bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventional Pain Procedures in Physical Medicine and Rehabilitation Residencies
Authors: Agarwal Sanjeev , Cicone Caitlin , Chang Philip 
Published: November 2017

Abstract
Exposure to interventional pain procedures is now a required component of training in physical medicine and rehabilitation residencies as mandated by the Accreditation Council for Graduate Medical Education. Data regarding resident exposure and competency in these procedures remain limited. Objectives were to determine the volume and type of exposure physical medicine and rehabilitation residents have to interventional pain procedures and to obtain faculty-perceived opinions regarding competency of incoming fellows as it pertains to interventional pain management. Online surveys were sent to program directors of physical medicine and rehabilitation residencies and fellowship directors of interventional spine, sports medicine, and pain medicine fellowships. Surveys inquired about educational methods, the volume of procedures in which residents actively participate, and faculty-perceived competency of trainees performing procedures. Thirty-nine residency programs and 27 fellowships responded to the surveys. Of the 39 residencies that responded, there was great variation in the exposure residents receive. Most programs reported that residents have moderate exposure to common procedures such as ultrasound-guided knee injections and lumbar epidural injections. In addition, while most residency program directors report graduates to be “fairly prepared” (33%) to “well prepared” (20.5%) with regard to spine procedures, most fellowship directors (63%) describe incoming fellows to be at the “beginner” level.
Computed Tomographic Artifacts in Maxillofacial Surgery
Authors: Kim Jun Ho , Arita Emiko Saito , Pinheiro Lucas Rodrigues , Yoshimoto Marcelo , Watanabe Plauto Christopher Aranha , Cortes Arthur Rodriguez Gonzalez 
Published: November 2017

Objectives:
The present study aimed to present 4 cases and to undertake a systematic review on the current knowledge of the impact of cone beam computed tomographic (CBCT) artifacts on oral and maxillofacial surgical planning and follow-up.

Methods:
The MEDLINE (PubMed) database was searched for the period from February 2004 to February 2017, for studies on the impact of CBCT artifacts on surgical planning of oral and maxillofacial surgeries. The PRISMA statement was followed during data assessment and extraction. As a result, data extraction included information regarding: the use of CBCT to plan or follow-up oral and maxillofacial surgeries, presence and type identification of a CBCT artifact, and details on the impact of artifacts on image quality and/or surgical planning. Four cases were selected to illustrate the topic.

Results:
The search strategy yielded 408 publications in MEDLINE (PubMed). An initial screening of the publications was performed using abstracts and key words. After application of exclusion criteria, a total of 11 studies were finally identified as eligible to be discussed. Studies revealed 3 main types of artifact: beam hardening, streak, and motion artifacts. Most of the studies suggest that artifacts significantly affect oral and maxillofacial surgical planning and follow-up, despite of allowing for identification of metal projectiles in cases of maxillofacial trauma.

Conclusion:
CBCT artifacts have a significant impact on oral and maxillofacial surgical planning and follow-up.
Total Cheek Reconstruction Using the Pre-Expanded Medial Arm Flap With Functional and Aesthetic Donor Site Closure
Authors: Xue Bingjian , Liu Yuanbo , Zhu Shan , Zang Mengqing , Chen Bo , Li Shanshan 
Published: November 2017

Abstract
This clinical study aimed at introducing a reconstructive method for total cheek soft tissue defects using the pre-expanded medial arm flap and to maximally reduce donor site morbidities simultaneously. A retrospective review of data was performed for 3 patients requiring the pre-expanded medial arm flap to reconstruct total cheek defects. The donor site in the medial arm was primarily closed using a pedicle parascapular or thoracodorsal artery perforator flap. All patients had a total unilateral cheek defect after lesion removal. Three pre-expanded medial arm flaps measuring 17 × 11 cm, 22 × 15 cm, and 20 × 15 cm were separately used for cheek defect reconstruction. The donor sites in the medial arm were closed using a pedicle parascapular flap, measuring 22 × 9.5 cm, and 2 pedicle thoracodorsal artery perforator flaps, measuring 22 × 10 cm and 23 × 10 cm. No major complications occurred in any patient. Patients were followed up for 3, 12, and 18 months. Patients (and/or their family members) were satisfied with the final outcomes. Total cheek defect reconstruction using a pre-expanded medial arm flap, with the donor site closed using a pedicle axial back flap, can not only provide sufficient tissue for cheek resurfacing, but also guarantee primary donor site closure and could be an alternative reconstructive option for patients who have a total cheek defect.
Is Osteoplasty With Unilateral Osteotomy Effective in the Correction of the Crooked Nose?
Authors: Koçak Ilker , Gökler Ozan , Şentürk Erol 
Published: November 2017

Objective:
The crooked nose is frequently observed, and a significant number of correction methods have previously been described. Nevertheless, the condition remains a challenging problem for rhinoplastic surgeons. Here, the authors present a technique that the authors have used to correct a crooked nose in selected patients.

