bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells
Authors: Jang Gyu-Beom , Hong In-Sun , Kim Ran-Ju , Lee Su-Youn , Park Se-Jin , Lee Eun-Sook , Park Jung Hyuck , Yun Chi-Ho , Chung Jae-Uk , Lee Kyoung-June , Lee Hwa-Yong , Nam Jeong-Seok 
Published: February 2015

Abstract
Breast cancer stem cells (BCSC) are resistant to conventional chemotherapy and radiotherapy, which may destroy tumor masses but not all BCSC that can mediate relapses. In the present study, we showed that the level of Wnt/β-catenin signaling in BCSC is relatively higher than in bulk tumor cells, contributing to a relatively higher level of therapeutic resistance. We designed a highly potent small-molecule inhibitor, CWP232228, which antagonizes binding of β-catenin to T-cell factor (TCF) in the nucleus. Notably, although CWP232228 inhibited the growth of both BCSC and bulk tumor cells by inhibiting β-catenin–mediated transcription, BCSC exhibited greater growth inhibition than bulk tumor cells. We also documented evidence of greater insulin-like growth factor-I (IGF-I) expression by BCSC than by bulk tumor cells and that CWP232228 attenuated IGF-I–mediated BCSC functions. These results suggested that the inhibitory effect of CWP232228 on BCSC growth might be achieved through the disruption of IGF-I activity. Taken together, our findings indicate that CWP232228 offers a candidate therapeutic agent for breast cancer that preferentially targets BCSC as well as bulk tumor cells. Cancer Res; 75(8); 1691–702. ©2015 AACR.
Signaling-Mediated Regulation of MicroRNA Processing
Authors: Shen Jia , Hung Mien-Chie 
Published: February 2015

Abstract
miRNAs are important regulatory elements for gene expression that are involved in diverse physiologic and pathologic processes. Canonical miRNA biogenesis consists of a two-step processing, from primary transcripts (pri-miRNA) to precursor miRNAs (pre-miRNA) mediated by Drosha in the nucleus and from pre-miRNAs to mature miRNAs mediated by Dicer in the cytoplasm. Various routes of miRNA maturation that are tightly regulated by signaling cascades and specific to an individual or a subclass of miRNAs have been recently identified. Here, we review the current findings in signaling-mediated miRNA processing as well as their potential clinical relevance in cancer. Cancer Res; 75(5); 783–91. ©2015 AACR.
Breast Cancer Prevention: Lessons to be Learned from Mechanisms of Early Pregnancy–Mediated Breast Cancer Protection
Authors: Meier-Abt Fabienne , Bentires-Alj Mohamed , Rochlitz Christoph 
Published: February 2015

Abstract
Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy–mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. Cancer Res; 75(5); 803–7. ©2015 AACR.
The Emerging Protumor Role of γδ T Lymphocytes: Implications for Cancer Immunotherapy
Authors: Rei Margarida , Pennington Daniel J. , Silva-Santos Bruno 
Published: February 2015

Abstract
Tumor-infiltrating lymphocytes are key mediators of tumor immune surveillance and are important prognostic indicators in cancer progression. Among the various lymphocyte subsets implicated in protection against cancer are γδ T lymphocytes, which can kill tumor cells and secrete potent antitumor cytokines. By contrast, recent reports have revealed an unexpected series of protumor functions of γδ T cells in mouse models and human patients. In particular, specific γδ T-cell subsets are capable of recruiting immunosuppressive myeloid populations, inhibiting antitumor responses, and enhancing angiogenesis, thus promoting cancer progression. A common mediator of such functions appears to be the cytokine IL17, whose pathogenic effects can override the antitumor immune response orchestrated by IFNγ. Here, we review these studies and discuss their implications for the manipulation of γδ T cells in cancer immunotherapy. Cancer Res; 75(5); 798–802. ©2015 AACR.
Comparative Outcomes of Catheter-Directed Thrombolysis Plus Anticoagulation Versus Anticoagulation Alone in the Treatment of Inferior Vena Caval Thrombosis
Authors: Alkhouli Mohamad , Zack Chad J. , Zhao Huaqing , Shafi Irfan , Bashir Riyaz 
Published: February 2015

Background—
The contemporary practice patterns and role of catheter-directed thrombolysis (CDT) in the treatment of inferior vena cava thrombosis is unknown.

