bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0
Authors: Soggia Ana Priscila , Correa-Giannella Maria Lúcia , Fortes Maria Angela Henriques , Luna Ana Mercedes Cavaleiro , Pereira Maria Adelaide Albergaria 
Published: January 2010

Abstract

Background
Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver.

Case Presentation
Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the GYS2 gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c.736 C>T; R243X) and a novel frameshift mutation (966_967delGA/insC) which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion.

Conclusion
The current results expand the spectrum of known mutations in GYS2 and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions.
Long-term follow-up of beryllium sensitized workers from a single employer
Authors: Duggal Mona , Deubner David C , Curtis Anne M , Cullen Mark R 
Published: January 2010

Abstract

Background
Up to 12% of beryllium-exposed American workers would test positive on beryllium lymphocyte proliferation test (BeLPT) screening, but the implications of sensitization remain uncertain.

Methods
Seventy two current and former employees of a beryllium manufacturer, including 22 with pathologic changes of chronic beryllium disease (CBD), and 50 without, with a confirmed positive test were followed-up for 7.4 +/-3.1 years.

Results
Beyond predicted effects of aging, flow rates and lung volumes changed little from baseline, while DLCO dropped 17.4% of predicted on average. Despite this group decline, only 8 subjects (11.1%) demonstrated physiologic or radiologic abnormalities typical of CBD. Other than baseline status, no clinical or laboratory feature distinguished those who clinically manifested CBD at follow-up from those who did not.

Conclusions
The clinical outlook remains favorable for beryllium-sensitized individuals over the first 5-12 years. However, declines in DLCO may presage further and more serious clinical manifestations in the future. These conclusions are tempered by the possibility of selection bias and other study limitations.
Long-term prognosis of diabetic patients with acute myocardial infarction in the era of acute revascularization
Authors: Takara Ayako , Ogawa Hiroshi , Endoh Yasuhiro , Mori Fumiaki , Yamaguchi Jun-ichi , Takagi Atsushi , Koyanagi Ryo , Shiga Tsuyoshi , Kasanuki Hiroshi , Hagiwara Nobuhisa 
Published: January 2010

Abstract

Background
The long-term prognosis of diabetic patients with acute myocardial infarction (AMI) treated by acute revascularization is uncertain, and the optimal pharmacotherapy for such cases has not been fully evaluated.

Methods
To elucidate the long-term prognosis and prognostic factors in diabetic patients with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was conducted. All patients discharged alive from hospital were followed to monitor their prognosis every year. The primary endpoint of the study was all-cause mortality, and the secondary endpoint was the occurrence of major cardiovascular events. To elucidate the effect of various factors on the long-term prognosis of AMI patients with diabetes, the patients were divided into two groups matched by propensity scores and analyzed retrospectively.

Results
Diabetes was diagnosed in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty and coronary thrombolysis were performed in 58.1% and 16.3% of patients, respectively. In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total, 2736 patients (90.6%) were discharged alive and followed for a median of 4.2 years (follow-up rate, 96.0%). The long-term survival rate was worse in the diabetic group than in the non-diabetic group, but not significantly different (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group (1.40 [1.20-1.64], p < 0.0001). Multivariate analysis revealed that three factors were significantly associated with favorable late outcomes in diabetic AMI patients: acute revascularization (HR, 0.62); prescribing aspirin (HR, 0.27); and prescribing renin-angiotensin system (RAS) inhibitors (HR, 0.53). There was no significant correlation between late outcome and prescription of beta-blockers (HR, 0.97) or calcium channel blockers (HR, 1.27). Although standard Japanese-approved doses of statins were associated with favorable outcome in AMI patients with diabetes, this was not statistically significant (0.67 [0.39-1.06], p = 0.11).

Conclusions
Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI, the present results suggest that acute revascularization and standard therapy with aspirin and RAS inhibitors may improve their prognosis.
Geocoding police collision report data from California: a comprehensive approach
Authors: Bigham John M , Rice Thomas M , Pande Swati , Lee Junhak , Park Shin Hyoung , Gutierrez Nicolas , Ragland David R 
Published: January 2010

Abstract

Background
Collision geocoding is the process of assigning geographic descriptors, usually latitude and longitude coordinates, to a traffic collision record. On California police reports, relative collision location is recorded using a highway postmile marker or a street intersection. The objective of this study was to create a geocoded database of all police-reported, fatal and severe injury collisions in the California Statewide Integrated Traffic Records System (SWITRS) for years 1997-2006 for use by public agencies.

