bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible antiviral effect of ciprofloxacin treatment on polyomavirus BK replication and analysis of non-coding control region sequences
Authors: Umbro Ilaria , Anzivino Elena , Tinti Francesca , Zavatto Assunta , Bellizzi Anna , Rodio Donatella Maria , Mancini Carlo , Pietropaolo Valeria , Mitterhofer Anna Paola 
Published: September 2013

AbstractAcute renal dysfunction (ARD) is a common complication in renal transplant recipients. Multiple factors contribute to ARD development, including acute rejection and microbial infections. Many viral infections after kidney transplantation result from reactivation of “latent” viruses in the host or from the graft, such as the human Polyomavirus BK (BKV). We report the case of a 39 year-old recipient of a 2ndkidney graft who experienced BKV reactivation after a second episode of acute humoral rejection. A 10-day treatment with the quinolone antibiotic ciprofloxacin was administered with an increase of immunosuppressive therapy despite the active BKV replication. Real Time PCR analysis performed after treatment with ciprofloxacin, unexpectedly showed clearance of BK viremia and regression of BK viruria. During the follow-up, BK viremia persisted undetectable while viruria decreased further and disappeared after 3 months.BKV non-coding control region sequence analysis from all positive samples always showed the presence of archetypal sequences, with two single-nucleotide substitutions and one nucleotide deletion that, interestingly, were all representative of the subtype/subgroup I/b-1 we identified by the viral protein 1 sequencing analysis.We report the potential effect of the quinolone antibiotic ciprofloxacin in the decrease of the BKV load in both blood and urine.
Proliferation inhibition and apoptosis induction of imatinib-resistant chronic myeloid leukemia cells via PPP2R5C down-regulation
Authors: Shen Qi , Liu Sichu , Chen Yu , Yang Lijian , Chen Shaohua , Wu Xiuli , Li Bo , Lu Yuhong , Zhu Kanger , Li Yangqiu 
Published: September 2013

Abstract
Despite the success of imatinib and other tyrosine kinase inhibitors (TKIs), chronic myeloid leukemia (CML) remains largely incurable, and a number of CML patients die due to Abl mutation-related drug resistance and blast crisis. The aim of this study was to evaluate proliferation inhibition and apoptosis induction by down-regulating PPP2R5C gene expression in the imatinib-sensitive and imatinib-resistant CML cell lines K562, K562R (imatinib resistant without an Abl gene mutation), 32D-Bcr-Abl WT (imatinib-sensitive murine CML cell line with a wild type Abl gene) and 32D-Bcr-Abl T315I (imatinib resistant with a T315I Abl gene mutation) and primary cells from CML patients by RNA interference. PPP2R5C siRNAs numbered 799 and 991 were obtained by chemosynthesis. Non-silencing siRNA scrambled control (SC)-treated, mock-transfected, and untreated cells were used as controls. The PPP2R5C mRNA and protein expression levels in treated CML cells were analyzed by quantitative real-time PCR and Western blotting, and in vitro cell proliferation was assayed with the cell counting kit-8 method. The morphology and percentage of apoptosis were revealed by Hoechst 33258 staining and flow cytometry (FCM). The results demonstrated that both siRNAs had the best silencing results after nucleofection in all four cell lines and primary cells. A reduction in PPP2R5C mRNA and protein levels was observed in the treated cells. The proliferation rate of the PPP2R5C-siRNA-treated CML cell lines was significantly decreased at 72 h, and apoptosis was significantly increased. Significantly higher proliferation inhibition and apoptosis induction were found in K562R cells treated with PPP2R5C-siRNA799 than K562 cells. In conclusion, the suppression of PPP2R5C by RNA interference could inhibit proliferation and effectively induce apoptosis in CML cells that were either imatinib sensitive or resistant. Down-regulating PPP2R5C gene expression might be considered as a new therapeutic target strategy for CML, particularly for imatinib-resistant CML.
Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers
Authors: Yera-Alos Isis B , Alonso-Carbonell Liuba , Valenzuela-Silva Carmen M , Tuero-Iglesias Angela D , Moreira-Martínez Martha , Marrero-Rodríguez Ivonne , López-Mola Ernesto , López-Saura Pedro A 
Published: September 2013

