tbuckley/cabot-search huggingface dataset:
Mobilizing Doses Of G-CSF Stop Medullary Erythropoiesis By Depleting F4/80+ VCAM1+ ER-HR3+ CD169+ Erythroid-Island Macrophages
Authors: Rebecca Jacobsen, Allison R Pettit, Liza J Raggatt, Bianca Nowlan, Valerie Barbier, Catherine E Forristal, Ingrid G Winkler, Jean-Pierre Levesque
Journal: Blood (2013)
Treatment results of trabectedin (T) in patients (pts) with myxoid-round cell liposarcoma (MRCL)
Authors: Akira Kawai, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Mitsuru Takahashi, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Shunji Takahashi
Journal: Annals of Oncology (2015)
Auranofin Induces a Reversible In-Vivo Stress Response That Correlates With a Transient Clinical Effect In Patients With Chronic Lymphocytic Leukemia
Authors: Nakhle S Saba, Mondana Ghias, Rekha Manepalli, Kevin Schorno, Scott Weir, Christopher Austin, Kami Maddocks, John C. Byrd, Suman Kambhampati, Kapil Bhalla, Adrian Wiestner
Journal: Blood (2013)
Male breast cancer: Pathology, treatment, and outcome
Authors: J. Floyd, M. Meadors, T. Hopkins, S. Westgate, N. Shahab, M. Perry
Journal: Journal of Clinical Oncology (2005)

814 Background: A single-institution retrospective review of the clinical/pathologic presentation, treatment, and outcome of male breast cancer was conducted. Methods: Data pertaining to clinical/pathologic presentation, treatment, and outcome were obtained by chart review of 21 male breast cancer patients from 1976–2004. Results: Patients presented at a median age of 67 years (34–90), with 71.4% presenting with a self-detected breast mass. Left sided breast cancer was present in 61.9% of patients and there were no reported cases of bilateral disease. The pathologic subtypes were infiltrating ductal carcinoma (80.9%), DCIS (9.5%), adenocarcinoma (4.7%), and intraductal papillary carcinoma (4.7%). Additionally, ER and PR positivity were 80.9 and 76.2% respectively, with 90.5% of tumors >1 cm in greatest diameter. Modified radical mastectomy was performed in 90.4% of patients revealing positive lymph nodes in 52.3% of patients. Adjuvant chemotherapy and/or hormonal therapy were prescribed in 23.8 and 47.6% of cases, respectively. Adjuvant radiation therapy was administered in 14.3% of patients. Documented local and distant recurrences were 9.5 and 19.0% respectively, while 9/15 (60%) of patients were alive at 5 years. Two patients died secondary to metastatic disease, one died from unrelated ventricular fibrillation/AMI, and an additional three patients were lost to follow-up. Of the two patients that died from breast cancer, one patient had lymph node positive disease and did not receive adjuvant chemotherapy, the other patient recurred in the chest wall and had not received adjuvant radiation therapy for a 5 cm, 11/12 lymph node positive primary tumor. Conclusions: Despite many similarities in male and female breast cancer, because of lack of screening in men, a majority of tumors were larger in size (>1 cm) and more often had regional lymph node involvement at the time of diagnosis. Furthermore, historically adjuvant chemotherapy and hormonal therapy were prescribed in relatively few patients as compared with females. With only 60% of patients surviving 5 years, physicians should be encouraged to prescribe adjuvant therapy in an attempt to improve outcome. No significant financial relationships to disclose.
Validation of a time-frequency wheeze detector in cystic fibrosis: A pilot study
Authors: Daniela Oliveira, Catia Pinho, Alda Marques, Joao Dinis
Journal: European Respiratory Journal (2011)

Background: Computerised lung-sound analysis can be used to identify and quantify wheezes which are associated with pulmonary diseases. However, this type of analysis requires further validation before it can be implemented routinely in the clinical practice across different respiratory pathologies.

Objective: This pilot study aimed to validate a time-frequency wheeze detector (TF-WD) in the cystic fibrosis disease.

