bluuebunny/crossref_metadata_2025 huggingface dataset:
Repair of the Ruptured Distal Biceps Tendon
Authors: Chavan Prithviraj R. , Duquin Thomas R. , Bisson Leslie J.
Published: July 2008

Background

Reinsertion of the acutely ruptured distal biceps is the preferred method of treatment for most patients and is designed to restore flexion and supination strength. It is not clear which, if any, method of fixation is superior or whether a 2-incision or single-incision approach is associated with fewer complications or better outcomes.

Hypotheses

(1) There is no difference in biomechanical performance between currently used fixation methods, (2) there is no difference in incidence of complications between the 2-incision and single-incision approach, and (3) there is no difference in clinical outcomes between the 2-incision and single-incision approach.

Study Design

Systematic review; Level of evidence, 4.

Methods

The authors performed a systematic review of the literature studying treatment of the ruptured distal biceps tendon to determine optimal fixation method as well as surgical approach with lowest incidence of complications and highest proportion of satisfactory results.

Results

The review identified 8 articles that had relevant biomechanical data, 23 with relevant complication data, and 19 with relevant clinical results data. EndoButton fixation performed best in comparative biomechanical studies. There was no difference in overall incidence of complications between 2-incision approaches (16%) and single-incision approaches (18%), but there were significantly more instances of significant loss of forearm rotation with the 2-incision approach. There were significantly more unsatisfactory clinical results in the 2-incision repair group (31 % vs 6%; odds ratio, 7.6; 95% confidence interval, 3.2-17.7), with the majority of unsatisfactory results in the 2-incision group due to loss of forearm rotation or rotational strength.

Conclusion

EndoButton fixation has the highest load and stiffness of currently available fixation methods. Two-incision repairs have a significantly greater proportion of unsatisfactory results than do single-incision repairs.
Deletion 2q37: An Identifiable Clinical Syndrome With Mental Retardation and Autism
Authors: Galasso Cinzia , Lo-Castro Adriana , Lalli Cristina , Nardone Anna Maria , Gullotta Francesca , Curatolo Paolo
Published: July 2008

Terminal deletion of the long arm of chromosome 2 is a rare chromosomal disorder characterized by low birth weight, delayed somatic and mental development, craniofacial defects, short neck, heart and lung congenital defects, and autistic features. We report on a girl with 46,XX.ish del(2)(q37.1) de novo karyotype, mental retardation, dysmorphic features, gastrointestinal anomalies, and autistic traits and compare her clinical manifestations with patients with the same deletion previously described in literature.
Congenital Muscle Fiber-Type Disproportion in a Patient With Congenital Central Hypoventilation Syndrome Due to PHOX2B Mutations
Authors: Khan Aneal , Sarnat Harvey B. , Spaetgens Renee
Published: July 2008

Increasing numbers of genetic origins are being reported for congenital muscle fiber-type disproportion. Most of these identified disorders are genetic myopathies. This is the first case report (to our knowledge) demonstrating congenital central hypoventilation syndrome due to PHOX2B mutations with congenital muscle fiber-type disproportion. The muscle histopathologic findings in the patient showed no changes of disuse atrophy and suggest that PHOX2B mutations may have an additional role in muscle development, contributing to respiratory failure in congenital central hypoventilation syndrome.
Severe Methylenetetrahydrofolate Reductase (MTHFR) Deficiency: A Case Report of Nonclassical Homocystinuria
Authors: Bishop Lisa , Kanoff Richard , Charnas Lawrence , Krenzel Charles , Berry Susan A. , Schimmenti Lisa A.
Published: July 2008

Severe methylenetetrahydrofolate reductase deficiency is an autosomal recessive metabolic disorder of folate metabolism causing elevated plasma homocysteine levels and homocystinuria (MIM 236250). A developmentally delayed 10-year-old girl presented with symptoms of progressive ataxia, dysarthria, tremor, mental status changes, and white-matter changes on magnetic resonance imaging. These changes occurred during a 3- to 4-month time period, with an acceleration of symptoms during 2 to 3 weeks. The patient was found to have extremely high serum homocysteine and low—normal serum methionine. She received treatment with vitamin B12, folate, betaine, multivitamins, and aspirin, with subsequent improvement of her symptoms and reduction in her serum homocysteine level. This case emphasizes the need to include homocystinuria in the differential diagnosis of children with acute/subacute neurological changes, particularly in the context of developmental delay.
Atypical Presentations of Benign Childhood Epilepsy With Centrotemporal Spikes: A Review
Authors: Kramer Uri
Published: July 2008

Benign childhood epilepsy with centrotemporal spikes is the most common epileptic syndrome in childhood. Atypical forms of benign childhood epilepsy with centrotemporal spikes are common. The different atypical forms of the condition are believed to represent a continuum of the same underlying genetic mechanism. The atypical forms of benign childhood epilepsy with centrotemporal spikes include electrical status epilepticus in slow waves sleep, Landau-Kleffner syndrome, status epilepticus of benign childhood epilepsy with centrotemporal spikes, “classic” atypical form, and others. This review delineates the different forms with emphasis on the cognitive hazards of the more malignant types.
Attention-Deficit Hyperactivity Disorder (ADHD): Does New Research Support Old Concepts?
Authors: Furman Lydia Mary
Published: July 2008

