bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of pre-diabetes and undiagnosed diabetes in the Mollerussa prospective observational cohort study in a semi-rural area of Catalonia
Authors: Falguera Mireia , Vilanova Maria Belén , Alcubierre Nuria , Granado-Casas Minerva , Marsal Josep Ramón , Miró Neus , Cebrian Cristina , Molló Àngels , Franch-Nadal Josep , Mata-Cases Manel , Castelblanco Esmeralda , Mauricio Didac
Published: January 2020

Objectives

To assess the prevalence of undiagnosed diabetes and pre-diabetes in the healthy population in the Mollerussa cohort. As a secondary objective, to identify the variables associated with these conditions and to describe the changes in glycaemic status after 1 year of follow-up in subjects with pre-diabetes.

Design

Prospective observational cohort study.

Setting

General population from a semi-rural area.

Participants

The study included 583 participants without a diagnosis of diabetes recruited between March 2011 and July 2014.

Results

The prevalence of undiagnosed diabetes was 20, 3.4% (95% CI 2.6 to 4.2) and that of pre-diabetes was 229, 39.3% (37.3 to 41.3). Among those with pre-diabetes, 18.3% had isolated impaired fasting plasma glucose (FPG) (FPG: 100 to <126 mg/dL), 58.1% had isolated impaired glycated haemoglobin (HbA1c) (HbA1c 5.7 to <6.5) and 23.6% fulfilled both criteria. Follow-up data were available for 166 subjects; 41.6%(37.8 to 45.4) returned to normoglycaemia, 57.6% (57.8 to 61.4) persisted in pre-diabetes and 0.6% (0 to 1.2) progressed to diabetes. Individuals with pre-diabetes had worse cardiometabolic risk profiles and sociodemographic features than normoglycaemic subjects. In the logistic regression model, variables significantly associated with pre-diabetes were older age (OR; 95% CI) (1.033; 1.011 to 1.056), higher physical activity (0.546; 0.360 to 0.827), body mass index (1.121; 1.029 to 1.222) and a family history of diabetes (1.543; 1.025 to 2.323). The variables significantly associated with glycaemic normalisation were older age (0.948; 0.916 to 0.982) and body mass index (0.779; 0.651 to 0.931).

Conclusions

Among adults in our region, the estimated prevalence of undiagnosed diabetes was 3.4% and that of pre-diabetes was 39.3%. After a 1-year follow-up, a small proportion of subjects (0.6%) with pre-diabetes progressed to diabetes, while a high proportion (41.6%) returned to normoglycaemia. Individuals with pre-diabetes who returned to normoglycaemia were younger and had a lower body mass index.
International development and implementation of a core measurement set for research and audit studies in implant-based breast reconstruction: a study protocol
Authors: Potter Shelley , Davies Charlotte , Holcombe Christopher , Weiler-Mithoff Eva , Skillman Joanna , Vidya Raghavan , Masannat Yazan , Weber Walter , Heil Joerg , Wilson Sherif , Thrush Steven , Whisker Lisa , Blazeby Jane , Metcalfe Chris , Avery Kerry
Published: January 2020

Introduction

Outcome reporting in research studies of breast reconstruction is inconsistent and lacks standardisation. The results of individual studies therefore cannot be meaningfully compared or combined limiting their value. A core outcome set (COS) has been developed to address these issues and identified 11 key outcomes to be measured and reported in all future research and audit studies in reconstructive breast surgery (RBS). A COS represents what key outcomes should be measured. The next step is to determine how and when this should be done. The aim of this study is to develop a core measurement set (CMS) for use in research and audit studies in implant-based breast reconstruction.

Methods and analysis

The CMS will be developed in accordance with the guidance developed by the Core Outcome Measures in Effectiveness Trials initiative (COMET) and COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) group for the selection of outcome measurement instruments (OMIs) for relevant outcome domains included in the RBS COS. This will involve three phases with strategies to promote implementation as a final additional phase. The phases are (1) conceptual considerations in which the target population, procedures and settings are defined; (2) systematic reviews to identify existing clinical, patient-reported and cosmetic OMIs and, if appropriate, assess their quality using COSMIN methodology; (3) a modified Delphi process including sequential Delphi surveys involving approximately 100 healthcare professionals and a face to face consensus meeting to agree and ratify which outcome definitions and OMIs should be used and standardised time points for assessment; (4) strategies to promote dissemination and adoption of the CMS.

Ethics and dissemination

Ethical approval has been granted by University of Bristol Faculty Research Ethics Committee FREC ID 60221. Dissemination strategies will include scientific meeting presentations and peer-reviewed journal publications. Implementation activities will include engagement with journal editors and funders to promote uptake and use of the CMS.
Cannabinoids for adult cancer-related pain: systematic review and meta-analysis
Authors: Boland Elaine G , Bennett Michael I , Allgar Victoria , Boland Jason W
Published: January 2020

Objectives

There is increased interest in cannabinoids for cancer pain management and legislative changes are in progress in many countries. This study aims to determine the beneficial and adverse effects of cannabis/cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults.

