bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Throughput Mutant Screening inVibrio choleraevia Transposon Sequencing
Authors: Bourgeois Jacob , Camilli Andrew
Published: October 2023

Transposon mutagenesis greatly facilitates the study of gene function in microorganisms ranging from viruses to fungi. Traditionally, one would study individual transposon mutants with interesting phenotypes one mutant at a time. Here, we describe methods for the study of tens of thousands of transposon mutants in parallel in the bacterial pathogenVibrio choleraeusing transposon-sequencing. The first section outlines methods for making a saturated transposon mutant library. The second section outlines methods for massively parallel sequencing of the transposon junctions. The third section outlines methods for analyzing the sequence data to calculate the fitness contribution of genes.
Assessing the high-quality development strategy of mineral resource enterprises
Authors: Cheng Jingyu , Wang Minxi , Wu Lilin , Li Xin
Published: October 2023

Purpose

The purpose of this paper is to explore the high-quality development (HQD) strategy of Chinese mineral resource enterprises, which is important for Chinese mineral resource enterprises to improve the efficiency and benefit of resource utilization, reduce the intensity of resource and energy consumption and gradually form resource-saving and environment-friendly enterprises.

Design/methodology/approach

This study establishes an evaluation index system with four dimensions: economy, environment, society and management innovation. The entropy value method assigns weights to them and then uses the system dynamics (SD) model for case simulation.

Findings

The results of the SD simulation conclude that the fulfillment of social responsibility and the implementation of management innovation can accelerate the realization of HQD of mineral resource enterprises; profitability plays a crucial role in economic indicators; the improvement of energy-saving volume has the most significant impact on environmental benefits; the social contribution is the key element to measure social indicators; and the sales rate of core products has the most significant impact on the benefits of management innovation.

Originality/value

Based on the few studies on the evaluation of the development strategy of mineral resource enterprises, this study establishes an evaluation index system that considers the interactions between indicators, combines the entropy value method with SD and uses the SD model to comprehensively and systematically analyze the impact and degree of each factor on the HQD of mineral resource enterprises.
A knowledge graph of interlinking digital records: the case of the 1997 Korean financial crisis
Authors: Kim Haklae
Published: October 2023

Purpose

Despite ongoing research into archival metadata standards, digital archives are unable to effectively represent records in their appropriate contexts. This study aims to propose a knowledge graph that depicts the diverse relationships between heterogeneous digital archive entities.

Design/methodology/approach

This study introduces and describes a method for applying knowledge graphs to digital archives in a step-by-step manner. It examines archival metadata standards, such as Records in Context Ontology (RiC-O), for characterising digital records; explains the process of data refinement, enrichment and reconciliation with examples; and demonstrates the use of knowledge graphs constructed using semantic queries.

Findings

This study introduced the 97imf.kr archive as a knowledge graph, enabling meaningful exploration of relationships within the archive’s records. This approach facilitated comprehensive record descriptions about different record entities. Applying archival ontologies with general-purpose vocabularies to digital records was advised to enhance metadata coherence and semantic search.

Originality/value

Most digital archives serviced in Korea are limited in the proper use of archival metadata standards. The contribution of this study is to propose a practical application of knowledge graph technology for linking and exploring digital records. This study details the process of collecting raw data on archives, data preprocessing and data enrichment, and demonstrates how to build a knowledge graph connected to external data. In particular, the knowledge graph of RiC-O vocabulary, Wikidata and Schema.org vocabulary and the semantic query using it can be applied to supplement keyword search in conventional digital archives.
Determining cybersecurity culture maturity and deriving verifiable improvement measures
Authors: Dornheim Peter , Zarnekow Ruediger
Published: October 2023

Purpose

The human factor is the most important defense asset against cyberattacks. To ensure that the human factor stays strong, a cybersecurity culture must be established and cultivated in a company to guide the attitudes and behaviors of employees. Many cybersecurity culture frameworks exist; however, their practical application is difficult. This paper aims to demonstrate how an established framework can be applied to determine and improve the cybersecurity culture of a company.

Design/methodology/approach

Two surveys were conducted within eight months in the internal IT department of a global software company to analyze the cybersecurity culture and the applied improvement measures. Both surveys comprised the same 23 questions to measure cybersecurity culture according to six dimensions: cybersecurity accountability, cybersecurity commitment, cybersecurity necessity and importance, cybersecurity policy effectiveness, information usage perception and management buy-in.

Findings

Results demonstrate that cybersecurity culture maturity can be determined and improved if accurate measures are derived from the results of the survey. The first survey showed potential for improving the dimensions of cybersecurity accountability, cybersecurity commitment and cybersecurity policy effectiveness, while the second survey proved that these dimensions have been improved.

