bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of co‐expression modules related to survival by WGCNA and identification of potential prognostic biomarkers in glioblastoma
Authors: Zhou Jing , Guo Hao , Liu Likun , Hao Shulan , Guo Zhi , Zhang Fupeng , Gao Yu , Wang Zhi , Zhang Weiwei
Published: January 2021

Glioblastoma (GBM) is a malignant brain tumour with poor prognosis. The potential pathogenesis and therapeutic target are still need to be explored. Herein, TCGA expression profile data and clinical information were downloaded, and the WGCNA was conducted. Hub genes which closely related to poor prognosis of GBM were obtained. Further, the relationship between the genes of interest and prognosis of GBM, and immune microenvironment were analysed. Patients from TCGA were divided into high‐ and low‐risk group. WGCNA was applied to the high‐ and low‐risk group and the black module with the lowest preservation was identified which could distinguish the prognosis level of these two groups. The top 10 hub genes which were closely related to poor prognosis of patients were obtained. GO analysis showed the biological process of these genes mainly enriched in: Cell cycle, Progesterone‐mediated oocyte maturation and Oocyte meiosis. CDCA5 and CDCA8 were screened out as the genes of interest. We found that their expression levels were closely related to overall survival. The difference analysis resulted from the TCGA database proved both CDCA5 and CDCA8 were highly expressed in GBM. After transfection of U87‐MG cells with small interfering RNA, it revealed that knockdown of the CDCA5 and CDCA8 could influence the biological behaviours of proliferation, clonogenicity and apoptosis of GBM cells. Then, single‐gene analysis was performed. CDCA5 and CDCA8 both had good correlations with genes that regulate cell cycle in the p53 signalling pathway. Moreover, it revealed that high amplification of CDCA5 was correlated with CD8+ T cells while CDCA8 with CD4+ T cells in GBM. These results might provide new molecular targets and intervention strategy for GBM.
Knockout of MYOM1 in human cardiomyocytes leads to myocardial atrophy via impairing calcium homeostasis
Authors: Hang Chengwen , Song Yuanxiu , Li Ya’nan , Zhang Siyao , Chang Yun , Bai Rui , Saleem Amina , Jiang Mengqi , Lu Wenjing , Lan Feng , Cui Ming
Published: January 2021

Myomesin‐1 (encoded by MYOM1 gene) is expressed in almost all cross‐striated muscles, whose family (together with myomesin‐2 and myomesin‐3) helps to cross‐link adjacent myosin to form the M‐line in myofibrils. However, little is known about its biological function, causal relationship and mechanisms underlying the MYOM1‐related myopathies (especially in the heart). Regrettably, there is no MYMO1 knockout model for its study so far. A better and further understanding of MYOM1 biology is urgently needed. Here, we used CRISPR/Cas9 gene‐editing technology to establish an MYOM1 knockout human embryonic stem cell line (MYOM1−/− hESC), which was then differentiated into myomesin‐1 deficient cardiomyocytes (MYOM1−/− hESC‐CMs) in vitro. We found that myomesin‐1 plays an important role in sarcomere assembly, contractility regulation and cardiomyocytes development. Moreover, myomesin‐1‐deficient hESC‐CMs can recapitulate myocardial atrophy phenotype in vitro. Based on this model, not only the biological function of MYOM1, but also the aetiology, pathogenesis, and potential treatments of myocardial atrophy caused by myomesin‐1 deficiency can be studied.
Comparative genomic analysis of head and body/tail of pancreatic ductal adenocarcinoma at early and late stages
Authors: Zhang Xueyou , Feng Shi , Wang Qian , Huang Haitao , Chen Ruihan , Xie Qinfen , Zhang Wu , Wang Aodi , Zhang Shuirong , Wang Lingjian , Yao Ming , Ling Qi
Published: January 2021

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers, can be divided into head and body/tail cancers anatomically. We previously reported a prognostic relevance of tumour location in resectable PDAC. This study aimed to further explore the mechanism underlying the molecular diversity between the head and body/tail of PDACs. We detected tumour genomes in 154 resectable (surgery) and non‐resectable (biopsy) PDACs using a next‐generation sequencing panel. Wilcoxon's rank test or Fisher's exact test was used for evaluating associations between clinical characteristics, mutation frequency and survival probability between the two cohorts. Compared with pancreatic head cancers, pancreatic body/tail cancers showed significantly more enriched genomic alterations in KRAS (97.1% vs 82.4%, P = 0.004) and SMAD4 (42.0% vs 21.2%, P = 0.008). At early stages (I‐II), the SMAD4 mutation rate was significantly higher in pancreatic body/tail cancers than pancreatic head cancers (56.0% vs 26.5%, P = 0.021). At late stages (III‐IV), pancreatic body/tail cancers presented significantly higher KRAS mutation rate (100.0% vs 75.8%, P = 0.001), higher frequency of MAPK pathway mutation (100% vs 87.8%, P = 0.040) and lower rates of druggable genomic alterations (30.8% vs 57.6%, P = 0.030) than pancreatic head cancers. Our work points out that pancreatic body/tail cancer seems to be more malignant than pancreatic head cancer at late stages.
Exploring the five different genes associated with PKCα in bladder cancer based on gene expression microarray
Authors: Zhang Xiaotong , Zhang Jiarun , Zhang Hao , Liu Yang , Yin Lei , Liu Xi , Li Xuejie , Yu Xiuyue , Yao Jinlong , Zhang Zhe , Kong Chuize
Published: January 2021

