tbuckley/cabot-search huggingface dataset:
Emergency Brain Resuscitation
Authors: A Working Group on Emergency Brain Resuscitation.
Journal: Annals of Internal Medicine (1995)

Past efforts to reverse or limit the effects of acute stroke have been largely unsuccessful, in part because of the inability to evaluate and treat most patients soon after stroke onset.One important factor in the delay of treatment has been the nihilistic attitude of medical personnel, including physicians, toward the need to rapidly evaluate and treat patients with stroke. This is important for non-neurologists because most patients with stroke are cared for by internists, family physicians, and emergency physicians. We present the concept of emergency brain resuscitation as one method of galvanizing and motivating health professionals to take a more proactive and aggressive approach to treating the patient with acute stroke. Laboratory and clinical data support the potential efficacy of emergency brain resuscitation teams, which will use standard and experimental techniques to treat patients with stroke. A cost–benefit analysis suggests that emergency brain resuscitation may lower the costs associated with stroke by reducing length of hospital stay, disability, and lost wages. The formation of pilot programs is a logical first step toward evaluating and refining this concept. *For a listing of members of A Working Group on Emergency Brain Resuscitation, see the Appendix.
Left Ventricular Geometry Determines Prognosis and Reverse J-Shaped Relation Between Blood Pressure and Mortality in Ischemic Stroke Patients
Authors: Chan Soon Park, Jun-Bean Park, Yerim Kim, Yeonyee E. Yoon, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim, Goo-Yeong Cho, Dae-Won Sohn, Seung-Hoon Lee
Journal: JACC. Cardiovascular imaging (2017)
Risk factors and short-term projections for serotype-1 poliomyelitis incidence in Pakistan: A spatiotemporal analysis
Authors: Natalie A. Molodecky, Isobel M. Blake, Kathleen M. O’Reilly, Mufti Zubair Wadood, Rana M. Safdar, Amy Wesolowski, Caroline O. Buckee, Ananda S. Bandyopadhyay, Hiromasa Okayasu, Nicholas C. Grassly
Journal: PLoS Medicine (2017)

Background Pakistan currently provides a substantial challenge to global polio eradication, having contributed to 73% of reported poliomyelitis in 2015 and 54% in 2016. A better understanding of the risk factors and movement patterns that contribute to poliovirus transmission across Pakistan would support evidence-based planning for mass vaccination campaigns. Methods and findings We fit mixed-effects logistic regression models to routine surveillance data recording the presence of poliomyelitis associated with wild-type 1 poliovirus in districts of Pakistan over 6-month intervals between 2010 to 2016. To accurately capture the force of infection (FOI) between districts, we compared 6 models of population movement (adjacency, gravity, radiation, radiation based on population density, radiation based on travel times, and mobile-phone based). We used the best-fitting model (based on the Akaike Information Criterion [AIC]) to produce 6-month forecasts of poliomyelitis incidence. The odds of observing poliomyelitis decreased with improved routine or supplementary (campaign) immunisation coverage (multivariable odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.67–0.84; and OR = 0.75, 95% CI 0.66–0.85, respectively, for each 10% increase in coverage) and increased with a higher rate of reporting non-polio acute flaccid paralysis (AFP) (OR = 1.13, 95% CI 1.02–1.26 for a 1-unit increase in non-polio AFP per 100,000 persons aged <15 years). Estimated movement of poliovirus-infected individuals was associated with the incidence of poliomyelitis, with the radiation model of movement providing the best fit to the data. Six-month forecasts of poliomyelitis incidence by district for 2013–2016 showed good predictive ability (area under the curve range: 0.76–0.98). However, although the best-fitting movement model (radiation) was a significant determinant of poliomyelitis incidence, it did not improve the predictive ability of the multivariable model. Overall, in Pakistan the risk of polio cases was predicted to reduce between July–December 2016 and January–June 2017. The accuracy of the model may be limited by the small number of AFP cases in some districts. Conclusions Spatiotemporal variation in immunization performance and population movement patterns are important determinants of historical poliomyelitis incidence in Pakistan; however, movement dynamics were less influential in predicting future cases, at a time when the polio map is shrinking. Results from the regression models we present are being used to help plan vaccination campaigns and transit vaccination strategies in Pakistan.
People in US are less concerned about health inequality than those in other countries
Authors: Michael McCarthy
Journal: BMJ (2017)

US citizens experience “relatively low levels of moral discomfort” over the gap in access to healthcare between rich and poor people, a study has found.1

The international study, which analyzed people’s perception of their health in relation to their income, found that Americans were less concerned about differences in access to healthcare related to income than people in other countries.

