bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of Helicobacter pylori Peptidoglycan Enhances NOD1 Activation and Promotes Cancer of the Stomach
Authors: Suarez Giovanni , Romero-Gallo Judith , Piazuelo M. Blanca , Wang Ge , Maier Robert J. , Forsberg Lennart S. , Azadi Parastoo , Gomez Martin A. , Correa Pelayo , Peek Richard M. 
Published: March 2015

Abstract
Helicobacter pylori (H. pylori) is the strongest known risk factor for gastric carcinogenesis. One cancer-linked locus is the cag pathogenicity island, which translocates components of peptidoglycan into host cells. NOD1 is an intracellular immune receptor that senses peptidoglycan from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering peptidoglycan structure. We previously demonstrated that the H. pylori cag+ strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. Using 2D-DIGE and mass spectrometry, we identified a novel mutation within the gene encoding the peptidoglycan deacetylase PgdA; therefore, we sought to define the role of H. pylori PgdA in NOD1-dependent activation of NF-κB, inflammation, and cancer. Coculture of H. pylori strain 7.13 or its pgdA− isogenic mutant with AGS gastric epithelial cells or HEK293 epithelial cells expressing a NF-κB reporter revealed that pgdA inactivation significantly decreased NOD1-dependent NF-κB activation and autophagy. Infection of Mongolian gerbils with an H. pylori pgdA− mutant strain led to significantly decreased levels of inflammation and malignant lesions in the stomach; however, preactivation of NOD1 before bacterial challenge reciprocally suppressed inflammation and cancer in response to wild-type H. pylori. Expression of NOD1 differs in human gastric cancer specimens compared with noncancer samples harvested from the same patients. These results indicate that peptidoglycan deacetylation plays an important role in modulating host inflammatory responses to H. pylori, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche. Cancer Res; 75(8); 1749–59. ©2015 AACR.
Evaluation of Diffusion-Weighted Magnetic Resonance Imaging for Follow-up and Treatment Response Assessment of Lymphoma: Results of an 18F-FDG-PET/CT–Controlled Prospective Study in 64 Patients
Authors: Mayerhoefer Marius E. , Karanikas Georgios , Kletter Kurt , Prosch Helmut , Kiesewetter Barbara , Skrabs Cathrin , Porpaczy Edit , Weber Michael , Knogler Thomas , Sillaber Christian , Jaeger Ulrich , Simonitsch-Klupp Ingrid , Ubl Philipp , Müllauer Leonhard , Dolak Werner , Lukas Julius , Raderer Markus 
Published: March 2015

Abstract
Purpose: To determine the value of diffusion-weighted MRI (DWI-MRI) for treatment response assessment in 2-[18F]fluoro-2-deoxy-D-glucose (FDG)–avid lymphoma.
Experimental Design: Patients with FDG-avid Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at pretherapeutic 18F-FDG-PET/CT, who had also undergone pretherapeutic whole-body DWI-MRI, were included in this prospective study. Depending on the histologic lymphoma subtype, patients received different systemic treatment regimens, and follow-up DWI-MRI and 18F-FDG-PET/CT were performed at one or more time points, depending on the clinical course. For each follow-up DWI-MRI, region-based rates of agreement, and rates of agreement in terms of treatment response (complete remission, partial remission, stable disease, or progressive disease), relative to the corresponding 18F-FDG-PET/CT, were calculated.
Results: Sixty-four patients were included: 10 with HL, 22 with aggressive NHL, and 32 with indolent NHL. The overall region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.4%. For the 51 interim examinations (performed after 1–3 therapy cycles), region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.2%, and for the 48 end-of-treatment examinations, agreement was 99.8%. No significant differences, in terms of region-based agreement between DWI-MRI and 18F-FDG-PET/CT, were observed between the three lymphoma groups (HL, aggressive NHL, indolent NHL; P = 0.25), or between interim and end-of-treatment examinations (P = 0.21). With regard to treatment response assessment, DWI-MRI agreed with 18F-FDG-PET/CT in 99 of 102 follow-up examinations (97.1%), with a κ value of 0.94 (P &lt; 0.0001).
Conclusions: In patients with FDG-avid lymphoma, DWI-MRI may be a feasible alternative to 18F-FDG-PET/CT for follow-up and treatment response assessment. Clin Cancer Res; 21(11); 2506–13. ©2015 AACR.
Characterization of ABT-806, a Humanized Tumor-Specific Anti-EGFR Monoclonal Antibody
Authors: Reilly Edward B. , Phillips Andrew C. , Buchanan Fritz G. , Kingsbury Gillian , Zhang Yumin , Meulbroek Jonathan A. , Cole Todd B. , DeVries Peter J. , Falls Hugh D. , Beam Christine , Gu Jinming , Digiammarino Enrico L. , Palma Joann P. , Donawho Cherrie K. , Goodwin Neal C. , Scott Andrew M. 
Published: March 2015

