bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Application of Nerve Injury Unit Mode in Patients with Moderate or Severe Traumatic Brain Injury
Authors: Zhou Bin , Dong Baizhuo , Fu Haitao , Yang Xiaolong , Sun Zhigang , Zhao Wei , Huang Shengming , Nie Honghua , Chen Guohui
Published: September 2019

Objective:

To explore the efficacy of nerve injury unit mode and conventional management mode for the treatment of patients with moderate or severe traumatic brain injury (TBI).

Methods:

Eighty patients with TBI in our hospital from July 2016 to December 2017 were included as observation groups (Treated with injury unit mode). Eighty-three patients with TBI from January 2015 to June 2016 were included as control group (Treated with conventional management mode). The incidence of complications, satisfaction rate, Glasgow Coma Scale (GCS) scores, Barthel index (BI), National Institutes of Health Stroke Scale (NIHSS) scores and average length of hospital stay of 2 groups were compared.

Results:

Observation group achieved lower incidence of complications, higher satisfaction rate, higher GCS scores, higher GOS prognosis scores, higher BI, lower NIHSS scores, and shorter average length of hospital stay compared with control group (P < 0.05). There were no significant differences in the average hospitalization cost between 2 groups (P > 0.05).

Conclusion:

For patients with TBI, the nerve injury unit mode can reduce the incidence of complications, improve patient satisfaction rate, shorten the hospitalization time, enhance the daily living ability, improve the patient's neurological function, improve the ability to return to society and have a significant role in promoting the rehabilitation of patients.
Permanent Pancreatic Duct Occlusion With Neoprene-based Glue Injection After Pancreatoduodenectomy at High Risk of Pancreatic Fistula
Authors: Mazzaferro Vincenzo , Virdis Matteo , Sposito Carlo , Cotsoglou Christian , Droz Dit Busset Michele , Bongini Marco , Flores Maria , Prinzi Natalie , Coppa Jorgelina
Published: September 2019

Objective:

The aim of this study was to assess safety and efficacy of pancreatic duct occlusion (PDO) with neoprene-based glue in selected patients undergoing pancreatoduodenectomy (PD) at high risk of postoperative pancreatic fistula (POPF).

Background Data:

PD is the reference standard approach for tumors of the pancreaticoduodenal region. POPF is the most relevant complication after PD. PDO has been proposed as an alternative to anastomosis to manage the pancreatic stump.

Methods:

A single-center, prospective, nonrandomized trial enrolled 100 consecutive PD for cancer. Patients at high risk for POPF according to Fistula Risk Score (FRS) >15% (≥6 points) were treated with PDO using neoprene glue (study cohort); patients with FRS ≤15% (≤5 points) received pancreaticojejunal anastomosis (PJA: control cohort). Primary endpoint was complication rate grade ≥3 according to Dindo–Clavien Classification (DCC). Other postoperative outcomes were monitored (ClinicalTrials.gov NCT03738787).

Results:

Fifty-one patients underwent PDO and 49 PJA. DCC ≥3, postoperative mortality, and POPF grade B-C were 25.5% versus 24.5% (P = 0.91), 5.9% versus 2% (P = 0.62), and 11.8% versus 16.3% (P = 0.51) in the study versus control cohort, respectively. At 1 and 3 years, new-onset diabetes was diagnosed in 13.7% and 36.7% of the study cohort versu 4.2% and 12.2% in controls (P = 0.007).

Conclusions:

PDO with neoprene-based glue is a safe technique that equalizes early outcome of selected patients at high risk of POPF to those at low risk undergoing PJA. Neoprene-based PDO, however, triples the risk of diabetes at 1 and 3 years.
Chronic circadian disruption modulates breast cancer cell stemness and their immune microenvironment to drive metastasis in mice
Authors: Hadadi Eva , Taylor William , Li Xiaomei , Aslan Yetki , Villote Marthe , Rivière Julie , Duvallet Gaelle , Auriau Charlotte , Dulong Sandrine , Letron Isabelle Raymond , Provot Sylvain , Bennaceur-Griscelli Annelise , Acloque Hervé
Published: September 2019

Breast cancer is the most common type and one of the major causes of cancer death in woman worldwide. Epidemiological studies have established a link between night shift work and increased cancer risk, suggesting that circadian disruption may interfere with carcinogenesis. We aim to shed light on the effect of chronic jetlag on mammary tumour development. Therefore, we used a mouse model of spontaneous mammary tumorigenesis that we exposed to chronic circadian disruption. We observed that circadian disruption significantly increases cancer cell dissemination and metastasis. It also enhances the stemness and tumour–initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. We finally showed that all these defects can be corrected by the use of a CXCR2 inhibitor. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
In-vivo crystals reveal protein interactions
Authors: Martin Eleanor R. , Barbieri Alessandro , Ford Robert C. , Robinson Robert C.
Published: September 2019

