bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Genetic Variants, QT Interval, and Sudden Cardiac Death in a Finnish Population-Based Study
Authors: Noseworthy Peter A. , Havulinna Aki S. , Porthan Kimmo , Lahtinen Annukka M. , Jula Antti , Karhunen Pekka J. , Perola Markus , Oikarinen Lasse , Kontula Kimmo K. , Salomaa Veikko , Newton-Cheh Christopher 
Published: April 2011

Background—
Although sudden cardiac death (SCD) is heritable, its genetic underpinnings are poorly characterized. The QT interval appears to have a graded relationship to SCD, and 35% to 45% of its variation is heritable. We examined the relationship among recently reported common genetic variants, QT interval, and SCD.

Methods and Results—

We genotyped 15 common (minor allele frequency >1%) candidate single nucleotide polymorphisms (SNPs), based on association with the QT interval in prior studies, in individuals in 2 cohort studies (Health 2000, n=6597; Mini-Finland, n=801). After exclusions, we identified 116 incident SCDs from the remaining sample (n=6808). We constructed a QT genotype score (QT
score
) using the allele copy number and previously reported effect estimates for each SNP. Cox proportional hazards models adjusting for age, sex, and geographical area were used for time to SCD analyses. The QT
score
was a continuous independent predictor of the heart rate–corrected QT interval (
P
<10
−107
). Comparing the top with the bottom quintile of QT
score
, there was a 15.6-ms higher group mean QT interval (
P
<10
−84
). A 10-ms increase in the observed QT interval was associated with an increased risk of SCD (hazard ratio, 1.19; 95% confidence interval, 1.07 to 1.32;
P
=0.002). There was no linear relationship between QT
score
and SCD risk; although in post hoc secondary analysis there was increased risk in the top compared with the middle QT
score
quintile (hazard ratio, 1.92; 95% confidence interval, 1.05 to 3.58;
P
=0.04).

Conclusions—

Our study strongly replicates the relationship between common genetic variants and the QT interval and confirms the relationship between the QT interval and SCD but does not show evidence for a linear relationship between QT
score
and SCD risk.
Comparative Lipidomics Profiling of Human Atherosclerotic Plaques
Authors: Stegemann Christin , Drozdov Ignat , Shalhoub Joseph , Humphries Julia , Ladroue Christophe , Didangelos Athanasios , Baumert Mark , Allen Mark , Davies Alun H. , Monaco Claudia , Smith Alberto , Xu Qingbo , Mayr Manuel 
Published: April 2011

Background—
We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques.

Methods and Results—
A chip-based robotic nanoelectrospray platform interfaced to a triple quadrupole mass spectrometer was adapted to analyze lipids in tissue sections and extracts from human endarterectomy specimens by shotgun lipidomics. Eighteen scans for different lipid classes plus additional scans for fatty acids resulted in the detection of 150 lipid species from 9 different classes of which 24 were detected in endarterectomies only. Further analyses focused on plaques from symptomatic and asymptomatic patients and stable versus unstable regions within the same lesion. Polyunsaturated cholesteryl esters with long-chain fatty acids and certain sphingomyelin species showed the greatest relative enrichment in plaques compared to plasma and formed part of a lipid signature for vulnerable and stable plaque areas in a systems-wide network analysis. In principal component analyses, the combination of lipid species across different classes provided a better separation of stable and unstable areas than individual lipid classes.

Conclusions—
This comprehensive analysis of plaque lipids demonstrates the potential of lipidomics for unraveling the lipid heterogeneity within atherosclerotic lesions.
One-year prognosis of patients with normal myocardial perfusion imaging using technitium-99m sestamibi in suspected coronary artery disease: a single-center experience of 1,047 patients
Authors: Raziei Ghasem , Tavakoli Alireza , Shahram Seifollahi asl  , Amoiei Mahasti , Javadi Hamid , Assadi Majid 
Published: April 2011

