bluuebunny/crossref_metadata_2025_split huggingface dataset:
MBL2Variations and Malaria Susceptibility in Indian Populations
Authors: Jha Aditya Nath , Sundaravadivel Pandarisamy , Singh Vipin Kumar , Pati Sudhanshu S. , Patra Pradeep K. , Kremsner Peter G. , Velavan Thirumalaisamy P. , Singh Lalji , Thangaraj Kumarasamy 
Published: October 2013

ABSTRACTHuman mannose-binding lectin (MBL) encoded by theMBL2gene is a pattern recognition protein and has been associated with many infectious diseases, including malaria. We sought to investigate the contribution of functionalMBL2gene variations toPlasmodium falciparummalaria in well-defined cases and in matched controls. We resequenced the 8.7 kb of the entireMBL2gene in 434 individuals clinically classified with malaria from regions of India where malaria is endemic. The study cohort included 176 patients with severe malaria, 101 patients with mild malaria, and 157 ethnically matched asymptomatic individuals. In addition, 830 individuals from 32 socially, linguistically, and geographically diverse endogamous populations of India were investigated for the distribution of functionalMBL2variants. TheMBL2 −221C(X) allelic variant is associated with increased risk of malaria (mild malaria odds ratio [OR] = 1.9, correctedPvalue [PCorr] = 0.0036; severe malaria OR = 1.6,PCorr= 0.02). The exon1 variantsMBL2*B(severe malaria OR = 2.1,PCorr= 0.036; mild versus severe malaria OR = 2.5,PCorr= 0.039) andMBL2*C(mild versus severe malaria OR = 5.4,PCorr= 0.045) increased the odds of having malaria. The exon1MBL2*D/*B/*Cvariant increased the risk for severe malaria (OR = 3.4,PCorr= 0.000045). The frequencies of low MBL haplotypes were significantly higher in severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%). TheMBL2*LYPAhaplotypes confer protection, whereasMBL2*LXPAincreases the malaria risk. Our findings in Indian populations demonstrate thatMBL2functional variants are strongly associated with malaria and infection severity.
Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis
Authors: Lattar Santiago M. , Noto Llana Mariángeles , Denoël Philippe , Germain Sophie , Buzzola Fernanda R. , Lee Jean C. , Sordelli Daniel O. 
Published: October 2013

ABSTRACT

Staphylococcus aureus
is an invasive bacterial pathogen, and antibiotic resistance has impeded adequate control of infections caused by this microbe. Moreover, efforts to prevent human infections with single-component
S. aureus
vaccines have failed. In this study, we evaluated the protective efficacy in rats of vaccines containing both
S. aureus
capsular polysaccharides (CPs) and proteins. The serotypes 5 CP (CP5) and 8 CP (CP8) were conjugated to tetanus toxoid and administered to rats alone or together with domain A of clumping factor A (ClfA) or genetically detoxified alpha-toxin (dHla). The vaccines were delivered according to a preventive or a therapeutic regimen, and their protective efficacy was evaluated in a rat model of osteomyelitis. Addition of dHla (but not ClfA) to the CP5 or CP8 vaccine induced reductions in bacterial load and bone morphological changes compared with immunization with either conjugate vaccine alone. Both the prophylactic and therapeutic regimens were protective. Immunization with dHla together with a pneumococcal conjugate vaccine used as a control did not reduce staphylococcal osteomyelitis. The emergence of unencapsulated or small-colony variants during infection was negligible and similar for all of the vaccine groups. In conclusion, addition of dHla to a CP5 or CP8 conjugate vaccine enhanced its efficacy against
S. aureus
osteomyelitis, indicating that the inclusion of multiple antigens will likely enhance the efficacy of vaccines against both chronic and acute forms of staphylococcal disease.
Hemoglobin Receptor Protein from Porphyromonas gingivalis Induces Interleukin-8 Production in Human Gingival Epithelial Cells through Stimulation of the Mitogen-Activated Protein Kinase and NF-κB Signal Transduction Pathways
Authors: Fujita Yuki , Nakayama Masaaki , Naito Mariko , Yamachika Eiki , Inoue Tetsuyoshi , Nakayama Koji , Iida Seiji , Ohara Naoya 
Published: October 2013

