bluuebunny/crossref_metadata_2025 huggingface dataset:
Presenting Health Statistics on the Web
Authors: Killam H. William , Han Paul K.
Published: June 2013

There has been a significant amount of research looking at the issue of displaying statistical data to the general public. Much of this work has been in the area of presenting risk data. Despite a significant amount of research, many organizations still fail to utilize this research when presenting this information in web-based tools and applications. This paper reviews a specific effort to apply this research knowledge to the design of a specific tool for displaying risk data to the general public.
Patient and Provider Perspectives on Electronic Helath Record (EHR) Information Access and Rights
Authors: Vallette Marissa A. , Caldwell Barrett S.
Published: June 2013

Electronic health records (EHRs) are becoming an important aspect of how members of a healthcare organization organize and share patient information effectively and efficiently in patient care. EHRs can provide substantial potential benefits to healthcare providers, if roles and tasks are well coordinated between providers and patients. Poor or incompatible implementation of the EHR and information flow between patients and providers represents barriers to accurate and valid information dissemination. The authors’ research expands on previous studies, and examines privacy and security issues and the perspective of distributed expertise incorporating both providers and patients. The case study to be highlighted examines patient and provider perspectives of expertise, communication effectiveness, and the sharing of information (with and without the EHR) in outpatient OB/GYN clinical care.
Designing Automated Aids for Patient Monitoring Systems in Intensive Care Units
Authors: Li Huiyang , Ku Melody , Schumacher Robert , Seagull F. Jacob
Published: June 2013

This study investigated the challenges faced by care givers in using patient monitoring systems, specifically focusing on the needs for automation support in patient monitoring tasks. User interactions with monitors in a Neonatal Intensive Care Unit were studied through field observation, interviews, and cognitive task analysis. Results show that physicians are primarily interested in the patient health trends and progress, while the nurses prefer more routine operating abilities. Based on these results, two automation aids were developed in support of (1) CRG (cardiorespirography) trends retrieval (an information integration task), and (2) alarm limits adjusting (a decision making task). Future studies will involve evaluation and refinement of the designs through both heuristic evaluation and simulation experiments to further improve the monitor’s functions. This work has implications on the design of patient monitoring systems in intensive care units as well as other medical environments.
Medical Device Usability Analyses
Authors: Campoe Kristi R.
Published: June 2013

Errors committed during healthcare providers’ use of patient controlled analgesia (PCA) systems in the acute care setting are poorly understood. A PCA is a complex, medical device that delivers a prescribed pain medication primarily through the intravenous route into the patient. The benefits of PCA use are numerous, but PCAs are also a known source of errors resulting in patient injury. Human factors usability analyses are methods to identify and mitigate factors that contribute to errors during user-device interaction. The purpose of this paper is to present the findings from an integrative review of published medical device usability analyses and to provide the foundation for future empirical research to improve our understanding of PCA system errors.
‘Excuse Me’
Authors: O’Connor Paul , Byrne Dara , O’Dea Angela
Published: June 2013

A consistent finding in healthcare is that juniors are unwilling to ‘speak up’ to seniors. Training designed to encourage junior doctors to speak up was designed, delivered, and evaluated. The training was constructed around filmed stories of senior doctors describing situations in which their communication and assertiveness skills were challenged. A total of 110 interns attended the training. The feedback from participants was positive. There was a significant increase in knowledge as a result of the training, and some evidence to support a shift in attitudes in the desirable direction relating to the need to speak-up to seniors. No effect of the training was found on behavior. The results are encouraging in terms of reactions and learning, but further training is required to impact the behavior of junior doctors.
Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P)
Authors: Zhang Lin , Urtz Nicole , Gaertner Florian , Legate Kyle R. , Petzold Tobias , Lorenz Michael , Mazharian Alexandra , Watson Steve P. , Massberg Steffen
Published: June 2013

Key Points

Sphk2 provides a source of intracellular S1P that tightly controls thrombopoiesis by regulating SFK expression and activity in MKs. Modulation of intracellular S1P by regulating Sphk2 may provide a new strategy to enhance platelet production in patients with thrombocytopenia.
CX3CR1 reduces Ly6Chigh-monocyte motility within and release from the bone marrow after chemotherapy in mice
Authors: Jacquelin Sébastien , Licata Fabrice , Dorgham Karim , Hermand Patricia , Poupel Lucie , Guyon Elodie , Deterre Philippe , Hume David A. , Combadière Christophe , Boissonnas Alexandre
Published: June 2013

Key Points

CX3CR1 mediates monocyte retention in the bone marrow. Myelorestoration after chemotherapy is controlled by chemokine receptors.
Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results
Authors: Gay Francesca , Magarotto Valeria , Crippa Claudia , Pescosta Norbert , Guglielmelli Tommasina , Cavallo Federica , Pezzatti Sara , Ferrari Samantha , Liberati Anna Marina , Oliva Stefania , Patriarca Francesca , Offidani Massimo , Omedé Paola , Montefusco Vittorio , Petrucci Maria Teresa , Giuliani Nicola , Passera Roberto , Pietrantuono Giuseppe , Boccadoro Mario , Corradini Paolo , Palumbo Antonio
Published: June 2013

