bluuebunny/crossref_metadata_2025 huggingface dataset:
P98 UNSATURATED LIPIDS ARE SIGNIFICANTLY UPREGULATED IN OESOPHAGEAL ADENOCARCINOMA
Authors: Pranav H Patel , Sacheen Kumar , Luisa Doria , Renata Soares , Zsolt Bodai , Mina Adam , Nima Abbassi-Ghadi , Zoltan Takats , George B Hanna
Published: November 2019

Aim

This work aims to determine the glycerophospholipid (GPL) abundance between Oesophageal adenocarcinoma (OA) and proximal non-cancerous tissue at multiple levels using Desorption Electrospray Ionisation Mass spectrometry (DESI-MS) tissue imaging.

Background & Methods

The prevalence of Oesophageal cancer in the United Kingdom has steadily risen since the 1970s. The prognosis for most patients is poor, with two thirds presenting with incurable disease. The abundance of lipids in OA has been shown to be atypical of normal cellular metabolism.1 This work utilises mass spectrometry imaging to identify variations in lipid abundance between OA and normal oesophagus (NO).

Tissue was sampled from specimens dissected immediately post-resection from the tumour and at 5-centimetre intervals in the proximal oesophagus. DESI-MS tissue imaging, an ambient form of Mass Spectrometry, was performed to identify GPLs.2 DESI-MS images were correlated with Hematoxylin and Eosin staining (current gold standard). Principle component analysis with a supervised model classified tissue types by sensitivity and specificity.

Results

Tissue analysis confirmed unsaturated Phosphatidylglycerols and Phosphatidic acids were most abundant in OA compared to NO (p<0.001). Tissue analysis by a Partial Least Square (PLS) supervised linear regression model classified cancer and non-cancer tissue with 85% sensitivity and 88% specificity.

The abundance of several unsaturated GPL classes decreased proportionally in tissue sections at 5 and 10 centimetres from the primary tumour. Gene set enrichment has demonstrated potential dysregulation of this pathway in the literature.

Conclusions

This work highlights an important variant of lipid metabolism in OA, identified by DESI-MS. There is a significant overabundance of unsaturated Phosphatidylglycerol’s in OA compared to proximal NO. In addition, the unsaturated GPL classes found in the cancer become increasingly saturated at 5cm and 10cm from the tumour site. This variation in lipid molecular structure suggests a novel pathway for potential therapeutic modulation.
P99 A STRUCTURED TRAINING PATHWAY TO IMPLEMENT ROBOT-ASSISTED MINIMALLY INVASIVE ESOPHAGECTOMY (RAMIE): LEARNING CURVE RESULTS FROM A HIGH VOLUME CENTER
Authors: BF Kingma , E Hadzijusufovic , PC van der Sluis , H Lang , JP Ruurda , R van Hillegersberg , PP Grimminger
Published: November 2019

Aim

The aim of this study was to describe the results of a structured training pathway that was developed to implement robot-assisted minimally invasive esophagectomy (RAMIE) in new centers.

Background & Methods

To safely and effectively implement RAMIE in new centers, the learning process needs to be optimized. In this context, a structured training pathway was created (Table 1). The results of this training pathway were investigated by evaluating consecutive patients who underwent RAMIE by a single surgeon who followed the structured training pathway. These patients were included from the trainee center’s prospective database. Cumulative sum (CUSUM) learning curves were plotted for thoracic operating time and intraoperative blood loss. Perioperative outcomes were compared between patients who underwent surgery before and after a learning curve plateau occurred.

Results

Between 2017-2018, the trainee team adhered to the structured training pathway and a total of 70 patients were included. The learning curves showed plateaus after 22 cases. In cases 23-70, the operating time was shorter for both the thoracic phase (median 215 vs. 249 minutes, P=0.001) and overall procedure (median 394 vs. 440 minutes, P=0.005), intraoperative blood loss was less (median 210 vs. 400 milliliters, P=0.029), and lymph node yield was higher (median 32 vs. 23 nodes, P=0.001) when compared to the first 22 cases. No significant differences were found for conversion rates, postoperative complications, length of hospital stay, radicality, or mortality.

Conclusions

The structured RAMIE training pathway results in a short learning curve and is an effective way to introduce RAMIE without compromising the oncological outcomes and complication rates. The pathway is therefore advised to surgeons who are willing to adopt this technique.
How bacteria recognise and respond to surface contact
Authors: Kimkes Tom E P , Heinemann Matthias
Published: November 2019

