bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the Road to Recovery: Shorter Stays and Satisfied Patients in Posterior Spinal Fusion
Authors: Rao Rameshwar R. , Hayes MaryAnn , Lewis Cathy , Hensinger Robert N. , Farley Frances A. , Li Ying , Caird Michelle S. 
Published: May 2016

Background:
Adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF) experience variations in their hospital care, which may lead to differences in objective and patient-reported outcomes. The purpose of this study was to demonstrate that using plan of care—educating families preoperatively and standardizing some aspects of care—would decrease time to mobility and time to discharge while maintaining pain control and patient satisfaction.

Methods:
Chart review was conducted in 3 groups—preprotocol (December 2008 to December 2009, n=51), first protocol (December 2, 2009 to July 24, 2013, n=100), and second protocol (July 25, 2013 to June 1, 2014, n=39)—to track pain scores (0 to 10), time to regular diet, Foley catheter removal, epidural catheter removal, mobility, and discharge. Patient satisfaction surveys (0 to 10) were administered before discharge. Statistical analysis was performed using a 1-way analysis of variance test with Tukey post hoc analysis.

Results:
Average pain scores were similar in all groups. Time to sitting was significantly reduced in both first protocol (27.2±9.8 h, P=1×10−8) and second protocol (28.4±13.6 h, P=3×10−5) compared with preprotocol (40.2±15.4 h). Time to discharge was significantly lower in second protocol (84.3±27.2 h, P=0.036) compared with first protocol (98.4±27.8 h). Patient satisfaction with care was significantly higher in first protocol (9.1/10, P=2×10−6) and second protocol (8.6/10, P=5×10−4) compared with preprotocol (6.5/10).

Conclusions:
By educating families preoperatively and standardizing portions of postoperative care in PSF for AIS, pain scores were significantly reduced while overall satisfaction remained high. Specifically, by removing the epidural and Foley catheters on postoperative day 2, time to discharge was dramatically decreased by 15 hours. The application of a multidisciplinary, evidence-driven plan of care for AIS patients undergoing PSF improves throughput and has beneficial effects on objective and patient-reported outcomes.

Level of Evidence:
Level III—retrospective case series.
Growth Patterns of the Neurocentral Synchondrosis (NCS) in Immature Cadaveric Vertebra
Authors: Blakemore Laurel , Schwend Richard , Akbarnia Behrooz A. , Dumas Megan , Schmidt John 
Published: May 2016

Study Design:
Gross anatomic study of osteological specimens.

Objectives:
To evaluate the age of closure for the neurocentral synchondrosis (NCS) in all 3 regions of the spine in children aged 1 to 18 years old.

Summary of Background Data:
The ossification of the human vertebra begins from a vertebral body ossification center and a pair of neural ossification centers located within the centrum called the NCS. These bipolar cartilaginous centers of growth contribute to the growth of the vertebral body, spinal canal, and posterior elements of the spine. The closure of the synchondroses is dependent upon location of the vertebra and previous studies range from 2 to 16 years of age. Although animal and cadaveric studies have been performed regarding NCS growth and early instrumentation’s effect on its development, the effects of NCS growth disturbances are still not completely understood.

Methods:
The vertebrae of 32 children (1 to 18 y old) from the Hamann-Todd Osteological collection were analyzed (no 2 or 9 y old specimens available). Vertebrae studied ranged from C1 to L5. A total of 768 vertebral specimens were photographed on a background grid to allow for measurement calibration. Measurements of the right and left NCS, pedicle width at the NCS, and spinal canal area were taken using Scandium image-analysis software (Olympus Soft Imaging Solutions, Germany). The percentage of the growth plate still open was found by dividing the NCS by the pedicle width and multiplying by 100. Data were analyzed with JMP 11 software (SAS Institute Inc., Cary, NC).

