tbuckley/cabot-search huggingface dataset:
Perioperative care of children with sickle cell disease: A systematic review and clinical recommendations
Authors: Frederica Schyrr, Mirko Dolci, Martine Nydegger, Giorgia Canellini, Heidrun Andreu‐Ullrich, Jean‐Marc Joseph, Manuel Diezi, Francois Cachat, Mattia Rizzi, Raffaele Renella
Journal: American Journal of Hematology (2019)

Abstract Children with sickle cell disease (SCD) require specific perioperative care, and clinical practice in this area remains poorly defined. We aimed to conduct a systematic, PRISMA‐based review of the literature, available clinical guidelines and practice recommendations. We also aimed to extract any valuable information for the “best of available‐evidence”‐based prevention of perioperative adverse events in children with SCD, and highlight the most urgent priorities in clinical research. As data sources, US National Library of Medicine, Medline, National Guideline Clearinghouse, International Guideline Network, TRIP databases were searched for any content until January 2019. We also included institutional, consortia and expert group guidelines. Included were reports/guidelines in English, French, German, and Italian. Excluded were reports on obstetrical and fetal management. We identified 202 reports/guidelines fulfilling the criteria outlined above. A majority focused on visceral, cardiovascular and orthopedic surgery procedures, and only five were multicenter randomized controlled trials and two prospective randomized studies. After grading of the quality of the evidence, the extracted data was summarized into clinical recommendations for daily practice. Additionally, we designed a risk‐grading algorithm to identify contexts likely to be associated with adverse outcomes. In conclusion, we provide a systematic PRISMA‐based review of the existing literature and ancillary practice and delineate a set of clinical recommendations and priorities for research.
Exosome-like nanoplatform modified with targeting ligand improves anti-cancer and anti-inflammation effects of imperialine
Authors: Qing Lin, Mengke Qu, Bingjie Zhou, Hirak K. Patra, Zihan Sun, Qiong Luo, Wenyu Yang, Yongcui Wu, Yu Zhang, Lin Li, Lang Deng, Leilei Wang, Tao Gong, Qin He, Ling Zhang, Xun Sun, Zhirong Zhang
Journal: Journal of Controlled Release (2019)
STAT6 deficiency enhances immunity to spontaneous mammary carcinoma in neuT transgenic mice.
Authors: Seth M. Miller, Cordula F. Davis, Samudra K. Dissanayake, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2004)

2150  Deletion of the gene encoding the transcription factor Signal Transducer and Activator of Transcription 6 (STAT6) results in increased immunity and survival of mice inoculated with the 4T1 mammary carcinoma, a highly malignant and spontaneously metastatic transplantable tumor. To determine if deletion of the STAT6 gene also confers resistance to naturally occurring breast cancer, we have interbred BALB/c STAT6-deficient (STAT6-/-) with BALB/c neuT (neuT+/−) transgenic mice, which contain the activated ErbB-2 gene and spontaneously develop lethal mammary carcinoma. (STAT6-/- × NeuT) F1 mice were backcrossed to STAT6-/- mice and the offspring screened by PCR to identify STAT6-/-neuT+/− individuals. Female neuT+/− and STAT6-/-neuT+/− mice were palpated weekly at each of 8 mammary glands to compare 1) age at tumor onset, 2) size of tumors, 3) number of tumors per mouse, and 4) survival time of mice. Two groups, each consisting of 7-10 STAT6-/-neuT+/− and 9-10 neuT+/− mice were monitored for up to 28 weeks each. STAT6-/-neuT+/− mice showed a statistically significant increase in survival time relative to neuT+/− mice, fewer tumors per mouse, decreased tumor size, and statistically significant delayed tumor onset when compared with neuT+/− mice. These results demonstrate that STAT6-deficiency increases survival time of mice with spontaneously occurring breast cancer, and suggest that STAT6-deficiency may be exploitable as an immunotherapy strategy. (NIH R01CA52521, R01CA84232, DOD DAMD-17-01-0312, and DAMD-17-01-0313, and MARC U*STAR grant T34 GM08663, NIH/NIGMS Grant 08663-05)
Risk Factors and Impact of Neurological Complications after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Mark R. Dowling, Shuli Li, Ashmeet Bhatia, Areej El-Jawahri, Bimal R. Dey, Steven L. McAfee, Hanno Hock, Thomas R. Spitzer, Yi-Bin Chen, Karen K. Ballen
Journal: Blood (2016)
Ancient Mitochondrial Gene Transfer between Fungi and the Orchids
Authors: Brandon T Sinn, Craig F Barrett
Journal: Molecular Biology and Evolution (2019)

