tbuckley/cabot-search huggingface dataset:
Analyses of genetic association and DNA methylation in the ORMDL3/GSDMB locus
Authors: Nathalie Acevedo, Lovisa Reinius, Anna Gref, Erik Melen, Annika Sääf, Göran Pershagen, Annika Scheynius, Juha Kere, Cilla Söderhäll
Journal: European Respiratory Journal (2013)

Background: Several independent studies have replicated the genetic association between polymorphisms in ORMDL3 and GSDMB and the risk of childhood asthma. The causal mechanisms remain unknown but there is evidence suggesting that epigenetic alterations, e.g. DNA methylation, might contribute. We aim to analyze the methylation status of the genes GSDMB/ORMDL3 and the risk of asthma.

Methods: We genotyped 17 SNPs in GSDMB and ORMDL3 in the Swedish birth cohort (BAMSE, n =2033) including the GWAS hits rs2305480 and rs7216389. DNA methylation levels at 20 CpG sites were quantified in whole blood in the 17q12-21 region by EpiTYPER or pyrosequencing in a subset of the BAMSE study (n=261).

Results and conclusions: We confirmed the genetic association between the 17q12-21 region and physician-diagnosed asthma and wheezing. No association was seen to rhinitis, atopic sensitization, or allergic or non-allergic asthma after correction for multiple testing. Our analyses show that the CpG sites in GSDMB are in general highly methylated, and no differences were seen in methylation levels between asthmatic children and controls in 10 non-polymorphic CpG sites analyzed in GSDMB . However, in ORMDL3 DNA methylation levels in two CpG sites were significantly lower in asthmatic children compared to healthy controls.
Route of antigen delivery impacts the immunostimulatory activity of dendritic cell-based vaccines for hepatocellular carcinoma
Authors: Angela D. Pardee, Hiroshi Yano, Aliyah M. Weinstein, Aaron A. K. Ponce, Alexander D. Ethridge, Daniel P. Normolle, Lazar Vujanovic, Gerald J. Mizejewski, Simon C. Watkins, Lisa H. Butterfield
Journal: Journal for ImmunoTherapy of Cancer (2015)

Dendritic cells (DC) are uniquely equipped to capture, process, and present antigens from their environment. The context in which an antigen is acquired by DC helps to dictate the subsequent immune response. Cancer vaccination promotes antitumor immunity by directing an immune response to antigens expressed by tumors. We have tested the tumor-associated antigen alpha-fetoprotein (AFP) as an immunotherapy target. The majority of hepatocellular carcinomas (HCC) upregulate and secrete this oncofetal antigen. To develop cancer vaccines for HCC capable of promoting potent tumor-specific T cell responses, we tested adenovirally-encoded synthetic AFP, with or without its signal sequence, as well as protein forms of AFP and compared intracellular routing and subsequent antigen-specific CD8+ and CD4+ T cell responses. Surprisingly, the secreted form of antigen was superior for both CD4+ and CD8+ T cell activation. We also examined the mechanism through which AFP protein is endocytosed and trafficked in human DC. We identify the mannose receptor (MR/CD206) as the primary uptake pathway for both normal cord blood-derived AFP (nAFP) and tumor-derived AFP (tAFP) proteins. While in healthy donors, nAFP and tAFP were cross-presented to CD8+ T cells similarly and CD4+ T cell responses were dependent upon MR-mediated uptake. In HCC patient cells, tAFP was more immunogenic, and CD4+ T cell responses were not MR-dependent. Secreted, cytoplasmically retained, and endocytosed forms of AFP utilize unique uptake and processing pathways, resulting in different immunologic responses from the induced antigen-specific CD4+ and CD8+ T cells and between healthy donors and HCC patients. Collectively, these data elucidate pathways of spontaneous and induced anti-tumor immunity in HCC patients to this secreted antigen.
Abstract 9302: Electrocardiographic Criteria for ST-Elevation Myocardial Infarction in Patients with Left Ventricular Hypertrophy
Authors: Ehrin J Armstrong, Prashant D Bhave, Kurt S Hoffmayer, Peter Ganz, James M McCabe
Journal: Circulation (2011)

