bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal pneumonia caused by Penicillium digitatum: a case report
Authors: Oshikata Chiyako , Tsurikisawa Naomi , Saito Akemi , Watanabe Maiko , Kamata Yoichi , Tanaka Maki , Tsuburai Takahiro , Mitomi Hiroyuki , Takatori Kosuke , Yasueda Hiroshi , Akiyama Kazuo 
Published: March 2013

Abstract

Background

Penicillium species are among the most common fungi present in the environment and are usually considered non-pathogenic to humans. However, in immunocompromised hosts they can be virulent pathogens and can cause death. Penicillium digitatum is a plant pathogen that commonly causes a postharvest fungal disease of citrus called green mould; it very rarely causes systemic mycosis in humans. Here, we report a case of fatal pneumonia due to P. digitatum infection, as confirmed by repeated examination of cultured sputum.

Case presentation
A cavity was found in the left upper lung on routine chest X-ray in a 78-year-old undernourished male who had been diagnosed at age 66 with bronchial asthma and pulmonary emphysema. No increased sputum production was present. The presence of antigen-specific precipitating antibodies to Aspergillus flavus and P. digitatum was confirmed in the patient’s serum and also later pleural fluid by using Ouchterlony double immunodiffusion testing with A. flavus and P. digitatum antigens. The patient was treated over a period of months with itraconazole, micafungin, voriconazole, amphotericin B, and antibacterials. However, the cavity enlarged, the pleural effusion increased, and the patient began producing purulent sputum. He died from progressive renal failure. From sputum culture only one fungus was isolated repeatedly on potato-dextrose agar in large quantities. This fungus was confirmed to be P. digitatum by molecular identification. Partial sequences of the beta-tubulin gene were determined by using the primers Bt2a and Bt2b for PCR amplification and sequencing and underwent a BLAST search at the National Centre for Biotechnology Information, these results confirmed that the isolated fungus was P. digitatum.

Conclusion
To our knowledge, this is the first report of pulmonary infection with P. digitatum. Our patient had pulmonary emphysema and was elderly, and undernourished. These factors might have facilitated the infection. In his case, antimycotics were ineffective in treating the lung involvement. Although human infection with P. digitatum is considered rare, it appears that this organism can be very virulent and resistant to antimycotics.
Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals
Authors: Meloni Alison R , DeYoung Mary Beth , Han Jenny , Best Jennie H , Grimm Michael 
Published: March 2013

Abstract

Background
Diabetes is associated with a higher risk for adverse cardiovascular outcomes. To improve the health outcomes of patients with type 2 diabetes (T2DM), the American Diabetes Association (ADA) recommended target goals for the improvement of glycemic control and the reduction of cardiovascular risk factors associated with the disease. This retrospective analysis calculated the absolute benefit increase (ABI) of using exenatide once weekly (QW), a glucagon-like peptide-1 (GLP-1) receptor agonist, vs an oral glucose-lowering medication or insulin glargine to achieve ADA-recommended goals. The number needed to treat (NNT) to achieve these goals was also calculated and provides a useful clinical metric for comparing potential therapies from different drug classes.

Methods
Patient data from three double-blind or open label, 26-week, randomized, controlled trials were retrospectively analyzed separately. ABI and NNT were calculated by comparing the percentage of patients treated with exenatide QW (N = 641) vs metformin (N = 246), sitagliptin (N = 329), pioglitazone (N = 328), or insulin glargine (N = 223), who achieved a single glycemic, weight, blood pressure, or lipid goal or a composite of these recommended goals, during the DURATION-2, -3, and -4 clinical trials.

Results
Significant ABIs favoring exenatide QW over all four glucose-lowering medications were observed for at least one HbA1c glycemic goal. NNTs of 4 and 5 were calculated when exenatide QW was compared to sitagliptin for attaining HbA1c goals of <7.0% and ≤6.5%, respectively. Additionally, significantly more patients using exenatide QW compared to sitagliptin, pioglitazone, or insulin glargine attained the composite goal of HbA1c <7% or ≤6.5%, without weight gain or hypoglycemia. Exenatide QW was also favored over sitagliptin and insulin glargine for the achievement of the composite goals of HbA1c <7% (or ≤6.5%), systolic blood pressure <130 mm Hg, and low-density lipoprotein <2.59 mmol/L. For most goals, exenatide QW and metformin had similar effects in treatment naïve patients.

