bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of Specialized Pediatric Palliative Care Involvement and Impact on Patterns of End-of-Life Care in Children With Cancer
Authors: Widger Kimberley , Sutradhar Rinku , Rapoport Adam , Vadeboncoeur Christina , Zelcer Shayna , Kassam Alisha , Nelson Katherine , Liu Ying , Wolfe Joanne , Earle Craig C. , Pole Jason D. , Gupta Sumit 
Published: January 2018

Purpose The impact of specialized pediatric palliative care (SPPC) teams on patterns of end-of-life care is unknown. We sought to determine (1) which children with cancer access SPPC and (2) the impact of accessing SPPC on the risk of experiencing high-intensity end-of-life care (intensive care unit admission, mechanical ventilation, or in-hospital death). Methods Using a provincial childhood cancer registry, we assembled a retrospective cohort of Ontario children with cancer who died between 2000 and 2012 and received care through pediatric institutions with an SPPC team. Patients were linked to population-based administrative data capturing inpatient, outpatient, and emergency visits. Children were classified as having SPPC, general palliative care, or no palliative care on the basis of SPPC clinical databases, physician billing codes, or inpatient diagnosis codes. Results Of the 572 children, 166 (29%) received care from an SPPC team for at least 30 days before death, and 100 (17.5%) received general palliative care. SPPC involvement was significantly less likely for children with hematologic cancers (OR, 0.3; 95% CI, 0.3 to 0.4), living in the lowest income areas (OR, 0.4; 95% CI, 0.2 to 0.8), and living further from the treatment center (OR, 0.5; 95% CI, 0.4 to 0.5). SPPC was associated with a five-fold decrease in odds of intensive care unit admission (OR, 0.2; 95% CI, 0.1 to 0.4), whereas general palliative care had no impact. Similar associations were seen with all secondary indicators. Conclusion When available, SPPC, but not general palliative care, is associated with lower intensity care at the end of life for children with cancer. However, access remains uneven. These results provide the strongest evidence to date supporting the creation of SPPC teams.
Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation
Authors: Panaliappan Tamilarasan K. , Wittmann Walter , Jidigam Vijay K. , Mercurio Sara , Bertolini Jessica A. , Sghari Soufien , Bose Raj , Patthey Cedric , Nicolis Silvia K. , Gunhaga Lena 
Published: January 2018

ABSTRACT
The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage. Our results also suggest that Sox2 activity promotes the neurogenic domain in the nasal epithelium by restricting Bmp4 expression. The Sox2-deficient olfactory epithelium displays diminished cell cycle progression and proliferation, a dramatic increase in apoptosis and finally olfactory pit atrophy. Moreover, chromatin immunoprecipitation data show that Sox2 directly binds to the Hes5 promoter in both the PNS and CNS. Taken together, our results indicate that Sox2 is essential to establish, maintain and expand the neuronal progenitor pool by suppressing Bmp4 and upregulating Hes5 expression.
Developmental abnormalities in supporting cell phalangeal processes and cytoskeleton in the Gjb2 knockdown mouse model
Authors: Chen Sen , Xie Le , Xu Kai , Cao Hai-Yan , Wu Xia , Xu Xiao-Xiang , Sun Yu , Kong Wei-Jia 
Published: January 2018