Background: Patients with electrocardiographic (ECG) left ventricular hypertrophy (LVH) have ST segment repolarization abnormalities that are difficult to differentiate from an ischemic current of injury. ACC/AHA criteria diagnose ST-elevation myocardial infarction (STEMI) as ≥ 1 mm STE in two contiguous leads, and 2 mm if the STE are isolated to leads V1-V3.Additional criteria are much needed to correctly diagnose STEMI in patients with LVH. Methods: We analyzed the ACTIVATE-SF database, a registry of consecutive Emergency Department STEMI diagnoses from 2 medical centers at UC San Francisco. Logistic regression was performed to identify ECG variables that predicted presence of an angiographic culprit lesion. Results: We identified 79 patients with electrocardiographic LVH who underwent cardiac catheterization for consideration of primary angioplasty. Just 22 (28%) patients were found to have an angiographic culprit lesion. Patients with a culprit lesion had greater magnitude of ST elevation (3.0 ± 1.8 vs. 1.9 ± 1.0 mm, p = 0.005), more leads with ST elevation (3.1 ± 1.6 vs. 2.0 ± 1.8 leads, p = 0.002), and a greater ratio of ST segment elevation to R wave height (median 25% vs. 9.2%, p = 0.003). Among these univariate factors, adding the median ratio of ST segment to R wave height &gt;25% to the ACC/AHA criteria significantly improved overall diagnostic discrimination: c-statistic 0.65 vs. 0.74, specificity 58 vs. 93%, sensitivity 64 vs. 73%, positive predictive value 40 vs. 78%, and negative predictive value 85 vs. 87%. Conclusion: Most patients with chest pain, electrocardiographic LVH and diagnostic ST segment elevation by ACC/AHA criteria have no culprit lesion at angiography. A ratio of the ST segment to R wave magnitude &gt; 25% increases specificity for diagnosis of STEMI without reducing sensitivity. This additional ECG criterion should appreciably improve STEMI diagnosis in LVH and lead to a more appropriate utilization of cardiac catheterization procedures.
Identification and Functional Validation of Reciprocal microRNA–mRNA Pairings in African American Prostate Cancer Disparities
Authors: Bi-Dar Wang, Kristin Ceniccola, Qi Yang, Ramez Andrawis, Vyomesh Patel, Youngmi Ji, Johng Rhim, Jacqueline Olender, Anastas Popratiloff, Patricia Latham, Yinglei Lai, Steven R. Patierno, Norman H. Lee
Journal: Clinical Cancer Research (2015)

African Americans (AA) exhibit higher rates of prostate cancer incidence and mortality compared with European American (EA) men. In addition to socioeconomic influences, biologic factors are believed to play a critical role in prostate cancer disparities. We investigated whether population-specific and -enriched miRNA-mRNA interactions might contribute to prostate cancer disparities.Integrative genomics was used, combining miRNA and mRNA profiling, miRNA target prediction, pathway analysis, and functional validation, to map miRNA-mRNA interactions associated with prostate cancer disparities.We identified 22 AA-specific and 18 EA-specific miRNAs in prostate cancer versus patient-matched normal prostate, and 10 "AA-enriched/-depleted" miRNAs in AA prostate cancer versus EA prostate cancer comparisons. Many of these population-specific/-enriched miRNAs could be paired with target mRNAs that exhibited an inverse pattern of differential expression. Pathway analysis revealed EGFR (or ERBB) signaling as a critical pathway significantly regulated by AA-specific/-enriched mRNAs and miRNA-mRNA pairings. Novel miRNA-mRNA pairings were validated by qRT-PCR, Western blot, and/or IHC analyses in prostate cancer specimens. Loss/gain of function assays performed in population-specific prostate cancer cell lines confirmed miR-133a/MCL1, miR-513c/STAT1, miR-96/FOXO3A, miR-145/ITPR2, and miR-34a/PPP2R2A as critical miRNA-mRNA pairings driving oncogenesis. Manipulating the balance of these pairings resulted in decreased proliferation and invasion, and enhanced sensitization to docetaxel-induced cytotoxicity in AA prostate cancer cells.Our data suggest that AA-specific/-enriched miRNA-mRNA pairings may play a critical role in the activation of oncogenic pathways in AA prostate cancer. Our findings also suggest that miR-133a/MCL1, miR-513c/STAT1, and miR-96/FOXO3A may have clinical significance in the development of novel strategies for treating aggressive prostate cancer.
Importance of location of neurointerventional skills in thrombectomy for acute stroke
Authors: Paul A Burns, Peter A Flynn, Ian M Rennie
Journal: BMJ (2015)

With emerging evidence on the efficacy of thrombectomy for selected patients with acute ischaemic stroke, Apps and colleagues suggested that the coronary primary angioplasty network could be used to cover the demand for this service.1

