bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate profiling of neurodegeneration-associated changes in a subcellular compartment of neurons via image processing
Authors: Kumarasamy Saravana K , Wang Yunshi , Viswanathan Vignesh , Kraut Rachel S 
Published: November 2008

Abstract

Background
Dysfunction in the endolysosome, a late endosomal to lysosomal degradative intracellular compartment, is an early hallmark of some neurodegenerative diseases, in particular Alzheimer's disease. However, the subtle morphological changes in compartments of affected neurons are difficult to quantify quickly and reliably, making this phenotype inaccessible as either an early diagnostic marker, or as a read-out for drug screening.

Methods
We present a method for automatic detection of fluorescently labeled endolysosomes in degenerative neurons in situ. The Drosophila blue cheese (bchs) mutant was taken as a genetic neurodegenerative model for direct in situ visualization and quantification of endolysosomal compartments in affected neurons. Endolysosomal compartments were first detected automatically from 2-D image sections using a combination of point-wise multi-scale correlation and normalized correlation operations. This detection algorithm performed well at recognizing fluorescent endolysosomes, unlike conventional convolution methods, which are confounded by variable intensity levels and background noise. Morphological feature differences between endolysosomes from wild type vs. degenerative neurons were then quantified by multivariate profiling and support vector machine (SVM) classification based on compartment density, size and contrast distribution. Finally, we ranked these distributions according to their profiling accuracy, based on the backward elimination method.

Results
This analysis revealed a statistically significant difference between the neurodegenerative phenotype and the wild type up to a 99.9% confidence interval. Differences between the wild type and phenotypes resulting from overexpression of the Bchs protein are detectable by contrast variations, whereas both size and contrast variations distinguish the wild type from either of the loss of function alleles bchs1 or bchs58. In contrast, the density measurement differentiates all three bchs phenotypes (loss of function as well as overexpression) from the wild type.

Conclusion
Our model demonstrates that neurodegeneration-associated endolysosomal defects can be detected, analyzed, and classified rapidly and accurately as a diagnostic imaging-based screening tool.
Catheter-related septic thrombophlebitis of the superior vena cava involving the atrial septum: a case report
Authors: Tzortzis Stavros , Apostolakis Stavros , Xenakis Konstantinos , Spiropoulos Georgios , Lazaridis Kyriakos 
Published: November 2008

Abstract

Background
Intravascular catheters provide necessary vascular access, for intravenous therapy, blood sampling and pressure monitoring. However, their use is often associated with serious local and systemic complications including local site infection, intravascular catheter-related bloodstream infections, septic thrombophlebitis, and endocarditis.

Case presentation
We present a case of a 72 year old postoperative patient presented with persistent fever. Transthoracic and transesophageal echocardiograms demonstrated a lesion in the superior vena cava, protruding into the right atrium and infiltrating the atrial septum. Candida albicans grew in blood cultures as well as in the subclavian catheter tip culture. Anti-fungal and antithrombotic therapy was initiated. After 2 weeks treatment the lesion was diminished.

Conclusion
Transthoracic and transesophageal echocardiography has been proved efficient and cost-effective in guiding therapy in cases of catheter related infections. In the presented case the lesions in vena cava and the involvement of the endocardium were early identified by echocardiography. Moreover, a follow-up echocardiogram confirmed the efficiency of the therapeutic approach.
Diarrhea, negative t-waves, fever and skin rash, rare manifestation of carbamazepine hypersensitivity: a case report
Authors: Aigner Felix , Aigner Wolfgang , Hoppichler Friedrich , Luef Gerhard , Bonatti Hugo 
Published: November 2008

Abstract

Introduction
Antiepileptic drug induced hypersensitivity syndrome is a rare side effect of some of the first line anticonvulsive drugs such as carbamazepine and other aromatic agents. We are the first to mention a rare case of gastrointestinal, skin and cardiac findings related to carbamazepine administration, which is very uncommon and needs to be reported.

Case presentation
We report on a 62-year-old Caucasian woman with carbamazepine associated hypersensitivity syndrome, who developed diarrhea, fever, skin lesions, pericardial effusion and pathology on electrocardiogram with terminal negative T waves in I, II, aVL, V5 and V6,. After withdrawal of carbamazepine and administration of methylprednisolone, all initial symptoms improved, white blood cell count normalized, pericardial effusion resolved and pathologic electrocardiogram findings resolved.