Methods: Recordings were made in a clinical setting from a stable cystic fibrosis adult outpatient with a digital stethoscope following the CORSA guidelines. Several TF-WD algorithms were tested and the best performance was obtained with the Taplidou et al. (2007) algorithm, which was validated in four sound files. The number, duration and type of wheezes were blindly analysed independently by three experienced respiratory physiotherapists. Their evaluation was then compared with the automatic method. The statistics accuracy of the wheezes detection was quantified through sensitivity, specificity and performance measures using MatlabR2007b. True positives/negatives and false positives/negatives were counted by comparing each point of the sound file.

Results: Inter-rater agreement between the physiotherapists was 96.9%. The sensitivity, specificity and performance of the automated method were 77.2%, 98.4% and 87.1%, respectively.

Conclusion: The automated method tested shows sufficient reliability to continue the study and implement a future clinical validation with a larger sample. Wheezes detection through computerised analysis can provide an objective measure to assess and monitor cystic fibrosis patients, however further research is needed to validate the most robust algorithm.
TB in healthcare workers in the UK: a cohort analysis 2009–2013
Authors: Jennifer A Davidson, Maeve K Lalor, Laura F Anderson, Surinder Tamne, Ibrahim Abubakar, H Lucy Thomas
Journal: Thorax (2016)

To describe the burden of TB in healthcare workers (HCWs) in the UK and determine whether HCWs are at increased risk of TB due to occupational exposure.Retrospective cohort analysis of national UK TB surveillance and genotyping data between 2009 and 2013. The rate of TB in HCWs compared with non-HCWs to calculate incidence rate ratios stratified by country of birth.2320 cases of TB in HCWs were notified in the study period, 85% were born abroad. The TB rate in HCWs was 23.4 (95% CI 22.5 to 24.4) per 100 000 compared with 16.2 (95% CI 16.0 to 16.3) per 100 000 in non-HCWs. After stratifying by country of birth, there was not an increased TB incidence in HCWs for the majority of countries of birth, including in the UK-born. Using combined genotyping and epidemiological data, only 10 confirmed nosocomial transmission events involving HCWs were identified between 2010 and 2012. Of these, only two involved transmission to patients.The lack of an increased risk of TB after stratifying by country of birth, and the very few transmission events involving nosocomial transmission in the UK suggests that TB in HCWs in the UK is not generally acquired through UK occupational exposure. The majority of cases in foreign-born HCWs are likely to result from reactivation of latent TB infection (LTBI) acquired abroad, and is not likely to be prevented by BCG vaccination in the UK. Testing and treatment of LTBI in HCWs with exposure to high TB burden countries should be the focus of occupational health prevention activities.
Vaccine immunotherapy with MVA-Muc1-IL2 (TG4010) in prostate cancer patients with biochemical failure
Authors: R. Dreicer, R. Ahman, A. Pantuck, W. M. Stadler, N. Bizouarne, B. Acres, A. Derbij, J.-M. Limacher, P. Squiban
Journal: Journal of Clinical Oncology (2005)