ABSTRACTPeriodontitis is an inflammatory disease of polymicrobial origin affecting the tissues supporting the tooth. The oral anaerobic bacteriumPorphyromonas gingivalis, which is implicated as an important pathogen for chronic periodontitis, triggers a series of host inflammatory responses that promote the destruction of periodontal tissues. Among the virulence factors ofP. gingivalis, hemoglobin receptor protein (HbR) is a major protein found in culture supernatants. In this study, we investigated the roles of HbR in the production of inflammatory mediators. We found that HbR induced interleukin-8 (IL-8) production in the human gingival epithelial cell line Ca9-22. p38 mitogen-activated protein kinase (MAPK) and extracellular signal-related kinase 1/2 (Erk1/2) were activated in HbR-stimulated Ca9-22 cells. Inhibitors of p38 MAPK (SB203580) and Erk1/2 (PD98059) blocked HbR-induced IL-8 production. Additionally, HbR stimulated the translocation of NF-κB-p65 to the nucleus, consistent with enhancement of IL-8 expression by activation of the NF-κB pathway. In addition, small interfering RNA (siRNA) targeting activating transcription factor 2 (ATF-2) or cyclic AMP-response element-binding protein (CREB) inhibited HbR-induced IL-8 production. Moreover, pretreatment with SB203580 and PD98059 reduced HbR-induced phosphorylation of CREB and ATF-2, respectively. Combined pretreatment with an inhibitor of NF-κB (BAY11-7082) and SB203580 was more efficient in inhibiting the ability of HbR to induce IL-8 production than pretreatment with either BAY11-7082 or SB203580 alone. Thus, in Ca9-22 cells, the direct activation of p38 MAPK and Erk1/2 by HbR caused the activation of the transcription factors ATF-2, CREB, and NF-κB, thus resulting in the induction of IL-8 production.
Optical Metabolic Imaging Identifies Glycolytic Levels, Subtypes, and Early-Treatment Response in Breast Cancer
Authors: Walsh Alex J. , Cook Rebecca S. , Manning H. Charles , Hicks Donna J. , Lafontant Alec , Arteaga Carlos L. , Skala Melissa C. 
Published: October 2013

Abstract
Abnormal cellular metabolism is a hallmark of cancer, yet there is an absence of quantitative methods to dynamically image this powerful cellular function. Optical metabolic imaging (OMI) is a noninvasive, high-resolution, quantitative tool for monitoring cellular metabolism. OMI probes the fluorescence intensities and lifetimes of the autofluorescent metabolic coenzymes reduced NADH and flavin adenine dinucleotide. We confirm that OMI correlates with cellular glycolytic levels across a panel of human breast cell lines using standard assays of cellular rates of glucose uptake and lactate secretion (P &lt; 0.05, r = 0.89). In addition, OMI resolves differences in the basal metabolic activity of untransformed from malignant breast cells (P &lt; 0.05) and between breast cancer subtypes (P &lt; 0.05), defined by estrogen receptor and/or HER2 expression or absence. In vivo OMI is sensitive to metabolic changes induced by inhibition of HER2 with the antibody trastuzumab (herceptin) in HER2-overexpressing human breast cancer xenografts in mice. This response was confirmed with tumor growth curves and stains for Ki67 and cleaved caspase-3. OMI resolved trastuzumab-induced changes in cellular metabolism in vivo as early as 48 hours posttreatment (P &lt; 0.05), whereas fluorodeoxyglucose-positron emission tomography did not resolve any changes with trastuzumab up to 12 days posttreatment (P &gt; 0.05). In addition, OMI resolved cellular subpopulations of differing response in vivo that are critical for investigating drug resistance mechanisms. Importantly, OMI endpoints remained unchanged with trastuzumab treatment in trastuzumab-resistant xenografts (P &gt; 0.05). OMI has significant implications for rapid cellular-level assessment of metabolic response to molecular expression and drug action, which would greatly accelerate drug development studies. Cancer Res; 73(20); 6164–74. ©2013 AACR.
Exploration of Genome-Wide Circulating MicroRNA in Hepatocellular Carcinoma: MiR-483-5p as a Potential Biomarker
Authors: Shen Jing , Wang Antai , Wang Qiao , Gurvich Irina , Siegel Abby B. , Remotti Helen , Santella Regina M. 
Published: October 2013

