bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial Small-Molecule Therapy Prevents Uropathogenic Escherichia coli Catheter-Associated Urinary Tract Infections in Mice
Authors: Guiton Pascale S. , Cusumano Corinne K. , Kline Kimberly A. , Dodson Karen W. , Han Zhenfu , Janetka James W. , Henderson Jeffrey P. , Caparon Michael G. , Hultgren Scott J. 
Published: June 2012

ABSTRACT

Catheter-associated urinary tract infections (CAUTIs) constitute the majority of nosocomial urinary tract infections (UTIs) and pose significant clinical challenges. These infections are polymicrobial in nature and are often associated with multidrug-resistant pathogens, including uropathogenic
Escherichia coli
(UPEC). Urinary catheterization elicits major histological and immunological alterations in the bladder that can favor microbial colonization and dissemination in the urinary tract. We report that these biological perturbations impact UPEC pathogenesis and that bacterial reservoirs established during a previous UPEC infection, in which bacteriuria had resolved, can serve as a nidus for subsequent urinary catheter colonization. Mannosides, small molecule inhibitors of the type 1 pilus adhesin, FimH, provided significant protection against UPEC CAUTI by preventing bacterial invasion and shifting the UPEC niche primarily to the extracellular milieu and on the foreign body. By doing so, mannosides potentiated the action of trimethoprim-sulfamethoxazole in the prevention and treatment of CAUTI. In this study, we provide novel insights into UPEC pathogenesis in the context of urinary catheterization, and demonstrate the efficacy of novel therapies that target critical mechanisms for this infection. Thus, we establish a proof-of-principle for the development of mannosides to prevent and eventually treat these infections in the face of rising antibiotic-resistant uropathogens.
Molecular Identification andIn VitroResponse to Antifungal Drugs of Clinical Isolates of Exserohilum
Authors: da Cunha Keith Cássia , Sutton Deanna A. , Gené Josepa , Capilla Javier , Cano Josep , Guarro Josep 
Published: June 2012

ABSTRACTExserohilumis an agent of human and animal mycoses. Although classification has been based on a few subtle morphological differences, three species of clinical interest have been traditionally accepted. In this study, by using a multigene sequence analysis, we have demonstrated thatExserohilum longirostratumandE. mcginnisiiare probable synonyms ofE. rostratum. The isolates tested were mainly from the nasal region. Antifungal susceptibility testing demonstrated high activity of the eight agents tested against this fungus.
Genome Sequences of Three Species in the Family Planctomycetaceae
Authors: Guo Min , Han Xifang , Jin Tao , Zhou Lisha , Yang Jinlong , Li Zihua , Chen Jing , Geng Bin , Zou Yuanqiang , Wan Daiwei , Li Daocheng , Dai Wenkui , Wang Hui , Chen Yanling , Ni Peixiang , Fang Chengxiang , Yang Ruifu 
Published: June 2012

ABSTRACT

Most of the species in the family
Planctomycetaceae
are of interest for their eukaryotic-like cell structures and characteristics of resistance to extreme environments. Here, we report draft genome sequences of three aquatic parasitic species of this family,
Singulisphaera acidiphila
(DSM 18658T),
Schlesneria paludicola
(DSM 18645T), and
Zavarzinella formosa
(DSM 19928T).
Perceived role in end-of-life decision making in the NICU affects long-term parental grief response
Authors: Caeymaex Laurence , Jousselme Catherine , Vasilescu Caroline , Danan Claude , Falissard Bruno , Bourrat Marie-Michèle , Garel Micheline , Speranza Mario 
Published: June 2012