Much progress has been made in understanding the mechanism of bladder cancer (BC) progression. Protein kinase C‐α (PKCα) is overexpressed in many kinds of cancers. Additionally, PKCα is considered an oncogene that regulates proliferation, invasion, migration, apoptosis and cell cycle in multiple cancers. However, the mechanism underlying how these cellular processes are regulated by PKCα remains unknown. In the present study, we used PKCα siRNA to knock down PKCα gene expression and found that down‐regulation of PKCα could significantly inhibit cell proliferation, migration and invasion and induce apoptosis and G1/S cell cycle arrest in vitro. Overexpression of PKCα promotes tumour growth in vivo. We applied cDNA microarray technology to detect the differential gene expression in J82 cells with PKCα knockdown and found that five key genes (BIRC2, BIRC3, CDK4, TRAF1 and BMP4) were involved in proliferation and apoptosis according to GO analysis and pathway analyses. Correlation analysis revealed a moderate positive correlation between PKCα expression and the expression of five downstream genes. BIRC2 and BIRC3 inhibit apoptosis, whereas CDK4, TRAF1 and BMP4 promote proliferation. Essentially, all five of these target genes participated in proliferation, and apoptosis was regulated by PKCα via the NF‐kB signalling pathway.
Freshening effect on the osmotic response of the Antarctic spiny plunderfish Harpagifer antarcticus
Authors: Vargas‐Chacoff Luis , Dann Francisco , Paschke Kurt , Oyarzún‐Salazar Ricardo , Nualart Daniela , Martínez Danixa , Wilson Jonathan M. , Guerreiro Pedro M. , Navarro Jorge M.
Published: January 2021

Global warming is having a significant impact around the world, modifying environmental conditions in many areas, including in zones that have been thermally stable for thousands of years, such as Antarctica. Stenothermal sedentary intertidal fish species may suffer due to warming, notably if this causes water freshening from increased freshwater inputs. Acute decreases in salinity, from 33 down to 5, were used to assess osmotic responses to environmental salinity fluctuations in Antarctic spiny plunderfish Harpagifer antarcticus, in particular to evaluate if H. antarcticus is able to cope with freshening and to describe osmoregulatory responses at different levels (haematological variables, muscle water content, gene expression, NKA activity). H. antarcticus were acclimated to a range of salinities (33 as control, 20, 15, 10 and 5) for 1 week. At 5, plasma osmolality and calcium concentration were both at their lowest, while plasma cortisol and percentage muscle water content were at their highest. At the same salinity, gill and intestine Na+‐K+‐ATPase (NKA) activities were at their lowest and highest, respectively. In kidney, NKA activity was highest at intermediate salinities (15 and 10). The salinity‐dependent NKA mRNA expression patterns differed depending on the tissue. Marked changes were also observed in the expression of genes coding membrane proteins associated with ion and water transport, such as NKCC2, CFTR and AQP8, and in the expression of mRNA for the regulatory hormone prolactin (PRL) and its receptor (PRLr). Our results demonstrate that freshening causes osmotic imbalances in H. antarcticus, apparently due to reduced capacity of both transport and regulatory mechanisms of key organs to maintain homeostasis. This has implications for fish species that have evolved in stable environmental conditions in the Antarctic, now threatened by climate change.
Concomitant use of an immunomodulator with ustekinumab as an induction therapy for Crohn's disease: A systematic review and meta‐analysis
Authors: Yoshihara Takeo , Shinzaki Shinichiro , Amano Takahiro , Iijima Hideki , Takehara Tetsuo , Inoue Nagamu , Uchino Motoi , Esaki Motohiro , Kobayashi Taku , Saruta Masayuki , Sugimoto Ken , Nakamura Shiro , Hata Keisuke , Hirai Fumihito , Hiraoka Sakiko , Fujii Toshimitsu , Matsuura Minoru , Matsuoka Katsuyoshi , Watanabe Kenji , Nakase Hiroshi , Watanabe Mamoru
Published: January 2021

Background and aim

Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin‐12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta‐analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients.

Methods

A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6–12 weeks. The quality of the included studies was assessed using the risk of bias in non‐randomized studies of interventions (ROBINS‐I) tools. The fixed‐effects model was used to calculate the pooled odds ratios.

Results

From 189 yielded articles, six including a total of 1507 patients were considered in this meta‐analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed‐effects model: 1.35, 95% confidence interval [1.06–1.71], P = 0.015). The heterogeneity among studies was low (I2 = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed.

Conclusion

The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST.
Older Adults without Desired Surrogates in a Nationally Representative Sample
Authors: Cohen Andrew B. , Costello Darcé M. , OʼLeary John R. , Fried Terri R.
Published: January 2021

BACKGROUND/OBJECTIVES

Little is known about older adults who have intact capacity but do not have a desired surrogate to make decisions if their capacity becomes impaired.

DESIGN

Cross‐sectional study of a nationally representative sample.

SETTING

National Social Life, Health, and Aging Project (NSHAP), 2005–2006.