Bacterial biofilms can cause medical problems and issues in technical systems. While a large body of knowledge exists on the phenotypes of planktonic and of sessile cells in mature biofilms, our understanding of what happens when bacteria change from the planktonic to the sessile state is still very incomplete. Fundamental questions are unanswered: for instance, how do bacteria sense that they are in contact with a surface, and what are the very initial cellular responses to surface contact. Here, we review the current knowledge on the signals that bacteria could perceive once they attach to a surface, the signal transduction systems that could be involved in sensing the surface contact and the cellular responses that are triggered as a consequence to surface contact ultimately leading to biofilm formation. Finally, as the main obstacle in investigating the initial responses to surface contact has been the difficulty to experimentally study the dynamic response of single cells upon surface attachment, we also review recent experimental approaches that could be employed to study bacterial surface sensing, which ultimately could lead to an improved understanding of how biofilm formation could be prevented.
Spectral Multipliers of Self-Adjoint Operators on Besov and Triebel–Lizorkin Spaces Associated to Operators
Authors: Bui The Anh , Duong Xuan Thinh
Published: November 2019

Let $X$ be a space of homogeneous type and let $L$ be a nonnegative self-adjoint operator on $L^2(X)$ that satisfies a Gaussian estimate on its heat kernel. In this paper we prove a Hörmander-type spectral multiplier theorem for $L$ on the Besov and Triebel–Lizorkin spaces associated to $L$. Our work not only recovers the boundedness of the spectral multipliers on $L^p$ spaces and Hardy spaces associated to $L$ but also is the 1st one that proves the boundedness of a general spectral multiplier theorem on Besov and Triebel–Lizorkin spaces.
Cartan Triples
Authors: Donsig Allan P , Fuller Adam H , Pitts David R
Published: November 2019

We introduce the class of Cartan triples as a generalization of the notion of a Cartan MASA in a von Neumann algebra. We obtain a one-to-one correspondence between Cartan triples and certain Clifford extensions of inverse semigroups. Moreover, there is a spectral theorem describing bimodules in terms of their support sets in the fundamental inverse semigroup and, as a corollary, an extension of Aoi’s theorem to this setting. This context contains that of Fulman’s generalization of Cartan MASAs and we discuss his generalization in an appendix.
medExtractR: A targeted, customizable approach to medication extraction from electronic health records
Authors: Weeks Hannah L , Beck Cole , McNeer Elizabeth , Williams Michael L , Bejan Cosmin A , Denny Joshua C , Choi Leena
Published: November 2019

Objective

We developed medExtractR, a natural language processing system to extract medication information from clinical notes. Using a targeted approach, medExtractR focuses on individual drugs to facilitate creation of medication-specific research datasets from electronic health records.

Materials and Methods

Written using the R programming language, medExtractR combines lexicon dictionaries and regular expressions to identify relevant medication entities (eg, drug name, strength, frequency). MedExtractR was developed on notes from Vanderbilt University Medical Center, using medications prescribed with varying complexity. We evaluated medExtractR and compared it with 3 existing systems: MedEx, MedXN, and CLAMP (Clinical Language Annotation, Modeling, and Processing). We also demonstrated how medExtractR can be easily tuned for better performance on an outside dataset using the MIMIC-III (Medical Information Mart for Intensive Care III) database.

Results

On 50 test notes per development drug and 110 test notes for an additional drug, medExtractR achieved high overall performance (F-measures >0.95), exceeding performance of the 3 existing systems across all drugs. MedExtractR achieved the highest F-measure for each individual entity, except drug name and dose amount for allopurinol. With tuning and customization, medExtractR achieved F-measures >0.90 in the MIMIC-III dataset.

Discussion

The medExtractR system successfully extracted entities for medications of interest. High performance in entity-level extraction provides a strong foundation for developing robust research datasets for pharmacological research. When working with new datasets, medExtractR should be tuned on a small sample of notes before being broadly applied.

Conclusions

The medExtractR system achieved high performance extracting specific medications from clinical text, leading to higher-quality research datasets for drug-related studies than some existing general-purpose medication extraction tools.
Economic and Social-Class Voting in a Model of Redistribution with Social Concerns
Authors: Gallice Andrea , Grillo Edoardo
Published: November 2019

We investigate how social status concerns may affect voters’ preferences for redistribution. Social status is given by a voter’s relative standing in two dimensions: consumption and social class. By affecting the distribution of consumption levels, redistribution modifies the weights attached to the two dimensions. Thus, redistribution not only transfers resources from the rich to the poor, but it also amplifies or reduces the importance of social class differences. Social status concerns can simultaneously lead some members of the working class to oppose redistribution and some members of the socioeconomic elites to favor it. They also give rise to interclass coalitions of voters that, despite having different monetary interests, support the same tax rate. We characterize these coalitions and discuss the resulting political equilibrium.
What factors affect fluoroscopy use during Bernese periacetabular osteotomy for acetabular dysplasia?
Authors: Wylie James D , McClincy Michael P , Stieler Evan K , Millis Michael B , Kim Young-Jo , Peters Christopher L , Novais Eduardo N
Published: November 2019