BackgroundShared decision making (DM) is increasingly advocated as the most appropriate model to support parents confronted with end-of-life (EoL) decisions for a child in the neonatal intensive care unit (NICU). However, few studies have explored its impact on their long-term grief.ObjectivesThe aim of this study was to investigate whether parental perception of the type of involvement in the EoL decision-making process (EoL DMP) for their child in the NICU is related to their long-term grief outcome.MethodsA retrospective study with mixed methods. The study included parents whose child died from 2002 through 2005 in one of four NICUs in different areas in France, with interviews of 78 individual parents of 53 children, 2.7±0.6 years after the child's death. Parental perception of the type of involvement in the EoL DMP was determined by qualitative analysis of face-to-face interviews and classified as follows: shared, medical, informed parental and no decision. Grief reactions were assessed with the Texas Revised Inventory of Grief (TRIG-F).ResultsCurrent grief scores differed significantly according to the perceived type of EoL DM. Shared DM was associated with lower TRIG-F scores (less grief) than were the other types of EoL DM (F=7.95; p=0.05). The baby's perceived suffering was also associated with higher grief scores (F=6.51, p=0.01).ConclusionsIn decisions to forego life-sustaining treatment in the NICU, the perception of a shared decision is associated in the long term with lower grief scores than perceptions of the other types of DM.
Gene cloning, molecular modeling, and phylogenetics of serine protease P32 and serine carboxypeptidase SCP1 from nematophagous fungiPochonia rubescensandPochonia chlamydosporia
Authors: Larriba Eduardo , Martín-Nieto José , Lopez-Llorca Luis Vicente 
Published: June 2012

The fungi Pochonia chlamydosporia and Pochonia rubescens are parasites of nematode eggs and thus are biocontrol agents of nematodes. Proteolytic enzymes such as the S8 proteases VCP1 and P32, secreted during the pathogenesis of nematode eggs, are major virulence factors in these fungi. Recently, expression of these enzymes and of SCP1, a new putative S10 carboxypeptidase, was detected during endophytic colonization of barley roots by these fungi. In our study, we cloned the genomic and mRNA sequences encoding P32 from P. rubescens and SCP1 from P. chlamydosporia. P32 showed a high homology with the serine proteases Pr1A from the entomopathogenic fungus Metarhizium anisopliae and VCP1 from P. chlamydosporia (86% and 76% identity, respectively). However, the catalytic pocket of P32 showed differences in the amino acids of the substrate-recognition sites compared with the catalytic pockets of Pr1A and VCP1 proteases. Phylogenetic analysis of P32 suggests a common ancestor with protease Pr1A. SCP1 displays the characteristic features of a member of the S10 family of serine proteases. Phylogenetic comparisons show that SCP1 and other carboxypeptidases from filamentous fungi have an origin different from that of yeast vacuolar serine carboxypeptidases. Understanding protease genes from nematophagous fungi is crucial for enhancing the biocontrol potential of these organisms.
P1-11-01: Strong Socioeconomic Disparities in Breast Cancer Quality of Care in Switzerland.
Authors: Rapiti E , Blanc A , Benhamou S , Schubert H , Vlastos G , Schaffar R , Bouchardy C 
Published: June 2012

Abstract
Background Despite substantial research on socioeconomic disparities in breast cancer prognosis, important gaps remain concerning the causes of over mortality among socially deprived patients. In this population-based study, we identify disparities by socioeconomic status (SES) in diagnosis assessment and management of breast cancer in Geneva, Switzerland, where the average income and the health care system cost are among the highest in the world.
Methods We included in the study all 1110 women reported with invasive breast cancer at the Geneva Cancer Registry between 2003 and 2005. SES was regrouped in three levels: low (manual employees, skilled and unskilled workers), middle (nonmanual employees and administrative staff) and high (professionals, executive administrators, entrepreneurs) based on the patient's last occupation or, if unemployed, that of the spouse. We compared patients, tumour, treatment characteristics, surgeon caseload and delay of diagnosis as well as some of the management quality indicators established by the European School of Mastology among SES classes by heterogeneity tests. To assess the independent effect of each factor we used multivariate logistic regression, comparing women of high vs. low SES.
Results Compared with patients of high SES, low SES patients were older, more often born outside Switzerland and treated in the public system. Low SES women had less often screen detected cancers (29% vs. 41%; OR multi-adjusted for breast self-examination vs. mammography: 1.7, 95%CI: 1.1−2.6, p=0.020), and less frequently magnetic resonance imaging to assess tumour size/focality (4% vs. 15%; OR multi-adjusted for breast MRI vs. ultrasound: 0.2, 95%CI: 0.1−0.5, p=0.001). They had more often a delay longer than 4 weeks between diagnosis and treatment (53.8% vs. 32.7%; OR multi-adjusted for 4 weeks and more vs. less: 2.6, 95%CI: 1.7−4.1, p&lt;0.000). Also, women of low SES were more frequently operated by surgeons with a lower caseload (&lt;5 new breast cancer operations per year) (55% vs. 30%; OR multi-adjusted for surgeon's caseload of 5–15 vs. &lt;5: 0.4, 95%CI: 0.1−0.9, p=0.020), had more often positive surgical margins (11.4% vs. 5.4%; OR multi-adjusted for negative vs. positive margins: 0.4, 95% CI 0.2−1.0, p=0.057) and lower access to anti-aromatase treatments (29.6% vs. 43.6%). In particular, the probability to receive anastrozole vs. tamoxifen was 70% lower (OR multi-adjusted for anastrozole vs. tamoxifen: 0.3, 95%CI: 0.2−0.6, p&lt;0.000).
Conclusions: This study shows strong SES differences all along the continuum of breast cancer management, even in the highly medicalized county of Geneva. Only by improving the quality of care provided to women of low SES we will be able to prevent the excess breast cancer mortality observed among these women.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-01.
P2-09-01: First-in-Human Whole-Body HER2−Receptor Mapping Using Affibody Molecular Imaging.
Authors: Sandberg D , Wennborg A , Feldwisch J , Sörensen J , Garske U , Carlsson J , Lindman H 
Published: June 2012