Introduction: The aim of the present study was to evaluate the clinical outcome of a normal stress technetium-99m (99mTc)-Sestamibi single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with different probabilities of coronary artery disease (CAD). Material and Methods: A total of 1,047 subjects with a normal 99mTc-MIBI SPECT were followed up for one year and hard and soft cardiac events were assessed. Hard cardiac events were defined as cardiac death or non-fatal myocardial infarction (MI). Soft cardiac events included the patient’s development of recurrent chest pain requiring coronary revascularization or significant stenosis in coronary arteries on angiography. Results: Overall, 1,047 patients (248 men and 799 women; mean age: 60.07 ± 12.31, range 29—92) were enrolled. Three hard cardiac events occurred in the groups; two had cardiac arrest and one non-fatal MI. As a result, the annualized hard cardiac event rate was 0.28%, the annualized cardiac mortality rate was 0.19%, and the rate of overall annualized cardiac events was 1.25%. Furthermore, there was a significant difference in cardiac events among patients with various pretest likelihoods of CAD (p value=0.04). Conclusion: Our data confirmed that patients with a normal 99mTc-Sestamibi myocardial SPECT are associated with a very low incidence of cardiovascular events.
Migraine, migraine aura, and cervical artery dissection: A systematic review and meta-analysis
Authors: Rist Pamela M , Diener Hans-Christoph , Kurth Tobias , Schürks Markus 
Published: April 2011

Objective: We evaluated the current evidence on the association between migraine, including aura status, and cervical artery dissection. Methods: We performed a systematic review and meta-analysis of studies investigating the association between migraine or migraine subtypes (e.g. migraine with aura) and cervical artery dissection published through October 2010. Results: We identified five case-control studies investigating the association between migraine and cervical artery dissection. In pooled analysis, migraine doubled the risk of cervical artery dissection (pooled odds ratio [OR] = 2.06, 95% confidence interval [CI] 1.33–3.19). All studies allowed evaluation of migraine aura status. While the effect estimate for migraine without aura (pooled OR = 1.94, 95% CI 1.21–3.10) was similar to overall migraine, the association was weaker for migraine with aura (pooled OR = 1.50, 95% CI 0.76–2.96). However, there is no evidence that aura status significantly modifies the association between migraine and cervical artery dissection (meta-regression on aura status p = .58). The risk does not appear to differ between women and men; however, only few studies presented gender-specific data. Heterogeneity among studies was low to moderate. Conclusion: In this meta-analysis migraine is associated with a two-fold increased risk of cervical artery dissection. This risk does not appear to significantly differ by migraine aura status or gender.
Increased risk of stroke after trigeminal neuralgia – a population-based follow-up study
Authors: Pan Shin-Liang , Chen Li-Sheng , Yen Ming-Fang , Chiu Yueh-Hsia , Chen Hsiu-Hsi 
Published: April 2011

Background: There are no reports on the risk of stroke after trigeminal neuralgia (TN). The aim of this population-based follow-up study was to investigate whether the occurrence of TN is associated with a higher risk of developing stroke. Methods: A total of 1453 people with at least three ambulatory visits in 2001 with the principal diagnosis of TN were enrolled in the TN cohort. The non-TN cohort consisted of 5812 age- and sex-matched, randomly sampled subjects without TN. The 2-year stroke-free survival rate between the two groups was compared using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of stroke after adjustment for demographic and clinical covariates. Results: In the TN cohort, 73 patients developed stroke during follow-up, while in the non-TN cohort, 157 subjects suffered a stroke. The crude hazard ratio of stroke for the subjects with TN was 1.86 (95% CI, 1.41–2.45; p < 0.0001). The adjusted hazard ratio was 1.76 (95% CI, 1.33–2.33; p < 0.0001) after adjusting for demographic characteristics and comorbid medical disorders. Conclusion: This study showed a significantly increased risk of developing stroke after TN. Further studies are needed to investigate the underlying mechanism of this association.
Spinal manipulations for the treatment of migraine: A systematic review of randomized clinical trials
Authors: Posadzki P , Ernst E 
Published: April 2011

Aims: The objective of this systematic review was to assess the effectiveness of spinal manipulations as a treatment for migraine headaches. Method: Seven databases were searched from inception to November 2010. All randomized clinical trials (RCTs) investigating spinal manipulations performed by any type of healthcare professional for treating migraine headaches in human subjects were considered. The selection of studies, data extraction and validation were performed independently by two reviewers. Results: Three RCTs met the inclusion criteria. Their methodological quality was mostly poor and ranged between 1 and 3 on the Jadad scale. Two RCTs suggested no effect of spinal manipulations in terms of Headache Index or migraine duration and disability compared with drug therapy, spinal manipulation plus drug therapy, or mobilization. One RCT showed significant improvements in migraine frequency, intensity, duration and disability associated with migraine compared with detuned interferential therapy. The most rigorous RCT demonstrated no effect of chiropractic spinal manipulation compared with mobilization or spinal manipulation by medical practitioner or physiotherapist on migraine duration or disability. Conclusions: Current evidence does not support the use of spinal manipulations for the treatment for migraine headaches.
Galectin-1–expressing stromal cells constitute a specific niche for pre-BII cell development in mouse bone marrow
Authors: Mourcin Frédéric , Breton Caroline , Tellier Julie , Narang Priyanka , Chasson Lionel , Jorquera Audrey , Coles Mark , Schiff Claudine , Mancini Stéphane J. C. 
Published: April 2011

