tbuckley/cabot-search huggingface dataset:
Effect and cost-effectiveness of pneumococcal conjugate vaccination: a global modelling analysis
Authors: Cynthia Chen, Francisco Cervero Liceras, Stefan Flasche, Sucitro Sidharta, Joanne Yoong, Neisha Sundaram, Mark Jit
Journal: The Lancet Global Health (2018)

BackgroundIntroduction of pneumococcal conjugate vaccines (PCVs) has substantially reduced disease burden due to Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. However, PCVs are among the most expensive vaccines, hindering their introduction in some settings and threatening sustainability in others. We aimed to assess the effect and cost-effectiveness of introduction of 13-valent PCV (PCV13) vaccination globally.MethodsWe assessed the incremental cost-effectiveness ratio of PCV13 introduction by integrating two models: an ecological model (a parsimonious, mechanistic model validated with data from post-seven-valent PCV introduction in 13 high-income settings) to predict the effect of PCV on childhood invasive pneumococcal disease, and a decision-tree model to predict a range of clinical presentations and economic outcomes under vaccination and no-vaccination strategies. The models followed 30 birth cohorts up to age 5 years in 180 countries from 2015 to 2045. One-way scenario and probabilistic sensitivity analyses were done to explore model uncertainties.FindingsWe estimate that global PCV13 use could prevent 0·399 million child deaths (95% credible interval 0·208 million to 0·711 million) and 54·6 million disease episodes (51·8 million to 58·1 million) annually. Global vaccine costs (in 2015 international dollars) of $15·5 billion could be partially offset by health-care savings of $3·19 billion (2·62 billion to 3·92 billion) and societal cost savings of $2·64 billion (2·13 billion to 3·28 billion). PCV13 use is probably cost-effective in all six UN regions. The 71 countries eligible for support from Gavi, the Vaccine Alliance, account for 83% of PCV13-preventable deaths but only 18% of global vaccination costs. The expected cost of PCV vaccination globally is around $16 billion per year.InterpretationOur findings highlight the value of Gavi's support for PCV introduction in low-income countries and of efforts to improve the affordability of PCVs in countries not eligible for, or transitioning from, Gavi support.FundingWorld Health Organization; Gavi, the Vaccine Alliance; and the Bill & Melinda Gates Foundation.
Can Local Ablative Radiotherapy Revert Castration-resistant Prostate Cancer to an Earlier Stage of Disease?
Authors: Fabian Lohaus, Klaus Zöphel, Steffen Löck, Manfred Wirth, Jörg Kotzerke, Mechthild Krause, Michael Baumann, Esther G.C. Troost, Tobias Hölscher
Journal: European Urology (2018)
The PIK3CA E542K and E545K mutations promote glycolysis and proliferation via induction of the β-catenin/SIRT3 signaling pathway in cervical cancer
Authors: Wei Jiang, Tiancong He, Shuai Liu, Yingying Zheng, Libing Xiang, Xuan Pei, Ziliang Wang, Huijuan Yang
Journal: Journal of Hematology & Oncology (2018)