AbstractBackgroundAfter several exploratory and confirmatory clinical trials, the intralesional administration of human recombinant epidermal growth factor (hrEGF) has been approved for the treatment of advanced diabetic foot ulcers (DFU). The aim of this work was to evaluate the effectiveness and safety of this procedure in medical practice.MethodsA prospective, post-marketing active pharmacosurveillance was conducted in 41 hospitals and 19 primary care polyclinics. Patients with DFU received hrEGF, 25 or 75 μg, intralesionally 3 times per week until complete granulation of the ulcer or 8 weeks maximum, adjuvant to standard wound care. Outcomes measured were complete granulation, amputations, and adverse events (AE) during treatment; complete lesion re-epithelization and relapses in follow-up (median: 1.2; maximum 4.2 years).ResultsThe study included 1788 patients with 1835 DFU (81% Wagner’s grades 3 or 4; 43% ischemic) treated from May 2007 to April 2010. Complete granulation was observed in 76% of the ulcers in 5 weeks (median). Ulcer non-ischemic etiology (OR: 3.6; 95% CI: 2.8-4.7) and age (1.02; 1.01-1.03, for each younger year) were the main variables with influence on this outcome. During treatment, 220 (12%) amputations (171 major) were required in 214 patients, mostly in ischemic or Wagner’s grade 3 to 5 ulcers. Re-epithelization was documented in 61% of the 1659 followed-up cases; 5% relapsed per year. AE (4171) were reported in 47% of the subjects. Mild or moderate local pain and burning sensation, shivering and chills, were 87% of the events. Serious events, not related to treatment, occurred in 1.7% of the patients.ConclusionsThe favorable benefit/risk balance, confirms the beneficial clinical profile of intralesional hrEGF in the treatment of DFUs.
Should sperm be cryopreserved after spinal cord injury?
Authors: Karsenty Gilles , Bernuz Benjamin , Metzler-Guillemain Catherine , Grillo Jean-Marie , Saïas-Magnan Jacqueline , Rigot Jean-Marc , Perrin Jeanne 
Published: September 2013

AbstractIn spinal cord injured (SCI) patients, three main factors may cause infertility: erectile dysfunction, ejaculatory dysfunction and impaired semen quality. This letter aims to discuss how we can manage SCI patients’ fertility in accordance with patient-centred care. For such SCI patients aged 20 to 40, having children represents hope for the future. Furthermore, it is a way to rebuild a life after the spinal injury and must be seen as an important part of the rehabilitation program. We suggest that sperm cryopreservation may contribute to patient-centred care management of SCI patients’ fertility, although there is no scientific evidence that cryopreservation will improve fertility outcome after SCI. Indeed, sperm cryopreservation is an affordable and simple technique in specialised centres with trained staff. Here, a protocol to manage SCI patients’ fertility is discussed: we propose PVS for sperm banking to all SCI patients after the phase of spinal shock during the rehabilitation program. If live sperm are retrieved, they are frozen and stored; however, if no live sperm are retrieved, electroejaculation and/or surgical sperm extraction are proposed only for patients who desire biological fatherhood. Prospective studies on the evolution of semen parameters, ejaculatory dysfunction, post-infectious obstructions and spermatogenesis impairment in chronic SCI patients are urgently needed to provide robust data for the evidence-based management of SCI patients’ fertility. Even if use rates are expected to be low, sperm banking may be a simple and affordable preventative measure for selected male SCI patients.
Increase methylmercury accumulation in Arabidopsis thaliana expressing bacterial broad-spectrum mercury transporter MerE
Authors: Sone Yuka , Nakamura Ryosuke , Pan-Hou Hidemitsu , Sato Masa H , Itoh Tomoo , Kiyono Masako 
Published: September 2013

