bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of endoderm formation in a cartilaginous fish reveal ancestral and homoplastic traits in jawed vertebrates
Authors: Godard Benoit G. , Coolen Marion , Le Panse Sophie , Gombault Aurélie , Ferreiro-Galve Susana , Laguerre Laurent , Lagadec Ronan , Wincker Patrick , Poulain Julie , Da Silva Corinne , Kuraku Shigehiro , Carre Wilfrid , Boutet Agnès , Mazan Sylvie 
Published: November 2014

ABSTRACT
In order to gain insight into the impact of yolk increase on endoderm development, we have analyzed the mechanisms of endoderm formation in the catshark S. canicula, a species exhibiting telolecithal eggs and a distinct yolk sac. We show that in this species, endoderm markers are expressed in two distinct tissues, the deep mesenchyme, a mesenchymal population of deep blastomeres lying beneath the epithelial-like superficial layer, already specified at early blastula stages, and the involuting mesendoderm layer, which appears at the blastoderm posterior margin at the onset of gastrulation. Formation of the deep mesenchyme involves cell internalizations from the superficial layer prior to gastrulation, by a movement suggestive of ingressions. These cell movements were observed not only at the posterior margin, where massive internalizations take place prior to the start of involution, but also in the center of the blastoderm, where internalizations of single cells prevail. Like the adjacent involuting mesendoderm, the posterior deep mesenchyme expresses anterior mesendoderm markers under the control of Nodal/activin signaling. Comparisons across vertebrates support the conclusion that endoderm is specified in two distinct temporal phases in the catshark as in all major osteichthyan lineages, in line with an ancient origin of a biphasic mode of endoderm specification in gnathostomes. They also highlight unexpected similarities with amniotes, such as the occurrence of cell ingressions from the superficial layer prior to gastrulation. These similarities may correspond to homoplastic traits fixed separately in amniotes and chondrichthyans and related to the increase in egg yolk mass.
Membrane-anchored human Rab GTPases directly mediate membrane tethering in vitro
Authors: Tamura Naoki , Mima Joji 
Published: November 2014

ABSTRACT
Rab GTPases are master regulators of eukaryotic endomembrane systems, particularly functioning in membrane tethering to confer the directionality of intracellular membrane trafficking. However, how exactly Rab GTPases themselves act upon membrane tethering processes has remained enigmatic. Here, we thoroughly tested seven purified Rab GTPases in human, which localize at the various representative organelles, for their capacity to support membrane tethering in vitro. Strikingly, we found that three specific human Rabs (endoplasmic reticulum/Golgi Rab2a, early endosomal Rab5a, and late endosomal/lysosomal Rab7a) strongly accelerated membrane aggregation of synthetic liposomes even in the absence of any additional components, such as classical tethers, tethering factors, and Rab effectors. This Rab-induced membrane aggregation was a reversible membrane tethering reaction that can be strictly controlled by the membrane recruitment of Rab proteins on both apposing membranes. Thus, our current reconstitution studies establish that membrane-anchored human Rab GTPases are an essential tethering factor to directly mediate membrane tethering events.
Deficiency of the bone mineralization inhibitor NPP1 protects against obesity and diabetes
Authors: Huesa Carmen , Zhu Dongxing , Glover James D. , Ferron Mathieu , Karsenty Gerard , Milne Elspeth M. , Millan José Luis , Ahmed S. Faisal , Farquharson Colin , Morton Nicholas M. , MacRae Vicky E. 
Published: November 2014

Abstract
The emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate and is elevated in dermal fibroblast cultures and muscle of patients with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the NPP1 gene (Enpp1-/- mice). Enpp1-/- mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high fat feeding. Enpp1-/- mice had increased levels of the insulin sensitising bone-derived hormone osteocalcin but unchanged insulin signaling within osteoblasts. A fuller understanding of the pathways of NPP1 may inform the development of novel therapeutic strategies for treating insulin resistance.
Interaktive Kunden als Herausforderung: Die Fallstudie „JOSEPHS® – Die Service-Manufaktur“
Authors: Roth Angela , Fritzsche Albrecht , Jonas Julia , Danzinger Frank , Möslein Kathrin M. 
Published: November 2014