However, the skill in endovascularly opening arteries quickly is not generic, as the authors imply. Despite the similar …
Consistent amplification of JAK2 in hematological malignancies with hsr(9)(p).
Authors: Iwona Wlodarska, Lucienne Michaux, Jan Cools, Patrick Peeters, S. Franke, G. Verhoef, R. Achten, C. De Wolf-Peeters, Anne Hagemeijer, Peter Marynen
Journal: Blood (2000)
Flooding and human health
Authors: C. A Ohl
Journal: BMJ (2000)

News p 1178 

Over the past few weeks England and Wales have endured the most widespread flooding for more than 50 years. By the end of the first week of November more than 3000 homes had been flooded and transport had been disrupted; in some areas water supplies have been contaminated, and a hospital has been evacuated.1

Flooding accounts for 40% of all natural disasters worldwide and causes about half of all deaths from natural disasters.2 Most floods occur in developing regions and tropical regions where the impact on public health is substantial, the number of people displaced is often large, and the number of deaths is high. In the aftermath of a flood deaths and injuries not only result from the physical characteristics of the event but are also determined by the prevailing socioeconomic and health conditions of the community and any endemic infectious diseases. Increased rates of diarrhoea (including cholera and dysentery), respiratory infections, hepatitis A and E, typhoid fever, leptospirosis, and diseases borne by insects have been described as occurring after floods in developing areas. 3 4 Malnutrition caused by inadequate supplies of food and problems with distribution …
Is admission screening for Pseudomonas aeruginosa useful in haematologic patients? A prospective study with 1310 patients
Authors: J.A. Sidler, R. Frei, S. Tschudin-Sutter, M. Dangel, M. Battegay, M. Weisser, J. Passweg, A.F. Widmer
Journal: Clinical Microbiology and Infection (2015)
Analysis of Tumor Growth Curves2
Authors: Lyle A. Dethlefsen, J. M. S. Prewitt, M. L. Mendelsohn
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article Analysis of Tumor Growth Curves Get access Lyle A. Dethlefsen, Lyle A. Dethlefsen Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. S. Prewitt, J. M. S. Prewitt Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. L. Mendelsohn M. L. Mendelsohn Department of Radiology, Schools of Medicine and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 40, Issue 2, February 1968, Pages 389–405, https://doi.org/10.1093/jnci/40.2.389 Published: 01 February 1968 Article history Received: 17 July 1967 Accepted: 06 September 1967 Published: 01 February 1968
A phase II study of high-dose continuous infusion interleukin-2 with lymphokine-activated killer cells in patients with metastatic melanoma.
Authors: J P Dutcher, E R Gaynor, D H Boldt, J H Doroshow, M H Bar, M Sznol, J Mier, J Sparano, R I Fisher, G Weiss
Journal: Journal of Clinical Oncology (1991)

Thirty-three patients with metastatic melanoma were treated in a phase II study with an intravenous continuous infusion (IVCI) of interleukin-2 (IL2) given with lymphokine-activated killer (LAK) cells. The dose of IL2 was the optimal priming dose for LAK-cell induction, followed by the maximally tolerated LAK-cell dose that could be given by an IVCI schedule as determined by a previous phase I trial. The CI schedule was chosen for evaluation because of a postulated reduction in toxicity with the possibility of administering a more prolonged IL2 infusion and because greater rebound lymphocytosis and LAK-cell generation had been reported using this dose and schedule. The 33 patients were similar in age, performance status, and sites of disease to those treated in previous IL2 trials. All patients were assessable for response and toxicity. One patient (3%) achieved a partial response of 10 months duration. There were no other clinically significant responses. Significant toxicity included hypotension requiring pressors (45%), dyspnea (36%), renal insufficiency (24%), hepatic dysfunction (66%), and cardiac arrhythmias (18%). These toxicities reversed with cessation of the infusion. There were four deaths during the first 30 days of treatment, three from infection (one related to central line, one related to LAK cells, one related to tumor), and one from tumor-related hemorrhage. Toxicity was unexpectedly high and at least comparable to that seen in previous studies using a high-dose IV bolus schedule of IL2. When comparing the IVCI schedule with high-dose bolus IL2 to LAK cells in nonrandomized but sequential studies in patients with advanced melanoma, it appears that CI IL2 is less efficacious.
Molecular epidemiology of the nasal colonization by methicillin-susceptible Staphylococcus aureus in Swiss children
Authors: C. Mégevand, A. Gervaix, U. Heininger, C. Berger, C. Aebi, B. Vaudaux, C. Kind, H.-P. Gnehm, M. Hitzler, G. Renzi, J. Schrenzel, P. François
Journal: Clinical Microbiology and Infection (2009)
Prediction modeling and temporal validation of sleep disordered breathing from large community samples
Authors: Neil M. Skjodt, Ronald S. Platt
Journal: European Respiratory Journal (2012)

AIM: Common sleep apnea prediction tools (e.g. the STOP-BANG score) were derived using laboratory-based polysomnography in academic centers. In contrast, we assessed and temporally validated the sleep apnea risk factors in patients undergoing ambulatory screening and testing in community practice.