Methods

Systematic review and meta-analysis to identify randomised controlled trials of cannabinoids compared with placebo/other active agents for the treatment of cancer-related pain in adults to determine the effect on pain intensity (primary outcome) and adverse effects, including dropouts. Searches included Embase, MEDLINE, PsycINFO, Web of Science, ClinicalTrials.gov, Cochrane and grey literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.

Results

We identified 2805 unique records, of which six randomised controlled trials were included in this systematic review (n=1460 participants). Five studies were included in the meta-analysis (1442 participants). All had a low risk of bias. There was no difference between cannabinoids and placebo for the difference in the change in average Numeric Rating Scale pain scores (mean difference −0.21 (−0.48 to 0.07, p=0.14)); this remained when only phase III studies were meta-analysed: mean difference −0.02 (−0.21 to 0.16, p=0.80). Cannabinoids had a higher risk of adverse events when compared with placebo, especially somnolence (OR 2.69 (1.54 to 4.71), p<0.001) and dizziness (OR 1.58 (0.99 to 2.51), p=0.05). No treatment-related deaths were reported. Dropouts and mortality rates were high.

Conclusions

Studies with a low risk of bias showed that for adults with advanced cancer, the addition of cannabinoids to opioids did not reduce cancer pain.

Trial registration number

CRD42018107662.
Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery
Authors: West Kiana Ashley , Kanu Chidimma , Maric Tanya , McDonald Julie Anne Kathryn , Nicholson Jeremy K , Li Jia V , Johnson Mark R , Holmes Elaine , Savvidou Makrina D
Published: January 2020

Objective

Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development.

Design

A parallel metabonomic (molecular phenotyping based on proton nuclear magnetic resonance spectroscopy) and gut bacterial (16S ribosomal RNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared with women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed.

Results

Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine,p-cresol sulfate, indoxyl sulfate andp-hydroxyphenylacetate), and a shift in the gut microbiota. The urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (p=0.001) and was also elevated in urine of neonates born from these mothers (p=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight.

Conclusion

Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further.
My approach to endoscopic ultrasound-guided fine-needle aspiration biopsy specimens of the pancreas
Authors: Wong Newton A C S
Published: January 2020

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is the optimal method for sampling lesions of the pancreas. This procedure is being performed at increasing numbers of hospitals and therefore, more and more cellular pathology departments are having to process and report EUS-FNAB specimens. This article outlines the advantages of using tissue/cell block preparation to process these specimens. In particular, such preparation concentrates, conserves and preserves sampled material which is then available for a full array of further analyses. Tissue/cell block preparation also enables EUS-FNAB specimens to be assessed by a wider range of cellular pathologists. This article demonstrates how a tissue/cell block protocol permits the diagnosis of the full range of pancreatic pathologies sampled by EUS-FNAB. The protocol is identical for all these pathologies (including both solid and cystic lesions) and is simple at all stages of the specimen pathway, from collection to processing to assessment.
How should we think about clinical data ownership?
Authors: Ballantyne Angela
Published: January 2020

The concept of ‘ownership’ is increasingly central to debates, in the media, health policy and bioethics, about the appropriate management of clinical data. I argue that the language of ownership acts as a metaphor and reflects multiple concerns about current data use and the disenfranchisement of citizens and collectives in the existing data ecosystem. But exactly which core interests and concerns ownership claims allude to remains opaque. Too often, we jump straight from ‘ownership’ to ‘private property’ and conclude ‘the data belongs to the patient’. I will argue here that private property is only one type of relevant relationship between people, communities and data. There are several reasons to doubt that conceptualising data as private property presents a compelling response to concerns about clinical data ownership. In particular I argue that clinical data are co-constructed, so a property account would fail to confer exclusive rights to the patient. A non-property account of ownership acknowledges that the data are ‘about the patient’, and therefore the patient has relevant interests, without jumping to the conclusion that the data ‘belongs to the patient’. On this broader account of ownership, the relevant harm is the severing of the connection between the patient and their data, and the solution is to re-engage and re-connect patients to the data research enterprise.
A Review of Traditional Uses, Phytochemistry, and Pharmacological Properties of the Genus Saururus
Authors: Liu Guangxin , Zhao Zefeng , Shen Meilun , Zhao Xue , Xie Jing , He Xirui , Li Cuiqin
Published: January 2020

