bluuebunny/crossref_metadata_2025_split huggingface dataset:
DMP1β, a splice isoform of the tumour suppressor DMP1 locus, induces proliferation and progression of breast cancer
Authors: Maglic Dejan , Stovall Daniel B , Cline J. Mark , Fry Elizabeth A , Mallakin Ali , Taneja Pankaj , Caudell David L , Willingham Mark C , Sui Guangchao , Inoue Kazushi 
Published: December 2014

AbstractOur recent work has indicated that the DMP1 locus on 7q21, encoding a haplo‐insufficient tumour suppressor, is hemizygously deleted at a high frequency in breast cancer. The locus encodes DMP1α protein, an activator of the p53 pathway leading to cell cycle arrest and senescence, and two other functionally undefined isoforms, DMP1β and DMP1γ. In this study, we show that the DMP1 locus is alternatively spliced in ∼30% of breast cancer cases with relatively decreased DMP1α and increased DMP1β expression. RNA‐seq analyses of a publicly available database showed significantly increased DMP1β mRNA in 43–55% of human breast cancers, dependent on histological subtypes. Similarly, DMP1β protein was found to be overexpressed in ∼60% of tumours relative to their surrounding normal tissue. Importantly, alteration of DMP1 splicing and DMP1β overexpression were associated with poor clinical outcomes of the breast cancer patients, indicating that DMP1β may have a biological function. Indeed, DMP1β increased proliferation of non‐tumourigenic mammary epithelial cells and knockdown of endogenous DMP1 inhibited breast cancer cell growth. To determine DMP1β's role in vivo, we established MMTV‐DMP1β transgenic mouse lines. DMP1β overexpression was sufficient to induce mammary gland hyperplasia and multifocal tumour lesions in mice at 7–18 months of age. The tumours formed were adenosquamous carcinomas with evidence of transdifferentiation and keratinized deposits. Overall, we identify alternative splicing as a mechanism utilized by cancer cells to modulate the DMP1 locus through diminishing DMP1α tumour suppressor expression, while simultaneously up‐regulating the tumour‐promoting DMP1β isoform. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer
Authors: Bradfield Scott M. , Sandler Eric , Geller Thomas , Tamura Roy N. , Krischer Jeffrey P. 
Published: December 2014

BackgroundVincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known.ProcedureWe performed a randomized, placebo‐controlled, double‐blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1 = Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2 = Acute lymphoblastic leukemia and non‐Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity.ResultsBetween 2007 and 2012, 250 patients were enrolled (Stratum 1 = 50, Stratum 2 = 200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (P = 0.055) compared to patients less than 13 years (P = 1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity.ConclusionVincristine‐associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre‐adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone. Pediatr Blood Cancer 2015;62:1004–1010. © 2014 Wiley Periodicals, Inc.
Postmarketing Review of Intravenous Acetaminophen Dosing Based on Food and Drug Administration Prescribing Guidelines
Authors: Ubaldo Catherine dela Cruz , Hall Natalie Semaan , Le Brenden 
Published: December 2014