Crystallisation of recombinant proteins has been fundamental to our understanding of protein function, dysfunction, and molecular recognition. However, this information has often been gleaned under non-physiological extremes of protein, salt, and H+ concentrations. Here, we describe the development of the robust iBox-PAK4cat system that spontaneously crystallises in several mammalian cell types. The developments described here allow the quantitation of in-vivo protein-protein interactions using a novel GFP-linked reporter system. Here, we have combined this assay with in-vitro X-ray crystallography and molecular dynamics studies characterise the molecular determinants of the interaction between NHERF1 PDZ2 and CFTR, a protein complex pertinent to the genetic disease cystic fibrosis. These studies have revealed the crystal structure of the extended PDZ domain of NHERF1, and indicated, contrary to previous reports, that residue selection at −1 and −3 PDZ-binding motif positions influence the affinity and specificity of the interaction. The results presented here demonstrate that the iBox-PAK4cat assay could easily be utilised to screen other protein-protein interactions.
Horizontal gene transfer to a defensive symbiont with a reduced genome amongst a multipartite beetle microbiome
Authors: Waterworth Samantha C. , Flórez Laura V. , Rees Evan R. , Hertweck Christian , Kaltenpoth Martin , Kwan Jason C.
Published: September 2019

The loss of functions required for independent life when living within a host gives rise to reduced genomes in obligate bacterial symbionts. Although this phenomenon can be explained by existing evolutionary models, its initiation is not well understood. Here, we describe the microbiome associated with eggs of the beetleLagria villosa, containing multiple bacterial symbionts related toBurkholderia gladioliincluding a reduced-genome symbiont thought to produce the defensive compound lagriamide. We find that the putative lagriamide producer is the only symbiont undergoing genome reduction, and that it has already lost most primary metabolism and DNA repair pathways. The horizontal acquisition of the lagriamide biosynthetic gene cluster likely preceded genome reduction, and unexpectedly we found that the symbiont accepted additional genes horizontally during genome reduction, even though it lacks the capacity for homologous recombination. These horizontal gene transfers suggest that absolute genetic isolation is not a requirement for genome reduction.
Systematic profiling of full-length immunoglobulin and T-cell receptor repertoire diversity in rhesus macaque through long read transcriptome sequencing
Authors: Brochu Hayden N. , Tseng Elizabeth , Smith Elise , Thomas Matthew J. , Jones Aiden , Diveley Kayleigh , Law Lynn , Hansen Scott G. , Picker Louis J. , Gale Michael , Peng Xinxia
Published: September 2019

The diversity of immunoglobulin (Ig) and T-cell receptor (TCR) repertoires is a focal point of immunological studies. Rhesus macaques are key for modeling human immune responses, placing critical importance on the accurate annotation and quantification of their Ig and TCR repertoires. However, due to incomplete reference resources, the coverage and accuracy of the traditional targeted amplification strategies for profiling rhesus Ig and TCR repertoires are largely unknown. Here, using long read sequencing, we sequenced four Indian-origin rhesus macaque tissues and obtained high quality, full-length sequences for over 6,000 unique Ig and TCR transcripts, without the need for sequence assembly. We constructed the first complete reference set for the constant regions of all known isotypes and chain types of rhesus Ig and TCR repertoires. We show that sequence diversity exists across the entire variable regions of rhesus Ig and TCR transcripts. Consequently, existing strategies using targeted amplification of rearranged variable regions comprised of V(D)J gene segments miss a significant fraction (27% to 53% and 42% to 49%) of rhesus Ig/TCR diversity. To overcome these limitations, we designed new rhesus-specific assays that remove the need for primers conventionally targeting variable regions and allow single cell-level Ig and TCR repertoire analysis. Our improved approach will enable future studies to fully capture rhesus Ig and TCR repertoire diversity and is applicable for improving annotations in any model organism.
CIViCpy: a Python software development and analysis toolkit for the CIViC knowledgebase
Authors: Wagner Alex H. , Kiwala Susanna , Coffman Adam C. , McMichael Joshua F. , Cotto Kelsy C. , Mooney Thomas B. , Barnell Erica K. , Krysiak Kilannin , Danos Arpad M. , Griffith Obi L. , Griffith Malachi
Published: September 2019

Purpose

Precision oncology is dependent upon the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, open-access knowledgebase, providing a structured framework for evaluating genomic variants of various types (e.g., fusions, SNVs) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented API for accessing CIViC records: Assertions, Evidence, Variants, and Genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this API, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC web application.

Methods

To address this limitation, we developed CIViCpy (civicpy.org), a software development kit (SDK) for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples.

Results

We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the AACR Project GENIE dataset. We demonstrate that CIViCpy enables annotation of >1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors.

