bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining Interrater Reliability of the Cornell Assessment of Pediatric Delirium Screening Tool Among PICU Nurses
Authors: Valdivia Hector R. , Carlin Kristen E.
Published: February 2019

Objectives:

To determine the interrater reliability of the Cornell Assessment of Pediatric Delirium Screening Tool amount PICU nurses.

Design:

The design was setup as a cross-sectional study and conducted over the course of a year.

Setting:

This study setting was a PICU and a pediatric cardiac ICU at Seattle Children’s Hospital, a tertiary freestanding university-affiliated hospital in Seattle, Washington.

Patients:

A total sample of 108 patients were included in this study. Patients were selected using a convenience sample. Inclusion in this study involved all patients eligible for a Cornell Assessment of Pediatric Delirium assessment, reflecting practice standards. Exclusion criteria included patients who had a Richmond Agitation and Sedation Score of (–4) or (–5), based on the Cornell Assessment of Pediatric Delirium procedure. There were 113 patients screened, but five were excluded from the final sample size due to missing information.

Interventions:

The research nurse would screen the patient using the Cornell Assessment of Pediatric Delirium during the 12:00 noon hour, which coincided with the clinical nurse Cornell Assessment of Pediatric Delirium assessment. The clinical and research nurse were kept blind to each other’s assessment. Scores were then analyzed to determine the kappa coefficient.

Measurements and Main Results:

The kappa coefficient between nurses was found to be 0.60 (95% CI, 0.44–0.76), indicating moderate agreement. Age was found to have a higher association with agreement. In children 2 years old or greater, the kappa coefficient was 0.85 (95% CI, 0.68–1.00). Children whose raters did not agree on scoring were more likely to be younger than those who had raters that agreed (p < 0.01).

Conclusions:

Evaluating the interrater reliability of clinical tool, such as the Cornell Assessment of Pediatric Delirium, may be important to more accurately identify patients at high risk of delirium in a PICU or pediatric cardiac ICU. The evaluation of the tool’s performance in practice may also be helpful to ensure ongoing consistency among the clinical nurses that complete these assessments on a daily basis.
Traumatic Retroclival Epidural Hematoma
Authors: Samanci Yavuz , Baskurt Ismet , Celik Suat Erol
Published: February 2019

Retroclival epidural hematomas are particularly rare conditions that are frequently the result of high-energy, hyperflexion-hyperextension injuries in pediatric patients. We present the case of a 7-year-old previously healthy girl with traumatic retroclival epidural hematoma after a fall from a swing. She presented with a Glasgow Coma Scale score of 15 with severe neck pain and limitation of cervical movements in all directions. Radiological examination revealed retroclival epidural hematoma, and the patient was managed conservatively with good recovery. Although conservative management leads to good recovery in most cases, retroclival epidural hematomas should always be kept in mind regardless of the severity of trauma.
Value of Three-Dimensional Ultrasound in Differentiating Malignant From Benign Breast Tumors
Authors: Bin Lian , Huihui Yang , Weiping Yang , Changyuan Wei , Qinghong Qin , Weiyu Meng
Published: February 2019

Currently, the aim of differentiating malignant from benign breast tumors and diagnosing early breast cancer is more accurately fulfilled with the addition of ultrasound (US) scans. Some studies have shown that three-dimensional (3D) imaging opens a new diagnostic window because of a better and more detailed impression of the spatial arrangement of focal breast masses. Therefore, we carried out this study to assess the efficacy of 3D-US diagnostic techniques for the detection of breast cancer using systemic analyses. We searched the MEDLINE, Pubmed, EMBASE, and Cochrane Library for using 3D-US for the diagnosis of breast cancer. The terms used were “three-dimensional ultrasound”, “breast neoplasms”, “sensitivity and specificity”, and “accuracy”. Patients were adults. The quality of the studies was checked according to Quality Assessment of Diagnostic Accuracy Studies criteria. We calculated the diagnostic accuracy rates and developed a meta-analysis to synthesize the results. Twelve studies of diagnostic tests were selected, which were of moderate to high quality. The pooled sensitivity was 0.923 (95% confidence interval [CI], 0.896–0.945), and the pooled specificity was 0.872 (95% CI, 0.849–0.893). The meta-analysis detected a threshold effect and heterogeneity between studies. The pooled positive likelihood ratio was 6.965 (95% CI, 5.242–9.255), the negative likelihood ratio was 0.106 (95% CI, 0.079–0.142), and the diagnostic odds ratio was 84.239 (95% CI, 52.237–135.84). This meta-analysis indicates that 3D-US has acceptable diagnostic accuracy rates in differentiating malignant from benign breast tumors.
A Preliminary Comparative Study of Young's Modulus Versus Shear Modulus in the Diagnosis of Breast Cancer
Authors: Wu Huaiyu , Liang Weiyu , Jiao Yang , Song Hong , Peng Quanzhou , Luo Hui , Zhang Yuanji , Xu Jinfeng , Dong Fajin
Published: February 2019

Purpose

The purpose of this study was to compare the diagnostic value of Young's modulus (E) and shear modulus (G) in the differential diagnosis of benign and malignant breast masses using sound touch elastography (STE) and to explore the relationship between G and E in breast lesions.

