bluuebunny/crossref_metadata_2025_split huggingface dataset:
TLX1-Induced T-cell Acute Lymphoblastic Leukemia
Authors: De Keersmaecker Kim , Ferrando Adolfo A. 
Published: June 2011

Abstract
The TLX1 transcription factor oncogene is frequently activated by chromosomal translocations in T-cell acute lymphoblastic leukemia (T-ALL) and defines a distinct molecular group of tumors characterized by differentiation arrest at the early cortical stage of thymocyte differentiation and excellent response to therapy. Recent developments from the analysis of genomic data on TLX1-specific transcriptional targets and analysis of the molecular mechanisms of TLX1 transformation in human- and mouse-induced leukemias have shown novel insight into the activity of this transcription factor oncogene. Aberrant expression of TLX1 in T-cell progenitors disrupts normal T-cell development and triggers the development of aneuploidy during T-cell transformation. Importantly, the disruption of the mitotic checkpoint in TLX1-induced tumors may be linked not only to the acquisition of secondary genetic alterations in T-ALL but also to increased sensitivity of these tumors to chemotherapy with drugs targeting the formation of the mitotic spindle. Clin Cancer Res; 17(20); 6381–6. ©2011 AACR.
The Two Faces of Interferon-γ in Cancer
Authors: Zaidi M. Raza , Merlino Glenn 
Published: June 2011

AbstractInterferon-γ is a cytokine whose biological activity is conventionally associated with cytostatic/cytotoxic and antitumor mechanisms during cell-mediated adaptive immune response. It has been used clinically to treat a variety of malignancies, albeit with mixed results and side effects that can be severe. Despite ample evidence implicating a role for IFN-γ in tumor immune surveillance, a steady flow of reports has suggested that it may also have protumorigenic effects under certain circumstances. We propose that, in fact, IFN-γ treatment is a double-edged sword whose anti- and protumorigenic activities are dependent on the cellular, microenvironmental, and/or molecular context. As such, inhibition of the IFN-γ/IFN-γ receptor pathway may prove to be a viable new therapeutic target for a subset of malignancies. Clin Cancer Res; 17(19); 6118–24. ©2011 AACR.
Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome
Authors: De Smedt Ann , Brouns Raf , Uyttenboogaart Maarten , De Raedt Sylvie , Moens Maarten , Wilczak Nadine , Luijckx Gert-Jan , De Keyser Jacques 
Published: June 2011

Background and Purpose—
Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome.

Methods—
Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival.

Results—
After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group.

Conclusions—
Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.
The von Willebrand Inhibitor ARC1779 Reduces Cerebral Embolization After Carotid Endarterectomy
Authors: Markus Hugh S. , McCollum Charles , Imray Chris , Goulder Michael A. , Gilbert Jim , King Alice 
Published: June 2011

Background and Purpose—
Inhibition of von Willebrand factor offers a novel approach to prevention of stroke and myocardial ischemia but has not yet been demonstrated to show efficacy on clinically relevant end points. ARC1779 is an aptamer that inhibits the prothrombotic function of von Willebrand factor by binding to the A1 domain of von Willebrand factor and thereby blocking its interaction with glycoprotein. Phase 1 studies suggest it inhibits platelet aggregation with less increase in bleeding than conventional antiplatelet agents. The effect of ARC 1779 on cerebral emboli immediately after carotid endarterectomy was investigated in a randomized clinical trial.

Methods—
Patients undergoing carotid endarterectomy were randomized double-blind to ARC1779 or placebo administered intravenously. Transcranial Doppler recording, to detect cerebral embolic signals, was performed in the first 3 hours postoperatively. The primary end point was time to first embolic signals.

Results—

Thirty-six patients were recruited, 18 in each arm. The Kaplan-Meier median time to first embolic signals was 83.6 minutes for ARC1779 compared with 5.5 minutes for placebo. Using Cox proportional hazards embolic signals occurred statistically significantly later on ARC1779 (
P
=0.007). Reduced embolic signals counts were correlated with inhibition of von Willebrand factor activity (
P
=0.03). Increased perioperative bleeding and anemia were seen with ARC1779.