Conclusions

The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, an SDK for downstream applications and rapid analysis. CIViCpy (civicpy.org) is fully documented, open-source, and freely available online.
Pathway engineering in yeast for synthesizing the complex polyketide bikaverin
Authors: Zhao Meng , Zhao Yu , Hu Qi , Iqbal Hala , Yao Mingdong , Liu Hong , Qiao Bin , Li Chun , Skovbjerg Christine A. S. , Nielsen Jens Christian , Nielsen Jens B. , Frandsen Rasmus J.N. , Yuan Yingjin , Boeke Jef D.
Published: September 2019

Fungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recoded, constructed and characterized the biosynthetic pathway of the formation of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We used a green fluorescent protein (GFP) tagging strategy to identify the low expression of Bik1 (polyketide synthase) as the bottleneck step in the pathway, and a promoter exchange strategy to increase expression of Bik1 and bikaverin yield. To further increase product yield, we used an enzyme-fusion strategy to couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to a dramatic improvement of Bikaverin yield of nearly 60-fold. This study demonstrates that the biosynthesis of complex polyketides biosynthesis can be established and efficiently engineered in S. cerevisiae, highlighting the great potential for natural product synthesis and large-scale fermentation in yeast.
Temporal discounting correlates with directed exploration but not with random exploration
Authors: Sadeghiyeh Hashem , Wang Siyu , Alberhasky Maxwell R. , Kyllo Hannah M. , Shenhav Amitai , Wilson Robert C.
Published: September 2019

The explore-exploit dilemma describes the trade off that occurs any time we must choose between exploring unknown options and exploiting options we know well. Implicit in this trade off is how we value future rewards — exploiting is usually better in the short term, but in the longer term the benefits of exploration can be huge. Thus, in theory there should be a tight connection between how much people value future rewards, i.e. how much they discount future rewards relative to immediate rewards, and how likely they are to explore, with less ‘temporal discounting’ associated with more exploration. By measuring individual differences in temporal discounting and correlating them with explore-exploit behavior, we tested whether this theoretical prediction holds in practice. We used the 27-item Delay-Discounting Questionnaire to estimate temporal discounting and the Horizon Task to quantify two strategies of explore-exploit behavior: directed exploration, where information drives exploration by choice, and random exploration, where behavioral variability drives exploration by chance. We find a clear correlation between temporal discounting and directed exploration, with more temporal discounting leading to less directed exploration. Conversely, we find no relationship between temporal discounting and random exploration. Unexpectedly, we find that the relationship with directed exploration appears to be driven by a correlation between temporal discounting and uncertainty seeking at short time horizons, rather than information seeking at long horizons. Taken together our results suggest a nuanced relationship between temporal discounting and explore-exploit behavior that may be mediated by multiple factors.
No evidence for immune-gene specific signals of selection in termites
Authors: Meusemann Karen , Korb Judith , Schughart Maximilian , Staubach Fabian
Published: September 2019

It has been hypothesized that selection pressure from pathogens plays an important role in shaping social evolution. Social behaviour, in particular brood care, is associated with pathogen pressure in wood-dwelling “lower” termites. Yet, generally pathogen pressure is low in wood-dwelling termite species that never leave the nest except for the mating flight. In comparison, pathogen pressure is higher in species that leave the nest to forage, and thus constantly encounter a diversity of microbes from their environment. We hypothesized that such differences in pathogen pressure are also reflected by differences in the intensity of natural selection on immune genes. We tested this hypothesis in a phylogenetic framework, analyzing rates of non-synonymous and synonymous substitutions on single-copy immune genes. Therefore, we leveraged recent genomic and transcriptomic data from eight termite species, representing wood-dwelling and foraging species as well as 14 additional species spanning the winged insects (Pterygota). Our results provide no evidence for a role of pathogen pressure in selection intensity on single-copy immune genes. Instead, we found evidence for a genome-wide pattern of relaxed selection in termites.

Life Science Identifiers (as available Zoobank)

Ephemera danica:

urn:lsid:zoobank.org:act:06633F75-4809-4BB3-BDCB-6270795368D5

Coptotermes sp.

urn:lsid:zoobank.org:pub:D6724B7F-F27A-47DC-A4FC-12859ECA0C71

Blattella germanica:

rn:lsid:zoobank.org:pub:1EA126BA-E9D2-4AA6-8202-26BA5B09B8AD

Locusta migratoria

urn:lsid:zoobank.org:pub:D792A09E-844A-412A-BFCA-5293F8388F8C

Periplaneta americana (Blatta americana):

urn:lsid:zoobank.org:act:95113A55-4C6D-4DC7-A0E5-620BACADFFE5

Apis mellifera:

urn:lsid:zoobank.org:act:9082C709-6347-4768-A0DC-27DC44400CB2

Bombyx mori (Phalæna (Bombyx) mori)

urn:lsid:zoobank.org:act:215466E3-E77F-46E9-8097-372837D7A375

Drosophila melanogaster:

urn:lsid:zoobank.org:act:5B39F0AA-270D-4AA8-B9A3-C36A3A265910
Computational reconstruction of the complete Piezo1 structure reveals a unique footprint and specific lipid interactions
Authors: Chong Jiehan , De Vecchis Dario , Hyman Adam J , Povstyan Oleksandr V , Shi Jian , Beech David J , Kalli Antreas C
Published: September 2019

