bluuebunny/crossref_metadata_2025 huggingface dataset:
Silent mating‐type information regulation 2 homolog 1 overexpression is an important strategy for the survival of adapted suspension tumor cells
Authors: Park Ji Young , Han Sora , Ka Hye In , Joo Hyun Jeong , Soh Su Jung , Yoo Kyung Hyun , Yang Young
Published: July 2019

Characterization of circulating tumor cells (CTC) is important to prevent death caused by the metastatic spread of cancer cells because CTC are associated with distal metastasis and poor prognosis of breast cancer. We have previously developed suspension cells (SC) using breast cancer cell lines and demonstrated their high metastatic potential. As survival of CTC is highly variable from a few hours to decades, herein we cultured SC for an extended time and named them adapted suspension cells (ASC). Silent mating‐type information regulation 2 homolog 1 (SIRT1) expression increased in ASC, which protected the cells from apoptosis. High SIRT1 expression was responsible for the suppression of nuclear factor kappa B (NF‐κB) activity and downregulation of reactive oxygen species (ROS) in ASC. As the inhibition of NF‐κB and ROS production in SIRT1‐depleted ASC contributed to the development of resistance to apoptotic cell death, maintenance of a low ROS level and NF‐κB activity in ASC is a crucial function of SIRT1. Thus, SIRT1 overexpression may play an important role in growth adaptation of SC because SIRT1 expression is increased in long‐term rather than in short‐term cultures.
Allergic contact dermatitis in atopic individuals: Results of a 30‐year retrospective study
Authors: Teo Ying , McFadden John P. , White Ian R. , Lynch Magnus , Banerjee Piu
Published: July 2019

Background

The association between atopic dermatitis (AD) and contact allergy, remains unclear, with studies to date showing conflicting results.

Objectives

To investigate the prevalence of contact allergy in AD individuals compared to those without AD.

Methods

Results of 46 250 patients patch tested in a single centre over a span of 30 years were reviewed, comparing those with AD with those without AD. Collected data were analysed with corrections for multiple confounding variables, including date of patch testing to account for changes in allergens tested over the period.

Results

Nine allergens showed a statistically significant difference between the two groups. Contact allergy to nickel, cobalt and primin was less likely to arise in those with AD, whilst substances found in topical dermatological products were more likely to be associated with AD.

Conclusions

This is the largest single centre study of contact sensitization in atopy reported to date. The previously reported association between contact allergy to sesquiterpene lactone and AD is reinforced. The decreased incidence of metal allergy suggests distinct immunological effector mechanisms in sensitization to these allergens. In keeping with previous publications, exposure to topical treatments for AD can result in sensitisation and contact allergy and clinicians should consider patch testing in AD individuals who report worsening of their skin despite continued treatment with topical medicaments.
Caspase‐3‐mediated GSDME activation contributes to cisplatin‐ and doxorubicin‐induced secondary necrosis in mouse macrophages
Authors: Mai Feng‐Yi , He Pengyan , Ye Jie‐Zhou , Xu Li‐Hui , Ouyang Dong‐Yun , Li Chen‐Guang , Zeng Qiong‐Zhen , Zeng Chen‐Ying , Zhang Cheng‐Cheng , He Xian‐Hui , Hu Bo
Published: July 2019

Objective

Induction of secondary necrosis/pyroptosis contributes to the toxicity of chemotherapeutic drugs, in which gasdermin E (GSDME) plays critical roles. This study aimed to explore whether GSDME is involved in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages.

Methods

RAW 264.7 cells and bone marrow‐derived macrophages (BMDMs) were treated with cisplatin or doxorubicin. Propidium iodide staining was used to assay necrosis, and immunoblotting was performed to detect protein expression. GSDME was knocked down by using small interfering RNA. Mice were injected intraperitoneally to evaluate toxicity to macrophages in vivo. Flow cytometry and immunofluorescence microscopy were adopted to analyse phenotypes of peritoneal cells. Cytokine levels were assayed by cytometric bead array.

Results

Both cisplatin and doxorubicin dose‐dependently induced necrosis in mouse RAW 264.7 macrophages and BMDMs. Accompanying this, multiple caspases were activated, concomitant with the cleavage of poly (ADP‐ribose) polymerase. Consistent with caspase‐3 activation, GSDME was cleaved to generate its N‐terminal fragment (GSDME‐NT), thus leading to secondary necrosis/pyroptosis. Inhibition of caspase‐3 significantly attenuated the generation of GSDME‐NT concurrently with decreased necrosis in macrophages. GSDME knockdown also evidently decreased the necrosis in RAW 264.7 and BMDMs. Besides, cisplatin administration depleted peritoneal macrophages in mice, which was associated with caspase‐3 activation and GSDME‐NT generation. Consistent with the macrophage depletion, cisplatin administration significantly decreased survival of mice with bacterial infection.

