tbuckley/cabot-search huggingface dataset:
Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer
Authors: Nicholas J. Roberts, Alexis L. Norris, Gloria M. Petersen, Melissa L. Bondy, Randall Brand, Steven Gallinger, Robert C. Kurtz, Sara H. Olson, Anil K. Rustgi, Ann G. Schwartz, Elena Stoffel, Sapna Syngal, George Zogopoulos, Syed Z. Ali, Jennifer Axilbund, Kari G. Chaffee, Yun-Ching Chen, Michele L. Cote, Erica J. Childs, Christopher Douville, Fernando S. Goes, Joseph M. Herman, Christine Iacobuzio-Donahue, Melissa Kramer, Alvin Makohon-Moore, Richard W. McCombie, K. Wyatt McMahon, Noushin Niknafs, Jennifer Parla, Mehdi Pirooznia, James B. Potash, Andrew D. Rhim, Alyssa L. Smith, Yuxuan Wang, Christopher L. Wolfgang, Laura D. Wood, Peter P. Zandi, Michael Goggins, Rachel Karchin, James R. Eshleman, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Ralph H. Hruban, Alison P. Klein
Journal: Cancer Discovery (2015)

Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genomes of 638 patients with familial pancreatic cancer and the tumor exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A, and ATM, and identify novel candidate genes harboring rare, deleterious germline variants for further characterization. We also show how somatic point mutations that occur during hematopoiesis can affect the interpretation of genome-wide studies of hereditary traits. Our observations have important implications for the etiology of pancreatic cancer and for the identification of susceptibility genes in other common cancer types.The genetic basis of disease susceptibility in the majority of patients with familial pancreatic cancer is unknown. We whole genome sequenced 638 patients with familial pancreatic cancer and demonstrate that the genetic underpinning of inherited pancreatic cancer is highly heterogeneous. This has significant implications for the management of patients with familial pancreatic cancer.
Donor and Recipient STR Analysis Before Allogeneic Haematopoietic Stem Cell Transplantation: Possible Correlation With Post-Transplant Outcome
Authors: Patrizia Chiusolo, Silvia Bellesi, Sabrina Giammarco, Elisabetta Metafuni, Sara Marietti, Federica Sorà, Luca Laurenti, Giuseppe Leone, Simona Sica
Journal: Blood (2013)
Low blood levels of bicarbonate are linked to premature death in healthy older people, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Low blood levels of bicarbonate, which helps to regulate the blood’s pH, are associated with increased risk of premature death in healthy older people, a 10 year follow-up study has found.1

Low serum bicarbonate is a known risk factor for mortality and progression in people with chronic kidney disease, but its role in kidney function and mortality in healthy people is less clear.

To investigate this question, researchers analysed data on pH, carbon dioxide, and bicarbonate levels in blood samples from 2287 healthy …
Abstract 18808: Two-dimensional Speckle-tracking Echocardiography to Assess the Viability of Acute Myocardial Infarction
Authors: Makoto Orii, Kumiko Hirata, Takashi Tanimoto, Yasutsugu Shiono, Kunihiro Shimamura, Kouhei Ishibashi, Takashi Yamano, Yasushi Ino, Hironori Kitabata, Tomoyuki Yamaguchi, Takashi Kubo, Toshio Imanishi, Takashi Akasaka
Journal: Circulation (2012)

