bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race-ethnic differences in the association of genetic loci with HbA1c levels and mortality in U.S. adults: the third National Health and Nutrition Examination Survey (NHANES III)
Authors: Grimsby Jonna L , Porneala Bianca C , Vassy Jason L , Yang Quanhe , Florez José C , Dupuis Josée , Liu Tiebin , Yesupriya Ajay , Chang Man-Huei , Ned Renee M , Dowling Nicole F , Khoury Muin J , Meigs James B ,   the MAGIC Investigators
Published: April 2012

Abstract

Background
Hemoglobin A1c (HbA1c) levels diagnose diabetes, predict mortality and are associated with ten single nucleotide polymorphisms (SNPs) in white individuals. Genetic associations in other race groups are not known. We tested the hypotheses that there is race-ethnic variation in 1) HbA1c-associated risk allele frequencies (RAFs) for SNPs near SPTA1, HFE, ANK1, HK1, ATP11A, FN3K, TMPRSS6, G6PC2, GCK, MTNR1B; 2) association of SNPs with HbA1c and 3) association of SNPs with mortality.

Methods
We studied 3,041 non-diabetic individuals in the NHANES (National Health and Nutrition Examination Survey) III. We stratified the analysis by race/ethnicity (NHW: non-Hispanic white; NHB: non-Hispanic black; MA: Mexican American) to calculate RAF, calculated a genotype score by adding risk SNPs, and tested associations with SNPs and the genotype score using an additive genetic model, with type 1 error = 0.05.

Results
RAFs varied widely and at six loci race-ethnic differences in RAF were significant (p < 0.0002), with NHB usually the most divergent. For instance, at ATP11A, the SNP RAF was 54% in NHB, 18% in MA and 14% in NHW (p < .0001). The mean genotype score differed by race-ethnicity (NHW: 10.4, NHB: 11.0, MA: 10.7, p < .0001), and was associated with increase in HbA1c in NHW (β = 0.012 HbA1c increase per risk allele, p = 0.04) and MA (β = 0.021, p = 0.005) but not NHB (β = 0.007, p = 0.39). The genotype score was not associated with mortality in any group (NHW: OR (per risk allele increase in mortality) = 1.07, p = 0.09; NHB: OR = 1.04, p = 0.39; MA: OR = 1.03, p = 0.71).

Conclusion
At many HbA1c loci in NHANES III there is substantial RAF race-ethnic heterogeneity. The combined impact of common HbA1c-associated variants on HbA1c levels varied by race-ethnicity, but did not influence mortality.
Extragonadal mixed germ cell tumor of the right arm: description of the first case in the literature
Authors: Benali Hicham Ait , Lalya lssam , Allaoui Mohamed , Benmansour Aniss , Elkhanoussi Basma , Benjelloun Samir , Benjaafar Noureddine , Elyaacoubi Mourad 
Published: April 2012

Abstract

Background
Extragonadal localization of germ cell tumors (GCTs) is rare; to the best of our knowledge, a location in the soft tissue of the arm has never been previously reported in the literature.

Case presentation
We report the case of a 37-year-old man who presented with a primary malignant mixed non-seminomatous GCT (teratocarcinoma variety) in the right arm, treated by a combination of cisplatin-based chemotherapy and surgery. After 18 months of close follow-up, no locoregional recurrence or distant metastases have been detected.

Conclusions
A combination of chemotherapy and surgery is the most appropriate treatment strategy for extragonadal GCTs, to ensure both local and systemic control.
Expression of the T regulatory cell transcription factor FoxP3 in peri-implantation phase endometrium in infertile women with endometriosis
Authors: Chen Shufang , Zhang Jian , Huang Changxiao , Lu Wen , Liang Yan , Wan Xiaoping 
Published: April 2012

Abstract

Background
Endometriosis (EM) is highly associated with infertility. The precise mechanism underlying EM-associated infertility remains controversial. This study aimed to investigate the pathogenesis of infertility in women with EM by comparing FoxP3+ T regulatory cells (Tregs) expression in the eutopic endometrium of infertile women with EM and endometrium from healthy fertile women.

