bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of Isolated Meniscal Injury and Its Effect on Performance in Athletes From the National Basketball Association
Authors: Yeh Peter C. , Starkey Chad , Lombardo Stephen , Vitti Gary , Kharrazi F. Daniel 
Published: December 2011

Background: The current incidence and outcomes of meniscal injury have not been quantified in professional athletes. Purpose: To describe the incidence, risk, amount of time lost, and effect on performance for isolated meniscal injury in athletes from the National Basketball Association (NBA). Demographic factors predicting the risk of meniscal tears and the effect of injury in return to play were also investigated. Study Design: Descriptive epidemiology study. Methods: A centralized database was queried to identify meniscal injuries occurring in the NBA over 21 seasons. The frequency of injury, time lost, game exposures, and incidence, rate, and risk were calculated. The preinjury and postinjury player efficiency rating (PER) was used to identify changes in player performance. Results: We identified 129 isolated meniscal tears in NBA athletes during a 21-season span. From this number, 77 (59.7%) involved the lateral meniscus and 52 (40.3%) the medial meniscus. Injuries occurred more frequently in games. The lateral meniscus had a statistically significant higher injury rate. Both left and right knees were equally affected. The number of days missed for lateral meniscal tears and medial meniscal tears was 43.8 ± 35.7 days and 40.9 ± 29.7 days, respectively, and was not statistically different. There was a significant inverse relationship between age and rate of lateral meniscal tears, with lateral meniscal tears more likely to occur up to age 30 years; beyond that medial meniscal tears were more common. Players with a body mass index (BMI) greater than 25 had a significantly increased risk of meniscal tears compared with players with a BMI less than 25, specifically with an increased risk of lateral meniscal tears. Twenty-five players (19.4%) did not return to play. For those who did, upon returning to competition, there was no statistical change in PER from their preinjury status, and the mean number of seasons completed was 4.1 ± 3.7 seasons. Conclusion: The lateral meniscus is more frequently torn than the medial meniscus, but there was no difference in the amount of playing time lost. Both right and left knees were equally affected. There was an inverse relationship between age and the rate of lateral meniscal tears. Risk of tears was increased in players having a BMI greater than 25. Injury did not negatively affect playing performance.
Thermoplastic–lignocellulose composites enhanced by chemically treated Alcell lignin as compatibilizer
Authors: Tay GS , Shannon-Ong SH , Goh SW , Rozman HD 
Published: December 2011

In this study, chemically treated Alcell lignin was used as a compatibilizer in the preparation of polypropylene–oil palm empty fruit bunch (PP-EFB) composites. Basically, this study was divided into two stages. In the first stage, glycidyl methacrylate (GMA) and allyl glycidyl ether (AGE) were used to treat Alcell lignin in different ratios (1:1, 1:2 and 1:3) based on equivalent weight. Then, the treated lignin was used as a compatibilizer at different percentages (1%, 3% and 5%, based on the weight of EFB filler) in the preparation of lignocellulosic–thermoplastic composites. The size of the EFB filler used for this study was 53–180 µm and the ratio of PP to EFB filler was fixed at 40%:60% (based on weight). The results showed that the incorporation of GMA- and AGE-treated lignin had enhanced the mechanical properties and increased the hydrophobicity of lignocellulosic–thermoplastic composites. By comparison, those with the GMA-treated lignin exhibited better enhancement in mechanical properties as compared to those with AGE-treated lignin.
Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?
Authors: Neher Miriam D , Weckbach Sebastian , Flierl Michael A , Huber-Lang Markus S , Stahel Philip F 
Published: December 2011

AbstractTrauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.
Novel base triples in RNA structures revealed by graph theoretical searching methods
Authors: Firdaus-Raih Mohd , Harrison Anne-Marie , Willett Peter , Artymiuk Peter J 
Published: December 2011

Abstract

Background
Highly hydrogen bonded base interactions play a major part in stabilizing the tertiary structures of complex RNA molecules, such as transfer-RNAs, ribozymes and ribosomal RNAs.

