bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing
Authors: Leung Nelson , Nasr Samih H. , Sethi Sanjeev 
Published: September 2012

AbstractAmyloidosis is a rare group of diseases characterized by deposition of amyloid fibrils in soft tissues. More than 28 types of amyloid have been identified. They all share common ultrastructural and chemical characteristics. Treatments are available for many types but are type specific. Therefore, confirmation and typing of amyloid are essential before initiating treatment. Monoclonal protein studies should be performed on suspected cases, but the diagnosis requires a tissue biopsy. Congo red stain and electron microscopy are helpful to discriminate between amyloid and other pathologic fibrils. Once amyloid is confirmed, typing should be performed. Immunofluorescence and immunohistochemistry are frequently used and are helpful, but this approach has limitations, such as availability, specificity and sensitivity of commercial antibodies. Genetic mutational analysis is vital for ruling in and out hereditary amyloidoses but is unhelpful in nonmutated forms. The most advanced technique of amyloid typing is laser microdissection followed by mass spectrometry. Using proteomics, laser microdissection followed by mass spectrometry can directly identify proteins with or without mutations. Finally, imaging studies, such as cardiac MRI with gadolinium and 123I-labeled SAP scintigraphy not only assist in evaluation of patients with known amyloidosis but cardiac MRI has detected amyloid in patients previously unsuspected of the disease.
Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura
Authors: Callewaert Filip , Roodt Jan , Ulrichts Hans , Stohr Thomas , van Rensburg Walter Janse , Lamprecht Seb , Rossenu Stefaan , Priem Sofie , Willems Wouter , Holz Josefin-Beate 
Published: September 2012

Abstract
ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In the present study, we report the efficacy and safety profile of ALX-0681 in a baboon model of acquired TTP. In this model, acute episodes of TTP are induced by administration of an ADAMTS13-inhibiting mAb. ALX-0681 completely prevented the rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia. After induction of TTP, platelet counts also rapidly recovered on administration of ALX-0681. This effect was corroborated by the full neutralization of VWF activity. The schistocytic hemolytic anemia was also halted and partially reversed by ALX-0681 treatment. Brain CT scans and post mortem analysis did not reveal any sign of bleeding, suggesting that complete neutralization of VWF by ALX-0681 under conditions of thrombocytopenia was not linked with an excessive bleeding risk. The results obtained in this study demonstrate that ALX-0681 can successfully treat and prevent the most important hallmarks of acquired TTP without evidence of a severe bleeding risk. Therefore, ALX-0681 offers an attractive new therapeutic option for acquired TTP in the clinical setting.
Mitochondrial genome evolution in species belonging to the Phialocephala fortinii s.l. - Acephala applanata species complex
Authors: Duò Angelo , Bruggmann Rémy , Zoller Stefan , Bernt Matthias , Grünig Christoph R 
Published: September 2012

Abstract

Background
Mitochondrial (mt) markers are successfully applied in evolutionary biology and systematics because mt genomes often evolve faster than the nuclear genomes. In addition, they allow robust phylogenetic analysis based on conserved proteins of the oxidative phosphorylation system. In the present study we sequenced and annotated the complete mt genome of P. subalpina, a member of the Phialocephala fortinii s.l. – Acephala applanata species complex (PAC). PAC belongs to the Helotiales, which is one of the most diverse groups of ascomycetes including more than 2,000 species. The gene order was compared to deduce the mt genome evolution in the Pezizomycotina. Genetic variation in coding and intergenic regions of the mtDNA was studied for PAC to assess the usefulness of mt DNA for species diagnosis.

Results
The mt genome of P. subalpina is 43,742 bp long and codes for 14 mt genes associated with the oxidative phosphorylation. In addition, a GIY-YIG endonuclease, the ribosomal protein S3 (Rps3) and a putative N-acetyl-transferase were recognized. A complete set of tRNA genes as well as the large and small rRNA genes but no introns were found. All protein-coding genes were confirmed by EST sequences. The gene order in P. subalpina deviated from the gene order in Sclerotinia sclerotiorum, the only other helotialean species with a fully sequenced and annotated mt genome. Gene order analysis within Pezizomycotina suggests that the evolution of gene orders is mostly driven by transpositions. Furthermore, sequence diversity in coding and non-coding mtDNA regions in seven additional PAC species was pronounced and allowed for unequivocal species diagnosis in PAC.