Conclusions
This analysis assessed the between-therapy differences in achieving therapeutic goals with therapies commonly used for glycemic control in patients with T2DM. In clinical trials, exenatide QW assisted more patients in reaching the majority of ADA-recommended therapeutic goals than treatment with sitagliptin, pioglitazone, or insulin glargine.

Trial registration

NCT00637273, NCT00641056, NCT00676338
Complete remission by transarterial infusion with cisplatin for recurrent bile duct tumor thrombus of hepatocellular carcinoma: report of a case
Authors: Ebara Chiharu , Yamazaki Shintaro , Moriguchi Masamichi , Mitsuka Yusuke , Funada Tomoya , Higaki Tokio , Takayama Tadatoshi 
Published: March 2013

Abstract
Bile duct tumor thrombus (BDTT) of a hepatocellular carcinoma (HCC) is a rare entity which was found microscopically in 1 to 9.2% of the resected specimen.
A 54-year-old male was found to have a 65-mm hepatocellular carcinoma in segment VI of the liver with a huge intrahepatic bile duct tumor thrombus. As the main trunk of the posterior segment branched from the left bile duct, the BDTT of the posterior branch extended to the common bile duct via the left bile duct. When the posterior segment was resected along with the left lobe, the estimated remnant liver volume was less than 30%. Therefore, the patient underwent extended posterior segmentectomy with choledochotomy and all of the BDTT was removed via the common bile duct.
Three months later, his serum bilirubin (6.63 mg/dL) and des-gamma-carboxy prothrombin (410 ng/mL) were re-elevated due to recurrent BDTT. A well-enhanced BDTT was observed by computed tomography (CT) at the left bile duct. Transarterial chemotherapy with cisplatin was scheduled, followed by endoscopic retrograde bile duct drainage. After four sessions of this chemotherapy, the BDTT had vanished and the tumor marker was decreased to within the normal range. The patient was stably treated with this regimen and has remained recurrence-free for five years.
Clinical implication of centrosome amplification and expression of centrosomal functional genes in multiple myeloma
Authors: Dementyeva Elena , Kryukov Fedor , Kubiczkova Lenka , Nemec Pavel , Sevcikova Sabina , Ihnatova Ivana , Jarkovsky Jiri , Minarik Jiri , Stefanikova Zdena , Kuglik Petr , Hajek Roman 
Published: March 2013

AbstractBackgroundMultiple myeloma (MM) is a low proliferative tumor of postgerminal center plasma cell (PC). Centrosome amplification (CA) is supposed to be one of the mechanisms leading to chromosomal instability. Also, CA is associated with deregulation of cell cycle, mitosis, DNA repair and proliferation. The aim of our study was to evaluate the prognostic significance and possible role of CA in pathogenesis and analysis of mitotic genes as mitotic disruption markers.Design and methodsA total of 173 patients were evaluated for this study. CD138+ cells were separated by MACS. Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification in PCs. Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) and qRT-PCR were performed on PCs.ResultsBased on the immunofluorescent staining results, all patients were divided into two groups: CA positive (38.2%) and CA negative (61.8%). Among the newly diagnosed patients, worse overall survival was indicated in the CA negative group (44/74) in comparison to the CA positive group (30/74) (P = 0.019).Gene expression was significantly down-regulated in the CA positive group in comparison to CA negative in the following genes:AURKB, PLK4, TUBG1(P < 0.05). Gene expression was significantly down-regulated in newly diagnosed in comparison to relapsed patients in the following genes:AURKA, AURKB, CCNB1, CCNB2, CETN2, HMMR, PLK4, PCNT,andTACC3(P < 0.05).ConclusionsOur findings indicate better prognosis for CA positive newly diagnosed patients. Considering revealed clinical and gene expression heterogeneity between CA negative and CA positive patients, there is a possibility to characterize centrosome amplification as a notable event in multiple myeloma pathogenesis.
Medicinal and useful plants in the tradition of Rotonda, Pollino National Park, Southern Italy
Authors: Di Sanzo Paola , De Martino Laura , Mancini Emilia , Feo Vincenzo De 
Published: March 2013

Abstract

Background
This paper reports an ethnobotanical survey of the traditional uses of medicinal and useful plants in an area of the Pollino National Park, Basilicata, Southern Italy. The study, conducted between 2009 and 2010, gathered information on the medicinal plants traditionally used in the neighbourhood of town of Rotonda, in the Pollino National Park, that appears have very rich and interesting ethnopharmacological traditions.

