bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative prediction of variant effects on alternative splicing using endogenous pre-messenger RNA structure probing
Authors: Kumar Jayashree , Lackey Lela , Waldern Justin M. , Dey Abhishek , Mathews David H. , Laederach Alain
Published: September 2021

Splicing is a highly regulated process that depends on numerous factors. It is particularly challenging to quantitatively predict how a mutation will affect precursor messenger RNA (mRNA) structure and the subsequent functional consequences. Here we use a novel Mutational Profiling (-MaP) methodology to obtain highly reproducible endogenous precursor and mature mRNA structural probing data in vivo. We use these data to estimate Boltzmann suboptimal ensembles, and predict the structural consequences of mutations on precursor mRNA structure. Together with a structural analysis of recent cryo-EM spliceosome structures at different stages of the splicing cycle, we determined that the footprint of the Bact complex on precursor mRNA is best able to predict splicing outcomes for exon 10 inclusion of the alternatively spliced MAPT gene. However, structure alone only achieves 74% accuracy. We therefore developed a β-regression weighting framework that incorporates splice site strength, structure and exonic/intronic splicing regulatory elements which together achieves 90% accuracy for 47 known and six newly discovered splice-altering variants. This combined experimental/computational framework represents a path forward for accurate prediction of splicing related disease-causing variants.
Competition Between Cell-Cell and Cell-Substrate Adhesion Determines Epithelial Monolayer Architecture in Culture
Authors: Cammarota Christian M. , Dawney Nicole S. , Jia Qingyuan , Jüng Maren M. , Glichowski Joseph A. , Bellomio Philip M. , Fletcher Alexander G. , Bergstralh Dan T.
Published: September 2021

Organ surfaces are lined by epithelial monolayers - sheets of cells that are one-cell thick. This architecture underlies tissue function, and its loss is associated with disease, including cancer. Studies of in-plane epithelial cell behaviors show that a developing epithelium behaves as a fluid in respect to the tissue plane, and can therefore readily adapt to varying mechanical influences during morphogenesis. We asked the question of how monolayer architecture is achieved, and whether it demonstrates the same fluid behavior. To address this problem, we cultured MDCK (Madin-Darby Canine Kidney) cell layers at different densities and timepoints and analyzed their architectures using a novel tool, Automated Layer Analysis (ALAn), which we introduce here. Our experimental and theoretical results lead us to propose that epithelial monolayer architecture is governed by a balance of counteracting forces due to cell-cell and cell-substrate adhesion, and that this balance is influenced by cell density. MDCK cells do not undergo obvious rearrangement along the apical-basal axis; instead, cells that do not contact the substrate aggregate on top of the monolayer. Our findings therefore imply that monolayered architecture is under more rigid control than planar tissue shape in epithelia.
Seasonal phenology of Coffee Berry Borer (Hypothenemus hampeiFerrari) in Hawaii and the influence of weather on flight activity
Authors: Johnson Melissa A. , Manoukis Nicholas C.
Published: September 2021

Coffee berry borer (CBB,Hypothenemus hampeiFerrari) is the most serious insect pest of coffee worldwide, yet little is known about its seasonal flight behavior or the effect that weather variables have on its activity. We sampled flying female CBB adults bi-weekly over a three-year period using red funnel traps baited with an alcohol lure at 14 commercial coffee farms on Hawaii Island to characterize seasonal phenology and the influence of five weather variables on flight activity. We captured almost 5 million Scolytid beetles during the sampling period, with 81-93% of the trap catch comprised of CBB. Of the captured non-target beetles, the majority were tropical nut borer, black twig borer and a species ofCryphalus. Two major flight events were consistent across all three years: an initial emergence from January-April that coincided with early fruit development and a second flight during the harvest season from September-December. A linear regression showed a moderate but significant negative relationship between elevation and total trap catch. A generalized additive mixed model (GAMM) revealed that mean daily air temperature has the most significant (positive) effect on CBB flight, with most flight events occurring between 20-26 °C. Mean daily solar radiation also had a significant positive effect, while maximum daily relative humidity negatively influenced flight at values above ∼94%. Flight was positively influenced by maximum daily wind speeds up to ∼2.5 m/s and cumulative rainfall up to 100 mm, after which activity declined. Our findings provide important insight into CBB flight patterns across a highly variable landscape and will serve as a starting point for the development of flight prediction models.
In vivophotopharmacology with a caged mu opioid receptor agonist drives rapid changes in behavior
Authors: Ma Xiang , Johnson Desiree A. , He Xinyi Jenny , Layden Aryanna E. , McClain Shannan P. , Yung Jean C. , Banghart Matthew R.
Published: September 2021

Photoactivatable drugs and peptides can drive quantitative studies into receptor signaling with high spatiotemporal precision, yet few are compatible with behavioral studies in mammals. We developed CNV-Y-DAMGO, a caged derivative of the mu opioid receptor-selective peptide agonist DAMGO. Photoactivation in the mouse ventral tegmental area produced an opioid-dependent increase in locomotion within seconds of illumination. These results demonstrate the power ofin vivophotopharmacology for dynamic studies into animal behavior.
Comparison of modified Karnik-Mendel algorithm-based interval type-2 ANFIS and type-1 ANFIS
Authors: Öztürk Muhammet , Özkol İbrahim
Published: September 2021

Purpose

This study aims to propose, as the first time, the interval type-2 adaptive network-fuzzy inference system (ANFIS) structure, which is given better results compared to previously presented in the open literature. So, the ANFIS can be used effectively for training of interval type-2 fuzzy logic system (IT2FLS) parameters.