Abstract
The bacterial merE gene derived from the Tn21 mer operon encodes a broad-spectrum mercury transporter that governs the transport of methylmercury and mercuric ions across bacterial cytoplasmic membranes, and this gene is a potential molecular tool for improving the efficiency of methylmercury phytoremediation. A transgenic Arabidopsis engineered to express MerE was constructed and the impact of expression of MerE on methylmercury accumulation was evaluated. The subcellular localization of transiently expressed GFP-tagged MerE was examined in Arabidopsis suspension-cultured cells. The GFP-MerE was found to localize to the plasma membrane and cytosol. The transgenic Arabidopsis expressing MerE accumulated significantly more methymercury and mercuric ions into plants than the wild-type Arabidopsis did. The transgenic plants expressing MerE was significantly more resistant to mercuric ions, but only showed more resistant to methylmercury compared with the wild type Arabidopsis. These results demonstrated that expression of the bacterial mercury transporter MerE promoted the transport and accumulation of methylmercury in transgenic Arabidopsis, which may be a useful method for improving plants to facilitate the phytoremediation of methylmercury pollution.
Gout impacts on function and health-related quality of life beyond associated risk factors and medical conditions: results from the KING observational study of the Italian Society for Rheumatology (SIR)
Authors: Scirè Carlo Alberto , Manara Maria , Cimmino Marco Amedeo , Govoni Marcello , Salaffi Fausto , Punzi Leonardo , Monti Maria Cristina , Carrara Greta , Montecucco Carlomaurizio , Matucci-Cerinic Marco , Minisola Giovanni ,   KING Study Collaborators
Published: September 2013

Abstract
Introduction
Gout is the most prevalent arthritis and significantly impacts on function and quality of life. Given that gout associates with disabling comorbid conditions, it is not clear whether such a complex of diseases accounts for the increased disability or if gout may play a role by itself. This study aims to evaluate the specific influence of gout and disease-related features on functional disability and health-related quality of life (HRQoL) in patients with gout followed in rheumatology clinics.

Methods
A random sample of patients was drawn from clinical registries of 30 rheumatology clinics across Italy. Sociodemographic, general health and gout-specific variables were collected. Functional disability and HRQoL were assessed by the health assessment questionnaire (HAQ) and the Physical and Mental Component Summary scores (PCS and MCS) of the Short Form-36 (SF-36). Crude and adjusted ordinal logistic and linear regression models were applied to investigate the specific contribution of different variables on HAQ and SF-36 scores. Results are presented as odds ratio (OR) or mean difference (MD) and 95% confidence intervals.

Results
Out of 446 patients with gout, 90% were males with a mean age of 63.9 years and median disease duration of 3.8 years; the majority of patients were overweight or obese, and with several comorbidities; 21.1% showed at least moderate disability; the PCS score was significantly lower than expected age- and gender-matched samples in the general population, while MCS score was not. After adjusting for potential sociodemographic and general-health confounders, gout-specific variables significantly impacted on HAQ, including polyarticular involvement OR 3.82 (1.63, 8.95), presence of tophi OR 1.92 (1.07, 3.43) and recent attacks OR 2.20 (1.27, 3.81). Consistent results were found for PCS. The impairment of PCS compared to the general population was limited to patients with features of chronic gout. MCS was only affected by recent attacks (MD -2.72 [-4.58, -0.86]) and corticosteroid treatment (-3.39 [-5.30,-1.48]).

Conclusions
The data from the KING study confirm that gout impacts on disability and provide evidence for an independent association of gout and gout-related features with functional outcome and HRQoL. This result supports the need to improve specific treatment in gout.
Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage
Authors: Nguyen Christelle , Bazin Dominique , Daudon Michel , Chatron-Colliet Aurore , Hannouche Didier , Bianchi Arnaud , Côme Dominique , So Alexander , Busso Nathalie , Lioté Frédéric , Ea Hang-Korng 
Published: September 2013

Abstract
Introduction
Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage.

Methods
We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transform infra-red spectrometry and scanning electron microscopy of 8 to 10 cartilage zones of each knee, including medial and lateral femoral condyles and tibial plateaux and the intercondyle zone. Differential expression of genes involved in the mineralization process between cartilage with and without calcification was assessed in samples from 8 different patients by RT-PCR. Immunohistochemistry and histology studies were performed in 6 different patients.

