bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highlights of Anesthetic Considerations for Intraoperative Neuromonitoring
Authors: Deiner Stacie 
Published: May 2010

Though relatively new, intraoperative neurophysiological monitoring (IONM) has become standard of care for many neurosurgical procedures. The use of IONM has substantially decreased the rate of paralysis after deformity surgery, and has been validated in cervical spine surgery, and thoracic and lumbar laminectomy ((1) (2), (3). The main modalities are: somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), and electromyography (EMGs). Each test examines a functionally separate area of the spinal cord, which test is chosen depends on the location of the surgery and the patient’s preexisting injuries and deficits (6). Inhaled anesthetics decrease the waveform amplitude and increase latency, intravenous anesthetics have the same effect but to a lesser degree. Best anesthetic regimen for surgery involving intraoperative monitoring is controversial. Both inhaled and intravenous agents depress signal attainment, however for equal MAC concentrations inhaled agents cause more depression(11). While studies have shown that halogenated agents and nitrous oxide do in fact depress MEP signals more than total intravenous anesthesia, less is known on the relationship between IONM and patient characteristics. Lo’s study documenting MEP attainment with 0.5 MAC was done in an otherwise healthy scoliosis population (12), and no study to date has analyzed signal attainment in correlation with patient characteristics and anesthetic technique. While it is clear that anesthetic technique is extremely important, certain patient characteristics appear to be more common in difficult to monitor patients. The identification of these characteristics would suggest to the anesthesiologist the need for a more stringent technique (TIVA) and avert surgical delay or cancellation due to inability to obtain baseline or worse- loss of intraoperative waveform and need for a Stagnara wake-up test. Our group at Mt. Sinai has retrospectively studied patient characteristics, anesthetic technique and attainment of neuromonitoring signals. Hypertension and diabetes are independent predictors of monitoring failure, and these are preferentially sensitive to inhalational agents. Age and weight are also predictors, but less significant. In summary, neurophysiologic monitoring has evolved to be a consistent part of many procedures. The anesthesiologist should strive to understand the rationale behind monitoring and the basis of its utility. IONM has many implications for anesthetic technique and need for control of the physiologic milieu. With this knowledge the anesthesiologist can work together with the neuromonitoring team and surgeon to ensure patient safety during and after surgery.
Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells
Authors: Nakamura Yuka , Arai Fumio , Iwasaki Hiroko , Hosokawa Kentaro , Kobayashi Isao , Gomei Yumiko , Matsumoto Yoshiko , Yoshihara Hiroki , Suda Toshio 
Published: May 2010

Abstract
The endosteal niche is critical for the maintenance of hematopoietic stem cells (HSCs). However, it consists of a heterogeneous population in terms of differentiation stage and function. In this study, we characterized endosteal cell populations and examined their ability to maintain HSCs. Bone marrow endosteal cells were subdivided into immature mesenchymal cell-enriched ALCAM−Sca-1+ cells, osteoblast-enriched ALCAM+Sca-1−, and ALCAM–Sca-1− cells. We found that all 3 fractions maintained long-term reconstitution (LTR) activity of HSCs in an in vitro culture. In particular, ALCAM+Sca-1− cells significantly enhanced the LTR activity of HSCs by the up-regulation of homing- and cell adhesion–related genes in HSCs. Microarray analysis showed that ALCAM−Sca-1+ fraction highly expressed cytokine-related genes, whereas the ALCAM+Sca-1− fraction expressed multiple cell adhesion molecules, such as cadherins, at a greater level than the other fractions, indicating that the interaction between HSCs and osteoblasts via cell adhesion molecules enhanced the LTR activity of HSCs. Furthermore, we found an osteoblastic markerlow/− subpopulation in ALCAM+Sca-1− fraction that expressed cytokines, such as Angpt1 and Thpo, and stem cell marker genes. Altogether, these data suggest that multiple subsets of osteoblasts and mesenchymal progenitor cells constitute the endosteal niche and regulate HSCs in adult bone marrow.
Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis
Authors: Silasi-Mansat Robert , Zhu Hua , Popescu Narcis I. , Peer Glenn , Sfyroera Georgia , Magotti Paola , Ivanciu Lacramioara , Lupu Cristina , Mollnes Tom E. , Taylor Fletcher B. , Kinasewitz Gary , Lambris John D. , Lupu Florea 
Published: May 2010

