bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Proterosuchia’: the origin and early history of Archosauriformes
Authors: Ezcurra Martín D. , Butler Richard J. , Gower David J. 
Published: April 2013

Abstract

The earliest history of Archosauriformes is mainly represented by members of Proterosuchidae and Erythrosuchidae, which are known worldwide from latest Permian to Middle Triassic beds. These two groups were historically combined within ‘Proterosuchia’, with approximately 30 nominal species. Two morphotypes have been recognized among proterosuchians: proterosuchids with a generally more sprawling gait and elongated and low skulls with an overhanging premaxilla, and the more heavily built erythrosuchids, with a probably less sprawling gait and large, presumably hypercarnivorous, skulls. The systematics of ‘Proterosuchia’ was relatively chaotic throughout most of the twentieth century, but currently there exists consensus regarding the non-monophyly of proterosuchians and their phylogenetic position outside all other archosauriforms. In contrast, the delimitation and taxonomic content of Proterosuchidae and Erythrosuchidae remain unstable. Few studies of proterosuchian palaeobiology have been carried out. Current lines of evidence favour a predominantly terrestrial lifestyle for proterosuchians. Limb bone histology indicates rapid continuous growth rates in
Proterosuchus
and
Erythrosuchus
before reaching sexual maturity. A better knowledge of proterosuchian anatomy, systematics, evolution and ecology is important for advancing understanding of the origin and early radiation of Archosauriformes and the patterns of biotic recovery following the Permo-Triassic mass extinction event. There remains much research to be carried out in proterosuchian palaeobiology.
Prorotodactylus
and
Rotodactylus
tracks: an ichnological record of dinosauromorphs from the Early–Middle Triassic of Poland
Authors: Niedźwiedzki Grzegorz , Brusatte Stephen L. , Butler Richard J. 
Published: April 2013

Abstract

We present the first comprehensive description of
Prorotodactylus
and
Rotodactylus
dinosauromorph tracks from the Early and Middle Triassic of the Holy Cross Mountains, Poland. We describe and comprehensively figure tracks that have been mentioned briefly in previous accounts as well as new, recently discovered material, and analyse the variation and stratigraphic distribution of these specimens. Tracks have been recorded from four sites – Koszary, Stryczowice, Wióry and Baranów – which span the early Olenekian–early Anisian (
c.
250–246 Ma). These tracks therefore represent an ichnological record of the evolutionary succession of early dinosauromorphs during the earliest part of their evolutionary history. Recognized track types include cf.
Prorotodactylus
isp
.
,
Prorotodactylus
isp.,
Prorotodactylus mirus
,
Rotodactylus cursorius
,
Rotodactylus
isp. and cf.
Rotodactylus
isp. At least three distinct Early and early Middle Triassic early dinosauromorph ichnofaunas can be recognized. The oldest, which is early Olenekian in age, is characterized by the presence of
Prorotodactylus
isp., cf.
Prorotodactylus
isp
.
and non-archosaurian archosauromorph or archosaur tracks (e.g.
Synaptichnium
isp.,
Protochirotherium
isp.), recorded at the Stryczowice and Koszary sites. The following assemblage, recorded at the late Olenekian Wióry site, displays the highest ichnodiversity of dinosauromorphs, with four track types present (
Prorotodactylus
isp.,
Prorotodactylus mirus
,
Rotodactylus cursorius
and cf.
Rotodactylus
isp.). The youngest site, Baranów, includes
Rotodactylus
isp., as well as other larger dinosauromorph tracks. The first body fossil evidence of dinosauromorphs is a few million years younger than the youngest Polish tracks, so
Prorotodactylus
and
Rotodactylus
tracks currently provide the oldest record of dinosauromorph morphology, biology and evolution.
RXRα Inhibits the NRF2-ARE Signaling Pathway through a Direct Interaction with the Neh7 Domain of NRF2
Authors: Wang Hongyan , Liu Kaihua , Geng Miao , Gao Peng , Wu Xiaoyuan , Hai Yan , Li Yangxia , Li Yulong , Luo Lin , Hayes John D. , Wang Xiu Jun , Tang Xiuwen 
Published: April 2013