Methods

A total of 96 consecutive women with 110 pathologically confirmed breast masses were included. All masses were detected by conventional and STE ultrasound. E
mean, E
max, E
min, E
SD, G
mean, G
max, G
min, and G
SD were determined and evaluated for evidence of significant differences between benign and malignant breast masses. Receiver operator characteristics were used to compare the diagnostic efficacy of E and G and to determine the G cutoff value that would aid in the differential diagnosis of breast cancer.

Results

E
mean, E
max, E
SD, G
mean, G
max, and G
SD in cases of malignant breast masses were significantly higher than those in cases of benign masses (P < 0.05). There was no significant difference between E
min and G
min (P = 0.565). In applying the E
mean, E
max, E
SD, G
mean, G
max, and G
SD to the receiver operator characteristics: (1) the area under the curve (AUC) of G
mean and G
max is greater than the AUC of E
mean and E
max, and the AUC of E
SD is equal to the AUC of G
SD. (2) The sensitivity and specificity were highest when the G
mean was 10.14 kPa. They were 84.1% and 80.3% respectively. (3) The sensitivity and specificity were highest when the G
max was 52.20 kPa. They were 88.6% and 87.9% respectively.

Conclusions

These preliminary results of STE evaluation of breast masses suggest that the diagnostic value of G is greater than E. Furthermore, STE is a valuable tool in the differential diagnosis of breast lesions.
Correlation Between Mandible and External Ear in Patients with Treacher-Collins Syndrome
Authors: Ma Xiaoyang , Xie Fang , Zhang Chao , Xu Jiajie , Lu Jianjian , Teng Li
Published: February 2019

Background:

Patients with Treacher-Collins syndrome (TCS) are frequently affected by congenital ear deformities. The external ear in patients with TCS tends to have both abnormal morphology and reduced overall volume. Previous studies considered a correlation exists between TCS mandibular skeletal features and external ear volume. The purpose of this study was to assess the external ear volume in patients with TCS 3-dimensionally. Furthermore, this study evaluated the relationship between mandibular morphology, external ear profile, and external ear volume.

Methods:

A total of 36 nonoperated patients with TCS were compared to 39 age- and gender-matched normal controls. Morphologic variables of the mandible and the external ear were compared between TCS group and controls by 3-dimensional cephalometrics. The external ear volume and morphologic variables were analyzed with independent sample T-tests and Pearson correlation coefficient analyses (level of evidence: level III).

Results:

The external ear volume was reduced by approximately 50% in patients with TCS compared to controls (P < 0.001). External ear length and width were positively correlated with external ear volume (length: r = 0.809, P < 0.001 on left and r = 0.732, P < 0.001 on right; width: r = 0.518, P = 0.001 on left and r = 0.447, P < 0.010 on right). A negative correlation of right ear inclination angle and external ear volume was shown in patients with TCS (r = −0.396, P = 0.027). However, no correlation was shown for the mandibular anatomic variables.

Conclusions:

Three-dimensional analysis confirmed that external ear volume is significantly reduced in patients with TCS. The external ear dimensions and orientation correlated significantly with ear volume. There was no intrinsic association between the severity of mandibular deformity and external ear volume.
Basal Ganglionic Germinoma With Syncytiotrophoblastic Giant Cells Mimicking a Growing Hematoma
Authors: Yan Jihong , Zhang Yongna , Yang Yucheng , Yuan Xunhui , Xiao Hang , Niu Jianyi , Gu Yinghao
Published: February 2019

Basal ganglionic germinoma (BGG) with syncytiotrophoblastic giant cells (STGC) is a rare type of ectopic germ cell tumors with mild elevation of human chorionic gonadotropin level. Intratumoral hemorrhage is not uncommon for BGG, but presenting with repeated hemorrhage is very rare. Herein, we described an extremely rare case of BGG with STGC mimicking a growing hematoma. Furthermore, the characteristics, treatment, and prognosis of BGG with STGC were investigated and reviewed.
Patient Specific Three-Dimensional Implant for Reconstruction of Complex Mandibular Defect
Authors: U Vignesh , Mehrotra Divya , Howlader Debraj , Singh Praveen Kumar , Gupta Sneha
Published: February 2019