Abstract
Background: MicroRNAs (miRNA) are abundant in the circulation and play a central role in diverse biologic processes; they may be useful for early diagnosis of hepatocellular carcinoma.
Methods: We conducted a two-phase, case–control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiates hepatocellular carcinoma cases from controls. Taqman low-density arrays were used to examine genome-wide miRNA expression for the discovery set, and quantitative real-time PCR was used to validate candidate miRNAs for both discovery and validation sets.
Results: Sixty-six miRNAs were found to be significantly overexpressed in plasma of hepatocellular carcinoma cases compared with controls after adjusting for false discovery rate (P &lt; 0.05). A volcano plot indicated that seven miRNAs had greater than 2-fold case–control differences with P &lt; 0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p, and miR-520b) detectable in all samples with varied expression levels were further validated in a validation set. MiR-483-5p was statistically significantly overexpressed in hepatocellular carcinoma cases compared with controls (3.20 vs. 0.82, P &lt; 0.0001). Hepatocellular carcinoma risk factors and clinic-pathological characteristics did not influence miR-483-5p expression. The combination of plasma miR-483-5p level and hepatitis C virus status can significantly differentiate hepatocellular carcinoma cases from controls with an area under the curve of 0.908 (P &lt; 0.0001). The sensitivity and specificity were, respectively, 75.5% and 89.8%.
Conclusions: These preliminary results suggest the importance of dysregulated circulating miR-483-5p as a potential hepatocellular carcinoma biomarker.
Impact: Confirmation of aberrant expression of miR-483-5p in a large prospective hepatocellular carcinoma study will provide support for its application to hepatocellular carcinoma detection. Cancer Epidemiol Biomarkers Prev; 22(12); 2364–73. ©2013 AACR.
Body Mass Index and Microsatellite Instability in Colorectal Cancer: A Population-based Study
Authors: Hoffmeister Michael , Bläker Hendrik , Kloor Matthias , Roth Wilfried , Toth Csaba , Herpel Esther , Frank Bernd , Schirmacher Peter , Chang-Claude Jenny , Brenner Hermann 
Published: October 2013

Abstract
Background: Previous studies reported a positive association of body mass index (BMI) with microsatellite-stable (MSS) but not with microsatellite-instable (MSI-high) colorectal cancer. However, information from population-based studies conducted in representative age groups is so far limited.
Methods: We conducted a population-based case–control study (DACHS) in Southern Germany, including 1,215 patients with incident colorectal cancer and 1,891 matched controls with no upper age limit. Information on risk factors of colorectal cancer was obtained in standardized interviews. Microsatellite instability was analyzed using a mononucleotide marker panel.
Results: Median age among cases was 69 years, and 115 cases were classified MSI-high (9.5%). In multivariate analyses, BMI was positively associated with both risk of MSI-high colorectal cancer [per 5 kg/m2: OR, 1.71; 95% confidence interval (CI), 1.35–2.17] and risk of MSS colorectal cancer (OR, 1.20; 95% CI, 1.07–1.33). The association with MSI-high colorectal cancer was limited to women (OR, 2.04; 95% CI, 1.50–2.77; P interaction = 0.02) and most pronounced among ever users of postmenopausal hormone replacement therapy (OR, 4.68; 95% CI, 2.36–9.30; P interaction = 0.01). In case-only analyses, BMI was more strongly associated with MSI-high colorectal cancer than with MSS colorectal cancer among women (OR, 1.84; 95% CI, 1.13–1.82; P interaction = 0.01).
Conclusions: This population-based study confirms previous findings of increased risk of MSS colorectal cancer with obesity between both sexes and suggests that overweight and obesity may also be associated with increased risk of MSI-high colorectal cancer among women.
Impact: These findings extend available data on the association of BMI and microsatellite instability in colorectal cancer and may suggest a link between overweight and obesity with sporadic MSI-high colorectal cancer in women. Cancer Epidemiol Biomarkers Prev; 22(12); 2303–11. ©2013 AACR.
Apigenin Sensitizes Colon Cancer Cells to Antitumor Activity of ABT-263
Authors: Shao Huanjie , Jing Kai , Mahmoud Esraa , Huang Haihong , Fang Xianjun , Yu Chunrong 
Published: October 2013