Abstract
The transcription factor NRF2 (NFE2L2) is a pivotal activator of genes encoding cytoprotective and detoxifying enzymes that limit the action of cytotoxic therapies in cancer. NRF2 acts by binding antioxidant response elements (ARE) in its target genes, but there is relatively limited knowledge about how it is negatively controlled. Here, we report that retinoic X receptor alpha (RXRα) is a hitherto unrecognized repressor of NRF2. RNAi-mediated knockdown of RXRα increased basal ARE-driven gene expression and induction of ARE-driven genes by the NRF2 activator tert-butylhydroquinone (tBHQ). Conversely, overexpression of RXRα decreased ARE-driven gene expression. Biochemical investigations showed that RXRα interacts physically with NRF2 in cancer cells and in murine small intestine and liver tissues. Furthermore, RXRα bound to ARE sequences in the promoters of NRF2-regulated genes. RXRα loading onto AREs was concomitant with the presence of NRF2, supporting the hypothesis that a direct interaction between the two proteins on gene promoters accounts for the antagonism of ARE-driven gene expression. Mutation analyses revealed that interaction between the two transcription factors involves the DNA-binding domain of RXRα and a region comprising amino acids 209-316 in human NRF2 that had not been defined functionally, but that we now designate as the NRF2-ECH homology (Neh) 7 domain. In non–small cell lung cancer cells where NRF2 levels are elevated, RXRα expression downregulated NRF2 and sensitized cells to the cytotoxic effects of therapeutic drugs. In summary, our findings show that RXRα diminishes cytoprotection by NRF2 by binding directly to the newly defined Neh7 domain in NRF2. Cancer Res; 73(10); 3097–108. ©2013 AACR.
Targeting the BRAF V600E Mutation in Multiple Myeloma
Authors: Andrulis Mindaugas , Lehners Nicola , Capper David , Penzel Roland , Heining Christoph , Huellein Jennifer , Zenz Thorsten , von Deimling Andreas , Schirmacher Peter , Ho Anthony D. , Goldschmidt Hartmut , Neben Kai , Raab Marc S. 
Published: April 2013

Abstract
In multiple myeloma, there has been little progress in the specific therapeutic targeting of oncogenic mutations. Whole-genome sequencing data have recently revealed that a subset of patients carry an activating mutation (V600E) in the BRAF kinase. To uncover the clinical relevance of this mutation in multiple myeloma, we correlated the mutation status in primary tumor samples from 379 patients with myeloma with disease outcome. We found a significantly higher incidence of extramedullary disease and a shorter overall survival in mutation carriers when compared with controls. Most importantly, we report on a patient with confirmed BRAF V600E mutation and relapsed myeloma with extensive extramedullary disease, refractory to all approved therapeutic options, who has rapidly and durably responded to low doses of the mutation-specific BRAF inhibitor vermurafenib. Collectively, we provide evidence for the development of the BRAF V600E mutation in the context of clonal evolution and describe the prognostic and therapeutic relevance of this targetable mutation.
Significance: This is the first evidence of the clinical and therapeutic relevance of BRAF V600E mutations in multiple myeloma, proving the principle of specific inhibition of driver mutations in this disease. Cancer Discov; 3(8); 862–9. ©2013 AACR.
See related commentary by O'Donnell and Raje, p. 840
This article is highlighted in the In This Issue feature, p. 826
MiRNA-424 Protects Against Permanent Focal Cerebral Ischemia Injury in Mice Involving Suppressing Microglia Activation
Authors: Zhao Haiping , Wang Jun , Gao Li , Wang Rongliang , Liu Xiangrong , Gao Zhi , Tao Zhen , Xu Changmin , Song Juexian , Ji Xunming , Luo Yumin 
Published: April 2013

Background and Purpose—
We observed that microRNA-424 (miR-424) significantly decreased in an miRNA profile of circulating lymphocytes of patients with ischemic stroke. The present study focused on the potential and mechanism of miR-424 in protecting ischemic brain injury in mice.

Methods—
Cerebral ischemia was induced by middle cerebral artery occlusion in C57/BL6 mice. Cerebral infarction volume, neuronal apoptosis, and microglia activation were determined by 2,3,5-triphenyltetrazolium chloride staining, immunofluorescence, and Western blot. BV2 microglial cell activity, cell cycle, mRNA, and protein levels of miR-424 targets were accessed by enzyme-linked immunosorbent assay, flow cytometry, real-time polymerase chain reaction, and Western blot, respectively.