Conclusions
The combination of non-interrupted ORFs and EST sequences resulted in a high quality annotation of the mt genome of P. subalpina, which can be used as a reference for the annotation of other mt genomes in the Helotiales. In addition, our analyses show that mtDNA loci will be the marker of choice for future analysis of PAC communities.
Characterization of copper-resistant bacteria and bacterial communities from copper-polluted agricultural soils of central Chile
Authors: Altimira Fabiola , Yáñez Carolina , Bravo Guillermo , González Myriam , Rojas Luis A , Seeger Michael 
Published: September 2012

Abstract

Background
Copper mining has led to Cu pollution in agricultural soils. In this report, the effects of Cu pollution on bacterial communities of agricultural soils from Valparaiso region, central Chile, were studied. Denaturing gradient gel electrophoresis (DGGE) of the 16S rRNA genes was used for the characterization of bacterial communities from Cu-polluted and non-polluted soils. Cu-resistant bacterial strains were isolated from Cu-polluted soils and characterized.

Results
DGGE showed a similar high number of bands and banding pattern of the bacterial communities from Cu-polluted and non-polluted soils. The presence of copA genes encoding the multi-copper oxidase that confers Cu-resistance in bacteria was detected by PCR in metagenomic DNA from the three Cu-polluted soils, but not in the non-polluted soil. The number of Cu-tolerant heterotrophic cultivable bacteria was significantly higher in Cu-polluted soils than in the non-polluted soil. Ninety two Cu-resistant bacterial strains were isolated from three Cu-polluted agricultural soils. Five isolated strains showed high resistance to copper (MIC ranged from 3.1 to 4.7 mM) and also resistance to other heavy metals. 16S rRNA gene sequence analyses indicate that these isolates belong to the genera Sphingomonas, Stenotrophomonas and Arthrobacter. The Sphingomonas sp. strains O12, A32 and A55 and Stenotrophomonas sp. C21 possess plasmids containing the Cu-resistance copA genes. Arthrobacter sp. O4 possesses the copA gene, but plasmids were not detected in this strain. The amino acid sequences of CopA from Sphingomonas isolates (O12, A32 and A55), Stenotrophomonas strain (C21) and Arthrobacter strain (O4) are closely related to CopA from Sphingomonas, Stenotrophomonas and Arthrobacter strains, respectively.

Conclusions
This study suggests that bacterial communities of agricultural soils from central Chile exposed to long-term Cu-pollution have been adapted by acquiring Cu genetic determinants. Five bacterial isolates showed high copper resistance and additional resistance to other heavy metals. Detection of copA gene in plasmids of four Cu-resistant isolates indicates that mobile genetic elements are involved in the spreading of Cu genetic determinants in polluted environments.
Acceptability of early infant male circumcision among chinese parents: strategy implications of HIV prevention for china
Authors: Pan Lianjun , Zhang Aixia , Shen Rong , Wang Zhong 
Published: September 2012