PARTICIPANTS

Community‐dwelling older adults without known cognitive impairment, aged 57 to 85, interviewed as part of NSHAP (n = 2,767).

MEASUREMENTS

We examined demographic, medical, and social connectedness characteristics associated with answering “no” to this question: “Do you have someone who you would like to make medical decisions for you if you were unable, as for example if you were seriously injured or very sick?” Because many states permit nuclear family to make decisions for persons with no legally appointed health care agent, we used logistic regression to identify factors associated with individuals who were ill suited to this paradigm in the sense that they had nuclear family but did not have a desired surrogate.

RESULTS

Among NSHAP respondents, 7.5% (95% confidence interval = 6.4–8.7) did not have a desired surrogate. Nearly 90% of respondents without desired surrogates had nuclear family. Compared with respondents with desired surrogates, those without desired surrogates had lower indicators of social connectedness. On average, however, they had four confidants, approximately 70% socialized at least monthly, and more than 90% could discuss their health with a confidant. Among respondents who had nuclear family, few characteristics distinguished those with and without desired surrogates.

CONCLUSION

Nearly 8% of older adults did not have a desired surrogate. Most had nuclear family and were not socially disconnected. Older adults should be asked explicitly about a desired surrogate, and strategies are needed to identify surrogates for those who do not have family or would not choose family to make decisions for them.
Interrelationships between electricity, gas, and water consumption in large‐scale buildings
Authors: Movahedi Ali , Derrible Sybil
Published: January 2021

As cities keep growing worldwide, so does the demand for key resources such as electricity, gas, and water that residents consume. Meeting the demand for these resources can be challenging and it requires an understanding of the consumption patterns. In this study, we apply extreme gradient boosting to predict and analyze electricity, gas, and water consumption in large‐scale buildings in New York City and use SHapley Additive exPlanation to interpret the results. For this, the New York City's local law 84 extensive dataset was merged with the Primary Land Use Tax Lot Output dataset as well as with other socio‐economic datasets. Specifically, we developed and validated three models: electricity, gas, and water consumption. Overall, we find that electricity, gas, and water consumptions are highly interrelated, but the interrelationships are complex and not universal. The main factor influencing these interrelationships seems to be the technology used for space and water heating (i.e., electricity vs. gas). Building type also has a large impact on interrelationships (i.e., residential vs. nonresidential), especially between electricity and water. Moreover, we also find a nonlinear relationship between gas consumption and building intensity. The main results are summarized into seven major findings. Overall, this study contributes to the urban metabolism literature that ultimately aims to gain a fundamental understanding of how energy and resources are consumed in cities.
The Hippo pathway: Horizons for innovative treatments of peripheral nerve diseases
Authors: Feltri M. Laura , Weaver Michael R. , Belin Sophie , Poitelon Yannick
Published: January 2021

Initially identified in Drosophila, the Hippo signaling pathway regulates how cells respond to their environment by controlling proliferation, migration and differentiation. Many recent studies have focused on characterizing Hippo pathway function and regulation in mammalian cells. Here, we present a brief overview of the major components of the Hippo pathway, as well as their regulation and function. We comprehensively review the studies that have contributed to our understanding of the Hippo pathway in the function of the peripheral nervous system and in peripheral nerve diseases. Finally, we discuss innovative approaches that aim to modulate Hippo pathway components in diseases of the peripheral nervous system.
MULTISIDED PLATFORMS AND MARKETS: A SURVEY OF THE THEORETICAL LITERATURE
Authors: Sanchez‐Cartas Juan Manuel , León Gonzalo
Published: January 2021

Platforms are everywhere. The rise of Uber, Netflix, and Facebook has attracted a lot of attention to this business model. However, despite its relevance and presence in the digital economy, the definition of platforms, their main characteristics, the intuitions about how they set prices, solve coordination issues, or choose their ownership structure seem to be scattered in many papers. This review attempts to organize the last two decades of research on multisided platforms around three essential elements of platforms: price structure, network effects, and control rights. We highlight which definitions are used in the literature, how they are related to the defining characteristics of platforms, and what research has been made on those characteristics. We pay special attention to the research done on pricing, coordination problems, and ownership structure. We conclude by reviewing the theoretical evidence around monopolization and competition policy in multisided markets.
Grieving a Grandparent: The Importance of Gender and Multigenerational Relationships
Authors: Stokes Jeffrey E. , Kim Yijung K. , Kim Kyungmin , Fingerman Karen L.
Published: January 2021

Objective

This study examined adult grandchildren's experience of losing a grandparent in the context of a multigenerational family.

Background

Although the death of a grandparent in adulthood is often an expected life event, this loss may still result in grief for adult grandchildren. Furthermore, bereavement is not merely an individual experience, but a family one. Characteristics of the relationship between bereaved adult grandchildren and their bereaved middle‐generation parents may influence adult grandchildren's grief responses. This includes both structural (e.g., gender of parent; coresidence with parent) and emotional (e.g., relationship quality; worry about parent) aspects of this tie.

Method

Young adult grandchildren from Wave 2 of the Family Exchanges Study (2013, N = 204) reported on their recent grandparent loss experiences (N = 216) and relationships with their middle‐generation parents (N = 142).

