bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gallium Nitrate Is Efficacious in Murine Models of Tuberculosis and Inhibits Key Bacterial Fe-Dependent Enzymes
Authors: Olakanmi Oyebode , Kesavalu Banurekha , Pasula Rajamouli , Abdalla Maher Y. , Schlesinger Larry S. , Britigan Bradley E. 
Published: September 2013

ABSTRACTAcquiring iron (Fe) is critical to the metabolism and growth ofMycobacterium tuberculosis. Disruption of Fe metabolism is a potential approach for novel antituberculous therapy. Gallium (Ga) has many similarities to Fe. Biological systems are often unable to distinguish Ga3+from Fe3+. Unlike Fe3+, Ga3+cannot be physiologically reduced to Ga2+. Thus, substituting Ga for Fe in the active site of enzymes may render them nonfunctional. We previously showed that Ga inhibits growth ofM. tuberculosisin broth and within cultured human macrophages. We now report that Ga(NO3)3shows efficacy in murine tuberculosis models. BALB/c SCID mice were infected intratracheally withM. tuberculosis, following which they received daily intraperitoneal saline, Ga(NO3)3, or NaNO3. All mice receiving saline or NaNO3died. All Ga(NO3)3-treated mice survived.M. tuberculosisCFU in the lungs, liver, and spleen of the NaNO3-treated or saline-treated mice were significantly higher than those in Ga-treated mice. When BALB/c mice were substituted for BALB/c SCID mice as a chronic (nonlethal) infection model, Ga(NO3)3treatment significantly decreased lung CFU. To assess the mechanism(s) whereby Ga inhibits bacterial growth, the effect of Ga onM. tuberculosisribonucleotide reductase (RR) (a key enzyme in DNA replication) and aconitase activities was assessed. Ga decreasedM. tuberculosisRR activity by 50 to 60%, but no additional decrease in RR activity was seen at Ga concentrations that completely inhibited mycobacterial growth. Ga decreased aconitase activity by 90%. Ga(NO3)3shows efficacy in murineM. tuberculosisinfection and leads to a decrease in activity of Fe-dependent enzymes. Additional work is warranted to further define Ga's mechanism of action and to optimize delivery forms for possible therapeutic uses in humans.
Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine
Authors: Martinez-Becerra Francisco J. , Chen Xiaotong , Dickenson Nicholas E. , Choudhari Shyamal P. , Harrison Kelly , Clements John D. , Picking William D. , Van De Verg Lillian L. , Walker Richard I. , Picking Wendy L. 
Published: September 2013

ABSTRACT

Shigellosis is an important disease in the developing world, where about 90 million people become infected with
Shigella
spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested
Shigella
antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly α-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against
Shigella flexneri
and
S. sonnei
in the lethal pulmonary challenge. It also offered limited protection against
S. dysenteriae
challenge. Our results show the feasibility of generating a protective
Shigella
vaccine comprised of the DB fusion.
Substrate Specificity and Function of the Pheromone Receptor AinR in Vibrio fischeri ES114
Authors: Kimbrough John H. , Stabb Eric V. 
Published: September 2013

ABSTRACT

Two distinct but interrelated pheromone-signaling systems, LuxI/LuxR and AinS/AinR, positively control bioluminescence in
Vibrio fischeri
. Although each system generates an acyl-homoserine lactone (AHL) signal, the protein sequences of LuxI/LuxR and AinS/AinR are unrelated. AinS and LuxI generate the pheromones
N
-octanoyl-AHL (C
8
-AHL) and
N
-3-oxo-hexanoyl-AHL (3OC
6
-AHL), respectively. LuxR is a transcriptional activator that responds to 3OC
6
-AHL, and to a lesser extent to C
8
-AHL. AinR is hypothesized to respond to C
8
-AHL and, based on homology to
Vibrio harveyi
LuxN, to mediate the repression of a Qrr regulatory RNA. However, a Δ
ainR
mutation decreased luminescence, which was not predicted based on
V. harveyi
LuxN, raising the possibility of a distinct regulatory mechanism for AinR. Here we show that
ainR
can complement a
luxN
mutant, suggesting functional similarity. Moreover, in
V. fischeri
, we observed
ainR
-dependent repression of a P