Design/methodology/approach

Karnik–Mendel algorithm (KMA) is modified to use in interval type-2 ANFIS. The modified Karnik–Mendel algorithm (M-KMA) is implemented to change the uncertain ANFIS parameters into known ones. In this way, the interval type-2 ANFIS removes uncertainties of IT2FLS. Therefore, the interval type-2 ANFIS is reduced to a simple one, i.e. less mathematical operation required. Only consequent parameters are trained, and the consequent parameters are chosen in the form of crisp.

Findings

By applying the mentioned procedure, it can be shown that interval type-2 ANFIS has generally better results compared to type-1 ANFIS. However, it was noticed that the worst results obtained in the case of interval type-2 ANFIS are equal to the best result obtained in the case of type-1 ANFIS. Therefore, users in this field can use this approach in solving nonlinear problems.

Practical implications

The interval type-2 ANFIS can be used as controller for highly nonlinear systems such as air vehicles.

Originality/value

As stated in the open literature, it is ineffective to use ANFIS for IT2FLS. In this study, the KMA is modified for IT2FLS, and it is seen that the ANFIS can be used effectively for IT2FLS.
A smart objects library for BIM-based construction site and emergency management to support mobile VR safety training experiences
Authors: Getuli Vito , Capone Pietro , Bruttini Alessandro , Sorbi Tommaso
Published: September 2021

Purpose

Health and safety training via immersive virtual reality (VR) in the construction sector is still limited to few early adopters despite the benefits it could provide in terms of training effectiveness. To foster its adoption, in this work, the authors address the lack of an organized asset of digital contents dedicated to the production of VR site scenarios that emerged as one of the most limiting factors for the implementation of building information modeling (BIM) and VR for construction workers’ safety training. To improve this critically time-consuming process, a dedicated site object library is proposed.

Design/methodology/approach

The development of the site object library for the production of BIM-based VR safety training experiences followed a four-step process: definition of the object list and categories from the analysis of heterogeneous knowledge sources – construction sectors’ regulations, case studies and site scenarios’ imagery; definition of the object requirements (e.g. information, graphics, sounds, animations and more); design of an object information sheet as a library implementation support tool; and library implementation and validation via collaborative VR sessions.

Findings

This work provides the definition of a structured library of construction site objects dedicated to the production of VR scenarios for safety training comprising 168 items, implemented and validated.

Originality/value

The research contributes to facilitate and standardize the time-consuming contents’ production and modeling process of site scenarios for VR safety training, addressing the lack of a dedicated site object library. Furthermore, the novel library framework could serve as a base for future extensions dedicated to other applications of VR site simulations (e.g. constructability analysis).
The impact of smart specialization strategies on sub-cluster efficiency: simulation exercise for the case of Mexico
Authors: Zárate-Mirón Viviana Elizabeth , Moreno Serrano Rosina
Published: September 2021

Purpose

This paper aims to evaluate whether the integration of smart specialization strategies (S3) into clusters significantly impacts their efficiency for countries that still do not implement this policy. This study tests three effects: whether the kind of policies envisaged through an S3 strategy impacts cluster’s efficiency; whether this impact changes with the technological intensity of the clusters; to determine which S3 is more suitable for sub-clusters at different levels of technological intensity.

Design/methodology/approach

The Mexican economy is taken as case of study because it has a proper classification of its industries intro Porter’s cluster’s definition but still does not adopt the S3 policy. Through data envelopment analysis (DEA), this study evaluates the cluster’s efficiency increment when variables representing the S3 elements are included.

Findings

The results show that strategies following the S3 had a significant impact in all clusters, but when clusters were classified by technological intensity, the impact on efficiency is higher in clusters in the medium low-tech group.

Practical implications

According to the results in the DEA, it can be concluded that these S3 strategies have the potential to increase the clusters’ productivity significantly. These results make convenient the adoption of the S3 policy by countries that already count with a properly cluster definition.

Originality/value

These findings contribute to the lack of studies that analyze the join implementation of S3 on clusters.
An inductorless piezoelectric energy harvesting interface circuit using gyrator induced voltage flip technique
Authors: Zalke Jitendra B. , Pandey Sandeepkumar R. , Nandanwar Ruchir V. , Pande Atharva Sandeep , Nikam Pravin Balu
Published: September 2021

Purpose

The purpose of this research paper is to explore the possibility to enhance the power transfer from piezoelectric energy harvester (PEH) source to the load. As the proposed gyrator-induced voltage flip technique (GIVFT) does not require bulky components such as physical inductors, it is easily realizable in small integrated circuits (IC) package thereby offering performance benefits, reducing area overhead and providing cost benefits for constrained self-powered autonomous Internet-of-Things (IoT) applications.

Design/methodology/approach

This paper presents an inductorless interface circuit for PEH. The proposed technique is called GIVFT and is demonstrated using active elements. The authors use gyrator to induce voltage flip at the output side of PEH to enhance the charge extraction from PEH. The proposed technique uses the current-voltage (I-V) relationship of gyrator to get appropriate phasor response necessary to induce the voltage flip at the output of PEH to gain power transfer enhancement at the load.

