tbuckley/cabot-search huggingface dataset:
Pilot Study Using Molecular Profiling of Patients' Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers
Authors: Daniel D. Von Hoff, Joseph J. Stephenson, Peter Rosen, David M. Loesch, Mitesh J. Borad, Stephen Anthony, Gayle Jameson, Susan Brown, Nina Cantafio, Donald A. Richards, Tom R. Fitch, Ernesto Wasserman, Cristian Fernandez, Sylvan Green, William Sutherland, Michael Bittner, Arlet Alarcon, David Mallery, Robert Penny
Journal: Journal of Clinical Oncology (2010)

Purpose To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control). Patients and Methods Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [ CLIA ] –certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3. Results In 86 patients who had MP attempted, there was a molecular target detected in 84 (98%). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38%; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15% of this patient population would have a PFS ratio of ≥ 1.3) was rejected. Conclusion It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.
Initiating oral breathing in response to nasal loading: asthmatics versus healthy subjects
Authors: M. Hallani, J. R. Wheatley, T. C. Amis
Journal: European Respiratory Journal (2007)

Factors influencing nasal versus oral breathing in asthmatics are not well understood. The current authors hypothesised that asthmatic subjects have enhanced perception of nasal threshold loads, and switch from nasal to oral breathing at a lower load than healthy subjects. In total, 15 mild asthmatic and 20 healthy control subjects breathed nasally via an inspiratory threshold loading device. Nasal loading was progressively increased until subjects switched to oral breathing. Load perception at switching was rated using a Borg scale. Nasal resistance was measured using posterior rhinomanometry. The protocol was repeated before and after nasal decongestant administration in subgroups of 10 healthy control and six asthmatic subjects. Inspiratory nasal resistance was within normal limits for most subjects and was not significantly different between asthmatics and healthy controls. Compared with controls, asthmatics switched to oral breathing at a significantly lower nasal load but rated “difficulty breathing in” at the same level. Decongestant significantly lowered nasal resistance but did not change the nasal load initiating switching in either subgroup. Enhanced perception of nasal loading may trigger increased oral breathing in asthmatics, potentially enhancing exposure to nonconditioned inhaled gas and contributing to the occurrence and/or severity of bronchoconstrictive exacerbations.
<i>Runx2</i> Disruption Promotes Immortalization and Confers Resistance to Oncogene-Induced Senescence in Primary Murine Fibroblasts
Authors: Anna Kilbey, Karen Blyth, Sandy Wotton, Anne Terry, Alma Jenkins, Margaret Bell, Linda Hanlon, Ewan R. Cameron, James C. Neil
Journal: Cancer Research (2007)

Abstract The Runx genes play paradoxical roles in cancer where they can function either as dominant oncogenes or tumor suppressors according to context. We now show that the ability to induce premature senescence in primary murine embryonic fibroblasts (MEF) is a common feature of all three Runx genes. However, ectopic Runx–induced senescence contrasts with Ras oncogene–induced senescence, as it occurs directly and lacks the hallmarks of proliferative stress. Moreover, a fundamental role for Runx function in the senescence program is indicated by the effects of Runx2 disruption, which renders MEFs prone to spontaneous immortalization and confers an early growth advantage that is resistant to stress-induced growth arrest. Runx2−/− cells are refractory to H-RasV12–induced premature senescence, despite the activation of a cascade of growth inhibitors and senescence markers, and are permissive for oncogenic transformation. The aberrant behavior of Runx2−/− cells is associated with signaling defects and elevated expression of S-G2-M cyclins and their associated cyclin dependent kinase activities that may override the effects of growth inhibitory signals. Coupling of stress responses to the cell cycle represents a novel facet of Runx tumor suppressor function and provides a rationale for the lineage-specific effects of loss of Runx function in cancer. [Cancer Res 2007;67(23):11263–71]
selscan: An Efficient Multithreaded Program to Perform EHH-Based Scans for Positive Selection
Authors: Zachary A. Szpiech, Ryan D. Hernandez
Journal: Molecular Biology and Evolution (2014)

