bluuebunny/crossref_metadata_2025 huggingface dataset:
General Anesthesia Versus Conscious Sedation in Endovascular Thrombectomy for Stroke: A Meta-analysis of 4 Randomized Controlled Trials
Authors: Campbell Doug , Diprose William K. , Deng Carolyn , Barber P. Alan
Published: September 2019

Background:

In ischemic stroke patients, studies have suggested that clinical outcomes following endovascular thrombectomy are worse after general anesthesia (GA) compared with conscious sedation (CS). Most data are from observational trials, which are prone to measure and unmeasure confounding. We performed a systematic review and meta-analysis of thrombectomy trials where patients were randomized to GA or CS, and compared efficacy and safety outcomes.

Methods:

The Medline, Embase, and Cochrane databases were searched for randomized controlled trials comparing GA to CS in endovascular thrombectomy. Efficacy outcomes included successful recanalization (Thrombolysis in Cerebral Infarction score of 2b to 3), and good functional outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included intracerebral hemorrhage and 3-month mortality.

Results:

Four studies were identified and included in the random effects meta-analysis. Patients treated with GA achieved a higher proportion of successful recanalization (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.26-3.62; P=0.005) and good functional outcome (OR: 1.71, 95% CI: 1.13-2.59; P=0.01). For every 7.9 patients receiving GA, one more achieved good functional outcome compared with those receiving CS. There were no significant differences in intracerebral hemorrhage (OR: 0.61, 95% CI: 0.20-1.85; P=0.38) or 3-month mortality (OR: 0.62, 95% CI: 0.33-1.17; P=0.14) between GA and CS patients.

Conclusions:

In centers with high quality, specialized neuroanesthesia care, GA treated thrombectomy patients had superior recanalization rates and better functional outcome at 3 months than patients receiving CS.
Medicaid Reimbursement for Common Spine Procedures
Authors: Casper David S. , Schroeder Gregory D. , McKenzie James , Zmistowski Benjamin , Vatson Jayanth , Mangan John , Stull Justin , Kurd Mark , Rihn Jeffrey A. , Anderson D. Greg , Kaye David I. , Radcliff Kris , Woods Barrett , Hilibrand Alan S. , Vaccaro Alexander R. , Kepler Christopher K.
Published: September 2019

Study Design.

Health Services Research.

Objective.

The purpose of this study is to determine the variability of Medicaid (MCD) reimbursement for patients who require spine procedures, and to assess how this compares to regional Medicare (MCR) reimbursement as a marker of access to spine surgery.

Summary of Background Data.

The current health care environment includes two major forms of government reimbursement: MCD and MCR, which are regulated and funded by the state and federal government, respectively.

Methods.

MCD reimbursement rates from each state were obtained for eight spine procedures, utilizing online web searches: anterior cervical decompression and fusion, posterior cervical decompression and fusion, posterior lumbar decompression, single-level posterior lumbar fusion, posterior fusion for deformity (less than six levels; six to 12 levels; 13+ levels), and lumbar microdiscectomy. Discrepancy in reimbursement for these procedures on a state-to-state basis, as well as overall differences in MCD versus MCR reimbursement, was determined. Procedures were examined to identify whether certain surgical interventions have greater discrepancy in reimbursement.

Results.

The average MCD reimbursement was 78.4% of that for MCR. However, there was significant variation between states (38.8%–140% of MCR for the combined eight procedures). On average, New York, New Jersey, Florida, and Rhode Island provided MCD reimbursements <50% of MCR reimbursements in the region. In total, 20 and 42 states provided <75% and 100% of MCR reimbursements, respectively. Based upon relative reimbursement, MCD appears to value microdiscectomy (84.1% of MCR; P = 0.10) over other elective spine procedures. Microdiscectomy also had the most interstate variation in MCD reimbursement: 39.0% to 207.0% of MCR.

Conclusion.

Large disparities were found between MCR and MCD when comparing identical procedures. Further research is necessary to fully understand the effect of these significant differences. However, it is likely that these discrepancies lead to suboptimal access to necessary spine care.

Level of Evidence: 4
Endoscopic Evaluation of Lacrimal Mucosa With Indigo Carmine Stain
Authors: Mimura Masashi , Alameddine Ramzi M. , Korn Bobby S. , Kikkawa Don O. , Oku Hidehiro , Sato Bunpei , Ikeda Tsunehiko
Published: September 2019

Use of indigo carmine dye as an in vivo adjunct in lacrimal microendoscopy is useful for accurately detecting areas of highly damaged lacrimal mucosa.

Purpose:

Histological investigation in the use of indigo carmine for detection of mucosal pathology in lacrimal microendoscopy. To investigate the histopathological correlation of staining found on lacrimal microendoscopy.

Methods:

A prospective case series was conducted in patients with a history of nasolacrimal duct obstruction and dacryocystitis requiring treatment with dacryocystorhinostomy or dacryocystectomy. Prior to lacrimal surgery, all patients underwent endolacrimal evaluation using transpunctal lacrimal microendoscopy. Indigo carmine dye (0.2 mg/0.5 ml) was injected into the lacrimal system via the irrigation channel of the endoscope, and after copious irrigation, the differential mucosal staining was recorded. Histopathologic analysis of tissue samples of positively and negatively stained lacrimal sac mucosa collected after surgery was performed to investigate the correlation with the results of each endoscopic evaluation.

