bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical Spine Involvement in a Challenging Case of Accidental Strangulation
Authors: De-Giorgio Fabio , Grassi Simone , Miscusi Massimo , Ricciardi Luca , Polli Filippo Maria
Published: March 2019

Although strangulation is generally homicidal, the scientific literature reports several cases in which it is suicidal or even accidental. The former eventuality is particularly interesting because extremely atypical ligatures (such as locks of hair), complex dynamics, and uncommon findings can be involved. Only a meticulous evaluation of the body and of both direct and circumstantial evidence can help in the complex differential diagnosis that includes murder, suicide, and accident. In accidental strangulation, the number and severity of injuries depend on the magnitude of applied force. This implies that high-energy strangulation (in our case, caused by the entanglement of a scarf in an electrical generator) can produce a complex polytrauma. In this case, accidental self-strangulation caused widespread, posttraumatic subarachnoid hemorrhaging, laceration of the larynx, and fracture-dislocation of the C2/C3 vertebrae. We believe that all these events contributed to the death of the victim, but the complexity of the polytrauma and the lack of direct evidence did not allow us to determine a univocal cause-effect chain.
Metastatic Renal Cell Carcinoma to the Brain: A Contemporary Clinicopathologic Analysis With Comparison of Immunohistochemical Profiles to Selected Primary Brain Tumors With Clear Cell Features
Authors: Zheng Wei , Goodman Abigail L. , Velázquez Vega José E. , Yin Feng , Fung Kar-Ming , Osunkoya Adeboye O.
Published: March 2019

Brain metastases from renal cell carcinoma (RCC) are associated with significant morbidity and mortality. However, there are only few large series in the pathology literature specifically analyzing the clinicopathologic and immunohistochemical features in comparison with primary brain tumors with clear cell features. We identified 34 cases of metastatic RCC to the brain from the Urologic Pathology and Neuropathology files of 2 institutions between 2000 and 2018. Mean patient age at diagnosis of primary RCC was 59 years (range: 37 to 82 y). The mean size of 34 primary RCC was 7.9 cm (range: 2.5 to 19.5 cm). Twenty of 34 (59%) cases of brain metastases had primary RCC categorized as pT3. Brain imaging showed a solitary, well circumscribed, enhancing lesion in 18 of 34 (53%) patients and multifocal lesions in 16 of 34 (47%) patients. The mean size of metastatic RCC to the brain was 2.3 cm (range: 0.3 to 5.5 cm). Fifteen of 34 (44%) cases had isolated brain metastases and 19 of 34 (56%) cases had concomitant extracerebral metastases. The histologic subtypes were clear cell RCC 29 of 34 (85%) cases, RCC unclassified 4 of 34 (12%) cases, and papillary RCC 1 of 34 (3%) cases. We also included primary brain tumors with clear cell features including hemangioblastoma (30 cases), microcystic meningioma (11 cases), and clear cell meningioma (3 cases). The utility of an immunohistochemical panel that includes PAX8, carbonic anhydrase IX, SST2Ra, and inhibin is very useful in the distinction of these entities in a subset of patients.
Improving Pediatric Diabetic Ketoacidosis Management in Community Emergency Departments Using a Simulation-Based Collaborative Improvement Program
Authors: Abulebda Kamal , Whitfill Travis , Montgomery Erin E. , Kirby Michele L. , Ahmed Rami A. , Cooper Dylan D. , Nitu Mara E. , Auerbach Marc A. , Lutfi Riad , Abu-Sultaneh Samer
Published: March 2019

Objectives

The majority of pediatric patients with diabetic ketoacidosis (DKA) present to community emergency departments (CEDs) that are less prepared to care for acutely ill children owing to low pediatric volume and limited pediatric resources and guidelines. This has impacted the quality of care provided to pediatric patients in CEDs. We hypothesized that a simulation-based collaborative program would improve the quality of the care provided to simulated pediatric DKA patients presenting to CEDs.

Methods

This prospective interventional study measured adherence of multiprofessional teams caring for pediatric DKA patients preimplementation and postimplementation of an improvement program in simulated setting. The program consisted of (a) a postsimulation debriefing, (b) assessment reports, (c) distribution of educational materials and access to pediatric resources, and (d) ongoing communication with the academic medical center (AMC). All simulations were conducted in situ (in the CED resuscitation bay) and were facilitated by a collaborative team from the AMC. A composite adherence score was calculated using a critical action checklist. A mixed linear regression model was performed to examine the impact of CED and team-level variables on the scores.

Results

A total of 91 teams from 13 CEDs participated in simulated sessions. There was a 22-point improvement of overall adherence to the DKA checklist from the preintervention to the postintervention simulations. Six of 9 critical checklist actions showed statistically significant improvement. Community emergency departments with medium pediatric volume showed the most overall improvement. Teams from CEDs that are further from the AMC showed the least improvement from baseline.

