bluuebunny/crossref_metadata_2025 huggingface dataset:
Computed Tomography Cholangiography Using the Magnetic Resonance Contrast Agent Gadoxetate Disodium
Authors: Dilger Samantha K.N. , Nelson Noelle , Venkatesh Sudhakar K. , Ehman Eric C. , Fidler Jeff L. , Fletcher Joel G. , McCollough Cynthia H. , Yu Lifeng
Published: July 2019

Objective

The purpose of this work is to determine whether low doses of gadoxetate disodium (Eovist; Bayer Healthcare LLC, Whippany, NJ), a gadolinium-based contrast agent used for magnetic resonance liver imaging, can be visualized for computed tomography (CT) cholangiography using a phantom setup.

Materials and Methods

Vials containing 4 concentrations of gadoxetate disodium (1.9, 3.4, 4.8, and 9.6 mg Gd/mL) were placed in a 35 × 26-cm2 water phantom and imaged on 2 CT scanners: Siemens Somatom Flash and Force (Siemens Healthcare, Erlangen, Germany). These concentrations correspond to the estimated concentration in the bile duct for a 40-, 70-, or 100-kg patient, and twice the concentration of a 100-kg patient, respectively. Single-energy (SE) scans were acquired at 70, 80, 90, 100, 120, and 140 kVp, and dual-energy scans were acquired at 90/150Sn (Force) and 100/150 (Flash) for 2 dose levels (CTDIvol 13 and 23 mGy). Virtual monoenergetic images at 50 keV were created (Mono+; Siemens Healthcare, Erlangen, Germany). The mean intensity and standard deviation for each concentration of gadoxetate disodium and the water background were extracted from each image set and used to compute the contrast and contrast-to-noise ratio (CNR). To determine whether the signal provided by gadoxetate disodium was clinically sufficient, the measures were compared with those acquired from 12 clinical CT cholangiography examinations performed with iodine-containing iodipamide meglumine.

Results

From the retrospective clinical cohort, mean contrast (± standard deviation) of 239 ± 107 HU and CNR of 12.8 ± 4.2 were found in the bile duct relative to the liver. Comparing these metrics to the gadoxetate disodium samples, the highest concentration (9.6 mg Gd/mL) surpassed these thresholds at all energy levels. The 4.8 mg Gd/mL had sufficient CNR in the Force, but not in the Flash. The 3.4 mg Gd/mL had clinically relevant CNR at low kV of SE (<100 kVp) and 50 keV of dual energy in the Force but was insufficient in the Flash. Images acquired by the Force had a lower noise level and greater CNR compared with the Flash. Similar trends were seen at both dose levels.

Conclusions

Gadoxetate disodium shows promise as a viable contrast agent for CT cholangiography, with CNR similar to those seen clinically with an iodine-based contrast agent. Dual-energy CT or low kV SE-CT is helpful to enhance the signal.
Can Virtual Contrast Enhancement in Brain MRI Replace Gadolinium?
Authors: Kleesiek Jens , Morshuis Jan Nikolas , Isensee Fabian , Deike-Hofmann Katerina , Paech Daniel , Kickingereder Philipp , Köthe Ullrich , Rother Carsten , Forsting Michael , Wick Wolfgang , Bendszus Martin , Schlemmer Heinz-Peter , Radbruch Alexander
Published: July 2019

Objectives

Gadolinium-based contrast agents (GBCAs) have become an integral part in daily clinical decision making in the last 3 decades. However, there is a broad consensus that GBCAs should be exclusively used if no contrast-free magnetic resonance imaging (MRI) technique is available to reduce the amount of applied GBCAs in patients. In the current study, we investigate the possibility of predicting contrast enhancement from noncontrast multiparametric brain MRI scans using a deep-learning (DL) architecture.

Materials and Methods

A Bayesian DL architecture for the prediction of virtual contrast enhancement was developed using 10-channel multiparametric MRI data acquired before GBCA application. The model was quantitatively and qualitatively evaluated on 116 data sets from glioma patients and healthy subjects by comparing the virtual contrast enhancement maps to the ground truth contrast-enhanced T1-weighted imaging. Subjects were split in 3 different groups: enhancing tumors (n = 47), nonenhancing tumors (n = 39), and patients without pathologic changes (n = 30). The tumor regions were segmented for a detailed analysis of subregions. The influence of the different MRI sequences was determined.

Results

Quantitative results of the virtual contrast enhancement yielded a sensitivity of 91.8% and a specificity of 91.2%. T2-weighted imaging, followed by diffusion-weighted imaging, was the most influential sequence for the prediction of virtual contrast enhancement. Analysis of the whole brain showed a mean area under the curve of 0.969 ± 0.019, a peak signal-to-noise ratio of 22.967 ± 1.162 dB, and a structural similarity index of 0.872 ± 0.031. Enhancing and nonenhancing tumor subregions performed worse (except for the peak signal-to-noise ratio of the nonenhancing tumors). The qualitative evaluation by 2 raters using a 4-point Likert scale showed good to excellent (3–4) results for 91.5% of the enhancing and 92.3% of the nonenhancing gliomas. However, despite the good scores and ratings, there were visual deviations between the virtual contrast maps and the ground truth, including a more blurry, less nodular-like ring enhancement, few low-contrast false-positive enhancements of nonenhancing gliomas, and a tendency to omit smaller vessels. These “features” were also exploited by 2 trained radiologists when performing a Turing test, allowing them to discriminate between real and virtual contrast-enhanced images in 80% and 90% of the cases, respectively.