This study was planned to evaluate the improvement in mandibular function, facial esthetics and quality of life after reconstruction of complex mandibular defects using patient-specific three-dimensional (3D) titanium implant. A total of 7 patients, who visited our outpatient clinic for reconstruction of mandibular defects after removal of their primary mandibular lesion and refused treatment with autologous bone grafts were treated with patient-specific implant for reconstruction of mandible. Three-dimensional virtual treatment planning was carried out using their 3D computed-tomographic data. The unaffected contralateral side of mandible was superimposed on the defect side and a customized implant was designed in the desired size and shape on the virtual model using computer aided designing and milled in titanium using selective laser melting, for precise anatomic mandibular reconstruction. There was significant improvement in their esthetics, function, and quality of life. The symmetry of the face and occlusion was restored with adequate mouth opening, closing, and lateral movements of the mandible with no deviation of jaw during movements. The patient specific implants appear to be very useful for precise reconstruction of mandible with greater accuracy. The concept of using customized implant with the help of 3D virtual treatment planning, stereolithographic models and computer aided designing greatly improves mandibular restoration and helps to achieve good facial profile, aesthetics and dental rehabilitation preventing severe complications related to autologous grafts.
Migration of a Distal Ventriculoperitoneal Shunt Catheter Into the Pulmonary Vasculature: a Report of an Unusual Case and a Review of the Literature
Authors: Li Wende , Li Yunjun , Sun Yue , Chen Lihua
Published: February 2019

The authors report an unusual case of distal ventriculoperitoneal shunt catheter into the pulmonary vasculature. The migrated catheter was extracted through a thoracotomy and venotomy, with the cooperation of Neuroneurosurgery and Cardiovascular team. This rare complication after ventriculoperitoneal shunt surgery should be paid enough attention. There were 2 possible mechanisms. To solve the problem, multidisciplinary cooperation should be applied.
Intraoperative Detection of Leakage Using Topical Fluorescein Following Free Flap Inset in Head and Neck Reconstruction
Authors: Cha Han Gyu , Kwon Jin Geun , Kim Eun Key
Published: February 2019

In microsurgical head and neck reconstruction, a watertight closure following flap inset is essential to prevent saliva leakage and subsequent complications, such as wound dehiscence and fistulas. However, no standard method has been established to detect and localize the leakage following flap inset. The authors introduce a simple, easy, mobile, and inexpensive method to intraoperatively detect the leakage using topical fluorescein sodium mixed saline and Wood lamp. This simple procedure will allow surgeons to be confident of watertight closure.
Three-Dimensional Craniofacial Bone Reconstruction With SmartBone on Demand
Authors: Facciuto Enzo , Grottoli Carlo Francesco , Mattarocci Maurizio , Illiano Fausto , Compagno Mara , Ferracini Riccardo , Perale Giuseppe
Published: February 2019

This is a report of a 34-year-old male lacking of bone development in the frontal and orbital part of the skull due to a surgical removal of a right orbital-front osteoma at the age of 5. The integrity of the craniofacial district was important for the young patient also for social acceptance and self-esteem.

Based on computed tomography patient images, a skull model was reconstructed, both digitally and on 3-dimensional real model, to best design the needed bone graft. Defect wide extension and surface curvature called for the use of the puzzle technique, where the whole graft is composed by several elements, mechanically slotting into each other. The realization was made possible thanks to the use of a composite xenohybrid bone substitute specifically developed for reconstructive surgery (SmartBone, by Industrie Biomediche Insubri SA). SmartBone technology allowed the realization of custom-made grafts which perfectly joined each other and fitted the bone defect thanks to mechanical strength, also at low thicknesses and wide extensions.

The postoperative course was uneventful and computed tomography scans showed new bone formation and complete calvaria continuity already 10 months after surgery, with no signs of inflammation over the entire follow-up.

This case study represents a proof of concept that SmartBone on Demand custom-made bone grafts, together with puzzle technique, are effective, easy to handle and provide final excellent functional and aesthetic results.
Impact of Venous Outflow Pattern on Flap Compromise in Head and Neck Reconstruction: Review of 309 Radial Forearm Free Flaps
Authors: Kim Young Chul , Kim Min Ji , Kim Hyung Bae , Kim Sung Chan , Choi Jong Woo
Published: February 2019

There is ongoing controversy regarding the most appropriate venous drainage pattern for anastomosing the radial forearm free flap in head and neck reconstruction. Although the various perforator flaps have been used in our practice, the authors evaluated the impact of venous outflow pattern on the incidence of only the radial forearm free flap compromise for minimizing the bias. The authors retrospectively reviewed 309 radial forearm free flaps used for head and neck reconstruction following cancer ablation (January 2005 to December 2015), and evaluated the association between the incidence of venous insufficiency and the choice of venous system in the flap and at the recipient site, the number of venous anastomoses, and the combination of flap and recipient venous systems. No significant association was found between the incidence of venous insufficiency and the risk factors evaluated. Compared with single or dual anastomosis involving only the vena comitantes, dual anastomosis involving distinct venous systems was associated with lower incidence of venous insufficiency (P = 0.039). The dual anastomosis of separate venous system was correlated with lower incidence of venous insufficiency compared with the single or dual anastomosis of vena comitantes only (P = 0.039).
Treatment of Various Types of Gummy Smile With Botulinum Toxin-A
Authors: Duruel Onurcem , Ataman-Duruel Emel Tuğba , Berker Ezel , Tözüm Tolga Fikret
Published: February 2019