Results

Three‐level multilevel models revealed that (a) grandsons who lost a grandmother reported significantly fewer grief symptoms than all other gender combinations; (b) worry about a middle‐generation parent was associated with higher grief symptoms, but; (c) this effect was significantly stronger when the middle‐generation parent was a mother, and when adult grandchildren were coresident with that bereaved parent. Finally, relationship quality with the middle‐generation parent was not associated with grief symptoms, irrespective of context.

Conclusion

Results highlight the intersection of emotional and structural aspects of multigenerational relationships following the death of a family member.
Estimating extreme cancellation rates in life insurance
Authors: Biagini Francesca , Huber Tobias , Jaspersen Johannes G. , Mazzon Andrea
Published: January 2021

This paper assesses the risk of a mass lapse event in life insurance. The rarity of the event and the complexity of policyholder behavior make the risk assessment of such a scenario difficult. Using a simulation study, we evaluate how different estimation methods can assess the risk of this scenario, using panel data at the company level. We then use the best‐performing method to estimate the probability distribution function of a mass cancellation event in the United States and Germany. We identify dependencies of the event on company and country characteristics, which have not been taken into account by regulating agencies. We also find that the current mass lapse scenario in Solvency II has no empirical foundation for the German market. We show that an empirically valid scenario leads to a significantly lower solvency capital requirement for the average German life insurer.
Meridionella gen. nov., a New Genus of Cystocloniaceae (Gigartinales, Rhodophyta) from the Southern Hemisphere, Including M. obtusangula comb. nov. and M. antarctica sp. nov.
Authors: Tonicelli Gina A. , Croce Maria Emilia , Díaz‐Tapia Pilar , Fredericq Suzanne , Freshwater David Wilson , Gauna Maria Cecilia , Parodi Elisa R. , Verbruggen Heroen , Hommersand Max H.
Published: January 2021

The classification of Cystoclonium obtusangulum has been questioned since the species was first described by Hooker and Harvey as Gracilaria? obtusangula. The objective of this study was to provide the first comprehensive taxonomic analysis of Cystoclonium obtusangulum, based on DNA sequences coupled with morphological observations made on syntype specimens and new collections. Sequence divergences of rbcL, UPA, and COI‐5P, and maximum‐likelihood phylogenies for rbcL and 18S demonstrated that specimens identified as Cystoclonium obtusangulum represent a clade of two distinct species that are distantly related to the generitype Cystoclonium purpureum. A new genus, Meridionella gen. nov., is proposed for this clade. The two species placed in this new genus were morphologically indistinguishable cryptic species, but have disjunct distributions, with Meridionella obtusangula comb. nov. found from temperate to cold coasts of South America and the Falkland Islands and Meridionella antarctica sp. nov., occurring in Antarctic waters. Vegetative and reproductive characters of Meridionella gen. nov. are described, and implications of our results for the biogeography of the family Cystocloniaceae are discussed.
Evaluation of argon‐induced hydrogen production as a method to measure nitrogen fixation by cyanobacteria
Authors: Wilson Samuel T. , Caffin Mathieu , White Angelicque E. , Karl David M.
Published: January 2021

The production of dihydrogen (H2) is an enigmatic yet obligate component of biological dinitrogen (N2) fixation. This study investigates the effect on H2 production by N2 fixing cyanobacteria when they are exposed to either air or a gas mixture consisting of argon, oxygen, and carbon dioxide (Ar:O2:CO2). In the absence of N2, nitrogenase diverts the flow of electrons to the production of H2, which becomes a measure of Total Nitrogenase Activity (TNA). This method of argon‐induced hydrogen production (AIHP) is much less commonly used to infer rates of N2 fixation than the acetylene reduction (AR) assay. We provide here a full evaluation of the AIHP method and demonstrate its ability to achieve high‐resolution measurements of TNA in a gas exchange flow‐through system. Complete diel profiles of H2 production were obtained for N2 fixing cyanobacteria despite the absence of N2 that broadly reproduced the temporal patterns observed by the AR assay. Comparison of H2 production under air versus Ar:O2:CO2 revealed the efficiency of electron usage during N2 fixation and place these findings in the broader context of cell metabolism. Ultimately, AIHP is demonstrated to be a viable alternative to the AR assay with several additional merits that provide an insight into cell physiology and promise for successful field application.
From NAFLD to MAFLD: Nurse and allied health perspective
Authors: Clayton Michelle , Fabrellas Núria , Luo Jinkai , Alghamdi Mohammed G. , Hafez Azaa , Qadiri Tahani Al , Owise Nevin , Attia Dina
Published: January 2021

Fatty liver disease associated with metabolic dysfunction is the most prevalent liver disease worldwide, though both patient and health professional still lack awareness of it. An international consensus panel has produced what is sure to be an influential report renaming the disease from non‐alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction) associated fatty liver disease (MAFLD) and suggesting how the disease should be diagnosed. This viewpoint explores the call from the perspective of nurse and allied health practitioners. This group have raised serious concerns on the existing nomenclature, which labels the disease as NAFLD, and its diagnostic criteria, including provoking nurse role confusion and representing a major barrier to various key aspects; patient‐nurse communications, patient awareness, partnership working, motivation of patients to undertake lifestyle changes and multiple health behaviour change promotion and nurse‐led clinics. Therefore, they are enthusiastically supportive of this call to reframe the disease that we believe will ultimately have a positive impact on nurse‐patient communication, and through this, improve patient care and quality of life and reduce burden on health system.
Demography, genetic diversity and expansion load in the colonizing species Leontodon longirostris (Asteraceae) throughout its native range
Authors: de Pedro Manuel , Riba Miquel , González‐Martínez Santiago C. , Seoane Pedro , Bautista Rocío , Claros Manuel Gonzalo , Mayol Maria
Published: January 2021

