tbuckley/cabot-search huggingface dataset:
Physicians' responsibility for planetary health
Authors: Adrian Mathias Moser, Florian L Stigler, Bernd Haditsch
Journal: The Lancet Planetary Health (2017)

Ecosystems worldwide are threatened by climate change and a massive reduction in biodiversity.1Scheffers BR De Meester L Bridge TC et al.The broad footprint of climate change from genes to biomes to people.Science. 2016; 354: 6313Crossref Scopus (606) Google Scholar The main causes are human emissions of greenhouse gases, agriculture, deforestation, and overfishing, all of which are often driven by food production.2Tilman D Clark M Global diets link environmental sustainability and human health.Nature. 2014; 515: 518-522Crossref PubMed Scopus (1745) Google Scholar Because human life depends on the stability of the earth's ecosystems, the destabilisation of planetary health3Whitmee S Haines A Beyrer C et al.Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation-Lancet Commission on planetary health.Lancet. 2015; 386: 1973-2028Summary Full Text Full Text PDF PubMed Scopus (1122) Google Scholar represents the greatest challenge of our time, and the future of our species will depend on the actions we take. Physicians around the world counsel millions of patients every day and enjoy societies' recognition and trust. These attributes offer physicians large personal and political influence; as such, physicians should become aware of their potentially healing role, not only for patients' health, but also for planetary health. In promoting healthy lifestyles, physicians should consider that animal products are not only an independent risk factor for cardiovascular disease4Koeth RA Wang Z Levison BS et al.Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.Nat Med. 2013; 19: 576-585Crossref PubMed Scopus (2700) Google Scholar and cancer,5Bouvard V Loomis D Guyton KZ et al.Carcinogenicity of consumption of red and processed meat.Lancet Oncol. 2015; 16: 1599-1600Summary Full Text Full Text PDF PubMed Scopus (1031) Google Scholar but also that their production causes 25% of global greenhouse gas emissions2Tilman D Clark M Global diets link environmental sustainability and human health.Nature. 2014; 515: 518-522Crossref PubMed Scopus (1745) Google Scholar and harms biodiversity2Tilman D Clark M Global diets link environmental sustainability and human health.Nature. 2014; 515: 518-522Crossref PubMed Scopus (1745) Google Scholar due to its large land requirements. Therefore, physicians should use their societal influence for the common good and advocate for healthy lifestyles and healthy public policies aligning efforts of medicine, public health, and planetary health.3Whitmee S Haines A Beyrer C et al.Safeguarding human health in the Anthropocene epoch: report of The Rockefeller Foundation-Lancet Commission on planetary health.Lancet. 2015; 386: 1973-2028Summary Full Text Full Text PDF PubMed Scopus (1122) Google Scholar In moving towards a locally produced, biologically grown, plant-based diet, everyone can participate in promoting planetary ecosystem stability and global health. We declare no competing interests.
CRISPR/Cas9-Mediated CCR5 Ablation in Human Hematopoietic Stem/Progenitor Cells Confers HIV-1 Resistance In Vivo
Authors: Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Journal: Molecular Therapy (2017)

Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4+ T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34+ HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdcscid/IL-2Rγnull mice. The CCR5 disruption efficiency in our system remained robust in secondary transplanted repopulating hematopoietic cells. More importantly, an HIV-1 resistance effect was observed as indicated by significant reduction of virus titration and enrichment of human CD4+ T cells. Hence, we successfully established a CRISPR/Cas9 mediated CCR5 ablating system in long-term HSCs, which confers HIV-1 resistance in vivo. Our study provides evidence for translating CCR5 gene-edited HSC transplantation for an HIV cure to the clinic. Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4+ T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34+ HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdcscid/IL-2Rγnull mice. The CCR5 disruption efficiency in our system remained robust in secondary transplanted repopulating hematopoietic cells. More importantly, an HIV-1 resistance effect was observed as indicated by significant reduction of virus titration and enrichment of human CD4+ T cells. Hence, we successfully established a CRISPR/Cas9 mediated CCR5 ablating system in long-term HSCs, which confers HIV-1 resistance in vivo. Our study provides evidence for translating CCR5 gene-edited HSC transplantation for an HIV cure to the clinic.
Progress Toward Measles Elimination — African Region, 2013–2016
Authors: Balcha G. Masresha, Meredith G. Dixon, Jennifer L. Kriss, Reggis Katsande, Messeret E. Shibeshi, Richard Luce, Amadou Fall, Annick R.G.A. Dosseh, Charles R. Byabamazima, Alya J. Dabbagh, James L. Goodson, Richard Mihigo
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In 2011, the 46 World Health Organization (WHO) African Region (AFR) member states established a goal of measles elimination* by 2020, by achieving 1) ≥95% coverage of their target populations with the first dose of measles-containing vaccine (MCV1) at national and district levels; 2) ≥95% coverage with measles-containing vaccine (MCV) per district during supplemental immunization activities (SIAs); and 3) confirmed measles incidence of <1 case per 1 million population in all countries (1). Two key surveillance performance indicator targets include 1) investigating ≥2 cases of nonmeasles febrile rash illness per 100,000 population annually, and 2) obtaining a blood specimen from ≥1 suspected measles case in ≥80% of districts annually (2). This report updates the previous report (3) and describes progress toward measles elimination in AFR during 2013-2016. Estimated regional MCV1 coverage† increased from 71% in 2013 to 74% in 2015.§ Seven (15%) countries achieved ≥95% MCV1 coverage in 2015.¶ The number of countries providing a routine second MCV dose (MCV2) increased from 11 (24%) in 2013 to 23 (49%) in 2015. Forty-one (79%) of 52 SIAs** during 2013-2016 reported ≥95% coverage. Both surveillance targets were met in 19 (40%) countries in 2016. Confirmed measles incidence in AFR decreased from 76.3 per 1 million population to 27.9 during 2013-2016. To eliminate measles by 2020, AFR countries and partners need to 1) achieve ≥95% 2-dose MCV coverage through improved immunization services, including second dose (MCV2) introduction; 2) improve SIA quality by preparing 12-15 months in advance, and using readiness, intra-SIA, and post-SIA assessment tools; 3) fully implement elimination-standard surveillance††; 4) conduct annual district-level risk assessments; and 5) establish national committees and a regional commission for the verification of measles elimination.
Novel Linear Peptides with High Affinity to αvβ3 Integrin for Precise Tumor Identification
Authors: Yi Ma, Guanhua Ai, Congying Zhang, Menglu Zhao, Xue Dong, Zhihao Han, Zhaohui Wang, Min Zhang, Yuxi Liu, Weidong Gao, Siwen Li, Yueqing Gu
Journal: Theranostics (2017)

Development of alternative linear peptides for targeting αvβ3 integrin has attracted much attention, as the traditional peptide ligand, cyclic RGD, is limited by inferior water-solubility and complex synthesis.Using pharmacophore-based virtual screening and high-throughput molecular docking, we identified two novel linear small peptides RWr and RWrNM with high affinity and specificity to αvβ3 integrin.The competitive binding with cyclic RGD (c(RGDyK)) and cellular uptake related to the integrin expression levels verified their affinity to αvβ3 integrin.The intermolecular interaction measurement and dynamics simulation demonstrated the high binding affinity and stability, especially for RWrNM.In vivo peptide-guided tumor imaging and targeted therapy further confirmed their specificity.Results indicated that the newly identified small linear peptide RWrNM, with high affinity and specificity to αvβ3 integrin, better water-solubility, and simplified synthetic process, could overcome limitations of the current cyclic RGD peptides, paving the way for diverse use in diagnosis and therapy.
1997 update of recommendations for the use of tumor markers in breast and colorectal cancer. Adopted on November 7, 1997 by the American Society of Clinical Oncology.
Journal: Journal of Clinical Oncology (1998)