Results
We describe the graph theoretical identification and searching of highly hydrogen bonded base triples, where each base is involved in at least two hydrogen bonds with the other bases. Our approach correlates theoretically predicted base triples with literature-based compilations and other actual occurrences in crystal structures. The use of ‘fuzzy’ search tolerances has enabled us to discover a number of triple interaction types that have not been previously recorded nor predicted theoretically.

Conclusions
Comparative analyses of different ribosomal RNA structures reveal several conserved base triple motifs in 50S rRNA structures, indicating an important role in structural stabilization and ultimately RNA function.
Non-nucleosidic inhibition of Herpes simplex virus DNA polymerase: mechanistic insights into the anti-herpetic mode of action of herbal drug withaferin A
Authors: Grover Abhinav , Agrawal Vibhuti , Shandilya Ashutosh , Bisaria Virendra S , Sundar Durai 
Published: December 2011

Abstract

Background
Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores and encephalitis. Previous antiviral studies on herpes viruses have focussed on developing nucleoside analogues that can inhibit viral polymerase and terminate the replicating viral DNA. However, these drugs bear an intrinsic non-specificity as they can also inhibit cellular polymerase apart from the viral one. The present study is an attempt to elucidate the action mechanism of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus providing an evidence for its development as a novel anti-herpetic drug.

Results
Withaferin A was found to bind very similarly to that of the previously reported 4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617, Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning of the polymerase. A comparison of the conformation obtained from docking and the molecular dynamics simulations shows that substantial changes in the binding conformations have occurred. These results indicate that the initial receptor-ligand interaction observed after docking can be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favoured.

Conclusions
We have performed docking and molecular dynamics simulation studies to elucidate the binding mechanism of prospective herbal drug withaferin A onto the structure of DNA polymerase of Herpes simplex virus. Our docking simulations results give high binding affinity of the ligand to the receptor. Long de novo MD simulations for 10 ns performed allowed us to evaluate the dynamic behaviour of the system studied and corroborate the docking results, as well as identify key residues in the enzyme-inhibitor interactions. The present MD simulations support the hypothesis that withaferin A is a potential ligand to target/inhibit DNA polymerase of the Herpes simplex virus. Results of these studies will also guide the design of selective inhibitors of DNA POL with high specificity and potent activity in order to strengthen the therapeutic arsenal available today against the dangerous biological warfare agent represented by Herpes Simplex Virus.
Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum
Authors: López-Barragán María J , Lemieux Jacob , Quiñones Mariam , Williamson Kim C , Molina-Cruz Alvaro , Cui Kairong , Barillas-Mury Carolina , Zhao Keji , Su Xin-zhuan 
Published: December 2011

Abstract

Background
It has been shown that nearly a quarter of the initial predicted gene models in the Plasmodium falciparum genome contain errors. Although there have been efforts to obtain complete cDNA sequences to correct the errors, the coverage of cDNA sequences on the predicted genes is still incomplete, and many gene models for those expressed in sexual or mosquito stages have not been validated. Antisense transcripts have widely been reported in P. falciparum; however, the extent and pattern of antisense transcripts in different developmental stages remain largely unknown.

Results
We have sequenced seven bidirectional libraries from ring, early and late trophozoite, schizont, gametocyte II, gametocyte V, and ookinete, and four strand-specific libraries from late trophozoite, schizont, gametocyte II, and gametocyte V of the 3D7 parasites. Alignment of the cDNA sequences to the 3D7 reference genome revealed stage-specific antisense transcripts and novel intron-exon splicing junctions. Sequencing of strand-specific cDNA libraries suggested that more genes are expressed in one direction in gametocyte than in schizont. Alternatively spliced genes, antisense transcripts, and stage-specific expressed genes were also characterized.

