tbuckley/cabot-search huggingface dataset:
Abstract IA19: Human melanoma neoantigens: Identification and vaccination
Authors: Gerald P. Linette
Journal: Clinical Cancer Research (2016)

Abstract Cancer medicine is in the midst of a dramatic shift towards new therapeutics directed by alterations in the cancer genome. Melanoma genomes harbor somatic mutations that are caused by exposure to mutagens such as ultraviolet light. Tumor missense mutations (MM), translated into amino acid substitutions (AAS), may provide a form of non-self that elicits tumor specific T cell immunity. Indeed, T cell immunity directed against tumor encoded AAS has been reported in humans with cutaneous melanoma, thus implicating MM as a source of patient specific (private) neoantigens. However, a systematic evaluation of these putative neoantigens as validated targets is lacking and it is unknown whether the immune response directed against tumor encoded AAS can be augmented by vaccination. We show that vaccination against melanoma AAS-encoding peptides augments naturally occurring T cell immunity and reveals new HLA class I restricted private neoantigens in patients with advanced melanoma. Neoantigen specific T cells recognized naturally processed and presented antigen but failed to recognize wild type (non-mutated) antigen. The presentation of neoantigens by HLA-A*02:01 in human melanoma was confirmed by mass spectrometry. As determined by TCR beta CDR3 DNA sequencing, vaccination promotes a repertoire of neoantigen-specific T cells that is highly diverse in terms of both TCR beta usage and clonal composition. No evidence of autoimmunity was apparent after vaccination. Our results demonstrate that tumor MM can be targeted as neoantigens and vaccination directed at tumor AAS somatic mutations broadens the antigenic breadth and clonal diversity of anti-tumor immunity. Personalized cancer immunotherapies targeting private somatic tumor alterations may become feasible in the near future. Citation Format: Gerald P. Linette. Human melanoma neoantigens: Identification and vaccination. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA19.
The Role of Bisphosphonates in Breast Cancer
Authors: Richard L. Theriault
Journal: Journal of the National Comprehensive Cancer Network (2003)

Breast cancer frequently metastasizes to bone. Metastases result in skeletal morbidity including pathologic fractures, the need for radiation or surgery to bone, spinal cord compression and hypercalcemia. The pathophysiology of bone destruction is related to activation of osteoclasts by tumor-derived and bone marrow microenvironmental factors. One prominent osteoclast–activating factor associated with breast cancer is parathyroid hormone-related peptide (PTHrP). Bisphosphonates have been shown to impair osteoclast activity by decreasing recruitment from the monocyte macrophage cell line, inhibiting osteoclast function at the bone site and causing osteoclasts to undergo apoptosis. Clinical studies with bisphosphonates show an improvement in the control of hypercalcemia and a reduction in skeletal related morbidity with administration of pamidronate and zoledronic acid. Bisphosphonates have become the standard of care for osteolytic metastases associated with breast cancer. Recent data with zoledronic acid found that skeletal related morbidity may be reduced regardless of the radiographic picture of skeletal metastases. Thus, zoledronic acid may be valuable in osteolytic and osteoblastic disease as well as in disease with an osteolytic or osteoblastic radiographic appearance. In breast cancer with osteolytic disease, zoledronic acid may be more effective than pamidronate in reducing skeletal morbidity and prolonging the time to first skeletal event.
Cancer in Utah: Risk by Religion and Place of Residence&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. L. Lyon, M.D., M.P.H.
 4, J. W. Gardner, M.D., M.P.H., D. W. West, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1980)

We compared cancer incidence during 1967--75 between Mormons and non-Mormons living in urban and rural areas of Utah. The non-Mormon urban men had a 34% higher risk of cancer compared with their rural counterparts. Most of this increase in risk occurred in sites associated with tobacco and for cancers of the stomach, colon, and prostate gland. Urban Mormon males had no significant increase in risk. The urban female population was at higher risk than was the rural regardless of religion. The increase was not as striking as that observed in non-Mormon men (8 vs. 34%); cancers of the respiratory and gastrointestinal tracts and female genitalia contributed to the elevated risk. We concluded that personal habits such as smoking and drinking and reproductive factors were possible explanations for the previously observed urban-rural gradients in cancer risk.
Response to Open Peer Commentaries on “Not Just ‘Study Drugs’ for The Rich: Stimulants as Moral Tools for Creating Opportunities for Socially Disadvantaged Students”
Authors: Keisha Shantel Ray
Journal: The American Journal of Bioethics (2016)