AbstractSevere sepsis leads to massive activation of coagulation and complement cascades that could contribute to multiple organ failure and death. To investigate the role of the complement and its crosstalk with the hemostatic system in the pathophysiology and therapeutics of sepsis, we have used a potent inhibitor (compstatin) administered early or late after Escherichia coli challenge in a baboon model of sepsis-induced multiple organ failure. Compstatin infusion inhibited sepsis-induced blood and tissue biomarkers of complement activation, reduced leucopenia and thrombocytopenia, and lowered the accumulation of macrophages and platelets in organs. Compstatin decreased the coagulopathic response by down-regulating tissue factor and PAI-1, diminished global blood coagulation markers (fibrinogen, fibrin-degradation products, APTT), and preserved the endothelial anticoagulant properties. Compstatin treatment also improved cardiac function and the biochemical markers of kidney and liver damage. Histologic analysis of vital organs collected from animals euthanized after 24 hours showed decreased microvascular thrombosis, improved vascular barrier function, and less leukocyte infiltration and cell death, all consistent with attenuated organ injury. We conclude that complement-coagulation interplay contributes to the progression of severe sepsis and blocking the harmful effects of complement activation products, especially during the organ failure stage of severe sepsis is a potentially important therapeutic strategy.
Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?
Authors: Vajdic Claire M. , Mao Limin , van Leeuwen Marina T. , Kirkpatrick Philippa , Grulich Andrew E. , Riminton Sean 
Published: May 2010

Abstract
Analysis of cancer risk in primary immune deficiency (PID) offers insight into the relationship between immune function and cancer. Data on Australian patients (n = 1132) notified voluntarily to the Australasian Society of Clinical Immunology and Allergy PID Registry (1990-2008) were linked with national death and cancer registries. Person-years of follow-up commenced from up to 15 years before registration on the PID Registry or January 1982, the inception of national cancer registration. Site-specific, 5-year age-, sex-, calendar year–, and state-standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs) were calculated for all cancers except nonmelanocytic skin cancer. During an average of 16 person-years follow-up, a 1.6-fold excess relative risk of cancer was observed (n = 58; SIR 1.60, 95% CI 1.22-2.07) for all PID combined. Relative risk was increased for non-Hodgkin lymphoma (n = 16; SIR 8.82, 95% CI 5.04-14.30), leukemia (n = 4; SIR 5.36, 95% CI 1.46-13.73), and stomach cancer (n = 3; SIR 6.10, 95% CI 1.26-17.84). Excess cancer risk was observed for predominantly antibody deficiencies and other well-defined immunodeficiency syndromes. Results suggest that predominantly antibody deficiencies may be associated with a narrower range of solid cancers than immunodeficiency characterized by predominantly T-cell deficiency, such as iatrogenic and HIV-related immunodeficiency, although this requires confirmation in larger cohorts.
New components of the Dictyostelium PKA pathway revealed by Bayesian analysis of expression data
Authors: Parikh Anup , Huang Eryong , Dinh Christopher , Zupan Blaz , Kuspa Adam , Subramanian Devika , Shaulsky Gad 
Published: May 2010

Abstract

Background
Identifying candidate genes in genetic networks is important for understanding regulation and biological function. Large gene expression datasets contain relevant information about genetic networks, but mining the data is not a trivial task. Algorithms that infer Bayesian networks from expression data are powerful tools for learning complex genetic networks, since they can incorporate prior knowledge and uncover higher-order dependencies among genes. However, these algorithms are computationally demanding, so novel techniques that allow targeted exploration for discovering new members of known pathways are essential.

