tbuckley/cabot-search huggingface dataset:
Apolipoprotein E lipoprotein particles inhibit amyloid-β uptake through cell surface heparan sulphate proteoglycan
Authors: Yuan Fu, Jing Zhao, Yuka Atagi, Henrietta M. Nielsen, Chia-Chen Liu, Honghua Zheng, Mitsuru Shinohara, Takahisa Kanekiyo, Guojun Bu
Journal: Molecular Neurodegeneration (2016)

The accumulation, aggregation and deposition of amyloid-β (Aβ) peptides in the brain are central to the pathogenesis of Alzheimer's disease (AD). Alzheimer's disease risk increases significantly in individuals carrying one or two copies of APOE ε4 allele compared to individuals with an ε3/ε3 genotype. Growing evidence has demonstrated that apolipoprotein E (apoE) strongly influences AD pathogenesis by controlling Aβ aggregation and metabolism. Heparan sulphate proteoglycans (HSPGs) are abundant cell surface molecules that bind to both apoE and Aβ. HSPGs have been associated with Aβ aggregation and deposition. Although several lines of research have shown that apoE influences Aβ clearance in the brain, it is not clear how apoE influences HSPG-mediated cellular uptake of Aβ.
Fatal and Serious Anaphylaxis Following Peginesatide Administration
Authors: Charles L. Bennett, Sony Jacob, Iain C Macdougall, Tom Moore, Peter Georgantopoulos, Judy Nichols, Paul Yarnold, Oliver Sartor, Dennis W. Raisch, Ashraf Mikhail, LeAnn Norris, Samuel Kessler, Jametta Magwood, David Goldsmith
Journal: Blood (2013)
Genomic Analysis of Lymphoma: Potential for Clinical Application
Authors: Wing C. Chan, James O. Armitage
Journal: Journal of the National Comprehensive Cancer Network (2010)

The application of gene expression profiling to the study of lymphomas will significantly influence the way these tumors are diagnosed and treated. Diffuse large B-cell lymphoma is now known to consist of several different genetic entities with different clinical presentations and therapeutic outcomes. In both follicular and diffuse large B-cell lymphoma, these studies have shown that host-tumor interactions have a major impact on the clinical course. Findings of gene expression profiling in diffuse large B-cell lymphoma has indicated the frequent up-regulation of the nuclear factor-kappaB and B-cell receptor signaling pathways in the activated B-cell type. Drugs targeting these pathways may be effective in the treatment of these cases and clinical trials have been initiated based on these findings. Gene expression profiling may assist in the selection of treatments based on specific metabolic pathways shown to be active in a particular lymphoma. These techniques offer the promise of truly personalized medicine for patients with lymphoma.
Association Between Artificially Sweetened Beverage Consumption During Pregnancy and Infant Body Mass Index
Authors: Meghan B. Azad, Atul K. Sharma, Russell J. de Souza, Vernon W. Dolinsky, Allan B. Becker, Piushkumar J. Mandhane, Stuart E. Turvey, Padmaja Subbarao, Diana L. Lefebvre, Malcolm R. Sears
Journal: JAMA Pediatrics (2016)