Conclusions

The introduced model for virtual gadolinium enhancement demonstrates a very good quantitative and qualitative performance. Future systematic studies in larger patient collectives with varying neurological disorders need to evaluate if the introduced virtual contrast enhancement might reduce GBCA exposure in clinical practice.
Real-Time Magnetic Resonance Imaging
Authors: Frahm Jens , Voit Dirk , Uecker Martin
Published: July 2019

Objective

The aim of this study is to evaluate a real-time magnetic resonance imaging (MRI) method that not only promises high spatiotemporal resolution but also practical robustness in a wide range of scientific and clinical applications.

Materials and Methods

The proposed method relies on highly undersampled gradient-echo sequences with radial encoding schemes. The serial image reconstruction process solves the true mathematical task that emerges as a nonlinear inverse problem with the complex image and all coil sensitivity maps as unknowns. Extensions to model-based reconstructions for quantitative parametric mapping further increase the number of unknowns, for example, by adding parameters for phase-contrast flow or T1 relaxation. In all cases, an iterative numerical solution that minimizes a respective cost function is achieved with use of the iteratively regularized Gauss-Newton method. Convergence is supported by regularization, for example, to the preceding frame, whereas temporal fidelity is ensured by downsizing the regularization strength in comparison to the data consistency term in each iterative step. Practical implementations of highly parallelized algorithms are realized on a computer with multiple graphical processing units. It is “invisibly” integrated into a commercial 3-T MRI system to allow for conventional usage and to provide online reconstruction, display, and storage of regular DICOM image series.

Results

Depending on the application, the proposed method offers serial imaging, that is, the recording of MRI movies, with variable spatial resolution and up to 100 frames per second (fps)—corresponding to 10 milliseconds image acquisition times. For example, movements of the temporomandibular joint during opening and closing of the mouth are visualized with use of simultaneous dual-slice movies of both joints at 2 × 10 fps (50 milliseconds per frame). Cardiac function may be studied at 30 to 50 fps (33.3 to 20 milliseconds), whereas articulation processes typically require 50 fps (20 milliseconds) or orthogonal dual-slice acquisitions at 2 × 25 fps (20 milliseconds). Methodological extensions to model-based reconstructions achieve improved quantitative mapping of flow velocities and T1 relaxation times in a variety of clinical scenarios.

Conclusions

Real-time gradient-echo MRI with extreme radial undersampling and nonlinear inverse reconstruction allows for direct monitoring of arbitrary physiological processes and body functions. In many cases, pertinent applications offer hitherto impossible clinical studies (eg, of high-resolution swallowing dynamics) or bear the potential to replace existing MRI procedures (eg, electrocardiogram-gated cardiac examinations). As a consequence, many novel opportunities will require a change of paradigm in MRI-based radiology. At this stage, extended clinical trials are needed.
Evaluation of Skeletal Muscle Microcirculation and Reserve Function of the Type 2 Diabetes with Contrast-Enhanced Ultrasonography
Authors: Xu Zhen-Hong , Chen Jiao-Hong , Huang Feng-Bin , Lv Guo-Rong
Published: July 2019

Objective

This study aimed to discuss clinical application value of contrast-enhanced ultrasonography on lesion skeletal muscle microcirculation and arterial perfusion reserve in type 2 diabetes mellitus and complicated microvessels.

Methods

Patients in the control group, type 2 diabetes mellitus (DM) group, diabetic microangiopathy (DM + MC) group underwent contrast-enhanced ultrasonography before and after temporary arterial occlusion to observe blood perfusion of gastrocnemius muscle; draw the time-intensity curve of arteriole, muscular tissue, and venule, and obtain perfusion parameters such as contrast agent arrival time and contrast agent transit time. Blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters were measured.

Results

Contrast agent transit time of the DM + MC group before arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of the DM + MC group after temporary arterial occlusion was significantly longer than that of the DM group and control group (P < 0.05). Contrast agent transit time of △artery-muscle, △artery-vein, and △muscle-vein of the DM group and control group and △artery-muscle of the DM + MC group after arterial occlusion was significantly shortened, when compared with that before arterial occlusion (P < 0.05). For △muscle-vein and △artery-vein contrast agent transit time in the DM + MC group, the difference was not statistically significant. By comparing blood glucose, insulin, insulin resistance index, and relevant blood rheology parameters among the DM + MC group, DM group, and control group, the difference was statistically significant, and there was a good correlation.

Conclusion

Contrast-enhanced ultrasonography can be used to evaluate skeletal muscle microcirculation disturbance and arterial reserve function of patients who had type 2 diabetic microangiopathy.
Assessment of Somatosensory Reorganization by Functional Magnetic Resonance Imaging After Hand Replantation
Authors: Guillier David , Moris Vivien , Daubail Benoit , Rizzi Philippe , Tchurukdichian Alain , Baudoin Nathalie , Bejot Yannick , Zwetyenga Narcisse , Jacquin-Piques Agnes
Published: July 2019

Introduction

Amputation of the hand is a rare and extremely intense trauma. Replanting and allografting after this type of injury require a major reorganization of the brain. Brain plasticity, though better known in the context of disorders of the central nervous system, is just as indispensable when the extremities are damaged.