The mitochondrial genomes (mitogenomes) of plants are known to incorporate and accumulate DNA from intra- and extracellular donors. Despite the intimate relationships formed between flowing plants (angiosperms) and fungi, lengthy fungal-like sequence has not been identified in angiosperm mitogenomes to date. Here, we present multiple lines of evidence documenting horizontal gene transfer (HGT) between the mitogenomes of fungi and the ancestors of the orchids, plants that are obligate parasites of fungi during their early development. We show that the ancestor of the orchids acquired an ∼270-bp fungal mitogenomic region containing three transfer RNA genes. We propose that the short HGT was later replaced by a second HGT event transferring >8 kb and 14 genes from a fungal mitogenome to that of the ancestor of the largest orchid subfamily, Epidendroideae. Our results represent the first evidence of genomic-scale HGT between fungal and angiosperm mitogenomes and demonstrate that the length intergenic spacer regions of angiosperm mitogenomes can effectively fossilize the genomic remains of ancient, nonplant organisms.
Molecular bases for sensitivity to figitumumab (CP-751,871) in NSCLC
Authors: A. Gualberto, M. P. Dolled-Filhart, M. L. Hixon, J. Christensen, D. L. Rimm, A. V. Lee, Y. Wang, M. Pollak, L. G. Paz-Ares, D. D. Karp
Journal: Journal of Clinical Oncology (2009)

8091 Background: Signaling of Insulin like Growth Factors (IGFs) through the IGF type 1 receptor (IGF-IR) induces tumor resistance to cancer therapy. Bioavailability of IGFs is regulated by IGF-binding proteins (IGFBP), of which IGFBP3 is the most abundant. Figitumumab (F) (CP-751,871), a specific IGF-IR inhibitor, has shown phase 2 activity in NSCLC in some histologies (i.e., squamous cell and adenocarcinoma) but not others (i.e, large cell or NOS tumors). Methods: Protein expression of members of the IGF-IR pathway, EGFR and differentiation markers was determined in core biopsies from 230 NSCLC pts, including 52 pts enrolled in F trials. Plasma concentration of IGF-1 and related proteins was determined in 159 NSCLC pts in F trials. Gene expression profiling was conducted in 35 NSCLC cell lines treated with F. Results: Squamous NSCLC had the highest IGF-IR expression (p=0.057). An association with better outcome was seen for E-cadherin expression (HR =0.62, 0.46–0.82 95% CI, p=0.005) and clustering by E-cadherin levels revealed a strong correlation between IGF-IR and EGFR expression in the high E-cadherin group (p&lt;0.001). This subset included 73% of the squamous cell tumors investigated (N=44). Plasma levels of free IGF-1 (fIGF-1) were low and not predictive of response in squamous cell. In contrast, pts with adenocarcinoma had high plasma fIGF-1 levels (p=0.06) that correlated with vimentin expression (Rho=0.732, p=0.06), and both fIGF-1 and vimentin were predictive of F clinical benefit (p=0.03). Large cell/NOS NSCLC expressed the highest levels of vimentin (p&lt;0.001) but had low E-cadherin and IGF-IR expression and low fIGF-1 plasma levels. Analysis of anchorage independent growth in NSCLC cell lines confirmed that F activity is independently associated to IGF-IR overexpression (p=0.02) and IGFBP3 under-expression (p=0.009). Conclusions: IGF-IR overexpression and increased free IGFs/low IGFBP are key independent mechanisms of sensitivity to F in NSCLC of squamous and adenocarcinoma cell histologies. [Table: see text] [Table: see text]
Acute Limb Ischemia in Peripheral Artery Disease
Authors: Connie N. Hess, Zhen Huang, Manesh R. Patel, Iris Baumgartner, Jeffrey S. Berger, Juuso I. Blomster, F. Gerry R. Fowkes, Peter Held, W. Schuyler Jones, Brian Katona, Kenneth W. Mahaffey, Lars Norgren, Frank W. Rockhold, William R. Hiatt
Journal: Circulation (2019)