Results
Mean (SEM) age and body mass index of patients at the time of TKR was 74.6 (1.7) years and 28.1 (1.6) kg/m², respectively. Preoperative X-rays showed joint calcifications (chondrocalcinosis) in 4 cases only. The medial femoro-tibial compartment was the most severely affected in all cases, and mean (SEM) Kellgren-Lawrence score was 3.8 (0.1). All 20 OA cartilages showed CaC crystals. The mineral content represented 7.7% (8.1%) of the cartilage weight. All patients showed BCP crystals, which were associated with CPP crystals for 8 joints. CaC crystals were present in all knee joint compartments and in a mean of 4.6 (1.7) of the 8 studied areas. Crystal content was similar between superficial and deep layers and between medial and femoral compartments. BCP samples showed spherical structures, typical of biological apatite, and CPP samples showed rod-shaped or cubic structures. The expression of several genes involved in mineralization, including human homolog of progressive ankylosis, plasma-cell-membrane glycoprotein 1 and tissue-nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages.

Conclusions
CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process.
Prolactin-Stat5 signaling in breast cancer is potently disrupted by acidosis within the tumor microenvironment
Authors: Yang Ning , Liu Chengbao , Peck Amy R , Girondo Melanie A , Yanac Alicia F , Tran Thai H , Utama Fransiscus E , Tanaka Takemi , Freydin Boris , Chervoneva Inna , Hyslop Terry , Kovatich Albert J , Hooke Jeffrey A , Shriver Craig D , Rui Hallgeir 
Published: September 2013

Abstract
Introduction
Emerging evidence in estrogen receptor-positive breast cancer supports the notion that prolactin-Stat5 signaling promotes survival and maintenance of differentiated luminal cells, and loss of nuclear tyrosine phosphorylated Stat5 (Nuc-pYStat5) in clinical breast cancer is associated with increased risk of antiestrogen therapy failure. However, the molecular mechanisms underlying loss of Nuc-pYStat5 in breast cancer remain poorly defined.

Methods
We investigated whether moderate extracellular acidosis of pH 6.5 to 6.9 frequently observed in breast cancer inhibits prolactin-Stat5 signaling, using in vitro and in vivo experimental approaches combined with quantitative immunofluorescence protein analyses to interrogate archival breast cancer specimens.

Results
Moderate acidosis at pH 6.8 potently disrupted signaling by receptors for prolactin but not epidermal growth factor, oncostatin M, IGF1, FGF or growth hormone. In breast cancer specimens there was mutually exclusive expression of Nuc-pYStat5 and GLUT1, a glucose transporter upregulated in glycolysis-dependent carcinoma cells and an indirect marker of lactacidosis. Mutually exclusive expression of GLUT1 and Nuc-pYStat5 occurred globally or regionally within tumors, consistent with global or regional acidosis. All prolactin-induced signals and transcripts were suppressed by acidosis, and the acidosis effect was rapid and immediately reversible, supporting a mechanism of acidosis disruption of prolactin binding to receptor. T47D breast cancer xenotransplants in mice displayed variable acidosis (pH 6.5 to 6.9) and tumor regions with elevated GLUT1 displayed resistance to exogenous prolactin despite unaltered levels of prolactin receptors and Stat5.

Conclusions
Moderate extracellular acidosis effectively blocks prolactin signaling in breast cancer. We propose that acidosis-induced prolactin resistance represents a previously unrecognized mechanism by which breast cancer cells may escape homeostatic control.
Mammary Carcinoma Cell Derived Cyclooxygenase 2 Suppresses Tumor Immune Surveillanceby Enhancing Intratumoral Immune Checkpoint Activity
Authors: Markosyan Nune , Chen Edward P , Evans Rebecca A , Ndong Victoire , Vonderheide Robert H , Smyth Emer M 
Published: September 2013

Abstract
Introduction
Systemic inhibition of the inflammatory enzyme cyclooxygenase (COX) 2 decreasesthe risk of breast cancer and its recurrence. However, the biology of COX-2 in themulticellular tumor microenvironment is poorly defined.

Methods
Mammary tumor onset and multiplicity were examined in ErbB2 transgenic mice thatwere deficient in mammary epithelial cell COX-2 (COX-2MECKO) comparedto wild type (WT) mice.
Tumors were analyzed, by real time PCR, immune-staining and flow cytometry, forproliferation, apoptosis, angiogenesis and immune microenvironment. LentiviralshRNA delivery was used to knock down (KD) COX-2 in ErbB2-transformed mouse breastcancer cells (COX-2KD), and growth as orthotopic tumors was examined in syngenicrecipient mice, with or without depletion of CD8+ immune cells.