Objective: To examine the evidence for and against the classification of attention-deficit hyperactivity disorder (ADHD) as a valid disease entity, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM-IV ), criteria. Data Sources: Sources included but were not limited to published literature on ADHD accessed via PubMed (http://www.ncbi.nlm.nih.gov/PubMed/). Study Selection: Peer-reviewed research, review articles, consensus statements, “white papers,” and proceedings of professional meetings were used. Data Extraction: Focused on evidence base and scientific validity of conclusions. Data Synthesis: Evidence for a genetic or neuroanatomic cause of ADHD is insufficient. Experimental work shows that executive function deficits do not explain ADHD. The psychometric properties of widely used ADHD rating scales do not meet standards expected for disease identification. Conclusions: ADHD is unlikely to exist as an identifiable disease. Inattention, hyperactivity, and impulsivity are symptoms of many underlying treatable medical, emotional, and psychosocial conditions affecting children.
Church and Spirituality in the Lives of the African American Community
Authors: Giger Joyce Newman , Appel Susan J. , Davidhizar Ruth , Davis Claudia
Published: July 2008

The African American church is held in the highest esteem by most African Americans. Although the influence of the African American church has been underestimated by physicians and nurses, it could be pivotal in optimizing health status among African Americans. Because of this influence, health care practitioners, including nurses, are now recognizing the important role that the African American church plays in improving the health status of individuals in the African American community. This article illuminates the health and health care concerns of the African American community by considering the traditional lack of equal access for this population and the role that the church can play in not only offering church-based health care services but also improving the health status of church congregations. Future roles of the African American church for improved health status are also suggested.
Speaking About the Unspeakable
Authors: Peter Tracey
Published: July 2008

By embarking on multiple interviews with eight survivors (a total of 29 interviews), this article examines the impact of maternal sexual abuse on daughters. Although it is important to recognize the abuse that women lived through, it tells little about their struggles. Thus, as a way to honor the lives of the women interviewed, I have chosen to follow the model of Liz Kelly (1988), who focuses on the impact of sexual abuse in terms of coping, resisting, and surviving. Findings suggest that the impact of mother-daughter sexual abuse on survivors is particularly profound and experiences of maternal violence are often fraught with disbelief.
Plotting the lives of others: narrative structure in some recent British autobiography
Authors: King Nicola
Published: July 2008

Some recent British memoirs or autobiographies are discussed, focusing on narrative structure, using theories developed by Bernstein, Ricoeur, Cavarero and others to explore the relationship between `life', `story' and the effects of emplotment. Writing the lives of others, it is argued, always has an ethical dimension, as the writer is able to take advantage of the hindsight not available to his or her subjects — here parents or grandparents. The means by which the writers concerned negotiate this privilege of hindsight, and the implications of the narrative choices they inevitably have to make, are explained.
Analysing men's written friendship narratives
Authors: Guy Lauren , Montague Jane
Published: July 2008

People make sense of their lives through their narratives, which provide a set of culturally shared plots that give their lives meaning and represent belonging. A range of personal and cultural experiences is made available through analysing these narratives. Here, analysis of men's personal narratives is considered as a valuable means by which the culture of men's friendship can be explored and defined. We present a method for generating narratives, where respondents were asked in an online survey to describe a deep connection or fall-out with a friend. One of these written narratives is analysed here by adapting Labov's framework for analysing narrative in conversation and supplementing it with insights from discursive work.
What can be known and how? Narrated subjects and the Listening Guide
Authors: Doucet Andrea , Mauthner Natasha S.
Published: July 2008

This article grapples with the question of ` what can be known?' about research subjects and how we can come to know them. Set against a backdrop of theoretical tensions over the concept of subjectivity in feminist theory, our article makes a three-fold argument. First, we argue that theoretical impasses between critical and constructed subjects can be addressed through the evolving concept of a narrated subject. Second, we suggest that this concept needs to be further interrogated by asking what can be known about narrated subjects both inside and outside of narrative. Third, we argue that greater attention must be given to how narrated subjects can be operationalized within research methodology, and we suggest that an emerging interpretive approach, the Listening Guide, provides a multi-layered way of tapping into methodological, theoretical, epistemological, and ontological dimensions of the narrated subject.
Cancer narratives and methodological uncertainties
Authors: Thomas Carol
Published: July 2008

This article considers the methodological uncertainties arising in the early months of a research project that involves the secondary data analysis, using narrative analysis methods, of lengthy interview transcripts with cancer patients and their main informal carers. It revisits the particular social contexts, purposes and intentions involved in the creation of the interview transcripts, then considers the new methodological challenges involved. A sociological preference for the analysis of narrative content rather than narrative form is examined, before being set aside in favour of exploring both content and form in broader social context.
Madness to the method? Using a narrative methodology to analyse large-scale complex social phenomena
Authors: Stanley Liz
Published: July 2008