ZusammenfassungKunden möchten vielfach mitgestalten. Mindestens das Produkt, das sie am Ende käuflich erwerben, soll nach Möglichkeit individuelle Wünsche erfüllen oder schlicht individualisiert auf den jeweiligen Kunden zugeschnitten sein. Dieser Trend setzt sich seit Jahrzehnten fort und hat dazu geführt, dass Kundenorientierung stark in den Fokus von Unternehmen gerückt ist und sich dies z. B. in der Anzahl an Varianten und Individualisierungsmöglichkeiten, die für ein Produkt angeboten werden, niederschlägt. Die Forschung hat auf dieses Phänomen mit Konzepten der interaktiven Wertschöpfung wie Open Innovation und Mass Customization reagiert, welche Produktivität trotz Individualisierung und Produktionseffizienz trotz Produktvielfalt ermöglichen. Doch in welchen Schritten der Entstehung und Entwicklung eines Produktes bietet sich die Interaktion mit dem Kunden vor dem Hintergrund ökonomischer Effizienzziele an? Und wie lässt sich die Partizipation des Kunden mit den Möglichkeiten der Wirtschaftsinformatik gestalten? In diesem Papier erfolgt zunächst eine Systematisierung sogenannter „Orte interaktiver Wertschöpfung“. Je nachdem, ob die interaktive Wertschöpfung in realer face-to-face-Umgebung eher ereignis-orientiert mit Kampagnencharakter stattfindet oder längerfristig und auf Kontinuität angelegt institutionalisiert wird, lassen sich temporäre und kontinuierliche Engagements unterscheiden. Zusätzlich können verschiedene Trägerschaften unterschieden werden. Schließlich wird die Fallstudie JOSEPHS®–Die Service Manufaktur vorgestellt, in der ein solcher Ort für interaktive Wertschöpfung konzipiert, implementiert, technologisch unterstützt und schließlich einer ersten Evaluierung zugeführt wird.
Next Generation Digital PCR Measurement of Hepatitis B Virus Copy Number in Formalin-Fixed Paraffin-Embedded Hepatocellular Carcinoma Tissue
Authors: Huang Jing-Tao , Liu Ying-Juan , Wang Jin , Xu Zhi-Gao , Yang Ying , Shen Fan , Liu Xing-hui , Zhou Xin , Liu Song-Mei 
Published: November 2014

Abstract

BACKGROUND
Hepatocellular carcinoma (HCC) is strongly associated with hepatitis B virus (HBV) infection. False-negative results are common in routine serological tests and quantitative real-time PCR because of HBV surface antigen (HBsAg) variation and low HBV copy number. Droplet digital PCR (ddPCR), a next generation digital PCR, is a novel, sensitive, and specific platform that can be used to improve HBV detection.

METHODS
A total of 131 HCC cases with different tumor stages and clinical features were initially classified with a serological test as HBsAg positive (n = 107) or negative (n = 24) for HBV infection. Next, DNA templates were prepared from the corresponding formalin-fixed paraffin-embedded (FFPE) tissues to determine HBV copy number by ddPCR.

RESULTS
HBV copy numbers, successfully determined for all clinical FFPE tissues (n = 131), ranged from 1.1 to 175.5 copies/μL according to ddPCR. The copy numbers of HBV were positively correlated with tumor-nodes-metastasis (P = 0.008) and Barcelona-Clinic Liver Cancer (P = 0.045) classification. Moreover, serum cholinesterase correlated with hepatitis B viral load (P = 0.006).

CONCLUSIONS
HBV infection is a key factor that influences tumorigenesis in HCC by regulating tumor occurrence and development. ddPCR improves the analytical sensitivity and specificity of measurements in nucleic acids at a single-molecule level and is suitable for HBV detection.
Variability of the Reverse Transcription Step: Practical Implications
Authors: Bustin Stephen , Dhillon Harvinder S , Kirvell Sara , Greenwood Christina , Parker Michael , Shipley Gregory L , Nolan Tania 
Published: November 2014

Abstract

BACKGROUND
The reverse transcription (RT) of RNA to cDNA is a necessary first step for numerous research and molecular diagnostic applications. Although RT efficiency is known to be variable, little attention has been paid to the practical implications of that variability.