Abstract
Despite clinical efficacy, current approved agents targeting EGFR are associated with on-target toxicities as a consequence of disrupting normal EGFR function. MAb 806 is a novel EGFR antibody that selectively targets a tumor-selective epitope suggesting that a mAb 806-based therapeutic would retain antitumor activity without the on-target toxicities associated with EGFR inhibition. To enable clinical development, a humanized variant of mAb 806 designated ABT-806 was generated and is currently in phase 1 trials. We describe the characterization of binding and functional properties of ABT-806 compared with the clinically validated anti-EGFR antibody cetuximab. ABT-806 binds the mutant EGFRvIII with high affinity and, relative to cetuximab, exhibits increased potency against glioblastoma multiforme cell line and patient-derived xenografts expressing this form of the receptor. ABT-806 also inhibits the growth of squamous cell carcinoma xenograft models expressing high levels of wild-type EGFR, associated with inhibition of EGFR signaling, although higher doses of ABT-806 than cetuximab are required for similar activity. ABT-806 enhances in vivo potency of standard-of-care therapies used to treat glioblastoma multiforme and head and neck squamous cell carcinoma. An indium-labeled version of ABT-806, [111In]-ABT-806, used to investigate the relationship between dose and receptor occupancy, revealed greater receptor occupancy at lowers doses in an EGFRvIII-expressing model and significant uptake in an orthotopic model. Collectively, these results suggest that ABT-806 may have antitumor activity superior to cetuximab in EGFRvIII-expressing tumors, and similar activity to cetuximab in tumors highly overexpressing wild-type EGFR with reduced toxicity. Mol Cancer Ther; 14(5); 1141–51. ©2015 AACR.
Rapidly rule out acute myocardial infarction by combining copeptin and heart-type fatty acid-binding protein with cardiac troponin
Authors: Jacobs Leo HJ , van Borren Marcel , Gemen Eugenie , van Eck Martijn , van Son Bas , Glatz Jan FC , Daniels Marcel , Kusters Ron 
Published: March 2015

Background The rapid exclusion of acute myocardial infarction in patients with chest pain can reduce the length of hospital admission, prevent unnecessary diagnostic work-up and reduce the burden on our health-care systems. The combined use of biomarkers that are associated with different pathophysiological aspects of acute myocardial infarction could improve the early diagnostic assessment of patients presenting with chest pain. Methods We measured cardiac troponin I, copeptin and heart-type fatty acid-binding protein concentrations in 584 patients who presented to the emergency department with acute chest pain. The diagnostic performances for the diagnosis of acute myocardial infarction and NSTEMI were calculated for the individual markers and their combinations. Separate calculations were made for patients presenting to the emergency department <3 h, 3–6 h and 6–12 h after chest pain onset. Results For ruling out acute myocardial infarction, the net predictive values (95% CI) of cardiac troponin I, copeptin and heart-type fatty acid-binding protein were 90.4% (87.3–92.9), 84% (79.8–87.6) and 87% (83.5–90), respectively. Combining the three biomarkers resulted in a net predictive value of 95.8% (92.8–97.8). The improvement was most pronounced in the early presenters (<3 h) where the combined net predictive value was 92.9% (87.3–96.5) compared to 84.6% (79.4–88.9) for cardiac troponin I alone. The area under the receiver operating characteristic for the triple biomarker combination increased significantly ( P < 0.05) compared to that of cardiac troponin I alone (0.880 [0.833–0.928] vs. 0.840 [0.781–0.898], respectively). Conclusions Combining copeptin, heart-type fatty acid-binding protein and cardiac troponin I measurements improves the diagnostic performance in patients presenting with chest pain. Importantly, in patients who present early (<3 h) after chest pain onset, the combination improves the diagnostic performance compared to the standard cardiac troponin I measurement alone.
Faecal calprotectin as a marker for oesophago-gastric cancer
Authors: Vincent Zoe , Hornby Steve , Ball Susan , Sanders Grant , Ayling Ruth M 
Published: March 2015

