bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell transcriptomic analysis unveils spinal motor neuron subtype diversity underpinning the water-to-land transition in vertebrates
Authors: Liau Ee Shan , Jin Suoqin , Chen Yen-Chung , Liu Wei-Szu , Yong Luok Wen , Tsai Chang-Tai , Calon Maëliss , Yu Jr-Kai , Su Yi-Hsien , Nedelec Stéphane , Nie Qing , Chen Jun-An
Published: September 2021

Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate motor movements in vertebrates. Distinct MN populations and their diversity has long been hypothesized to co-evolve with motor circuit to provide the neural basis from undulatory to ambulatory locomotion during aquatic-to-terrestrial transition of vertebrates. However, how these subtypes are evolved remains largely enigmatic. Using single-cell transcriptomics, we investigate heterogeneity in mouse MNs and discover novel segment-specific subtypes. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. We further uncovered that axial MNs are subdivided by three conserved and molecularly distinct subpopulations, defined by Satb2, Nr2f2 or Bcl11b expression. Although axial MNs are conserved from cephalochordates to humans, subtype diversity becomes prominent in land animals and appears to continue evolving in humans. Overall, our study provides a unified classification system for spinal MNs and paves the way towards deciphering how neuronal subtypes are evolved.
Biochemical and structural characterization of the fused Bacteroides fragilis NFeoAB domain reveals a role for FeoA
Authors: Sestok Alex E. , Brown Janae B. , Obi Juliet O. , O’Sullivan Sean M. , Garcin Elsa D. , Deredge Daniel J. , Smith Aaron T.
Published: September 2021

Iron is an essential element for nearly all organisms, and under anoxic and/or reducing conditions, Fe2+ is the dominant form of iron available to bacteria. The ferrous iron transport (Feo) system has been identified as the primary prokaryotic Fe2+ import machinery, and two proteins (FeoA and FeoB) are conserved across most bacterial species. However, how FeoA and FeoB function relative to one another remained enigmatic. In this work we explored the distribution of feoAB operons predicted to encode for a fusion of FeoA tethered to the soluble N-terminal, G-protein domain of FeoB via a connecting linker region. We hypothesized that this fusion might poise FeoA to interact with FeoB in order to affect function. To test this hypothesis, we cloned, expressed, purified, and biochemically characterized the soluble NFeoAB fusion protein from Bacteroides fragilis, a commensal organism implicated in drug-resistant peritoneal infections. Using X-ray crystallography, we determined to 1.50 Å resolution the structure of BfFeoA, which adopts an SH3-like fold implicated in protein-protein interactions. In combination with structural modeling, small-angle X-ray scattering, and hydrogen-deuterium exchange mass spectrometry, we show that FeoA and NFeoB indeed interact in a nucleotide-dependent manner, and we have mapped the protein-protein interaction interface. Finally, using GTP hydrolysis assays, we demonstrate that BfNFeoAB exhibits one of the slowest known rates of Feo-mediated GTP hydrolysis and is not potassium-stimulated, indicating that FeoA-NFeoB interactions may function to stabilize the GTP-bound form of FeoB. Our work thus reveals a role for FeoA function in the fused FeoAB systems and suggests a broader role for FeoA function amongst prokaryotes.
De novo variants in Chinese ASD trios reveal genetic basis underlying autism without developmental delay and intellectual disabilities
Authors: Wang Jincheng , Yu Juehua , Wang Mengdi , Zhang Lingli , Yang Kan , Du Xiujuan , Wu Jinyu , Wang Xiaoqun , Li Fei , Qiu Zilong
Published: September 2021

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that causes a range of social communication and behavioral impairments. ASD typically manifests in young children, often with developmental delay or intellectual disabilities (DD/ID) as comorbidities. Accruing evidence indicates that ASD is highly heritable and genomewide studies on ASD cohorts have defined numerous genetic contributors. Notably, most of these studies have been performed with individuals of European and Hispanic ancestry and thus there is a paucity of genetic analyses of ASD in the East Asian population. Here, we performed whole-exome sequencing on 772 ASD trios from China, combining with a previous study of 369 Chinese ASD trios, to identify de novo variants in a total of 1141 ASD trios. We found that ASD probands without DD/ID carried less disruptive de novo variants, including protein-truncating and missense variants, than ASD with DD/ID. Surprisingly, we showed that expression of genes with de novo variants found in ASD probands without DD/ID were enriched in a specific group of neural progenitor cells, suggesting a potential mechanism underlying high-functioning autism. Importantly, some ASD risk genes from this study are not present in the current ASD gene database, suggesting that there are novel genetic contributors to ASD in East Asian populations. We validated one such novel ASD risk gene – SLC35G1 by showing that mice harboring heterozygous deletion of Slc35g1 exhibited defects in social interaction behaviors. Together, this work nominates novel ASD risk genes and indicates that ASD genetic studies in different geographic populations are essential to reveal the comprehensive genetic architecture of ASD.
Why and how informatics and applied computing can still create structural changes and competitive advantage
Authors: Mitropoulos Sarandis , Douligeris Christos
Published: September 2021

