bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up‐regulation of survivin by AKT and hypoxia‐inducible factor 1α contributes to cisplatin resistance in gastric cancer
Authors: Sun Xue‐Pu , Dong Xuesong , Lin Lele , Jiang Xian , Wei Zheng , Zhai Bo , Sun Bo , Zhang Qiang , Wang Xiaolong , Jiang Hongchi , Krissansen Geoffrey W. , Qiao Haiquan , Sun Xueying 
Published: October 2013

This study investigated the contribution of survivin and its upstream regulators, AKT and hypoxia‐inducible factor 1α (HIF–1α), to the resistance of gastric cancer cells to cisplatin (CDDP). We found that over‐expression of survivin increased the resistance of SGC7901 and BGC823 gastric cancer cells to CDDP. Its over‐expression abrogated CDDP‐induced inhibition of cell proliferation and CDDP‐induced cell apoptosis. In contrast, down‐regulation of survivin expression using small hairpin RNA (shRNA) vectors and the small‐molecule inhibitor YM155, or inhibition of survivin function using a recombinant cell‐permeable dominant‐negative survivin protein (dNSur9), promoted CDDP‐induced apoptosis. CDDP‐resistant sub‐lines generated from the parental SGC7901 and BGC823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF–1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (pAKT). Specific inhibition of AKT reduced the expression of HIF–1α and survivin, whereas specific inhibition or depletion of HIF–1α reduced survivin expression but had no effect on the expression of phosphorylated AKT. The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF–1α enhanced the sensitivity of CDDP‐resistant cells to CDDP. Specific inhibition of survivin, AKT and HIF‐1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up‐regulation of survivin by AKT and HIF–1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.
Histone methylation mediates plasticity of human FOXP3+ regulatory T cells by modulating signature gene expressions
Authors: He Haiqi , Ni Bing , Tian Yi , Tian Zhiqiang , Chen Yanke , Liu Zhengwen , Yang Xiaomei , Lv Yi , Zhang Yong 
Published: October 2013

SummaryCD4+ FOXP3+ regulatory T (Treg) cells constitute a heterogeneous and plastic T‐cell lineage that plays a pivotal role in maintaining immune homeostasis and immune tolerance. However, the fate of human Treg cells after loss of FOXP3 expression and the epigenetic mechanisms contributing to such a phenotype switch remain to be fully elucidated. In the current study, we demonstrate that human CD4+ CD25high CD127low/− Treg cells convert to two subpopulations with distinctive FOXP3+ and FOXP3− phenotypes following in vitro culture with anti‐CD3/CD28 and interleukin‐2. Digital gene expression analysis showed that upon in vitro expansion, human Treg cells down‐regulated Treg cell signature genes, such as FOXP3, CTLA4, ICOS, IKZF2 and LRRC32, but up‐regulated a set of T helper lineage‐associated genes, especially T helper type 2 (Th2)‐associated, such as GATA3, GFI1 and IL13. Subsequent chromatin immunoprecipitation‐sequencing of these subpopulations yielded genome‐wide maps of their H3K4me3 and H3K27me3 profiles. Surprisingly, reprogramming of Treg cells was associated with differential histone modifications, as evidenced by decreased abundance of permissive H3K4me3 within the down‐regulated Treg cell signature genes, such as FOXP3, CTLA4 and LRRC32 loci, and increased abundance of H3K4me3 within the Th2‐associated genes, such as IL4 and IL5; however, the H3K27me3 modification profile was not significantly different between the two subpopulations. In conclusion, this study revealed that loss of FOXP3 expression from human Treg cells during in vitro expansion can induce reprogramming to a T helper cell phenotype with a gene expression signature dominated by Th2 lineage‐associated genes, and that this cell type conversion may be mediated by histone methylation events.
‘How do we know if this is the best?’ Mental health‐care professionals' views on national guidelines for psychosocial interventions
Authors: Sandström Boel , Willman Ania , Svensson Bengt , Borglin Gunilla 
Published: October 2013

AbstractNational guidelines are released regularly, and professionals are expected to adopt and implement them. However, studies dealing with mental health‐care professionals' views about guidelines are sparse. The aim of the present study was to highlight mental health‐care staff's views on the Swedish national guidelines for ‘psychosocial interventions for schizophrenia or schizophrenia‐type symptoms’ and their implementation. The study took place in the southeast parts of Sweden, and data were collected through five group interviews consisting of 16 professionals working either in the county council or in the municipalities. The transcribed text was analysed by content analysis, revealing two categories. The first category ‘a challenge to the practice of care as known’ reflected that the release of guidelines could be perceived as a challenge to prevailing care and culture. The second category ‘anticipating change to come from above’ mirrored views on how staff expected the implementation process to flow from top to bottom. To facilitate working in accordance with guidelines, we suggest that future guidelines should be accompanied by an implementation plan, where the educational needs of frontline staff are taken into account. There is also a need for policy makers and managers to assume responsibility in supporting the implementation of evidence‐based practice.
Perceived Professional Gains of Master's Level Students Following a Person‐of‐the‐Therapist Training Program: A Retrospective Content Analysis
Authors: Niño Alba , Kissil Karni , Apolinar Claudio Florina L. 
Published: October 2013