Results
Geocoding was completed with a multi-step process. First, pre-processing was performed using a scripting language to clean and standardize street name information. A state highway network with postmile values was then created using a custom tool written in Visual Basic for Applications (VBA) in ArcGIS software. Custom VBA functionality was also used to incorporate the offset direction and distance. Intersection and address geocoding was performed using ArcGIS, StreetMap Pro 2003 digital street network, and Google Earth Pro. A total of 142,007 fatal and severe injury collisions were identified in SWITRS. The geocoding match rate was 99.8% for postmile-coded collisions and 86% for intersection-coded collisions. The overall match rate was 91%.

Conclusions
The availability of geocoded collision data will be beneficial to clinicians, researchers, policymakers, and practitioners in the fields of traffic safety and public health. Potential uses of the data include studies of collision clustering on the highway system, examinations of the associations between collision occurrence and a variety of variables on environmental and social characteristics, including housing and personal demographics, alcohol outlets, schools, and parks. The ability to build maps may be useful in research planning and conduct and in the delivery of information to both technical and non-technical audiences.
THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo
Authors: Mancini Annalisa , Niemann-Seyde Susanne C , Pankow Rüdiger , El Bounkari Omar , Klebba-Färber Sabine , Koch Alexandra , Jaworska Ewa , Spooncer Elaine , Gruber Achim D , Whetton Anthony D , Tamura Teruko 
Published: January 2010

Abstract

Background
The transcription/export complex is evolutionarily conserved from yeast to man and is required for coupled transcription elongation and nuclear export of mRNAs. FMIP(Fms interacting protein) is a member of the THO (suppressors of the transcriptional defects of hpr1delta by overexpression) complex which is a subcomplex of the transcription/export complex. THO complex (THOC) components are not essential for bulk poly (A)+ RNA export in higher eukaryotes, but for the nuclear export of subset of mRNAs, however, their exact role is still unclear.

Results
To study the role of THOC5/Fms interacting protein in vivo, we generated THOC5/Fms interacting protein knockout mice. Since these mice are embryonic lethal, we then generated interferon inducible conditional THOC5/Fms interacting protein knockout mice. After three poly injections all of the mice died within 14 days. No pathological alterations, however, were observed in liver, kidney or heart. Thus we considered the hematopoietic system and found that seven days after poly injection, the number of blood cells in peripheral blood decreased drastically. Investigation of bone marrow cells showed that these became apoptotic within seven days after poly injection. Committed myeloid progenitor cells and cells with long term reconstituting potential were lost from bone marrow within four days after poly injection. Furthermore, infusion of normal bone marrow cells rescued mice from death induced by loss of THOC5/Fms interacting protein.

Conclusion
THOC5/Fms interacting protein is an essential element in the maintenance of hematopoiesis. Furthermore, mechanistically depletion of THOC5/Fms interacting protein causes the down-regulation of its direct interacting partner, THOC1 which may contribute to altered THO complex function and cell death.
Mimosa: Mixture model of co-expression to detect modulators of regulatory interaction
Authors: Hansen Matthew , Everett Logan , Singh Larry , Hannenhalli Sridhar 
Published: January 2010

Abstract

Background
Functionally related genes tend to be correlated in their expression patterns across multiple conditions and/or tissue-types. Thus co-expression networks are often used to investigate functional groups of genes. In particular, when one of the genes is a transcription factor (TF), the co-expression-based interaction is interpreted, with caution, as a direct regulatory interaction. However, any particular TF, and more importantly, any particular regulatory interaction, is likely to be active only in a subset of experimental conditions. Moreover, the subset of expression samples where the regulatory interaction holds may be marked by presence or absence of a modifier gene, such as an enzyme that post-translationally modifies the TF. Such subtlety of regulatory interactions is overlooked when one computes an overall expression correlation.