Results
Here we describe a Bayesian network approach that addresses a specific network within a large dataset to discover new components. Our algorithm draws individual genes from a large gene-expression repository, and ranks them as potential members of a known pathway. We apply this method to discover new components of the cAMP-dependent protein kinase (PKA) pathway, a central regulator of Dictyostelium discoideum development. The PKA network is well studied in D. discoideum but the transcriptional networks that regulate PKA activity and the transcriptional outcomes of PKA function are largely unknown. Most of the genes highly ranked by our method encode either known components of the PKA pathway or are good candidates. We tested 5 uncharacterized highly ranked genes by creating mutant strains and identified a candidate cAMP-response element-binding protein, yet undiscovered in D. discoideum, and a histidine kinase, a candidate upstream regulator of PKA activity.

Conclusions
The single-gene expansion method is useful in identifying new components of known pathways. The method takes advantage of the Bayesian framework to incorporate prior biological knowledge and discovers higher-order dependencies among genes while greatly reducing the computational resources required to process high-throughput datasets.
In-silico prediction of blood-secretory human proteins using a ranking algorithm
Authors: Liu Qi , Cui Juan , Yang Qiang , Xu Ying 
Published: May 2010

Abstract

Background
Computational identification of blood-secretory proteins, especially proteins with differentially expressed genes in diseased tissues, can provide highly useful information in linking transcriptomic data to proteomic studies for targeted disease biomarker discovery in serum.

Results
A new algorithm for prediction of blood-secretory proteins is presented using an information-retrieval technique, called manifold ranking. On a dataset containing 305 known blood-secretory human proteins and a large number of other proteins that are either not blood-secretory or unknown, the new method performs better than the previous published method, measured in terms of the area under the recall-precision curve (AUC). A key advantage of the presented method is that it does not explicitly require a negative training set, which could often be noisy or difficult to derive for most biological problems, hence making our method more applicable than classification-based data mining methods in general biological studies.

Conclusion
We believe that our program will prove to be very useful to biomedical researchers who are interested in finding serum markers, especially when they have candidate proteins derived through transcriptomic or proteomic analyses of diseased tissues. A computer program is developed for prediction of blood-secretory proteins based on manifold ranking, which is accessible at our website http://csbl.bmb.uga.edu/publications/materials/qiliu/blood_secretory_protein.html.
High quality protein sequence alignment by combining structural profile prediction and profile alignment using SABERTOOTH
Authors: Teichert Florian , Minning Jonas , Bastolla Ugo , Porto Markus 
Published: May 2010

Abstract

Background
Protein alignments are an essential tool for many bioinformatics analyses. While sequence alignments are accurate for proteins of high sequence similarity, they become unreliable as they approach the so-called 'twilight zone' where sequence similarity gets indistinguishable from random. For such distant pairs, structure alignment is of much better quality. Nevertheless, sequence alignment is the only choice in the majority of cases where structural data is not available. This situation demands development of methods that extend the applicability of accurate sequence alignment to distantly related proteins.

Results
We develop a sequence alignment method that combines the prediction of a structural profile based on the protein's sequence with the alignment of that profile using our recently published alignment tool SABERTOOTH. In particular, we predict the contact vector of protein structures using an artificial neural network based on position-specific scoring matrices generated by PSI-BLAST and align these predicted contact vectors. The resulting sequence alignments are assessed using two different tests: First, we assess the alignment quality by measuring the derived structural similarity for cases in which structures are available. In a second test, we quantify the ability of the significance score of the alignments to recognize structural and evolutionary relationships. As a benchmark we use a representative set of the SCOP (structural classification of proteins) database, with similarities ranging from closely related proteins at SCOP family level, to very distantly related proteins at SCOP fold level. Comparing these results with some prominent sequence alignment tools, we find that SABERTOOTH produces sequence alignments of better quality than those of Clustal W, T-Coffee, MUSCLE, and PSI-BLAST. HHpred, one of the most sophisticated and computationally expensive tools available, outperforms our alignment algorithm at family and superfamily levels, while the use of SABERTOOTH is advantageous for alignments at fold level. Our alignment scheme will profit from future improvements of structural profiles prediction.