Conclusions—
von Willebrand factor inhibition reduces thromboembolism in humans. It may play a role in treatment of stroke and myocardial ischemia. The extent to which bleeding complications occur in nonoperated patients needs to be assessed in further studies.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00742612.
In vivo versus in vitro protein abundance analysis of Shigella dysenteriaetype 1 reveals changes in the expression of proteins involved in virulence, stress and energy metabolism
Authors: Kuntumalla Srilatha , Zhang Quanshun , Braisted John C , Fleischmann Robert D , Peterson Scott N , Donohue-Rolfe Arthur , Tzipori Saul , Pieper Rembert 
Published: June 2011

Abstract

Background

Shigella dysenteriae serotype 1 (SD1) causes the most severe form of epidemic bacillary dysentery. Quantitative proteome profiling of Shigella dysenteriae serotype 1 (SD1) in vitro (derived from LB cell cultures) and in vivo (derived from gnotobiotic piglets) was performed by 2D-LC-MS/MS and APEX, a label-free computationally modified spectral counting methodology.

Results
Overall, 1761 proteins were quantitated at a 5% FDR (false discovery rate), including 1480 and 1505 from in vitro and in vivo samples, respectively. Identification of 350 cytoplasmic membrane and outer membrane (OM) proteins (38% of in silico predicted SD1 membrane proteome) contributed to the most extensive survey of the Shigella membrane proteome reported so far. Differential protein abundance analysis using statistical tests revealed that SD1 cells switched to an anaerobic energy metabolism under in vivo conditions, resulting in an increase in fermentative, propanoate, butanoate and nitrate metabolism. Abundance increases of transcription activators FNR and Nar supported the notion of a switch from aerobic to anaerobic respiration in the host gut environment. High in vivo abundances of proteins involved in acid resistance (GadB, AdiA) and mixed acid fermentation (PflA/PflB) indicated bacterial survival responses to acid stress, while increased abundance of oxidative stress proteins (YfiD/YfiF/SodB) implied that defense mechanisms against oxygen radicals were mobilized. Proteins involved in peptidoglycan turnover (MurB) were increased, while β-barrel OM proteins (OmpA), OM lipoproteins (NlpD), chaperones involved in OM protein folding pathways (YraP, NlpB) and lipopolysaccharide biosynthesis (Imp) were decreased, suggesting unexpected modulations of the outer membrane/peptidoglycan layers in vivo. Several virulence proteins of the Mxi-Spa type III secretion system and invasion plasmid antigens (Ipa proteins) required for invasion of colonic epithelial cells, and release of bacteria into the host cell cytosol were increased in vivo.

Conclusions
Global proteomic profiling of SD1 comparing in vivo vs. in vitro proteomes revealed differential expression of proteins geared towards survival of the pathogen in the host gut environment, including increased abundance of proteins involved in anaerobic energy respiration, acid resistance and virulence. The immunogenic OspC2, OspC3 and IpgA virulence proteins were detected solely under in vivo conditions, lending credence to their candidacy as potential vaccine targets.
Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B Leukemic Cells
Authors: Ishdorj Ganchimeg , Johnston James B , Gibson Spencer B 
Published: June 2011

