tbuckley/cabot-search huggingface dataset:
A corn oil diet, but not a fish oil diet enhances the expression of apolipoprotein A-I in the lung of rats treated with 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone (NNK): A proteomic approach
Authors: Sung Il Chang, Indu Sinha, Neil Trushin, Bruce Stanley, Karam El-Bayoumy, Bogdan Prokopczyk
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3174 

Cigarette smoking is an established risk factor for cancer of the lung and the pancreas. Certain epidemiological studies indicate that the development of lung and pancreatic cancer in smokers is influenced by the type and amount of dietary polyunsaturated fatty acids (PUFA). A nicotine-derived nitrosamine, NNK, is known to induce lung and pancreatic cancers in rodents. Hoffmann et al. showed that compared to a low-corn oil diet (5.0%), a high-corn oil diet (23.5%) increased the potency of NNK to induce cancers of the pancreas and the lung in rats (Cancer Res., 53: 2758-2761, 1993). However, the biochemical and molecular mechanisms by which the type of dietary fat alters NNK-induced carcinogenesis remains unknown. Toward this end, we initiated a study to better understand the effect of the type of PUFA in NNK-induced lung cancer in rats at the protein level. Male F344 rats were divided into 4 groups and fed high fat diets containing either corn oil (CO) or fish oil (FO). Two groups also received 2 ppm of NNK in drinking water. The FO diet contained 17% fish oil and 3% corn oil, while the CO diet contained 20% corn oil. Rats were sacrificed at 3 month intervals and the lung and pancreatic tissues were excised and snap-frozen in liquid nitrogen. Whole lung tissue proteins were separated by two-dimensional liquid chromatography in which separation was based on isoelectric point (p I ) in a first-dimension chromatofocusing step, followed by hydrophobicity in a reversed-phase step in the second dimension. Using a peak height threshold value of 0.001 in the second-dimension chromatograms we observed over 500 separate protein peaks in the p I range of 4.0 to 8.0. Overall two-dimensional protein fingerprints were very similar among samples. Comparison of two-dimensional proteome maps, however, showed that two proteins in the p I range of 5.4 to 5.7 were overexpressed in the lungs of rats fed CO as compared FO, while the remaining 35 proteins in this p I range did not change. These two overexpressed proteins were identified as apolipoprotein A-I (Apo-AI) and Clara cell 17-KDa protein (CC17) by MALDI-TOF-MS/MS analysis and confirmed by Western blot analyses. Additionally, NNK treatment further increased the expression of Apo-AI in rats fed CO, showing a three fold increase compared to those fed FO. NNK supplementation had no measurable effect on the expression of CC17 in both groups of rats fed either CO or FO. These findings are consistent with previous studies demonstrating that the elevated expression of Apo-AI in human serum and tissues is associated with the risk of breast and colonic adenocarcinoma progression. Supported by NCI grants PO1 CA70972 and CA76228.
Use of computerised dynamic posturography for the assessment of the sensory integration after a head trauma
Authors: Mani Karin, Bizzini Mario, Meier Cornelia, Müller Alfred, Straumann Dominik, Feddermann Nina
Journal: British Journal of Sports Medicine (2017)

Objective Apart from headache dizziness, vertigo or visual problems are common symptoms after a head trauma. Making an adequate diagnose of the symptoms remains challenging and only a few laboratory tests exist. The computerised sensory organisation test (SOT) differentiates the sensory integration between somatosensory, vision, vestibular and visual preference and therefore helps to objectify symptoms. Design consecutive case series. Setting rehabilitation centre. Participants 29 consecutive post injury symptomatic and asymptomatic athletes with a diagnosed concussion (n=24) or combined injury (concussion plus commotio/contusio labyrinthi (n=5)). Interventions All athletes performed a post injury SOT on the computerised dynamic posturograph (Smart Equitest, 6 conditions). The sensory scores (somatosensory, vestibular and vision) were compared to the normative data (n=112). Outcome measures The main aim was to determine the sensory source of post-concussive symptoms by application of the sensory analysis after performance of the SOT. Main results Half of the athletes (n=15) achieved a normal sensory score, the other half (n=14) were below average (−9.4%) in visual (n=2), vestibular system (n=5) or both (n=7). In these athletes an individual specific vestibulo-oculomotor therapy was recommended. Conclusions The computerised SOT is a useful tool to determine the specific sensory deficits in patients with or without symptoms after a head trauma. Competing interests None.
Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Acute Myeloid Leukemia Progression and Drug Response
Authors: Diana Passaro, Alessandro Di Tullio, Ander Abarrategi, Kevin Rouault-Pierre, Katie Foster, Linda Ariza McNaughton, Francois Lassailly, Dominique Bonnet
Journal: Blood (2016)
Dot1L mediated histone H3-(Lys 79) methylation activates the p21Waf1 gene and functions as a biomarker for apoptotic sensitivity towards HDAC inhibitors
Authors: Walter Stunkel, Kian Peng Koh, Vasantha Nayagam, Yong Cheng Tan, Xiaofeng Wu, ChangYong Hu, Zahid Bonday, Xukun Wang, Alice Lo, Kelly Ying, Eng Boon, Robert Hewitt, Kanda Sangthongpitag, Michael Entzeroth, Jeanette Wood
Journal: Clinical Cancer Research (2007)