Building on earlier research, two related narrative inquiry projects were conducted, concerned with Boer (later, Afrikaner) women's testimonies of their wartime and concentration camp experiences, and with commemoration of the people who died in these camps. Putting the design into practice, and the advantages and disadvantages of the approach, are both discussed. Overall, using a narrative inquiry approach for investigating large-scale complex social phenomena, in this case connected with the rise of proto-nationalism in South Africa and women's role in it, was methodologically and analytically problematic although interesting and instructive.
Common knowledge: reflections on narratives in community
Authors: Seaton Erin E.
Published: July 2008

Drawing on ethnographic and narrative research with eighth grade students from rural New Hampshire, this article explores the rich complexity of narratives built in a communal context. In close-knit rural communities, such as the one at the center of this article, personal stories may become part of a larger communal history. As such, narratives retold as communal stories highlight the relational context in which stories are crafted and underscore the ambiguity of memory, the multiplicity of truth, and the dynamics of power within a community. Here, communal stories strip individuals of the ability to craft individual narratives, as personal stories serve to create a larger communal understanding of events and history. However, for narratives of trauma in particular, as in the case at the center of this article, communal narratives may also serve as therapeutic, lightening the burden of unspeakable knowledge through the shared experience of knowing, remembering, and retelling what might otherwise remain silent. Consequently, narrative researchers must attend to the relational context in which all stories are constructed.
Visual Studies and the Iconic Turn
Authors: Moxey Keith
Published: July 2008

What are the challenges and opportunities posed to the dominant interpretive paradigms of visual studies by the rise of a new fascination with the object? How can the study of visual culture respond to what has been variously termed a `pictorial' or an `iconic' turn? Can this phenomenological concern for the power of the image to determine its own reception be incorporated into approaches that emphasize its political implications? Is it possible to conceive of the image as both a representation and a presentation at the same time?
Veiled Subjects: Shirin Neshat and Non-liberatory Agency
Authors: Rounthwaite Adair
Published: July 2008

The controversy over Shirin Neshat's representations of Muslim women has been dominated by interpretations that use an unexamined liberatory model of agency to understand the artist and her subjects. Consequently, criticism of Neshat has become polarized by readings of Islam and women's agency as fundamentally incompatible, and the possibility of female subjects whose agency is grounded in and who aspire to Islamic values has been ignored. Using Saba Mahmood's theory of non-liberatory agency as a way to approach women's embodiment in Islamic culture, this article provides re-readings of the films Turbulent, Rapture and Fervor that suggest how Neshat's art can be read as depicting pious Islamic modes of embodiment.
The accidental nation
Authors: Lawrence Quil
Published: July 2008

In 1991 the US-led effort to evict the Iraqi Army from Kuwait produced many unintended consequences. Perhaps the most significant and the least noticed was the creation of a de facto Kurdish state in northern Iraq. The Kurdish safe haven, which was the first United Nations-approved humanitarian intervention against the will of a sovereign state, would never have come to pass without worldwide media pressure on the USA and Europe to do something about Saddam Hussein's brutal repression of the Kurdish rebellion against his regime. The Kurds did with press coverage what they had failed to achieve in decades of armed struggle. This article is an adaptation from Invisible Nation: How the Kurds' Quest for Statehood is Shaping Iraq and the Middle East, published by Walker & Company, New York, April 2008.
Foreign policy and the framing of the 2003 Iraq War in elite Swedish and US newspapers
Authors: Dimitrova Daniela V. , Strömbäck Jesper
Published: July 2008

This study investigated the framing of the Iraq War in the elite newspapers in Sweden and the USA during the official war period, 20 March—1 May 2003. The content analysis revealed significant cross-cultural differences in the framing of the war in terms of tone, frames and use of sources. The differences in framing were consistent with the characteristics of the national political environment and foreign policy stances in each country.
The death of news
Authors: Bell Martin
Published: July 2008

Martin Bell argues that war reporting as it has been practised from the time of William Howard Russell in the Crimea is no longer possible. He describes this commentary as its obituary. Twenty-first century warfare as conducted in Iraq and Afghanistan offers no foothold for independent and free-ranging journalism. Reporters are driven back into green zones and fortified compounds where they no longer have a function as eyewitnesses. Embedded reporting is so limited in scope that it serves as little more than a recruiting movie. Wars which are fought among the people are no longer reported from among the people. The news agenda has also retreated from the real world into a comfort zone of its own. A cloud of obscurity has settled over the battlefield.
The Effectiveness of Physician-Directed External Fixation Pin Site Care in Preventing Pin Site Infection in a High-Risk Patient Population
Authors: Schweinberger Monica H. , Roukis Thomas S.
Published: July 2008

Pin tract infection is one of the most frequently reported complications associated with the use of external fixation. Application of compression dressings to prevent motion at the pin-skin interface as well as periodic antiseptic cleansing of the pin sites has been advocated; however, no consensus has been reached on the most effective method of pin site care. This retrospective study was conducted to evaluate the effectiveness of a weekly, physician-directed pin site care protocol on reducing the rate of pin tract infections in a high-risk patient population.
Salvage of the First Ray With External Fixation in the High-Risk Patient
Authors: Schweinberger Monica H. , Roukis Thomas S.
Published: July 2008