Conclusion

Chemotherapeutic cisplatin and doxorubicin exerted their cytotoxicity on macrophages partly by inducing caspase‐3/GSDME‐mediated secondary necrosis.
Increased pulmonary artery diameter is associated with reduced FEV1 in former World Trade Center workers
Authors: de la Hoz Rafael E. , Jeon Yunho , Reeves Anthony P. , San José Estépar Raúl , Liu Xiaoyu , Doucette John T. , Celedón Juan C. , Nolan Anna
Published: July 2019

Rationale

Occupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. Pulmonary arterial enlargement, as suggested by an increased ratio of the diameter of the pulmonary artery to the diameter of the aorta (PAAr) has been reported as a computed tomographic (CT) scan marker of adverse respiratory health outcomes, including WTC‐related disease. In this study, we sought to utilize a novel quantitative CT (QCT) measurement of PAAr to test the hypothesis that an increased ratio is associated with FEV1 below each subject's statistically determined lower limit of normal (FEV1 < LLN).

Methods

In a group of 1,180 WTC workers and volunteers, we examined whether FEV1 < LLN was associated with an increased QCT‐measured PAAr, adjusting for previously identified important covariates.

Results

Unadjusted analyses showed a statistically significant association of FEV1 < LLN with PAAr (35.3% vs 24.7%, P = 0.0001), as well as with height, body mass index, early arrival at the WTC disaster site, shorter WTC exposure duration, post‐traumatic stress disorder checklist (PCL) score, wall area percent and evidence of bronchodilator response. The multivariate logistic regression model confirmed the association of FEV1 < LLN with PAAr (OR 1.63, 95% CI 1.21, 2.20, P = 0.0015) and all the unadjusted associations, except for PCL score.

Conclusions

In WTC workers, FEV1 < LLN is associated with elevated PAAr which, although likely multifactorial, may be related to distal vasculopathy, as has been hypothesized for chronic obstructive pulmonary disease.
ARCHAEOMUSICA – Making the Past Audible
Authors: Both Arnd Adje
Published: July 2019

The author addresses the challenge and possible solutions related to museum display of archaeological sounds and music in museum contexts. By reflecting on his own work as a curator, the author illustrates his approach through examples drawn from the travelling exhibition ARCHAEOMUSICA – The Sounds and Music of Ancient Europe. The exhibition was presented in a variety of museums between 2016 and 2018.
Pain or Gain? Chinese Experience of Capital Account Liberalization
Authors: Peng Hongfeng , Yu Jingwen
Published: July 2019

The neoclassical growth model predicts that capital account liberalization could potentially enhance economic performance; however, there is no consistent empirical evidence to support this positive association. Using a novel dataset of Chinese capital account openness, this paper demonstrates a positive relationship between capital account liberalization and aggregate economic performance. The difference‐indifferences method is used to capture the causal effect of capital account liberalization on economic performance by taking advantage of variations in both external financial dependence and the progress of capital account openness. We investigate three channels that could strengthen this positive relationship using a firm‐level dataset. We find that capital account liberalization could: (i) alleviate the degree of resource misallocation, and this effect is more significant in industries relying heavily on external finance and in regions with more favorable business environments; (ii) enhance firms’ total factor productivity; and (iii) promote innovation. Our findings suggest that a strategy of gradual openness will leave some leeway not only for improvement in domestic markets but also to mitigate exposure to unfavorable global shocks.
Medical and non‐medical cannabis use and risk of prescription opioid use disorder: Findings from propensity score matching
Authors: Liang Di , Wallace Mark S. , Shi Yuyan
Published: July 2019

Introduction and Aims

Previous research suggested that cannabis use was associated with increased risks of prescription opioid misuse and use disorder. This study examined whether these associations differed by cannabis use purpose.

Design and Methods

This is a secondary analysis of cross‐sectional surveys with propensity score matching. Medical cannabis users (N = 1295), cannabis dual users with both medical and non‐medical purposes (N = 707) and non‐medical cannabis users (N = 18 666) were compared with cannabis non‐users (N = 57 196) in the pooled 2013–2016 US nationally representative National Survey on Drug Use and Health. Propensity score models were applied to match cannabis non‐users to cannabis users with different purposes with respect to potential confounders in individual socioeconomic characteristics, other substance use disorders and health conditions. In a matched sample, logistic regressions were used to assess associations.

Results

Propensity score matching considerably improved the balance of the potential confounders between cannabis non‐users and users. In a matched sample, non‐medical cannabis use was associated with increased risks of prescription opioid misuse (OR = 3.15, 95%CI: 2.89–3.44) and use disorder (OR = 2.52, 95%CI: 2.06–3.10). Cannabis dual use and medical cannabis use were associated with increased risks of prescription opioid misuse (OR = 2.55, 95%CI: 1.78–3.65; OR = 2.15, 95%CI: 1.58–2.91, respectively), but they were not associated with prescription opioid use disorder.