Methods
As a marker of Tregs, FoxP3 expression was analyzed in eutopic endometrium during the peri-implantation phase in infertile women with mild EM (n = 7), advanced EM (n = 20), and normally fertile women without EM (n = 20). FoxP3 mRNA expression was analyzed by quantitative real-time RT-PCR. FoxP3 protein expression was assessed by immunohistochemistry.

Results

FoxP3 mRNA expression in all infertile patients with EM was significantly higher than the control group (P < 0.05) by non-parametric Mann–Whitney U-test. Further analysis based on the extent of EM revealed that FoxP3 mRNA expression in infertile patients with advanced EM was significantly higher than the mild EM group and the control group (P < 0.05). Immunohistochemistry analysis showed predominant positive staining for FoxP3 protein in the endometrial stroma. In addition, the number of FoxP3+ cells in the eutopic endometrium of infertile women with advanced EM was marginally higher than the mild EM group and the control group, although the differences were not statistically significant (P > 0.05) by two-tailed t-tests.

Conclusions
These findings suggest that FoxP3+ Tregs in the peri-implantation endometrium might participate in the pathogenesis of advanced EM. However, they are not directly involved in the pathogenesis of advanced EM associated with infertility. The differential expression of FoxP3 in infertile women with mild EM and advanced EM implicates that notable differences in the uterine immune status are likely involved in the pathogenesis of mild EM associated with infertility in the peri-implantation endometrium.
Fabrication of palladium/graphene oxide composite by plasma reduction at room temperature
Authors: Yu Yue , Li Yingzhi , Pan Yunxiang , Liu Chang-jun 
Published: April 2012

Abstract
Pd nanoparticles were fabricated on graphene oxide (GO) using a deposition-precipitation method with a glow discharge plasma reduction at room temperature. Argon was employed as the plasma-generating gas. The novel plasma method selectively reduces the metal ions. The graphene oxide has no change with this plasma reduction according to the Fourier transform infrared analysis. The Pd nanoparticles on the GO were uniformly distributed with an average diameter of 1.6 nm. The functional groups on the GO not only prevent Pd nanoparticles from further aggregation but also provide a strong hydrophilic property to the Pd/GO composite, which can form stable colloidal dispersions in water.
An improved method for the removal of ring artifacts in high resolution CT imaging
Authors: Rashid Sabrina , Lee Soo Yeol , Hasan Md Kamrul 
Published: April 2012

Abstract
In high resolution computed tomography (CT) using flat panel detectors, imperfect or defected detector elements cause stripe artifacts in sinogram which results in concentric ring artifacts in the image. Such ring artifacts obscure image details in the regions of interest of the image. In this article, novel techniques are proposed for the detection, classification, and correction of ring artifacts in the sinogram domain. The proposed method is suitable for multislice CT with parallel or fan beam geometry. It can also be employed for ring artifact removal in 3D cone beam volume CT by adopting a sinogram by sinogram processing technique. The detection algorithm is based on applying data driven thresholds on the mean curve and difference curve of the sinogram. The ring artifacts are classified into three types and a separate correction algorithm is used for each class. The performance of the proposed techniques is evaluated on a number of real micro-CT images. Experimental results corroborate that the proposed algorithm can remove ring artifacts from micro-CT images more effectively as compared to other recently reported techniques in the literature.
UBXN7 docks on neddylated cullin complexes using its UIM motif and causes HIF1α accumulation
Authors: Bandau Susanne , Knebel Axel , Gage Zoe O , Wood Nicola T , Alexandru Gabriela 
Published: April 2012

Abstract

Background
The proteins from the UBA-UBX family interact with ubiquitylated proteins via their UBA domain and with p97 via their UBX domain, thereby acting as substrate-binding adaptors for the p97 ATPase. In particular, human UBXN7 (also known as UBXD7) mediates p97 interaction with the transcription factor HIF1α that is actively ubiquitylated in normoxic cells by a CUL2-based E3 ligase, CRL2. Mass spectrometry analysis of UBA-UBX protein immunoprecipitates showed that they interact with a multitude of E3 ubiquitin-ligases. Conspicuously, UBXN7 was most proficient in interacting with cullin-RING ligase subunits. We therefore set out to determine whether UBXN7 interaction with cullins was direct or mediated by its ubiquitylated targets bound to the UBA domain.