Results
Here we present a novel mixture modeling approach where a TF-Gene pair is presumed to be significantly correlated (with unknown coefficient) in an (unknown) subset of expression samples. The parameters of the model are estimated using a Maximum Likelihood approach. The estimated mixture of expression samples is then mined to identify genes potentially modulating the TF-Gene interaction. We have validated our approach using synthetic data and on four biological cases in cow, yeast, and humans.

Conclusions
While limited in some ways, as discussed, the work represents a novel approach to mine expression data and detect potential modulators of regulatory interactions.
Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells
Authors: Bowen Nathan J , Walker L DeEtte , Matyunina Lilya V , Logani Sanjay , Totten Kimberly A , Benigno Benedict B , McDonald John F 
Published: January 2010

AbstractBackgroundAccumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE) and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube.MethodsComparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI) isolated by laser capture micro-dissection (LCM) from human serous papillary ovarian adenocarcinomas. The results of the gene expression analyses were randomly confirmed in paraffin embedded tissues from ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using immunohistochemistry. Differentially expressed genes were analyzed using gene ontology, molecular pathway, and gene set enrichment analysis algorithms.ResultsConsistent with multipotent capacity, genes in pathways previously associated with adult stem cell maintenance are highly expressed in ovarian surface epithelia and are not expressed or expressed at very low levels in serous ovarian adenocarcinoma. Among the over 2000 genes that are significantly differentially expressed, a number of pathways and novel pathway interactions are identified that may contribute to ovarian adenocarcinoma development.ConclusionsOur results are consistent with the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as the origin of ovarian adenocarcinoma. While our findings do not rule out the possibility that ovarian cancers may also arise from other sources, they areinconsistentwith claims that ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating cells.
Expression of semaphorin 3A and its receptors in the human intervertebral disc: potential role in regulating neural ingrowth in the degenerate intervertebral disc
Authors: Tolofari Sotonye K , Richardson Stephen M , Freemont Anthony J , Hoyland Judith A 
Published: January 2010

Abstract
Introduction
Intervertebral disc (IVD) degeneration is considered a major underlying factor in the pathogenesis of chronic low back pain. Although the healthy IVD is both avascular and aneural, during degeneration there is ingrowth of nociceptive nerve fibres and blood vessels into proximal regions of the IVD, which may contribute to the pain. The mechanisms underlying neural ingrowth are, however, not fully understood. Semaphorin 3A (sema3A) is an axonal guidance molecule with the ability to repel nerves seeking their synaptic target. This study aimed to identify whether members of the Class 3 semaphorins were expressed by chondrocyte-like cells of the IVD addressing the hypothesis that they may play a role in repelling axons surrounding the healthy disc, thus maintaining its aneural condition.

Methods
Human IVD samples were investigated using reverse transcription polymerase chain reaction (RT-PCR) to identify gene expression of sema3A, 3F and their receptors: neuropilins (1 and 2) and plexins (A1-4). Sema3A protein was also localised within sections of normal and degenerate human IVD and immunopositivity quantified. Serial sections were stained using PGP9.5 and CD31 to correlate semaphorin 3A expression with nerve and blood vessel ingrowth, respectively.

Results
Sema3A protein was expressed highly in the healthy disc, primarily localised to the outer annulus fibrosus. In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues. CD31 and PGP9.5 were expressed most highly in degenerate tissues correlating with low expression of sema3A.

Conclusions
This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD. Sema3A may therefore, amongst other roles, act as a barrier to neuronal ingrowth within the healthy disc.
Intensivists' base specialty of training is associated with variations in mortality and practice patterns
Authors: Billington Emma O , Zygun David A , Stelfox H Tom , Peets Adam D 
Published: January 2010

Abstract
Introduction
Current evidence regarding whether the staffing of intensive care units (ICUs) with a trained Intensivist benefits patient outcomes is discordant. We sought to determine whether, among certified Intensivists, base specialty of training could contribute to variation in practice patterns and patient outcomes in ICUs.

Methods
The records of all patients who were admitted to one of three closed multi-system ICUs within tertiary care centers in the Calgary Health Region, Alberta, Canada, during a five year period were retrospectively reviewed. Outcomes for patients admitted by Intensivists with base training in General Internal Medicine, Pulmonary Medicine, or other eligible base specialties (Anesthesia, General Surgery, and Emergency Medicine combined) were compared.