Key Points

Bortezomib-induction/Mel100-ASCT/lenalidomide consolidation-maintenance is effective in elderly patients with excellent performance status. Deaths related to AEs were higher in patients ≥70 years, suggesting the need of a more careful patient selection.
HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10
Authors: Takahashi Masahiko , Higuchi Masaya , Makokha Grace Naswa , Matsuki Hideaki , Yoshita Manami , Tanaka Yuetsu , Fujii Masahiro
Published: June 2013

Key Points

Interaction of HTLV-1 Tax with USP10 reduces arsenic-induced stress granule formation and enhances ROS production. USP10 controls sensitivities of leukemia cell lines to arsenic-induced apoptosis.
Tc-knirps plays different roles in the specification of antennal and mandibular parasegment boundaries and is regulated by a pair-rule gene in the beetle Tribolium castaneum
Authors: Peel Andrew D , Schanda Julia , Grossmann Daniela , Ruge Frank , Oberhofer Georg , Gilles Anna F , Schinko Johannes B , Klingler Martin , Bucher Gregor
Published: June 2013

Background

The Drosophila larval head is evolutionarily derived at the genetic and morphological level. In the beetle Tribolium castaneum, development of the larval head more closely resembles the ancestral arthropod condition. Unlike in Drosophila, a knirps homologue (Tc-kni) is required for development of the antennae and mandibles. However, published Tc-kni data are restricted to cuticle phenotypes and Tc-even-skipped and Tc-wingless stainings in knockdown embryos. Hence, it has remained unclear whether the entire antennal and mandibular segments depend on Tc-kni function, and whether the intervening intercalary segment is formed completely. We address these questions with a detailed examination of Tc-kni function.

Results

By examining the expression of marker genes in RNAi embryos, we show that Tc-kni is required only for the formation of the posterior parts of the antennal and mandibular segments (i.e. the parasegmental boundaries). Moreover, we find that the role of Tc-kni is distinct in these segments: Tc-kni is required for the initiation of the antennal parasegment boundary, but only for the maintenance of the mandibular parasegmental boundary. Surprisingly, Tc-kni controls the timing of expression of the Hox gene Tc-labial in the intercalary segment, although this segment does form in the absence of Tc-kni function. Unexpectedly, we find that the pair-rule gene Tc-even-skipped helps set the posterior boundary of Tc-kni expression in the mandible. Using the mutant antennaless, a likely regulatory Null mutation at the Tc-kni locus, we provide evidence that our RNAi studies represent a Null situation.

Conclusions

Tc-kni is required for the initiation of the antennal and the maintenance of the mandibular parasegmental boundaries. Tc-kni is not required for specification of the anterior regions of these segments, nor the intervening intercalary segment, confirming that Tc-kni is not a canonical ‘gap-gene’. Our finding that a gap gene orthologue is regulated by a pair rule gene adds to the view that the segmentation gene hierarchies differ between Tribolium and Drosophila upstream of the pair rule gene level. In Tribolium, as in Drosophila, head and trunk segmentation gene networks cooperate to pattern the mandibular segment, albeit involving Tc-kni as novel component.
Cubilin expression is monoallelic and epigenetically augmented via PPARs
Authors: Aseem Obaidullah , Barth Jeremy L , Klatt Sandra C , Smith Brian T , Argraves W Scott
Published: June 2013

Background

Cubilin is an endocytic receptor that is necessary for renal and intestinal absorption of a range of ligands. Endocytosis mediated by cubilin and its co-receptor megalin is the principal mechanism for proximal tubule reabsorption of proteins from the glomerular filtrate. Cubilin is also required for intestinal endocytosis of intrinsic factor-vitamin B12 complex. Despite its importance, little is known about the regulation of cubilin expression.

Results

Here we show that cubilin expression is under epigenetic regulation by at least two processes. The first process involves inactivation of expression of one of the cubilin alleles. This monoallelic expression state could not be transformed to biallelic by inhibiting DNA methylation or histone deacetylation. The second process involves transcriptional regulation of cubilin by peroxisome proliferator-activated receptor (PPAR) transcription factors that are themselves regulated by DNA methylation and histone deacetylation. This is supported by findings that inhibitors of DNA methylation and histone deacetylation, 5Aza and TSA, increase cubilin mRNA and protein in renal and intestinal cell lines. Not only was the expression of PPARα and γ inducible by 5Aza and TSA, but the positive effects of TSA and 5Aza on cubilin expression were also dependent on both increased PPAR transcription and activation. Additionally, 5Aza and TSA had similar effects on the expression of the cubilin co-receptor, megalin.

Conclusions

Together, these findings reveal that cubilin and megalin mRNA expression is under epigenetic control and thus point to new avenues for overcoming pathological suppression of these genes through targeting of epigenetic regulatory processes.
Comparative analysis of the alveolar macrophage proteome in ALI/ARDS patients between the exudative phase and recovery phase
Authors: Dong Haiyun , Li Jinxiu , Lv Youdi , Zhou Yanyan , Wang Guyi , Hu Shuang , He Xiaoyu , Yang Ping , Zhou Zhiguang , Xiang Xudong , Wang Cong-Yi
Published: June 2013

Background

Despite decades of extensive studies, the morbidity and mortality for acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remained high. Particularly, biomarkers essential for its early diagnosis and prognosis are lacking.

