bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with Fluoroquinolones or with β-Lactam-β-Lactamase Inhibitor Combinations Is a Risk Factor for Isolation of Extended-Spectrum-β-Lactamase-Producing
Klebsiella
Species in Hospitalized Patients
Authors: Wener Kenneth M. , Schechner Vered , Gold Howard S. , Wright Sharon B. , Carmeli Yehuda 
Published: March 2010

ABSTRACT

Antibiotic exposure exerts strong selective pressure and is an important modifiable risk factor for antibiotic resistance. We aimed to identify the role of various antibiotics as risk factors for the isolation of extended-spectrum-β-lactamase (ESBL)-producing
Klebsiella
spp. in hospitalized patients at a tertiary-care hospital. A parallel multivariable model was created to compare two groups of cases with either nosocomially acquired ESBL- or non-ESBL-producing
Klebsiella
spp. to a common control group of hospitalized patients (a case-case-control design). Seventy-eight ESBL cases, 358 non-ESBL cases, and 444 controls were analyzed. Significant factors associated with the isolation of
Klebsiella
spp. were an age of >65 years, transfer from a health care facility, an intensive care unit (ICU) stay, and the presence of a comorbid malignancy or lung, hepatic, or renal disease. A propensity score was generated from the above, and our ability to discriminate between
Klebsiella
cases and controls (area under the receiver-operating-characteristic [ROC] curve, 0.78) was good. The ESBL phenotype was tightly linked with fluoroquinolone resistance (95% versus 18%,
P
< 0.001). Factors associated with isolation of ESBL
Klebsiella
spp. in a multivariable analysis, adjusting for the propensity score, included exposure to β-lactam-β-lactamase inhibitor combinations (odds ratio [OR], 10.17; 95% confidence interval [CI], 1.19 to 86.92) and to fluoroquinolones (OR, 2.86; 95% CI, 1.37 to 5.97). Exposure to broad-spectrum cephalosporins was statistically associated with ESBL
Klebsiella
spp. only among the subgroup of patients not treated with fluoroquinolones. In our institution, where the ESBL
-
producing-
Klebsiella
phenotype is coselected with fluoroquinolone resistance, fluoroquinolone and β-lactam-β-lactamase inhibitor combinations, rather than cephalosporins, are the main risk factors for ESBL isolates. Formulary interventions to limit the spread of ESBL-producing isolates should be tailored to each setting.
Systematic Approach to Optimizing Specifically Targeted Antimicrobial Peptides against
Streptococcus mutans
Authors: He Jian , Yarbrough Daniel K. , Kreth Jens , Anderson Maxwell H. , Shi Wenyuan , Eckert Randal 
Published: March 2010

ABSTRACT

Previously we reported a novel strategy of “targeted killing” through the design of narrow-spectrum molecules known as specifically targeted antimicrobial peptides (STAMPs) (R. Eckert et al., Antimicrob. Agents Chemother. 50:3651-3657, 2006; R. Eckert et al., Antimicrob. Agents Chemother. 50:1480-1488, 2006). Construction of these molecules requires the identification and the subsequent utilization of two conjoined yet functionally independent peptide components: the targeting and killing regions. In this study, we sought to design and synthesize a large number of STAMPs targeting
Streptococcus mutans
, the primary etiologic agent of human dental caries, in order to identify candidate peptides with increased killing speed and selectivity compared with their unmodified precursor antimicrobial peptides (AMPs). We hypothesized that a combinatorial approach, utilizing a set number of AMP, targeting, and linker regions, would be an effective method for the identification of STAMPs with the desired level of activity. STAMPs composed of the Sm6
S. mutans
binding peptide and the PL-135 AMP displayed selectivity at MICs after incubation for 18 to 24 h. A STAMP where PL-135 was replaced by the B-33 killing domain exhibited both selectivity and rapid killing within 1 min of exposure and displayed activity against multispecies biofilms grown in the presence of saliva. These results suggest that potent and selective STAMP molecules can be designed and improved via a tunable “building-block” approach.
Identification of
katG
Mutations Associated with High-Level Isoniazid Resistance in
Mycobacterium tuberculosis
Authors: Ando Hiroki , Kondo Yuji , Suetake Toshinori , Toyota Emiko , Kato Seiya , Mori Toru , Kirikae Teruo 
Published: March 2010