Findings

The experimental results show the efficacy of the GIVFT realization for enhanced power extraction. The authors have compared their proposed design with popular earlier reported interface circuits. Experimentally measured performance improvement is 1.86×higher than the baseline comparison of full-wave bridge rectifier circuit. The authors demonstrated a voltage flip using GIVFT to gain power transfer improvement in piezoelectric energy harvesting.

Originality/value

To the best of the authors’ knowledge, pertaining to the field of PEH, this is the first reported GIVFT based on the I-V relationship of the gyrator. The proposed approach could be useful for constrained self-powered autonomous IoT applications, and it could be of importance in guiding the design of new interface circuits for PEH.
Smart workplace solutions – can they deliver the offices that employees have been waiting for?
Authors: Remes Laura , Dooley Kenneth , Ketomäki Jaakko , Ihasalo Heikki
Published: September 2021

Purpose

User-centred intelligent buildings (IBs) should respond to users’ needs holistically and the demand for end user applications is steadily growing. The purpose of this study is to answer: What are end user applications, what should they be called, and what are their key features?

Design/methodology/approach

This is a mixed-method study. The authors have used different data sources, such as online research and interviews. In data processing, the authors have used word counting and Latent Dirichlet Allocation topic modeling.

Findings

These end user applications can provide the missing user-centered elements of IBs. The authors have found that “smart workplace solution” (SWS) is the best term to describe these applications, and they also describe the key features, which include booking, showing free spaces, occupancy tracking, wayfinding and searching.

Research limitations/implications

As the end user applications are constantly and rapidly evolving, the latest evolving of such applications might not be covered. Furthermore, the authors have relied on companies’ information as given.

Originality/value

IBs have emerged over 20 years ago, and these are the first solutions that can be considered truly user-centered.
Strength and microstructure behaviour of high calcium fly ash based sustainable geo polymer concrete
Authors: Prasad B. Vijaya , Daniel Arumairaj Paul , N. Anand , Yadav Siva Kumar
Published: September 2021

Purpose

Concrete is a building material widely used for the infrastructural development. Cement is the binding material used for the development of concrete. It is the primary cause of CO2 emission globally. The purpose of this study is to develop sustainable concrete material to satisfy the present need of construction sector. Geopolymer concrete (GPC) is a sustainable concrete developed without the use of cement. Therefore, investigations are being conducted to replace the cement by 100% with high calcium fly ash (FA) as binding material.

Design/methodology/approach

High calcium FA is used as cementitious binder, sodium hydroxide (NaOH) and sodium silicates (Na2SiO3) are used as alkaline liquids for developing the GPC. Mix proportions with different NaOH molarities of 4, 6, 8 and 10 M are considered to attain the appropriate mix. The method of curing adopted is ambient and oven curing. Workability, compressive strength and microstructure characteristics of GPC are analysed and presented.

Findings

An increase of NaOH in the mix decreases the workability. Compressive strength of 29 MPa is obtained for Mix-I with 8 M under ambient curing. A polynomial relationship is obtained to predict the compressive strength of GPC. Scanning electron microscope analysis is used to confirm the geo-polymerisation process in the microstructure of concrete.

Originality/value

This research work focuses on finding some alternative cementitious material for concrete that can replace ordinary portland cement (OPC) to overcome the CO2 emission owing to the utilisation of cement in the construction industry. An attempt has been made to use the waste material (high calcium FA) from thermal power plant for the production of GPC. GPC concrete is the novel building material and alternative to conventional concrete. It is the ecofriendly product contributing towards the improvement of the circular economy in the construction industry. There are several factors that affect the property of GPC such as type of binder material, molarity of activator solution and curing condition. The novelty of this work lies in the approach of using locally available high calcium FA along with manufactured sand for the development of GPC. As this approach is rarely investigated, to prove the attainment of compressive strength of GPC with high calcium FA, an attempt has been made during the present investigation. Other influencing parameter which affects the strength gain has also been analysed in this paper.
Interactions between silicon and alkaloid defences in endophyte‐infected grasses and the consequences for a folivore
Authors: Cibils‐Stewart Ximena , Mace Wade J. , Popay Alison J. , Lattanzi Fernando A. , Hartley Susan (Sue) E. , Hall Casey R. , Powell Jeff R. , Johnson Scott N.
Published: September 2021

Grasses have developed a wide range of morphological and physiological mechanisms to resist herbivory. For instance, they accumulate silicon (Si) in tissue, as physical defence, and associate symbiotically with foliarEpichloë‐endophytes that provide chemical defence via antiherbivore alkaloids. Recent evidence showed that someEpichloë‐endophytes increase foliar Si in forage grasses; however, whether this impacts insect herbivores is unknown. Furthermore, while Si is primarily a physical defence, it also affects production of plant defensive secondary metabolites; Si supply might therefore affectEpichloë‐alkaloids, although this remains untested.

We grew endophyte‐free (Nil) andEpichloë‐infected tall fescue and perennial ryegrass in a factorial combination with or without Si supplementation, in the absence or presence ofHelicoverpa armigera.Epichloë‐endophyte strains were AR584 for tall fescue, and AR37, AR1 or Wild‐type (WT) for perennial ryegrass. We assessed how Si supply andEpichloë‐endophytes in interaction with herbivory affected foliar Si and mutualist‐derived alkaloid concentrations. Subsequently, their effects onH. armigerarelative growth rates (RGRs) were evaluated.