Periacetabular osteotomy (PAO) is the treatment of choice for acetabular dysplasia in the skeletally mature. Little is known about factors affecting fluoroscopy use in PAO. Therefore, we strived to determine patient and surgery factors are associated with the amount of fluoroscopy time and radiation dose during PAO. We performed a retrospective review of 378 patients who underwent PAO between January 2012 and August 2017. The mean age was 21.7 years and 326 (86%) were females. A total of 85 patients underwent concomitant arthroscopy and 60 underwent open arthrotomy. We recorded fluoroscopy time in minutes and radiation dose area product (DAP) in mGy·m2. Multivariate general linear modeling identified independent predictors of fluoroscopy time and radiation dose. Mean fluoroscopy time was 1.21 minutes and mean fluoroscopy DAP was 0.71 mGy·m2. Multivariate predictors of increased fluoroscopy time were male gender (P = 0.001), surgeon (P < 0.001) and whether an arthroscopy was performed (P < 0.001). Multivariate predictors of increased fluoroscopy DAP were increased body mass index (BMI) (P = 0.001), surgeon (P < 0.001) and whether an arthroscopy was performed (P < 0.001). Patients undergoing hip arthroscopy concomitant to PAO are at higher risk of longer fluoroscopy time and higher radiation dose. Other factors affecting fluoroscopy time included male gender and surgeon, while radiation dose was further affected by surgeon and BMI. Our findings can facilitate discussion about the risk of radiation exposure during PAO.
Characterization of Nest Architecture of an Indian Ant Diacamma indicum (Hymenoptera: Formicidae)
Authors: Bhattacharyya Kushankur , Annagiri Sumana
Published: November 2019

Nests are physical entities that give shelter to the inhabitants from natural adversities, predators and act as a platform for organization of tasks particularly in social insects. Social insect nests can range from simple structures consisting of a single entrance leading to a chamber to complex nests containing hundreds of connected shafts and chambers. This study characterizes nest architecture of a tropical ponerine ant Diacamma indicum (Hymenoptera: Formicidae), which has small colony sizes and is known to be a scavenger. We also examined if these nests vary seasonally. By examining the microhabitat in the vicinity of the nest, the nest entrance characteristics and casting 77 natural nests of D. indicum across a year, we found that this species occupies relatively simple nests consisting of a single entrance that leads to a single chamber. This chamber progressed to a secondary tunnel that terminated at a greater depth than the chamber. The nest volume was not correlated to the number of adult members in the colony. Even though the microhabitat around the nest and the entrance itself change across seasons, principle component analysis showed that the nest architecture remained similar. Only one parameter, the entrance tunnel showed significant difference and was longer during postmonsoon. Nests of colonies living in the immediate vicinity of human habitation were comparable to other nests. We conclude that D. indicum found in the Gangetic plains live in relatively simple nests that do not vary across seasons.
Chronic exposure of soybean plants to nanomolar cadmium reveals specific additional high-affinity targets of cadmium toxicity
Authors: Andresen Elisa , Lyubenova Lyudmila , Hubáček Tomáš , Bokhari Syed Nadeem Hussain , Matoušková Šárka , Mijovilovich Ana , Rohovec Jan , Küpper Hendrik
Published: November 2019

Solving the global environmental and agricultural problem of chronic low-level cadmium (Cd) exposure requires better mechanistic understanding. Here, soybean (Glycine max) plants were exposed to Cd concentrations ranging from 0.5 nM (background concentration, control) to 3 µM. Plants were cultivated hydroponically under non-nodulating conditions for 10 weeks. Toxicity symptoms, net photosynthetic oxygen production and photosynthesis biophysics (chlorophyll fluorescence: Kautsky and OJIP) were measured in young mature leaves. Cd binding to proteins [metalloproteomics by HPLC-inductively coupled plasma (ICP)-MS] and Cd ligands in light-harvesting complex II (LHCII) [X-ray absorption near edge structure (XANES)], and accumulation of elements, chloropyll, and metabolites were determined in leaves after harvest. A distinct threshold concentration of toxicity onset (140 nM) was apparent in strongly decreased growth, the switch-like pattern for nutrient uptake and metal accumulation, and photosynthetic fluorescence parameters such as Φ RE10 (OJIP) and saturation of the net photosynthetic oxygen release rate. XANES analyses of isolated LHCII revealed that Cd was bound to nitrogen or oxygen (and not sulfur) atoms. Nutrient deficiencies caused by inhibited uptake could be due to transporter blockage by Cd ions. The changes in specific fluorescence kinetic parameters indicate electrons not being transferred from PSII to PSI. Inhibition of photosynthesis combined with inhibition of root function could explain why amino acid and carbohydrate metabolism decreased in favour of molecules involved in Cd stress tolerance (e.g. antioxidative system and detoxifying ligands).
Distribution and spectrophotometric classification of basaltic asteroids
Authors: Mansour J-A , Popescu M , de León J , Licandro J
Published: November 2019