Conclusions

This study demonstrated a significant improvement in adherence to pediatric DKA guidelines in CEDs across the state after execution of an in situ simulation-based collaborative improvement program.
Hypernatremia in a Sleepy 2-Month-Old With Mention of Abnormal Eye Movements
Authors: Frazier Steven Barron , Fitzgerald Nina M.
Published: March 2019

Septo-optic dysplasia is a rare congenital heterogeneous malformation comprising at least 2 components of the triad: optic nerve hypoplasia, pituitary hormone abnormalities, and midline brain defects. We report a 2-month-old girl who presented with hypernatremia, constipation, and increased sleepiness with mother's recent appreciation of abnormal eye movements. We discuss the diagnosis and management of this patient who avoided significant morbidity by prompt diagnosis based initially on clinical suspicion. This case report emphasizes that thorough laboratory and physical evaluation of similar cases as presentation can vary considerably based on degree of pituitary dysfunction. Because of this variable presentation, diagnosis is typically delayed in otherwise healthy appearing infants early in their course of illness. To our knowledge, this is the first emergency medicine case report to discuss this diagnosis.
The Racoon Eye Sign in the Investigation of Dementia Using 18F-Florbetaben
Authors: Ordidge Katherine , Gandy Nemi , Arshad Mubarik , Win Zarni
Published: March 2019

Differentiating Alzheimer disease (AD) from other forms of cognitive impairment and from normal aging can be challenging. As a consequence, the diagnosis of AD can be delayed, often occurring too late for meaningful intervention. The role of β-amyloid plaques in the pathogenesis of AD provides a target for highly sensitive and specific image quantification of amyloid plaque burden using β-amyloid PET (18F-florbetaben). Here we present the case of a 77-year-old woman with increasing memory impairment and striking white matter changes on MRI, with the “racoon eye” sign on 18F-florebetaben PET imaging.
Extraosseous Colonic Uptake of 99mTc-MDP Associated With Iodinated Contrast CT
Authors: Ng Thomas S. C. , Sakellis Christopher G. , Jacene Heather A.
Published: March 2019

Extraosseous 99mTc-MDP uptake on bone scans is frequently encountered and has a broad differential diagnosis. A small subset of such patients can present with intestinal 99mTc-MDP uptake. We present the case of a 35-year-old woman with status after right nephrectomy for renal cell carcinoma, being followed with bone scan for osseous metastases. Follow-up imaging revealed new faint 99mTc-MDP uptake in the right hemiabdomen. Correlation with contrast-enhanced CT localized this uptake to the ascending colon. Enteric 99mTc-MDP uptake and its association with iodinated contrast should be considered in the differential diagnosis of extraosseous enteric 99mTc-MDP uptake.
Excellent Response to Lower Dose of 177Lu-PSMA-617 in a Metastatic Castration–Resistant Prostate Cancer Patient With a Transplanted Kidney
Authors: Norouzi Ghazal , Aghdam Ramin Akbarian , Hashemifard Hamidreza , Pirayesh Elahe
Published: March 2019

A 68-year-old man with metastatic castration-resistant prostate cancer and widespread bone metastases as well as a history of kidney transplant, underwent 5 cycles of 177Lu–prostate-specific membrane antigen 617 therapies in our department. Being more cautious of the radiation burden imposed on the transplanted kidney, a lower average dose of 4 GBq per cycle was administered (instead of the more routine 6.0-7.4 GBq per cycle). However, excellent response was noted and serum creatinine level of 0.8 mg/dL remained stable.
Cholesterol Granuloma Masquerading as Gallbladder Carcinoma on 18F-FDG PET/CT
Authors: Fu Zhanli , Chen Xueqi , Yang Xing , Li Qian
Published: March 2019

18F-FDG PET/CT was performed on a 70-year-old man to stage the newly diagnosed multiple myeloma. A hypermetabolic lesion in the gallbladder fundus was revealed incidentally and suspected for gallbladder carcinoma, but was finally proven to be a cholesterol granuloma by the pathology of cholecystectomy.
Ochronosis Involvement and Extensity With 18F-FDG PET/CT
Authors: Acar Emine , Bekiş Recep , Zengin Berin , Birlik Merih
Published: March 2019

Ochronosis (alkaptonuria) is an autosomal recessive inherited metabolic disease that causes pigmentation by accumulation of homogenous acid in the connective tissue. The most important causes of morbidity are ochronotic arthropathy and cardiovascular involvement seen in fourth and sixth decades, respectively. In this case report, we report the prevalence of 18F-FDG PET/BT findings in a 48-year-old man with ochronosis who underwent 18F-FDG PET/BT imaging for the evaluation of mediastinal lymphadenopathy.
18F-FDG PET/CT Findings in Disseminated Genital Herpes in an Immunocompetent Patient With Anaplastic Lymphoma Kinase Rearranged Advanced Nonsmall Cell Lung Cancer
Authors: Dejanovic Danijela , Amtoft Annemarie Gjelstrup , Sørensen Jens Benn , Pøhl Mette
Published: March 2019

We present the PET/CT findings of extensive disseminated genital herpes simplex virus infection in a 29-year-old woman known with disseminated anaplastic lymphoma kinase–mutated nonsmall lung cancer. PET/CT revealed extensive involvement of the outer and inner genitalia, multiple lymph nodes extending from the porta hepatis to the groins, and involvement of the liver. Disseminated herpes simplex virus infection is well described in neonates and immunocompromised individuals but very rare in immunocompetent adults as was the case with this patient.
Remyelination in multiple sclerosis: from concept to clinical trials
Authors: Kremer David , Göttle Peter , Flores-Rivera Jose , Hartung Hans-Peter , Küry Patrick
Published: March 2019

Purpose of review

Medications for relapsing multiple sclerosis (MS) effectively reduce relapse rate, mitigate disability progression and improve MRI measures of inflammation. However, they have virtually no impact on remyelination which is the major mechanism preventing MS-associated neurodegeneration. Stimulating the generation of myelin-(re)producing cells is therefore a central focus of current MS research and a yet unmet clinical need. Here, we present and evaluate key scientific studies from the field of (therapeutic) remyelination research covering the past 1.5 years.

