bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between microRNA-27a and efficacy of neoadjuvant chemotherapy in gastric cancer and its mechanism in gastric cancer cell growth and metastasis
Authors: Xu Chunlei , Cheng Hong , Li Na , Zhou Ning , Tang Xushan 
Published: March 2019

Abstract
Objective: The aim of the present study is to investigate the relationship between microRNA-27a (miR-27a) and the efficacy of neoadjuvant chemotherapy in gastric cancer (GC) and its mechanism in the growth and metastasis of GC cells.
Methods: The expression of miR-27a in serum of 74 GC patients received neoadjuvant chemotherapy was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Clinical value and prognosis of miR-27a expression in predicting the efficacy of neoadjuvant chemotherapy in GC were evaluated. Besides, GC cells with low miR-27a expression were transfected with miR-27a mimics, and cells with high miR-27a expression were transfected with miR-27a inhibitors and secreted frizzled-related protein 1 (SFRP1) siRNA. A series of experiments were applied for the determination of cell viability, invasion and migration of GC cells.
Results: After neoadjuvant chemotherapy, the expression of miR-27a in serum of GC patients decreased significantly. Additionally, the expression of miR-27a in GC cell line was significantly higher than that in normal gastric mucosa cell line. Meanwhile, after down-regulating the expression of miR-27a in GC cells, the mRNA and protein expression of SFRP1 increased, the proliferation rate of cells slowed down, and the ability of invasion and migration decreased. Furthermore, combined with low expression of miR-27a and SFRP1, the proliferation rate of GC cells increased and the ability of invasion and migration increased.
Conclusion: Collectively, our study highlights that the high expression of miR-27a indicates the poor efficacy and prognosis of neoadjuvant chemotherapy in GC patients. Down-regulation of miR-27a can inhibit the growth and metastasis of GC cells via up-regulation of SFRP1.
Endothelial-to-haematopoietic transition: an update on the process of making blood
Authors: Ottersbach Katrin 
Published: March 2019

Abstract
The first definitive blood cells during embryogenesis are derived from endothelial cells in a highly conserved process known as endothelial-to-haematopoietic transition (EHT). This conversion involves activation of a haematopoietic transcriptional programme in a subset of endothelial cells in the major vasculature of the embryo, followed by major morphological changes that result in transitioning cells rounding up, breaking the tight junctions to neighbouring endothelial cells and adopting a haematopoietic fate. The whole process is co-ordinated by a complex interplay of key transcription factors and signalling pathways, with additional input from surrounding tissues. Diverse model systems, including mouse, chick and zebrafish embryos as well as differentiation of pluripotent cells in vitro, have contributed to the elucidation of the details of the EHT, which was greatly accelerated in recent years by sophisticated live imaging techniques and advances in transcriptional profiling, such as single-cell RNA-Seq. A detailed knowledge of these developmental events is required in order to be able to apply it to the generation of haematopoietic stem cells from pluripotent stem cells in vitro — an achievement which is of obvious clinical importance. The aim of this review is to summarise the latest findings and describe how these may have contributed towards achieving this goal.
Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments
Authors: Perrin Sally L. , Samuel Michael S. , Koszyca Barbara , Brown Michael P. , Ebert Lisa M. , Oksdath Mariana , Gomez Guillermo A. 
Published: March 2019

Abstract
Glioblastoma is the deadliest form of brain cancer. Aside from inadequate treatment options, one of the main reasons glioblastoma is so lethal is the rapid growth of tumour cells coupled with continuous cell invasion into surrounding healthy brain tissue. Significant intra- and inter-tumour heterogeneity associated with differences in the corresponding tumour microenvironments contributes greatly to glioblastoma progression. Within this tumour microenvironment, the extracellular matrix profoundly influences the way cancer cells become invasive, and changes to extracellular (pH and oxygen levels) and metabolic (glucose and lactate) components support glioblastoma growth. Furthermore, studies on clinical samples have revealed that the tumour microenvironment is highly immunosuppressive which contributes to failure in immunotherapy treatments. Although technically possible, many components of the tumour microenvironment have not yet been the focus of glioblastoma therapies, despite growing evidence of its importance to glioblastoma malignancy. Here, we review recent progress in the characterisation of the glioblastoma tumour microenvironment and the sources of tumour heterogeneity in human clinical material. We also discuss the latest advances in technologies for personalised and in vitro preclinical studies using brain organoid models to better model glioblastoma and its interactions with the surrounding healthy brain tissue, which may play an essential role in developing new and more personalised treatments for this aggressive type of cancer.
United colours of chromatin? Developmental genome organisation in flies
Authors: Delandre Caroline , Marshall Owen J. 
Published: March 2019