Methods
In all, we interviewed 120 key informants, whose age ranged between 50 and 95 years.

Results
The research resulted to the identification of 78 medicinal plants belonging to 46 families. Among the species reported, 59 are used in human medicine, 18 for domestic use, 8 in veterinary medicine. Several plants have been reported in previous studies, but with different uses, or never reported.

Conclusions
Data obtained showed that in the studied area the folk use of plants is alive and still derives from daily practice.
Cloud-based solution to identify statistically significant MS peaks differentiating sample categories
Authors: Ji Jun , Ling Jeffrey , Jiang Helen , Wen Qiaojun , Whitin John C , Tian Lu , Cohen Harvey J , Ling Xuefeng B 
Published: March 2013

AbstractBackgroundMass spectrometry (MS) has evolved to become the primary high throughput tool for proteomics based biomarker discovery. Until now, multiple challenges in protein MS data analysis remain: large-scale and complex data set management; MS peak identification, indexing; and high dimensional peak differential analysis with the concurrent statistical tests based false discovery rate (FDR). “Turnkey” solutions are needed for biomarker investigations to rapidly process MS data sets to identify statistically significant peaks for subsequent validation.FindingsHere we present an efficient and effective solution, which provides experimental biologists easy access to “cloud” computing capabilities to analyze MS data. The web portal can be accessed athttp://transmed.stanford.edu/ssa/.ConclusionsPresented web application supplies large scale MS data online uploading and analysis with a simple user interface. This bioinformatic tool will facilitate the discovery of the potential protein biomarkers using MS.
Sccmec type II gene is common among clinical isolates of methicillin-resistant Staphylococcus aureus in Jakarta, Indonesia
Authors: Buntaran Latre , Hatta Mochammad , Sultan Andi R , Dwiyanti Ressy , Sabir Muhammad 
Published: March 2013

Abstract

Background
Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA) is a strain of MRSA that can cause infections in patients in the community, in which these patients had no previous risk factors for MRSA infection and the patient received 72 hours prior to infection when admitted to hospital. This study aims to determine and compare the characteristics of epidemiological, clinical, and molecular biology of CA-MRSA with HA-MRSA.

Methods
A total of 11 clinical strains of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Stapylococcus aureus (MSSA) were collected from 2 hospitals in Jakarta, Indonesia in 2012. SCCmec typing was performed by multiplex polymerase chain reaction (PCR) and the presence of six genes (vraR, vraG, vraA, vraF,fruA, and fruB) associated with vancomycin resistance was examined by simple PCR analysis.

Results
We found three strains of community-acquired MRSA with SCCmec type II and one strain of hospital-acquired MRSA with SCCmec type IV. The other seven strains did not contain mecA genes and SCCmec. Plasmid pUB110 was found in one strain of community-acquired MRSA and two strains of hospital-acquired MRSA. vraA genes were present in 9 of the 11 strains, vraF in 4, vraG in 5, and vraR in 4. Note worthily, three quarters of strains without pUB110 contained vraR and vraF, and 70% contained vraA, whereas 60% of strains with pUB110 contained vraG.

Conclusion
Based on these results, we should be concerned about the possibility of transition from MRSA strains sensitive to vancomycin in VISA strains of MRSA strains obtained in clinical trials. But first we need to look the existence of natural VISA or hVISA among these MRSA strains.
Fluorometric immunocapture assay for the specific measurement of matrix metalloproteinase-9 activity in biological samples: application to brain and plasma from rats with ischemic stroke
Authors: Hawkins Kimberly E , DeMars Kelly M , Yang Changjun , Rosenberg Gary A , Candelario-Jalil Eduardo 
Published: March 2013

Abstract

Background
Matrix metalloproteinases are important factors in the molecular mechanisms leading to neuronal injury in many neurological disorders. Matrix metalloproteinase (MMP)-9 is up-regulated after cerebral ischemia and neuroinflammation and is actively involved in blood–brain barrier disruption. Current methods of measuring MMP-9 activity, such as gelatin-substrate zymography, are unspecific and arduous. Here we developed an immunocapture assay with high efficiency, specificity, and sensitivity for quantifying endogenously active as well as total MMP-9 activity.