Piezo1 is a critical mechanical sensor in many cells. It is activated by mechanical force thus allowing cells to sense the physical environment and respond to stress. Structural data have suggested that Piezo1 has a curved shape. Here, we use computational approaches to model, for the first time, the 3D structure of the full-length Piezo1 in an asymmetric membrane. A number of novel insights emerge: (i) Piezo1 creates a dome in the membrane with a trilobed topology that extends beyond the radius of the protein, (ii) Piezo1 changes the lipid environment in its vicinity via specific interactions with cholesterol and PIP2molecules, (iii) changes in cholesterol concentration that change the membrane stiffness result in changes in the depth of the dome created by Piezo1, and iv) modelling of the N-terminal region that is missing from current structures modifies Piezo1 membrane footprint, suggesting the importance of this region in Piezo1 function.
Microbiomes in the insectivorous bat species Mops condylurus rapidly converge in captivity
Authors: Edenborough Kathryn M , Mu Andre , Mühldorfer Kristin , Lechner Johanna , Lander Angelika , Bokelmann Marcel , Couacy-Hymann Emmanuel , Radonic Aleksandar , Kurth Andreas
Published: September 2019

Bats are well known reservoir hosts for RNA and DNA viruses. The use of captive bats in research has intensified over the past decade as researchers aim to examine the virus-reservoir host interface. In this study, we investigated the effects of captivity on the fecal bacterial microbiome of an insectivorous microbat, Mops condylurus, a bat species that roosts in close proximity to humans and has likely transmitted viral infections to humans. Using amplicon 16S rRNA gene sequencing, we characterized changes in fecal bacterial community composition for individual bats directly at the time of capture and again after six weeks in captivity. We found that microbial community richness by measure of the number of observed operational taxonomic units (OTUs) in bat feces does increase significantly in captivity. Importantly, we found the similarity of microbial community structures of fecal microbiomes between different bats to converge during captivity. We propose a six week-acclimatization period prior to carrying out infection studies or other research influenced by the microbiome composition, which may be advantageous to reduce variation in microbiome composition and minimize biological variation inherent to in vivo experimental studies.
KV1.2 channels inactivate through a mechanism similar to C-type inactivation
Authors: Suárez-Delgado Esteban , Rangel-Sandín Teriws G. , Ishida Itzel G. , Rangel-Yescas Gisela E. , Rosenbaum Tamara , Islas León D.
Published: September 2019

C-type inactivation has been described in multiple voltage-gated K+ channels and in great detail in the Drosophila Shaker channel. As channels have moved into the structural era, atomic details of this and other gating mechanisms have started to be better understood. To date, the only voltage-gated channels whose structure has been solved are KvAP (X-ray diffraction), the KV1.2- KV2.1 “paddle” chimera (X-ray diffraction), KV1.2 (Cryo-EM); and ether-á-go-go (Cryo-EM) (Wang and MacKinnon, 2017), however, the characteristics and mechanisms of slow inactivation in these channels are unknown or poorly characterized. Here we present a detailed study of slow inactivation in the rat KV1.2 and show that it has some properties consistent with the C-type inactivation described in Shaker. We also study the effects of some mutations that are known to modulate C-type inactivation in Shaker and show that qualitative and quantitative differences exist in their functional effects, possibly underscoring subtle but important structural differences between the C-inactivated states in Shaker and KV1.2.
Human Rotavirus Diarrhea Is Associated with Altered Trafficking and Expression of Apical Membrane Transport Proteins
Authors: Zachos Nicholas C. , Baetz Nicholas W. , Gupta Akshita , Kapoor Anirudh , Cole Robert N. , Verkman Alan S. , Turner Jerrold R. , Estes Mary K. , Donowtiz Mark
Published: September 2019

Background

Rotavirus (RV) is the 5th leading cause of death in children <5 years old but the leading cause of diarrhea related deaths in this age group. The mechanism of RV diarrhea involves decreased activity of Na+-dependent solute transporters with increased luminal secretion of Cl- in the absence of significant histologic damage. While our understanding of RV diarrhea has come from studies in animal models and cancer cell lines, the mechanism of the diarrhea and the transport proteins affected in human RV disease remains only partially understood. This understanding is likely to impact drug development therapy for RV diarrhea.

Methods

Formalin-fixed paraffin-embedded small intestinal specimens from patients diagnosed with RV diarrhea (confirmed by anti-RV antibodies) were analyzed by immunofluorescence for changes in apical/basolateral ion/nutrient transporters/channels as well as tight junctional and cytoskeletal proteins. Proximal small intestinal enteroids generated from biopsies obtained from healthy human subjects were grown as monolayers, differentiated to resemble villus epithelial cells, and infected with human RV.

Results

RV diarrhea was associated with reduced expression and intracellular localization of transport proteins normally found in the brush border membranes, including SGLT1, NHE3, NHE2, the Na+-dependent amino acid transporter SLC6A19, and CFTR. In contrast, basolateral proteins, including Na+/K+-ATPase, NKCC1, and β-catenin, the brush border marker ezrin, as well as the tight junction protein, ZO-1, were expressed and localized normally. RV-induced mislocalization of NHE3, SGLT1, SLC6A19 and CFTR was also seen when human small intestinal enteroids were infected with RV.