The Person‐of‐the‐Therapist Training (POTT) is a program designed to facilitate clinicians' ability to consciously and purposefully use themselves at the moment of contact with their clients in order to connect, assess, and intervene effectively. This qualitative study explored the experiences of 54 master's‐level students who were enrolled in an accredited marriage and family therapy program in the United States and examined their perceived professional gains following a 9‐month POTT course. Content analysis of trainees' reflections which they wrote at the end of the training revealed 6 primary themes: (a) increased awareness, (b) emotions, (c) improved clinical work, (d) humanity and woundedness, (e) meta‐awareness, and (f) factors that contributed to the learning process. Findings suggest that key outcomes of this training curriculum are congruent with its stated goals. Clinical and training recommendations are additionally provided.Video Abstract
Signal‐to‐noise ratio estimation on SEM images using cubic spline interpolation with Savitzky–Golay smoothing
Authors: SIM K.S. , KIANI M.A. , NIA M.E. , TSO C.P. 
Published: October 2013

SummaryA new technique based on cubic spline interpolation with Savitzky–Golay noise reduction filtering is designed to estimate signal‐to‐noise ratio of scanning electron microscopy (SEM) images. This approach is found to present better result when compared with two existing techniques: nearest neighbourhood and first‐order interpolation. When applied to evaluate the quality of SEM images, noise can be eliminated efficiently with optimal choice of scan rate from real‐time SEM images, without generating corruption or increasing scanning time.
Identification of two novel Shank3 transcripts in the developing mouse neocortex
Authors: Waga Chikako , Asano Hirotsugu , Sanagi Tomomi , Suzuki Eri , Nakamura Yasuko , Tsuchiya Akiko , Itoh Masayuki , Goto Yu‐ichi , Kohsaka Shinichi , Uchino Shigeo 
Published: October 2013

AbstractSHANK3 is a synaptic scaffolding protein enriched in the post‐synaptic density of excitatory synapses. Since several SHANK3 mutations have been identified in a particular phenotypic group of patients with autism spectrum disorder (ASD), SHANK3 is strongly suspected of being involved in the pathogenesis and neuropathology of ASD. Several SHANK3 isoforms are known to be produced in the developing brain, but they have not been fully investigated. Here, we identified two different amino‐terminus truncated Shank3 transcripts. One transcript, designated as Shank3c‐3, produces an isoform that contains the entire carboxyl‐terminus, but the other transcript, designated as Shank3c‐4, produces a carboxyl‐terminus truncated isoform. During development, expression of the novel Shank3 transcripts increased after birth, transiently decreased at P14 and then gradually increased again thereafter. We also determined that methyl CpG‐binding protein 2 (MeCP2) is involved in regulating expression of the novel Shank3 transcripts. MeCP2 is a transcriptional regulator that has been identified as the causative molecule of Rett syndrome, a neurodevelopmental disorder that includes autistic behavior. We demonstrated a difference between the expression of the novel Shank3 transcripts in wild‐type mice and Mecp2‐deficient mice. These findings suggest that the SHANK3 isoforms may be implicated in the synaptic abnormality in Rett syndrome.
imageSHANK3 is a synaptic scaffolding protein and is suspected of being implicated in the pathogenesis and neuropathology of ASD. We here identified two different amino‐terminus truncated Shank3 transcripts, Shank3c‐3 and Shank3c‐4, expressed from the intron 10 of the Shank3 gene, and also suggested the epigenetic regulation of their expression via methyl CpG‐binding protein 2 (MeCP2) that has been identified as the causative molecule of Rett syndrome.
Actin dynamics in growth cone motility and navigation
Authors: Gomez Timothy M. , Letourneau Paul C. 
Published: October 2013

