bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotypic Resistance in
Helicobacter pylori
Strains Correlates with Susceptibility Test and Treatment Outcomes after Levofloxacin- and Clarithromycin-Based Therapies
Authors: Liou Jyh-Ming , Chang Chi-Yang , Sheng Wang-Huei , Wang Yu-Chi , Chen Mei-Jyh , Lee Yi-Chia , Hung Hsu-Wei , Chian Hung , Chang San-Chun , Wu Ming-Shiang , Lin Jaw-Town 
Published: December 2010

ABSTRACT

The accuracy of genotypic resistance to levofloxacin (
gyrA
mutations) and its agreement with treatment outcomes after levofloxacin-based therapy have not been reported. We aimed to assess the correlation.
Helicobacter pylori
strains isolated from patients who received levofloxacin-based and clarithromycin-based triple therapies in a previous randomized trial were analyzed for point mutations in
gyrA
and 23S rRNA. PCR followed by direct sequencing was used to assess the
gyrA
and 23S rRNA mutations. An agar dilution test was used to determine the MICs of clarithromycin and levofloxacin. We found that the agreement between genotypic and phenotypic resistance to levofloxacin was best when the MIC breakpoint was >1 μg/ml (kappa coefficient, 0.754). The eradication rates in patients with and without
gyrA
mutations were 41.7% and 82.7%, respectively (
P
= 0.003). The agreement between genotypic and phenotypic resistance to clarithromycin was best when the MIC breakpoint was >2 μg/ml (kappa, 0.694). The eradication rates in patients with and without 23S rRNA mutations were 7.7% and 93.5%, respectively (
P
< 0.001). The agreements (kappa coefficient) between therapeutic outcomes after clarithromycin-based triple therapy and genotypic and phenotypic resistance were 0.671 and 0.356, respectively. The agreements (kappa coefficient) between therapeutic outcomes after levofloxacin-based triple therapy and genotypic and phenotypic resistance were 0.244 and 0.190, respectively. In conclusion,
gyrA
and 23S rRNA mutations in
H. pylori
strains appeared to be better markers than phenotypic resistance in the prediction of treatment outcomes. The optimal breakpoints for levofloxacin and clarithromycin resistance appeared to be >1 μg/ml and >2 μg/ml, respectively.
Early Dissemination of NDM-1- and OXA-181-Producing
Enterobacteriaceae
in Indian Hospitals: Report from the SENTRY Antimicrobial Surveillance Program, 2006-2007
Authors: Castanheira Mariana , Deshpande Lalitagauri M. , Mathai Dilip , Bell Jan M. , Jones Ronald N. , Mendes Rodrigo E. 
Published: December 2010

ABSTRACT

Among 39 carbapenem-resistant
Enterobacteriaceae
(2.7% overall;
Escherichia coli
,
Enterobacter cloacae
, and
Klebsiella pneumoniae
strains) isolated in 2006 and 2007 in India, 15 strains carried
bla
NDM-1
and 10 harbored a gene encoding a variant of the carbapenemase OXA-48, named
bla
OXA-181
. One
E. cloacae
strain harbored
bla
VIM-6
, and one
K. pneumoniae
strain carrying
bla
OXA-181
also possessed
bla
VIM-5
. Multiple pulsed-field gel electrophoresis patterns and clonal dissemination within and among sites were observed. Isolates producing NDM-1 were disseminated in Indian health care facilities as early as 2006.
Antimicrobial Susceptibility of Clinically Relevant Gram-Positive Anaerobic Cocci Collected over a Three-Year Period in the Netherlands
Authors: Veloo A. C. M. , Welling G. W. , Degener J. E. 
Published: December 2010

ABSTRACT

The susceptibility of 14 species of 115 Gram-positive anaerobic cocci (GPAC) was determined for 14 antibiotics. To assure correct identification, strains were genotypically identified by fluorescence
in situ
hybridization and sequencing. Susceptibility differences (MIC
50
and MIC
90
) for penicillin G, clindamycin, tigecycline, levofloxacin, amoxicillin-clavulanic acid, cefoxitin, ertapenem, meropenem, metronidazole, and doxycycline were found for the three clinically most relevant GPAC species:
Finegoldia magna
,
Parvimonas micra
, and
Peptoniphilus harei
.
Strain-Transcending Fc-Dependent Killing ofPlasmodium falciparumby Merozoite Surface Protein 2 Allele-Specific Human Antibodies
Authors: Stubbs Janine , Olugbile Sope , Saidou Balam , Simpore Jacques , Corradin Giampietro , Lanzavecchia Antonio 
Published: December 2010

