tbuckley/cabot-search huggingface dataset:
Managing chronic diseases in less developed countries
Authors: L. Swartz
Journal: BMJ (2002)

<h3>Abstract</h3> <h3>Background</h3> <i>Salmonella enterica</i> serovar Paratyphi A (<i>Salmonella</i> Paratyphi A) is the primary causative agent of paratyphoid fever, which is responsible for an estimated 3.4 million infections annually. However, little genomic information is available on population structure, antimicrobial resistance (AMR), and spatiotemporal distribution of the pathogen. With rising antimicrobial resistance and no licensed vaccines, genomic surveillance is important to track the evolution of this pathogen and monitor transmission. <h3>Results</h3> We performed whole-genome sequencing of 817 <i>Salmonella</i> Paratyphi A isolates collected from Bangladesh, Nepal, and Pakistan and added publicly available 562 genomes to build a global database representing 37 countries, covering 1917-2019. To track the evolution of <i>Salmonella</i> Paratyphi A, we used the existing lineage scheme, developed earlier based on a small dataset, but certain sub-lineages were not homologous, and many isolates could not be assigned a lineage. Therefore, we developed a single nucleotide polymorphism based genotyping scheme, Paratype, a tool that segregates <i>Salmonella</i> Paratyphi A into three primary and nine secondary clades, and 18 genotypes. Each genotype has been assigned a unique allele definition located on a conserved gene. Using Paratype, we identified genomic variation between different sampling locations and specific AMR markers, and mutations in the O2-polysaccharide synthesis locus, a candidate for vaccine development. <h3>Conclusions</h3> This large-scale global analysis proposes the first genotyping tool for <i>Salmonella</i> Paratyphi A. Paratype has already been released (https://github.com/CHRF-Genomics/Paratype) as an open-access, command-line tool and is being adopted for large scale genomic analysis. This tool will assist future genomic surveillance and help inform prevention and treatment strategies.
Comparison of antibody responses to hen's egg and cow's milk proteins in orally sensitized rats and food‐allergic patients
Authors: L.M.J. Knippels, H.P.M. Van Der Kleij, S. J. Koppelman, G. F. Houben, A. H. Penninks, L.M.J. Knippels, A. H. Penninks, A.A. Felius
Journal: Allergy (2000)

Background : No adequate enteral sensitization models are available to study food allergy and the allergenicity of food proteins. To further validate a enteral brown Norway (BN) rat sensitization model under development, we studied specific protein recognition to determine whether a comparable pattern of proteins is recognized by the rat immune system and the human immune system. Methods : The animals were exposed to either ovalbumin as a positive reference control, hen's egg‐white‐protein extract, or a cow's milk preparation by daily gavage dosing (0.5, 1, 2.5, 5, 10, or 15 mg protein per rat/day) for 9 weeks. No adjuvants were used during the sensitization studies. The specificities of antibodies against hen's egg‐white proteins or cow's‐milk proteins in sera from orally sensitized rats and food‐allergic patients were studied and compared by immunoblotting. Results : The IgG and IgE antibodies to hen's egg‐white proteins and cow's‐milk proteins present in sera from orally sensitized rats and food‐allergic patients showed a comparable pattern of protein recognition. Conclusions : Upon daily intragastric exposure to food allergens, the specificities of the induced antibody responses in the BN rat resemble those found in food‐allergic patients. These studies add further support to the hypothesis that the BN rat may provide a suitable animal model for food allergy research and research on the allergenicity of food proteins.
The role of adrenal medullary catecholamine release in the response to a cold pressor test
Authors: M. F CUMMINGS, P. M STEELE, L. J M MAHAR, D. B FREWIN, W J. RUSSELL
Journal: Cardiovascular Research (1983)

We studied the effects of a cold pressor test on the plasma catecholamine levels of ten patients undergoing coronary angiography, to determine whether the pressor changes were related to adrenergic activity. To investigate the relative contribution of adrenal medullary catecholamine release, we subjected two adrenalectomised volunteers to the same test. Arterial blood was assayed for dopamine (DA), adrenaline (A) and noradrenaline (NA). We found significant rises in the levels of all three catecholamines in the angiography patients, accompanied by a significant elevation in arterial blood pressure. In both the adrenalectomised patients a rise in blood pressure was seen but no significant rise in plasma catecholamines could be demonstrated. We postulate that although adrenal medullary catecholamine release occurs in response to the cold pressor test, the blood pressure elevation is independent of such adrenal activity. Sampling radial arterial blood may not reflect changes in plasma levels of peripherally released NA.
Horizontal Gene Transfer Accelerates Genome Innovation and Evolution
Authors: R. Jain
Journal: Molecular Biology and Evolution (2003)

