcomes. However, there is always more to learn and improve upon, so constant evaluations of quality metrics are essential to provide the very best to patients, providors and payers.
The impact of physician communication on diabetes management in cancer survivors.
Authors: Yvonne Okaka, Kimberly A. Muellers, Juan P. Wisnivesky, Jenny J. Lin
Journal: Journal of Clinical Oncology (2018)

77 Background: As cancer survivors live longer and many die from other comorbidities, it becomes increasingly important to understand factors associated with self-management behaviors for common comorbidities such as diabetes (DM). Provider guidance and inclusive communication have been found to promote self- management behaviors (SMB) in patients with DM. This study aims to explore the impact of provider communication on DM SMB in cancer survivors with DM. Methods: Patients with pre-existing DM who were newly diagnosed with early-stage breast, prostate, colorectal or lung cancer were enrolled. The Summary of Diabetes Self-Care Activities instrument was used to assess patients’ SMBs. The Patient Reaction Assessment scale was used to assess physician communication. Additional survey questions elicited the range of DM self-care recommendations made by patients’ healthcare providers. Mann-Whitney U test was used to assess the association between provider recommendations and communication and SMBs. Results: Of the 74 patients enrolled, the average age was 62 years and 64% were female. Patients who reported their healthcare providers recommended exercise reported more days of specific physical activity (median 5 vs. 0, p = 0.029). Patients who reported that their providers recommended checking their sugar checked their blood sugar more days out of the last 7 days (median 4 vs. 0, p &lt; 0.001). Patients who reported that is hard to talk to their provider about how their treatment is going reported eating more sweets per week (median 2 vs. 1, p = 0.015) and fewer vegetables (median 0 vs. 1, p = 0.043). Conversely, patients who felt that their providers were interested in them as a person reported following a healthful eating plan for more days in a week (median 5.5 vs. 2, p = 0.016) and checked their feet more often (median 6.5 vs. 0, p = 0.008). Conclusions: Cancer survivors with DM whose healthcare providers recommend specific DM SMBs and who report better provider relationships perform DM SMBs more often. Healthcare providers should recognize that supportive recommendations for diet and exercise may improve survivors’ self-management of comorbidities.
Patient (pt)-reported function and symptoms in APHINITY: A randomized comparison of chemotherapy (C) + trastuzumab (H) + placebo (Pla) versus C + H + pertuzumab (P) as adjuvant therapy in pts with HER2-positive early breast cancer (EBC).
Authors: Jose Baselga, Jennifer A. Petersen, Emma Clark, Claire Barton, Eleonora Restuccia, Marion Jennifer Procter, Amir Sonnenblick, Debora Fumagalli, Damian Parlier, Amal Arahmani, Giuseppe Viale, Linda L. Reaby, Elizabeth Frank, Richard D. Gelber, Martine J. Piccart-Gebhart, Jose Bines, Gunter von Minckwitz, Sabina McGarrahan Gasper
Journal: Journal of Clinical Oncology (2018)

521 Background: In APHINITY (NCT01358877), adding P to H + C significantly improved invasive disease-free survival in pts with HER2-positive EBC (von Minckwitz, NEJM 2017). Pt-reported health-related quality of life (HRQoL; symptoms of therapy, patient functioning, and global health status) was a secondary outcome, assessed by EORTC QLQ-C30, QLQ-BR23, and EQ-5D 3L questionnaires. Methods: Pts received 1 year (18 cycles) of P or Pla and H + standard adjuvant C (3–4 cycles of anthracycline-based C followed by 3–4 cycles of taxane, or 6 cycles of docetaxel + carboplatin). Pts completed measures until recurrence or 36 months post-randomization (whichever was first). Assessments were performed at screening, end of anthracycline, taxane, and HER2-targeted therapy, at Week 25, and at 6, 12, and 24 months following the end of HER2-targeted therapy. Mean and mean change from baseline (BL) scores were assessed in each arm and time point; results were defined as clinically meaningful if they differed by ± 10 points (Osoba, JCO 1998). Results: Questionnaire completion rates were > 85% throughout. Mean physical function scores (SD; 95% CI) decreased from BL to Week 13 (end of taxane): –10.7 (17.2; –11.4, –10.0) with P and –10.6 (17.7; –11.4, –9.9) with Pla during C. Scores returned to BL during HER2-targeted treatment. There was no clinically meaningful decline in role function from BL to Week 13 in either arm: –8.0 (28.6; –9.2, –6.8) with P and –8.5 (29.5; –9.8, –7.3) with Pla during C. Diarrhea symptom score differences from BL were clinically meaningful with P (at Week 13), and scores returned to BL at the end of targeted therapy (P + H). Diarrhea symptom scores were worst at Week 13 in both arms (P +22.3 [29.8; 21.0, 23.6]; Pla +9.2 [23.9; 8.2, 10.2]). Conclusions: In one of the largest HRQoL data sets reported to date in HER2-positive EBC, there was no clinically meaningful worsening of role function, indicating that patients' abilities to conduct daily activities did not differ by treatment arm. Patient-reported diarrhea symptoms worsened to a greater extent in the P arm during both C and HER2-targeted treatment. Clinical trial information: NCT01358877.