We aim to determine the distribution of basaltic asteroids (classified as V-types) based on the spectrophotometric data reported in the MOVIS-C catalogue. A total of 782 asteroids were identified. The observations with all four filters (Y, J, H, Ks), available for 297 of these candidates, allow a reliable comparison with the laboratory data of howardite, eucrite, and diogenite meteorites. We found that the majority of the basaltic candidates (≈95${{\ \rm per\ cent}}$) are located in the inner main belt, while only 29 (≈4${{\ \rm per\ cent}}$) and 8 (≈1${{\ \rm per\ cent}}$) are located in the middle (MMB) and outer main belt (OMB), respectively. A fraction of ≈33${{\ \rm per\ cent}}$ from the V-type candidates is associated with the Vesta family (with respect to AstDyS). We also identified four MMB V-type candidates belonging to (15) Eunomia family, and another four low inclination ones corresponding to (135) Hertha. We report differences between the colour indices and albedo distributions of the V-type candidates located in the inner main belt compared to those from the MMB and OMB. These results support the hypothesis of a different origin for the basaltic asteroids with a semimajor axis beyond 2.5 au. Furthermore, lithological differences are present between the vestoids and the inner low inclination basaltic asteroids. The data allow us to estimate the unbiased distribution of basaltic asteroids across the main asteroid belt. We highlight that at least 80${{\ \rm per\ cent}}$ of the ejected basaltic material from (4) Vesta is missing or is not yet detected because it is fragmented in sizes smaller than 1 km.
Comments on ‘numerical stability of detonations in white dwarf simulations’
Authors: Kushnir Doron , Katz Boaz
Published: November 2019

Katz & Zingale (KZ19) recently studied a one-dimensional test problem, intended to mimic the process of detonation ignition in head-on collisions of two carbon–oxygen (CO) white dwarfs. They do not obtain ignition of a detonation in pure CO compositions unless the temperature is artificially increased or $5{{\ \rm per\ cent}}$ He is included. In both of these cases they obtain converged ignition only for spatial resolutions better than $0.1\, \textrm{km}$, which are beyond the capability of multidimensional simulations. This is in a contradiction with the claims of Kushnir et al. (K13) that a convergence to $\mathord {\sim}10{{\ \rm per\ cent}}$ is achieved for a resolution of a few km. Using Eulerian and Lagrangian codes we show that a converged and resolved ignition is obtained for pure CO in this test problem without the need for He or increasing the temperature. The two codes agree to within $1{{\ \rm per\ cent}}$ and convergence is obtained at resolutions of several km. We calculate the case that includes He and obtain a similar slow convergence, but find that it is due to a boundary numerical artefact that can (and should) be avoided. Correcting the boundary conditions allows convergence with resolution of ${\sim}10\, \textrm{km}$ in an agreement with the claims of K13. It is likely that the slow convergence obtained by KZ19 in this case is because of a similar boundary numerical artefact, but we are unable to verify this. KZ19 further recommended to avoid the use of the burning limiter introduced by K13. We show that their recommendation is not justified.
A dual role of dLsd1 in oogenesis: regulating developmental genes and repressing transposons
Authors: Lepesant Julie M J , Iampietro Carole , Galeota Eugenia , Augé Benoit , Aguirrenbengoa Marion , Mercé Clemèntine , Chaubet Camille , Rocher Vincent , Haenlin Marc , Waltzer Lucas , Pelizzola Mattia , Di Stefano Luisa
Published: November 2019

The histone demethylase LSD1 is a key chromatin regulator that is often deregulated in cancer. Its ortholog, dLsd1 plays a crucial role in Drosophila oogenesis; however, our knowledge of dLsd1 function is insufficient to explain its role in the ovary. Here, we have performed genome-wide analysis of dLsd1 binding in the ovary, and we document that dLsd1 is preferentially associated to the transcription start site of developmental genes. We uncovered an unanticipated interplay between dLsd1 and the GATA transcription factor Serpent and we report an unexpected role for Serpent in oogenesis. Besides, our transcriptomic data show that reducing dLsd1 levels results in ectopic transposable elements (TE) expression correlated with changes in H3K4me2 and H3K9me2 at TE loci. In addition, our results suggest that dLsd1 is required for Piwi dependent TE silencing. Hence, we propose that dLsd1 plays crucial roles in establishing specific gene expression programs and in repressing transposons during oogenesis.
Is self-care dialysis associated with social deprivation in a universal health care system? A cohort study with data from the Renal Epidemiology and Information Network Registry
Authors: Beaumier Mathilde , Béchade Clémence , Dejardin Olivier , Lassalle Mathilde , Vigneau Cécile , Longlune Nathalie , Launay Ludivine , Couchoud Cécile , Ficheux Maxence , Lobbedez Thierry , Châtelet Valérie
Published: November 2019

Background

Socioeconomic status is associated with dialysis modality in developed countries. The main objective of this study was to investigate whether social deprivation, estimated by the European Deprivation Index (EDI), was associated with self-care dialysis in France.

Methods

The EDI was calculated for patients who started dialysis in 2017. The event of interest was self-care dialysis 3 months after dialysis initiation [self-care peritoneal dialysis (PD) or satellite haemodialysis (HD)]. A logistic model was used for the statistical analysis, and a counterfactual approach was used for the causal mediation analysis.

