bluuebunny/crossref_metadata_2025 huggingface dataset:
2-year Change in Revised Hammersmith Scale scores in a large cohort of untreated paediatric type 2 and 3 SMA participants
Authors: Stimpson Georgia , Ramsey Danielle , Wolfe Amy , Mayhew Anna , Scoto Mariacristina , Baranello Giovanni , Lofra Robert Muni , Main Marion , Milev Evelin , Coratti Giorgia , Pane Marika , Sansone Valeria , D’Amico Adele , Bertini Enrico , Messina Sonia , Bruno Claudio , Albamonte Emilio , Mazzone Elena , Montes Jacqueline , Glanzman Allan M. , Zolkipli-Cunningham Zarazuela , Pasternak Amy , Duong Tina , Young Sally Dunaway , Civitello Matthew , Marini-Bettolo Chiara , Day John W , Darras Basil T , De Vivo Darryl C , Finkel Richard S , Mercuri Eugenio , Muntoni Francesco
Published: January 2023

The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale–Expanded (HFMSE). These change scores were considered by SMA type, motor function and baseline RHS score. We consider a new tran-sitional group, spanning crawlers, standers and walkers-with-assistance, and analyse that alongside non-sitters, sitters and walkers. The transitional group exhibit the most de-finitive change score trend, with an average 1-year decline of 3 points. The RHS has a re-duced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. In the stronger participants (between 10 and 42 on the RHS) in the 5-7 age group, both the RHS and HFMSE can detect 1-year change. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items.
Discovery and Verification of Extracellular microRNA Biomarkers for Diagnostic and Prognostic Assessment of Preeclampsia at Triage
Authors: Morey Robert , Poling Lara , Srinivasan Srimeenakshi , Martinez-King Carolina , Anyikam Adanna , Zhang-Rutledge Kathy , Cuong To , Hakim Abbas , Mochizuki Marina , Verma Kajal , Mason Antoinette , Tran Vy , Meads Morgan , Lamale-Smith Leah , Horii Mariko , Ramos Gladys A. , DeHoff Peter , Parast Mana M. , Pantham Priya , Laurent Louise C.
Published: January 2023

Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality. Current methods for evaluation of patients with suspected PE do not reliably predict which patients will later develop PE nor distinguish between PE with and without severe features. The objective of this study was to identify candidate extracellular miRNA (ex-miRNA) biomarkers for early diagnosis and prognosis of PE in a cohort of subjects presenting for evaluation of suspected PE. Small RNA-seq libraries were created from maternal serum samples, prospectively collected from participants undergoing evaluation for suspected PE between 20-40 weeks gestational age. Measurements for bivariate biomarkers, consisting of ratios of pairs of ex-miRNAs were performed. 110 bivariate ex-miRNA biomarkers passed both discovery (48 cases, 34 controls) and verification (23 cases, 18 controls) criteria. Specific biomarkers differed in their patterns of expression among different categories of hypertensive disorders in pregnancy (HDP). An iterative machine learning method was then used to identify 3 bivariate miRNA biomarkers that, when applied serially, differentiated cases from controls with a sensitivity of 93% and a positive predictive value (PPV) of 55%, and additionally distinguished between PE cases of different severity. In an independent validation cohort of 11 cases and 7 controls, these three biomarkers had a sensitivity of 91% and a PPV of 85%. We have discovered, verified, and validated 3 bivariate ex-miRNA biomarkers, which, when applied serially, enable accurate early diagnosis of preeclampsia. Bivariate ex-miRNA biomarkers can distinguish between different subtypes of HDP.
Structural characterization and extended substrate scope analysis of two Mg2+-dependent O-methyltransferases from bacteria
Authors: Sokolova Nika , Zhang Lili , Deravi Sadaf , Oerlemans Rick , Groves Matthew R. , Haslinger Kristina
Published: January 2023

Oxygen-directed methylation is a ubiquitous tailoring reaction in natural product pathways catalysed by O-methyltransferases (OMTs). Promiscuous OMT biocatalysts are thus a valuable asset in the toolkit for sustainable synthesis and optimization of known bioactive scaffolds for drug development. Here, we characterized two bacterial OMTs fromDesulforomonas acetoxidansandStreptomyces avermitilisin terms of their enzymatic properties and substrate scope and determined their crystal structures. Both OMTs methylated a wide range of catechol-like substrates, including flavonoids, coumarins, hydroxybenzoic acids and their respective aldehydes, an anthraquinone and an indole. One enzyme also accepted a steroid. The product range included pharmaceutically relevant compounds such as (iso)fraxidin, iso(scopoletin), chrysoeriol, alizarin 1-methyl ether and 2-methoxyestradiol. Interestingly, certain non-catechol flavonoids and hydroxybenzoic acids were also methylated. This study expands the knowledge on substrate preference and structural diversity of bacterial catechol OMTs and paves the way for their use in (combinatorial) pathway engineering.