Haplotype-based scans to detect natural selection are useful to identify recent or ongoing positive selection in genomes. As both real and simulated genomic datasets grow larger, spanning thousands of samples and millions of markers, there is a need for a fast and efficient implementation of these scans for general use. Here we present selscan, an efficient multi-threaded application that implements Extended Haplotype Homozygosity (EHH), Integrated Haplotype Score (iHS), and Cross-population Extended Haplotype Homozygosity (XPEHH). selscan accepts phased genotypes in multiple formats, including TPED, and performs extremely well on both simulated and real data and over an order of magnitude faster than existing available implementations. It calculates iHS on chromosome 22 (22,147 loci) across 204 CEU haplotypes in 353s on one thread (33s on 16 threads) and calculates XPEHH for the same data relative to 210 YRI haplotypes in 578s on one thread (52s on 16 threads). Source code and binaries (Windows, OSX and Linux) are available at https://github.com/szpiech/selscan .
Tracing cellular and molecular mechanisms involved in endometriosis
Authors: A Starzinski-Powitz
Journal: Human Reproduction Update (1998)

The aetiology and pathogenesis of endometriosis, defined as the presence of endometrium-like tissue outside the uterine cavity, is largely unknown. In this paper we present and discuss possibilities to study the putative pathogenic properties of endometriotic cells in vitro. The current focus of our investigations is on the invasive phenotype of the disease, assuming that this might contribute to the pathogenesis of endometriosis. So far, we have shown that: (i) cytokeratin-positive and E-cadherin-negative endometriotic cells have an invasive phenotype in a collagen invasion assay in vitro similar to metastatic carcinoma cells; (ii) the invasiveness of endometriotic but not of eutopic endometrial cells can be stimulated by a heat-stable protein present in peritoneal fluid; and (iii) the endometriotic cell line EEC145T, which we established, may be a useful tool for the identification of gene products which are, positively or negatively, invasion-related. Finally, our studies suggest that the invasive phenotype in endometriosis shares aspects with tumour metastasis, but might also have unique mechanisms.
Successful implementation of asthma guidelines in Thailand: The Easy Asthma Clinic model
Authors: Watchara Boonsawat
Journal: European Respiratory Journal (2011)

Introduction: Asthma management guidelines were published in Thailand in 1994 and revised in 1997 following the publication of the GINA guidelines. However, the audit made by the National Health Security Office (NHSO) showed that asthma management in Thailand fell short of the goals determined for long-term asthma care indicated the failure of guidelines implementation.

Method: We have developed Easy Asthma Clinic Network as a model to enhance the implementation of GINA guidelines in Thailand since 2004. Easy Asthma Clinic runs by GPs in general hospitals. In the clinic we simplified asthma guidelines and organized the system to facilitate the team work, emphasized the role of nurses and pharmacists to help doctors. We also developed on-line web database for registering and monitoring patients.In 2009 NHSO support the set up of Easy Asthma Clinic in all hospitals in Thailand.

Results: Easy Asthma Clinic was set up in more than 900 hospitals in Thailand. 99,535 asthmatics were registered with 548,583 visits. Easy asthma clinics improve quality of asthma care in general hospitals. Peak flow measurement were improved from 1.08% to 98.47% of the visits. Inhaled corticosteroids used increased 10.92% to 79.30%. Asthma controlled were achieved in 23.19% of visits and partly controlled in 46.35%.

Conclusions: Setting up Easy Asthma Clinic help implementation of asthma guidelines in Thailand.
CKD Associates with Cognitive Decline
Authors: Minesh Khatri, Thomas Nickolas, Yeseon P. Moon, Myunghee C. Paik, Tatjana Rundek, Mitchell S. V. Elkind, Ralph L. Sacco, Clinton B. Wright
Journal: Journal of the American Society of Nephrology (2009)

Cognitive impairment and chronic kidney disease (CKD) will become increasingly prevalent in the aging US population. Although evidence exists that CKD is a risk factor for cognitive decline, longitudinal studies are limited and largely have excluded ethnically diverse populations. The Northern Manhattan Study includes a population-based, prospective, stroke-free cohort. We assessed global cognitive function annually using the modified Telephone Interview for Cognitive Status (TICS-m) and estimated kidney function using Cockcroft-Gault creatinine clearance (CCl), Modification of Diet in Renal Disease estimated GFR (eGFR), and serum creatinine (sCr). We examined the association between CKD and change in TICS-m scores over time, adjusting for sociodemographic and vascular risk factors. Of 2172 subjects (mean age 71.5 yr, mean follow-up 2.9 yr), 59% were Hispanic, 20% were black, and 63% were women. Participants with a CCl <60 ml/min and those with a CCl between 60 and 90 ml/min performed significantly worse on the TICS-m over time than those with a CCl >90 ml/min, adjusting for potential confounders. Our results were similar when we used eGFR or sCr to estimate kidney function. In conclusion, decreased kidney function associates with greater cognitive decline, even in those with mild CKD. Kidney disease may represent a novel mechanism leading to cognitive impairment and a target for early intervention.
ANGIOTENSIN-CONVERTING ENZYME INSERTION/DELETION POLYMORPHISMS CONTRIBUTES TO FAVORABLE CLINICAL COURSES OF HYPERTROPHIC CARDIOMYOPATHY CAUSED BY MYBPC3 GENE MUTATIONS
Authors: Akira Funada, Noboru Fujino, Eiichi Masuta, Hidekazu Ino, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2010)
Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy.
Authors: E Y Skolnik, Z Yang, Z Makita, S Radoff, M Kirstein, H Vlassara
Journal: The Journal of Experimental Medicine (1991)