I thank the commenters for their thoughtful critiques and responses to my argument in “Not Just ‘Study Drugs’ for the Rich: Stimulants as Moral Tools for Creating Opportunities for Socially Disadva...
Accountability, public policy, and psychiatry
Authors: A R Somers
Journal: American Journal of Psychiatry (1977)

The author identifies the direction of changes in health policy in the United States that need to be taken into account by the health professions in their dealings with government. She discusses three areas in which these changes will call for adjustment on the part of the medical profession and major health care institutions and defines the special challenge to psychiatry implicit in the changes. She concludes that the public's need for attention to the psychosocial aspects of health and the renewed interest in prevention present psychiatry with an opportunity to provide leadership in health care delivery.
Abstract 568: Decoding shared antigenic epitopes and their cognate TCR genes in melanoma TILs using a library of paired human cell-based pHLA multimers and artificial APCs
Authors: Kenji Murata, Kayoko Saso, Linh T. Nguyen, Douglas Millar, Marcus O. Butler, Pamela S. Ohashi, Naoto Hirano
Journal: Cancer Research (2019)

The NZB mouse strain is genetically predisposed to develop, at approximately 6 months of age, a spontaneous and severe autoimmune anaemia caused by the production of pathogenic anti-mouse red blood cell (MRBC) autoantibodies. Although it is believed that the predisposition to autoimmune anaemia is multigenic in nature, the main pathogenic mechanism is attributed to anti-MRBC autoantibodies. We have generated eight anti-MRBC monoclonal antibody (mAb)-producing hybridomas derived from splenocytes of 9- and 12-month-old NZB mice with spontaneous autoimmune anaemia to dissect the molecular and cellular mechanisms resulting in the production of these pathogenic antibodies. The predominant immunoglobulin isotype was IgG2a, produced by five out of eight hybridomas (63%), while IgM, IgG1 and IgG2b were each produced by one hybridoma cell line (12%). Antigen specificity analysis of all eight hybridomas revealed that antibodies from seven out of eight hybridomas were monospecific for MRBC antigen(s). Only one hybridoma (clone 4-16-1) cross-reacted with rat RBC. None of the hybridomas produced antibodies reactive with single- or double-stranded DNA (ss- or dsDNA). Surface and cytoplasmic staining for the CD5 antigen revealed that none of the hybridomas was derived from CD5+ B lymphocytes. All hybridomas cause anaemia when implanted intraperitoneally into normal BALB/c mice. Molecular studies of five of the eight anti-MRBC mAb reveal that all use functionally rearranged genes from the VH J558 gene family. Three of these five mAb used FL16.1 DH genes while one had a CDR3 that resulted from a fusion between two DH genes (SP2.3 and SP2.2) from the SP family.
P0497 : Secretory leukocyte protease inhibitor (SLPI) suppresses innate immune responses and promotes resolution of inflammation in an auto/paracrine manner during acute liver failure (ALF)
Authors: E. Triantafyllou, E. Liaskou, W. Khamri, O.T. Pop, S. Davies, C. Bernsmeier, Z. Stamataki, R.D. Goldin, Y. Ma, A. Quaglia, M.R. Thursz, J. Wendon, S.M. Curbishley, C.J. Weston, D.H. Adams, C.G. Antoniades
Journal: Journal of Hepatology (2015)
Women's Susceptibility to Tobacco Carcinogens and Survival After Diagnosis of Lung Cancer
Authors: Claudia I Henschke, Rowena Yip, Olli S Miettinen
Journal: JAMA (2006)