Conclusions

These data demonstrate a new pathophysiologic mechanism of acute diarrhea in which expression of multiple apical transport proteins are reduced. This acute diarrhea is likely to be caused by an effect on a common apical trafficking pathway, as exemplified by RV diarrhea, and its contribution to other enteric pathogen-induced diarrheal diseases should be determined.
Persistent transcriptional programs are associated with remote memory in diverse cells of the medial prefrontal cortex
Authors: Chen Michelle B. , Jiang Xian , Quake Stephen R. , Südhof Thomas C.
Published: September 2019

It is thought that memory is stored in ‘engrams’, a subset of neurons that undergo learning-induced alterations. The role of gene-expression during learning and short-term memory has been studied extensively, but little is known about remote memory that can persist for a lifetime. Using long-term contextual fear memory as a paradigm, an activity-dependent transgenic model for engram-specific labeling, and single-cell transcriptomics we probed the gene-expression landscape underlying remote memory consolidation and recall in the medial prefrontal cortex. Remarkably, we find sustained activity-specific transcriptional alterations in diverse populations of neurons that persist even weeks after fear-learning and are distinct from those previously identified in learning. Out of a vast plasticity-coding space, we uncover select membrane-fusion genes that could play important roles in maintaining remote memory traces. Unexpectedly, astrocytes and microglia also acquire new persistent gene signatures upon recall of remote memory, suggesting that they actively contribute to memory circuits. Our discovery of novel distinct gene-expression programs involved in long term memory adds an important dimension of activity-dependent cellular states to existing brain taxonomy atlases and sheds light on the elusive mechanisms of remote memory storage.
Rv3722c governs aspartate-dependent nitrogen metabolism inMycobacterium tuberculosis
Authors: Jansen Robert , Mandyoli Lungelo , Hughes Ryan , Wakabayashi Shoko , Pinkham Jessica , Selbach Bruna , Guinn Kristine , Rubin Eric , Sacchettini James , Rhee Kyu
Published: September 2019

Organisms are defined by their genomes, yet many distinguishing features of a given organism are encoded by genes that are functionally unannotated.Mycobacterium tuberculosis(Mtb), the leading cause of death due to a single microbe, co-evolved with humans as its only known natural reservoir, yet the factors mediatingMtb’spathogenicity remain incompletely defined.rv3722cis a gene of unknown function predicted to encode a pyridoxal phosphate binding protein and to be essential forin vitrogrowth ofMtb. Using metabolomic, genetic and structural approaches, we show that Rv3722c is the primary aspartate aminotransferase ofMtband mediates an essential but underrecognized role in metabolism: nitrogen distribution. Together with the attenuation of Rv3722c-deficientMtbin macrophages and mice, these results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets inMtb.
Establishment and characterization of a cell line and patient-derived xenograft (PDX) from peritoneal metastasis of low-grade serous ovarian carcinoma
Authors: De Thaye Elien , Van de Vijver Koen , Van der Meulen Joni , Taminau Joachim , Wagemans Glenn , Denys Hannelore , Van Dorpe Jo , Berx Geert , Ceelen Wim , Van Bocxlaer Jan , De Wever Olivier
Published: September 2019

Peritoneal spread indicates poor prognosis in patients with serous ovarian carcinoma (SOC) and is generally treated by surgical cytoreduction and chemotherapy. Novel treatment options are urgently needed to improve patient outcome. Clinically relevant cell lines and patient-derived xenograft (PDX) models are of critical importance to therapeutic regimen evaluation. Here, a PDX model was established by orthotopic engraftment, subperitoneal tumor slurry injection, of low-grade SOC resulting in an early-stage transplantable peritoneal metastasis (PM)-PDX model. Histology confirmed the micropapillary and cribriform growth pattern with intraluminal tumor budding and positivity for PAX8 and WT1. PM-PDX dissociated cells show an epithelial morphotype with a 42h doubling time and 40% colony forming efficiency, they are insensitive to estrogen signaling, low sensitive to platinum derivatives and highly sensitive to paclitaxel (IC50: 6.3 ± 2.2 nM, mean ± SE). The patient primary tumor, PM, PM-PDX and derived cell line all show aKRASc.35G>T (p.(Gly12Val)) mutation and show sensitivity to the MEK inhibitor trametinib in vitro (IC50: 7.2 ± 0.5 nM, mean ± SE) and in the PM mouse model. These preclinical models closely reflecting patient tumors are useful to further elucidate LGSOC disease progression, therapy response and resistance mechanisms.
Defined extracellular ionic solutions to study and manipulate the cellular resting membrane potential
Authors: Bonzanni Mattia , Payne Samantha L. , Adelfio Myriam , Kaplan David L. , Levin Michael , Oudin Madeleine J.
Published: September 2019

All cells possess an electric potential across their plasma membranes. While familiar in the context of excitable cells such as neurons, healthy non-excitable cells are also able to generate and receive bioelectric signals. The cellular resting membrane potential (RMP) regulates many factors in cell homeostasis, such as cell proliferation, differentiation and apoptosis. It is therefore critical to develop simple strategies to measure, manipulate and characterize this feature. Current studies to evaluate RMP rely on the patch clamp approach, which is technically challenging, low-throughput and not widely available to the scientific community. Here, we present a relatively simple methodology to functionally study the role of RMP in non-excitable cells by modulating it pharmacologically, and using a voltage-sensitive dye to characterize the contribution of individual ions to the RMP. Specifically, we define protocols for using extracellular solutions in which permeable ions (Na+, Cl− and K+) are substituted with non-permeable ions (N-Methyl-D-glucamine (NMDG), gluconate, choline, SO42−) to study and manipulate RMP in vitro. The resulting RMP modifications were assessed with both patch clamp and a voltage sensitive dye. Using an epithelial and cancer cell line, we demonstrate that the proposed ionic solutions can determine the relative contribution of ionic species in setting the RMP and be used to actively and selectively modify the RMP. The proposed method is simple and reproducible and will make the study of bioelectricity more readily available to the cell biology community by enabling functional modulation of RMP in most cellular assays.