ABSTRACTIt is widely accepted that antibody responses against the human parasitic pathogenPlasmodium falciparumprotect the host from the rigors of severe malaria and death. However, there is a continuing need for the development ofin vitrocorrelate assays of immune protection. To this end, the capacity of human monoclonal and polyclonal antibodies in eliciting phagocytosis and parasite growth inhibition via Fcγ receptor-dependent mechanisms was explored. In examining the extent to which sequence diversity in merozoite surface protein 2 (MSP2) results in the evasion of antibody responses, an unexpectedly high level of heterologous function was measured for allele-specific human antibodies. The dependence on Fcγ receptors for opsonic phagocytosis and monocyte-mediated antibody-dependent parasite inhibition was demonstrated by the mutation of the Fc domain of monoclonal antibodies against both MSP2 and a novel vaccine candidate, peptide 27 from the genePFF0165c. The described flow cytometry-based functional assays are expected to be useful for assessing immunity in naturally infected and vaccinated individuals and for prioritizing among blood-stage antigens for inclusion in blood-stage vaccines.
Iron Content Differs between
Francisella tularensis
Subspecies
tularensis
and Subspecies
holarctica
Strains and Correlates to Their Susceptibility to H
2
O
2
-Induced Killing
Authors: Lindgren Helena , Honn Marie , Salomonsson Emelie , Kuoppa Kerstin , Forsberg Åke , Sjöstedt Anders 
Published: December 2010

ABSTRACT

Francisella tularensis
, the causative agent of tularemia, is one of the most infectious bacterial pathogens known and is classified as a category A select agent and a facultative intracellular bacterium. Why
F. tularensis
subsp.
tularensis
causes a more severe form of tularemia than
F. tularensis
subsp.
holarctica
does is not known. In this study, we have identified prominent phenotypic differences between the subspecies, since we found that
F. tularensis
subsp.
tularensis
strains contained less iron than
F. tularensis
subsp.
holarctica
strains. Moreover, strain SCHU S4 of
F. tularensis
subsp.
tularensis
was less susceptible than FSC200 and the live vaccine strain (LVS) of
F. tularensis
subsp.
holarctica
to H
2
O
2
-induced killing. The activity of the H
2
O
2
-degrading enzyme catalase was similar between the strains, whereas the iron content affected their susceptibility to H
2
O
2
, since iron starvation rendered
F. tularensis
subsp.
holarctica
strains more resistant to H
2
O
2
. Complementing LVS with
fupA
, which encodes an important virulence factor that regulates iron uptake, reduced its iron content and increased the resistance to H
2
O
2
-mediated killing. By real-time PCR, it was demonstrated that FSC200 and LVS expressed higher levels of gene transcripts related to iron uptake and storage than SCHU S4 did, and this likely explained their high iron content. Together, the results suggest that
F. tularensis
subsp.
tularensis
strains have restricted iron uptake and storage, which is beneficial for their resistance to H
2
O
2
-induced killing. This may be an important factor for the higher virulence of this subspecies of
F. tularensis
, as reactive oxygen species, such as H
2
O
2
, are important bactericidal components during tularemia.
Identification ofAnaplasma marginaleOuter Membrane Protein Antigens Conserved betweenA. marginaleSensu Stricto Strains and the LiveA. marginalesubsp.centraleVaccine
Authors: Agnes Joseph T. , Brayton Kelly A. , LaFollett Megan , Norimine Junzo , Brown Wendy C. , Palmer Guy H. 
Published: December 2010