Originality/value

This paper proves that practical application of cybersecurity culture frameworks is possible if they are appropriately tailored to a given organization. In this regard, scientific research and practical application combine to offer real value to researchers and cybersecurity executives.
Demographic, experience, and organisational factors effect on local enforcement officers’ ethical integrity
Authors: Zakaria Nor Balkish , Nordin Muhammad Farhan , Ismail Allezawati , Ahmad Shukri Nurul Huda , Baykal Elif
Published: October 2023

Purpose

This study departed from the aim to progress Malaysia as a high-income nation in 2025 via decent work and economic growth (Sustainable Development Goal 8). Thus, this study aims to examine the effects of demographic, experience and organisational factors on the ethical integrity of local enforcement officers from self-proclaim and colleague perception perspectives.

Design/methodology/approach

The data of this study was collected from Pusat Latihan Penguatkuasa Selangor (PULAPES), a training centre for local enforcement officers in Selangor. Based on a survey in 2019, this study used primary data based on a scenario-based questionnaire survey with a total sample of 535 respondents.

Findings

From a self-proclaim perspective, the results show that secondment and training factors have a positive relationship with the ethical integrity of local enforcement officers. From a colleague perception perspective, the results indicate that the secondment factor has a positive relationship with ethical integrity. In contrast, the officer rank factor has a negative relationship with the ethical integrity of local enforcement officers.

Practical implications

This research seeks to develop new theories or refine existing ones to explain how diverse circumstances affect law enforcement ethics. Learning people’s habits through observation and consequences like rewards or punishments impact behaviour recurrence are suggested. Law enforcement ethics can be examined by examining how peers, supervisors and organisational culture shape officers’ ethics.

Social implications

The finding of this study could serve to evaluate training programmes or rewards and punishments for ethical behaviour including how accountability and community involvement aid to promote law enforcement ethics.

Originality/value

The survey results of this study are based on local enforcement officers’ ethics that serve to aid in illuminating the elements which affect ethical behaviour among law enforcement personnel and identify the tactics for fostering ethical behaviour.
Can insurance ensure economic growth in an emerging economy? Fresh evidence from a non-linear ARDL approach
Authors: Tran Quang Thien , Huynh Nhan
Published: October 2023

Purpose

This study aims to explore the nexus between insurance penetration and economic development in Vietnam, one of the fastest-growing economies over the past two decades.

Design/methodology/approach

This study uses an updated data set of the insurance sector in Vietnam from 1996 to 2020. The autoregressive lagging distribution and cointegrating non-linear autoregressive lagging distribution (NARDL) models are used to explore the nexus between the insurance market development and economic growth.

Findings

This study confirms the unidirectional causality and positive impacts of insurance market development on economic growth both in the short and long term, supporting the “supply-leading” hypothesis. Nonlife insurance has more significant but slower impacts on contributing to economic development in the long run. From the NARDL approach, this study also discloses the asymmetric relationship between the insurance industry and economic growth. Aggregate and life insurance display short- and long-term asymmetric impacts, whereas nonlife insurance shows long-term asymmetry.

Originality/value

To the best of the authors’ knowledge, this is the first study to examine the hidden asymmetries of the insurance-growth nexus in Vietnam from non-linear models. Notwithstanding the theoretical contributions to the prior literature, several practical implications are proposed for insurance businesses, policymakers and investors.
Consumer confusion and negative eWOM in the e-hospitality marketplace: the moderated moderation model of gender and technology self-efficacy
Authors: Sharma Anuradha , Pandher Jagwinder Singh , Prakash Gyan
Published: October 2023

Purpose

The goal of this paper is to use the stimulus-organism-response (S-O-R) paradigm to understand how ineffective marketplace stimuli affect perceptions related to online travel package booking, which in turn cultivate various types of confusion, and how these confusions are channelled into behavioural dispositions of consumers, such as negative electronic word-of-mouth (eWOM). It also aims to investigate the moderating effects of gender and technology self-efficacy for the suggested framework.

Design/methodology/approach

A sample of 437 participants who had recently booked an online travel package, underwent an analysis using a survey study design. Structural equation modelling with multigroup analysis was used to evaluate the hypotheses and the moderation effect.

Findings

The findings suggest that inefficient market stimulus results in various forms of confusion, further contributing to negative eWOM. The results also imply that technology self-efficacy lessens the effect of various confusions on adverse eWOM, and gender is found to have a moderating effect on the relationships between ineffective marketplace stimuli, confusion and negative eWOM.

Practical implications

The research offers tourism and hospitality management advice on how to deal with inefficient marketplace stimulation to lessen confusion, which then reduces unfavourable eWOM. Additionally, the moderate impact of technology self-efficacy and gender established through the current study has important ramifications from a tourism managers' perspective.