Study ObjectivesTo evaluate the appropriateness of intravenous acetaminophen dosing—prescribed dose, frequency, duration, and indication—based on United States Food and Drug Administration (FDA)‐approved prescribing guidelines and to evaluate the adverse effect profile of intravenous acetaminophen.DesignRetrospective chart review.SettingUnited States Navy medical center.PatientsThree hundred patients who received intravenous acetaminophen from August 1, 2011, to August 1, 2012.Measurements and Main ResultsThe indications, dose, frequency, and duration of intravenous acetaminophen were recorded for each patient. Adverse effects of intravenous acetaminophen were analyzed by thoroughly reviewing any adverse effects documented, including nausea, vomiting, headache, or any symptom specifically attributed to the drug. Baseline liver function tests, including aspartate aminotransferase and alanine aminotransferase levels, and elevations 3 times the upper limit of normal during intravenous acetaminophen therapy were recorded. The average patient weight was 78 ± 21 kg, with 12 patients (4%) weighing less than 50 kg and 288 (96%) patients weighing 50 kg or greater. Two hundred forty‐one patients (80%) were appropriately dosed, whereas 59 (20%) patients were not appropriately dosed based on the FDA‐approved dosing. No patients exceeded the FDA‐approved maximum daily dosing recommendations for intravenous acetaminophen (4 g). Sixty‐five patients (22%) received intravenous acetaminophen for longer than 24 hours. Intravenous acetaminophen was well tolerated, without any reported adverse effects, including the commonly reported adverse effects of nausea, vomiting, headache, and insomnia. Ten patients (3%) had a documented history of liver disease and did not experience any adverse effects or increases in liver function tests after the administration of intravenous acetaminophen.ConclusionIntravenous acetaminophen appeared to be a safe and effective analgesic and antipyretic agent. Dosing for patients weighing less than 50 kg needs to be appropriately weight adjusted. Intravenous acetaminophen can be used alone or in conjunction with opioids and other analgesics. Limitations of this study include its retrospective design, inability to assess outcomes of reducing opioid use, and short‐term observation period.
Prolonged Hypoxia Induces Monocarboxylate Transporter-4 Expression in Mesenchymal Stem Cells Resulting in a Secretome that is Deleterious to Cardiovascular Repair
Authors: Saraswati Sarika , Guo Yan , Atkinson James , Young Pampee P. 
Published: December 2014

Abstract
MSCs encounter extended hypoxia in the wound microenvironment yet little is known about their adaptability to this prolonged hypoxic milieu. In this study, we evaluated the cellular and molecular response of MSCs in extended hypoxia (1% O2) versus normoxia (20% O2) culture. Prolonged hypoxia induced a switch toward anaerobic glycolysis transcriptome and a dramatic increase in the transcript and protein levels of monocarboxylate transporter-4 (MCT4) in MSCs. To clarify the impact of MCT4 upregulation on MSC biology, we generated MSCs which stably overexpressed MCT4 (MCT4-MSCs) at levels similar to wild-type MSCs following prolonged hypoxic culture. Consistent with its role to efflux lactate to maintain intracellular pH, MCT4-MSCs demonstrated reduced intracellular lactate. To explore the in vivo significance of MCT4 upregulation in MSC therapy, mice were injected intramuscularly following MI with control (GFP)-MSCs, MCT4-MSCs, or MSCs in which MCT4 expression was stably silenced (KDMCT4-MSCs). Overexpression of MCT4 worsened cardiac remodeling and cardiac function whereas silencing of MCT4 significantly improved cardiac function. MCT4-overexpressing MSC secretome induced reactive oxygen species-mediated cardiomyocyte but not fibroblast apoptosis in vitro and in vivo; lactate alone recapitulated the effects of the MCT4-MSC secretome. Our findings suggest that lactate extruded by MCT4-overexpressing MSCs preferentially induced cell death in cardiomyocytes but not in fibroblasts, leading ultimately to a decline in cardiac function and increased scar size. A better understanding of stem cells response to prolonged hypoxic stress and the resultant stem cell-myocyte/fibroblast cross-talk is necessary to optimize MSC-based therapy for cardiac regeneration. Stem Cells 2015;33:1333–1344
Prospectively Isolated Human Bone Marrow Cell-Derived MSCs Support Primitive Human CD34-Negative Hematopoietic Stem Cells
Authors: Matsuoka Yoshikazu , Nakatsuka Ryusuke , Sumide Keisuke , Kawamura Hiroshi , Takahashi Masaya , Fujioka Tatsuya , Uemura Yasushi , Asano Hiroaki , Sasaki Yutaka , Inoue Masami , Ogawa Hiroyasu , Takahashi Takayuki , Hino Masayuki , Sonoda Yoshiaki 
Published: December 2014