OBJECTIVE The primary objective was to update the 1996 clinical practice guidelines for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast and colorectal cancers. These guidelines are intended for use in the care of patients outside of clinical trials. OPTIONS Six tumor markers for colorectal cancer and eight for breast cancer were considered. They could be recommended or not for routine use or for special circumstances. In addition to carcinoembryonic antigen (CEA) and cancer antigen (CA) 15-3, CA 27.29 also was considered in regard to circulatory tumor markers for breast cancer. OUTCOMES In general, the significant health outcomes identified for use in making clinical practice guidelines (overall survival, disease-free survival, quality of life, lesser toxicity, and cost effectiveness) were used. EVIDENCE A computerized literature search from 1994 to July 1997 was performed. VALUES The same values for Use, Utility, and Levels of Evidence were used by the Committee. BENEFITS, HARMS, AND COSTS The same benefit, harms, and costs were used. RECOMMENDATION No changes in any guidelines were recommended (see text). VALIDATION External review by the American Society of Clinical Oncology (ASCO) Health Services Research Committee and by ASCO Board of Directors. SPONSOR American Society of Clinical Oncology.
A Randomized Phase II Trial of Interferon (IFN)/GM-CSF Versus K562/GM-CSF Vaccination in Chronic Phase CML Patients on Frontline Tyrosine Kinase Inhibitor (TKI) Therapy: Potential of IFN to Enhance Molecular Remissions
Authors: Jonathan Allen Webster, Anna Ferguson, Christopher Gocke, Richard J Jones, Hyam Levitsky, B. Douglas Smith
Journal: Blood (2016)
First-line ribociclib + letrozole in HR+, HER2– ABC: Efficacy by baseline tumor markers
Authors: M. Campone, N. Marschner, C. Villanueva, G.S. Sonke, E. Alba, E. Jakobsen, F. Su, W. He, C. Germa, F. André
Journal: Annals of Oncology (2017)
Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis
Authors: Julia Baumgartl, Stephanie Baudler, Maximilian Scherner, Vladimir R. Babaev, Liza Makowski, Jill Suttles, Marcia McDuffie, Kazuyuki Tobe, Takashi Kadowaki, Sergio Fazio, C. Ronald Kahn, Gökhan S. Hotamisligil, Wilhelm Krone, MacRae F. Linton, Jens C. Brüning
Journal: Cell Metabolism (2006)
Drug “Pent‐Up” in Hollow Magnetic Prussian Blue Nanoparticles for NIR‐Induced Chemo‐Photothermal Tumor Therapy with Trimodal Imaging
Authors: Jinghua Li, Fengshou Zhang, Zhigang Hu, Weidong Song, Guangda Li, Gaofeng Liang, Jun Zhou, Ke Li, Yang Cao, Zhong Luo, Kaiyong Cai
Journal: Advanced Healthcare Materials (2017)

The study reports a biocompatible smart drug delivery system based on a doxorubicin (DOX) blending phase-change material of 1-pentadecanol loaded hollow magnetic Prussian blue nanoparticles, resulting in HMNP-PB@Pent@DOX. The system possesses concentration-dependent high thermogenesis (>50 °C) when applying a near-infrared (NIR) laser irradiation only for 5 min. Furthermore, the system realizes near "zero release" of drug and is efficiently triggered by NIR for drug delivery in an "on" and "off" manner, thus inducing cell apoptosis in vitro and in vivo. Moreover, the system clearly indicates tumor site with trimodal imaging of magnetic resonance imaging, photoacoustic tomography imaging, and infrared thermal imaging. Furthermore, the system achieves efficient chemo-photothermal combined tumor therapy in vivo with 808 nm laser irradiation for 5 min at 1.2 W cm-2 , revealing the good tumor inhibition effect comparing with those of chemotherapy or photothermal therapy alone. The system is also confirmed to be biocompatible in regard to the mortality rate.
Survival analysis of non-small cell lung cancer patients with adjuvant chemotherapy.
Authors: Jian Ni, Jurong Ding, Jianfang Xu, ChunXia Su, Ying Xu, Meijun Lv
Journal: Journal of Clinical Oncology (2014)