Conclusion
Anticonvulsive drug hypersensitivity syndromes can present with a wide spectrum of unspecific symptoms, which the prescribing clinician should be aware of.
Pedunculated uterine leiomyoma mimicking abdominal mass: a case report
Authors: Spanoudaki Athina , Oikonomou Anastasia , Dimitrova Krasimira , Prassopoulos Panos 
Published: November 2008

Abstract
A 48-year-old woman presented with abdominal fullness and a palpable "mass" in the left lower quadrant. Ultrasonography showed a large, rounded, hypoechoic mass. Contrast-enhanced helical CT of the abdomen demonstrated a well-circumscribed, heterogeneously but vividly enhancing mass. The uterus had a leiomyomatous configuration on CT. Uterus and mass revealed the same enhancing pattern. Thin section CT revealed a long, thin stalk connecting the mass with the body of the uterus. Surgical removal of both uterus and the mass confirmed the diagnosis of a pedunculated subserosal leiomyoma originating from a leiomyomatous uterus.
Anaesthesiologic protocol for kidney transplantation in two patients with Fabry Disease: a case series
Authors: Sorbello Massimiliano , Veroux Massimiliano , Cutuli Melania , Morello Gianluigi , Paratore Annalaura , Sidoti Mirko Tindaro , Maugeri Jessica Giuseppina , Gagliano Massimiliano , Giuffrida Giuseppe , Corona Daniela , Veroux Pierfrancesco 
Published: November 2008

Abstract
Fabry's Disease is a rare genetic syndrome, with a classic X-linked alpha -galactosidase A deficiency phenotype, responsible for glico-sphyngolypids metabolism impairment with clinical effects in several organs and functions. We describe the anaesthesiologic implications of two patients with Fabry disease who underwent a kidney transplantation from a deceased donor. We recommend careful preoperative evaluation, including cardiac sonography study and spirometry for Fabry disease patients, and according to our experience, we recommend advanced haemodynamic monitoring during surgery. Careful airway examination should be further performed, with particular attention to patient ventilability prediction and available alternative strategies for airway management in case of difficulties. A nephroprotective strategy and a particular care to the associated end-stage organ disease may significantly improve the long-term outcome of patients with Fabry Disease.
Heat shock protein-90-alpha, a prolactin-STAT5 target gene identified in breast cancer cells, is involved in apoptosis regulation
Authors: Perotti Christian , Liu Ruixuan , Parusel Christine T , Böcher Nadine , Schultz Jörg , Bork Peer , Pfitzner Edith , Groner Bernd , Shemanko Carrie S 
Published: November 2008

Abstract
Introduction
The prolactin-Janus-kinase-2-signal transducer and activator of transcription-5 (JAK2-STAT5) pathway is essential for the development and functional differentiation of the mammary gland. The pathway also has important roles in mammary tumourigenesis. Prolactin regulated target genes are not yet well defined in tumour cells, and we undertook, to the best of our knowledge, the first large genetic screen of breast cancer cells treated with or without exogenous prolactin. We hypothesise that the identification of these genes should yield insights into the mechanisms by which prolactin participates in cancer formation or progression, and possibly how it regulates normal mammary gland development.

Methods
We used subtractive hybridisation to identify a number of prolactin-regulated genes in the human mammary carcinoma cell line SKBR3. Northern blotting analysis and luciferase assays identified the gene encoding heat shock protein 90-alpha (HSP90A) as a prolactin-JAK2-STAT5 target gene, whose function was characterised using apoptosis assays.

Results
We identified a number of new prolactin-regulated genes in breast cancer cells. Focusing on HSP90A, we determined that prolactin increased HSP90A mRNA in cancerous human breast SKBR3 cells and that STAT5B preferentially activated the HSP90A promoter in reporter gene assays. Both prolactin and its downstream protein effector, HSP90α, promote survival, as shown by apoptosis assays and by the addition of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in both untransformed HC11 mammary epithelial cells and SKBR3 breast cancer cells. The constitutive expression of HSP90A, however, sensitised differentiated HC11 cells to starvation-induced wild-type p53-independent apoptosis. Interestingly, in SKBR3 breast cancer cells, HSP90α promoted survival in the presence of serum but appeared to have little effect during starvation.