Abstract
Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) niche, which consists of osteoblasts, endothelial cells, and a variety of mesenchymal stem/stromal cells (MSCs). However, precisely what types of MSCs support human HSCs in the BM remain to be elucidated because of their heterogeneity. In this study, we succeeded in prospectively isolating/establishing three types of MSCs from human BM-derived lineage- and CD45-negative cells, according to their cell surface expression of CD271 and stage-specific embryonic antigen (SSEA)−4. Among them, the MSCs established from the Lineage−CD45−CD271+SSEA-4+ fraction (DP MSC) could differentiate into osteoblasts and chondrocytes, but they lacked adipogenic differentiation potential. The DP MSCs expressed significantly higher levels of well-characterized HSC-supportive genes, including IGF-2, Wnt3a, Jagged1, TGFβ3, nestin, CXCL12, and Foxc1, compared with other MSCs. Interestingly, these osteo-chondrogenic DP MSCs possessed the ability to support cord blood-derived primitive human CD34-negative severe combined immunodeficiency-repopulating cells. The HSC-supportive actions of DP MSCs were partially carried out by soluble factors, including IGF-2, Wnt3a, and Jagged1. Moreover, contact between DP MSCs and CD34-positive (CD34+) as well as CD34-negative (CD34−) HSCs was important for the support/maintenance of the CD34+/− HSCs in vitro. These data suggest that DP MSCs might play an important role in the maintenance of human primitive HSCs in the BM niche. Therefore, the establishment of DP MSCs provides a new tool for the elucidation of the human HSC/niche interaction in vitro as well as in vivo. Stem Cells 2015;33:1554–1565
Age-Associated Increase in BMP Signaling Inhibits Hippocampal Neurogenesis
Authors: Yousef Hanadie , Morgenthaler Adam , Schlesinger Christina , Bugaj Lukasz , Conboy Irina M. , Schaffer David V. 
Published: December 2014

Abstract
Hippocampal neurogenesis, the product of resident neural stem cell proliferation and differentiation, persists into adulthood but decreases with organismal aging, which may contribute to the age-related decline in cognitive function. The mechanisms that underlie this decrease in neurogenesis are not well understood, although evidence in general indicates that extrinsic changes in an aged stem cell niche can contribute to functional decline in old stem cells. Bone morphogenetic protein (BMP) family members are intercellular signaling proteins that regulate stem and progenitor cell quiescence, proliferation, and differentiation in various tissues and are likewise critical regulators of neurogenesis in young adults. Here, we establish that BMP signaling increases significantly in old murine hippocampi and inhibits neural progenitor cell proliferation. Furthermore, direct in vivo attenuation of BMP signaling via genetic and transgenic perturbations in aged mice led to elevated neural stem cell proliferation, and subsequent neurogenesis, in old hippocampi. Such advances in our understanding of mechanisms underlying decreased hippocampal neurogenesis with age may offer targets for the treatment of age-related cognitive decline. Stem Cells 2015;33:1577–1588
Prediction of delivery mode by ultrasound‐assessed fetal position in nulliparous women with prolonged first stage of labor
Authors: Eggebø T. M. , Hassan W. A. , Salvesen K. Å. , Torkildsen E. A. , Østborg T. B. , Lees C. C. 
Published: December 2014

ABSTRACTObjectivesTo ascertain if fetal head position on transabdominal ultrasound is associated with delivery by Cesarean section in nulliparous women with a prolonged first stage of labor.MethodsThis was a prospective observational study performed at Stavanger University Hospital, Norway, and Addenbrooke's Hospital, Cambridge, UK, between January 2012 and April 2013. Nulliparous pregnant women with a singleton cephalic presentation at term and prolonged labor had fetal head position assessed by ultrasound. The main outcome was Cesarean section vs vaginal delivery, and secondary outcomes were association of fetal head position with operative vaginal delivery and duration of remaining time in labor.ResultsFetal head position was assessed successfully by ultrasound examination in 142/150 (95%) women. In total, 19/50 (38%) women with a fetus in the occiput posterior (OP) position were delivered by Cesarean section compared with 16/92 (17%) women with a fetus in a non‐OP position (P = 0.01). On multivariable logistic regression analysis, the OP position predicted delivery by Cesarean section with an odds ratio (OR) of 2.9 (95% CI, 1.3–6.7; P = 0.01) and induction of labor with an OR of 2.4 (95% CI, 1.0–5.6; P = 0.05). Fetal head position was not associated with operative vaginal delivery or with remaining time in labor. The agreement between a digital and an ultrasound assessment of OP position was poor (Cohen's kappa = 0.19; P = 0.18).ConclusionOP fetal head position assessed by transabdominal ultrasound was significantly associated with delivery by Cesarean section. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
How hot is too hot? Live‐trapped gray wolf rectal temperatures and 1‐year survival
Authors: Barber‐Meyer Shannon M. , Mech L. David 
Published: December 2014