Endophytes generally increased Si concentrations in Si‐supplied plants. In tall fescue AR584 and perennial ryegrass AR37, endophytes increased constitutive (herbivore‐free) and induced (herbivore‐inoculated) Si concentrations by at least 25%; in contrast, in perennial ryegrass, the AR1 endophyte only increased constitutive levels. Si supply did not affect alkaloids produced by AR584 or AR1/WT endophytes; however, in the presence of herbivory, Si supply decreased the induction of alkaloids produced by AR37 endophytes by 33%. For tall fescue, Si supply reducedH. armigeraRGR by at least 76%, regardless of endophytic status, whereas, endophyte‐alkaloids played a secondary role only reducing herbivore growth in the absence of Si supply. Conversely, in perennial ryegrass, both Si and endophyte‐alkaloids (regardless of Si supply) reduced herbivore RGR although not synergised.

Novel interactions between constitutive and induced Si‐ and alkaloid‐based antiherbivore defences in grasses were observed. Overall, Si had a greater effect on the folivore than endophytes in both grasses. Endophyte defences contributed more to herbivore resistance in perennial ryegrass than tall fescue. We demonstrate that Si and endophytes were not antagonistic and highlight that the protective nature of their interaction varies with the grass‐endophyte species tested.

A freePlain Language Summarycan be found within the Supporting Information of this article.
‘Look on my works ye mighty…’: Iconoclasm, education and the fate of statues
Authors: Davis Robert A
Published: September 2021

In pursuit of an alternative perspective on the so-called ‘statues controversy’, this essay brings recent interpretations of the enduring ‘power’, ‘gaze’ and ‘magic’ of statues into alignment with critical histories of iconoclasm, sacred and secular, and New Materialist accounts of our multiple entanglements with the object histories of inherited monuments. Opening with a close reading of Percy Bysshe Shelley's renowned 1818 sonnet, ‘Ozymandias’, the essay applies the resultant theoretical synthesis to argue for the general restraint of popular iconoclastic and demolitionary acts and largely to caution against the mimetic violence of statue removal in favour of fresh, educative and iconotropic ways of ‘making legible’, and ‘re-reading’, statues, pedestals, inscriptions and their diverse contexts past and present.
Fasting plasma glucose, diagnosis of gestational diabetes and the risk of large for gestational age: a regression discontinuity analysis of routine data
Authors: Tennant PWG , Doxford‐Hook E , Flynn L , Kershaw K , Goddard J , Stacey T
Published: September 2021

Objective

To estimate the causal effects of fasting plasma glucose (FPG) and diagnosis of gestational diabetes (GDM) on birthweight and the risks of large for gestational age (LGA).

Design

Regression discontinuity analysis of routine data.

Setting

Two district general hospitals in West Yorkshire, UK.

Population

A cohort of 7062 women with singleton pregnancies who were screened for GDM and gave birth to a baby at ≥24 weeks of gestation in 2017–2019, inclusive.

Methods

The causal effects of FPG and GDM diagnosis were estimated using the two‐stage least‐squares approach, around the diagnostic threshold of FPG ≥ 5.6 mmol/l recommended by the UK’s National Institute for Health and Care Excellent (NICE), controlling for ethnicity, maternal age, parity, height and weight.

Main outcome measures

Birthweight (standardised for sex and gestational age) and large for gestational age (standardised as birthweight above the 90th centile).

Results

For each 1 mmol/l increase in FPG the observed birthweight increased by Z‐score = 0.48 standard deviations (95% CI 0.39 to 0.57) and the odds of LGA increased by OR = 2.61 (95% CI 1.86 to 3.66). Conversely, GDM diagnosis reduced the observed birthweight by Z = −0.61 (95% CI −0.94 to −0.29) and lowered the odds of LGA by OR = 0.33 (95% CI 0.15 to 0.74). Similar, but less certain, patterns were observed for caesarean section, shoulder dystocia and perinatal death.

Conclusions

The relationship between FPG and LGA is potent but is dramatically reduced by GDM diagnosis (and all the consequences thereof). Women with mild hyperglycaemia (with an FPG of 5.1–5.5 mmol/l) who fall below the current NICE threshold for GDM diagnosis have the highest risks of adverse outcomes, suggesting a need to reconsider their current care.

Tweetable abstract

Regression discontinuity analysis shows that untreated mild hyperglycaemia increases the odds of large for gestational age, but that a diagnosis of gestational #diabetes lowers the odds by three times.
The Role of Disclosure and Information Intermediaries in an Unregulated Capital Market: Evidence from Initial Coin Offerings
Authors: BOURVEAU THOMAS , DE GEORGE EMMANUEL T. , ELLAHIE ATIF , MACCIOCCHI DANIELE
Published: September 2021

