bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Costs and Outcomes for In-Office and Operating Room Excision of Nonmelanoma Skin Cancer
Authors: Ovadia Steven A. , Spector Seth A. , Thaller Seth R. 
Published: January 2019

Introduction
With increasing health care expenses and limited resources, it is important to evaluate potential means of reducing cost while maintaining efficacy and safety. The purpose of our study was to compare the cost and outcomes of surgical excision of nonmelanoma skin cancer (NMSC) in the operating room versus an outpatient procedure clinic.

Methods
A retrospective review of patients undergoing excision of biopsy-confirmed NMSC at the Miami Veterans Affairs Hospital between December 1, 2015, and December 1, 2016, was completed. Patients treated in the operating room and procedure clinic were included. Treatment outcomes were assessed for all identified patients. Patients undergoing excision and primary closure were included for cost comparison.
Procedure costs were estimated using Current Procedural Terminology codes for treatments provided and the 2017 conversion factor of $35.7751. If a second operation for positive margins was necessary, cost to treat the lesion included costs from both procedures. If multiple lesions were treated, total cost was divided by the number of lesions to calculate cost per lesion treated. Costs per lesion managed in the operating room and clinic were compared using the Student t test.

Results
Sixty-five patients underwent excision of 94 NMSCs in the operating room. Nineteen patients underwent excision of 20 NMSCs in the procedure clinic. One patient treated in the clinic required re-excision in the operating room with frozen section for a positive margin.
Thirty-three patients managed in the operating room and 19 patients managed in the procedure clinic were included for cost analysis. Average costs per lesion excised in the operating room and procedure clinic were calculated to be $1923.43 ± 616.27 and $674.88 ± 575.22, respectively (P < 0.001).

Conclusions
Excellent oncologic outcomes were achieved for both operating room and procedure clinic excision. Excision in the operating room excision was significantly more expensive than in the procedure clinic. Excision in a procedure clinic offers an opportunity to reduce costs while maintaining quality care.
Correction of Tanzer Type IIB Constricted Ears via Z-shaped Double V-Y Advancement Flaps
Authors: Duan Weiqiang , Liu Yong 
Published: January 2019

Background
Correction of Tanzer type IIB constricted ears requires sufficient expansion of the auricular skin to cover the reconstructed cartilaginous framework. To obtain an adequately sized skin cover, skin flap transposition from periauricular donor sites has been described; however, it remains challenging to obtain enough skin to enable satisfactory reconstruction. Herein, we describe a novel method that uses 2 local flaps comprising superoauricular, retroauricular, and preauricular soft tissue to expand the skin cover and correct Tanzer type IIB deformity.

Methods
Fifteen constricted ears in 15 patients were treated via this novel method from June 2013 to July 2017. Two adjoining V-Y advancement flaps shaped like a backward “Z” were created to expand the skin envelope of the upper one-third of the ear. The advancement of these 2 flaps toward each other expanded the skin of the upper one-third of the ear by creating a skin arch, which was then used to wrap the reconstructed cartilaginous framework. The auricular cartilage was refashioned via a method that combined several previously reported techniques.

Results
A satisfactory outcome was achieved in all 15 constricted ears, with resultant improvements in size and shape, and an elevated auricular position.

Conclusions
The preauricular, superoauricular, and retroauricular skin areas can be used to successfully expand the skin envelope of the upper auricle via the creation of 2 adjoining V-Y advancement flaps. This results in an ample skin cover with which to accommodate the auricular cartilaginous framework reconstructed by multiple techniques. This novel Z-shaped double V-Y advancement flap method can effectively correct Tanzer type IIB constricted ears.
Health-Related Quality of Life After Ventral Hernia Repair With Biologic and Synthetic Mesh
Authors: Nissen Andreas T. , Henn Dominic , Moshrefi Shawn , Gupta Deepak , Nazerali Rahim , Lee Gordon K. 
Published: January 2019

Background
Quality of life (QOL) is an important outcome measure after ventral hernia repair (VHR). The Hernia-Related QOL Survey (HerQLes) is a specific survey tool for QOL after VHR. Studies comparing QOL in patients with biologic mesh repairs (BMRs) and synthetic mesh repairs (SMRs) are lacking.