Results
ICU mortality in the entire cohort (n = 9,808) was 17.2% and in-hospital mortality was 32.0%. After controlling for potential confounders, ICU mortality (odds ratio (OR): 0.69; 95% confidence interval (CI): 0.52 to 0.94) was significantly lower for patients admitted by Intensivists with Pulmonary Medicine as a base specialty of training, but not ICU length of stay (LOS) (coefficient: 0.11; -0.20 to 0.42) or hospital mortality (OR: 0.88; 0.68 to 1.13). There was no difference in ICU or hospital mortality or length of stay between the three base specialty groups for patients who were admitted and managed by a single Intensivist for their entire ICU admission (n = 4,612). However, we identified significant variation in practice patterns between the three specialty groups for the number of invasive procedures performed and decisions to limit life-sustaining therapies.

Conclusions
Intensivists' base specialty of training is associated with practice pattern variations. This may contribute to differences in processes and outcomes of patient care.
Olive Tree community treatment centre for individuals with personality disorder: naturalistic service evaluation
Authors: Pretorius Johannes L. , Albeniz Alberto , Broome Matthew 
Published: January 2010

Aims and methodCommunity treatment for individuals with personality disorder is a fast developing field. We report here on the effectiveness of one such approach. We examine the referral pathway of all clients between January 2005 and April 2008, including the mean days spent in our unit, the days spent in a psychiatric hospital before and after admission to our unit, and the results of changes in the rating scales we routinely use.ResultsDrop-out rates and the mean duration of therapy were acceptable. There has been a clear reduction of in-patient bed use and a small but significant improvement of most psychometric test results.Clinical implicationsThis study provides further evidence for the effectiveness of community treatment for individuals with personality disorder.
Current role of service increment for teaching funding in psychiatry
Authors: Dave Subodh , Dogra Nisha , Leask Stuart J. 
Published: January 2010

SummaryUniversities are the main provider of medical student education in the UK; however, its delivery, especially the clinical years but increasingly also the pre-clinical years, often takes place in National Health Service hospitals. Trusts are paid for this privilege through service increment for teaching (SIFT). Developments in clinical governance structures have meant that there is now increased scrutiny and transparency in the funding of clinical services. Lack of similarly robust educational governance structures has led to the risk of educational funds being used to deliver clinical services. This paper examines the current role of SIFT funding and the possible ways forward, using a case study.
Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP
Authors: Evens Andrew M. , Sehn Laurie H. , Farinha Pedro , Nelson Beverly P. , Raji Adekunle , Lu Yi , Brakman Adam , Parimi Vamsi , Winter Jane N. , Schumacker Paul T. , Gascoyne Randy D. , Gordon Leo I. 
Published: January 2010

PurposeHypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1α in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated.Patients and MethodsWe studied the immunohistochemical protein expression of HIF-1α on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome.ResultsMedian follow-up for all patients was 80 months. Among all patients, HIF-1α was expressed in 62% of germinal center and 59% of non–germinal center patients. With HIF-1α analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1α protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1α–positive patients was 71% v 43% for HIF-1α–negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1α remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1α correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1α and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2).ConclusionThe expression of HIF-1α protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.
Evaluation of errors in a clinical laboratory: a one-year experience
Authors: Goswami Binita , Singh Bhawna , Chawla Ranjna , Mallika Venkatesan 
Published: January 2010

Abstract

Background: Efficient laboratory service is the cornerstone of modern health care systems. Scientific innovations have contributed to substantial improvements in the field of laboratory science, but errors still prevail. These errors are classified as preanalytical, analytical and postanalytical, depending upon the time of presentation.

Methods: The data for 67,438 routine venous blood specimens were scrutinized, and errors were documented over the period of 1 year in the clinical biochemistry laboratory of Govind Ballabh Pant Hospital in Delhi, India.

Results: Preanalytical errors were most common, with a frequency of 77.1% followed by postanalytical 15% and analytical 7.9%, respectively.

Conclusions: Our study illustrates the importance of proper venipuncture procedures, analytical expertise and correct transcription of numerical data for precise and accurate reporting of results to clinicians. There is an urgent need for close inter-departmental cooperation to meet the goal of ensuring patient well being.
Clin Chem Lab Med 2010;48:63–6.