Conclusions
It is necessary to continue to sequence cDNA from different developmental stages, particularly those of non-erythrocytic stages. The presence of antisense transcripts in some gametocyte and ookinete genes suggests that these antisense RNA may play an important role in gene expression regulation and parasite development. Future gene expression studies should make use of directional cDNA libraries. Antisense transcripts may partly explain the observed discrepancy between levels of mRNA and protein expression.
Liverome: a curated database of liver cancer-related gene signatures with self-contained context information
Authors: Lee Langho , Wang Kai , Li Gang , Xie Zhi , Wang Yuli , Xu Jiangchun , Sun Shaoxian , Pocalyko David , Bhak Jong , Kim Chulhong , Lee Kee-Ho , Jang Ye Jin , Yeom Young Il , Yoo Hyang-Sook , Hwang Seungwoo 
Published: December 2011

Abstract

Background
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. A number of molecular profiling studies have investigated the changes in gene and protein expression that are associated with various clinicopathological characteristics of HCC and generated a wealth of scattered information, usually in the form of gene signature tables. A database of the published HCC gene signatures would be useful to liver cancer researchers seeking to retrieve existing differential expression information on a candidate gene and to make comparisons between signatures for prioritization of common genes. A challenge in constructing such database is that a direct import of the signatures as appeared in articles would lead to a loss or ambiguity of their context information that is essential for a correct biological interpretation of a gene’s expression change. This challenge arises because designation of compared sample groups is most often abbreviated, ad hoc, or even missing from published signature tables. Without manual curation, the context information becomes lost, leading to uninformative database contents. Although several databases of gene signatures are available, none of them contains informative form of signatures nor shows comprehensive coverage on liver cancer. Thus we constructed Liverome, a curated database of liver cancer-related gene signatures with self-contained context information.

Description
Liverome’s data coverage is more than three times larger than any other signature database, consisting of 143 signatures taken from 98 HCC studies, mostly microarray and proteome, and involving 6,927 genes. The signatures were post-processed into an informative and uniform representation and annotated with an itemized summary so that all context information is unambiguously self-contained within the database. The signatures were further informatively named and meaningfully organized according to ten functional categories for guided browsing. Its web interface enables a straightforward retrieval of known differential expression information on a query gene and a comparison of signatures to prioritize common genes. The utility of Liverome-collected data is shown by case studies in which useful biological insights on HCC are produced.

Conclusion
Liverome database provides a comprehensive collection of well-curated HCC gene signatures and straightforward interfaces for gene search and signature comparison as well. Liverome is available at http://liverome.kobic.re.kr.
INDUS - a composition-based approach for rapid and accurate taxonomic classification of metagenomic sequences
Authors: Mohammed Monzoorul Haque , Ghosh Tarini Shankar , Reddy Rachamalla Maheedhar , Reddy Chennareddy Venkata Siva Kumar , Singh Nitin Kumar , Mande Sharmila S 
Published: December 2011

Abstract

Background
Taxonomic classification of metagenomic sequences is the first step in metagenomic analysis. Existing taxonomic classification approaches are of two types, similarity-based and composition-based. Similarity-based approaches, though accurate and specific, are extremely slow. Since, metagenomic projects generate millions of sequences, adopting similarity-based approaches becomes virtually infeasible for research groups having modest computational resources. In this study, we present INDUS - a composition-based approach that incorporates the following novel features. First, INDUS discards the 'one genome-one composition' model adopted by existing compositional approaches. Second, INDUS uses 'compositional distance' information for identifying appropriate assignment levels. Third, INDUS incorporates steps that attempt to reduce biases due to database representation.

Results
INDUS is able to rapidly classify sequences in both simulated and real metagenomic sequence data sets with classification efficiency significantly higher than existing composition-based approaches. Although the classification efficiency of INDUS is observed to be comparable to those by similarity-based approaches, the binning time (as compared to alignment based approaches) is 23-33 times lower.

Conclusion
Given it's rapid execution time, and high levels of classification efficiency, INDUS is expected to be of immense interest to researchers working in metagenomics and microbial ecology.

Availability
A web-server for the INDUS algorithm is available at http://metagenomics.atc.tcs.com/INDUS/
Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer
Authors: Huijts Charlotte M , Santegoets Saskia J , van den Eertwegh Alfons J , Pijpers Laura S , Haanen John B , de Gruijl Tanja D , Verheul Henk M , van der Vliet Hans J 
Published: December 2011

Abstract

Background
For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide.

Methods/design
This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels.

Discussion
This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus.