Originality/value

This study develops and validates an empirical model, which will be utilised as a framework to fully understand consumer confusion brought on by ineffective marketplace stimulation, which causes adverse eWOM. The study also gives new perspectives on the moderating roles of gender and technology self-efficacy, which have received little attention in earlier studies.
Life after digital displacement: analog entrepreneurship and the revitalization of legacy technologies
Authors: Roundy Philip T. , Bayer Mark A.
Published: October 2023

Purpose

Research at the interface of marketing and entrepreneurship has emphasized digital entrepreneurship and how entrepreneurs pursue business opportunities centered on new technologies. However, a different type of entrepreneurship focused on opportunities involving consumers’ (re)adoption of displaced analog technologies when digital alternatives are dominant – analog entrepreneurship – is a trend and counter phenomenon to digital entrepreneurship that is receiving intense practitioner interest but limited scholarly attention. The purpose of this article is to present a theoretical framework that explains the role of analog entrepreneurship in technology revitalization.

Design/methodology/approach

In this conceptual paper, the authors use the microfoundations perspective to develop a multilevel theory of analog entrepreneurship. The authors define and delineate the “analog entrepreneurship” concept and formulate a midrange theory explaining how entrepreneurs influence the reemergence of analog technologies.

Findings

The theory’s main insight is that the renewal of analog technologies is not confined to consumers. Entrepreneurs are creating businesses that stimulate demand for analog technologies. As a result of entrepreneurs’ activities, legacy analog technologies do not fade into nonexistence in the face of rival digital technologies.

Originality/value

The theory of analog entrepreneurship contributes to research at the intersection of entrepreneurship and marketing by expanding its focus to consider the entrepreneurs who revitalize displaced analog technologies when digital alternatives are dominant. The authors provide insight into the potential trajectories of technologies after their initial displacement and the role entrepreneurs play in shaping the late stages of technology lifecycles. The theory draws attention to an underexplored phenomenon made increasingly prevalent by recent technological disruptions and suggests an agenda for studying how entrepreneurs renew analog technologies.
Strengthening customer loyalty through financial satisfaction in the banking industry
Authors: Tegambwage Amani Gration , Kasoga Pendo Shukrani
Published: October 2023

Purpose

This study aims to investigate the effect of financial satisfaction (FS) on customer loyalty in the banking industry.

Design/methodology/approach

The study followed an explanatory research design using responses from 334 respondents from commercial banks in Tanzania. A stepwise regression analysis was used to validate the relevance of the study model.

Findings

The results indicate a positive and statistically significant association between customer loyalty and FS with levels of assets (β = 0.598, p < 0.001), savings (β = 0.186, p < 0.001) and debts (β = 0.065, p < 0.001). Of the three dimensions of FS, the level of assets had the strongest contribution to customer loyalty, followed by the level of savings and debts, in that order.

Research limitations/implications

The study used a model of FS that was linked to customer loyalty in the Tanzanian banking industry. It is recommended that the model be tested in other environments to increase the generalizability of the findings.

Practical implications

This study provides an alternative way for banks to strengthen customer loyalty by enhancing FS.

Originality/value

The FS model (Joo and Grable, 2004) and the social exchange theory (Blau, 1964) are used in this study to propose a model of customer loyalty in the banking industry. Customer loyalty and FS have not been connected in prior studies.
An empirical study on implementation of sustainable production practices in Indian manufacturing industry
Authors: Jha Neeraj Kumar , Jasti Naga Vamsi Krishna , Chaganti Phaneendra Kiran , Kota Srinivas , Nagpal Gaurav
Published: October 2023

Purpose

Sustainable production (SP) is an efficient and influential approach of production for Indian manufacturing industries as it preserves the social, environmental and economic aspects of production activities altogether. The objective of this research work is to investigate the implementation status of SP practices in Indian manufacturing industries by utilizing empirical survey methodology.

Design/methodology/approach

A questionnaire survey methodology was adapted, and the questionnaire was prepared by intense literature survey along with by opinions from experts in the field of SP. This questionnaire was sent to 753 different organizations at different locations across India. This study collected responses from manufacturing industries as per 2021 directory of Confederation of Indian Industries for the duration of 7 week. Top level managers were the target respondents. The study propagated with 242 responses which were observed complete in all respects.

Findings

The study identified that though the majority of the organizations are claiming to follow SP practices since long time, they actually are lagging in proper understanding SP practices. Majority of them are implementing it in specific departments in their organization. They are coming across multiple barriers in the implementation of SP practices among which unrecognized financial benefits and lack of proper government policies are prime. The study suggests that the Indian organizations needs feasible framework with adaptable guidelines.

Research limitations/implications

This work is centered towards manufacturing organizations and targets only the leading industrial sectors in India. Thus, the outcomes of this study may not be generalized for all the sectors of Indian industries. Additionally, it can also be assumed that higher number of responses would have contributed to more clear visualization of implementation status of SP practices among Indian industries.