ABSTRACT

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in
Mycobacterium tuberculosis
, and
katG
mutations are major causes of INH resistance. In the present study, we sequenced
katG
of 108 INH-resistant
M. tuberculosis
clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant
M. tuberculosis
isolates.
Anaplasma phagocytophilumAPH_1387 Is Expressed throughout Bacterial Intracellular Development and Localizes to the Pathogen-Occupied Vacuolar Membrane
Authors: Huang Bernice , Troese Matthew J. , Ye Shaojing , Sims Jonathan T. , Galloway Nathan L. , Borjesson Dori L. , Carlyon Jason A. 
Published: March 2010

ABSTRACTObligate vacuolar pathogens produce proteins that localize to the host cell-derived membranes of the vacuoles in which they reside, yielding unique organelles that are optimally suited for pathogen survival.Anaplasma phagocytophilumis an obligate vacuolar bacterium that infects neutrophils and causes the emerging and potentially fatal disease human granulocytic anaplasmosis. Here we identified APH_1387 as the firstA. phagocytophilum-derived protein that associates with theA. phagocytophilum-occupied vacuolar membrane (AVM). APH_1387, also referred to as P100, is a 61.4-kDa acidic protein that migrates with an apparent molecular weight of 115 kDa on SDS-PAGE gels. It carries 3 tandem direct repeats that comprise 58% of the protein. Each APH_1387 repeat carries a bilobed hydrophobic alpha-helix domain, which is a structural characteristic that is consistent with the structure of chlamydia-derived proteins that traverse inclusion membranes. APH_1387 is not detectable on the surfaces ofA. phagocytophilumdense core organisms bound at the HL-60 cell surface, but abundant APH_1387 is detected on the surfaces of intravacuolar reticulate cell and dense core organisms. APH_1387 accumulates on the AVM throughout infection. It associates with the AVM in human HL-60, THP-1, and HMEC-1 cells and tick ISE6 cells. APH_1387 is expressed and localizes to the AVM in neutrophils recovered fromA. phagocytophilum-infected mice. This paper presents the first direct evidence thatA. phagocytophilumactively modifies its host cell-derived vacuole.
New payload attribution methods for network forensic investigations
Authors: Ponec Miroslav , Giura Paul , Wein Joel , Brönnimann Hervé 
Published: March 2010

Payload attribution can be an important element in network forensics. Given a history of packet transmissions and an excerpt of a possible packet payload, a payload attribution system (PAS) makes it feasible to identify the sources, destinations, and the times of appearance on a network of all the packets that contained the specified payload excerpt. A PAS, as one of the core components in a network forensics system, enables investigating cybercrimes on the Internet by, for example, tracing the spread of worms and viruses, identifying who has received a phishing e-mail in an enterprise, or discovering which insider allowed an unauthorized disclosure of sensitive information.
Due to the increasing volume of network traffic in today's networks, it is infeasible to effectively store and query all the actual packets for extended periods of time in order to allow analysis of network events for investigative purposes; therefore, we focus on extremely compressed digests of the packet activity. We propose several new methods for payload attribution, which utilize Rabin fingerprinting, shingling, and winnowing. Our best methods allow building practical payload attribution systems, which provide data reduction ratios greater than 100:1 while supporting efficient queries with very low false positive rates. We demonstrate the properties of the proposed methods and specifically analyze their performance and practicality when used as modules of a network forensics system ForNet. Our experimental results outperform current state-of-the-art methods both in terms of false positives and data reduction ratio. Finally, these approaches directly allow the collected data to be stored and queried by an untrusted party without disclosing any payload information nor the contents of queries.
Fixed Point Results for Multivalued Maps in Metric Spaces with Generalized Inwardness Conditions
Authors: Frigon M 
Published: March 2010

AbstractWe establish fixed point theorems for multivalued mappings defined on a closed subset of a complete metric space. We generalize Lim's result on weakly inward contractions in a Banach space. We also generalize recent results of Azé and Corvellec, Maciejewski, and Uderzo for contractions and directional contractions. Finally, we present local fixed point theorems and continuation principles for generalized inward contractions.
Is Human Papillomavirus Viral Load a Clinically Useful Predictive Marker? A Longitudinal Study
Authors: Constandinou-Williams Christothea , Collins Stuart I. , Roberts Sally , Young Lawrence S. , Woodman Ciaran B.J. , Murray Paul G. 
Published: March 2010