BACKGROUND [[Unable to Display Character: ―]]Increasing infarct extent is associated with impaired prognosis after acute myocardial infarction (AMI). Two-dimensional speckle-tracking echocardiography (2DSTE) enables the assessment of myocardium deformation and identifies the amount and transmural distribution of viable myocardium. The objective of the study was to evaluate the predictive value of 2DSTE for improvement in cardiac function after AMI in comparison with contrast-enhanced cardiac magnetic resonance imaging (ceMRI). METHODS and RESULTS [[Unable to Display Character: ―]]In 25 patients with first-time acute ST elevation myocardial infarction, myocardial viability was assessed using 2DSTE and ceMRI to predict recovery of function at 6 months follow-up. For each left ventricular segment in a 16-segment model, peak radial, circumferential and longitudinal strain was determined using 2DSTE, and the relative extent of hyperenhancement using ceMRI. Of 128 segments with impaired function early after AMI, 65 showed regional recovery. Compared with segments showing functional improvement, those that failed to recover had lower peak radial (18 ± 16 % vs. 34 ± 23 %; p &lt; 0.001), circumferential (-8 ± 5 % vs. -18 ± 7 %; p &lt; 0.001) and longitudinal (-9 ± 5 % vs. -13 ± 5 %; p &lt; 0.001) strain and a greater extent of hyperenhancement (71 ± 21% vs. 25 ± 20%; p &lt; 0.001). Among strain parameters, circumferential strain yielded greater area under the curve (0.914) than radial and longitudinal strain (0.717 and 0.743, respectively). The predictive value of circumferential strain (sensitivity 83.1%, specificity 81.2%, at a cutoff value of -12.5%) could be comparable to that of hyperenhancement by ceMRI (sensitivity 87.8%, specificity 88.1%, area under the curve 0.939, at a cutoff of 46% hyperenhancement) (p=0.44). CONCLUSIONS [[Unable to Display Character: ―]]Circumferential strain by 2DSTE is a powerful novel parameter to identify reversible myocardial dysfunction after AMI.
Encouraging Outcomes In Older Patients (Pts) Following Nonmyeloablative (NMA) Haploidentical Blood or Marrow Transplantation (haploBMT) With High-Dose Posttransplantation Cyclophosphamide (PT/Cy)
Authors: Yvette L. Kasamon, Gabrielle Prince, Javier Bolaños-Meade, Hua-Ling Tsai, Leo Luznik, Richard F. Ambinder, Ephraim J. Fuchs, Richard J. Jones
Journal: Blood (2013)
Abstract 3681: Ultrasound Triggered Nitric Oxide Release from Echogenic Liposomes Improves Arterial Vasodilation
Authors: Stephen Chrzanowski, Hyunggun Kim, David D McPherson, Shoaling Huang
Journal: Circulation (2008)

Background: Nitric oxide (NO) has been identified as a vasodilator. Delivering external NO to the arterial wall is hampered by hemoglobin scavenging. NO-containing echogenic liposomes (EL) can prot...
Plaque rupture possibly induced by coronary spasm. An autopsy case of acute myocardial infarction.
Authors: Shin-Ichiro Morimoto, Yukio Shiga, Shinya Hiramitsu, Kenji Yamada, Shinichi Nomura, Yutaka Miyagi, Masanori Nomura, Yasushi Mizuno
Journal: Circulation (1988)

The histological picture of sites of coronary spasms has not yet been made sufficiently clear. A histopathological examination was performed on the coronary artery of a patient who died of acute myocardial infarction after a refractory coronary spasm was identified by coronary arteriography. In the site of the coronary spasm, intimal bleeding as well as infiltration by lymphocytes and plasma cells in the adventitia were seen. In the same region, fracture of intimal collagen fibers and rupture of atheromatous plaque were observed. Although it is very difficult to prove in individual cases of acute myocardial infarction that spasms played a part, some cases involving spasms may possibly exist among the cases of acute myocardial infarction showing atheromatous plaque rupture--thrombus formation.
Patterns of HER2/neu, hormonal receptor expression, and proliferative activity in primary and metastatic breast cancer
Authors: F. Giotta, G. Simone, V. Fazio, S. Longo, S. Petroni, V. Rubini, M. Liuzzi, T. Addati, G. Colucci
Journal: Journal of Clinical Oncology (2009)