Trial Registration
ClinicalTrials.gov Identifier NCT01462214, EudraCT number 2010-024515-13, Netherlands Trial Register number NTR3085.
A genome-wide analysis reveals that the Drosophila transcription factor Lola promotes axon growth in part by suppressing expression of the actin nucleation factor Spire
Authors: Gates Michael A , Kannan Ramakrishnan , Giniger Edward 
Published: December 2011

Abstract

Background
The phylogenetically conserved transcription factor Lola is essential for many aspects of axon growth and guidance, synapse formation and neural circuit development in Drosophila. To date it has been difficult, however, to obtain an overall view of Lola functions and mechanisms.

Results
We use expression microarrays to identify the lola-dependent transcriptome in the Drosophila embryo. We find that lola regulates the expression of a large selection of genes that are known to affect each of several lola-dependent developmental processes. Among other loci, we find lola to be a negative regulator of spire, an actin nucleation factor that has been studied for its essential role in oogenesis. We show that spire is expressed in the nervous system and is required for a known lola-dependent axon guidance decision, growth of ISNb motor axons. We further show that reducing spire gene dosage suppresses this aspect of the lola phenotype, verifying that derepression of spire is an important contributor to the axon stalling phenotype of embryonic motor axons in lola mutants.

Conclusions
These data shed new light on the molecular mechanisms of many lola-dependent processes, and also identify several developmental processes not previously linked to lola that are apt to be regulated by this transcription factor. These data further demonstrate that excessive expression of the actin nucleation factor Spire is as deleterious for axon growth in vivo as is the loss of Spire, thus highlighting the need for a balance in the elementary steps of actin dynamics to achieve effective neuronal morphogenesis.
Mechanisms of sex disparities in influenza pathogenesis
Authors: Klein Sabra L , Hodgson Andrea , Robinson Dionne P 
Published: December 2011

Abstract
Review on gender-associated immune responses to influenza viruses, which though protective following vaccination, can cause immunopathology following exposure to pathogenic viruses.
Epidemiological evidence from influenza outbreaks and pandemics reveals that morbidity and mortality are often higher for women than men. Sex differences in the outcome of influenza are age-dependent, often being most pronounced among adults of reproductive ages (18–49 years of age) and sometimes reflecting the unique state of pregnancy in females, which is a risk factor for severe disease. Small animal models of influenza virus infection illustrate that inflammatory immune responses also differ between the sexes and impact the outcome of infection, with females generating higher proinflammatory cytokine and chemokine responses and experiencing greater morbidity and mortality than males. Males and females also respond differently to influenza vaccines, with women initiating higher humoral immune responses but experiencing more adverse reactions to seasonal influenza vaccines than men. Small animal models further show that elevated immunity following vaccination in females leads to greater cross-protection against novel influenza viruses in females compared with males. Sex steroid hormones, including estradiol and testosterone, as well as genetic differences between the sexes may play roles in modulating sex differences in immune responses to influenza virus infection and vaccination. Future studies must elucidate the pathways and cellular responses that differ between the sexes and determine how best to use this knowledge to inform public health policy-makers about prophylaxis and therapeutic treatments of influenza virus infections to ensure adequate protection in both males and females.
Knowledge of mental health legislation in junior doctors training in psychiatry
Authors: Wadoo Ovais , Shah Aadil Jan , Jehaanandan Nadarajah , Laing Michelle , Agarwal Manoj , Kinderman Peter 
Published: December 2011

Aims and methodTo assess junior doctors' knowledge of the procedures involved in involuntary admission of patients detained under Sections 5(2), 2 and 3 of the Mental Health Act 1983. A semi-quantitative research study of junior trainees affiliated to two psychiatry training schemes was carried out.ResultsTrainees' knowledge of professionally relevant sections of the Mental Health Act was patchy. Knowledge correlated significantly with experience in clinical practice and with experience of using mental health legislation. Surprisingly, in-service training in mental health legislation had no effect on participants' knowledge.Clinical implicationsLack of knowledge and understanding raises the possibility of inappropriate use of the mental health legislation. This threatens patients' fundamental rights and can lead to complaints or litigation. There is a clear need to address this at an early stage in psychiatry training.