The genus Saururus, belonging to Saururaceae, contains two species, S. cernuus L. and S. chinensis (Lour) Baill. with common utilization in traditional medicine from Asia to North America for the treatment of edema, beriberi, jaundice, leucorrhea, urinary tract infections, hypertension, hepatitis diseases, and tumors. An extensive review of literature was made on traditional uses, phytochemistry, and ethnopharmacology of Saururus using ethno-botanical books, published articles, and electronic databases. The 147 of chemical constituents have been isolated and identified from S. cernuus and S. chinensis, and lignans, flavonoids, alkaloids, anthraquinones, saponins, and phenols are the major constituents. Various pharmacological investigations in many in vitro and in vivo models have revealed the potential of the genus Saururus with anti-inflammatory, antitumor, anti-oxidant, hepatoprotective, antimelanogenic, lipid-lowering, and bone protective activities, supporting the rationale behind numerous of its traditional uses. Due to the noteworthy pharmacological properties, Saururus can be a better option for new drug discovery. Data regarding many aspects of this plant such as toxicology, pharmacokinetics, quality-control measures, and the clinical value of the active compounds is still limited which call for additional studies.
Molecular dynamics study on composition and temperature dependences of mechanical properties of CdTeSe nanowires under uniaxial stretching
Authors: Köylüoğlu Bilal , Alaei Sholeh , Kurban Mustafa
Published: January 2020

In this study, a molecular dynamics (MD) study has been performed on composition and temperature dependences of mechanical properties of CdTe[Formula: see text]Se[Formula: see text] ([Formula: see text], 0.50 and 0.75) nanowires with a diameter of 6.93 nm. The simulation results show that CdTe[Formula: see text]Se[Formula: see text] nanowire seems to be more ductile, whereas CdTe[Formula: see text]Se[Formula: see text] nanowire seems to be more brittle at 1 K. Moreover, the temperature and composition exert significant effects on the mechanical properties of CdTeSe nanowires under stretching. We conclude that the dominancy of Se atoms yields a higher stability and strength at the lower temperature of 1 K, whilst it is the same for the nanowires with both higher Te and Se contents at the higher temperature of 300 K. The radial distribution functions (RDFs) have also been calculated for the CdTeSe nanowires based on the pair separation distance at 1 and 300 K.
Exploring novel biomedical applications of rocksalt CdS system with various Eu concentrations (A theoretical study)
Authors: Junaid Iqbal Khan M. , Kanwal Zarfishan , Liu Juan , Ijaz Abera , Usmani Nauman
Published: January 2020

Current research is a computational study in which we focus on calculating optical properties of Eu-doped Cadmium Sulfide (CdS) system. We employ Perdew–Burke–Ernzerhof (PBE)–generalized gradient approximation (GGA) for accomplishment of our study and we assume various Eu concentrations (3.12%, 6.25% and 9.37%) for doping into host CdS lattice. We substitute Cd atoms with Eu atoms while supercell size is kept fixed ([Formula: see text]. We present a detailed comparison among optical properties of pure CdS and various Eu concentrations. Partial density of states (PDOS) plots reveal hybridization among Cd [Formula: see text]-states, S [Formula: see text]-states and Eu [Formula: see text]-states and because of it, material (CdS:Eu) shows exceptional energy transfer which influences optical spectra and electronic properties. A considerable change in absorption spectra is noted, where in comparison to pure CdS, absorption shows blueshift with increasing Eu concentrations. Our DFT results were found to have great resemblance with existing literature. Addition of Eu into the CdS lattice originates novelty in CdS:Eu system and number of potential applications related to the field of biomedical physics, amperometric biosensors, quantum dots (QDs) sensors, photonics, bioprinting, biosensing luminophores, solar cells and optoelectronics industry may be explored in technological perspectives.
Impact of Expected Shortfall Approach on Capital Requirement Under Basel
Authors: Siu Yam Wing
Published: January 2020

This paper proposes a method that uses volatility index of US and six other markets of Pacific Basin, namely Hong Kong, Australia, India, Japan, Korea, and China, to provide value-at-risk (VaR) and expected shortfall (ES) forecasts. Empirical constants that are used to multiply the levels of volatility indexes for estimating VaR and ES of various significance levels for 1–22 days ahead, one by one, for seven market indexes have been statistically determined using daily data spanning from 4.75 to 16 years. It is because it would be inappropriate to simply scale up the one-day volatility by multiplying the square root of time (or the number of days) ahead to determine the risk over a longer horizon of [Formula: see text] days. Results show that the shift to ES approach generally increases the regulatory capital requirements from 2.09% of India market to 8.56% of Korea market except for the China market where ES approach yields an unexpected decrease of 3.21% of capital requirement.
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Ar mica dating of late Cenozoic sediments in SE Tibet: implications for sediment recycling and drainage evolution
Authors: Sun Xilin , Kuiper K. F. , Tian Yuntao , Li Chang'an , Zhang Zengjie , Gemignani L. , Guo Rujun , de Breij Vincent, H.L. , Wijbrans J. R.
Published: January 2020