Results:

Four patients underwent dacryocystorhinostomy and 2 patients underwent dacryocystectomy. Histopathology of positive-stained lacrimal sac mucosa corresponded to areas of the advanced fibrous stage of mucosal changes resulting from dacryocystitis, which showed atrophy of epithelium associated with the loss of goblet cells and subepithelium fibrous scarring. In contrast, areas of lacrimal mucosa that did not stain with indigo carmine were still in an active inflammatory stage of dacryocystitis preserving columnar epithelium with goblet cells.

Conclusions:

This study suggests that indigo carmine staining is a useful adjunct in lacrimal microendoscopy for accurately detecting areas of highly damaged fibrous lacrimal mucosa, as it allows for direct visualization of lacrimal mucosal pathology and can provide prognostic insight and guidance in regard to treatment options for patients with lacrimal drainage obstruction.
Relationship between the fall in blood pressure in the standing position and diaphragmatic muscle thickness: proof of concept study
Authors: Ichikawa Atsushi , Yamasaki Fumiyasu , Ueda Motoko , Todaka Hiroshi , Miyao Emi , Yoshinaga Yuna , Yamanaka Shigeo , Matsumura Yoshihisa , Sato Takayuki
Published: September 2019

Background

The diaphragm is an important muscle of respiration, and regulates the intrathoracic pressure. Blood pressure is regulated by the baroreceptor reflex system, and is also affected by intrathoracic pressure. We examined the relationship between the diaphragmatic muscle thickness and the degree of drop in blood pressure in the standing position.

Methods

We prospectively studied 15 healthy subjects. The diaphragmatic muscle thickness was measured using a B-mode ultrasonic imaging device. The blood pressure before and after standing was measured by a head-up tilt test.

Results

The diastolic blood pressure difference during expiration and inspiration showed a significant correlation with the diaphragmatic muscle thickness (r = 0.578, P = 0.024 and r = 0.518, P = 0.048, respectively).

Conclusion

The diaphragmatic muscle thickness was related to the fall in diastolic blood pressure in the standing position. This indicates that adequate diaphragmatic muscle thickness helps to maintain intrathoracic pressure and prevents excessive drop in blood pressure in the standing position.
Assessment of the relationship between coronary flow rates and myocardial perfusion abnormality in patients with nonobstructive coronary artery disease: an observational study in cardiac syndrome X and coronary slow flow
Authors: Özde Cem , Aktüre Gülşah , Aytekin Seda , Sayin Ahmet Egemen , Ay Esra Koç , Coçkun Gökhan , Kaya Adnan , Kayapinar Osman
Published: September 2019

Objectives

In this study, we evaluated and compared the level of myocardial ischaemia caused by cardiac syndrome X (CSX) and coronary slow flow (CSF) with single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI), and determined if changes in the level of myocardial ischaemia exist in CSF and CSX cases according to thrombolysis in myocardial infarction frame count (TFC).

Materials and methods

The study population consisted of 66 patients with CSF and 78 angiographically normal patients (36 of them with CSX and 42 of them healthy controls). The coronary flow rates of all patients were documented using TFC. Subsequently, all patients were evaluated with SPECT-MPI and categorized into the following groups according to their results: patients with CSF, patients with CSX, and patients with normal coronary arteries. Finally, we investigated whether a relationship existed between the SPECT-MPI and TFC results from these three groups.

Results

All ischaemia scores for MPI were significantly higher in the CSF group than in the CSX and control groups (P < 0.05). TFC was significantly associated with the severity of ischaemia in the CSF patients. There was a significant positive correlation between the summon difference score (SDS) and mean TFC value (P < 0.05) as well as between the SDS and each individual coronary TFC value in the CSF patients (P < 0.05). The number of vessels involved in CSF was positively correlated with the SDS.

Conclusion

CSF is associated with more severe myocardial ischaemia than CSX. The level of myocardial ischaemia on SPECT-MPI was correlated with the TFC and the number of affected coronary vessels in patients with CSF. These results suggest that CSF is a more serious clinical entity than CSX, and that the clinical severity of CSF appears to increase as the coronary flow rate decreases.
Predictors of Outcome in Mammary Adenoid Cystic Carcinoma
Authors: Slodkowska Elzbieta , Xu Bin , Kos Zuzana , Bane Anita , Barnard Maja , Zubovits Judit , Iyengar Pratibha , Faragalla Hala , Turbin Dmitry , Williams Phillip , Barnes Penny J. , Mulligan Anna Marie
Published: September 2019