The study aims to present the effect of PIK3CA E542K and E545K mutations on glucose metabolism and proliferation and identify their underlying mechanisms in cervical cancer. The maximum standard uptake value (SUVmax) of tumors was detected by18F-FDG PET/CT scan. In vitro, glycolysis analysis, extracellular acidification rate analysis, and ATP production were used to evaluate the impact of PIK3CA E542K and E545K mutations on glucose metabolism. The expression level of key glycolytic enzymes was evaluated by western blotting and immunohistochemical staining in cervical cancer cells and tumor tissues, respectively. Immunofluorescence analysis was used to observe the nuclear translocation of β-catenin. The target gene of β-catenin was analyzed by using luciferase reporter system. The glucose metabolic ability of the xenograft models was assessed by SUVmax from microPET/CT scanning. Cervical cancer patients with mutant PIK3CA (E542K and E545K) exhibited a higher SUVmax value than those with wild-type PIK3CA (P = 0.037), which was confirmed in xenograft models. In vitro, enhanced glucose metabolism and proliferation was observed in SiHa and MS751 cells with mutant PIK3CA. The mRNA and protein expression of key glycolytic enzymes was increased. AKT/GSK3β/β-catenin signaling was highly activated in SiHa and MS751 cells with mutant PIK3CA. Knocking down β-catenin expression decreased glucose uptake and lactate production. In addition, the nuclear accumulation of β-catenin was found in SiHa cells and tumors with mutant PIK3CA. Furthermore, β-catenin downregulated the expression of SIRT3 via suppressing the activity of the SIRT3 promotor, and the reduced glucose uptake and lactate production due to the downregulation of β-catenin can be reversed by the transfection of SIRT3 siRNA in SiHa cells with mutant PIK3CA. The negative correlation between β-catenin and SIRT3 was further confirmed in cervical cancer tissues. These findings provide evidence that the PI3K E542K and E545K/β-catenin/SIRT3 signaling axis regulates glucose metabolism and proliferation in cervical cancers with PIK3CA mutations, suggesting therapeutic targets in the treatment of cervical cancers. FUSCC 050432–4-1212B. Registered 24 December 2012 (retrospectively registered).
Abstract P279: Racial/Ethnic Differences in the Association Between Ready-to-eat and Ready-to-heat Meal Consumption and Obesity
Authors: Chelsea R Singleton, Angela Odoms-Young, Lisa M Powell
Journal: Circulation (2017)

Introduction: Convenience meals that are ready-to-eat (RTE) or ready-to-heat (RTH) are typically considered unhealthy choices because they are often high in saturated fat, sodium, sugar, or processed foods. Frequent RTE and RTH meal consumption is hypothesized to increase obesity risk. This research aimed to examine differences in RTE and RTH meal consumption by race/ethnicity in a large sample of US adults. Furthermore, we aimed to determine if associations between RTE and RTH meal consumption and obesity differ by race/ethnicity. Hypothesis: Differences in RTE and RTH meal consumption will exist between racial/ethnic groups. RTE and RTH meal consumption will be associated with increased body mass index (BMI) among all racial/ethnic groups. Methods: Cross-sectional data on 14,307 participants of the National Health and Nutrition Examination Survey (NHANES) years 2009-2012 were analyzed. Participants were 49.0% Non-Hispanic white, 23.2% Non-Hispanic black, and 27.8% Hispanic or Latino. Self-reported food purchasing behaviors were captured via a questionnaire. Participants were asked to record the total number of RTE meals (i.e. meals prepared away from home at a food retail outlet) they consumed in the past 7 days, and the total number of RTH meals (i.e. frozen meals) they consumed in the past 30 days. Stratified multivariable-adjusted linear regression models were used to examine associations between RTE and RTH meal consumption and BMI by racial/ethnic group. Analyses were adjusted for the NHANES sampling scheme. Results: Mean BMI was 28.1 (±0.1). About 39% of participants were obese. On average, Non-Hispanic white participants consumed significantly more RTE meals and RTH meals than Non-Hispanic black and Hispanic participants. Hispanic participants, on average, consumed RTE and RTH meals the least. After adjusting for covariates such as age, education level, household size, and participation in the Supplemental Nutrition Assistance Program, increased consumption of RTE meals was significantly associated with increased BMI among Non-Hispanic whites and Non-Hispanic blacks. There was no association between RTE meal consumption and BMI among Hispanics. RTH meal consumption was not associated with BMI among any racial/ethnic group. Conclusions: Racial/ethnic differences in the association between RTE and RTH meal consumption and obesity were observed. More research is needed to better understand the contribution of food purchasing behaviors to racial disparities in chronic disease.
When should surgeons begin surveillance with CT scans after lobectomy for stage 1A non-small cell lung cancer?
Authors: Mohan K. Mallipeddi, Walid R. Eltaraboulsi, Adam R. Shoffner, Ibtehaj A. Naqvi, Thomas A. D'Amico, Mark W. Onaitis, Mark F. Berry
Journal: Journal of Clinical Oncology (2014)