Abstract
The organisation of DNA into differing forms of packaging, or chromatin, controls many of the cell fate decisions during development. Although early studies focused on individual forms of chromatin, in the last decade more holistic studies have attempted to determine a complete picture of the different forms of chromatin present within a cell. In the fruit fly, Drosophila melanogaster, the study of chromatin states has been aided by the use of complementary and cell-type-specific techniques that profile the marks that recruit chromatin protein binding or the proteins themselves. Although many questions remain unanswered, a clearer picture of how different chromatin states affect development is now emerging, with more unusual chromatin states such as Black chromatin playing key roles. Here, we discuss recent findings regarding chromatin biology in flies.
The role of the 12(S)-HETE/GPR31/12-HETER axis in cancer and ischemia–reperfusion injury
Authors: Napolitano Monica 
Published: March 2019

Abstract
The G protein-coupled receptors (GPCRs) constitute a large superfamily of seven transmembrane-spanning receptors that are activated by several classes of ligands, including bioactive lipids. GPCRs are attractive therapeutic targets for the treatment of human diseases, as they finely regulate a wide array of cellular functions. In this minireview, we summarized what is currently known about the G protein-coupled receptor GPR31/12-HETER. We highlighted, in particular, its structural similarity with human homologs, the biological functions of its recognized ligand 12(S)-hydroxyeicosatetraenoic acid (HETE), an arachidonic acid metabolite, and the role that GPR31/12-HETER-mediated signals play in cancer cell growth, invasion and metastasis, and in liver ischemia–reperfusion (IR) injury. Recent studies shed light and interest on the 12(S)-HETE/GPR31/12-HETER-activated signaling pathways and functions. The full spectrum of GPR31/12-HETER-mediated biological functions has yet to be characterized. Further studies are needed to identify other potential ligands, i.e. other than 12(S)-HETE. Another important remaining question is whether the multiple 12(S)-HETE-induced biological activities, including its role in diabetes, neurodegeneration, neuroprotection, and platelet function, occur via GPR31/12-HETER and/or involve the activation of other receptor molecules and pathways.
Unraveling the multiplex folding of nucleosome chains in higher order chromatin
Authors: Grigoryev Sergei A. , Schubert Michael 
Published: March 2019

Abstract
The DNA of eukaryotic chromatin and chromosomes is repeatedly supercoiled around histone octamers forming ‘beads-on-a-string’ chains of nucleosomes. The extent of nucleosome chain folding and DNA accessibility vary between different functional and epigenetic states of nuclear chromatin and change dramatically upon cell differentiation, but the molecular mechanisms that direct 3D folding of the nucleosome chain in vivo are still enigmatic. Recent advances in cell imaging and chromosome capture techniques have radically challenged the established paradigm of regular and hierarchical chromatin fibers by highlighting irregular chromatin organization and the importance of the nuclear skeletal structures hoisting the nucleosome chains. Here, we argue that, by analyzing individual structural elements of the nucleosome chain – nucleosome spacing, linker DNA conformations, internucleosomal interactions, and nucleosome chain flexibility – and integrating these elements in multiplex 3D structural models, we can predict the features of the multiplex chromatin folding assemblies underlying distinct developmental and epigenetic states in living cells. Furthermore, partial disassembly of the nuclear structures suspending chromatin fibers may reveal the intrinsic mechanisms of nucleosome chain folding. These mechanisms and structures are expected to provide molecular cues to modify chromatin structure and functions related to developmental and disease processes.
Zebra-stripe sources in the double-plasma resonance model of solar radio zebras
Authors: Karlický M. , Yasnov L. 
Published: March 2019