A33  Histone decacetylase inhibitors (HDACi) are promising new anti-cancer agents with tumor specific selectivity over non-transformed cells. However, there is a clear need to select the right patients to receive treatment with these new agents. We have identified an epigenetic marker, methylation of histone H3 at lysine 79 (K79), which was found to be predictive for apoptotic response to HDAC inhibition. Both, lack of basal K79 methylation-and HDACi mediated methylation response are predictive of sensitivity to apoptosis after treatment of cells with HDACi. The increase in lysine 79-methylation of histone H3 appears specific for HDACi induced apoptosis and is mediated by the histone methyltransferase Dot1L. We further show by chromatin-immunoprecipitation (ChIP)-analyses and Dot1L gene knockdown studies that histone (K79)-methylation response occurs at the proximal promoter region of the p21 gene leading to its activation. In summary, assessing the (K79) histone methylation status or ex vivo response to a HDACi of tumor specimens in clinical trials with HDAC inhibitors may help to select patients that will respond to HDACi treatment.
The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation
Authors: David P. Kodack, Vasileios Askoxylakis, Gino B. Ferraro, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Z. Alexander Cao, Rakesh R. Ramjiawan, Divya Bezwada, Bhushankumar Patel, Yongchul Song, Carlotta Costa, Kamila Naxerova, Christina S. F. Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G. Duda, C. Ryan Miller, Marni B. Siegel, Carey K. Anders, Melinda Sanders, Monica V. Estrada, Robert Schlegel, Carlos L. Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A. Engelman, Rakesh K. Jain
Journal: Science Translational Medicine (2017)

The brain microenvironment triggers HER3-dependent de novo resistance to therapies targeting PI3K or HER2 in HER2-positive and/or PIK3CA -mutant breast cancer cells.
FRI0001 Folinic acid supplementation reverses macrocytosis without altering efficacy in patients with arthritis treated with methotrexate
Authors: B Mukerji
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Methotrexate is known to cause folate deficiency which can be manifested early on as macrocytosis in a complete blood count. Some clinical manifestations of folate deficiency such as cytopenia, anorexia, stomatitis, and gastrointestinal intolerance are also observed during low dose methotrexate (MTX) treatment in various forms of arthritis. <h3>Objectives</h3> The purpose of this study was to determine the effectiveness of daily folinic acid supplementation in reversing macrocytosis noted in some patients with rheumatoid arthritis (RA) and psoriatric arthritis (PsA) treated with low dose methotrexate and folic acid and to see if it altered the disease modifying activity of the drug. <h3>Methods</h3> Twenty-eight patients were studied. There were 20 women and eight men with an age range of 34–82 years. Twenty-four patients had RA and four had PsA. They were all treated with low dose MTX between 5–15 mg. weekly and folic acid two mg. orally daily, as well as a nonsteroidal antiinflammatory drug and in some patients low dose oral prednisone. Additionally, 16 patients took hydroxychloroquine sulfate, eight patients sulfasalazine, and two patients auranofin. All patients had normal thyroid function. Twenty-three patients (82%) developed macrocytosis after an interval of three to four years on MTX and folic acid. A favourable response was noted in two patients by reversal of their macrocytosis when their daily folic acid dose was increased to three mg. For 21 patients the folic acid was discontinued and supplemented orally with five mg. folinic acid daily. Of the five patients who did not develop macrocytosis, four took weekly MTX of seven and a half mg. or less. One took 15 mg. MTX weekly but also received intramuscular testosterone every three weeks for hypogonadism. <h3>Results</h3> Patients were followed for three to seven years. Of the 21 patients on folinic acid supplementation, 20 (95%) had a reversal of their macrocytosis in 12–15 months. There was no exacerbation of their underlying arthritis. This was determined by joint count, tenderness, limitation of motion and flexion contractures of affected joints. When the folinic acid was discontinued and folic acid reinstituted, macrocytosis recurred in two to three years in five patients and responded to another course of folinic acid. Eight patients who had active disease from the onset continued to have active disease and six were subsequently given etanercept injections. The remaining 13 patients continued to show improvement of all parameters of disease activity. The one non-respondent had active PsA. <h3>Conclusion</h3> These observations suggest that reversal of macrocytosis can be accomplished with daily use of five mg. folinic acid without diminishing the effectiveness of low dose MTX in patients with RA and PsA.
Pediatric Emergency Department Adherence to the 2014 National Heart, Lung and Blood Institute Guidelines Targeting Analgesic Therapy in the Management of Vaso-Occlusive Pain Episodes in Children with Sickle Cell Disease: a Multicenter Perspective
Authors: Claudia R. Morris, Fahd Ahmad, Jonathan Bennett, Seema Bhatt, Amanda Bogie, Kathleen M Brown, T.Charles Casper, Laura L. Chapman, Corrie E. Chumpitazi, Daniel M. Cohen, Carlton Dampier, Angela M. Ellison, Hartmut Grasemann, Robert W. Hickey, Lewis L. Hsu, Peter A. Lane, Sara Leibovich, Prahbumallikarjum Patil, Elizabeth C. Powell, Rachel Richards, Syana Sarnaik, Debra L. Weiner, David C. Brousseau
Journal: Blood (2016)
Multistate Outbreak of Listeriosis—United States, 2000
Journal: JAMA (2001)