Horizontal gene transfer (HGT) spreads genetic diversity by moving genes across species boundaries. By rapidly introducing newly evolved genes into existing genomes, HGT circumvents the slow step of ab initio gene creation and accelerates genome innovation. However, HGT can only affect organisms that readily exchange genes (exchange communities). In order to define exchange communities and understand the internal and external environmental factors that regulate HGT, we analyzed approximately 20,000 genes contained in eight free-living prokaryotic genomes. These analyses indicate that HGT occurs among organisms that share similar factors. The most significant are genome size, genome G/C composition, carbon utilization, and oxygen tolerance.
THU0488-HPR Health care utilization in patients with systemic sclerosis:
Authors: L. Willems, L. Kwakkenbos, C. Bode, F.H. van den Hoogen, E.H. van den Ende
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (scleroderma, SSc) is a rare and complex connective-tissue disease with heterogeneous manifestations. The disease has a large impact on functioning and quality of life in the majority of patients [1]. No effective treatment is available yet. In addition to medical treatment, non-pharmacological treatment is often provided, with the aim to support patients in living with the consequences of the disease. So far, little is known about the amount and diversity of health care services use by SSc patients. Studying health care utilization might help improve and optimize care of patients with SSc. <h3>Objectives</h3> To assess health care utilization in SSc. <h3>Methods</h3> In 2011, the Dutch patient association for patients with systemic autoimmune diseases contacted 699 patients with SSc or Mixed Connective Tissue Disease (MCTD) to complete an anonymous survey. In total, 198 patients with SSc completed the survey consisting of questionnaires on sociodemographics, disease characteristics, quality of life and health care utilization. Descriptive statistics were used to describe demographic characteristics and health care use. <h3>Results</h3> Most respondents were female (86.4%) with an average age of 58.1 years (range 29-85) and a mean time since diagnosis of 11.1 years (SD 9.5). The majority of the patients (65.2%) were diagnosed with limited SSc/CREST. Health care use is displayed in Table 1. In the last 12 months, the majority of the patients (95%) had contact with at least one medical specialist, and two-third contacted at least one health professional. The median number of different health care providers contacted since the onset of SSc and in the last 12 months was 8 and 4, respectively. A median of 7 visits per year to medical specialists and 7.5 visits to health professionals were reported. <h3>Conclusions</h3> Health care use in SSc is substantial, as is reflected in both the high number of visits to health care providers and the number of different health care providers. Due to the complexity of the disease and the high number of different health care providers patients might receive overlap in treatment or contradictory advices. Therefore, attention should also be given to coordination and communication among health care providers. <h3>References</h3> Hudson M, Thombs BD, Steele R, Panopalis P, Newton E, Baron M, Canadian Scleroderma Research Group. Health-related quality of life in systemic sclerosis: a systematic review. Arthritis Rheum 2009; 61: 1112-20. <h3>Disclosure of Interest</h3> None Declared
Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions
Authors: Luisa L. Villa, Gonzalo Perez, Susanne K. Kjaer, Jorma Paavonen, Matti Lehtinen, Nubia Muñoz, Kristján Sigurdsson, Mauricio Hernandez-Avila, Finn Egil Skjeldestad, Steinar Thoresen, Patricia García, Slawomir Majewski, Joakim Dillner, Sven Eric Olsson, Hseon Tay Eng, F. Xavier Bosch, Kevin A. Ault, Darron R. Brown, Daron Gale Ferris, Laura A. Koutsky, Robert J. Kurman, Evan R. Myers, Eliav Barr, John Boslego, Janine Bryan, Mark T. Esser, Christine K. Gause, Teresa M. Hesley, Lisa C. Lupinacci, Heather L. Sings, Frank J. Taddeo, Annemarie R. Thornton
Journal: New England Journal of Medicine (2007)

Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18.
Tumor-growth–promoting cyclooxygenase-2 prostaglandin E2 pathway provides medulloblastoma therapeutic targets
Authors: Ninib Baryawno, Baldur Sveinbjörnsson, Staffan Eksborg, Abiel Orrego, Lova Segerström, Carl Otto Öqvist, Stefan Holm, Bengt Gustavsson, Bertil Kågedal, Per Kogner, John Inge Johnsen
Journal: Neuro-Oncology (2008)

Prostaglandin E2 (PGE2) has been shown to play important roles in several aspects of tumor development and progression. PGE2 is synthesized from arachidonic acid by cyclooxygenases (COX) and prostaglandin E synthases (PGES) and mediates its biological activity through binding to the four prostanoid receptors EP1 through EP4. In this study, we show for the first time that medulloblastoma (MB), the most common malignant childhood brain tumor, expresses high levels of COX-2, microsomal prostaglandin E synthase-1, and EP1 through EP4 and secretes PGE2. PGE2 and the EP2 receptor agonist butaprost stimulated MB cell proliferation. Treatment of MB cells with COX inhibitors suppressed PGE2 production and induced caspase-dependent apoptosis. Similarly, specific COX-2 silencing by small interfering RNA inhibited MB cell growth. EP1 and EP3 receptor antagonists ONO-8713 and ONO-AE3-240, but not the EP4 antagonists ONO-AE3-208 and AH 23848, inhibited tumor cell proliferation, indicating the significance of EP1 and EP3 but not EP4 for MB growth. Administration of COX inhibitors at clinically achievable nontoxic concentrations significantly inhibited growth of established human MB xenografts. Apoptosis was increased, proliferation was reduced, and angiogenesis was inhibited in MBs treated with COX inhibitors. This study suggests that PGE2 is important for MB growth and that therapies targeting the prostanoid metabolic pathway are potentially beneficial and should be tested in clinical settings for treatment of children with MB.
Electrochemical Sensor for Multiplex Biomarkers Detection
Authors: Fang Wei, Prabhudas Patel, Wei Liao, Kishore Chaudhry, Lei Zhang, Martha Arellano-Garcia, Shen Hu, David Elashoff, Hui Zhou, Shilin Shukla, Franky Shah, Chih-Ming Ho, David T. Wong
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Multiplexing assay of biomarkers at the point-of-care is an elusive goal for molecular diagnostics. Experimental Design: Here, we report an electrochemical (EC) sensor for oral cancer detection based on the simultaneous detection of two salivary biomarkers: interleukin (IL)-8 mRNA and IL-8 protein. Results: Under the multiplexing mode, the limit of detection of salivary IL-8 mRNA reaches to 3.9 fM and 7.4 pg/mL for IL-8 protein in saliva. Multiplex assay of these 2 biomarkers directly from 28 cancer and 28 matched control saliva samples shows significant difference between the two groups. From the receiver operating characteristic analysis, the EC sensor yields around 90% sensitivity and specificity for both IL-8 mRNA and IL-8 protein, which are very close to the data measured by traditional assays (ELISA and PCR) with the same group of saliva. Combined IL-8 mRNA and protein show better AUC compared with single biomarker. Conclusions: We show, for the first time, concurrently multiplexing detection of salivary mRNA and protein biomarkers using point-of-care EC sensor.
Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Neoadjuvant Chemotherapy in Bladder Cancer: Ready for Prime Time?
Authors: Damien Pouessel, Hélène Gauthier, Camille Serrate, Christian Pfister, Stéphane Culine
Journal: Journal of Clinical Oncology (2014)
Epidermal Growth Factor Receptor Protein Expression and Gene Amplification in Small Cell Carcinoma of the Urinary Bladder
Authors: Xiaoyan Wang, Shaobo Zhang, Gregory T. MacLennan, John N. Eble, Antonio Lopez-Beltran, Ximing J. Yang, Chong-Xian Pan, Honghong Zhou, Rodolfo Montironi, Liang Cheng
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Small cell carcinoma of the urinary bladder is a highly aggressive malignancy with an average life expectancy of only a few months. Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis and progression of many malignancies. This study was done to investigate EGFR protein expression and gene amplification in a large series of small cell carcinomas of the urinary bladder. Experimental Design: Fifty-two cases of urinary bladder small cell carcinoma were included in this study. Immunostaining for EGFR was done on paraffin-embedded tissue sections, and gene amplification for EGFR was done by fluorescence in situ hybridization. EGFR expression was correlated with clinicopathologic characteristics and clinical outcome. Results: All 52 patients, except 1, had advanced disease (T2 or above) at presentation. Immunohistochemically, positive EGFR expression was observed in 14 of 52 (27%) cases. No EGFR gene amplification was observed in any of 52 cases by fluorescence in situ hybridization. Forty cases had polysomy and the remaining 12 cases displayed disomy. No correlation between EGFR protein expression and gene amplification was shown. There was no correlation between EGFR expression and clinicopathologic characteristics. Conclusions: EGFR is expressed in a subset of urinary bladder small cell carcinomas; however, expression of EGFR does not correlate with clinicopathologic variables. At the molecular level, EGFR overexpression in small cell carcinoma of the urinary bladder does not seem to be caused by gene amplification. The expression of EGFR raises the possibility that EGFR may be a potential therapeutic target in the treatment of this malignancy.
Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism
Authors: Laura S Dieter, Steven Estus
Journal: Molecular Neurodegeneration (2010)

