bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity
Authors: Hynes Tristan J. , Hrelja Kelly M. , Hathaway Brett A. , Hounjet Celine D. , Chernoff Chloe S. , Ebsary Sophie A. , Betts Graeme D. , Russell Brittney , Ma Lawrence , Kaur Sukhbir , Winstanley Catharine A.
Published: February 2021

Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision‐making. Drug‐associated cues have long been known to facilitate habitual drug‐seeking, and the salient audiovisual cues embedded within modern gambling products may likewise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward‐paired cues and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we first gained specific inhibitory control over VTA dopamine neurons by transducing a floxed inhibitory DREADD (AAV5‐hSyn‐DIO‐hM4D(Gi)‐mCherry) in rats expressing Cre recombinase in tyrosine hydroxylase neurons. We then trained rats in our cued rat gambling task (crGT), inhibiting dopamine neurons throughout task acquisition and performance, before allowing them to self‐administer cocaine in the same diurnal period as crGT sessions. The trajectories of addiction differ in women and men, and the dopamine system may differ functionally across the sexes; therefore, we used male and female rats here. We found that inhibition of VTA dopamine neurons decreased cue‐induced risky choice and reduced motor impulsivity in males, but surprisingly, enhanced risky decision making in females. Inhibiting VTA dopamine neurons also prevented cocaine‐induced changes in decision making in both sexes, but nevertheless drove all animals to consume more cocaine. These findings show that chronic dampening of dopamine signalling can have both protective and deleterious effects on addiction‐relevant behaviours, depending on biological sex and dependent variable of interest.
Support can increase use of the AUDIT‐C in Australian Aboriginal Community Controlled Health Services: a cluster randomized trial
Authors: Conigrave James H. , Harrison Kristie H. , Lee K. S. Kylie , Dobbins Timothy A. , Hummerston Beth , Hayman Noel , Perry Jimmy , Ivers Rowena , Haber Paul S. , Wilson Scott , Johnson David , Conigrave Katherine M.
Published: February 2021

Background and Aims

Unhealthy alcohol consumption is a key concern for Aboriginal and Torres Strait Islander (‘Indigenous’) communities. It is important to identify and treat at‐risk drinkers, to prevent harms to physical or social wellbeing. We aimed to test whether training and support for Aboriginal Community Controlled Health Service (ACCHS) staff would increase rates of alcohol screening and brief intervention.

Design

Cluster randomized trial.

Setting

Australia.

Cases/Intervention/Measurements

Twenty‐two ACCHSs that see at least 1000 clients per year and use Communicare as practice management software. The study included data on 70 419 clients, training, regular data feedback, collaborative support and funding for resources ($9000). Blinding was not used. The comparator was waiting‐list control (equal allocation). Alcohol Use Disorder Identification Test (AUDIT‐C) screening and records of brief interventions were extracted from practice management software at 2‐monthly intervals. Observations described the clinical actions taken for clients over each 2‐month interval. The baseline period (28 August 2016–28 August 2017) was compared with the post‐implementation period (29 August 2017–28 August 2018). We used multi‐level logistic regression to test the hypotheses that clients attending a service receiving active support would be more likely to be screened with AUDIT‐C (primary outcome) or to receive a brief intervention (secondary outcome).

Findings

We observed an increase in the odds of screening with AUDIT‐C for both groups, but the increase was 5.52 [95% confidence interval (CI) = 4.31, 7.07] times larger at services receiving support. We found little evidence that the support programme increased the odds of a recorded brief intervention relative to control services (odds ratio = 2.06; 95% CI = 0.90, 4.69). Differences in baseline screening activity between treatment and control reduce the certainty of our findings.

Conclusions

Providing Aboriginal Community Controlled Health Services with training and support can improve alcohol (AUDIT‐C) screening rates.
Comparison of e‐cigarette use prevalence and frequency by smoking status among youth in the United States, 2014–19
Authors: Tam Jamie , Brouwer Andrew F.
Published: February 2021

Background and aims

Reports of youth e‐cigarette use often do not disaggregate by underlying smoking status. This study compared annual 2014–19 youth estimates of past 30‐day e‐cigarette use prevalence and frequency by smoking status in the United States.

Design

Nationally representative, cross‐sectional, school‐based survey [National Youth Tobacco Surveys (NYTS)]. General linear models accounting for complex survey design compared e‐cigarette use prevalence by smoking status by year, overall and stratified by frequency, separately for high school (HS) and middle school (MS) students. The 2019 survey was analyzed separately because of its change in survey methodology.

Setting

MSs and HSs in the United States.

Participants

A total of 116 704 students from 1268 schools, ages 9–19.

Measurements

Students self‐reported (paper 2014–18, electronic 2019) ever and past 30‐day (current) use of e‐cigarettes and cigarettes, as well as frequent use (20–30 days of month).

Findings

From 2014 to 2018, current e‐cigarette use prevalence increased among never, current and former smokers in HS, but only among never and current smokers in MS (each P‐value < 0.001). E‐cigarette use increases for current HS smokers were primarily among frequent e‐cigarette users. In 2018, the absolute number of HS frequent users who were never or former smokers (420 000 combined) surpassed current smokers (370 000). In 2019, current e‐cigarette use prevalence for never, former and current smokers was 17.5% [95% confidence interval (CI) = 16.0–19.0], 53.6% (95% CI = 45.2–61.9) and 85.8% (95% CI = 81.6–89.9) for HS students, respectively, and 6.8% (95% CI = 5.9–7.7), 40.8% (95% CI = 34.7–47.0) and 78.0% (95% CI = 71.9–84.2) for MS students. That year, the number of HS never (420 000) and former smokers (570 000) using e‐cigarettes frequently eclipsed that of current smokers (390 000).