Author Disclosure Statements

No competing financial interests exist.
The crystal structures and Hirshfeld surface analysis of 6-(naphthalen-1-yl)-6a-nitro-6,6a,6b,7,9,11a-hexahydrospiro[chromeno[3′,4′:3,4]pyrrolo[1,2-c]thiazole-11,11′-indeno[1,2-b]quinoxaline] and 6′-(naphthalen-1-yl)-6a′-nitro-6′,6a′,6b′,7′,8′,9′,10′,12a′-octahydro-2H-spiro[acenaphthylene-1,12′-chromeno[3,4-a]indolizin]-2-one
Authors: Foize Ahmad G. , Syed Mohammed Mujaheer A. , NizamMohideen M. , Gulam Mohamed M. , Viswanathan V.
Published: September 2019

The title compounds, 6-(naphthalen-1-yl)-6a-nitro-6,6a,6 b,7,9,11a-hexahydrospiro[chromeno[3′,4′:3,4]pyrrolo[1,2-c]thiazole-11,11′-indeno[1,2-b]quinoxaline], C37H26N4O3S, (I), and 6′-(naphthalen-1-yl)-6a′-nitro-6′,6a′,6b′,7′,8′,9′,10′,12a′-octahydro-2H-spiro[acenaphthylene-1,12′-chromeno[3,4-a]indolizin]-2-one, C36H28N2O4, (II), are new spiro derivatives, in which both the pyrrolidine rings adopt twisted conformations. In (I), the five-membered thiazole ring adopts an envelope conformation, while the eight-membered pyrrolidine-thiazole ring adopts a boat conformation. An intramolecular C—H...N hydrogen bond occurs, involving a C atom of the pyran ring and an N atom of the pyrazine ring. In (II), the six-membered piperidine ring adopts a chair conformation. An intramolecular C—H...O hydrogen bond occurs, involving a C atom of the pyrrolidine ring and the keto O atom. For both compounds, the crystal structure is stabilized by intermolecular C—H...O hydrogen bonds. In (I), the C—H...O hydrogen bonds link adjacent molecules, forming R
2
2(16) loops propagating along the b-axis direction, while in (II) they form zigzag chains along the b-axis direction. In both compounds, C—H...π interactions help to consolidate the structure, but no significant π–π interactions with centroid–centroid distances of less than 4 Å are observed.
Crystal structure of tetrakis(tetrahydrofuran-κO)bis(trifluoromethanesulfonato-κO)iron(II)
Authors: Riemersma Charl F. , Monkcom Emily C. , Klein Gebbink Robertus J. M. , Lutz Martin
Published: September 2019

The title compound, [Fe(CF3SO3)2(C4H8O)4], is octahedral with two trifluoromethanesulfonate ligands in trans positions and four tetrahydrofurane molecules in the equatorial plane. By the conformation of the ligands the complex is chiral in the crystal packing. The compound crystallizes in the Sohncke space group P212121 and is enantiomerically pure. The packing of the molecules is determined by weak C—H...O hydrogen bonds. The crystal studied was refined as a two-component inversion twin.
1,1′,3,3′-Tetramesitylquinobis(imidazole)-2,2′-dithione
Authors: Selvakumar Jayaraman , Arumugam Kuppuswamy
Published: September 2019

The solid-state structural analysis of the title compound [systematic name: 5,11-disulfanylidene-4,6,10,12-tetrakis(2,4,6-trimethylphenyl)-4,6,10,12-tetraazatricyclo[7.3.0.03,7]dodeca-1(9),3(7)-diene-2,8-dione], C44H44N4O2S2 [+solvent], reveals that the molecule crystallizes in a highly symmetric cubic space group so that one quarter of the molecule is crystallographically unique, the molecule lying on special positions (two mirror planes, two twofold axes and a center of inversion). The crystal structure exhibits large cavities of 193 Å3 accounting for 7.3% of the total unit-cell volume. These cavities contain residual density peaks but it was not possible to unambiguously identify the solvent therein. The contribution of the disordered solvent molecules to the scattering was removed using a solvent mask and is not included in the reported molecular weight. No classical hydrogen bonds are observed between the main molecules.
Post-regulation effect on factors driving environmental disclosures among Chinese listed firms
Authors: Yekini Kemi , Adelopo Ismail , Wang Yan , Song Surong
Published: September 2019

Purpose

The purpose of this study is to re-examine the factors that affect the level of environmental information disclosures (EID) following the issuance of the “Environmental Information Disclosure Guidelines for Chinese Listed Companies”.