Methods

Recent studies suggest that alveolar macrophages (AMs) at the exudative phase of ALI/ARDS initiate, amplify and perpetuate inflammatory responses, while they resolve inflammation in the recovery phase to prevent further tissue injury and perpetuated inflammation in the lung. Therefore, proteins relevant to this functional switch could be valuable biomarkers for ALI/ARDS diagnosis and prognosis. We thus conducted comparative analysis of the AM proteome to assess its dynamic proteomic changes during ALI/ARDS progression and recovery.

Results

135 proteins were characterized to be differentially expressed between AMs at the exudative and recovery phase. MALDI-TOF-MS and peptide mass fingerprint (PMF) analysis characterized 27 informative proteins, in which 17 proteins were found with a marked increase at the recovery phase, while the rest of 10 proteins were manifested by the significantly higher levels of expression at the exudative phase.

Conclusions

Given the role of above identified proteins played in the regulation of inflammatory responses, cell skeleton organization, oxidative stress, apoptosis and metabolism, they have the potential to serve as biomarkers for early diagnosis and prognosis in the setting of patients with ALI/ARDS.
Polymyxin P is the active principle in suppressing phytopathogenic Erwinia spp. by the biocontrol rhizobacterium Paenibacillus polymyxa M-1
Authors: Niu Ben , Vater Joachim , Rueckert Christian , Blom Jochen , Lehmann Maik , Ru Jin-Jiang , Chen Xiao-Hua , Wang Qi , Borriss Rainer
Published: June 2013

Background

Nine gene clusters dedicated to nonribosomal synthesis of secondary metabolites with possible antimicrobial action, including polymyxin and fusaricidin, were detected within the whole genome sequence of the plant growth-promoting rhizobacterium (PGPR) Paenibacillus polymyxa M-1. To survey the antimicrobial compounds expressed by M-1 we analyzed the active principle suppressing phytopathogenic Erwinia spp.

Results

P. polymyxa M-1 suppressed the growth of phytopathogenic Erwinia amylovora Ea 273, and E. carotovora, the causative agents of fire blight and soft rot, respectively. By MALDI-TOF mass spectrometry and reversed-phase high-performance liquid chromatography (RP-HPLC), two antibacterial compounds bearing molecular masses of 1190.9 Da and 1176.9 Da were detected as being the two components of polymyxin P, polymyxin P1 and P2, respectively. The active principle acting against the two Erwinia strains was isolated from TLC plates and identified by postsource decay (PSD)-MALDI-TOF mass spectrometry as polymyxin P1 and polymyxin P2. These findings were corroborated by domain structure analysis of the polymyxin (pmx) gene cluster detected in the M-1 chromosome which revealed that corresponding to the chemical structure of polymyxin P, the gene cluster is encoding D-Phe in position 6 and L-Thr in position 7.

Conclusions

Identical morphological changes in the cell wall of the bacterial phytopathogens treated with either crude polymyxin P or culture supernatant of M-1 corroborated that polymyxin P is the main component of the biocontrol effect exerted by strain M-1 against phytopathogenic Erwinia spp.
Quantitative expression analysis and prognostic significance of the BCL2-associated Xgene in nasopharyngeal carcinoma: a retrospective cohort study
Authors: Kontos Christos K , Fendri Ali , Khabir Abdelmajid , Mokdad-Gargouri Raja , Scorilas Andreas
Published: June 2013

Background

Nasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy showing high prevalence in Southeast Asia and North Africa. TheBCL2-associated X(BAX) gene encodes the most important pro-apoptotic member of the BCL2 family. We have recently shown thatBCL2andBCL2L12, two other members of the same apoptosis-related family, possess significant prognostic value in NPC. The objective of the current study was to analyzeBAXmRNA expression in nasopharyngeal biopsies of NPC patients, and to assess its prognostic potential in this disease.

Methods

Total RNA was isolated from 88 malignant and 9 hyperplastic nasopharyngeal biopsies, resected from Tunisian patients. After cDNA synthesis by reverse transcription of polyadenylated RNA,BAXmRNA expression was analyzed using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method.

Results

LowerBAXmRNA levels were detected in NPC biopsies than in hyperplastic nasopharyngeal samples.BAXmRNA expression status was associated with low tumor extent, negative regional lymph node status, and absence of distant metastases. Kaplan-Meier survival analysis demonstrated that patients withBAXmRNA-positive NPC have significantly longer disease-free survival (DFS) and overall survival (OS). In accordance with these findings, Cox regression analysis revealed thatBAXmRNA expression can be considered as a favorable prognostic indicator of DFS and OS in NPC, independent of their gender, age, tumor histology, tumor extent, and nodal status. Furthermore, NPC patients without distant metastases are less likely to relapse when their primary tumor isBAXmRNA-positive, compared to metastasis-free patients with aBAX-negative nasopharyngeal malignancy.