Methods:
A total of 23 patients underwent surgery for a C-shaped crooked nose, and were followed up for an average of 11.4 months. Pre- and postoperative photographs were taken, and these were analyzed to evaluate the results.

Results:
Osteoplasty and unilateral osteotomy were carried out in all 23 patients and a spreader graft was contralaterally placed. Unilateral osteoplasty was conducted in 17 patients, while bilateral osteoplasty was performed in 6 patients. In 19 patients, a single spreader graft was sufficient, but it was necessary to use a double spreader graft in 4 patients. In summary, 23 C-shaped crooked noses were corrected with osteoplasty plus unilateral osteotomy.

Conclusions:
Osteoplasty plus unilateral osteotomy, combined with a contralateral spreader graft, is an efficient method that can be safely used in the correction of a C-shaped crooked nose.
Human Cytomegalovirus Infection Increases Both Antibody- and Non–Antibody-Dependent Cellular Reactivity by Natural Killer Cells
Authors: Michelo Clive M. , van Cranenbroek Bram , Touw Peran , Claas Frans H. J. , van der Meer Arnold , Joosten Irma 
Published: November 2017

Background
Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity.

Methods
We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells.

Results
First, we showed that within the NKG2C+ NK cells, it is specifically the NKG2C+/A− subset that is enriched in CMV+ individuals. We then observed that in particular the NK cell antibody-dependent cell mediated cytotoxicity (ADCC), but also non-ADCC alloreactivity toward HLA-positive target cells was increased in CMV+ individuals as compared to CMV− ones. This enhanced ADCC as well as non-ADCC NK cell reactivity in CMV+ individuals was particularly characterized by a significantly higher number of ILT2+ and NKG2C+ NK cells that possessed cytolytic activity and/or produced IFNγ in response to HLA-positive target cells.

Conclusions
With regard to organ transplantation, these data suggest that CMV infection enhances NK cell alloreactivity, which may pose an additional adverse effect on graft survival, especially in the presence of donor specific antibodies.
Global orientation in space and the lateralization of brain functions
Authors: Dieterich Marianne , Brandt Thomas 
Published: November 2017

Purpose of reviewThe functional role of the vestibular system for multisensory orientation and sensorimotor control is reviewed with a special focus on hemispherical lateralization and its consequences for neurological disorders of higher cortical function.Recent findingsThe peripheral and central vestibular systems are bilaterally organized with ipsilateral and contralateral ascending pathways and two multisensory cortical networks in the right and left hemisphere. The vestibular cortical system shows a structural and functional lateralization with a dominance of the right hemisphere in right-handers and the left hemisphere in left-handers. Although the vestibular brainstem pathways are evenly distributed at lower pontine level, an increasing lateralization builds up because of an asymmetric number of pontine and mesencephalic crossing fibers from left to right in right-handers. This vestibular lateralization causes more frequent and more severe disorders of higher sensorimotor dysfunction in lesions of the right hemisphere such as in hemispatial neglect and the pusher syndrome.SummaryThere is evidence that multisensory higher vestibular functions including large-scale spatial orientation, spatial memory and navigation are dominated by the right temporo-parietal cortex. A beneficial result of lateralization of brain functions in healthy individuals is that it enables the individual to produce a global sensorimotor response even in case of a mismatch of the actual right and left sensory inputs. The consequence for neurology, however, is that lesions in the dominant hemisphere cause more frequently and more severe disorders such as the visuo-spatial hemineglect and the pusher syndrome.
Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype
Authors: Oushy Soliman , Hellwinkel Justin E. , Wang Mary , Nguyen Ger J. , Gunaydin Dicle , Harland Tessa A. , Anchordoquy Thomas J. , Graner Michael W. 
Published: November 2017

Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting.
This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Why the need and how to approach the functional diversity of extracellular vesicles
Authors: Tkach Mercedes , Kowal Joanna , Théry Clotilde 
Published: November 2017