Background: Acute limb ischemia (ALI) is an important clinical event and an emerging cardiovascular clinical trial outcome. Risk factors for and outcomes after ALI have not been fully evaluated. Methods: EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized patients with peripheral artery disease to ticagrelor versus clopidogrel. Enrollment criteria included an ankle-brachial index ≤0.80 or previous lower extremity revascularization. Patients were grouped according to the primary outcome, postrandomization ALI hospitalization. Baseline factors associated with ALI were identified using Cox proportional hazards modeling. Models with ALI hospitalization as a time-dependent covariate were developed for secondary outcomes of major adverse cardiovascular events (myocardial infarction, cardiovascular death, ischemic stroke), all-cause mortality, and major amputation. Results: Among 13 885 patients, 1.7% (n=232) had 293 ALI hospitalizations (0.8 per 100 patient-years). Patients with versus without ALI were younger and more often had previous peripheral revascularization and lower baseline ankle-brachial index. Treatment during ALI hospitalization included endovascular revascularization (39.2%, n=115), surgical bypass (24.6%, n=72), and major amputation (13.0%, n=38). After multivariable adjustment, any previous peripheral revascularization (Hazard Ratio [HR] 4.7, 95% CI 3.3–6.8, P &lt;0.01), baseline atrial fibrillation (HR 1.8, 95% CI 1.1–3.2, P =0.03), and baseline ankle-brachial index ≤0.60 (HR 1.3 per 0.10 decrease, 95% CI 1.1–1.5, P &lt;0.01) were associated with higher ALI risk. Older age (HR 0.8 per 10-year increase, 95% CI 0.7–1.0, P =0.02) and baseline statin use (HR 0.7, 95% CI 0.5–0.9, P &lt;0.01) were associated with lower risk for ALI. There was no relationship between randomized treatment to ticagrelor or clopidogrel and ALI. Among patients with previous revascularization, surgical versus endovascular procedures performed more than 6 months prior were associated with ALI (adjusted HR 2.63, 95% CI 1.75–3.96). In the overall population, ALI hospitalization was associated with subsequent MACE (adjusted HR 1.4, 95% CI 1.0–2.1, P =0.04), all-cause mortality (adjusted HR 3.3, 95% CI 2.4–4.6, P &lt;0.01), and major amputation (adjusted HR 34.2, 95% CI 9.7–20.8, P &lt;0.01). Conclusions: Previous peripheral revascularization, baseline atrial fibrillation, and lower ankle-brachial index identify peripheral artery disease patients at heightened risk for ALI, an event associated with subsequent cardiovascular and limb-related morbidity and mortality. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.
Soluble CD14 and <i>CD14</i> Variants, Other Inflammatory Markers, and Glucose Dysregulation in Older Adults: The Cardiovascular Health Study
Authors: Sanyog G. Shitole, Mary L. Biggs, Alexander P. Reiner, Kenneth J. Mukamal, Luc Djoussé, Joachim H. Ix, Joshua I. Barzilay, Russell P. Tracy, David Siscovick, Jorge R. Kizer
Journal: Diabetes Care (2019)