Results:
The NCS was 100% open in all 3 regions of the spine in the 1- to 3-year age group. The cervical NCS closed first with completion around 5 years of age. The lumbar NCS was nearly fully closed by age 11. Only the thoracic region remained open through age 17 years. The left and right NCS closed simultaneously as there was no statistical difference between them. In all regions of the spine, the NCS appeared to close sooner in males than in females. Spinal canal area increased with age up to 12 years old in the cervical and thoracic spine but did not significantly change after age 3 in the lumbar spine.

Conclusions:
In conclusion, closure of the NCS differed among the cervical, thoracic, and lumbar spine regions. The NCS reached closure in males before females even though females mature faster and reach skeletal maturity sooner than males. However, it is not determined whether the continued open NCS in females to a later age may be a factor in their increased rate of scoliosis.
Immune-mediated respiratory adverse events of checkpoint inhibitors
Authors: Tabchi Samer , Messier Christine , Blais Normand 
Published: May 2016

Purpose of review
Immune checkpoint inhibitors have demonstrated remarkable efficacy with durable responses in the treatment of various malignancies. This new class of therapeutic agents is associated with a toxicity profile that differs from conventional cytotoxic therapy. The present review is focused on one of these toxicities affecting the respiratory system.

Recent findings
Many types of immune-related adverse events (irAEs) have been identified since the emergence of checkpoint inhibitors including colitis, nephritis, myasthenia gravis-like syndromes, acute interstitial nephritis, pneumonitis, and endocrinopathies. Although pneumonitis is relatively less frequent than other irAEs, this toxicity is by no means inconsequential as it has led to treatment-related deaths during the initial testing phases.

Summary
Immune-mediated pneumonitis is a potentially serious but relatively infrequent adverse event associated with the use of immune checkpoint inhibitors. IrAEs can be challenging for oncologists who are still unfamiliar with the early presenting symptoms and subsequent management of these toxicities, especially in the context of a rapidly expanding science. A high index of suspicion for pneumonitis must be maintained in patients receiving checkpoint inhibitors and who present new onset respiratory symptoms because this type of toxicity can be severe and potentially fatal.
Will clinical heterogeneity of neuroendocrine tumors impact their management in the future? Lessons from recent trials
Authors: Cives Mauro , Soares Heloisa P. , Strosberg Jonathan 
Published: May 2016

Purpose of review
Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms arising from the diffuse neuroendocrine system. In the last few years, advances in our understanding of the biology of these tumors have translated into an expansion of treatment options for patients with NETs. Current treatment modalities include somatostatin analogs (SSAs), radiolabeled SSAs, targeted agents, cytotoxic drugs and liver-directed therapies for the management of metastatic disease.

Recent findings
Recent studies have expanded the role of SSAs in gastroenteropancreatic (GEP)-NETs, and everolimus has shown robust antitumor activity across a broad range of NETs of the lung and GEP tract. The radiolobeled SSA 177Lu-DOTATATE has been investigated in a randomized phase III trial, and has demonstrated exceptional efficacy and tolerability in patients with progressive midgut NETs. The new serotonin inhibitor telotristat etiprate has shown significant activity in the palliation of symptoms of carcinoid syndrome, and its approval by regulatory authorities is expected soon.

Summary
The field of NETs has been transformed from one dominated by limited treatment options to one characterized by an increasing number of therapeutic agents and active clinical trials. Navigating the current therapeutic algorithm may be challenging, and requires an understanding both of the heterogeneity of NETs and of characteristics that are shared by NETs across tumor subtypes.
The slow-pull capillary technique increases the quality of endoscopic ultrasound fine needle biopsy samples in solid pancreatic lesions
Authors: El Haddad Rana , Barret Maximilien , Beuvon Frédéric , Grabar Sophie , Leblanc Sarah , Terris Benoit , Coriat Romain , Chaussade Stanislas , Prat Frédéric 
Published: May 2016

Introduction
Endoscopic ultrasound-guided sampling is used routinely for the diagnosis of solid pancreatic masses. We aimed to compare the standard suction technique with the recently described ‘slow-pull’ technique.