Recent findings

On the one hand, recent research in the field of remyelination has strongly focused on repurposing drugs that are already approved for other indications by the Food and Drug Administration or the European Medicines Agency. On the other hand, emerging agents such as the mAbs opicinumab and GNbAC1 target entirely new and unconventional pathways. Some of them have already been tested in clinical trials in which they were found to exert beneficial effects on remyelination as well as on neuroregeneration/neuroprotection.

Several of the agents discussed in this review have shown a high potential as future neuroregenerative drugs. However, future trials with more sensitive clinical and paraclinical primary endpoints will be necessary to prove their effectiveness in MS.
Molecular chain networks and strain energy functions in rubber elasticity
Authors: Carroll Michael M.
Published: March 2019

A relatively simple molecular–statistical model for rubber elasticity, similar to the Wang–Guth and the Arruda–Boyce (AB) models, is presented. Discussion of some approximate inverse Langevin functions leads to the selection of a new one as the most attractive balance between accuracy and simplicity. Use of this approximation with the AB model, in particular, yields the logarithmic strain energy introduced by Gent that exhibits limiting chain extensibility. A rather unusual facet of the relationship between the three strain energies is that the new one is the mean of the other two.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
Likely equilibria of the stochastic Rivlin cube
Authors: Mihai L. Angela , Woolley Thomas E. , Goriely Alain
Published: March 2019

The problem of the Rivlin cube is to determine the stability of all homogeneous equilibria of an isotropic incompressible hyperelastic body under equitriaxial dead loads. Here, we consider the stochastic version of this problem where the elastic parameters are random variables following standard probability laws. Uncertainties in these parameters may arise, for example, from inherent data variation between different batches of homogeneous samples, or from different experimental tests. As for the deterministic elastic problem, we consider the following questions: what are the likely equilibria and how does their stability depend on the material constitutive law? In addition, for the stochastic model, the problem is to derive the probability distribution of deformations, given the variability of the parameters.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
Flow of a new class of non-Newtonian fluids in tubes of non-circular cross-sections
Authors: Gomez-Constante Juan P. , Rajagopal Kumbakonam R.
Published: March 2019

Fluids described by constitutive relations wherein the symmetric part of the velocity gradient is a function of the stress can be used to describe the flows of colloids and suspensions. In this paper, we consider the flow of a fluid obeying such a constitutive relation in a tube of elliptic and other non-circular cross-sections with the view towards determining the velocity field and the stresses that are generated at the boundary of the tube. As tubes are rarely perfectly circular, it is worthwhile to study the structure of the velocity field and the stresses in tubes of non-circular cross-section. After first proving that purely axial flows are possible, that is, there are no secondary flows as in the case of many viscoelastic fluids, we determine the velocity profile and the shear stresses at the boundaries. We find that the maximum shear stress is attained at the co-vertex of the ellipse. In general tubes of non-circular cross-section, the maximum shear stress occurs at the point on the boundary that is closest to the centroid of the cross-section.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
Physics of growing biological tissues: the complex cross-talk between cell activity, growth and resistance
Authors: Ben Amar Martine , Nassoy Pierre , LeGoff Loic
Published: March 2019

For many organisms, shapes emerge from growth, which generates stresses, which in turn can feedback on growth. In this review, theoretical methods to analyse various aspects of morphogenesis are discussed with the aim to determine the most adapted method for tissue mechanics. We discuss the need to work at scales intermediate between cells and tissues and emphasize the use of finite elasticity for this. We detail the application of these ideas to four systems: active cells embedded in tissues, brain cortical convolutions, the cortex ofCaenorhabditis elegansduring elongation and finally the proliferation of epithelia on extracellular matrix. Numerical models well adapted to inhomogeneities are also presented.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
An Eulerian formulation of inelasticity: from metal plasticity to growth of biological tissues
Authors: Rubin M. B.
Published: March 2019

The purpose of this paper is to review and contrast the Lagrangian and Eulerian formulations of inelasticity as they apply to metal plasticity and growth of biological tissues. In contrast with the Lagrangian formulation of inelasticity, the Eulerian formulation is unaffected by arbitrary choices of the reference configuration, an intermediate configuration, a total deformation measure and an inelastic deformation measure. Although the Eulerian formulation for growth of biological tissues includes a rate of mass supply and can be used to understand the mechanics of growth, it does not yet model essential mechanobiological processes that control growth. Much research is needed before this theory can help design medical treatments for growth related disease.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
Soft metamaterials with dynamic viscoelastic functionality tuned by pre-deformation
Authors: Parnell William J. , De Pascalis Riccardo
Published: March 2019