1071 Background: The modification of biological features of metastatic sites (MS) in breast cancer patients arise some debatable questions regarding clinically usefull information and safe/efficient methods to detect them. Fine needle aspiration (FNA) of visceral MS is an available tool to characterize tumoral lesion and liquid based citology technique provides usefull cell samples for immunocytochemical and/or molecular assays. Methods: The aim of this study was to compare prognostic and predictive factors obtained from primary tumors (PT) and corresponding MS. Fluorescent in situ hybridization (FISH) was performed for HER2/Neu determination, while ER, PgR, and MIB-1 were detected by immunochemistry using specific monoclonal antibodies on monolayered cell sample and in the corresponding cytoinclusion. FNA with a 21–23 G needle was performed in 20 consecutive breast cancer patients with distant metacronous MS. Results: In 8/20 patients, both ER and PgR were absent in PT and in MS, in 7 were both present, in 4 cases only ER was detected, and only 1 case was ER negative with a low PgR. About the proliferative activity (MIB-1 index: cut off value &gt;20%) only 3 MS presented an higher value. With regard to HER2/Neu, 4/20 cases were amplified and no discrepancies were found between cytological and cytoinclusion specimens. No substantial changes were found about kinetic activity. HER2/Neu status as assessed in PT was confirmed in MS in 10/12 cases; a lung mestastasis showed amplification while primary was not amplified and a liver lesion lost the amplification which was detected in the PT. Conclusions: Our study strongly suggest the opportunity in using FNA for detection of prognostic and predictive factors in MS. Pectasides et al. (Anticancer Res. 2006) found in patients with altered or conserved HER2/Neu in PT and in MS different response rates between the two groups and a significant poorer prognosis in patients with altered Neu. We think that liquid-based cytology applied on FNA of distant metastases could help us to understand some more in this issue. No significant financial relationships to disclose.
Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study.
Authors: M K Samson, L P Wasser, E C Borden, H J Wanebo, R H Creech, M Phillips, L H Baker
Journal: Journal of Clinical Oncology (1987)

In 1980, a consensus chemotherapy intergroup study for advanced malignant mesothelioma was initiated based on a collaborative agreement among the Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group (SWOG), and the Southeastern Cancer Study Group (SECSG). The purpose of the study was to evaluate cyclophosphamide (500 mg/m2 day 1), imidazole carboxamide (250 mg/m2 days 1 through 5), and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (50 mg/m2 day 1) v cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) in a randomized prospective clinical trial involving 76 fully evaluable patients with advanced stages II to IV malignant mesothelioma. A total of nine responses (12%) were documented, including three complete and six partial responses. There was no significant difference in response duration or survival between treatment arms. Leukopenia (greater than 2,000/microL) was observed in 46% of patients treated with the three-drug combination and 38% of patients receiving the two-drug combination. The variables of performance status 0-1 and the absence of prior chemotherapy/radiotherapy were significant with respect to favorable impact on survival. We conclude, based on the minimal benefit observed, that the combination of cyclophosphamide and doxorubicin with or without imidazole carboxamide does not warrant further investigation in patients with advanced-stage malignant mesothelioma.
Abstract 17672: Interaction of Global Coronary Vasomotor Dysfunction and Early Revascularization on Adverse Cardiovascular Outcomes
Authors: Viviany R Taqueti, Rory Hachamovitch, Venkatesh Murthy, Masanao Naya, Courtney Foster, Jon Hainer, Sharmila Dorbala, Ron Blankstein, Marcelo F Di Carli
Journal: Circulation (2014)