In diabetic patients, hallux and first-ray amputations significantly increase the risk of recurrent ulceration and more proximal amputation over time. This small, retrospective study demonstrates that salvage of the first ray can be reliably accomplished, even in high-risk patients, when basic principles of infection management are followed in conjunction with the appropriate use of external fixation. These techniques may help to improve the quality of life and reduce the overall medical resources required for the treatment of recurrent ulceration and amputation in this patient population.
Percutaneous Distal Soft Tissue Release–Akin Procedure, Clinical and Podobarometric Assessment With the BioFoot In-Shoe System
Authors: Martínez-Nova Alfonso , Sánchez-Rodríguez Raquel , Leal-Muro Alejo , Sánchez-Barrado Emilio , Pedrera-Zamorano Juan Diego
Published: July 2008

Hallux valgus (HV) is a common, complex, and progressive deformity of the first ray, leading to biomechanical changes. The purpose of this study is to describe the midterm outcomes of the percutaneous distal soft tissue release–Akin procedure for mild hallux valgus on plantar pressures distribution, clinical outcome, and radiographic parameters. Twenty-six patients (30 feet) who had undergone this procedure were evaluated prospectively. The BioFoot in-shoe system was used for an objective functional evaluation of dynamic plantar pressures in the heel, midfoot, first through fifth metatarsal heads, hallux, and lesser toes. The clinical outcome measurements included preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) score. The radiological parameters measured were hallux abductus angle (HAA) and first intermetatarsal angle in weight-bearing radiographs. The average follow-up was 12.1 months. There were improvements in the AOFAS rating scale score from 68.7 to 88.1, in HAA from 25.4° to 11.4°, and in the first intermetatarsal angle from 12.0° to 9.2° . The pedobarographic analysis showed a statistically significant decrease (P < .001) in the maximum peak pressure (from 1037 to 498 kPa) and mean pressure (from 487 to 159 kPa) under the hallux. The percutaneous distal soft tissue release–Akin procedure improved the patients' clinical status and reduced the plantar pressures beneath the hallux. This improvement could be attributable to the removal of the medial eminence, which avoids pain around the first metatarsophalangeal joint, and to the Akin procedure, which provides a more physiological postoperative position of the hallux.
Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis
Authors: Hasan Syed Khizer , Mays Ashley N. , Ottone Tiziana , Ledda Antonio , La Nasa Giorgio , Cattaneo Chiara , Borlenghi Erika , Melillo Lorella , Montefusco Enrico , Cervera José , Stephen Christopher , Satchi Gnanam , Lennard Anne , Libura Marta , Byl Jo Ann W. , Osheroff Neil , Amadori Sergio , Felix Carolyn A. , Voso Maria Teresa , Sperr Wolfgang R. , Esteve Jordi , Sanz Miguel A. , Grimwade David , Lo-Coco Francesco
Published: July 2008

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17) translocation is a well-recognized complication of cancer treatment with agents targeting topoisomerase II. However, cases are emerging after mitoxantrone therapy for multiple sclerosis (MS). Analysis of 12 cases of mitoxantrone-related t-APL in MS patients revealed an altered distribution of chromosome 15 breakpoints versus de novo APL, biased toward disruption within PML intron 6 (11 of 12, 92% vs 622 of 1022, 61%: P = .035). Despite this intron spanning approximately 1 kb, breakpoints in 5 mitoxantrone-treated patients fell within an 8-bp region (1482-9) corresponding to the “hotspot” previously reported in t-APL, complicating mitoxantrone-containing breast cancer therapy. Another shared breakpoint was identified within the approximately 17-kb RARA intron 2 involving 2 t-APL cases arising after mitoxantrone treatment for MS and breast cancer, respectively. Analysis of PML and RARA genomic breakpoints in functional assays in 4 cases, including the shared RARA intron 2 breakpoint at 14 446-49, confirmed each to be preferential sites of topoisomerase IIα-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this subtype of leukemia after exposure to this agent.
Generation of enhanced stability factor VIII variants by replacement of charged residues at the A2 domain interface
Authors: Wakabayashi Hironao , Varfaj Fatbardha , DeAngelis Jennifer , Fay Philip J.
Published: July 2008