Context. Radio bursts with fine structures are used in diagnostics of solar flare plasmas, of which zebra structures are the most important. However, there is still a debate about their origin.Aims. The most probable model of zebras is that based on double-plasma resonance (DPR) instability. The paper wants to contribute to a verification of this model.Methods. We used analytical methods.Results. We studied the DPR model in two scenarios: a model with the zebra-stripe sources in a single loop and a model with the zebra-stripe sources moving through a fan of magnetic field lines. In the first case, we found several new relations among the parameters of zebra stripes and their sources, which can be used to analyze observed zebras and thus to verify if the zebra is generated according to the DPR model. These relations were derived for the zebra-stripe sources distributed along the loop and also for those having some extent in the loop radius. In the scenario with the moving zebra-stripe sources, we determined the parameters of the 14 December 2006 zebra and estimated a change of the ratio of magnetic field and density scales causing the change of zebra-stripe frequencies. In this case we found that this zebra can be also explained in the model with the zebra-stripe sources in a single loop. Both the interpretations are discussed.
Particularités de la paranoïa sensitive
Authors: Brémaud Nicolas 
Published: March 2019

L’auteur se propose de revenir sur ce délire bien particulier qu’est le délire de relation des sensitifs (ou paranoïa sensitive), isolé par Kretschmer en 1918. Si le nom de Kretschmer est assez peu cité dans la littérature, les « caractères » sensitifs mis en avant sont pourtant encore souvent repris dans la description de tableaux cliniques de certaines formes de paranoïa, et nous montrerons ainsi que ce délire est bien d’actualité. Après avoir exposé les grandes lignes de la conception kretschmérienne et donc les particularités de la paranoïa sensitive, nous proposons une courte revue de la littérature, la façon dont ce délire fut reçue dans le champ psychanalytique, et nous proposerons enfin en guise d’ouverture un regard lacanien qui permet à certains égards de rapprocher la paranoïa sensitive de la psychose dite « ordinaire ». Cette forme singulière de paranoïa se révèle bien différente du tableau classique dressé en son temps par Kraepelin, éloigné des délires systématisés et extra-ordinaires de type Schreber. Nous aurions affaire ici à des sujets décrits - avant le déclenchement du délire - comme des sujets sensibles, introvertis, timides, hyperémotifs, intériorisant les affects, réfrénant leurs pulsions, s’auto-dévalorisant, susceptibles, mal assurés dans leur relation à la sexualité, etc. Un événement, une « expérience vécue »(Erlebnis),souvent une remarque, un reproche, un regard, va déclencher le délire, comme la goutte d’eau faisant déborder le vase. Pas d’hallucination, pas de grand délire, mais un délire essentiellement de « relation », avec sentiment de persécution, sentiment surtout d’échec, d’insuffisance et d’humiliation, impression de malveillance de l’entourage, interprétations délirantes de menus faits du quotidien, ressentiment, insécurité, auto-dévalorisation. L’ensemble du tableau se situerait donc sur le plan relationnel. On peut dire de la conception de Kretschmer qu’elle rompt avec les conceptions déficitaires; en ce sens on peut la qualifier de psychodynamique. Nous verrons combien les descriptions fines qui ont été faites de ce tableau clinique sont dans le fond assez fréquemment rencontrées en pratique et qu’elles nous poussent à repenser le cadre de la paranoïa.
Neurovascular anatomy around the knee: Relevance of the dangers of self-drilling external fixator pin tips
Authors: Reipond Lucy , Trompeter Alex , Szarko Matthew 
Published: March 2019

Introduction: With external fixation of the femur and tibia, iatrogenic injury to neurovasculature from self-drilling tips of fixation pins is an important consideration in pin placement. Precise knowledge of the neurovascular anatomy in the distal femur and proximal tibia is important to limit potential pin misplacement.

Method: Six pin placement sites on six cadaveric legs were used in accordance with current placement techniques. After pin placement, the soft tissue around each pin was dissected and the distances between the pin tips and the surrounding neurovasculature were measured.