qrr

-
lacZ
transcriptional reporter in the presence of C
8
-AHL, consistent with its hypothesized regulatory role. The system appears quite sensitive, with a half-maximal effect on a P

qrr

reporter at 140 pM C
8
-AHL. Several other AHLs with substituted and unsubstituted acyl chains between 6 and 10 carbons also displayed an AinR-dependent effect on P

qrr

-
lacZ
; however, AHLs with acyl chains of four carbons or 12 or more carbons lacked activity. Interestingly, 3OC
6
-AHL also affected expression from the
qrr
promoter, but this effect was largely
luxR
dependent, indicating a previously unknown connection between these systems. Finally, we propose a preliminary explanation for the unexpected luminescence phenotype of the Δ
ainR
mutant.
A qualitative study examining the influences on situation awareness and the identification, mitigation and escalation of recognised patient risk
Authors: Brady Patrick W , Goldenhar Linda M 
Published: September 2013

BackgroundSituation awareness (SA)—the perception of data elements, comprehension of their meaning and projection of their status in the near future—has been associated with human performance in high-risk environments, including aviation and the operating room. The influences on SA in inpatient medicine are unknown.MethodsWe conducted seven focus groups with nurses, respiratory therapists and resident physicians using a standardised semistructured focus group guide to promote discussion. Recordings of the focus groups were transcribed verbatim, and transcripts were qualitatively analysed by two independent reviewers to identify convergent and divergent themes.ResultsThree themes emerged: (1) team-based care, (2) availability of standardised data and (3) standardised processes and procedures. We categorised these into social, technological and organisational influences on SA. Subthemes that emerged from each focus group were shared language to describe at-risk patients, provider experience in critical care/deterioration and interdisciplinary huddles to identify and plan for at-risk patients. An objective early warning score, proactive assessment and planning, adequate clinician staffing and tools for entering, displaying and monitoring data trends were identified by six of seven groups. Our data better reflected the concepts of team SA and shared SA than individual SA.ConclusionsTeam-based care and standardisation support SA and the identification and treatment of patient risk in the complex environment of inpatient care. These findings can be used to guide the development and implementation of targeted interventions such as huddles to proactively scan for risk and electronic health record displays of data trends.
Epithelial–mesenchymal transition phenotypes are associated with patient survival in intrahepatic cholangiocarcinoma
Authors: Gu Mi Jin , Choi Joon Hyuk 
Published: September 2013

BackgroundThe aim of this study was to evaluate the epithelial–mesenchymal transition (EMT) and to assess its prognostic significance in intrahepatic cholangiocarcinoma.MethodsWe performed immunohistochemical stainings for E-cadherin, β-catenin, vimentin and fibronectin in a total of 85 cases.ResultsExpression of vimentin and reduced expression of E-cadherin were found to show correlation with poor differentiation (p=0.017, p=0.010). Reduced expression of β-catenin showed significant association with poor differentiation (p=0.023), tumour size (p=0.028) and lymph node metastasis (p=0.011). According to the expression pattern of E-cadherin, β-catenin, vimentin and fibronectin we categorised four phenotypes: complete type, hybrid type, null type and wild type. The complete type of β-catenin with vimentin or fibronectin was found to show an association with lymph node metastasis (p=0.048, p=0.012). Significantly worse overall survival (OS) and disease-free survival (DFS) was observed for the complete type, and the best OS and DFS were observed for the wild type.ConclusionsEMT phenotypes can be useful markers for prediction of patient outcomes.
Mid and long term outcomes of dural arteriovenous fistula endovascular management with Onyx. Experience of a single tertiary center
Authors: Rangel-Castilla Leonardo , Barber Sean M , Klucznik Richard , Diaz Orlando 
Published: September 2013

