bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline results of the first malaria indicator survey in Iran at the health facility level
Authors: Raiesi Ahmad , Nikpour Fatemeh , Ansari-Moghaddam Alireza , Ranjbar Mansoor , Rakhshani Fatemeh , Mohammadi Mahdi , Haghdost Aliakbar , Taghizadeh-Asl Rahim , Sakeni Mohammad , Safari Reza , Saffari Mehdi 
Published: October 2011

Abstract

Background
Malaria continues to be a global public health challenge, particularly in developing countries. Delivery of prompt and effective diagnosis and treatment of malaria cases, detection of malaria epidemics within one week of onset and control them in less than a month, regular disease monitoring and operational classification of malaria are among the major responsibilities of the national malaria programme. The study was conducted to determine these indicators at the different level of primary health care facilities in malaria-affected provinces of Iran

Methods
In this survey, data was collected from 223 health facilities including health centres, malaria posts, health houses and hospitals as well as the profile of all 5, 836 recorded malaria cases in these facilities during the year preceding the survey. Descriptive statistics (i.e. frequencies, percentages) were used to summarize the results and Chi square test was used to analyse data.

Results
All but one percent of uncomplicated cases took appropriate and correctly-dosed of anti-malarial drugs in accordance to the national treatment guideline. A larger proportion of patients [85.8%; 95% CI: 84.8 - 86.8] were also given complete treatment including anti-relapse course, in line with national guidelines. About one third [35.0%; 95% CI: 33.6 - 36.4] of uncomplicated malaria cases were treated more than 48 hours after first symptoms onset. Correspondingly, half of severe malaria cases took recommended anti-malarial drugs for severe or complicated disease more than 48 hours of onset of first symptoms. The latter cases had given regular anti-malarial drugs promptly.
The majority of malaria epidemics [97%; 95% CI: 90.6 - 100] in study areas were detected within one week of onset, but only half of epidemics were controlled within four weeks of detection. Just half of target districts had at least one health facility/emergency site with adequate supply and equipment stocks. Nevertheless, only one-third of them [33% (95% CI: 0.00 - 67.8)] had updated inventory of malaria foci on quarterly basis.

Conclusion
To sum up, malaria case management still constitutes a public health problem in Iran. Additionally, data suggest scarcity in management and evaluation of malaria foci, detection and control of malaria epidemics as well as assignment of emergency sites across different regions of the country. Consequently, massive and substantial investments need to be made at the Ministry of Health to coordinate national malaria control programmes towards achieving determined goals and targets.
Immune risk phenotype is associated with nosocomial lung infections in elderly in-patients
Authors: Plonquet A , Bastuji-Garin S , Tahmasebi F , Brisacier C , Ledudal K , Farcet JP , Paillaud E 
Published: October 2011

AbstractBackgroundNosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters.ResultsWe included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180;p= 0.036).ConclusionImmunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term.
Identification of gene fusion transcripts by transcriptome sequencing in BRCA1-mutated breast cancers and cell lines
Authors: Ha Kevin CH , Lalonde Emilie , Li Lili , Cavallone Luca , Natrajan Rachael , Lambros Maryou B , Mitsopoulos Costas , Hakas Jarle , Kozarewa Iwanka , Fenwick Kerry , Lord Chris J , Ashworth Alan , Vincent-Salomon Anne , Basik Mark , Reis-Filho Jorge S , Majewski Jacek , Foulkes William D 
Published: October 2011

Abstract

Background
Gene fusions arising from chromosomal translocations have been implicated in cancer. However, the role of gene fusions in BRCA1-related breast cancers is not well understood. Mutations in BRCA1 are associated with an increased risk for breast cancer (up to 80% lifetime risk) and ovarian cancer (up to 50%). We sought to identify putative gene fusions in the transcriptomes of these cancers using high-throughput RNA sequencing (RNA-Seq).