Results: The resultant data allow for a description of safe and unsafe corridors which can be used for external fixator pin placement. Safe sagittal insertion into the distal femur should consist of two pins: (1) 90 mm ± proximal from the proximal pole of the patella and 3 mm ± medially, (2) 55 mm ± proximal from the proximal pole of the patella and 2 mm ± laterally. Safe coronal insertion into the distal femur should consist of two pins: (1) 30 mm ± proximal to the lateral epicondyle, (2) 100 mm ± proximal to the lateral epicondyle. Safe proximal tibial pin placement should consist of two pins and be placed at an oblique angle: (1) 20 mm ± distal to the tibial tuberosity and 2 mm ± medially, (2) 55 mm ± distal to the tibial tuberosity and 2 mm ± medially.

Discussion: This study forms an investigation into the safe areas for placement of external fixator pins, within the distal femur and proximal tibia, specifically, detailing the best practice for pin placement in relation to the tips of the external fixation pins.
An innovative laparoscopic and endoscopic technique in an animal model: combined gastric full-thickness tumor resection
Authors: Morita Flavio , Sakai Christiano , Kawamoto Flavio , de Moura Eduardo , Sakai Paulo 
Published: March 2019

Abstract
Background and study aims The combination of endoscopy with laparoscopy for full-thickness gastric resection has received much attention. The advantage in using it is removak of the target lesion without resection of excessive normal tissue. The technique could prevent deformed scars, particularly at the cardia and in the prepyloric area. The aim of this protocol was to evaluate a new combined operation for full-thickness resection of the gastric wall.
Materials and methods Gastric subepithelial lesions in multiple topographic locations of the stomach were simulated in seven live pigs. Full-thickness gastric resection was undertaken and after assessment of the outcome, the animals were euthanized. The primary endpoint was accomplishment of the procedure following all steps in the new technique, in various gastric locations. The secondary endpoints were duration of the procedure, quality of specimen margins, and complications.
Results Resections were successful, complete, and complication-free, ensuring a safe surgical margin of healthy tissue. The procedure was completed in 50 minutes. No mucosal perforation or gas escape occurred.
Conclusions The combined technique was safe, effective and minimally invasive. No expensive materials were used. Lesion exposure, gastric content leakage, incomplete resection, and excessive normal tissue elimination were avoided. Human trials of this technique may be warranted.
Long Term Effects of Behavioural Interventions to Increase Exercise Among Breast Cancer Patients After Medical Rehabilitation: secondary Analysis of a Randomized Controlled Trial
Authors: Exner Anne-Kathrin , Kähnert Heike , Sauzet Odile , Leibbrand Birgit , Berg-Beckhoff Gabriele 
Published: March 2019

Abstract
Purpose Physical activity (PA) as secondary prevention for breast cancer patients has many positive effects. To evaluate the effectiveness of an intervention involving behavioural and volitional strategies to increase exercise.
Materials and Methods The study designed as a randomized controlled trail with 2 follow-up (6 and 12 months after rehabilitation). 1,143 participants were randomized to one of the 4 study groups. Group differences were analysed by multi-level-models.
Results After rehab, patients with the combined modules, aftercare-planning (AP) and telephone-support (TS), did exercise 69 min per week (95% CI: 42.85; 94.90) more than the control group. Inactive patients at the beginning of the rehabilitation benefit from the combined intervention. The phone-based intervention alone did not show any effect.
Discussion and Conclusion Rehab with the AP module combined with the TS module is associated with patients undertaking more PA.
Feasibility and safety of third-space endoscopic full-thickness resection in ex vivo and in vivo porcine models
Authors: Goto Osamu , Sasaki Motoki , Akimoto Teppei , Tatsuguchi Atsushi , Kaise Mitsuru , Iwakiri Katsuhiko , Yahagi Naohisa 
Published: March 2019

Abstract
Background and study aims Endoscopic full-thickness resection (EFTR) involves several technical issues that need to be addressed. We devised a novel technique termed third-space EFTR and investigated its feasibility and safety in animal models.
Methods Third-space EFTR was performed in three isolated porcine stomachs (ex vivo) and four live pigs (in vivo, 1-week survival). The technique involved a circumferential mucosal incision, submucosal tunnelling on the proximal side, endoscopic suturing of the surrounding mucosa, a circumferential seromuscular incision in the submucosal tunnel, transoral retrieval and entry site closure of the tunnel. The technical outcomes were investigated.
Results In the ex vivo study, the procedure was successfully completed with R0 resection. In the in vivo study, the procedure was completed in all pigs; however, R0 resection failed in one pig owing to snaring resection. All pigs survived without severe adverse events.
Conclusions Our findings indicate that third-space EFTR is feasible and safe. This technique may be useful as a minimally invasive endoscopic option for reliable treatment of small gastric submucosal tumours.
Commercial Pharmacogenetic Tests in Psychiatry: Do they Facilitate
the Implementation of Pharmacogenetic Dosing Guidelines?
Authors: Fan Mikayla , Bousman Chad A. 
Published: March 2019