The Indo-Asia collision significantly changed the topography and drainage network of rivers around the Tibetan Plateau. Debate continues as to when and how the current drainage system of the Yangtze River was formed. Here we use
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Ar dating of detrital micas (muscovite and biotite) to constrain provenances of the Pliocene sediments from the Jianchuan and Yuanmou basins in SE Tibet. Muscovite and biotite data of the same Pliocene samples from the Jianchuan Basin suggest contrasting distal v. local sources, respectively. Similarly, muscovite data of the Yuanmou Basin suggest a derivation of sediments from the Yalong River, but the characteristics of the Pliocene cobbles (palaeocurrent and subrounded cobbles) suggest that these sediments are locally sourced. Sediment reworking is proposed as an explanation for the different sediment provenance signals in the Jianchuan and Yuanmou basins that have led to the controversy of an either Pleistocene or pre-Miocene age of formation of the current Yangtze. Based on sediment provenance constraints, the evolution of the Jinsha River is reconstructed. The upper Jinsha River lost its connection with the southward flowing Red River upstream from the Jianchuan basin at least before the Pliocene. At the same time a parallel site in the Yuanmou Basin shows that the Yalong River stopped flowing southward into this basin. Detrital mica from early Pleistocene sediments at the Panzhihua site between the Jianchuan and Yuanmou basins is sourced from the current Jinsha and Yalong rivers. These results would suggest that the current upper Yangtze drainage system should have been established before the Pliocene.

Supplementary material:
Muscovite
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Ar data, biotite
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Ar data and muscovite geochemistry are available at
https://doi.org/10.6084/m9.figshare.c.4821573
Revealing the Critical Role of Human Performance in Software
Authors: Woods David D. , Allspaw John
Published: January 2020

Understanding, supporting, and sustaining the capabilities above the line of representation require all stakeholders to be able to continuously update and revise their models of how the system is messy and yet usually manages to work. This kind of openness to continually reexamine how the system really works requires expanding the efforts to learn from incidents.
Beyond the Fix-it Treadmill
Authors: Reed J. Paul
Published: January 2020

Given that humanity’s study of the sociological factors in safety is almost a century old, the technology industry’s post-incident analysis practices and how we create and use the artifacts those practices produce are all still in their infancy. So don’t be surprised that many of these practices are so similar, that the cognitive and social models used to parse apart and understand incidents and outages are few and cemented in the operational ethos, and that the byproducts sought from post-incident analyses are far-and-away focused on remediation items and prevention.
We've Only Just Begun
Authors: Armstrong Deborah J.
Published: January 2020

It is a new year and a new editorial team. We are pleased to introduce the editors-in-chief for The DATA BASE for Advances in Information Systems for the next three years: Deb Armstrong and Tom Stafford.

The DATA BASE for Advances in Information Systems has been in continuous publication since 1969, marking it as one of the longest-published research journals in the field of information systems. Having just celebrated our 50th year of publication, we are pleased to begin our editorial term with initiatives intended to continue to move The DATA BASE for Advances in Information Systems toward an even more impactful and notable presence in the field of information systems scholarship and practice. We have truly only just begun!
The Regulation of Mitochondrial Replacement Techniques Around the World
Authors: Cohen I. Glenn , Adashi Eli Y. , Gerke Sara , Palacios-González César , Ravitsky Vardit
Published: January 2020

Mitochondrial replacement techniques (MRTs, also referred to as mitochondrial replacement therapies) have given hope to many women who wish to have genetically related children but have mitochondrial DNA mutations in their eggs. MRTs have also spurred deep ethical disagreements and led to different regulatory approaches worldwide. In this review, we discuss the current regulation of MRTs across several countries. After discussing the basics of the science, we describe the current law and policy directions in seven countries: the United Kingdom, the United States, Canada, Australia, Germany, Israel, and Singapore. We also discuss the emerging phenomenon of medical tourism (also called medical travel) for MRTs to places like Greece, Spain, Mexico, and Ukraine. We then pull out some key findings regarding similarities and differences in regulatory approaches around the world.
Regulatory Focus and Fit Effects in Organizations
Authors: Higgins E. Tory , Pinelli Federica
Published: January 2020

Regulatory focus theory distinguishes between two different value concerns: promotion concerns with advancement and growth, and prevention concerns with safety and security. Since its publication more than 20 years ago, regulatory focus theory has generated a substantial amount of research and it has been applied to numerous organizational contexts. We identified four main domains: decision making, messaging, people management (e.g., leadership, organizational development, wellness and employees’ productivity), and entrepreneurship. We selected significant findings in those domains based on individuals, teams, and organizations being motivated by promotion or prevention goals and on the consequences of the match between regulatory focus goal orientation and the manner in which the goal is pursued, as conceptualized by regulatory fit theory. We also highlighted whether the research was concerned with the individual or with a broader group within the organization (including the organization itself). We conclude by suggesting future avenues for research.
Multiteam Systems: An Integrated Review and Comparison of Different Forms
Authors: Zaccaro Stephen J. , Dubrow Samantha , Torres Elisa M. , Campbell Lauren N.P.
Published: January 2020