Methods
We used Illumina sequencing technology to sequence the transcriptomes of five BRCA1-mutated breast cancer cell lines, three BRCA1-mutated primary tumors, two secretory breast cancer primary tumors and one non-tumorigenic breast epithelial cell line. Using a bioinformatics approach, our initial attempt at discovering putative gene fusions relied on analyzing single-end reads and identifying reads that aligned across exons of two different genes. Subsequently, latter samples were sequenced with paired-end reads and at longer cycles (producing longer reads). We then refined our approach by identifying misaligned paired reads, which may flank a putative gene fusion junction.

Results
As a proof of concept, we were able to identify two previously characterized gene fusions in our samples using both single-end and paired-end approaches. In addition, we identified three novel in-frame fusions, but none were recurrent. Two of the candidates, WWC1-ADRBK2 in HCC3153 cell line and ADNP-C20orf132 in a primary tumor, were confirmed by Sanger sequencing and RT-PCR. RNA-Seq expression profiling of these two fusions showed a distinct overexpression of the 3' partner genes, suggesting that its expression may be under the control of the 5' partner gene's regulatory elements.

Conclusions
In this study, we used both single-end and paired-end sequencing strategies to discover gene fusions in breast cancer transcriptomes with BRCA1 mutations. We found that the use of paired-end reads is an effective tool for transcriptome profiling of gene fusions. Our findings suggest that while gene fusions are present in some BRCA1-mutated breast cancers, they are infrequent and not recurrent. However, private fusions may still be valuable as potential patient-specific biomarkers for diagnosis and treatment.
Can anti-cyclic citrullinated peptide antibody-negative RA be subdivided into clinical subphenotypes?
Authors: De Rooy Diederik PC , Willemze Annemiek , Mertens Bart , Huizinga Tom WJ , Van der Helm-van Mil Annette HM 
Published: October 2011

Abstract
Introduction
Studies investigating genetic risk factors for susceptibility to rheumatoid arthritis (RA) studied anti-citrullinated peptide antibody (CCP)-positive RA more frequently than anti-CCP-negative RA. One of the reasons for this is the perception that anti-CCP-negative RA may include patients that fulfilled criteria for RA but belong to a wide range of diagnoses. We aimed to evaluate the validity of this notion and explored whether clinical subphenotypes can be discerned within anti-CCP-negative RA.

Methods
The 318 patients with anti-CCP-negative RA (1987 ACR criteria), included in the Leiden Early Arthritis Clinic between 1993 and 2006, were studied for baseline characteristics and radiologic progression data during a mean follow-up of 5 years. Grouping was studied both at variable and patient levels. Principal components analysis and partial least-squares regression were applied to study for clustering of variables. A cluster analysis was performed to look for clustering of patients.

Results
The simultaneous presence of patient characteristics at disease presentation was observed for several groups; however, the three largest groups of patients' characteristics explained only 26.5% of the total variance. Plotting the contribution of each patient to these three groups did not reveal clustering of patients. Comparable observations were made when data on progression of joint destruction were studied in relation to baseline clinical data. A cluster analysis, evaluating whether patients resemble each other, revealed no grouping of patients. Altogether, no clinically distinguishable subphenotypes were observed.

Conclusions
The current data provide evidence that, for risk-factor studies, anti-CCP-negative RA patients can be studied as one group.
MMP-13 stimulates osteoclast differentiation and activation in tumour breast bone metastases
Authors: Pivetta Eliana , Scapolan Martina , Pecolo Marina , Wassermann Bruna , Abu-Rumeileh Imad , Balestreri Luca , Borsatti Eugenio , Tripodo Claudio , Colombatti Alfonso , Spessotto Paola 
Published: October 2011

Abstract
Introduction
The increased bone degradation in osteolytic metastases depends on stimulation of mature osteoclasts and on continuous differentiation of new pre-osteoclasts. Metalloproteinases (MMP)-13 is expressed in a broad range of primary malignant tumours and it is emerging as a novel biomarker. Recent data suggest a direct role of MMP-13 in dissolving bone matrix complementing the activity of MMP-9 and other enzymes. Tumour-microenvironment interactions alter gene expression in malignant breast tumour cells promoting osteolytic bone metastasis. Gene expression profiles revealed that MMP-13 was among the up-regulated genes in tumour-bone interface and its abrogation reduced bone erosion. The precise mechanism remained not fully understood. Our purpose was to further investigate the mechanistic role of MMP-13 in bone osteolytic lesions.