The consumption of artificial sweeteners has increased substantially in recent decades, including among pregnant women. Animal studies suggest that exposure to artificial sweeteners in utero may predispose offspring to develop obesity; however, to our knowledge, this has never been studied in humans.To determine whether maternal consumption of artificially sweetened beverages during pregnancy is associated with infant body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]).This cohort study included 3033 mother-infant dyads from the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a population-based birth cohort that recruited healthy pregnant women from 2009 to 2012. Women completed dietary assessments during pregnancy, and their infants' BMI was measured at 1 year of age (n = 2686; 89% follow-up). Statistical analysis for this study used data collected after the first year of follow-up, which was completed in October 2013. The data analysis was conducted in August 2015.Maternal consumption of artificially sweetened beverages and sugar-sweetened beverages during pregnancy, determined by a food frequency questionnaire.Infant BMI z score and risk of overweight at 1 year of age, determined from objective anthropometric measurements and defined according to World Health Organization reference standards.The mean (SD) age of the 3033 pregnant women was 32.4 (4.7) years, and their mean (SD) BMI was 24.8 (5.4). The mean (SD) infant BMI z score at 1 year of age was 0.19 (1.05), and 5.1% of infants were overweight. More than a quarter of women (29.5%) consumed artificially sweetened beverages during pregnancy, including 5.1% who reported daily consumption. Compared with no consumption, daily consumption of artificially sweetened beverages was associated with a 0.20-unit increase in infant BMI z score (adjusted 95% CI, 0.02-0.38) and a 2-fold higher risk of infant overweight at 1 year of age (adjusted odds ratio, 2.19; 95% CI, 1.23-3.88). These effects were not explained by maternal BMI, diet quality, total energy intake, or other obesity risk factors. There were no comparable associations for sugar-sweetened beverages.To our knowledge, we provide the first human evidence that maternal consumption of artificial sweeteners during pregnancy may influence infant BMI. Given the current epidemic of childhood obesity and widespread use of artificial sweeteners, further research is warranted to confirm our findings and investigate the underlying biological mechanisms, with the ultimate goal of informing evidence-based dietary recommendations for pregnant women.
Indication of an involvement of interleukin-1 beta converting enzyme- like protease in intramedullary apoptotic cell death in the bone marrow of patients with myelodysplastic syndromes
Authors: SD Mundle, P Venugopal, JD Cartlidge, DV Pandav, L Broady-Robinson, S Gezer, EL Robin, SR Rifkin, M Klein, DE Alston, BM Hernandez, D Rosi, S Alvi, VT Shetty, SA Gregory, A Raza
Journal: Blood (1996)
DPD mutations and expression in patients with serious toxicity during therapy with 5FU based regimens: National project
Authors: M. Zimovjanova, Z. Kleibl, V. Sykora, J. Novotny, L. Petruzelka
Journal: Journal of Clinical Oncology (2004)

3118 Background: DPD is the key enzyme of the 5FU catabolism. Patients with the low DPD activity due to the mutation or low expression are highly threatened by the severe toxicity, when treated with 5FU. We introduced the detection of the DPD expression and mutations for those patients, who experience grade III or IV toxicity during therapy with 5FU based regimens. The positive findings can serve as the information for the clinician to switch the therapy to non5FU based regimen. The finding of the type and frequency of DPD mutations and low DPD expression in Czech population will be used for the development of the cheap and rapid methods, that can be performed in all patients before 5FU based therapy is administered. Methods: Patients are registered for the analysis through the website www.koc.cz. Blood samples are delivered to our department within one day. Total RNA is isolated from peripheral blood using PAXGene RNA purification kit. Quantitative RT-PCR is performed with random hexanucleotides. Coding sequence of DPD gene is divided among seven overlapping PCR fragments. PCR fragments are directly sequenced on ABI310. DPD expression is determined by the quantitative PCR (LightCycler, Roche). Results: The tests are available since 1st november 2003. Until now, we have analyzed eight patients (3-head and neck, 4-GI and 1-breast cancers). In one case we have identified IVS14 + 1G>A mutation. The genetic abnormality in the second patient needs further confirmation. These two patients died due to toxicity. We did not detect any mutation in six other patients. The DPD/G6PDH ratio was found in range 0,68 to 7,01, median 2,95, mean 3,43. Conclusions: The enrolment to the study continues. Preliminary results indicate, that this method is capable to identify high risk patients in terms of seriuos 5FU toxicity. Acknowledgement: The study is supported by the research grant J13/98 1111 0000–4. No significant financial relationships to disclose.
The Transcription Repressor Gfi1 Directly Interacts With and Is Phosphorylated By Aurora A Kinase, Which Abrogates Myeloma-Induced Gfi1 Repression Of The Runx2 Promoter In Pre-Osteoblasts
Authors: Jixin Ding, Fengming Wang, ShunQian Jin, Judy Anderson, Deborah L. Galson, G. David Roodman
Journal: Blood (2013)
Response to: ‘Comparing the immunogenicity of the etanercept biosimilar SB4 with the innovator etanercept: another consideration’ by Marshall<i>et al</i>
Authors: Paul Emery, Jiří Vencovský, Jeehoon Ghil, Jung Won Kang
Journal: Annals of the Rheumatic Diseases (2016)