Purpose

In the new digital age, enterprises are facing an increasing global competition. In this paper, we first examine how Information Technology (IT) can play an important role in giving significant competitive advantage in the modern enterprises. The business value of IT is examined, as well as the limitations and the trade-offs that its applicability faces. Next, we present the basic principles for a successful IT strategy, considering the development of a long-term IT renovation plan, the strategic alignment of IT with the business strategy, and the adoption of an integrated, distributed, and interoperable IT platform. Finally, we examine how a highly functional and efficient IT organization can be developed.

Design/methodology/approach

Our methodological approach was based to the answers of the following questions: 1. Does IT still matter? 2. What is the business value created by IT along with the corresponding limitations and trade-offs? 3. How could a successful IT Strategy be build up? 4. How could an effective? T planning aligned with the business strategy be build up? 5. How could a homogenized and distributed corporate IT platform be developed? and finally, 6. How could a high-performance IT-enabled enterprise be build up?

Findings

The enterprises in order to succeed in the new digital area need to: 1. synchronize their IT strategy with their business strategy, 2. formulate a long-term IT strategy, 3. adopt IT systems and solutions that are implemented with elasticity, interoperability, distribution, and service-orientation. 4. keep a strategic direction towards the creation of an exceptional organization based on IT.

Originality/value

This paper is original with respect to the integrated approach the overall problem is examined. There is a prototype combined investigation of all perspectives for an effective enforcement of IT in a way that causes acceleration in competitive advantage when conducting business.
Governance and sustainability in Southeast Asia
Authors: Tran Mi , Beddewela Eshani , Ntim Collins G.
Published: September 2021

Purpose

This paper aims to examine the relationship between a diverse set of corporate governance (CG) mechanisms and corporate sustainability disclosure (CSD) in Southeast Asian countries under national stakeholder reform.

Design/methodology/approach

Data analysis is based on 171 of the largest companies across six Southeast Asian countries using a 30-item CSD measure.

Findings

The authors find that there are wide variations in the levels of CSD across the countries. The findings indicate that board size, board gender diversity, block ownership and the presence of a sustainability committee are significant determinants of CSD. Additionally, whilst more stringent stakeholder governance reform motivates firms to publish more sustainability information, it fails to influence the effectiveness of the board of directors in promoting CSD.

Practical implications

Findings of this study highlight the essential role internal governance structure plays in monitoring corporate actions and enabling corporations to reduce their legitimacy gap. The findings further encourage regulators and policymakers to question, with utmost importance, the effectiveness of stakeholder reform in making significant organisational changes.

Originality/value

There is a dearth of studies that examine the CG-CSD nexus in relation to specific institutional characteristics. Existing studies mainly focus on a single country with similar institutional environments and thus limiting the ability to understand the “context specificity” of sustainability content development. This paper provides an overview of stakeholder reform in Southeast Asian countries and empirically substantiates the relationship between CG and CSD across six countries undergoing such reforms in the region.
A conceptual framework for managing post-disaster reconstruction projects in emerging economies: the case of Angola
Authors: Sospeter Nyamagere Gladys , Rwelamila Pantaleo D. , Gimbi Joaquim J.
Published: September 2021

Purpose

This study develops a conceptual framework appropriate for managing Post-Disaster Reconstruction Projects (PDRPs) so as to avoid cost and time overruns in Angola.

Design/methodology/approach

An explanatory sequential mixed research approach was used. Data was collected from project participants within the ministry of planning, the provincial government office of planning and the local government in Angola. A questionnaire with closed questions was completed by 130 survey respondents. Semi-structured focus group interviews were conducted with seven participants selected through purposive sampling. Descriptive statistics, t-test and content analysis were used to analyse quantitative and qualitative data, respectively.

Findings

The study indicates that there is presently no formal project management process. Neither have government project management standards been developed and broadcast. This results in ad hoc processes being mostly used for managing PDRPs. The study further presents disaster preparation programme, community engagement, resources and stakeholder's engagement, post-disaster procurement policies, financial guides, post-disaster recovery legislation, context-specific (social economic, demographic, political and cultural variables), programme preparation as essential components to be considered for developing an appropriate framework for managing PDRPs.

Research limitations/implications

The study is limited by its geographical settings which focussed the results on one province in Angola. However, the findings can be useful for other countries wishing to gain insights on the framework with “overlooked components” for managing DPRPs in emerging countries with similar disaster environment, government policies and same business environment.