The objective of this article is to present 3 various types of gummy smile treated with botulinum toxin-A injection per site at Yonsei points. The patients, who visited the department to demand a more aesthetic smile, were classified according to gummy smile type: asymmetric, anterior, and mixed. Botulinum toxin-A injection at Yonsei point was considered. Preinjection and postinjection pictures were taken, and the severity of excessive gingival display was measured for each tooth between second premolars. Two weeks after botulinum toxin injections, no complication was noted. The amount of excessive gingival display for each tooth between second premolars was measured less than 3 mm, and the percentage of improvement for each case was calculated 100%. The botulinum toxin injection at Yonsei point may be a predictable and noninvasive treatment option for various types of gummy smile.
Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, in the Oral Cavity
Authors: Costa Sara Ferreira dos Santos , Silva André Myller Barbosa , Amaral-Silva Gleyson Kleber , Pontes Hélder Antônio Rebelo , Pontes Flávia Sirotheau Corrêa , Fonseca Felipe Paiva , Almeida Oslei Paes de
Published: February 2019

Lymphomas of the oral cavity are rare and the most frequent type is diffuse large B-cell lymphoma (DLBCL). Epstein–Barr virus (EBV) is known to be associated with the development of different lymphomas. In 2008, the World Health Organization provisionally included the EBV-positive DLBCL of the elderly in the classification of hematopoietic and lymphoid tumors as a lymphoma occurring in older individuals without any known immunodeficiency. However, it has since been recognized that this entity may occur in younger individuals and present similar clinical parameters in both age groups. As a result, the 2017 revision has declined the term elderly and modified it to EBV-positive DLBCL, not otherwise specified (NOS). In this report, we describe a rare case of EBV-positive DLBCL, NOS, presenting as a painless swelling in the oral cavity. This entity shows a more aggressive clinical course than EBV-negative DLBCL, and other lymphoproliferative disorders should be considered in the differential diagnosis.
Volumetric Analysis of Fat Injection by Computerized Tomography in Orthognathic Surgery: Preliminary Report on a Novel Volumetric Analysis Process for the Quantification of Aesthetic Results
Authors: Lazzarotto Andrea , Franz Leonardo , Stella Enrica , Tel Alessandro , Sembronio Salvatore , Costa Fabio , Bertossi Dario , Nocini Riccardo , Robiony Massimo
Published: February 2019

Background:

Integrated approaches to orthognathic surgery should include accurate volumetric evaluation of the skull and soft tissues. In patients with dentofacial deformities, the most frequent aesthetic deficits are attributable to an underdevelopment of hard and soft tissues. Traditional osteotomic procedures often fail to guarantee a stability of soft tissues over time. For this reason, in selecting a surgical strategy, the surgeon should consider not only traditional osteotomies, but also soft-tissue improving procedures, such as lipofilling. Preoperative surgical planning systems, such as the Virtual surgical planning (VSP) protocol, are based mainly on skeletal movement prediction. Quantitative estimation of soft-tissue modifications is not part of common clinical practice. Most commonly, the evaluation of soft-tissue modifications after orthognathic procedures is instead performed by clinical qualitative means.

The purpose of this study was to describe a novel computed tomography (CT)-based volumetric analysis process for the quantification of injected autologous adipose tissue in patients who have undergone simultaneous orthognathic and lipofilling procedures.

Methods:

This was a retrospective review of consecutive patients who underwent combined orthognathic surgery and lipofilling from June 2016 to May 2017 for malocclusion with functional and aesthetic impairments. Preoperative planning included clinical evaluation and virtual osteotomy planning according to the VSP protocol. The volume of fat to be injected was estimated clinically by comparing virtual renderings with preoperative clinical photographs. The surgical technique involved Le Fort I and sagittal split mandibular osteotomies, combined with autologous fat injection in the malar and perioral regions. Postoperative evaluation was performed with a novel imaging process based on CT image segmentation to quantify the exact volume of injected fat. Skeletal stability was also evaluated at 3 months.

Results:

Sixteen patients were enrolled in the study, all females, with a mean age of 24.5 years (range, 18–36 years). The mean difference between the fat tissue injected and that quantified postoperatively was 6.01 cm3. All patients had clinically satisfactory facial convexity, with complete restoration of the cheekbone contour, at 3 months.