Results

Among the 9588 patients included, 2894 (30%) were in the most deprived quintile of the EDI. A total of 1402 patients were treated with self-care dialysis. In the multivariable analysis with the EDI in quintiles, there was no association between social deprivation and self-care dialysis. Compared with the other EDI quintiles, patients from Quintile 5 (most deprived quintile) were less likely to be on self-care dialysis (odds ratio 0.81, 95% confidence interval 0.71–0.93). Age, sex, emergency start, cardiovascular disease, chronic respiratory disease, cancer, severe disability, serum albumin and registration on the waiting list were associated with self-care dialysis. The EDI was not associated with self-care dialysis in either the HD or in the PD subgroups.

Conclusions

In France, social deprivation estimated by the EDI is associated with self-care dialysis in end-stage renal disease patients undergoing replacement therapy.
Information theory of metasurfaces
Authors: Wu Haotian , Bai Guo Dong , Liu Shuo , Li Lianlin , Wan Xiang , Cheng Qiang , Cui Tie Jun
Published: November 2019

We propose a theory to characterize the information and information processing abilities of metasurfaces, and demonstrate the relation between the information of the metasurface and its radiation pattern in the far-field region. By incorporating a general aperture model with uncertainty relation in L2-space, we propose a theory to predict the upper bound of information contained in the radiation pattern of a metasurface, and reveal the theoretical upper limit of orthogonal radiation states. The proposed theory also provides guidance for inverse design of the metasurface with respect to given functionalities. Through investigation of the information of disordered-phase modulated metasurfaces, we find the information invariance (1−γ, where γ is Euler's constant) of chaotic radiation patterns. That is to say, the information of the disordered-phase modulated radiation patterns is always equal to 1−γ, regardless of variations in size, the number of elements and the phase pattern of metasurface. This value might be the lower bound of radiation-pattern information of the metasurface, which can provide a theoretical limit for information modulation applications, including computational imaging, stealth technologies and wireless communications.
Left Retrosigmoid Craniotomy for Resection of Cavernous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: November 2019

Pontine cavernous malformations are highly morbid lesions that require thorough preoperative planning of the surgical approach and meticulous surgical technique to successfully remove. The patient in this case has a large pontine cavernous malformation coming to the parenchymal surface along the pontine–middle cerebellar peduncle interface. The depth of the surgical field and narrow trajectory of approach require use of lighted suction, lighted bipolar forceps, and stereotactic neuronavigation to successfully locate and remove the entire lesion. The cavernous malformation is removed in a piecemeal manner with close inspection of the resection cavity for any remnants. Postoperative imaging demonstrates gross total resection of the lesion. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Ipsilateral Internal Carotid Artery Bifurcation Aneurysm and Contralateral Middle Cerebral Artery Aneurysm Clipping: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: November 2019

Contralateral clipping of a middle cerebral artery (MCA) aneurysm is challenging but possible with favorable anatomy. This patient had bilateral aneurysms, an ipsilateral internal carotid artery bifurcation aneurysm and a contralateral MCA aneurysm. The surgical goal was to clip both aneurysms if possible. After opening the ipsilateral sylvian fissure, the arachnoid planes were opened along the anterior cerebral arteries to the contralateral sylvian fissure. The arachnoid planes within the sylvian fissure were dissected to permit visualization of the contralateral proximal MCA and anatomy, which permitted the MCA to be followed to the aneurysm. If adequate proximal and distal control is present, the aneurysm is clipped. The surgeon needs to be comfortable in backing out if the exposure is too limited. The sequence of clipping should be to clip the contralateral aneurysm first to avoid inadvertent manipulation of the ipsilateral clip during the contralateral procedure. Postoperative angiography demonstrated that the bilateral aneurysms were clipped and that all vessels were patent. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Cervical 7-Thoracic 3 Laminoplasty for Resection of Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: November 2019

Symptomatic spinal arteriovenous malformations (AVMs) are most frequently associated with hypoperfusion of the spinal cord, either from venous congestion or vascular steal, and are less frequently associated with hemorrhage. This patient had a large cervicothoracic spinal AVM and presented with right hemibody sensory deficit with intact motor function. The AVM had significant preoperative mass effect on the dorsal spinal cord with cord signal change. Preoperative digital subtraction angiography demonstrated a left supreme intercostal feeding artery and left thyrocervical feeding artery, which was embolized preoperatively. A laminoplasty was performed from cervical 7 to thoracic 3 to allow for adequate visualization. The lesion demonstrated an intradural extramedullary presence, which made preservation of the pia mater paramount during the resection. The AVM was disconnected and removed in its entirety as determined by operative visualization and postoperative imaging. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Thoracic 11-Lumbar 1 Laminoplasty for Resection of Conus Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: November 2019