Results—
MiR-424 levels were decreased in the plasma of patients with acute ischemic stroke, as well as in mouse plasma and ipsilateral brain tissue at 4, 8, and 24 hours after ischemia, likewise, in the cortex, hippocampus, and basal ganglia, respectively, after 8-hour ischemia. Interestingly, pre- and post-treatment with overexpression of miR-424 both decreased cerebral infarction size and brain edema after middle cerebral artery occlusion. Meanwhile, lentiviral overexpression of miR-424 inhibited neuronal apoptosis and microglia activation, including suppressing ionized calcium binding adaptor molecule-1 immunoreactivity and protein level, and reduced tumor necrosis factor-α production. In vitro study demonstrated that miR-424 mimics caused G1 phase cell-cycle arrest, inhibited BV2 microglia activity, and reduced the mRNA and protein levels of CDC25A, cyclin D1, and CDK6 in BV2 microglial cells, which were upregulated in brain of middle cerebral artery occlusion mice.

Conclusions—
MiR-424 overexpression lessened the ischemic brain injury through suppressing microglia activation by translational depression of key activators of G1/S transition, suggesting a novel miR-based intervention strategy for stroke.
Modification of cellulose non-woven substrates for preparation of modern wound dressings
Authors: Pivec Tanja , Peršin Zdenka , Kolar Mitja , Maver Tina , Dobaj Andreja , Vesel Alenka , Maver Uroš , Stana-Kleinschek Karin 
Published: April 2013

Different ways are presented of modifying cellulosic non-woven substrates, which can serve as potential wound dressings with satisfactory antimicrobial and hydrophilic properties. For safe attachment of silver particles without a measurable release from the used materials, a sol–gel derived process was used. Alkaline and oxygen plasma treatments were used to improve the hydrophilicity of the materials. Their efficiency was determined by measuring contact angles and water retention values. Scanning electron microscopy (SEM) was used for determination of sample morphology prior to and after treatment. The efficiency of silver attachment and activity was evaluated by in vitro release studies and antimicrobial tests. Atomic force microscopy (AFM) and SEM, combined with dynamic light scattering, were used for determination of silver particle size. Additionally, we evaluated the influence of treatment on technological parameters, important for application performance, i.e. mechanical properties and air permeability.
Preferred place of death for children and young people with life-limiting and life-threatening conditions: A systematic review of the literature and recommendations for future inquiry and policy
Authors: Bluebond-Langner Myra , Beecham Emma , Candy Bridget , Langner Richard , Jones Louise 
Published: April 2013

Background: Home is often cited as preferred place of death in the United Kingdom and elsewhere. This position, however, usually relies on data concerning adults and not evidence about children. The latter data are scant, primarily retrospective and from parents. Aim: To review the literature on preference for place of death for children and young people with life-limiting or life-threatening illnesses. Design and data sources: The databases MEDLINE, CINAHL and EMBASE were searched from 2004 to 2012, as well as bibliography, key author and grey literature searches. Policy documents, empirical, theoretical and peer-reviewed studies and conference abstracts were included. Articles were assessed for study quality. Results: Nine studies were included from five countries. Six reported a majority of parents (only one study interviewed adolescents) expressing preference for death at home. Other studies differed significantly in their findings; one reporting 35.1% and another 0% preferring death at home. Some parents did not express a preference. Six of the studies included only parents of children who died from cancer while being treated at tertiary centres that offered palliative care services. Such results cannot be generalised to the population of all life-limiting and life-threatening illnesses. Furthermore, the methods of the studies reviewed failed to accommodate the full range and dynamic character of preference. Conclusion: The evidence base for current policies that stress the need to increase home death rates for children and young people with life-limiting and life-threatening conditions is inadequate. Further rigorous research should collect data from parents, children and siblings.
Informal hospice caregiver pain management concerns: A qualitative study
Authors: Kelley Marjorie , Demiris George , Nguyen Huong , Oliver Debra P , Wittenberg-Lyles Elaine 
Published: April 2013