We thank Marshall et al for the interest in and comments on our SB4 Phase III study publication and subsequent correspondence regarding immunogenicity.[1-3
Randomized phase III trial comparing postoperative adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation in stage II (T3-T4N0M0) melanoma: Final results of study EORTC 18961.
Authors: A. M. Eggermont, S. Suciu, P. Rutkowski, J. Marsden, A. Testori, P. Corrie, S. Aamdal, P. A. Ascierto, P. Patel, A. Spatz
Journal: Journal of Clinical Oncology (2010)

8505 Background: In the largest adjuvant phase III study in stage II melanoma to date, EORTC 18961 assessed the efficacy and toxicity of ganglioside GM2-KLH/QS-21 vaccination versus observation (OBS). Methods: Patients (Pts) were observed or received vaccine sc once weekly weeks 1-4, every 3 months from week 12 for first 2 years and every 6 months during third year (total of 14 vaccinations). Stratification factors at randomization were: Breslow thickness, ulceration, being staged yes vs no by sentinel node or elective lymph node dissection, sex and institution. Relapse-free survival (RFS) was the prespecified primary endpoint; distant metastasis-free survival (DMFS) and overall survival (OS) were secondary endpoints. An intent-to-treat analysis was performed. Results: Between March 2002 and December 2005, 1,314 pts entered the trial. Patient demographics showed excellent balance for prognostic factors. The second interim analysis was performed when 267 RFS events were reported. For the primary endpoint, RFS, the criteria for stopping for futility were met and for DMFS and OS, there was a trend favoring OBS. Thus, the EORTC IDMC recommended that GM2-KLH/QS-21 vaccine be stopped in the patients still receiving treatment. Patients continued to be followed for the trial's endpoints. Results are shown in the Table (median follow-up of 4.2 years). Grade 3 toxicities occurred in < = 3% (GM2-KLH/QS-21) and in < 1% (OBS). Grade 2 toxicities comprised fatigue (15% vs. 3%), fever (9% vs. 1%), nausea (3% vs. 1%). Local toxicity occurred in 3% (grade 3) and 60% (grade 2). Conclusions: Adjuvant GM2-KLH/QS-21 vaccination is ineffective and could even be detrimental in stage II melanoma patients. RFS DMFS OS OBS GM2-KLH/QS-21 OBS GM2-KLH/QS- 21 OBS GM2-KLH/QS-21 No. events 204 205 143 152 112 124 4-yr % (SE%) 69.4% (1.9%) 68.2% (1.9%) 78.8% (1.7%) 76.1% (1.8%) 83.6% (1.6%) 81.5% (1.6%) HR (95% CI)* 1.03 (0.84, 1.25) 1.11 (0.88, 1.40) 1.16 (0.90, 1.51) p value* 0.81 0.36 0.25 Abbreviation: HR, hazard ratio. * Cox model, stratified for stratification factors. No significant financial relationships to disclose.
Differences in primary care clinicians’ approach to non-small cell lung cancer (NSCLC) patients compared to breast cancer (BrCa)
Authors: T. R. Wassenaar, J. C. Eickhoff, D. R. Jarzemsky, S. S. Smith, M. L. Larson, J. H. Schiller
Journal: Journal of Clinical Oncology (2006)