Table of contents

Two promiscuous O-methyltransferasesfrom bacteria were found to methylate a panel of catechol substrates towards high-value medicinal compounds. Surprisingly, the non-catechol substrates 5-hydroxyflavonoids ando-hydroxybenzoic acids/aldehydes were also methylated at low conversion rates. The crystal structures reveal potential target sites for enzyme engineering for biocatalytic applications.
The transcriptome of soybean reproductive tissues subjected to water deficit, heat stress, and a combination of water deficit and heat stress
Authors: Sinha Ranjita , Induri Sai Preethi , Peláez-Vico María Ángeles , Tukuli Adama , Shostak Benjamin , Zandalinas Sara I. , Joshi Trupti , Fritschi Felix B. , Mittler Ron
Published: January 2023

Global warming and climate change are driving an alarming increase in the frequency and intensity of extreme climate events, such as droughts, heat waves, and their combination, inflicting heavy losses to agricultural production. Recent studies revealed that the transcriptomic responses of different crops to water deficit (WD) or heat stress (HS) is very different from that to a combination of WD+HS. In addition, it was found that the effects of WD, HS, and WD+HS are significantly more devastating when these stresses occur during the reproductive growth phase of crops, compared to vegetative growth. As the molecular responses of different reproductive and vegetative tissues of plants to WD, HS, or WD+HS could be different from each other, and these differences could impact many current and future breeding and/or engineering attempts to enhance the resilience of crops to climate change, we conducted a transcriptomic analysis of different soybean (Glycine max) tissues to WD, HS, and WD+HS. Here we present a reference transcriptomic dataset that includes the response of soybean leaf, pod, anther, stigma, ovary, and sepal to WD, HS, and WD+HS conditions. Mining this data set for the expression pattern of different stress-response transcripts revealed that each tissue had a unique transcriptomic response to each of the different stress conditions. This finding is important as it suggests that attempting to enhance the overall resilience of crops to climate change could require a coordinated approach that simultaneously alters the expression of different groups of transcripts in different tissues in a stress-specific manner.

SIGNIFICANCE STATEMENT

A reference transcriptomic dataset of different reproductive tissues of soybean subjected to water deficit, heat stress, and their combination, generated by this study, reveals that different tissues display different responses to these stress conditions. Attempting to enhance the resilience of crops to different stress combinations, associated with climate change, might therefore require simultaneously altering the expression of different sets of transcripts in different tissues in a coordinated and stress-specific manner.
Metadata creation practices at the Lilongwe University of Agriculture and Natural Resources library’s institutional repository
Authors: Chapepa Gobbrey George , Ngwira Fiskani , Mapulanga Patrick
Published: January 2023

Purpose

The purpose of this study was to investigate metadata creation practices in a functional academic institution repository in Malawi, with a specific focus on the Lilongwe University of Agriculture and Natural Resources (LUANAR) library.

Design/methodology/approach

The study used a qualitative approach with a case study design. The study adopted a case study strategy that focuses on the in-depth, holistic and in-context examination of one or more cases. The researcher used non-probability purposive sampling to include all three LUANAR Digital Repository (LDR) staff at LUANAR library because they were thought to be knowledgeable about the LDR metadata work. The three library staff members directly involved in repository metadata were investigated for the study. Data collection techniques used in a case study approach included semi-structuring face-to-face interviews and documentary analysis. Data from interviews and documentary reviews were manually analyzed and presented in thematic categories based on the study’s objectives.