METHODS
We investigated the reproducibility of the RT step with commercial reverse transcriptases and RNA samples of variable quality and concentration. We quantified several mRNA targets with either singleplex SYBR Green I or dualplex probe-based reverse transcription real-time quantitative PCR (RT-qPCR), with the latter used to calculate the correlation between quantification cycles (Cqs) of mRNA targets amplified in the same real-time quantitative PCR (qPCR) assay.

RESULTS
RT efficiency is enzyme, sample, RNA concentration, and assay dependent and can lead to variable correlation between mRNAs from the same sample. This translates into relative mRNA expression levels that generally vary between 2- and 3-fold, although higher levels are also observed.

CONCLUSIONS
Our study demonstrates that the variability of the RT step is sufficiently large to call into question the validity of many published data that rely on quantification of cDNA. Variability can be minimized by choosing an appropriate RTase and high concentrations of RNA and characterizing the variability of individual assays by use of multiple RT replicates.
MALT1 protease: equilibrating immunity versus tolerance
Authors: Bertossi Arianna , Krappmann Daniel 
Published: November 2014

MALT1 paracaspase links signaling cascades emanating from adaptive or innate immune receptors to the canonical NF‐κB pathway. Now, Jaworski et al () investigate the physiological role of MALT1 protease activity in mice. Besides the expected requirement of MALT1 activity for immune activation, the study unveils a novel function for MALT1 activity for the development of peripheral tolerance. Thus, MALT1 protease can act immunogenic or tolerogenic, and this interplay will be highly relevant for the clinical development of MALT1 inhibitors.
Neoadjuvant antiangiogenic therapy reveals contrasts in primary and metastatic tumor efficacy
Authors: Ebos John ML , Mastri Michalis , Lee Christina R , Tracz Amanda , Hudson John M , Attwood Kristopher , Cruz‐Munoz William R , Jedeszko Christopher , Burns Peter , Kerbel Robert S 
Published: November 2014

AbstractThousands of cancer patients are currently in clinical trials evaluating antiangiogenic therapy in the neoadjuvant setting, which is the treatment of localized primary tumors prior to surgical intervention. The rationale is that shrinking a tumor will improve surgical outcomes and minimize growth of occult micrometastatic disease—thus delaying post‐surgical recurrence and improving survival. But approved VEGF pathway inhibitors have not been tested in clinically relevant neoadjuvant models that compare pre‐ and post‐surgical treatment effects. Using mouse models of breast, kidney, and melanoma metastasis, we demonstrate that primary tumor responses to neoadjuvant VEGFR TKI treatment do not consistently correlate with improved post‐surgical survival, with survival worsened in certain settings. Similar negative effects did not extend to protein‐based VEGF pathway inhibitors and could be reversed with altered dose, surgical timing, and treatment duration, or when VEGFR TKIs are combined with metronomic ‘anti‐metastatic’ chemotherapy regimens. These studies represent the first attempt to recapitulate the complex clinical parameters of neoadjuvant therapy in mice and identify a novel tool to compare systemic antiangiogenic treatment effects on localized and disseminated disease.
A General Unified Framework to Assess the Sampling Variance of Heritability Estimates Using Pedigree or Marker-Based Relationships
Authors: Visscher Peter M , Goddard Michael E 
Published: November 2014

Abstract
Heritability is a population parameter of importance in evolution, plant and animal breeding, and human medical genetics. It can be estimated using pedigree designs and, more recently, using relationships estimated from markers. We derive the sampling variance of the estimate of heritability for a wide range of experimental designs, assuming that estimation is by maximum likelihood and that the resemblance between relatives is solely due to additive genetic variation. We show that well-known results for balanced designs are special cases of a more general unified framework. For pedigree designs, the sampling variance is inversely proportional to the variance of relationship in the pedigree and it is proportional to 1/N, whereas for population samples it is approximately proportional to 1/N2, where N is the sample size. Variation in relatedness is a key parameter in the quantification of the sampling variance of heritability. Consequently, the sampling variance is high for populations with large recent effective population size (e.g., humans) because this causes low variation in relationship. However, even using human population samples, low sampling variance is possible with high N.
Positional Information, Positional Error, and Readout Precision in Morphogenesis: A Mathematical Framework
Authors: Tkačik Gašper , Dubuis Julien O , Petkova Mariela D , Gregor Thomas 
Published: November 2014