Advanced glycosylation endproducts (AGEs) are derived from the nonenzymatic addition of glucose to proteins. AGEs have been found to accumulate on tissue proteins in patients with diabetes, and their accumulation is thought to play a role in the development of diabetic complications. The finding that macrophages and endothelial cells contain AGE-specific receptors led us to examine whether mesangial cells (MCs) also possess a mechanism for recognizing and processing AGEs. Membrane extracts isolated from rat and human MCs were found to bind AGE-bovine serum albumin (BSA) in a saturable fashion, with a binding affinity of 2.0 +/- 0.4 x 10(6) M-1 (500 nM). The binding was specific for the AGE adduct, since AGE-modified collagen I and ribonuclease both competitively inhibited 125I-AGE-BSA binding to MC membranes, while the unmodified proteins did not compete. Binding of AGE proteins was followed by slow internalization and degradation of the ligand. Ligand blotting of MC membrane extracts demonstrated three distinct AGE-binding membrane proteins of 50, 40, and 30 kD. Growth of MCs on various AGE-modified matrix proteins resulted in alterations in MC function, as demonstrated by enhanced production of fibronectin and decreased proliferation. These results point to the potential role that the interaction of AGE-modified proteins with MCs may play in vivo in promoting diabetic kidney disease.
Interferon-γ Release Assays for the Evaluation of Tuberculosis Infection
Authors: Henry M. Blumberg, Russell R. Kempker
Journal: JAMA (2014)

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Predicting High-Grade Cancer at Ten-Core Prostate Biopsy Using Four Kallikrein Markers Measured in Blood in the ProtecT Study
Authors: Richard J. Bryant, Daniel D. Sjoberg, Andrew J. Vickers, Mary C. Robinson, Rajeev Kumar, Luke Marsden, Michael Davis, Peter T. Scardino, Jenny Donovan, David E. Neal, Hans Lilja, Freddie C. Hamdy
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome.
Doctors in UK alcohol network may refuse to sign action pledge because it is too weak
Authors: A. O'Dowd
Journal: BMJ (2011)

Doctors in the UK government’s “responsibility deal” network on alcohol are considering refusing to sign the group’s plan of action because the policies don’t go far enough in tackling the price and availability of alcohol. 

The health secretary, Andrew Lansley, set up five such networks last summer. They cover alcohol, food, physical activity, health at work, and behaviour change in general and are made up of representatives of the government, industry, and healthcare organisations.

The threat by members of the alcohol group comes in the same week that an editorial in the Lancet by liver disease specialists predicted that an additional 250 000 people could die over the next 20 years if the government fails to take decisive action to tackle alcohol abuse in England and Wales (doi:10.1016/S0140-6736(11)60022-6). 

The comment piece in the Lancet says that the government should act now to limit the price and availability of alcohol and …
The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER)
Authors: M. Aapro, A. Molassiotis, M. Dicato, I. Peláez, Á. Rodríguez-Lescure, D. Pastorelli, L. Ma, T. Burke, A. Gu, P. Gascon, F. Roila
Journal: Annals of Oncology (2012)
Neoadjuvant Chemotherapy Followed by Extrapleural Pneumonectomy in Malignant Pleural Mesothelioma
Authors: Walter Weder, Peter Kestenholz, Christian Taverna, Stefan Bodis, Didier Lardinois, Monika Jerman, Rolf A. Stahel
Journal: Journal of Clinical Oncology (2004)