Methods and Results—

The Nationwide Inpatient Sample database was used to identify patients with a principal discharge diagnosis of inferior vena cava thrombosis (
International Classification of Diseases
-
Ninth Revision
-Clinical Modification, 453.2) from 2005 to 2011. We compared patients treated with CDT plus anticoagulation with patients treated with anticoagulation alone. We used propensity scores to construct 2 matched groups of 563 patients for comparative outcomes analysis. Among 2674 patients admitted with inferior vena cava thrombosis, 718 (26.9%) underwent CDT. The national CDT utilization rates increased from 16.0% in 2005 to 34.7% in 2011 (
P
<0.001). Based on the propensity-matched comparison, the inhospital mortality was not significantly different between the CDT and the anticoagulation groups (2.0% versus 1.4%;
P
=0.49). The rates of pulmonary embolism (12.1% versus 7.8%;
P
=0.02), intracranial hemorrhage (1.6% versus 0.2%;
P
=0.03), and acute renal failure (13.9% versus 9.4%;
P
=0.02) were significantly higher in the CDT group. The CDT group had longer length of stay and higher hospital charges compared with the anticoagulation group.

Conclusions—
There has been a steady increase in the use of CDT in the treatment of patients with inferior vena cava thrombosis in the United States. This observational study showed no significant difference in mortality between CDT versus anticoagulation alone; however, the bleeding events and resource utilization were higher in the CDT group. Adequately powered randomized controlled trials are needed in this area.
O
-Linked β-
N
-Acetylglucosamine Transferase Directs Cell Proliferation in Idiopathic Pulmonary Arterial Hypertension
Authors: Barnes Jarrod W. , Tian Liping , Heresi Gustavo A. , Farver Carol F. , Asosingh Kewal , Comhair Suzy A. A. , Aulak Kulwant S. , Dweik Raed A. 
Published: February 2015

Background—
Idiopathic pulmonary arterial hypertension (IPAH) is a cardiopulmonary disease characterized by cellular proliferation and vascular remodeling. A more recently recognized characteristic of the disease is the dysregulation of glucose metabolism. The primary link between altered glucose metabolism and cell proliferation in IPAH has not been elucidated. We aimed to determine the relationship between glucose metabolism and smooth muscle cell proliferation in IPAH.

Methods and Results—

Human IPAH and control patient lung tissues and pulmonary artery smooth muscle cells (PASMCs) were used to analyze a specific pathway of glucose metabolism, the hexosamine biosynthetic pathway. We measured the levels of
O
-linked β-
N
-acetylglucosamine modification,
O
-linked β-
N
-acetylglucosamine transferase (OGT), and
O
-linked β-
N
-acetylglucosamine hydrolase in control and IPAH cells and tissues. Our data suggest that the activation of the hexosamine biosynthetic pathway directly increased OGT levels and activity, triggering changes in glycosylation and PASMC proliferation. Partial knockdown of OGT in IPAH PASMCs resulted in reduced global
O
-linked β-
N
-acetylglucosamine modification levels and abrogated PASMC proliferation. The increased proliferation observed in IPAH PASMCs was directly impacted by proteolytic activation of the cell cycle regulator, host cell factor-1.