In general, Americans were less likely to consider disparities resulting from income differences to be unfair. Although 67% of US respondents said that “many” people in the country did not have access to …
Abstract B43: ADAM12 is a novel regulator of stem-like cells in triple-negative breast cancer
Authors: Yue Qi, Sara Duhachek-Muggy, Hui Li, Linda Alyahya, Randi Wise, Anna Zolkiewska
Journal: Cancer Research (2016)

Abstract High expression of metalloprotease ADAM12 is associated with increased metastasis in triple-negative breast cancers (TNBC) and is an independent prognostic factor of chemoresistance in TNBC. ADAM12 is up-regulated in the claudin-low subtype of breast tumors and in the mesenchymal stem-like subtype of TNBC. Furthermore, expression of ADAM12 is elevated in post-therapy tumors. The goal of our study was to examine whether ADAM12 may serve as a marker or a therapeutic target in cells with enhanced metastatic cancer stem cell phenotype, using two representative TNBC cell lines with aggressive and metastatic phenotype, SUM159PT and Hs578T. We found that sorted cell subpopulations with the highest cell surface expression of ADAM12 had increased expression of cancer stem cell markers, decreased proliferation rates in 2-D cultures, and increased ability to form mammospheres under suspension conditions. ADAM12 knockdown decreased mammosphere formation, increased apoptotic cell death upon detachment, and decreased cell migration and invasion. ADAM12 knockdown also decreased the population of CD44+/CD24- cells and ALDEFLUOR+ cells and reduced tumor formation in mice in vivo, suggesting that ADAM12 might be necessary for maintaining cancer stem cell phenotype of TNBC cells. To get insight into molecular pathways modulated by ADAM12, we performed RNA sequencing in cells with inducible knockdown of ADAM12 and identified several candidate pathways. Our results indicate that ADAM12 is a novel regulator of the plasticity of TNBC stem cells and it may serve as a future target in anti-metastatic breast cancer therapies. Citation Format: Yue Qi, Sara Duhachek-Muggy, Hui Li, Linda Alyahya, Randi Wise, Anna Zolkiewska. ADAM12 is a novel regulator of stem-like cells in triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B43.
An Instrumental Variable Analysis Comparing Medicare Expenditures for Laparoscopic vs Open Colectomy
Authors: Kyle H. Sheetz, Edward C. Norton, Scott E. Regenbogen, Justin B. Dimick
Journal: JAMA Surgery (2017)