Discussion and Conclusions

Medical and non‐medical cannabis use both were both associated with increased risks of prescription opioid misuse. Medical cannabis use, however, was not associated with prescription opioid use disorder, and non‐medical cannabis was. There appeared to be differential associations between cannabis use and prescription opioid use disorder by cannabis use purpose.
Towards a unified framework for connectivity that disentangles movement and mortality in space and time
Authors: Fletcher Robert J. , Sefair Jorge A. , Wang Chao , Poli Caroline L. , Smith Thomas A. H. , Bruna Emilio M. , Holt Robert D. , Barfield Michael , Marx Andrew J. , Acevedo Miguel A.
Published: July 2019

Predicting connectivity, or how landscapes alter movement, is essential for understanding the scope for species persistence with environmental change. Although it is well known that movement is risky, connectivity modelling often conflates behavioural responses to the matrix through which animals disperse with mortality risk. We derive new connectivity models using random walk theory, based on the concept of spatial absorbing Markov chains. These models decompose the role of matrix on movement behaviour and mortality risk, can incorporate species distribution to predict the amount of flow, and provide both short‐ and long‐term analytical solutions for multiple connectivity metrics. We validate the framework using data on movement of an insect herbivore in 15 experimental landscapes. Our results demonstrate that disentangling the roles of movement behaviour and mortality risk is fundamental to accurately interpreting landscape connectivity, and that spatial absorbing Markov chains provide a generalisable and powerful framework with which to do so.
Prospective study of the additional benefit of plexus magnetic resonance imaging in the diagnosis of chronic inflammatory demyelinating polyneuropathy
Authors: Jomier F. , Bousson V. , Viala K. , Péréon Y. , Magot A. , Cauquil C. , Bouhour F. , Vial C. , Bedat‐Millet A.‐L. , Taithe F. , Bresch S. , Siri A. , Kubis N. , Lozeron P.
Published: July 2019

Background and purpose

Hypertrophy/signal hyperintensity and/or gadolinium enhancement of plexus structures on magnetic resonance imaging (MRI) are observed in two‐thirds of cases of typical chronic inflammatory demyelinating polyneuropathy (CIDP). The objective of our study was to determine the additional benefit of plexus MRI in patients referred to tertiary centers with baseline clinical and electrophysiological characteristics suggestive of typical or atypical CIDP.

Methods

A total of 28 consecutive patients with initial suspicion of CIDP were recruited in nine centers and followed for 2 years. Plexus MRI data from the initial assessment were reviewed centrally. Physicians blinded to the plexus MRI findings established the final diagnosis (CIDP or neuropathy of another cause). The proportion of patients with abnormal MRI was analyzed in each group.

Results

Chronic inflammatory demyelinating polyneuropathy was confirmed in 14 patients (50%), as were sensorimotor CIDP (n = 6), chronic immune sensory polyradiculoneuropathy (n = 2), motor CIDP (n = 1) and multifocal acquired demyelinating sensory and motor neuropathy (n = 5). A total of 37 plexus MRIs were performed (17 brachial, 19 lumbosacral and 8 in both localizations). MRI was abnormal in 5/37 patients (14%), all of whom were subsequently diagnosed with CIDP [5/14(36%)], after an atypical baseline presentation. With plexus MRI results masked, non‐invasive procedures confirmed the diagnosis of CIDP in all but one patient [1/14 (7%)]. Knowledge of the abnormal MRI findings in the latter could have prevented nerve biopsy being performed.

Conclusion

Systematic plexus MRI in patients with initially suspected CIDP provides little additional benefit in confirming the diagnosis of CIDP.
Recent insights into the genotype–phenotype relationship from massively parallel genetic assays
Authors: Kemble Harry , Nghe Philippe , Tenaillon Olivier
Published: July 2019

With the molecular revolution in Biology, a mechanistic understanding of the genotype–phenotype relationship became possible. Recently, advances in DNA synthesis and sequencing have enabled the development of deep mutational scanning assays, capable of scoring comprehensive libraries of genotypes for fitness and a variety of phenotypes in massively parallel fashion. The resulting empirical genotype–fitness maps pave the way to predictive models, potentially accelerating our ability to anticipate the behaviour of pathogen and cancerous cell populations from sequencing data. Besides from cellular fitness, phenotypes of direct application in industry (e.g. enzyme activity) and medicine (e.g. antibody binding) can be quantified and even selected directly by these assays. This review discusses the technological basis of and recent developments in massively parallel genetics, along with the trends it is uncovering in the genotype–phenotype relationship (distribution of mutation effects, epistasis), their possible mechanistic bases and future directions for advancing towards the goal of predictive genetics.
The interplay of protein–ligand and water‐mediated interactions shape affinity and selectivity in the LAO binding protein
Authors: Vergara Renan , Romero‐Romero Sergio , Velázquez‐López Isabel , Espinoza‐Pérez Georgina , Rodríguez‐Hernández Annia , Pulido Nancy O. , Sosa‐Peinado Alejandro , Rodríguez‐Romero Adela , Fernández‐Velasco Daniel Alejandro
Published: July 2019