Validation of the prognostic value of the knowledge bank approach to determine AML prognosis in real life
Authors: Sarah Huet, Etienne Paubelle, Camille Lours, Beatrice Grange, Lucien Courtois, Kaddour Chabane, Carole Charlot, Isabelle Mosnier, Thomas Simonet, Sandrine Hayette, Isabelle Tigaud, Xavier Thomas, Gilles Salles, Fabien Subtil, Pierre Sujobert
Journal: Blood (2018)
Platinum(IV) complex-based two-in-one polyprodrug for a combinatorial chemo-photodynamic therapy
Authors: Dongbo Guo, Shuting Xu, Yu Huang, Huangyong Jiang, Wumaier Yasen, Nan Wang, Yue Su, Jiwen Qian, Jing Li, Chuan Zhang, Xinyuan Zhu
Journal: Biomaterials (2018)
Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With<i>EGFR</i>-Mutated Advanced Non–Small Cell Lung Cancer
Authors: Pedro N. Aguiar, Benjamin Haaland, Wungki Park, Pui San Tan, Auro del Giglio, Gilberto de Lima Lopes
Journal: JAMA Oncology (2018)

The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients.The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC.For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time horizon. All direct costs were based on US and Brazilian payer perspectives.The main outcome of this study was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained by using osimertinib compared with first- or second-generation EGFR-TKIs in previously untreated EGFR-mutated NSCLC.In the base case using the data as reported in the FLAURA trial, the incremental QALY for osimertinib was 0.594 compared with the first- and second-generation EGFR-TKIs. In the United States, the osimertinib ICERs were $226 527 vs erlotinib, $231 123 vs gefitinib, and $219 874 vs afatinib. In Brazil, the ICERs were $162 329, $180 804, and $175 432, respectively. The overall survival (95% CI) reported in the FLAURA trial (hazard ratio, 0.63; 95% CI, 0.45-0.88) had the strongest association with the ICER (ranging from $84 342 to $859 771). Osimertinib price adjustments to the FLAURA trial data improved cost-effectiveness. For example, a discount of 10% on osimertinib acquisition cost was associated with a 20% decreased ICER compared with the base case ICER, and a discount of 20% on osimertinib acquisition cost was associated with a 40% decreased ICER compared with the base case ICER.At current costs, by World Health Organization cost-effectiveness threshold criteria, osimertinib is not cost-effective for first-line therapy of EGFR-mutated NSCLC in either the United States or Brazil.