In the past decade, cell-to-cell communication mediated by exosomes has attracted growing attention from biomedical scientists and physicians, leading to several recent publications in top-tier journals. Exosomes are generally defined as secreted membrane vesicles, or extracellular vesicles (EVs), corresponding to the intraluminal vesicles of late endosomal compartments, which are secreted upon fusion of multi-vesicular endosomes with the cell's plasma membrane. Cells, however, were shown to release other types of EVs, for instance, by direct budding off their plasma membrane. Some of these EVs share with exosomes major biophysical and biochemical characteristics, such as size, density and membrane orientation, which impose difficulties in their efficient separation. Despite frequent claims in the literature, whether exosomes really display more important patho/physiological functions, or are endowed with higher potential as diagnostic or therapeutic tools than other EVs, is not yet convincingly demonstrated. In this opinion article, we describe reasons for this lack of precision knowledge in the current stage of the EV field, we review recently described approaches to overcome these caveats, and we propose ways to improve our knowledge on the respective functions of distinct EVs, which will be crucial for future development of well-designed EV-based clinical applications.This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Functional role of extracellular vesicles and lipoproteins in the tumour microenvironment
Authors: Menard Julien A. , Cerezo-Magaña Myriam , Belting Mattias 
Published: November 2017

Cancer can be regarded as an invasive organ that exhibits unique plasticity provided by coordinated, cancer cell-stromal cell communication in the tumour microenvironment. Typical stress factors in the tumour niche, such as hypoxia and acidosis, are major drivers and modulators of these events. Recent findings reveal an important role of extracellular vesicles and lipoproteins in cancer cell adaption to exogenous stress. Adaptive mechanisms include stimulation of angiogenesis and increased metastasis. Here, we will discuss the similarities and distinct features of these endogenous nanoparticles and their roles as signalosomes and nutrient sources in cancer. We will focus on the accumulating evidence for a central role of cell-surface heparan sulphate proteoglycans in the uptake of extracellular vesicles and lipoproteins.
This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Tumour–adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles
Authors: Robado de Lope Lucía , Alcíbar Olwen Leaman , Amor López Ana , Hergueta-Redondo Marta , Peinado Héctor 
Published: November 2017

During metastasis, tumour cells must communicate with their microenvironment by secreted soluble factors and extracellular vesicles. Different stromal cell types (e.g. bone marrow–derived cells, endothelial cells and fibroblasts) influence the growth and progression of tumours. In recent years, interest has extended to other cell types in the tumour microenvironment such as adipocytes and adipose tissue–derived mesenchymal stem cells. Indeed, obesity is becoming pandemic in some developing countries and it is now considered to be a risk factor for cancer progression. However, the true impact of obesity on the metastatic behaviour of tumours is still not yet fully understood. In this ‘Perspective’ article, we will discuss the potential influence of obesity on tumour metastasis, mainly in melanoma, breast and ovarian cancer. We summarize the main mechanisms involved with special attention to the role of extracellular vesicles in this process. We envisage that besides having a direct impact on tumour cells, obesity systemically preconditions the tumour microenvironment for future metastasis by favouring the formation of pro-inflammatory niches.This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
MicroRNAs and miRceptors: a new mechanism of action for intercellular communication
Authors: Fabbri Muller 
Published: November 2017

MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) that control the expression of target genes by modulating (usually inhibiting) their translation into proteins. This ‘traditional’ mechanism of action of miRs has been recently challenged by new discoveries pointing towards a role of miRs as ‘hormones’, capable of binding to proteic receptors (miRceptors) and triggering their downstream signalling pathways. These findings harbour particular significance within the tumour microenvironment (TME), defined as the variety of non-cancerous cells surrounding cancer cells, but are relevant also for other diseases. In recent years it has become clearer that the TME does not passively assist the growth of cancer cells but contributes to its biology. Some of the mediators of the intercellular communication between cancer cells and TME are miRs shuttled within exosomes, a subtype of cellular released extracellular vesicles. This article will highlight the most recent findings on the biological implications of miR–miRceptor interactions for the biology of the TME and other diseases, and will provide some perspectives on the future development of this fascinating research.This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
An apoptosis-driven ‘onco-regenerative niche’: roles of tumour-associated macrophages and extracellular vesicles
Authors: Gregory Christopher D. , Paterson Margaret 
Published: November 2017