Mammary adenoid cystic carcinoma (ACC) is a rare subtype of breast cancer with a favorable prognosis. Here we report on predictors of outcome based on a detailed morphologic review and analysis of 108 mammary ACC. Sixty-four tumors (59.2%) were pure conventional ACC, 23 (21.3%) were pure basaloid ACC. Follow-up was available for 87 patients (median: 51 mo). Eighteen patients (20.7%) developed recurrence: 7 (8%) had local recurrence and 14 (16%) had distant metastasis. Two patients died of disease, 1 died of an unrelated cause, 14 were alive with disease (including 8 in palliative care), and 70 (80.5%) were alive with no evidence of disease. Of 90 patients with known lymph node (LN) status 9 (10%) had nodal involvement (all with basaloid ACC). Distant metastases in patients with predominantly basaloid ACC compared with pure conventional ACC were more common (40% vs. 7.7%) and occurred earlier (22 vs. 84 mo). The following factors were found to be predictive of recurrence-free survival: positive margin, Nottingham grade, neovascularization, basaloid component, perineural invasion, lymphovascular invasion, >30% solid growth, necrosis and LN involvement; the first 3 remained statistically significant on multivariate analysis. Factors predictive of distant disease-free survival were neovascularization, Nottingham grade, lymphovascular invasion, solid component >50%, LN involvement, basaloid component >50%, tumor necrosis, perineural invasion, and final margin. Only neovascularization remained statistically significant on multivariate analysis. Basaloid ACC is an aggressive variant of mammary ACC with more frequent nodal involvement and higher incidence of distant spread. LN staging should be performed for all mammary basaloid ACC.
Helping Patients Eat Better During and Beyond Cancer Treatment
Authors: Greenlee Heather , Santiago-Torres Margarita , McMillen Kerry K. , Ueland Kate , Haase Anne M.
Published: September 2019

Cancer patients and survivors are at risk of poor clinical outcomes due to poor nutritional intake following cancer diagnosis. During cancer treatment, treatment toxicities can affect eating patterns and can lead to malnutrition resulting in loss of lean body mass and excessive weight loss. Following treatment and throughout survivorship, patients are at risk of not meeting national nutrition guidelines for cancer survivors, which can affect recurrence and survival. Obesity, which is highly prevalent in cancer patients and survivors, can affect clinical outcomes during treatment by masking malnutrition and is also a risk factor for cancer recurrence and poorer survival in some cancers. Appropriate and effective nutritional education and guidance by trained clinicians are needed throughout the cancer continuum. This article presents an overview of recommendations and guidelines for nutrition and weight management and provides recent examples of behavioral theory-based targeted lifestyle interventions designed to increase adherence to recommendation by cancer patients and survivors.
Securing the exchange of synthetic genetic constructs using digital signatures
Authors: Gallegos Jenna E , Kar Diptendu M. , Ray Indrakshi , Ray Indrajit , Peccoud Jean
Published: September 2019

Synthetic biology relies on an ever-growing supply chain of synthetic genetic material. Technologies to secure the exchange of this material are still in their infancy. Solutions proposed thus far have focused on watermarks, a dated security approach that can be used to claim authorship, but is subject to counterfeit, and does not provide any information about the integrity of the genetic material itself. We describe how data encryption and digital signature algorithms can be used to ensure the integrity and authenticity of synthetic genetic constructs. Using a pilot software that generates digital signatures and other encrypted data for plasmids, we demonstrate that we can predictably extract information about the author, the identity, and the integrity of plasmid sequences from sequencing data alone without a reference sequence, all without compromising the function of the plasmids. We discuss how this technology can be improved, applied, and expanded to support the new bioeconomy.
Files removed following a technical error
Authors: bioRxiv
Published: September 2019

This manuscript was removed because it posted owing to a technical error
DNA-mediated assembly of multi-specific antibodies for T cell engaging and tumor killing
Authors: Pan Liqiang , Cao Chan , Run Changqing , Zhou Liujuan , Chou James J.
Published: September 2019

Targeting T-cells against cancer cells is a direct means of treating cancer, and already showed great responses in clinical treatment of B-cell malignancies. A simple way to redirect T-cells to cancer cells is using multi-specific antibody (MsAb) that contains different arms for specifically “grabbing” the T-cells and cancer cells; as such, the T-cells are activated upon target engagement and the killing begins. Here, a Nucleic Acid mediated Protein-Protein Assembly (NAPPA) approach is implemented to construct a MsAb for T-cell engaging and tumor killing. Anti -CD19 and -CD3 single-chain variable fragments (scFvs) each are conjugated to different L-DNAs with sequences that form the Holliday junction, thus allowing spontaneous assembly of homogeneous protein-DNA oligomers containing two anti-CD19 and one anti-CD3 scFvs. The new MsAb shows strong efficacy in inducing Raji tumor cell cytotoxicity in the presence of T-cells with EC50~ 0.2 nM; it also suppresses tumor growth in the Raji xenograft mouse model. The data indicate that MsAbs assembled from protein-DNA conjugates are effective macromolecules for directing T-cells for tumor killing. The modular nature of the NAPPA platform allows rapid generation of complex MsAbs from simple antibody fragments, while offering a general solution for preparing antibodies with high-order specificity.
A sheath of motile cells supports collective migration in of the Zebrafish posterior lateral line primordium under the skin
Authors: Nogare Damian Dalle , Natesh Naveen , Chitnis Ajay
Published: September 2019