OBJECTIVE Experimental studies have implicated soluble (s)CD14, an effector of lipopolysaccharide-induced inflammation, in insulin resistance, but its role in human metabolic endotoxemia has not been studied. We evaluated sCD14 in relation to dysglycemia in older adults and how this compares to other markers of inflammation. RESEARCH DESIGN AND METHODS We investigated associations of sCD14, interleukin-6 (IL-6), CRP, and white blood cell (WBC) count with insulin resistance (quantitative insulin-sensitivity check index and HOMA 2 of insulin resistance) and incident type 2 diabetes in a population-based cohort of older adults. We also assessed the causal role of sCD14 in insulin resistance using an instrumental variable approach by Mendelian randomization. RESULTS After adjustment for conventional risk factors, each of the four biomarkers showed positive cross-sectional associations with both insulin resistance measures. These associations persisted after mutual adjustment for all markers except sCD14. Over a median follow-up of 11.6 years, 466 cases of diabetes occurred. All biomarkers except sCD14 were positively associated with diabetes, although only WBC count remained associated (hazard ratio 1.43 per doubling [95% CI 1.07, 1.90]) after mutual adjustment. Instrumental variable analysis did not support a causal role for sCD14 in insulin resistance. CONCLUSIONS Among older adults, sCD14 was associated with insulin resistance, but this disappeared after adjustment for other biomarkers, showed no evidence of a causal basis, and was not accompanied by a similar association with diabetes. IL-6, CRP, and WBC count were each associated with insulin resistance and diabetes, WBC count most robustly. These findings do not support a central role for sCD14, but they highlight the preeminence of WBC count as an inflammatory measure of diabetes risk in this population.
Clinical features and prognosis of patients with liposarcoma: Single-center experience.
Authors: Metin Demir, Deniz Can Guven, Burak Yasin Aktas, Gürkan Güner, Oktay Halit Aktepe, Hakan Taban, Saadettin Kilickap, Ayse Kars, Alev Turker, Suayib Yalcin, Omer Dizdar
Journal: Journal of Clinical Oncology (2019)

e22557 Background: Liposarcomas constitute 15% of all soft tissue sarcomas.They consist of four subtypes;well-differentiated,dedifferentiated,myxoid and pleomorphic.In this trial we assessed demographic and clinical features of patients with liposarcoma who were treated in our hospital.Methods: Patients who were diagnosed with liposarcoma in Hacettepe University Medical Oncology Department between 2005and2015(n = 119) were included. Patients’ data were collected from hospital registration system.Survival analyses were performed with Kaplan Meier analyses.Results: At the time of diagnosis, the vast majority of patients had localized and/or node positive disease(n = 98),8 patients had metastatic disease.Further analyses hold for only early stage disease:Median age was 52(min:18-max:81).105 patients(94.6%) had upfront surgery.26(23.4%) and 30 patients(27%) received perioperative chemotherapy(CT) and radiotherapy(RT),respectively.The most commonly used CT agents were ifosfamide, anthracyclines, etoposide,taxanes and gemcitabine.At a median follow-up of 45months, relapses were observed in 34 patients(30.6%) and 35 patients(31.5%) died.Median overall survival(OS) was 113.1 months and median relapse free survival (RFS) was 23.8 months.Perioperative CT and RT were not associated with improved RFS and OS.Among patients with early stage disease; median RFS of patients with well-differentiated, dedifferentiated, myxoid and pleomorphic subtypes were 31.8,34.3,28 and 5.2months,respectively(p = 0.013).Well-differentiated group had significantly higher RFS than those with pleomorphic liposarcomas(p = 0.003).The mostly used CT drugs in recurrent setting were ifosfamide+doxorubicine(42.9%) and ifosfamide+etoposide(21.4%).Conclusions: Liposarcoma prognosis varies significantly with histological subtype and the efficacy of systemic chemotherapy is limited both in early stage and advanced disease.[Table: see text]
Lung health and exposure to air pollution in Malawian children (CAPS): a cross-sectional study
Authors: Sarah Rylance, Rebecca Nightingale, Andrew Naunje, Frank Mbalume, Chris Jewell, John R Balmes, Jonathan Grigg, Kevin Mortimer
Journal: Thorax (2019)