Findings

Qualified Dublin Core (DC) was chosen by all participants as the only metadata structure scheme that they will use to create and implement metadata in the repository. DC application profile was the only scheme used to enforce uniform naming and capitalization conventions in the application of Qualified DC element definitions. The scheme, however, was discovered to be the Qualified DC default format in the DSpace system. All participants indicated that the Agricultural Organization of the United Nations Vocabulary is used. Participants highlighted that institutional repository system compatibility, the subject matter of the resources, resource types and staff expertise influenced the selection criteria for the metadata schemes. The repository policy had been developed but had yet to be adopted by the LUANAR management.

Research limitations/implications

The current study was limited to LUANAR library. A wider study across public and private universities in Malawi is needed to ascertain the role of metadata policy, technical knowledge and metadata specialist institutional repositories.

Practical implications

Metadata policy is to aid in the understanding of the data, ensuring that appropriate security measures are used to protect the data and for metadata harvesting purposes.

Social implications

Academic libraries should lobby for management support towards metadata policy for institutional repositories.

Originality/value

Very little is known about challenges affecting the growth of institutional repositories and standards adopted, including metadata harvesting. This paper bridges the gap in metadata standards for institutional repositories in developing countries.
Numerical optimization of highly loaded microtextured contacts: understanding and mastering complexity
Authors: Orgeldinger Christian , Rosnitscheck Tobias , Tremmel Stephan
Published: January 2023

Purpose

Microtextured surfaces can reduce friction in tribological systems under certain contact conditions. Because it is very time-consuming to determine suitable texture patterns experimentally, numerical approaches to the design of microtextures are increasingly gaining acceptance. The purpose of this paper is to investigate to what extent the selected modeling approach affects optimized texturing.

Design/methodology/approach

Using the cam/tappet contact as an application-oriented example, a simplified 2D and a full 3D model are developed for determining the best possible texturing via a design study. The study explores elongated Gaussian-shaped texture elements for this purpose. The optima of the simplified 2D simulation model and the full 3D model are compared with each other to draw conclusions about the influence of the modeling strategy. The target value here is the solid body friction in contact.

Findings

For the elongated texture elements used, both the simplified 2D model and the full model result in very similar optimal texture patterns. In the selected application, the simplified simulation model can significantly reduce the computational effort without affecting the optimization result.

Originality/value

Depending on the selected use case, the simulation effort required for microtexture optimization can be significantly reduced by comparing different models first. Therefore, an exact physical replica of the real contact is not necessarily the primary goal when it comes to texture selection based on numerical simulations.
Adaptive fractional-order admittance control for force tracking in highly dynamic unknown environments
Authors: Li Kaixin , He Ye , Li Kuan , Liu Chengguo
Published: January 2023

Purpose

With the increasing demands of industrial applications, it is imperative for robots to accomplish good contact-interaction with dynamic environments. Hence, the purpose of this research is to propose an adaptive fractional-order admittance control scheme to realize a robot–environment contact with high accuracy, small overshoot and fast response.

Design/methodology/approach

Fractional calculus is introduced to reconstruct the classical admittance model in this control scheme, which can more accurately describe the complex physical relationship between position and force in the interaction process of the robot–environment. In this control scheme, the pre-PID controller and fuzzy controller are adopted to improve the system force tracking performance in highly dynamic unknown environments, and the fuzzy controller is used to improve the trajectory, transient and steady-state response by adjusting the pre-PID integration gain online. Furthermore, the stability and robustness of this control algorithm are theoretically and experimentally demonstrated.

Findings

The excellent force tracking performance of the proposed control algorithm is verified by constructing highly dynamic unstructured environments through simulations and experiments. In simulations and experiments, the proposed control algorithm shows satisfactory force tracking performance with the advantages of fast response speed, little overshoot and strong robustness.

Practical implications

The control scheme is practical and simple in the actual industrial and medical scenarios, which requires accurate force control by the robot.

Originality/value

A new fractional-order admittance controller is proposed and verified by experiments in this research, which achieves excellent force tracking performance in dynamic unknown environments.
Linking experimental culture, improvisation capability and firm’s performance: a theoretical view
Authors: Liao Zhongju , Huang Chao , Yu Yubing , Xiao Shufeng (Simon) , Zhang Justin Zuopeng , Behl Abhishek , Pereira Vijay , Ishizaka Alessio
Published: January 2023

Purpose

This study aims to investigate the causal relationships within an experimental culture of improvisation capability and firm performance, following the logic of “culture-capability-performance” and building on informal institution theory and dynamic capability theory.