During embryonic development, cells must navigate through diverse three-dimensional environments robustly and reproducibly. The zebrafish posterior lateral line primordium (PLLp), a group of approximately 120 cells which migrates from the otic vesicle to the tip of the tail, spearheading the development of the lateral line sensory system, is an excellent model to study such collective migration in an in vivo context. This system migrates in a channel formed by the underlying horizontal myoseptum and somites, and the overlying skin. While cells in the leading part of the PLLp are flat and have a more mesenchymal morphology, cells in the trailing part progressively reorganize to form epithelial rosettes, called protoneuromasts. These epithelial cells extend basal cryptic lamellipodia in the direction of migration in response to both chemokine and FGF signals. In this study, we show that, in addition to these cryptic lamellipodia, the core epithelial cells are in fact surrounded by a population of motile cells which extend actin-rich migratory processes apposed to the overlying skin. These thin cells wrap around the protoneuromasts, forming a continuous sheath of cells around the apical and lateral surface of the PLLp. The processes extended by these cells are highly polarized in the direction of migration and this directionality, like that of the basal lamellipodia, is dependent on FGF signaling. Consistent with interactions of sheath cells with the overlying skin contributing to migration, removal of the skin stalls migration. However, this is accompanied by some surprising changes. There is a profound change in the morphology of the sheath cells, with directional superficial lamellipodia being replaced with the appearance of undirected blebs or ruffles. Furthermore, removal of the skin not only affects underlying lamellipodia, it simultaneously alters the morphology and behavior of the deeper basal cryptic lamellipodia, even though these cells do not directly contact the skin. Directional actin-rich protrusions on both the apical and basal surface and migration are completely and simultaneously restored upon regrowth of the skin over the PLLp. We suggest that this system utilizes a circumferential sheath of motile cells to allow the internal epithelial cells to migrate collectively in the confined space of the horizontal myopseptum and that elastic confinement provided by the overlying skin is essential for effective collective migratory behavior of primordium cells.
Pick Your Poison: Benzalkonium Chloride and Copper Enable Nanocellulose Derivatives to Form Antimicrobial Properties Against a Spectrum of Microorganisms
Authors: Winans Matthew J. , Gallagher Jennifer E.G. , Jaczynski Jacek , Oporto Gloria
Published: September 2019

TEMPO nanofibrillated cellulose (TNFC), nanofibrillated cellulose (NFC), carboxymethyl cellulose (CMC), and lignin were used as templates for the addition of two well-known antimicrobial substances, benzalkonium chloride (BZK) and copper. The resulting hybrid of cellulose and antimicrobial materials were analyzed for biocidal activity in three separate products. Assays of the nanocellulose-antimicrobials were assayed for viability againstEscherichia coliin suspension, againstSaccharomyces cerevisiaeon PVA plastic, and againstbacillus lincheniformisin paper additives. Instant biocidal activity was achieved with a minimal inhibitory concentration of 0.116 M BZK-TNFC hybrid suspension. BZK-Lignin and BZK-CMC suspensions demonstrated increased antimicrobial activity with longer exposure times during a 24-hour exposure which completely inhibited the bacteria. BZK was slowly released into the suspension, a desirable trait for long-term antimicrobial activity. PVA plastic incorporated with BZK/Cu-nanocellulose scaffolds created solid films that completely inhibited yeast growth by 270 seconds. Interestingly, lignin-BZK PVA films counteracted each other and showed no biocidal activity at all. The multiple combinations of nanocellulose and biocidal agents in the surface viability assay demonstrates the importance of synergy between both components in designing nanocellulose antimicrobials. TNFC-Cu was more suited to inhibit growth in paper than NFC-Cu as seen in a zone of inhibition assay. The most potent biocidal material in PVA was NFC-BZK. Here we show the diversity of the cellulosic derivatives and their impact on the antimicrobial additive. We employed a variety of assays to assess to biocidal of these nanoparticles against three species of bacteria and yeast relevant to food packaging and medical fields. From our study, there are many factors that play a role in the design of antimicrobial materials; cellulose derivative scaffold, antimicrobial agent, type of final material in which to be incorporated, target organism, and duration of application.
Single-cell analyses identify tobacco smoke exposure-associated, dysfunctional CD16+ CD8 T cells with high cytolytic potential in peripheral blood
Authors: Martos Suzanne N. , Campbell Michelle R. , Lozoya Oswaldo A. , Bennett Brian D. , Thompson Isabel J.B. , Wan Ma , Pittman Gary S. , Bell Douglas A.
Published: September 2019

