bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I diagnose and treat splenic lymphomas
Authors: Iannitto Emilio , Tripodo Claudio 
Published: December 2010

AbstractThe incidental finding of an isolated splenomegaly during clinical assessment of patients evaluated for unrelated causes has become increasingly frequent because of the widespread use of imaging. Therefore, the challenging approach to the differential diagnosis of spleen disorders has emerged as a rather common issue of clinical practice. A true diagnostic dilemma hides in distinguishing pathologic conditions primarily involving the spleen from those in which splenomegaly presents as an epiphenomenon of hepatic or systemic diseases. Among the causes of isolated splenomegaly, lymphoid malignancies account for a relevant, yet probably underestimated, number of cases. Splenic lymphomas constitute a wide and heterogeneous array of diseases, whose clinical behavior spans from indolent to highly aggressive. Such a clinical heterogeneity is paralleled by the high degree of biologic variation in the lymphoid populations from which they originate. Nevertheless, the presenting clinical, laboratory, and pathologic features of these diseases often display significant overlaps. In this manuscript, we present our approach to the diagnosis and treatment of these rare lymphomas, whose complexity has been so far determined by the lack of prospectively validated prognostic systems, treatment strategies, and response criteria.
The Fer tyrosine kinase regulates interactions of Rho GDP-Dissociation Inhibitor α with the small GTPase Rac
Authors: Fei Fei , Kweon Soo-Mi , Haataja Leena , De Sepulveda Paulo , Groffen John , Heisterkamp Nora 
Published: December 2010

Abstract

Background
RhoGDI proteins are important regulators of the small GTPase Rac, because they shuttle Rac from the cytoplasm to membranes and also protect Rac from activation, deactivation and degradation. How the binding and release of Rac from RhoGDI is regulated is not precisely understood.

Results
We report that the non-receptor tyrosine kinase Fer is able to phosphorylate RhoGDIα and form a direct protein complex with it. This interaction is mediated by the C-terminal end of RhoGDIα. Activation of Fer by reactive oxygen species caused increased phosphorylation of RhoGDIα and pervanadate treatment further augmented this. Tyrosine phosphorylation of RhoGDIα by Fer prevented subsequent binding of Rac to RhoGDIα, but once a RhoGDIα-Rac complex was formed, the Fer kinase was not able to cause Rac release through tyrosine phosphorylation of preformed RhoGDIα-Rac complexes.

Conclusions
These results identify tyrosine phosphorylation of RhoGDIα by Fer as a mechanism to regulate binding of RhoGDIα to Rac.
A Bayesian approach for identifying miRNA targets by combining sequence prediction and gene expression profiling
Authors: Liu Hui , Yue Dong , Zhang Lin , Chen Yidong , Gao Shou-Jiang , Huang Yufei 
Published: December 2010

Abstract

Background
MicroRNAs (miRNAs) are single-stranded non-coding RNAs shown to plays important regulatory roles in a wide range of biological processes and diseases. The functions and regulatory mechanisms of most of miRNAs are still poorly understood in part because of the difficulty in identifying the miRNA regulatory targets. To this end, computational methods have evolved as important tools for genome-wide target screening. Although considerable work in the past few years has produced many target prediction algorithms, most of them are solely based on sequence, and the accuracy is still poor. In contrast, gene expression profiling from miRNA transfection experiments can provide additional information about miRNA targets. However, most of existing research assumes down-regulated mRNAs as targets. Given the fact that the primary function of miRNA is protein inhibition, this assumption is neither sufficient nor necessary.

Results
A novel Bayesian approach is proposed in this paper that integrates sequence level prediction with expression profiling of miRNA transfection. This approach does not restrict the target to be down-expressed and thus improve the performance of existing target prediction algorithm. The proposed algorithm was tested on simulated data, proteomics data, and IP pull-down data and shown to achieve better performance than existing approaches for target prediction. All the related materials including source code are available at http://compgenomics.utsa.edu/expmicro.html.

Conclusions
The proposed Bayesian algorithm integrates properly the sequence paring data and mRNA expression profiles for miRNA target prediction. This algorithm is shown to have better prediction performance than existing algorithms.
A solute-binding protein for iron transport in Streptococcus iniae
Authors: Zou Lili , Wang Jun , Huang Baofeng , Xie Mingquan , Li Anxing 
Published: December 2010

Abstract

Background

Streptococcus iniae (S. iniae) is a major pathogen that causes considerable morbidity and mortality in cultured fish worldwide. The pathogen's ability to adapt to the host affects the extent of infection, hence understanding the mechanisms by which S. iniae overcomes physiological stresses during infection will help to identify potential virulence determinants of streptococcal infection. Grow S. iniae under iron-restricted conditions is one approach for identifying host-specific protein expression. Iron plays an important role in many biological processes but it has low solubility under physiological condition. Many microorganisms have been shown to be able to circumvent this nutritional limitation by forming direct contacts with iron-containing proteins through ATP-binding cassette (ABC) transporters. The ABC transporter superfamilies constitute many different systems that are widespread among living organisms with different functions, such as ligands translocation, mRNA translation, and DNA repair.