Factor VIII consists of a heavy chain (A1A2B domains) and light chain (A3C1C2 domains), whereas the contiguous A1A2 domains are separate subunits in the cofactor, factor VIIIa. The intrinsic instability of the cofactor results from weak affinity interactions of the A2 subunit within factor VIIIa. The charged residues Glu272, Asp519, Glu665, and Glu1984 appear buried at the interface of the A2 domain with either the A1 or A3 domain, and thus may impact protein stability. To determine the effects of these residues on procofactor/cofactor stability, these residues were individually replaced with either Ala or Val, and stable BHK cell lines expressing the B-domainless proteins were prepared. Specific activity and thrombin generation parameters for 7 of the 8 variants were more than 80% the wild-type value. Factor VIII activity at 52°C to 60°C and the decay of factor VIIIa activity after thrombin activation were monitored. Six of the 7 variants showing wild-type-like activity demonstrated enhanced stability, with the Glu1984Val variant showing a 2-fold increase in thermostability and an approximately 4- to 8-fold increase in stability of factor VIIIa. These results indicate that replacement of buried charged residues is an effective alternative to covalent modification in increasing factor VIII (VIIIa) stability.
Large-scale Gene Ontology analysis of plant transcriptome-derived sequences retrieved by AFLP technology
Authors: Botton Alessandro , Galla Giulio , Conesa Ana , Bachem Christian , Ramina Angelo , Barcaccia Gianni
Published: July 2008

Background

After 10-year-use of AFLP (Amplified Fragment Length Polymorphism) technology for DNA fingerprinting and mRNA profiling, large repertories of genome- and transcriptome-derived sequences are available in public databases for model, crop and tree species. AFLP marker systems have been and are being extensively exploited for genome scanning and gene mapping, as well as cDNA-AFLP for transcriptome profiling and differentially expressed gene cloning. The evaluation, annotation and classification of genomic markers and expressed transcripts would be of great utility for both functional genomics and systems biology research in plants. This may be achieved by means of the Gene Ontology (GO), consisting in three structured vocabularies (i.e. ontologies) describing genes, transcripts and proteins of any organism in terms of their associated cellular component, biological process and molecular function in a species-independent manner. In this paper, the functional annotation of about 8,000 AFLP-derived ESTs retrieved in the NCBI databases was carried out by using GO terminology.

Results

Descriptive statistics on the type, size and nature of gene sequences obtained by means of AFLP technology were calculated. The gene products associated with mRNA transcripts were then classified according to the three main GO vocabularies. A comparison of the functional content of cDNA-AFLP records was also performed by splitting the sequence dataset into monocots and dicots and by comparing them to all annotated ESTs of Arabidopsis and rice, respectively. On the whole, the statistical parameters adopted for the in silico AFLP-derived transcriptome-anchored sequence analysis proved to be critical for obtaining reliable GO results. Such an exhaustive annotation may offer a suitable platform for functional genomics, particularly useful in non-model species.

Conclusion

Reliable GO annotations of AFLP-derived sequences can be gathered through the optimization of the experimental steps and the statistical parameters adopted. The Blast2GO software was shown to represent a comprehensive bioinformatics solution for an annotation-based functional analysis. According to the whole set of GO annotations, the AFLP technology generates thorough information for angiosperm gene products and shares common features across angiosperm species and families. The utility of this technology for structural and functional genomics in plants can be implemented by serial annotation analyses of genome-anchored fragments and organ/tissue-specific repertories of transcriptome-derived fragments.
Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer
Authors: Heinonen Henna , Nieminen Anni , Saarela Matti , Kallioniemi Anne , Klefström Juha , Hautaniemi Sampsa , Monni Outi
Published: July 2008

Background

The 70 kDa ribosomal protein S6 kinase (RPS6KB1), located at 17q23, is amplified and overexpressed in 10–30% of primary breast cancers and breast cancer cell lines. p70S6K is a serine/threonine kinase regulated by PI3K/mTOR pathway, which plays a crucial role in control of cell cycle, growth and survival. Our aim was to determine p70S6K and PI3K/mTOR/p70S6K pathway dependent gene expression profiles by microarrays using five breast cancer cell lines with predefined gene copy number and gene expression alterations. The p70S6K dependent profiles were determined by siRNA silencing of RPS6KB1 in two breast cancer cell lines overexpressing p70S6K. These profiles were further correlated with gene expression alterations caused by inhibition of PI3K/mTOR pathway with PI3K inhibitor Ly294002 or mTOR inhibitor rapamycin.

Results

Altogether, the silencing of p70S6K altered the expression of 109 and 173 genes in two breast cancer cell lines and 67 genes were altered in both cell lines in addition to RPS6KB1. Furthermore, 17 genes including VTCN1 and CDKN2B showed overlap with genes differentially expressed after PI3K or mTOR inhibition. The gene expression signatures responsive to both PI3K/mTOR pathway and p70S6K inhibitions revealed previously unidentified genes suggesting novel downstream targets for PI3K/mTOR/p70S6K pathway.

Conclusion

Since p70S6K overexpression is associated with aggressive disease and poor prognosis of breast cancer patients, the potential downstream targets of p70S6K and the whole PI3K/mTOR/p70S6K pathway identified in our study may have diagnostic value.
Structural characterization of CA1462, the Candida albicans thiamine pyrophosphokinase
Authors: Santini Sébastien , Monchois Vincent , Mouz Nicolas , Sigoillot Cécile , Rousselle Tristan , Claverie Jean-Michel , Abergel Chantal
Published: July 2008

Background

In search of new antifungal targets of potential interest for pharmaceutical companies, we initiated a comparative genomics study to identify the most promising protein-coding genes in fungal genomes. One criterion was the protein sequence conservation between reference pathogenic genomes. A second criterion was that the corresponding gene in Saccharomyces cerevisiae should be essential. Since thiamine pyrophosphate is an essential product involved in a variety of metabolic pathways, proteins responsible for its production satisfied these two criteria.