AbstractBackgroundRecent evidence has confirmed that circumcision can be performed as a preventive strategy for HIV and early infant male circumcision (EIMC) is regarded to be safer than circumcision in adulthood; however, limited data are available in the literature about EIMC in China. Therefore, the present study was designed to determine the willingness and attitudes of Chinese parents on newborn male circumcision so as to provide data for exploring the feasibility of implementing EIMC as an HIV prevention strategy in China.MethodsSimple random sampling was used to draw participants from parents who had a newborn son delivered at Nanjing Maternity and Child Health Care Hospital, which is affiliated to Nanjing Medical University, between March and December 2010. A questionnaire was used to determine general medical knowledge or information about circumcision, attitudes about EIMC, and level of decision-making on circumcision for the newborn son.ResultsData derived from 558 responses were analyzed and the ratio of respondents was 56.3% for fathers and 43.6% for mothers. Of the respondents, 34.4% agreed to circumcise their newborn son, and the level of agreement was 3.25 ± 1.17 (range, 1–5 with “1” being “reluctantly agree” and “5” being “very strongly agree”). The major reason for EIMC was for health (44.8%), followed by doctor’s advice (31.2%). The major reason not to agree to EIMC was concern about pain (50.5%), followed by the risk of the procedure (23.5%).ConclusionThe willingness and acceptability of EIMC in China is low and the parents of newborn sons are usually not very affirmative when making a decision on such a procedure, suggesting that significant effort will be needed if EIMC is to be implemented as an HIV prevention strategy for China.
Childhood caries in the state of Kentucky, USA: a cross-sectional study
Authors: Kandel Elizabeth A , Richards Jenna M , Binkley Catherine J 
Published: September 2012

Abstract

Background
Untreated dental caries afflicts almost one third of school-aged children in the United States and many of them are from disadvantaged families. This cross-sectional study was undertaken to investigate the prevalence of untreated caries in north central Kentucky, USA and to examine the relationships between the available demographic variables and untreated childhood caries as reported on the forms from the Smile Kentucky! program.

Methods
During the fall of 2008, caries status was assessed during the visual oral screening examination component of “SmileKentucky!”– a model of the American Dental Association’s Give Kids A Smile program. Parents had completed brief surveys concerning 3,488 elementary school children aged 5 to 13 years who participated in the program. A secondary analysis was conducted using univariate, bivariate and multivariate statistical methods.

Results
Untreated caries was reported in 33% of children. Bivariate and logistic regression analyses found that the most significant risk factors for having untreated caries were living in the metropolitan Louisville, Kentucky area, not having had a dental visit in the previous 3 years and not having any form of dental insurance.

Conclusions
Untreated caries in elementary school children is prevalent in north-central Kentucky despite efforts to improve access to care. The results suggest that additional family and community preventive initiatives are needed to reduce the development of childhood caries in this area of the United States.
Nanostructured materials with biomimetic recognition abilities for chemical sensing
Authors: Bajwa Sadia Zafar , Mustafa Ghulam , Samardzic Renata , Wangchareansak Thipvaree , Lieberzeit Peter A 
Published: September 2012

Abstract
Binding features found in biological systems can be implemented into man-made materials to design nanostructured artificial receptor matrices which are suitable, e.g., for chemical sensing applications. A range of different non-covalent interactions can be utilized based on the chemical properties of the respective analyte. One example is the formation of coordinative bonds between a polymerizable ligand (e.g., N-vinyl-2-pyrrolidone) and a metal ion (e.g., Cu(II)). Optimized molecularly imprinted sensor layers lead to selectivity factors of at least 2 compared to other bivalent ions. In the same way, H-bonds can be utilized for such sensing purposes, as shown in the case of Escherichia coli. The respective molecularly imprinted polymer leads to the selectivity factor of more than 5 between the W and B strains, respectively. Furthermore, nanoparticles with optimized Pearson hardness allow for designing sensors to detect organic thiols in air. The ‘harder’ MoS2 yields only about 40% of the signals towards octane thiol as compared to the ‘softer’ Cu2S. However, both materials strongly prefer molecules with -SH functionality over others, such as hydrocarbon chains. Finally, selectivity studies with wheat germ agglutinin (WGA) reveal that artificial receptors yield selectivities between WGA and bovine serum albumin that are only about a factor of 2 which is smaller than natural ligands.
Characterization of fatty acid modifying enzyme activity in staphylococcal mastitis isolates and other bacteria
Authors: Lu Thea , Park Joo Youn , Parnell Kelleen , Fox Larry K , McGuire Mark A 
Published: September 2012