4518 Background: Over-expression, non-polarity and under-glycosylation of the mucin glycoprotein molecule, MUC1, are associated with many cancers, making MUC1 an attractive target antigen for vaccine immunotherapy of cancer. TG4010 is a recombinant MVA (Modified Vaccinia Ankara) virus which expresses both MUC1 and IL2 (TG4010). TG4010 has now been injected into over 150 patients with good tolerance. Methods: A randomized, phase II study in patients (pts) with prostate cancer. Eligible pts were required to have no evidence of metastatic disease following curative intent local therapy, evidence of PSA failure (PSA over 2 ng/ml) and PSA doubling time (PSA-DT) less than 10 months. Arm 1: TG4010 injected sc weekly, at a dose of 108 pfu, for six weeks, then every three weeks. Arm 2: 108 pfu TG4010 injected sc every three weeks. Therapy was continued to disease progression or a max of 36 weeks. Objective response: decrease of 50% or more in the PSA level compared to baseline. Secondary endpoints: modification in the rate of PSA increase and time to treatment failure. Results: To date, 40 patients have been enrolled and 38 are evaluable for response. No objective response has yet been observed. Twenty-seven of 38 patients (71%) have lengthened their PSA-DT after vaccination (Memorial Sloan Kettering online PSA-DT calculator). A statistically significant increase (p < 0.001) in PSA-DT is observed in treatment Arm 1 (weekly administration) with a median increase of 2.5 fold (mean increase 3.8 fold). Therapy has been very well tolerated with grade 1 injection site reactions being the most common adverse event noted. Conclusions: Immunization with TG4010 appears to have some biologic activity manifested by a increase in PSA doubling time. Accrual to the study is ongoing. The acceptable toxicity profile makes this an encouraging therapy paradigm to pursue in this prostate cancer subset. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Transgene Transgene Celgene, sanofi-aventis
MAF1 suppresses AKT‐mTOR signaling and liver cancer through activation of PTEN transcription
Authors: Yue Li, Chi Kwan Tsang, Suihai Wang, Xiao‐Xing Li, Yang Yang, Liwu Fu, Wenlin Huang, Ming Li, Hui‐Yun Wang, X.F. Steven Zheng
Journal: Hepatology (2016)

The phosphatidylinositol 3‐kinase/phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphatase/protein kinase B/mammalian target of rapamycin (PI3K‐PTEN‐AKT‐mTOR) pathway is a central controller of cell growth and a key driver for human cancer. MAF1 is an mTOR downstream effector and transcriptional repressor of ribosomal and transfer RNA genes. MAF1 expression is markedly reduced in hepatocellular carcinomas, which is correlated with disease progression and poor prognosis. Consistently, MAF1 displays tumor‐suppressor activity toward in vitro and in vivo cancer models. Surprisingly, blocking the synthesis of ribosomal and transfer RNAs is insufficient to account for MAF1's tumor‐suppressor function. Instead, MAF1 down‐regulation paradoxically leads to activation of AKT‐mTOR signaling, which is mediated by decreased PTEN expression. MAF1 binds to the PTEN promoter, enhancing PTEN promoter acetylation and activity. Conclusion : In contrast to its canonical function as a transcriptional repressor, MAF1 can also act as a transcriptional activator for PTEN, which is important for MAF1's tumor‐suppressor function. These results have implications in disease staging, prognostic prediction, and AKT‐mTOR‐targeted therapy in liver cancer. (H epatology 2016;63:1928‐1942)
Erythrocyte Membrane Defects Associated With a Transplantable Lymphoid Tumor2
Authors: Francis W. Chandler, Oscar J. Fletcher
Journal: JNCI Journal of the National Cancer Institute (1973)

By scanning electron microscopy, pits and craters were observed on the surfaces of erythrocytes from anemic chickens bearing a transplantable lymphoid tumor and on normal erythrocytes incubated with extracts of this tumor. These membrane defects were possibly caused by enzymes released from necrotic portions of the tumor, since necrotic pectoral muscle extract produced similar, but less severe, membrane alterations. Normal erythrocytes incubated with serum from tumor-bearing chickens, physiologic saline, extracts of normal pectoral muscle, and the bursa of Fabricius were unaffected. The observed membrane defects explain the decreased erythrocyte lifespan in chickens inoculated with transplantable lymphoid tumor.
Presurgical diagnostic accuracy of five imaging procedures in chemotherapy-naive (group A) or chemotherapy-pretreated (group B) patients with colorectal liver metastases (Italian PROMETEO Study).
Authors: F. L. Rojas Llimpe, F. Di Fabio, G. Ercolani, C. Serra, P. Castellucci, S. Pini, V. Mutri, R. Golfieri, A. Martoni, C. Pinto
Journal: Journal of Clinical Oncology (2010)