Results
A fluorescence resonance energy transfer (FRET) peptide-based immunocapture assay was developed that enables the accurate assessment of total and active forms of MMP-9 in complex biological samples. The FRET assay demonstrated correct and efficient binding of MMP-9 to a mouse monoclonal MMP-9 antibody and high specificity of the immunocapture antibody for MMP-9. Total and active levels of MMP-9 were measured in rat brain homogenates, plasma, human HT-1080 conditioned media, and RBE4 endothelial cell lysates. The FRET immunocapture assay yielded highly similar results for total MMP-9 activity when compared to gelatin-substrate zymography.

Conclusions
We suggest that the new FRET peptide-based immunocapture assay is a viable replacement of zymography for sensitive and high throughput quantification of MMP-9 activity in biological samples.
A hybrid ENO reconstruction with limiters for systems of hyperbolic conservation laws
Authors: Iqbal Peer Arshad Ahmud , Tangman Désiré Yannick , Bhuruth Muddun 
Published: March 2013

Abstract
We consider a new class of essentially non-oscillatory (ENO) piecewise polynomial reconstructions together with interpolants based on Monotone Upwind Schemes for Conservation Laws. We improve the second-order ENO polynomial reconstruction by choosing an additional point inside the stencil in order to obtain the highest accuracy when combined with various non-linear limiters. The resulting algorithms are based on only one stencil selection, and we show that they can be efficiently implemented with largest allowable CFL numbers using optimal strong stability-preserving Runge-Kutta time evolution methods. The numerical results indicate that in some cases the schemes yield errors smaller in magnitude as compared to the fourth-order ENO scheme.
miR-26a Plays an Important Role in Cell Cycle Regulation in ACTH-Secreting Pituitary Adenomas by Modulating Protein Kinase Cδ
Authors: Gentilin Erica , Tagliati Federico , Filieri Carlo , Molè Daniela , Minoia Mariella , Rosaria Ambrosio Maria , degli Uberti Ettore C , Zatelli Maria Chiara 
Published: March 2013

Abstract
The functional aftermath of microRNA (miRNA) dysregulation in ACTH-secreting pituitary adenomas has not been demonstrated. miRNAs represent diagnostic and prognostic biomarkers as well as putative therapeutic targets; their investigation may shed light on the mechanisms that underpin pituitary adenoma development and progression. Drugs interacting with such pathways may help in achieving disease control also in the settings of ACTH-secreting pituitary adenomas. We investigated the expression of 10 miRNAs among those that were found as most dysregulated in human pituitary adenoma tissues in the settings of a murine ACTH-secreting pituitary adenoma cell line, AtT20/D16v-F2. The selected miRNAs to be submitted to further investigation in AtT20/D16v-F2 cells represent an expression panel including 5 up-regulated and 5 down-regulated miRNAs. Among these, we selected the most dysregulated mouse miRNA and searched for miRNA targets and their biological function. We found that AtT20/D16v-F2 cells have a specific miRNA expression profile and that miR-26a is the most dysregulated miRNA. The latter is overexpressed in human pituitary adenomas and can control viable cell number in the in vitro model without involving caspase 3/7-mediated apoptosis. We demonstrated that protein kinase Cδ (PRKCD) is a direct target of miR-26a and that miR26a inhibition delays the cell cycle in G1 phase. This effect involves down-regulation of cyclin E and cyclin A expression via PRKCD modulation. miR-26a and related pathways, such as PRKCD, play an important role in cell cycle control of ACTH pituitary cells, opening new therapeutic possibilities for the treatment of persistent/recurrent Cushing's disease.
Developmental Programming: Gestational Bisphenol-A Treatment Alters Trajectory of Fetal Ovarian Gene Expression
Authors: Veiga-Lopez Almudena , Luense Lacey J. , Christenson Lane K. , Padmanabhan Vasantha 
Published: March 2013