Abstract
Background: It has been suggested that in women who test positive for high-risk human papillomavirus (HPV) types, viral load can distinguish women who are at increased risk of cervical neoplasia from those who are not.
Methods: Quantitative PCR (qPCR) was used to measure HPV copy number in serial samples taken from 60 and 58 young women previously found to have incident cervical HPV16 or HPV18 infections, respectively, using GP5+/GP6+ primers; women provided at least three samples for qPCR testing, at least one of which was positive.
Results: A 10-fold increase in HPV16 or HPV18 copy number was associated with a modestly increased risk of acquiring a cytologic abnormality [HPV16: hazards ratio, 1.76 (95% confidence interval, 1.38-2.25); HPV18: hazards ratio, 1.59 (95% confidence interval, 1.25-2.03)]. However, in most women, copy number increased during follow-up, before decreasing again. In women with a HPV16 infection, the median copy number per 1,000 cells was 7.7 in their first qPCR HPV-positive sample, 1,237 in the sample yielding the maximum copy number, and 7.8 in their last qPCR HPV-positive sample; corresponding copy numbers for women with HPV18 infection were 2.3, 87, and 2.4. Maximum HPV16 and HPV18 copy number did not differ significantly between women who acquired an incident cervical cytologic abnormality and those who did not.
Conclusion: Whereas large relative increases in copy number are associated with an increased risk of abnormality, a single measurement of viral load made at an indeterminate point during the natural history of HPV infection does not reliably predict the risk of acquiring cervical neoplasia. Therefore, a single measure of HPV viral load cannot be considered a clinically useful biomarker. Cancer Epidemiol Biomarkers Prev; 19(3); 832–7
Glutathione Pathway Genetic Polymorphisms and Lung Cancer Survival After Platinum-Based Chemotherapy
Authors: Moyer Ann M. , Sun Zhifu , Batzler Anthony J. , Li Liang , Schaid Daniel J. , Yang Ping , Weinshilboum Richard M. 
Published: March 2010

Abstract
Background: Lung cancer is commonly treated with platinum compounds. The “glutathione pathway” participates in the metabolism of platinum compounds. We set out to test the hypotheses that single nucleotide polymorphisms (SNPs) or copy number polymorphisms for genes within the glutathione pathway might influence survival in lung cancer patients treated with these drugs.
Methods: Germline DNA samples from 973 lung cancer patients were genotyped for 290 glutathione pathway SNPs. GSTT1 copy number was also assayed. We determined the association of these polymorphisms with survival for lung cancer patients, followed by functional genomic validation.
Results: We observed suggestive associations between survival and GSTT1 copy number (P = 0.017), and GSTA5, GSTM4, and ABCC4 SNPs, adjusted for covariates (P = 0.018, 0.002, and 0.002, respectively) or not (P = 0.005, 0.011, and 0.002). One hundred lymphoblastoid cell lines were then treated with cisplatin, and IC50 values were significantly associated with the GSTM4 SNP (P = 0.019). Furthermore, GSTM4, GSTT1, and ABCC4 overexpression significantly decreased cisplatin sensitivity in lung cancer and HEK293T cell lines.
Conclusions: These results suggest that GSTM4 polymorphisms are biomarkers for the prediction of cisplatin response. ABCC4 polymorphisms, as well as GSTT1 copy number, may also help to predict cisplatin response, but further validation is required. These results represent a step toward the individualized chemotherapy of lung cancer. Cancer Epidemiol Biomarkers Prev; 19(3); 811–21
Lower Risk of Lung Cancer after Multiple Pneumonia Diagnoses
Authors: Koshiol Jill , Rotunno Melissa , Consonni Dario , Pesatori Angela Cecilia , De Matteis Sara , Goldstein Alisa M. , Chaturvedi Anil K. , Wacholder Sholom , Landi Maria Teresa , Lubin Jay H. , Caporaso Neil E. 
Published: March 2010

Abstract
Background: Although pneumonia has been suggested as a risk factor for lung cancer, previous studies have not evaluated the influence of number of pneumonia diagnoses in relation to lung cancer risk.
Methods: The Environment And Genetics in Lung cancer Etiology (EAGLE) population-based study of 2,100 cases and 2,120 controls collected information on pneumonia more than 1 year before enrollment from 1,890 cases and 2,078 controls.
Results: After adjusting for study design variables, smoking, and chronic bronchitis, pneumonia was associated with decreased risk of lung cancer [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.64-0.97], especially among individuals with three or more diagnoses versus none (OR, 0.35; 95% CI, 0.16-0.75). Adjustment for chronic bronchitis contributed to this inverse association. In comparison, pulmonary tuberculosis was not associated with lung cancer (OR, 0.96; 95% CI, 0.62-1.48).
Conclusions: The apparent protective effect of pneumonia among individuals with multiple pneumonia diagnoses may reflect an underlying difference in immune response and requires further investigation and confirmation. Therefore, careful evaluation of the number of pneumonia episodes may shed light on lung cancer etiology. Cancer Epidemiol Biomarkers Prev; 19(3); 716–21
TP53, MDM2, NQO1, and Susceptibility to Cervical Cancer
Authors: Hu Xiaoxia , Zhang Zhengyan , Ma Duanduan , Huettner Phyllis C. , Massad L. Stewart , Nguyen Loan , Borecki Ingrid , Rader Janet S. 
Published: March 2010