7041 Background: Lung cancer is a disease associated with a stigma of being primarily self-induced via smoking and therefore avoidable. It is unclear if this stigma results in feelings of guilt and shame on the part of the patient, and a difference in care on the part of primary care physicians (MDs), both of which could lead to differences in treatment and patient self-advocacy, and ultimately poorer outcomes. Methods: We conducted a prospective survey study of 1,132 MDs who were randomized into 4 groups. Each group received a questionnaire representing a clinical scenario (smoker/NSCLC; nonsmoker/NSCLC; smoker/BrCa; nonsmoker/BrCa). The scenarios were identical in terms of stage, gender and outcome; but varied in the disease and smoking history (smoker (S) vs. nonsmoker (NS)). The primary objective was to collect preliminary data to determine if these MDs approached the care and referral of patients (pts) with NSCLC or BrCa differently. A secondary objective was to determine whether or not tobacco use influenced the MD’s approach to the cancer pts. Comparisons of response patterns between the groups were evaluated by Chi-square analysis. Results: 672 questionnaires were completed: 175 in the NS/BrCa, 177 in the S/BrCa, 166 in the NS/NSCLC and 154 in the S/NSCLC scenarios. We observed that MDs were less likely to refer pts with advanced NSCLC to an oncologist than BrCa pts (p=&lt;0.001). More MDs knew that chemotherapy improved survival in pts with advanced BrCa than did MDs regarding chemotherapy use in advanced NSCLC (p=0.0145). In addition, more MDs stated they did not know the benefit of adjuvant therapy for NSCLC than for BrCa (p= &lt;0.001). As a result, more pts with advanced BrCa were referred for further therapy vs. NSCLC pts, who were more likely to be referred only for symptom control (p=0.0092). BrCa pts also had more aggressive follow up than did pts with NSCLC (p=0.0256). There was no statistical significant difference when comparing smoking vs. non-smoking pts. Conclusions: We conclude that there is a significant lack of knowledge in the primary care physician regarding the treatment of pts with advanced stage NSCLC, and the role and benefit of adjuvant therapy. This might lead to a less aggressive referral pattern in these pts to clinical oncologists. [Table: see text]
Accuracy of optical coherence tomography for the diagnosis of superficial basal cell carcinoma: a prospective, consecutive, cohort study of 168 cases
Authors: H.M. Cheng, S. Lo, R. Scolyer, A. Meekings, G. Carlos, P. Guitera
Journal: British Journal of Dermatology (2016)

Superficial basal cell carcinoma (sBCC) can be safely treated topically. Potentially noninvasive imaging techniques, such as optical coherence tomography (OCT), may be useful to diagnose and manage patients with sBCC and obviate the need for biopsy.To evaluate in OCT (i) the sensitivity and specificity for sBCC diagnosis, (ii) the accuracy in determining BCC depth and (iii) the role in management of sBCC mimickers.A prospective, consecutive cohort of lesions for which sBCC was considered in the differential diagnosis. These lesions underwent clinical, dermoscopic and OCT assessment. Diagnosis and its confidence were recorded for each modality and were correlated with the histopathological diagnosis (punch biopsy). Interpretation of the OCT images and assessment of individual features were performed blinded to the biopsy results.In total, 168 lesions were recruited: 52% were sBCC, 26% were other BCC variants and the remaining lesions were actinic keratosis, squamous cell carcinoma in situ, other benign inflammatory processes and two other malignant tumours. The sensitivity and specificity of OCT for diagnosis of sBCC were 0·87 and 0·80, respectively. There was excellent correlation between OCT and biopsy for tumour depth amongst tumours ≤ 0·4 mm (Pearson correlation r = 0·86, P < 0·001), but the correlation was less as depth increased (Pearson correlation r = 0·71, P < 0·001 for all tumours < 1·0 mm).OCT has good diagnostic accuracy for diagnosing sBCC and measuring depth in tumours ≤ 0·4 mm. Potentially OCT can reduce the need for biopsy in clinically suspected sBCCs. However, careful follow-up is required in such cases as there is a small risk (5%) of misdiagnosis.
Open Grafting of Raw Surfaces
Authors: Bradford Cannon
Journal: New England Journal of Medicine (1957)