Results

We report the enzymatic characterization and the crystallographic structure of the Candida albicans Thiamine pyrophosphokinase. The protein was co-crystallized with thiamine or thiamine-PNP.

Conclusion

The presence of an inorganic phosphate in the crystallographic structure opposite the known AMP binding site relative to the thiamine moiety suggests that a second AMP molecule could be accommodated in the C. albicans structure. Together with the crystallographic structures of the enzyme/substrate complexes this suggests the existence of a secondary, less specific, nucleotide binding site in the Candida albicans thiamine pyrophosphokinase which could transiently serve during the release or the binding of ATP. The structures also highlight a conserved Glutamine residue (Q138) which could interact with the ATP α-phosphate and act as gatekeeper. Finally, the TPK/Thiamine-PNP complex is consistent with a one step mechanism of pyrophosphorylation.
Automated de-identification of free-text medical records
Authors: Neamatullah Ishna , Douglass Margaret M , Lehman Li-wei H , Reisner Andrew , Villarroel Mauricio , Long William J , Szolovits Peter , Moody George B , Mark Roger G , Clifford Gari D
Published: July 2008

Background

Text-based patient medical records are a vital resource in medical research. In order to preserve patient confidentiality, however, the U.S. Health Insurance Portability and Accountability Act (HIPAA) requires that protected health information (PHI) be removed from medical records before they can be disseminated. Manual de-identification of large medical record databases is prohibitively expensive, time-consuming and prone to error, necessitating automatic methods for large-scale, automated de-identification.

Methods

We describe an automated Perl-based de-identification software package that is generally usable on most free-text medical records, e.g., nursing notes, discharge summaries, X-ray reports, etc. The software uses lexical look-up tables, regular expressions, and simple heuristics to locate both HIPAA PHI, and an extended PHI set that includes doctors' names and years of dates. To develop the de-identification approach, we assembled a gold standard corpus of re-identified nursing notes with real PHI replaced by realistic surrogate information. This corpus consists of 2,434 nursing notes containing 334,000 words and a total of 1,779 instances of PHI taken from 163 randomly selected patient records. This gold standard corpus was used to refine the algorithm and measure its sensitivity. To test the algorithm on data not used in its development, we constructed a second test corpus of 1,836 nursing notes containing 296,400 words. The algorithm's false negative rate was evaluated using this test corpus.

Results

Performance evaluation of the de-identification software on the development corpus yielded an overall recall of 0.967, precision value of 0.749, and fallout value of approximately 0.002. On the test corpus, a total of 90 instances of false negatives were found, or 27 per 100,000 word count, with an estimated recall of 0.943. Only one full date and one age over 89 were missed. No patient names were missed in either corpus.

Conclusion

We have developed a pattern-matching de-identification system based on dictionary look-ups, regular expressions, and heuristics. Evaluation based on two different sets of nursing notes collected from a U.S. hospital suggests that, in terms of recall, the software out-performs a single human de-identifier (0.81) and performs at least as well as a consensus of two human de-identifiers (0.94). The system is currently tuned to de-identify PHI in nursing notes and discharge summaries but is sufficiently generalized and can be customized to handle text files of any format. Although the accuracy of the algorithm is high, it is probably insufficient to be used to publicly disseminate medical data. The open-source de-identification software and the gold standard re-identified corpus of medical records have therefore been made available to researchers via the PhysioNet website to encourage improvements in the algorithm.
Increased plasma apoM levels in the patients suffered from hepatocellular carcinoma and other chronic liver diseases
Authors: Jiang Jingting , Zhang Xiaoying , Wu Changping , Qin Xihu , Luo Guanghua , Deng Haifeng , Lu Minyang , Xu Bin , Li Min , Ji Mei , Xu Ning
Published: July 2008

Objective

To determine plasma apolipoprotein M (apoM) levels and other lipid profiles in hepatocellular carcinoma (HCC) patients compared to other chronic liver diseases and normal subjects.

Materials and methods

36 HCC, 68 chronic hepatitis, 29 liver cirrhosis patients and 64 normal controls were subjected in the present study. Serum lipids, lipoproteins, apolipoprotein AI (apoAI) and apoB were determined by the conventional methods. Plasma apoM levels were semi-quantitatively determined by both dot-blotting and western blotting analysis.

Results

Serum levels of triglycerides (TG), HDL-cholesterol, apoAI and lipoprotein (a) (Lp(a)) were significantly lower in the HCC patients than in the normal subjects, whereas there were no obvious differences on serum total cholesterol, LDL-cholesterol and apoB between HCC patients and normal subjects. However, plasma apoM levels in HCC patients were significantly increased than those in the normal subjects, but lower than those in the chronic hepatitis and cirrhosis patients.