3621 Background: The aim of the study was to define the specific diagnostic accuracy of 5 imaging techniques in group A or group B patients (pts) with potentially resectable colorectal cancer liver metastasis (CLMs). Methods: Seventy consecutive CLMs pts referred to the Multidisciplinary Team of Bologna S. Orsola Malpighi Hospital performed computed tomography scan (CT), magnetic resonance (MR), 18F-FDG-PET, and liver contrast-enhanced ultrasonography (CEUS1); CEUS2 was also performed intra-operatively. Every pathological lesion was compared with imaging data. Results: From December 2007 to December 2009, 49/70 pts underwent liver resection. Pt characteristics: 28M/29F; 30(61%) synchronous/19(39%) metachronous metastasis. Twenty-five (51%) pts were in group A, 24 (49%) in group B. Fifty-eight liver lesions were resected in group A (median number per pt 1, range 1-7), 94 in group B (median 2.5, range 1-15). Two lesions at pathological examination were not CLMs (1 giant-cell reaction, 1 cholangiocarcinoma) in group A and 7 (1 hamartoma, 1 steatosis, 3 necrosis, 2 fibrosis) in group B. Conclusions: As compared with pathological evaluation, diagnostic accuracy of all 5 imaging procedures was high in group A, but decreased in group B. This was particularly evident with FDG-PET (p<0.001). CEUS2 presented the higher predictive value. CT % MR % PET % CEUS1 % CEUS2 % Sensitivity Group A 50/56 89 45/49 92 47/56 84 47/54 87 50/51 98 Group B 67/87 77 75/84 89 32/78 41 68/85 80 83/87 95 Positive predictive value Group A 50/52 96 45/47 96 47/48 98 47/49 96 50/53 94 Group B 67/73 92 75/80 94 32/35 91 68/73 93 83/89 93 Specificity Group A 0/2 0 0/2 0 1/2 50 0/2 0 0/3 0 Group B 1/7 14 2/7 29 3/6 50 1/6 17 1/7 14 Negative predictive value Group A 0/6 0 0/4 0 1/10 10 0/7 0 0/1 0 Group B 1/21 5 2/11 18 3/49 6 1/18 5.5 1/5 20 Accuracy Group A 50/58 86 45/51 88 48/58 83 47/56 84 50/54 93 Group B 68/94 72 77/91 85 35/84 42 69/91 76 84/94 89 No significant financial relationships to disclose.
Relation between perceived cognitive function and neuropsychological performance in survivors of breast and colorectal cancer
Authors: J. L. Vardy, W. Xu, C. M. Booth, A. Park, A. Dodd, S. Rourke, H. Dhillon, S. J. Clarke, L. Wagner, I. F. Tannock
Journal: Journal of Clinical Oncology (2008)

9520 Background: Previous studies have shown dissociation between self-reported cognitive impairment and formal testing of cognitive function in cancer survivors, but are limited by small samples and variable assessment methods. Here we evaluate perceived cognitive function (PCF) and formal neuropsychological performance (NP) in a large sample of patients with colorectal (CRC) and breast cancer (BC). Methods: Patients with CRC were evaluated at baseline (post-surgery, before chemotherapy CT), 6, 12 and 24 months. Group A received adjuvant CT, group B no CT, & Group C first line metastatic CT. Women without recurrence of BC were evaluated once within 5 years of diagnosis: Group D had received adjuvant CT, Group E no CT. All patients completed the FACT-COG to evaluate PCF; NP was assessed by classical and computerized (CANTAB) tests, and quantified by Global Deficit Scores (GDS). Patients completed concurrent questionnaires for fatigue, QOL (FACT-F) and anxiety/depression (GHQ). We sought an association between PCF and NP using mixed model regression adjusted for repeated measures, group, and disease. Results: We performed 637 assessments on 302 patients. Median age: 55(23–75) years, 58% female. Overall 15% (11%CRC, 36%BC) perceived major cognitive impairment (FACT-COG<64/100), with impairment on NP (GDS≥0.5) at 20% of assessments. A weak association was found between self-report and test-evaluated cognitive impairment (p=0.05), with a stronger association in CRC patients, primarily at baseline. Perceived (but not test-evaluated) cognitive impairment was greatest in breast cancer survivors and associated with fatigue, anxiety/depression and QOL (Pearson 0.41–0.76, p<0.0001). Patients who received CT perceived greater impairment (p<0.0001), worse QOL (p=0.07) and fatigue (p=0.01) but there was no difference in results of NP testing compared to non-CT patients. Conclusions: Perceived cognitive impairment is associated with fatigue, QOL, anxiety/depression and receipt of CT, but minimally with NP performance on cognitive tests. PCF cannot be used as a substitute for neuropsychological testing. Both perceived cognitive function and formal tests of neuropsychological performance are important endpoints for survivors. No significant financial relationships to disclose.
Abstract 206: Accumulation of Mitochondrial DNA Mutations Impairs Survival, Proliferation, and Differentiation of Cardiac Progenitor Cells
Authors: Amabel M Orogo, Dieter A Kubli, Anne N Murphy, Åsa B Gustafsson
Journal: Circulation Research (2014)