Results
We show that UBXN7 interaction with cullins is independent of ubiquitin- and substrate-binding. Instead, it relies on the UIM motif in UBXN7 that directly engages the NEDD8 modification on cullins. To understand the functional consequences of UBXN7 interaction with neddylated cullins, we focused on HIF1α, a CUL2 substrate that uses UBXD7/p97 as a ubiquitin-receptor on its way to proteasome-mediated degradation. We find that UBXN7 over-expression converts CUL2 to its neddylated form and causes the accumulation of non-ubiquitylated HIF1α. Both of these effects are strictly UIM-dependent and occur only when UBXN7 contains an intact UIM motif. We also show that HIF1α carrying long ubiquitin-chains can recruit alternative ubiquitin-receptors, lacking p97's ATP-dependent segregase activity.

Conclusions
Our study shows that independently of its function as a ubiquitin-binding adaptor for p97, UBXN7 directly interacts with neddylated cullins and causes the accumulation of the CUL2 substrate HIF1α. We propose that by sequestering CUL2 in its neddylated form, UBXN7 negatively regulates the ubiquitin-ligase activity of CRL2 and this might prevent recruitment of ubiquitin-receptors other than p97 to nuclear HIF1α.
Metabolic network analysis predicts efficacy of FDA-approved drugs targeting the causative agent of a neglected tropical disease
Authors: Chavali Arvind K , Blazier Anna S , Tlaxca Jose L , Jensen Paul A , Pearson Richard D , Papin Jason A 
Published: April 2012

Abstract

Background
Systems biology holds promise as a new approach to drug target identification and drug discovery against neglected tropical diseases. Genome-scale metabolic reconstructions, assembled from annotated genomes and a vast array of bioinformatics/biochemical resources, provide a framework for the interrogation of human pathogens and serve as a platform for generation of future experimental hypotheses. In this article, with the application of selection criteria for both Leishmania major targets (e.g. in silico gene lethality) and drugs (e.g. toxicity), a method (MetDP) to rationally focus on a subset of low-toxic Food and Drug Administration (FDA)-approved drugs is introduced.

Results
This metabolic network-driven approach identified 15 L. major genes as high-priority targets, 8 high-priority synthetic lethal targets, and 254 FDA-approved drugs. Results were compared to previous literature findings and existing high-throughput screens. Halofantrine, an antimalarial agent that was prioritized using MetDP, showed noticeable antileishmanial activity when experimentally evaluated in vitro against L. major promastigotes. Furthermore, synthetic lethality predictions also aided in the prediction of superadditive drug combinations. For proof-of-concept, double-drug combinations were evaluated in vitro against L. major and four combinations involving the drug disulfiram that showed superadditivity are presented.

Conclusions
A direct metabolic network-driven method that incorporates single gene essentiality and synthetic lethality predictions is proposed that generates a set of high-priority L. major targets, which are in turn associated with a select number of FDA-approved drugs that are candidate antileishmanials. Additionally, selection of high-priority double-drug combinations might provide for an attractive and alternative avenue for drug discovery against leishmaniasis.
Therapeutic efficacy of milbemycin oxime/praziquantel oral formulation (Milbemax®) against Thelazia callipaeda in naturally infested dogs and cats
Authors: Motta Bruna , Schnyder Manuela , Basano Fabrizio Solari , Nägeli Fabio , Nägeli Catherine , Schiessl Brigitte , Mallia Egidio , Lia Riccardo P , Dantas-Torres Filipe , Otranto Domenico 
Published: April 2012