Tobacco smoke exposure has been found to impact immune response, leukocyte subtypes, DNA methylation, and gene expression in human whole blood. Analysis with single cell technologies will resolve smoking associated (sub)population compositions, gene expression differences, and identification of rare subtypes masked by bulk fraction data. To characterize smoking-related gene expression changes in primary immune cells, we performed single-cell RNA sequencing (scRNAseq) on >45,000 human peripheral blood mononuclear cells (PBMCs) from smokers (n=4) and nonsmokers (n=4). Major cell type population frequencies showed strong correlation between scRNAseq and mass cytometry. Transcriptomes revealed an altered subpopulation of Natural Killer (NK)-like T lymphocytes in smokers, which expressed elevated levels of FCGR3A (gene encoding CD16) compared to other CD8 T cell subpopulations. Relatively rare in nonsmokers (median: 1.8%), the transcriptionally unique subset of CD8 T cells comprised 7.3% of PBMCs in smokers. Mass cytometry confirmed a significant increase (p = 0.03) in the frequency of CD16+ CD8 T cells in smokers. The majority of CD16+ CD8 T cells were CD45RA positive, indicating an effector memory re-expressing CD45RA T cell (TEMRA) phenotype. We expect that cigarette smoke alters CD8 T cell composition by shifting CD8 T cells toward differentiated functional states. Pseudotemporal ordering of CD8 T cell clusters revealed that smokers’ cells were biased toward later pseudotimes, and characterization of established markers in CD8 T cell subsets indicates a higher frequency of terminally differentiated cells in smokers than in nonsmokers, which corresponded with a lower frequency in naïve CD8 T cells. Consistent with an end-stage TEMRA phenotype, FCGR3A-expressing CD8 T cells were inferred as the most differentiated cluster by pseudotime analysis and expressed markers linked to senescence. Examination of differentially expressed genes in other PBMCs uncovered additional senescence-associated genes in CD4 T cells, NKT cells, NK cells, and monocytes. We also observed elevated Tregs, inducers of T cell senescence, in smokers. Taken together, our results suggest smoking-induced, senescence-associated immune cell dysregulation contributes to smoking-mediated pathologies.
Optimization of interferential stimulation of the human brain with electrode arrays
Authors: Huang Yu , Datta Abhishek , Parra Lucas C.
Published: September 2019

Objective

Interferential stimulation (IFS) has generated considerable interest recently because of its potential to achieve focal electric fields in deep brain areas with transcranial currents. Conventionally, IFS applies sinusoidal currents through two electrode pairs with close-by frequencies. Here we propose to use an array of electrodes instead of just two electrode pairs; and to use algorithmic optimization to identify the currents required at each electrode to target a desired location in the brain.

Approach

We formulate rigorous optimization criteria for IFS to achieve either maximal modulation-depth or maximally focal stimulation. We find the solution for optimal modulation-depth analytically and maximize for focal stimulation numerically.

Main results

Maximal modulation is achieved when IFS equals conventional high-definition multi-electrode transcranial electrical stimulation (HD-TES) with a modulated current source. This optimal solution can be found directly from a current-flow model, i.e. the “lead field” without the need for algorithmic optimization. Once currents are optimized numerically to achieve optimal focal stimulation, we find that IFS can indeed be more focal than conventional HD-TES, both at the cortical surface and deep in the brain. Generally, however, stimulation intensity of IFS is weak and the locus of highest intensity does not match the locus of highest modulation.

Significance

This proof-of-principle study shows the potential of IFS over HD-TES for focal non-invasive deep brain stimulation. Future work will be needed to improve on intensity of stimulation and convergence of the optimization procedure.
MapCaller – An integrated and efficient tool for short-read mapping and variant calling using high-throughput sequenced data
Authors: Lin Hsin-Nan , Hsu Wen-Lian
Published: September 2019

With the advance of next-generation sequencing (NGS) technologies, more and more medical and biological researches adopt NGS technologies to characterize the genetic variations between individuals. The identification of personal genome variants using NGS technology is a critical factor for the success of clinical genomics studies. It requires an accurate and consistent analysis procedure to distinguish functional or disease-associated variants from false discoveries due to sequencing errors or misalignments. In this study, we integrate the algorithms for read mapping and variant calling to develop an efficient and versatile NGS analysis tool, called MapCaller. It not only maps every short read onto a reference genome, but it also detects single nucleotide variants, indels, inversions and translocations at the same time. We evaluate the performance of MapCaller with existing variant calling pipelines using three simulated datasets and four real datasets. The result shows that MapCaller can identify variants accurately. Moreover, MapCaller runs much faster than existing methods. It is available at https://github.com/hsinnan75/MapCaller.
Tissue-ABPP enables high-resolution confocal fluorescence imaging of serine hydrolase activity in cryosections – Application to glioma brain unveils activity hotspots originating from tumor-associated neutrophils
Authors: Aaltonen Niina , Singha Prosanta K. , Jakupović Hermina , Wirth Thomas , Samaranayake Haritha , Pasonen-Seppänen Sanna , Rilla Kirsi , Varjosalo Markku , Edgington-Mitchell Laura E. , Kasperkiewicz Paulina , Drag Marcin , Kälvälä Sara , Moisio Eemeli , Savinainen Juha R. , Laitinen Jarmo T.
Published: September 2019

Serine hydrolases (SHs) are a functionally diverse family of enzymes playing pivotal roles in health and disease and have emerged as important therapeutic targets in many clinical conditions. Activity-based protein profiling (ABPP) using fluorophosphonate (FP) probes has been a powerful chemoproteomic approach in studies unveiling roles of SHs in various biological systems. The ABPP approach utilizes cell/tissue proteomes and features the FP warhead, linked to a fluorescent reporter for in-gel fluorescence imaging or a biotin tag for streptavidin enrichment and LC-MS/MS-based target identification. Here, we advance the ABPP methodology to glioma brain cryosections, enabling high-resolution confocal fluorescence imaging of SH activity in different cell types of the tumor microenvironment, identified by using extensive immunohistochemistry on activity probe labeled sections. We name this technique tissue-ABPP to distinguish it from conventional gel-based ABPP. We show heightened SH activity in glioma vs. normal brain and unveil activity hotspots originating from tumor-associated neutrophils. Thorough optimization and validation is provided by parallel gel-based ABPP combined with LC-MS/MS-based target verification. Tissue-ABPP enables a wide range of applications for confocal imaging of SH activity in any type of tissue or animal species.
Lens Transmittance Shapes UV Sensitivity in the Eyes of Frogs from Diverse Ecological and Phylogenetic Backgrounds
Authors: Yovanovich Carola A. M. , Pierotti Michele E. R. , Kelber Almut , Jorgewich-Cohen Gabriel , Ibáñez Roberto , Grant Taran
Published: September 2019