IntroductionThe natural history of intracranial dural arteriovenous fistulas (DAVFs) with cortical venous drainage is unfavorable, and treatment is recommended in most cases. Early reports have documented excellent initial clinical and radiographic outcomes after Onyx embolization of DAVFs but little evidence is available regarding the long term durability of this technique.MethodsWe retrospectively reviewed a database of 63 DAVFs in 53 consecutive patients who underwent Onyx embolization of a DAVF between 2001 and 2012 at our institution. Cognard types I and III were seen most commonly.ResultsA total of 72 Onyx embolization procedures were successfully completed during the study period, resulting in complete or near complete occlusion by the end of the study period in 58 (92.1%) DAVFs. For DAVFs in which complete or near complete obliteration was attained, stability of obliteration at 6, 12, 24, and 46 months was 100%, 95.4%, 93.8%, and 92.3%, respectively. DAVF recanalization/regrowth was discovered on delayed follow-up angiography in only five instances in which immediate post-embolization angiography revealed complete obliteration. Complications were seen in seven embolization procedures and included cranial nerve palsies (n=3), embolic infarcts (n=2), intraparenchymal hemorrhage (n=1), and unintentional stent deployment (n=1).ConclusionsEarly evidence has indicated that endovascular Onyx embolization is safe and effective at achieving an initial angiographic cure. Results of our series suggest that angiographic and clinical outcomes of Onyx embolization remain relatively stable at mid and long term follow-up.
Glomerular Function Time Trends in Long-Term Survivors of Childhood Cancer: A Longitudinal Study
Authors: Mulder Renée L. , Knijnenburg Sebastiaan L. , Geskus Ronald B. , van Dalen Elvira C. , van der Pal Helena J.H. , Koning Caro C.E. , Bouts Antonia H. , Caron Huib N. , Kremer Leontien C.M. 
Published: September 2013

AbstractBackground: Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends and predictors of glomerular function in CCS.Methods: We evaluated repeated observations of estimated glomerular filtration rate (GFR) and glomerular dysfunction (GFR &lt;90 mL/min/1.73 m2) among adult five-year CCS treated in the EKZ/AMC between 1966 and 2003. Ifosfamide, cisplatin, carboplatin, high-dose (HD) methotrexate, HD-cyclophosphamide, radiotherapy to the kidney region, and nephrectomy (i.e., potentially nephrotoxic therapy) were investigated as predictors of glomerular function patterns over time in multivariable longitudinal analyses.Results: At a median follow-up of 21 years after diagnosis, glomerular function was assessed in 1,122 CCS aged ≥18 years. CCS treated with potentially nephrotoxic therapy had a significantly lower GFR and higher glomerular dysfunction probability up to 35 years after cancer diagnosis compared with CCS treated without nephrotoxic therapy (P &lt; 0.001). Especially ifosfamide, cisplatin, and nephrectomy were associated with worse glomerular function that persisted during the entire follow-up period (P &lt; 0.001). Glomerular function deteriorated over time in all CCS (P &lt; 0.001). CCS treated with higher doses of cisplatin seem to have a higher deterioration rate as compared with other CCS (P &lt; 0.005).Conclusions: The loss in glomerular function starts early, especially for CCS treated with ifosfamide, higher doses of cisplatin, and nephrectomy, and seems to be persistent. We have an indication that CCS treated with higher doses of cisplatin experience faster decline than other CCS.Impact: As glomerular function continues to deteriorate, CCS are at risk for premature chronic renal failure. Cancer Epidemiol Biomarkers Prev; 22(10); 1736–46. ©2013 AACR.
The Novel ATP-Competitive Inhibitor of the MET Hepatocyte Growth Factor Receptor EMD1214063 Displays Inhibitory Activity against Selected MET-Mutated Variants
Authors: Medová Michaela , Pochon Benoît , Streit Bruno , Blank-Liss Wieslawa , Francica Paola , Stroka Deborah , Keogh Adrian , Aebersold Daniel M. , Blaukat Andree , Bladt Friedhelm , Zimmer Yitzhak 
Published: September 2013