METHODS: Two consecutive sets of 2000 ambulatory sleep monitor recordings referred for interpretation by community physicians and CPAP vendors were used for modeling and validation. With each study the patient's age, gender, mass, height, neck circumference, use of anti-hypertensive drugs, reported gasping awakenings, reported disruptive snoring and Epworth sleepiness score were reported. An estimated respiratory disturbance index (RDI) was derived from each study's signals. Modeling of the predicted RDI was done using linear regression and reduced error pruning tree methods on the first sample with temporal validation testing on the second sample (WEKA, v. 3.7.5).

RESULTS: Linear regression modeling showed all risk factors significantly associated with RDI, however, the model's correlation coefficient was poor in both the training (0.3953) and validation (0.4604) samples. Tree modeling showed sequential cutoffs for neck circumference < 44 cm, Epworth score < 18.5 and mass < 107 kg best modeled the estimated RDI. The tree model's training (0.375) and validation (0.3015) correlation coefficients were, like the regression model values, also poor.

CONCLUSION: Common sleep apnea risk factors have poor statistical validity for predicting sleep disordered breathing in patients undergoing ambulatory screening and testing.
Morphological features of the endobronchial microhemocirculation of nephrological patients
Authors: Shcherban Natalia, Landyshev Yuriy, Tsheluyko Sergey
Journal: European Respiratory Journal (2011)

Pneumofibrosis is one of the respiratory aftereffects developing at late stages of chronic kidney disease (CKD).  The research was aimed at revealing the microhemacirculatory disturbances role in the course of bronchopulmonary aftereffects development for CKD patients.   Methods:  The endobronchial biopsy was applied to 48 CKD patients at the point of 1cm distally aside from the right lung9s proximal bronchus spur. The ultrathin sections were analyzed, using the Tecnai G2 Spirit TWIN electron microscope (of the “FEI Company” - Netherlands) after its preliminary staining by the uranyl acetate and the lead citrate.   Results:  The normal plan of bronchi mucosa structure is revealed in 16,6% of cases, mainly at CKD initial stages. 25,4% of CKD 2nd and 3rd stage patients had epithelium initial planocellular metaplasia, sometimes with the bronchi submucosa connective tissue edema. In 50% of the cases dystrophia and epithelium metaplasia combined with the microcirculatory bed reduction. At the later stages of the disease the number of the elastic fibers increased which surrounded the spasmodic blood capillaries and dilated venules. 19,4% of the patients at the fifth CKD stage showed atrophy of the epithelium against the expressed submucosa sclerotic changes. Here one could observe distinct damages of endothelial cells containing numerous vacuoles in the cytoplasma, sometimes they protruded into the vessel lumen.   The conclusion:  Due to various factors the CKD leads to the structural reorganization of the microhemocirculatory bed which then causes the fabric hypoxia, atrophy of the bronchus mucosa and occurrence of the expressed sclerotic processes in the submucosal layer of the bronchial tree.
Linking Broad Consent to Biobank Governance: Support From a Deliberative Public Engagement in California
Authors: Sarah B. Garrett, Daniel Dohan, Barbara A. Koenig
Journal: The American Journal of Bioethics (2015)

In “Broad Consent for Research With Biological Samples: Workshop Conclusions” (Grady et al. 2015), Grady and participants in a National Institutes of Health (NIH)-sponsored workshop endorse the pra...
Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines.
Authors: K A Margolin, A A Rayner, M J Hawkins, M B Atkins, J P Dutcher, R I Fisher, G R Weiss, J H Doroshow, H S Jaffe, M Roper
Journal: Journal of Clinical Oncology (1989)