The amount of short wavelength (UV, violet and blue) light that reaches the retina depends on the transmittance properties of the ocular media, especially the lens, and varies greatly across species in all vertebrate groups studied previously. We measured the lens transmittance in 32 anuran amphibians with different habits, geographic distributions, and phylogenetic positions and used them together with eye size and pupil shape to evaluate the relationship with diel activity pattern, elevation and latitude. We found an unusually high lens UV transmittance in the most basal species, and a range that extends into the visible spectrum for the rest of the sample, with lenses even absorbing violet light in some diurnal species. However, other diurnal frogs had lenses that transmit UV light like the nocturnal species. This unclear pattern in the segregation of ocular media transmittance and diel activity is shared with other vertebrates and is consistent with the absence of significant correlations in our statistical analyses. Although we did not detect a significant phylogenetic effect, closely related species tend to have similar transmittances, irrespective of whether they share the same diel pattern or not, suggesting that ocular media transmittance properties might be related to phylogeny.
Acute toxicity of the plant volatile indole depends on herbivore specialization
Authors: Maurya Abhinav K. , Patel Rakhi C. , Frost Christopher J.
Published: September 2019

Herbivore-induced plant volatiles (HIPVs) provide direct benefits to plants as antimicrobials and herbivore repellents, but their potential as direct toxins to herbivores is unclear. Here we assayed the larvicidal activity of six common HIPVs from three different biochemical pathways and tested the hypothesis that the larvicidal activity of HIPVs is related to the host specialization of the insect pest. We first assessed β-caryophyllene, linalool, z-3-hexenyl acetate, z-3-hexenol, e-2-hexenol, and indole against the beet armyworm (Spodoptera exigua), and found that indole was 7-fold more toxic compared to the other volatiles when incorporated into diet. Then, we tested the larvicidal activity of indole against six common, destructive pest caterpillars with varying host ranges. Consistent with our hypothesis, indole toxicity varied with caterpillar host range: indole toxicity was seven-fold higher in more specialized insect species relative to generalist insect species. That said, the LC50 of indole was comparable to other reported anti-herbivore agents even against the generalist caterpillars. Yet, indole in headspace had neither larvicidal nor ovicidal activity on any caterpillar species tested. These results support a key ecological precept regarding tradeoffs between host specialization and chemical detoxification, and also indicate that indole functions as a direct defense against herbivores that could be potentially useful in integrated pest management strategies.

Key message

We measured the direct toxicity of six common HIPVs against the beet armyworm.

Indole was the most toxic HIPV against the beet armyworm.

We determined the toxicity of indole against six different pest caterpillar species.

Toxicity of indole was associated with the host preference of the insect species.

Indole exposure in headspace had no effect on egg hatching or caterpillar survival.

Indole has the potential to be developed as an insecticide against crop pests.

Author Contribution Statement

CJF and AKM designed research. AKM and RCP conducted experiments. AKM and CJF analyzed data and wrote the manuscript. All authors read and approved the manuscript.
Effect of interictal epileptiform discharges on EEG-based functional connectivity networks
Authors: Hu Derek K. , Shrey Daniel W. , Lopour Beth A.
Published: September 2019

Objective

Functional connectivity networks (FCNs) based on interictal electroencephalography (EEG) can identify pathological brain networks associated with epilepsy. FCNs are altered by interictal epileptiform discharges (IEDs), but it is unknown whether this is due to the morphology of the IED or the underlying pathological activity. Therefore, we characterized the impact of IEDs on the FCN through simulations and EEG analysis.

Methods

We introduced simulated IEDs to sleep EEG recordings of eight healthy controls and analyzed the effect of IED amplitude and rate on the FCN. We then generated FCNs based on epochs with and without IEDs and compared them to the analogous FCNs from eight subjects with infantile spasms (IS), based on 1,340 visually marked IEDs. Differences in network structure and strength were assessed.

Results

IEDs in IS subjects caused increased connectivity strength but no change in network structure. In controls, simulated IEDs with physiological amplitudes and rates did not alter network strength or structure.

Conclusions

Increases in connectivity strength in IS subjects are not artifacts caused by the interictal spike waveform and may be related to the underlying pathophysiology of IS.

Significance

Dynamic changes in EEG-based FCNs during IEDs may be valuable for identification of pathological networks associated with epilepsy.