Conclusion

This is the first study examining the potential clinical utility ofBAXas a prognostic tumor biomarker in NPC. We provide evidence thatBAXmRNA expression can be considered as an independent favorable prognostic indicator of DFS and OS in NPC.
Antithrombotic and antiplatelet activities of Soshiho-tang extract
Authors: Lee Jung-Jin , Kim Taesoo , Cho Won-Kyung , Ma Jin Yeul
Published: June 2013

Background

Soshiho-tang (SH; Chinese name, Xiao-Chai-Hu-Tang; Japanese name, Shosaiko-to) is a traditional Korean, Chinese, and Japanese medicine, which has been used to treat various conditions, including hepatitis, liver cirrhosis, and chronic and acute liver disease. SH consists of seven herbal components, of which Scutellaria baicalensis Georgi and Zingiber officinale Roscoe, are reported to have antithrombotic and antiplatelet activities. We investigated the antithrombotic activity of SH, including S. baicalensis and Z. officinale, as an integrative therapy.

Methods

To identify the antithrombotic activity of SH, we used a FeCl3-induced thrombus formation model. The mechanism of SH-mediated antithrombotic activity was assessed by determining platelet aggregation and coagulation times ex vivo, washed platelet aggregation, serotonin secretion, and thromboxane B2 formation.

Results

SH prolonged the occlusion time of thrombus formation when applied in a FeCl3-induced thrombus formation model. SH also inhibited collagen-induced platelet aggregation ex vivo in a concentration-dependent manner; however, it did not affect coagulation. Hence, to identify the antiplatelet effect of SH, we investigated washed platelet aggregations in vitro. SH significantly inhibited various agonist-induced platelet aggregations, and it completely inhibited serotonin secretion and thromboxane B2 formation.

Conclusions

The findings suggest that SH inhibited FeCl3-induced thrombus formation through antiplatelet activity, including inhibition of platelet aggregation, and serotonin and TXB2 production. Thus, SH may be useful as an integrative herbal formula for the treatment of thrombosis.
Effect of black tea extract on herpes simplex virus-1 infection of cultured cells
Authors: Cantatore Anthony , Randall Sade D , Traum Daniel , Adams Sandra D
Published: June 2013

Background

The purpose of this investigation was to determine if black tea extract (BTE), consisting primarily of flavanol compounds called theaflavins, could inhibit herpes simplex virus type-1 (HSV-1) infection in cultured A549 (human epithelial) and Vero cells.

Methods

The effect of BTE both on A549 and Vero cultured cells and on HSV-1 was assessed by using phase contrast and fluorescent microscopy, and cell viability and proliferation assays. After establishing the maximum non-cytotoxic concentration of BTE, A549 and Vero cells and HSV-1 virions were treated with varying concentrations of BTE, respectively. A549 and Vero cells were infected with HSV-1 with green fluorescent protein (GFP) insert at the UL46 gene. The effect of infectivity was determined by viral DNA extraction followed by PCR, plaque assays, adsorption assays, and electrophoresis of PCR products.

Results

BTE was not cytotoxic to A549 and Vero cells, as confirmed by cell viability and proliferation assays, in which BTE treated groups paralleled the positive control group. For both cell lines, plaque assays and fluorescent microscopy indicated an inverse relationship between BTE concentration (from 0.14 μM – 1.4 mM) and HSV-1 infectivity. Specifically, PCR and electrophoresis showed a reduction in the viral genome following treatment with BTE. In addition, there was a noticeable decrease in the amount of viral plaques for BTE treated samples in the adsorption assays.

Conclusions

BTE consisting primarily of theaflavins is not cytotoxic and can reduce or block the production of infectious HSV-1 virions in cultured A549 and Vero cells, thus inhibiting the infectivity of the virus by interfering in the attachment, penetration and viral DNA replication of HSV-1 particles. These findings indicate that BTE enriched with theaflavins has the potential to be developed as a safe, therapeutic antiviral agent to prevent the spread of HSV-1.
Heat stress-induced response of the proteomes of leaves from Salvia splendens Vista and King
Authors: Liu Hui , Shen Guozheng , Fang Xianping , Fu Qiaojuan , Huang Kangkang , Chen Yi , Yu Hong , Zhao Yun , Zhang Le , Jin Liang , Ruan Songlin
Published: June 2013

Background

Salvia splendens Ker-Gawl, most commonly used in China to add a splash of brilliant color to the surroundings during the warm season, is subject to heat stress, which can greatly affect its growth and yield.

Results

To gain a comprehensive understanding of heat-tolerance mechanisms of S. splendens, we assessed the heat-stress responses and characterized the proteomes of leaves from two varieties, Vista (heat resistant) and King (heat sensitive). Denaturing two-dimensional gel electrophoresis (2–DE) and tandem mass spectrometry were used to identify heat-responsive proteins. Heat stress induced the reversible inactivation of photosystem II reaction centers and increased the amounts of antioxidative enzymes, thereby decreasing oxidative damage. Vista leaves had a much greater ability than King leaves to develop light-protective and oxygen-scavenging systems in response to heat stress. More than 1213 leaf proteome spots were reproducibly detected in the gels, with a total of 33 proteins in each leaf type differentially regulated when Salvia splendens were heat stress treated. Of these proteins, 23 and 28 from Vista and King, respectively, were identified.