Conclusion:

This study introduces a novel CT-image based technique to quantitatively assess the contribution of injected fat to the postoperative soft-tissue volume increase after combined orthognathic surgery with autologous lipofilling. In the future, this CT-based volumetric analysis technique could be the gold standard for evaluating facial lipofilling outcomes, and for assessing clinical aesthetic outcomes based on the injected volume of fat.
Maxillofacial Fractures Associated With Interpersonal Violence
Authors: Yamamoto Kazuhiko , Matsusue Yumiko , Horita Satoshi , Murakami Kazuhiro , Sugiura Tsutomu , Kirita Tadaaki
Published: February 2019

Interpersonal violence is a major cause of maxillofacial fractures. The aim of this study was to analyze the characteristics of these fractures associated in an effort to develop more effective management. The clinical records and radiographs of 272 patients with maxillofacial fractures associated with interpersonal violence collected during a 36-year period were retrospectively analyzed. Two hundred and nineteen patients were male (80.5%) and 53 (19.5%) were female. The patients ranged in age from 1 to 77 years. Two hundred and two patients (74.3%) were aged 10 to 29 years. The injury was the result of impact by a fist/hand/elbow in 224 patients (82.3%). The fracture site was the mandible in 191 patients (70.2%), the midface in 78 (28.7%), and both sites in 3 (1.1%). One hundred and eight (39.6%) of 273 mandibular fractures were in the angle, 75 (27.5%) were in the symphysis, and 90 (33.0%) were at other sites. Forty-three (53.1%) of 81 fractures in the midface were in the zygoma, 19 (23.5%) were in the maxilla, and 19 (23.5%) were at other sites. Fractures were more common on the left side. Nine patients (3.3%) also had injuries at other body sites. Ninety-five patients (34.9%) were treated by maxillomandibular fixation, 84 (30.9%) by open reduction and internal fixation, 59 (21.7%) by observation, 14 (5.1%) by intramaxillary splinting, 14 (5.1%) by transcutaneous reduction, and 6 (2.2%) by other procedures. Interpersonal violence-related maxillofacial fractures have characteristic features, especially with regard to site and laterality.
The Use of Integra in Extensive Full-Thickness Scalp Burn Involving the Skull in a Child
Authors: de Haas Louise E.M. , Gardien Kim L.M. , van Trier Antoine J.M. , Vloemans Adrianus F.P.M. , Buis Dennis R.
Published: February 2019

Extensive full-thickness burn injury of the scalp involving the skull is a challenge to reconstruct. Here, the authors report a case of a 6-year old girl who suffered extensive flame burn injury involving a scalp defect of 1,5% total body surface area. After necrosectomy, full table damage of the skull was observed with a partially exposed dura mater. Neurosurgical consultation was necessary to accomplish a vital wound bed. Subsequently, in the absence of enough adequate tissue available for flap surgery reconstruction, reconstruction was performed by using a bilayer Integra Dermal Regeneration Template (IDRT) resulting in a lasting and stable coverage of the defect. This is the first case-report describing application of IDRT on a full-thickness scalp and skull defect with exposed dura mater in a child. Our results are encouraging and demonstrate that Integra can be used in a child to successfully cover exposed dura when no viable skull remains.
Classification of RNA backbone conformation into rotamers using 13C′ chemical shifts: How far we can go?
Authors: Icazatti A. A. , Loyola J.M. , Szleifer I. , Vila J.A. , Martin O. A.
Published: February 2019

The conformational space of the ribose–phosphate backbone is very complex as is defined in terms of six torsional angles. To help delimit the RNA backbone conformational preferences 46 rotamers have been defined in terms of the these torsional angles. In the present work, we use the ribose experimental and theoretical 13C′ chemical shifts data and machine learning methods to classify RNA backbone conformations into rotamers and families of rotamers. We show to what extent the use of experimental 13C′ chemical shifts can be used to identify rotamers and discuss some problem with the theoretical computations of 13C′ chemical shifts.
Asparagine endopeptidase cleaves tau at N167 after uptake into microglia
Authors: Behrendt Annika , Bichmann Maria , Ercan-Herbst Ebru , Haberkant Per , Schöndorf David C. , Wolf Michael , Fahim Salma A. , Murolo Enrico , Ehrnhoefer Dagmar E.
Published: February 2019

Background

Tau cleavage by different proteolytic enzymes generates short, aggregation-prone fragments that have been implicated in the pathogenesis of Alzheimer’s disease (AD). Asparagine endopeptidase (AEP) activity in particular has been associated with tau dysfunction and aggregation, and the activity of the protease is increased in both aging and AD.

Methods and Results

Using a mass spectrometry approach we identified a novel tau cleavage site at N167 and confirmed its processing by AEP. In combination with the previously known site at N368, we show that AEP cleavage yields a tau fragment that is present in both control and AD brains at similar levels. AEP is a lysosomal enzyme, and our data suggest that it is expressed in microglia rather than in neurons. Accordingly, we observe tau cleavage at N167 and N368 after endocytotic uptake into microglia, but not neurons. However, tau168-368 does not accumulate in microglia and we thus conclude that the fragment is part of a proteolytic cascade leading to tau degradation.