The study of binding thermodynamics is essential to understand how affinity and selectivity are acquired in molecular complexes. Periplasmic binding proteins (PBPs) are macromolecules of biotechnological interest that bind a broad number of ligands and have been used to design biosensors. The lysine‐arginine‐ornithine binding protein (LAO) is a PBP of 238 residues that binds the basic amino acids l‐arginine and l‐histidine with nm and μm affinity, respectively. It has been shown that the affinity difference for arginine and histidine binding is caused by enthalpy, this correlates with the higher number of protein–ligand contacts formed with arginine. In order to elucidate the structural bases that determine binding affinity and selectivity in LAO, the contribution of protein–ligand contacts to binding energetics was assessed. To this end, an alanine scanning of the LAO‐binding site residues was performed and arginine and histidine binding were characterized by isothermal titration calorimetry and X‐ray crystallography. Although unexpected enthalpy and entropy changes were observed in some mutants, thermodynamic data correlated with structural information, especially, the binding heat capacity change. We found that selectivity is conferred by several residues rather than exclusive arginine–protein interactions. Furthermore, crystallographic structures revealed that protein–ligand contributions to binding thermodynamics are highly influenced by the solvent. Finally, we found a similar backbone conformation in all the closed structures obtained, but different structures in the open state, suggesting that the binding site residues of LAO play an important role in stabilizing not only the holo conformation, but also the apo state.

Database

Structural data are available in the Protein Data Bank database under the accession numbers 6MLE, 6MLN, 6MLG, 6MKX, 6MLI, 6MLA, 6MKU, 6MKW, 6ML0, 6MLD, 6MLV, 6MLO, 6MLP, 6ML9, 6MLJ.
Measuring the symptomatic, physical, emotional and social impacts of dry mouth: A qualitative study
Authors: Gibson Barry , Periyakaruppiah Karthik , Thornhill Martin H. , Baker Sarah R. , Robinson Peter G.
Published: July 2019

Objective

To explore the impacts of dry mouth in order to develop a comprehensive condition‐specific OHRQoL measure.

Background

Dry mouth has been shown to have significant, if not more severe impacts on OHRQoL, than dental caries. Yet there remain few studies reporting on how to develop a comprehensive measure of the impact of dry mouth on OHRQoL.

Methods

This study was a qualitative study using semi‐structured interviews. Data were collected from a purposive sample of 17 people with dry mouth (14 women, three men). The sample was drawn to capture a comprehensive range of impacts of dry mouth. These interviews were analysed using a framework approach informed by existing functionalist approaches to OHRQoL.

Results

Participants reported a huge range of symptoms associated with perceived dry mouth resulting in extensive impacts on physical, emotional (psychological) and social functioning. Dry mouth could also result in restrictions in social participation which, under some conditions, could be disabling. These impacts were modified by psychological, social and environmental factors.

Conclusions

If we are to measure the impacts of oral conditions, it is important that this is done systematically and with reference to existing conceptual models of health. Current measures of the impact of dry mouth cover symptoms, discomfort and physical impacts along with some aspects of how people cope with the condition. This study proposes a more comprehensive approach that includes the full range of impacts people experience. Such an approach may enable us to focus on “downstream” and “upstream” interventions for dry mouth.
Real‐world effects of long‐term rifaximin treatment for Japanese patients with hepatic encephalopathy
Authors: Suzuki Hiroyuki , Sezaki Hitomi , Suzuki Fumitaka , Kasuya Kayoko , Sano Tomoya , Fujiyama Shunichiro , Kawamura Yusuke , Hosaka Tetsuya , Akuta Norio , Saitoh Satoshi , Kobayashi Masahiro , Arase Yasuji , Ikeda Kenji , Suzuki Yoshiyuki , Kumada Hiromitsu
Published: July 2019

Aim

Rifaximin (RFX) improves hepatic encephalopathy (HE). However, information on long‐term treatment with RFX is limited. In this study, we aimed to investigate the effect of long‐term treatment with RFX on HE and liver function. Moreover, we investigated factors associated with the recurrence of HE under RFX treatment.

Methods

In this retrospective cohort study, we consecutively enrolled 65 patients with HE who initiated RFX treatment (1200 mg/day) in our hospital from January 2017 to June 2018. We evaluated liver function test results, including blood ammonia levels, and the recurrence rate of HE after RFX treatment.

Results

The median follow‐up duration was 41.6 weeks (range, 1.4–96.7 weeks). The blood ammonia level significantly declined from 157 to 86 μg/dL at 4 weeks after RFX treatment (P < 0.01), and the effect was prolonged. Furthermore, Child–Pugh score decreased in 51% (26/51) of the patients at 12 weeks during RFX treatment. The recurrence rate of HE after RFX treatment was 26.2% (17/65), and presence of ascites at baseline was identified as the only independent risk factor for HE recurrence (hazard ratio 4.71; 95% confidence interval, 1.27–17.5; P = 0.02). The cumulative recurrence rate of HE was significantly lower in patients without ascites than in patients with ascites at baseline (13.8% vs. 50.8%, P = 0.001).