AbstractBackgroundFatty acid modifying enzyme (FAME) has been shown to modify free fatty acids to alleviate their bactericidal effect by esterifying fatty acids to cholesterol or alcohols. Although it has been shown in previous studies that FAME is required forStaphylococcus aureussurvival in skin abscesses, FAME is poorly studied compared to other virulence factors. FAME activity had also been detected in coagulase-negative staphylococci (CNS). However, FAME activity was only surveyed after a bacterial culture was grown for 24 h. Therefore if FAME activity was earlier in the growth phase, it would not have been detected by the assay and those strains would have been labeled as FAME negative.ResultsFifty CNS bovine mastitis isolates and severalS. aureus, Escherichia coli, andStreptococcus uberisstrains were assayed for FAME activity over 24 h. FAME activity was detected in 54% of CNS and 80% S. aureusstrains surveyed but none inE. coliorS. uberis. While some CNS strains produced FAME activity comparable to the lab strain ofS. aureus, the pattern of FAME activity varied among strains and across species of staphylococci. All CNS that produced FAME activity also exhibited lipase activity. Lipase activity relative to colony forming units of these CNS decreased over the 24 h growth period. No relationship was observed between somatic cell count in the milk and FAME activity in CNS.ConclusionsSome staphylococcal species surveyed produced FAME activity, butE. coliandS. uberisstrains did not. All FAME producing CNS exhibited lipase activity which may indicate that both these enzymes work in concert to alter fatty acids in the bacterial environment.
Use of cognitive enhancers for mild cognitive impairment: protocol for a systematic review and network meta-analysis
Authors: Tricco Andrea C , Soobiah Charlene , Lillie Erin , Perrier Laure , Chen Maggie H , Hemmelgarn Brenda , Majumdar Sumit R , Straus Sharon E 
Published: September 2012

Abstract

Background
Elderly individuals who have memory problems without significant limitations in activities of daily living are often diagnosed as having mild cognitive impairment (MCI). Some of these individuals progress to dementia. Several cognitive enhancers (for example donepezil, galantamine, rivastigmine, memantine) have been approved for use in people with Alzheimer’s dementia but their use in patients with MCI is unclear. We aimed to determine the comparative effectiveness, safety, and cost of cognitive enhancers for MCI through a systematic review and network (that is, indirect comparisons) meta-analysis.

Design/Methods
We will include studies that examine the use of cognitive enhancers compared to placebo, supportive care, or other cognitive enhancers among patients diagnosed with MCI. Outcomes of interest include cognition and function (primary outcomes), as well as behavior, quality of life, safety, and cost (secondary outcomes). We will include all experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials), quasi-experimental studies (controlled before-after, interrupted time series), and observational studies (cohort, case–control). Studies will be included regardless of publication status (that is, we will include unpublished studies), year, or language of dissemination.
To identify potentially relevant material, we will search the following electronic databases from inception onwards: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and Ageline. The electronic database search will be supplemented by scanning the reference lists of included studies, searching Google and organization websites for unpublished or difficult to locate material literature, and contacting experts.
Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational epidemiology studies. Meta-analysis and network meta-analysis are planned, if the studies are deemed statistically, methodologically, and clinically homogenous.

Discussion
Our systematic review will provide important information regarding the benefits, costs, and harms of cognitive enhancers for patients with MCI. This information can be used to assist healthcare providers, policy-makers, MCI patients and their family regarding the use of these agents.

PROSPERO registry number
CRD42012002234
Analysis of variation at transcription factor binding sites in Drosophila and humans
Authors: Spivakov Mikhail , Akhtar Junaid , Kheradpour Pouya , Beal Kathryn , Girardot Charles , Koscielny Gautier , Herrero Javier , Kellis Manolis , Furlong Eileen EM , Birney Ewan 
Published: September 2012

Abstract
Background
Advances in sequencing technology have boosted population genomics and made it possible to map the positions of transcription factor binding sites (TFBSs) with high precision. Here we investigate TFBS variability by combining transcription factor binding maps generated by ENCODE, modENCODE, our previously published data and other sources with genomic variation data for human individuals and Drosophila isogenic lines.

