bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Horizontally Acquired Transcription Factor Coordinates
Salmonella
Adaptations to Host Microenvironments
Authors: Brown Nat F. , Rogers Lindsay D. , Sanderson Kristy L. , Gouw Joost W. , Hartland Elizabeth L. , Foster Leonard J. 
Published: September 2014

ABSTRACT

The transcription factors HilA and SsrB activate expression of two type III secretion systems (T3SSs) and cognate effectors that reprogram host cell functions to benefit infecting
Salmonella
in the host. These transcription factors, the secretion systems, and the effectors are all encoded by horizontally acquired genes. Using quantitative proteomics, we quantified the abundance of 2,149 proteins from
hilA
or
ssrB Salmonella in vitro
. Our results suggest that the HilA regulon does not extend significantly beyond proteins known to be involved in direct interactions with intestinal epithelium. On the other hand, SsrB influences the expression of a diverse range of proteins, many of which are ancestral to the acquisition of
ssrB
. In addition to the known regulon of T3SS-related proteins, we show that, through SodCI and bacterioferritin, SsrB controls resistance to reactive oxygen species and that SsrB down-regulates flagella and motility. This indicates that SsrB-controlled proteins not only redirect host cell membrane traffic to establish a supportive niche within host cells but also have adapted to the chemistry and physical constraints of that niche.

IMPORTANCE
Expression of T3SSs typically requires a transcription factor that is linked in a genomic island. Studies of the targets of HilA and SsrB have focused on almost exclusively on T3SS substrates that are either linked or encoded in distinct genomic islands. By broadening our focus, we found that the regulon of SsrB extended considerably beyond T3SS-2 and its substrates, while that of HilA did not. That at least two SsrB-regulated processes streamline existence in the intracellular niche afforded by T3SS-2 seems to be a predictable outcome of evolution and natural selection. However, and importantly, these are the ﬁrst such functions to be implicated as being SsrB dependent. The concept of T3SS-associated transcription factors coordinating manipulations of host cells together with distinct bacterial processes for increased efficiency has unrealized implications for numerous host-pathogen systems.
Influences on human papillomavirus (HPV)-related information needs among women having HPV tests for follow-up of abnormal cervical cytology
Authors: O'Connor Mairead , Costello Liza , Murphy Judith , Prendiville Walter , Martin Cara M , O'Leary John J , Sharp Linda 
Published: September 2014

ObjectivesTesting for human papillomavirus (HPV) infection has recently been introduced into cervical screening programmes. We investigated (1) barriers to accessing and absorbing information and (2) factors that influence information needs among women undergoing HPV tests.MethodsIn-depth interviews were conducted with 27 women who had HPV tests performed in a colposcopy clinic as part of follow-up of low-grade abnormal cytology or post-treatment for cervical intraepithelial neoplasia (CIN). Interviews were transcribed verbatim, coded and analysed using Framework Analysis, to identify main themes and sub-themes.ResultsAmong these women, barriers to accessing and absorbing HPV information were: being overwhelmed with information; context of the HPV test; colposcopy clinic experience(s); women's perceptions of medical professionals’ behaviours and attitudes, and information available on the Internet. Factors influencing women's HPV information needs were: concerns surrounding abnormal cytology or diagnosis of CIN; amount of information provided about HPV; awareness HPV is sexually transmitted; previous negative health care experience(s); and the HPV test in relation to other life events. The timing of delivery of HPV information was key to women absorbing or remembering the information given; it was important that information was given in stages rather than altogether.ConclusionsIn women undergoing HPV testing during follow-up, the amount and timing of delivery of HPV information requires careful consideration. Significant barriers exist to accessing and absorbing HPV information which, unless addressed, could have serious implications in terms of women's comprehension of HPV tests. Given the expanding use of HPV testing within cervical screening, further research on HPV-related information issues is needed.
Breast Cancer Prognostic Biomarker Using Attractor Metagenes and the FGD3–SUSD3 Metagene
Authors: Ou Yang Tai-Hsien , Cheng Wei-Yi , Zheng Tian , Maurer Matthew A. , Anastassiou Dimitris 
Published: September 2014