Methods
MDA-MB-231 breast cancer cells that express MMP-13 were used as a model for in vitro and in vivo experiments. Conditioned media from MDA-MB-231 cells were added to peripheral blood mononuclear cultures to monitor pre-osteoclast differentiation and activation. Bone erosion was evaluated after injection of MMP-13-silenced MDA-MB-231 cells into nude mice femurs.

Results
MMP-13 was co-expressed by human breast tumour bone metastases with its activator MT1-MMP. MMP-13 was up-regulated in breast cancer cells after in vitro stimulation with IL-8 and was responsible for increased bone resorption and osteoclastogenesis, both of which were reduced by MMP inhibitors. We hypothesized that MMP-13 might be directly involved in the loop promoting pre-osteoclast differentiation and activity. We obtained further evidence for a direct role of MMP-13 in bone metastasis by a silencing approach: conditioned media from MDA-MB-231 after MMP-13 abrogation or co-cultivation of silenced cells with pre-osteoclast were unable to increase pre-osteoclast differentiation and resorption activity. MMP-13 activated pre-MMP-9 and promoted the cleavage of galectin-3, a suppressor of osteoclastogenesis, thus contributing to pre-osteoclast differentiation. Accordingly, MMP-13 abrogation in tumour cells injected into the femurs of nude mice reduced the differentiation of TRAP positive cells in bone marrow and within the tumour mass as well as bone erosion.

Conclusions
These results indicate that within the inflammatory bone microenvironment MMP-13 production was up-regulated in breast tumour cells leading to increased pre-osteoclast differentiation and their subsequent activation.
Variation in global codon usage bias among prokaryotic organisms is associated with their lifestyles
Authors: Botzman Maya , Margalit Hanah 
Published: October 2011

Abstract
Background
It is widely acknowledged that synonymous codons are used unevenly among genes in a genome. In organisms under translational selection, genes encoding highly expressed proteins are enriched with specific codons. This phenomenon, termed codon usage bias, is common to many organisms and has been recognized as influencing cellular fitness. This suggests that the global extent of codon usage bias of an organism might be associated with its phenotypic traits.

Results
To test this hypothesis we used a simple measure for assessing the extent of codon bias of an organism, and applied it to hundreds of sequenced prokaryotes. Our analysis revealed a large variability in this measure: there are organisms showing very high degrees of codon usage bias and organisms exhibiting almost no differential use of synonymous codons among different genes. Remarkably, we found that the extent of codon usage bias corresponds to the lifestyle of the organism. Especially, organisms able to live in a wide range of habitats exhibit high extents of codon usage bias, consistent with their need to adapt efficiently to different environments. Pathogenic prokaryotes also demonstrate higher extents of codon usage bias than non-pathogenic prokaryotes, in accord with the multiple environments that many pathogens occupy. Our results show that the previously observed correlation between growth rate and metabolic variability is attributed to their individual associations with codon usage bias.

Conclusions
Our results suggest that the extent of codon usage bias of an organism plays a role in the adaptation of prokaryotes to their environments.
Detection of 3-Iodothyronamine in Human Patients: A Preliminary Study
Authors: Galli Elena , Marchini Maja , Saba Alessandro , Berti Sergio , Tonacchera Massimo , Vitti Paolo , Scanlan Thomas S. , Iervasi Giorgio , Zucchi Riccardo 
Published: October 2011

Context and Objective:
The primary purpose of this study was to detect and quantify 3-iodothyronamine (T1AM), an endogenous biogenic amine related to thyroid hormone, in human blood.

Design:
T1AM, total T3, and total T4 were assayed in serum by a novel HPLC tandem mass spectrometry assay, which has already been validated in animal investigations, and the results were related to standard clinical and laboratory variables.

Setting and Patients:
The series included one healthy volunteer, 24 patients admitted to a cardiological ward, and 17 ambulatory patients suspected of thyroid disease, who underwent blood sampling at admission for routine diagnostic purposes. Seven patients were affected by type 2 diabetes, and six patients showed echocardiographic evidence of impaired left ventricular function.