Conclusions

Long‐term treatment with RFX was beneficial for HE and liver function in patients with HE. Furthermore, the recurrence rate of HE was low in RFX‐treated patients without ascites. Thus, long‐term treatment with RFX could be effective for the management of Japanese patients with HE.
An Examination of the Biblical Evidence for Open Theism
Authors: Yöney Ferhat
Published: July 2019

Open Theist theologians argue that their view of divine foreknowledge and providence is the correct interpretation of the Bible, and suggest some biblical evidence to support this claim. Among these theologians, Gregory A. Boyd’s case is the most systematic, and also the most comprehensive and rigorous. Taking into consideration (1) the main philosophical claims of Open Theism and its main rivals, namely Calvinism and Molinism, and (2) Open Theist theologians’ interpretative principles for the Bible, the biblical evidence for Open Theism suggested by Boyd can be classified into three groups according to their strength. I will argue that the first group of themes has no evidential value for Open Theism, since these themes can be interpreted just as plausibly from a Calvinist or Molinist perspective. By contrast, the second group of themes has some evidential value and thus constitutes prima facie evidence for Open Theism, since these themes make most sense under an Open Theist interpretation. However, these themes also make some sense on a Molinist reading. The third group of themes, I argue, has most evidential value for Open Theism, since it seems hard to reconcile these themes either with Calvinism or Molinism.
Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma
Authors: Weyerer Veronika , Weisser Rebecca , Moskalev Evgeny A , Haller Florian , Stoehr Robert , Eckstein Markus , Zinnall Ulrike , Gaisa Nadine T , Compérat Eva , Perren Aurel , Keck Bastian , Allory Yves , Kristiansen Glen , Wullich Bernd , Agaimy Abbas , Hartmann Arndt , Bertz Simone
Published: July 2019

Aims

Nested variant of urothelial carcinoma (NVUC) is rare, and only a few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. The aim of this study was to characterise NVUC at the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype.

Methods and results

Sixty NVUC cases were collected from different departments. TERT promoter mutation analysis was carried out in all samples using SNaPshot analysis. Targeted sequencing of 48 cancer‐related genes by next‐generation sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 and CK20 were used to elucidate the molecular subtype. A total of 62.5% of NVUC cases harboured a mutation of the TERT promoter. Additionally, TP53, JAK3 and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20.

Conclusions

In summary, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterised by mutations of the Wnt and inflammatory pathways, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer.
Evaluating Elizabeth Grosz's Biological Turn
Authors: Trappes Rose
Published: July 2019

Elizabeth Grosz's interpretation of Darwinian evolutionary theory to ground a feminist ontology of biology has been particularly controversial. Most critics have understood Grosz as supporting her theory with empirical evidence, and they criticize her for being either inaccurate or uncritical of and overly dependent on science. I argue that Grosz reads Darwin as a philosopher in a Deleuzian and Irigarayan sense, and that Grosz's project is therefore better understood in terms of its ethical and political goals rather than in terms of empirical adequacy. Employing this evaluative framework leads to a novel route for critique of Grosz's ontology in terms of its reliance on the Darwinian distinction between organism and environment. I conclude that Grosz's work is valuable for the way it maintains ethical and political considerations in feminist ontological debates, and that introducing a more sensitive understanding of the organism–environment relation will lead us closer to a truly feminist ontology of biology.
Legal Techniques for Rationalizing Biased Judicial Decisions: Evidence from Experiments with Real Judges
Authors: Liu John Zhuang , Li Xueyao
Published: July 2019

Judges rarely reveal their real reasoning in their opinions when they are influenced by factors that they know they should not consider. The natural next question is how, when a judge is improperly influenced, he or she reasons to justify a biased decision. In a set of experiments using incumbent Chinese judges, we first replicated the findings of previous studies that showed judges can be influenced by extra‐legal factors. More importantly, we showed that judges may employ a range of legal techniques to rationalize decision biases: they interpret legal standards and legal concepts strategically, finesse the applicability of law, infer or deny causation and foreseeability, and draw different conclusions from facts. Our findings provide a more realistic understanding of how judges behave, and cast doubt on reasoned elaboration as a guarantee of judicial transparency and trustworthiness.
Formation and characterization of the gas–solid phase in rice cake fermented with Brettanomyces (ZSM‐001) and Lactobacillus (ZSM‐002)
Authors: Chen Chen , Wen Ya , Jia CaiHua , Zhao SiMing , Niu Meng , Zhang BinJia , Xiong ShanBai
Published: July 2019