Abstract
Background: The winning model of the Sage Bionetworks/DREAM Breast Cancer Prognosis Challenge made use of several molecular features, called attractor metagenes, as well as another metagene defined by the average expression level of the two genes FGD3 and SUSD3. This is a follow-up study toward developing a breast cancer prognostic test derived from and improving upon that model.
Methods: We designed a feature selector facility calculating the prognostic scores of combinations of features, including those that we had used earlier, as well as those used in existing breast cancer biomarker assays, identifying the optimal selection of features for the test.
Results: The resulting test, called BCAM (Breast Cancer Attractor Metagenes), is universally applicable to all clinical subtypes and stages of breast cancer and does not make any use of breast cancer molecular subtype or hormonal status information, none of which provided additional prognostic value. BCAM is composed of several molecular features: the breast cancer–specific FGD3–SUSD3 metagene, four attractor metagenes present in multiple cancer types (CIN, MES, LYM, and END), three additional individual genes (CD68, DNAJB9, and CXCL12), tumor size, and the number of positive lymph nodes.
Conclusions: Our analysis leads to the unexpected and remarkable suggestion that ER, PR, and HER2 status, or molecular subtype classification, do not provide additional prognostic value when the values of the FGD3–SUSD3 and attractor metagenes are taken into consideration.
Impact: Our results suggest that BCAM's prognostic predictions show potential to outperform those resulting from existing breast cancer biomarker assays. Cancer Epidemiol Biomarkers Prev; 23(12); 2850–6. ©2014 AACR.
Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Authors: Holkova Beata , Kmieciak Maciej , Perkins E. Brent , Bose Prithviraj , Baz Rachid C. , Roodman G. David , Stuart Robert K. , Ramakrishnan Viswanathan , Wan Wen , Peer Cody J. , Dawson Jana , Kang Loveleen , Honeycutt Connie , Tombes Mary Beth , Shrader Ellen , Weir-Wiggins Caryn , Wellons Martha , Sankala Heidi , Hogan Kevin T. , Colevas A. Dimitrios , Doyle L. Austin , Figg William D. , Coppola Domenico , Roberts John D. , Sullivan Daniel , Grant Steven 
Published: September 2014

Abstract
Purpose: This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).
Experimental Design: Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted.
Results: A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m2 for bortezomib and 40 mg/m2 for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses.
Conclusions: The combination of bortezomib and alvocidib is tolerable, and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. Clin Cancer Res; 20(22); 5652–62. ©2014 AACR.
Pseudogene PTENP1 Functions as a Competing Endogenous RNA to Suppress Clear-Cell Renal Cell Carcinoma Progression
Authors: Yu Gan , Yao Weimin , Gumireddy Kiranmai , Li Anping , Wang Ji , Xiao Wei , Chen Ke , Xiao Haibing , Li Heng , Tang Kun , Ye Zhangqun , Huang Qihong , Xu Hua 
Published: September 2014

Abstract
PTENP1 is a pseudogene of the PTEN tumor suppression gene (TSG). The functions of PTENP1 in clear-cell renal cell carcinoma (ccRCC) have not yet been studied. We found that PTENP1 is downregulated in ccRCC tissues and cells due to methylation. PTENP1 and PTEN are direct targets of miRNA miR21 and their expression is suppressed by miR21 in ccRCC cell lines. miR21 expression promotes ccRCC cell proliferation, migration, invasion in vitro, and tumor growth and metastasis in vivo. Overexpression of PTENP1 in cells expressing miR21 reduces cell proliferation, invasion, tumor growth, and metastasis, recapitulating the phenotypes induced by PTEN expression. Overexpression of PTENP1 in ccRCC cells sensitizes these cells to cisplatin and gemcitabine treatments in vitro and in vivo. In clinical samples, the expression of PTENP1 and PTEN is correlated, and both expressions are inversely correlated with miR21 expression. Patients with ccRCC with no PTENP1 expression have a lower survival rate. These results suggest that PTENP1 functions as a competing endogenous RNA (ceRNA) in ccRCC to suppress cancer progression. Mol Cancer Ther; 13(12); 3086–97. ©2014 AACR.
Splenectomy Promotes Indirect Elimination of Intraocular Tumors by CD8+ T Cells That Is Associated with IFNγ- and Fas/FasL-Dependent Activation of Intratumoral Macrophages
Authors: Miller Maxine R. , Mandell Jonathan B. , Beatty Kelly M. , Harvey Stephen A.K. , Rizzo Michael J. , Previte Dana M. , Thorne Stephen H. , McKenna Kyle C. 
Published: September 2014

AbstractOcular immune privilege (IP) limits the immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized the immune mechanisms responsible for rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. CD8+ T cells, IFNγ, and FasL, but not perforin, or TNFα were required for the elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthisis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1−/− mice and Fas-defective lpr mice failed to eliminate intraocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras revealed that IFNγR1 and Fas expression on immune cells was most critical for rejection, and SPLNX increased the frequency of activated macrophages (Mφ) within intraocular tumors in an IFNγ- and Fas/FasL-dependent manner, suggesting an immune cell target of IFNγ and Fas. As depletion of Mφs limited CD8 T cell–mediated rejection of intraocular tumors in SPLNX mice, our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral Mφs by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis, and suggests that immunosuppressive mechanisms that maintain ocular IP interfere with the interaction between CD8+ T cells and Mφs to limit the immunosurveillance of intraocular tumors. Cancer Immunol Res; 2(12); 1175–85. ©2014 AACR.
Validation of an immunoassay for anti-Müllerian hormone measurements and reference intervals in healthy Brazilian subjects
Authors: Woloszynek Renata Reis , Brito Luciana Pinto , Batista Marcelo Cidade , Valassi Helena Panteliou Lima , Mendonca Berenice Bilharinho , Brito Vinicius Nahime 
Published: September 2014