Abstract
Background: ABY-025 is a member of a promising class of scaffold-based antibody alternatives known as Affibody molecules with superior properties for molecular imaging compared to monoclonal antibodies. It is a minimal-size, high-affinity HER2 binder, noncompetitive with trastuzumab allowing imaging even during trastuzumab therapy. This pilot clinical study set out to establish a safe clinical procedure for further tests and to verify whether breast cancer lesions could be identified and characterized for HER2 expression using single-photon emission computed tomography (SPECT) imaging.
Patients and methods: Seven patients with metastatic breast cancer, five with HER2 positive primary tumors and two HER2 negative controls were included. A standard 3-hour 18F-FDG-PET was performed to locate the lesions and 5 days later an injection with 111Inlabeled ABY-025 was given followed by whole body scanning at 30 minutes with additional SPECT at 4, 24 and 48 hours. Biopsies were taken from amenable lesions and analyzed by immunohistochemistry to verify the HER2 status.
Results: Large metastases were visualized already at 30 minutes and at later registrations a majority of all known lesions could be identified. A brain metastasis showed exceptionally high HER2 signal-to-background-ratio. Two fundamental behaviors were observed: High tumor to background ratio, increasing over time, was predominant in the HER2−positive group while the HER2−negative group generally presented a lower ratio. One patient in the positive group unexpectedly showed low tumor to background ratio similar to the negative group. Biopsy verified that the initially positive patient had converted to low HER2 expression. All other biopsies confirmed that the metastases were still positive or negative in line with the subject's primary lesions. None of the subjects had any adverse reactions due to the investigations.
Conclusion: ABY-025 can be used safely in humans with similar excellent whole body HER2−receptor molecular imaging capabilities as have already been observed in animal models. Promising indications of in vivo HER2−receptor status discriminatory capabilities were observed.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-09-01.
P3-13-07: The TARGIT-A Trial Update Confirms No Increase in Local Recurrence.
Authors: Vaidya JS , Baum M , Wenz F , Bulsara M , Tobias J , Alvarodo M , Saunders C , Williams N , Joseph D ,   On Behalf of the TARGIT Trialists Group
Published: June 2012