Abstract
Host genetic variability modifies the risk of cervical cancer in women infected with oncogenic human papillomavirus (HPV). Studies have reported an association of the TP53 codon 72 arginine and cervical cancer, but the results are inconsistent. We examined the association of this single nucleotide polymorphism (SNP) in women with cervical cancer and cervical intraepithelial neoplasia grade 3, using a family-based association test. We further explored SNPs in two genes that regulate p53 stability: MDM2 (SNP309) and NQO1 (SNP609, SNP465). We also examined the relationship between host genotype and tumor HPV type. We genotyped 577 patients and their biological parents and/or siblings, using PCR-RFLP or Taqman assays. HPVs were typed by sequence-based methods. The transmission/disequilibrium test was used to detect disease-susceptibility alleles. The arginine peptide of TP53 codon 72 was overtransmitted in Caucasian families (P = 0.043), and the significance of this finding was enhanced in a subgroup of women infected with HPV16- and/or HPV18-related HPVs (P = 0.026). Allele C of NQO1 SNP609 was also overtransmitted in all cases (P = 0.026). We found no association between MDM2 SNP309 or NQO1 SNP465 and cervical cancer. Our results indicate that functional polymorphisms in TP53 codon 72 and NQO1 SNP609 associate with the risk of cervical cancer especially in women infected with type 16– and/or type 18–related HPVs. Cancer Epidemiol Biomarkers Prev; 19(3); 755–61
Accuracy of Perceived Risk of Recurrence Among Patients With Early-Stage Breast Cancer
Authors: Liu Ying , Pérez Maria , Aft Rebecca L. , Massman Kerry , Robinson Erica , Myles Stephanie , Schootman Mario , Gillanders William E. , Jeffe Donna B. 
Published: March 2010

Abstract
Background: Accurate breast cancer recurrence risk perceptions might motivate health-promoting behaviors and alleviate undue anxiety. Although a few studies have examined early-stage breast cancer survivors' perceived risk of recurrence, none have assessed the accuracy of survivors' perceived risk of recurrence.
Methods: First primary ductal carcinoma in situ and early-invasive breast cancer survivors reported their perceived risk of recurrence during 6- and 12-month postsurgery interviews. We estimated the patients' 10-year risk of recurrence from published clinical trials, and for early-invasive breast cancer patients, risk of distant recurrence was based on their breast cancer–specific mortality calculated using Adjuvant! Online. Patients' perceived risk was compared with their calculated risk and categorized as “Accurate,” “Underestimated,” “Overestimated,” and “Uncertain.” Multinomial logit marginal effect models were fitted using Accurate as the reference.
Results: Only 17% of 531 patients accurately perceived their risk at 6 months, most of whom inaccurately perceived their risk at 12 months (P = 0.0143). Patients who were nonwhite [odds ratio (OR), 1.70; 95% confidence interval (95% CI), 1.12-2.56] and received radiation therapy (OR, 2.01; 95% CI, 1.07-3.77) were more likely to underestimate their risk. Patients with ductal carcinoma in situ (OR, 1.69; 95% CI, 1.08-2.70), lower social support (OR, 0.71; 95% CI, 0.53-0.95), and anxiety (OR, 1.58; 95% CI, 1.01-2.47) were more likely to overestimate their risk.
Conclusion: Few breast cancer survivors accurately perceived their risk of recurrence.
Impact: The accuracy of perceived risk may be increased by better physician-patient communications about their prognosis, provision of social support, and treatment for coexisting anxiety. Cancer Epidemiol Biomarkers Prev; 19(3); 675–80
Marijuana Use is Not Associated with Cervical Human Papillomavirus Natural History or Cervical Neoplasia in HIV-Seropositive or HIV-Seronegative Women
Authors: D'Souza Gypsyamber , Palefsky Joel M. , Zhong Ye , Minkoff Howard , Massad L. Stewart , Anastos Kathy , Levine Alexandra M. , Moxley Michael , Xue Xiao N. , Burk Robert D. , Strickler Howard D. 
Published: March 2010