AbstractBackgroundCucurbitacin-I (JSI-124) is potent inhibitor of JAK/STAT3 signaling pathway and has anti-tumor activity in a variety of cancer including B cell leukemia. However, other molecular targets of JSI-124 beyond the JAK/STAT3 pathway are not fully understood.MethodsBJAB, I-83, NALM-6 and primary CLL cells were treated with JSI-124 as indicated. Apoptosis was measured using flow cytometry for accumulation of sub-G1 phase cells (indicator of apoptosis) and Annexin V/PI staining. Cell cycle was analyzed by FACS for DNA content of G1 and G2 phases. Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. STAT3 and c-Jun genes were knocked out using siRNA transfection. VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. Streptavidin Pull-Down Assay was used to determine c-Jun binding to the AP-1 DNA binding site.ResultsHerein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. The JNK pathway activation c-Jun leads to transcriptional activation of many genes. Treatment of BJAB, I-83, and NALM-6 cells with JSI-124 lead to an increase of Vascular Endothelial Growth Factor (VEGF) at both the mRNA and protein level. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Pretreatment with recombinant VEGF reduced JSI-124 induced apoptosis.ConclusionsTaken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression.
Patient education integrated with acupuncture for relief of cancer-related fatigue randomized controlled feasibility study
Authors: Johnston Michael F , Hays Ron D , Subramanian Saskia K , Elashoff Robert M , Axe Eleanor K , Li Jie-Jia , Kim Irene , Vargas Roberto B , Lee Jihey , Yang LuGe , Hui Ka-Kit 
Published: June 2011

Abstract

Background
Cancer-related fatigue (CRF) is a prominent clinical problem. There are calls for multi-modal interventions.

Methods
We assessed the feasibility of delivering patient education integrated with acupuncture for relief of CRF in a pilot randomized controlled trial (RCT) with breast cancer survivors using usual care as control. Social cognitive and integrative medicine theories guided integration of patient education with acupuncture into a coherent treatment protocol. The intervention consisted of two parts. First, patients were taught to improve self-care by optimizing exercise routines, improving nutrition, implementing some additional evidence-based cognitive behavioral techniques such as stress management in four weekly 50-minute sessions. Second, patients received eight weekly 50-minute acupuncture sessions. The pre-specified primary outcome, CRF, was assessed with the Brief Fatigue Inventory (BFI). Secondary outcomes included three dimensions of cognitive impairment assessed with the FACT-COGv2.

Results
Due to difficulties in recruitment, we tried several methods that led to the development of a tailored recruitment strategy: we enlisted oncologists into the core research team and recruited patients completing treatment from oncology waiting rooms. Compared to usual care control, the intervention was associated with a 2.38-point decline in fatigue as measured by the BFI (90% Confidence Interval from 0.586 to 5.014; p <0.10). Outcomes associated with cognitive dysfunction were not statistically significant.

Conclusions
Patient education integrated with acupuncture had a very promising effect that warrants conducting a larger RCT to confirm findings. An effective recruitment strategy will be essential for the successful execution of a larger-scale trial.

Trial registration

NCT00646633
Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda
Authors: Kebede Senait , Gatabazi John B , Rugimbanya Pierre , Mukankwiro Therese , Perry Helen N , Alemu Wondimagegnehu , Ndihokubwayo Jean B , Kramer Michael H , Mukabayire Odette 
Published: June 2011

Abstract

Background
The recent emergence of a novel strain of influenza virus with pandemic potential underscores the need for quality surveillance and laboratory services to contribute to the timely detection and confirmation of public health threats. To provide a framework for strengthening disease surveillance and response capacities in African countries, the World Health Organization Regional Headquarters for Africa (AFRO) developed Integrated Disease Surveillance and Response (IDSR) aimed at improving national surveillance and laboratory systems. IDSR emphasizes the linkage of information provided by public health laboratories to the selection of relevant, appropriate and effective public health responses to disease outbreaks.

Methods
We reviewed the development of Rwanda's National Reference Laboratory (NRL) to understand essential structures involved in creating a national public health laboratory network. We reviewed documents describing the NRL's organization and record of test results, conducted site visits, and interviewed health staff in the Ministry of Health and in partner agencies. Findings were developed by organizing thematic categories and grouping examples within them. We purposefully sought to identify success factors as well as challenges inherent in developing a national public health laboratory system.

Results
Among the identified success factors were: a structured governing framework for public health surveillance; political commitment to promote leadership for stronger laboratory capacities in Rwanda; defined roles and responsibilities for each level; coordinated approaches between technical and funding partners; collaboration with external laboratories; and use of performance results in advocacy with national stakeholders. Major challenges involved general infrastructure, human resources, and budgetary constraints.