Highlights

Infantile spasms subjects exhibit broadly increased connectivity strength during interictal spikes

Functional connectivity network structure is unaltered by interictal spikes in infantile spasms

Simulated spikes in healthy control EEG did not alter network strength or structure
Interhemispheric gamma synchrony between parvalbumin interneurons supports behavioral adaptation
Authors: Cho Kathleen K.A. , Davidson Thomas J. , Marshall Jesse D. , Schnitzer Mark J. , Sohal Vikaas S.
Published: September 2019

Organisms must learn novel strategies to adapt to changing environments. Synchrony, which enhances neuronal communication, might create dynamic brain states, facilitating such adaptation. Although synchronization is common in neural systems, its functional significance remains controversial. We studied the role of gamma-frequency (~40 Hz) synchronization, promoted by parvalbumin interneurons, in mice learning multiple new cue-reward associations. Voltage imaging revealed cell type-specific increases of interhemispheric gamma synchrony within prefrontal parvalbumin interneurons, when mice received feedback that previously-learned associations were no longer valid. Disrupting this synchronization by delivering out-of-phase optogenetic stimulation caused mice to perseverate on outdated associations, an effect not reproduced by stimulating in-phase or out-of-phase at other frequencies. Gamma synchrony was specifically required when new associations utilized familiar cues that were previously irrelevant to behavioral outcomes, not when associations involved novel cues, or for reversing previously learned associations. Thus, gamma synchrony is indispensable for reappraising the behavioral salience of external cues.
Electrostatics and Solvation: Essential Determinants of Chromatin Compaction
Authors: Bendandi A. , Dante S. , Rehana Zia S. , Diaspro A. , Rocchia W.
Published: September 2019

Chromatin compaction is a process of fundamental importance in Biology, as it greatly influences cellular function and gene expression. The dynamics of compaction is determined by the interactions between DNA and histones, which are mainly mechanical and electrostatic. The high charge of DNA makes electrostatics extremely important for chromatin topology and dynamics. Besides their mechanical and steric role in the chromatin fibre, linker DNA length and linker histone presence and binding position also bear great electrostatic consequences. Electrostatics in chromatin is also indirectly linked to the DNA sequence: the presence of high-curvature AT-rich segments in DNA can cause conformational variations with electrostatic repercussions, attesting to the fact that the role of DNA is both structural and electrostatic. Electrostatics in this system has been analysed by extensively examining at the computational level the repercussions of varying ionic concentration, using all-atom, coarse-grained, and continuum models. There have been some tentative attempts to describe the force fields governing chromatin conformational changes and the energy landscapes of these transitions, but the intricacy of the system has hampered reaching a consensus. Chromatin compaction is a very complex issue, depending on many factors and spanning orders of magnitude in space and time in its dynamics. Therefore, comparison and complementation of theoretical models with experimental results is fundamental. Here, we present existing approaches to analyse electrostatics in chromatin and the different points of view from which this issue is treated. We pay particular attention to solvation, often overlooked in chromatin studies. We also present some numerical results on the solvation of nucleosome core particles. We discuss experimental techniques that have been combined with computational approaches and present some related experimental data such as the Z-potential of nucleosomes at varying ionic concentrations. Finally, we discuss how these observations support the importance of electrostatics and solvation in chromatin models.

SIGNIFICANCE

This work explores the determinants of chromatin compaction, focusing on the importance of electrostatic interactions and solvation. Chromatin compaction is an intrinsically multiscale issue, since processes concerning chromatin occur on a wide range of spatial and temporal scales. Since DNA is a highly charged macromolecule, electrostatic interactions are extremely significant for chromatin compaction, an effect examined in this work from many angles, such as the importance of ionic concentration and different ionic types, DNA-protein interactions, and solvation. Solvation is often overlooked in chromatin studies, especially in coarse-grained models, where the nucleosome core, the building block of the chromatin fibre, is represented as a rigid body, even though it has been observed that solvation influences chromatin even at the base-pair level.
Crystal structure and Hirshfeld surface analysis of 2-[(1,3-benzoxazol-2-yl)sulfanyl]-N-(2-methoxyphenyl)acetamide
Authors: Aydin Abdullah , Celikesir Sevim Turktekin , Akkurt Mehmet , Saylam Merve , Pabuccuoglu Varol
Published: September 2019

In the title compound, C16H14N2O3S, the 1,3-benzoxazole ring system is essentially planar (r.m.s deviation = 0.004 Å) and makes a dihedral angle of 66.16 (17)° with the benzene ring of the methoxyphenyl group. Two intramolecular N—H...O and N—H...N hydrogen bonds occur, forming S(5) and S(7) ring motifs, respectively. In the crystal, pairs of C—H...O hydrogen bonds link the molecules into inversion dimers with R
2
2(14) ring motifs, stacked along the b-axis direction. The inversion dimers are linked by C—H...π and π–π-stacking interactions [centroid-to-centroid distances = 3.631 (2) and 3.631 (2) Å], forming a three-dimensional network. Two-dimensional fingerprint plots associated with the Hirshfeld surface show that the largest contributions to the crystal packing come from H...H (39.3%), C...H/H...C (18.0%), O...H/H...O (15.6) and S...H/H...S (10.2%) interactions.
Methodology for the preparation of rescue plans – a Polish case study
Authors: Kunikowski Grzegorz , Kosieradzka Anna , Kąkol Urszula
Published: September 2019

Purpose

The purpose of this paper is to present a proposal for the methodology of developing rescue plans and the concepts of applying recommended response schedules in the context of the State Fire Service’s planning responsibilities (preparation) and public administration (reconciliation and approval), according to the legal order in force in Poland. In the proposed concept, recommended schedules are built on the basis of the matches and successes identified according to the criteria, i.e. the best carried out rescue actions from the register of reports.