Context It has been hypothesized that women are more susceptible to tobacco carcinogens than men, but after diagnosis of lung cancer, they have better survival rates than men. ObjectiveTo add to the evidence on the lung cancer risk of women who smoke and their survival after diagnosis of lung cancer, conditional on other prognostic indicators and compared with men of the same age who smoke. Design, Setting, and ParticipantsNonexperimental, etiologic study with prospective collection of data based on baseline computed tomographic screening for lung cancer and follow-up of diagnosed cases of lung cancer in North America in 1993-2005.A total of 7498 women and 9427 men were screened, all of whom were asymptomatic, aged at least 40 years, and had a history of cigarette smoking. Main Outcome MeasuresComparing women with men, the prevalence odds ratio (OR) for screen-detectable lung cancer (conditional on age and smoking history) and the hazard ratio of fatal outcome of lung cancer (conditional on smoking history, disease stage, tumor cell type, and resection). ResultsLung cancer was diagnosed in 156 women and 113 men (rates of 2.1% and 1.2%, respectively).The prevalence OR comparing women with men was 1.9 (95% confidence interval [CI], 1.5-2.5).The hazard ratio of fatal outcome of lung cancer comparing women with men was 0.48 (95% CI, 0.25-0.89). ConclusionWomen appear to have increased susceptibility to tobacco carcinogens but have a lower rate of fatal outcome of lung cancer compared with men.
The Virchow Memorial Fund
Authors: F. Semon
Journal: BMJ (1902)

<h3>Problem</h3> The need to develop a patient pathway for emergency admissions who have a previously undiagnosed cancer. <h3>Design</h3> The existing patient pathway was audited and process-mapped to identify delays and areas for improvement. Discussions with key stakeholders were held to identify their needs from an acute oncology service. <h3>Strategies for change</h3> A new patient pathway was developed, and a new online referral process was implemented. The publicity and education campaign was repeatedly aimed at referring physicians at consultant and junior level, and took the form of emails and presentations with handouts at all teaching sessions, multidisciplinary team meetings, the Consultants Committee and Junior Doctors9 induction. <h3>Effects of change</h3> The new system was piloted for 6 months. 12/18 patients were referred via the new pathway. 15/18 patients were referred via the new online system. Length of stay, endoscopies, biopsies and blood tests were all statistically significantly reduced during the study period compared with the original audit. <h3>Lessons learnt</h3> The challenge was to convince the referring general physicians to use the new patient pathway and referral method. Incorporating their ideas for improvement and implementation made it more likely that they would take up the new ideas. Education and publicity were also extensive, often repeated, and at both junior and senior level. Having the Lead Cancer Clinician and Acute Medicine Consultant engage directly with consultant colleagues, as well as strong support from the Medical Director, was also crucial to the project9s success.
Cyclosporine for Treatment of Psoriasis
Authors: W P Gulliver
Journal: New England Journal of Medicine (1991)

The efficacy of cyclosporine is well documented in multiple clinical trials. Patients with severe psoriasis who require systemic treatment should be considered for this therapeutic agent. The need for both a careful evaluation prior to therapy and strict monitoring of the patient cannot be over emphasized because untreated hypertension, renal dysfunction, and other disorders may lead to serious, nonreversible morbidity. Physicians are encouraged to follow the published guidelines for controlling psoriasis in their patients and lowering the risk of potential drug toxicity.
Abstract P1-09-10: Mammographic density: Its inherent epidemiology in 12000 women from 22 diverse countries
Authors: VA McCormack
Journal: Cancer Research (2016)