Materials and Methods

A 17-year-old patient underwent replantation of the nondominant hand after transmetaphyseal amputation after traumatic injury. After 18 days in hospital and subsequent treatment in a physical rehabilitation center, the patient attended clinical and radiology follow-up sessions over the next 2 years.

Results

The management of this patient led to an excellent functional outcome in conjunction with successful social and professional reintegration. Electromyography at 18 months confirmed nerve regrowth. Functional magnetic resonance imaging was done at 2 years to evaluate cerebral plasticity. Motor function, largely dependent on the primary motor area, is aided by the addition of secondary and accessory motor areas for both simple and complex movements. A change in sensory information is stimulation in its own right hemisphere and increases solicitation of the contralateral precentral and postcentral gyrus.

Conclusions

There seems to be a real reversible dynamic plasticity under the balance of inhibitory and excitatory influences exerted on the cortical neurons. Any disruption of this balance requires the brain to adapt to the new circumstances to reestablish the hand as a functioning part of the body.
Cranial Erosion Associated With Non-Midline Dermoid Cysts in the Pediatric Population
Authors: Van Kouwenberg Emily , Kanth Aditi M. , Mountziaris Paschalia , Adetayo Oluwaseun A.
Published: July 2019

Background:

While the risk for intracranial extension of midline nasoglabellar dermoid cysts is well-described, the risk in non-midline dermoid cysts and role of preoperative imaging in these lesions is less understood. This study aims to address this gap and provide preoperative recommendations.

Materials and Methods:

A retrospective review was performed evaluating patients who underwent excision of craniofacial dermoid cysts by a single surgeon. Findings on preoperative physical examination and imaging modalities were compared to intraoperative findings to assess effectiveness of each in predicting bony erosion. A treatment algorithm is proposed.

Results:

Twenty-eight patients were included and 50% had intraoperatively confirmed bony erosion. Bony erosion was identified in 100% of lesions immobile on examination, compared to 30% of mobile lesions (P = 0.001). Bony erosion was identified in 40.9% of lateral brow cysts compared to 83.3% of lesions located elsewhere (P = 0.03), in 60% of patients with periorbital sequelae compared to 47.8% without periorbital sequelae, and in 66.7% of patients with reported change in cyst size with Valsalva compared to 48.0% without change with Valsalva. Sensitivities for preoperative identification of bony erosion were as follows: physical examination 57.1%, US 11.1%, MRI 66.7%, and CT 100%.

Conclusions:

A management algorithm for non-midline dermoid cysts is presented. CT or MRI is recommended for lesions that are immobile, in atypical locations, or have associated periorbital sequelae or change with Valsalva. The authors feel there is no role for ultrasound and don’t recommend routine imaging in patients with non-midline dermoid cysts without features suggestive of bony erosion.
Autologous Fat Grafting for the Treatment of Mild to Moderate Velopharyngeal Insufficiency
Authors: Adams Saleigh , Xoagus Elizabeth A. , Lazarus Dirk , Lentin Roslyn , Hudson Donald A.
Published: July 2019

Background:

To assess speech results following the treatment of mild to moderate velopharyngeal insufficiency (VPI) post cleft palate surgery with autologous fat grafting to the velopharynx.

Methods:

A retrospective study was conducted on 9 consecutive patients who underwent velopharyngeal fat grafting for the treatment of VPI at the Red Cross War Memorial Children's hospital from 2010 to 2014. All the patients previously had primary palatoplasty performed and subsequently developed VPI. Patients were assessed pre- and postoperatively by an experienced speech and language therapist looking at perceptual speech and by 2 senior cleft surgeons interpreting lateral view videofluoroscopies.

Results:

Eleven fat grafting procedures were performed on 9 patients and an average of 5.64 mL (range 1–7 mL) of autologous fat was transferred to the velopharynx. The average age at the time of operation was 6.5 years (range 3–14 years) with a follow-up period of 18 months (range 7–34 months). Most of the patients (7 out of 9) showed improved speech after fat grafting. One of the 7 patients had multiple procedures. The 2 who did not show speech improvement only had a single procedure. There were no complications related to the fat grafting procedure.

Conclusion:

This small study suggests that fat grafting either as a single procedure or as multiple procedures is an effective, safe, minimally invasive surgical alternative, and/or adjunct for the treatment of mild to moderate VPI in patients following cleft palate surgery and to the knowledge, is the first reported study from Africa.
Perioperative Outcomes Following Pediatric Cranial Vault Remodeling: Are Improvements Possible?
Authors: Morrow Brad T. , Ditthakasem Kanlaya , Herbert Morley , Fearon Jeffrey A.
Published: July 2019

Purpose:

The Pediatric Craniofacial Collaborative Group recently reported pooled perioperative data from 31 North American centers performing open cranial vault remodeling procedures. The authors sought to determine if outcomes were different at a single higher-volume center and if identified, ascertain reasons for any differences and propose strategies for improvement.

Methods:

A retrospective review was performed of all open pediatric cranial vault procedures performed at our center during the identical 3.25-year period reported by the Collaborative group, including demographic, perioperative management and outcome data, to permit multiple comparative analyses.