Design/methodology/approach

Data was mainly collected via on-site questionnaires from firm managers, and 196 valid questionnaires were analyzed using structural equation modeling to test the relationship among experimental culture, improvisation capability and firms’ performance.

Findings

Trust and support had a positive impact on firm spontaneity, while the effect of action promotion and error tolerance was not significant. Action promotion, trust and support demonstrate substantial positive effects on the creativity of a firm. Both dimensions of improvisation capability positively and significantly influence a firm’s performance.

Research limitations/implications

The research respondents were firm managers. Cross-sectional data were used to analyze the model, which may cause common method variance. The research context was limited to China, and the generalizability of the results needs to be considered.

Practical implications

Firms can cultivate a culture of trust and support to enhance their spontaneity and improvisation capability. They can encourage cross-departmental communication, empower employees with autonomy in decision-making, provide appropriate resource support for employees’ decisions and use praise and reward incentives to spur further innovation achievements.

Originality/value

This study addresses the gaps in a firm’s improvisation capability within a Chinese market context by theoretically and empirically examining the role of experimental culture and assessing the relationship among each of the dimensions of improvisation capability in relation to firm performance identified in this study.
TMT transactive memory system and business model design: the moderating effect of strategic orientation
Authors: Chen Yu , Yi Yaqun
Published: January 2023

Purpose

Top management team (TMT) serves as the critical designer of a firm’s business model, whose cognition exerts key influence on business model design (BMD). Drawing insights from the managerial cognition and knowledge-based views, this paper aims to examine the effect of TMT transactive memory system on BMD and investigate how the relationship between TMT transactive memory system and BMD is contingent upon the firm’s strategic orientation.

Design/methodology/approach

Survey data collected from 210 Chinese firms was used to test the research hypotheses through multivariate regression analysis.

Findings

This paper reveals that TMT transactive memory system facilitates novelty- and efficiency-centered BMD. Furthermore, both differentiation orientation and cost leadership orientation can strengthen the effect of TMT transactive memory system on novelty-centered BMD; the impact of TMT transactive memory system on efficiency-centered BMD is weakened by differentiation orientation but strengthened by cost leadership orientation.

Originality/value

This paper adds to the business model literature by unraveling the effect of TMT transactive memory system on BMD, which not only enriches the internal cognitive antecedents of BMD but also provides an in-depth understanding of how TMTs can use their knowledge structure to proactively design a certain business model. Moreover, this paper also offers insights into how TMTs can better use transactive memory system to design business models according to the specific strategic orientation.
In the classroom I enhance students understanding of entrepreneurship development – the culturo–techno-contextual approach
Authors: Awaah Fred
Published: January 2023

Purpose

This study aims to present a step-by-step implementation of the culturo–techno-contextual approach (CTCA) in a university classroom to teach industry and competitive analysis in the Ghanaian undergraduate entrepreneurship development curriculum. It further investigates the efficacy of the CTCA in breaking difficulties related to the study of industry and competitive analysis as a difficult concept in the Ghanaian entrepreneurship development curriculum. In doing this, the CTCA is compared with the lecture method.

Design/methodology/approach

The study adopts a quantitative approach. A quasi-experimental design is employed to gather data from 215 level 400 (4th-year undergraduate students) entrepreneurship development students at a Ghanaian public university. The experimental group was taught with CTCA, while the control group used the lecture method. The data was collected using the industry and competitive analysis achievement test (ICAAT). As random assignment to experimental and control groups were not possible, the data were subjected to an analysis of covariance approach with pre-test scores added as a covariate.

Findings

The results show that the experimental group significantly outperformed the control group. The results further indicate the efficacy of CTCA in improving undergraduate students’ performance in complex concepts of entrepreneurship.