Conclusions

E‐cigarette use prevalence and frequency among youth vary by smoking status, with highest levels of use among current smokers. However frequent e‐cigarette use among never smokers and former smokers has increased.
Inferences with spatial autocorrelation
Authors: Pawley Matthew David McDonald , McArdle Brian H.
Published: February 2021

Spatial autocorrelation is a general phenomenon within biogeographical studies. However, considerable confusion exists about how to analyse spatially autocorrelated data collected using classical sampling methods (e.g. simple random sampling). We show that the two common discordant views about autocorrelated data depend upon the desired scale of inference. Although inferential statistics seeking to generalise to different unsampled spatial areas need to be adjusted for autocorrelation, if the inference is restricted to the area from which samples have been taken, then standard tests are applicable. In the latter case, incorporating autocorrelation into the model may actually improve the precision and power of the analysis. We found that the scale of spatial inference is rarely discussed, despite being of central importance to any spatial analysis. We suggest that spatial inference should rarely be formally generalised to unsampled areas, since it typically requires some assumption of stationarity and is thus vulnerable to accusations of ‘pseudo‐replication’.
Majority world successes and European and American failure to contain COVID‐19: Cultural collectivism and global leadership
Authors: Liu James H.
Published: February 2021

United Nations and World Health Organization data show a positive correlation, r = .53, p < .0001, N = 189, between COVID‐19 infection rates and the human development index (HDI). Less wealthy, less educated countries with lower life spans were also more successful in maintaining lower fatality rates, r = .46, p < .0001, N = 189 whereas 9 of the top‐10 countries in the world in per capita fatalities due to COVID‐19 were Western societies high in HDI. Similar positive correlations were found between COVID‐19 infection and fatality rates and a smaller sample of 76 countries measured on Schwartz intellectual autonomy (or individualism), and negative correlations of similar magnitude were found for embeddedness (or collectivism). East Asia was a global leader in preventing the spread of COVID‐19 because of a vigilant public concerned for public safety and compliant with public safety measures. African Union leaders coordinated their responses, and bought into a continent‐wide African Medical Supplies Platform that prevented panicked competition for scare supplies. Western global media and scholars have not paid attention to the successes of East Asia, Africa, and the South Pacific in fighting the pandemic. It is worth asking why this should be the case; understand the weaknesses of extreme individualism in fighting a pandemic requiring coordinated and unified public response, and consider the lessons for global scholars from the pandemic for doing research in the future.
Looking ahead to the future of GeogEd: Creating spaces of exchange between communities of practice
Authors: Finn Matt , Hammond Lauren , Healy Grace , Todd Jay J. D. , Marvell Alan , McKendrick John H. , Yorke Lynda
Published: February 2021

As part of the special issue marking the transition of the Higher Education Research Group to the Geography and Education Research Group, in this final paper we argue that the reformed group has a key role to play in promoting spaces of exchange between the communities of practice that have a stake in the shared endeavours of geography and education. We draw on structured conversations from the group’s launch event, existing literature, and our particular vantage points to identify a range of influences – both heritages that we work with and challenges that we face – that shape the interplay of geography and education in our pedagogical contexts. We argue that the GeogEd Research Group can create spaces of productive exchange between three communities of practice: geographies of education research, geography education research, and pedagogic research. As the research group brings these communities of practice together, it facilitates dialogue, creates new avenues for research, and connects and enhances geography teaching practice across education levels.
Real‐world outcomes with bortezomib‐containing regimens and lenalidomide plus dexamethasone for the treatment of transplant‐ineligible multiple myeloma: a multi‐institutional report from the Canadian Myeloma Research Group database
Authors: Jimenez‐Zepeda Victor H. , Venner Christopher , McCurdy Arleigh , Masih‐Khan Esther , Atenafu Eshetu G. , Sebag Michael , Stakiw Julie , Song Kevin , LeBlanc Richard , Reiman Tony , Louzada Martha , Kotb Rami , Gul Engin , Reece Donna
Published: February 2021

Bortezomib‐containing regimens (BCRs) represented standard, first‐line therapy for transplant‐ineligible multiple myeloma (TIMM) in Canada until the introduction of lenalidomide and low‐dose dexamethasone (Ld). However, little comparative data exist to inform the selection of regimens. We assessed the outcomes for TIMM patients treated with cyclophosphamide, bortezomib and dexamethasone or prednisone (CyBorD/P), bortezomib, melphalan and prednisone (VMP), bortezomib and dexamethasone or prednisone (VD/P) and lenalidomide and low‐dose dexamethasone (Ld) using the Canadian Myeloma Research Group database. Of 1156 TIMM patients evaluated, 82% received bortezomib combinations while 18% received Ld. Median progression‐free survival (PFS) was 21·0, 21·1, 13·2 and 28·5 months (P = 0·0002) and median overall survival (OS) was 52·0, 63·6, 30·8 and 65·7 months (P < 0·0001) in the CyBorD/P, VMP, VD/P and Ld groups respectively. There was no significant difference in PFS and OS between the two triplet bortezomib regimens (VMP and CyBorD/P). Ld was associated with a longer PFS but not a significantly superior OS to date. Outcomes with the bortezomib‐steroid doublet were inferior (VD/P). However, multivariable analysis identified features related to disease biology as the most important prognostic factors for PFS and OS. Such factors, as well as those affecting the physician’s choice of regimen, are likely to influence the results observed with different regimens. This study demonstrated real‐world outcomes in TIMM similar to those reported in clinical trials.
Achieving better outcomes for schizophrenia patients in Hong Kong: Strategies for improving treatment adherence
Authors: Lo William Tak‐Lam , Ki‐Yan Mak Daniel , Ming‐Cheuk Wong Michael , Chan Oi‐Wah , Mo‐Ching Chui Eileena , Wai‐Sau Chung Dicky , Suk‐Han Ip Glendy , Lau Ka‐Shing , Lee Che‐Kin , Mui Jolene , Tam Ka‐Lok , Tse Samson , Wong Kwong‐Lui ,   the Hong Kong Association of Psychosocial Rehabilitation (HKAPR)
Published: February 2021