AbstractBackgroundOver the last few decades, canine and feline thelaziosis caused byThelazia callipaedaeye worms has gained the attention of the veterinary community due to the spread of this ocular infestation in geographical areas previously regarded as non endemic. The therapeutic efficacy of milbemycin oxime/praziquantel tablets (Milbemax®) againstT. callipaedawas tested in naturally infested dogs and cats.MethodsFrom January 2009 to July 2011 a placebo controlled and randomized field study was conducted inT. callipaedaendemic areas of Switzerland (CH) and Italy (ITA) involving client-owned animals. Dogs (n = 56) and cats (n = 31) were physically examined at enrolment Day 0 (D0) and twice afterwards (D7 and D14). Infested animals were orally treated with Milbemax® or with placebo tablets on D0 and, if an animal was found still infested withT. callipaeda, also on D7. On D14 nematodes were flushed from the conjunctiva, identified and counted.ResultsOut of 56 dogs, 43 were included in the statistical analysis, whereas 13 were excluded because the products under investigation were not administered with food, as required by the label. On D7 and D14, 72.7% and 90.9% of treated dogs were eye worm free, whereas in the placebo group 95.2% and 76.2% still harbored nematodes, resulting in a mean percentage worm count reduction for the Milbemax® group of 86.1% and 96.8%, respectively. Both results were significantly higher (p = 0.0001) than the placebo group. Out of the 31 cats included in the study at D7 and D14, 53.3% and 73.3% treated with Milbemax® were free ofT. callipaeda, while 81.3% and 73.3 in the placebo group were still harbouring eye worms, resulting in a mean percentage worm count reduction for the treated group of 62.2% and 80.0%, respectively. Both results were significantly higher (p = 0.0106 andp = 0.0043) than the placebo group.ConclusionsThe commercial formulation of milbemycin oxime at the minimal dose of 0.5 mg/kg and 2 mg/k in dogs and cats, respectively, showed a high therapeutic efficacy in curingT. callipaedainfestations. The advantages of an oral application are additionally increased by the large spectrum of activity of praziquantel and milbemycin oxime against Cestodes and Nematodes infesting dogs and cats.
Autogenous osteochondral graft transplantation for steroid-induced osteonecrosis of the femoral condyle: A report of three young patients
Authors: Fujita Norifumi , Matsumoto Tomoyuki , Kubo Seiji , Matsushita Takehiko , Ishida Kazunari , Hoshino Yuichi , Nishimoto Koji , Kurosaka Masahiro , Kuroda Ryosuke 
Published: April 2012

Abstract
Steroid-induced osteonecrosis of the femoral condyle is a relatively uncommon condition and is often difficult to select appropriate treatment especially in young patients. Three young men (aged 25, 18, and 24) presented with severe pain and dysfunction of the knee diagnosed as steroid-induced osteonecrosis of the femoral condyle by magnetic resonance imaging (MRIs). Full-thickness cartilage defects sized 20 × 10, 15 × 10, and 30 × 20 mm respectively were classified as International Cartilage Repair Society Grade IV lesions and treated with osteochondral autograft transplantation. They were treated successfully with osteochondral autograft transplantation certificated by post-operative MRI and second look arthroscopy.
Therapeutic potential of targeting IL‐17 and IL‐23 in sepsis
Authors: Bosmann Markus , Ward Peter A 
Published: April 2012

AbstractSevere sepsis is a major concern of public health in industrialized countries. It is estimated that in the United States 200,000‐400,000 cases occur annually and resulting in an extensive burden for the health care systems. To date, no FDA‐approved pharmacologic agents for the treatment or prevention of human sepsis are available. The current modalities of therapy in sepsis include the standard arsenal of supportive interventions in critical care medicine and pharmacotherapy, with use of antibiotics and catecholamines. Despite such efforts, the mortality rates of sepsis have remained around 30‐50 %. Extensive scientific studies have utilized animal models of disease and aimed for a better understanding of the pathophysiologic mechanisms during sepsis. Members of the IL‐17 family of cytokines, as well as the functionally related IL‐23, have been identified as new players in the molecular events during sepsis. Strategies for targeting these mediators with neutralizing antibodies during experimental sepsis in rodents have demonstrated efficacy, resulting in improved survival outcomes. Currently, it is not clear whether such findings can be translated to human sepsis. This review highlights the current knowledge on the biology of IL‐17 isoforms and IL‐23 as well as potential applications to clinical medicine.
Water quality legislation in Palestine over the past century
Authors: Marie Amer , Khayat Saed , Dajani Muna 
Published: April 2012

Abstract

Background
This paper deals with the water quality legislation that has been enforced in Palestine over the past century, from the Ottoman era through the British Mandate and Jordanian reign, to the Israeli occupation and current Palestinian autonomy.