Study Design
A survey based on the HerQLes was administered via e-mail to 974 patients who had undergone VHR at Stanford Medical Center. From 175 patients who were included in the study, the mean HerQLes scores and postoperative complications were compared between patients with suture repairs (SR), BMR, SMR, with and without component separation, and different types of SMR.

Results
Quality of life was lower in patients with hernias of 50 cm2 or greater, obesity, history of tobacco use, previous abdominal surgeries, hernia recurrences, and postoperative complications (P < 0.05). Patients with SR and SMR had a comparable QOL (71.58 vs 70.12, P = 0.75). In patients with Modified Ventral Hernia Working Group grade 2 hernias, a significantly lower QOL was found after BMR compared with SMR. Postoperative complications did not significantly differ between the groups. Recurrence rates were comparable between MR (10.4%) and SR (8.3%, P = 0.79), but higher in BMR (21.7%) compared with SMR (6.6%, P < 0.05).

Conclusions
Previous abdominal surgeries, previous hernia repairs, tobacco use, and hernia sizes of 50 cm2 or greater negatively affect QOL after VHR. Our data indicate that QOL is comparable between patients with SMR and SR, however, is lower in patients with Modified Ventral Hernia Working Group grade 2 and BMR compared with SMR, raising the benefit of BMR in light of its higher cost into question.
Clinical Utility of Postoperative Computed Tomography Imaging in Orbital Floor Fracture Management
Authors: Sharma Ajay N. , Tiourin Ekaterina , Banyard Derek A. , Sharma Shonit N. , Ng Wendy K. Y. 
Published: January 2019

Background
Surgical repair of orbital floor fractures aims to improve visual function and appearance. Postoperative care often involves computed tomography (CT) imaging in addition to physical examination. It has yet to be investigated whether postoperative CT imaging influences treatment of orbital floor fractures.

Methods
A retrospective chart review was conducted for all patients who underwent orbital floor fracture repair at University of California, Irvine, from 2008 to 2017. Demographics, injury characteristics, and presurgical and postsurgical management were retrospectively extracted for 217 cases. Patients who experienced a change of care following postoperative CT (n = 6) were compared with the entire patient cohort.

Results
Postoperative CT imaging influenced orbital floor fracture management in 6 patients (7.2% of patients with imaging). The positive predictive value of a postoperative CT scan was 10.3%, compared with 17.6% for a physical examination. An estimated $2013.76 was spent to obtain a postoperative CT scan that revealed 1 additional patient who needed reoperation (number needed to treat = 14). A multivariate regression model demonstrated no association between postoperative CT scans and change in management (P = 0.995).

Conclusions
In this patient cohort, postoperative CT imaging and its associated costs did not significantly benefit management of orbital floor fracture repair. Careful clinical physical examination should be emphasized over postoperative CT imaging to reliably determine the necessity for reoperation in orbital floor fracture management.
The Diagnostic Utility of Ambulatory EEG Following Nondiagnostic Epilepsy Monitoring Unit Admissions
Authors: Fox Jonah , Ajinkya Shaun , Chopade Pramod , Schmitt Sarah 
Published: January 2019

Purpose:
Epilepsy monitoring unit (EMU) admissions provide a definitive diagnosis for approximately three-quarters of patients. However, many patients do not receive a definitive diagnosis following EMU admission. Ambulatory EEG following nondiagnostic EMU admissions was evaluated as a means of providing a diagnosis for these patients.

Methods:
In this retrospective study, we performed a chart review of 62 pediatric and adult patients who had a 72-hour ambulatory EEG following a nondiagnostic EMU admission.

Results:
In total, there were 62 patients with nondiagnostic EMU admissions who subsequently underwent ambulatory EEG. Mean age was 33.8 (SD, 18.5) years. Forty-one patients (66.2%) were female and 46 (74.2%) adult. Fifty patients (80.7%) had an additional comorbid neurologic, somatoform, or psychiatric diagnoses. Of the original 62 patients, 32 (51.6%) had no events, 3 (4.8%) had events with and without EEG changes, 4 (6.5%) had only events with EEG changes, and 23 (37.1%) had only events without EEG changes. Ambulatory EEG thus provided clinically useful information in 30 (48.4%) cases, with 20 (66.7%) reaching diagnosis within 24 hours.