Abstract
The receptor tyrosine kinase MET is a prime target in clinical oncology due to its aberrant activation and involvement in the pathogenesis of a broad spectrum of malignancies. Similar to other targeted kinases, primary and secondary mutations seem to represent an important resistance mechanism to MET inhibitors. Here, we report the biologic activity of a novel MET inhibitor, EMD1214063, on cells that ectopically express the mutated MET variants M1268T, Y1248H, H1112Y, L1213V, H1112L, V1110I, V1206L, and V1238I. Our results show a dose-dependent decrease in MET autophosphorylation in response to EMD1214063 in five of the eight cell lines (IC50 2–43 nmol/L). Blockade of MET by EMD1214063 was accompanied by a reduced activation of downstream effectors in cells expressing EMD1214063-sensitive mutants. In all sensitive mutant-expressing lines, EMD1214063 altered cell-cycle distribution, primarily with an increase in G1 phase. EMD1214063 strongly influenced MET-driven biologic functions, such as cellular morphology, MET-dependent cell motility, and anchorage-independent growth. To assess the in vivo efficacy of EMD1214063, we used a xenograft tumor model in immunocompromised mice bearing NIH3T3 cells expressing sensitive and resistant MET-mutated variants. Animals were randomized for the treatment with EMD1214063 (50 mg/kg/d) or vehicle only. Remarkably, five days of EMD1214063 treatment resulted in a complete regression of the sensitive H1112L-derived tumors, whereas tumor growth remained unaffected in mice with L1213V tumors and in vehicle-treated animals. Collectively, the current data identifies EMD1214063 as a potent MET small-molecule inhibitor with selective activity towards mutated MET variants. Mol Cancer Ther; 12(11); 2415–24. ©2013 AACR.
Validation of Contrast-Enhanced Magnetic Resonance Imaging to Monitor Regenerative Efficacy After Cell Therapy in a Porcine Model of Convalescent Myocardial Infarction
Authors: Malliaras Konstantinos , Smith Rachel R. , Kanazawa Hideaki , Yee Kristine , Seinfeld Jeffrey , Tseliou Eleni , Dawkins James F. , Kreke Michelle , Cheng Ke , Luthringer Daniel , Ho Chak-Sum , Blusztajn Agnieszka , Valle Ileana , Chowdhury Supurna , Makkar Raj R. , Dharmakumar Rohan , Li Debiao , Marbán Linda , Marbán Eduardo 
Published: September 2013

Background—
Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI.

Methods and Results—

Yucatan minipigs underwent induction of MI and 2–3 weeks later were randomized to receive intracoronary infusion of 12.5×10
6
mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size, and increased viable myocardium compared with placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass, and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis).

Conclusions—
Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy.
In-Hospital Complications Associated With Catheter Ablation of Atrial Fibrillation in the United States Between 2000 and 2010
Authors: Deshmukh Abhishek , Patel Nileshkumar J. , Pant Sadip , Shah Neeraj , Chothani Ankit , Mehta Kathan , Grover Peeyush , Singh Vikas , Vallurupalli Srikanth , Savani Ghanshyambhai T. , Badheka Apurva , Tuliani Tushar , Dabhadkar Kaustubh , Dibu George , Reddy Y. Madhu , Sewani Asif , Kowalski Marcin , Mitrani Raul , Paydak Hakan , Viles-Gonzalez Juan F. 
Published: September 2013

Background—
Atrial fibrillation ablation has made tremendous progress with respect to innovation, efficacy, and safety. However, limited data exist regarding the burden and trends in adverse outcomes arising from this procedure. The aim of our study was to examine the frequency of adverse events attributable to atrial fibrillation (AF) ablation and the influence of operator and hospital volume on outcomes.