Activation and participation of cardiac progenitor cells (CPCs) in regeneration are critical for effective repair in the wake of pathologic injury. Stem cell activation and commitment involve increased energy demand and mitochondrial biogenesis. To date, little attention has been paid to the importance of mitochondria in CPC survival, proliferation and differentiation. CPC function is reduced with age but the underlying mechanism is still unclear. Mitochondrial DNA (mtDNA) is more susceptible to oxidative attacks than nuclear DNA due to its proximity to the mitochondrial respiratory chain and lack of protective histone-like proteins. With age, mtDNA accumulates mutations that can impair mitochondrial respiration and increase ROS production. In this study, we examined the effects of accumulating mtDNA mutations on CPC proliferation and survival. We have found that incubation of uncommitted c-kit+ CPCs in differentiation medium increased mitochondrial mass and expansion of the mitochondrial network, which correlated with increased cell size and expression of cardiac lineage commitment markers. Differentiation activated mitochondrial biogenesis, increased mtDNA copy number, and enhanced oxidative capacity and cellular ATP levels in CPCs. To investigate the effect of mtDNA mutations and aging on CPC survival and function, we utilized a mouse model in which a mutation in the mtDNA polymerase γ (POLG m/m ) leads to accumulation of mtDNA mutations, mitochondrial dysfunction, and accelerated aging. Isolated CPCs from hearts of 2-month old POLG m/m mice had reduced proliferation and were more susceptible to oxidative stress and chemotherapeutic agents compared to WT CPCs. The majority of POLG m/m CPCs contained fragmented mitochondria as shown by immunostaining. Incubation in differentiation medium resulted in fewer GATA-4 positive POLG m/m CPCs compared to WT CPCs. The reduced differentiation in these POLG m/m CPCs correlated with reduced PGC-1α expression and OXPHOS protein levels, suggesting that mitochondrial biogenesis is impaired. These data demonstrate that mitochondria play a critical role in CPC function, and accumulation of mtDNA mutations impairs CPC function and reduces their repair potential.
Abstract 16331: Alcohol Consumption and Its Relation to Obesity in a Population-Based Study in Finland
Authors: Satu Männistö, Jukka Kontto, Katja Borodulin, Noora Kanerva, Tiina Laatikainen, Pekka Jousilahti
Journal: Circulation (2014)