Conclusions:
Ambulatory EEG following a nondiagnostic EMU admission may yield positive results in approximately half of all patients. A substantial proportion of the events that were captured in this setting were without EEG changes. In the absence of video and supportive clinical information, these events not only may represent nonepileptic events but also could represent focal seizures without EEG changes. The presence of particular stressors in the home environment may explain why many patients, specifically those who are nonepileptic, had events relatively quickly following discharge.
SGK1.1 activation causes early seizure termination via effects on M-current
Authors: Armas-Capote Natalia , Maglio Laura E. , Pérez-Atencio Leonel , Martin-Batista Elva , Reboreda Antonio , Barios Juan A. , Hernandez Guadalberto , la Rosa Diego Alvarez de , Lamas José Antonio , Barrio Luis C. , Giraldez Teresa 
Published: January 2019

AbstractEarly termination of status epilepticus affords protection against brain damage and associated pathologies. Regulation of Kv7.2/7.3 potassium channels, underlying the neuronal M-current, is key for seizure control. This conductance is maintained during initiation of action potentials, affecting neuronal excitability and thus inhibiting epileptic discharges. The M-current is upregulated by the neuronal isoform of the serum and glucocorticoid-regulated kinase SGK1 (SGK1.1). We tested whether SGK1.1 is an anticonvulsant factor using the kainic acid (KA) model of acute seizures in a transgenic mouse model with expression of a constitutively active form of the kinase. Our results demonstrate that SGK1.1 confers robust protection against seizures associated to lower mortality levels, independently of sex or genetic background. SGK1.1-dependent protection results in reduced number, shorter duration, and early termination of EEG seizures. At the cellular level, it is associated to increased M-current amplitude mediated by Nedd4-2 phosphorylation, leading to decreased excitability of hippocampal CA1 neurons without alteration of basal synaptic transmission. Altogether, our results reveal that SGK1.1-mediated M-current upregulation in the hippocampus is a key component of seizure resistance in the KA epileptic paradigm, suggesting that regulation of this anticonvulsant pathway may improve adverse outcomes to status epilepticus, constituting a potential target for antiepileptic drugs.
Draft Genome Sequence and intraspecific diversification of the wild crop relativeBrassica creticaLam. using demographic model selection
Authors: Kioukis Antonis , Michalopoulou Vassiliki A. , Briers Laura , Pirintsos Stergios , Studholme David J. , Pavlidis Pavlos , Sarris Panagiotis F. 
Published: January 2019

AbstractCrop wild relatives contain great levels of genetic diversity, representing an invaluable resource for crop improvement. Many of their traits have the potential to help crops become more resistant and resilient, and adapt to the new conditions that they will experience due to climate change. An impressive global effort occurs for the conservation of various wild crop relatives and facilitates their use in crop breeding for food security.The genusBrassicais listed in Annex I of the International Treaty on Plant Genetic Resources for Food and Agriculture.Brassica oleracea(or wild cabbage) is a species native to coastal southern and western Europe that has become established as an important human food crop plant because of its large reserves stored over the winter in its leaves.Brassica creticaLam. is a wild relative crop in the brassica group andB. creticasubsp.niveahas been suggested as a separate subspecies. The speciesB. creticahas been proposed as a potential gene donor to a number of crops in the brassica group, including broccoli, Brussels sprout, cabbage, cauliflower, kale, swede, turnip and oilseed rape.Here, we present the draftde novogenome assemblies of fourB. creticaindividuals, including twoB. creticasubsp.niveaand twoB. cretica.De novoassembly of Illumina MiSeq genomic shotgun sequencing data yielded 243,461 contigs totalling 412.5 Mb in length, corresponding to 122 % of the estimated genome size ofB. cretica(339 Mb). According to synteny mapping and phylogenetic analysis of conserved genes,B. creticagenome based on our sequence data reveals approximately 30.360 proteins.Furthermore, our demographic analysis based on whole genome data, suggests that distinct populations ofB. creticaare not isolated. Our findings suggest that the classification of theB. creticain distinct subspecies is not supported from the genome sequence data we analyzed.
Mesenchymal stem cells (MSCs) offer a drug tolerant and immune- privileged niche to Mycobacterium tuberculosis
Authors: Jain Neharika , Kalam Haroon , Singh Lakshyaveer , Sharma Vartika , Kedia Saurabh , Das Prasenjit , Ahuja Vineet , Kumar Dhiraj 
Published: January 2019