AbstractIn the bone marrow (BM), stromal cells constitute a supportive tissue indispensable for the generation of pro-B/pre-BI, pre-BII, and immature B lymphocytes. IL-7–producing stromal cells constitute a cellular niche for pro-B/pre-BI cells, but no specific stromal cell microenvironment was identified for pre-BII cells expressing a functional pre-B cell receptor (pre-BCR). However expression of the pre-BCR represents a crucial checkpoint during B-cell development. We recently demonstrated that the stromal cell derived-galectin1 (GAL1) is a ligand for the pre-BCR, involved in the proliferation and differentiation of normal mouse pre-BII cells. Here we show that nonhematopoietic osteoblasts and reticular cells in the BM express GAL1. We observed that pre-BII cells, unlike the other B-cell subsets, were specifically localized in close contact with GAL1+ reticular cells. We also determined that IL-7+ and GAL1+ cells represent 2 distinct mesenchymal populations with different BM localization. These results demonstrate the existence of a pre-BII specific stromal cell niche and indicate that early B cells move from IL-7+ to GAL1+ supportive BM niches during their development.
New sources of drugs for hematologic malignancies
Authors: Sukhai Mahadeo A. , Spagnuolo Paul A. , Weir Scott , Kasper James , Patton Lavonne , Schimmer Aaron D. 
Published: April 2011

Abstract
Advancing novel therapeutic agents for the treatment of malignancy into the marketplace is an increasingly costly and lengthy process. As such, new strategies for drug discovery are needed. Drug repurposing represents an opportunity to rapidly advance new therapeutic strategies into clinical trials at a relatively low cost. Known on-patent or off-patent drugs with unrecognized anticancer activity can be rapidly advanced into clinical testing for this new indication by leveraging their known pharmacology, pharmacokinetics, and toxicology. Using this approach, academic groups can participate in the drug discovery field and smaller biotechnology companies can “de-risk” early-stage drug discovery projects. Here, several scientific approaches used to identify drug repurposing opportunities are highlighted, with a focus on hematologic malignancies. In addition, a discussion of the regulatory issues that are unique to drug repurposing and how they impact developing old drugs for new indications is included. Finally, the mechanisms to enhance drug repurposing through increased collaborations between academia, industry, and nonprofit charitable organizations are discussed.
Organogenesis during budding and lophophoral morphology of Hislopia malayensis Annandale, 1916 (Bryozoa, Ctenostomata)
Authors: Schwaha Thomas , Wood Timothy S 
Published: April 2011

Abstract
Background
Bryozoans represent a large lophotrochozoan phylum with controversially discussed phylogenetic position and in group relationships. Developmental processes during the budding of bryozoans are in need for revision. Just recently a study on a phylactolaemate bryozoan gave a comprehensive basis for further comparisons among bryozoans. The aim of this study is to gain more insight into developmental patterns during polypide formation in the budding process of bryozoans. Particular focus is laid upon the lophophore, also its condition in adults. For this purpose we studied organogenesis during budding and lophophoral morphology of the ctenostome bryozoan Hislopia malayensis.

Results
Polypide buds develop on the frontal side of the developing cystid as proliferation of the epidermal and peritoneal layer. Early buds develop a lumen bordered by the inner budding layer resulting in the shape of a two-layered sac or vesicle. The hind- and midgut anlagen are first to develop as outpocketing of the prospective anal area. These grow towards the prospective mouth area where a comparatively small invagination marks the formation of the foregut. In between the prospective mouth and anus the ganglion develops as an invagination protruding in between the developing gut loop. Lophophore development starts with two lateral ridges which form tentacles very early. At the lophophoral base, intertentacular pits, previously unknown for ctenostomes, develop. The ganglion develops a circum-oral nerve ring from which the tentacle nerves branch off in adult zooids. Tentacles are innervated by medio-frontal nerves arising directly from the nerve ring, and medio-frontal and abfrontal nerves which originate both from an intertentacular fork.