Purpose To investigate neoadjuvant chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy with or without radiation therapy in patients with potentially resectable malignant pleural mesothelioma (MPM). Patients and Methods Eligible patients had MPM with clinical stage T1-3, N0-2, M0 disease considered to be completely resectable and a WHO performance status of 0 to 2. Neoadjuvant chemotherapy consisted of three cycles of cisplatin 80 mg/m 2 on day 1 and gemcitabine 1,000 mg/m 2 on days 1, 8, and 15, given every 28 days. Surgery had to consist of a complete extrapleural pneumonectomy, including resection of pericardium and diaphragm. Postoperative radiotherapy was to be considered for all patients. Results Nineteen patients with MPM were included in this pilot study. According to the European Organization for Research and Treatment of Cancer prognostic score, two patients were in the good prognosis group, and 17 patients were in the poor prognosis group. The response rate to neoadjuvant chemotherapy was 32%. The major toxicity was thrombocytopenia. Extrapleural pneumonectomy was performed in 16 patients with no perioperative mortality. Major surgical complications occurred in six patients, and all were treated successfully. Thirteen patients received postoperative radiotherapy. The median survival time was 23 months. Two patients remain alive and free of disease 41 and 38 months after initiation of therapy. Conclusion For patients with potentially operable MPM, the availability of active and well-tolerated chemotherapy regimens, the fact that extrapleural pneumonectomy can be safely performed after neoadjuvant chemotherapy in an experienced center, and the promising results regarding survival in our pilot study warrant further investigation of the role of neoadjuvant chemotherapy in a multimodality strategy.
Genome-wide association study dissects the genetic architecture of oil biosynthesis in maize kernels
Authors: Hui Li, Zhiyu Peng, Xiaohong Yang, Weidong Wang, Junjie Fu, Jianhua Wang, Yingjia Han, Yuchao Chai, Tingting Guo, Ning Yang, Jie Liu, Marilyn L Warburton, Yanbing Cheng, Xiaomin Hao, Pan Zhang, Jinyang Zhao, Yunjun Liu, Guoying Wang, Jiansheng Li, Jianbing Yan
Journal: Nature Genetics (2012)
Lines of Evidence on the Risks of Suicide with Selective Serotonin Reuptake Inhibitors
Authors: David Healy
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; There has been a long-standing controversy about the possibility that selective serotonin reuptake inhibitor (SSRI) antidepressants might induce suicidality in some patients. &lt;i&gt;Methods:&lt;/i&gt; Starting from the clinical studies that gave rise to this issue, this paper reviews an unselected cohort of randomized clinical trials (RCTs), a series of meta-analyses undertaken to investigate aspects of the problem, studies in recurrent brief depressive disorders, epidemiological studies and healthy volunteer studies using SSRIs to shed light on this issue. &lt;i&gt;Results:&lt;/i&gt; The original clinical studies produced evidence of a dose-dependent link, present on a challenge, dechallenge and rechallenge basis, between SSRIs and both agitation and suicidality. Meta-analyses of RCTs conducted around this time indicate that SSRIs may reduce suicidal ideation in some patients. These same RCTs, however, yield an excess of suicides and suicide attempts on active treatments compared with placebos. This excess also appears in the best-controlled epidemiological studies. Finally, healthy volunteer studies give indications that SSRIs may induce agitation and suicidality in some individuals. &lt;i&gt;Conclusions:&lt;/i&gt; The data reviewed here, which indicate a possible doubling of the relative risk of both suicides and suicide attempts on SSRIs compared with older antidepressants or non-treatment, make it difficult to sustain a null hypothesis, i.e. that SSRIs do not cause problems in some individuals to whom they are given. Further studies or further access to data are indicated to establish the magnitude of any risk and the characteristics of patients who may be most at risk.
Diagnostic Agreement of Different IgE Assay Methods, Immunocap and ‘Extended Range' Immulite 2000 3gAllergy in Japanese School Age Children
Authors: Mari Kondo, Mayumi Sugimoto, Keigo Kainuma, Reiko Tokuda, Mizuho Nagao, Takao Fujisawa
Journal: Journal of Allergy and Clinical Immunology (2013)
CCR4-bearing T cells participate in autoimmune diabetes
Authors: Soon H. Kim, Mary M. Cleary, Howard S. Fox, David Chantry, Nora Sarvetnick
Journal: Journal of Clinical Investigation (2002)

Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4(+) T cells during the progression of disease in NOD mice. Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice. Interestingly, neutralization of macrophage-derived chemokine (MDC) with Ab caused a significant reduction of CCR4-positive T cells within the pancreatic infiltrates and inhibited the development of insulitis and diabetes. Furthermore, enhanced recruitment of CCR4-bearing cells in NOD mice resulting from transgenic expression of MDC resulted in acceleration of clinical disease. Cumulatively, the results demonstrate that CCR4-bearing T cells participate in the development of such tissue-driven autoimmune reactions.