SummaryAnti-tuberculosis (TB) drugs while being highly potent in vitro require prolonged treatment to control Mycobacterium tuberculosis (Mtb) infections in vivo. We report here, mesenchymal stem cells (MSCs) shelter Mtb to help tolerate anti-TB drugs. MSCs uptake Mtb readily and allow them grow unabated despite having functional innate pathway of phagosome maturation. Unlike macrophage-resident ones, MSC-resident Mtb tolerates anti-TB drugs remarkably well, a phenomenon requiring proteins ABCC1, ABCG2 and vacuolar-type H+ATPases. Additionally, contrary to what is classically known, IFNγ and TNFα aid mycobacterial growth within MSCs. Mechanistically, evading drugs and inflammatory cytokines by MSC-resident Mtb is dependent on elevated PGE2 signaling, which we subsequently verified in vivo analyzing sorted CD45-CD73+SCA1+-MSCs from the lungs of infected mice. Moreover granulomas from human pulmonary and extra-pulmonary TB show presence of MSCs co-inhabiting with Mtb. Together the results show targeting the immune-privileged niche, provided by MSCs to Mtb, can revolutionize tuberculosis prevention and cure.
Autophagy regulates the localization and degradation of p16INK4a
Authors: Coryell Philip R. , Goraya Supreet K. , Griffin Katherine A. , Redick Margaret A. , Sisk Samuel R. , Purvis Jeremy E. 
Published: January 2019

AbstractThe tumor suppressor protein p16INK4a (p16) is a well-established hallmark of aging that induces cellular senescence in response to stress. Previous studies have focused primarily on p16 regulation at the transcriptional level; comparatively little is known about the protein’s intracellular localization and degradation. The autophagy-lysosomal pathway has been implicated in the subcellular trafficking and turnover of various stress-response proteins, but it is unclear whether p16 is involved in these pathways. Here, we investigate the role of autophagy, vesicular trafficking, and lysosomal degradation on p16 expression and localization in human epithelial cells. Time-lapse fluorescence microscopy using an endogenous p16-mCherry reporter revealed that autophagy induced by genotoxic stress stimulates rapid p16 recruitment to acidic cytoplasmic vesicles. When vesicular acidification was inhibited by NH4Cl, nuclear p16 levels increased. Single-cell imaging revealed that p16 localizes to lysosomes upon stress, implicating the autophagy pathway as a regulator of p16 localization. Blocking autophagy with bafilomycin, chloroquine, or NH4Cl resulted in elevated p16 protein levels without increased transcription. Increased p16 coincided with accumulation of autophagosome chaperone p62/SQSTM1 (p62) and decreased levels of phosphorylated-Rb. Furthermore, chloroquine caused p16 aggregation within stalled vesicles containing autophagosome marker LC3, demonstrating that p16 is transported and degraded by the autophagy-lysosomal pathway. Knockdown of p62 resulted in delocalization of p16 aggregates to autophagosomes, suggesting that p16 is targeted to these vesicles by p62. Taken together, these results implicate the autophagy pathway as a novel regulator of p16 degradation and localization, which could play a role in the etiology of cancer and age-related diseases.
Cardiac interstitial tetraploid cells that escape replicative senescence are found in rodents but not large mammals
Authors: Broughton Kathleen , Khieu Tiffany , Nguyen Nicky , Rosa Michael , Mohsin Sadia , Quijada Pearl , Wang Bingyan , Echeagaray Oscar , Kubli Dieter , Kim Taeyong , Firouzi Fareheh , Monsanto Megan , Gude Natalie , Adamson Robert M. , Dembitsky Walter P. , Davis Michael , Sussman Mark A. 
Published: January 2019

AbstractPloidy for cardiomyocytes is well described but remains obscure in cardiac interstitial cells (CICs). Ploidy of c-kit+CICs (cCICs) were assessed using a combination of confocal, karyotypic, and flow cytometric assessments coupled with molecular and bioinformatic analyses. Fundamental differences were found between cultured rodent (rat, mouse) cCICs possessing mononuclear tetraploid (4n) content versus large mammal (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in cCICs from human and a mixture of diploid and tetraploid nuclei in mouse. Molecular assessment of the p53 signaling pathway provides a plausible explanation for escape from replicative senescence in rodent but not human cCICs. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse cCICs, alluding to functional divergences. Collectively, these data reveal fundamental species-specific biological differences in cCICs that could account for challenges in extrapolation of myocardial preclinical studies from rodent to large animal models.
De Novo Peptide Sequencing Reveals a Vast Cyclopeptidome in Human Gut and Other Environments
Authors: Behsaz Bahar , Mohimani Hosein , Gurevich Alexey , Prjibelski Andrey , Fisher Mark F. , Smarr Larry , Dorrestein Pieter C. , Mylne Joshua S. , Pevzner Pavel A. 
Published: January 2019