Originality/value

Sustainable approaches in production activities are very lucrative for industries worldwide, due to their advantages. Numerous researchers are also putting their efforts to explore more about various aspects of sustainability. Mostly they are focusing on single or few aspects of SP and its implementation in particular region or country. Very few research works are dedicated to knowing the implementation status of SP in Indian manufacturing industries and they are limited in various aspects. This study presents a dedicated approach to investigate the implementation status of SP practices in Indian manufacturing industries.
A minimalist approach for improved time imaging of a noisy vibroseis data: A case study from Jaisalmer Basin, Rajasthan
Authors: Das Subhra Pratim , Mukhopadhyay Sagarika , Kumar Anil , Jain Mamta , Singh Ranbir
Published: October 2023

Processing land seismic data, especially vibroseis data, is often challenging due to complicated near‐surface situations and source‐generated noise. The case study deals with noisy vibroseis data acquired in the Jaisalmer Basin. The near‐surface estimation in this area is difficult due to a possible velocity reversal manifested in the shingled patterns of the first breaks. The near‐surface workflow incorporates a model‐adaptive first break‐picking approach, essentially integrating two problems of first‐break‐picking and model estimation into a single problem. The signal‐conditioning workflow is based on cascaded scaling and single‐channel‐based noise reduction to prevent the removal of weak signals. Horizon‐based migration velocity analysis was used to focus reflectors on the constant velocity‐migrated stacks. This was particularly useful in areas with dubious velocity trends based on semblance panels. The velocity volume has structural consistency, which provides a better time‐migrated image. The workflow also incorporates a targeted post‐stack processing sequence to enhance continuity, sharpen discontinuities and improve the resolution, as notable by comparing the legacy‐processing results of the same dataset.
Attitudes to Pregnancy, Childbirth and Postnatal Complications in Medieval English Miracula
Authors: Nilson Ben , Frost Ruth
Published: October 2023

This article re‐examines the evidence about childbirth and related topics in the posthumous miracle collections of English saints. It finds forty‐eight such miracles in collections of thirteen English saints, mostly from the century or so after 1170. The article argues that the context in which the stories were composed is vitally important to understanding how they can be used. Contemporary concerns with miracles that could be verified constrained what stories the hagiographers could use. The nature of pregnancy and birth also limited what information could come to the keepers at the shrine in charge of collecting such stories. However, the writers were not acting as an elite vetting the information, but rather cooperated with their informants and had a sympathetic and positive view of the pregnant women. The miracula reveal that, unfazed by even gruesome gynaecological issues, the male hagiographers showed some knowledge about the birthing process. By examining the body of stories, we show what the miracula can and cannot tell us about pregnancy and childbirth.
Stories and Histories: Gendered Performances, Caste and Sociability in some Punjabi Domestic Tales
Authors: Malhotra Anshu
Published: October 2023

The article traces the performative, familial, women‐centric, intergenerational storytelling tradition through studying Punjabi domestic tales collected in a private, intimate archive, in an ambience of mourning and celebration. Deploying the ‘archival turn’ in history‐writing, the author argues to include personal archive as a valid source in disciplinary history. Using the idea of ‘genders as genres’, the article argues that in female‐centred folktales, told to women and children, women assert their point of view, speak of their needs and desires, and hold their own. Though they may not dismantle caste‐specific patriarchies, patriarchies in folktales are also unable to subdue women.
BITS: A Bayesian Isotope Turnover and Sampling model for strontium isotopes in proboscideans and its potential utility in movement ecology
Authors: Yang Deming , Bowen Gabriel J. , Uno Kevin T. , Podkovyroff Katya , Carpenter Nancy A. , Fernandez Diego P. , Cerling Thure E.
Published: October 2023

Strontium isotope ratios (87Sr/86Sr) of incrementally grown tissues have been widely used to study movement ecology and migration of animals. However, the time scale of 87Sr/86Sr incorporation from the environment into tissue and how it may influence data interpretation are still poorly understood. Using the relocation of a zoo elephant (Loxodonta africana) named Misha, we characterise and model the 87Sr/86Sr turnover process using high‐resolution measurements of its tusk dentine. We seek to develop a framework that can improve quantitative interpretation of 87Sr/86Sr data in tissues.

The 87Sr/86Sr transition associated with the relocation is measured using laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) on a prepared tusk slab. We develop a turnover model (BITS), with a rapidly exchanging central pool and a slowly exchanging peripheral pool, in a Bayesian statistical framework. The measured dentine data are first used to calibrate model parameters. The parameters are then used to estimate possible 87Sr/86Sr input time series from two datasets via model inversion: a fidelity test using Misha's dentine data and a case study using published dentine measurements from an Alaskan Woolly Mammoth (Mammuthus primigenius).

The LA‐ICP‐MS data are consistent with a two‐compartment turnover process with equivalent half‐lives of 41 days for the central pool and 170 days for the peripheral pool. The model inversion shows good fidelity when estimating the intake 87Sr/86Sr time series associated with Misha's relocation. In the case study, the model suggests an abrupt pattern of change in, and a much wider range of, intake 87Sr/86Sr values than expressed in the woolly mammoth dentine data themselves.