PROMPT spontaneous and firm adhesion between a split skin graft and a healthy granulating surface has been observed by surgeons for many decades. The nature of the reaction between the tissues that produces the adhesion is unexplained, but this is thought to be due to the formation of a fibrin network, which seals the graft in place.1 A number of methods of enhancing the adhesion have been suggested in the past, including the coagulum contact method of Sano,2 chicken-embryo extract, chicken plasma, thromboplastin, fibrinogen and plasmathrombin fixation.3 Studies by Brown4 using each of these methods for promoting the adhesion of . . .
Molecular imaging in ovarian cancer
Authors: A.K.L. Reyners, K.E. Broekman, A.W.J.M. Glaudemans, A.H. Brouwers, H.J.G. Arts, A.G.J. van der Zee, E.G.E. de Vries, M. Jalving
Journal: Annals of Oncology (2016)
Preclinical disease and preventive strategies in IBD: perspectives, challenges and opportunities
Authors: Joana Torres, Johan Burisch, Mark Riddle, Marla Dubinsky, Jean-Frédéric Colombel
Journal: Gut (2016)

IBDs, encompassing Crohn's disease (CD) and UC, are chronic, relapsing and remitting, inflammatory diseases of the GI tract. IBD is emerging as a globally important disease with epidemiological studies showing that there is a significant increase in IBD’s incidence in most regions of the world.1 In high-incidence areas such as North America, disease already affects around 0.6% of the population.1 As low/middle-income countries continue to become more industrialised, an increasing incidence is also expected to occur in areas of the globe where IBD was previously considered rare.2 ,3 Furthermore, as trends in life expectancy increase globally, the emergence of chronic health conditions, including IBD, will represent a growing proportion of individual and society health impact.

The recent acknowledgement that IBD is a progressive disease has changed the focus of therapeutic strategies. It is now widely accepted that treating effectively at earlier stages of disease, before bowel damage occurs, is likely to produce better outcomes, resulting in reduced rates of hospitalisation and surgery.4 Unfortunately, despite ongoing efforts to change therapeutic paradigms, combining early diagnosis with best available effective therapies, drug-free remission or absence of progression of bowel wall damage remains a challenge in many patients.5 ,6 Once the diagnosis of IBD is made, bowel damage has already occurred in a significant number of patients, and the immune dysregulation, dysbiosis and tissue injury associated with full-blown disease is set, and in many cases, irreversible.6 At present, all therapeutic interventions in IBD target well-established disease, and even the most potent agents are not able to prevent or reverse chronic damage often present at diagnosis. In order to truly change the natural history and long-term consequences of IBD, an effective intervention should ideally occur at an earlier phase, targeting the primary biological processes that drive disease …
Responses of Serum From Breast Cancer Patients to Murine Mammary Tumor Virus: Fact or Artifact?&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A S Dion, A J Girardi, C C Williams, A A Pomenti, E S Redfield
Journal: JNCI Journal of the National Cancer Institute (1987)