Conclusions—
Our data demonstrate that hexosamine biosynthetic pathway flux is increased in IPAH and drives OGT-facilitated PASMC proliferation through specific proteolysis and direct activation of host cell factor-1. These findings establish a novel regulatory role for OGT in IPAH, shed a new light on our understanding of the disease pathobiology, and provide opportunities to design novel therapeutic strategies for IPAH.
Multi-material 3D Models for Temporal Bone Surgical Simulation
Authors: Rose Austin S. , Kimbell Julia S. , Webster Caroline E. , Harrysson Ola L.A. , Formeister Eric J. , Buchman Craig A. 
Published: February 2015

Hypothesis: A simulated, multicolor, multi-material temporal bone model can be created using 3-dimensional (3D) printing that will prove both safe and beneficial in training for actual temporal bone surgical cases. Background: As the process of additive manufacturing, or 3D printing, has become more practical and affordable, a number of applications for the technology in the field of Otolaryngology–Head and Neck Surgery have been considered. One area of promise is temporal bone surgical simulation. Methods: Three-dimensional representations of human temporal bones were created from temporal bone computed tomography (CT) scans using biomedical image processing software. Multi-material models were then printed and dissected in a temporal bone laboratory by attending and resident otolaryngologists. A 5-point Likert scale was used to grade the models for their anatomical accuracy and suitability as a simulation of cadaveric and operative temporal bone drilling. Results: The models produced for this study demonstrate significant anatomic detail and a likeness to human cadaver specimens for drilling and dissection. Conclusion: Simulated temporal bones created by this process have potential benefit in surgical training, preoperative simulation for challenging otologic cases, and the standardized testing of temporal bone surgical skills.
Galileo and the humanities
Authors: Crease Robert P 
Published: February 2015

Galileo’s greatest contribution did not involve lenses, pendulums or mathematics. His most revolutionary act – what is at the core of what might be called the Galilean moment – was to usher in a way of looking at the world in which we can look at the heavens with lenses, think of its chandeliers and swings as pendulums, and read its book in the language of mathematics. This is more than a scientific development; it is at once an intellectual and a cultural transformation. The Galilean moment connects with the humanities in two ways. One is that Galileo, thanks to his training in the humanities, was able to transform mathematics from what was essentially a branch of philosophy and theology, studied by artists and humanists, into a tool for scientists. But if the humanities were a legacy that made the Galilean achievement possible, that achievement now posed a fundamental challenge for the humanities: how to characterize the relation between that mathematically structured world and our own. This is a second way in which the humanities are connected with the Galilean moment. The humanities still struggle to cope with that challenge, which will eventually force the humanities to rethink their role.
Micturition in Göttingen minipigs: first reference in vivo data for urological research and review of literature
Authors: Huppertz ND , Tolba RH , Grosse JO 
Published: February 2015

One possible symptom of overactive bladder (OAB) is urinary incontinence, which is generally considered to be an age-associated disease and which is rapidly increasing with demographic changes. Rodent models are commonly used for the investigation of lower urinary tract functions, although the use of these species has limitations in several translational aspects. In biomedical research and preclinical toxicology, Göttingen minipigs are used increasingly. But in urological research, only few data are available for Göttingen minipigs. To the best of our knowledge, this study is one of the first to provide reference data of micturition in female Göttingen minipigs. Micturition frequency and volumes were monitored and analyzed in five female Göttingen minipigs. Voided volume was 520 ± 383 mL (mean ± standard deviation of mean [SD]) and micturition frequency 6.17 ± 3.68 (mean ± SD). We also performed a review of the literature to compare our data with data from different species (humans, pigs, rats and mice). Our findings revealed that micturition volume and frequency of Göttingen minipigs are more comparable with that of humans, leading to the conclusion that Göttingen minipigs may be the better choice for translational research in different research fields, such as urology, neurology and nephrology, etc. The provision of in vivo reference values meets with the 3R concept of ‘reduction, refinement and replacement’ of laboratory animals, because they allow comprehensive statistical power calculations (reduction), planning of telemetric approaches (refinement), and generation of computer-based modulation for the development of intravesical drug delivery systems (replacement).
Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in nonsmall-cell lung cancer
Authors: Chen Cheng , Chen Zhijun , Chen Dongdong , Zhang Binjie , Wang Zhaoye , Le Hanbo 
Published: February 2015