Using an international sample of 2,113 initial coin offerings (ICOs), we explore the role of disclosure and information intermediaries in the unregulated crypto‐tokens market. First, we document substantial cross‐sectional variation in the voluntary disclosure practices of ventures seeking to raise capital through ICOs, such as the extent of information released in a prospectus‐type document called a white paper; releasing the technical source code; and communicating through social media platforms. Second, we find that, even with limited disclosure verifiability, ventures with higher levels of disclosure have a greater ability to raise capital. Finally, we find that this association is stronger in the presence of mechanisms that lend credibility to ventures’ voluntary disclosures, such as internal governance practices or external scrutiny from information intermediaries. Overall, our results suggest that voluntary disclosure and information intermediaries facilitate the functioning of ICOs as an alternative capital market.
Cost effectiveness of dietary interventions for individuals with mental disorders: A scoping review of experimental studies
Authors: Burrows Tracy , Teasdale Scott , Rocks Tetyana , Whatnall Megan , Schindlmayr Julia , Plain Janice , Roberton Michelle , Latimer Georgina , Harris Deanne , Forsyth Adrienne
Published: September 2021

Aim

This scoping review aimed to explore the extent of the evidence of experimental studies evaluating the cost effectiveness of dietary interventions in individuals with mental disorders.

Methods

Five databases (CINAHL, EMBASE, MEDLINE, PsycINFO and Scopus) were searched to October 2020 for cost‐analysis studies of interventions aiming to improve dietary intake in people with mental disorders. No restriction was placed on participant age, mental disorder type or intervention design. Results are presented narratively.

Results

Of 2753 articles identified, 13 articles reporting on eight studies were included. Studies were RCTs (n = 5), cluster RCT (n = 1), cluster preference RCT (n = 1), and pre‐post test (n = 1). Seven studies were in community settings (eg, outpatient clinics), and one study in the community housing setting. All studies were in adults, seven included male and female participants, and one included only females. Defined mental disorder diagnoses included serious/severe mental disorders (n = 3), major depression (n = 2), schizophrenia, schizoaffective disorder or first‐episode psychosis (n = 1), any mental disorder (n = 1), and bulimia nervosa (n = 1). Five interventions were multi‐behaviour, two were diet only and one was eating disorder treatment. Cost analyses included cost‐utility (n = 3), cost‐effectiveness (n = 1), cost‐utility and cost‐effectiveness (n = 3), and a costing study (n = 1). Two studies (25%) reported positive results in favour of cost effectiveness, and four studies reported a mix of positive and neutral results.

Conclusions

There is limited evidence evaluating the cost effectiveness of dietary interventions in individuals with mental disorders. Additional studies in various settings are needed to confirm cost effectiveness of different interventions.
Concurrent use of anlotinib overcomes acquired resistance to EGFR‐TKI in patients with advanced EGFR‐mutant non‐small cell lung cancer
Authors: Zhang Chen , Cao Honggang , Cui Yanan , Jin Shidai , Gao Wen , Huang Chenjun , Guo Renhua
Published: September 2021

Background

Acquired resistance development is a major challenge in the epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR–TKI) treatment of non–small cell lung cancer (NSCLC). Here, we investigated the potential effects of the concurrent use of anlotinib and EGFR‐TKI to overcome acquired resistance.

Methods

We conducted a preclinical study to evaluate the antitumor effects of gefitinib + anlotinib in gefitinib‐resistant lung adenocarcinoma models in vitro and in vivo. We then investigated the treatment effect of EGFR–TKI + anlotinib therapy in 24 advanced EGFR‐mutant NSCLC patients after EGFR‐TKI acquired resistance between January 2018 and August 2020.

Results

Anlotinib reversed gefitinib resistance in gefitinib‐resistant lung adenocarcinoma models by enhancing the antiproliferative and proapoptotic effects of gefitinib. The gefitinib + anlotinib treatment exerted a synergistic antitumor effect by downregulating the activation of VEGFR2 and downstream effectors, Akt and ERK. The EGFR–TKI + anlotinib therapy exhibited an objective response rate of 20.8% and a disease control rate of 95.8%. Median progression‐free survival (PFS) was 11.53 ± 2.41 months, but median overall survival was not reached. The median PFS was longer in patients experiencing gradual progression (13.30 ± 1.69 months) than in patients with dramatic progression (6.80 ± 1.75 months, p = 0.017). One grade 3 adverse event was noted (diarrhea, n = 2, 8.3%), and grade 4 or 5 adverse events were absent.

Conclusions

EGFR–TKI combined with anlotinib demonstrated powerful antitumor activity in vitro and in vivo. Concurrent use of anlotinib overcomes acquired resistance to EGFR‐TKI in advanced EGFR‐mutant NSCLC patients.
Accounting as a Normalizing Tool for Transitional Dirtiness: The Case of theUS Adult‐UseCannabis Industry*
Authors: Romi Andrea M. , Carrasco Heather , Camors Casey A. , Masselli John J.
Published: September 2021