The small amplitude dynamic response of materials can be tuned by employing inhomogeneous materials capable of large deformation. However, soft materials generally exhibit viscoelastic behaviour, i.e. loss and frequency-dependent effective properties. This is the case for inhomogeneous materials even in the homogenization limit when propagating wavelengths are much longer than phase lengthscales, since soft materials can possess long relaxation times. These media, possessing rich frequency-dependent behaviour over a wide range of low frequencies, can be termed
metamaterials
in modern terminology. The sub-class that are periodic are frequently termed
soft phononic crystals
although their strong dynamic behaviour usually depends on wavelengths being of the same order as the microstructure. In this paper we describe how the effective loss and storage moduli associated with longitudinal waves in thin inhomogeneous rods are tuned by pre-stress. Phases are assumed to be quasi-linearly viscoelastic, thus exhibiting time-deformation separability in their constitutive response. We illustrate however that the effective incremental response of the inhomogeneous medium does
not
exhibit time-deformation separability. For a range of nonlinear materials it is shown that there is strong coupling between the frequency of the small amplitude longitudinal wave and initial large deformation.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
A microstructural model of cross-link interaction between collagen fibrils in the human cornea
Authors: Pandolfi A. , Gizzi A. , Vasta M.
Published: March 2019

We propose a simplified micromechanical model of the fibrous reinforcement of the corneal tissue. We restrict our consideration to the structural function of the collagen fibrils located in the stroma and disregard the other all-important components of the cornea. The reinforcing structure is modelled with two sets of parallel fibrils, connected by transversal bonds within the single fibril family (inter-cross-link) and across the two families (intra-cross-link). The particular design chosen for this ideal structure relies on the fact that its ability to sustain loads is dependent on the degree of the cross-link and, therefore, on the density and stiffness of the bonds. We analyse the mechanical response of the system according to the type of interlacing and on the stiffness of fibres and bonds. Results show that the weakening of transversal bonds is associated with a marked increase of the deformability of the system. In particular, the deterioration of transversal bonds due to mechanical, chemical or enzymatic reasons can justify the loss of stiffness of the stromal tissue resulting in localized thinning and bulging typically observed in keratoconus corneas.

This article is part of the theme issue ‘Rivlin's legacy in continuum mechanics and applied mathematics’.
Overt and covert paths for sound in the auditory system of mammals
Authors: Auriol B. , Auriol B. , Béard J. , Bibé B. , Broto J.-M. , Descouens D.F. , Durand L.J.S. , Florens J.-P. , Garcia F. , Gillieaux C. , Joiner E.G. , Libes B. , Pergent P. , Ruiz R. , Thalamas C.
Published: March 2019

Current scientific consensus holds that sound is transmitted, solely mechanically, from the tympanum to the cochlea via ossicles.

But this theory does not explain the hearing extreme quality regarding high frequencies in mammals. So, we propose a bioelectronic pathway (the covert path) that is complementary to the overt path.

We demonstrate experimentally that the tympanum produces piezoelectric potentials isochronous to acoustic vibrations thanks to its collagen fibers and that their amplitude increases along with the frequency and level of the vibrations. This finding supports the existence of an electrical pathway, specialized in transmitting high-frequency sounds, that works in unison with the mechanical pathway. A bio-organic triode, similar to a field effect transistor, is the key mechanism of our hypothesized pathway. We present evidence that any deficiency along this pathway produces hearing impairment. By augmenting the classical theory of sound transmission, our discovery offers new perspectives for research into both normal and pathological audition and may contribute to an understanding of genetic and physiological problems of hearing.
Vaccine blunts fentanyl potency in male rhesus monkeys
Authors: Tenney Rebekah D. , Blake Steven , Bremer Paul T. , Zhou Bin , Hwang Candy S. , Poklis Justin L. , Janda Kim D. , Banks Matthew L.
Published: March 2019

One proposed factor contributing to the increased opioid overdose deaths is the increased frequency of synthetic opioids, including fentanyl and fentanyl analogs. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness and selectivity of a fentanyl-tetanus toxoid conjugate vaccine to alter the behavioral effects of fentanyl and a structurally dissimilar mu-opioid agonist oxycodone in male rhesus monkeys (n=3-4). Fentanyl and oxycodone produced dose-dependent suppression of behavior in an assay of schedule-controlled responding and antinociception in an assay of thermal nociception (50°C). Acute naltrexone (0.032 mg/kg) produced an approximate 10-fold potency shift for fentanyl to decrease operant responding. The fentanyl vaccine was administered at weeks 0, 2, 4, 9, 19, and 44 and fentanyl or oxycodone potencies in both behavioral assays were redetermined over the course of 49 weeks. The vaccine significantly and selectively shifted fentanyl potency at least 10-fold in both assays at several time points over the entire experimental period. Mid-point titer levels were significantly correlated with fentanyl antinociceptive potency shifts. Antibody affinity for fentanyl as measured by a competitive binding assay increased over time to around 3-4 nM. The fentanyl vaccine also significantly increased fentanyl plasma levels approximately 6-fold consistent with the hypothesis that the vaccine sequesters fentanyl in the blood. Overall, these results support the continued development and evaluation of this fentanyl vaccine to address the ongoing opioid crisis.