Abstract
Marijuana use was recently reported to have a positive cross-sectional association with human papillomavirus (HPV)–related head and neck cancer. Laboratory data suggest that marijuana could have an immunomodulatory effect. Little is known, however, regarding the effects of marijuana use on cervical HPV or neoplasia. Therefore, we studied the natural history (i.e., prevalence, incident detection, clearance/persistence) of cervical HPV and cervical neoplasia (i.e., squamous intraepithelial lesions; SIL) in a large prospective cohort of 2,584 HIV-seropositive and 915 HIV-seronegative women. Marijuana use was classified as ever/never, current/not current, and by frequency and duration of use. No positive associations were observed between use of marijuana, and either cervical HPV infection or SIL. The findings were similar among HIV-seropositive and HIV-seronegative women, and in tobacco smokers and nonsmokers. These data suggest that marijuana use does not increase the burden of cervical HPV infection or SIL. Cancer Epidemiol Biomarkers Prev; 19(3); 869–72
Perceived Cancer Risk: Why Is It Lower Among Nonwhites than Whites?
Authors: Orom Heather , Kiviniemi Marc T. , Underwood Willie , Ross Levi , Shavers Vickie L. 
Published: March 2010

Abstract
Background: We explored racial/ethnic differences in perceived cancer risk and determinants of these differences in a nationally representative sample of whites, blacks, Hispanics, and Asians.
Methods: Multiple regression techniques, including mediational analyses, were used to identify determinants and quantify racial/ethnic differences in the perception of the risk of developing cancer among 5,581 adult respondents to the 2007 Health Information Trends Survey (HINTS).
Results: Blacks, Hispanics, and Asians reported lower perceived cancer risk than whites [Bs = −0.40, −0.34, and −0.69, respectively; (Ps &lt; 0.001)]. Contributing factors included relatively lower likelihood of reporting a family history of cancer, lower likelihood of having smoked, and a less strong belief that everything causes cancer among nonwhites than among whites. Racial/ethnic differences in perceived risk were attenuated in older respondents because perceived cancer risk was negatively associated with age for whites but not for nonwhites.
Conclusions: Nonwhites had lower perceptions of cancer risk than whites. Some of the racial/ethnic variability in perceived risk may be due to racial and ethnic differences in awareness of one's family history of cancer and its relevance for cancer risk, experiences with behavioral risk factors, and salience of cancer risk information. Cancer Epidemiol Biomarkers Prev; 19(3); 746–54
PTGER2 Overexpression in Colorectal Cancer Is Associated with Microsatellite Instability, Independent of CpG Island Methylator Phenotype
Authors: Baba Yoshifumi , Nosho Katsuhiko , Shima Kaori , Goessling Wolfram , Chan Andrew T. , Ng Kimmie , Chan Jennifer A. , Giovannucci Edward L. , Fuchs Charles S. , Ogino Shuji 
Published: March 2010

Abstract
Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, the HUGO Gene Nomenclature Committee–approved official symbol for cycloxygenase-2, COX-2) and its enzymatic product prostaglandin E2 have critical roles in inflammation and carcinogenesis through the G protein–coupled receptor PTGER2 (EP2). The PTGS2 (COX-2) pathway is a promising target for cancer therapy and chemoprevention. PTGS2 (COX-2) expression in colon cancer has been inversely associated with survival as well as tumoral microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). However, the prognostic significance of PTGER2 expression or its relationship with MSI, CIMP, LINE-1 hypomethylation, or PTGS2 (COX-2) remains uncertain.
Methods: Using the database of 516 colorectal cancers in two prospective cohort studies with clinical outcome data, we detected PTGER2 overexpression in 169 (33%) tumors by immunohistochemistry. We analyzed MSI using 10 microsatellite markers; CIMP by MethyLight (real-time methylation-specific PCR) on an eight-marker panel [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1]; BRAF, KRAS, PIK3CA, and methylation in LINE-1 by Pyrosequencing; and CTNNB1 (β-catenin) and TP53 (p53) by immunohistochemistry.
Results: PTGER2 overexpression was positively associated with the mucinous component (P = 0.0016), signet ring cells (P = 0.0024), CIMP-high (P = 0.0023), and MSI-high (P &lt; 0.0001). In multivariate analysis, the significant relationship between PTGER2 and MSI-high persisted (adjusted odds ratio, 2.82; 95% confidence interval, 1.69-4.72; P &lt; 0.0001). PTGER2 was not significantly associated with PTGS2 (COX-2), TP53, or CTNNB1 expression, patient survival, or prognosis.
Conclusion: PTGER2 overexpression is associated with MSI-high in colorectal cancer.
Impact: Our data imply potential roles of inflammatory reaction by PTGER2 upregulation in carcinogenic process to MSI-high colorectal cancer. Cancer Epidemiol Biomarkers Prev; 19(3); 822–31