Conclusion

It is concluded that serum TG, apoAI, HDL-C and Lp(a) were significantly decreased in HCC patients than in controls, whereas plasma apoM levels were significantly increased in the HCC patients. Decreased serum TG, apoAI, HDL-C and Lp(a) may reflect the liver damage in HCC patients, whereas the clinical significance of increased plasma apoM levels in relation to HCC is not clear.
Characterization of eight novel proteins with male germ cell-specific expression in mouse
Authors: Baek Namhoe , Woo Jong-Min , Han Cecil , Choi Eunyoung , Park Inju , Kim Do Han , Eddy Edward M , Cho Chunghee
Published: July 2008

Background

Spermatogenesis and fertilization are highly unique processes. Discovery and characterization of germ cell-specific genes are important for the understanding of these reproductive processes. We investigated eight proteins encoded by novel spermatogenic cell-specific genes previously identified from the mouse round spermatid UniGene library.

Methods

Polyclonal antibodies were generated against the novel proteins and western blot analysis was performed with various protein samples. Germ cell specificity was investigated using testes from germ cell-less mutant mice. Developmental expression pattern was examined in testicular germ cells, testicular sperm and mature sperm. Subcellular localization was assessed by cell surface biotin labeling and trypsinization. Protein localization and properties in sperm were investigated by separation of head and tail fractions, and extractabilities by a non-ionic detergent and urea.

Results

The authenticity of the eight novel proteins and their specificity to spermatogenic cells were confirmed. In examining the developmental expression patterns, we found the presence of four proteins only in testicular germ cells, a single protein in testicular germ cells and testicular sperm, and three proteins in the testicular stages and mature sperm from the epididymis. Further analysis of the three proteins present in sperm disclosed that one is located at the surface of the acrosomal region and the other two are associated with cytoskeletal structures in the sperm flagellum. We name the genes for these sperm proteins Shsp1 (Sperm head surface protein 1), Sfap1 (Sperm flagellum associated protein 1) and Sfap2 (Sperm flagellum associated protein 2).

Conclusion

We analyzed eight novel germ cell-specific proteins, providing new and inclusive information about their developmental and cellular characteristics. Our findings will facilitate future investigation into the biological roles of these novel proteins in spermatogenesis and sperm functions.
Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways
Authors: Agbottah Emmanuel , Yeh Wen-I , Berro Reem , Klase Zachary , Pedati Caitlin , Kehn-Hall Kyleen , Wu Weilin , Kashanchi Fatah
Published: July 2008

Human T-cell leukemia virus type-1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATL/L), a fatal lymphoproliferative disorder, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive disease of the central nervous system after a long period of latent infection. Although the mechanism of transformation and leukemogenesis is not fully elucidated, there is evidence to suggest that the viral oncoprotein Tax plays a crucial role in these processes through the regulation of several pathways including NF-κB and the cell cycle pathways. The observation that NF-κB, which is strongly induced by Tax, is indispensable for the maintenance of the malignant phenotype of HTLV-1 by regulating the expression of various genes involved in cell cycle regulation and inhibition of apoptosis provides a possible molecular target for these infected cells. To develop potential new therapeutic strategies for HTLV-1 infected cells, in this present study, we initially screened a battery of NF-κB and CDK inhibitors (total of 35 compounds) to examine their effects on the growth and survival of infected T-cell lines. Two drugs namely BMS-345541 and Purvalanol A exhibited higher levels of growth inhibition and apoptosis in infected cell as compared to uninfected cells. BMS-345541 inhibited IKKβ kinase activity from HTLV-1 infected cells with an IC50 (the 50% of inhibitory concentration) value of 50 nM compared to 500 nM from control cells as measured by in vitro kinase assays. The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. Combination of both BMS-345541 and Purvalanol A showed a reduced level of HTLV-1 p19 Gag production in cell culture. The apparent apoptosis in these infected cells were associated with increased caspase-3 activity and PARP cleavage. The potent and selective apoptotic effects of these drugs suggest that both BMS-345541 and Purvalanol A, which target both NF-κB and CDK complex and the G1/S border, might be promising new agents in the treatment of these infected patients.
Machine learning based analyses on metabolic networks supports high-throughput knockout screens
Authors: Plaimas Kitiporn , Mallm Jan-Phillip , Oswald Marcus , Svara Fabian , Sourjik Victor , Eils Roland , König Rainer
Published: July 2008

Background

Computational identification of new drug targets is a major goal of pharmaceutical bioinformatics.

Results

This paper presents a machine learning strategy to study and validate essential enzymes of a metabolic network. Each single enzyme was characterized by its local network topology, gene homologies and co-expression, and flux balance analyses. A machine learning system was trained to distinguish between essential and non-essential reactions. It was validated by a comprehensive experimental dataset, which consists of the phenotypic outcomes from single knockout mutants of Escherichia coli (KEIO collection). We yielded very reliable results with high accuracy (93%) and precision (90%). We show that topologic, genomic and transcriptomic features describing the network are sufficient for defining the essentiality of a reaction. These features do not substantially depend on specific media conditions and enabled us to apply our approach also for less specific media conditions, like the lysogeny broth rich medium.