The formation and characteristics of the gas–solid phase in rice cakes fermented with Brettanomyces custersii (ZSM‐001) and Lactobacillus plantarum (ZSM‐002) were investigated. The morphological structure and microstructure of fermented rice cakes were observed with a LIDE 210 scanner and a confocal laser scanning microscope respectively. The results showed that the number of holes significantly increased through the whole phase, whereas the average pore size initially decreased significantly, and then increased during 8–12 hr. In addition, differences in pressure and temperature promoted the combination of bubbles, resulting in the appearance of radial morphological structures during the steaming process. This study found that the main ingredients were linked to the morphological structure and microstructural characteristics of fermented rice cake, further influencing the texture. The content of soluble protein and water at 12 hr were 2.66 mg/g and 50.76%, and the amount of reduce sugar at 8 hr was 46.45 mg/g. These maximums could contribute to the formation of more holes with smaller size, and improve the pliable and viscoelastic texture (i.e., 596.73 g of hardness, 0.97 of elasticity, and 0.78 of viscosity). Overall, this work may provide a theoretical basis for the quality control of fermented rice cake.

Practical Applications

A high content of soluble protein and moisture in the rice paste could promote the formation of the film, wrapping of bubbles and development of dense holes. More and smaller bubbles could generate a uniform continuous solid matrix, resulting in the ideal textural parameters of fermented rice cake (low hardness, high elasticity, and high viscosity). This work may provide a theoretical basis for the quality control of fermented rice cake through an improved understanding of the gas–solid phase formation.
Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation
Authors: Ruiz‐Sauri Amparo , Orduña‐Valls Jorge M. , Blasco‐Serra Arantxa , Tornero‐Tornero Carlos , Cedeño David L. , Bejarano‐Quisoboni Daniel , Valverde‐Navarro Alfonso A. , Benyamin Ramsin , Vallejo Ricardo
Published: July 2019

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, intersection T9/T10, T10 and T11) were obtained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between the glial cells in a segment, and glial cells in white and gray matter. Results show that glia to neuron ratio in the posterior gray matter of the human spinal cord within the T8–T11 vertebral region is in the range 11 : 1 to 13 : 1, although not significantly different among vertebral segments. Glia cells are more abundant in gray matter than in white matter, whereas astrocytes and oligodendrocytes are more abundant than microglia (40 : 40 : 20). Interestingly, the population of oligodendrocytes in the T9/T10 intersection is significantly larger than in any other segment. In conclusion, glial cells are the predominant bodies in the posterior gray and white matter of the T8–T11 segments of the human spinal cord. Given the crucial role of glial cells in the development and maintenance of neuropathic pain, and their electrophysiological characteristics, anatomical determination of the ratio of different cell populations in spinal segments commonly exposed to SCS is fundamental to understand fully the biological effects observed with this therapy.
Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β
Authors: Mannino Giuseppe , Caradonna Fabio , Cruciata Ilenia , Lauria Antonino , Perrone Anna , Gentile Carla
Published: July 2019

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.
STAT1‐NFκB crosstalk triggered by interferon gamma regulates noradrenaline‐induced pineal hormonal production
Authors: Barbosa Lima Leila Eliza , Muxel Sandra Marcia , Kinker Gabriela S. , Carvalho‐Sousa Cláudia Emanuele , da Silveira Cruz‐Machado Sanseray , Markus Regina P. , Fernandes Pedro Augusto Carlos Magno
Published: July 2019

Melatonin production by pineal glands is modulated by several immune signals. The nuclear translocation of nuclear factor kappa‐B (NFκB) homodimers, lacking transactivation domains, once induced by lipopolysaccharide (LPS) or tumor necrosis factor (TNF), inhibits the expression of Aanat gene and the synthesis of noradrenaline (NA)‐induced melatonin. Interferon gamma (IFN‐γ), on the other hand, increases melatonin synthesis. Furthermore, this cytokine activates the signal transducer as well as the activator of transcription 1 (STAT1) pathway, which was never evaluated as a melatonin synthesis modulator before. Reports demonstrated that IFN‐γ might also activate NFκB. The present study evaluated the role of STAT1‐NFκB crosstalk triggered by IFN‐γ regarding the regulation of NA‐induced pineal glands’ hormonal production. Moreover, IFN‐γ treatment increased NA‐induced Aanat transcription, in addition to the synthesis of N‐acetylserotonin (NAS) and melatonin. These effects were associated with STAT1 nuclear translocation, confirmed by the co‐immunoprecipitation of STAT1 and Aanat promoter. Pharmacological STAT1 enhancement augmented NA‐induced Aanat transcription as well as NAS and melatonin production. Additionally, IFN‐γ induced the nuclear translocation of RelA‐NFκB subunits. The blockade of this pathway prevented IFN‐γ effects on the pineal function. The present data show that STAT1 and NFκB crosstalk controls melatonin production through a synergistic mechanism, disclosing a new integrative mechanism regarding pineal hormonal activity control.
Young drivers who continue to drive while sleepy: What are the associated sleep‐ and driving‐related factors?
Authors: Watling Christopher N.
Published: July 2019