Conclusions

While we confirm previous studies showing increased overall AEP activity in AD brains, our data suggests that AEP-mediated cleavage of tau is a physiological event occurring during microglial degradation of the secreted neuronal protein. The disease-associated increase in active AEP may thus be related to pro-inflammatory conditions in AD brains, and our findings argue against AEP inhibition as a therapeutic approach in AD.
Range-wide spatial mapping reveals convergent character displacement of bird song
Authors: Kirschel Alexander N. G. , Seddon Nathalie , Tobias Joseph A.
Published: February 2019

A long-held view in evolutionary biology is that character displacement generates divergent phenotypes in closely related coexisting species to avoid the costs of hybridisation or ecological competition, whereas an alternative possibility is that signals of dominance or aggression may instead converge to facilitate coexistence among ecological competitors. Although this counter-intuitive process—termed convergent agonistic character displacement—is supported by recent theoretical and empirical studies, the extent to which it drives spatial patterns of trait evolution at continental scales remains unclear. By modeling variation in song structure of two ecologically similar species ofHypocnemisantbird across western Amazonia, we show that their territorial signals converge such that trait similarity peaks in the sympatric zone, where intense interspecific territoriality between these taxa has previously been demonstrated. We also use remote sensing data to show that signal convergence is not explained by environmental gradients and is thus unlikely to evolve by sensory drive (i.e. acoustic adaptation to the sound transmission properties of habitats). Our results suggest that agonistic character displacement driven by interspecific competition can generate spatial patterns opposite to those predicted by classic character displacement theory, and highlight the potential role of social selection in shaping geographical variation in signal phenotypes of ecological competitors.
Selective culture enrichment and sequencing of faeces to enhance detection of antimicrobial resistance genes
Authors: Peto Leon , Fawcett Nicola J. , Crook Derrick W. , Peto Tim E.A. , Llewelyn Martin J. , Walker A. Sarah
Published: February 2019

Metagenomic sequencing of faecal DNA can usefully characterise an individual’s intestinal resistome but is limited by its inability to detect important pathogens that may be present at low abundance, such as carbapenemase or extended-spectrum beta-lactamase producingEnterobacteriaceae. Here we aimed to develop a hybrid protocol to improve detection of resistance genes inEnterobacteriaceaeby using a short period of culture enrichment prior to sequencing of DNA extracted directly from the enriched sample. Volunteer faeces were spiked with carbapenemase-producingEnterobacteriaceaeand incubated in selective broth culture for 6 hours before sequencing. Different DNA extraction methods were compared, including a plasmid extraction protocol to increase the detection of plasmid-associated resistance genes. Although enrichment prior to sequencing increased the detection of carbapenemase genes, the differing growth characteristics of the spike organisms precluded accurate quantification of their concentration prior to culture. Plasmid extraction protocols increased detection of resistance genes present on plasmids, but the effects were heterogeneous and dependent on plasmid size. Our results demonstrate methods of improving the limit of detection of selected resistance mechanisms in a faecal resistome assay, but they also highlight the difficulties in using these techniques for accurate quantification and should inform future efforts to achieve this goal.
Spt6 is a maintenance factor for centromeric CENP-A
Authors: Bobkov Georg OM , Huang Anming , van den Berg Sebastiaan J.W. , Mitra Sreyoshi , Anselm Eduard , Lazou Vasiliki , Schunter Sarah , Federle Regina , Imhof Axel , Lusser Alexandra , Jansen Lars E.T. , Heun Patrick
Published: February 2019

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This constitutes both an opportunity to remodel the underlying chromatin as well as the potential danger of losing epigenetic information. Centromeric transcription has been shown to be required for stable incorporation of the centromere-specific histone dCENP-A in M/G1-phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and shows enhanced association with non-phosphorylatable dCENP-A mutants compared to histone H3, while phosphomimetic residues alleviate association with Spt6. We conclude that Spt6 acts as a conserved CENP-A maintenance factor, which is required during transcription-mediated chromatin remodelling at the centromere to ensure long-term stability of epigenetic centromere identity.
Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells
Authors: Samudyata  , Amaral Paulo P. , Engström Pär G. , Robson Samuel C. , Nielsen Michael L. , Kouzarides Tony , Castelo-Branco Gonçalo
Published: February 2019

Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role of Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interact with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but might rather regulate other processes in the nucleoplasm.

Summary blurb

Sox2 interacts with RNA-binding proteins and diverse RNAs
Absolute quantification of cohesin, CTCF and their regulators in human cells
Authors: Holzmann Johann , Politi Antonio Z. , Nagasaka Kota , Hantsche-Grininger Merle , Walther Nike , Koch Birgit , Fuchs Johannes , Dürnberger Gerhard , Tang Wen , Ladurner Rene , Stocsits Roman R. , Busslinger Georg A. , Novak Bela , Mechtler Karl , Davidson Iain F. , Ellenberg Jan , Peters Jan-Michael
Published: February 2019

The organisation of mammalian genomes into loops and topologically associating domains (TADs) contributes to chromatin structure, gene expression and recombination. Loops and TADs are formed by cohesin and positioned by CTCF. In proliferating cells, cohesin also mediates sister chromatid cohesion, which is essential for chromosome segregation. Current models of chromatin folding and cohesion are based on assumptions of how many cohesin and CTCF molecules organise the genome. Here we have measured absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells. In G1-phase there are ~245,000 cohesin complexes, of which ~139,000 are on chromatin. Comparison with chromatin immunoprecipitation-sequencing data implies that some genomic cohesin and CTCF enrichment sites are unoccupied in single cells at any one time. We discuss the implications of these findings for how cohesin can contribute to genome organisation and cohesion.
BICORN: An R package for integrative inference of de novo cis-regulatory modules
Authors: Chen Xi
Published: February 2019