While prior accounting research documents normalizing strategies within the accounting profession and in instances of accounting adoption, the potential of accounting itself as a strategic tool toward normalizing that which is considered socially abnormal (i.e., dirty) remains an important and unexamined area of inquiry. In this study, we conduct in‐depth interviews to examine the role accounting plays in the development of the US cannabis industry (CI) as it transitions from the illicit market in which formal accounting was systematically avoided to a state‐legal market in which participants are subject to conventional business processes. Facing impediments to traditional operating practices and pressures to increase normative conformity for industry survival, cannabis operators (COs) incorporated the use of accounting in three normalizing strategies (creative concession, collaborative facilitation, and experimentation), seemingly influenced by the incongruencies between prior illicit‐market culture and experiences and the state‐legal operating environment. In response to what operators perceived to be coercive regulation, they employed creative concession strategies, including influencing, bargaining, challenging, escaping, and cessation tactics. However, in response to pressures to adopt more commonly accepted forms of accounting, COs instead deployed two different strategies, one focused on acquiescence to normalizing pressures when doing so facilitated essential relationship building (i.e., collaborative facilitation strategies), and one deployed as strategic experimentation, working to normalize industry activities in areas of perceived threats to industry acceptance and continuity. Given CO accounting naiveté, its usefulness was often introduced by peripheral industry parties attempting to normalize their own participation with the CI. Notably, we also find that normalizing pressures occasionally resulted in unintended consequences, including reversion to the illicit market and forgoing normalizing strategies in favor of retaining some level of dirtiness to fend off pending competition, both of which threaten to reemphasize the industry's dirtiness. Our study, therefore, points to accounting itself as a central mechanism in the complex, multidirectional strategy to normalize transitional dirtiness.
An altered sputum macrophage transcriptome contributes to the neutrophilic asthma endotype
Authors: Fricker Michael , Qin Ling , Sánchez‐Ovando Stephany , Simpson Jodie L. , Baines Katherine J. , Riveros Carlos , Scott Hayley A. , Wood Lisa G. , Wark Peter AB. , Kermani Nazanin Z. , Chung Kian Fan , Gibson Peter G.
Published: September 2021

Background

Neutrophilic asthma (NA) is a clinically important asthma phenotype, the cellular and molecular basis of which is not completely understood. Airway macrophages are long‐lived immune cells that exert important homeostatic and inflammatory functions which are dysregulated in asthma. Unique transcriptomic programmes reflect varied macrophage phenotypes in vitro. We aimed to determine whether airway macrophages are transcriptomically altered in NA.

Methods

We performed RNASeq analysis on flow cytometry‐isolated sputum macrophages comparing NA (n = 7) and non‐neutrophilic asthma (NNA, n = 13). qPCR validation of RNASeq results was performed (NA n = 13, NNA n = 23). Pathway analysis (PANTHER, STRING) of differentially expressed genes (DEGs) was performed. Gene set variation analysis (GSVA) was used to test for enrichment of NA macrophage transcriptomic signatures in whole sputum microarray (cohort 1 ‐ controls n = 16, NA n = 29, NNA n = 37; cohort 2 U‐BIOPRED ‐ controls n = 16, NA n = 47, NNA n = 57).

Results

Flow cytometry‐sorting significantly enriched sputum macrophages (99.4% post‐sort, 44.9% pre‐sort, p < .05). RNASeq analysis confirmed macrophage purity and identified DEGs in NA macrophages. Selected DEGs (SLAMF7, DYSF, GPR183, CSF3, PI3, CCR7, all p < .05 NA vs. NNA) were confirmed by qPCR. Pathway analysis of NA macrophage DEGs was consistent with responses to bacteria, contribution to neutrophil recruitment and increased expression of phagocytosis and efferocytosis factors. GSVA demonstrated neutrophilic macrophage gene signatures were significantly enriched in whole sputum microarray in NA vs. NNA and controls in both cohorts.

Conclusions

We demonstrate a pathophysiologically relevant sputum macrophage transcriptomic programme in NA. The finding that there is transcriptional activation of inflammatory programmes in cell types other than neutrophils supports the concept of NA as a specific endotype.
Development of a multivariable prediction model for congenital unilateral absence of the vas deferens in male partners of infertile couples
Authors: Brusq Clara , Mieusset Roger , Hamdi Safouane M.
Published: September 2021

Background

Congenital unilateral absence of vas deferens has been diagnosed in fertile and normozoospermic males and is associated with the risk of unilateral renal absence or cystic fibrosis transmembrane conductance regulator mutations; but no prediction model currently exists to diagnose this condition.

Objectives

The study aims to identify clinical and biological variables that may have a predictive value for the diagnosis of congenital unilateral absence of vas deferens in male partners of infertile couples

Materials and methods

We designed a retrospective, cross‐sectional, case‐control study on electronic health records of a single tertiary‐care andrological centre collected between 1998 and 2018. We included all subjects diagnosed with congenital unilateral absence of vas deferens using combined scrotal and transrectal ultrasounds. Controls were confirmed free of congenital unilateral absence of vas deferens by the same way. Both groups received standardised exploration procedures. Multivariable logistic regression model was built in a backward stepwise manner. Model performance and calibration were assessed. The study is reported according to TRIPOD statement.

Results

We included 69 congenital unilateral absence of vas deferens cases and 78 controls. Cases had a lower semen volume than controls. The congenital unilateral absence of vas deferens risk was associated with history of cryptorchidism and both levels of semen fructose and α‐glucosidase. These predictors were confirmed by a random forest algorithm. The area under the curve was 0.886 (95% interval: 0.81–0.92). Calibration was performed with the Hosmer‐Lemeshow test (p = 0.88).