Conclusion

Our analysis is feasible to validate experimental knockout data of high throughput screens, can be used to improve flux balance analyses and supports experimental knockout screens to define drug targets.
Henry Woltman (1889–1964): pioneering American neurologist
Authors: Todman Don
Published: July 2008

Henry Woltman became the first neurologist at the Mayo Clinic in Rochester, Minnesota at a time when there were few practitioners working full-time in this field in North America. The remarkable growth in the neurology section at Mayo mirrored the expansion that occurred in the Mayo Clinic in the early 20th century. His leadership was instrumental in establishing neurology as a viable specialty, distinct from psychiatry and aligned more closely with internal medicine. The distinctive features he instituted included an original scoring and notation system, and a close collaboration with neurosurgery. He is also remembered for Woltman's sign, the finding of slow relaxation of the muscle when the tendon reflex is elicited in hypothyroidism.
Alexandre Yersin (1863–1943): discoverer of the plague bacillus, explorer and agronomist
Authors: Hawgood Barbara J
Published: July 2008

Alexandre Yersin was born in French Switzerland and later took French nationality. While a medical student he worked in Paris with Emile Roux to discover the exotoxin produced by the diphtheria bacillus. Two years after graduation, he left Paris for French Indochina where he was the first European to explore and map the central highlands of Vietnam. As a member of the French Colonial Health Service he was sent to Hong Kong in 1894 to investigate the outbreak of bubonic plague. He isolated from buboes the causative bacillus that later was named Yersinia pestis in his honour. In Vietnam, Yersin established a Pasteur Institute at the coastal village of Nha Trang where he lived for the rest of his life. He developed vaccines and antisera for both men and animals and, as an agronomist, he introduced the Brazilian rubber tree and Peruvian cinchona tree (for quinine) into the country. In Vietnam, as in France, the name of Yersin continues to be venerated.
C Walton Lillehei (1918–99): the versatile pioneer of open-heart surgery
Authors: Banerjee Ashis
Published: July 2008

Walton Lillehei can be truly regarded as the ‘Father of Open-Heart Surgery’. His career demonstrates the virtues of tenacity and the ability to overcome adversity and opposition in the taking forward of significant innovation.
The marriage (1878) of Emile Roux (1853–1933) and Rose Anna Shedlock (b. c. 1850)
Authors: Mcintyre Neil
Published: July 2008

The great French scientist Emile Roux is widely believed to have been a confirmed bachelor, who on occasion expressed his antipathy towards marriage. However, UK records show that in August 1878 he married Rose Anna Shedlock in London. Her subsequent fate is unknown. While Roux became famous, his marriage remained a secret.
Social rejection in social anxiety disorder: The role of performance deficits, evoked negative emotions and dissimilarity
Authors: Voncken Marisol J. , Alden Lynn E. , Bögels Susan M. , Roelofs Jeffrey
Published: July 2008

Objectives

Patients with social anxiety disorder (SAD) not only fear social rejection, but accumulating evidence also shows that they are indeed less liked than their non‐anxious counterparts. Three factors are hypothesized to play a role in this social anxiety–social rejection relationship: (1) social performance; (2) elicited negative emotions, and (3) perceived similarity.

Method

Patients with SAD (N = 63) and control participants (N = 27) were observed during a 5 minutes ‘getting acquainted’ conversation with a male and female confederate who rated their social performance. Video‐observers rated their own negative emotions and perceived similarity with the patients, while other video‐observers rated their wish to engage in future contact with them (a measure of social rejection).

Results

Analysed by way of structural equation modelling (SEM), the results supported the social anxiety–social rejection relationship. More specifically, poor social performance was associated with perceived dissimilarity ratings and mediated by evoked negative emotions, both of which were in turn associated with social rejection.

Conclusion

These results suggest that a sequence of events links social anxiety to social rejection. Treatment should aim to improve social performance and perceived similarity to reverse SAD's vicious, negative interpersonal cycle.
Defected/decorated benzenoid/graphitic nanostructures
Authors: Klein D. J.
Published: July 2008

Various decorations, functionalizations, or defects of conjugated benzenoid or graphitic networks are considered, with special attention to the case that the structures are possibly extended in one or two dimensions. This includes various polymers, their end structures, and defects of side groups or vacancies along the chain, strip, or nanotube. This approach further includes various boundary (or edge) structures on semi-infinite graphite, as well as various "quasi-local" defects in what is otherwise two-dimensionally infinite graphite, such defects encompassing vacancy defects, selected substitutional defects, and perhaps even dislocations and disclinations. There are many possible such nanostructures, but property characterization is ultimately desired. Attention is paid to consequent occurrences of defect-localized unpaired (or weakly paired) electrons, as formulated within a resonating valence bond (RVB) framework, especially as regards simple classically appealing theorems or rules. But a further molecular orbital (MO) view is developed. Note is made of associated modifications in the local density of states near the Fermi energy. Consonance of predictions from RVB and MO viewpoints is taken as an indicator of reliable prediction.