Interventions:
No intervention or any patient selection was performed.

Main Outcome Measures:
serum T1AM, total and free T3 and T4, routine chemistry, routine hematology, and echocardiographic parameters were measured.

Results:
T1AM was detected in all samples, and its concentration averaged 0.219 ± 0.012 pmol/ml. The T1AM concentration was significantly correlated to total T4 (r = 0.654, P &lt; 0.001), total T3 (r = 0.705, P &lt; 0.001), glycated hemoglobin (r = 0.508, P = 0.013), brain natriuretic peptide (r = 0.543, P = 0.016), and γ-glutamyl transpeptidase (r = 0.675, P &lt; 0.001). In diabetic vs. nondiabetic patients T1AM concentration was significantly increased (0.232 ± 0.014 vs. 0.203 ± 0.006 pmol/ml, P = 0.044), whereas no significant difference was observed in patients with cardiac dysfunction.

Conclusions:
T1AM is an endogenous messenger that can be assayed in human blood. Our results are consistent with the hypothesis that circulating T1AM is produced from thyroid hormones and encourage further investigations on the potential role of T1AM in insulin resistance and heart failure.
De Sitter spacetime as a momentum measuring apparatus
Authors: Nicolaevici Nistor 
Published: October 2011

Abstract
We discuss the evolution of a quantum wave packet in the expanding de Sitter spacetime using the plane wave solutions of the Dirac equation. We concentrate on the case of large negative times when the packet approaches the event horizon and confirm that the evolution accords with that expected from the classical trajectories. We point out that in certain conditions the packet can split into two components that become localized at different parts of the horizon and that this effect can be seen, in an idealized sense, as a measuring process for the momentum of the particle, in direct analogy with the measurement of spin in a Stern-Gerlach experiment.
What Impact Has the Introduction of a Synoptic Report for Rectal Cancer Had on Reporting Outcomes for Specialist Gastrointestinal and Nongastrointestinal Pathologists?
Authors: Messenger David E. , McLeod Robin S. , Kirsch Richard 
Published: October 2011

Context.—Synoptic pathology reports increase the completeness of reporting for colorectal cancer. Despite the perceived superiority of specialist reporting, service demands dictate that general pathologists report colorectal cancer specimens in many centers.
Objective.—To determine differences in the completeness of rectal cancer reporting between specialist gastrointestinal and nongastrointestinal pathologists in both the narrative and synoptic formats.
Design.—Pathology reports from rectal cancer resections performed between 1997 and 2008 were reviewed. A standardized, synoptic report was formally introduced in 2001. Reports were assessed for completeness according to 10 mandatory elements from the College of American Pathologists checklist.
Results.—Overall, synoptic reports (n  =  315) were more complete than narrative reports (n  =  183) for TNM stage, distance to the circumferential radial margin, tumor grade, lymphovascular invasion, extramural venous invasion, perineural invasion, and regional deposits (all P &lt; .01). Compared with those by nonspecialist pathologists, narrative reports by gastrointestinal pathologists were more complete for lymphovascular invasion (59.3% versus 35.9%, P  =  .02) and extramural venous invasion (70.4% versus 35.9%, P  =  .001), but there was no difference in completeness once a synoptic report was adopted. Gastrointestinal pathologists tended to report the presence of extramural venous invasion more frequently in both the narrative (18.5% versus 5.1%, P  =  .01) and synoptic formats (25.5% versus 14.6%, P  =  .02).
Conclusions.—Completeness of reporting, irrespective of subspecialist interest, was dramatically increased by the use of a synoptic report. Improvements in completeness were most pronounced among nongastrointestinal pathologists, enabling them to attain a level of report completeness comparable to that of gastrointestinal pathologists. Further studies are required to determine whether there are actual discrepancies in the detection of prognostic features between specialist gastrointestinal and nongastrointestinal pathologists.
Circulating Endothelial Cells as a Marker of Vascular Dysfunction in Patients With Systemic Lupus Erythematosus by Real-Time Polymerase Chain Reaction
Authors: Attia Fadia M. , Maaty Ahmed , Kalil Fawzy Attia 
Published: October 2011