Abstract
Bisphenol-A (BPA), a ubiquitous environmental endocrine disrupting chemical, is a component of polycarbonate plastic and epoxy resins. Because of its estrogenic properties, there is increasing concern relative to risks from exposures during critical periods of early organ differentiation. Prenatal BPA treatment in sheep results in low birth weight, hypergonadotropism, and ovarian cycle disruptions. This study tested the hypothesis that gestational exposure to bisphenol A, at an environmentally relevant dose, induces early perturbations in the ovarian transcriptome (mRNA and microRNA). Pregnant Suffolk ewes were treated with bisphenol A (0.5 mg/kg, sc, daily, produced ∼2.6 ng/mL of unconjugated BPA in umbilical arterial samples of BPA treated fetuses approaching median levels of BPA measured in maternal circulation) from days 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, key ovarian regulators, and microRNA biogenesis components were measured by RT-PCR using RNA derived from fetal ovaries collected on gestational days 65 and 90. An age-dependent effect was evident in most steroidogenic enzymes, steroid receptors, and key ovarian regulators. Prenatal BPA increased Cyp19 and 5α-reductase expression in day 65, but not day 90, ovaries. Fetal ovarian microRNA expression was altered by prenatal BPA with 45 down-regulated (&gt;1.5-fold) at day 65 and 11 down-regulated at day 90 of gestation. These included microRNAs targeting Sry-related high-mobility-group box (SOX) family genes, kit ligand, and insulin-related genes. The results of this study demonstrate that exposure to BPA at an environmentally relevant dose alters fetal ovarian steroidogenic gene and microRNA expression of relevance to gonadal differentiation, folliculogenesis, and insulin homeostasis.
Free Fatty Acids Induce Lhb mRNA but Suppress Fshb mRNA in Pituitary LβT2 Gonadotropes and Diet-Induced Obesity Reduces FSH Levels in Male Mice and Disrupts the Proestrous LH/FSH Surge in Female Mice
Authors: Sharma Shweta , Morinaga Hidetaka , Hwang Vicky , Fan WuQiang , Fernandez Marina O. , Varki Nissi , Olefsky Jerrold M. , Webster Nicholas J. G. 
Published: March 2013

Abstract
Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction. We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production. FFAs caused a time- and dose-dependent increase in phosphorylation of the MAPKs p38MAPK, c-Jun N-terminal kinase (JNK)-1/2, and ERK1/2 in LβT2 gonadotrope cells. Furthermore, FFAs up-regulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling. FFAs enhanced the activation of the MAPKs in the presence of GnRH, although the cotreatment did not alter Lhb induction but did eliminate the GnRH induction of Fshb. FFAs also suppressed activin-induced Fshb expression. Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via toll-like receptor-2 and toll-like receptor-4 and was mimicked by lipopolysaccharide stimulation. In vivo, male C57BL/6 mice on a high-fat diet showed reduced FSH levels consistent with the suppression of Fshb seen in vitro. Histological analysis of the testes showed an increased number of abnormal seminiferous tubules. Female mice on a high-fat diet lacked the expected proestrus LH and FSH surge and exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea. Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.
Drug Ligand-Induced Activation of Translocator Protein (TSPO) Stimulates Steroid Production by Aged Brown Norway Rat Leydig Cells
Authors: Chung J.-Y. , Chen H. , Midzak A. , Burnett A. L. , Papadopoulos V. , Zirkin B. R. 
Published: March 2013

AbstractTranslocator protein (TSPO; 18 kDA) is a high-affinity cholesterol-binding protein that is integrally involved in cholesterol transfer from intracellular stores into mitochondria, the rate-determining step in steroid formation. Previous studies have shown that TSPO drug ligands are able to activate steroid production by MA-10 mouse Leydig tumor cells and by mitochondria isolated from steroidogenic cells. We hypothesized herein that the direct, pharmacological activation of TSPO might induce aged Leydig cells, which are characterized by reduced T production, to produce significantly higher levels of T both in vitro and in vivo. To test this, we first examined the in vitro effects of the TSPO selective and structurally distinct drug ligands N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27) and benzodiazepine 4′-chlorodiazepam (Ro5-4864) on steroidogenesis by Leydig cells isolated from aged (21-24 months old) and young adult (3-6 months old) Brown Norway rats. The ligands stimulated Leydig cell T production significantly, and equivalently, in cells of both ages, an effect that was significantly inhibited by the specific TSPO inhibitor 5-androsten-3,17,19-triol (19-Atriol). Additionally, we examined the in vivo effects of administering FGIN-1-27 to young and aged rats. In both cases, serum T levels increased significantly, consistent with the in vitro results. Indeed, serum T levels in aged rats administered FGIN-1-27 were equivalent to T levels in the serum of control young rats. Taken together, these results indicate that although there are reduced amounts of TSPO in aged Leydig cells, its direct activation is able to increase T production. We suggest that this approach might serve as a therapeutic means to increase steroid levels in vivo in cases of primary hypogonadism.