Abstract
Introduction Expert groups have created dosing guidelines to
facilitate the implementation of pharmacogenetic knowledge into clinical
practice and commercial pharmacogenetic tests are becoming increasingly
accessible. However, the extent to which these commercial tests facilitate
the implementation of dosing guidelines is not clear.
Methods Gene-drug pairs included on 22 commercial pharmacogenetic
test panels were extracted and cross-referenced with the 74 gene-drug pairs
with dosing guidelines in the Pharmacogenetics Knowledgebase, with
particular attention given to the 28 gene-drug pairs relevant to
psychiatry.
Results On average, 70% of the 28 gene-drug pairs most
relevant to psychiatry were covered by the examined tests. Six gene-drug
pairs (CYP2D6-venlafaxine, CYP2D6-paroxetine,
CYP2D6-amitriptyline, CYP2C19-sertraline,
CYP2C19-citalopram, CYP2C19-amitriptyline) were included by
all tests. Gene-drug pairs included on less than half of the test panels
included HLA-B-phenytoin (14%), HLA-A-carbamazepine
(24%), HLA-B-carbamazepine (29%), and
CYP2D6-zuclopenthixol (43%).
Discussion Most commercial pharmacogenetic tests we examined are
well-equipped to facilitate implementation of the majority of dosing
guidelines relevant to psychiatry but are limited in their ability to
facilitate implementation of the full spectrum of dosing guidelines
currently available.
Non-Vitamin K Oral Anticoagulants in Comparison to Phenprocoumon in Geriatric and Non-Geriatric Patients with Non-Valvular Atrial Fibrillation
Authors: Hohmann Christopher , Hohnloser Stefan H. , Jacob Josephine , Walker Jochen , Baldus Stephan , Pfister Roman 
Published: March 2019

AbstractGeriatric characteristics such as high age, multi-morbidity, polypharmacy and frailty are common in patients with atrial fibrillation (AF). In a retrospective study using a German claims database, effectiveness (ischaemic stroke/systemic embolism) and safety (intracerebral, gastrointestinal and major extracranial bleeding) were compared in patients with non-valvular AF starting non-vitamin K oral antagonists (NOACs) (apixaban, dabigatran and rivaroxaban) and phenprocoumon. Cox proportional hazards models were used to calculate adjusted hazard ratios, and interaction terms of the treatment group and geriatric status (defined by age ≥75 years, frailty, ≥ 4 co-morbidities and polypharmacy) were entered into the model. A total of 42,562 and 27,939 patients initiated NOAC and phenprocoumon treatment (mean age 74 years ± 11, 51% male) with a follow-up time of 147,785 person-years. Note that 52.9% of patients were elderly, 50.8% were frail, 37.0% were co-morbid and 46.5% had polypharmacy. NOAC use was not associated with effectiveness and gastrointestinal bleeding, neither in geriatric nor in non-geriatric patients. The hazard of major extracranial and intracranial bleeding was significantly decreased for NOAC use, with similar risk reduction in geriatric and non-geriatric patients: major extracranial bleeding 0.70 (95% confidence interval [CI], 0.56–0.87) to 0.73 (95% CI, 0.60–0.89) for the geriatric groups and 0.71 (95% CI, 0.56–0.93) to 0.76 (0.59–0.98) for the non-geriatric groups (p-values for interaction > 0.6); and intracranial bleeding 0.52 (95% CI, 0.39–0.69) to 0.59 (95% CI, 0.47–0.73) for the geriatric groups and 0.54 (95% CI, 0.37–0.79) to 0.65 (95% CI, 0.49–0.86) for the non-geriatric groups (p-values for interaction > 0.2). Hence, NOACs showed similar effectiveness and superior safety in geriatric and non-geriatric patients.