Practical implications

The framework for managing PDRPs may positively impact project realization, hence minimization of time and cost overruns. The findings are vital for managers, local practitioners and policy/decision-makers in emerging countries of essential components and lessons useful for managing PDRPs and making decisions when they intend to participate in such projects. An understanding of which approaches are critical and essential components of the framework serves as a basis for improving project delivery. Future research studies should describe its practical application.

Originality/value

The study provides insights by identifying an ordered grouped set of project management models/approaches mostly applicable for managing PDRPs in Angola, better understanding of appropriate components/variables to be considered and develops a conceptual framework for managing PDRPs in emerging countries, post-war context.
New wine in old bottles: governing logics for applying sustainability management control systems in Austrian electric utilities
Authors: Slacik Johannes , Grüb Birgit , Greiling Dorothea
Published: September 2021

Purpose

Literature shows that a strong link between sustainability control systems and sustainability management (SM) fosters sustainability development (SD) and compliance with regulatory requirements and stakeholder expectations. Research on the integration of SM and its control mechanisms in corporate business remains scarce. This study aims to focus on Sustainability Management Control Systems (S)MCS applied in Electric Utility Companies (EUC), which experience close scrutiny by its stakeholders in as much as they play an important role in climate change agendas.

Design/methodology/approach

The methodological approach includes in-depth expert interviews within seven Austrian EUC followed by qualitative content analysis. This study builds on “MCS as a package” by Malmi and Brown (2008). Institutional logics (IL) are used for the theoretical approach.

Findings

Results show that several IL are involved in implementing strategic SMCS in EUC. Managers cope by integrating emerging hybrid logics, selectively coupled SMCS and making sense by building a communication bridge between the strategic and operative levels to create awareness.

Research limitations/implications

Results show that managers in EUC have to acquire a new hybrid logic for SD. This implies the use of informal controls and a strong focus on administrative and cultural controls as the main control mechanisms for SM.

Originality/value

The paper contributes to MCS research by using the scarcely applied theoretical framework of IL. Findings facilitate a better understanding of the control mechanisms behind SM and the coping strategies of managers in applying SMCS.
The use and knowledge of export promotion programs in the early internationalization of Brazilian SMEs
Authors: Machado Marcelo André , Bischoff Viviane
Published: September 2021

Purpose

This paper aimed to evaluate the differences in the use and knowledge of export promotion programs (EPPs) between Brazilian SMEs that internationalized early and SMEs that internationalized in a gradual, traditional fashion. Additionally, it tested hypotheses that distinguish these two types of SME internationalization processes in an emerging market context.

Design/methodology/approach

The authors tested four hypotheses in a sample of 540 SME Brazilian exporters. The sample was divided into two groups according to the born global (BG) criteria: 379 SMEs with gradual or traditional internationalization (TI) and 161 SMEs with early internationalization (EI).

Findings

The results indicate that Brazilian EI SMEs operate in more countries and continents than TI SMEs. In emerging countries such as Brazil, the domestic market continues to play an important role both for SMEs that internationalize early and those whose process is slower. Even though logistic regression could not classify the sample of TI and EI SMEs according to their knowledge about EPPs, the results led to the idea that EI SMEs currently use more specific EPPs than do TI SMEs.

Practical implications

Managers of successful SMEs from emerging markets need to incorporate EPPs into their internationalization strategy. In emerging markets with large domestic markets, SME managers can meet their growth needs by exploiting opportunities in both domestic and international markets.

Originality/value

Research on the early internationalization of SMEs has long focused on SMEs from developed markets and on internal factors. Moreover, the effects of EPPs on the firm' performance of large and SME firms has also been the subject of study. The value of this paper relies on the intersection of EPPs and the early internationalization of SMEs, even for firms in developed markets.
Teachers, researchers, but not innovators? Rethinking university-industry collaboration
Authors: Lundberg Heléne , Öberg Christina
Published: September 2021

Purpose

Universities, when collaborating with industry, are generally assumed to be the motors for innovation. Inspired by a case on a university’s collaboration with small- and medium-sized enterprises (SMEs) in a regional strategic network (RSN), this paper aims to put forth how the university makes important contributions through transferring knowledge on innovation processes that is a teaching role, rather than sees itself as the party producing innovations. This paper describes and discusses the university’s teaching role and its consequences in university-industry collaborations for innovation.

Design/methodology/approach

Empirically, the paper departs from a mid-Swedish RSN where nine SMEs started to work with a university. Interviews with representatives of the nine SMEs participating in the innovation project, along with university and RSN representatives, comprise the main data source. The paper analyzes the university’s teaching role and the consequences of it.

Findings

Findings point at how the SMEs developed structured innovation processes, improved their market intelligence and increased their efficiency in providing new solutions. The university facilitated knowledge, while the SMEs responded through creating knowledge both on how to innovate and in terms of innovations.