Abstract
Apigenin is an edible plant-derived flavonoid that shows modest antitumor activities in vitro and in vivo. Apigenin treatment resulted in cell growth arrest and apoptosis in various types of tumors by modulating several signaling pathways. In the present study, we evaluated interactions between apigenin and ABT-263 in colon cancer cells. We observed a synergistic effect between apigenin and ABT-263 on apoptosis of colon cancer cells. ABT-263 alone induced limited cell death while upregulating expression of Mcl-1, a potential mechanism for the acquired resistance to ABT-263. The presence of apigenin antagonized ABT-263–induced Mcl-1 upregulation and dramatically enhanced ABT-263–induced cell death. Meanwhile, apigenin suppressed AKT and ERK activation. Inactivation of either AKT or ERK by lentivirus-transduced shRNA or treatment with specific small-molecule inhibitors of these pathways enhanced ABT-263–induced cell death, mirroring the effect of apigenin. Moreover, the combination response was associated with upregulation of Bim and activation of Bax. Downregulation of Bax eliminated the synergistic effect of apigenin and ABT-263 on cell death. Xenograft studies in SCID mice showed that the combined treatment with apigenin and ABT-263 inhibited tumor growth by up to 70% without obvious adverse effects, while either agent only inhibited around 30%. Our results demonstrate a novel strategy to enhance ABT-263–induced antitumor activity in human colon cancer cells by apigenin via inhibition of the Mcl-1, AKT, and ERK prosurvival regulators. Mol Cancer Ther; 12(12); 2640–50. ©2013 AACR.
Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy
Authors: Gold Michael R. , Daubert Jean-Claude , Abraham William T. , Hassager Christian , Dinerman Jay L. , Hudnall J. Harrison , Cerkvenik Jeff , Linde Cecilia 
Published: October 2013

Background—
Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT-D). However, there are little data comparing mortality between these 2 device types.

Methods and Results—

REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) was a multicenter, randomized trial of CRT among patients with mild heart failure. Long-term annual follow-up for 5 years was preplanned. The present analysis was confined to the 419 patients who were randomized to active CRT group. CRT-pacemakers or CRT-D devices were implanted based on national guidelines at the time of enrollment, with 74 patients receiving CRT pacemaker devices and the remaining 345 patients receiving CRT-D devices. After 12 months of CRT, changes in the clinical composite score, left ventricular end systolic volume index, 6-minute walk time, and quality of life indices were similar between CRT pacemaker and CRT-D patients. However, long-term follow-up showed lower morality in the CRT-D group. Specifically, multivariable analysis showed that CRT-D (hazard ratio, 0.35;
P
=0.003) was a strong independent predictor of survival. Female sex, longer unpaced QRS duration, and smaller baseline left ventricular end systolic volume index also were also associated with better survival.

Conclusions—
REVERSE demonstrated that the addition of implantable cardioverter-defibrillator therapy to CRT is associated with improved long-term survival compared with CRT pacing alone in mild heart failure.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00271154.
Correlation of Ventricular Arrhythmias With Genotype in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Bao Jingru , Wang Jizheng , Yao Yan , Wang Yilu , Fan Xiaohan , Sun Kai , He Ding Sheng , Marcus Frank I. , Zhang Shu , Hui Rutai , Song Lei 
Published: October 2013

Background—
Although mutations of several genes are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), the exact correlation between genotype and ventricular arrhythmia features remains unclear. This study was aimed to examine the possible association of the 9 known genes of ARVC with clinical and electrophysiological characteristics.

Methods and Results—

Ninety subjects diagnosed with ARVC who underwent electrophysiological study were recruited for screening the 9 known ARVC-causing genes. A total of 53 mutations were identified in 57 (63%) subjects. Mutation carriers had more frequent clinical ventricular tachycardia (VT; 89% versus 55%;
P
<0.001) and negative T waves in V
1
to V
3
(61% versus 33%;
P
=0.016). Subjects with plakophilin-2 (
PKP2
) mutations also had more frequent VT than those without mutations in
PKP2
. Comparison between subjects with multiple and single mutations showed that syncope occurred more often in the former group (58% versus 24%;
P
=0.018). VT was significantly more often induced in mutation carriers compared with noncarriers (75% versus 39%;
P
=0.001), as well as in
PKP2
mutation carriers compared with subjects without
PKP2
mutations (80% versus 48%;
P
=0.002). Induced VT with a rate ≥200 bpm was more often documented in mutation carriers (88% versus 54%;
P
=0.013), as well as in
PKP2
mutation carriers (91% versus 67%;
P
=0.041).