Crashes due to sleepiness account for a substantial proportion of road crash incidents. The purpose of the current study was to examine several sleep‐related factors and driving‐related factors for their association with self‐reports of continuing to drive while sleepy. In total 257 young drivers aged 18–25 years completed an online survey that assessed factors such as sleep quality, sleep duration and consistency, excessive daytime sleepiness, experiences with sleepiness and their driving‐related behaviours. The results demonstrate that being older, having a perceived ability to overcome sleepiness, committing more highway code violations and having experienced a sleep‐related close call were positively associated with an increased likelihood of continuing to drive while sleepy. The obtained results highlight the acceptance of risky driving behaviours among some younger drivers. Younger drivers’ risky driving behaviour is certainly a road safety concern given the impairment associated with sleepiness and their over‐representation in road crash incidents.
Identifying dimensions of fatigue in haemodialysis important to patients, caregivers and health professionals: An international survey
Authors: Ju Angela , Unruh Mark , Davison Sara N , Dapueto Juan , Dew Mary A , Fluck Richard , Germain Michael , Jassal Sarbjit V , Obrador Gregorio , O'Donoghue Donal , Howell Martin , O'Lone Emma , Shen Jenny I , Craig Jonathan C , Tong Allison ,   for The SONG‐HD Initiative
Published: July 2019

Background

Patient‐reported outcome measures of fatigue used in research in haemodialysis vary widely in the dimensions assessed; and the importance of these dimensions to patients and health professionals is unknown. This study aimed to identify the most important dimensions of fatigue to assess in patients on haemodialysis participating in trials.

Methods

In an international survey, patients/caregivers and health professionals rated the absolute and relative importance of content and measurement dimensions to include in a core outcome measure of fatigue. A 9‐point Likert scale (7–9 indicating critical importance) was used to assess absolute importance and best‐worst scale was used to assess importance of each dimension compared to others.

Results

In total, 169 patients/caregivers and 336 health professionals from 60 countries completed the survey. Both groups (patients/caregivers and health professionals) rated life participation (7.55), tiredness (7.40), level of energy (7.37), ability to think clearly (7.15), post‐dialysis fatigue (7.13), motivation (7.03) and ability to concentrate (7.03) as critically important (mean Likert score greater than 7) content dimensions to include in a core outcome measure. Compared to patients and caregivers, health professionals rated post‐dialysis fatigue, memory and verbal abilities more highly. Based on the relative importance scores, life participation was ranked most highly above all content dimensions. Severity was rated and ranked the most important measurement dimension by all stakeholders.

Conclusion

A core outcome measure of fatigue should assess impact of fatigue on life participation, tiredness and level of energy, using a severity scale. A consistent and valid measurement of fatigue will improve the value of trials in supporting decision‐making based on this important outcome.
Toxoplasmic encephalitis of basal ganglia with tumor‐like features proven by pathogen‐specific polymerase chain reaction and direct DNA sequencing
Authors: Li Yunyun , Zhu Zhi , Wang Jianjun
Published: July 2019

We report a case of a young female patient who developed progressive neurological dysfunction with a ring‐enhancing tumor‐like nodule on brain magnetic resonance imaging. Urgent surgery was performed to remove the mass in the left basal ganglia. Pathological findings showed that the necrotic brain areas were accompanied by congestion, edema, discrete hemorrhage, and intestinal and perivascular lymphohistiocytic infiltration. Immunohistochemical staining results showed that Toxoplasma gondii (T. gondii) immunoreactivity was detected in both cysts and tachyzoites in these areas. The glycerol‐3‐phosphate dehydrogenase gene (B1) of T. gondii was amplified by sequence‐specific polymerase chain reaction (PCR) and the PCR products were bi‐directional Sanger sequenced. A 195 bp consensus sequence of the gene B1 was found to be 98% identical to a reference T. gondii sequence (GenBank accession No. kx270373). The final diagnosis was toxoplasmic encephalitis in the left basal ganglia. This report suggests that PCR and bi‐directional DNA sequencing of T. gondii gene might be the most convenient and rapid tools for accurate diagnosis of toxoplasmic encephalitis .
On the evolutionary significance of horizontal gene transfers in plants
Authors: Wickell David A. , Li Fay‐Wei
Published: July 2019

Horizontal gene transfer (HGT) has long been seen as a crucial process in the evolution of prokaryotic species, but until recently it was thought to have little, if any, effect on the evolution of eukaryotic life forms. Detecting and describing HGT events in eukaryotes is difficult, making this phenomenon at times controversial. However, modern advances in genomics and bioinformatics have radically altered our view of HGT in eukaryotes, especially in plants. It now appears that HGT to and from plant lineages is more common than previously suspected. Importantly, the transfer of functional nuclear genes with adaptive significance has been reported in numerous taxa. Here we review several recent studies that have found evidence of the horizontal transfer of nuclear genes, and argue that HGT has undoubtedly had profound impacts on plant evolution as a whole.
The association between psychological stress and metabolic syndrome: A systematic review and meta‐analysis
Authors: Kuo Wan‐chin , Bratzke Lisa C. , Oakley Linda D. , Kuo Fanglin , Wang Haocen , Brown Roger L.
Published: July 2019