Conclusions
We are able to show distinct similarities among bryozoans in the formation of the different organ systems: a two-layered vesicle-like early bud, the ganglion forming as an invagination of the epidermal layer in between the prospective mouth and anal area, the digestive tract mainly forming as an outpocketing of the prospective anal area, and the lophophore forming from two lateral anlagen that first fuse on the oral and afterwards on the anal side. Future studies will concentrate on cyclostome budding to complement our knowledge on developmental patterns of bryozoans.
Do agreements between adolescent and parent reports on family socioeconomic status vary with household financial stress?
Authors: Pu Christy , Huang Nicole , Chou Yiing-Jenq 
Published: April 2011

Abstract

Background
Many studies compared the degree of concordance between adolescents' and parents' reports on family socioeconomic status (SES). However, none of these studies analyzed whether the degree of concordance varies by different levels of household financial stress. This research examines whether the degree of concordance between adolescents' and parent reports for the three traditional SES measures (parental education, parental occupation and household income) varied with parent-reported household financial stress and relative standard of living.

Methods
2,593 adolescents with a mean age of 13 years, and one of their corresponding parents from the Taiwan Longitudinal Youth Project conducted in 2000 were analyzed. Consistency of adolescents' and parents' reports on parental educational attainment, parental occupation and household income were examined by parent-reported household financial stress and relative standard of living.

Results
Parent-reported SES variables are closely associated with family financial stress. For all levels of household financial stress, the degree of concordance between adolescent's and parent's reports are highest for parental education (κ ranging from 0.87 to 0.71) followed by parental occupation (κ ranging from 0.50 to 0.34) and household income (κ ranging from 0.43 to 0.31). Concordance for father's education and parental occupation decreases with higher parent-reported financial stress. This phenomenon was less significant for parent-reported relative standard of living.

Conclusions
Though the agreement between adolescents' and parents' reports on the three SES measures is generally judged to be good in most cases, using adolescents reports for family SES may still be biased if analysis is not stratified by family financial stress.
Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin
Authors: Ryan Ali J , Chung Chun-wa , Curry Stephen 
Published: April 2011

Abstract

Background
Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA.

Results
We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound.

Conclusions
The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.
Daily Plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage
Authors: Pollock Tzvi , Leitao Ricardo , Galan-Rodriguez Cristina , Wong Kurt A , Rodriguez Ana 
Published: April 2011

Abstract

Background
Human populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. However, sterile immunity against Plasmodium liver stage can be achieved after repeated exposure to radiation attenuated sporozoites. The reasons for this different response remain largely unknown, but a suppressive effect of blood stage Plasmodium infection has been proposed as a cause for the lack of liver stage protection.

Methods
Using Plasmodium yoelii 17XNL, the response generated in mice subjected to daily infective bites from normal or irradiated mosquitoes was compared. The effect of daily-infected mosquito bites on mice that were previously immunized against P. yoelii liver stage was also studied.

Results
It was observed that while the bites of normal infected mosquitoes do not generate strong antibody responses and protection, the bites of irradiated mosquitoes result in high levels of anti-sporozoite antibodies and protection against liver stage Plasmodium infection. Exposure to daily infected mosquito bites did not eliminate the protection acquired previously with a experimental liver stage vaccine.

Conclusions
Liver stage immunity generated by irradiated versus normal P. yoelii infected mosquitoes is essentially different, probably because of the blood stage infection that follows normal mosquito bites, but not irradiated. While infective mosquito bites do not induce a protective liver stage response, they also do not interfere with previously acquired liver stage protective responses, even if they induce a complete blood stage infection. Considering that the recently generated anti-malaria vaccines induce only partial protection against infection, it is encouraging that, at least in mouse models, immunity is not negatively affected by subsequent exposure and infection with the parasite.
A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases
Authors: Xie Chong , Kim Hyun J , Haw Jonathan G , Kalbasi Anusha , Gardner Brian K , Li Gang , Rao Jianyu , Chia David , Liong Monty , Punzalan Rubio R , Marks Leonard S , Pantuck Allan J , de la Taille Alexandre , Wang Guomin , Mukouyama Hideki , Zeng Gang 
Published: April 2011

Abstract

Background
The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA).

Methods
To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay.

Results
Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve.

Conclusions
The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.