Methods and Results—

With the use of the Nationwide Inpatient Sample, we identified AF patients treated with catheter ablation. We investigated common complications including cardiac perforation and tamponade, pneumothorax, stroke, transient ischemic attack, vascular access complications (hemorrhage/hematoma, vascular complications requiring surgical repair, and accidental arterial puncture), and in-hospital death described with AF ablation, and we defined these complications by using validated
International Classification of Diseases, Ninth Revision, Clinical Modification
diagnosis codes. An estimated 93 801 AF ablations were performed from 2000 to 2010. The overall frequency of complications was 6.29% with combined cardiac complications (2.54%) being the most frequent. Cardiac complications were followed by vascular complications (1.53%), respiratory complications (1.3%), and neurological complications (1.02%). The in-hospital mortality was 0.46%. Annual operator (<25 procedures) and hospital volume (<50 procedures) were significantly associated with adverse outcomes. There was a small (nonsignificant) rise in overall complication rates.

Conclusions—
The overall complication rate was 6.29% in patients undergoing AF ablation. There was a significant association between operator and hospital volume and adverse outcomes. This suggests a need for future research into identifying the safety measures in AF ablations and instituting appropriate interventions to improve overall AF ablation outcomes.
Stroke Unit Care Benefits Patients With Intracerebral Hemorrhage
Authors: Langhorne Peter , Fearon Patricia , Ronning Ole M. , Kaste Markku , Palomaki Heikki , Vemmos Kostos , Kalra Lalit , Indredavik Bent , Blomstrand Christian , Rodgers Helen , Dennis Martin S. , Salman Rustam Al-Shahi ,   The following collaborators provided new data, advice and comment, and assisted with the redrafting of the report:, Blomstrand C. , Indredavik B. , Kalra L. , Kaste M. , Palomaki H. , Rodgers H. , Ronning M.O. , Vemmos K. ,   The Stroke Unit Trialists’ Collaboration supported and provided for the main stroke unit review:, Asplund K. , Berman P. , Blomstrand C. , Britton M. , Cabral N.L. , Cavallini A. , Dey P. , Hamrin E. , Hankey G. , Indredavik B. , Kalra L. , Kaste M. , Laursen S.O. , Ma R.H. , Patel N. , Rodgers H. , Ronning M.O. , Sivenius J. , Stevens R. , Sulter G. , Svensson A. , Vemmos K. , Wood-Dauphinee S. , Yagura H. 
Published: September 2013

Background and Purpose—
Patients with any type of stroke managed in organized inpatient (stroke unit) care are more likely to survive, return home, and regain independence. However, it is uncertain whether these benefits apply equally to patients with intracerebral hemorrhage and ischemic stroke.

Methods—
We conducted a secondary analysis of a systematic review of controlled clinical trials comparing stroke unit care with general ward care, including only trials published after 1990 that could separately report outcomes for patients with intracerebral hemorrhage and ischemic stroke. We performed random-effects meta-analyses and tested for subgroup interactions by stroke type.

Results—

We identified 13 trials (3570 patients) of modern stroke unit care that recruited patients with intracerebral hemorrhage and ischemic stroke, of which 8 trials provided data on 2657 patients. Stroke unit care reduced death or dependency (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.471–0.92;
P
=0.0009;
I
2
=60%) with no difference in benefits for patients with intracerebral hemorrhage (RR, 0.79; 95% CI, 0.61–1.00) than patients with ischemic stroke (RR, 0.82; 95% CI, 0.70–0.97;
P
interaction
=0.77). Stroke unit care reduced death (RR, 0.79; 95% CI, 0.64–0.97;
P
=0.02;
I
2
=49%) to a greater extent for patients with intracerebral hemorrhage (RR, 0.73; 95% CI, 0.54–0.97) than patients with ischemic stroke (RR, 0.82; 95%, CI 0.61–1.09), but this difference was not statistically significant (
P
interaction
=0.58).

Conclusions—
Patients with intracerebral hemorrhage seem to benefit at least as much as patients with ischemic stroke from organized inpatient (stroke unit) care.