In this review, we examine the burgeoning body of research on multiteam systems (MTSs) since the introduction of the concept in 2001. MTSs refer to networks of interdependent teams that coordinate at some level to achieve proximal and distal goals. We summarize MTS findings around three core processes and states: within- and between-team coordination processes/structures, leadership structures/processes, and cognitive and affective/motivation emergent states. Furthermore, we explore how these processes and states vary according to MTS boundary status (internal or external), component team distance (geographic, functional, cultural, and discipline), and superordinate goal type (intellectual or physical). We identify several process and state similarities across levels of these attributes, as well as highlight some important differences. We conclude with a set of propositions and future directions prompted by our review, which can serve as a guide for future MTS research.
Review—Electrical Manipulation of DNA Self-Assembled Monolayers: Electrochemical Melting of Surface-Bound DNA
Authors: West Ryan M.
Published: January 2020

DNA provides a powerful framework for the development of biosensors, DNA chips, bioelectronics, and other established and emerging technologies. Many of these applications involve DNA self-assembled monolayers (SAM) on conducting surfaces where the high molecular density, the two-dimensional nature of the interface, and the limited mobility of the strands significantly impact the behavior of the DNA. The unique steric and electrostatic conditions present in the SAM dominate hybridization, melting, and motion of the tethered oligonucleotides. At neutral pH the charged sugar-phosphate backbone makes the DNA sensitive to the electric fields present in the electrical double-layer. Electrode charge provides a means of modifying the reactivity of DNA monolayers; facilitating enhanced rates of hybridization, controlling orientation, and inducing melting (i.e. denaturation). Understanding the effects of electric fields on DNA monolayers is a prerequisite to the optimization of next generation DNA biosensors and other applications that take advantage of DNA’s selective self-assembly. This mini-review will give an overview of the ways in which electrochemical control can be used to manipulate DNA SAMs. In particular, the process of electric field-assisted melting of DNA, i.e. electrochemical melting, will be reviewed. Electrochemical melting has the potential for providing biophysical insights and for the development of new diagnostic applications.
Perspective—Application of Micro Photosynthetic Power Cells for IoT in Automotive Industry
Authors: Kuruvinashetti Kiran , Guoqing Geng , Haobin Jiang , Packirisamy Muthukumaran
Published: January 2020

Global warming is increasing at the alarming rate in the recent years. One of the best solutions to reduce the global warming is generation of power from the carbon neutral and negative technologies. In view of this, harvesting energy from the photosynthesis is one of the best viable solution. The Microphotosynthetic cell (μPSC), presented in this work, functions on the principle of photosynthesis and respiration. Typical power produced by a μPSC varies in the range of 0.1–10 mW. In this paper, we discussed the potential applications of the Microphotosynthetic power cells to the automotive sector and Autonomous Vehicles (AV).
TGF-β1 promotes vitamin D-induced prostaglandin E2 synthesis by upregulating vitamin D receptor expression in human granulosa-lutein cells
Authors: Wang Fuxin , Chang Hsun-Ming , Yi Yuyin , Lin Yung-Ming , Li Hong , Leung Peter C. K.
Published: January 2020

There is increasing evidence showing the importance of vitamin D (Vit D) and its nuclear receptor, the Vit D receptor (VDR), in female reproductive health. Transforming growth factor-β1 (TGF-β1) and its functional receptors are expressed in human oocytes and granulosa cells that participate in follicular development and ovulation. Recently, Sma- and Mad-related protein 3 (SMAD3; a downstream effector of TGF-β1) has been proposed to mediate crosstalk between the Vit D and TGF-β1 signaling pathways, but this relationship has not been fully explored and has yet to be tested in human granulosa-lutein (hGL) cells. In this study, we showed that TGF-β1 significantly promoted the expression of VDR, and this stimulatory effect occurred through the activin receptor-like kinase 5 type I receptor-mediated SMAD3 and ERK1/2 signaling pathways in hGL cells. Additionally, we showed that Vit D increased the expression of cyclooxygenase 2 (COX-2) and the synthesis of prostaglandin E2 (PGE2) in a time- and dose-dependent manner. Furthermore, we demonstrated a synergistic effect of TGF-β1 and Vit D on the expression of COX-2 and synthesis of PGE2, and this effect could be attenuated by silencing the expression of VDR. Our findings indicate that TGF-β1 upregulates the expression of VDR, which promotes Vit D-induced COX-2 expression and subsequent PGE2 production by activating the SMAD3 and ERK1/2 signaling pathways in hGL cells.
Fibrotic liver has prompt recovery after ischemia-reperfusion injury
Authors: Konishi Takanori , Schuster Rebecca M. , Goetzman Holly S. , Caldwell Charles C. , Lentsch Alex B.
Published: January 2020