Highlights

Vaccine blunted fentanyl rate-suppression potency ∼ 10-fold

Vaccine blunted fentanyl antinociceptive potency ∼25-fold

Fentanyl vaccine was as effective as acute 0.032 mg/kg naltrexone

Vaccine was selective for fentanyl and not oxycodone

Antibody immune response ∼ 3 nM affinity for fentanyl
Shared risk alleles with discordant polygenic effects: Disentangling the genetic overlap between ASD and ADHD
Authors: Verhoef Ellen , Grove Jakob , Shapland Chin Yang , Demontis Ditte , Burgess Stephen , Rai Dheeraj , Børglum Anders D. , St Pourcain Beate
Published: March 2019

Insight into shared polygenetic architectures affects our understanding of neurodevelopmental disorders. Here, we investigate evidence for pleiotropic mechanisms that may explain the comorbidity between Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). These complex neurodevelopmental conditions often co-occur, but differ in their polygenetic association patterns, especially with educational attainment (EA), showing discordant association effects. Using multivariable regression analyses and existing genome-wide summary statistics based on 10,610 to 766,345 individuals, we demonstrate that EA-related polygenic variation is shared between ASD and ADHD. We show that different combinations of the same ASD and ADHD risk-increasing alleles can simultaneously re-capture known ASD-related positive and ADHD-related negative associations with EA. Such patterns, although to a lesser degree, were also present for combinations of other psychiatric disorders. These findings suggest pleiotropic mechanisms, where the same polygenic sites can encode multiple independent, even discordant, association patterns without involving distinct loci, and have implications for cross-disorder investigations.
Visualization of Loki- and Heimdallarchaeia (Asgardarchaeota) by fluorescence in situ hybridization and catalyzed reporter deposition (CARD-FISH)
Authors: Salcher Michaela M. , Andrei Adrian-Ştefan , Bulzu Paul-Adrian , Keresztes Zsolt G. , Banciu Horia L. , Ghai Rohit
Published: March 2019

Metagenome-assembled genomes (MAGs) of Asgardarchaeota are starting to be recovered from a variety of habitats, broadening their environmental distribution and providing access to the genetic makeup of this archaeal lineage. Despite their singular phylogenetic position at the base of the eukaryotic tree of life, the morphology of these bewildering organisms remains a mystery. In order to visualize this elusive group, we applied a combination of CARD-FISH and epifluorescence microscopy on coastal hypersaline sediment samples, using specifically designed CARD-FISH probes for Heimdallarchaeia and Lokiarchaeia lineages and provide the first visual evidence for both these groups. Here, we show that while Heimdallarchaeia are characterized by a uniform cellular morphology typified by central DNA localization, Lokiarchaeia display a plethora of shapes and sizes that likely reflect their broad phylogenetic diversity and ecological distribution.
Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition
Authors: Wasnick RM , Korfei M , Piskulak K , Henneke I , Wilhelm J , Mahavadi P , von der Beck D , Koch M , Shalashova I , Klymenko O , Fink L , Witt H , Hackstein H , El Agha E , Bellusci S , Klepetko W , Königshoff M , Eickelberg O , Braun T , Seeger W , Ruppert C , Guenther A
Published: March 2019

Alveolar epithelial cell type II (AEC2) injury underlies idiopathic pulmonary fibrosis (IPF). Here we show increased Notch1 signaling in AEC2s in human IPF and IPF models, causing enhanced proliferation and de-differentiation of AEC2s. As a result, we observed defective surfactant protein (SP)-B/C processing, elevated alveolar surface tension, repetitive alveolar collapse and development of lung fibrosis. Similar changes were encountered upon pharmacological inhibition of SP-B/C processing in vivo by pepstatin A. Inhibition of Notch signaling in cultured human IPF precision cut lung slices improved surfactant processing capacity of AEC2s and reversed fibrosis. Notch1 therefore offers as novel therapeutic target.

One sentence summary

Notch1 inhibition restores alveolar epithelial differentiation and surface tension and reverses matrix deposition in lung fibrosis
Differential Expression of N- and O-glycans on HeLa Cells-Revealed by Direct Fluorescent Glycan Labeling with Recombinant Sialyltransferases
Authors: Wu Zhengliang L , Person Anthony D , Burton Andrew J. , Singh Ravinder , Burroughs Barbara , Fryxell Dan , Tatge Timothy J. , Manning Timothy , Wu Guoping , Swift Karl A.D. , Kalabokis Vassili
Published: March 2019