BICORN is an R package developed to integrate prior transcription factor binding information and gene expression data for cis-regulatory module (CRM) inference. BICORN searches for a list of candidate CRMs from binary bindings on potential target genes. Applying Gibbs sampling, BICORN samples CRMs for each gene using the fitting performance of transcription factor activities and regulation strengths of TFs in each CRM on gene expression. Consequently, sparse regulatory networks are inferred as functional CRMs regulating target genes. The BICORN package is implemented in R and is available at https://cran.r-project.org/web/packages/BICORN/index.html.
Cardiac Metabolic Limitations Contribute to Diminished Performance of the Heart in Aging
Authors: Gao X. , Jakovljevic D. G. , Beard D. A.
Published: February 2019

Changes in the myocardial energetics associated with aging—reductions in creatine phosphate (CrP)/ATP ratio, total creatine, and ATP—mirror changes observed in failing hearts compared to healthy controls. Similarly, both aging and heart failure are associated with significant reductions in cardiac performance and maximal left ventricular cardiac power output (CPO) compared to young healthy individuals. Based on these observations, we hypothesize that reductions in the concentrations cytoplasmic adenine nucleotide, creatine, and phosphate pools that occur with aging impair the myocardial capacity to synthesize ATP at physiological free energy levels, and that the resulting changes to myocardial energetic status impair the mechanical pumping ability of the heart. The purpose of this study is to test theses hypotheses using an age-structured population model for myocardial metabolism in the adult female population and to determine the potential impact of reductions in key myocardial metabolite pools in causing metabolic/energetic and cardiac mechanical dysfunction associated with aging. To test these hypotheses, we developed a population model for myocardial energetics to predict myocardial ATP, ADP, CrP, creatine, and inorganic phosphate concentrations as functions of cardiac work and age in the adult female population. Model predictions support our hypotheses and are consistent with previous experimental observations. The major findings provide a novel theoretical and computational framework for further probing complex relationships between the energetics and performance of the heart with aging.

Significance

Normal mechanical function of the heart requires that ATP be continuously synthesized at a hydrolysis potential of roughly −60 kJ mol−1. Yet in both the aging and diseased heart the relationships between cardiac work rate and concentrations of ATP, ADP, and inorganic phosphate are altered. Important outstanding questions are: To what extent do changes in metabolite concentrations that occur in aging and heart disease affect metabolic/molecular processes in the myocardium? How are systolic and diastolic functions affected by changes in metabolite concentrations? This study addresses these questions by analyzing relationships between cardiac energy demand and supply using an age-structured population model for human myocardial energetics in women.
Single cell q-PCR derived expression profiles of identified sensory neurons
Authors: Adelman Peter , Baumbauer Kyle , Friedman Robert , Shah Mansi , Wright Margaret , Young Erin , Jankowski Michael P. , Albers Kathryn M. , Koerber H. Richard
Published: February 2019

Sensory neurons are chemically and functionally heterogeneous and this heterogeneity has been examined extensively over the last several decades. These studies have employed a variety of different methodologies, including anatomical, electrophysiological and molecular approaches. Recent studies using next generation sequencing techniques have examined the transcriptome of single sensory neurons. Although, these reports have provided a wealth of exciting new information on the heterogeneity of sensory neurons, correlation with functional types is lacking. Here, we employed retrograde tracing of cutaneous and muscle afferents to examine the variety of mRNA expression profiles of individual, target-specific sensory neurons. In addition, we used an ex vivo skin/nerve/DRG/ spinal cord preparation to record and characterize the functional response properties of individual cutaneous sensory neurons that were then intracellularly labeled with fluorescent dyes, recovered from dissociated cultures and analyzed for gene expression. We found that by using single cell qPCR techniques and a limited set of genes, we can identify transcriptionally distinct groups. We have also used calcium imaging and single cell qPCR to determine the correlation between levels of mRNA expression and functional protein expression and how functional properties correlated with the different transcriptional groups. These studies show that although transcriptomics does map to functional types, within any one functional subgroup, there are highly variable patterns of gene expression. Thus, studies that rely on the expression pattern of one or a few genes as a stand in for physiological experiments, runs a high risk of data misinterpretation with respect to function.