Conus medullaris spinal arteriovenous malformations are uniquely classified by the Spetzler classification. They possess a glomus (type II) nidus in either or both the intra- and extramedullary compartments, with multiple feeding arteries and niduses resulting in complex venous drainage patterns. These characteristics make resection of these lesions challenging, and these lesions are associated with a high risk for recurrence. This patient presented with a subarachnoid hemorrhage, and thorough imaging evaluation revealed a conus arteriovenous malformation. The patient underwent thoracic 11 to lumbar 1 laminoplasty for resection of the lesion. The arteriovenous malformation was circumdissected off the conus and lumbosacral nerve roots using sharp dissection and bipolar forceps. It was visualized both before and after resection with indocyanine green fluoroscopy. The patient tolerated the procedure well, and postoperative angiography demonstrated complete resection. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Orbitozygomatic Craniotomy for Clipping a Complex Middle Cerebral Artery Aneurysm: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: November 2019

Middle cerebral artery (MCA) aneurysms pose a surgical challenge because of the large caliber of the parent artery and the common need to dissect the sylvian fissure to permit access to the proximal and distal control. The neck of the aneurysm should be generously dissected to permit visualization of any adjacent lenticulostriate perforators. This patient demonstrated a left-sided wide-necked bilobed MCA aneurysm at the M1 bifurcation. The aneurysm was approached using a left orbitozygomatic craniotomy with distal sylvian fissure dissection. A single curved clip was applied for aneurysm occlusion, and postoperative angiography demonstrated aneurysm obliteration with parent vessel patency. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Grade 4 Temporal Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Hendricks Benjamin K , Spetzler Robert F
Published: November 2019

The 2% to 4% annual rupture rate for arteriovenous malformations (AVMs) must be weighed against the risk of intervention during surgery within an eloquent brain region. Following a hemorrhage event, AVMs that were initially considered to be nonoperative or unfavorable for surgical resection can be intervened on to avoid the significantly elevated risk of rehemorrhage. This patient had a dominant temporal lobe Spetzler–Martin grade 4 AVM with deep venous drainage, representing a significant surgical challenge. The arachnoid plane microdissection was performed using microscissors but was tenuous, and it was necessary to define the draining vein and adjacent feeding arteries. This video demonstrates the major principles of AVM resection during the circumdissection and disconnection of the nidus. The postoperative angiography demonstrated complete resection. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.
Bulk Liquid for the Skaergaard Intrusion and Its PGE-Au Mineralization: Composition, Correlation, Liquid Line of Descent, and Timing of Sulphide Saturation and Silicate–Silicate Immiscibility
Authors: Nielsen Troels F D , Brooks C Kent , Keiding Jakob K
Published: November 2019

Preferred and modelled bulk composition of the Skaergaard intrusion are compared to coeval basaltic compositions in East Greenland and found to relate to the second evolved cycle of Geikie Plateau Formation lavas and coeval Skaergaard-like dikes in major and trace element (Mg# ∼45, Ce/Nb ∼2·5, (Dy/Yb)N ∼1·35), and precious metal composition (Pd/Pt ∼3, Au/Pt ∼2) as well as in age (∼56 Ma). Successful comparisons of precious metal compositions only occur with Skaergaard models based on mass balance. The bulk liquid of the intrusion evolved along the liquid line of descent to immiscibility between Si- and Fe-rich silicate liquids after ∼90% of crystallization (F = ∼0·10) in agreement with experimental constraints. Immiscibility led to accumulation and fractionation of the Fe-rich silicate melt in the mushy floor of the intrusion and continued accumulation of granophyre component in the remaining bulk liquid. The composition of plagioclase in the precious metal mineralized gabbro and modelling of Pd/Pt and Au/Pt in first formed droplets of sulphide melt suggest that sulphide saturation was reached in interstitial melts in crystal mushes in the floor and roof and in bulk liquid with a composition equivalent to that of the bulk liquid at lower UZa times and after crystallization of 82–85% of the bulk liquid (F = 0·19–0·16). Prior to sulphide saturation in UZa type melt, the precious metals ratios of the bulk liquid were controlled by the loss of Pt relative to Pd and Au in agreement with the low empirical and experimental solubility of Pt of ∼9ppb compared to a much higher value for Pd and Au. The relative timing between sulphide saturation (F = ∼0·18) and immiscibility between silicate melts (F = ∼0·10) and modelled precious metal ratios underpin the proposed multi-stage model for the mineralization, advocating initial accumulation in the mushy floor of the magma chamber controlled by sulphide saturation in mush melts rather than bulk melt, followed by redistribution of precious metals in a macro-rhythmic succession of gabbroic layers of the upward migrating crystallization zone.
Democratic Backsliding, Populism, and Public Administration
Authors: Bauer Michael W , Becker Stefan
Published: November 2019

What happens to public administration when populists are elected into government? This article argues that populists seek to realize an anti-pluralist reform agenda, thereby fuelling trends of democratic backsliding. Against this background, the article discusses potential goals and strategies of populist public administration policy and introduces examples of how populists sought to capture (Orbán in Hungary), dismantle (Fujimori in Peru), sabotage (Trump in the United States), and reform (Blocher in Switzerland) the state bureaucracy. In doing so, populists in government aim at structures, resources, personnel, norms, and accountability relationships. The examples suggest that populist public administration policies can have profound impact on policymaking and democracy, underlining the need for a broader research agenda on this issue area.
Low-dose corticosteroid and mycophenolate for primary treatment of minimal change disease
Authors: Ma M K M , Yap D Y H , Li C L , Mok M M Y , Chan G C W , Kwan L P Y , Lai K N , Tang S C W
Published: November 2019

Background

Mycophenolate has been shown to be effective in glomerular disease. However, the role of mycophenolate in the first-line treatment of adult-onset idiopathic minimal change disease (MCD) has not been systematically studied in a randomized fashion.