Background Non-communicable lung disease and exposure to air pollution are major problems in sub-Saharan Africa. A high burden of chronic respiratory symptoms, spirometric abnormalities and air pollution exposures has been found in Malawian adults; whether the same would be true in children is unknown. Methods This cross-sectional study of children aged 6–8 years, in rural Malawi, included households from communities participating in the Cooking and Pneumonia Study (CAPS), a trial of cleaner-burning biomass-fuelled cookstoves. We assessed; chronic respiratory symptoms, anthropometry, spirometric abnormalities (using Global Lung Initiative equations) and personal carbon monoxide (CO) exposure. Prevalence estimates were calculated, and multivariable analyses were done. Results We recruited 804 children (mean age 7.1 years, 51.9% female), including 476 (260 intervention; 216 control) from CAPS households. Chronic respiratory symptoms (mainly cough (8.0%) and wheeze (7.1%)) were reported by 16.6% of children. Average height-for-age and weight-for-age z-scores were −1.04 and −1.10, respectively. Spirometric abnormalities (7.1% low forced vital capacity (FVC); 6.3% obstruction) were seen in 13.0% of children. Maximum CO exposure and carboxyhaemoglobin levels (COHb) exceeded WHO guidelines in 50.1% and 68.5% of children, respectively. Children from CAPS intervention households had lower COHb (median 3.50% vs 4.85%, p=0.006) and higher FVC z-scores (−0.22 vs −0.44, p=0.05) than controls. Conclusion The substantial burden of chronic respiratory symptoms, abnormal spirometry and air pollution exposures in children in rural Malawi is concerning; effective prevention and control strategies are needed. Our finding of potential benefit in CAPS intervention households calls for further research into clean-air interventions to maximise healthy lung development in children.
Cytoscape Automation: empowering workflow-based network analysis
Authors: David Otasek, John H. Morris, Jorge Bouças, Alexander R. Pico, Barry Demchak
Journal: Genome biology (2019)

Cytoscape is one of the most successful network biology analysis and visualization tools, but because of its interactive nature, its role in creating reproducible, scalable, and novel workflows has been limited. We describe Cytoscape Automation (CA), which marries Cytoscape to highly productive workflow systems, for example, Python/R in Jupyter/RStudio. We expose over 270 Cytoscape core functions and 34 Cytoscape apps as REST-callable functions with standardized JSON interfaces backed by Swagger documentation. Independent projects to create and publish Python/R native CA interface libraries have reached an advanced stage, and a number of automation workflows are already published.
Genome Editing and Hematologic Malignancy
Authors: Brian T. Emmer, David Ginsburg
Journal: Annual Review of Medicine (2019)

The modern genomic era has seen remarkable advancement in our understanding of the molecular basis for disease, yet translation of basic discoveries into new disease treatments has arguably lagged behind. Recently, breakthroughs in genome editing technologies have created hope for their potential to directly treat the genetic causes of disease. Like any therapeutic intervention, genome editing should be considered in light of its potential risks and benefits. In this review, we highlight the promise of genome editing therapies, as well as the conceptual and technical barriers to their clinical application, with a special emphasis on hematologic malignancies.
Learning from best scalp cooling practices in a registry: Differences in results from n&gt;7000 patients with solid tumors.
Authors: Corina van den Hurk, Martin W Dercksen, J. W. R. Nortier, Wim Breed
Journal: Journal of Clinical Oncology (2019)