Design/methodology/approach

The study is underpinned by stakeholder and legitimacy theories. Level of EID was measured for 100 Chinese companies using a scoring system and content analysis of their annual reports. The study explored the effect of ownership structure, managerial shareholding, economic power and industry classification on the level of EID using panel regression.

Findings

The study revealed that with clearly spelt out guidelines, Chinese companies are prepared to disclose environmental information regardless of their economic power. It was found that the overall level of EID in China remains lower than in developed economies. The findings are robust across several econometric models that sufficiently address various endogeneity problems.

Originality/value

This paper contributes to the existing literature by using new and updated data to re-examine the factors that affect the level of EID among Chinese listed companies. The study is important and timely as it covers the period 2014-2016, which is after the Chinese Government strengthened the enforcement of EID. It highlights the effects of new regulations and underscored areas that still require government attention to foster effective environmental protection.
The long-term effect of economic value added adoption on the firm’s business decision
Authors: Guermat Cherif , Misirlioglu Ismail U. , Al-Omush Ahmed M.
Published: September 2019

Purpose

This study aims to examine the long-term effects of adopting economic value added (EVA) as a compensation tool on managers’ behaviour.

Design/methodology/approach

The authors extend the sample used in prior studies both in the time and the cross-section dimensions.

Findings

The study conclusions are distinct from those offered by existing studies. The authors show that EVA adopters, relative to non-EVA adopters, increase the working capital cycle, use their assets less intensively and decrease their payouts to shareholders via a decrease in dividends and share repurchases. In investing decisions, the authors find a decrease in new investments, but no change in asset dispositions after the adoption of EVA compensation plans.

Originality/value

The study results highlight that the EVA adoption provides more incentives to reduce the total cost for capital rather than increasing operations and maximising shareholder wealth. The results also have implication for corporate management, particularly in the area of management compensation scheme design.
Material weakness disclosures and restatements: value of external auditor attestation
Authors: Guragai Binod , Hutchison Paul D.
Published: September 2019

Purpose

The purpose of this study is to examine the value of auditor attestation in internal control over financial reporting (ICFR) disclosures. The authors argue that internal control material weakness (ICMW) disclosures issued without auditor attestation by non-accelerated filers provide weaker signal to the impaired financial reporting quality compared to those issued with auditor attestation by accelerated filers.

Design/methodology/approach

This study investigates the differences in the association between ICMW disclosures and impaired financial reporting quality, as proxied by financial statement restatements, for accelerated and non-accelerated filers. The authors use propensity score matching to find control groups for both accelerated and non-accelerated filers.

Findings

The authors find that ICMW disclosures signal impaired financial reporting quality for both accelerated and non-accelerated filers, but such signaling is weaker for non-accelerated filers compared to accelerated filers.

Research limitations/implications

Although propensity score matching was used to match firms with and without ICMW disclosures, any unobservable fundamental differences between these groups may affect the results of this study.

Originality/value

This study shows that auditors’ involvement in the assessment of internal control effectiveness improves the signaling effect of ICMW disclosures on impaired financial reporting quality. As approved by the House Financial Services (HFS) Committee on November 4, 2009, non-accelerated filers are permanently exempt from auditor attestation requirement. This study provides some evidence that the exemption of non-accelerated filers from auditor attestation may have unintended consequences, and these results should be of interest to regulators and investors.
Political competition and debt: evidence from New Zealand local governments
Authors: Chatterjee Bikram , Bhattacharya Sukanto , Taylor Grantley , West Brian
Published: September 2019

Purpose

This paper aims to investigate whether the amount of local governments’ debt can be predicted by the level of political competition.

Design/methodology/approach

The study uses the artificial neural network (ANN) to test whether ANN can “learn” from the observed data and make reliable out-of-sample predictions of the target variable value (i.e. a local government’s debt level) for given values of the predictor variables. An ANN is a non-parametric prediction tool, that is, not susceptible to the common limitations of regression-based parametric forecasting models, e.g. multi-collinearity and latent non-linear relations.

Findings

The study finds that “political competition” is a useful predictor of a local government’s debt level. Moreover, a positive relationship between political competition and debt level is indicated, i.e. increases in political competition typically leads to increases in a local government’s level of debt.

Originality/value

The study contributes to public sector reporting literature by investigating whether public debt levels can be predicted on the basis of political competition while discounting factors such as “political ideology” and “fragmentation”. The findings of the study are consistent with the expectations posited by public choice theory and have implications for public sector auditing, policy and reporting standards, particularly in terms of minimising potential political opportunism.
Exploring health-related motive orientations among Dutch seniors
Authors: Sijtsema Siet J. , Raaijmakers Ireen , Onwezen Marleen C. , Doets Esmee
Published: September 2019

Purpose

Generally, food intake of older consumers is not in line with dietary guidelines. Insight into personal health-related motive orientations (HRMO) in this target group is useful for developing tailored interventions that support healthy food consumption, a better understanding is needed. The purpose of this paper is twofold: first, to identify older consumer groups based on HRMO; and second, to compare their consumption of different food groups and functionalities associated with a main meal.