Conclusions

Most of the identified proteins are involved in photosynthesis, metabolism, protein processing, or stress response, indicating that many different processes work together to establish a new cellular homeostasis in response to heat stress.
ECM-related gene expression profile in vascular smooth muscle cells from human saphenous vein and internal thoracic artery
Authors: Zhu Tian-xiang , Lan Bin , Meng Ling-ying , Yang Yan-long , Li Rui-xiong , Li En-min , Zheng Shao-yi , Xu Li-yan
Published: June 2013

Background

Currently, Saphenous vein (SV) and internal thoracic artery (ITA) are still the most common graft materials in Coronary Artery Bypass Grafting (CABG) whereas SV graft have a lower long-term patency than ITA. Vascular smooth muscle cells (VSMCs) phenotype conversion, proliferation and migration may play a key role in mechanism of vein graft restenosis. To explore differential gene expression profile in VSMCs from SV and ITA will help to further elucidate the mechanism of VSMCs in vein graft restenosis after CABG and to provide new thread of gene therapy.

Methods

VSMCs from paired SV and ITA were cultured for experiments of Affymetrix microarrays and verification using FQ RT-PCR, while the database for annotation, visualization and integrated discovery bioinformatics resources (DAVID 2.0) was utilized for bioinformatics analysis of differential gene expression profile between SV VSMCs and ITA VSMCs. RNA of tunica media from SV and ITA segments were extracted for FQ RT-PCR to display differential expression of PLAT

Results

54,613 probe sets were examined by gene microarray experiments. In SV VSMCs, 1,075 genes were up-regulated and 406 of them were higher than two-fold; 1,399 genes were down-regulated and 424 of them were lower than two-fold as compare with ITA VSMCs.14 ECM-related genes differentially expressed were verificated and listed as following: COL4A4, COL11A1, FN1, TNC, THBS, FBLN, MMP3, MMP9, TIMP3, WNT5A, SGCD were higher whereas COL14A1, ELN, PLAT lower in SV VSMCs than ITA VSMCs. In addition, PLAT was lower in tunica media from SV segments than ITA.

Conclusion

VSMCs from SV and ITA have distinct phenotypes characteristics. Both promoting and inhibiting migration ECM-related genes were higher in VSMCs from SV as compared with ITA, suggesting that VSMCs from SV have more potential migrating capability whereas less PLAT both in SV VSMCs and vascular tissue,implying that SV may prone to be restenosis after CABG.
Intestinal ischemia after cardiac surgery: analysis of a large registry
Authors: Nilsson Johan , Hansson Erika , Andersson Bodil
Published: June 2013

Background

Intestinal ischemia after cardiac surgery is a rare but severe complication with a high mortality. Early surgery can be lifesaving. The aim was to analyze the incidence, outcome, and risk factors for these patients.

Methods

A prospectively collected database with patients who underwent 18,879 cardiac surgical procedures between 1996 and 2011 was investigated. All patients with registered gastrointestinal complications were retrospectively reviewed. Univariate and multivariate analyses were performed to compare patients with and without intestinal ischemia.

Results

Seventeen patients suffered from intestinal ischemia (0.09%), 10 of whom (59%) died. By investigating preoperative parameters independent risk factors were steroids, peripheral vascular disease, cardiogenic shock, and New York Heart Association class 4. When including pre-, per-, and postoperative parameters, only postoperative ones were significant, including elevated creatinine (> 200 μmol/L), prolonged ventilator time, need for intra-aortic balloon pump, and cerebrovascular insult (CVI). The gastrointestinal complications score (GICS) showed a ROC area of 0.87. This was superior compared with EuroSCORE (0.74), to predict intestinal ischemia.

Conclusions

Intestinal ischemia after cardiac surgery is more common in patients with a poor cardiac state, but the use of steroids, peripheral vascular disease, postoperative kidney failure, and CVI were also predictive. GICS score, developed for all GI complications after cardiac surgery, is also of value in predicting this particular complication. The risk factors presented can be used as an aid in the diagnosis of these patients.
Novel agents and biomarkers for acute lymphoid leukemia
Authors: Zhao Yanmin , Huang He , Wei Guoqing
Published: June 2013

New genetic markers for adult acute lymphoblastic leukemia (ALL) have been found to have prognostic impact, such as the lymphoid transcription factor gene IKZF1 alterations, which are associated with a high rate of leukemic relapse in B-ALL. Although complete remission rates by induction chemotherapy in ALL are now high, the long-term survival is still disappointing. Improvements in the survival outcome of ALL have been observed in young adults as a result of the use of pediatric inspired regimens and the broadening of the number of patients who are eligible for allogeneic SCT. Development of new and less toxic agents also provide promise to improve the outcome in adult ALL, such as tyrosine kinase inhibitors in Ph-positive ALL, rituximab in CD20-positive disease, blinatumomab in precursor B-ALL and nelarabine in T-lineage ALL. Challenges for the future are to implement genomic profiling into the clinical setting to guide risk stratification and providing novel targets for tailored therapies.
Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29
Authors: Lui Yan Long Edmund , Timms Peter , Hafner Louise Marie , Tan Tuan Lin , Tan Kian Hwa , Tan Eng Lee
Published: June 2013

Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16 (CA16). However some HFMD caused by EV71 may further develop into severe neurological complications such as encephalitis and meningitis. The route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular fluid or droplet from the infected or via faecal-oral route. To this end, this study utilised a human colorectal adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was first detected in HT29 cells as early as 12 h post infection (hpi) while viral protein was first detected at 48 hpi. A significant change in HT29 cells’ morphology was also observed after 48 hpi. Furthermore HT29 cell viability also significantly decreased at 72 hpi. Together, data from this study demonstrated that co-culture of HT29 with EV71 is a useful in vitro model to study the pathogenesis of EV71.
Improving outcomes of acute kidney injury using mouse renal progenitor cells alone or in combination with erythropoietin or suramin
Authors: Han Xiao , Zhao Li , Lu Guodong , Ge Junke , Zhao Yalin , Zu Shulu , Yuan Mingzhen , Liu Yuqiang , Kong Feng , Xiao Zhiying , Zhao Shengtian
Published: June 2013

Introduction

So far, no effective therapy is available for acute kidney injury (AKI), a common and serious complication with high morbidity and mortality. Interest has recently been focused on the potential therapeutic effect of mouse adult renal progenitor cells (MRPC), erythropoietin (EPO) and suramin in the recovery of ischemia-induced AKI. The aim of the present study is to compare MRPC with MRPC/EPO or MRPC/suramin concomitantly in the treatment of a mouse model of ischemia/reperfusion (I/R) AKI.

Methods

MRPC were isolated from adult C57BL/6-gfp mice. Male C57BL/6 mice (eight-weeks old, n = 72) were used for the I/R AKI model. Serum creatinine (Cr), blood urea nitrogen (BUN) and renal histology were detected in MRPC-, MRPC/EPO-, MRPC/suramin- and PBS-treated I/R AKI mice. E-cadherin, CD34 and GFP protein expression was assessed by immunohistochemical assay.

Results

MRPC exhibited characteristics consistent with renal stem cells. The features of MRPC were manifested by Pax-2, Oct-4, vimentin, α-smooth muscle actin positive, and E-cadherin negative, distinguished from mesenchymal stem cells (MSC) by expression of CD34 and Sca-1. The plasticity of MRPC was shown by the ability to differentiate into osteoblasts and lipocytes in vitro. Injection of MRPC, especially MRPC/EPO and MRPC/suramin in I/R AKI mice attenuated renal damage with a decrease of the necrotic injury, peak plasma Cr and BUN. Furthermore, seven days after the injury, MRPC/EPO or MRPC/suramin formed more CD34+ and E-cadherin+ cells than MRPC alone.

Conclusions

These results suggest that MRPC, in particular MRPC/EPO or MRPC/suramin, promote renal repair after injury and may be a promising therapeutic strategy.
Follicular Lymphoma Cells Induce Changes in T-Cell Gene Expression and Function: Potential Impact on Survival and Risk of Transformation
Authors: Kiaii Shahryar , Clear Andrew J. , Ramsay Alan G. , Davies Derek , Sangaralingam Ajanthah , Lee Abigail , Calaminici Maria , Neuberg Donna S. , Gribben John G.
Published: June 2013

Purpose

Previous studies have demonstrated the prognostic importance of the immune microenvironment in follicular lymphoma (FL). To investigate the molecular mechanisms during which tumor-infiltrating T cells (TILs) are altered in the FL microenvironment, we studied highly purified CD4 and CD8 TILs from lymph node biopsies at diagnosis in treatment-naive patients with FL compared with reactive tonsils and the peripheral blood of healthy donors.

Patients and Methods

Gene expression profiling of highly purified CD4 and CD8 TILs was performed on the Affymetrix platform. Diagnostic tissue microarrays from an independent patient set (n = 172) were used to verify protein expression and analyze any impact of TIL-expressed genes on outcome. Time-lapse imaging was used to assess T-cell motility.

Results

The most upregulated genes in both CD4 and CD8 TILs were PMCH, ETV1, and TNFRSF9. PMCH is not expressed in peripheral blood T cells, but expression is highly induced on culture with FL. Both CD4 and CD8 TILs from patients with FL have significantly impaired motility compared with those of healthy TILs from reactive tonsils and this can be induced on healthy T cells by FL cells. During multivariate analysis, a model incorporating the number and location of T cells expressing PMCH, NAMPT, and ETV1 showed prognostic significance for overall survival and for time to transformation.

Conclusion

We showed altered gene expression in TILs in FL and demonstrated that altering the immune microenvironment in FL affects overall survival and time to transformation in this disease.
Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non–Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2
Authors: Zukin Mauro , Barrios Carlos H. , Rodrigues Pereira Jose , De Albuquerque Ribeiro Ronaldo , de Mendonça Beato Carlos Augusto , do Nascimento Yeni Neron , Murad Andre , Franke Fabio A. , Precivale Maristela , de Lima Araujo Luiz Henrique , Da Rocha Baldotto Clarissa Serodio , Vieira Fernando Meton , Small Isabele A. , Ferreira Carlos G. , Lilenbaum Rogerio C.
Published: June 2013

Purpose

To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non–small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2.

Patients and Methods

In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m2) or CP (area under the curve of 5 and 500 mg/m2, respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS).

Results

A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm.

Conclusion

Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.
Expectations About the Effectiveness of Radiation Therapy Among Patients With Incurable Lung Cancer
Authors: Chen Aileen B. , Cronin Angel , Weeks Jane C. , Chrischilles Elizabeth A. , Malin Jennifer , Hayman James A. , Schrag Deborah
Published: June 2013

Purpose

Although radiation therapy (RT) can palliate symptoms and may prolong life, it is not curative for patients with metastatic lung cancer. We investigated patient expectations about the goals of RT for incurable lung cancers.