Patients and methods
Patients with a solid pancreatic mass of more than 2 cm undergoing endoscopic ultrasound-guided fine needle biopsy with the same endoscopist using a 22 G core biopsy needle were included in the study. Patients had a first suction pass, followed by either another suction pass or a slow-pull pass. The rate of samples contributive to the diagnosis, cellularity, presence of tissue microfragments, and blood contamination were assessed and compared between each pass and each technique.

Results
A total of 98 patients with a lesion diameter of 33.1±10 mm were analyzed. Lesions were adenocarcinomas in 83%, neuroendocrine tumors in 6%, and benign lesions in 11% of the cases. The rate of contributive samples of the first suction pass, the slow-pull pass, and the second suction pass were 96.9, 97.9, and 90.2%, respectively (P=NS). The slow-pull capillary technique, compared with the suction technique, provided samples with better cellularity, higher proportion of representative and tumor cells, and more tissue microfragments (P=0.002, 0.0004, 0.006, and 0.005, respectively).

Conclusion
Endoscopic ultrasound-guided fine needle biopsy sampling of solid pancreatic lesions using the slow-pull technique yielded overall outcomes similar to the standard suction technique in terms of diagnostic performance. However, the slow-pull capillary technique improved the histological quality of the samples, mainly through a higher proportion of tissue microfragments and tumor cells.
Update on mandibular condylar fracture management
Authors: Weiss Joshua P. , Sawhney Raja 
Published: May 2016

Purpose of review
Fractures of the mandibular condyle have provided a lasting source of controversy in the field of facial trauma. Concerns regarding facial nerve injury as well as reasonable functional outcomes with closed management led to a reluctance to treat with an open operative intervention. This article reviews how incorporating new technologies and surgical methods have changed the treatment paradigm.

Recent findings
Multiple large studies and meta-analyses continue to demonstrate superior outcomes for condylar fractures when managed surgically. Innovations, including endoscopic techniques, three-dimensional miniplates, and angled drills provide increased options in the treatment of condylar fractures. The literature on pediatric condylar fractures is limited and continues to favor a more conservative approach.

Summary
There continues to be mounting evidence in radiographic, quality of life, and functional outcome studies to support open reduction with internal fixation for the treatment of condylar fractures in patients with malocclusion, significant displacement, or dislocation of the temporomandibular joint. The utilization of three-dimensional trapezoidal miniplates has shown improved outcomes and theoretically enhanced biomechanical properties when compared with traditional fixation with single or double miniplates. Endoscopic-assisted techniques can decrease surgical morbidity, but are technically challenging, require skilled assistants, and utilize specialized equipment.
Correction of saddle and short noses
Authors: Lee Ho Jun , Jang Yong Ju 
Published: May 2016

Purpose of review
The review summarizes the basic concepts and recent updates on the management of saddle and short noses, with a particular focus on the selection of septal reconstruction techniques and dorsal augmentation material.

Recent findings
Different techniques have been reported for septal cartilage reconstruction, including various combinations of extended spreader and caudal septal extension grafts, as well as L-strut grafts. For dorsal augmentation, materials that help avoid costal cartilage warping including, diced costal cartilage with or without fascia, costal cartilage obtained by oblique cutting, diced conchal cartilage with perichondrial attachments, and lipofilling of the nasal dorsum have been reported.

Summary
The article highlights the importance of rebuilding the septal cartilage support system by the proper use of costal cartilage and selection of an appropriate technique for the successful management of saddle and short noses. In addition, the importance of selecting suitable dorsal augmentation materials and other adjunctive maneuvers are emphasized.
Tendon Regeneration with Tendon Hydrogel–Based Cell Delivery: A Comparison of Fibroblasts and Adipose-Derived Stem Cells
Authors: Chattopadhyay Arhana , Galvez Michael G. , Bachmann Michael , Legrand Anais , McGoldrick Rory , Lovell Alberto , Jacobs Mollie , Crowe Chris , Umansky Elise , Chang James 
Published: May 2016

Background:
Tendon hydrogel is a promising biomaterial for improving repair strength after tendon injury. This study compares the capacity of fibroblasts and adipose-derived stem cells to proliferate, survive, and acquire tenogenic properties when seeded into tendon hydrogel in vitro and in vivo.