11610 Background: Hair loss is a frequently occurring and stigmatizing side effect of chemotherapy. Worldwide scalp cooling is being introduced to prevent chemotherapy-induced alopecia (CIA). In the Netherlands scalp cooling is implemented in many hospitals since 2005. FDA clearance has been approved for scalp cooling among breast cancer patients in the USA in 2016. Recently approval has been expended for solid tumors. Methods: In a prospective, longitudinal registry data have been collected between 2006 and 2017. Patients could be included if they received chemotherapy that induced severe alopecia, regardless type of solid tumor, stage of disease, age, gender or receiving adjuvant or palliative treatment. Patients were eligible for evaluation of hair loss after they received at least 2 cycles of chemotherapy or if they ceased scalp cooling because of severe hair loss after the first cycle. Failure was defined as feeling the need to use a wig or head cover. Data will be presented using descriptive statistics and multivariate regression analysis to explore determinants of scalp cooling efficacy per largest groups of chemotherapy regimen, and evaluate variety between hospitals. Results: Preliminary results show data of 7378 patients from 68 hospital locations of whom 75% had breast cancer and 8% prostate cancer. Overall 57% of patients did not feel the need to wear a wig or head cover. Variation was observed between hospitals in scalp cooling procedures: e.g. wetting the hair (0-100% of patient) and cooling- and infusion times that varied per type of chemotherapy. Also results varied between hospitals per type and dose of chemotherapy (n &gt; 10 patients), e.g. minimal 37% and maximal 86% success rates between hospitals for paclitaxel-carboplatin (n = 498), 17-54% success for irinotecan monotherapy (n = 275), 25-79% success for 5FU/epirubicin/cyclophosphamide-docetaxel (n = 843) and 79-94% for docetaxel monotherapy (n = 824). Also variation in satisfaction with information about scalp cooling and nursing expertise was observed. Results from the regression analyses will be presented at the conference. Conclusions: Scalp cooling efficacy varied enormously between hospitals. A registry is a useful tool to identify best practices and to provide guidance to further improve results. An international registry has been set up to also collect data on CIA among scalp cooled and non-scalp cooled patients in the USA, Australia and the UK.
Association between high-cost imaging and hospice use at the end of life of cancer patients.
Authors: Michaela A Dinan, Soko Setoguchi, Lesley H Curtis, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

6504 Background: Use of high cost imaging modalities can inform prognosis and potentially de-escalate unnecessary care at the end of life of cancer patients, but it may also be associated with increased health care expenditures. This analysis investigated the association of hospital-level use of advanced imaging studies with aggressiveness of care near death, as measured by hospice enrollment. Methods: Using SEER-Medicare, patients who died from common solid tumors between 2002 and 2007 were identified and hospital-level utilization of CT, MRI and PET scans were categorized into quartiles. Patients were assigned to the hospital at which they spent the majority of their inpatient days during the last 6 months of life. Multivariate-adjusted logistic regression models based on tumor type were constructed to correlate imaging use with late as well as all hospice admissions, defined as enrollment within 3 days and 18 months of death, respectively. Results: A total of 7,876 breast, 31,933 lung, 12,877 colorectal and 9,137 prostate cancer patients were included. High cost imaging varied across tumor types with rates being highest for lung cancer (mean of 2.29 CT, 0.58 MRI and 0.21 PET scans per patient) and lowest for prostate cancer (mean of 1.25 CT, 0.41 MRI, and 0.01 PET scans per patient) in the 6 months before death. Overall hospice use was least frequent in colorectal cancer (50% of patients) while late hospice admission was most common in lung cancer (11% of patients). Hospitals within the top quartile of imaging use generally had decreased odds of hospice utilization and higher likelihood of late hospice enrollment across most cancer types (Table). Conclusions: In this large cohort, receipt of care near end of life in hospitals with the highest rates of advanced imaging use was associated with lower use of and later enrollment to hospice. High cost imaging is not correlated with de-escalation of aggressive care. [Table: see text]