Aim

To evaluate the therapeutic efficacy of enteric-coated mycophenolate sodium combined with low-dose corticosteroid as first-line treatment for MCNS.

Design

A prospective, open-label, randomized clinical trial.

Methods

Twenty adult patients with biopsy proven MCD were recruited and randomly assigned to receive either enteric-coated Mycophenolate Sodium (EC-MPS) plus low-dose prednisolone (Group 1: Prednisolone 0.25 mg/kg/day, n = 10) or standard-dose prednisolone (Group 2: Prednisolone 1 mg/kg/day, n = 10).

Results

After 24 weeks of therapy, eight patients in Group 1 vs. seven of patients in Group 2 achieved complete remission (P = 0.606). Both groups showed a significant reduction of urine protein excretion (P < 0.05) and increased serum albumin (P < 0.001) vs. baseline levels. However, no significant between-group differences were demonstrated. The relapse rate was also similar in both groups. Both treatment regimens were well tolerated but there were more patient reported adverse effects in the standard-dose prednisolone group.

Conclusion

EC-MPS plus low-dose prednisolone is non-inferior to standard-dose prednisolone therapy in inducing clinical remission and preventing relapse in adult-onset idiopathic MCD and is associated with better tolerability and less adverse effects. This trial is registered with the ClinicalTrials.gov number NCT01185197.
AGE DEPENDENCE OF INDIVIDUAL EXTERNAL DOSES IN AN EARLY STAGE AFTER THE FUKUSHIMA NUCLEAR ACCIDENT
Authors: Ishikawa Tetsuo , Yasumura Seiji , Akahane Keiichi , Yonai Shunsuke , Ohtsuru Akira , Sakai Akira , Ohira Tetsuya , Kamiya Kenji
Published: November 2019

Individual external doses for the first 4 months after the Fukushima accident have been estimated by the ‘Basic Survey’ of the Fukushima Health Management Survey. On the other hand, the UNSCEAR 2013 report presented the first-year effective dose due to external radiation for each municipality in nonevacuated areas of Fukushima Prefecture. In this study, the doses estimated by the Basic Survey were averaged for each of three age groups (infants, 0–5 y; children, 6–15 y; and adults, >16 y), in accordance with the categories adopted by the UNSCEAR report. The average dose ratios (infants/adults and children/adults) obtained from the Basic Survey were 1.08 and 1.06 for nonevacuated areas, respectively. These were smaller than the estimation by the UNSCEAR report (1.7 and 1.4, respectively). Three factors (body size factor, location factor and occupancy factor) were discussed and the location and occupancy factors were likely to be reasons for the difference.
A hydrogel beads based platform for single-cell phenotypic analysis and digital molecular detection
Authors: Zhu Yanzhe , Li Jing , Lin Xingyu , Huang Xiao , Hoffmann Michael R.
Published: November 2019

Microfluidic platforms integrating phenotyping and genotyping approaches have the potential to advance the understanding of single cell genotype-to-phenotype correlations. These correlations can play a key role in tackling antibiotic heteroresistance, cancer cell heterogeneity, and other related fundamental problems. Herein, we report a novel platform that enables both high-throughput digital molecular detection and single-cell phenotypic analysis, utilizing nanoliter-sized biocompatible polyethylene glycol hydrogel beads produced by a convenient and disposable centrifugal droplet generation device. The hydrogel beads have been demonstrated enhanced thermal stability, and achieved uncompromised efficiencies in digital polymerase chain reaction, digital loop-mediated isothermal amplification, and single cell phenotyping. The crosslinked hydrogel network highlights the prospective linkage of various subsequent molecular analyses to address the genotypic differences between cellular subpopulations exhibiting distinct phenotypes. Our platform shows great potential for applications in clinical practice and medical research, and promises new perspectives in mechanism elucidation of environment-evolution interaction and other basic research areas.
Integrative genomic analysis unifying epigenetic inheritance in adaptation and canalization
Authors: Sharma Abhay
Published: November 2019