Results
An ABC transporter system, named as mtsABC (metal transport system) was cloned from S. iniae HD-1, and was found to be involved in heme utilization. mtsABC is cotranscribed by three downstream genes, i.e., mtsA, mtsB, and mtsC. In this study, we cloned the first gene of the mtsABC transporter system (mtsA), and purified the corresponding recombinant protein MtsA. The analysis indicated that MtsA is a putative lipoprotein which binds to heme that can serve as an iron source for the microorganism, and is expressed in vivo during Kunming mice infection by S. iniae HD-1.

Conclusions
This is believed to be the first report on the cloning the ABC transporter lipoprotein from S. iniae genomic DNA. Together, our data suggested that MtsA is associated with heme, and is expressed in vivo during Kunming mice infection by S. iniae HD-1 which indicated that it can be a potential candidate for S. iniae subunit vaccine.
Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain
Authors: Hammock Elizabeth AD , Eagleson Kathie L , Barlow Susan , Earls Laurie R , Miller David M , Levitt Pat 
Published: December 2010

Abstract

Background
In an effort to identify genes that specify the mammalian forebrain, we used a comparative approach to identify mouse homologs of transcription factors expressed in developing Caenorhabditis elegans GABAergic neurons. A cell-specific microarray profiling study revealed a set of transcription factors that are highly expressed in embryonic C. elegans GABAergic neurons.

Results
Bioinformatic analyses identified mouse protein homologs of these selected transcripts and their expression pattern was mapped in the mouse embryonic forebrain by in situ hybridization. A review of human homologs indicates several of these genes are potential candidates in neurodevelopmental disorders.

Conclusions
Our comparative approach has revealed several novel candidates that may serve as future targets for studies of mammalian forebrain development.
Clinical and genetic characterization of chanarin-dorfman syndrome patients: first report of large deletions in the ABHD5 gene
Authors: Redaelli Chiara , Coleman Rosalind A , Moro Laura , Dacou-Voutetakis Catherine , Elsayed Solaf Mohamed , Prati Daniele , Colli Agostino , Mela Donatella , Colombo Roberto , Tavian Daniela 
Published: December 2010

Abstract

Background
Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder characterized by nonbullous congenital ichthyosiform erythroderma (NCIE) and an intracellular accumulation of triacylglycerol (TG) droplets in most tissues. The clinical phenotype involves multiple organs and systems, including liver, eyes, ears, skeletal muscle and central nervous system (CNS). Mutations in ABHD5/CGI58 gene are associated with CDS.

Methods
Eight CDS patients belonging to six different families from Mediterranean countries were enrolled for genetic study. Molecular analysis of the ABHD5 gene included the sequencing of the 7 coding exons and of the putative 5' regulatory regions, as well as reverse transcript-polymerase chain reaction analysis and sequencing of normal and aberrant ABHD5 cDNAs.

Results
Five different mutations were identified, four of which were novel, including two splice-site mutations (c.47+1G>A and c.960+5G>A) and two large deletions (c.898_*320del and c.662-1330_773+46del). All the reported mutations are predicted to be pathogenic because they lead to an early stop codon or a frameshift producing a premature termination of translation. While nonsense, missense, frameshift and splice-site mutations have been identified in CDS patients, large genomic deletions have not previously been described.

Conclusions
These results emphasize the need for an efficient approach for genomic deletion screening to ensure an accurate molecular diagnosis of CDS. Moreover, in spite of intensive molecular screening, no mutations were identified in one patient with a confirmed clinical diagnosis of CDS, appointing to genetic heterogeneity of the syndrome.
Systems biology approach reveals that overflow metabolism of acetate in Escherichia coli is triggered by carbon catabolite repression of acetyl-CoA synthetase
Authors: Valgepea Kaspar , Adamberg Kaarel , Nahku Ranno , Lahtvee Petri-Jaan , Arike Liisa , Vilu Raivo 
Published: December 2010

Abstract

Background
The biotechnology industry has extensively exploited Escherichia coli for producing recombinant proteins, biofuels etc. However, high growth rate aerobic E. coli cultivations are accompanied by acetate excretion i.e. overflow metabolism which is harmful as it inhibits growth, diverts valuable carbon from biomass formation and is detrimental for target product synthesis. Although overflow metabolism has been studied for decades, its regulation mechanisms still remain unclear.