Hepatic ischemia-reperfusion (I/R) is a major complication of liver resection, trauma, and liver transplantation; however, liver repair after I/R in diseased liver has not been studied. The present study sought to determine the manner in which the fibrotic liver repairs itself after I/R. Liver fibrosis was established in mice by CCl4 administration for 6 wk, and then liver I/R was performed to investigate liver injury and subsequent liver repair in fibrotic and control livers. After I/R, fibrotic liver had more injury compared with nonfibrotic, control liver; however, fibrotic liver showed rapid resolution of liver necrosis and reconstruction of liver parenchyma. Marked accumulation of hepatic stellate cells and macrophages were observed specifically in the fibrotic septa in early reparative phase. Fibrotic liver had higher numbers of hepatic stellate cells, macrophages, and hepatic progenitor cells during liver recovery after I/R than did control liver, but hepatocyte proliferation was unchanged. Fibrotic liver also had significantly greater number of phagocytic macrophages than control liver. Clodronate liposome injection into fibrotic mice after I/R caused decreased macrophage accumulation and delay of liver recovery. Conversely, CSF1-Fc injection into normal mice after I/R resulted in increased macrophage accumulation and concomitant decrease in necrotic tissue during liver recovery. In conclusion, fibrotic liver clears necrotic areas and restores normal parenchyma faster than normal liver after I/R. This beneficial response appears to be directly related to the increased numbers of nonparenchymal cells, particularly phagocytic macrophages, in the fibrotic liver.

NEW & NOTEWORTHY This study is the first to reveal how diseased liver recovers after ischemia-reperfusion (I/R) injury. Although it was not completely unexpected that fibrotic liver had increased hepatic injury after I/R, a novel finding was that fibrotic liver had accelerated recovery and repair compared with normal liver. Enhanced repair after I/R in fibrotic liver was associated with increased expansion of phagocytic macrophages, hepatic stellate cells, and progenitor cells.
Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma
Authors: Nabeshima Tatsuhide , Hamada Shin , Taguchi Keiko , Tanaka Yu , Matsumoto Ryotaro , Yamamoto Masayuki , Masamune Atsushi
Published: January 2020

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma.

NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.
Inhibition of PDE4/PDE4B improves renal function and ameliorates inflammation in cisplatin-induced acute kidney injury
Authors: Xu Man , Yu Xiaowen , Meng Xia , Huang Songming , Zhang Yue , Zhang Aihua , Jia Zhanjun
Published: January 2020

Nephrotoxicity is a known clinical complication of cisplatin that limits the use of this potent antitumor drug. Cyclic nucleotide phosphodiesterases (PDEs) play complex roles in physiology and pathology. PDE4, which is a member of the PDE family, has four subtypes (PDE4A–PDE4D), and PDE4B plays an important role in inflammation. Thus, in the present study, we investigated the effect of PDE4/PDE4B inhibition on renal function and inflammation in a cisplatin nephrotoxicity model. In mice, cisplatin enhanced mRNA and protein expression of PDE4B in renal tubules. After treatment with the PDE4 inhibitor cilomilast, cisplatin-induced renal dysfunction, renal tubular injury, tubular cell apoptosis, and inflammation were all improved. Next, after silencing PDE4B in vivo, we observed a protective effect against cisplatin nephrotoxicity similar to that of the PDE4 inhibitor. In vitro, cisplatin-induced renal tubular cell death was strikingly ameliorated by the PDE4 inhibitor and PDE4B knockdown along with the blockade of the inflammatory response. Considering the known roles of some cell survival pathways in antagonizing insults, we examined levels of PDE4-associated proteins sirtuin 1, phosphatidylinositol 3-kinase, and phosphorylated AKT in cisplatin-treated renal tubular cells with or without cilomilast treatment. Strikingly, cisplatin treatment downregulated the expression of the above proteins, and this effect was largely abolished by the PDE4 inhibitor. Together, these findings indicate the beneficial role of PDE4/PDE4B inhibition in treating cisplatin nephrotoxicity, possibly through antagonizing inflammation and restoring cell survival signaling pathways.
Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer’s disease
Authors: Souza Lucas A. C. , Trebak Fatima , Kumar Veena , Satou Ryousuke , Kehoe Patrick G. , Yang Wei , Wharton Whitney , Feng Earley Yumei
Published: January 2020

High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na+] from hypertensive and normotensive human subjects with family histories of Alzheimer’s disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na+] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na+] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na+], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na+] and BP but showed no correlation between plasma [Na+] and BP. In sum, CSF [Na+] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na+] in chronic hypertension in humans.
Age-Related Physiologic Thinning Rate of the Retinal Nerve Fiber Layer in Different Levels of Myopia
Authors: Jeong Daun , Sung Kyung Rim , Jo Youn Hye , Yun Sung-cheol
Published: January 2020