Cells are covered with glycans. The expression and distribution of specific glycans on cell surface are important for various cellular functions. Imaging these glycans is essential to elucidate their biological roles. Here, utilizing enzymatic incorporation of fluorophore-conjugated sialic acids, dubbed asdirectfluorescentglycanlabeling (DFGL), we report the imaging of N- and O-glycans and particularly tumor specific sialyl T antigen on HeLa cells. It is found that while Core-1 O-glycans are relatively evenly distributed on cells, the expression of N-glycans tend to be more peripheral. More interestingly, the expression of sialyl T antigen displays random and sporadic patterns. In technique side, DFGL allows convenient labeling or imaging of various glycans on intact glycoproteins or cell surfaces with variety of fluorescent dyes.
PAK1, PAK1Δ15, and PAK2: similarities, differences and mutual interactions
Authors: Grebeňová D. , Holoubek A. , Röselová P. , Obr A. , Brodská B. , Kuželová K.
Published: March 2019

P21-activated kinases (PAK) are key effectors of the small GTPases Rac1 and Cdc42, as well as of Src family kinases. In particular, PAK1 has several well-documented roles, both kinase-dependent and kinase-independent, in cancer-related processes, such as cell proliferation, adhesion, and migration. However, PAK1 properties and functions have not been attributed to individual PAK1 isoforms: besides the full-length kinase (PAK1-full), a splicing variant lacking the exon 15 (PAK1Δ15) is annotated in protein databases. In addition, it is not clear if PAK1 and PAK2 are functionally overlapping. Using fluorescently tagged forms of human PAK1-full, PAK1Δ15, and PAK2, we analyzed their intracellular localization and mutual interactions. Effects of PAK inhibition or depletion on cell-surface adhesion were monitored by real-time microimpedance measurement. We show that PAK1Δ15 is in many aspects similar to PAK2, rather than to PAK1-full. Both PAK1Δ15 and PAK2, but not PAK1-full, were enriched in focal adhesions, indicating that the C-terminus might be important for PAK intracellular localization. Using immunoprecipitation, we documented direct interactions among the studied PAK group I members: PAK1 and PAK2 form homodimers, but all possible heterodimers were also detected. Our results indicate that PAK1 and PAK2 have distinct roles in cell adhesion and mutually affect their function. PAK1-full is required for formation of membrane protrusions, whereas PAK2 is involved in focal adhesion assembly. We have also noted that PAK inhibition was associated with a large reduction of the cell glycolytic rate. Altogether, our data suggest a complex interplay among different PAK group I members, which have largely non-redundant functions.
Substrate-rigidity dependent migration of an idealized twitching bacterium
Authors: Simsek Ahmet Nihat , Braeutigam Andrea , Koch Matthias D. , Shaevitz Joshua W. , Shaevitz Joshua W. , Huang Yunfei , Gompper Gerhard , Sabass Benedikt
Published: March 2019

Mechanical properties of the extracellular matrix are important determinants of cellular migration in diverse processes, such as immune response, wound healing, and cancer metastasis. Moreover, recent studies indicate that even bacterial surface colonization can depend on the mechanics of the substrate. Here, we focus on physical mechanisms that can give rise to substrate-rigidity dependent migration. We study a “twitcher”, a cell driven by extension-retraction cycles, to idealize bacteria and perhaps eukaryotic cells that employ a slip-stick mode of motion. The twitcher is asymmetric and always pulls itself forward at its front. Analytical calculations show that the migration speed of a twitcher depends non-linearly on substrate rigidity. For soft substrates, deformations do not lead to build-up of significant force and the migration speed is therefore determined by stochastic adhesion unbinding. For rigid substrates, forced adhesion rupture determines the migration speed. Depending on the force-sensitivity of front and rear adhesions, forced bond rupture implies an increase or a decrease of the migration speed. A requirement for the occurrence of rigidity-dependent stick-slip migration is a “sticky” substrate, with binding rates being an order of magnitude larger than unbinding rates in absence of force. Computer simulations show that small stall forces of the driving machinery lead to a reduced movement on high rigidities, regardless of force-sensitivities of bonds. The simulations also confirm the occurrence of rigidity-dependent migration speed in a generic model for slip-stick migration of cells.
Asymmetric sampling in human auditory cortex reveals spectral processing hierarchy
Authors: Giroud Jérémy , Trébuchon Agnès , Schön Daniele , Marquis Patrick , Liegeois-Chauvel Catherine , Poeppel David , Morillon Benjamin
Published: March 2019

Speech perception is mediated by both left and right auditory cortices, but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex. We presented short acoustic transients to reveal the stereotyped spectro-spatial oscillatory response profile of the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with preferred processing modes in the theta (∼4-8 Hz) and low gamma (∼25-50 Hz) ranges. These results highlight that the human auditory system employs a two-timescale processing mode. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (∼3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (∼6/40 Hz) activity in the left. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the two hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.