ILLNESSES CAUSED by a strain of Listeria monocytogenes (LM) have been identified in 10 states: New York (15 cases); Georgia (three); Connecticut, Ohio, and Michigan (two each); and California, Pennsylvania, Tennessee, Utah, and Wisconsin (one each).Dates of LM isolation ranged from May 17 through November 26 with 26 (90%) infections occurring since July 15.When subtyped, the LM isolates from these cases were indistinguishable by pulsedfield gel electrophoresis (PulseNet pattern numbers GX6A16.0014by Asc1 and GX6A12.0017by Apa1) and ribotyping (DUP-1053).This report summarizes the investigation, which linked these cases of listeriosis to eating deli turkey meat.Eight perinatal and 21 nonperinatal cases were reported.Among the 21 nonperinatal case-patients, the median age was 65 years (range: 29-92 years); 13 (62%) were female.The 29 cases have been associated with four deaths and three miscarriages/stillbirths.A case-control study conducted by five state and two local health departments and CDC implicated eating deli turkey meat as the probable source of infection.Thirteen (76%) of 17 casepatients and five (21%) of 24 controls ate deli turkey meat during the 30 days before illness onset (Mantel-Haenszel weighted odds ratio = 8.0; 95% confidence interval=1.2-43.3).State health and agriculture departments investigated 13 stores and delicatessens where 11 patients reported purchasing turkey; these stores and delicatessens carried turkey meat produced by at least 27 federally inspected establishments.Two establishments were linked to 10 of 11 patients; one of these establishments produced turkey meat for the second establishment.On December 8, investigators from the Food Safety and Inspection Service, U.S. Department of Agriculture (USDA) began investigating the implicated establishments.On December 12, Cargill Turkey Products, Inc.
LGG-08. A PHASE II PROSPECTIVE STUDY OF SELUMETINIB IN CHILDREN WITH RECURRENT OR REFRACTORY LOW-GRADE GLIOMA (LGG): A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY
Authors: Jason Fangusaro, Arzu Onar-Thomas, Tina Y Poussaint, Shengjie Wu, Azra H Ligon, Neal Lindeman, Anu Banerjee, Roger J Packer, Lindsay B Kilburn, Ian F Pollack, Regina I Jakacki, Ibrahim Qaddoumi, Paul G Fisher, Girish Dhall, Patricia Baxter, Susan G Kreissman, Clinton F Stewart, Stefan M Pfister, David TW Jones, Gilbert Vezina, Jessica Stern, Ashok Panigrahy, Blaise V Jones, Zoltan Patay, Benita Tamrazi, Jeremy Y Jones, Sofia S Haque, David S Enterline, Soonmee Cha, Laurence A Doyle, Malcolm Smith, James M Boyett, Ira J Dunkel, Maryam Fouladi
Journal: Neuro-Oncology (2017)