Originality/value

The teaching role, which would mean that the university stays with one of its core functions, indicates a need to rethink university-industry collaboration related to expectations and role division. Moving from producing innovations to facilitating knowledge on how to innovate, would, for universities, mean that they minimize those conflicts emerging from their various roles and indicate that the production of innovation is placed at those devoted to run and grow businesses.
Developing leadership styles and green entrepreneurial orientation to measure organization growth: a study on Indian green organizations
Authors: Verma Pratima , Kumar Vimal
Published: September 2021

Purpose

Due to environmental and health awareness, there are a number of green startups increasing day by day and consumers want to use organic products over conventional products. The green enterprise faces unique challenges and opportunities in attracting the right investors, organization growth and their performance. The purpose of this study is to better understand the relationship between green entrepreneurship (GE) and different leadership styles (LS) and their association with organizational growth (OG).

Design/methodology/approach

This paper proposes a methodology based on multiple independent variables and one dependent variable i.e. multiple regression analysis. A numerical analysis of the Indian organization is presented to demonstrate the use of the proposed method.

Findings

The findings indicate that different LSs (charismatic, transformational, visionary and servant leadership) feature an influence on entrepreneurial activity. The result of the study also found that GE and LS have a positive effect on OG.

Research limitations/implications

This research will help the industry reflect on the style of leadership and attempt to introduce a new style of leadership that supports and is suitable for the green organization’s growth.

Originality/value

The study identified diverse LSs that specifically plays an important role in green entrepreneurship organizations. Additionally, investigate the relationship between OG and GE.
Terrorist groups in Syria and Libya: a study of regional policies
Authors: Mohamed Abd Elgawad Osama Mahmoud
Published: September 2021

Purpose

This study is not intended to be a prescriptive blueprint for any nation or region to fight terrorism, but rather it aims to analyze the development of policies supporting terrorism and their impact on regional as well as international relations. It is an examination of relevant facts, which might hopefully benefit policy makers and practitioners who diligently work on reducing or eliminating terrorist activities.

Design/methodology/approach

In order to achieve the objectives of the paper and in light of the pool of the available literature and data, the study adopts the system-analysis method in analyzing the impact of policies supporting terrorism and the countermeasures to apply based on the inputs, outputs and conversions associated with the phenomenon of terrorism.

Findings

Policies supporting terrorism differ from a state to another starting from providing safe haven to terrorist groups to providing direct finance and armaments to directly intervening militarily in a targeting country. Or deter such policies. This raised the concerns of many States in the region regarding the domination tendency of Turkey and called for a firm and pragmatic international, regional and Arab stand beyond verbal condemnation to deter Turkey from pursuing such policies.

Originality/value

The importance of the academic study stems from the importance of addressing one of the central issues in the field of regional and international relations, which is the policies some states adopt to support terrorism, not only by financing terrorism but also by incubating terrorism. Most studies on terrorism focus on the concept and situations and not on policies that support terrorism and their impact on regional and international relations and the means of encountering terrorism.
How to Catch a Phish with Statistics
Authors: Verma Rakesh M. , Marchette David J.
Published: September 2021

Rakesh M. Verma and David J. Marchette show how text analysis can be used to spot scam emails and prevent so-called “phishing” attacks
Establishing a palliative Advanced Practice Radiation Therapist role: A viable alternative to a Rapid Access Palliative Radiation Therapy clinic in Australia
Authors: Roos Daniel , Job Mary , Holt Tanya
Published: September 2021

Introduction

A recent survey found that Rapid Access Palliative Radiation Therapy (RAPRT) clinics have not been widely embraced in Australia and New Zealand for many reasons. The purpose of this narrative is to describe the transition of a Brisbane, Queensland, RAPRT clinic to an Advanced Practice Radiation Therapist (APRT) model to further improve access and delivery of palliative radiation therapy at that centre.

Methods

The weekly RAPRT clinic commenced in 2005, run by one Radiation Oncologist (RO). The role of the attending senior Radiation Therapist (RT) was mainly to facilitate rapid passage of patients from clinic to treatment. However, because individual ROs preferred to retain care of their own patients, capture of the relevant population was limited. It was therefore decided in 2012 to gradually transition to a model where the RT would work with all ROs and manage all palliative patients from referral to follow‐up, under RO supervision.

Results

The steps to this palliative APRT pathway involved formulation of the role description, mentoring/training of the RT, overseas site visits, further post‐graduate education, funding of the position, staff feedback surveys, evaluation studies and endorsement by professional bodies, leading to formal credentialing in 2017. Importantly, the APRT undertakes all steps in the pathway including field or volume delineation (with approval and sign‐off by the responsible RO). The role has come to be highly valued by all disciplines.