Background: Coronary vasomotor dysfunction identifies patients at risk for cardiac death. We sought to determine the association between global coronary flow reserve (CFR, an integrated measure of coronary vasomotor function) and adverse cardiovascular events, in patients referred for coronary angiography with or without subsequent revascularization. Methods and Results: Consecutive patients (n=329) without prior coronary artery bypass surgery (CABG), heart failure, or left ventricular (LV) systolic dysfunction referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography (PET) were followed (median 3.1 years) for cardiovascular death and heart failure admission. Extent and severity of coronary angiographic stenosis was estimated using the CAD prognostic index (CADPI) and CFR measured noninvasively by PET. A subset of patients (n=193) underwent early revascularization, defined as CABG and/or percutaneous coronary intervention (PCI) within 90 days after PET. After adjusting for clinical risk score, LV ejection fraction, LV ischemia, CADPI, and time-dependent early revascularization with CABG and/or PCI, CFR remained independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95% CI 1.20-3.40, p=0.008). In adjusted analysis, there was a significant interaction (p=0.04) between CFR and early revascularization by CABG, such that patients with impaired CFR who underwent CABG (n=39), but not PCI (n=154), experienced event rates comparable to those with preserved CFR, independently of revascularization. Conclusions: CFR associated with adverse cardiovascular outcomes independently of angiographic severity, and modified the effect of early revascularization. Diffuse atherosclerosis and microvascular dysfunction may contribute to the pathophysiology of cardiovascular death and heart failure, and impact upon the outcomes of revascularization.
Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study.
Authors: A S Freedman, T Takvorian, D Neuberg, P Mauch, S N Rabinowe, K C Anderson, R J Soiffer, N Spector, M Grossbard, M J Robertson
Journal: Journal of Clinical Oncology (1993)

PURPOSE Using high-dose therapy and autologous bone marrow transplantation (ABMT) to overcome cellular resistance and eradicate minimal disease, we initiated a pilot study during first remission in patients with non-Hodgkin's lymphoma (NHL) to examine whether the long-term disease-free survival (DFS) rate can be improved for patients with poor-prognosis intermediate/high-grade NHL. PATIENTS AND METHODS Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved-cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. RESULTS Following ABMT, no acute in-hospital treatment deaths occurred, and engraftment of granulocytes and platelets was significantly faster than for patients undergoing ABMT who were in second or subsequent remission. Of 26 patients, 21 remain in CR maintained without continued therapy, three relapsed in sites of prior nodal disease (4.8, 5.4, and 28 months post-ABMT), and two died in remission. The DFS rate is estimated to be 85% at 28 months and thereafter. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. CONCLUSION This pilot study suggests that consolidation of first remission with ABMT may improve the long-term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse.
Platelet alpha 2-adrenoreceptor binding in elderly depressed patients
Authors: M C Doyle, A J George, A V Ravindran, R Philpott
Journal: American Journal of Psychiatry (1985)

Specific binding of 3H-clonidine to platelet membranes was measured in depressed elderly patients and in an elderly control group. Maximum specific binding was significantly higher in depressed patients than in the control group, whereas the binding affinity was not significantly different.
Work situation and work-related difficulties in stomach cancer survivors compared with the general population
Authors: K. Lee, M. Lee, J. Bae, S. Kim, Y. Kim, K. Ryn, J. Lee, J. Noh, T. Sohn, S. Hong, Y. Yun
Journal: Journal of Clinical Oncology (2007)