Patients and Methods

The Cancer Care Outcomes Research and Surveillance Consortium enrolled a population- and health system–based cohort of patients diagnosed with lung cancer from 2003 to 2005. We identified patients with stage wet IIIB or IV lung cancer who received RT and answered questions on their expectations about RT. We assessed patient expectations about the goals of RT and identified factors associated with inaccurate beliefs about cure.

Results

In all, 384 patients completed surveys on their expectations about RT. Seventy-eight percent of patients believed that RT was very or somewhat likely to help them live longer, and 67% believed that RT was very or somewhat likely to help them with problems related to their cancer. However, 64% did not understand that RT was not at all likely to cure them. Older patients and nonwhites were more likely to have inaccurate beliefs, and patients whose surveys were completed by surrogates were less likely to have inaccurate beliefs. Ninety-two percent of patients with inaccurate beliefs about cure from RT also had inaccurate beliefs about chemotherapy.

Conclusion

Although patients receiving RT for incurable lung cancer believe it will help them, most do not understand that it is not at all likely to cure their disease. This indicates a need to improve communication regarding the goals and limitations of palliative RT.
Monitoring the development of xenograft triple-negative breast cancer models using diffusion-weighted magnetic resonance imaging
Authors: Stephen Renu M , Page Mark D , Brown Kathy , Baker Amanda F , Meuillet Emmanuelle J , Gillies Robert J
Published: June 2013

Evaluations of tumor growth rates and molecular biomarkers are traditionally used to assess new mouse models of human breast cancers. This study investigated the utility of diffusion weighted (DW)-magnetic resonance imaging (MRI) for evaluating cellular proliferation of new tumor models of triple-negative breast cancer, which may augment traditional analysis methods. Eleven human breast cancer cell lines were used to develop xenograft tumors in severe combined immunodeficient mice, with two of these cell lines exhibiting sufficient growth to be serially passaged. DW-MRI was performed to measure the distributions of the apparent diffusion coefficient (ADC) in these two tumor xenograft models, which showed a correlation with tumor growth rates and doubling times during each passage. The distributions of the ADC values were also correlated with expression of Ki67, a biomarker of cell proliferation, and hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor receptor-2 (VEGFR2), which are essential proteins involved in regulating aerobic glycolysis and angiogenesis that support tumor cell proliferation. Although phosphatase and tensin homolog (PTEN) levels were different between the two xenograft models, AKT levels did not differ nor did they correlate with tumor growth. This last result demonstrates the complexity of signaling protein pathways and the difficulty in interpreting the effects of protein expression on tumor cell proliferation. In contrast, DW-MRI may be a more direct assessment of tumor growth and cancer cell proliferation.
The incidence and etiology of community-acquired pneumonia in fever outpatients
Authors: Bao Zhongying , Yuan Xiaodong , Wang Lei , Sun Yuling , Dong Xiaoqun
Published: June 2013

The purpose of this study was to analyze the incidence, etiology and clinical characteristics of community-acquired pneumonia (CAP) among outpatients with sore throat and/or cough, and thus to provide theoretical basis for timely and accurate diagnosis and treatment for CAP. We used chest X-rays for fever (a temperature greater than 37.58C) patients, who were recruited since 2007, presenting with sore throat and/or cough. The patients’ age, gender, days of fever, respiratory symptoms (e.g. cough and sputum), peripheral blood count and etiology (pathogens) of CAP were recorded. Of all the 6539 fever outpatients, those aged 10-39 and above 60 years old accounted for 61.0% and 15.6%, respectively. In total, 402 were diagnosed with CAP with an incidence rate of 6.1%. Among them, 38.1% were above 60 years old. The prevalence increased with age. Of the 402 CAP patients, 36.8% (148/402) presented no respiratory symptoms and 30.1% (121/402) had positive etiology. The top three pathogens were Mycoplasma pneumoniae (23.1%), Streptococcus pneumoniae (17.3%) and Haemophilus influenzae (9.1%). Among the 121 etiology-positive patients, 14 cases were mixed infections (at least one atypical pathogen). Nine cases were M. pneumoniae mixed with bacterial/virus infection, and five cases were Chlamydia pneumoniae mixed with other bacteria/ mycoplasma infection. We found that fever outpatients have a higher prevalence of CAP, which increases with age, i.e. older people are more susceptible to CAP. S. pneumoniae and H. influenzae are common pathogens in CAP; however, atypical pathogens, especially M. pneumoniae, remain the most common pathogens in CAP.
Endoplasmic reticulum stress and C/EBP homologous protein-induced Bax translocation are involved in angiotensin II-induced apoptosis in cultured neonatal rat cardiomyocytes
Authors: Zou Xiao-Jing , Yang Le , Yao Shang-Long
Published: June 2013