Conclusion

The successful establishment of a palliative APRT role in one Australian centre serves as a template for others wishing to create a similar position.
drpToolkit: An automated workflow for aligning and analysing vegetation and ground surface time‐series imagery
Authors: John Christian , Shilling Fraser , Post Eric
Published: September 2021

Analysis of ecological data from digital repeat photography requires consistent file and metadata management, image alignment and data extraction across the time series of data collection. Current open‐source methods facilitate one or a few of these tasks, but in many cases require manual intervention by the user, as well as associating independent processes into an overall workflow.

We introduce ‘drpToolkit’, an open‐source Python package that automates the workflow of data management, image alignment and data extraction from time‐series image sets. The toolkit operates on a folder of images and generates an aligned image time series using a user‐defined keyframe, and extracts derived greenness and snow indices from user‐defined regions of interest.

Imagery alignment improves the spatial consistency among images in a set and allows repeated measures within the set. Particularly among small regions of interest, data extracted from aligned imagery reflects observed changes in greenness compared to unaligned imagery.

This software simplifies the process of converting raw imagery stored on an SD card to useful ecological data. It automatically refiles imagery using a standardized format used in other applications, increasing the opportunity for cross‐study comparisons of phenology, and collaboration among researchers and agencies to improve understanding of fine‐scale ecological response to climate change.
Prevalence of fetal alcohol spectrum disorder in Greater Manchester, UK: An active case ascertainment study
Authors: McCarthy Robyn , Mukherjee Raja A. S. , Fleming Kate M. , Green Jonathan , Clayton‐Smith Jill , Price Alan D. , Allely Clare S. , Cook Penny A.
Published: September 2021

Background

Despite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school.

Methods

A 2‐phase active case ascertainment study was conducted in 3 mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8–9 years used prespecified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen‐positive children were invited for detailed ascertainment of FASD using gold standard measures that included medical history, facial dysmorphology, neurological impairment, executive function, and behavioral difficulties.

Results

Of 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to Phase 2 assessment. Twenty had a developmental disorder, of whom 4 had FASD and 4 were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95% CI: 1.0%, 3.4%) and when including possible cases was 3.6% (2.1%, 6.3%). None of these children had previously been identified with a developmental diagnosis.

Conclusions

FASD was found to be common in these schools and most of these children's needs had not previously been identified. A larger, more definitive study that uses a random sampling technique stratified by deprivation level to select schools is needed to make inferences regarding the population prevalence of FASD.
Moderate dose alcohol protects against serum amyloid protein A1‐induced endothelial dysfunction via both notch‐dependent and notch‐independent pathways
Authors: Rajendran Naresh K. , Liu Weimin , Chu Charles C. , Cahill Paul A. , Redmond Eileen M.
Published: September 2021

Background

Arterial endothelium plays a critical role in maintaining vessel homeostasis and preventing atherosclerotic cardiovascular disease (CVD). Low‐to‐moderate alcohol (EtOH) consumption is associated with reduced atherosclerosis and stimulates Notch signaling in endothelial cells. The aim of this study was to determine whether EtOH protects the endothelium against serum amyloid A1 (SAA1)‐induced activation/injury, and to determine whether this protection is exclusively Notch‐dependent.

Methods and Results

Human coronary artery endothelial cells (HCAEC) were stimulated or not with “pro‐atherogenic” SAA1 (1 μM) in the absence or presence of EtOH (25 mM), the Notch ligand DLL4 (3 μg/ml), or the Notch inhibitor DAPT (20 μM). EtOH stimulated Notch signaling in HCAEC, as evidenced by increased expression of the Notch receptor and hrt target genes. Treatment with EtOH alone or stimulation of Notch signaling by DLL4 increased eNOS activity and enhanced HCAEC barrier function as assessed by trans‐endothelial electrical resistance. Moreover, EtOH and DLL4 both inhibited SAA1‐induced monolayer leakiness, cell adhesion molecule (ICAM, VCAM) expression, and monocyte adhesion. The effects of EtOH were Notch‐dependent, as they were blocked with DAPT and by Notch receptor (N1, N4) knockdown. In contrast, EtOH’s inhibition of SAA1‐induced inflammatory cytokines (IL‐6, IFN‐γ) and reactive oxygen species (ROS) was Notch‐independent, as these effects were unaffected by DAPT or by N1 and/or N4 knockdown.

Conclusions

EtOH at moderate levels protects against SAA1‐induced endothelial activation via both Notch‐dependent and Notch‐independent mechanisms. EtOH's maintenance of endothelium in a nonactivated state would be expected to preserve vessel homeostasis and protect against atherosclerosis development.
Understanding long‐term trends in smoking in England, 1972–2019: an age–period–cohort approach
Authors: Opazo Breton Magdalena , Gillespie Duncan , Pryce Robert , Bogdanovica Ilze , Angus Colin , Hernandez Alava Monica , Brennan Alan , Britton John
Published: September 2021

Background and aims

Smoking prevalence has been falling in England for more than 50 years, but remains a prevalent and major public health problem. This study used an age–period–cohort (APC) approach to measure lifecycle, historical and generational patterns of individual smoking behaviour.