e18506 Background: Clinical trials have demonstrated that adjuvant chemotherapy (ACT) can improve survival in selected patients with completely resected NSCLC. Even though, those patients are still at high risk of recurrence and death. More researches should be completed to decide who and when (time to adjuvant chemotherapy, TTAC) will derive the greatest benefit from ACT. Methods: This is a retrospective study of patients with stage I-IIIA NCSLC treated between 2006 and 2008 in Shanghai pulmonary hospital. Inclusion criteria were: age >18 years, complete resection, pathologically confirmed as stage IA-IIIA NSCLC and receiving ACT . KM survival curves and the Cox regression model were used to assess the risk factors. Results: This study included 1,436 patients . The following factors suggested the better overall survival: Female, no or lighter smokers, lower N stage, II and IIIA pTNM stage, completion of 4 cycles of ACT and cisplatin-based ACT, no ART and TTAT >8 weeks. Multivariate analysis identified sex, N and pTNM stage were the independent prognostic factors for the overall survival outcome of receiving ACT patients. TTAT has the marginal tendency for patients' survival (p=0.074). N, pTNM stage, cisplatin-based ACT and completion of 4 cycles of ACT were the independent prognostic factors for the PFS. Conclusions: Sex, N invasion, and pTNM stage were the independent prognostic factors for the overall survival of completely resected I-IIIA NSCLC patients with ACT. N invasion, pTNM stage, regimes of ACT and ACT cycles were the independent prognostic factors for the PFS of those patients. Longer TTAT (>8 weeks) might benefit for patients’ survival. n P value Gender Male 1,022 Female 414 0.004 Age < 70 1,260 ≥ 70 176 0.076 Smoking (py) no 848 < 20 102 ≥ 20 486 0.02 Pathology Adenocarcinoma 623 Squamous cell cancer 495 Mixed 230 Others 85 0.068 T T1 (1a/1b) 750 (323/427) T2 (2a/2b) 639 (490/149) T3 47 0.320 N N0 908 N1 204 N2 324 0.000 pTNM stage IA 416 IB 494 IIA 99 IIB 116 III 300 0.034 Surgery Pneumonectomy 108 Lobectomy 1,310 Segmentectomy 18 0.121 Cycles of ACT <4 385 4 1,051 0.001 Regimes of ACT Cisplatin-based doublet 935 Carboplatin-based doublet 459 Single 42 0.001 Adjuvant radiotherapy(ART) Yes 112 No 1,324 0.000 TTAT ≤ 8 weeks 1,311 > 8 weeks 125 0.004
Abstract 80: Activation of Nrf2 by Sulforaphane via the AKT/GSK-3β/Fyn Pathway Prevents Angiotensin II-induced Cardiomyopathy
Authors: Ying Xin, Yang Bai, Xin Jiang, Shanshan Zhou, Yuehui Wang, Kupper A Wintergerst, Yi Tan, Taixing Cui, Lu Cai
Journal: Circulation Research (2015)

Aims: Sulforaphane (SFN) as a nuclear factor erythroid 2-related factor 2 (Nrf2) activator protects the heart from, and deletion of the Nrf2 gene exaggerates, the effects of diabetes. Angiotensin II (Ang II) plays a critical role in the development of diabetic cardiomyopathy; therefore, whether SFN prevents Ang II-induced cardiomyopathy through activation of Nrf2 was examined. Methods and Results: The chronic cardiac effects of Ang II with and without SFN were examined in wild-type mice, transgenic Nrf2 knockout (Nrf2-KO) mice, and mice in which cardiac tissue overexpressed Nrf2 (Nrf2-TG). The signaling pathways of SFN-mediated Nrf2 activation were examined in H9C2 cells. Administration of a subpressor dose of Ang II to WT mice induced cardiac oxidative stress, inflammation, remodeling and dysfunction, all of which could be prevented by SFN treatment, which also up-regulated Nrf2 expression and activation. Nrf2-TG mice showed resistance and Nrf2-KO mice displayed resistance to Ang II-induced cardiomyopathy. Meanwhile, the ability of SFN to protect against Ang II-induced cardiac damage was lost in Nrf2-KO mice. Up-regulation and activation of Nrf2 by SFN is accompanied by activation of AKT, inhibition of glycogen synthase kinase (GSK)-3β, and increased nuclear accumulation of Fyn. In vitro up-regulation of Nrf2 by SFN in H9C2 cells was abolished and nuclear Fyn accumulation was increased when cells were exposed to a PI3K inhibitor or GSK-3β-specific activator. Conclusion: Nrf2 plays a central role in the prevention of Ang II-induced pathological effects, and SFN can prevent Ang II-induced cardiomyopathy through activation of Nrf2 partially via the AKT/GSK-3β/Fyn pathway.
Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study
Authors: Benjamin Lebwohl, Yin Cao, Geng Zong, Frank B Hu, Peter H R Green, Alfred I Neugut, Eric B Rimm, Laura Sampson, Lauren W Dougherty, Edward Giovannucci, Walter C Willett, Qi Sun, Andrew T Chan
Journal: BMJ (2017)