Recent research on second‐generation long‐acting injectable antipsychotics (LAI SGAs) has proven its effectiveness in minimizing medication nonadherence problem and reducing relapses. Administered by medical professionals, making quick detection of nonadherence possible, long‐acting injectable antipsychotics (LAIs) facilitate immediate intervention and recovery process, and thus are favored by psychiatrists. Despite a higher initial cost with LAIs, the subsequent schizophrenia‐related health costs for hospitalizations and outpatients are greatly reduced. With reference to guidelines published by psychiatric associations around the globe, this article looks at scenarios in Hong Kong on the management of severe mentally ill patients with regard to the use of a host of psychosocial interventions as well as LAI SGAs as a preferable treatment. In particular, it examines the benefits of using LAI SGAs for Hong Kong patients who demonstrated high nonadherence treatment rates due to their social environment. It assesses the rationale behind the early usages of LAI SGAs, which help to provide better recovery outcomes for patients.
Albumin‐to‐alkaline phosphatase ratio: A novel prognostic index for patients with driver mutation‐negative advanced non‐small cell lung cancer
Authors: Liu Xiaoqin , Li Yan , Zhao Qi , Jiang Hanyi , Ni Jun , Cai Hourong
Published: February 2021

Introduction

Albumin‐to‐Alkaline Phosphatase Ratio (AAPR), a novel developed prognostic index for cancers. Chemotherapy was the only method for driver mutation‐negative advanced non‐small cell lung cancer (DANSCLC).

Objectives

To evaluate the clinical significance of AAPR in these patients.

Methods

We retrospectively reviewed 167 DANSCLCs and 58 healthy controls. Associations of clinicopathological characteristics and survival analysis were conducted.

Results

Significantly decreased AAPR level was uncovered in DANSCLC patients compared to healthy controls. The correlation analysis revealed that the low AAPR level in DANSCLCs was correlated with poor differentiation (P = .024). Cox regression analysis showed that N stage, M stage, and different levels of AAPR were the independent risk factors of PFS and OS. The median PFS and OS survival ratio in patients with high and low AAPR level was, respectively, 17 months and 8 months, and 23 months and 13 months. The AUC of AAPR for both PFS and OS were higher than that of albumin and alkaline phosphatase (p < 0.05). The low AAPR was associated with much shorter PFS and OS than the high AAPR (mPFS: 8 vs. 25 months; mOS: 12 vs. 36 months). In the AP cohort, the low AAPR group experienced significantly shorter PFS and OS than the high AAPR (mPFS: 7 vs. 25 months; mOS: 12 vs. 36 months). Meanwhile, there was no significance in lung squamous cell carcinoma (LUSC) patients and GP regimens cohort.

Conclusion

AAPR significantly decreased in patients with DANSCLC, and it affects the prognosis of patients with DANSCLC and is a biomarker for DANSCLCs prognosis and treatment choice.
Time elapsed between choices in a probabilistic task correlates with repeating the same decision
Authors: Jabłońska Judyta , Szumiec Łukasz , Zieliński Piotr , Rodriguez Parkitna Jan
Published: February 2021

Reinforcement learning causes an action that yields a positive outcome more likely to be taken in the future. Here, we investigate how the time elapsed from an action affects subsequent decisions. Groups of C57BL6/J mice were housed in IntelliCages with access to water and chow ad libitum; they also had access to bottles with a reward: saccharin solution, alcohol, or a mixture of the two. The probability of receiving a reward in two of the cage corners changed between 0.9 and 0.3 every 48 hr over a period of ~33 days. As expected, in most animals, the odds of repeating a corner choice were increased if that choice was previously rewarded. Interestingly, the time elapsed from the previous choice also influenced the probability of repeating the choice, and this effect was independent of previous outcome. Behavioral data were fitted to a series of reinforcement learning models. Best fits were achieved when the reward prediction update was coupled with separate learning rates from positive and negative outcomes and additionally a “fictitious” update of the expected value of the nonselected choice. Additional inclusion of a time‐dependent decay of the expected values improved the fit marginally in some cases.
CD36 – A novel molecular target in the neurovascular unit
Authors: Ioghen Octavian , Chițoiu Leona , Gherghiceanu Mihaela , Ceafalan Laura Cristina , Hinescu Mihail Eugen
Published: February 2021