Numerous study findings suggest that the use of laparoscopy is associated with lower health care costs for many operations, including colectomy. The extent to which these differences are due to the laparoscopic approach itself or selection bias from healthier patients undergoing the less invasive procedure is unclear.To evaluate the differences in Medicare expenditures for laparoscopic and open colectomy.A population-based study was conducted of Medicare beneficiaries undergoing laparoscopic or open colectomy between January 1, 2010, and December 31, 2012. The dates of the analysis were November 13 to December 10, 2016. Using instrumental variable methods to account for selection bias, actual Medicare payments after each procedure were evaluated. To identify the mechanisms of potential cost savings, the frequency and amount of physician, readmission, and postacute care payments were evaluated. Several sensitivity analyses were performed restricting the study population by patient demographic or surgeon specialty.Actual Medicare expenditures up to 1 year after the index operation.The study population included 428 799 patients (mean [SD] age, 74 [10] years; 57.0% female). When using standard methods, patients undergoing laparoscopic colectomy (vs open) had lower total Medicare expenditures (mean, -$5547; 95% CI, -$5408 to -$5684; P < .01). When using instrumental variable methods, which account for potentially unmeasured patient characteristics, patients undergoing laparoscopic colectomy (vs open) still had lower Medicare expenditures (mean, -$3676; 95% CI, -$2444 to -$4907; P < .01), although the magnitude of the association was reduced. When examining the root causes of the difference in costs between patients who underwent laparoscopic and open colectomy, the key drivers were a reduction in costs from readmissions (mean, -$1102; 95% CI, -$1373 to -$831) and postacute care (mean, -$1446; 95% CI, -$1988 to -$935; P < .01).This population-based study demonstrates the influence of selection bias on cost estimates in comparative effectiveness research. While the use of laparoscopy reduced total episode payments, the source of savings is in the postacute care period, not the index hospitalization.
Polymorphism of the MTHFR Gene is Associated with Altered Gene Expression in Colorectal Cancer
Authors: K Collins, GA Doherty, MR Sweeney, SM Byrne, AA Aftab, EW Kay, FE Murray, DC Shields
Journal: Endoscopy (2004)

Aims: Folate supplementation appears to reduce colorectal cancer (CRC) risk. CRC risk is also modulated by the C to T polymorphism at position 677 of the methylenetetrahydrofolate reductase (MTHFR) gene which results in a thermolabile variant of MTHFR and is associated with reduced cellular folate levels. We looked for a relationship between MTHFR expression in colorectal tumour tissue and the C677T polymorphism.
A c-met inhibitor in the treatment of metastatic non small cell lung cancer with c-met amplification.
Authors: Tongtong Zhang, Junling Li
Journal: Journal of Clinical Oncology (2016)

e20524 Background: Amplification of the mesenchymal-epithelial transition factor (MET) gene plays a vital role in non-small cell lung cancer (NSCLC). The anti-MET therapeutic strategies are still unclear in epidermal growth factor receptor (EGFR) mutant patients and EGFR-naive patients. Aims of our study are to discuss role of MET amplification in Chinese NSCLC patients, and evaluate the antitumor activity of crizotinib (MET inhibitor) in Chinese NSCLC patients with MET gene amplification. Methods: From Jun 2015 to Jan 2016, we detected 11 metastatic NSCLC patients with MET amplification by fluorescence in situ hybridization (FISH). MET amplification was defined as gene focal amplification or high polysomy (at least 15% cells with ≥ 5 copy numbers). Patients with MET de novo amplification received crizotinib, patients with concomitant MET acquired amplification and EGFR mutation received combined therapy of EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib, icotinib)and crizotinib. All enrolled subjects received tumor measurement according to RECIST1.1 Results: The frequency of MET de novo amplification was 54.5%(6/11), and that of concomitant MET acquired amplification and EGFR mutation was 45.5%(5/11) respectively. 4 of 6 patients with MET de novo amplification received crizotinib, 2 patients had partial response (PR), 1 patient had stable disease (SD), 1 patient died due to heart disease. Response rate (RR) of crizotinib was 50%(2/4). Encouraging response was observed in one case ,a CT scan performed 31 days after starting crizotinib revealed 42.2% decrease , until now, a 7-month CT revealed 60.0% decrease in tumor measurement. 3 of 5 patients with concomitant MET acquired amplification and EGFR mutation received the combined therapy of EGFR-TKIs and crizotinib. 1 patient achieved PR, 2 patients had SD. RR of combined therapy was 33.3%(1/3). Dramatic response was observed in one case with combined therapy, a 2-month CT revealed 31.0% decrease in tumor measurement. Conclusions: According to our study, patients with MET amplification benefited from crizotinib, and RR was inspiring. Patients with concomitant MET acquired amplification and EGFR mutation need combined targeted therapy.
The feasibility of the ACOSOG Z0011 criteria for omitting axillary lymph node dissection after positive sentinel lymph node biopsy in Chinese breast cancer patients: A multicenter study.
Authors: Miao Liu, Shude Cui, Xuening Duan, Zhimin Fan, Zhigang Yu, Shu Wang
Journal: Journal of Clinical Oncology (2015)