Results:

The 310 procedures were performed by our center during this time period, compared to 1223 by the combined 31 institutions (median: 29.5 cases/center; interquartile range: 12–54.5). Multiple outcome differences were found: our higher-volume center had a significantly lower overall red blood cell transfusion rate (≤2 years: 7.5 percent vs 91 percent, P <0.001), those requiring transfusions were transfused considerably smaller volumes (≤2 years: 3.8mL/kg vs 45.3 mL/kg, P <0.001), and exposure to ≥3 blood donors was significantly less (none vs 20 percent, P <0.001). There were no mortalities in either group, but almost all matched adverse events were less common at our center. Both the intensive care unit and hospital lengths of stay were significantly shorter at our center (1 vs 2 days, 2 vs 4 days, both P <0.001).

Conclusions:

Perioperative outcomes following pediatric craniosynostosis corrections performed at a single higher-volume center compare favorably to median national data. Multiple potential strategies to reduce blood utilization, minimize perioperative complications, and shorten hospitalizations are proposed.
A Promising New Technique for Correcting a Deviated Nose: Partial Disarticulation of Keystone Area
Authors: Cabbarzade Cavid
Published: July 2019

Correction of the septum is essential for the correction of deviated nose. If no intervention is made to the septum that does not start from midline at the keystone area, either the crookedness will persist or thicker spreader grafts will need to be placed at the opposite side of the crookedness or further camouflaging will be required. The latter may cause dorsum to get wider. In the present study, partial disarticulation of keystone (PDK) method is presented for the correction of septum that does not start from the midline at the keystone area. This retrospective study included 18 patients in whom PDK method was employed to correct nasal deformity. The keystone area was repositioned by disarticulating the cartilage from the bone on the anterior part of the junction of the ethmoid bone with the septal cartilage. The patients were followed up for the duration of 12 to 33 (mean: 22.5) months. No patients developed a serious complication or required revision surgery. The PDK method can be applied to patients if dorsal septum does not start from the midline at the keystone area. This is a minimally invasive, time-saving method that has a short learning curve and decreases the possibility of further widening of dorsum.
Cone-Beam Computed Tomography Study of Mandibular Condylar Morphology
Authors: Yalcin Eda Didem , Ararat Emine
Published: July 2019

Objective:

The purpose of this study was to evaluate the morphology of mandibular condyle using cone-beam computed tomography (CBCT) on coronal sections in a South-Eastern Anatolian population.

Methods:

A total of 1820 joints in 910 subjects with age range of 18 to 86 years were examined retrospectively on CBCT images. The mandibular condylar morphology was examined in right and left sides on coronal sections and classified as convex, round, flat, and angled. In addition, condyle morphology was assessed according to age, gender, edentulism, Angle's classification.

Results:

The study sample contained CBCT scans of 910 patients (50.3% female, 49.7% male) with a mean age of 42.31 ± 15.74. Condylar morphologies were analyzed as convex in 40.5%, angled in 34.3%, flat in 15.5%, round in 9.6% of the cases. Condyle shape was found statistically related to group age, gender, edentulism (P <0.05).

Conclusion:

The findings suggest that mandibular condyle shape is associated with age, gender, and edentulism. CBCT may be considered as an appropriate imaging method for detection of condyle alterations of temporomandibular joints and it could provide early diagnosis of temporomandibular joint disorder.
Incidence of Preventable Nonfatal Craniofacial Injuries and Implications for Facial Transplantation
Authors: Kantar Rami S. , Alfonso Allyson R. , Ramly Elie P. , Diaz-Siso J. Rodrigo , Jacoby Adam , Sosin Michael , Ceradini Daniel J. , Rodriguez Eduardo D.
Published: July 2019

Introduction:

The number of patients who may benefit from evaluation for face transplantation in the United States (US) remains largely unknown. The goal of our study was to better delineate the pool of patients who might benefit from face transplant evaluation based on the characteristics and mechanisms of injury of previously reported face transplant recipients.

Methods:

The authors utilized data from the National Electronic Injury Surveillance System-All Injury Program in this study. The US Census Bureau data were used for population estimates. Inclusion and exclusion criteria were determined based on the characteristics of face transplant recipients to date, and the mechanisms of injury they sustained ultimately necessitating face transplantation. Statistical significance was reached if P <0.05.

Results:

The estimated annual incidence of preventable craniofacial injuries from firearms (44,266–58,299; 31.7% increase), burns (5712–19,433; 240.2% increase), and animal attacks (5355–14,666; 173.9% increase) increased from 2005 to 2014, whereas the estimated annual incidence of craniofacial injuries from machinery (3927–2933; 25.3% decrease) decreased between 2005 and 2014. The authors estimate the annual incidence rate to fall between 32.1 per 100,000 and 58.1 per 100,000 among individuals aged 20 to 64 in the US.

Conclusion:

In this study, the authors estimate the annual incidence rate of individuals aged 20 to 64 in the US who may benefit from face transplant evaluation and believe that this quantification has the potential to initiate actionable discussions regarding geographical and financial factors affecting access to care in this patient population.
Management of Frontal Bone Fractures
Authors: Schultz Jerette J. , Chen Jeffrey , Sabharwal Samir , Halsey Jordan N. , Hoppe Ian C. , Lee Edward S. , Granick Mark S.
Published: July 2019

Background:

The purpose of this study was to examine a level 1 trauma center's 12-year experience treating frontal sinus fractures with regards to patient demographics, management strategies, and treatment outcomes.