Alleles of apolipoprotein E (APOE) are the major genetic risk factor for late onset Alzheimer's Disease (LOAD). Recently, an APOE splice variant that retains intron 3 (APOE-I3) was identified. To gain insight into the possible role of this isoform in LOAD, we quantified its expression in a cohort of 56 human brain specimens by using quantitative RT-PCR. We found that APOE-I3 generally represents a low percentage (< 0.5%) of overall APOE expression. However, in one specimen, the proportion of APOE-I3 was increased about ~13 fold. This specimen was unique in the cohort for possessing the minor allele of an intron 3 single nucleotide polymorphism (SNP), rs12982192. Additionally, an allelic expression imbalance study indicated that the rs12982192 minor allele was associated with increased APOE-I3 expression. Overall, we interpret our results as suggesting that APOE-I3 represents a minor portion of APOE expression and that rs12982192 is associated with APOE intron 3 retention. Since the minor allele of this SNP is on the same haplotype as the minor allele of rs429358, which defines the APOE4 allele, we speculate that rs12982192 may reflect a modest loss of mRNA encoding functional APOE4.
Impact factor number reflects sustained high quality
Authors: W. K. Alfred Yung
Journal: Neuro-Oncology (2010)

Neuro-Oncology is pleased to announce that its most recent Impact Factor number (published annually by Thomson Scientific in the Journal Citation Reports) demonstrates superb stability of editorial quality during a period of rapid and marked change. The 2009 Impact Factor of 4.984 is marginally lower than the 2008 number (5.000), showing that the rate at which Neuro-Oncology articles are cited has been maintained, even as the number of articles published has risen dramatically.

The Impact Factor is just one measure meant to represent a journal's quality (in fact, Thomson Scientific publishes several metrics, including a Five-Year Impact Factor and an Immediacy Index). The Impact Factor for a particular year is calculated by dividing the number of articles published in the two previous years into the number of citations to those articles in the current year (that is, the 2009 number was calculated by dividing the number of citations in 2009 to articles published in 2007 and 2008 by the total number of articles published in those years).

It is worth noting that in 2007, Neuro-Oncology was still being published quarterly; our publication frequency jumped to bimonthly starting in 2008, with a concomitant increase in the number of scientific articles (from 46 in 2007 to 76 in 2008). We were pleased to see, then, that the rate at which our articles are cited remains steady, despite our very aggressive growth. We interpret this stability as a representation of the scientific quality and significance of our publications and our commitment to publishing the highest quality articles in the field.

We are also proud to note that Neuro-Oncology's 2009 rankings place it in the top 20% of both oncology journals (where it is ranked 26th of 165 journals) and clinical neurology titles (where it is 17th of 167 journals). The table summarizes our performance over the last 4 years.

As always, we invite you to join us in ensuring that the journal remains at the top of its game by contributing as reviewers, authors, and critics.