CD36 is an integral membrane protein primarily known for its function as a fatty acid transporter, yet also playing other biological roles from lipid metabolism to inflammation modulation. These pleiotropic effects are explained by the existence of multiple different ligands and the extensive distribution in numerous cell types. Moreover, the receptor is related to various pathologies and it may prove to be a good target for prospective therapeutic strategies. In the neurovascular unit (NVU), CD36 is expressed in cells like microglia, microvascular endothelial cells, astrocytes and neurons. In the normal brain, CD36 was proven to be involved in phagocytosis of apoptotic cells, oro‐sensory detection of dietary lipids, and fatty acid transport across the blood brain barrier (BBB). CD36 was also acknowledged as a potentially important player in central nervous system (CNS) disorders, such as Alzheimer Disease‐associated vascular dysfunction and oxidative stress and the neuroinflammatory response in stroke. Despite continuous efforts, the therapeutic arsenal for such diseases is still scarce and there is an increasing interest in discovering new molecular targets for more specific therapeutic approaches. In this review, we summarize the role of CD36 in the normal function of the NVU and in several CNS disorders, focusing on the dysregulation of the NVU and the potential therapeutic modulation.
Whole‐exome sequencing reveals the major genetic factors contributing to neuromyelitis optica spectrum disorder in Chinese patients with aquaporin 4‐IgG seropositivity
Authors: Zhong Xiaonan , Chen Chen , Sun Xiaobo , Wang Jingqi , Li Rui , Chang Yanyu , Fan Ping , Wang Yuge , Wu Yunting , Peng Lisheng , Lu Zhengqi , Qiu Wei
Published: February 2021

Background and objective

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease. Although genetic factors are involved in its pathogenesis, limited evidence is available in this area. The aim of the present study was to identify the major genetic factors contributing to NMOSD in Chinese patients with aquaporin 4 (AQP4)‐IgG seropositivity.

Methods

Whole‐exome sequencing (WES) was performed on 228 Chinese NMOSD patients seropositive for AQP4‐IgG and 1400 healthy controls in Guangzhou, South China. Human leukocyte antigen (HLA) sequencing was also utilized. Genotype model and haplotype, gene burden, and enrichment analyses were conducted.

Results

A significant region of the HLA composition is on chromosome 6, and great variation was observed in DQB1, DQA2 and DQA1. HLA sequencing confirmed that the most significant allele was HLA‐DQB1*05:02 (p < 0.01, odds ratio [OR] 3.73). The genotype model analysis revealed that HLA‐DQB1*05:02 was significantly associated with NMOSD in the additive effect model and dominant effect model (p < 0.05). The proportion of haplotype “HLA‐DQB1*05:02‐DRB1*15:01” was significantly greater in the NMOSD patients than the controls, at 8.42% and 1.23%, respectively (p < 0.001, OR 7.39). The gene burden analysis demonstrated that loss‐of‐function mutations in NOP16 were more common in the NMOSD patients (11.84%) than the controls (5.71%; p < 0.001, OR 2.22). The IgG1‐G390R variant was significantly more common in NMOSD, and the rate of the T allele was 0.605 in patients and 0.345 in the controls (p < 0.01, OR 2.92). The enrichment analysis indicated that most of the genetic factors were mainly correlated with nervous and immune processes.

Conclusions

Human leukocyte antigen is highly correlated with NMOSD. NOP16 and IgG1‐G390R play important roles in disease susceptibility.
Prospects and limitations of genomic offset in conservation management
Authors: Rellstab Christian , Dauphin Benjamin , Exposito‐Alonso Moises
Published: February 2021

In nature conservation, there is keen interest in predicting how populations will respond to environmental changes such as climate change. These predictions can help determine whether a population can be self‐sustaining under future alterations of its habitat or whether it may require human intervention such as protection, restoration, or assisted migration. An increasingly popular approach in this respect is the concept of genomic offset, which combines genomic and environmental data from different time points and/or locations to assess the degree of possible maladaptation to new environmental conditions. Here, we argue that the concept of genomic offset holds great potential, but an exploration of its risks and limitations is needed to use it for recommendations in conservation or assisted migration. After briefly describing the concept, we list important issues to consider (e.g., statistical frameworks, population genetic structure, migration, independent evidence) when using genomic offset or developing these methods further. We conclude that genomic offset is an area of development that still lacks some important features and should be used in combination with other approaches to inform conservation measures.
Psychological Components of Infertility
Authors: Swanson Amelia , Braverman Andrea Mechanick
Published: February 2021

Infertility is a medical diagnosis impacting 48.5 million couples globally. Infertility impacts physical and emotional health as well as social and romantic relationships. People with infertility report feelings of distress, grief, anxiety and depression. Couples notice changes in their relationships; some report becoming emotionally closer while others report relationship difficulties. People may feel more isolated due to lack of social support. People that use third party reproduction, such as donor egg, sperm, embryo or gestational carriers, have additional emotional impacts during pregnancy and parenting. Continuing changes to laws complicate international fertility care, particularly given the ongoing COVID‐19 pandemic.
Vital roles of soil microbes in driving terrestrial nitrogen immobilization
Authors: Li Zhaolei , Zeng Zhaoqi , Song Zhaopeng , Wang Fuqiang , Tian Dashuan , Mi Wenhai , Huang Xin , Wang Jinsong , Song Lei , Yang Zhongkang , Wang Jun , Feng Haojie , Jiang Lifen , Chen Ye , Luo Yiqi , Niu Shuli
Published: February 2021