ABSTRACTLive vaccination withAnaplasma marginalesubsp.centrale(synonym forAnaplasma centrale) induces protection against severe disease upon challenge withA. marginalesensu stricto strains. Despite over a century of field use, the targets of protective immunity remained unknown. Using a broad proteomic approach, we identified the proteins in a challenge sensu stricto strain that were bound by the relevant antibody isotype induced by live vaccination withAnaplasma marginalesubsp.centrale.A core of 15 proteins was identified in vaccinated animals across multiple major histocompatibility complex (MHC) haplotypes. This core separated into two structural/functional classes: “housekeeping” proteins involved in replication and metabolism and outer membrane proteins (OMPs). Orthologous proteins of both classes were identified within the vaccine strain and among sensu stricto strains. In contrast to the broad conservation among strains in the sequences of the housekeeping proteins, there was significantly greater divergence in the OMPs and greater divergence in both OMP sequences and the encoding locus structure between the vaccine strain and the sensu stricto strains than among the sensu stricto strains. The OMPs bound by live vaccine-induced antibody overlapped with OMPs that were immunogenic in animals vaccinated with inactivated vaccines and subsequently protected against bacteremia and disease. The identification of this core set of OMPs is consistent with the hypothesis that “subdominant” immunogens are required for vaccine-induced protection againstA. marginaleand provides clear direction for development of a safer, more effective vaccine.
Iterative Methods for Finding Common Solution of Generalized Equilibrium Problems and Variational Inequality Problems and Fixed Point Problems of a Finite Family of Nonexpansive Mappings
Authors: Kangtunyakarn Atid 
Published: December 2010

AbstractWe introduce a new method for a system of generalized equilibrium problems, system of variational inequality problems, and fixed point problems by using "Equation missing"-mapping generated by a finite family of nonexpansive mappings and real numbers. Then, we prove a strong convergence theorem of the proposed iteration under some control condition. By using our main result, we obtain strong convergence theorem for finding a common element of the set of solution of a system of generalized equilibrium problems, system of variational inequality problems, and the set of common fixed points of a finite family of strictly pseudocontractive mappings.
A General Iterative Approach to Variational Inequality Problems and Optimization Problems
Authors: Jung JongSoo 
Published: December 2010

AbstractWe introduce a new general iterative scheme for finding a common element of the set of solutions of variational inequality problem for an inverse-strongly monotone mapping and the set of fixed points of a nonexpansive mapping in a Hilbert space and then establish strong convergence of the sequence generated by the proposed iterative scheme to a common element of the above two sets under suitable control conditions, which is a solution of a certain optimization problem. Applications of the main result are also given.
New Iterative Approximation Methods for a Countable Family of Nonexpansive Mappings in Banach Spaces
Authors: Nammanee Kamonrat , Wangkeeree Rabian 
Published: December 2010

AbstractWe introduce new general iterative approximation methods for finding a common fixed point of a countable family of nonexpansive mappings. Strong convergence theorems are established in the framework of reflexive Banach spaces which admit a weakly continuous duality mapping. Finally, we apply our results to solve the the equilibrium problems and the problem of finding a zero of an accretive operator. The results presented in this paper mainly improve on the corresponding results reported by many others.
Reduced SMAD7 Leads to Overactivation of TGF-β Signaling in MDS that Can Be Reversed by a Specific Inhibitor of TGF-β Receptor I Kinase
Authors: Zhou Li , McMahon Christine , Bhagat Tushar , Alencar Cristina , Yu Yiting , Fazzari Melissa , Sohal Davendra , Heuck Christoph , Gundabolu Krishna , Ng Chun , Mo Yongkai , Shen Wa , Wickrema Amittha , Kong Guanghui , Friedman Ellen , Sokol Lubomir , Mantzaris Giannis , Pellagatti Andrea , Boultwood Jacqueline , Platanias Leonidas C. , Steidl Ulrich , Yan Lei , Yingling Jonathan M. , Lahn Michael M. , List Alan , Bitzer Markus , Verma Amit 
Published: December 2010