ABSTRACT
Mutations in the GJB2 gene [which encodes connexin 26 (Cx26)] are the most common causes of hereditary hearing loss in humans, and previous studies showed postnatal development arrest of the organ of Corti in different Cx26-null mouse models. To explore the pathological changes and the mechanism behind the cochlear abnormalities in these mice further, we established transgenic mouse models by conditional knockdown of cochlear Cx26 at postnatal day (P) 0 and P8. Auditory brainstem responses were recorded and the morphological features in the organ of Corti were analyzed 18 days after Cx26 knockdown. Mice in the P0 knockdown group displayed severe hearing loss at all frequencies, whereas mice in the P8 knockdown group showed nearly normal hearing. In the P8 knockdown group, the organ of Corti displayed normal architecture, and no ultrastructural changes were observed. In the P0 knockdown group, the phalangeal processes of Deiter's cells did not develop into finger-like structures, and the formation of microtubules in the pillar cells was significantly reduced; moreover, the amount of acetylated α-tubulin was reduced in pillar cells. Our results indicate that Gjb2 participates in postnatal development of the cytoskeleton in pillar cells during structural maturation of the organ of Corti. In P0 knockdown mice, the reduction in microtubules in pillar cells might be responsible for the failure of the tunnel of Corti to open, and the malformed phalangeal processes might negatively affect the supporting framework of the organ of Corti, which would be a new mechanism of Gjb2-related hearing loss.
The fibronectin ED-A domain enhances recruitment of latent TGF-β-binding protein-1 to the fibroblast matrix
Authors: Klingberg Franco , Chau Grace , Walraven Marielle , Boo Stellar , Koehler Anne , Chow Melissa L. , Olsen Abby L. , Im Michelle , Lodyga Monika , Wells Rebecca G. , White Eric S. , Hinz Boris 
Published: January 2018

ABSTRACT
Dysregulated secretion and extracellular activation of TGF-β1 stimulates myofibroblasts to accumulate disordered and stiff extracellular matrix (ECM) leading to fibrosis. Fibronectin immobilizes latent TGF-β-binding protein-1 (LTBP-1) and thus stores TGF-β1 in the ECM. Because the ED-A fibronectin splice variant is prominently expressed during fibrosis and supports myofibroblast activation, we investigated whether ED-A promotes LTBP-1–fibronectin interactions. Using stiffness-tuneable substrates for human dermal fibroblast cultures, we showed that high ECM stiffness promotes expression and colocalization of LTBP-1 and ED-A-containing fibronectin. When rescuing fibronectin-depleted fibroblasts with specific fibronectin splice variants, LTBP-1 bound more efficiently to ED-A-containing fibronectin than to ED-B-containing fibronectin and fibronectin lacking splice domains. Function blocking of the ED-A domain using antibodies and competitive peptides resulted in reduced LTBP-1 binding to ED-A-containing fibronectin, reduced LTBP-1 incorporation into the fibroblast ECM and reduced TGF-β1 activation. Similar results were obtained by blocking the heparin-binding stretch FNIII12-13-14 (HepII), adjacent to the ED-A domain in fibronectin. Collectively, our results suggest that the ED-A domain enhances association of the latent TGF-β1 by promoting weak direct binding to LTBP-1 and by enhancing heparin-mediated protein interactions through HepII in fibronectin.
The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for renal fibrogenesis
Authors: Sun Qi , Miao Jiao , Luo Jing , Yuan Qi , Cao Hongdi , Su Weifang , Zhou Yang , Jiang Lei , Fang Li , Dai Chunsun , Zen Ke , Yang Junwei 
Published: January 2018

ABSTRACT
Renal fibrosis is a final common pathway of chronic kidney disease. Sustained activation of fibroblasts is considered to play a key role in perpetuating renal fibrosis but the driving force in the perpetuation stage is only partially understood. To date, some investigations have specifically identified overexpression of microRNA 21 (miR-21) in the progression of kidney fibrosis. Nevertheless, the precise role of miR-21 in fibroblast activation remains largely unknown. In this study, we found that miR-21 was significantly upregulated in activated fibroblasts and that it maintained itself at constant high levels by employing an auto-regulatory loop between miR-21, PDCD4 and AP-1. Persistently upregulated miR-21 suppressed protein expression of Smad7 and, eventually, enhanced the TGF-β1/Smad pathway to promote fibroblast activation. More importantly, we found miR-21 sequestration with miR-21 antagomir or AP-1 inhibitors attenuated unilateral ureteral obstruction (UUO)-induced renal ﬁbrosis. miR-21-knockout mice also suffered far less interstitial fibrosis in response to kidney injury. Altogether, these data suggest that miR-21 is a main driving force of fibroblast activation and keeps its high expression level by employing a double negative autoregulatory loop. Targeting this aberrantly activated feedback loop may provide new therapeutic strategy in treating fibrotic kidneys.
Functional analysis after rapid degradation of condensins and 3D-EM reveals chromatin volume is uncoupled from chromosome architecture in mitosis
Authors: Samejima Kumiko , Booth Daniel G. , Ogawa Hiromi , Paulson James R. , Xie Linfeng , Watson Cara A. , Platani Melpomeni , Kanemaki Masato T. , Earnshaw William C. 
Published: January 2018