Abstract
The concept of positional information is central to our understanding of how cells determine their location in a multicellular structure and thereby their developmental fates. Nevertheless, positional information has neither been defined mathematically nor quantified in a principled way. Here we provide an information-theoretic definition in the context of developmental gene expression patterns and examine the features of expression patterns that affect positional information quantitatively. We connect positional information with the concept of positional error and develop tools to directly measure information and error from experimental data. We illustrate our framework for the case of gap gene expression patterns in the early Drosophila embryo and show how information that is distributed among only four genes is sufficient to determine developmental fates with nearly single-cell resolution. Our approach can be generalized to a variety of different model systems; procedures and examples are discussed in detail.
What Keeps Oncologists From Addressing Palliative Care Early on With Incurable Cancer Patients? An Active Stance Seems Key
Authors: Pfeil Timo A. , Laryionava Katsiaryna , Reiter-Theil Stella , Hiddemann Wolfgang , Winkler Eva C. 
Published: November 2014

AbstractBackground.Sympathetic and frank communication about the terminal nature of advanced cancer is important to improve patients’ prognostic understanding and, thereby, to allow for adjustment of treatment intensity to realistic goals; however, decisions against aggressive treatments are often made only when death is imminent. This qualitative study explores the factors that hinder such communication and reconstructs how physicians and nurses in oncology perceive their roles in preparing patients for end-of-life (EOL) decisions.Methods.Qualitative in-depth interviews were conducted with physicians (n = 12) and nurses (n = 6) working at the Department of Hematology/Oncology at the university hospital in Munich, Germany. The data were analyzed using grounded theory methodology and discussed from a medical ethics perspective.Results.Oncologists reported patients with unrealistic expectations to be a challenge for EOL communication that is especially prominent in comprehensive cancer centers. Oncologists responded to this challenge quite differently by either proactively trying to facilitate advanced care planning or passively leaving the initiative to address preferences for care at the EOL to the patient. A major impediment to the proactive approach was uncertainty about the right timing for EOL discussions and about the balancing the medical evidence against the physician's own subjective emotional involvement and the patient's wishes.Conclusion.These findings provide explanations of why EOL communication is often started rather late with cancer patients. For ethical reasons, a proactive stance should be promoted, and oncologists should take on the task of preparing patients for their last phase of life. To do this, more concrete guidance on when to initiate EOL communication is necessary to improve the quality of decision making for advanced cancer patients.
Use of Prednisone With Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer
Authors: Auchus Richard J. , Yu Margaret K. , Nguyen Suzanne , Mundle Suneel D. 
Published: November 2014

AbstractAbiraterone acetate, a prodrug of the CYP17A1 inhibitor abiraterone that blocks androgen biosynthesis, is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone or prednisolone 5 mg twice daily. This review evaluates the basis for the effects of prednisone on mineralocorticoid-related adverse events that arise because of CYP17A1 inhibition with abiraterone. Coadministration with the recommended dose of glucocorticoid compensates for abiraterone-induced reductions in serum cortisol and blocks the compensatory increase in adrenocorticotropic hormone seen with abiraterone. Consequently, 5 mg prednisone twice daily serves as a glucocorticoid replacement therapy when coadministered with abiraterone acetate, analogous to use of glucocorticoid replacement therapy for certain endocrine disorders. We searched PubMed to identify safety concerns regarding glucocorticoid use, placing a focus on longitudinal studies in autoimmune and inflammatory diseases and cancer. In general, glucocorticoid-related adverse events, including bone loss, immunosuppression, hyperglycemia, mood and cognitive alterations, and myopathy, appear dose related and tend to occur at doses and/or treatment durations greater than the low dose of glucocorticoid approved in combination with abiraterone acetate for the treatment of mCRPC. Although glucocorticoids are often used to manage tumor-related symptoms or to prevent treatment-related toxicity, available evidence suggests that prednisone and dexamethasone might also offer modest therapeutic benefit in mCRPC. Given recent improvements in survival achieved for mCRPC with novel agents in combination with prednisone, the risks of these recommended glucocorticoid doses must be balanced with the benefits shown for these regimens.
Heel Pain—Plantar Fasciitis: Revision 2014
Authors: Martin Robroy L. , Davenport Todd E. , Reischl Stephen F. , McPoil Thomas G. , Matheson James W. , Wukich Dane K. , McDonough Christine M. , Altman Roy D. , Beattie Paul , Cornwall Mark , Davis Irene , DeWitt John , Elliott James , Irrgang James J. , Kaplan Sandra , Paulseth Stephen , Torburn Leslie , Zachazewski James , Godges Joseph J. 
Published: November 2014