Background Faecal calprotectin has been shown to be useful as a non-invasive screening test to differentiate functional from organic bowel disease, and it has been noted to be elevated in colorectal cancer. The aim of this study was to describe concentrations of faecal calprotectin in patients with oesophago-gastric cancer and investigate any potential discriminatory power of the test. Patients Faecal calprotectin was measured in samples from 39 patients with known oesophago-gastric cancer and in 191 samples from control subjects. Results The median calprotectin concentration was < 20 µg/g (range <  20–421 µg/g) in control subjects and 97 µg/g (range < 20–940 µg/g) in patients with oesophago-gastric cancer (P < 0.001). A receiver operating characteristic curve gave an area under the ROC curve of 0.84 and a sensitivity of 76.9% (95% CI: 63.7–90.1%) and specificity of 88.0% (95% CI: 83.3–92.6%) at a cutoff of 50 µg/g. Conclusion Faecal calprotectin is elevated in patients with cancer of the upper gastrointestinal tract. This study suggests that calprotectin may be promising in discriminating cancer patients from controls, but further work is required to explore any potential role of faecal calprotectin in screening for, or diagnosis of, oesophago-gastric cancer.
Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis
Authors: Martínez M Alba Mañé , Olsson Bob , Bau Laura , Matas Elisabet , Calvo Álvaro Cobo , Andreasson Ulf , Blennow Kaj , Romero-Pinel Lucia , Martínez-Yélamos Sergio , Zetterberg Henrik 
Published: March 2015

Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.
A multi-site randomized clinical trial to reduce suicidal ideation in suicidal adult outpatients with Major Depressive Disorder: Development of a methodology to enhance safety
Authors: McCall William Vaughn , Benca Ruth M , Rosenquist Peter B , Riley Mary Anne , Hodges Chelsea , Gubosh Brittany , McCloud Laryssa , Newman Jill C , Case Doug , Rumble Meredith , Mayo Mark , White Kaitlin Hanley , Phillips Marjorie , Krystal Andrew D 
Published: March 2015

Background/aims: Suicide is a major public health concern, yet there are very few randomized clinical trials that have been conducted to reduce suicidal ideation in patients at risk of suicide. We describe the rationale and refinements of such a trial that is designed to assess the effect of a hypnotic medication on suicidal ideation in adult outpatients currently experiencing suicidal ideation. Methods: “Reducing Suicidal Ideation Through Insomnia Treatment” is a multi-site randomized clinical trial that includes three recruiting sites and one data management site. This 4-year study is in its second year of recruitment. The purpose of the study is to compare hypnotic medication versus placebo as an add-on treatment to a selective serotonin reuptake inhibitor as a means of reducing suicidal ideation in depressed adult outpatients with insomnia and suicidal ideation. The safety features of the study follow the 2001 National Institutes of Health guidelines for studies that include patients at risk of suicide. Results: In total, 584 potential participants have undergone telephone screening; 67% of these failed the phone screen, most often due to an absence of expressed suicidal ideation (26% of the telephone screen fails). A total of 115 people appeared for a face-to-face baseline assessment, and 40 of these had completed a taper off of their ineffective psychotropic medications before the baseline assessments. In all, 64% of those who completed baseline assessments failed to proceed to randomization, most commonly because of no clinically significant suicidal ideation (51% of those excluded at baseline). One participant was offered and accepted voluntary psychiatric hospitalization in lieu of study participation. Thus far, 40 participants have been randomized into the study and 88.7% of scheduled visits have been attended, with 93.8% adherence to the selective serotonin reuptake inhibitor and 91.6% adherence to the randomized hypnotic versus placebo. None of the randomized participants have required hospitalization or had a suicide attempt. Conclusion: By carefully considering the inclusion and exclusion criteria and other safety features, the safe conduct of randomized clinical trials in suicidal adult patients is possible, including the inclusion of participants who have undergone a prescribed tapering off of psychotropic medications prior to baseline assessment.
Memory complaints in older adults: Prognostic value and stability in reporting over time
Authors: Howieson Diane B , Mattek Nora , Dodge Hiroko H , Erten-Lyons Deniz , Zitzelberger Tracy , Kaye Jeffrey A 
Published: March 2015