Results
We introduce a metric of TFBS variability that takes into account changes in motif match associated with mutation and makes it possible to investigate TFBS functional constraints instance-by-instance as well as in sets that share common biological properties. We also take advantage of the emerging per-individual transcription factor binding data to show evidence that TFBS mutations, particularly at evolutionarily conserved sites, can be efficiently buffered to ensure coherent levels of transcription factor binding.

Conclusions
Our analyses provide insights into the relationship between individual and interspecies variation and show evidence for the functional buffering of TFBS mutations in both humans and flies. In a broad perspective, these results demonstrate the potential of combining functional genomics and population genetics approaches for understanding gene regulation.
The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications
Authors: Shachar Idit , Karin Nathan 
Published: September 2012

Abstract
Review of pro- and anti-inflammatory cytokines, and their dependence on the local concentration of a given cytokine, the stage of disease in which it is administered, and its combination with other cytokines.
Cytokines and chemokines are secreted, small cell-signaling protein molecules, whose receptors are expressed on immune cells. These factors play a critical role in immune cell differentiation, migration, and polarization into functional subtypes and in directing their biological functions. Much attention has been devoted to exploring the role of key inflammatory cytokines and promigratory chemokines in autoimmune, autoinflammatory, and allergic diseases, leading to development of therapeutic strategies that are based on their targeted neutralization. Recent studies, including those coming from our groups, show that several major proinflammatory cytokines and chemokines, including IFN-γ, IL-2, CCL2, and CXCL12, may also function as anti-inflammatory mediators and therefore, may have potential as anti-inflammatory drugs. Likewise, major anti-inflammatory mediators, such as TGF-β, may under certain conditions, in combination with other cytokines, exhibit proinflammatory function and direct the polarization of the highly inflammatory CD4+ Th17 cells. We show here that the biological function of pro- and anti-inflammatory cytokines is dependent on three key parameters: the local concentration of a given cytokine, the stage of disease in which it is administered, and its combination with other cytokines. The therapeutic implications of these findings are discussed, including two very recent studies summarizing clinical trials, in which low-dose administration of IL-2 was used to successfully suppress HCV and GVHD.
Long-Term Survivors of Gastric Cancer: A California Population-Based Study
Authors: Kunz Pamela L. , Gubens Matthew , Fisher George A. , Ford James M. , Lichtensztajn Daphne Y. , Clarke Christina A. 
Published: September 2012

Purpose In the United States, gastric cancer is rapidly fatal with a 25% 5-year survival. Of the few patients who survive, little is known about their demographic, clinical, and tumor characteristics. Patients and Methods Data regarding all cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed in California between 1988 and 2005 were obtained from the California Cancer Registry, a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. A Cox proportional hazards model was constructed to understand the independent relationships of patient demographic, disease, and treatment factors with survival. Results We identified 47,647 patients diagnosed with gastric or GEJ cancer. Of those, only 9,325 (20%) survived at least 3 years. Variables associated with longer survival were localized stage (hazard ratio [HR], 0.20), surgery with diagnosis in 2002 or later (HR, 0.34), surgery with diagnosis in 2001 or before (0.37), regional stage (HR, 0.53), chemotherapy (HR, 0.56), intestinal histology (HR, 0.74), well- or moderately differentiated tumors (HR, 0.76), radiation (HR, 0.80), Asian/Pacific Islander race (HR, 0.81), treatment at an academic hospital (HR, 0.85), fundus/body/antrum location (HR, 0.90), highest socioeconomic status quintile (HR, 0.91), female sex (HR, 0.92), Hispanic race (HR, 0.92), and hospital size more than 150 beds (HR, 0.94). Kaplan-Meier curves showed longer median disease-specific survival (DSS) in patients with tumors originating in the fundus/body/antrum compared with esophagus/cardia (13.4 v 10.8 months). Intestinal histology had significantly longer median DSS (28.9 months) compared with other (11.0 months) or diffuse (10.1 months) histology. Conclusion Patients who survive gastric and GEJ cancer more than 3 years after diagnosis have demographic and pathologic characteristics distinct from those who do not survive.