Design/methodology/approach

The paper is based on the analysis of existing legal status and policy in Poland as well as the selected relevant academic literature.

Findings

The result is the formulation of a methodology for drawing up the rescue plans to the extent required by law and proposing a concept for the method of developing and applying recommended response schedules, supporting operational planning and conducting rescue operations.

Practical implications

The proposed methodology is to support the procedure of drawing up rescue plans by implying and implementing them into IT solutions. The suggested recommended response schedules, based on observations and conclusions from the analysis of the past rescue operations, may present circumstances and sequences of the use of forces and measures that have had beneficial effects in the past. An in-depth analysis of historical data from the conducted rescue operations may also be used to determine time indicators for the response phase.

Originality/value

The proposed solutions complement the methods currently used by public administration in Poland. The concept can also be inspiring for the State Fire Service (PSP) which has its own analytical tools in the form of a decision support system and registers of rescue operations carried out. The PSP may undertake the practical verification of the presented methodology for preparing rescue plans and recommended response schedules.
Transcending the threshold limitation: a fifth industrial revolution?
Authors: Callaghan Chris William
Published: September 2019

Purpose

The purpose of this paper is to present the argument that there exists a threshold limitation to new knowledge creation, associated with a global productivity growth slowdown, a global decline in research and development (R&D) productivity and a decline in the growth of globalisation.

Design/methodology/approach

Taking the form of a conceptual paper, this paper seeks to advance the polemic that despite discussions of a ‘fourth industrial revolution,’ there has been no substantive change in a global decline in productivity growth, particularly in developed countries. Specific threats are identified and related to the consequences of technological proliferation in the absence of an effective research response to address them. Certain theoretical propositions are derived, with the suggestion that novel theory promises a ‘fifth industrial revolution,’ one that might ultimately reverse the downward trend in global productivity growth.

Findings

Drawing on management theory, derivation of the theoretical propositions suggests the existence of a mechanism related to research productivity enhancement. Discussions suggest that this mechanism might ultimately explain how the R&D productivity decline, evident since the 1970s, may ultimately be reversed.

Originality/value

The paper seeks to provoke novel thinking about the consequences of a failure to develop a research agenda explicitly focused on the attainment of economies of scale in the research process itself.
The impact of financial regulation policy uncertainty on bank profits and risk
Authors: Killins Robert Neil , Johnk David W. , Egly Peter V.
Published: September 2019

Purpose

The purpose of this paper is to explore the impact of financial regulation policy uncertainty (FRPU) on bank profit and risk.

Design/methodology/approach

This study applies dynamic panel techniques and uses the Baker et al. (2016) FRPU index and macroeconomic variables to assess FRPU’s impact on bank profit and risk using Federal Deposit Insurance Corporation call reports from Q1 2000 to Q4 2016 for over 4,760 commercial banks.

Findings

The effect of FRPU on profitability (Return on Assets [ROA] and Return on Equity [ROE]) and risk (standard deviation of ROA and ROE) produces complex results. FRPU negatively (positively) impacts profits for small and large banks (money center banks). There is a positive impact on FRPU for small and medium-sized banks, with no impact reported for the large and money center banks.

Practical implications

Findings lead to several implications for financial services regulators, investors and executives as summarized in the conclusion. It is essential to ensure that clear communication channels are open especially to small and medium-sized banks for proper strategic planning, given their greater sensitivity to regulatory uncertainty.

Originality/value

This paper contributes to the literature as follows. First, it explores the impact of FRPU on bank profits and risk using a novel index introduced by Baker et al. (2016). This news-based continuous measure presents a bank profit modeling approach that differs from traditional event study methodology. Second, a large sample of US commercial banks is used which represents an important departure from banking regulation studies.
Nonconformity and socialism: the case of J. G. Greenhough, 1880–1914
Authors: Ryan Liam
Published: September 2019

This article examines the life, thought and activism of the prominent Baptist minister John Gershom Greenhough. Existing scholarly and popular narratives generally focus on the key role played by Nonconformity in nurturing the labour movement in late Victorian and Edwardian Britain. Using Greenhough as a case study this article posits an alternative interpretation of this relationship, contending that the individualistic religious culture of Nonconformity was often deeply hostile to socialism. This hostility motivated Greenhough, and others like him, to abandon their historical allegiance to the Liberal party in the early twentieth century in favour of the Conservatives. More broadly, this article investigates the process of political and ideological conversion and challenges dominant historical readings that characterize anti-socialism as being synonymous with middle-class economic self-interest.
The earls of Edward III and the polity: the earls of Arundel and Northampton in the localities, 1330–60
Authors: Raven Matt
Published: September 2019

This article examines the retinues of two English earls from 1330–60 to ascertain the extent and nature of their local influence, within a wider context of military activity and the changing form of local government and peacekeeping. It demonstrates that the followers of the earl of Northampton in Essex were recruited largely for military purposes but that those of the earl of Arundel in Sussex enjoyed a substantial degree of influence over local government. Ultimately, this article argues that comital influence in local government was imposed by Edward III as part of the growth of government through the mid fourteenth century.