Our framework bridges the gap between environmental 87Sr/86Sr variation and data measured in tusk dentine or other incrementally grown tissues. It could be coupled with movement models and additional isotope tracers to study seasonal residency or the spatial and temporal patterns of movement/migration. The generic turnover processes can be adapted to other isotope systems, additional incremental tissues, or other organisms, thus expanding our modelling toolkit to investigate niche partitioning, life history traits and behavioural patterns in conservation biology, archaeology and paleoecology.
Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI‐AS‐ODT)
Authors: Fishe Jennifer N. , Garvan Gerard , Bertrand Andrew , Burcham Shannon , Hendry Phyllis , Shah Manish , Kothari Kathryn , Ashby David W. , Ostermeyer Daniel , Riney Lauren , Semenova Olga , Abo Benjamin , Abes Benjamin , Shimko Nichole , Myers Emily , Frank Marshall , Turner Tim , Kemp Mac , Landry Kim , Roland Greg , Blake Kathryn V.
Published: October 2023

Background

In the emergency department (ED), prompt administration of systemic corticosteroids for pediatric asthma exacerbations decreases hospital admission rates. However, there is sparse evidence for whether earlier administration of systemic corticosteroids by emergency medical services (EMS) clinicians, prior to ED arrival, further improves pediatric asthma outcomes.

Methods

Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial is a multicenter, observational, nonrandomized stepped‐wedge design study with seven participating EMS agencies who adopted an oral systemic corticosteroid (OCS) into their protocols for pediatric asthma treatment. Using univariate analyses and multivariable mixed‐effects models, we compared hospital admission rates for pediatric asthma patients ages 2–18 years before and after the introduction of a prehospital OCS and for those who did and did not receive a systemic corticosteroid from EMS.

Results

A total of 834 patients were included, 21% of whom received a systemic corticosteroid from EMS. EMS administration of systemic corticosteroids increased after the introduction of an OCS from 14.7% to 28.1% (p < 0.001). However, there was no significant difference between hospital admission rates and ED length of stay before and after the introduction of OCS or between patients who did and did not receive a systemic corticosteroid from EMS. Mixed‐effects models revealed that age 14–18 years (coefficient −0.83, p = 0.002), EMS administration of magnesium (coefficient 1.22, p = 0.04), and initial EMS respiratory severity score (coefficient 0.40, p < 0.001) were significantly associated with hospital admission.

Conclusions

In this multicenter study, the addition of an OCS into EMS agency protocols for pediatric asthma exacerbations significantly increased systemic corticosteroid administration but did not significantly decrease hospital admission rates. As overall EMS systemic corticosteroid administration rates were low, further work is required to understand optimal implementation of EMS protocol changes to better assess potential benefits to patients.
Improved intra‐atrial conduction delay after successful ablation for atrial fibrillation by scar homogenization in right atrium
Authors: Seo Jeongduk , Park Yae Min , Shin Yong Hoon , Jang Albert Youngwoo , Kang Woong Chol , Chung Wook‐Jin , Kim Young‐Hoon , Choi In Suck
Published: October 2023

Atrial fibrosis in the right atrium (RA) presenting as a low‐voltage zone might be the mechanism of atrial fibrillation (AF) and intra‐atrial conduction delay. The impact of scar homogenization in RA on intra‐atrial conduction delay is unknown. We describe a patient with paroxysmal AF and significant intra‐atrial conduction delay with repetitive atrial flutter, triggered from the lateral free wall in the RA between the significant low‐voltage zone and slow conduction area after pulmonary vein isolation. Linear ablation along the trabeculated lateral free wall in the RA to homogenize the scar was successfully performed, and the intra‐atrial conduction delay improved ultimately.
Textbook outcomes for liver resection: can a medium sized centre have acceptable outcomes?
Authors: Mclauchlan Jared , de Burlet Kirsten , Nonis Maria , Hore Todd , Connor Saxon
Published: October 2023

Background

Textbook outcome (TO) is an objective, composite measure of clinical outcomes in surgery. TO in liver surgery has been used in previous international studies to define and compare performance across centres. This study aimed to review TO rates following liver resection at a single institution. The secondary aim was to use a CuSum analysis to evaluate monitoring of performance quality over time for colorectal cancer liver metastases (CRCLM).

Methods

All patients undergoing liver resection for benign and malignant causes from Christchurch Hospital hepatobiliary unit between 2005 and 2022 were included. Textbook outcomes measures were the absence of; intraoperative incidents, Clavien‐Dindo >3 complication, 90 day re‐admission, 90 day mortality, R1 resection, and post‐operative bile leak/liver failure. Sequential CuSum analysis was performed to review achievement of TO in liver resections for colorectal cancer liver metastases (CRCLM).