Methods:

An institutional review board-approved retrospective review of all facial fractures at a level 1 trauma center was performed for the years 2000 to 2012. Patient demographics, location of fractures, concomitant injuries, use of antibiotics, surgical management strategies and outcomes were collected for all frontal sinus fractures. A significance value of 5% was used.

Results:

There were 291 frontal sinus fractures treated at our institution. The mean age of patients was 34.4 years with a male predominance (90%). The most common mechanisms of injury were assault in 82 (28.2%) and motor vehicle accidents in 80 (27.5%). Anterior table fractures were seen in 261 patients (89.7%) and posterior table fractures were seen in 181 (62.2%). Treatment included ORIF with sinus preservation in 18 (6.2%), ORIF with sinus obliteration in 20 (6.9%), and cranialization in 18 (6.2%). Antibiotics were started on admission in 152 patients (52.2%). Fatality occurred in 9.3% of patients and complications included meningitis (1%), frontal sinusitis (1%), early wound infection (0.3%), and mucopyelocele (0.3%).

Conclusions:

Frontal sinus fractures in our center are most often caused by interpersonal violence. Anterior table fractures were more common than posterior table fractures and ORIF with sinus obliteration was the most common surgical intervention. Most frontal sinus fractures at our institution (82%) were treated conservatively with no surgical intervention and we observed a low rate of long term complications.
Effects of Auricular Acupressure on Women With Irritable Bowel Syndrome
Authors: Go Gee Youn , Park Hyojung
Published: July 2019

The purpose of this study was to examine the effect of auricular acupressure on bowel symptoms, stress, mental health, and heart rate variability in women with irritable bowel syndrome (IBS). A quasi-experimental study design with a nonequivalent control group assessed a total sample of 56 women diagnosed with IBS according to Rome III criteria. There were 29 women in the experimental group who received auricular acupressure; 27 women were in the control group. Semen sinapis albae seeds were used to administer acupressure to four auricular points: endocrine, large intestine, lung, and Shenmen for 5 days/week for 4 weeks; the control group received no treatment. Bowel symptoms, stress, mental health, and heart rate variability were measured twice, once before and once after the intervention. Chi-square tests,ttests, and pairedttests were used for analysis. The experimental group had decreased loose stools, abdominal pain, diarrhea, abdominal discomfort, stress, and heart rate variability compared with the control group (p< .05). Auricular acupressure was effective for symptom improvement in patients with IBS.
Big problems in little patients: Nationwide blunt cerebrovascular injury outcomes in the pediatric population
Authors: Marenco Christopher W. , Do Woo S. , Lammers Daniel T. , Morte Kaitlin R. , Eckert Matthew J. , Eckert Carly M. , Bensard Denis , Martin Matthew J.
Published: July 2019

BACKGROUND

Blunt cerebrovascular injuries (BCVI) are uncommon but potentially devastating. The epidemiology, outcomes, and screening criteria are well described in adults, but data in pediatric patients are extremely limited. The purpose of this study was to characterize pediatric BCVI in a large nationwide sample. We hypothesized that outcomes of BCVI in the pediatric blunt trauma population will vary by age.

METHODS

We conducted a retrospective cohort study of the Kids' Inpatient Database for pediatric BCVI from 2000 to 2012. Epidemiology, associated injuries, outcomes (including stroke and mortality), and the utility of standard screening criteria were analyzed.

RESULTS

There were 1,182 cases of BCVI identified, yielding an incidence of 0.21%. Patients were predominately male (69%; mean age, 15 ± 5 years). Injuries were 59% carotid, 13% vertebral, and 28% unspecified, with 15% having bilateral or multivessel BCVI. Although younger patients (<11 years) had significantly lower ISS and decreased severe associated injuries (all p < 0.01), they had a similar mortality rate (10%) versus the older cohort. Additionally, the stroke rate was significantly higher among the younger patients versus their older peers (29% mortality for <11 years vs. 15% for ≥11 years, p < 0.01). Only four of seven commonly utilized risk factors were associated with BCVI overall, but none were significantly associated with BCVI in younger children (<11 years).

CONCLUSION

This represents the first nationwide assessment of BCVI in the pediatric population. Pediatric BCVI carry considerable mortality and stroke risk. Despite being less severely injured, younger children (<11 years) had similar a mortality rate and a significantly higher stroke rate compared with older pediatric patients. Furthermore, commonly utilized adult screening criteria had limited utility in the younger cohorts. These findings suggest pediatric BCVI may require screening and treatment protocols that are significantly different than currently utilized adult-based programs.