7549 Background: Guidelines for surveillance after resection of stage 1A non-small cell lung cancer (NSCLC) vary in terms of recommended modality and frequency. The purpose of this study was to assess the optimal time to start surveillance when using CT scans. Methods: All patients who underwent lobectomy from 1996 to 2010 for stage 1A NSCLC without induction or adjuvant therapy and who had CT surveillance that started within 15 months of resection were reviewed. Only patients followed for at least two years or until new or recurrent disease was discovered were included. Patients were grouped as “early CT” if their initial surveillance CT scan was 6±3 months after lobectomy and “late CT” if their initial surveillance CT scan was 12±3 months after lobectomy. Between the two groups, the incidence of new or recurrent disease on the initial CT scan was compared using Fisher’s exact test and overall survival was compared using the log-rank test. Results: During the study period, 198 patients met inclusion criteria. There were 99 cases in both the early and late CT groups. Overall, 11% of patients (21/198; 8 local only, 13 distant) had recurrent disease and 16% of patients (31/198) were found to have new primaries over their follow up period. On average, recurrent disease was found 26±19.8 months and new primaries were found 45.7±28.9 months after resection (p=0.009). For the 31 patients with new primaries, 29 (94%) received some form of local therapy; surgery was used in 21 patients (68%). Repeat surgery was used in 3 of the 8 patients with local recurrence (37.5%), though 2 of these 3 developed contralateral lung metastases within 4 years of reoperation. In the early CT group, new or recurrent disease was found on the initial surveillance scan in 2% of patients (2/99) compared to 4% of patients (4/99) in the late CT group (p=0.7). The 5-year survival from initial resection of the two groups was not significantly different. Conclusions: Both recurrent disease and new primary cancers are relatively common after lobectomy for stage 1A NSCLC, but rarely are evident on CT scan within 15 months of surgery. Waiting to starting CT scan surveillance until 9 to 15 months after surgery is unlikely to miss clinically important findings.
FPA144, a humanized monoclonal antibody for both <i>FGFR2</i>-amplified and nonamplified, <i>FGFR2b</i>-overexpressing gastric cancer patients.
Authors: Kristen L. Pierce, Amit M. Deshpande, Bradley A. Stohr, Abigael T. Gemo, Namrata S. Patil, Thomas J. Brennan, David I. Bellovin, Servando Palencia, Tina Giese, Carol Huang, Kevin P. Baker, W. Michael Kavanaugh, Julie Hambleton, Gerrit Los
Journal: Journal of Clinical Oncology (2014)