ABSTRACT
The requirement for condensin in chromosome formation in somatic cells remains unclear, as imperfectly condensed chromosomes do form in cells depleted of condensin by conventional methodologies. In order to dissect the roles of condensin at different stages of vertebrate mitosis, we have established a versatile cellular system that combines auxin-mediated rapid degradation with chemical genetics to obtain near-synchronous mitotic entry of chicken DT40 cells in the presence and absence of condensin. We analyzed the outcome by live- and fixed-cell microscopy methods, including serial block face scanning electron microscopy with digital reconstruction. Following rapid depletion of condensin, chromosomal defects were much more obvious than those seen after a slow depletion of condensin. The total mitotic chromatin volume was similar to that in control cells, but a single mass of mitotic chromosomes was clustered at one side of a bent mitotic spindle. Cultures arrest at prometaphase, eventually exiting mitosis without segregating chromosomes. Experiments where the auxin concentration was titrated showed that different condensin levels are required for anaphase chromosome segregation and formation of a normal chromosome architecture.
This article has an associated First Person interview with the first author of the paper.
The developing Drosophila eye – a new model to study centriole reduction
Authors: Riparbelli Maria G. , Persico Veronica , Gottardo Marco , Callaini Giuliano 
Published: January 2018

ABSTRACT
In the developing Drosophila eye, the centrioles of the differentiating retinal cells are not surrounded by the microtubule-nucleating γ-tubulin, suggesting that they are unable to organize functional microtubule-organizing centers. Consistent with this idea, Cnn and Spd-2, which are involved in γ-tubulin recruitment, and the scaffold protein Plp, which plays a role in the organization of the pericentriolar material, are lost in the third-instar larval stage. However, the centrioles maintain their structural integrity, and both the parent centrioles accumulate Asl and Ana1. Although the loading of Asl points to the acquisition of the motherhood condition, the daughter centrioles fail to recruit Plk4 and do not duplicate. However, it is surprising that the mother centrioles that accumulate Plk4 also never duplicate. This suggests that the loading of Plk4 is not sufficient, in this system, to allow centriole duplication. By halfway through pupal life, the centriole number decreases and structural defects, ranging from being incomplete or lacking B-tubules, are detected. Asl, Ana1 and Sas-4 are still present, suggesting that the centriole integrity does not depend on these proteins.
Cell-specific cis-natural antisense transcripts (cis-NATs) in the sperm and the pollen vegetative cells of Arabidopsis thaliana
Authors: Qin Peng , Loraine Ann E. , McCormick Sheila 
Published: January 2018

Background: cis-NATs (cis-natural antisense transcripts) are transcribed from opposite strands of adjacent genes and have been shown to regulate gene expression by generating small RNAs from the overlapping region. cis-NATs are important for plant development and resistance to pathogens and stress. Several genome-wide investigations identified a number of cis-NAT pairs, but these investigations predicted cis-NATS using expression data from bulk samples that included lots of cell types. Some cis-NAT pairs identified from those investigations might not be functional, because both transcripts of cis-NAT pairs need to be co-expressed in the same cell. Pollen only contains two cell types, two sperm and one vegetative cell, which makes cell-specific investigation of cis-NATs possible. Methods: We investigated potential protein-coding cis-NATs in pollen and sperm using pollen RNA-seq data and TAIR10 gene models using the Integrated Genome Browser. We then used sperm microarray data and sRNAs in sperm and pollen to determine possibly functional cis-NATs in the sperm or vegetative cell, respectively. Results: We identified 1471 potential protein-coding cis-NAT pairs, including 131 novel pairs that were not present in TAIR10 gene models. In pollen, 872 possibly functional pairs were identified. 72 and 56 pairs were potentially functional in sperm and vegetative cells, respectively. sRNAs were detected at 794 genes, belonging to 739 pairs. Conclusion: These potential candidates in sperm and the vegetative cell are tools for understanding gene expression mechanisms in pollen.
Management of osteonecrosis of the femoral head in children with sickle cell disease: Results of conservative and operative treatments at skeletal maturity
Authors: Mallet C. , Abitan A. , Vidal C. , Holvoet L. , Mazda K. , Simon A.-L. , Ilharreborde B. 
Published: January 2018