The cell-death programme, apoptosis, is well established as a tumour suppressor mechanism. Paradoxically, high levels of apoptosis in tumours are closely coupled with poor prognosis. Indeed, where it has been studied, cell loss is a striking feature of high-grade cancers, illustrating the importance of considering malignant disease as an imbalance between cell gain and cell loss that favours cell gain rather than as a unidirectional disorder of cell gain alone. In addition to orchestrating cell loss, apoptosis can signal regenerative responses—for example compensatory proliferation—in neighbouring cells. Accumulating evidence suggests that normal tissue repair and regenerative processes are hijacked in the malignant tissue microenvironment such that cancer may be likened to a ‘wound that fails to stop repairing’. We have proposed that a critical requirement for the successful growth, progression and re-growth of malignant tumours is a complex milieu, conceptually termed the ‘onco-regenerative niche’, which is composed, in addition to transformed neoplastic cells, of a network of normal cells and factors activated as if in tissue repair and regeneration. Our work is based around the hypothesis that tumour cell apoptosis, macrophage activation and endothelial activation are key, interlinked elements of the onco-regenerative niche and that apoptotic tumour cell–derived extracellular vesicles provide critical intercellular communication vehicles of the niche. In aggressive B-cell lymphoma, tumour cell apoptosis promotes both angiogenesis and the accumulation of pro-tumour macrophages in the lymphoma microenvironment. Furthermore, apoptotic lymphoma-derived extracellular vesicles have potent pro-tumour potential. These findings have important implications for the roles of apoptosis in regulation of malignant diseases and for the efficacy of apoptosis-inducing anti-cancer therapies.
This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Spatial variation of the native colon microbiota in healthy adults
Authors: Flynn Kaitlin J. , Ruffin Mack T. , Turgeon D. Kim , Schloss Patrick D. 
Published: November 2017

AbstractThe microbiome has been implicated in the development of colorectal cancer (CRC) and inflammatory bowel diseases (IBD). The specific traits of these diseases vary along the axis of the digestive tract. Further, variation in the structure of the gut microbiota has been associated with both diseases. Here we profiled the microbiota of the healthy proximal and distal mucosa and lumen to better understand how bacterial populations vary along the colon. We used a two-colonoscope approach to sample proximal and distal mucosal and luminal contents from the colons of 20 healthy subjects that had not undergone any bowel preparation procedure. The biopsies and home-collected stool were subjected to 16S rRNA gene sequencing and Random Forest classification models were built using taxa abundance and location to identify microbiota specific to each site. The right mucosa and lumen had the most similar community structures of the five sites we considered from each subject. The distal mucosa had higher relative abundance ofFinegoldia, Murdochiella, Peptoniphilus, PorphyromonasandAnaerococcus. The proximal mucosa had more of the generaEnterobacteriaceae, BacteroidesandPseudomonas. The classification model performed well when classifying mucosal samples into proximal or distal sides (AUC = 0.808). Separating proximal and distal luminal samples proved more challenging (AUC = 0.599) and specific microbiota that differentiated the two were hard to identify. By sampling the unprepped colon, we identified distinct bacterial populations native to the proximal and distal sides. Further investigation of these bacteria may elucidate if and how these groups contribute to different disease processes on their respective sides of the colon.
A GenoChemetic strategy for derivatization of the violacein natural product scaffold
Authors: Lai Hung-En , Obled Alan M. C. , Chee Soo Mei , Morgan Rhodri M. , Lynch Rosemary , Sharma Sunil V. , Moore Simon J. , Polizzi Karen M. , Goss Rebecca J. M. , Freemont Paul S. 
Published: November 2017

AbstractNatural products and their analogues are often challenging to synthesise due to their complex scaffolds and embedded functional groups. Solely relying on engineering the biosynthesis of natural products may lead to limited compound diversity. Integrating synthetic biology with synthetic chemistry allows rapid access to much more diverse portfolios of xenobiotic compounds which may accelerate the discovery of new therapeutics. As a proof-of-concept, by supplementing an Escherichia coli strain expressing the violacein biosynthesis pathway with 5-bromo-tryptophan in vitro or tryptophan 7-halogenase RebH in vivo, 6 halogenated analogues of violacein or deoxyviolacein were generated, demonstrating promiscuity of the violacein biosynthesis pathway. Furthermore, 20 new derivatives were generated from 5-brominated violacein analogues via Suzuki-Miyaura cross-coupling reaction directly using the crude extract without prior purification. Herein, we demonstrate a flexible and rapid approach to access diverse chemical space that can be applied to a wide range of natural product scaffolds.