Unravelling the evolutionary processes underlying range expansions is fundamental to understand the distribution of organisms, as well as to predict their future responses to environmental change. Predictions for range expansions include a loss of genetic diversity and an accumulation of deleterious alleles along the expansion axis, which can decrease fitness at the range‐front (expansion load). In plants, empirical studies supporting expansion load are scarce, and its effects remain to be tested outside a few model species. Leontodon longirostris is a colonizing Asteraceae with a widespread distribution in the Western Mediterranean, providing a particularly interesting system to gain insight into the factors that can enhance or mitigate expansion load. In this study, we produced a first genome draft for the species, covering 418 Mbp (~53% of the genome). Although incomplete, this draft was suitable to design a targeted sequencing of ~1.5 Mbp in 238 L. longirostris plants from 21 populations distributed along putative colonization routes in the Iberian Peninsula. Inferred demographic history supports a range expansion from southern Iberia around 40,000 years ago, reaching northern Iberia around 25,000 years ago. The expansion was accompanied by a loss of genetic diversity and a significant increase in the proportion of putatively deleterious mutations. However, levels of expansion load in L. longirostris were smaller than those found in other plant species, which can be explained, at least partially, by its high dispersal ability, the self‐incompatible mating system, and the fact that the expansion occurred along a strong environmental cline.
Rapid changes in DNA methylation associated with the initiation of reproduction in a small songbird
Authors: Lindner Melanie , Laine Veronika N. , Verhagen Irene , Viitaniemi Heidi M. , Visser Marcel E. , van Oers Kees , Husby Arild
Published: January 2021

Species with a circannual life cycle need to match the timing of their life history events to the environment to maximize fitness. However, our understanding of how circannual traits such as timing of reproduction are regulated on a molecular level remains limited. Recent studies have implicated that epigenetic mechanisms can be an important part in the processes that regulate circannual traits. Here, we explore the role of DNA methylation in mediating reproductive timing in a seasonally breeding bird species, the great tit (Parus major), using genome‐wide DNA methylation data from individual females that were blood sampled repeatedly throughout the breeding season. We demonstrate rapid and directional changes in DNA methylation within the promoter region of several genes, including a key transcription factor (NR5A1) known from earlier studies to be involved in the initiation of timing of reproduction. Interestingly, the observed changes in DNA methylation at NR5A1 identified here are in line with earlier gene expression studies of reproduction in chicken, indicating that the observed shifts in DNA methylation at this gene can have a regulatory role. Our findings provide an important step towards elucidating the genomic mechanism that mediates seasonal timing of a key life history traits and provide support for the idea that epigenetic mechanisms may play an important role in circannual traits.
Nationalism in the 21st century: Neo‐tribal or plural?
Authors: Triandafyllidou Anna
Published: January 2021

Nations are faced today with a new set of social and economic challenges: economic globalisation has intensified bringing with it a more intense phase of cultural interconnectedness and political interdependence. Nation‐states see their sovereign powers eroded and are transformed to post‐national states as the political space they govern is no longer congruent with the socio‐economic space which transcends the national borders. Nonetheless, the nation continues to be a powerful source of identity and legitimacy. We are actually witnessing in Europe and worldwide a comeback of nationalism oftentimes in an aggressive, nativist and populist guise. This paper seeks to offer a new analytical lens through which to make sense of this new tide of nationalism. It therefore reviews critically the ethnic vs civic and perennialist, primordialist, modernist and ethnosymbolist approaches to suggest that they are no longer fit for purpose in explaining where nations and nationalism come from and where they are headed to. The paper proposes a new analytical framework which distinguishes between plural and neo‐tribal nationalism, focusing on how nations interact with diversity and permeability in the 21st century context.
Alteration of sphingosine‐1‐phosphate with aging induces contractile dysfunction of colonic smooth muscle cells via Ca2+‐activated K+ channel (BKCa) upregulation
Authors: Shen Xiaoxue , Zhang Ling , Jiang Ling , Xiong Wenjie , Tang Yurong , Lin Lin , Yu Ting
Published: January 2021

Background

Age‐associated changes alter calcium‐activated potassium channel (BKCa) expression of colon. Sphingolipids (SLs) are important cell membrane structural components; altered composition of SLs may affect BKCa expression. This study investigated the mechanism by which sphingosine‐1‐phosphate (S1P) contributes to age‐associated contractile dysfunction.