Significance statement

Expression profiles of unidentified sensory neurons have been recently studied using RNASeq techniques. Here, we utilize a multifactorial approach to target identified cutaneous and muscle afferents to examine expression and functional levels of specific high priority candidate genes using ex vivo electrophysiology, Ca2+ imaging, and single cell qPCR. Using this methodology, we were able to identify specific groups of neurons with distinct functional properties that corresponded to unique transcriptional profiles. This represents the first attempt to relate neuronal phenotype with levels of gene expression in single identified afferents and highlights the importance of combining functional analysis with transcriptomics.
Prevalence of sleep-disordered breathing and associations with malocclusion in children
Authors: Aroucha Lyra Maria Carlla , Aguiar Débora , Paiva Mabel , Arnaud Manuela , Filho Arnoldo Alencar , Rosenblatt Aronita , Thérèse Innes Nicola Patricia , Heimer Mônica Vilela
Published: February 2019

Objective

This study aimed to determine the prevalence of sleep-disordered breathing (SDB) and its association with malocclusion among children in Recife, Brazil.

Methods

390 children aged seven to eight years took part in the study, comprised by the body mass measurement, orthodontic examination and parent’s information required by the Sleep Disturbance Scale for Children. Statistics tools were Pearson’s chi-square and Lemeshow test.

Results

SDB was found in 33.3% of the children and associated with overjet (p= 0.007), anterior open bite (p=0.008) and posterior crossbite (p= 0.001). There was no association between BMI and SDB. The multivariate logistic regression model indicated that the anterior open bite (p= 0.002) and posterior crossbite (p = 0.014) have an association with SDB.

Conclusions

Results of this study indicated that the prevalence of SDB was high and highly associated with malocclusion; anterior open bite and posterior crossbite are risk factors for SDB.
Increased synaptic facilitation and exploratory behavior in mice lacking the presynaptic protein Mover
Authors: Viotti Julio S. , Ott Frederik W. , Schleicher Eva M. , Wagner Jannek M. , Bouter Yvonne , Bayer Thomas A. , Dresbach Thomas
Published: February 2019

In vertebrates and invertebrates, neurotransmitter release relies on a highly conserved molecular machinery. A surprisingly small number of presynaptic proteins evolved specifically in vertebrates. How they expand the power or versatility of the conserved core machinery is unclear. One of these vertebrate-specific proteins, called Mover / TPRGL / SVAP30, is heterogeneously expressed throughout the brain, suggesting that it adds special functions to subtypes of presynaptic terminals. In this study we generated Mover knockout mice to investigate the role of Mover from synaptic transmission to behavior. Deletion of Mover did not affect synaptic transmission at CA3 to CA1 synapses. In contrast, Mover deficient mice had strongly increased short-term facilitation at mossy fiber to CA3 synapses. This increase included frequency facilitation, a hallmark of mossy fiber terminal function. The effect was age- and Ca2+-dependent, and relied on the Kainate receptor/cAMP pathway in the mossy fiber terminals. Despite this change in presynaptic plasticity, the absence of Mover did not affect long-term spatial reference memory or working memory, but led to reduced anxiety. These discoveries suggest that Mover has distinct roles at different synapses. At mossy-fiber terminals, it acts to constrain the extent of presynaptic facilitation. Its role in activity-dependent neurotransmission could be necessary for normal anxiety responses.

Significance Statement

The enormous increase in the complexity of brains during evolution is accompanied by a remarkably small number of new, vertebrate-specific presynaptic proteins. These proteins are unlikely to be essential for transmitter release, because invertebrate synapses do not need them. But what functions do they fulfill? We show that the vertebrate-specific protein Mover is involved in constraining the release of neurotransmitters in some synapses in the hippocampus, while not affecting others. We further demonstrate that the absence of this protein leads to decreased anxiety levels. Understanding the function of such a protein can help us further understand synaptic transmission, the specializations that are brought about in vertebrate synapses, and how this can help or hinder neurological or psychiatric disorders.
Interdependent Phenotypic and Biogeographic Evolution Driven by Biotic Interactions
Authors: Quintero Ignacio , Landis Michael J.
Published: February 2019

Biotic interactions are hypothesized to be one of the main processes shaping trait and biogeographic evolution during lineage diversification. Theoretical and empirical evidence suggests that species with similar ecological requirements either spatially exclude each other, by preventing the colonization of competitors or by driving coexisting populations to extinction, or show niche divergence when in sympatry. However, the extent and generality of the effect of interspecific competition in trait and biogeographic evolution has been limited by a dearth of appropriate process-generating models to directly test the effect of biotic interactions. Here, we formulate a phylogenetic parametric model that allows interdependence between trait and biogeographic evolution, thus enabling a direct test of central hypotheses on how biotic interactions shape these evolutionary processes. We adopt a Bayesian data augmentation approach to estimate the joint posterior distribution of trait histories, range histories, and co-evolutionary process parameters under this analytically intractable model. Through simulations, we show that our model is capable of distinguishing alternative scenarios of biotic interactions. We apply our model to the radiation of Darwin’s finches—a classic example of adaptive divergence—and find support for in situ trait divergence in beak size, convergence in traits such as beak shape and tarsus length, and strong competitive exclusion throughout their evolutionary history. Our modeling framework opens new possibilities for testing more complex hypotheses about the processes underlying lineage diversification. More generally, it provides a robust probabilistic methodology to model correlated evolution of continuous and discrete characters.