Design

APC analysis of repeated cross‐sectional smoking prevalence data obtained from three nationally representative surveys.

Setting

England (1972–2019).

Participants

Individuals aged 18–90 years.

Measurements

We studied relative odds of current smoking in relation to age in single years from 18 to 90, 24 groups of 2‐year survey periods (1972–73 to 2018–19) and 20 groups of 5‐year birth cohorts (1907–11 to 1997–2001). Age and period rates were studied for two groups of birth cohorts: those aged 18–25 years and those aged over 25 years.

Findings

Relative to age 18, the odds of current smoking increased with age until approximately age 25 [odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.41–1.56] and then decreased progressively to age 90 (OR = 0.06, 95% CI = 0.04–0.08). They also decreased almost linearly with period relative to 1972–73 (for 2018–19: OR = 0.30, 95% CI = 0.26–0.34) and with birth cohort relative to 1902–06, with the largest decreased observed for birth cohort 1992–96 (OR = 0.44, 95% CI = 0.35–0.46) and 1997–2001 (OR = 0.35, 95% CI = 0.74–0.88). Smoking declined in the 18–25 age group by an average of 7% over successive 2‐year periods and by an average of 5% in those aged over 25.

Conclusions

Smoking in England appears to have declined over recent decades mainly as a result of reduced smoking uptake before age 25, and to a lesser extent to smoking cessation after age 25.
Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood
Authors: Deak Joseph D. , Clark D. Angus , Liu Mengzhen , Schaefer Jonathan D. , Jang Seon Kyeong , Durbin C. Emily , Iacono William G. , McGue Matt , Vrieze Scott , Hicks Brian M.
Published: September 2021

Background and Aims

Molecular genetic studies of alcohol and nicotine use have identified many genome‐wide association study (GWAS) loci. We measured associations between drinking and smoking polygenic scores (PGS) and trajectories of alcohol and nicotine use outcomes from late childhood to early adulthood, substance‐specific versus broader‐liability PGS effects, and if PGS performance varied for consumption versus problematic substance use.

Design, setting, participants and measurements

We fitted latent growth curve models with structured residuals to scores on measures of alcohol and nicotine use and problems from ages 14 to 34 years. We then estimated associations between the intercept (initial status) and slope (rate of change) parameters and PGSs for drinks per week (DPW), problematic alcohol use (PAU), cigarettes per day (CPD) and ever being a regular smoker (SMK), controlling for sex and genetic principal components. All data were analyzed in the United States. PGSs were calculated for participants of the Minnesota Twin Family Study (n = 3225) using results from the largest GWAS of alcohol and nicotine consumption and problematic use to date.

Findings

Each PGS was associated with trajectories of use for their respective substances [i.e. DPW (βmean = 0.08; βrange = 0.02–0.12) and PAU (βmean = 0.12; βrange = −0.02 to 0.31) for alcohol; CPD (βmean = 0.08; βrange = 0.04–0.14) and SMK (βmean = 0.18; βrange = 0.05–0.36) for nicotine]. The PAU and SMK PGSs also exhibited cross‐substance associations (i.e. PAU for nicotine‐specific intercepts and SMK for alcohol intercepts and slope). All identified SMK PGS effects remained as significant predictors of nicotine and alcohol trajectories (βmean = 0.15; βrange = 0.02–0.33), even after adjusting for the respective effects of all other PGSs.

Conclusions

Substance use‐related polygenic scores (PGSs) vary in the strength and generality versus specificity of their associations with substance use and problems over time. The regular smoking PGS appears to be a robust predictor of substance use trajectories and seems to measure both nicotine‐specific and non‐specific genetic liability for substance use, and potentially externalizing problems in general.
The International Cannabis Toolkit (iCannToolkit): a multidisciplinary expert consensus on minimum standards for measuring cannabis use
Authors: Lorenzetti Valentina , Hindocha Chandni , Petrilli Kat , Griffiths Paul , Brown Jamie , Castillo‐Carniglia Álvaro , Caulkins Jonathan P. , Englund Amir , ElSohly Mahmoud A. , Gage Suzanne H. , Groshkova Teodora , Gual Antoni , Hammond David , Lawn Will , López‐Pelayo Hugo , Manthey Jakob , Mokrysz Claire , Pacula Rosalie Liccardo , van Laar Margriet , Vandrey Ryan , Wadsworth Elle , Winstock Adam , Hall Wayne , Curran H. Valerie , Freeman Tom P.
Published: September 2021

Background

The lack of an agreed international minimum approach to measuring cannabis use hinders the integration of multidisciplinary evidence on the psychosocial, neurocognitive, clinical and public health consequences of cannabis use.