LEVEL OF EVIDENCE

Prognostic/Epidemiological Study, level III.
The plasma membrane as a mechanochemical transducer
Authors: Le Roux Anabel-Lise , Quiroga Xarxa , Walani Nikhil , Arroyo Marino , Roca-Cusachs Pere
Published: July 2019

Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment that is also a biochemical platform, the plasma membrane (PM) is a key interface mediating both cellular response to mechanical stimuli, and subsequent biochemical responses. Here, we review the role of the PM as a mechanosensing structure. We first analyse how the PM responds to mechanical stresses, and then discuss how this mechanical response triggers downstream biochemical responses. The molecular players involved in PM mechanochemical transduction include sensors of membrane unfolding, membrane tension, membrane curvature or membrane domain rearrangement. These sensors trigger signalling cascades fundamental both in healthy scenarios and in diseases such as cancer, which cells harness to maintain integrity, keep or restore homeostasis and adapt to their external environment.

This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Mechanotransduction: from the cell surface to the nucleus via RhoA
Authors: Burridge Keith , Monaghan-Benson Elizabeth , Graham David M.
Published: July 2019

Cells respond and adapt to their physical environments and to the mechanical forces that they experience. The translation of physical forces into biochemical signalling pathways is known as mechanotransduction. In this review, we focus on two aspects of mechanotransduction. First, we consider how forces exerted on cell adhesion molecules at the cell surface regulate the RhoA signalling pathway by controlling the activities of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). In the second part of the review, we discuss how the nucleus contributes to mechanotransduction as a physical structure connected to the cytoskeleton. We focus on recent studies that have either severed the connections between the nucleus and the cytoskeleton, or that have entirely removed the nucleus from cells. These actions reduce the levels of active RhoA, thereby altering the mechanical properties of cells and decreasing their ability to generate tension and respond to external mechanical forces.

This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’.
Aquirufa antheringensis gen. nov., sp. nov. and Aquirufa nivalisilvae sp. nov., representing a new genus of widespread freshwater bacteria
Authors: Pitt Alexandra , Schmidt Johanna , Koll Ulrike , Hahn Martin W.
Published: July 2019

Three bacterial strains, 30S-ANTBAC, 103A-SOEBACH and 59G- WUEMPEL, were isolated from two small freshwater creeks and an intermittent pond near Salzburg, Austria. Phylogenetic reconstructions with 16S rRNA gene sequences and, genome based, with amino acid sequences obtained from 119 single copy genes showed that the three strains represent a new genus of the family

Cytophagaceae

within a clade formed by the genera

Pseudarcicella

,

Arcicella

and

Flectobacillus

. blast searches suggested that the new genus comprises widespread freshwater bacteria. Phenotypic, chemotaxonomic and genomic traits were investigated. Cells were rod shaped and were able to glide on soft agar. All strains grew chemoorganotrophically and aerobically, were able to assimilate pectin and showed an intense red pigmentation putatively due to various carotenoids. Two strains possessed genes putatively encoding proteorhodopsin and retinal biosynthesis. Genome sequencing revealed genome sizes between 2.5 and 3.1 Mbp and G+C contents between 38.0 and 42.7 mol%. For the new genus we propose the name Aquirufa gen. nov. Pairwise-determined whole-genome average nucleotide identity values suggested that the three strains represent two new species within the new genus for which we propose the names Aquirufa antheringensis sp. nov. for strain 30S-ANTBACT (=JCM 32977T =LMG 31079T=DSM 108553T) as type species of the genus, to which also belongs strain 103A-SOEBACH (=DSM 108555=LMG 31082) and Aquirufa nivalisilvae sp. nov. for strain 59G-WUEMPELT (=LMG 31081T =DSM 108554T).
Ranking of Major Classes of Antibiotics for Activity against Stationary Phase Pseudomonas aeruginosa and Identification of Clinafloxacin + Cefuroxime + Gentamicin Drug Combination that Eradicates Persistent P. aeruginosa Infection in a Murine Cystic Fibrosis Model
Authors: Yuan Yuting , Yee Rebecca , Gour Naina , Dong Xinzhong , Feng Jie , Shi Wanliang , Zhang Ying
Published: July 2019

Pseudomonas aeruginosa can cause serious persistent infections such as ventilator-associated pneumonia, sepsis, biofilm-related infections as in cystic fibrosis (CF) patients. Although CF lung infections can be treated with antibiotics, full clearance is difficult due to P. aeruginosa persistence. While antibiotic activity against growing P. aeruginosa is well documented, their activity against the non-growing persisters enriched in stationary phase cultures has not been well studied. Here, we systematically evaluated and ranked the six major classes of antibiotics, cell wall and cell membrane inhibitors, protein synthesis inhibitors, DNA synthesis inhibitors, RNA synthesis inhibitors, sulfa drugs, and nitrofurantoin, for their activity against both growing and persister forms of P. aeruginosa using colony forming count (CFU) and SYBR Green I/Propidium Iodide (PI) viability assay. Among the six major classes of antibiotics, cell wall and cell membrane inhibitors (Cefuroxime and Colistin), DNA synthesis inhibitors (Clinafloxacin) and sulfa drugs (Sulfamethoxazole) had good activity against stationary phase cells. In contrast, protein synthesis inhibitors (Gentamicin), RNA synthesis inhibitor (Rifampicin) and Nitrofurantoin had relatively poor activity against the stationary phase P. aeruginosa but relatively high activity against log phase P. aeruginosa. Clinafloxacin is the only single drug that could completely kill all (109 CFU) stationary phase cells in a 4 day drug exposure. The Cefuroxime + Gentamicin+ Clinafloxacin combination could kill all biofilm bacteria in 2 days whereas the clinically used drug combination Cefuroxime + Gentamicin + Colistin only partially killed the biofilm bacteria with 103 CFU remaining. In a murine persistent CF lung infection model, only Cefuroxime + Gentamicin+ Clinafloxacin cleared all bacteria in the infected lungs, whereas Clinafloxacin alone, or Cefuroxime + Clinafloxacin, or the current recommended drug combination Cefuroxime + Gentamicin, all failed to completely clear the bacterial load in the lungs. The complete sterilization of the bacterial load is a property of Clinafloxacin combination, as Cefuroxime + Gentamicin+ Levofloxacin combination was unable to clear the bacterial load in the lungs. Our findings demonstrate the importance of persister drug clinafloxacin, offer new therapeutic approaches for more effective treatment of persistent P. aeruginosa infections, and may have implications for treating other persistent infections.
Monoclonal IgM antibodies raised againstCandida albicansHyr1 provide cross-kingdom protection against Gram negative bacteria
Authors: Youssef Eman G. , Alkhazraji Sondus , Ghebremariam Teclegiorgis , Zhang Lina , Singh Shakti , Yount Nannette Y. , Yeaman Michael R. , Uppuluri Priya , Ibrahim Ashraf S.
Published: July 2019