The Orthopaedic Section of the American Physical Therapy Association (APTA) has an ongoing effort to create evidence-based practice guidelines for orthopaedic physical therapy management of patients with musculoskeletal impairments described in the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). The purpose of these revised clinical practice guidelines is to review recent peer-reviewed literature and make recommendations related to nonarthritic heel pain. J Orthop Sports Phys Ther 2014;44(11):A1–A23. doi:10.2519/jospt.2014.0303
Measurement Properties of the Brazilian Portuguese Version of the MedRisk Instrument for Measuring Patient Satisfaction With Physical Therapy Care
Authors: de Fátima Costa Oliveira Nubia , Oliveira Pena Costa Leonardo , Nelson Roger , Maher Chris G. , Beattie Paul F. , de Bie Rob , Oliveira WarleyMelo , Camara Azevedo Daniel , da Cunha Menezes Costa Luciola 
Published: November 2014

Study Design Clinical measurement study. Objectives To translate and cross-culturally adapt the MedRisk Instrument for Measuring Patient Satisfaction With Physical Therapy Care (MRPS) into Brazilian Portuguese and to test its measurement properties. Background To date, there is no standardized instrument for measuring patient satisfaction with physical therapy care in Brazil. Methods The MRPS was translated and cross-culturally adapted into Brazilian Portuguese. Patients completed the MRPS and a global change measure after 5 or more treatment visits. A subset of patients also completed the instrument a second time, 24 to 48 hours after the first assessment. We evaluated factorial validity, internal consistency, reproducibility, construct validity, and ceiling and floor effects. Results Three hundred three patients with different musculoskeletal conditions receiving physical therapy care in Brazil participated in this study. A 3-factor solution labeled as interpersonal, convenience and efficiency, and patient education provided the best factor loadings. Cronbach alpha coefficients ranged from .63 to .77, intraclass correlation coefficients ranged from 0.64 to 0.79, and standard errors of measurement ranged from 0.86 to 1.75 points. Thirteen items of the MRPS were moderately correlated with the global measure of change. A large ceiling effect was detected. Conclusion Although we did not fully achieve the measurement properties suggested by the guidelines, we believe that the MRPS can be used among Brazilian Portuguese-speaking patients. Some differences with regard to factor structure of the Brazilian Portuguese MPRS compared with the English version were observed. The reason for this is likely a combination of cultural aspects, differences in clinical settings, and patient expectation. J Orthop Sports Phys Ther 2014;44(11):879–889. doi:10.2519/jospt.2014.5150
Prognostic value of newborn hearing screening in patients with myelomeningocele
Authors: Satzer David , Guillaume Daniel J. 
Published: November 2014

Object
Brainstem dysfunction occurs in a minority of patients with myelomeningocele (MMC), most of whom have Chiari Type II malformation. Some surgeons advocate early identification of these patients for craniocervical decompression to avoid significant mortality. The auditory brainstem response has been found to be abnormal in most children with MMC. The present study examines whether failure of routine newborn hearing screening (NHS) predicts brainstem dysfunction in MMC patients.

Methods
The charts of 40 newborns with MMC and 50 newborns without MMC who stayed in the neonatal intensive care unit were reviewed. Results of NHS, brainstem symptoms, birth demographics, and surgical history were retrospectively examined. Differences in the presence and onset of brainstem symptoms by NHS result were assessed.

Results
Failure of NHS was more common among newborns with MMC who developed brainstem symptoms (31%, 4 of 13 patients) than among newborns without MMC (0%, 0 of 50 patients; p = 0.001). Among the 40 newborns with MMC, brainstem symptoms were more common in those who failed NHS (80%, 4 of 5 patients) than in those who passed (26%, 9 of 35 patients; p = 0.031). Respiratory symptom onset occurred later in patients who failed NHS (median 16 months) than among those who passed (median 0 months; p = 0.022). The positive and negative predictive values of NHS for brainstem dysfunction in MMC were 0.80 and 0.74, respectively.

Conclusions
Results of NHS may help predict future brainstem dysfunction in patients with MMC and may be useful to incorporate into prognostic assessment and surgical decision making.