Results
In the current work, growth rate dependent acetate overflow metabolism of E. coli was continuously monitored using advanced continuous cultivation methods (A-stat and D-stat). The first step in acetate overflow switch (at μ = 0.27 ± 0.02 h-1) is the repression of acetyl-CoA synthethase (Acs) activity triggered by carbon catabolite repression resulting in decreased assimilation of acetate produced by phosphotransacetylase (Pta), and disruption of the PTA-ACS node. This was indicated by acetate synthesis pathways PTA-ACKA and POXB component expression down-regulation before the overflow switch at μ = 0.27 ± 0.02 h-1 with concurrent 5-fold stronger repression of acetate-consuming Acs. This in turn suggests insufficient Acs activity for consuming all the acetate produced by Pta, leading to disruption of the acetate cycling process in PTA-ACS node where constant acetyl phosphate or acetate regeneration is essential for E. coli chemotaxis, proteolysis, pathogenesis etc. regulation. In addition, two-substrate A-stat and D-stat experiments showed that acetate consumption capability of E. coli decreased drastically, just as Acs expression, before the start of overflow metabolism. The second step in overflow switch is the sharp decline in cAMP production at μ = 0.45 h-1 leading to total Acs inhibition and fast accumulation of acetate.

Conclusion
This study is an example of how a systems biology approach allowed to propose a new regulation mechanism for overflow metabolism in E. coli shown by proteomic, transcriptomic and metabolomic levels coupled to two-phase acetate accumulation: acetate overflow metabolism in E. coli is triggered by Acs down-regulation resulting in decreased assimilation of acetic acid produced by Pta, and disruption of the PTA-ACS node.
Inequality: an underacknowledged source of mental illness and distress
Authors: Pickett Kate E. , Wilkinson Richard G. 
Published: December 2010

SummaryGreater income inequality is associated with higher prevalence of mental illness and drug misuse in rich societies. There are threefold differences in the proportion of the population suffering from mental illness between more and less equal countries. This relationship is most likely mediated by the impact of inequality on the quality of social relationships and the scale of status differentiation in different societies.
Treatment adherence therapy in people with psychotic disorders: randomised controlled trial
Authors: Staring A. B. P. , Van der Gaag M. , Koopmans G. T. , Selten J. P. , Van Beveren J. M. , Hengeveld M. W. , Loonen A. J. M. , Mulder C. L. 
Published: December 2010

BackgroundInterventions to improve adherence to treatment in people with psychotic disorders have produced inconclusive results. We developed a new treatment, treatment adherence therapy (TAT), whose intervention modules are tailored to the reasons for an individual's non-adherence.AimsTo examine the effectiveness of TAT with regard to service engagement and medication adherence in out-patients with psychotic disorders who engage poorly.MethodRandomised controlled study of TAT v. treatment as usual (TAU) in 109 out-patients. Most outcome measurements were performed by masked assessors. We used intention-to-treat multivariate analyses (Dutch Trial Registry: NTR1159).ResultsTreatment adherence therapy v. TAU significantly benefited service engagement (Cohen's d = 0.48) and medication adherence (Cohen's d = 0.43). Results remained significant at 6-month follow-up for medication adherence. Near-significant effects were also found regarding involuntary readmissions (1.9% v. 11.8%, P = 0.053). Symptoms and quality of life did not improve.ConclusionsTreatment adherence therapy helps improve engagement and adherence, and may prevent involuntary admission.
Parental help-seeking in primary care for child and adolescent mental health concerns: qualitative study
Authors: Sayal Kapil , Tischler Victoria , Coope Caroline , Robotham Sarah , Ashworth Mark , Day Crispin , Tylee Andre , Simonoff Emily 
Published: December 2010

BackgroundChild and adolescent mental health problems are common in primary care. However, few parents of children with mental health problems express concerns about these problems during consultations.AimsTo explore the factors influencing parental help-seeking for children with emotional or behavioural difficulties.MethodFocus group discussions with 34 parents from non-specialist community settings who had concerns about their child's mental health. All groups were followed by validation groups or semi-structured interviews.ResultsMost children had clinically significant mental health symptoms or associated impairment in function. Appointment systems were a key barrier, as many parents felt that short appointments did not allow sufficient time to address their child's difficulties. Continuity of care and trusting relationships with general practitioners (GPs) who validated their concerns were perceived to facilitate help-seeking. Parents valued GPs who showed an interest in their child and family situation. Barriers to seeking help included embarrassment, stigma of mental health problems, and concerns about being labelled or receiving a diagnosis. Some parents were concerned about being judged a poor parent and their child being removed from the family should they seek help.ConclusionsPrimary healthcare is a key resource for children and young people with emotional and behavioural difficulties and their families. Primary care services should be able to provide ready access to health professionals with an interest in children and families and appointments of sufficient length so that parents feel able to discuss their mental health concerns.
Stigmatised attitudes in independent pharmacies associated with discrimination towards individuals with opioid dependence
Authors: Luty Jason , Kumar Pramod , Stagias Konstantinos 
Published: December 2010