Abstract
Introduction: In June 2010, we published the results of the TARGIT-A trial (1) that compared “one-size fits” all radiotherapy (whole breast radiotherapy-EBRT group) with risk -adjusted radiotherapy (TARGIT- group: single dose TARGeted Intraoperative radioTherapy with additional whole breast radiotherapy if adverse prognostic factors were found). These results showed that the risk of local recurrence in the TARGIT group was non-inferior to that of the EBRT group (the difference between the two arms was 0.25% at 4 years). We now report the results analyzed after further follow up of the total trial cohort without unblinding.
Method: As often repeated, unplanned analysis comparing two groups in a randomized trial can result in an increased alpha-spent as well as carry the risk of a false positive result, we have remained blinded to the further recurrences in the trial according to allocated treatment, since the original publication in the Lancet. Instead we proposed and performed a blinded analysis of the local recurrence rate for the whole cohort. We plotted the Kaplan Meier plots and compared the estimated 4-year recurrences.
Results: Amongst the 2232 patients randomized, there were 13 recurrences at the time of Lancet publication and since then, we have had 8 additional recurrences. The number of patients who have completed at least 4 years of follow up has increased from 420 to 717. We found that the 4-year Kaplan Meier estimate of local recurrence was 1.08% (95% CI 0.59 −1.96) at the time of the Lancet publication and it is 1.09% (95% CI 0.65 - 1.85) now.
Conclusion: We found that the overall 4-year recurrence rates of the TARGIT-A trial have remained stable with a longer follow up and therefore; it is statistically implausible, that one particular arm has a significantly higher local recurrence.
References
1. Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, Alvarado M, Flyger HL, Massarut S, Eiermann W, Keshtgar M, Dewar J, Kraus-Tiefenbacher U, Sutterlin M, Esserman L, Holtveg HM, Roncadin M, Pigorsch S, Metaxas M, Falzon M, Matthews A, Corica T, Williams NR, Baum M. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 2010;376(9735):91–102.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-07.
P4-08-03: Serum Autoantibodies to Breast Cancer Associated Antigens Reflect Tumor Biology: An Opportunity for Early Detection & Prevention?
Authors: Eiermann W , Jackson L , Murray A , Chapman CJ , Peek LJ , Widschwendter P , Allen J , Graham H , Robertson JF 
Published: June 2012

Abstract
Autoantibodies (AABs) are produced as an immune response to abnormal ('non-self') cancer antigens. Previous studies have reported that AABs can be measured in the blood long before cancers are presently diagnosed, e.g., up to 4 years before screening mammography identified breast cancers and up to 5 years before screening CT detected lung cancers. EarlyCDT™-Lung is currently available as an aid to early detection of lung cancer in high risk patients and measures a panel of seven AABs to general cancer antigens and also lung cancer (LC) specific antigens. These AABs have previously been reported to be associated with the two main types of LC i.e., non-small cell and small cell LC. This study looked at AABs to 4 general cancer antigens to evaluate whether their levels reflected different biology in primary breast tumors.
Methods
770 patients presented with primary breast cancer to three centers (Nottingham, UK n=323; Munich, Germany n=320; Oklahoma, USA n=127); the median ages and ranges were 61 (26-82), 61 (20-88) & 65 (54-84) years, respectively. All had serum samples taken post-diagnosis and pre-treatment. The tumors were well characterized for histological grade, estrogen receptor (ER), progesterone receptor (PgR) and HER2 status. Serum samples were tested for AABs to four generic cancer antigens(Ags) (p53, SOX2, NY-ESO-1 and Annexin1) originally included as part of Oncimmune's EarlyCDT™-Lung assay. The AABs were measured by ELISA on the Oncimmune platform, and the EarlyCDT™-Lung cutoffs were used to determine positivity.
Results
131/770 (17%) of primary breast cancers showed elevated AAB levels to one or more of the limited panel of four generic antigens. Positivity for each AAB was correlated with histological grade, ER, PgR and HER2 status. The results, which were similar for each of the three centres, were combined, and the results are shown in Table 1 below.

p53 AAB positive cancers tended to be hormone receptor negative and HER2 positive. NY-ESO-1 positive tumors were almost all higher grade with the majority hormone receptor and HER2 negative. SOX2 positive cancers tended to have a hormone sensitive phenotype (i.e., hormone receptor positive and HER2 negative). Annexin 1 positive cancers also tended to have a hormone sensitive phenotype as well as HER2 negative. The pattern was statistically different for the four AABs (p&lt;0.001). The autoantibody profile for ER positive tumours was not statistically different from PgR positive tumors.
Conclusions
These data show that specific AABs measured in the serum reflected the biology of the breast cancers. Confirmation of this finding could, in the future, lead to using immuno-biomarkers such as these to guide early therapeutic intervention (e.g. prevention) in a targeted group of women.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-03.
P4-12-01: The Breast-Activity and Healthy Eating after Diagnosis (B-AHEAD) Study – A Randomised Comparison of Weight Control Programmes during Adjuvant Treatment.
Authors: Harvie M , Pegington M , Bundred N , Campbell A , Wolstenholme J , Adams J , Speed S , Morris J , Howell A 
Published: June 2012