Purpose Sickle cell disease (SCD) is the most common cause of femoral head osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In children, spontaneous revascularization can occur, as in Legg-Calve-Perthes disease. Consequently, the aim of treatment is to restore proper hip containment to prevent joint arthritis. This is the first study reporting long-term results at skeletal maturity of non-operative and surgical treatments for ONFH in SCD children. Methods All children with ONFH due to SCD were retrospectively reviewed. At initial evaluation, extension of osteonecrosis was radiographically defined using Catterall, lateral pillar Herring and Ficat classifications. Subluxation of the femoral head with Reimers migration index > 30% required surgical treatment including femoral varus osteotomy and/or pelvic osteotomies. Conservative treatment including non-weight bearing and physiotherapy was performed in the remaining cases. Outcomes were assessed at skeletal maturity using the Harris Hip Score (HHS) and the Stulberg classification. Total hip arthroplasty and Stulberg 5 were defined as failures. Results A total of 25 hips in 17 patients were included (mean follow-up 7.5 years SD 3.4). Mean age at diagnosis was 11.4 years SD 2.9. In all, 15 hips (60%) were classified Catterall 3 and 4 and Herring B and C. A total of 13 patients (52%) underwent surgical treatment. At skeletal maturity, mean HHS was good (81 SD 17), 12 hips (48%) were classified Stulberg 1 and 2, seven hips (28%) were classified Stulberg 3 and 4. Conclusion Both treatments led to good functional results with 75% of congruent hips at skeletal maturity. Level of Evidence IV
KONTRIBUSI LINGKUNGAN KELUARGA DALAM MEMBANGUN PERILAKU SEKSUAL ANAK USIA DASAR
Authors: NINGSIH ISTI 
Published: January 2018

Sexual behavior is all behavior that is driven by sexual desire that is naturally owned by each human being. But the influence of various environments on child sexual behavior, making each child has different sexual behavior. One environment that plays a major role in contributing to child sexual behavior is the family environment. The contribution of the family in building the child’s sexual behavior can be done in the form of: (1) Provision of sex education for the child (2)Parental supervision on child sex behavior and (3) Parental attention to children’s activities. By considering these three things, the child’s sexual behavior can be safeguarded early and can prevent sexual behaviors that should not have occurred at the age of the basic child.
Keywords: Family Contribution, Sexual Behavior, Basic Age
Humanistic, artistic and pedagogic aspects of Orff-Schulwerk music and dance pedagogy<p>Orff-Schulwerk müzik ve hareket eğitiminin insani, sanatsal ve pedagojik yönleri
Authors: Özevin Banu 
Published: January 2018