Nitrogen immobilization usually leads to nitrogen retention in soil and, thus, influences soil nitrogen supply for plant growth. Understanding soil nitrogen immobilization is important for predicting soil nitrogen cycling under anthropogenic activities and climate changes. However, the global patterns and drivers of soil nitrogen immobilization remain unclear. We synthesized 1350 observations of gross soil nitrogen immobilization rate (NIR) from 97 articles to identify patterns and drivers of NIR. The global mean NIR was 8.77 ± 1.01 mg N kg−1 soil day−1. It was 5.55 ± 0.41 mg N kg−1 soil day−1 in croplands, 15.74 ± 3.02 mg N kg−1 soil day−1 in wetlands, and 15.26 ± 2.98 mg N kg−1 soil day−1 in forests. The NIR increased with mean annual temperature, precipitation, soil moisture, soil organic carbon, total nitrogen, dissolved organic nitrogen, ammonium, nitrate, phosphorus, and microbial biomass carbon. But it decreased with soil pH. The results of structural equation models showed that soil microbial biomass carbon was a pivotal driver of NIR, because temperature, total soil nitrogen, and soil pH mostly indirectly influenced NIR via changing soil microbial biomass. Moreover, microbial biomass carbon accounted for most of the variations in NIR among all direct relationships. Furthermore, the efficiency of transforming the immobilized nitrogen to microbial biomass nitrogen was lower in croplands than in natural ecosystems (i.e., forests, grasslands, and wetlands). These findings suggested that soil nitrogen retention may decrease under the land use change from forests or wetlands to croplands, but NIR was expected to increase due to increased microbial biomass under global warming. The identified patterns and drivers of soil nitrogen immobilization in this study are crucial to project the changes in soil nitrogen retention.
Black lives and bodywork matters: A postcolonial critique of gender and embodiment in Nigeria
Authors: Kagher Loliya Akobo , Otaye‐Ebede Lilian , Metcalfe Beverly
Published: February 2021

Drawing on the theories of “Womanism” and “African feminism,” this paper explores the concept of embodiment within an African context. More specifically, we focus on exploring the lived experiences of Nigerian women in male‐dominated organizations (sector) to provide an in‐depth understanding of the dynamics of how the Nigerian society marginalizes qualities and aspects of embodiment and disembodiment of women. Based on 39 interviews, our findings reveal that cultural and social practices significantly influence the concept of gendered embodiment in the Nigerian context. We further highlight the spatialized dynamic of the religious, ethical, and classed identity formations, and the multiplicities of violence experienced on African women's bodies every day. Using a feminist standpoint as a lens, we highlight the practice and relevance of social constructivism in understanding the concept of spatialized embodiment in a Nigerian context. We emphasize the complexity and diversity in African feminisms as we highlight the multiplicities of difference in understanding African experiences. Additionally, we emphasize that men are part of the social construct, and hence cannot be left out of the story, given that their influence and perceptions provide further insight into the concept of gendered embodiment and existing marginalization of and discrimination against women.
The effects of nanocurcumin supplementation on inflammation in hemodialysis patients: A randomized controlled trial
Authors: Vafadar‐Afshar Golchin , Rasmi Yousef , Yaghmaei Parichehreh , Khadem‐Ansari Mohammad‐Hassan , Makhdoomi Khadijeh , Rasouli Javad
Published: February 2021

Introduction

Serum levels of several pro‐inflammatory cytokines are higher in hemodialysis patients compared to healthy people. Curcumin has been shown to be able to decrease cytokines levels in nonuremic subjects. Our goal was to evaluate the effect of nanocurcumin administration on cytokines levels in hemodialysis patients.

Methods

The study was performed over a 3 months period on 54 hemodialysis patients who had been randomized to receive either nanocurcumin or placebo. Serum levels and gene expressions of tumor necrosis factor‐alpha (TNF‐α) and interleukin 6 (IL‐6) were evaluated using enzyme‐linked immunosorbent assay (ELISA) and real‐time polymerase chain reaction (RT‐PCR).

Findings

Serum levels of IL‐6 and TNF‐α were similar in the two groups at baseline but were lower after 12 weeks of treatment with nanocurcumin compared to placebo (P = 0.024 for IL‐6 and 0.02 for TNF). In the group given nanocurcumin, serum levels of both cytokines decreased substantially (P < 0.001 for each), whereas they were unchanged in the group given placebo. Gene expression for each cytokine in peripheral blood mononuclear cells (PBMCs) was reduced at 12 weeks vs. baseline in the group given nanocurcumin, and changes in gene expression correlated with changes in serum level for each of the two cytokines.

Discussion

The results indicate that nanocurcumin supplementation reduces both serum levels and gene expression of IL‐6 and TNF‐α in hemodialysis patients. The feasibility and potential clinical benefits of nanocurcumin treatment to reduce inflammation in hemodialysis patients warrant further study.
Early warning systems for more effective student counselling in higher education: Evidence from a Dutch field experiment
Authors: Plak Simone , Cornelisz Ilja , Meeter Martijn , van Klaveren Chris
Published: February 2021

Early Warning Systems (EWS) in higher education accommodate student counsellors by identifying at‐risk students and allow them to intervene in a timely manner to prevent student dropout. This study evaluates an EWS that shares student‐specific risk information with student counsellors, which was implemented at a large Dutch university. A randomised field experiment was conducted to estimate the effect of EWS‐assisted counselling on first‐year student dropout and academic performance. The results show that the EWS accurately predicts at‐risk students. Yet, EWS‐assisted counselling did not reduce dropout, nor improved academic performance. Solving the underlying problem of poor academic performance might require additional actionable feedback and recommended counselling practices.
U–Pb ages of zircons from metamorphic rocks in the upper sequence of the Hidaka Metamorphic Belt, Hokkaido, Japan: Identification of two metamorphic events and implications for regional tectonics
Authors: Takahashi Yutaka , Mikoshiba Masumi , Shimura Toshiaki , Nagata Mitsuhiro , Iwano Hideki , Danhara Tohru , Hirata Takafumi
Published: February 2021