Results

Four hundred and seventy‐eight patients were included in this study, 54 had resection for benign pathology, 290 for CRCLM and 134 for other malignancies. TO was achieved in 74% of cases overall, with rates for benign, CRCLM and other malignancy being 82%, 73% and 74% respectively (P = 0.405). CuSum analysis documented a deterioration in performance after patient 60, with return to baseline by end of study period.

Conclusions

TO for liver resection in a medium sized centre in New Zealand are comparable to published rates. It is possible to use process control techniques like CuSum with the binary result of TO to monitor performance, providing opportunity for continuous improvement in surgical units.
Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis
Authors: Harrison Stephen A. , Ratziu Vlad , Anstee Quentin M. , Noureddin Mazen , Sanyal Arun J. , Schattenberg Jörn M. , Bedossa Pierre , Bashir Mustafa R. , Schneider David , Taub Rebecca , Bansal Meena , Kowdley Kris V. , Younossi Zobair M. , Loomba Rohit
Published: October 2023

Background

Non‐alcoholic steatohepatitis (NASH) is a progressive form of non‐alcoholic fatty liver disease (NAFLD) associated with steatosis, hepatocellular injury, inflammation and fibrosis. In a Phase 2 trial in adults with NASH (NCT02912260), resmetirom, an orally administered, liver‐targeted thyroid hormone receptor‐β selective agonist, significantly reduced hepatic fat (via imaging) and resolved NASH without worsening fibrosis (via liver biopsy) in a significant number of patients compared with placebo.

Aims

To present the design of the Phase 3 MAESTRO clinical programme evaluating resmetirom for treatment of NASH (MAESTRO‐NAFLD‐1 [NCT04197479], MAESTRO‐NAFLD‐OLE [NCT04951219], MAESTRO‐NASH [NCT03900429], MAESTRO‐NASH‐OUTCOMES [NCT05500222]).

Methods

MAESTRO‐NASH is a pivotal serial biopsy trial in up to 2000 adults with biopsy‐confirmed at‐risk NASH. Patients are randomised to a once‐daily oral placebo, 80 mg resmetirom, or 100 mg resmetirom. Liver biopsies are conducted at screening, week 52 and month 54. MAESTRO‐NAFLD‐1 is a 52‐week safety trial in ~1400 adults with NAFLD/presumed NASH (based on non‐invasive testing); ~700 patients from MAESTRO‐NAFLD‐1 are enrolled in MAESTRO‐NAFLD‐OLE, a 52‐week active treatment extension to further evaluate safety. MAESTRO‐NASH‐OUTCOMES is enrolling 700 adults with well‐compensated NASH cirrhosis to evaluate the potential for resmetirom to slow progression to hepatic decompensation events. Non‐invasive tests (biomarkers, imaging) are assessed longitudinally throughout, in addition to validated patient‐reported outcomes.

Conclusion

The MAESTRO clinical programme was designed in conjunction with regulatory authorities to support approval of resmetirom for treatment of NASH. The surrogate endpoints, based on week 52 liver biopsy, serum biomarkers and imaging, are confirmed by long‐term clinical liver‐related outcomes in MAESTRO‐NASH (month 54) and MAESTRO‐NASH‐OUTCOMES (time to event).
Impaired neural circuitry of hippocampus in Pax2 nervous system‐specific knockout mice leads to restricted repetitive behaviors
Authors: Wang Ying , Wang Yizhuo , Tang Jiaming , Li Rui , Jia Yanan , Yang Hua , Wei Hongen
Published: October 2023

Introduction

Restricted repetitive behaviors (RRBs), which are associated with many different neurological and mental disorders, such as obsessive‐compulsive disorder (OCD) and autism, are patterns of behavior with little variation and little obvious function. Paired Box 2 (Pax2) is a transcription factor that is expressed in many systems, including the kidney and the central nervous system. The protein that is encoded by Pax2 has been implicated in the development of the nervous system and neurodevelopmental disorders. In our previous study, Pax2 heterozygous gene knockout mice (Pax2+/− mice) showed abnormally increased self‐grooming and impaired learning and memory abilities. However, it remains unclear which cell type is involved in this process. In this study, we deleted Pax2 only in the nervous system to determine the regulatory mechanism of Pax2 in RRBs.

Methods

In this study, Pax2 nervous system‐specific knockout mice (Nestin‐Pax2 mice) aged 6–8 weeks and Pax2 flox mice of the same age were recruited as the experimental group. Tamoxifen and vehicle were administered via intraperitoneal injection to induce Pax2 knockout after gene identification. Western blotting was used to detect Pax2 expression. After that, we assessed the general health of these two groups of mice. The self‐grooming test, marble burying test and T‐maze acquisition and reversal learning test were used to observe the lower‐order and higher‐order RRBs. The three‐chamber test, Y‐maze, and elevated plus‐maze were used to assess social ability, spatial memory ability, and anxiety. Neural circuitry tracing and transcriptome sequencing (RNA‐seq) were used to observe the abnormal neural circuitry, differentially expressed genes (DEGs) and signaling pathways affected by Pax2 gene knockout in the nervous system and the putative molecular mechanism.