ABSTRACTThe ability of physically restrained and anesthetized wolves to thermoregulate is lessened and could lead to reduced survival, yet no information is available about this subject. Therefore, we analyzed rectal temperatures related to survival 1 year post‐capture from 173 adult (non‐pup) gray wolves (Canis lupus) captured in modified foot‐hold traps for radiocollaring during June–August, 1988–2011, in the Superior National Forest of northeastern Minnesota, USA. The maximum observed rectal temperature (“maxtemp,” ° F, ° C) in each wolf during capture ( = 104.0, 40.0; SD = 2.0, 1.1; min. = 95.9, 35.5; max. = 108, 42.2) was not a significant predictor of survival to 1 year post‐capture. Although no weather or morphometric variable was a significant predictor of maxtemps, wolves initially anesthetized with ketamine–xylazine rather than telazol®–xylazine averaged higher maxtemps. This information does not fully address possible effects of high body temperatures related to live‐capture and handling of wolves, but it does provide a useful waypoint for future assessments of this relationship and a reassurance to wildlife practitioners that the maxtemps observed in our study did not appear to affect 1‐year survival. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Expression of VH-linker-VL orientation-dependent single-chain Fv antibody fragment derived from hybridoma 2E6 against aflatoxin B1 in Escherichia coli
Authors: Liu Aiping , Ye Yang , Chen Weifeng , Wang Xiaohong , Chen Fusheng 
Published: December 2014

Abstract
Aflatoxin B1 (AFB1) is a toxic secondary metabolic product, which threatens human and animal health. Antibody is a key factor for immunoassay against toxic stuff like AFB1, and single-chain Fv antibody fragment (scFv) has become a popular format of genetically engineered antibody. In this study, four hybridoma cell lines against AFB1 were obtained, and then scFvs 2E6 derived from hybridoma cell line 2E6 were constructed in different VH/VL orientations. Subsequently, scFvs 2E6 were expressed in E. coli BL21(DE3) mainly in the form of inclusion body. SDS-PAGE, Western blot and ELISA were employed to characterize scFvs 2E6. The results revealed that the yield of inclusion body of scFvs 2E6 in either VH/VL orientation was similar; however, only the scFv in VH-linker-VL orientation showed anti-AFB1 bioactivity after refolding. The present study underscores the importance of choosing optimal VH/VL orientation for scFv construction, and scFv may be favorable for immunoassays in food industry.
Precisely cyclic sand: Self-organization of periodically sheared frictional grains
Authors: Royer John R. , Chaikin Paul M. 
Published: December 2014

Significance
Granular materials are used for a wide variety of technological applications in nearly every industry and also serve as an instructive prototype for far-from-equilibrium behavior. Although they have received considerable attention, there are few general guidelines describing how they collectively organize and yield under shear, especially in physically relevant frictional grains. Using simulations, we explore the response of granular packings to slow periodic shear, systematically varying both the friction and shear. We discover a previously unidentified state in which the otherwise chaotic motion gives way to a precisely repetitive limit cycle for each individual grain. Understanding how grains self-organize into stable, periodic limit cycle configurations in this unlikely system foretells new approaches to understand yielding and memory formation in disordered materials.
Tuber physiological disorders.
Authors: Mikitzel L. 
Published: December 2014

Abstract

Defects in potato tubers that are brought about by unfavourable environmental factors that alter normal plant and tuber growth are called physiological disorders. The major causes of physiological disorders include improper cultural, storage or handling practices, high or low temperatures, and inadequate, excessive or uneven soil moisture or nutrient levels. Often, a disorder is caused by the combined effects of environment and cultural practices. Physiological disorders affect the external and internal appearance of tubers. Losses from many physiological disorders can be minimized by using good cultural practices that promote uniform plant and tuber growth over the course of the growing season, and by maintaining proper storage conditions. This chapter describes some tuber physiological disorders, including cracking, enlarged lenticels, greening, elephant hide, second growth, skinning and scald, pink eye, brown centre and hollow heart, bruise, blackheart, translucent end/jelly end, internal brown spot and heat necrosis, vascular discoloration, and internal anthocyanin discoloration.
Nutritional characteristics of potatoes.
Authors: Navarre D. , Goyer A. , Payyavula R. , Hellmann H. 
Published: December 2014