Results
The study reveals that, due to the instability and the short interrupted spans of these regimes, apart from the Ottoman era, the successive ruling administrations were unable to draft water legislation in the interest of the Palestinian population, though the more stable Jordanian rule is an exception to this. Moreover, the study shows that the subject of the enacted legislations has depended on the circumstances that the population is subjected to or simply as reaction that deals instantly with a certain problem without taking into account any planning or future socioeconomic development. However, major concerns over the quality of accessible water gained momentum with an ever-increasing demand for limited water resources and the need for water treatment.

Conclusions
Investments in legislation and its enforcement will lead to significant economic development and public health and environmental quality enhancement through equitable and reasonable management of shared water resources and community empowerment and awareness.
Routine chest x-rays in intensive care units: a systematic review and meta-analysis
Authors: Ganapathy Anusoumya , Adhikari Neill KJ , Spiegelman Jamie , Scales Damon C 
Published: April 2012

Abstract
Introduction
Chest x-rays (CXRs) are the most frequent radiological tests performed in the intensive care unit (ICU). However, the utility of performing daily routine CXRs is unclear.

Methods
We searched Medline and Embase (1948 to March 2011) for randomized and quasi-randomized controlled trials (RCTs) and before-after observational studies comparing a strategy of routine CXRs to a more restrictive approach with CXRs performed to investigate clinical changes among critically ill adults or children. In duplicate, we extracted data on the CXR strategy, study quality and clinical outcomes (ICU and hospital mortality; duration of mechanical ventilation and ICU and hospital stay).

Results
Nine studies (39,358 CXRs; 9,611 patients) were included in the meta-analysis. Three trials (N = 870) of moderate to good quality provided information on the safety of a restrictive routine CXR strategy; only one trial systematically assessed for missed findings. Pooled data from trials showed no evidence of effect of a restrictive approach on ICU mortality (risk ratio [RR] 1.04, 95% confidence interval [CI] 0.84 to 1.28, P = 0.72; two trials, N = 776), hospital mortality (RR 0.98, 95% CI 0.68 to 1.41, P = 0.91; two trials, N = 259), ICU length of stay (weighted mean difference [WMD] -0.86 days, 95% CI -2.38 to 0.66 days, P = 0.27; three trials, N = 870), hospital length of stay (WMD -2.50 days, 95% CI -6.62 to 1.61 days, P = 0.23; two trials, N = 259), or duration of mechanical ventilation (WMD -0.30 days, 95% CI -1.48 to 0.89 days, P = 0.62; three trials, N = 705). Adding data from six observational studies, one of which systematically screened for missed findings, gave similar results.

Conclusions
This meta-analysis did not detect any harm associated with a restrictive chest radiograph strategy. However, confidence intervals were wide and harm was not rigorously assessed. Therefore, the safety of abandoning routine CXRs in patients admitted to the ICU remains uncertain.
Neural basis of autobiographical memory retrieval in schizophrenia
Authors: Cuervo-Lombard Christine , Lemogne Cédric , Gierski Fabien , Béra-Potelle Céline , Tran Eric , Portefaix Christophe , Kaladjian Arthur , Pierot Laurent , Limosin Frédéric 
Published: April 2012

BackgroundAutobiographical memory retrieval is impaired in schizophrenia.AimsTo determine the neural basis of this impairment.MethodThirteen patients with schizophrenia and 14 healthy controls performed an autobiographical memory retrieval task based on cue words during functional magnetic resonance imaging. Patients were selected on the basis of their ability to perform the task and all participants received training.ResultsAlthough patients and controls activated a similar brain network during autobiographical memory retrieval, patients displayed decreased activation in several of these regions, including the anterior cingulate cortex, left lateral prefrontal cortex, right cerebellum and ventral tegmental area (k ≥ 10, P < 0.001, uncorrected). In addition, activation of the caudate nuclei was negatively correlated with retrieval performance in controls but positively correlated with performance in patients.ConclusionsThe autobiographical memory retrieval brain network is impaired in schizophrenia. Patients with schizophrenia display decreased activation of the cognitive control network during retrieval, possibly due to aberrant functioning of the dorsal striatum.