Background: Informal, unpaid, family caregivers provide much hospice care in the United States. These caregivers suffer physically, psychologically, emotionally, and socially from the burden of caring. The most often identified area of caregiver burden is the management of end-of-life pain. However, little empirical evidence exists of effective interventions to help caregivers manage end-of-life pain, and issues surrounding caregiver pain management remain vague and undefined. Understanding these concerns will inform the design of effective caregiver interventions. Aim: The purpose of this study was to describe and organize caregiver pain management challenges faced by home hospice caregivers of cancer patients. Design: A content analysis of secondary data, namely, recordings of caregiver interviews, was conducted to describe pain management issues. These interviews were part of a larger clinical trial. Setting/participants: Multiple sessions with 29 informal caregivers, of patients dying of cancer, were audio-recorded. Subjects were purposively selected from two hospice programs in the Northwestern United States. Caregivers of noncancer patients were excluded from the study sample. Results: A framework of six major themes with subordinate subthemes was developed through a literature review and peer review. The framework was used to organize the content of 87 caregiver interviews. The six major themes identified in the analysis included Caregiver-Centric Issues, Caregiver Medication Skills and Knowledge Issues, End-of-Life Symptom Knowledge Issues, Communication and Teamwork Issues, Organizational Skill Issues, and Patient-Centric Issues. Conclusion: This analysis clearly articulated and classified caregiver issues surrounding pain management. Future hospice research may benefit from the use of this analysis and framework in the development of tools to alleviate this major cause of caregiver burden.
Lower Injury Rates for Newcomers to Professional Soccer
Authors: Kristenson Karolina , Waldén Markus , Ekstrand Jan , Hägglund Martin 
Published: April 2013

Background: No study has investigated whether newcomers to professional soccer have a different injury rate than established players. Purpose: The primary objective was to investigate whether being a newcomer to professional soccer influences injury rates. The secondary objective was to evaluate whether playing position and player age influence injury rates. Study Design: Cohort study; Level of evidence, 2. Methods: Twenty-six soccer clubs, with 1401 players, were followed prospectively over 9 consecutive seasons between 2001 and 2010. Club medical staff recorded time-loss injuries and soccer exposure on an individual level. Cox regression analyses were used to evaluate associations between time-loss injuries and time in professional soccer, playing position, and age. Results: In total, 6140 injuries and 797,389 hours of exposure were registered. A decreased general injury rate was observed for newcomers (n = 116) compared with established players (n = 3091) (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.99). In contrast, newcomers had a higher rate of fractures (rate ratio [RR], 1.77; 95% CI, 1.05-2.97), especially stress-related bone injuries (RR, 2.68; 95% CI, 1.08-6.69). Using goalkeepers as a reference, all outfield playing positions had significantly higher adjusted injury rates: defenders with an HR of 1.91 (95% CI, 1.64-2.24), midfielders with an HR of 1.78 (95% CI, 1.53-2.07), and forwards with an HR of 1.82 (95% CI, 1.55-2.14). Using players aged ≤21 years as a reference, the overall adjusted injury rate increased with age, with a peak injury rate among players aged 29 to 30 years (HR, 1.44; 95% CI, 1.24-1.68). Conclusion: Newcomers to professional soccer had a lower general injury rate than established players but a higher rate of stress-related bone injuries. Being a goalkeeper was associated with lower injury rates than all outfield playing positions. Injury rates increased with age, a pattern that persisted after adjusting for playing position and match exposure.
A Homozygous Deletion in GRID2 Causes a Human Phenotype With Cerebellar Ataxia and Atrophy
Authors: Utine G. Eda , Haliloğlu Göknur , Salancı Bilge , Çetinkaya Arda , Kiper P. Özlem , Alanay Yasemin , Aktaş Dilek , Boduroğlu Koray , Alikaşifoğlu Mehmet 
Published: April 2013

GRID2 is a member of the ionotropic glutamate receptor family of excitatory neurotransmitter receptors. GRID2 encodes the glutamate receptor subunit delta-2, selectively expressed in cerebellar Purkinje cells. The phenotype associated with loss of GRID2 function was described only in mice until now, characterized by different degrees of cerebellar ataxia and usually relatively mild abnormalities of the cerebellum. This work describes for the first time the human phenotype associated with homozygous partial deletion of GRID2 in 3 children in one large consanguineous Turkish family. Homozygous deletion of exons 3 and 4 of GRID2 (94 153 589-94 298 037 bp) in the proband and similarly affected cousins, and heterozygous deletions in parental DNA were shown using Affymetrix® 6.0 single-nucleotide polymorphism array, confirmed by real-time polymerase chain reaction. The phenotype includes nystagmus, hypotonia with marked developmental delay in gross motor skills in early infancy followed by a static encephalopathy course with development of cerebellar ataxia, oculomotor apraxia, and pyramidal tract involvement.
Accuracy of Noninvasive and Continuous Hemoglobin Measurement by Pulse Co-Oximetry During Preoperative Phlebotomy
Authors: Dewhirst Elisabeth , Naguib Aymen , Winch Peter , Rice Julie , Galantowicz Mark , McConnell Patrick , Tobias Joseph D. 
Published: April 2013