Literature suggests that occupational stress is associated with a higher risk of metabolic syndrome; yet less is known whether other sources of stress have similar effects. This review aims to examine whether the relationship between psychological stress and metabolic syndrome differs by sources of stress. Three databases (PubMed, Web of Science, and CINAHL) were searched for eligible articles; meta‐analyses were conducted using the random effects model. After controlling for covariates, adults in the high‐stress groups had 45% higher chance of having metabolic syndrome than adults in the low‐stress groups (odds ratio [OR] = 1.450; 95% confidence interval [CI], 1.211‐1.735; P < .001). The subsequent meta‐analysis based on cross‐sectional studies suggested that occupational stress showed the strongest effect (OR = 1.692; 95% CI, 1.182‐2.424; P = .004), while perceived general stress showed the weakest effect (OR = 1.217; 95% CI, 1.017‐1.457; P = .032). Unfortunately, there is a lack of longitudinal studies for subsequent meta‐analysis based on sources of stress. There is a need for continued research to examine the long‐term relationship between different sources of stress and the risk of metabolic syndrome. Traditional recommendations for preventing metabolic syndrome (eg, low‐fat diet and exercise) may not achieve the best outcome if clinicians overlook patients' psychosocial stress.
I becomes we, but where is me? The unity–division paradox when caring for a relative with dementia: A qualitative study
Authors: Tierney Stephanie , Tutton Elizabeth , Seers Kate
Published: July 2019

Background

The number of older people living with dementia is increasing. Admiral Nurses work with these individuals and their families in the UK to manage challenges associated with the condition, providing guidance, advice and reassurance, alongside practical solutions.

Aim

To explore the input of Admiral Nurses as part of people's journey to becoming and being a carer for someone with dementia.

Design

A qualitative study was conducted to describe and understand how Admiral Nurses are experienced and encountered by carers as part of their narrative around supporting a relative with dementia.

Methods

Semi‐structured interviews were conducted with 19 carers between November 2017–April 2018. They lasted between 45 and 90 min. Thematic analysis was used to interpret data.

Findings

An overarching concept of “the unity–division paradox” was derived from the data. This highlights the complex interchange between the carer with (a) the person with dementia, (b) other individuals and (c) external services. Such interactions can make carers feel part of a larger network (unity) but also as if they are on their own, fighting on behalf of the person with dementia (division). This concept was underpinned by the following themes: (a) I becomes we; (b) My private world is encroached by dementia; (c) I’m left navigating an unwieldy system; (d) Are you with or against us?; and (e) Recreating boundaries to rediscover me.

Conclusion

The identity and unique characteristics and interests of those caring for a person with dementia may be lost as they encounter tensions associated with the unity–division paradox. Admiral Nurses can help carers feel less alone in managing internal and external struggles by supporting them to do their best for a loved one with dementia.

Implications for practice

Understanding carers’ experience and supporting their work may help to increase and sustain their capacity to provide care.
Clinical and brain structural effects of the Illness Management and Recovery program in middle‐aged and older patients with schizophrenia
Authors: Nakamura Ryota , Asami Takeshi , Yoshimi Asuka , Kato Daiji , Fujita Emi , Takaishi Masao , Yoshida Haruhisa , Yamaguchi Hiroyuki , Shiozaki Kazumasa , Kase Akihiko , Hirayasu Yoshio
Published: July 2019

Aims

In this study, we implemented the Illness Management and Recovery (IMR) program for middle‐aged and older patients with schizophrenia hospitalized for long periods and assessed the effect of the IMR program on psychiatric symptoms and psychosocial function. The effects of the IMR program on brain structure were also evaluated.

Methods

The IMR program was implemented for 19 patients with schizophrenia; 17 patients with schizophrenia receiving treatment as usual (TAU) were also recruited as controls. In all patients, mean age was 61.4 years (range, 50–77 years) and mean hospitalization duration was 13.1 years (range, 1–31 years) at enrollment. Structural magnetic resonance images and Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores as clinical variables were obtained at the beginning and end of the IMR program. Longitudinal analyses were performed to compare the effects of the IMR program on clinical symptoms and cortical thickness in the superior temporal gyrus (STG) between the IMR and TAU groups.

Results

Significant improvements in GAF scores and the total, Insight and Judgment, and Positive components of the PANSS were found in the IMR group compared with the TAU group. Cortical thickness in the left STG was preserved in the IMR group compared with the TAU group.

Conclusions

This is the first report demonstrating the effectiveness of the IMR program for improving psychotic symptoms and psychosocial function and protecting brain structure in middle‐aged and older inpatients with schizophrenia hospitalized for long periods.