Author summary

Speech processing is now known to be distributed across the two hemispheres, but the origin and function of lateralization continues to be vigorously debated. The asymmetric sampling in time (AST) hypothesis predicts that (1) the auditory system employs a two-timescales processing mode, (2) present in both hemispheres but with a different ratio of fast and slow timescales, (3) that emerges outside of primary cortical regions. Capitalizing on intracranial data from 96 epileptic patients we sensitively validated each of these predictions and provide a precise estimate of the processing timescales. In particular, we reveal that asymmetric sampling in associative areas is subtended by distinct two-timescales processing modes. Overall, our results shed light on the neurofunctional architecture of cortical auditory processing.
Sign-tracking behavior is difficult to extinguish and resistant to multiple cognitive enhancers
Authors: Fitzpatrick Christopher J. , Geary Trevor , Creeden Justin F. , Morrow Jonathan D.
Published: March 2019

The attribution of incentive-motivational value to drug-related cues underlies relapse and craving in drug addiction. One method of addiction treatment, cue-exposure therapy, utilizes repeated presentations of drug-related cues in the absence of drug (i.e., extinction learning); however, its efficacy has been limited due to an incomplete understanding of extinction and relapse processes after cues have been imbued with incentive-motivational value. To investigate this, we used a Pavlovian conditioned approach procedure to screen for rats that attribute incentive-motivational value to reward-related cues (sign-trackers; STs) or those that do not (goal-trackers; GTs). In Experiment 1, rats underwent Pavlovian extinction followed by reinstatement and spontaneous recovery tests. For comparison, a separate group of rats underwent PCA training followed by operant conditioning, extinction, and tests of reinstatement and spontaneous recovery. In Experiment 2, three cognitive enhancers (sodium butyrate, D-cycloserine, and fibroblast growth factor 2) were administered following extinction training to facilitate extinction learning. STs but not GTs displayed enduring resistance to Pavlovian, but not operant, extinction and were more susceptible to spontaneous recovery. In addition, none of the cognitive enhancers tested affected extinction learning. These results expand our understanding of extinction learning by demonstrating that there is individual variation in extinction and relapse processes and highlight potential difficulties in applying extinction-based therapies to drug addiction treatment in the clinic.
Performance investigation of an advanced diagnostic method for SSTPI-fed IM drives under single and multiple open IGBT faults
Authors: Zdiri Mohamed Ali , Bouzidi Badii , Hadj Abdallah Hsan
Published: March 2019

Purpose

This paper aims to analyze and investigate the performance of an improved fault detection and identification (FDI) method based on multiple criteria, applied to six-switch three-phase inverter (SSTPI)-fed induction motor (IM) drives under both single and multiple open insulated-gate bipolar transistors(IGBT) faults.

Design/methodology/approach

This paper proposes an advanced diagnostic method for both single and multiple open IGBT faults dedicated to SSTPI-fed IM drives considering five distinct faulty operating conditions as follows: a single IGBT open-circuit fault, a single-phase open-circuit fault, a non-crossed double fault in two different legs, a crossed double fault in two different legs and a three-IGBT open-circuit fault. This is achieved because of the introduction of a new diagnosis variable provided using the information of the slope of the current vector in (α-β) frame. The proposed FDI method is based on the synthesis and the analysis, under both healthy and faulty operations, of the behaviors of the introduced diagnosis variable, the three motor phase currents and their normalized average values. Doing so, the developed FDI method allows a best compromise of fast detection and precision localization of IGBT open-circuit fault of the inverter.

Findings

Simulation works, carried out considering the implementation of the direct rotor flux oriented control in an IM fed by the conventional SSTPI, have proved the high performance of the advanced FDI method in terms of fast fault detection associated with a high robustness against false alarms, against speed and load torque fast variations and against the oscillations of the DC-bus voltage in the case of both healthy and faulty operations.

Research limitations/implications

This work should be extended considering the validation of the obtained simulation results through experiments.

Originality/value

Different from other FDI methods, which suffer from a low diagnostic effectiveness for low load levels and false alarms during transient operation, this method offers the potentialities to overcome these drawbacks because of the introduction of the new diagnosis variable. This latter, combined with the information provided from the three motor phase currents and their normalized average values allow a more efficient detection and identification of IGBT open-circuit fault.
Nuances of microalgal technology in food and nutraceuticals: a review
Authors: Sahni Prashant , Aggarwal Poonam , Sharma Savita , Singh Baljit
Published: March 2019

Purpose

The purpose of this paper is to acquaint the readers with the insights regarding the interventions of microalgal technology for production of metabolites and functional ingredients from microalgae for food and nutraceutical application and exploration of microalgae biomass for food application.

Design/methodology/approach

Various information databases such as journals, library catalogues and professional websites were used to collect information pertaining to application of microalgae in food and nutraceutical sector. Systematic review was made with recent studies covering the vital aspects of art of microalgae cultivation for metabolite production, functional ingredients from microalgae, market scenario and utilisation of microalgae biomass for the valorisation of the food products. Key points have been discussed after every section to highlight the practical implications to make this review more insightful for the readers.

Findings

Microalgal technology provides sustainable solution for its application in food and nutraceutical sector. The heart of metabolite production lies in the optimisation of cultivation conditions of microalgae. Wide array of functional components are obtained from microalgae. Microalgae offer an alternative source for omega-3 fatty acids. Microalgae is widely exploited for production of pigments, namely, ß-carotene, astaxanthin, lutein, phycocyanin and chlorophyll, that have important implication as natural colourants and nutraceuticals in food. Larger diversity of sterols found in microalgae confers bioactivity. Microalgae is finding its place in market shelves as nutraceuticals where its functional ingredients are in the form of powder, tablets, extract and beverages and in innovative products such as microalgae protein and fat, culinary algae oil and butter. Sprulina and Chlorella are popular choice for the supplementation of food products with microalgae biomass.