Abstract The International Pooling Project on Mammographic Density Consortium Background: Over the past 25 years, the epidemiologic knowledge for mammographic density (MD), as a strong marker of breast cancer risk, has expanded greatly, aided by the availability of mammograms in countries with wide-scale mammography-based breast cancer screening programs. The known epidemiology of this breast-tissue specific marker is thus that of women in high incidence countries, and not of that in countries with lifestyles that are characterized by very different life-long hormonal influences, especially during the reproductive years. The International Pooling Project on Mammography Density (IPPMD) aimed to examine the epidemiology of MD internationally, to benefit from breast cancer risk and breast cancer risk factor heterogeneity. Methods: From diverse breast cancer risk populations, IPPMD sought to include samples of 200 premenopausal and 200 postmenopausal general population women for which risk factor data and mammograms, not taken for symptomatic reasons, were available. To date we have included 11447 women from 22 countries, consisting of 40 ethnicity and location-specific population groups. 5 to 6 countries were included in each of Europe, Africa and the Middle East, Asia and the Americas. Populations not previously studied in terms of MD include South Africa, Kenya, Turkey, Egypt and Brazil. Digitized/digital films for every woman were anonymised, transferred to the study and read using Cumulus 6 by 3 readers, to obtain standardized quantitative and comparable MD estimates across the entire sample. Readers were blind to all woman and study/country identifiers. Normal errors regression models were used to analyse square root percent density and absolute dense area, after standardizing reader-specific values to a single reader's distribution. Results: All risk factor data and MD readings have recently been pooled. Initial findings are as follows. Mean percent MD and absolute dense area varied over 2-fold between the 40 population groups, after adjusting for age and BMI. There is striking consistency in several epidemiologic features of MD across all population groups, including the rate of decline of density at both pre and post-menopausal ages and the decline associated with the menopausal transition. We are exploring to what extent these and other factors such as menarche, parity, age at first birth and breastfeeding, account for between population-group differences in MD. Conclusions: This international perspective provides a valuable insight to the epidemiology of MD worldwide. Citation Format: McCormack VA. Mammographic density: Its inherent epidemiology in 12000 women from 22 diverse countries. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-10.
Annual risk of tuberculosis infection in rural China: a population-based prospective study
Authors: Lei Gao, Liqiong Bai, Jianmin Liu, Wei Lu, Xinhua Wang, Xiangwei Li, Jiang Du, Xinchun Chen, Haoran Zhang, Henan Xin, Hongtao Sui, Hengjing Li, Haoxiang Su, Jian He, Shouguo Pan, Hong Peng, Zuhui Xu, Antonino Catanzaro, Thomas G. Evans, Zongde Zhang, Yu Ma, Mufei Li, Boxuan Feng, Zhen Li, Ling Guan, Fei Shen, Zhijian Wang, Tao Zhu, Shumin Yang, Hongyan Si, Yi Wang, Yunhong Tan, Tianzhu Chen, Chen Chen, Yinyin Xia, Shiming Cheng, Weiguo Xu, Qi Jin
Journal: European Respiratory Journal (2016)

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.
Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: immunofluorescent staining and platelet peroxidase detection in megakaryocyte colonies and in in vivo cells from normal and leukemic patients
Authors: W Vainchenker, JF Deschamps, JM Bastin, J Guichard, M Titeux, J Breton-Gorius, AJ McMichael
Journal: Blood (1982)
A slow epidemic of LGV in the Netherlands in 2004 and 2005
Authors: M J W van de Laar, F. D.H. Koedijk, H Götz, H JC de Vries
Journal: Eurosurveillance (2006)

In 2004, an outbreak of LGV was detected in MSM in the Netherlands. By January 2006, 179 confirmed cases of LGV had been reported; 65 (retrospectively) in 2002/2003, 76 in 2004 and 38 in 2005. The evolution of the LGV outbreak appears to have slowed down and only a few cases were found in the first months of 2006.
Case 26-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1985)

Presentation of Case A 43-year-old woman was admitted to the hospital because of a progressive saddle-nose deformity. She was well until 10 years earlier, when she began to notice a gradual decrease in prominence of the nasal bridge. Two years later polyarthralgia developed acutely, accompanied by morning stiffness, fatigue, and malaise. She was admitted to another hospital, where no specific diagnosis was made. After two years the polyarthralgia resolved. During the succeeding years the patient observed progressive shrinkage of the nasal bridge, accompanied by painful crusting and occasional bleeding within the nose and intermittent cyanosis of the nasal dorsum. Five . . .
Freud and Third-Party Payment: A Historical Note
Authors: Sydney E. Pulver
Journal: American Journal of Psychiatry (1974)