A smart bilayered scaffold supporting keratinocytes and muscle cells in micro/nano-scale for urethral reconstruction
Authors: XiangGuo Lv, Chao Feng, YiDong Liu, XuFeng Peng, ShiYan Chen, DongDong Xiao, HuaPing Wang, Zhe Li, YueMin Xu, MuJun Lu
Journal: Theranostics (2018)

Rationale:In urethral tissue engineering, the currently available reconstructive procedures are insufficient due to a lack of appropriate scaffolds that would support the needs of various cell types.To address this problem, we developed a bilayer scaffold comprising a microporous network of silk fibroin (SF) and a nanoporous bacterial cellulose (BC) scaffold and evaluated its feasibility and potential for long-segment urethral regeneration in a dog model.Methods: The freeze-drying and self-assembling method was used to fabricate the bilayer scaffold by stationary cultivation G. xylinus using SF scaffold as a template.The surface morphology, porosity and mechanical properties of all prepared SF-BC scaffolds were characterized using Scanning electron microscopy (SEM), microcomputed tomography and universal testing machine.To further investigate the suitability of the bilayer scaffolds for tissue engineering applications, biocompatibility was assessed using an MTT assay.The cell distribution, viability and morphology were evaluated by seeding epithelial cells and muscle cells on the scaffolds, using the 3D laser scanning confocal microscopy, and SEM.The effects of urethral reconstruction with SF-BC bilayer scaffold was evaluated in dog urethral defect models.Results: Scanning electron microscopy revealed that SF-BC scaffold had a clear bilayer structure.The SF-BC bilayer scaffold is highly porous with a porosity of 85%.The average pore diameter of the porous layer in the bilayer SF-BC composites was 210.2±117.8μm.Cultures established with lingual keratinocytes and lingual muscle cells confirmed the suitability of the SF-BC structures to support cell adhesion and proliferation.In addition, SEM demonstrated the ability of cells to attach to scaffold surfaces and the biocompatibility of the matrices with cells.At 3 months after implantation, urethra reconstructed with the SF-BC scaffold seeded with keratinocytes and muscle cells displayed superior structure compared to those with only SF-BC scaffold.Principal Conclusion: These results demonstrate that the bilayer SF-BC scaffold may be a promising biomaterial with good biocompatibility for urethral regeneration and could be used for numerous other types of hollow-organ tissue engineering grafts, including vascular, bladder, ureteral, bowel, and intestinal.
Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study
Authors: Atul Deodhar, Alice B Gottlieb, Wolf-Henning Boehncke, Bin Dong, Yuhua Wang, Yanli Zhuang, William Barchuk, Xie L Xu, Elizabeth C Hsia, Jacob AELION, Juan AMARELO-RAMOS, Alejandro BALSA, Florian BERGHEA, Jan BRZEZICKI, Michael BURNETTE, Scott FRETZIN, Sara GARCÍA-CARAZO, Geoffrey GLADSTEIN, Juan GOMEZ-REINO, Melinda GOODERHAM, Carlos GONZÁLEZ-FERNÁNDEZ, Alice GOTTLIEB, Jordi GRATACOS, Derek HAALAND, Rima KAMALOVA, Piotr LESZCZYNSKI, Emilio MARTIN-MOLA, Alexey MASLYANSKY, Federico NAVARRO, Daniela OPRIS, Kim PAPP, Yuriy PERLAMUTROV, Sandra PHILIPP, Artur RACEWICZ, Andrey REBROV, Maria RELL-BAKALARSKA, David ROSMARIN, Andrea RUBBERT-ROTH, William SHERGY, Ivan SHIRINSKY, Dmitry SONIN, Marina STANISLAV, Alexey SUKHAREV, Vadim TEMNIKOV, Irina VINOGRADOVA, Paul WAYTZ, Vladimir YAKUSHEVICH
Journal: The Lancet (2018)
A continuum of HIV care describing mortality and loss to follow-up: a longitudinal cohort study
Authors: Sophie Jose, Valerie Delpech, Alison Howarth, Fiona Burns, Teresa Hill, Kholoud Porter, Caroline A Sabin, Jonathan Ainsworth, Sris Allan, Jane Anderson, Abdel Babiker, David R Chadwick, Duncan Churchill, David Dunn, Richard Gilson, Mark Gompels, Phillip Hay, Margaret Johnson, Stephen Kegg, Clifford Leen, Fabiola Martin, Dushyant Mital, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Frank Post, Jillian Pritchard, Achim Scwenk, Anjum Tariq, Roy Trevelion, Andy Ustianowski, John Walsh
Journal: The Lancet HIV (2018)