The Hidaka Metamorphic Belt is a well‐known example of island‐arc crustal section, in which metamorphic grade increases westwards from unmetamorphosed sediment up to granulite facies. It is divided into lower (granulite to amphibolite facies) and upper (amphibolite to greenschist facies) metamorphic sequences. The metamorphic age of the belt was considered to be ~55 Ma, based on Rb–Sr whole‐rock isochron ages for granulites and related S‐type tonalities. However, zircons from the granulites in the lower sequence yield U–Pb ages of ~21–19 Ma, and a preliminary report on zircons from pelitic gneiss in the upper sequence gives a U–Pb age of ~40 Ma. In this paper we provide new zircon U–Pb ages from two pelitic gneisses in the upper sequence to assess the metamorphic age and also the maximum depositional age of the sedimentary protolith. The weighted mean 206Pb/238U ages from a biotite gneiss in the central area of the belt yield 39.6 ± 0.9 Ma for newly grown metamorphic rims and 53.1 ± 0.9 Ma for the youngest detrital cores. The ages of zircons from a cordierite–biotite gneiss in the southern area are 35.9 ± 0.7 Ma for metamorphic rims and 46.5 ± 2.8 Ma for the youngest detrital cores. These results indicate that metamorphism of the upper sequence took place at ~40–36 Ma, and that the sedimentary protolith was deposited after ~53–47 Ma. These metamorphic ages are consistent with the reported ages of ~37–36 Ma plutonic rocks in the upper sequence, but contrast with the ~21–19 Ma ages of metamorphic and plutonic rocks in the lower sequence. Therefore, we conclude that the upper and lower metamorphic sequences developed independently but coupled with each other before ~19 Ma as a result of dextral reverse tectonic movement.
Sleep‐wake patterns in newborns are associated with infant rapid weight gain and incident adiposity in toddlerhood
Authors: Petrov Megan E. , Whisner Corrie M. , McCormick David , Todd Michael , Reyna Lucy , Reifsnider Elizabeth
Published: February 2021

Background

Rapid weight gain (RWG) by 6 months of life is a significant risk factor of childhood overweight (OW)/obesity. Infant sleep patterns are associated with incident OW in childhood, but few have examined its relationship with RWG.

Objective

Examine associations between newborn sleep‐wake patterns and incident RWG at 6 months of life and OW at 36 months.

Methods

Low‐income Mexican/Mexican‐American women with OW/obesity and their infants (n = 126) enrolled in a 1‐year randomized controlled trial designed to prevent incident, infant RWG and toddlerhood OW/obesity. Sleep pattern metrics at 1 month were extracted from the Brief Infant Sleep Questionnaire‐Revised. Outcome measures included RWG (>0.67 positive change in weight‐for‐age Z‐score) from birth to 6 months and incident OW (body mass index percentile ≥85) at 36 months.

Results

By 6 months, 35.7% (n = 45) of infants experienced RWG, and by 36 months 42.3% (n = 41) of toddlers were OW. Napping ≥5x/day at 1‐month was significantly associated with decreased odds for RWG compared to napping <5x (OR = 0.11, 95%CI:0.02, 0.63). Each 1‐hour increase in nocturnal vs diurnal sleep was associated with greater odds of incident OW at 36 mos (OR = 1.51, 95%CI:1.13, 2.03).

Conclusions

Early‐life sleep patterns related to infant nap frequency and nocturnal vs diurnal sleep distribution were associated with obesity outcomes and may be important intervention targets to prevent lasting consequences on infant growth.
Melt infiltration studies of 2D Tyranno SA3@ ceramic matrix composite preforms with CrSi2 intermetallic alloy
Authors: Raj Sai
Published: February 2021

This paper reports the results of melt infiltrating 2D Tyranno SA3@ fiber woven preforms with molten CrSi2 between 1768 and 1896 K under a vacuum of 1.3 x 10−4 Pa (10−6 torr). The infiltration times varied between 1800 and 7200 s, which did not have any significant effect on the volume fraction of voids filled with the metal. Optical and scanning electron microscopy, backscattered electron imaging, energy dispersion spectroscopy, and Raman spectroscopy were used to characterize the infiltrated preforms. A plot of the volume fraction of open voids infiltrated against the absolute melt infiltration temperature showed a sharp peak at 1773 K with almost complete infiltration of the voids at this temperature. The extent of silicide infiltration of the preforms dropped steeply above 1773 K with an increasing melt infiltration temperature irrespective of the amount of infiltration time. Above 1805 K, the volume fraction of voids infiltrated with the melt was nearly 0%. It is demonstrated that CrSi2 did not show evidence of a reaction with the SiC fibers. The possibility that a resisting force due to contact angle hysteresis (CAH) may have influenced the diminishing amount of voids filled with increasing temperature above 1773 K was examined. The resistance force was estimated to be extremely small to be consequential. Another possibility that the CrSi2 may have decomposed into Cr(g) and Si(g) in the vacuum melt infiltration furnace appeared to be more plausible based on thermodynamic analyses. An empirical equation is proposed to calculate the amount of remaining charge left to infiltrate the preforms at the infiltration temperature. It is shown that an initial charge of 10 g would rationalize the present observations. While the decomposition of the CrSi2 appeared to mostly explain the present results, some discrepancies were observed, which were inconsistent with the decomposition model.
Scoparone alleviates Ang II‐induced pathological myocardial hypertrophy in mice by inhibiting oxidative stress
Authors: Lyu Linmao , Chen Jiazheng , Wang Wei , Yan Tao , Lin Jiamao , Gao Hongmei , Li Hui , Lv Ruijuan , Xu Feng , Fang Lijun , Chen Yuguo
Published: February 2021