Design/methodology/approach

An online survey was filled out by 459 Dutch adults aged 55–90 years (mean age=68.2 years), of the Sento network including 800 vital community-dwelling older consumers.

Findings

Analysis revealed five clusters of older adults with different HRMO profiles: appearance and achievement oriented, active oriented, altruistic oriented, achievement oriented and less health oriented. In addition, these segments differ in importance of functionalities associated with a main meal, i.e., physical, pleasure or rewarding, and in the consumption of specific food groups, i.e., unprocessed meat, meat replacers and unsalted nuts.

Research limitations/implications

Recommendations for interventions and communication strategies to support healthy food consumption in the different HRMO segments are presented.

Originality/value

This exploration showed that different segments of Dutch older adults can be identified based on HRMO. Between these segments there are differences in consumption of protein-rich food groups and functionalities associated with a main meal.
Enhancement of convergence characteristics of Newton-Raphson method with line search for nonlinear eddy current analysis based on time-periodic FEM
Authors: Kakita Shimpei , Okamoto Yoshifumi
Published: September 2019

Purpose

The paper aims to improve convergence characteristics of the Newton–Raphson (NR) method applied to time-periodic finite element method using various line searches, as time-periodic finite element method causes deterioration of convergence characteristic of nonlinear analysis based on NR method. The study also aims to accelerate and improve accuracy of electromagnetic field analysis for improvement of the performance of electrical machine.

Design/methodology/approach

The paper proposes new type line searches that set approximate step size for NR method. The line search evaluated step size using higher-order interpolation of functional derivative. In addition, two criteria for applying these line search were proposed. First method set one scalar value for every NR iteration that is named constant step size. Second method define different step size in each time step of time-periodic finite element method to update solution vector that is named different step size.

Findings

The paper provides efficient line searches to improve convergence characteristics for NR method. Nonlinear magnetic field analysis of two transformer models is demonstrated. The proposed methods achieve the following results: higher-order functional NR is efficient in improving convergence characteristics, and the proposed methods succeeded about twice faster in both models.

Originality/value

The paper fulfills improvement of convergence characteristics of the NR method applied to time-periodic finite element method using proposed line searches and accelerate electromagnetic field analysis.
Disaster preparedness and well-being among Cambodian– and Laotian–Americans
Authors: DeYoung Sarah E. , Lewis Denise C. , Seponski Desiree M. , Augustine Danielle A. , Phal Monysakada
Published: September 2019

Purpose

Using two main research questions, the purpose of this paper is to examine well-being and preparedness among Cambodian and Laotian immigrants living near the Gulf Coast of the USA, and the ways in which indicators such as sense of community and risk perception are related to these constructs.

Design/methodology/approach

This study employed a cross-sectional prospective design to examine disaster preparedness and well-being among Laotian and Cambodian immigrant communities. Quantitative survey data using purposive snowball sampling were collected throughout several months in Alabama, Mississippi, Florida and Louisiana.

Findings

Results from two multiple regressions revealed that sense of community and age contributed to well-being and were significant in the model, but with a negative relationship between age and well-being. Risk perception, confidence in government, confidence in engaging household preparedness and ability to cope with a financial crisis were significant predictors and positively related to disaster preparedness.

Practical implications

Well-being and disaster preparedness can be bolstered through community-based planning that seeks to address urgent needs of the people residing in vulnerable coastal locations. Specifically, immigrants who speak English as a second language, elder individuals and households in the lowest income brackets should be supported in disaster planning and outreach.

Originality/value

Cambodian and Laotian American immigrants rely upon the Gulf Coast’s waters for fishing, crab and shrimp income. Despite on-going hazard and disasters, few studies address preparedness among immigrant populations in the USA. This study fills a gap in preparedness research as well as factors associated with well-being, an important aspect of long-term resilience.
Two new Painlevé-integrable extended Sakovich equations with (2 + 1) and (3 + 1) dimensions
Authors: Wazwaz Abdul-Majid
Published: September 2019

Purpose

The purpose of this paper is to introduce two new Painlevé-integrable extended Sakovich equations with (2 + 1) and (3 + 1) dimensions. The author obtains multiple soliton solutions and multiple complex soliton solutions for these three models.

Design/methodology/approach

The newly developed Sakovich equations have been handled by using the Hirota’s direct method. The author also uses the complex Hirota’s criteria for deriving multiple complex soliton solutions.

Findings

The developed extended Sakovich models exhibit complete integrability in analogy with the original Sakovich equation.

Research limitations/implications

This paper is to address these two main motivations: the study of the integrability features and solitons solutions for the developed methods.

Practical implications

This paper introduces two Painlevé-integrable extended Sakovich equations which give real and complex soliton solutions.

Social implications

This paper presents useful algorithms for constructing new integrable equations and for handling these equations.

Originality/value

This paper gives two Painlevé-integrable extended equations which belong to second-order PDEs. The two developed models do not contain the dispersion term uxxx. This paper presents an original work with newly developed integrable equations and shows useful findings.