BackgroundThe cross-sectional HIV care continuum is widely used to assess the success of HIV care programmes among populations of people with HIV and the potential for ongoing transmission. We aimed to investigate whether a longitudinal continuum, which incorporates loss to follow-up and mortality, might provide further insights about the performance of care programmes.MethodsIn this longitudinal cohort study, we included individuals who entered the UK Collaborative HIV Cohort (CHIC) study between Jan 1, 2000, and Dec 31, 2004, and were linked to the national HIV cohort database (HIV and AIDS Reporting System). For each month during a 10 year follow up period, we classified individuals into one of ten distinct categories according to engagement in care, antiretroviral therapy (ART) use, viral suppression, loss to cohort follow-up and loss to care, and mortality, and assessed the proportion of person-months of follow-up spent in each stage of the continuum. 5 year longitudinal continuums were also constructed for three separate cohorts (baseline years of entry 2000–03, 2004–07, and 2008–09) to compare changes over time.FindingsWe included 12 811 people contributing 1 537 320 person-months in our analysis. During 10 years of follow-up, individuals spent 811 057 (52·8%) of 1 537 320 person-months on ART. Of the 811 057 person-months spent on ART, individuals had a viral load of 200 copies per mL or less for 607 185 (74·9%) person-months. 10 years after cohort entry, 3612 (28·1%) of 12 811 individuals were lost to follow-up, 954 (26·4%) of whom had transferred to a non-CHIC UK clinic for care. By 10 years, 759 (5·9%) of 12 811 participants who entered the cohort had died. Loss to follow-up decreased and the proportion of person-months that individuals spent virally suppressed increased over calendar time.InterpretationLoss to follow-up in HIV care programmes was high and rates of viral suppression were lower than previously reported. Complementary information provided by a longitudinal continuum might highlight areas for intervention along the HIV care pathway, however, transfers outside the cohort must be accounted for.FundingMedical Research Council, UK.
The growth and strategic functioning of One Health networks: a systematic analysis
Authors: Mishal S Khan, Peregrine Rothman-Ostrow, Julia Spencer, Nadeem Hasan, Mirzet Sabirovic, Afifah Rahman-Shepherd, Nabila Shaikh, David L Heymann, Osman Dar
Journal: The Lancet Planetary Health (2018)

The recent increase in attention to linkages between human health, animal health, and the state of the environment has resulted in the rapid growth of networks that facilitate collaboration between these sectors. This study ascertained whether duplication of efforts is occurring across networks, which stakeholders are being engaged, and how frequently monitoring and evaluation of investments is being reported.This study is a systematic analysis of One Health networks (OHNs) in Africa, Asia, and Europe. We defined an OHN as an engagement between two or more discrete organisations with at least two of the following sectors represented: animal health, human health, and the environment or ecosystem. Between June 5 and Sept 29, 2017, we systematically searched for OHNs in PubMed, Google, Google Scholar, and relevant conference websites. No language restrictions were applied, but we were only able to translate from English and French. Data about OHNs, including their year of initiation, sectors of engagement, regions of operation, activities conducted, and stakeholders involved, were extracted with a standardised template and analysed descriptively.After screening 2430 search results, we identified and analysed 100 unique OHNs, of which 86 were formed after 2005. 32 OHNs covered only human and animal health, without engaging with the role of the environment on health. 78 OHNs involved academic bodies and 78 involved government bodies, with for-profit organisations involved in only 23 and community groups involved in only ten. There were few collaborations exclusively between networks in the developing world (four OHNs) and only 15 OHNs reported monitoring and evaluation information. The majority of OHNs worked on supporting communication, collaboration, information sharing, and capacity building.Amid concerns about there being insufficient strategic direction and coordination in the growth of OHNs, our study provides empirical evidence about limitations in stakeholder representation, apparently absent or ambiguous monitoring and evaluation structures, and potential areas of duplication. The collective strategic functioning of OHNs might be improved by more transparent reporting of goals and outcomes of OHN activities, as well as more collaborations led by networks within the developing world and increased attention to environmental health.None.