Long‐term poorly controlled myocardial hypertrophy often leads to heart failure and sudden death. Activation of ras‐related C3 botulinum toxin substrate 1 (RAC1) by angiotensin II (Ang II) plays a pivotal role in myocardial hypertrophy. Previous studies have demonstrated that scoparone (SCO) has beneficial effects on hypertension and extracellular matrix remodelling. However, the function of SCO on Ang II‐mediated myocardial hypertrophy remains unknown. In our study, a mouse model of myocardial hypertrophy was established by Ang II infusion (2 mg/kg/day) for 4 weeks, and SCO (60 mg/kg bodyweight) was administered by gavage daily. In vitro experiments were also performed. Our results showed that SCO could alleviate Ang II infusion‐induced cardiac hypertrophy and fibrosis in mice. In vitro, SCO treatment blocks Ang II‐induced cardiomyocyte hypertrophy, cardiac fibroblast collagen synthesis and differentiation to myofibroblasts. Meanwhile, we found that SCO treatment blocked Ang II‐induced oxidative stress in cardiomyocytes and cardiac fibroblasts by inhibiting RAC1‐GTP and total RAC1 in vivo and in vitro. Furthermore, reactive oxygen species (ROS) burst by overexpression of RAC1 completely abolished SCO‐mediated protection in cardiomyocytes and cardiac fibroblasts in vitro. In conclusion, SCO, an antioxidant, may attenuate Ang II‐induced myocardial hypertrophy by suppressing of RAC1 mediated oxidative stress.
The impact of national lockdown on nutritional status of children with inflammatory bowel disease
Authors: Marino Luise V. , Ashton James J. , Beattie Robert Mark
Published: February 2021

Background

The COVID‐19 pandemic has had wide‐reaching primary and secondary health implications. The UK government implemented a national lockdown to slow the rate of infection at the end of March 2020, lasting until early summer 2020. The results from a UK nationwide survey suggest the majority of inflammatory bowel disease patients were followed up using technology‐enabled care services (TECS) during this time. We therefore aimed to explore the impact of the pandemic on nutritional status of children with inflammatory bowel disease, focusing on the effect of national lockdown from March to early summer 2020.

Methods

A retrospective study was conducted. All patients with a diagnosis of inflammatory bowel disease, aged <18 years, and under the care of Southampton Children's Hospital were eligible for inclusion. Those patients who attended an outpatient appointment during time period 1 (November 2019 to February 2020), and following the period of national lockdown, time period 2 (July to November 2020), were included in the analysis.

Results

In total, 116 patients had paired measures. Using the World Health Organization criteria of nutritional status, 19% (n = 22/116) were mildly malnourished with a body mass index Z score (BMIZ) < −1. In this group, the mean BMIZ was –1.3 ± 0.9 at time point 1 versus −1.9 ± 0.9 at time point 2 (p = 0.03). The mean BMIZ score of those children who were overweight at time point 1 was 1.2 ± 1.2 versus 1.6 ± 1.4 at time point 2 (p = 0.2) During the period of lockdown, 27% of malnourished children (n = 6/22), 2% of normally nourished children (BMIZ > −1 to < 1) (n = 1/51) (p ≤ 0.0001) and none of the overweight children (BMIZ > 1) (n = 0/43) children (p ≤ 0.0001) had a TECS nutrition review.

Conclusions

Dietetic reviews were severely restricted during the first national lockdown. Patients with low BMIZ prior to lockdown became more malnourished. During the ongoing pandemic, it is important to identify those children with nutrition risk, focusing support on this group of children.
MP3RNA‐seq: Massively parallel 3′ end RNA sequencing for high‐throughput gene expression profiling and genotyping
Authors: Chen Jian , Zhang Xiangbo , Yi Fei , Gao Xiang , Song Weibin , Zhao Haiming , Lai Jinsheng
Published: February 2021

Transcriptome deep sequencing (RNA‐seq) has become a routine method for global gene expression profiling. However, its application to large‐scale experiments remains limited by cost and labor constraints. Here we describe a massively parallel 3′ end RNA‐seq (MP3RNA‐seq) method that introduces unique sample barcodes during reverse transcription to permit sample pooling immediately following this initial step. MP3RNA‐seq allows for handling of hundreds of samples in a single experiment, at a cost of about $6 per sample for library construction and sequencing. MP3RNA‐seq is effective for not only high‐throughput gene expression profiling, but also genotyping. To demonstrate its utility, we applied MP3RNA‐seq to 477 double haploid lines of maize. We identified 19,429 genes expressed in at least 50% of the lines and 35,836 high‐quality single nucleotide polymorphisms for genotyping analysis. Armed with these data, we performed expression and agronomic trait quantitative trait locus (QTL) mapping and identified 25,797 expression QTLs for 15,335 genes and 21 QTLs for plant height, ear height, and relative ear height. We conclude that MP3RNA‐seq is highly reproducible, accurate, and sensitive for high‐throughput gene expression profiling and genotyping, and should be generally applicable to most eukaryotic species.
Analysis of low‐dose subgroups receiving NOACs
Authors: Jolobe O. M. P.
Published: February 2021

Click here to view the Original article by Lip et al.
When redistribution makes personalized pricing of externalities useless
Authors: Fleurbaey Marc , Kornek Ulrike
Published: February 2021

We consider a standard optimal taxation framework in which consumers' preferences are separable in consumption and labor and identical over consumption, but are affected by consumption externalities. For every nonlinear, income‐dependent pricing of goods there is a linear pricing scheme, combined with an adjusted income tax schedule, that leaves all consumers equally well‐off and weakly increases the government's budget. The result depends on whether a linear pricing scheme exists that keeps the aggregate amount of consumption at its initial level observed under nonlinear pricing. We provide sufficient conditions for the assumption to hold. If adjusting the income tax rate is not available, personalized prices for an externality can enhance social welfare if they are redistributive, that is, favor consumers with a larger marginal social value of income.
PoxCbh, a novel CENPB‐type HTH domain protein, regulates cellulase and xylanase gene expression in Penicillium oxalicum
Authors: Li Cheng‐Xi , Liao Lu‐Sheng , Wan Xu‐Dong , Zhang Feng‐Fei , Zhang Ting , Luo Xue‐Mei , Zhao Shuai , Feng Jia‐Xun
Published: February 2021