Epigenetic inheritance, especially its biomedical and evolutionary significance, is an immensely interesting but highly controversial subject. Notably, a recent analysis of existing multi-omics has supported the mechanistic plausibility of epigenetic inheritance and its implications in disease and evolution. The evolutionary support stemmed from the specific finding that genes associated with cold induced inheritance and with latitudinal adaptation in mice are exceptionally common. Here, a similar gene set overlap analysis is presented that integrates cold induced inheritance with evolutionary adaptation and genetic canalization in cold environment in Drosophila. Genes showing differential expression in inheritance specifically overrepresent gene sets associated with differential and allele specific expression, though not with genome-wide genetic differentiation, in adaptation. On the other hand, the differentiated outliers uniquely overrepresent genes dysregulated by radicicol, a decanalization inducer. Both gene sets in turn exclusively show enrichment of genes that accumulate, in intended experimental lines, de novo mutations, a potential source of canalization. Successively, the three gene sets distinctively overrepresent genes exhibiting, between mutation accumulation lines, invariable expression, a potential signal for canalization. Sequentially, the four gene sets solely display enrichment of genes grouped in gene ontology under transcription factor activity, a signature of regulatory canalization. Cumulatively, the analysis suggests that epigenetic inheritance possibly contributes to evolutionary adaptation in the form of cis regulatory variations, with trans variations arising in the course of genetic canalization.
microRNA profiling in the Weddell Seal suggests novel regulatory mechanisms contributing to diving adaptation
Authors: Penso-Dolfin Luca , Haerty Wilfried , Hindle Allyson , Di Palma Federica
Published: November 2019

The Weddell Seal (Leptonychotes weddelli) represents a remarkable example of adaptation to diving among marine mammals. This species is capable of diving >900 m deep and remaining underwater for more than 60 minutes. A number of key physiological specializations have been identified, including the low levels of aerobic, lipid-based metabolism under hypoxia, significant increase in oxygen storage in blood and muscle; high blood volume and extreme cardiovascular control. These adaptations have been linked to increased abundance of key proteins, suggesting an important, yet still understudied role for gene reprogramming.

In this study, we investigate the possibility that post-transcriptional gene regulation by microRNAs (miRNAs) has contributed to the adaptive evolution of diving capacities in the Weddell Seal.

Using small RNA data across 4 tissues (cortex, heart, muscle and plasma), in 3 biological replicates, we generate the first miRNA annotation in this species, consisting of 559 high confidence, manually curated miRNA loci. Evolutionary analyses of miRNA gain and loss highlight a high number of Weddell seal specific miRNAs.

416 miRNAs were differentially expressed (DE) among tissues, whereas 83 miRNAs were differentially expressed (DE) across all tissues between pups and adults and 221 miRNAs demonstrated developmental changes in specific tissues only. mRNA targets of these altered miRNAs identify possible protective mechanisms in individual tissues, particularly relevant to hypoxia tolerance, anti-apoptotic pathways, and nitric oxide signal transduction. Novel, lineage-specific miRNAs associated with developmental changes target genes with roles in angiogenesis and vasoregulatory signaling.

Altogether, we provide an overview of miRNA composition and evolution in the Weddell seal, and the first insights into their possible role in the specialization to diving.
Non-invasive neuromodulation using rTMS and the Electromagnetic-Perceptive Gene (EPG) facilitates plasticity after nerve injury
Authors: Cywiak Carolina , Ashbaugh Ryan C. , Metto Abigael C. , Udpa Lalita , Qian Chunqi , Gilad Assaf A. , Zhong Ming , Pelled Galit
Published: November 2019

Peripheral nerve injury leads to altered cortical excitation-inhibition balance which is associated with sensory dysfunctions. We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which has shown to induce neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from Kryptopterrus bicirrhis and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. A battery of behavioral tests, fMRI and immunochemistry were performed in the weeks following limb denervation in rats. The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The study also identifies the acute post-injury phase as a critical time for intervention. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.
Dendritic cells require TMEM176A/B ion channels for optimal MHC II antigen presentation to naive CD4+ T cells
Authors: Lancien Melanie , Bienvenu Geraldine , Gueno Lucile , Salle Sonia , Merieau Emmanuel , Remy Severine , Even Amandine , Moreau Aurelie , Molle Alice , Fourgeux Cynthia , Coulon Flora , Beriou Gaelle , Bouchet-Delbos Laurence , Chiffoleau Elise , Kirstetter Peggy , Chan Susan , Kerfoot Steven , Abdu Rahiman Saeed , De Simone Veronica , Matteoli Gianluca , Boncompain Gaelle , Perez Franck , Josien Regis , Poschmann Jeremie , Cuturi Maria Cristina , Louvet Cedric
Published: November 2019

Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. Here we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in RORγt+ cells and conventional dendritic cells (cDCs) using germline and conditional double knock-out (DKO) mice. While Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells (ILC3s) in the intestinal mucosa, we found that they were required in cDCs for optimal antigen processing and presentation to CD4+ T cells. Using a real-time imaging method, we show that TMEM176A/B accumulate in dynamic post-Golgi vesicles preferentially linked to the late endolysosomal system and strongly colocalize with HLA-DM. Together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC II compartment (MIIC) of DCs for the fine regulation of antigen presentation and naive CD4+ T cell priming.