Objective: The purpose of this longitudinal study was to examine the prognostic value of subjective memory complaints in 156 cognitively intact community-dwelling older adults with a mean age of 83 years. Methods: Participants were assessed for subjective memory complaints, cognitive performance, functional status, and mood at annual evaluations with a mean follow-up of 4.5 years. Results: Subjective memory complaint at entry (n = 24) was not associated with impaired memory performance and did not predict memory decline or progression to incipient dementia. Memory complaints were inconsistent across examinations for 62% of participants who reported memory problems. Conclusion: Memory complaints by older adults are inconsistent over time. Memory complaints’ value as a research criterion for selecting people at risk of dementia is weak among community-dwelling older adults. Age, length of follow-up, and other population characteristics may affect the implication of self-reported memory problems.
Sleep disturbances and quality of life in Sub-Saharan African migraineurs
Authors: Morgan Isabel , Eguia Francisco , Gelaye Bizu , Peterlin B Lee , Tadesse Mahlet G , Lemma Seblewengel , Berhane Yemane , Williams Michelle A 
Published: March 2015

Abstract

Background
Although in the past decade occidental countries have increasingly recognized the personal and societal burden of migraine, it remains poorly understood in Africa. No study has evaluated the impact of sleep disturbances and the quality of life (QOL) in sub-Saharan Africans with migraine.

Methods
This was a cross-sectional study evaluating adults, ≥ 18 years of age, attending outpatient clinics in Ethiopia. Standardized questionnaires were utilized to collect demographic, headache, sleep, lifestyle, and QOL characteristics in all participants. Migraine classification was based on International Classification of Headache Disorders (ICHD)-II criteria. The Pittsburgh Sleep Quality Index (PSQI) and the World Health Organization Quality of Life (WHOQOL-BREF) questionnaires were utilized to assess sleep quality and QOL characteristics, respectively. Multivariable logistic regression models were fit to estimate adjusted odds ratio (OR) and 95% confidence intervals (95% CI).

Results
Of 1,060 participants, 145 (14%) met ICHD-II criteria for migraine. Approximately three-fifth of the study participants (60.5%) were found to have poor sleep quality. After adjustments, migraineurs had over a two-fold increased odds (OR = 2.24, 95% CI 1.49-3.38) of overall poor sleep quality (PSQI global score >5) as compared with non-migraineurs. Compared with non-migraineurs, migraineurs were also more likely to experience short sleep duration (≤7 hours) (OR = 2.07, 95% CI 1.43-3.00), long sleep latency (≥30 min) (OR = 1.97, 95% CI 1.36-2.85), daytime dysfunction due to sleepiness (OR = 1.51, 95% CI 1.12-2.02), and poor sleep efficiency (<85%) (OR = 1.93, 95% CI 1.31-2.88). Similar to occidental countries, Ethiopian migraineurs reported a reduced QOL as compared to non-migraineurs. Specifically Ethiopian migraineurs were more likely to experience poor physical (OR = 1.56, 95% CI 1.08-2.25) and psychological health (OR = 1.75, 95% CI 1.20-2.56), as well as poor social relationships (OR = 1.56, 95% CI 1.08-2.25), and living environments (OR = 1.41, 95% CI 0.97-2.05) as compared to those without migraine.