The essential transcription factor PoxCxrA is required for cellulase and xylanase gene expression in the filamentous fungus Penicillium oxalicum that is potentially applied in biotechnological industry as a result of the existence of the integrated cellulolytic and xylolytic system. However, the regulatory mechanism of cellulase and xylanase gene expression specifically associated with PoxCxrA regulation in fungi is poorly understood. In this study, the novel regulator PoxCbh (POX06865), containing a centromere protein B‐type helix‐turn‐helix domain, was identified through screening for the PoxCxrA regulon under Avicel induction and genetic analysis. The mutant ∆PoxCbh showed significant reduction in cellulase and xylanase production, ranging from 28.4% to 59.8%. Furthermore, PoxCbh was found to directly regulate the expression of important cellulase and xylanase genes, as well as the known regulatory genes PoxNsdD and POX02484, and its expression was directly controlled by PoxCxrA. The PoxCbh‐binding DNA sequence in the promoter region of the cellobiohydrolase 1 gene cbh1 was identified. These results expand our understanding of the diverse roles of centromere protein B‐like protein, the regulatory network of cellulase and xylanase gene expression, and regulatory mechanisms in fungi.
The COMPASS‐like complex modulates fungal development and pathogenesis by regulating H3K4me3‐mediated targeted gene expression in Magnaporthe oryzae
Authors: Zhou Sida , Liu Xiuying , Sun Wanyu , Zhang Mengyu , Yin Yue , Pan Song , He Dan , Shen Mi , Yang Jun , Zheng Qi , Wang Weixiang
Published: February 2021

Histone‐3‐lysine‐4 (H3K4) methylation is catalysed by the multiprotein complex known as the Set1/COMPASS or MLL/COMPASS‐like complex, an element that is highly evolutionarily conserved from yeast to humans. However, the components and mechanisms by which the COMPASS‐like complex targets the H3K4 methylation of plant‐pathogenic genes in fungi remain elusive. Here we present a comprehensive analysis combining biochemical, molecular, and genome‐wide approaches to characterize the roles of the COMPASS‐like family in the rice blast fungus Magnaporthe oryzae, a model plant pathogen. We purified and identified six conserved subunits of COMPASS from M. oryzae: MoBre2 (Cps60/ASH2L), MoSpp1 (Cps40/Cfp1), MoSwd2 (Cps35), MoSdc1 (Cps25/DPY30), MoSet1 (MLL/ALL), and MoRbBP5 (Cps50), using an affinity tag on MoBre2. We determined the sequence repeat in dual‐specificity kinase splA and ryanodine receptors domain of MoBre2 can interact directly with the DPY30 domain of MoSdc1 in vitro. Furthermore, we found that deletion of the genes encoding COMPASS subunits of MoBre2, MoSPP1, and MoSwd2 caused similar defects regarding invasive hyphal development and pathogenicity. Genome‐wide profiling of H3K4me3 revealed that it has remarkable co‐occupancy at the transcription start site regions of target genes. Significantly, these target genes are often involved in spore germination and pathogenesis. Decreased gene expression caused by the deletion of MoBre2, MoSwd2, or MoSpp1 was highly correlated with a decrease in H3K4me3. These results suggest that MoBre2, MoSpp1, and MoSwd2 function as a whole COMPASS complex, contributing to fungal development and pathogenesis by regulating H3K4me3‐targeted genes in M. oryzae.
The OsmiRNA166b‐OsHox32 pair regulates mechanical strength of rice plants by modulating cell wall biosynthesis
Authors: Chen Hong , Fang Ruiqiu , Deng Rufang , Li Jianxiong
Published: February 2021

The plant cell wall provides mechanical strength to support plant growth and development and to determine plant architecture. Cellulose and mixed‐linkage glucan (MLG) present in primary cell wall, whereas cellulose, lignin and hemicellulose exist in secondary cell wall. Biosynthesis of the cell wall biopolymers needs the coordinated transcriptional regulation of all the biosynthetic genes. The module of OsmiR166b‐OsHox32 regulates expression levels of the genes related to biosynthesis of MLG, cellulose and lignin. Transgenic plants knocking down miR166b (STTM166b) by short tandem target mimic (STTM) technology or overexpressing OsHox32 (OEHox32) showed drooping leaves and brittle culms. Due to accumulation of less lignin and cellulose, the cell wall thickness of STTM166b and OEHox32 plants was reduced when compared to that of wild‐type plants. Overexpression of miR166b (OE166b) in rice plants or knocking down of OsHox32 by RNA interference (RNAiHox32) led to increased thickness of cell walls and enhanced mechanical strength of culms. Molecular analyses showed that OsmiR166b‐OsHox32 pair regulates cell wall‐related gene expression. OsHox32 binds to the promoters of OsCAD2 and OsCESA7 to suppress the expression levels of these two genes. The suppression of OsCAD2 is synergistic when OsHox32 is co‐expressed with OSH15 (Oryza sativa homeobox 15). OsHox32 interacts with OSH15, and the START domain of OsHox32, harbouring the miR166b cleavage site, is required for the interaction of these two proteins. Our results demonstrate that OsmiR166b‐OsHox32 pair plays important roles not only in plant growth and development but also in plant architecture by regulating the cell wall‐related gene expression.