Background Anti-Müllerian hormone is marker of ovarian and testicular reserve. The clinical use of this hormone requires proper standardization of reference intervals. The aims of this study were to validate the Anti-Müllerian hormone Gen II immunoassay, to establish Anti-Müllerian hormone reference intervals in healthy subjects, and to evaluate the influence of hormonal contraceptives, smoking, and body mass index on Anti-Müllerian hormone. Methods The validation of the Anti-Müllerian hormone Gen II assay (Beckman Coulter Company, TX, USA) was performed using a simplified protocol recommended by Clinical Laboratory Standard Institute. One-hundred and thirty-three healthy females and 120 males were prospectively selected for this study. Results The analytical and functional sensitivities of the Anti-Müllerian hormone Gen II immunoassay were 0.02 and 0.2 ng/mL, respectively. Intra-assay coefficients ranged from 5.2 to 9.0%, whereas inter-assay precision ranged from 4.6 to 7.8% at different concentrations. In females, Anti-Müllerian hormone showed progressive decline with increasing age (r = −0.4, p < 0.001), whereas in males, age showed no influence on Anti-Müllerian hormone concentrations. In females, Anti-Müllerian hormone concentrations did not differ between users and non-users of hormonal contraceptives, smokers, and non-smokers and obese and lean individuals. However, there was a negative and significant correlation between Anti-Müllerian hormone and body mass index in males (r = −0.3, p = 0.008). Conclusions Anti-Müllerian hormone Gen II assay was reliable for determining serum Anti-Müllerian hormone concentrations. Anti-Müllerian hormone concentrations declined with aging and presented a wide inter-individual variability. The lack of influence of hormonal contraceptives, smoking, and obesity on Anti-Müllerian hormone in both sexes allowed us to refine the normative concentrations for the Brazilian population.
Specificity of elevated cerebrospinal fluid bilirubin in the investigation of subarachnoid haemorrhage
Authors: Falconer Helen L , Walker Susan A , Peter Ashby J 
Published: September 2014

Background The spectrophotometric examination of cerebrospinal fluid for bilirubin is an established investigation in patients with suspected subarachnoid haemorrhage. This study assesses the diagnostic specificity of an elevated cerebrospinal fluid bilirubin and how this may be influenced by the presence of oxyhaemoglobin and the concentration of cerebrospinal fluid total protein. Methods One thousand cerebrospinal fluid spectroscopy reports were reviewed. Electronic patient records were examined to determine the clinical outcome in patients with an elevated cerebrospinal fluid bilirubin. Results Forty-four out of 1000 cerebrospinal fluid scans showed an increase in cerebrospinal fluid bilirubin unrelated to elevated serum bilirubin concentrations. This was associated with subarachnoid haemorrhage in 16 (36%) cases. Subarachnoid haemorrhage was confirmed in 5/17 (29%) patients positive for cerebrospinal fluid bilirubin alone and in 11/27 (41%) patients positive for both cerebrospinal fluid bilirubin and oxyhaemoglobin. At cerebrospinal fluid total protein concentrations <1 g/L, the specificity for subarachnoid haemorrhage improved: 4/9 (44%) vs. 1/8 (13%) with an increase in cerebrospinal fluid bilirubin alone; 6/10 (60%) vs. 5/17 (29%) in patients with increases in both bilirubin and oxyhaemoglobin. Conclusion While an increase in cerebrospinal fluid bilirubin may be considered consistent with subarachnoid haemorrhage, the likelihood that a subarachnoid haemorrhage has occurred is influenced by the presence of oxyhaemoglobin and the concentration of total protein in the cerebrospinal fluid.
Transient elevation of serum 5-HIAA by dietary serotonin and distribution of 5-HIAA in serum protein fractions
Authors: Tohmola Niina , Johansson Anna , Sane Timo , Renkonen Risto , Hämäläinen Esa , Itkonen Outi 
Published: September 2014