Purpose. To investigate the effect of refractive error on the physiologic thinning rate of the retinal nerve fiber layer (RNFL) in healthy eyes. Materials and Methods. This study analyzed 223 eyes of 141 healthy subjects followed for more than 5 years and underwent at least five serial spectral domain optical coherence tomography (SD-OCT) examinations. Longitudinal RNFL measurements were analyzed by linear mixed models incorporating follow-up duration, baseline RNFL thickness, spherical equivalent (SE), age, intraocular pressure, and visual field mean deviation. Thinning rates were classified according to SE into three groups: nonmyopic (NM; >0 D), mild-to-moderately myopic (MM; >–6 D and ≤0 D), and highly myopic (HM; ≤–6 D). Results. The overall slopes of change in RNFL thickness over time in the NM, MM, and HM groups were −0.305 ± 0.128, −0.294 ± 0.068, and −0.208 ± 0.097 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, in the superior quadrant; −0.084 ± 0.145, 0.107 ± 0.082, and −0.161 ± 0.112 μm/yr, in the temporal quadrant; −0.807 ± 0.242, −0.794 ± 0.130, and −0.727 ± 0.183 μm/yr, in the inferior quadrant; and 0.160 ± 0.157, 0.118 ± 0.084, and 0.429 ± 0.119 μm/yr, in the nasal quadrant. Overall and in all four quadrants, there was no significant difference in the rate of RNFL thickness change among the three groups. Conclusions. Refractive error did not affect the physiologic thinning rate of RNFL when assessed by SD OCT.
Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer: An Unusual Case Involving a Pulmonary Tumor
Authors: Marushima Hideki , Sakai Hiroki , Yoneyama Reimi , Kimura Hiroyuki , Miyazawa Tomoyuki , Chosokabe Motohiro , Hoshikawa Masahiro , Kojima Koji , Takagi Masayuki , Saji Hisashi
Published: January 2020

Pulmonary hyalinizing granuloma is a very rare benign condition. This study describes a case involving pulmonary hyalinizing granuloma in a 76-year-old man who presented with a solitary pulmonary nodule, determined through chest radiography and computed tomography, that mimicked primary lung cancer. To establish a definitive diagnosis, tumor resection was performed with histopathological analysis indicating pulmonary hyalinizing granuloma. Radiographic findings in previously reported cases showed that most patients had well-defined margins and usually bilateral, multiple lesions. In our case; however, the solitary ill-defined tumor mimicking lung cancer is an uncommon location for this rare condition.
Experimental Research on Dynamic Behavior of Circular Mild Steel Plates with Surface Cracks Subjected to Repeated Impacts in Low Temperature
Authors: Zeng Yang , Chen Hao , Yu Rong , Shen Zhiyuan , Yu Zixian , Liu Jingxi
Published: January 2020

Experimental investigations on the mechanical responses of fully clamped circular plates with prefabricated crack at room temperature and low temperature have been conducted. Initial cracks with different lengths were prefabricated by the electrical discharge machining method. Low ambient temperature was created by the liquid nitrogen in a low-temperature chamber, and a dropping hammer was dropped from the same height with a constant impact energy of 5 J to carry out the repeated impact. Experimental test results show that the prefabricated crack has a significant influence on the mechanical behavior of the thin plates. The maximum impact force decreases with increase of the crack length, and the threshold impact number until fracture decreases with increase of the crack length. It is also observed from the test results that the maximum impact force increases with decrease of the temperature, while threshold impact number until fracture and the plastic permanent deformation decreases due to the brittleness of the material in low temperature. The present investigations provide useful insight into the failure mechanism of the clamped thin plate with initial crack under low-velocity repeated impacts in low temperature, which will lead to a guideline for research and design of marine structures in the arctic area.
Automatic Search for the Linear (Hull) Characteristics of ARX Ciphers: Applied to SPECK, SPARX, Chaskey, and CHAM-64
Authors: Huang Mingjiang , Wang Liming
Published: January 2020