Methods:
The effect of cell density on hydrogel contraction was measured macroscopically. To assess tenogenic properties, RNA was isolated from cells seeded in vitro in hydrogel, and tenocyte markers were quantified. To assess in vitro proliferation and survival, MTS and live-dead assays were performed. Finally, to assess the in vivo survival of cells in hydrogel, subcutaneous injections were performed on rats and in vivo imaging was performed.

Results:
At 0.5 million cells/ml, both the fibroblasts and adipose-derived stem cells induced minimal hydrogel contraction compared with higher cellular concentrations. Fibroblasts and adipose-derived stem cells seeded at 0.5 million cells/ml in tendon hydrogel up-regulated several tenocyte markers after 1 week. On MTS assay, fibroblasts and adipose-derived stem cells proliferated in hydrogel at similar rates. On live-dead assay, fibroblasts survived longer than adipose-derived stem cells. With use of the in vivo imaging system and histologic evaluation, fibroblasts survived longer than adipose-derived stem cells in hydrogel in vivo.

Conclusions:
Tendon healing is mediated by the proliferation, survival, and tenogenic differentiation of cells at the site of injury. Tendon hydrogel delivering dermal fibroblasts may improve and stimulate this process compared with adipose-derived stem cells. Future studies will be needed to evaluate the effects of this hydrogel-based cell delivery on chronic tendon injuries.
CRISPR-Cas9 targeted deletion of theC9orf72repeat expansion mutation corrects cellular phenotypes in patient-derived iPS cells
Authors: Pribadi Mochtar , Yang Zhongan , Kim Tanya S. , Swartz Elliot W. , Huang Alden Y. , Chen Jason A. , Dokuru Deepika , Baek Jaeyun , Gao Fuying , Fua Andrea T. , Wojta Kevin , Wang Qing , Karydas Anna , Fong Jamie , Lezcano Ed , Ng Stephanie , Chehab Farid F. , Vinters Harry V. , Miller Bruce L. , Coppola Giovanni 
Published: May 2016

AbstractThe large hexanucleotide (GGGGCC) repeat expansion in the non-coding promoter region ofC9orf72is the leading cause of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Mechanisms underlying neurodegeneration are not clear, and both a C9orf72 loss of function and a gain of toxicity, in the form of RNA foci or dipeptide repeat deposition, are implicated. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-mediated genome editing is an attractive strategy for disease modeling and therapeutic intervention. Here we show that this system can be utilized to completely remove the large repeat expansion mutation withinC9orf72in patient-derived induced pluripotent stem (iPS) cells. Removal of the mutation prevented RNA foci formation and promoter hypermethylation, two phenotypes of theC9orf72mutation. Interestingly, these changes did not significantly alter C9orf72 expression at the mRNA or protein level. This work provides a proof-of-principle for the use of CRISPR-Cas9-mediated excision of the pathogenicC9orf72repeat expansion as a therapeutic strategy in FTD/ALS.One Sentence SummaryCRISPR-Cas9-mediated excision of the largeC9orf72repeat expansion mutation rescues RNA foci formation and promoter hypermethylation without altering C9orf72 transcript and protein expression.
The genetic basis of natural variation inC. eleganstelomere length
Authors: Cook D.C. , Zdraljevic S. , Tanny R.E. , Seo B. , Riccardi D.D. , Noble L.M. , Rockman M.V. , Alkema M.J. , Braendle C. , Kammenga J.E. , Wang J. , Kruglyak L. , Félix M.A. , Lee J. , Andersen E.C. 
Published: May 2016

AbstractTelomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across theCaenorhabditis elegansspecies. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligosaccharide/oligonucleotide-binding fold of POT-2, a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity inC. eleganswild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes inC. elegans.
Optimizing multiplex CRISPR/Cas9-based genome editing for wheat
Authors: Wang Wei , Akhunova Alina , Chao Shiaoman , Akhunov Eduard 
Published: May 2016

AbstractBackgroundCRISPR/Cas9-based genome editing holds great promise to accelerate the development of new crop varieties by providing a powerful tool to modify the genomic regions controlling major agronomic traits. To diversify the set of tools available for wheat genome engineering, we have established a tRNA-based multiplex gene editing strategy for hexaploid wheat.ResultsThe functionality of the various CRISPR/Cas9 components was assessed using the transient expression in the wheat protoplasts followed by next-generation sequencing (NGS) of the targeted genomic regions. The efficiency of wheat codon-optimized Cas9 for targeted gene editing in wheat was validated. Multiple single guide RNAs (gRNAs) were evaluated for the ability to edit the homoeologous copies of four genes affecting some important agronomic traits in wheat. Low correspondence was found between the gRNA efficiency predicted bioinformatically and that assessed in the transient expression assay. A multiplex gene editing construct with several gRNA-tRNA units under the control of a single promoter for the RNA polymerase III generated indels at the targets sites with the efficiency comparable to that obtained for a single gRNA construct.ConclusionsBy integrating the protoplast transformation assay with multiplexed NGS, it is possible to perform fast functional screens for a large number of gRNAs and to optimize constructs for effective editing of multiple independent targets in the wheat genome. The multiplexing capacity of the tandemly arrayed tRNA–gRNA construct is well suited for the simultaneous editing of the redundant gene copies in the allopolyploid genomes or genomic regions beneficially affecting multiple agronomic traits. A polycistronic gene construct that can be quickly assembled using the Golden Gate reaction along with the wheat codon optimized Cas9 will further expand the set of tools available for engineering the wheat genome.
Transcriptome Analysis Reveals Skin Lipid Metabolism Related to Wool Diameter in Sheep
Authors: Fu Shaoyin , Qi YunXia , He Xiaolong , Da Lai , Wang biao , Te rigele , Wu jianghong , Yang ding , Liu yongbin , Zhang wengguang 
Published: May 2016

AbstractWool is one of the most important animal fibers in the textile industry and the diameter directly affects its economic value. However, the molecular mechanisms underlying the wool diameter have not been fully elucidated. In the present study, high-throughput RNA-Seq technology was employed to explore the skin transcriptome using 3 sheep with fine wool (fiber diameter, FD<21.0μm) and 3 sheep with coarse wool (fiber diameter, FD>27.0μm). In total, 28,607,228 bp clean reads were obtained, and 78.88%+/-3.84% was uniquely aligned to the reference genome across the six samples. In total, 19,914 mRNA transcripts were expressed (FPKM>0) in the six skin samples, among which there were certain well-known genes affecting the skin hair cycle, such as KRTAP7-1, KRT14, Wnt10b, Wnt2b, β-catenin, and FGF5. Furthermore, 467 expressed genes were significantly differentially expressed between the two groups, including 21 genes up-regulated and 446 genes down-regulated in the sheep with the smaller fiber diameter. To verify the results, 13 differentially expressed genes were randomly selected to validate the expression patterns using qRT-PCR, and the correlation between the mRNA expression level from qRT-PCR and RNA-Seq data was 0.999 ( P<0.05). These differentially expressed genes were particularly enriched in GO processes related to lipid metabolism, skin development, differentiation, and immune function (P<0.05). The biological processes were involved in collagen catabolism, negative regulation of macromolecule metabolism, steroid hormone stimulation and lipid metabolism. A significant KEGG pathway involving the “metabolism of lipids and lipoproteins” was also enriched. This study revealed that the lipid metabolism might constitute one of the major factors related to wool diameter.