Conclusions
In addition to identifying new prolactin-regulated genes in breast cancer cells, we found that prolactin-JAK2-STAT5 induces expression of the HSP90A gene, which encodes the master chaperone of cancer. This identifies one mechanism by which prolactin contributes to breast cancer. Increased expression of HSP90A in breast cancer is correlated with increased cell survival and poor prognosis and HSP90α inhibitors are being tested in clinical trials as a breast cancer treatment. Our results also indicate that HSP90α promotes survival depending on the cellular conditions and state of cellular transformation.
Duration of salmeterol-induced bronchodilation in mechanically ventilated chronic obstructive pulmonary disease patients: a prospective clinical study
Authors: Malliotakis Polychronis , Linardakis Manolis , Gavriilidis George , Georgopoulos Dimitris 
Published: November 2008

Abstract
Introduction
Delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer device in mechanically ventilated patients has become a widespread practice. However, except for the short-acting β2-agonist salbutamol, the duration of action of other bronchodilators, including long-acting β2-agonists, delivered with this technique is not well established. The purpose of this study was to examine the duration of bronchodilation induced by the long-acting β2-agonist salmeterol administered with an MDI and a spacer in a group of mechanically ventilated patients with exacerbation of chronic obstructive pulmonary disease (COPD).

Methods
Ten mechanically ventilated patients with acute exacerbation of COPD received four puffs of salmeterol (25 μg/puff). Salmeterol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud enhance spacer. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance, and the difference between Rrs and Rint (ΔR) were measured before and at 15, 30, and 60 minutes as well as at 2, 3, 4, 6, 8, 10, and 12 hours after salmeterol administration. The overall effects of salmeterol on respiratory system mechanics and heart rate during the 12-hour study period were analyzed by nonparametric Wilcoxon signed rank test.

Results
Salmeterol caused a significant decrease in dynamic and static airway pressures, Rint, and Rrs. These changes were evident at 30 minutes and remained significant for 8 hours after salmeterol administration. The duration of bronchodilation varied significantly among patients, lasting in some patients more than 10 hours and wearing off in others in less than 6 hours.

Conclusions
It is concluded that four puffs of salmeterol delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD exacerbation, the duration of which is highly variable, precluding definite conclusions in regard to optimum dosing schedules.
Prophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis
Authors: Fritz Stefan , Hartwig Werner , Lehmann Ronny , Will-Schweiger Katja , Kommerell Mechthild , Hackert Thilo , Schneider Lutz , Büchler Markus W , Werner Jens 
Published: November 2008

Abstract
Introduction
High morbidity and mortality rates in patients with severe acute pancreatitis are mainly caused by bacterial superinfection of pancreatic necrosis and subsequent sepsis. The benefit of early prophylactic antibiotics remains controversial because clinical studies performed to date were statistically underpowered. Thus, the aim of this study was to evaluate on-demand versus prophylactic antibiotic treatment in a standardised experimental model.

Methods
Treatment groups received meropenem either therapeutically 24 hours after induction of necrotising pancreatitis or prophylactically before development of pancreatic superinfection. At 24 and 72 hours, pancreatic injury was investigated by histology and translocation by bacterial cultures of pancreatic tissue and mesenteric lymph nodes. Septic complications were evaluated by blood cultures and survival.

Results
Without antibiotic treatment, pancreatic superinfection was observed in almost all cases after induction of necrotising pancreatitis. The 72-hour-mortality rate was 42.9% and bacterial infection of mesenteric lymph nodes and bacteraemia was found in 87.5% of the surviving animals. Therapeutic administration of meropenem on-demand reduced bacteraemia to 50% and mortality to 27.3%. However, prophylactic antibiotic treatment significantly reduced bacteraemia to 25.0% (p = 0.04) and pancreatic superinfection as well as mortality to 0% (p < 0.001 and p = 0.05, respectively) compared with controls.

Conclusions
In the present study both prophylactic and delayed antibiotic treatment on-demand reduced septic complications in a standardised setting of experimental necrotising pancreatitis. However, pancreatic superinfection, bacteraemia and mortality rates were reduced significantly by early treatment. Thus, in the absence of statistically relevant and well-designed clinical trials, the study demonstrates that prophylactic antibiotic treatment is superior to antibiotic treatment on-demand.
Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial
Authors: Morelli Andrea , Ertmer Christian , Rehberg Sebastian , Lange Matthias , Orecchioni Alessandra , Laderchi Amalia , Bachetoni Alessandra , D'Alessandro Mariadomenica , Van Aken Hugo , Pietropaoli Paolo , Westphal Martin 
Published: November 2008

Abstract
Introduction
Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock.

Methods
We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance.

Results
No differences were found in any of the investigated parameters.

Conclusions
The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.