Neuro-Oncology impact factors and rankings


	Year	Impact factor	Ranking among oncology titles	Ranking among clinical neurology titles
2009	4.984	26th of 165	17th of 167	
2008	5.000	25th of 141	15th of 156	
2007	5.806	16th of 132	6th of 146	
2006	4.939	23rd of 127	14th of 146	


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Phase II, Multicenter, Uncontrolled Trial of Single-Agent Sorafenib in Patients With Relapsed or Refractory, Advanced Non–Small-Cell Lung Cancer
Authors: George R. Blumenschein, Ulrich Gatzemeier, Frank Fossella, David J. Stewart, Lisa Cupit, Frank Cihon, James O'Leary, Martin Reck
Journal: Journal of Clinical Oncology (2009)

Purpose Sorafenib is an oral multikinase inhibitor that targets the Ras/Raf/MEK/ERK mitogenic signaling pathway and the angiogenic receptor tyrosine kinases, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β. We evaluated the antitumor response and tolerability of sorafenib in patients with relapsed or refractory, advanced non–small-cell lung cancer (NSCLC), most of whom had received prior platinum-based chemotherapy. Patients and Methods This was a phase II, single-arm, multicenter study. Patients with relapsed or refractory advanced NSCLC received sorafenib 400 mg orally twice daily until tumor progression or an unacceptable drug-related toxicity occurred. The primary objective was to measure response rate. Results Of 54 patients enrolled, 52 received sorafenib. The predominant histologies were adenocarcinoma (54%) and squamous cell carcinoma (31%). No complete or partial responses were observed. Stable disease (SD) was achieved in 30 (59%) of the 51 patients who were evaluable for efficacy. Four patients with SD developed tumor cavitation. Median progression-free survival (PFS) was 2.7 months, and median overall survival was 6.7 months. Patients with SD had a median PFS of 5.5 months. Major grades 3 to 4, treatment-related toxicities included hand-foot skin reaction (10%), hypertension (4%), fatigue (2%), and diarrhea (2%). Nine patients died within a 30-day period after discontinuing sorafenib, and one patient experienced pulmonary hemorrhage that was considered drug related. Conclusion Continuous treatment with sorafenib 400 mg twice daily was associated with disease stabilization in patients with advanced NSCLC. The broad activity of sorafenib and its acceptable toxicity profile suggest that additional investigation of sorafenib as therapy for patients with NSCLC is warranted.
American Diabetes Association–European Association for the Study of Diabetes Position Statement: Due Diligence Was Conducted
Authors: William T. Cefalu
Journal: Diabetes Care (2012)

Almost everyone has heard the saying, “If you want to keep a friend, never talk about religion or politics.” In regard to the specific management of type 2 diabetes, we can alter this phrase somewhat and suggest, “If you want to keep a colleague, never talk about diabetes guidelines!” Most providers of diabetes care will readily admit that a forum for intense debate revolves around the issue of what is the best approach to manage individuals with diabetes. A provider can justify his decision for treatment based solely on a wide range of management strategies available in the literature. For example, if you really care to do the exercise by searching on PubMed, you will note that the search term “diabetes management” will result in >24,000 citations. The use of “diabetes guidelines” or “diabetes algorithm” as search terms will yield >8,900 and 3,100 citations, respectively. In addition to the debate based on publications, this topic also evokes considerable emotion. With the release of the latest statement on the management of hyperglycemia in type 2 diabetes, the debate will continue unabated. Specifically, this issue of Diabetes Care reports on the position statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Titled “Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach,” this effort results from a joint request of the ADA and EASD executive committees and represents the final product of years of work (1). As it has been the case when prior guidelines have been published, not only from these two organizations but also from other societies and federations, this position statement will generate considerable interest, heated debate, and published commentaries, editorials, and letters on the strengths and weaknesses of the approach.

In regard to the message delivered from previously published guidelines, …
Third Trimester Maternal Glucose Levels From Diurnal Profiles in Nondiabetic Pregnancies: Correlation With Sonographic Parameters of Fetal Growth: A response to Parretti et al. and Jovanovic
Authors: Robert Fraser
Journal: Diabetes Care (2002)

Parretti et al. (1) report an important study in which diurnal profiles performed on home blood-glucose monitoring were related to sonographic parameters of fetal growth. They imply in their introduction that the number of published studies concerning normoglycemia in nondiabetic pregnancies are few, a point that is also made by Jovanovic (2) in the accompanying editorial entitled “What is so bad about a big baby?”

Table 1 shows the diurnal plasma glucose profiles at 29 and 35 weeks gestation on identical diets from the subjects of our randomized controlled …