Abstract
Even though myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, the molecular alterations that lead to marrow failure have not been well elucidated. We have previously shown that the myelosuppressive TGF-β pathway is constitutively activated in MDS progenitors. Because there is conflicting data about upregulation of extracellular TGF-β levels in MDS, we wanted to determine the molecular basis of TGF-β pathway overactivation and consequent hematopoietic suppression in this disease. We observed that SMAD7, a negative regulator of TGF-β receptor I (TBRI) kinase, is markedly decreased in a large meta-analysis of gene expression studies from MDS marrow-derived CD34+ cells. SMAD7 protein was also found to be significantly decreased in MDS marrow progenitors when examined immunohistochemically in a bone marrow tissue microarray. Reduced expression of SMAD7 in hematopoietic cells led to increased TGF-β–mediated gene transcription and enhanced sensitivity to TGF-β–mediated suppressive effects. The increased TGF-β signaling due to SMAD7 reduction could be effectively inhibited by a novel clinically relevant TBRI (ALK5 kinase) inhibitor, LY-2157299. LY-2157299 could inhibit TGF-β–mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. Furthermore, in vivo administration of LY-2157299 ameliorated anemia in a TGF-β overexpressing transgenic mouse model of bone marrow failure. Most importantly, treatment with LY-2157199 stimulated hematopoiesis from primary MDS bone marrow specimens. These studies demonstrate that reduction in SMAD7 is a novel molecular alteration in MDS that leads to ineffective hematopoiesis by activating of TGF-β signaling in hematopoietic cells. These studies also illustrate the therapeutic potential of TBRI inhibitors in MDS. Cancer Res; 71(3); 955–63. ©2010 AACR.
Isokinetic Strength, Endurance, and Subjective Outcomes After Biceps Tenotomy Versus Tenodesis
Authors: Wittstein Jocelyn R. , Queen Robin , Abbey Alicia , Toth Alison , Moorman Claude T. 
Published: December 2010

Background: Similar subjective outcomes have been reported for tenotomy or tenodesis of the long head of the biceps. Few studies have reported on postoperative strength and endurance. Hypothesis: Biceps tenodesis results in superior subjective outcomes, strength, and endurance compared with tenotomy. Study Design: Cohort study; Level of evidence, 3. Methods: Participants completed isokinetic strength and endurance testing for elbow flexion and supination on the operative and nonoperative sides a minimum of 2 years after biceps tenotomy or tenodesis. Modified American Shoulder and Elbow Surgeons (MASES) and Single Assessment Numeric Evaluation (SANE) scores were obtained. The operative/nonoperative strength and endurance scores were compared for the tenotomy and tenodesis groups, with the nonoperative shoulder serving as the control for each participant’s operative shoulder. Change scores for strength and endurance were reported as percentage increase or decrease as compared with the nonoperative side. Change scores and MASES and SANE scores were compared between the 2 groups. The presence of a “popeye” deformity or pain at the tenodesis site was noted. Results: Thirty-five patients (19 tenotomy, 16 tenodesis) were studied. No significant difference was noted in postoperative MASES and SANE scores. Operative-side peak supination torque was significantly decreased relative to the nonoperative side in the tenotomy group, which had a significantly larger decrease in supination peak torque than did the tenodesis group on comparison of change scores. No significant difference was noted for peak flexion torque or flexion/supination endurance between operative and nonoperative sides in either group or between change scores for peak flexion torque or flexion/supination endurance in the tenotomy and tenodesis groups. Four tenotomy patients had a popeye deformity, 2 of whom reported painful cramping. Two patients had pain at the tenodesis site. Conclusion: Subjective outcomes are similar for patients treated with tenotomy and tenodesis. Tenotomy decreases supination peak torque relative to the nonoperative side and tenodesis.
Subcontracting and the Creation of Inequality in the Dutch Clothing Industry 1980-1992
Authors: Akkermans Dirk H. M. 
Published: December 2010

The paper analyzes a dual industry structure and its effects as hypothesized by segmentation theory. A dual industry structure refers to the simultaneous existence of two groups of firms within an industry which differ in terms of bargaining power and product and labor market performance: sales and job fluctuation levels should be higher in the dominated group, and job security lower. Empirical analysis of the clothing industry in the Netherlands for the period 1980-1992 confirms the hypotheses for the largest part. JEL classifications: J42, L14, L11
Alteration of Topoisomerase II–Alpha Gene in Human Breast Cancer: Association With Responsiveness to Anthracycline-Based Chemotherapy
Authors: Press Michael F. , Sauter Guido , Buyse Marc , Bernstein Leslie , Guzman Roberta , Santiago Angela , Villalobos Ivonne E. , Eiermann Wolfgang , Pienkowski Tadeusz , Martin Miguel , Robert Nicholas , Crown John , Bee Valerie , Taupin Henry , Flom Kerry J. , Tabah-Fisch Isabelle , Pauletti Giovanni , Lindsay Mary-Ann , Riva Alessandro , Slamon Dennis J. 
Published: December 2010