AbstractMotile growth cones lead growing axons through developing tissues to synaptic targets. These behaviors depend on the organization and dynamics of actin filaments that fill the growth cone leading margin [peripheral (P‐) domain]. Actin filament organization in growth cones is regulated by actin‐binding proteins that control all aspects of filament assembly, turnover, interactions with other filaments and cytoplasmic components, and participation in producing mechanical forces. Actin filament polymerization drives protrusion of sensory filopodia and lamellipodia, and actin filament connections to the plasma membrane link the filament network to adhesive contacts of filopodia and lamellipodia with other surfaces. These contacts stabilize protrusions and transduce mechanical forces generated by actomyosin activity into traction that pulls an elongating axon along the path toward its target. Adhesive ligands and extrinsic guidance cues bind growth cone receptors and trigger signaling activities involving Rho GTPases, kinases, phosphatases, cyclic nucleotides, and [Ca++] fluxes. These signals regulate actin‐binding proteins to locally modulate actin polymerization, interactions, and force transduction to steer the growth cone leading margin toward the sources of attractive cues and away from repellent guidance cues.
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Actin filament organization in motile growth cone leading margin (peripheral (P‐) domain) is regulated by actin‐binding proteins that control all aspects of filament assembly, turnover, interactions with other filaments or cytoplasmic components, and produce mechanical forces. This Review outlines key aspects of growth cone actin dynamics, as well as the roles of adhesion‐mediating proteins, like integrins, which stabilize actin‐based protrusions and transduce mechanical forces generated by actomyosin activity into traction that pulls an elongating axon along the path toward its target.
Platelet activating factor induces transient blood‐brain barrier opening to facilitate edaravone penetration into the brain
Authors: Fang Weirong , Zhang Rui , Sha Lan , Lv Peng , Shang Erxin , Han Dan , Wei Jie , Geng Xiaohan , Yang Qichuan , Li Yunman 
Published: October 2013

AbstractThe blood–brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra‐performance liquid chromatograph combined with a hybrid quadrupole time‐of‐flight mass spectrometer (UPLC‐MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to 125I‐albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule‐1, matrix‐metalloproteinase‐9 and P‐glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain.
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Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain.
Neuromedin U Partly Mimics Thyroid‐Stimulating Hormone and Triggers Wnt/β‐Catenin Signalling in the Photoperiodic Response of F344 Rats
Authors: Helfer G. , Ross A. W. , Morgan P. J. 
Published: October 2013

AbstractIn seasonal animals, photoperiod exerts profound effects on physiology, such as growth, energy balance and reproduction, via changes in the neuroendocrine axes. A key element of the photoperiodic response is the thyroid hormone level in the hypothalamus, which is controlled via retrograde transport of thyroid‐stimulating hormone (TSH) from the pars tuberalis of the pituitary. TSH regulates type II deiodinase (Dio2) expression, which transforms inactive thyroid hormone to its active form, via TSH receptors expressed in the ependymal cells of the hypothalamus. In the present study, we hypothesised that a second peptide hormone, neuromedin U (NMU), may play a role in the photoperiodic response alongside TSH because the gene for NMU is also expressed in a strongly photoperiod‐dependent manner in the pars tuberalis and its receptor NMU2 is expressed in the ependymal layer of the third ventricle in photoperiod‐sensitive F344 rats. Consistent with other studies conducted in nonseasonal mammals, we found that acute i.c.v. injections of NMU into the hypothalamus negatively regulated food intake and body weight and increased core body temperature in F344 rats. At the same time, NMU increased Dio2 mRNA expression in the ependymal region of the hypothalamus similar to the effects of TSH. These data suggest that NMU may affect acute and photoperiodically controlled energy balance through distinct pathways. We also showed that TSH inhibits the expression of type III deiodinase (Dio3) in F344 rats, a response not mimicked by NMU. Furthermore, NMU also increased the expression of genes from the Wnt/β‐catenin pathway within the ependymal layer of the third ventricle. This effect was not influenced by TSH. These data indicate that, although NMU acts with some similarities to TSH, it also has completely distinct signalling functions that do not overlap. In summary, the present study of NMU signalling reveals the potential for a new player in the control of seasonal biology.
Adopting a patient‐centred approach: an investigation into the introduction of bedside handover to three rural hospitals
Authors: Bradley Stacey , Mott Sarah 
Published: October 2013