Introduction: Alcohol is the second most energy-dense macronutrient and it is metabolized very effectively. The previous results, however, do not conclusively confirm a positive association between alcohol consumption and BMI. In several studies, moderate alcohol consumers have shown lower BMI than abstainers, despite their higher daily energy intake. Our aim was to determine associations of alcohol consumption with energy intake and BMI. Methods: The National FINRISK 2012 Health Study consisted of 4776 participants aged 25-74 years. The Study included questionnaires and measured weight and height. A validated food frequency questionnaire was used to assess participants’ whole diet. Findings: Of men, 12% were classified as abstainers and 6% as heavy drinkers, while the percentages for women were 25% and 3%, respectively. The mean daily alcohol consumption was 12.9 g among men and 4.4 g among women. Alcohol consumption had a highly skewed distribution; the participants in the highest alcohol quintile consumed about half of all reported alcohol (46% for men and 44% for women). Men consumed 71% of all the reported alcohol. In men and women, daily energy intake increased with rising alcohol consumption. However, there were no differences in the non-alcoholic energy intake from foods between alcohol consumption categories (p-value was 0.15 for men and 0.74 for women). The U-shaped association between low/moderate alcohol consumption and BMI was observed, especially in women. Moderate female alcohol consumers were 1.5-2 BMI units leaner than the others, whereas the difference was below 1 BMI unit in male. Conclusions: Alcohol consumers did not habitually substitute food items with alcohol beverages. The participants with low or moderate alcohol consumption, however, had the lowest BMI. The reasons for moderate drinkers being leaner than abstainers remain an interesting open question. Obesity, however, can partly explain the U-shaped association found between alcohol consumption and the risk of cardiovascular diseases.
P0052 : Infusion of third-party mesenchymal stromal cells after liver transplantation: A phase i, open-label, clinical study
Authors: O. Detry, M. Vandermeulen, M.-H. Delbouille, A. Deroover, J. Somja, N. Bletard, A. Briquet, C. Lechanteur, Y. Beguin
Journal: Journal of Hepatology (2015)
Sequence Analysis of the Epstein-Barr Virus (EBV) Latent Membrane Protein-1 Gene and Promoter Region: Identification of Four Variants Among Wild-Type EBV Isolates
Authors: Kristian Sandvej, Jan W. Gratama, Mette Munch, Xiao-Ge Zhou, Reinder L.H. Bolhuis, Brage Storstein Andresen, Niels Gregersen, Stephen Hamilton-Dutoit
Journal: Blood (1997)
<b>Megaphone diplomacy fails in junior doctor contract dispute</b>
Authors: Andy Cowper
Journal: BMJ (2016)

Jeremy Hunt’s imposition of a new junior doctors’ contract in England, after negotiations failed over pay for Saturday working and a second strike took place,1 is unlikely to mark the beginning of the end of this dispute. If clinicians and politicians remain as polarised as they are now, this could be only the end of the beginning. Patients, the NHS, and its less politicised clinicians may get stuck in a place of strife.

Both sides leaked to the media throughout, deepening mutual mistrust. The failure of NHS Employers (the representative body tasked with negotiating new contracts on behalf of the government) to make meaningful progress in talks with junior doctors’ leaders saw the senior NHS manager David Dalton take over negotiations, at Hunt’s request.

Hunt’s actions put him firmly in the frame of this dispute: intervening here (and elsewhere) contrary to the 2012 Health and Social Care Act’s intended political devolution.

Dalton’s public letter to Hunt,2 supporting his contract offer and apparently encouraging its imposition, unravelled with embarrassing haste, as 14 of its 20 NHS chief executive co-signatories publicly insisted that they did not support imposition of the deal.3

Successful negotiators avoid entrenching their positions, enabling give and take. Running commentary in the traditional and social media saw both sides contesting the moral high ground of patient safety. …
Transplantation and Mechanical Circulatory Support in Congenital Heart Disease
Authors: Heather J. Ross, Yuk Law, Wendy M. Book, Craig S. Broberg, Luke Burchill, Frank Cecchin, Jonathan M. Chen, Diego Delgado, Konstantinos Dimopoulos, Melanie D. Everitt, Michael Gatzoulis, Louise Harris, Daphne T. Hsu, Jeffrey T. Kuvin, Cindy M. Martin, Anne M. Murphy, Gautam Singh, Thomas L. Spray, Karen K. Stout
Journal: Circulation (2016)