Abstract
Background: Excess weight at diagnosis and weight gain during treatment are linked to increased mortality from breast cancer. Since 60% of breast cancer patients are overweight at diagnosis and 75% gain weight during treatment, weight control should improve outcome but the optimal intervention is unknown.
Aim: To compare 3 programmes for weight control after surgery for primary breast cancer.
Methods: We have recruited a randomised trial of 2 diet and exercise weight control interventions (1. a community based supervised group programme, 2. a mail and phone programme) compared to standard written advice (control). We are comparing the relative effects of the 3 programmes on body weight and composition (by dual energy x-ray absorptiometry), cardiovascular risk parameters (lipids, blood pressure), a marker of breast cancer prognosis (insulin resistance), fitness and quality of life over the first year after diagnosis.
In total 409 women have been randomised (45% of eligible women) and 21 women have left the trial (5.1%), 357 have completed the 6 month assessments, all are due to complete the trial in December 2011.
Results:

Weight and body fat results at 6 months indicate that the low cost mail and phone programme is equal to the supervised programme and both are significantly superior to written advice, but not in patients receiving chemotherapy.
The high uptake and adherence to the trial shows interest and motivation of a significant number of cancer patients to make positive changes to lifestyle at the time of diagnosis. The final trial results will be presented at the December meeting. This abstract presents independent research commissioned by the National Institute for Health Research under the Research for Patient Benefit programme. The views expressed here are those of the authors and not necessarily those of the funding organisations.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-01.
P5-18-09: The Incidence of Febrile Neutropenia in the First Course of Adjuvant Chemotherapy with Docetaxel/Cyclophosphamide with or without Pegfilgrastim.
Authors: Jones S , Paul D , Sedlacek S , Vukelja S , Wilks ST , Stokoe C , Osborne CR , Krekow L , McIntyre K , Holmes FA , Guerra L , Zhan F , Asmar L , O'Shaughnessy J , Blum JL 
Published: June 2012

Abstract
Background
In our original doxorubicin-cyclophosphamide/docetaxel-cyclophosphamide (AC/TC) adjuvant study (JCO 27: 1177–1183, 2009), we reported an incidence of febrile neutropenia (FN) of 5% (8% in women ≥65 years) with the TC regimen without prophylactic WBC growth factors but with a recommendation for prophylactic antibiotics. There is a paucity of data on the incidence of FN with the TC regimen aside from this clinical trial. Because we have been conducting a randomized adjuvant study of TC compared to other regimens, we used this opportunity to analyze the incidence of FN during the first course of chemotherapy with TC in the first cohort of randomized patients (US Oncology Network study 06090). The prophylactic use of WBC growth factors was at the investigator's discretion.
Patients and Methods
The study included 1298 patients entered between May 2007 and May 2009. Of these, 649 were included in the TC arm. Median age was 54 years (range 27–71), 75.5% were Caucasian, 561 (86.4%) were in PS 0 at baseline, and about half were node negative. Eight patients did not receive study treatment for various reasons. Among the 641 patients who received TC; 213 (33.3%) received pegfilgrastim, 48 (7.5%) received filgrastim and were not included in this analysis, and 380 (59.2%) patients did not receive either during the first cycle. Thus, this analysis focused on 593 women who did or did not receive prophylactic pegfilgrastim in cycle 1.
Results: All patients with a reported adverse event of FN or with a reported AE of fever with some degree of neutropenia (in order to capture all possible cases of FN) during the first cycle of TC were identified [Table 1]. FN and fever + neutropenia occurred in a total of 6 (2.8%) patients who received pegfilgrastim and 36 (9.5%) patients who did not. A comparison of age, race, performance status and stage of disease between these 2 groups revealed that they were similar. The 213 patients who received pegfilgrastim were slightly older (median 56 years, range 27–71) compared to those who did not (median 53 years, range 30–71).

During all 6 cycles, 41 patients reported FN, and 30 (73%) of these patients experienced FN during cycle 1.
Conclusion: Among 593 women who received TC as adjuvant chemotherapy, the incidence of FN during the first cycle was under 10% whether or not the patients received prophylactic pegfilgrastim.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-09.