Aims and objectivesTo study empirically the process and outcomes of the implementation of nurse‐to‐nurse bedside handover in three rural South Australian hospitals.BackgroundWhile the importance of handover is identified in literature, little is written about its implementation. It is, however, suggested that bedside handover is a more patient‐focussed approach than others available.DesignA mixed‐method, pretest post‐test evaluative approach involving quasi‐experimental and ethnographic elements was used. The self‐selected sample comprised nine inpatients (five women, four men) and forty‐eight self‐selected enrolled/registered nursing staff (forty‐seven women, one man) from three acute hospital wards in rural South Australia. Lewin's (Human Relations, 1, 1947a, 2; Readings in Social Psychology. Henry Holt, New York, 1947b, 197) 3‐stage model of change provided a theoretical basis and structure for the study.MethodsPatient perceptions were obtained using ethnographic interviewing. Staff perceptions of patient involvement were obtained through questions rated on a 7‐point Likert scale and ethnographic interviewing.ResultsResults indicated that patients preferred the bedside handover method over the traditional closed‐door office handover approach. The key differences (as defined by patients) are that the bedside handover process incorporates social aspects for the patient, patients have the opportunity to know who is looking after them and patients are included in discussion related to their care. Furthermore, results suggest that staff believed the level of patient involvement in their care had increased under the bedside handover process.ConclusionsThe results demonstrate that both patients and staff perceive patients to be more involved in their care under the bedside handover approach. The literature notes a recent move towards adopting patient‐centred care approaches in clinical settings and the many benefits associated with this style of care. This study has proven that implementing bedside handover has resulted in a patient‐centred approach.Relevance to clinical practiceThis study generates further knowledge about rural nursing and contributes insight into the importance of handover implementation method – areas that are not widely documented in existing literature.
Nine‐Month Angiographic and Intravascular Ultrasound Outcomes After Resolute Zotarolimus‐Eluting Stent Implantation for the Treatment of In‐Stent Restenosis
Authors: LEE SEUNG‐YUL , KIM BYEONG‐KEUK , KIM JUNG‐SUN , HONG MYEONG‐KI , CHO DEOK‐KYU , YOON JUNGHAN , JEON DONG WOON , LEE NAM‐HO , KWON HYUCK MOON , JANG YANGSOO 
Published: October 2013

AbstractObjectivesWe aimed to evaluate the mid‐term outcomes of resolute zotarolimus‐eluting stent (R‐ZES) implantation for in‐stent restenosis (ISR).BackgroundThere has been a paucity of data regarding the effects of new‐generation drug‐eluting stent to treat ISR.MethodsFrom 2009 to 2010, a total of 98 patients with 98 ISR lesions were prospectively enrolled after R‐ZES implantation for the treatment of ISR. Among 98 patients, 73 patients underwent follow‐up angiography at 9 months. Serial intravascular ultrasound (IVUS) at both postprocedure and 9 months was evaluated in 55 patients. The overlapped segment of R‐ZES was defined as the portion of R‐ZES superimposed on previous stent.ResultsLate loss and binary restenosis rate were 0.3 ± 0.5 mm and 5.5% at 9 months. On IVUS, the percentage of neointimal volume and maximum percentage of neointimal area were 3.9 ± 6.3% and 17.3 ± 15.5%, respectively. There was no significant change of vessel volume index between postprocedure and 9 months (16.9 ± 4.7 mm3/mm vs. 17.1 ± 4.6 mm3/mm, P = 0.251). Late‐acquired incomplete stent apposition was observed in 5 (5/55, 9.1%) cases. Compared with nonoverlapped segments of R‐ZES, the overlapped did not show larger neointimal volume index (0.3 ± 0.5 mm3/mm vs. 0.2 ± 0.3 mm3/mm, P = 0.187) on 9‐month IVUS. During follow‐up (median, 353 days), repeat target‐lesion revascularization was performed in four cases, but there were no death or stent thrombosis.ConclusionsThis study suggested that R‐ZES implantation for the treatment of ISR was effective up to 9 months and showed favorable vascular responses on serial IVUS assessment.
Low‐Dose Heparin for Elective Percutaneous Coronary Intervention
Authors: LEE MICHAEL S. , OYAMA JARED , IQBAL ZAHID , TARANTINI GIUSEPPE 
Published: October 2013

AbstractObjectivesWe evaluated the safety and efficacy of low‐dose heparin (40 IU/kg) for elective percutaneous coronary intervention (PCI).BackgroundCurrent guidelines recommend a 70–100 IU/kg bolus of heparin for elective PCI, but this dose may be associated with increased bleeding risk. Low‐dose heparin may have an advantage in this regard, but has not been well studied.MethodsFrom January 2008 to October 2012, 300 patients underwent elective transfemoral PCI and were treated with an initial bolus of 40 IU/kg of heparin at the UCLA Medical Center. Dual antiplatelet therapy with clopidogrel and aspirin was administered prior to or just after diagnostic coronary angiography. The primary end‐point was the composite of cardiac death, myocardial infarction, urgent target vessel revascularization for ischemia, or major bleeding within 30 days after PCI.ResultsThe mean activating clotting time was 233 ± 28 seconds. The primary end‐point occurred in 2.3%. The cardiac death rate was 0.3% but was not related to the PCI. The myocardial infarction rate was 1.3%. Urgent target vessel revascularization occurred in 1 patient (0.3%). The major bleeding rate was 0.3%. No stent thrombosis occurred.ConclusionUsing a lower dose of heparin with dual antiplatelet therapy is safe and is associated with a low bleeding risk after transfemoral PCI while providing suppression of ischemic events. This may also represent a cost savings compared with other antithrombotic strategies. A randomized clinical trial comparing low‐dose heparin with bivalirudin in patients is required to determine the optimal anticoagulation strategy. (J Interven Cardiol 2014;27:58–62)