Context.—Systemic lupus erythematosus (SLE) is associated with an increased risk of atherosclerosis; endothelial dysfunction represents the first step in its pathogenesis.
Objective.—To assess endothelial dysfunction in SLE by circulating endothelial cells (CECs) and to characterize SLE-specific factors that contribute to its appearance.
Design.—Case-control study was conducted on 60 subjects, divided into 2 groups: group A (30 patients with SLE) and group B (30 healthy sex- and age-matched controls). Total cholesterol, triglycerides, antinuclear antibodies, anti–double-stranded DNA antibodies, and C3 were determined in all patients. Systemic lupus erythematosus activity was assessed using the SLE Disease Activity Index. Endothelial function was assessed by means of flow-mediated dilation of the brachial artery using B-mode ultrasonography and relative quantification of CD 146 mRNA by real-time polymerase chain reaction.
Results.—The group of SLE patients was formed of 20 females and 10 males, with a mean age of 31.16 ± 9.69 years. The values of SLE-specific tests and SLE Disease Activity Index were represented by anti–double-stranded DNA antibodies 160 ± 40.5, C3 68.91 ± 11.91 mg/dL, total cholesterol 188.66 ± 49.63 mg/dL, triglycerides 143.41 ± 46.26 mg/dL, and SLE Disease Activity Index 12.66 ± 3.70. Values for flow-mediated dilation were 8.85% ± 2.02% (group A) and 20.33% ± 6.19% (group B), P &lt; .001, and CECs were 300 ± 40.5 μL−1 blood (group A) and 10 ± 2.5 μL−1 blood (group B). The statistical analysis showed a strong inverse correlation between CECs and SLE Disease Activity Index, a strong correlation between CECs and C3, a strong correlation between CECs and anti–double-stranded DNA antibodies, and a moderate inverse correlation between CECs and total cholesterol.
Conclusion.—Endothelial dysfunction is present in SLE patients even in the absence of traditional cardiovascular risk factors due to disease activity.
Cyst‐like lesions in finger joints detected by conventional radiography: Comparison with 320‐row multidetector computed tomography
Authors: de Bucourt Maximilian , Scheurig‐Münkler Christian , Feist Eugen , Juran Ralf , Diekhoff Torsten , Rogalla Patrik , Hamm Bernd , Hermann Kay‐Geert A. 
Published: October 2011

AbstractObjectiveMany rheumatologists and radiologists routinely assess conventional radiographs of the hands, and it is often unclear how to proceed if radiography reveals only cyst‐like lesions (CLLs), with otherwise normal findings. The present study was undertaken to evaluate the use of 320‐row multidetector computed tomography (MDCT) of the hands in the further assessment of CLLs of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints identified on conventional radiography.MethodsMCP and PIP joints (n = 1,120 joints) of 56 consecutive patients (44 women [mean age 55 years, range 31–72 years] and 12 men [mean age 57 years, range 37–77 years]) were prospectively scored for the presence of cysts, CLLs, and erosions of the PIP and MCP joints, first on conventional radiographs, then on MDCT. Scoring was performed by 2 independent readers under blinded conditions. Intraclass correlation coefficients were calculated.ResultsBy conventional hand radiography, 13 patients (total of 260 joints assessed) were identified as having CLLs in 1 or more joints (total of 36 joints [11 PIP and 25 MCP]). By MDCT, the findings in 19 of 36 joints (53%) were diagnosed as erosions, while 7 of 36 (19%) were confirmed as true cysts, and 10 joints (28%) were normal (false positive). Among the patients with CLLs, 10 of 224 joints with no abnormality seen radiographically had erosions as seen on MDCT. Interreader agreement for erosions was 0.854 (95% confidence interval [95% CI] 0.831–0.874) by conventional hand radiography and 0.952 (95% CI 0.943–0.959) by MDCT.ConclusionOur results indicate that radiographic appearance of cyst‐like lesions may actually represent erosions and should lead to initiation of further imaging tests.