The National Cancer Institute (NCI) Extramural IL2/LAK Working Group treated 93 patients with 114 cycles of high-dose intravenous (IV) interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells in three phase II trials. Thirty-six patients had metastatic melanoma, 35 had metastatic renal cell cancer, and 22 had colorectal cancer. All patients had a Karnofsky performance status greater than or equal to 80% and normal laboratory tests and organ function, and had received no more than one prior form of immunotherapy or chemotherapy. Objective responders were eligible to receive up to two additional courses of therapy at 12-week intervals. The most frequent toxicities were a capillary leak syndrome resulting in marked extravascular fluid shifts, and hypotension requiring treatment with large volumes of IV fluids and vasopressor agents. Laboratory and clinical evidence of hepatic and renal dysfunction were virtually universal. Intensive care-level support was routinely provided and the toxicity observations confirmed the need for this level of care. The life-threatening toxicities were cardiac and pulmonary. Five of the 27 patients who experienced significant respiratory compromise required intubation and mechanical ventilatory support. Twenty patients developed cardiac arrhythmias, the majority of which were supraventricular. There was a single episode of ventricular tachycardia requiring cardioversion. Four patients had transient cardiac ischemia, and an additional four had myocardial infarctions, one of which was fatal. With these exceptions, all toxicities were rapidly reversible. The occurrence of only a single therapy-related death and a very low incidence of other irreversible or life-threatening events is comparable to the level of toxicities often observed in other phase II trials. Although the intensity of this regimen limits this approach to a subset of cancer patients with excellent performance status and adequate organ function, because of the frequency and apparent durability of complete responses, this treatment warrants further investigation.
Commentary on “The effect of protective headgear on head injuries and concussions in adolescent football (soccer) playersThe effect of protective headgear on head injuries and concussions in adolescent football (soccer) players”
Authors: Faras H AbuZeyad
Journal: British Journal of Sports Medicine (2008)

This article is the first study to examine the effects of football (soccer) headgear outside of the laboratory setting. Similar to what had been proposed by Withnall et al 1 from their biomechanical research, this study showed …
Loss of Expression of Transplantation Antigens Encoded by the &lt;italic&gt;H-2K&lt;/italic&gt; Locus on Lewis Lung Carcinoma Cells and Its Relevance to the Tumor's Metastatic Properties&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: N Isakov, S Katzav, M Feldman, S Segal
Journal: JNCI Journal of the National Cancer Institute (1983)

The Lewis lung carcinoma 3LL, a C57BL/6 (H-2b)-originated spontaneous tumor that progresses at the site of transplantation in all mouse strains, produced lung metastases only in mice that shared the H-2D region and the non-H-2 genetic background with the tumor's strain of origin. In vitro cytotoxicity assays revealed that 3LL tumor cells were sensitive to lysis exerted by anti-H-2Db immune effector cells but were relatively resistant to lysis by anti-H-2Kb effector cells. In addition, the 3LL tumor cells could inhibit the anti-H-2Dd response against EL 4 (H-2b) target cells but had almost no inhibitory effect on the anti-H-2Kb response against the same targets. Immunization of C3HeB (H-2k) and B10.D2 (H-2d) mice with 3LL tumor cells resulted in antisera that could preferentially react with H-2Db-positive cells but reacted very weakly with H-2Kb-positive cells. The results indicate that 3LL tumor cells expressed H-2Db cell surface antigens at a high density and seemed to lack membrane glycoproteins that are encoded by the H-2Kb region.
Occipital Seizures Imitating Migraine Aura
Authors: C P Panayiotopoulos, I Ahmed Sharoqi, A Agathonikou
Journal: Journal of the Royal Society of Medicine (1997)

Three cases are reported in which symptoms of occipital seizures resembled the visual aura of migraine. Careful recording of the characteristics and timing of such visual effects will often resolve the diagnostic dilemma.
The risk of squamous cell carcinoma in women from exposure to UVA lamps used in cosmetic nail treatment
Authors: B.L. Diffey
Journal: British Journal of Dermatology (2012)

The use of ultraviolet (UV)A lamps for curing gel nails is widespread in the cosmetic nail industry. A report that two women who had undergone this treatment subsequently developed squamous cell carcinoma (SCC) on the dorsum of hands has prompted some concern about the safety of this procedure.To estimate the number of women who would need to be exposed to UVA nail lamps for one woman to develop SCC on the dorsum of hands, who would not have done so otherwise.A mathematical model that combines age and UV exposure was used to compare the risk of developing SCC due to typical sun exposure with the risk of inducing these cancers from exposure to UVA nail lamps.For typical usage, the analysis indicates that tens or hundreds of thousands of women would need to use a UVA nail lamp regularly for one to go on to develop SCC on the dorsum of the hands as a direct consequence.The risk of inducing an SCC from exposure to UVA nail lamps is very low and one that is likely to be accepted by most women. Even then, the risk can be reduced to virtually zero by wearing fingerless gloves when the hands are being exposed.