Conclusions
We present the automatic sequence alignment tool SABERTOOTH that computes pairwise sequence alignments of very high quality. SABERTOOTH is especially advantageous when applied to alignments of remotely related proteins. The source code is available at http://www.fkp.tu-darmstadt.de/sabertooth_project/, free for academic users upon request.
Phylogenetic nomenclature and evolution of mannose-binding lectin (MBL2) haplotypes
Authors: Boldt Angelica BW , Messias-Reason Iara J , Meyer Diogo , Schrago Carlos G , Lang Florian , Lell Bertrand , Dietz Klaus , Kremsner Peter G , Petzl-Erler Maria Luiza , Kun Jürgen FJ 
Published: May 2010

AbstractBackgroundPolymorphisms of the mannose-binding lectin gene (MBL2) affect the concentration and functional efficiency of the protein. We recently used haplotype-specific sequencing to identify 23MBL2haplotypes, associated with enhanced susceptibility to several diseases.ResultsIn this work, we applied the same method in 288 and 470 chromosomes from Gabonese and European adults, respectively, and found three new haplotypes in the last group. We propose a phylogenetic nomenclature to standardizeMBL2studies and found two major phylogenetic branches due to six strongly linked polymorphisms associated with high MBL production. They presented high Fst values and were imbedded in regions with high nucleotide diversity and significant Tajima's D values. Compared to others using small sample sizes and unphased genotypic data, we found differences in haplotyping, frequency estimation, Fu and Li's D* and Fst results.ConclusionUsing extensive testing for selective neutrality, we confirmed that stochastic evolutionary factors have had a major role in shaping this polymorphic gene worldwide.
How old is this mutation? - a study of three Ashkenazi Jewish founder mutations
Authors: Greenwood Celia MT , Sun Shuying , Veenstra Justin , Hamel Nancy , Niell Bethany , Gruber Stephen , Foulkes William D 
Published: May 2010

Abstract

Background
Several founder mutations leading to increased risk of cancer among Ashkenazi Jewish individuals have been identified, and some estimates of the age of the mutations have been published. A variety of different methods have been used previously to estimate the age of the mutations. Here three datasets containing genotype information near known founder mutations are reanalyzed in order to compare three approaches for estimating the age of a mutation. The methods are: (a) the single marker method used by Risch et al., (1995); (b) the intra-allelic coalescent model known as DMLE, and (c) the Goldgar method proposed in Neuhausen et al. (1996), and modified slightly by our group. The three mutations analyzed were MSH2*1906 G->C, APC*I1307K, and BRCA2*6174delT.

Results
All methods depend on accurate estimates of inter-marker recombination rates. The modified Goldgar method allows for marker mutation as well as recombination, but requires prior estimates of the possible haplotypes carrying the mutation for each individual. It does not incorporate population growth rates. The DMLE method simultaneously estimates the haplotypes with the mutation age, and builds in the population growth rate. The single marker estimates, however, are more sensitive to the recombination rates and are unstable. Mutation age estimates based on DMLE are 16.8 generations for MSH2 (95% credible interval (13, 23)), 106 generations for I1037K (86-129), and 90 generations for 6174delT (71-114).