The aim of this study was to identify the roles and potential mechanisms of endoplasmic reticulum stress (ER stress), proapoptotic transcription factor C/EBP homologous protein (CHOP) and Bax in angiotensin II (Ang II)-induced cardiomyocyte apoptosis. Cultured neonatal rat cardiomyocytes were incubated with Ang II or antisense CHOP oligonucleotide which was used to inhibit CHOP expression. Expressions of ER chaperone immunoglobulin heavy chain-binding protein (BiP), CHOP and cytochrome c were examined by Western blotting. Mitochondrial membrane potential (MMP) was detected by a spectrofluorimeter. Apoptosis was analyzed with flow cytometry. Bax translocation was determined by double-labeling of immunofluorescence and Western blotting. Our results showed that Ang II-induced cardiomyocyte apoptosis was associated with the upregulations of BiP and CHOP, Bax translocation, MMP deplorization and cytochrome c release. These above effects were suppressed by antisense CHOP oligonucleotide. Furthermore, BiP and CHOP expressions, reactive oxygen species (ROS) production and cardiomyocyte apoptosis, which were upregulated by Ang II, were depressed by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin. From our results, ROS, ER stress and CHOP-mediated Bax translocation may be involved in Ang II-induced cardiomyocyte apoptosis.
Corynebacterium pyruviciproducens, as an immune modulator, can promote the activity of macrophages and up-regulate antibody response to particulate antigen
Authors: Tong Jia , Han Qingzhen , Wang Shengjun , Su Zhaoliang , Zheng Dong , Shen Pei , Xia Sheng , Huang Xinxiang , Shao Qixiang , Xu Huaxi
Published: June 2013

Corynebacterium pyruviciproducens is a newly discovered Corynebacterium species with no known pathogenic components such as diphtheria toxin and tuberculostearic acid, and it has similar biological properties to Propionibacterium acnes, but its role of immunoregulation is drawing people's attention. In this work, based on the role of macrophages in removal of pathogenic bacteria as a primary scavenger and particulate antigen-presenting cell, the stimulation of macrophages by C. pyruviciproducens was analyzed through detecting the levels of cytokine secretion and expression of membrane molecules, and the effect of C. pyruviciproducens in promoting antibody response to sheep red blood cells (SRBC) in vivo was detected. In vitro, C. pyruviciproducens led to a sharp release of interleukin-6 and tumour necrosis factor-α and encouraged the activation of macrophages including enhanced expressions of MHC-II, CD40, CD80 and CD86. In vivo, it enhanced the humoral immune response against SRBC, a particulate antigen. These observations suggest that C. pyruviciproducens, as an immunoregulator, can promote the host humoral immune response to pathogenic microorganisms by regulating macrophage function.
A Numerical Scheme for Invariant Distributions of Constrained Diffusions
Authors: Budhiraja Amarjit , Chen Jiang , Rubenthaler Sylvain
Published: June 2013

Reflected diffusions in polyhedral domains are commonly used as approximate models for stochastic processing networks in heavy traffic. Stationary distributions of such models give useful information on the steady-state performance of the corresponding stochastic networks, and thus it is important to develop reliable and efficient algorithms for numerical computation of such distributions. In this work we propose and analyze a Monte-Carlo scheme based on an Euler type discretization of the reflected stochastic differential equation using a single sequence of time discretization steps which decrease to zero as time approaches infinity. Appropriately weighted empirical measures constructed from the simulated discretized reflected diffusion are proposed as approximations for the invariant probability measure of the true diffusion model. Almost sure consistency results are established That, in particular, show that weighted averages of polynomially growing continuous functionals evaluated on the discretized simulated system converge a.s. to the corresponding integrals with respect to the invariant measure. Proofs rely on constructing suitable Lyapunov functions for tightness and uniform integrability and characterizing almost sure limit points through an extension of Echeverria's criteria for reflected diffusions. Regularity properties of the underlying Skorohod problems play a key role in the proofs. Rates of convergence for suitable families of test functions are also obtained. A key advantage of Monte-Carlo methods is the ease of implementation, particularly for high-dimensional problems. A numerical example of an eight-dimensional Skorohod problem is presented to illustrate the applicability of the approach.
More Risk-Sensitive Markov Decision Processes
Authors: Bäuerle Nicole , Rieder Ulrich
Published: June 2013

We investigate the problem of minimizing a certainty equivalent of the total or discounted cost over a finite and an infinite horizon that is generated by a Markov decision process (MDP). In contrast to a risk-neutral decision maker this optimization criterion takes the variability of the cost into account. It contains as a special case the classical risk-sensitive optimization criterion with an exponential utility. We show that this optimization problem can be solved by an ordinary MDP with extended state space and give conditions under which an optimal policy exists. In the case of an infinite time horizon we show that the minimal discounted cost can be obtained by value iteration and can be characterized as the unique solution of a fixed-point equation using a “sandwich” argument. Interestingly, it turns out that in the case of a power utility, the problem simplifies and is of similar complexity than the exponential utility case, however has not been treated in the literature so far. We also establish the validity (and convergence) of the policy improvement method. A simple numerical example, namely, the classical repeated casino game, is considered to illustrate the influence of the certainty equivalent and its parameters. Finally, the average cost problem is also investigated. Surprisingly, it turns out that under suitable recurrence conditions on the MDP for convex power utility, the minimal average cost does not depend on the parameter of the utility function and is equal to the risk-neutral average cost. This is in contrast to the classical risk-sensitive criterion with exponential utility.