Originality/value

This is a comprehensive review that highlights the application of microalgal technology for the development of healthy food products and presents holistic intervention in food and nutraceutical sector.
Polyphenol intakes and risk of impaired lipid profile, elevated hepatic enzymes and nonalcoholic fatty liver disease
Authors: Nikkhah-Bodaghi Mehrnaz , Ghanavati Matin , Hekmatdoost Azita
Published: March 2019

Purpose

Polyphenols are plant-derived bioactive compounds with some known hepato-protective effects. The purpose of this study is to evaluate the association between polyphenol consumption and risk of nonalcoholic fatty liver disease (NAFLD) and its related conditions such as impaired lipid profile and elevated hepatic enzymes.

Design/methodology/approach

A total of 196 NAFLD patients and 803 controls were enrolled in this case-control study. Biochemical and anthropometric measurements as well as polyphenol consumption during the previous year were assessed.

Findings

In unadjusted model, participants who consumed the third and fourth quartiles of polyphenols intake were less likely to have NAFLD in comparison to those who consumed the first quartile [odds ratio, OR: 0.48; 95 per cent confidence interval, CI: (0.30-0.77) and OR: 0.62; 95 per cent CI: (0.40-0.96), respectively]. In separate analysis of genders, this effect was seen only in male participants [OR: 0.29; 95 per cent CI: (0.14-0.58) and OR: 0.21; 95 per cent CI (0.10-0.42), respectively], and the association remained significant after adjustment for energy, body mass index, age and smoking.

Originality/value

Higher total polyphenol intake is associated with a decreased risk of NAFLD. Prospective studies are needed to confirm these results.
Factors influencing sustainability reporting by Sri Lankan companies
Authors: Dissanayake Dinithi , Tilt Carol , Qian Wei
Published: March 2019

Purpose

This paper aims to investigate the key company characteristics which influence sustainability reporting by publicly listed companies in Sri Lanka.

Design/methodology/approach

Panel data analysis is conducted to analyse sustainability reporting of 84 publicly listed companies from 2012 to 2015.

Findings

Company size and usage of the GRI guidelines are found to be the most relevant company characteristics associated with sustainability reporting by listed companies in Sri Lanka. Unexpectedly, ownership and industry sector do not show strong influences on the extent of sustainability reporting over the study period compared with prior studies.

Research limitations/implications

Large companies which follow the GRI guidelines are more likely to report in an elaborate manner, indicating the influence of standards setting bodies in Sri Lanka. This means Sri Lankan companies pay attention to global business practices, given the current re-development phase Sri Lanka is experiencing after the end of the civil war.

Originality

This study is one of the few studies that examine sustainability reporting in a country set against a backdrop of war in the South Asian region. Besides this, it extends the previous research on sustainability reporting and variables such as company ownership, GRI usage, company size and industry sector in a developing country context.
Key issues and challenges in stakeholder engagement in sustainability reporting
Authors: Kaur Amanpreet , Lodhia Sumit K.
Published: March 2019

Purpose

This paper aims to explore the key issues and challenges that can affect the quality of stakeholder engagement processes and outcomes in relation to sustainability reporting.

Design/methodology/approach

Case study research was used to gain in-depth insights into the stakeholder engagement practices of three Australian local councils.

Findings

The findings of this study suggest that the effectiveness of stakeholder engagement can be undermined by certain difficulties and challenges faced by an organisation. These include limited resources, lack of commitment from internal stakeholders, political factors, heterogeneous concerns, inadequate representation and an unwillingness to engage.

Research limitations/implications

The study adds to the limited literature on stakeholder engagement in sustainability reporting specifically and on sustainability accounting and reporting in public sector organisations (PSOs) more generally.

Practical implications

This research provides practical guidance to government authorities on the challenges that need to be addressed to enable an effective stakeholder engagement process for sustainability reporting.

Social implications

Stakeholders have a critical role in holding organisations accountable and research into their engagement with these organisations has societal benefits.

Originality/value

This research while focused on the Australian context has international relevance as it provides unique insights into the stakeholder engagement process. The implications of this research apply to not just PSOs but also corporations that are grappling with the (difficult) process of effective engagement with stakeholders.
Molecular aspects of bacterial nanocellulose biosynthesis
Authors: Jacek Paulina , Dourado Fernando , Gama Miguel , Bielecki Stanisław
Published: March 2019

Bacterial nanocellulose (BNC) produced by aerobic bacteria is a biopolymer with sophisticated technical properties. Although the potential for economically relevant applications is huge, the cost of BNC still limits its application to a few biomedical devices and the edible product Nata de Coco, made available by traditional fermentation methods in Asian countries. Thus, a wider economic relevance of BNC is still dependent on breakthrough developments on the production technology. On the other hand, the development of modified strains able to overproduce BNC with new properties – e.g. porosity, density of fibres crosslinking, mechanical properties, etc. – will certainly allow to overcome investment and cost production issues and enlarge the scope of BNC applications. This review discusses current knowledge about the molecular basis of BNC biosynthesis, its regulations and, finally, presents a perspective on the genetic modification of BNC producers made possible by the new tools available for genetic engineering.