Trial registration
ClinicalTrial.gov NCT00639015
ArrayPlex: distributed, interactive and programmatic access to genome sequence, annotation, ontology, and analytical toolsets
Authors: Killion Patrick J , Iyer Vishwanath R 
Published: November 2008

AbstractArrayPlex is a software package that centrally provides a large number of flexible toolsets useful for functional genomics, including microarray data storage, quality assessments, data visualization, gene annotation retrieval, statistical tests, genomic sequence retrieval and motif analysis. It uses a client-server architecture based on open source components, provides graphical, command-line, and programmatic access to all needed resources, and is extensible by virtue of a documented application programming interface. ArrayPlex is available at http://sourceforge.net/projects/arrayplex/.
Characterization of the differentially methylated region of the Impactgene that exhibits Glires-specific imprinting
Authors: Okamura Kohji , Wintle Richard F , Scherer Stephen W 
Published: November 2008

Abstract
Background
Imprinted genes are exclusively expressed from one of the two parental alleles in a parent-of-origin-specific manner. In mammals, nearly 100 genes are documented to be imprinted. To understand the mechanism behind this gene regulation and to identify novel imprinted genes, common features of DNA sequences have been analyzed; however, the general features required for genomic imprinting have not yet been identified, possibly due to variability in underlying molecular mechanisms from locus to locus.

Results
We performed a thorough comparative genomic analysis of a single locus, Impact, which is imprinted only in Glires (rodents and lagomorphs). The fact that Glires and primates diverged from each other as recent as 70 million years ago makes comparisons between imprinted and non-imprinted orthologues relatively reliable. In species from the Glires clade, Impact bears a differentially methylated region, whereby the maternal allele is hypermethylated. Analysis of this region demonstrated that imprinting was not associated with the presence of direct tandem repeats nor with CpG dinucleotide density. In contrast, a CpG periodicity of 8 bp was observed in this region in species of the Glires clade compared to those of carnivores, artiodactyls, and primates.

Conclusions
We show that tandem repeats are dispensable, establishment of the differentially methylated region does not rely on G+C content and CpG density, and the CpG periodicity of 8 bp is meaningful to the imprinting. This interval has recently been reported to be optimal for de novo methylation by the Dnmt3a-Dnmt3L complex, suggesting its importance in the establishment of imprinting in Impact and other genes.
Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials
Authors: Arkenau Hendrik-Tobias , Arnold Dirk , Cassidy Jim , Diaz-Rubio Eduardo , Douillard Jean-Yves , Hochster Howard , Martoni Andrea , Grothey Axel , Hinke Axel , Schmiegel Wolff , Schmoll Hans-Joachim , Porschen Rainer 
Published: November 2008

Purpose Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX. Patients and Methods This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity. Results The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia—HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea—HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]—HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens. Conclusion The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.
Natural History of Osteonecrosis of the Jaw in Patients With Multiple Myeloma
Authors: Badros Ashraf , Terpos Evangelos , Katodritou Eirini , Goloubeva Olga , Kastritis Efstathios , Verrou Evgenia , Zervas Kostas , Baer Maria R. , Meiller Timothy , Dimopoulos Meletios A. 
Published: November 2008

Purpose To evaluate the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma. Patients and Methods Ninety-seven patients with myeloma from the United States (n = 37) and Greece (n = 60) were observed prospectively for a minimum 3.2 years after ONJ. Patients characteristics were similar with regard to age, bisphosphonate use, and myeloma therapy, except more autologous transplantations were performed on patients in the United States than in Greece (73% v 28%; P < .0001). Results ONJ resolved in 60 patients (62%), resolved and recurred in 12 patients (12%), and did not heal in 25 patients (26%). Dental procedures preceded ONJ in 46 patients (47%) and were more common in those with single episodes (35 of 60, 58%) than recurrent or nonhealing (11 of 37, 30%; P = .007). Recurrent ONJ followed reinitiation of bisphosphonates in six of 12 patients. Greek patients had more bone pain than United States patients (60% v 30%, P = .001) and were less likely to restart bisphosphonates (5% v 35%, P < .0002). Myeloma relapses were more common in patients with recurrent/nonhealing than single-episode ONJ (84% v 62%; P = .02). Median overall survival from myeloma diagnosis was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single, recurrent, and nonhealing ONJ (P = .2). Conclusion ONJ healed in 75% of patients. Patients with spontaneous ONJ have a higher risk of nonhealing and recurrence. Reinitiating bisphosphonates after healing of ONJ is a reasonable option in patients experiencing relapse who are at risk of skeletal complications. Further studies of the pathogenesis and healing of ONJ are needed.