Conclusions
For recent founder mutations where marker mutations are unlikely to have occurred, both DMLE and the Goldgar method can give good results. Caution is necessary for older mutations, especially if the effective population size may have remained small for a long period of time.
Comparative genomics reveals a functional thyroid-specific element in the far upstream region of the PAX8 gene
Authors: Nitsch Roberto , Di Dato Valeria , di Gennaro Alessandra , de Cristofaro Tiziana , Abbondante Serena , De Felice Mario , Zannini Mariastella , Di Lauro Roberto 
Published: May 2010

Abstract

Background
The molecular mechanisms leading to a fully differentiated thyrocite are still object of intense study even if it is well known that thyroglobulin, thyroperoxidase, NIS and TSHr are the marker genes of thyroid differentiation. It is also well known that Pax8, TTF-1, Foxe1 and Hhex are the thyroid-enriched transcription factors responsible for the expression of the above genes, thus are responsible for the differentiated thyroid phenotype. In particular, the role of Pax8 in the fully developed thyroid gland was studied in depth and it was established that it plays a key role in thyroid development and differentiation. However, to date the bases for the thyroid-enriched expression of this transcription factor have not been unraveled yet. Here, we report the identification and characterization of a functional thyroid-specific enhancer element located far upstream of the Pax8 gene.

Results
We hypothesized that regulatory cis-acting elements are conserved among mammalian genes. Comparison of a genomic region extending for about 100 kb at the 5'-flanking region of the mouse and human Pax8 gene revealed several conserved regions that were tested for enhancer activity in thyroid and non-thyroid cells. Using this approach we identified one putative thyroid-specific regulatory element located 84.6 kb upstream of the Pax8 transcription start site. The in silico data were verified by promoter-reporter assays in thyroid and non-thyroid cells. Interestingly, the identified far upstream element manifested a very high transcriptional activity in the thyroid cell line PC Cl3, but showed no activity in HeLa cells. In addition, the data here reported indicate that the thyroid-enriched transcription factor TTF-1 is able to bind in vitro and in vivo the Pax8 far upstream element, and is capable to activate transcription from it.

Conclusions
Results of this study reveal the presence of a thyroid-specific regulatory element in the 5' upstream region of the Pax8 gene. The identification of this regulatory element represents the first step in the investigation of upstream regulatory mechanisms that control Pax8 transcription during thyroid differentiation and are relevant to further studies on Pax8 as a candidate gene for thyroid dysgenesis.
Characterizing Ancylostoma caninum transcriptome and exploring nematode parasitic adaptation
Authors: Wang Zhengyuan , Abubucker Sahar , Martin John , Wilson Richard K , Hawdon John , Mitreva Makedonka 
Published: May 2010

Abstract

Background
Hookworm infection is one of the most important neglected diseases in developing countries, with approximately 1 billion people infected worldwide. To better understand hookworm biology and nematode parasitism, the present study generated a near complete transcriptome of the canine hookworm Ancylostoma caninum to a very high coverage using high throughput technology, and compared it to those of the free-living nematode Caenorhabditis elegans and the parasite Brugia malayi.

Results
The generated transcripts from four developmental stages, infective L3, serum stimulated L3, adult male and adult female, covered 93% of the A. caninum transcriptome. The broad diversity among nematode transcriptomes was confirmed, and an impact of parasitic adaptation on transcriptome diversity was inferred. Intra-population analysis showed that A. caninum has higher coding sequence diversity than humans. Examining the developmental expression profiles of A. caninum revealed major transitions in gene expression from larval stages to adult. Adult males expressed the highest number of selectively expressed genes, but adult female expressed the highest number of selective parasitism-related genes. Genes related to parasitism adaptation and A. caninum specific genes exhibited more expression selectivity while those conserved in nematodes tend to be consistently expressed. Parasitism related genes were expressed more selectively in adult male and female worms. The comprehensive analysis of digital expression profiles along with transcriptome comparisons enabled identification of a set of parasitism genes encoding secretory proteins in animal parasitic nematode.

Conclusions
This study validated the usage of deep sequencing for gene expression profiling. Parasitic adaptation of the canine hookworm is related to its diversity and developmental dynamics. This comprehensive comparative genomic and expression study substantially improves our understanding of the basic biology and parasitism of hookworms and, is expected, in the long run, to accelerate research toward development of vaccines and novel anthelmintics.