Results

(1) The Nestin‐Pax2 mouse model was successfully constructed, and the Nestin‐Pax2 mice showed decreased expression of Pax2. (2) Nestin‐Pax2 mice showed increased self‐grooming behavior and impaired T‐maze reversal behavior compared with Pax2 flox mice. (3) An increased number of projection fibers can be found in the mPFC projecting to the CA1 and BLA, and a reduction in IGFBP2 can be found in the hippocampus of Nestin‐Pax2 mice.

Conclusion

The results demonstrated that loss of Pax2 in the nervous system leads to restricted repetitive behaviors. The mechanism may be associated with impaired neural circuitry and a reduction in IGFBP2.
Lung transplantation in primary pulmonary arterial hypertension and pulmonary venous hypertension
Authors: Sainathan Sandeep , Ryan John , Mullinari Leonardo , Sanchez Pablo
Published: October 2023

Objectives

End‐stage lung disease from primary pulmonary hypertension (PPHTN) and pulmonary venous‐occlusive disease (PVOD) may require lung transplantation (LT). While medical therapies exist for the palliation of PPHTN, no therapies exist for PVOD. The study's objective is to compare outcomes of LT in these patients.

Methods

Patients with PPHTN and PVOD who had undergone LT were identified in the UNOS database (2005–2022). Univariable analyses compared differences between groups in demographic, clinical, and post‐transplant outcomes. Multivariable logistic regression examined the association between the diagnosis group and survival. Overall survival time between groups was compared using the Kaplan–Meier method.

Results

Six hundred and ninety‐six PPHTN and 78 PVOD patients underwent LT during the study period. Patients with PVOD had lower pulmonary artery mean pressure (47 vs. 53 mmHg, p < .001), but higher cardiac output (4.51 vs. 4.31 L/min, p = .04). PVOD patients were more likely to receive lungs from donation after cardiac death donors (7.7 vs. 2.9%, p = .04). There were no differences in postoperative complications or length of stay. PVOD was associated with superior survival at 30‐day (100 vs. 93%, p = .02) and 90‐day post‐transplant (93 vs. 83%, p = .03), but not at later time points. In multivariable analyses, PVOD and brain death donor use were associated with better survival up to 90‐day mark.

Conclusions

Patients undergoing LT for PVOD had better initial survival, which disappeared after 1 year of transplantation. Donation after circulatory death donor use had a short‐term survival disadvantage.
Experiential Marketing: A New Framework for Design and Communications By Bernd Schmitt
Authors: Rhea Darrel
Published: October 2023

A tectonic shift in design practice was underway in 1999. Both traditional features and benefits marketing and brand communications were giving way to customer experience design. Our community saw that this was a more powerful platform for integrating design and communications activities, and a whole new set of approaches, methods, and tools were beginning to be developed. While several authors, such as Pine and Gilmore, had successfully advocated for this new perspective, Bernd Schmitt from Columbia Business School was creating a systematized, practical framework for managing experience design.

The core ideas presented are still relevant today. In fact, designers are still having to make the same arguments to business 15 years later. Schmitt's article (in addition to his many other books and articles) reveals emerging distinctions that many of us in the design industry have built upon in our writings. While the concept of experience design has matured to include more robust models and more comprehensive frameworks for guiding design development, practitioners will find this piece both useful for what they do today and a good reminder of how we got here.
Walking the Walk: Putting Design at the Heart of Business By Paul Gardien and Ferdy Gilsing
Authors: Gillespie Brian
Published: October 2023

No matter how great your global reputation for design, no matter how comfortable you are in the ways and means you employ to create great design for your company, if you wish to maintain your success and relevance as a design professional and a design organization, you must continually be open to change and able to respond to it. This article, by Philips design managers Paul Gardien and Ferdy Gilsing, will inspire anyone who believes the business of design is not a static thing but rather dynamic and in constant evolution. What is clear is that this evolution is not so much a movement from one stage to another as it is an accumulation of roles and responsibilities. The authors clearly describe the evolution of the role of design in business over the past several decades and outline how Philips Design is tackling this challenge and succeeding.

Philips Design established a model that can be usefully employed to benchmark your own company's maturity and also to tackle the opportunities your self‐reflections reveal. However, some may gaze enviously at a company with a 500‐plus‐person design organization operating from 18 or locations and wonder, “Can this be relevant for my much smaller organization?” It would be interesting to hear whether the model and its approach are adaptable for organizations of all size and industry. Also, since our “connected” world invites greater integration across people, places, and things, new ways must be found to integrate multi‐disciplinary design teams. It would be interesting to learn how companies that are working with external preferred and integrated design entities are managing these relationships to advance the role of the internal design organization as it matures to become a strategic partner to the business.