Methods

Fifty male Sprague Dawley rats of different ages were randomly assigned to five age‐groups, namely 3, 6, 12, 18, and 24 months. BKCa expression, S1P levels, and phosphorylated myosin light chain (p‐MLC) levels were tested in colonic tissues. In the absence and presence of S1P treatment, BKCa expression, p‐MLC levels, and intracellular calcium mobilization were tested in vitro. BKCa small interfering RNA (siRNA) was used to investigate whether p‐MLC expression and calcium mobilization were affected by BKCa in colonic smooth muscle cells (SMCs). The expressions of phosphorylated protein kinase B, c‐Jun N‐terminal kinases (JNKs), extracellular‐regulated protein kinases, nuclear factor kappa‐B (NF‐κB), and protein kinase Cζ (PKCζ) were examined to investigate the correlation between S1P and BKCa.

Key Results

Sphingosine‐1‐phosphate levels and sphingosine‐1‐phosphate receptor 2 (S1PR2) and BKCa expressions were upregulated and p‐MLC expression was downregulated in the colonic tissues, age dependently. In the cultured SMCs, S1P treatment increased BKCa expression and reduced calcium concentration and p‐MLC was observed. BKCa siRNA increased calcium concentration, and p‐MLC levels significantly compared with control. We also showed that S1P upregulated BKCa through PKCζ, JNK, and NF‐κB pathways.

Conclusions and Inferences

In conclusion, S1P and S1PR2 participate in age‐associated contractile dysfunction via BKCa upregulation through PKCζ, JNK, and NF‐κB pathways.
How to see invisible objects
Authors: Munton Jessie
Published: January 2021

It is an apparent truism about visual perception that we can see only what is visible to us. It is also frequently accepted that visual perception is dynamic: our visual experiences are extended through, and can evolve over time. I argue that taking the dynamism of visual experience seriously renders certain simplistic interpretations of the first claim, that a subject at a given time can see only what is visible to her at that time, false: we can be meaningfully said to see invisible objects. This counterintuitive result in turn focuses our attention on the relationship between perception and memory. I show that it is difficult to draw a clear or simple distinction between the two. Memory and perception rely on, and blend with, one another. Together, these claims point us away from understanding visual perception as a simple reflection of the environment, and instead as closer to a process of dynamic modelling that draws together occurrent stimulation and stored information.
Shedding light on the dark side of xanthophyll cycles
Authors: Fernández‐Marín Beatriz , Roach Thomas , Verhoeven Amy , García‐Plazaola José Ignacio
Published: January 2021

Xanthophyll cycles are broadly important in photoprotection, and the reversible de‐epoxidation of xanthophylls typically occurs in excess light conditions. However, as presented in this review, compiling evidence in a wide range of photosynthetic eukaryotes shows that xanthophyll de‐epoxidation also occurs under diverse abiotic stress conditions in darkness. Light‐driven photochemistry usually leads to the pH changes that activate de‐epoxidases (e.g. violaxanthin de‐epoxidase), but in darkness alternative electron transport pathways and luminal domains enriched in monogalactosyl diacyl glycerol (which enhance de‐epoxidase activity) likely enable de‐epoxidation. Another ‘dark side’ to sustaining xanthophyll de‐epoxidation is inactivation and/or degradation of epoxidases (e.g. zeaxanthin epoxidase). There are obvious benefits of such activity regarding stress tolerance, and indeed this phenomenon has only been reported in stressful conditions. However, more research is required to unravel the mechanisms and understand the physiological roles of dark‐induced formation of zeaxanthin. Notably, the de‐epoxidation of violaxanthin to antheraxanthin and zeaxanthin in darkness is still a frequently ignored process, perhaps because it questions a previous paradigm. With that in mind, this review seeks to shed some light on the dark side of xanthophyll de‐epoxidation, and point out areas for future work.
Prevalence and risk factors of oral mucositis in paediatric patients undergoing haematopoietic stem cell transplantation
Authors: Alhussain Abdulmalik , Alkhayal Zikra , Ayas Mouhab , Abed Hassan
Published: January 2021

Background

A complete understanding of oral mucositis (OM) is crucial to develop appropriate interventions to aid in the successful overall health outcome of paediatric patients undergoing haematopoietic stem cell transplantation (HSCT).

Aims

This study aimed at determining the prevalence and severity of OM and at identifying the predictive factors that might aggravate OM at one‐week, two‐week and three‐week post‐HSCT.

Methods

This retrospective, hospital‐based study reviewed the medical records of 170 paediatric patients, summarising the patients’ characteristics using descriptive statistics. Binary logistic regression was used to identify factors associated with the development of OM.

Results

At one‐week post‐HSCT, 41% of 140 patients (n = 49) had developed OM, this was reduced at two‐week (n = 36, 33%) and three‐week (n = 13, 19%) post‐HSCT. Univariate logistic regression revealed that patients with cancer (OR = 0.16, 95% CI = 0.05–0.54; p‐value = .003) had a significantly lower prevalence of OM. Younger patients with an average age of 7.9 years old (OR = 0.85, 95% CI = 0.75–0.97; p‐value = 0.013) and the presence of GvHD (OR = 2.37, 95% CI = 1.03–5.45, p‐value = 0.042) were significantly related to a higher prevalence of OM. Multivariable logistic regression confirmed that the risk of OM is lower in patients with cancer compared to those with immunodeficiency syndromes or hereditary blood diseases (OR = 0.18, 95% CI = 0.04–0.77; p‐value = .021).