Purpose Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines. This study was designed to evaluate whether TOP2A gene alterations may predict incremental responsiveness to anthracyclines in some breast cancers. Methods A total of 4,943 breast cancers were analyzed for alterations in TOP2A and HER2. Primary tumor tissues from patients with metastatic breast cancer treated in a trial of chemotherapy plus/minus trastuzumab were studied for amplification/deletion of TOP2A and HER2 as a test set followed by evaluation of malignancies from two separate, large trials for changes in these same genes as a validation set. Association between these alterations and clinical outcomes was determined. Results Test set cases containing HER2 amplification treated with doxorubicin and cyclophosphamide (AC) plus trastuzumab, demonstrated longer progression-free survival compared to those treated with AC alone (P = .0002). However, patients treated with AC alone whose tumors contain HER2/TOP2A coamplification experienced a similar improvement in survival (P = .004). Conversely, for patients treated with paclitaxel, HER2/TOP2A coamplification was not associated with improved outcomes. These observations were confirmed in a larger validation set, where HER2/TOP2A coamplification was again associated with longer survival when only anthracycline-containing chemotherapy was used for treatment compared with outcome in HER2-positive cancers lacking TOP2A coamplification. Conclusion In a study involving nearly 5,000 breast malignancies, both test set and validation set demonstrate that TOP2A coamplification, not HER2 amplification, is the clinically useful predictive marker of an incremental response to anthracycline-based chemotherapy. Absence of HER2/TOP2A coamplification may indicate a more restricted efficacy advantage for breast cancers than previously thought.
Risk Factors for the Development of Secondary Malignancy After High-Dose Chemotherapy and Autograft, With or Without Rituximab: A 20-Year Retrospective Follow-Up Study in Patients With Lymphoma
Authors: Tarella Corrado , Passera Roberto , Magni Michele , Benedetti Fabio , Rossi Andrea , Gueli Angela , Patti Caterina , Parvis Guido , Ciceri Fabio , Gallamini Andrea , Cortelazzo Sergio , Zoli Valerio , Corradini Paolo , Carobbio Alessandra , Mulé Antonino , Bosa Marco , Barbui Anna , Di Nicola Massimo , Sorio Marco , Caracciolo Daniele , Gianni Alessandro M. , Rambaldi Alessandro 
Published: December 2010

Purpose High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. Patients and Methods A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%). Results At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages. Conclusion This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.
What Is the True Number Needed to Screen and Treat to Save a Life With Prostate-Specific Antigen Testing?
Authors: Loeb Stacy , Vonesh Edward F. , Metter E. Jeffrey , Carter H. Ballentine , Gann Peter H. , Catalona William J. 
Published: December 2010

PurposeThe European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 20% mortality reduction with prostate-specific antigen (PSA) screening. However, they estimated a number needed to screen (NNS) of 1,410 and a number needed to treat (NNT) of 48 to prevent one prostate cancer death at 9 years. Although NNS and NNT are useful statistics to assess the benefits and harms of an intervention, in a survival study setting such as the ERSPC, NNS and NNT are time specific, and reporting values at one time point may lead to misinterpretation of results. Our objective was to re-examine the effect of varying follow-up times on NNS and NNT using data extrapolated from the ERSPC report.Materials and MethodsOn the basis of published ERSPC data, we modeled the cumulative hazard function using a piecewise exponential model, assuming a constant hazard of 0.0002 for the screening and control groups for years 1 to 7 of the trial and different constant rates of 0.00062 and 0.00102 for the screening and control groups, respectively, for years 8 to 12. Annualized cancer detection and drop-out rates were also approximated based on the observed number of individuals at risk in published ERSPC data.ResultsAccording to our model, the NNS and NNT at 9 years were 1,254 and 43, respectively. Subsequently, NNS decreased from 837 at year 10 to 503 at year 12, and NNT decreased from 29 to 18.ConclusionDespite the seemingly simplistic nature of estimating NNT, there is widespread misunderstanding of its pitfalls. With additional follow-up in the ERSPC, if the mortality difference continues to grow, the NNT to save a life with PSA screening will decrease.