e12058 Background: The ACOSOG Z0011 trial has been described as practice-changing of sentinel lymph nodes (SLNs) positive breast cancers. This study was undertaken to examine current practice pattern in China, evaluate the impact of Z0011 on practice, and determine the exportability of the Z0011criteria for selecting Chinese patients who are eligible for omitting axillary lymph node dissection (ALND) with positive SLNs. Methods: A electronic survey about Z0011 trial was distributed to members of Surgical Group of Breast Cancer attached to Chinese Preventive Medicine Association. Surgeons were questioned about the impact of the trial results on their practice. At the mean time, we collected 658 consecutive patients with ALND after positive SLN biopsy from five centers’ database and grouped them as eligible or ineligible for omitting ALND according to Z0011 criteria. The eligible group was compared with the cohort included in the Z0011 trial and with the ineligible group. Results: Of the 427 respondents, 116(27.2%) answered familiarity with Z0011 data. 106(24.8%) would not routinely perform ALND in patients meeting Z0011 criteria before learning of the trial results and after learning of the trial, 130(30.4%) would not routinely perform ALND in such patients. Among the 658 patients enrolled in this study, 151 patients (22.9 %) were potentially eligible for omitting ALND and 507 patients were still needed to have ALND. The estrogen receptor status, T stage, and number of positive lymph nodes (LNs) and positive non-SLNs were not statistically different between the eligible group and the Z0011 cohort. Compared with the eligible Group in this study, the ineligible group had significantly more T2 and T3 stage tumors, positive LNs and positive non-SLNs (P < 0.01). Conclusions: Applying Z0011 criteria to Chinese patients could select the ones with similar clinical characteristics as Z0011 cohort and it suggests good exportability of Z0011criteria for Chinese patients omitting ALND. But maybe due to the slight impact of Z0011 trial on Chinese surgeons’ practice, it still need time to have the criteria feasible in China.
Abstract #2504: G\#945;15/16, promotes cellular invasion and migration via the small GTP-binding protein, Rho C
Authors: Michelle Lucey, Kenneth van Golen
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Heterotrimeric G-proteins play diverse roles in cellular signaling and have recently been shown to regulate cellular motility and invasion via activation of the Rho GTPases, specifically through G\#945;12/13 and Gq subunits. The Rho GTPases comprise a subfamily of the Ras Superfamily of monomeric G-proteins, which act as molecular switches to regulate reorganization of the actin cytoskeleton. One member of the Rho subfamily, RhoC GTPase, is overexpressed and specifically implicated in metastasis of many tumor types. However, the molecular mechanisms by which RhoC is activated during metastasis have not been demonstrated. During a cDNA microarray screen of laser capture microdissected patient samples, normal pancreatic ductal epithelial cells were compared with chronic pancreatitis and pancreatic adenocarcinomas. Expression of the Gq class heterotrimeric G-protein, G\#945;15/16, was found to be expressed 13- and 3-fold over normal and pancreatitis, respectively in the adenocarcinomas. In the current study we examined whether this unique Gq protein could activate RhoC GTPase. As proof-of-principal we transfected NIH3T3 cells with constitutively active or dominant negative G\#945;15/16, either alone or with a wild-type RhoC GTPase. We observed changes in cell morphology and a significant increase in RhoC-mediated invasion and migration in the cells expressing constitutively active G\#945;15/16.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2504.
Androgens MAY BOOST Hematologic Response to ANTI-Thymocyte Globulin in Acquired Aplastic Anemia
Authors: Sabrina Giammarco, Maria Teresa van Lint, Teresa Lamparelli, Francesca Gualandi, Carmen Di Grazia, Alida Dominietto, Stefania Bregante, Simona Sica, Andrea Bacigalupo
Journal: Blood (2016)
CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion
Authors: Haiwei Mou, Jordan L. Smith, Lingtao Peng, Hao Yin, Jill Moore, Xiao-Ou Zhang, Chun-Qing Song, Ankur Sheel, Qiongqiong Wu, Deniz M. Ozata, Yingxiang Li, Daniel G. Anderson, Charles P. Emerson, Erik J. Sontheimer, Melissa J. Moore, Zhiping Weng, Wen Xue
Journal: Genome biology (2017)

CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of β-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of β-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments.
Reply to: “Inaccuracies in SEER registry data on melanoma thickness”
Authors: Shoshana M. Landow, Annie Gjelsvik, Martin A. Weinstock
Journal: Journal of the American Academy of Dermatology (2017)

We thank Mayer et al for their comments on our publication. We agree that our unexpected finding regarding thinnest melanoma prognosis may at least in part be attributable to errors in our dataset, as they point out in referencing the recent demonstration by Gimotty et al of exactly this scenario in the SEER Detroit registry. Despite this valid concern, which we share, we remain puzzled that a finding somewhat similar to ours was noted in an Australian dataset; as described in our paper, the analysis by Green et al of melanoma deaths in Queensland also showed the surprising finding that prognosis worsened with depth only with melanomas with 0.25 mm or greater thickness.1Green A.C. Baade P. Coory M. et al.Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia.J Clin Oncol. 2012; 30: 1462-1467Crossref PubMed Scopus (139) Google Scholar Although it is possible that systematic error regarding decimal point placement could affect datasets in different parts of the world (though to our knowledge this concern has not been raised with Queensland data), it is equally possible that there are some ultrathin melanomas that have particularly lethal features that have led to similar results in 2 quite distinct geographic places. We would like to emphasize two points: (1) despite this potential issue in the accuracy of recorded thickness of some of the thinnest melanomas, T1 melanoma remains a large contributor to overall melanoma deaths and (2) meticulous attention to accuracy of parameters in the SEER database is critical, particularly given its widespread use and influence. Ultimately, we agree with Mayer et al that improving the accuracy of SEER data is of paramount importance and that awareness of T1 melanoma mortality burden must continue to focus our efforts on early detection. Inaccuracies in SEER registry data on melanoma thicknessJournal of the American Academy of DermatologyVol. 77Issue 1PreviewTo the Editor: We very much enjoyed reading the recent study by Landow et al1 on the prognosis of melanomas on the basis of their thickness. The data were expertly analyzed and unveiled a fascinating finding that ultrathin melanomas with a thickness of 0.01 to 0.25 mm carried a higher risk of death than melanomas with a thickness of 0.26 to 0.50 mm. Indeed, this finding is counterintuitive to the field's understanding of melanoma—the earlier that melanoma is detected, the thinner it should be and the greater the likelihood of patient survival. Full-Text PDF
Patients with Azathioprine/6-Mercaptopurine Refractory Inflammatory Bowel Disease are more prone to 6-Thioguanine Related Toxicity
Authors: A Qasim, S McDonald, S Sebastian, R McLoughlin, M Buckley, H O'Connor, C O'Morain
Journal: Endoscopy (2004)

Background: 6-thioguanine (6-TG) has been suggested for patients with refractory IBD. Recent reports suggest unpredictable occurrence of 6-TG related hepatic toxicity.
The Authors' reply
Authors: M. Romano, G. Nardone
Journal: Gut (2011)

We thank Drs Molina-Infante and Gisbert1 for their letter and for their appreciation of our study.2 We completely agree that the discrepancy between their study and our study as to the efficacy of levofloxacin-containing sequential treatment in Helicobacter pylori eradication might be at least in part due to the very low (ie, 3%) prevalence of H pylori strains resistant to this antimicrobial in our region compared with their geographical area. We also agree that clarithromycin-containing sequential treatment is achieving disappointing results in areas with a high prevalence of clarithromycin and/or dual (ie, metronidazole + clarithromycin) resistance and that, therefore, its role in this setting should be critically reconsidered.

Recently, a study by Hsu et al has demonstrated high efficacy of a 14-day sequential–concomitant hybrid treatment (ie, proton pump inhibitor (PPI) standard dose twice daily + amoxicillin 1 g twice daily for 7 days followed by a further 7 days of PPI + amoxicillin 1 g …