Conclusions

This study identified a significantly lower prevalence of OM in patients with cancer compared to other conditions and that young recipients and those who developed GvHD were more likely to have OM.
TEMPS‐A (short version) plays a supplementary role in the differential diagnosis between major depressive disorder and bipolar disorder
Authors: Morishita Chihiro , Kameyama Rie , Toda Hiroyuki , Masuya Jiro , Fujimura Yota , Higashi Shinji , Kusumi Ichiro , Inoue Takeshi
Published: January 2021

Aim

Early differential diagnosis between patients with major depressive disorder (MDD) and bipolar disorder (BD), and subsequently providing appropriate treatments are essential. There has been increased interest regarding the association between affective temperaments and mood disorder diagnosis. Our aim was to analyze the diagnostic validity of affective temperaments assessed by the short version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego‐autoquestionnaire version (TEMPS‐A), in mood disorder patients.

Methods

Inpatients with MDD (n = 146) or BD (n = 128) completed the short version of TEMPS‐A, and their depressive and manic symptom severities were evaluated. Data of MDD and BD patients were compared by univariable and multivariable analyses.

Results

Of the five affective temperament dimensions, substantially higher hyperthymic, irritable, and cyclothymic temperament scores were found in BD patients than in MDD patients. Using a multivariable logistic regression model built using the severities of depressed and manic conditions, and the five affective temperament subscale scores as independent variables, we identified two factors statistically associated with BD diagnosis (anxious temperament and cyclothymic temperament). The recommended cutoff point for the 12 items evaluating cyclothymic temperament to differentiate BD from MDD was 8 or more ‘True’ items (sensitivity: 35.9%, specificity: 87.7%).

Limitations

Our design was cross‐sectional, and therefore, there was a possibility of longitudinal diagnostic conversion of patients from MDD to BD.

Conclusion

Cyclothymic and anxious temperaments on the short version of TEMPS‐A, identified as diagnostic differentiating factors between MDD and BD, may play supplementary roles in the early identification of BD.
Greater insulin resistance in short children born small‐for‐gestational age than in children with growth hormone deficiency at the early period of growth hormone therapy
Authors: Suzuki Junichi , Urakami Tatsuhiko , Morioka Ichiro
Published: January 2021

Background

We compared insulin resistance and glucose metabolism during growth hormone (GH) therapy between 43 short children born small‐for‐gestational age (SGA) and 42 children identify as growth hormone deficiency (GHD).

Methods

The study compared fasting plasma glucose (FPG), fasting immunoreactive insulin (IRI) and homeostasis model assessment insulin resistance index (HOMA‐IR) during 24‐month GH therapy between the two groups.

Results

Mean FPG, fasting IRI, and HOMA‐IR values at 3‐month GH therapy were significantly higher than those before and at 12‐ and 24‐month GH therapy in both groups. These markers were significantly higher in short children born SGA than GHD children until 12‐month GH therapy but were not different at 24‐month GH therapy in both groups.

Conclusions

The increased secretion of insulin observed in short children born SGA might be a compensatory mechanism for the prevention of hyperglycemia that can progress to diabetes mellitus. However, these metabolic markers gradually declined after 3 months of GH therapy and returned to baseline values at 24 months. These results suggest that short children born SGA have greater insulin resistance than GHD children at the early period of GH therapy, however, increased insulin resistance is improved over a long period.
Inhibition of nitric oxide production under alkaline conditions regulates iron homeostasis in rice
Authors: Li Hao , Chen Haifei , Deng Suren , Cai Hongmei , Shi Lei , Xu Fangsen , Wang Chuang
Published: January 2021

Rice is one of the most susceptible plants to iron (Fe) deficiency under neutral and alkaline conditions. Alkaline stress induces H2O2 production and increases the deposition of Fe on the root surface, which causes leaf chlorosis and Fe deficiency in rice. Gene chip and qRT‐PCR analysis indicated that the expression of the nitrate reductase (NR) genes were downregulated by alkaline treatment, which resulted in significantly decreased nitrate activity and nitric oxide (NO) production in the epidermis and stele, where H2O2 accumulated. In contrast, treatment with sodium nitroprusside (SNP), a NO donor, strongly alleviated alkaline‐induced Fe deficiency by limiting Fe plaque formation. Increasing the NO signal significantly reduced the accumulation of H2O2 and the lignin barrier but enhanced phenolic acid secretion in the root epidermis and stele under alkaline conditions. The secreted phenolic acid effectively mobilized the apoplast Fe and increased Fe uptake in roots, thereby alleviating the Fe‐deficiency response and downregulating the expressions of Fe‐uptake genes under alkaline conditions. In conclusion, alkaline stress inhibits NR activity and NO production in the roots of rice, which play vital roles in the mobilization of the apoplast Fe by regulation of H2O2 and phenolic acid concentrations.
Dew absorption by leaf trichomes in Caragana korshinskii: An alternative water acquisition strategy for withstanding drought in arid environments
Authors: Waseem Muhammad , Nie Zheng‐Fei , Yao Guang‐Qian , Hasan Mahadi , Xiang Yun , Fang Xiang‐Wen
Published: January 2021