Objective To investigate the effect of gemcitabine plus cisplatin chemotherapy on the percentage of CD4+CD25+FOXP3+ and CD8+CD28– regulatory T cells (Tregs) in the peripheral blood of patients with nonsmall-cell lung cancer (NSCLC). Methods Peripheral blood was taken from patients with NCSLC (before and after chemotherapy) and control subjects with nonmalignant disease. The percentages of CD4+CD25+FOXP3+ and CD8+CD28– Tregs were analysed using flow cytometry. Results Patients ( n = 40) had significantly higher CD4+CD25+FOXP3+ and CD8+CD28– percentages than control subjects ( n = 24). CD4+CD25+FOXP3+ and CD8+CD28– percentages increased with tumour progression, fell significantly after chemotherapy, but remained significantly higher than control values. Conclusions CD4+CD25+FOXP3+ and CD8+CD28– Treg percentages were higher in patients with NSCLC than control subjects, and increased in line with tumour progression. Percentages of CD4+CD25+FOXP3+ and CD8+CD28– Tregs were significantly reduced following gemcitabine plus cisplatin chemotherapy.
Tensile Properties of the Human Acetabular Labrum and Hip Labral Reconstruction Grafts
Authors: Ferro Fernando P. , Philippon Marc J. , Rasmussen Matthew T. , Smith Sean D. , LaPrade Robert F. , Wijdicks Coen A. 
Published: February 2015

Background: In cases where the acetabular labrum is severely damaged and irreparable, labral reconstructions are becoming an increasingly preferred means of preserving the fluid seal effect of the labrum. However, the graft that most closely replicates the biomechanical properties of the native labrum remains undetermined. Purpose: To characterize the tensile properties and geometry of the labrum, as well as iliotibial band, semitendinosus, gracilis, and anterior tibialis grafts. Study Design: Controlled laboratory study. Methods: Five graft groups—(1) acetabular labrum, (2) iliotibial band, (3) semitendinosus, (4) gracilis, and (5) anterior tibialis—with 8 specimens per group were tested. Grafts were tested using a materials testing system in response to a stepwise sinusoidal cyclic loading protocol. Uniaxial tensile loads were initially applied from 20 to 50 N for 100 cycles at 0.5 Hz, followed by incremental increases of 50 N in the upper force every 100 cycles until failure or successful completion of 100 cycles at 300 N. This protocol was designed to be representative of progressive loading experienced during rehabilitation. Cyclic displacement was recorded after 100 (50 N), 200 (100 N), 300 (150 N), 400 (200 N), 500 (250 N), and 600 (300 N) cycles. Results: The mean elongation (95% CI) after 100 cycles from 20 to 50 N was similar for all groups: acetabular labrum, 0.68 mm (0.57-0.78 mm); iliotibial band, 0.68 mm (0.47-0.89 mm); semitendinosus, 0.68 mm (0.51-0.84 mm); gracilis, 0.62 mm (0.46-0.79 mm); and anterior tibialis, 0.66 mm (0.58-0.73 mm). After 100 cycles from 20 to 300 N (600 cycles total), the mean elongation of the labrum was 4.53 mm (3.71-5.35 mm), and the mean elongations of the iliotibial band, semitendinosus, gracilis, and anterior tibialis were 4.65 mm (3.23-6.07 mm), 4.41 mm (3.45-5.36 mm), 5.12 mm (3.09-7.16 mm), and 5.33 mm (4.40-6.25 mm), respectively. Conclusion: All tested grafts and the acetabular labrum exhibited similar cyclic elongation behavior in response to simulated physiologic forces. In addition, differences in variability in both elongation and geometry existed for all graft types. Clinical Relevance: All tested grafts can be considered viable acetabular labrum reconstruction graft options.
Policies Aren’t Enough
Authors: Anderson Jenn , Kuehl Rebecca A. , Drury Sara A. Mehltretter , Tschetter Lois , Schwaegerl Mary , Hildreth Marilyn , Bachman Charlotte , Gullickson Heidi , Yoder Julia , Lamp Jamison 
Published: February 2015