Aims and methodDispensing of methadone to individuals with opioid dependence is a discretionary service and many independent pharmacies remain unwilling to do this. We aimed to determine whether there was any correlation between negative stigmatised attitude towards these individuals and the likelihood of methadone dispensing. The 20-point Attitude to Mental Illness Questionnaire (AMIQ) was used to assess stigmatised attitudes in a cluster randomised sample of managers of community pharmacies in England.ResultsThe response rate was 66%. The AMIQ stigma scores had a median difference of 1 and effect size of 0.42 in favour of those pharmacies which dispensed methadone (mean = 0.53; n = 138) compared with those who did not (mean = 0.93; n = 69; P <0.001).Clinical implicationsThe results show a clear behavioural distinction (discrimination) based on stigmatised attitudes towards individuals with opioid dependence. This may arise because managers with stigmatised attitudes refuse to dispense methadone to this group. Conversely, familiarity with these individuals may have a de-stigmatising effect.
Experimental osteoarthritis induced by surgical realignment of the patella in BALB/c mice
Authors: Chia W.-T. , Pan R.-Y. , Tseng F.-J. , Chen Y.-W. , Feng C.-K. , Lee H.-S. , Chang D.-M. , Sytwu H.-K. 
Published: December 2010

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP.After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks.Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change.
Use of metal proximal radial endoprostheses for treatment of non-traumatic disorders
Authors: Gokaraju K. , Miles J. , Parratt M. T. R. , Blunn G. W. , Pollock R. C. , Skinner J. A. , Cannon S. R. , Briggs T. W. R. 
Published: December 2010

We have reviewed five adult patients treated with endoprosthetic reconstruction of the proximal radius following resection of non-traumatic lesions. The patients had a mean age of 33.4 years (20 to 60) at the time of surgery and the mean follow-up was 7.6 years (0.8 to 16). Following surgery, all elbows were clinically stable and there was 100% survivorship of the prosthesis. Evaluation of function was assessed clinically and by the Mayo Elbow Performance Score, achieving a mean of 86% (70 to 100). Results at medium-term follow-up are encouraging with regards to elbow stability, implant survivorship and functional outcome.
Cementless total hip replacement using second-generation components
Authors: McLaughlin J. R. , Lee K. R. 
Published: December 2010

We reviewed 123 second-generation uncemented total hip replacements performed on 115 patients by a single surgeon between 1993 and 1994. The acetabular component used in all cases was a fully porous-coated threaded hemispheric titanium shell (T-Tap ST) with a calcium ion stearate-free, isostatically compression-moulded polyethylene liner. The titanium femoral component used was a Taperloc with a reduced distal stem. No patient was lost to follow-up. Complete clinical and radiological follow-up was obtained for all 123 hips at a mean of 14 years (12 to 16). One femoral component was revised after a fracture, and three acetabular components for aseptic loosening. No additional femoral or acetabular components were judged loose by radiological criteria. Mild proximal femoral osteolysis was identified in two hips and minor acetabular osteolysis was present in four. The mean rate of penetration of the femoral head was 0.036 mm/year (0.000 to 0.227). These findings suggest that refinements in component design may be associated with excellent long-term fixation in cementless primary total hip replacement.
Injuries to the lower back in elite fast bowlers
Authors: Ranson C. A. , Burnett A. F. , Kerslake R. W. 
Published: December 2010

In our study, the aims were to describe the changes in the appearance of the lumbar spine on MRI in elite fast bowlers during a follow-up period of one year, and to determine whether these could be used to predict the presence of a stress fracture of the posterior elements. We recruited 28 elite fast bowlers with a mean age of 19 years (16 to 24) who were training and playing competitively at the start of the study. They underwent baseline MRI (season 1) and further scanning (season 2) after one year to assess the appearance of the lumbar intervertebral discs and posterior bony elements. The incidence of low back pain and the amount of playing and training time lost were also recorded. In total, 15 of the 28 participants (53.6%) showed signs of acute bone stress on either the season 1 or season 2 MR scans and there was a strong correlation between these findings and the later development of a stress fracture (p < 0.001). The prevalence of intervertebral disc degeneration was relatively low. There was no relationship between disc degeneration on the season 1 MR scans and subsequent stress fracture. Regular lumbar MR scans of asymptomatic elite fast bowlers may be of value in detecting early changes of bone stress and may allow prompt intervention aimed at preventing a stress fracture and avoiding prolonged absence from cricket.