9084 Background: We aimed to investigate the work situation and work-related difficulties among stomach cancer survivors compared with the general population. Methods: We enrolled 426 stomach cancer survivors diagnosed 2001 to 2003 from two hospitals and 994 members without a history of cancer selected randomly from a representative sample of Korea adults. We identified work situation and work-related difficulties in two groups using multivariate logistic regression. Results: An employment rate of stomach cancer survivors decreased from 66.2% to 53.1% at average 28 months after their diagnosis and it was lower than that of general population (63.5%). The primary reason for not-working in survivors were that they were easily fatigued (31.2%) and had limitations in physical functioning (13.0%). Examining work-related difficulties, 50.6% of survivors who were working at the time of survey reported that they were easily fatigued and 37.5% of survivors reported that their capacity of work decreased whereas only 22.4%, 10.6% of general population reported. Survivors had housework- related difficulties because they were easily fatigued (74.4%) and emotionally distressful (12.2%) whereas 58.0% and 4.0% of general population reported. Older age (adjusted odds ratio [aOR]=18.12; 95% confidence interval [CI]=6.59 to 49.81), female (aOR=5.30; 95% CI=7.37 to 31.31), low income (aOR=1.87; 95% CI=1.04 to 3.33), poor physical functioning (aOR=0.97; 95% CI=0.95 to 0.98) and total gastrectomy (aOR=2.40; 95% CI=1.26 to 4.60) were more likely to increase the likelihood of not working in stomach cancer survivors. Conclusions: Stomach cancer and its treatment had a negative impact on employment rate as previous studies with other type of cancer. Our study found that stomach cancer survivors had an experience not only work-related but also housework-related difficulties. This information on stomach survivors’ might be help to make a better plan for the intervention of stomach cancer survivors’ return to work. No significant financial relationships to disclose.
Abstract 15977: A Stabilizing Variant in Transthyretin, T119M, and Risk of Ischemic Vascular Disease
Authors: Louise S Hornstrup, Ruth Frikke-Schmidt, Borge G Nordestgaard, Anne Tybjaerg-Hansen
Journal: Circulation (2012)

Background: Senile systemic amyloidosis, which clinically may present as ischemic vascular disease, is a common aging phenomenon caused by deposition of wildtype transthyretin (TTR) fibrils mainly ...
Theme issue for medics and health informed public
Authors: J. D Curran
Journal: BMJ (2003)

Editor—It is a good idea for people to be informed about health matters, to take more responsibility for their health, and to realise the benefits and limits of medicine.1 Whether it is a good idea to try to accomplish this through altering the format and content of the BMJ is another matter.

I think that the BMJ is first and foremost a trade paper, and its primary purpose should be to educate and inform practitioners of that trade. I also think that the reason why it is read outside the profession is because of the characteristics that make it a successful trade paper: the quality and detail of its articles, which arise out of who they are aimed at—namely, the medical profession. Changes to the content and format to appeal to a broader readership, whether for the reasons proposed by Eaton in her editorial or simply to increase sales, would, I think, diminish the journal, making it of less use to its primary readership and ultimately unsatisfying also for the non-professionals who choose to read it.

An analogy with another trade may seem odd but may have some usefulness.

I am interested in cinema and occasionally read trade magazines such as Variety. Many articles in the magazine are abstruse or irrelevant to someone outside the film business, but some are of interest, and the film reviews are excellent. The reason for this is that the reviews are aimed at a specific audience which needs to know an unglossed assessment of the strengths and weaknesses of a film.

If the editors of Variety decided to change the format to appeal to a broader audience they would probably have to remove articles of relevance to those in the trade to make room for more lightweight, “moviegoer friendly” articles and reviews. In the process the paper would become less authoritative and so of less use to those in the trade and of less interest to outside readers who want to know more about films and the film business than can be found in the general press.

The same thing might happen if the changes of the proposed theme issue of the BMJ were to be adopted. If the editors at the BMJ are set on doing this, by all means let us see the result, but it seems that some of the suggestions for articles (a celebrity interview) do not sound very inspiring.
Dietary Factors and Hepatoma in Rainbow Trout (&lt;italic&gt;Salmo gairdneri&lt;/italic&gt;). I. Aflatoxins in Vegetable Protein Feedstuffs&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R. O. Sinnhuber, J. H. Wales, J. L. Ayres, R. H. Engebrecht, D. L. Amend
Journal: JNCI Journal of the National Cancer Institute (1968)

Aflatoxins (toxic metabolites of the mold Aspergillus flavus) were present in a commercial trout ration causing hepatoma in rainbow trout. Cottonseed meal and solvent extracts of cottonseed meal and of rations containing cottonseed meal and peanut meal were found by chemical assay and confirmed by duckling assay to contain aflatoxins. Diets containing these materials and a purified test diet to which aflatoxins had been added produced microscopic tumors in 6 months and gross lesions of hepatocarcinoma in 9 months. Similar diets without aflatoxin were negative.