Recent years have seen an unprecedented rise in the incidence of multidrug resistant (MDR) Gram negative bacteria (GNB) such asAcinetobacterandKlebsiellaspecies. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent and treat infections by GNB are urgently needed. Previously, we have reported that theC. albicanshyphal-regulated protein Hyr1 shares striking 3D structural homology with cell surface proteins ofA. baumannii; and active or passive vaccination with rHyr1p-N or anti-Hyr1p polyclonal antibody, respectively; protect mice fromAcinetobacterinfections. Here, we show that monoclonal antibodies (mAb) generated against Hyr1p, bind to the surface ofAcinetobacteras well asK. pneumoniae. The anti-Hyr1 mAb also block damage to primary endothelial cells by the bacteria, and protect mice from lethal pulmonary infections mediated byA. baumanniiandK. pneumoniae. Our current studies emphasize the potential of harnessing Hyr1p mAb as a cross-kingdom immunotherapeutic strategy against MDR GNB.
Peroxisome turnover and diurnal modulation of antioxidant activity in retinal pigment epithelia utilizes microtubule-associated protein 1 light chain 3B
Authors: Daniele Lauren L. , Caughey Jennifer , Volland Stefanie , Sharp Rachel C. , Dhingra Anuradha , Williams David S. , Philp Nancy J. , Boesze-Battaglia Kathleen
Published: July 2019

The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid the visual cycle, nutrient supply, ion exchange and waste removal. Each day the RPE removes the oldest ∼10% of photoreceptor outer segments through phagocytic uptake, which peaks in a synchronous burst following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation and cell death. OSs are rich in very long chain fatty acids which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in RPE function, the regulation of peroxisome number and activity relative to diurnal OS ingestion is relatively unexplored. Using immunohistochemistry, immunoblotting and catalase activity assays, we investigated peroxisome abundance and activity at 6 am, 7 am (at lights on), 8 am, and 3 pm, in WT mice and mice lacking microtubule-associated protein 1 light chain 3B (LC3B), that have impaired degradation of phagosomes. We found that catalase activity, but not protein expression, is 50% higher in the morning compared with 3 pm, in RPE of WT but not LC3B-/- mice. Surprisingly, we found that peroxisome abundance was stable during the day, however numbers are elevated overall in LC3B-/- mice, implicating LC3B in autophagic organelle turnover in RPE. Our data suggest that RPE peroxisome function is regulated in coordination with phagocytosis, possibly through direct enzyme regulation, and may serve to prepare RPE peroxisomes for daily surges in ingested lipid-rich OS.
Neurofeedback linked suppression of subthalamic beta oscillations speeds up movement initialisation in Parkinsonian Patients
Authors: He Shenghong , Mostofi Abteen , Syed Emilie , Torrecillos Flavie , Tinkhauser Gerd , Fischer Petra , Pogsyan Alek , Hasegawa Harutomo , Li Yuanqing , Ashkan Keyoumars , Pereira Erlick , Tan Huiling
Published: July 2019

Enhanced beta oscillations (13-30 Hz) in the subthalamic nucleus (STN) have been associated with clinical impairment in Parkinson’s disease (PD), such as rigidity and slowing of movement, with the suppression of STN beta activity through medication or deep brain stimulation correlating with improvement in these symptoms. Recent studies have also emphasized the importance of the time dynamics of the STN beta oscillations in the pathology of PD. An increased probability of prolonged beta bursts, defined as periods when beta band power exceeds a certain threshold, was more closely related to motor symptoms than average power; and the occurrence of beta bursts just before a go cue slows cued movements. Here we adopted a sequential neurofeedback-behaviour task paradigm to investigate whether patients with PD can learn to suppress pathological beta oscillations recorded from STN with neurofeedback training and whether the training improves the motor performance. Results from twelve patients showed that, compared with the control condition, the neurofeedback training led to reduced incidence and duration of beta bursts in the STN local field potential (LFP) and also reduced the synchrony between the STN LFP and cortical activities measured through EEG in the beta frequency band. The changes were accompanied by a reduced reaction time in cued movements. These results suggest that volitional suppression of beta bursts facilitated by neurofeedback training could help improve movement initialisation in Parkinson’s disease.