Background: In recent years, the continuous noninvasive hemoglobin measurement has been offered by devices using advanced pulse oximetry technology. Accuracy has been established in healthy adults as well as in surgical and intensive care unit patients but not in the setting of acute hemorrhage. In this study, we evaluated the accuracy of such a device in the clinical setting of preoperative phlebotomy thereby mimicking a scenario of acute blood loss. Methods: This prospective study included patients undergoing surgical repair of congenital heart disease (CHD) for whom preoperative phlebotomy was planned. Blood was removed after the induction of anesthesia and prior to the start of the surgical procedure. Replacement with crystalloid was guided by hemodynamic variables and cerebral oxygenation measured by near-infrared spectroscopy. Hemoglobin was measured by bedside whole blood analysis (total hemoglobin [tHb]) before and after phlebotomy, and concurrent measurements from the pulse co-oximeter (noninvasive, continuous, or spot-check testing of total hemoglobin [SpHb]) were recorded. Results: The study cohort included 45 patients ranging in age from 3 months to 50 years. Preoperative phlebotomy removed an average of 9.2 mL/kg of blood that was replaced with an average of 7.2 mL/kg of crystalloid. The pre- and postphlebotomy tHb values were 13.0 ± 1.9 and 12.4 ± 1.8 g/dL, respectively. The absolute difference between the tHb and SpHb (▵Hb) was 1.2 ± 0.1 g/dL. Bland-Altman analysis revealed a bias of 0.1 g/dL, a precision of 1.5 g/dL, and 95% limits of agreement of −2.8 to 3.1 g/dL. In 52.2% of the sample sets, the SpHb was within 1 g/dL of the actual hemoglobin value (tHb), and in 80% of the sample sets, the SpHb was within 2 g/dL. No variation in the accuracy of the deviation was noted based on the patient’s age, weight, or type of CHD (cyanotic versus acyanotic). Conclusion: The current study demonstrates that the accuracy of continuous, noninvasive hemoglobin measurement was not affected by acute blood loss simulated by preoperative phlebotomy. Although the device provided a clinically acceptable correlation with the actual hemoglobin value and offers the value of a continuous trend monitor, given the precision of the device, it does not appear that actual transfusion decisions can be based on the device alone.
Anti B-cell therapy against refractory thrombocytopenia in SLE and MCTD patients: long-term follow-up and review of the literature
Authors: Jovancevic B , Lindholm C , Pullerits R 
Published: April 2013

Objective The objective of this study was to retrospectively evaluate the clinical and immunological effects of anti-B cell treatment in patients with systemic lupus erythematosus (SLE) and mixed connective-tissue disease (MCTD) with autoimmune thrombocytopenia (AITP) refractory to conventional immunosuppressive treatment. Methods Rituximab (RTX) was added to the ongoing treatment of 16 patients (median age 36 years, range 17–84, all female) with treatment-resistant AITP. Thirteen patients had SLE and three had MCTD. RTX was given intravenously on four occasions during four consecutive weeks at a dose of 375 mg/m2. Clinical and laboratory disease activity variables recorded at every follow-up visit were analyzed. Results The median disease duration before RTX treatment was nine years (range 0.2–27) and the median post-treatment follow-up time was 28 months (range 3 to 92). Ten patients (63%) were treated repeatedly with RTX during the follow-up period. Complete depletion of B cells was achieved in 94% of cases one month after RTX treatment. A significant increase ( p = 0.0001) of platelet counts was seen already after one month (median 58 × 109/ml vs 110 × 109/ml) whereas within three months platelet counts normalized in 10 patients (median 223 × 109/ml). Three patients did not respond to RTX treatment (median platelet count 69 × 109/ml). High titers of anti-platelet antibodies were detected in seven patients before RTX treatment, and the autoantibody titers decreased significantly ( p < 0.03) after RTX treatment in six of these patients who also achieved complete remission. A review of the literature revealed 24 articles including 18 case reports, one retrospective cohort study and five prospective studies documenting the outcomes of 65 RTX-treated patients with SLE- or MCTD-related thrombocytopenia with an overall treatment response rate of 80%. In conclusion, these findings indicate that RTX is an additional potent therapeutic treatment option for SLE patients with AITP refractory to conventional immunosuppressive treatment whereas best response may be expected in patients with high titers of anti-platelet antibodies at baseline.