Conclusions
Rwanda's experience with collaborative partnerships contributed to creation of a functional public health laboratory network.
Recombinant expression and purification of the 2,5-diketocamphane 1,2-monooxygenase from the camphor metabolizing Pseudomonas putida strain NCIMB 10007
Authors: Kadow Maria , Saß Stefan , Schmidt Marlen , Bornscheuer Uwe T 
Published: June 2011

Abstract
Three different Baeyer-Villiger monooxygenases (BVMOs) were reported to be involved in the camphor metabolism by Pseudomonas putida NCIMB 10007. During (+)-camphor degradation, 2,5-diketocamphane is formed serving as substrate for the 2,5-diketocamphane 1,2-monooxygenase. This enzyme is encoded on the CAM plasmid and depends on the cofactors FMN and NADH and hence belongs to the group of type II BVMOs. We have cloned and recombinantly expressed the oxygenating subunit of the 2,5-diketocamphane 1,2-monooxygenase (2,5-DKCMO) in E. coli followed by His-tag-based affinity purification. A range of compounds representing different BVMO substrate classes were then investigated, but only bicyclic ketones were converted by 2,5-DKCMO used as crude cell extract or after purification. Interestingly, also (-)-camphor was oxidized, but conversion was about 3-fold lower compared to (+)-camphor. Moreover, activity of purified 2,5-DKCMO was observed in the absence of an NADH-dehydrogenase subunit.
Haemodynamic goal-directed therapy and postoperative infections: earlier is better. a systematic review and meta-analysis
Authors: Dalfino Lidia , Giglio Maria T , Puntillo Filomena , Marucci Massimo , Brienza Nicola 
Published: June 2011

Abstract
Introduction
Infectious complications are the main causes of postoperative morbidity. The early timing of their promoting factors is the rationale for perioperative strategies attempting to reduce them. Our aim was to determine the effects of perioperative haemodynamic goal-directed therapy on postoperative infection rates.

Methods
We performed a systematic review and meta-analysis. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched up to March 2011. Randomised, controlled trials of major surgery in adult patients managed with perioperative goal-directed therapy or according to routine haemodynamic practice were included. Primary outcome measure was specific type of infection.

Results
Twenty-six randomised, controlled trials with a combined total of 4,188 participants met our inclusion criteria. Perioperative goal-directed therapy significantly reduced surgical site infections (pooled OR 0.58, 95% CI 0.46 to 0.74; P < 0.0001), pneumonia (pooled OR 0.71, 95% CI 0.55 to 0.92; P = 0.009), and urinary tract infections (pooled OR 0.44, 95% CI 0.22 to 0.84; P = 0.02). A significant benefit was found regarding total infectious episodes (OR 0.40, 95% CI 0.28 to 0.58; P < 0.00001).

Conclusions
Flow-directed haemodynamic therapy designed to optimise oxygen delivery protects surgical patients against postoperative hospital-acquired infections and must be strongly encouraged, particularly in the high-risk surgical population.
The Benefits of Aggregate Performance Metrics in the Presence of Career Concerns
Authors: Arya Anil , Mittendorf Brian 
Published: June 2011

This paper considers the desirability of aggregate performance measures in light of the fact that many individuals' performance incentives are driven by a desire to shape external perceptions (and thus future pay). In contrast to the case of explicit incentive contracts, we find that when individuals' actions are driven by career incentives, an aggregate measure (e.g., group or team output) can sometimes alleviate moral hazard concerns and improve efficiency. Aggregation intermingles performance measures that may be differentially affected by skill and effort of many agents. When such entanglement increases the prospect that the external market will attribute an employee's effort-driven contribution to transferable skills, the employee exerts higher effort as a means of posturing to the market. The incentive benefit of aggregation is weighed against the incentive cost because of information loss. Information loss from aggregation can reduce the market's reliance on the measure and thus diminish agents' desire to undertake effort to influence the measure. This paper was accepted by Stefan Reichelstein, accounting.
Arthroscopy of the hip in patients following joint replacement
Authors: Bajwa A. S. , Villar R. N. 
Published: June 2011