For determination of whether breast cancer patients possessed specific serological responses to murine mammary tumor virus (MuMTV), IgG-binding levels were monitored by antibody binding to electrophoretically separated viral proteins (Western blotting and immunodetection) and by the enzyme-linked immunosorbent assay (ELISA) against a panel of five structural proteins (gp55, gp34, p28, p18, and p12) purified from milk-borne MuMTV of the RIII isogeneic mouse strain. No significant antibody reactions were found for sera from 30 cancer patients by the immunoblotting assay, and comparative ELISA studies of 111 patients with malignant mastopathies and 122 healthy, age-matched women revealed no significantly increased mean antibody responses against gp55, gp34, p28, or p12 in breast cancer patients as compared to the responses in the control group. Only for p18 was there a significant increase in mean IgG-binding levels in cancer patients. Additional assays of antibody binding to viral antigens were performed by the cellular immunofluorescence test on MuMTV-expressing cells. These studies also failed to demonstrate greater immunoreactivity of sera from patients as opposed to the immunoreactivity of sera from healthy controls.
Palliation of unresectable cholangiocarcinoma: can we do more than merely drain?
Authors: Guido Costamagna, Ivo Boškoski
Journal: Endoscopy (2015)

Oncologically radical surgical resection (R0) is the only chance of cure for perihilar and distal cholangiocarcinomas with 5-year survival rates of 25 % – 50 % and 70 %, respectively [1] [2].
Early infant HIV diagnosis and entry to HIV care cascade in Thailand: an observational study
Authors: Wasna Sirirungsi, Woottichai Khamduang, Intira Jeannie Collins, Artit Pusamang, Pranee Leechanachai, Suchada Chaivooth, Nicole Ngo-Giang-Huong, Tanawan Samleerat
Journal: The Lancet HIV (2016)
Association of Environmental Contamination in the Home With the Risk for Recurrent Community-Associated, Methicillin-Resistant<i>Staphylococcus aureus</i>Infection
Authors: Justin Knox, Sean B. Sullivan, Julia Urena, Maureen Miller, Peter Vavagiakis, Qiuhu Shi, Anne-Catrin Uhlemann, Franklin D. Lowy
Journal: JAMA Internal Medicine (2016)

The role of environmental contamination in recurrent Staphylococcus aureus infections within households and its potential effect on intervention strategies has been debated recently.To assess whether household environmental contamination increases the risk for recurrent infection among individuals with a community-associated methicillin-resistant S aureus (MRSA) infection.This cohort study was conducted from November 1, 2011, to June 30, 2014, in the Columbia University Medical Center catchment area. All patients within 72 hours of presentation with skin or soft-tissue infections and blood, urine, or sputum cultures positive for MRSA were identified. Two hundred sixty-two patients met study inclusion criteria; 83 of these (31.7%) agreed to participate (index patients) with 214 household members. Participants were followed up for 6 months, and 62 of the 83 households (74.7%) completed follow-up. Participants and researchers were blinded to exposure status throughout the study. Follow-up was completed on June 30, 2014, and data were assessed from July 1, 2014, to February 19, 2016.Concordant environmental contamination, defined as having an isolate with the identical staphylococcal protein A and staphylococcal chromosomal cassette mec type or antibiogram type as the index patient's clinical isolate, present on 1 or more environmental surfaces at the time of a home visit to the index patient after infection.Index recurrent infection, defined as any self-reported infection among the index patients during follow-up.One patient did not complete any follow-up. Of the remaining 82 index patients, 53 (64.6%) were female and 59 (72.0%) were Hispanic. The mean age was 30 (SD, 20; range, 1-79) years. Forty-nine of 61 MRSA infections where the clinical isolate could be obtained (80.3%) were due to the epidemic strain USA300. Among the 82 households in which a patient had an index MRSA infection, the clinical isolate was present in the environment in 20 (24.4%) and not found in 62 (75.6%). Thirty-five patients (42.7%) reported a recurrent infection during follow-up, of whom 15 (42.9%) required hospitalization. Thirteen recurrent infections were from the 20 households (65.0%) with and 22 were from the 62 households (35.5%) without environmental contamination (P = .04). Environmental contamination increased the rate of index recurrent infection (incident rate ratio, 2.05; 95% CI, 1.03-4.10; P = .04).Household environmental contamination was associated with an increased rate of recurrent infection. Environmental decontamination should be considered as a strategy to prevent future MRSA infections, particularly among households where an infection has occurred.