Methods

A group of 25 international expert cannabis researchers convened to discuss a multidisciplinary framework for minimum standards to measure cannabis use globally in diverse settings.

Results

The expert‐based consensus agreed upon a three‐layered hierarchical framework. Each layer—universal measures, detailed self‐report and biological measures—reflected different research priorities and minimum standards, costs and ease of implementation. Additional work is needed to develop valid and precise assessments.

Conclusions

Consistent use of the proposed framework across research, public health, clinical practice and medical settings would facilitate harmonisation of international evidence on cannabis consumption, related harms and approaches to their mitigation.
Spectrum of clinical applications of interlead ECG heterogeneity assessment: From myocardial ischemia detection to sudden cardiac death risk stratification
Authors: Verrier Richard L. , Nearing Bruce D. , D’Avila Andre
Published: September 2021

Heterogeneity in depolarization and repolarization among regions of cardiac cells has long been recognized as a major factor in cardiac arrhythmogenesis. This fundamental principle has motivated development of noninvasive techniques for quantification of heterogeneity using the surface electrocardiogram (ECG). The initial approaches focused on interval analysis such as interlead QT dispersion and Tpeak–Tend difference. However, because of inherent difficulties in measuring the termination point of the T wave and commonly encountered irregularities in the apex of the T wave, additional techniques have been pursued. The newer methods incorporate assessment of the entire morphology of the T wave and in some cases of the R wave as well. This goal has been accomplished using a number of promising vectorial approaches with the resting 12‐lead ECG. An important limitation of vectorcardiographic analyses is that they require exquisite stability of the recordings and are not inherently suitable for use in exercise tolerance testing (ETT) and/or ambulatory ECG monitoring for provocative stress testing or evaluation of the influence of daily activities on cardiac electrical instability. The objectives of the present review are to describe a technique that has been under clinical evaluation for nearly a decade, termed “interlead ECG heterogeneity.” Preclinical testing data will be briefly reviewed. We will discuss the main clinical findings with regard to sudden cardiac death risk stratification, heart failure evaluation, and myocardial ischemia detection using standard recording platforms including resting 12‐lead ECG, ambulatory ECG monitoring, ETT, and pharmacologic stress testing in conjunction with single‐photon emission computed tomography myocardial perfusion imaging.
Magic: A Theoretical Reassessment†
Authors: Winkelman Michael
Published: September 2021

Anthropological theories about the techniques broadly labeled magic and related practices as sorcery, witchcraft, divination, and ritual curing are in need of reformulation. Theoretical considerations of these phenomena within anthropology have neglected to consider the basic assumptions of magical belief, instead departing from Western cultural assumptions that beliefs about magic are empirically untenable and that there can be no such cause‐and‐effect relations as they imply. An impetus to the reformulation of theories of magic comes from experimental parapsychology where laboratory research has produced empirical support for some of the phenomena claimed by magical traditions. Parapsychologists interpret their findings as evidence for extrasensory perception, or clairvoyance and telepathy, and for foreknowledge or precognition, as well as evidence for the ability of human consciousness to effect physical systems. They postulate a force called psi responsible for such phenomena, and reports from anthropologists suggest that some aspects of magical practice involve psi. Consequently, anthropologists should examine more systematically the idea that magic has a psi‐related aspect—that some magical practices facilitate or produce empirically verifiable effects outside of the currently understood cause‐and‐effect processes of nature. This article reviews the findings of laboratory studies of parapsychology and their correspondences with principles of magical practices and beliefs reported by anthropologists. Magical theories, principles and practices share certain of the conditions found through parapsychological research to be conducive to psi manifestations: altered states of consciousness, visualization, positive expectation, and belief. This suggest that the indigenous rationale for magical practices are related to psi rather than delusional thought processes.
Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5 years of follow up
Authors: Sorda Juan Antonio , González Ballerga Esteban , Barreyro Fernando Javier , Avagnina Alejandra , Carballo Pilar , Paes de Lima Andrea , Daruich Jorge
Published: September 2021

Background

Ursodeoxycholic acid (UDCA) is the first‐line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients.

Aim

To evaluate the long‐term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA‐refractory PBC.

Methods

Fifty‐nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow‐up.

Results

Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA‐bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P < 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK‐PBC prognosis models.