e15074 Background: Amplification of the Fibroblast Growth Factor Receptor 2 (FGFR2) gene is reported in ~5% of gastric cancer patients and leads to the specific overexpression of the FGFR2b isoform of the receptor. Five Prime Therapeutics has developed an FGFR2b-specific antibody, FPA144, for treating gastric cancer patients with FGFR2 amplification. We are also investigating the utility of FPA144 in patients with FGFR2b overexpression that lack FGFR2 gene amplification. Results: We developed an FGFR2b-specific antibody for immunohistochemistry (IHC). In a cohort of 186 gastric cancer samples from mostly Asian and Eastern European patients, 6.7% of the samples had FGFR2 amplification as measured by fluorescent in situ hybridization, consistent with published reports. Using our proprietary antibody and IHC methods, we identified an additional 10% of cases with FGFR2b protein overexpression in the absence of FGFR2amplification. These data suggest that as many as 17% of gastric cancer patients may benefit from treatment with FPA144. Amplification of the FGFR2 gene is an oncogenic driver in gastric cancer. It is unknown whether tumors that overexpress FGFR2b without gene amplification are also dependent on FGFR2b signaling. To maximize the potential to treat patients efficaciously with both gene amplified, and non-gene amplified FGFR2b-overexpressing tumors, we designed FPA144 not only to block FGFR2b signaling but to also mediate direct tumor cell killing by enhanced antibody-dependent cellular cytotoxicity (ADCC). We show that FPA144 effectively mediates ADCC against cells that express FGFR2b, but not cells that express other FGFR isoforms. Data will be presented that FPA144 is highly effective in preclinical tumor models. Further, we show that FPA144, unlike small molecule FGFR tyrosine kinase inhibitors, does not produce hyperphosphatemia, and we therefore expect a favorable toxicology profile. Conclusions: We anticipate starting a clinical trial of FPA144 in the last quarter of 2014. We plan to enroll gastric cancer patients with either FGFR2 gene amplification or FGFR2b overexpression without amplification for evaluating efficacy in our Phase Ib trial.
Engineering Bioactive Self-Healing Antibacterial Exosomes Hydrogel for Promoting Chronic Diabetic Wound Healing and Complete Skin Regeneration
Authors: Chenggui Wang, Min Wang, Tianzhen Xu, Xingxing Zhang, Cai Lin, Weiyang Gao, Huazi Xu, Bo Lei, Cong Mao
Journal: Theranostics (2018)

Rationale: Chronic nonhealing diabetic wound therapy and complete skin regeneration remains a critical clinical challenge. The controlled release of bioactive factors from a multifunctional hydrogel was a promising strategy to repair chronic wounds. Methods: Herein, for the first time, we developed an injectable, self-healing and antibacterial polypeptide-based FHE hydrogel (F127/OHA-EPL) with stimuli-responsive adipose-derived mesenchymal stem cells exosomes (AMSCs-exo) release for synergistically enhancing chronic wound healing and complete skin regeneration. The materials characterization, antibacterial activity, stimulated cellular behavior and in vivo full-thickness diabetic wound healing ability of the hydrogels were performed and analyzed. Results: The FHE hydrogel possessed multifunctional properties including fast self-healing process, shear-thinning injectable ability, efficient antibacterial activity, and long term pH-responsive bioactive exosomes release behavior. In vitro, the FHE@exosomes (FHE@exo) hydrogel significantly promoted the proliferation, migration and tube formation ability of human umbilical vein endothelial cells (HUVECs). In vivo, the FHE@exo hydrogel significantly enhanced the healing efficiency of diabetic full-thickness cutaneous wounds, characterized with enhanced wound closure rates, fast angiogenesis, re-epithelization and collagen deposition within the wound site. Moreover, the FHE@exo hydrogel displayed better healing outcomes than those of exosomes or FHE hydrogel alone, suggesting that the sustained release of exosomes and FHE hydrogel can synergistically facilitate diabetic wound healing. Skin appendages and less scar tissue also appeared in FHE@exo hydrogel treated wounds, indicating its potent ability to achieve complete skin regeneration. Conclusion: This work offers a new approach for repairing chronic wounds completely through a multifunctional hydrogel with controlled exosomes release.
Genotype-Guided Medical Treatment of an Arteriovenous Malformation in a Child
Authors: Ramrada Lekwuttikarn, Young H. Lim, Shehla Admani, Keith A. Choate, Joyce M. C. Teng
Journal: JAMA Dermatology (2018)

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Abstract 13720: Mitral Valve Prolapse And Sudden Death: A Systematic Review
Authors: Chrishan J Nalliah, Rajiv Mahajan, Haris Haqqani, Dennis H Lau, Jitendra Vohra, Joseph B Morton, Jonathan M Kalman, Prashanthan Sanders
Journal: Circulation (2015)