ABSTRACTCyclic and branch cyclic peptides (cyclopeptides) represent an important class of bioactive natural products that include many antibiotics and anti-tumor compounds. However, little is known about cyclopeptides in the human gut, despite the fact that humans are constantly exposed to them. To address this bottleneck, we developed the CycloNovo algorithm for de novo cyclopeptide sequencing that employs de Bruijn graphs, the workhorse of DNA sequencing algorithms. CycloNovo reconstructed many new cyclopeptides that we validated with transcriptome, metagenome, and genome mining analyses. Our benchmarking revealed a vast hidden cyclopeptidome in the human gut and other environments and suggested that CycloNovo offers a much-needed step-change for cyclopeptide discovery. Furthermore, CycloNovo revealed a wealth of anti-microbial cyclopeptides from food that survive the complete human gastrointestinal tract, raising the question of how these cyclopeptides might affect the human microbiome.SIGNIFICANCEThe golden age of antibiotics was followed by a decline in the pace of antibiotics discovery in the 1990s. The key prerequisite for the resurgence of antibiotics research is the development of a computational discovery pipeline for antibiotics sequencing. We describe such pipeline for cyclic and branch cyclic peptides (cyclopeptides) that represent an important class of bioactive natural products such as antibiotics and anti-tumor compounds. Our CycloNovo algorithm for cyclopeptide sequencing reconstructed many new cyclopeptides that we validated with transcriptome, metagenome, and genome mining analyses. CycloNovo revealed a wealth of anti-microbial cyclopeptides from food that survive the complete human gastrointestinal tract, raising the question of how these cyclopeptides might affect the human microbiome.
Molecular mechanism of TRPV2 channel modulation by cannabidiol
Authors: Pumroy Ruth A. , Samanta Amrita , Liu Yuhang , Hughes Taylor E.T. , Zhao Siyuan , Yudin Yevgen , Huynh Kevin W. , Zhou Z. Hong , Rohacs Tibor , Han Seungil , Moiseenkova-Bell Vera Y. 
Published: January 2019

SUMMARYTransient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is a potent activator of TRPV2 and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length TRPV2 channel in a CBD-bound state in detergent and in PI(4,5)P2 enriched nanodiscs by cryo-electron microscopy. CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. Comparison between apo- and two CBD-bound TRPV2 structures reveals that the S4-S5 linker plays a critical role in channel gating upon CBD binding. The TRPV2 “vanilloid” pocket, which is critical for ligand-dependent gating in other TRPV channels, stays unoccupied by annular lipids, PI(4,5)P2, or CBD. Together these results provide a foundation to further understand TRPV channel gating properties and their divergent physiological functions and to accelerate structure-based drug design.
Assessing the performance of different approaches for functional and taxonomic annotation of metagenomes
Authors: Tamames Javier , Cobo-Simón Marta , Puente-Sánchez Fernando 
Published: January 2019

AbstractMetagenomes can be analysed using different approaches and tools. One of the most important distinctions is the way to perform taxonomic and functional assignment, choosing between the usage of assemblies or the direct analysis of raw sequence reads instead. Many instances of each approach can be found in the literature, but to the best of our knowledge no evaluation of their different performances has been carried on, and we question if their results are comparable. We have studied this point by analysing several real and mock metagenomes using different methodologies and tools, and comparing the resulting taxonomic and functional profiles. Our results show that database completeness is the main factor determining the performance of the methods relying on direct read assignment either by homology, k-mer composition or similarity to marker genes, while methods relying on assembly and assignment of predicted genes are most influenced by sequencing depth, that in turn determines the completeness of the assembly. Although differences exist, taxonomic profiles are rather similar between raw read assignment and assembly assignment methods, while they are more divergent for methods based on k-mers and marker genes. Regarding functional annotation, analysis of raw reads retrieves more functions, but it also makes a significant number of over-predictions. Assembly methods are more advantageous as the size of the metagenome grows bigger.