The author presents excerpts from the diary of Joseph Wortis to illustrate Freud's analysis of a man whose fees were paid by a third party. Freud made no specific recommendations concerning third-party payment, but the fact that he undertook Wortis' analysis seems to indicate that he did not find it an obstacle. Although this analysis was unsuccessful, the failure does not seem to be related to the type of payment.
PET study of greater visual activation in schizophrenia
Authors: S F Taylor, R Tandon, R A Koeppe
Journal: American Journal of Psychiatry (1997)

The authors tested the hypothesis that photic visual stimuli cause a greater blood flow activation response in subjects with schizophrenia than in normal subjects.Eleven medicated patients with schizophrenia and 10 normal subjects were studied with [15O]H2O positron emission tomography to measure perfusion during photic stimulation at four different rates.The activation at three out of four rates of visual stimulation was greater for the patients with schizophrenia than it was for the normal subjects.Further investigation into the mechanisms of activation during sensory stimulation in schizophrenia is warranted.
Cancer-Associated Serum Globulin Demonstrated by Polyacrylamide Gel Electrophoresis
Authors: C Tal, R B Herberman, M Gail, A Schutt
Journal: JNCI Journal of the National Cancer Institute (1980)

We evaluated the ability of polyacrylamide gel electrophoresis (PAGE) to measure protein band No. 1 (PB1) in serum as a means of discriminating between the sera of cancer patients and controls. Serum samples from 123 cancer patients, 155 subjects without clinically diagnosed cancer, and 6 members of families with a high incidence of cancer (total, 284) were obtained in Israel. An additional 214 serum samples from 80 cancer patients and 134 subjects without cancer were obtained from the Mayo Clinic-National Cancer Institute Serum Bank. Although a significantly higher proportion of serum specimens from cancer patients had positive results for PB1 by the PAGE method, the test at its current stage of development does not seem sufficiently discriminating for use in screening for cancer.
Abstract B14: Use of DNA methylation in circulating free DNA as a potent biomarker for pancreatic cancer detection
Authors: Keiko Shinjo, Yutaka Kondo
Journal: Cancer Research (2016)

Abstract Pancreatic cancer is highly lethal malignancy despite the recent clinical advancement. Since pancreatic cancer is often difficult to diagnose, there is an urgent need to develop novel biomarkers for early detection with blood tests. Epigenetic alterations have emerged as a common hallmark of many types of human cancers as well as pancreatic cancer. Studies have shown that epigenetic dysregulation is associated with multiple steps during carcinogenesis. Therefore, invention of blood-based DNA methylation biomarkers and their high-sensitive detection system may be a promising diagnostic tool for pancreatic cancer. In order to establish the diagnostic system, first, we performed genome-wide DNA methylation analysis of 38 EUS-FNA specimens of pancreatic cancer with clinical stage III-IV using Illumina Infinium HumanMethylation450 BeadChip. We further analyzed the DNA methylation profiles of other types of tumors in the public database, TCGA (The Cancer Genome Atlas), and identified five marker genes, which were specifically methylated in pancreatic cancers. In addition, analysis of DNA methylation status of pancreas cancers comparing 10 normal tissues in TCGA data set revealed that 99% of tumors were methylated at least one of the five markers (sensitivity, 98.9%; specificity, 44%). We next examined the DNA methylation status in the markers in the validation cohort (n=19) by bisulfite pyrosequencing and quantitative methylation specific PCR and found that 18/19 (95%) cases were methylated in at least one marker (AUC=0.95). Currently, our preliminary data showed that more than 95% of cancer patients have aberrant DNA methylation in circulating free DNA (cfDNA). Our results indicate that detection of DNA methylation in the cfDNA might be a promising and potent tool for diagnosis of pancreatic cancers. Citation Format: Keiko Shinjo, Yutaka Kondo. Use of DNA methylation in circulating free DNA as a potent biomarker for pancreatic cancer detection. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B14.