Conclusions—

Pathogenic gene mutations were found in nearly two thirds of subjects diagnosed with ARVC. Mutation carriers, especially
PKP2
, had a higher proportion of a history of VT and more inducible fast VT.
Prevalence and clinical characteristics of headache in adolescents: A Croatian epidemiological study
Authors: Cvetković Vlasta Vuković , Plavec Davor , Lovrenčić-Huzjan Arijana , Strineka Maja , Ažman Dražen , Bene Raphael 
Published: October 2013

Background Headaches are often under-diagnosed in adolescents. The aim of this study was to examine the one-year prevalence of primary headaches among high school students in the city of Zagreb, the capital of Croatia. Methods This was a population-based, cross-sectional study. A total of 2350 questionnaires consisting of questions on demographic data, the presence and clinical characteristics of headaches were distributed among students in eight high schools; 2057 (87.5%) questionnaires were eligible for analysis. Results The mean age of the students was 17.2 ± 1.2 years; 50.2% were female. The prevalence of recurrent headache was 30.1% (620/2057), girls 35.1%, boys 25.2%. Among students with headache, 291 (46.9%) had migraine, and 329 (53.1%) had tension-type headaches (TTHs). The mean frequency of headaches was 5.66 per month in girls and 4.42 in boys; mean duration of a headache attack was 8.94 hours in girls and 8.37 hours in boys (NS). Unilateral headache was present in 31.6%, throbbing quality in 22.6%, dull in 34.4% of students; 22.4% had severe intensity and 70.3% moderate. Nausea was present in 4.0% always and in 14.7% frequently (girls 18.8%), photophobia in 41.3%, phonophobia in 63.2%, osmophobia in 23.9% (NS among genders). Almost 30% of students were disabled and stayed at home, more frequently boys. Girls (33.4%) were more likely to take drugs for every attack; number per month was 3.7. The results of this study showed that the prevalence of migraine among adolescents in Croatia was 16.5% for girls and 11.8% for boys; the prevalence of TTH was 18.4% for girls and 13.4% for boys. Conclusions The prevalence of self-reported headache among high school students in Zagreb is relatively high. Significant gender differences in frequency and clinical characteristics were observed. Primary headaches among adolescents are an important public health problem and should receive more attention from school and health authorities.
Stimulation of dural vessels excites the SI somatosensory cortex of the cat via a relay in the thalamus
Authors: Lambert Geoffrey A , Hoskin Karen L , Michalicek Jan , Panahi Seyed E , Truong Linda , Zagami Alessandro S 
Published: October 2013

Aim We carried out experiments in cats to determine the thalamo-cortical projection sites of trigeminovascular sensory neurons. Methods 1) We stimulated the middle meningeal artery (MMA) with C-fibre intensity electrical shocks and made field potential recordings over the somatosensory cortical surface. 2) We then recorded neurons in the ventroposteromedial (VPM) nucleus of the thalamus in search of neurons which could be activated from the skin, MMA and superior sagittal sinus. 3) Finally, we attempted to antidromically activate the neurons found in stage 2 by stimulating the responsive cortical areas revealed in stage 1. Results VPM neurons received trigeminovascular input, input from the V1 facial skin and could also be activated by electrical stimulation of the somatosensory cortex. VPM neurons activated from the cortex responded with short and invariant latencies (6.7 ± 7.7 msec mean and SD). They could follow high rates of stimulation and sometimes showed collision with orthodromic action potentials. Conclusions We conclude that somatosensory (SI) cortical stimulation excites trigeminovascular VPM neurons antidromically. In consequence, these VPM neurons project to the somatosensory cortex. These findings may help to explain the ability of migraineurs with headache in the trigeminal distribution to localise their pain to a particular region in this distribution.