Conclusions

Adding bezafibrate to UDCA in patients with UDCA‐refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long‐term cohort studies and controlled trials.
Testing the applicability of zircon U‐Pb dating as a provenance method in a highly altered river system, Mississippi‐Missouri River, USA
Authors: Gregory Brittney , Herrmann Achim D. , Ireland Thomas , Clift Peter D.
Published: September 2021

Sediment transport through the Mississippi River affects the lives and economies of millions of people along its course, so that understanding the controls on this process is of scientific and societal importance. Detrital U‐Pb geochronology, supported by grain size and major element data, can be a robust tool for constraining sediment provenance in clastic sedimentary systems that has been applied to the Mississippi. However, sediment storage and reworking can complicate interpretation, and this can be further exacerbated by anthropogenic alteration via the construction of levees, dams, locks and river diversion projects. In this study, we date zircons from the modern Mississippi River and compare them to previously acquired data to illustrate the difference between samples taken from the same catchment in order to better understand the downstream propagation of the modern detrital zircon signal. The modern Mississippi River and tributary systems show distinct similarities and are comparable between studies when samples are not too far separated (<100 km). We estimate that the Arkansas River is more important than previously proposed, at least in terms of sand supply, supplying 7%–11% of the total load. The largest supplier of sediment to the Mississippi is the Missouri River (33%–43%), which derives much of its sediment from sedimentary rocks in the foredeep deposited during the Sevier and Laramide events. Anthropogenic alteration of the modern river system can be seen in the downstream propagation of a Red River cut‐off signal following construction of the “River Control Structure”, implying slow zircon transport rates (<2.8 km/year). Differences in the degree of recycling caused by sampling locations and low numbers of grains introduce significant uncertainties to mixing calculations.
circUSP34 accelerates osteosarcoma malignant progression by sponging miR‐16‐5p
Authors: Lou Jingbing , Zhang Hongliang , Xu Jiuhui , Ren Tingting , Huang Yi , Tang Xiaodong , Guo Wei
Published: September 2021

Osteosarcoma (OS) is a primary and highly malignant mesenchymal tissue tumor. The specific pathological mechanism underlying disease initiation or progression remains unclear. Circular RNAs (circRNAs) are a type of covalently circular RNA with a head‐to‐tail junction site. In this study, we aimed to investigate the sponging mechanism between circRNAs and microRNAs (miRNAs) in OS. Based on the inhibited effect of miR‐16‐5p reported on OS, circUSP34 was analyzed as a sponge of miR‐16‐5p via Starbase. We found that circUSP34 promoted the proliferation, migration, and invasion of OS in vitro and in vivo. circUSP34 increased but miR‐16‐5p decreased in OS by qRT‐PCR. Function assays showed that the malignancy of OS cells, including proliferation, migration, and invasion, was inhibited after knocking out circUSP34. Western blotting results showed that the expression level of vimentin and Ki‐67 decreased. Similarly, miR‐16‐5p mimic compromised the proliferation, migration, and invasion of OS cells. FISH assay results indicated that circUSP34 and miR‐16‐5p were colocalized in the cytoplasm. The sponging mechanism of circUSP34 and miR‐16‐5p was verified by dual‐luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down assays. Interestingly, the miR‐16‐5p inhibitor partly reversed the inhibitory effect of sh‐circUSP34 on the malignancy of OS cells. Further, mice tumors for IHC indicated that vimentin, N‐cadherin, and Ki‐67 protein expression decreased, but E‐cadherin protein expression increased. Collectively, circUSP34 promoted OS malignancy, including proliferation, migration, and invasion, by sponging miR‐16‐5p. It can serve as a potential therapeutic target and biomarker.
A minireview of 1,2,3‐triazole hybrids with O‐heterocycles as leads in medicinal chemistry
Authors: Saroha Bhavna , Kumar Gourav , Kumar Ramesh , Kumari Meena , Kumar Suresh
Published: September 2021

Over the past few decades, the dynamic progress in the synthesis and screening of heterocyclic compounds against various targets has made a significant contribution in the field of medicinal chemistry. Among the wide array of heterocyclic compounds, triazole moiety has attracted the attention of researchers owing to its vast therapeutic potential and easy preparation via copper and ruthenium‐catalyzed azide‐alkyne cycloaddition reactions. Triazole skeletons are found as major structural components in a different class of drugs possessing diverse pharmacological profiles including anti‐cancer, anti‐bacterial, anti‐fungal, anti‐viral, anti‐oxidant, anti‐inflammatory, anti‐diabetic, anti‐tubercular, and anti‐depressant among various others. Furthermore, in the past few years, a significantly large number of triazole hybrids were synthesized with various heterocyclic moieties in order to gain the added advantage of the improved pharmacological profile, overcoming the multiple drug resistance and reduced toxicity from molecular hybridization. Among these synthesized triazole hybrids, many compounds are available commercially and used for treating different infections/disorders like tazobactam and cefatrizine as potent anti‐bacterial agents while isavuconazole and ravuconazole as anti‐fungal activities to name a few. In this review, we will summarize the biological activities of various 1,2,3‐triazole hybrids with copious oxygen‐containing heterocycles as lead compounds in medicinal chemistry. This review will be very helpful for researchers working in the field of molecular modeling, drug design and development, and medicinal chemistry.