Results
Mammary tumor onset was delayed, and multiplicity halved, in COX-2MECKOmice compared to WT. COX-2MECKO tumors showed decreased expression ofKi67, a proliferation marker, as well as reduced VEGFA, its receptor VEGFR2,endothelial NOS and the vascular endothelial marker CD31, indicating reduced tumorvascularization. COX-2MECKO tumors contained more CD4+ Thelper (Th) cells and CD8+ cytotoxic immune cells (CTL)consistent with increased immune surveillance. The ratio of Th markersTbet (Th1) to GATA3 (Th2) was higher, and levels of Retnla,a M2 macrophage marker, lower, in COX-2MECKO tumor infiltratingleukocytes compared to WT, suggesting a prevalence of pro-immune Th1over immune suppressive Th2 lymphocytes, and reduced macrophagepolarization to the immune suppressive M2 phenotype. Enhanced immune surveillancein COX-2MECKO tumors was coincident with increased intratumoral CXCL9,a T cell chemoattractant, and decreased expression of T lymphocyte co-inhibitoryreceptors CTLA4 and PD-1, as well as PD-L1, the ligand for PD-1. PD-L1 was alsodecreased in IFNγ-treated COX-2KD mouse mammary cancer cells in vitro and, compared to control cells, growth of COX-2KD cells as orthotopic tumorsin immune competent mice was markedly suppressed. However, robust growth ofCOX-2KD tumor cells was evident when recipients were depleted of CD8+ cells.

Conclusions
The data strongly support that, in addition to its angiogenic function, tumor cellCOX-2 suppresses intratumoral cytotoxic CD8+ immune cell function,possibly through upregulation of immune checkpoints, thereby contributing to tumorimmune escape. COX-2 inhibition may be clinically useful to augment breast cancerimmunotherapy.
The subxiphoid view cannot replace the apical view for transthoracic echocardiographic assessment of hemodynamic status
Authors: Maizel Julien , Salhi Ahmed , Tribouilloy Christophe , Massy Ziad A , Choukroun Gabriel , Slama Michel 
Published: September 2013

Abstract
Introduction
This prospective study aimed to assess whether use of the subxiphoid acoustic window in transthoracic echocardiography (TTE) can be an accurate alternative in the absence of an apical view to assess hemodynamic parameters.

Methods
This prospective study took place in a teaching hospital medical ICU. Over a 4-month period, TTE was performed in patients admitted for more than 24 hours. Two operators rated the quality of parasternal, apical, and subxiphoid acoustic windows as Excellent, Good, Acceptable, Poor, or No image. In the subpopulation presenting adequate (rated as acceptable or higher) apical and subxiphoid views, we compared the left ventricular ejection fraction (LVEF), the ratio between right and left ventricular end-diastolic areas (RVEDA/LVEDA), the ratio between early and late mitral inflow on pulsed Doppler (E/A ratio), the aortic velocity time integral (Ao VTI), and the ratio between early mitral inflow and displacement of the mitral annulus on tissue Doppler imaging (E/Ea ratio).

Results
An adequate apical view was obtained in 80%, and an adequate subxiphoid view was obtained in 63% of the 107 patients included. Only 5% of patients presented an adequate subxiphoid view without an adequate apical view. In the subpopulation of patients with adequate apical and subxiphoid windows (n = 65), LVEF, E/A, and RVEDA/LVEDA were comparable on both views, and were strongly correlated (r > 0.80) with acceptable biases and precision. However, the Ao VTI and the E/Ea ratio were lower on the subxiphoid view than on the apical view (18 ± 5 versus 16 ± 5 cm and 9.6 ± 4.6 versus 7.6 ± 4 cm, respectively, P = 0.001 for both).

Conclusions
An adequate TTE subxiphoid window was obtained in fewer than two thirds of ICU patients. In addition to the classic indication for the subxiphoid window to study the vena cava and pericardium, this view can be used to study right and left ventricular morphology and function, but does not provide accurate hemodynamic Doppler information. ICU echocardiographers should therefore record both apical and subxiphoid views to assess comprehensively the cardiac function and hemodynamic status.