Linear cryptanalysis is an important evaluation method for cryptographic primitives against key recovery attack. In this paper, we revisit the Walsh transformation for linear correlation calculation of modular addition, and an efficient algorithm is proposed to construct the input-output mask space of specified correlation weight. By filtering out the impossible large correlation weights in the first round, the search space of the first round can be substantially reduced. We introduce a concept of combinational linear approximation table (cLAT) for modular addition with two inputs. When one input mask is fixed, another input mask and the output mask can be obtained by the Splitting-Lookup-Recombination approach. We first split the n-bit fixed input mask into several subvectors and then find the corresponding bits of other masks, and in the recombination phase, pruning conditions can be used. By this approach, a large number of search branches in the middle rounds can be pruned. With the combination of the optimization strategies and the branch-and-bound search algorithm, we can improve the search efficiency for linear characteristics on ARX ciphers. The linear hulls for SPECK32/48/64 with a higher average linear potential (ALP) than existing results have been obtained. For SPARX variants, an 11-round linear trail and a 10-round linear hull have been found for SPARX-64 and a 10-round linear trail and a 9-round linear hull are obtained for SPARX-128. For Chaskey, a 5-round linear trail with a correlation of 2−61 has been obtained. For CHAM-64, 34/35-round optimal linear characteristics with a correlation of 2−31/2−33 are found.
Antenatal and Postpartum Depression: Prevalence and Associated Risk Factors among Adolescents’ in KwaZulu-Natal, South Africa
Authors: Govender Desiree , Naidoo Saloshni , Taylor Myra
Published: January 2020

Background. Maternal depression is a major public health concern as it affects both mothers and their children. Antenatal depression, which is often underdiagnosed, has been associated with preterm labour, low birth weight, and intrauterine growth restriction. Research has demonstrated that postpartum depression is associated with mother-infant bonding impairment, child abuse, child neglect, maternal substance abuse, and self-harm. Globally, the prevalence of depression in pregnant and postpartum adolescents varies. This paper reports on the findings of the prevalence of depression and its associated risk factors among pregnant and postpartum adolescents in KwaZulu-Natal, South Africa. Methods. Data were generated by means of a descriptive cross-sectional study that was conducted between June and November 2017 utilizing a sample of 326 adolescent females accessing maternal health services in a medium-sized rural peripheral district hospital in Ugu, Southern KwaZulu-Natal. The Edinburgh Postnatal Depression Scale questionnaire was used to screen participating pregnant and postnatal adolescents for depression. A cut-off score of ≥13 was used to identify pregnant and postnatal adolescents with symptoms of depression. The data were analysed using R software. Results. The prevalence of depression among the pregnant participants was 15.9% (21/132), whereas it was 8.8% (17/194) among the postpartum participants. Antenatal depression was associated with physical violence (adjusted odds ratio (aOR) 6.47, 95% CI 1.36-30.53, p=0.01) and verbal abuse (adjusted odds ratio (aOR) 4.8, 95% CI 1.5-15.16, p=0.006). The pregnant participants who indicated they received a lot of support from their partners were 0.93% less likely to have depression. Postnatal depression was associated with physical violence (adjusted odds ratio (aOR) 7.32, 95% CI 1.66-29.44, p=0.005), verbal abuse (adjusted odds ratio (aOR) 4.3, 95% CI 1.03-15.79, p=0.03), and intimate partner violence (adjusted odds ratio (aOR) 9.58, 95% CI 1.58-48.82, p=0.008). Conclusion. The prevalence of antenatal depression was higher than postpartum depression in the study sample. In light of the findings, maternal healthcare professionals are cautioned to consider the mental health of pregnant and postpartum adolescents who seek their services at health facilities.
Activation of the NF-κB and MAPK Signaling Pathways Contributes to the Inflammatory Responses, but Not Cell Injury, in IPEC-1 Cells Challenged with Hydrogen Peroxide
Authors: Xiao Kan , Liu Congcong , Tu Zhixiao , Xu Qiao , Chen Shaokui , Zhang Yang , Wang Xiuying , Zhang Jing , Hu Chien-An Andy , Liu Yulan
Published: January 2020

Oxidative stress can lead to intestinal cell injury as well as the induction of inflammation. It is not clear whether inflammation is an important factor leading to cell injury caused by oxidative stress. The purpose of this study was to investigate the role of inflammation in intestinal injury caused by hydrogen peroxide (H2O2). Our results revealed that H2O2 stimulation significantly decreased the viability of intestinal porcine epithelial cells (IPEC-1), increased lactate dehydrogenase (LDH) activity, and disrupted the distribution of the tight junction protein claudin-1. H2O2 significantly increased the mRNA expression of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α (TNF-α). H2O2 stimulation also led to increased phosphorylation of p38 and jun N-terminal kinase (JNK), and p65 NF-κB protein translocation into the nucleus of IPEC-1 cells. Cells treated with the NF-κB inhibitor (BAY11-7082), the p38 inhibitor (SB202190), or the JNK inhibitor (PD98059) significantly decreased mRNA and protein expression of IL-6, IL-8, and TNF-α. However, treatment with mitogen-activated protein kinase (MAPK) or NF-κB inhibitors did not prevent the damage effect on cell viability, LDH activity, or the distribution of claudin-1 in cells challenged with H2O2. In summary, our data demonstrate that activation of the NF-κB and MAPK signaling pathways can contribute to the inflammatory response, but not cell injury, in IPEC-1 cells challenged with H2O2.