Introduction Dietary serotonin increases urinary secretion of 5-HIAA. A falsely elevated 5-HIAA may lead to incorrect suspicion of a neuroendocrine tumour. Therefore, we determined the effect and duration of dietary serotonin on serum 5-HIAA concentration. We also studied the distribution of 5-HIAA in serum fractions. Methods We used serum samples from healthy volunteers (31 women and four men). All test subjects avoided serotonin-containing foods for three days before sample collection. They then ate either pineapple, banana, kiwi fruit, tomato or walnuts and additional blood samples were taken after 2, 4, 6, 24, 48 and 72 h. To study the distribution of 5-HIAA in serum, samples from a healthy individual, a test person who had ingested walnuts, and from a neuroendocrine tumour patient were fractionated by gel filtration chromatography. The fractions were analysed for 5-HIAA. Results Serum 5-HIAA concentration increased significantly ( P ≤ 0.001) within 2 h after ingestion of serotonin-containing food. After 2 h, 5-HIAA concentration started to decrease and reached the baseline concentration within 24 h. A calculated half-life of 5-HIAA in circulation was 1.3 h. In fractionated serum, 5-HIAA was found not only in free form but also in the albumin and α2-globulin fractions. Conclusions The increase of serum 5-HIAA caused by dietary serotonin is significant but transient. Therefore, serotonin-containing foods should be avoided for one day before blood sampling. In serum, 5-HIAA is free and apparently bound to albumin. Minor amounts were also found in the α2-globulin fraction. Our liquid chromatography tandem mass spectrometry assay measures free 5-HIAA in serum.
Breaking bad news about transitions to dying: A qualitative exploration of the role of the District Nurse
Authors: Griffiths Jane , Ewing Gail , Wilson Charlotte , Connolly Michael , Grande Gunn 
Published: September 2014

Background: UK District Nurses have an important role in enabling a good death. Patients and families need to know the patient is approaching the dying phase, yet evidence suggests breaking bad news about the patient’s transition to dying rarely happens. District Nurses spend a lot of time with patients and families during the dying phase and are ideally placed to recognise and discuss the transition to dying. Aim: To explore the role of District Nurses in breaking bad news of transition to dying. Design: Qualitative focus groups. Setting: Primary care (District Nurse service); Four National Health Service Trusts, North West England. Participants: A total of 40 District Nurses across the Trusts, all Registered General Nurse qualified. Median number of years as a District Nurse was 12.5. All had palliative cancer patients on their caseloads. Results: District Nurses’ role in breaking bad news of transition to dying was challenging, but the conversation was described as essential preparation for a good death. Four main challenges with the conversations were patients’ responses to the prognosis (unawareness, denial and anger), timing the conversation, complexities of the home environment and limited preparation in this aspect of their work. Conclusions: District Nurses are with patients during their last weeks of life. While other colleagues can avoid breaking bad news of transition to dying, District Nurses have no choice if they are to provide optimal end of life care. While ideally placed to carry out this work, it is complex and they are unprepared for it. They urgently need carefully tailored training in this aspect of their work, to enable them to provide optimal end of life care.
Palliative Care Phase: Inter-rater reliability and acceptability in a national study
Authors: Masso Malcolm , Allingham Samuel Frederic , Banfield Maree , Johnson Claire Elizabeth , Pidgeon Tanya , Yates Patsy , Eagar Kathy 
Published: September 2014

Background: The concept of palliative care consisting of five distinct, clinically meaningful, phases (stable, unstable, deteriorating, terminal and bereavement) was developed in Australia about 20 years ago and is used routinely for communicating clinical status, care planning, quality improvement and funding. Aim: To test the reliability and acceptability of revised definitions of Palliative Care Phase. Design: Multi-centre cross-sectional study involving pairs of clinicians independently rating patients according to revised definitions of Palliative Care Phase. Setting/participants: Clinicians from 10 Australian palliative care services, including 9 inpatient units and 1 mixed inpatient/community-based service. Results: A total of 102 nursing and medical clinicians participated, undertaking 595 paired assessments of 410 patients, of which 90.7% occurred within 2 h. Clinicians rated 54.8% of patients in the stable phase, 15.8% in the unstable phase, 20.8% in the deteriorating phase and 8.7% in the terminal phase. Overall agreement between clinicians’ rating of Palliative Care Phase was substantial (kappa = 0.67; 95% confidence interval = 0.61–0.70). A moderate level of inter-rater reliability was apparent across all participating sites. The results indicated that Palliative Care Phase was an acceptable measure, with no significant difficulties assigning patients to a Palliative Care Phase and a good fit between assessment of phase and the definition of that phase. The most difficult phase to distinguish from other phases was the deteriorating phase. Conclusion: Policy makers, funders and clinicians can be confident that Palliative Care Phase is a reliable and acceptable measure that can be used for care planning, quality improvement and funding purposes.