Objective To examine the association of long term intake of gluten with the development of incident coronary heart disease.Design Prospective cohort study.Setting and participants 64 714 women in the Nurses' Health Study and 45 303 men in the Health Professionals Follow-up Study without a history of coronary heart disease who completed a 131 item semiquantitative food frequency questionnaire in 1986 that was updated every four years through 2010.Exposure Consumption of gluten, estimated from food frequency questionnaires.Main outcome measure Development of coronary heart disease (fatal or non-fatal myocardial infarction).Results During 26 years of follow-up encompassing 2 273 931 person years, 2431 women and 4098 men developed coronary heart disease. Compared with participants in the lowest fifth of gluten intake, who had a coronary heart disease incidence rate of 352 per 100 000 person years, those in the highest fifth had a rate of 277 events per 100 000 person years, leading to an unadjusted rate difference of 75 (95% confidence interval 51 to 98) fewer cases of coronary heart disease per 100 000 person years. After adjustment for known risk factors, participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0.95 (95% confidence interval 0.88 to 1.02; P for trend=0.29). After additional adjustment for intake of whole grains (leaving the remaining variance of gluten corresponding to refined grains), the multivariate hazard ratio was 1.00 (0.92 to 1.09; P for trend=0.77). In contrast, after additional adjustment for intake of refined grains (leaving the variance of gluten intake correlating with whole grain intake), estimated gluten consumption was associated with a lower risk of coronary heart disease (multivariate hazard ratio 0.85, 0.77 to 0.93; P for trend=0.002).Conclusion Long term dietary intake of gluten was not associated with risk of coronary heart disease. However, the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten-free diets among people without celiac disease should not be encouraged.
Serum Cystatin-C Levels in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial
Authors: Scott T. Miller, Russell E. Ware, Abdullah Kutlar, Ofelia A. Alvarez, Rathi V. Iyer, Sharada A. Sarnaik, Sohail R Rana, Zora R. Rogers, Peter A. Lane, Renee C Rees
Journal: Blood (2008)
Gene Sequencing and Cases of Chronic Lyme Disease—Reply
Authors: Clifford M. Marks, John E. Nawn, Julie A. Caplow
Journal: JAMA Internal Medicine (2017)

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Full-thickness resection of a rectal scar using a modified over-the-scope clip after piecemeal resection of intramucosal cancer
Authors: Amol Agarwal, Sandy Fang, Maryam Pezhouh, Vivek Kumbhari, Mouen Khashab, Saowanee Ngamruengphong
Journal: Endoscopy (2017)

A 51-year-old woman presented with rectal bleeding. Colonoscopy revealed a 2.5 cm rectal polyp at 15 cm from the anus, which was successfully removed via piecemeal endoscopic mucosal resection (EMR). Histopathology showed traditional serrated adenoma with high grade dysplasia and a focus that was suspicious for intramucosal adenocarcinoma. Positron emission tomography obtained 1 month later was notable for increased uptake in the rectum. She was referred to a colorectal surgeon for transanal minimally invasive surgery for excision of the scar and surrounding tissue.