Background: Formal policies can establish guidelines and expectations for workplace breastfeeding support. However, interpersonal communication between employees and managers is the context where such policies are explained, negotiated, and implemented. As such, this article focuses on interpersonal communication about breastfeeding support in the workplace. Objective: The objective of this article is to describe interpersonal communication related to workplace breastfeeding support. Methods: We conducted 3 focus groups with 23 business representatives from a rural city in the Midwest United States. Participants were recruited through the area chamber of commerce. We analyzed the transcripts of the focus groups and derived themes related to the study objective. Results: Our analysis of responses from business representatives in the focus groups revealed 3 major themes about interpersonal communication concerning breastfeeding support in the workplace: (1) interpersonal communication may be more important than written communication for enacting breastfeeding support, (2) multiple factors (age, sex, and power dynamics) complicate the interpersonal communication required to enact breastfeeding support in local businesses, and (3) positive interpersonal communication strategies may improve the success of workplace breastfeeding support. Conclusion: Interpersonal communication between employees and managers is where the specifics of workplace breastfeeding support (eg, policies) are determined and applied. Interpersonal communication about breastfeeding can be challenging due to issues such as age, sex, and power dynamics. However, positive and open interpersonal communication can enhance workplace breastfeeding support.
Managerial attitudes: Influences on workforce outcomes for working women with chronic illness
Authors: Werth Shalene 
Published: February 2015

AbstractIndividual managers may make judgements and decisions which reflect social expectations rather than organisational policy. Society generally requires that individuals with an illness take leave from their work, seek medical assistance and return when they are well. This is not possible for individuals with chronic illness. By its nature, chronic illness has no cure. Individuals who are diagnosed with diseases such as rheumatoid arthritis, diabetes or inflammatory bowel disease and who also undertake paid employment may need to disclose their illness and seek some form of accommodation in their workplace. Understanding attitudes of managers plays a significant role in the success of managing work and chronic illness. This article examines the working experiences of women with chronic illness where the attitudes of managers were less understanding.
Sampling sites for detection of feline herpesvirus-1, feline calicivirus and Chlamydia felis in cats with feline upper respiratory tract disease
Authors: Schulz Catharina , Hartmann Katrin , Mueller Ralf S , Helps Chris , Schulz Bianka S 
Published: February 2015

Objectives Feline herpesvirus-1 (FHV-1), feline calicivirus (FCV) and Chlamydia felis are involved in feline upper respiratory tract disease (FURTD). Clinical signs caused by these agents can overlap, and the involvement of certain pathogens is often unpredictable. The objectives of this study were to compare detection rates of FHV-1, FCV and C felis at different sampling sites, and to investigate the correlation between positive test results and clinical signs in cats with FURTD. Methods Swabs were taken from the nose, pharynx, tongue and conjunctiva of 104 cats with signs of FURTD. Real-time PCR was performed on all samples for the detection of FHV-1, FCV and C felis. Results Infectious agents were identified in 93 (89.4%) cats. Of these, 55.8% were positive for FHV-1, 50.0% for FCV and 35.6% for C felis. FCV was found more frequently in the oropharynx (92.3% of FCV-positive cats) and on the tongue (90.4%) than the conjunctiva (38.5%) ( P <0.001). There was no significant difference between the four sampling sites for the detection of FHV-1 and C felis. If nasal samples had also been taken, 94.9% of FHV-1-positive cats, 96.2% of FCV-positive cats and 81.1% of C felis-positive cats would have been detected. Conclusions and relevance The oropharynx can be recommended as the preferred single sampling site for the detection of FCV, FHV-1 and C felis if only one sample can be taken; however, taking samples at different sites significantly increases the detection rate for all pathogens studied. Interestingly, sampling from a site with FURTD-associated lesions did not increase the likelihood of detecting the infectious agents.