Discussion and conclusion

History of cryptorchidism, semen fructose and α‐glucosidase were identified as relevant and independent predictors for the diagnosis of congenital unilateral absence of vas deferens. The model enables to identify male patients with a high risk of congenital unilateral absence of vas deferens to whom a transrectal ultrasounds would be proposed to confirm the diagnosis, whatever their semen parameters. It will also help to address the risks of unilateral renal absence and of cystic fibrosis transmembrane conductance regulator mutations carrying during the management of infertile couples.
Differences in sex hormone recovery profile after cessation of 12‐week gonadotropin‐releasing hormone antagonist versus agonist therapy
Authors: Sasaki Hiroshi , Miki Kenta , Tashiro Kojiro , Mori Keiichiro , Urabe Fumihiko , Fukuokaya Wataru , Kimura Takahiro , Sato Shun , Takahashi Hiroyuki , Aoki Manabu , Egawa Shin
Published: September 2021

Background

Pharmacobiological behavior differs between gonadotropin‐releasing hormone (GnRH) antagonists and GnRH agonists. However, reliable evidence clarifying the difference between them is limited.

Objectives

We aimed to elucidate the difference in recovery profile between GnRH antagonist (degarelix) and GnRH agonist (leuprorelin acetate or goserelin acetate) as short‐term (12 weeks) neoadjuvant androgen deprivation therapy (ADT) prior to 125I‐transperineal prostate brachytherapy (TPPB) for localized prostate cancer.

Materials and Methods

This study was initially designed as a single‐center, prospective, open‐label, randomized controlled trial. The primary endpoint was a serum testosterone level above the castration range (>50 ng/dl) after the cessation of 12‐week neoadjuvant ADT (GnRH antagonist or GnRH agonists). All patients underwent 12 weeks of neoadjuvant ADT. The recovery profiles of hormones, prostate‐specific antigen, total prostate volume (TPV), bone mineral density, and quality of life scores were investigated.

Results

Testosterone recovery duration after the last injection was significantly longer in the GnRH antagonist arm than in the GnRH agonist arm (median, 27.3 vs. 4.8 weeks, p < 0.001). The serum levels of luteinizing hormone and follicle‐stimulating hormone in the GnRH antagonist arm also remained significantly lower than those in the GnRH agonist arm between 16 and 24 weeks (p < 0.01). Meanwhile, reduction in TPV at the time of TPPB was comparable between both arms (p = 0.128). There were also no significant between‐arm differences in the International Prostate Symptom Score and the International Index of Erectile Function scores.

Discussion and Conclusion

The recovery patterns of hormonal profiles after short‐term (12 weeks) neoadjuvant ADT differ between GnRH antagonists and GnRH agonists. The choice between these drugs matters and may have a clinical impact depending on the primary objective of ADT.
A quarter of century after: The changing ecology of psychiatric emergency services
Authors: Chen Wen‐Hao , Hsieh Ming H. , Liao Shih‐Cheng , Liu Chen‐Chung , Liu Chih‐Min , Wu Chi‐Shin , Lin Yi‐Ting , Hwang Tzung‐Jeng , Chien Yi‐Ling
Published: September 2021

Introduction

Previous studies demonstrated a trend of increasing common mental disorders among the Emergency Department (ED) visitors in Western countries. Little is known about the current conditions of the emergency psychiatric services in Asian countries. This study aims to survey the current epidemiology and the changing ecology of emergency psychiatry services in Taiwan.

Methods

A total of 804 psychiatry consultations were initiated at the ED during the 1‐year period from July 1, 2014 to June 30, 2015 in a medical center in northern Taiwan. Clinical data of gender, age, chief complaints, tentative diagnoses, dispositions, and ED staying hours were compared to a previous report in the same hospital in 1988.

Results

Psychiatry consultation was initiated in 0.72% of all ED visits (804/111,923). Among these visits, females were 1.73 times of the males. The most common chief complaints were psychosis/mania (33.5%) and suicide/self‐harm (33.2%), followed by homicide/violence (12.8%) and anxiety/depression (10.3%). Top tentative diagnoses were schizophrenia spectrum and other psychotic disorders (31.3%), trauma‐ and stressor‐related disorders (17.5%), bipolar disorders (15.9%), and depressive disorders (14.2%). Compared to 1988, there are three major changes: (1) over‐representation of female patients, (2) an increase of “neurosis” patients, and (3) an increase of suicide/self‐harm as chief problem.

Discussion

This study portrays the current epidemiology and changing ecology of psychiatric emergency in Taiwan. The increase of neurotic and suicide/self‐harm patients requires more services and clinical training in managing common mental disorders and suicide in the ED.
Analysis of the trends of polypharmacy and high‐dose prescriptions in Japan
Authors: Shinfuku Naotaka
Published: September 2021

Introduction

After extensive research, this study explored whether high‐dose prescriptions and polypharmacy remain more frequent in Japan than elsewhere. If confirmed, we aimed to identify the factors that contributed to this unique trend.

Methods

The psychotropic drug prescription patterns for patients with schizophrenia in Japan were reviewed. This was based on a large sample collected from surveys of the Research on Asian Psychotropic Prescription Patterns, an international collaborative research project conducted by Asian psychiatrists to monitor prescriptions of psychotropic drugs for people with mental disorders, in 2001, 2004, 2008, and 2016.

Results

The 2016 Research on Asian Psychotropic Prescription Patterns survey revealed that Japan continued to demonstrate the highest rate of polypharmacy and the highest dosages of psychotropic prescription drugs for patients with schizophrenia among the 15 countries and areas that participated in the survey.