Orff-Schulwerk Music and Movement Pedagogy is a contemporary music education philosophy, born out of the work of composer Carl Orff. Orff-Schulwerk has a holistic understanding in music education which is a combination of music, movement and language. Orff-Schulwerk enables the individual to develop his creative potential in group activities based on improvisation. Orff-Schulwerk's philosophy is that everyone can make music. With this understanding, everyone can take part in the Schulwerk lesson and have the opportunity for artistic expression of self without the distinction of gifted-talented, child-adult, and normal-developmental-disabled. As in many countries of the world, Orff-Schulwerk Pedagogy is used effectively in music education and preschool education in Turkey.In this study, in spite of the fact that it is a built-in structure, the human, artistic and pedagogical aspects of Orff-Schulwerk have been elaborated separately in order to better understand the approach. In the conclusion and discussion section, questions and problems about Orff-Schulwerk Music and Movement Education's place in Turkish Education System and adaptation to Turkish culture were shared.Extended English abstract is in the end of Full Text PDF (TURKISH) file. ÖzetOrff-Schulwerk Müzik ve Hareket Eğitimi, besteci Carl Orff’un çalışmalarından doğan, çağdaş bir müzik eğitimi felsefesidir. Orff-Schulwerk, müzik, hareket ve dil ögelerinin birlikte kullanıldığı, doğaçlamalara dayanan, grup aktiviteleri içinde bireyin yaratıcı potansiyelini geliştirmesine olanak sağlayan bütüncül bir müzik eğitimi anlayışıdır. Orff-Schulwerk’in felsefesi herkesin müzik yapabileceği yönündedir. Bu anlayış sayesinde yetenekli-yeteneksiz, çocuk-yetişkin, normal gelişim gösteren-engelli ayrımı olmadan herkes Schulwerk dersi içinde yer alabilir ve kendini sanatsal olarak ifade etme olanağını yakalayabilir. Dünyanın birçok ülkesinde olduğu gibi Türkiye’de de Orff-Schulwerk Pedagojisi müzik eğitimi ve okulöncesi eğitiminde etkin bir biçimde kullanılmaktadır.İçiçe geçmiş bir yapı olmasına rağmen, bu çalışmada yaklaşımın daha iyi anlaşılabilmesi için Orff-Schulwerk’in insani, sanatsal ve pedagojik yönleri ayrı ayrı ayrıntılı olarak irdelenmiştir. Sonuç ve tartışma bölümünde Orff-Schulwerk Müzik ve Hareket Eğitimi’nin Türk Eğitim sistemindeki yeri ve Türk kültürüne uyarlanması ile ilgili sorular ve sorunlar paylaşılmıştır.
Serotonin Disinhibits aCaenorhabditis elegansSensory Neuron by Suppressing Ca2+-Dependent Negative Feedback
Authors: Williams Paul D.E. , Zahratka Jeffrey A. , Rodenbeck Matthew , Wanamaker Jason , Linzie Hilary , Bamber Bruce A. 
Published: January 2018

Neuromodulators, such as serotonin (5-HT), alter neuronal excitability and synaptic strengths, and define different behavioral states. Neuromodulator-dependent changes in neuronal activity patterns are frequently measured using calcium reporters because calcium imaging can easily be performed on intact functioning nervous systems. With only 302 neurons, the nematodeCaenorhabditis elegansprovides a relatively simple, yet powerful, system to understand neuromodulation at the level of individual neurons.C. eleganshermaphrodites are repelled by 1-octanol, and the initiation of these aversive responses is potentiated by 5-HT. 5-HT acts on the ASH polymodal nociceptors that sense the 1-octanol stimulus. Surprisingly, 5-HT suppresses ASH Ca2+transients while simultaneously potentiating 1-octanol-dependent ASH depolarization. Here we further explore this seemingly inverse relationship. Our results show the following (1) 5-HT acts downstream of depolarization, through Gαq-mediated signaling and calcineurin, to inhibit L-type voltage-gated Ca2+channels; (2) the 1-octanol-evoked Ca2+transients in ASHs inhibit depolarization; and (3) the Ca2+-activated K+channel, SLO-1, acts downstream of 5-HT and is a critical regulator of ASH response dynamics. These findings define a Ca2+-dependent inhibitory feedback loop that can be modulated by 5-HT to increase neuronal excitability and regulate behavior, and highlight the possibility that neuromodulator-induced changes in the amplitudes of Ca2+transients do not necessarily predict corresponding changes in depolarization.SIGNIFICANCE STATEMENTNeuromodulators, such as 5-HT, modify behavior by regulating excitability and synaptic efficiency in neurons. Neuromodulation is often studied using Ca2+imaging, whereby neuromodulator-dependent changes in neuronal activity levels can be detected in intact, functioning circuits. Here we show that 5-HT reduces the amplitude of depolarization-dependent Ca2+transients in aC. elegansnociceptive neuron, through Gαqsignaling and calcineurin but that Ca2+itself inhibits depolarization, likely through Ca2+-activated K+channels. The net effect of 5-HT, therefore, is to increase neuronal excitability through disinhibition. These results establish a novel 5-HT signal transduction pathway, and demonstrate that neuromodulators can change Ca2+signals and depolarization amplitudes in opposite directions, simultaneously, within a single neuron.