Arthroscopy of the native hip is an established diagnostic and therapeutic procedure. Its application in the symptomatic replaced hip is still being explored. We describe the use of arthroscopy of the hip in 24 symptomatic patients following total hip replacement, resurfacing arthroplasty of the hip and partial resurfacing (study group), and compared it with arthroscopy of the native hip in 24 patients (control group). A diagnosis was made or confirmed at arthroscopy in 23 of the study group and a therapeutic arthroscopic intervention resulted in relief of symptoms in ten of these. In a further seven patients it led to revision hip replacement. In contrast, arthroscopy in the control group was diagnostic in all 24 patients and the resulting arthroscopic therapeutic intervention provided symptomatic relief in 21. The mean operative time in the study group (59.7 minutes (35 to 93)) was less than in the control group (71 minutes (40 to 100), p = 0.04) but the arthroscopic approach was more difficult in the arthroplasty group. We suggest that arthroscopy has a role in the management of patients with a symptomatic arthroplasty when other investigations have failed to provide a diagnosis.
Soft-tissue changes in hip abductor muscles and tendons after total hip replacement
Authors: Bremer A. K. , Kalberer F. , Pfirrmann C. W. A. , Dora C. 
Published: June 2011

The direct anterior approach in total hip replacement anatomically offers the chance to minimise soft-tissue trauma because an intermuscular and internervous plane is explored. This motivated us to abandon our previously used transgluteal approach and to adopt the direct anterior approach for total hip replacement. Using MRI, we performed a retrospective comparative study of the direct anterior approach with the transgluteal approach. There were 25 patients in each group. At one year post-operatively all the patients underwent MRI of their replaced hips. A radiologist graded the changes in the soft-tissue signals in the abductor muscles. The groups were similar in terms of age, gender, body mass index, complexity of the reconstruction and absence of symptoms. Detachment of the abductor insertion, partial tears and tendonitis of gluteus medius and minimus, the presence of peri-trochanteric bursal fluid and fatty atrophy of gluteus medius and minimus were significantly less pronounced and less frequent when the direct anterior approach was used. There was no significant difference in the findings regarding tensor fascia lata between the two approaches. We conclude that use of the direct anterior approach results in a better soft-tissue response as assessed by MRI after total hip replacement. However, the impact on outcome needs to be evaluated further.
The biomechanical performance of locking plate fixation with intramedullary fibular strut graft augmentation in the treatment of unstable fractures of the proximal humerus
Authors: Bae J.-H. , Oh J.-K. , Chon C.-S. , Oh C.-W. , Hwang J.-H. , Yoon Y.-C. 
Published: June 2011

We evaluated the biomechanical properties of two different methods of fixation for unstable fractures of the proximal humerus. Biomechanical testing of the two groups, locking plate alone (LP), and locking plate with a fibular strut graft (LPSG), was performed using seven pairs of human cadaveric humeri. Cyclical loads between 10 N and 80 N at 5 Hz were applied for 1 000 000 cycles. Immediately after cycling, an increasing axial load was applied at a rate of displacement of 5 mm/min. The displacement of the construct, maximum failure load, stiffness and mode of failure were compared. The displacement was significantly less in the LPSG group than in the LP group (p = 0.031). All maximum failure loads and measures of stiffness in the LPSG group were significantly higher than those in the LP group (p = 0.024 and p = 0.035, respectively). In the LP group, varus collapse and plate bending were seen. In the LPSG group, the humeral head cut out and the fibular strut grafts fractured. No broken plates or screws were seen in either group. We conclude that strut graft augmentation significantly increases both the maximum failure load and the initial stiffness of this construct compared with a locking plate alone.