Introduction: Mitral valve prolapse (MVP) is commonly observed as a benign finding in the general population. There is a suggestion from the literature that MVP is associated with unexplained sudden cardiac death (SCD) in patients with otherwise “structurally normal hearts”. Aim: We performed a systematic review 1) to determine the prevalence of MVP in unexplained SCD cohorts, 2) to determine the presence of MVP in the general population and 3) to evaluate the incidence of SCD in patients with MVP. Methods: An electronic search of the English medical literature (Pubmed, Medline, Cochrane and EMBase) was conducted on 1st July 2014. 667 references were imported into Endnote and reviewed. Reference lists of relevant studies and review articles were screened to retrieve non-indexed articles. All patients with known precipitants for death or cardiac arrest were excluded. 20 studies were identified with 13 examining MVP in unexplained SCD and 7 examining SCD in patients with MVP. A random effects model was utilized and meta-analysis was performed using STATA version 13.0. Results: The cause for SCD was not identified in 28.3% of autopsy studies. The prevalence of MVP in cohorts with unexplained SCD was 13.3% (95% CI 6.8, 21.3). The community prevalence of MVP was 1.6% (95% CI 1, 2.8) and the incidence of unexplained SCD in the MVP population was 0.2% (0.1, 0.3) per year. Based on current census data, we project that MVP presently affects approximately 5.1 million people in the United States and is estimated to climb to 6.3 million by 2050. Accordingly, the number of SCD victims with MVP will climb from 10, 200 to 12, 600. Bileaflet prolapse, moderate to severe mitral regurgitation, ventricular fibrosis and ventricular ectopy were observed more commonly in patients with unexplained SCD and MVP. Conclusion: The prevalence of MVP in victims of unexplained SCD is high. Although the incidence of life threatening arrhythmic events in the general MVP population remains low, the absolute number of people exposed to the risk of SCD will be large given the high prevalence of MVP. Further work is required to delineate potential risk factors for sudden death in patients with MVP.
Myeloid immune-checkpoint inhibition enters the clinical stage
Authors: Timo K. van den Berg, Thomas Valerius
Journal: Nature Reviews Clinical Oncology (2018)

The first-in-human study of anti-CD47 antibodies blocking CD47–SIRPα interactions in combination with rituximab in patients with non-Hodgkin lymphoma shows encouraging clinical responses accompanied with mild levels of toxicity. Inhibition of the CD47–SIRPα interaction might provide a generic method of promoting the effects of antitumour antibodies in a variety of cancer types. This reveals, for the first time, an innate immune checkpoint as a bona fide target for therapy.
Harnessing the untapped potential of nucleotide‐binding oligomerization domain ligands for cancer immunotherapy
Authors: Sanja Nabergoj, Irena Mlinarič‐Raščan, Žiga Jakopin
Journal: Medicinal Research Reviews (2018)

Abstract In the last decade, cancer immunotherapy has emerged as an effective alternative to traditional therapies such as chemotherapy and radiation. In contrast to the latter, cancer immunotherapy has the potential to distinguish between cancer and healthy cells, and thus to avoid severe and intolerable side‐effects, since the cancer cells are effectively eliminated by stimulated immune cells. The cytosolic nucleotide‐binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are important components of the innate immune system and constitute interesting targets in terms of strengthening the immune response against cancer cells. Many NOD ligands have been synthesized, in particular NOD2 agonists that exhibit favorable immunostimulatory and anticancer activity. Among them, mifamurtide has already been approved in Europe by the European Medicine Agency for treating patients with osteosarcoma in combination with chemotherapy after complete surgical removal of the primary tumor. This review is focused on NOD receptors as promising targets in cancer immunotherapy as well as summarizing current knowledge of the various NOD ligands exhibiting antitumor and even antimetastatic activity in vitro and in vivo.
Assessment of Quality of Life Following Allogeneic Stem Cell Transplant for Myelofibrosis
Authors: Jeanne Palmer, Heidi E. Kosiorek, Christine Wolschke, Veena D. S. Fauble, Richard Butterfield, Holly Geyer, Robyn M. Scherber, Amylou C. Dueck, Allison Gathany, Ruben A. Mesa, Nicolaus Kroeger
Journal: Blood (2018)