A greater understanding of the Ras-MAP kinase-signaling pathway in pediatric low-grade glioma (LGG) has led to the ability to target this pathway with therapeutic intent. The PBTC conducted a multi-institutional phase II study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/refractory LGG assigned to 6 strata and treated at 25 mg/m2/dose PO BID for up to two years. Here we present the data from three of these strata. Stratum I included children with non-NF-1 and non-optic pathway recurrent/refractory pilocytic astrocytoma (PA) harboring BRAF aberrations (BRAF V600e mutation or the BRAF-KIAA 1549 fusion). Eight of 25 (32%) patients achieved a partial response (PR) with 2-year PFS of 66+11%. Two of 7 (29%) patient tumors with a BRAF V600e mutation and 6/18 (33%) with a BRAF KIAA-1549 fusion had a PR. Stratum 3 enrolled NF-1-associated LGG. Tissue for tumor BRAF evaluation was not required for eligibility. Ten of 25 (40%) achieved PR with a 2-year PFS of 96+4%. Only one patient progressed while on treatment. Stratum 4 included children with non-NF-1 optic pathway/hypothalamic LGG. Tissue for tumor BRAF evaluation was not required for eligibility. Two of 16 (12.5%) had a PR with a 2-year PFS of 65+13%. The BRAF aberration status of the responders in strata 3 and 4 is mostly unknown. All responses were confirmed centrally and seven patients remain on treatment. The most common toxicities were grade 1/2 CPK elevation, diarrhea, hypoalbuminemia, elevated AST and rash. Rare grade 3/4 toxicities included elevated CPK, rash, neutropenia, emesis and paronychia. Selumetinib was effective in treating children with recurrent/refractory LGG, including those with NF-1 associated LGG and PA harboring BRAF V600e mutation or BRAF-KIAA 1549 fusion. Larger prospective studies are necessary to determine the future, specific role of this agent in treating children with various LGG molecular subtypes.
NSABP B-47: A phase III trial of adjuvant therapy comparing chemotherapy alone (six cycles of docetaxel plus cyclophosphamide or four cycles of doxorubicin plus cyclophosphamide followed by weekly paclitaxel) to chemotherapy plus trastuzumab in women with node-positive or high-risk, node-negative, HER2-low invasive breast cancer.
Authors: Louis Fehrenbacher, Jong-Hyeon Jeong, Priya Rastogi, Charles E. Geyer, Soonmyung Paik, Patricia A. Ganz, Stephanie R. Land, Joseph P. Costantino, Sandra M. Swain, Eleftherios P Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

TPS1142 Background: Adjuvant studies utilizing trastuzumab in early HER2+ breast cancer demonstrated a large reduction in recurrence and death. Post-enrollment central testing showed HER2 non-amplified participants derived similar benefit. Methods: Selection of one of the two chemotherapy regimens is by physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered IV every 3 weeks for 6 cycles; the anthracycline regimen is AC followed by WP (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered IV either every 3 weeks or every 2 weeks [per investigator discretion] for 4 cycles followed by paclitaxel 80 mg/m2 IV weekly for 12 doses). Patients are randomly assigned to receive chemotherapy with or without trastuzumab therapy. For patients receiving the TC chemotherapy regimen, trastuzumab is given every 3 weeks during and following chemotherapy until 1 year after the first trastuzumab dose (8 mg/kg loading dose; 6 mg/kg for the remaining doses). For patients receiving the AC followed by WP chemotherapy regimen, trastuzumab begins with the first dose of weekly paclitaxel and will be given weekly for 12 doses (4 mg/kg loading dose; 2 mg/kg for the remaining weekly doses). Following completion of WP, trastuzumab therapy continues with 6 mg/kg doses given every 3 weeks for a total of 1 year. Eligibility: Eligibility includes: node positive or high risk node negative female breast cancer patients; HER2 IHC 1+ or 2+ scores, but non amplified by FISH Statistical Design: The primary aim is to determine whether the addition of trastuzumab to chemotherapy improves invasive disease-free survival (IDFS). 3260 patients will be enrolled to provide statistical power of 0.9 to detect a 33% reduction in the hazard rate of IDFS using a one-sided alpha level of 0.025. Progress: Protocol was activated in January 2011. As of January 27, 2012, 486 of 3260 patients have been enrolled. Supported by NCI U10-12027, -37377, 69651, 69974, and Genentech, Inc.
The future burden of disability in the UK: the time for urgent action is now
Authors: Stuart Gilmour
Journal: The Lancet Public Health (2017)