Abstract

This chapter describes the basic tuber composition and nutrient content, including minerals, vitamin C, glycoalkaloids, phenylpropanoids and carotenoids, of potato. It is shown that potatoes contain numerous health-promoting compounds in addition to complex carbohydrates. In view of their nutritional content and yields per acre, potatoes will almost certainly have a key role in "feeding the future".
Is it time to rollback dengue? - Mini Review.
Authors: Gubler D. J. 
Published: December 2014

Abstract
The past 40 years have seen a dramatic increase in the frequency, magnitude and geographic expansion of epidemic dengue, making it the most important vector-borne viral disease in the world. Mosquito control, the only option available for dengue control, has failed. New and innovative tools in the pipeline, however, may provide the opportunity to rollback this disease.
Coastwide Otolith Signatures of Juvenile Atlantic Menhaden, 2009–2011
Authors: Anstead Kristen A. , Schaffler Jason J. , Jones Cynthia M. 
Published: December 2014

AbstractThe Atlantic MenhadenBrevoortia tyrannusis a clupeid that plays a critical role in the marine food web and supports one of the largest fisheries on the U.S. East Coast. Along with a decrease in overall numbers and spawning stock biomass, recruitment levels have remained low since the 1990s. Atlantic Menhaden use numerous estuaries along the Atlantic coast for juvenile development before recruiting to the adult population, but the contribution of each of these nursery grounds is currently unknown. Chesapeake Bay is thought to contribute 70% of the total recruits, although this estimate is over 20 years old and predates current low recruitment levels. We investigated the potential of trace element (Li, Mg, Mn, Rb, Sr, Y, Ba, and Pb) and stable isotope ratio (δ13C and δ18O) signatures in otoliths to distinguish among Atlantic Menhaden collected from various nursery grounds along the U.S. Atlantic coast (Connecticut to South Carolina) during 2009–2011. Juveniles were classified to four regional nursery areas with nearly 90% accuracy. Due to significant interannual variation in the chemical signatures, our attempts to classify juveniles from adjacent year‐classes or combined year‐classes resulted in lower accuracy. However, this study provides a 3‐year library of geochemical fingerprints for assigning adults to their regions of origin. This research builds the foundation for a comprehensive estimate of Atlantic Menhaden recruitment rates from each of the major nursery areas along the U.S. Atlantic coast for 2009–2011.Received May 28, 2014; accepted September 16, 2014
Cardiovascular fitness is associated with bias between self‐reported and objectively measured physical activity
Authors: Tomaz S. A. , Lambert E. V. , Karpul D. , Kolbe‐Alexander T. L. 
Published: December 2014

AbstractThe aim of this research study was to determine whether the level of agreement between self‐reported and objective measures of physical activity (PA) is influenced by cardiovascular fitness. Participants (n = 113) completed the Global Physical Activity Questionnaire (GPAQ), a health risk assessment and a sub‐maximal 12‐minute step test. Age‐predicted was used to classify participants as lower fit and higher fit (HF). ActiGraph (GT3X) accelerometers were worn for 7 consecutive days. Matthews cut points were used to calculate minutes of moderate and vigorous PA (MVPA) per week. Bland–Altman plots were used to measure limits of agreement between GPAQ and ActiGraph MVPA. The participants' mean age was 37.9 ± 12.7 years and more than 60% were categorised as HF (n = 71). Moderate PA was over‐reported in 39% of all participants. Most of the over‐reporters for moderate PA were in the HF group (64.1%). Vigorous PA was over‐reported by 72.6% of all participants. The discrepancy between self‐reported and objective measures of vigorous PA increased with increasing self‐reported time spent in vigorous PA. Fitter individuals appear to over‐report PA more than lesser fit participants, suggesting that fitness could influence the level of agreement between self‐reported and objective measures of PA.