Discussion

The Research on Asian Psychotropic Prescription Patterns surveys demonstrated that science plays a limited role in the decision‐making process for prescriptions of psychotropic medications. Such prescriptions are influenced by a wide range of factors, such as the national mental health policy, prescription‐financing systems, the history of psychiatry in each country, and the prevailing culture. Hospital‐based national mental health policies and mental health financing systems have been the primary obstacles to reducing polypharmacy in Japan.
Medication use and microscopic colitis
Authors: Sandler Robert S. , Keku Temitope O. , Woosley John T. , Galanko Joseph A. , Peery Anne F.
Published: September 2021

Background

Microscopic colitis is an increasingly common cause of watery diarrhoea. Several classes of medications have been associated with microscopic colitis in prior studies.

Aims

To determine the association between the use of previously implicated medications and microscopic colitis.

Methods

This was a case‐control study of patients referred for elective, outpatient colonoscopy for diarrhoea. Patients were excluded for inflammatory bowel disease, C difficile, or other infectious diarrhoea. Colon biopsies were reviewed by the study pathologist and patients were classified as microscopic colitis cases or non‐microscopic colitis controls.

Results

The study population included 110 microscopic colitis cases and 252 controls. The cases were older, better educated and more likely to be female. Cases reported a greater number of loose, watery, or liquid stools, nocturnal stools, more urgency and weight loss compared to controls. There was no association with proton pump inhibitors (PPIs), adjusted OR (aOR) 0.66, 95% CI 0.38‐1.13 or nonsteroidal anti‐inflammatory drugs, aOR 0.68, 95% CI 0.40‐1.17. Cholecystectomy was less common in cases, aOR 0.33, 95% CI 0.17‐0.64, but microscopic colitis cases had more frequent bowel movements following cholecystectomy.

Conclusion

Compared to similar patients with diarrhoea, cases with microscopic colitis were not more likely to have taken previously implicated medications. They had more diarrhoea following cholecystectomy, suggesting that bile may play a role in symptoms or aetiology. We conclude that the appropriate choice of controls is crucial to understanding risk factors for microscopic colitis.
Novel oral iron therapy for iron deficiency anaemia: How to value safety in a new drug?
Authors: Culeddu Giovanna , Su Li , Cheng Yafeng , Pereira Dora I. A. , Payne Rupert A. , Powell Jonathan J. , Hughes Dyfrig A.
Published: September 2021

Aims

Novel oral iron supplements may be associated with a reduced incidence of adverse drug reactions compared to standard treatments of iron deficiency anaemia. The aim was to establish their value‐based price under conditions of uncertainty surrounding their tolerability.

Methods

A discrete‐time Markov model was developed to assess the value‐based price of oral iron preparations based on their incremental cost per quality‐adjusted life year (QALY) gained from the perspective of the NHS in the UK. Primary and secondary care resource use and health state occupancy probabilities were estimated from routine electronic health records; and unit costs and health state utilities were derived from published sources. Patients were pre‐menopausal women with iron deficiency anaemia who were prescribed oral iron supplementation between 2000 and 2014.

Results

The model reflecting current use of iron salts yielded a mean total cost to the NHS of £779, and 0.84 QALYs over 12 months. If a new iron preparation were to reduce the risk of adverse drug reactions by 30–40%, then its value‐based price, based on a threshold of £20 000 per QALY, would be in the region of £10–£13 per month, or about 7–9 times the average price of basic iron salts.

Conclusions

There are no adequate, direct comparisons of new oral iron supplements to ferrous iron salts, and therefore other approaches are needed to assess their value. Our modelling shows that they are potentially cost‐effective at prices that are an order of magnitude higher than existing iron salts.
Transforming economics values toward life: From heterodoxy to orthodoxy
Authors: Waddock Sandra
Published: September 2021

In the face of numerous crises, including a global pandemic, it is time to challenge economic orthodoxy—neoliberalism—and develop a new economic orthodoxy built around values and principles that give life and prominence to socioecological systems. In this essay, I link six values of life‐affirming economics to principles that give life to systems. The life‐affirming economic values are stewardship of the whole; cocreating collective value; cosmopolitan localist‐governance; regenerativity, reciprocity, and circularity; relationality and connectedness; and equitable markets and trade. These values can be linked to principles that give life to systems, which include wholeness, purpose, boundedness, connectedness and diversity, and human consciousness or awareness. Because humans can design markets and trade to be equitable, if they so desire, all of the principles that give life are linked to that value. Combined these principles provide a platform for a set of assumptions underpinning a potential new economic orthodoxy to replace the flawed set of assumptions in the neoliberal economics currently dominant in industrialized nations.
Modelling publication bias andp‐hacking
Authors: Moss Jonas , De Bin Riccardo
Published: September 2021

Publication bias andp‐hacking are two well‐known phenomena that strongly affect the scientific literature and cause severe problems in meta‐analyses. Due to these phenomena, the assumptions of meta‐analyses are seriously violated and the results of the studies cannot be trusted. While publication bias is very often captured well by the weighting function selection model,p‐hacking is much harder to model and no definitive solution has been found yet. In this paper, we advocate the selection model approach to model publication bias and propose a mixture model forp‐hacking. We derive some properties for these models, and we compare them formally and through simulations. Finally, two real data examples are used to show how the models work in practice.