In the Lancet Public Health, Maria Guzman-Castillo and colleagues1 present a timely warning of the huge health system challenges looming in the UK's near future. The investigators used a detailed probabilistic Markov model to produce estimates of the prevalence of disability due to cardiovascular disease, dementia, and other causes in people aged 65 years or older in England and Wales to the year 2025. They found a 25% increase from 2015 in the number of older people who will be living with disability, representing 560 000 additional elderly people in England and Wales who will need care for their disabling condition, and showed that the largest relative increases will be in dementia cases.
Perianal Paget's disease
Authors: Rajni Amin
Journal: Journal of the Royal Society of Medicine (1998)

Perianal Paget's disease is rare. Unlike Paget's disease of the nipple, which is always associated with a subjacent breast adenocarcinoma, perianal Paget's disease is not always associated with a subjacent or visceral malignancy. The treatment recommendation in nearly all reported cases has been surgical excision. Radiation therapy is seldom used as a curative treatment. A case of perianal Paget's disease is described in whom radiation therapy was used with a curative intent after four unsuccessful surgical resections.
Biomechanical differences during a jump cut motion in those with and without a concussion history
Authors: Andrew P Lapointe, Luis Nolasco, Aniela Sosnowski, Eva Andrews, Douglas N Martini, Deanna H Gates, Steven P Broglio
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate differences in biomechanics between young adult participants with and without a history of concussion during a jump cut manoeuvre. Design Case control Setting Laboratory Subjects 7 controls (4 males, 3 females) and 7 concussed (4 males, 3 females) subjects, between the ages of 18 and 26, capable of engaging in a jump cut motion. Concussed subjects were tested on average 2.4 years post injury (SD=0.23 years). Intervention Participants jumped forward with both feet onto a force platform landing on their dominant leg, and directed their cut in response to the centre arrow of the Flanker task. A total five trials were performed. Kinematic variables were captured during the manoeuvres via motion capture. Outcome measures Peak knee flexion, abduction, and axial rotation Results Concussed subjects showed lower peak flexion of the knee on their non-dominant leg [F=25.455, p&lt;0.01,R=0.240] and greater peak external rotation of the knee on their dominant leg [F=9.97, p&lt;0.01, R=0.145]. Concussed subjects also showed a lower vertical centre of mass during the task [F=9.985, p&lt;0.05, R=0.119]. Conclusions There is a growing body of literature linking orthopaedic injury in those no longer displaying the acute signs and symptoms of concussion. This is the first study evaluating kinematic changes with findings demonstrating kinematic abnormalities long after clinical signs and symptoms have passed. Competing interests This project was funded by the Carl and Joan Kreager research fund. None.
Defining the elite: normative values for scat major components in healthy elite athletes
Authors: William J Moreau, Taylor Walden, Dustin Nabhan
Journal: British Journal of Sports Medicine (2017)

Objective Describe normative baseline SCAT 2 and 3 (SCAT) performance in elite athletes. Design Retrospective cohort. Setting United States Olympic Committee Sports Medicine Clinics. Participants Six hundred and forty-one SCAT baseline evaluations were performed on a population of 565 elite athletes (291 women and 350 men, mean age 24.9±5.2 years) representing 23 Summer and Winter Olympic sports as part of a multimodal concussion management program. Intervention No intervention was applied. The SCAT evaluations were administered as a component of baseline testing on healthy athletes. Main Outcome Measurements Baseline SCAT performance on major components is described. T-tests were used to compare differences in baseline performance by sex. Results During baseline evaluation elite athletes reported a mean of 2.1 (1.8–2.4) symptoms with average symptom severity scores of 3.4 (3.0–3.9). Mean scores on SCAT 3 components in this population were; orientation 4.9 (4.8–4.9), immediate memory 14.5 (14.4–14.5), concentration 3.9 (3.8–4.0), tandem gait 11.7 (11.4–12.0), delayed recall 3.7 (3.6–3.8), balance 2.83 (2.2–3.4), SAC total 26.9 (26.8–27.1). This population reported historys of 1.19 (1.0–1.4) previous concussions. Females reported significantly more symptoms (3.9 vs 3.0, P=0.04), and scored significantly higher on the orientation (4.9 vs. 4.8, P=0.004), immediate memory (14.6 vs. 14.4, P=0.003), concentration (4.1 vs 3.8, P=0.0013) SAC total score (27.3 vs. 26.6, P&lt;0.01) Conclusions Population specific normative values for baseline SCAT performance in a population of elite athletes are presented in this case series. Clinical relevance Clinicians are encouraged to reference population specific normative values when interpreting SCAT performance. Acknowledgements None. Competing interests None.