Investigating plant morphological traits can provide insights into plant drought tolerance. To date, many papers have focused on plant hydraulic responses to drought during dehydration, but atmospheric water absorption by trichomes to mitigate drought stress by influencing leaf hydraulics in plant species that inhabit arid environments has been largely ignored. The experiment in this study was designed to assess how dew absorbed by leaf trichomes helps Caragana korshinskii withstand drought. The results showed that under a drought stress and dew (DS & D) treatment, C. korshinskii displayed a strong capacity to absorb dew with trichomes; exhibited slow decreases in leaf water potential (Ψleaf), leaf hydraulic conductivity (Kleaf), and gas exchange; experienced 50% Kleaf and gas exchange losses at lower relative soil water content levels than plants treated with drought stress and no dew (DS & ND); and experienced 50% Kleaf loss (Kleaf P50) at similar Ψleaf levels as DS & ND plants. Its congener C. sinica, which does not have leaf trichomes, displayed little ability to absorb dew under drought stress and did not show any remarkable improvement in the above parameters under the DS & D treatment. Our results indicated that leaf trichomes are important epidermal dew‐uptake structures that assist in partially sustaining the leaf hydraulic assimilation system, mitigate the adverse effects of drought stress and contribute to the distribution of C. korshinskii in arid environments.
Personalised need of Care in an Ageing Society: The Making of a Prediction Tool Based on Register Data
Authors: Wright Marvin N. , Kusumastuti Sasmita , Mortensen Laust H. , Westendorp Rudi G. J. , Gerds Thomas A.
Published: January 2021

Danish municipalities monitor older persons who are at high risk of declining health and would later need home care services. However, there is no established strategy yet on how to accurately identify those who are at high risk. Therefore, there is great potential to optimise the municipalities’ prevention strategies. Denmark’s comprehensive set of electronic population registers provide longitudinal data that cover individual and household socio-demographics and medical history. Using these data, we developed and applied recurrent neural networks to predict the risk of a need of care services in the future and thus identify individuals who would benefit the most from the municipalities’ prevention strategies. We compared our recurrent neural network model to prediction models based on Cox regression and Fine–Gray regression in terms of calibration and discrimination. Challenges for the prediction modelling were the competing risk of death and the longitudinal information on the registered life course data.
Iterative Alpha Expansion for Estimating Gradient-Sparse Signals from Linear Measurements
Authors: Xu Sheng , Fan Zhou
Published: January 2021

We consider estimating a piecewise-constant image, or a gradient-sparse signal on a general graph, from noisy linear measurements. We propose and study an iterative algorithm to minimize a penalized least-squares objective, with a penalty given by the “ℓ0-norm” of the signal’s discrete graph gradient. The method uses a non-convex variant of proximal gradient descent, applying the alpha-expansion procedure to approximate the proximal mapping in each iteration, and using a geometric decay of the penalty parameter across iterations to ensure convergence. Under a cut-restricted isometry property for the measurement design, we prove global recovery guarantees for the estimated signal. For standard Gaussian designs, the required number of measurements is independent of the graph structure, and improves upon worst-case guarantees for total-variation (TV) compressed sensing on the 1-D line and 2-D lattice graphs by polynomial and logarithmic factors respectively. The method empirically yields lower mean-squared recovery error compared with TV regularization in regimes of moderate undersampling and moderate to high signal-to-noise, for several examples of changepoint signals and gradient-sparse phantom images.
Solutions to a phase‐field model for martensitic phase transformations driven by configurational forces
Authors: Wu Fan , Bian Xingzhi , Zhao Lixian
Published: January 2021

We study the existence of weak solutions to an initial‐boundary value problem for a new phase‐field model, which consists of a degenerate parabolic equation coupled to linear elasticity equations. This model is used to describe the evolution of interfaces in elastically deformable solid materials which moves by configurational forces, such as martensitic phase transformations in shape memory alloys. The existence proof is valid only for one‐dimensional case.
Modern coastal tempestite deposition by a non‐local storm: Swell‐generated transport of sand and boulders on Eleuthera, The Bahamas
Authors: Wilson Kat , Mohrig David
Published: January 2021

This paper presents an analysis of the transport conditions of a storm deposit (i.e. tempestite) produced by a non‐local cyclone. Observations and analysis of ‘sand to boulder’ transport and washover deposition in March 2018 at Gaulding Cay Quarry, Eleuthera, The Bahamas, confirm that swell waves can cause coastal change and affect the depositional record >1000 km from the storm centre. Drone video, news reporting, deposit stratigraphy, grain‐size measurements and wave data were all used to define three phases of washover fan construction: an aggradational phase associated with base‐level rise as the quarry filled with water; a progradational phase associated with quasi‐constant base‐level; and fan incision tied to base level fall as discharge through an outlet channel exceeded input discharge by overtopping waves. Washover fan location was controlled by antecedent topography and represented only a fraction of the swell‐impacted coastline. Sand and boulders were transported simultaneously, forming a complex poorly sorted deposit. Drone video, bedrock erosion and sediment‐transport estimates all indicated that overwash exceeded sediment availability. As a result, the measured washover fan was estimated to be an order of magnitude smaller than its potential volume if conditions had been transport‐limited. This study highlights the importance of pre‐event topography and independent measures of event duration on accurately reconstructing storm properties from the sedimentary record, as well as the challenges in reconstructing storm location, and therefore storm intensity and frequency, from sedimentary deposits alone.