Conclusion
Similar to occidental countries, migraine is highly prevalent among Ethiopians and is associated with poor sleep quality and a lower QOL. These findings support the need for physicians and policy makers to take action to improve the quality of headache care and access to treatment in Ethiopia.
Ligustrazinyl amides: a novel class of ligustrazine-phenolic acid derivatives with neuroprotective effects
Authors: Li Guoliang , Xu Xin , Xu Kuo , Chu Fuhao , Song Jixiang , Zhou Shen , Xu Bing , Gong Yan , Zhang Huazheng , Zhang Yuzhong , Wang Penglong , Lei Haimin 
Published: March 2015

Abstract

Background
Ligustrazine has potent effects of thrombolysis, neuroprotection and vascular protection, which were important for effectively protecting the nervous system. Previous study in our laboratory reported that ligustrazine-benzoic acid derivatives have been shown to exhibit beneficial effect against CoCl2-induced neurotoxicity in differentiated PC12 cells. To further improve ligustrazine’s neuroprotection, we integrated the ligustrazine and phenolic acid fragments into one molecule via an amide bond based on structural combination.

Results
In this study, 12 novel ligustrazine-phenolic acid derivatives were synthesized and nine others were prepared by improved methods. Furthermore, these compounds were evaluated for their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells. The amides conjunctional derivatives exhibited promising neuroprotective activities in comparison with ligustrazine. In addition, the most active congener (E)-3-(2,3,4-trimethoxyphenyl)-N-((3,5,6-trimethylpyrazin-2-yl)methyl)acrylamide (L10, EC50 = 25 μM), which is 2 times higher than that of ligustrazine, may be a potential candidate for intervention in neurological diseases. Structure-activity relationship was discussed briefly.

Conclusions
Results of series of ligustrazinyl amides enrich the study of ligustrazine derivatives with neuroprotective effects. Our completed work supports that the attempt to apply structure combination to discover more efficient neuroprotection lead compounds is viable.
Physical activity and risk of rheumatoid arthritis in women: a population-based prospective study
Authors: Di Giuseppe Daniela , Bottai Matteo , Askling Johan , Wolk Alicja 
Published: March 2015

Abstract
Introduction
Only one study has analysed the association between exercise and development of rheumatoid arthritis (RA), showing no association. Aim of this paper was to evaluate the association of physical activity in all its aspect with RA.

Methods
To examine this association, middle age and elderly women from the Swedish Mammography Cohort, a population-based prospective study, were analysed. Data on physical activity were collected in 1997 by self-administrated food-frequency questionnaire. Risk of RA associated with physical activity was estimated using Cox proportional hazard regression models.

Results
Among 30,112 women born between 1914 and 1948 followed-up from January 1, 2003 to December 31, 2010, 201 RA cases were identified (226,477 person-years). There was a statistically significant 35% lower risk of RA (relative risk (RR), 0.65; 95% confidence interval (CI), 0.43-0.96) among women in the highest category of leisure-time activity (combining more than 20 minute per day of walking/bicycling (median 40–60 minute per day) and more than 1 hour per week of exercise (median 2–3 hours per week)) as compared to women in the lowest category (less than 20 minute per day of walking/bicycling and less than 1 hour per week of exercise). A non-statistically significant decreased risk was observed for household work (−32%) and work/occupation (−15%), while an increased risk was observed for leisure-time physical inactivity (+27%). Daily energy expenditure was not associated with risk of RA.

Conclusions
This prospective population-based cohort study of women supports the hypothesis that physical activity can be a protective factor in the etiology of rheumatoid arthritis. Our results add to accumulated evidence on benefits of modifiable leisure-time physical activity for prevention of many other chronic diseases.