Significance Statement

Our study suggests that a neurofeedback paradigm which focuses on the time dynamics of the target neural signal can facilitate volitional suppression of pathological beta oscillations in the STN in Parkinson’s disease. Neurofeedback training was accompanied by reduced reaction time in cued movements, but associated with increased tremor in tremulous patients. The results strengthen the link between subthalamic beta oscillations and motor impairment, and also suggest that different symptom-specific neural signals could be targeted to improve neuromodulation strategies, either through brain stimulation or neurofeedback training, for patients with tremor and bradykinesia-rigidity.
Coexistence of fast and slow gamma oscillations in one population of inhibitory spiking neurons
Authors: Bi Hongjie , Segneri Marco , di Volo Matteo , Torcini Alessandro
Published: July 2019

Oscillations are a hallmark of neural population activity in various brain regions with a spectrum covering a wide range of frequencies. Within this spectrum gamma oscillations have received particular attention due to their ubiquitous nature and to their correlation with higher brain functions. Recently, it has been reported that gamma oscillations in the hippocampus of behaving rodents are segregated in two distinct frequency bands: slow and fast. These two gamma rhythms correspond to different states of the network, but their origin has been not yet clarified. Here, we show theoretically and numerically that a single inhibitory population can give rise to coexisting slow and fast gamma rhythms corresponding to collective oscillations of a balanced spiking network. The slow and fast gamma rhythms are generated via two different mechanisms: the fast one being driven by the coordinated tonic neural firing and the slow one by endogenous fluctuations due to irregular neural activity. We show that almost instantaneous stimulations can switch the collective gamma oscillations from slow to fast and vice versa. Furthermore, to make a closer contact with the experimental observations, we consider the modulation of the gamma rhythms induced by a slower (theta) rhythm driving the network dynamics. In this context, depending on the strength of the forcing and the noise amplitude, we observe phase-amplitude and phase-phase coupling between the fast and slow gamma oscillations and the theta forcing. Phase-phase coupling reveals on average different theta-phases preferences for the two coexisting gamma rhythms joined to a wide cycle-to-cycle variability.
Downscaling Satellite Soil Moisture using Geomorphometry and Machine Learning
Authors: Guevara Mario , Vargas Rodrigo
Published: July 2019

Annual soil moisture estimates are useful to characterize trends in the climate system, in the capacity of soils to retain water and for predicting land and atmosphere interactions. The main source of soil moisture spatial information across large areas (e.g., continents) is satellite-based microwave remote sensing. However, satellite soil moisture datasets have coarse spatial resolution (e.g., 25-50 km grids); and large areas from regional-to-global scales have spatial information gaps. We provide an alternative approach to predict soil moisture spatial patterns (and associated uncertainty) with higher spatial resolution across areas where no information is otherwise available. This approach relies on geomorphometry derived terrain parameters and machine learning models to improve the statistical accuracy and the spatial resolution (from 27km to 1km grids) of satellite soil moisture information across the conterminous United States on an annual basis (1991-2016). We derived 15 primary and secondary terrain parameters from a digital elevation model. We trained a machine learning algorithm (i.e., kernel weighted nearest neighbors) for each year. Terrain parameters were used as predictors and annual satellite soil moisture estimates were used to train the models. The explained variance for all models-years was >70% (10-fold cross-validation). The 1km soil moisture grids (compared to the original satellite soil moisture estimates) had higher correlations with field soil moisture observations from the North American Soil Moisture Database (n=668 locations with available data between 1991-2013; 0-5cm depth) than the original product. We conclude that the fusion of geomorphometry methods and satellite soil moisture estimates is useful to increase the spatial resolution and accuracy of satellite-derived soil moisture. This approach can be applied to other satellite-derived soil moisture estimates and regions across the world.
DNA Transfection by Electroporation
Authors: Kumar Priti , Nagarajan Arvindhan , Uchil Pradeep D.
Published: July 2019

Electroporation, which uses pulsed electrical fields, can be used to introduce DNA into a variety of animal cells, plant cells, and bacteria. Electroporation works well with cell lines that are refractory to other transfection techniques, such as lipofection and calcium phosphate–DNA coprecipitation. But, as with other transfection methods, the optimal conditions for electroporating DNA into untested cell lines must be determined empirically. Several different electroporation instruments are available commercially, and manufacturers supply detailed protocols for their use with specific cell types and guidelines for optimization with others. This method describes the conditions for electroporating mammalian cell lines using the Gene Pulser Xcell Electroporation System (Bio-Rad).
Direct Cyanine-dUTP Labeling of RNA for Microarrays
Authors: Rando Oliver
Published: July 2019

This is the simplest method to label RNA for use in expression analysis. RNA is reverse-transcribed using both oligo(dT) and random hexamers as primers. The random hexamers improve overall efficiency of labeling, especially at the 5′ end of the RNA. Fluorescently labeled dUTP is incorporated into the cDNA. After reverse transcription, the RNA is degraded, and the labeled cDNA is purified from unincorporated Cy dyes. Finally, samples labeled with Cy3 and Cy5 dyes are mixed and combined with blocking nucleotides and used for hybridization.