Finally, let's realize that the highest level of maturity, in which design is fully integrated as a strategy throughout the organization, is not just a pinnacle of design thinking but also a pinnacle of strategic design management. Let it be about design thinking, design managing, and design doing! Gardien and Gilsing hope the publication of this work is “to kick‐start a discussion within the wider design management community and find new ways to benchmark our work together.” Let's not fail them on this!
Science and Design: A Reluctant Partnership
Authors: Pfordresher Jeanne
Published: October 2023

Designers are striving to work more sustainably and ethically. The inevitable result is that science will play a bigger and bigger role in the design process. What will this mean for designers and scientists? What can they learn from each other?

Thoughts on the inevitable incursion of science into design—and how design can meet science halfway.
Designing the 3D‐Printed Prosthetic Hand
Authors: Elmansy Rafiq
Published: October 2023

3D printing is remarkably affordable and lends itself to this collaborative—and philanthropic—endeavor.

A lot of people, a little kindness, and a new technology make a huge difference around the world, especially for children.
Human Factors: The Diffusion of a Profession
Authors: Lee Mark
Published: October 2023

“Human factors” and “user experience (UX)”: one may be part of the other, but they are not synonymous.

What do we mean when we say “human factors?”
Ordinary Objects and Their New Design Overlords
Authors: McCracken Grant
Published: October 2023

Commodities were once designed by convention. Now that they are designed by designers, ordinary objects, from a man's watch to a woman's bicycle, give off an extraordinary amount of meaning.

Once upon a time, all refrigerators were white. All bicycles were designed for 5′9″ men. All hammers were brown. It was the convention that mattered. Now, it's the choice
The Design of Everyday Work
Authors: Hambrose Harold
Published: October 2023

Why does great design end at the door of the workplace?

The “design of everyday things”… goes to work.
Confessions of a Non‐Designer Designer
Authors: Lee Mark
Published: October 2023

The creation of a product design almost always involves competing visions within the team. Business, engineering, and design all have views on what makes for a successful product. News flash: The user should be the winner in that battle.

If you are a consumer, you want this human factors engineer to be on the design team.
Customer Experience at Veterans Affairs
Authors: Brooks Sarah
Published: October 2023

VA's veteran experience office is basically a startup of about 20 people, many from the private sector. Their brief: Shift Veterans Affairs toward a customer‐first perspective.

This Presidential Innovation Fellow helped start the first‐ever cabinet‐level customer experience office in the US government, at the Veterans Affairs Administration.
Fighting Fire with Diversity and Human‐Centered Design at the BLM
Authors: Spradlin Carrie
Published: October 2023

Wildland firefighting in America's wide‐open spaces has traditionally been the province of white men. To encourage and retain the talents of women and minorities in that workforce, the Bureau of Land Management has turned to the lessons of design.
The role of niche overlap, environmental heterogeneity, landscape roughness and productivity in shaping species abundance distributions along the Amazon–Andes gradient
Authors: Arellano Gabriel , Umaña María N. , Macía Manuel J. , Loza M. Isabel , Fuentes Alfredo , Cala Victoria , Jørgensen Peter M.
Published: October 2023

Aim

Statistical and ecological mechanisms shape species abundance distributions (SADs). A lack of correlation between ecological gradients and SAD shape would suggest that SADs are caused by purely statistical reasons. We evaluated the variation in the shape of SADs for communities in landscapes of differing variable connectivity, environmental heterogeneity, species niches overlap and productivity.

Location

Rainforests in the Madidi region (Bolivia).

Methods

We compiled biological and environmental information on 65 sites (a site being a group of two to six 0.1‐ha plots where woody plants of a diameter at breast height ≥ 2.5 cm were inventoried). We built unveiled (complete) SADs for each site and fitted Gambin models to those SADs. The Gambin α parameter served as a metric of SAD shape. Low α values characterize logseries‐like SADs, while high α values characterize lognormal‐like SADs. For each site, we estimated landscape roughness, environmental heterogeneity, species niche overlap and productivity. These variables were related to SAD shape by means of variation partitioning.

Results

SADs changed from logseries‐like to lognormal‐like along the elevational gradient. Many of our predictor variables were correlated: 40.4% of the variation in SAD shape could not be attributed to specific factors. However, 50.62% of the variation in the SAD shape could be assigned to individual predictor matrices: 28.4% was explained exclusively by niche overlap, 15.41% exclusively by environmental heterogeneity, 5.20% exclusively by landscape roughness and 1.6% exclusively by productivity.

Main conclusions

Ecological processes related to the topographical/environmental complexities that vary across the elevational gradient are correlated with the SAD shape. Purely statistical mechanisms are apparently not sufficient to explain the changes in SAD shape. The most important factor is the mean overlap of the niches of the species of an assemblage: avoiding competition with co‐occurring species could be the most important mechanism driving species relative success at the ≤100 km2 scale.