Originality/value

Researchers usually test alternative teaching methods to break down barriers to study difficulties. The study’s uniqueness stems from the CTCA’s ground-breaking application to the study of entrepreneurship development in a Ghanaian public university.
Manufacturing Relocation Ambiguity Model: A Prerequisite for Knowledge Management
Authors: Fjellström Daniella , Hilletofth Per , Fang Tony , Kumar V. , Kumar Ajay , Hua Tan Kim
Published: January 2023

Knowledge management and manufacturing relocation have been treated as independent spheres. However, for a relocation to be fruitful, knowledge management needs to be incorporated. The purpose of this research is to shed light on the lack of knowledge management in dynamic manufacturing relocation. In particular, the research focuses on the ability to change, adapt and revert manufacturing relocation decisions, that is, the dynamic nature (or use) of the concept. A Swedish company was used as a case study. Nine in‐depth interviews were conducted with key informants at the company's headquarters in Sweden and its factory in China to capture a dyadic perspective. The findings demonstrate that: (1) knowledge transfer is crucial to create/sustain competitive advantage in the offshoring and reshoring phase; (2) lack of knowledge transfer results in limited learning outcomes with operational and strategic consequences in the relocation; (3) resistance to knowledge transfer in the offshoring creates a knowledge gap that consequently leads to relocation ambiguity in the reshoring phase; and (4) companies need to develop knowledge management strategies to promote knowledge transfer and learn from their international relocation, to cope with relocation ambiguity. Our theoretical contribution introduces the knowledge ambiguity framework, which is a result of insufficient knowledge transfer in the dynamic manufacturing relocation. Even if an organization relocates efficiently, it can fail to take advantage of knowledge transfer and development as potential learning for the organization.
Buildings and Institutional Change: Stepping Stones or Stumbling Blocks?
Authors: Siebert Sabina
Published: January 2023

This study aims to throw some theoretical light on the relationship between institutions and the buildings housing them, particularly in the context of institutional change. Drawing on my ethnographic study of the UK Parliament buildings in London, I put forward a framework for analysing the effects that buildings and the artifacts within them may have on institutional change. This framework consists of three elements: (1) buildings enabling or constraining the activities performed inside; (2) spatial hierarchy; and (3) buildings as a resource. My intention is to draw scholars’ attention to the notion of buildings as sites of contestation – places where conflicts over nature and the extent of institutional change are played out. I conclude that redesigning buildings might be seen as a stepping stone to change, but also that buildings can be used to resist change and maintain the status quo. Although buildings ‘inhabited’ by institutions may appear to stand still, they never do; they change in time, both enabling and constraining those who use them and they have an ability to ‘act back’.
The Impact of Analyst, CEO, and Firm Reputations on Investors in the UK and Japanese Stock Markets
Authors: Hussain Simon , Su Chen
Published: January 2023

We examine the importance of multiple agents’ reputations on the market's reaction to analysts’ stock recommendation revisions (analyst revisions), individually and interactively, in the UK and Japanese stock markets. We find some notable variations in reputation effects between the two markets. In the UK, analyst reputation amplifies the market's reaction to analyst revisions, while in Japan, analyst reputation has no significant impact. Firm reputation diminishes (amplifies) the market's reaction to analyst revisions in the UK (Japan). Only CEO reputation generates similar effects in the UK and Japan, dampening the market's reaction to analyst revisions. We also find that reputations interact in different ways in the two markets. Specifically, firm reputation and CEO reputation tend to moderate the positive effect of analyst reputation in the UK; however, in Japan, CEO reputation tends to moderate the positive effect of firm reputation, but there is no significant interaction effect between analyst reputation and CEO/firm reputation. Our findings are explained using insights both from formal economic models and from various cultural and institutional characteristics.
Butter fortified with spray‐dried encapsulated Ferulago angulata extract nanoemulsion and postbiotic metabolite of Lactiplantibacillus plantarum subsp. plantarum improves its physicochemical, microbiological and sensory properties
Authors: Anvar Seyed Amirali , Rahimyan Dorsa , Golestan Leila , Shojaee Asiyeh , Pourahmad Rezvan
Published: January 2023

Butter is a valuable dairy product, and its sensory attributes can be changed due to oxidative rancidity and microbial contamination. This study investigated the effect of Ferulago angulata extract nanoemulsion (FAEN) on butter properties alone or in combination with postbiotic metabolites produced by Lactiplantibacillus plantarum subsp. plantarum (PMLP) into the butter in the free form or spray‐dried encapsulated. The combination of the encapsulated form of FAEN and PMLP in butter indicated that it is capable of controlling peroxide and acidity values and increases the antioxidant and antimicrobial activities consequently leading to the increased shelf life of butter.
Assimilating ecological theory with empiricism: Using constrained generalized additive models to enhance survival analyses
Authors: Ketz Alison C. , Storm Daniel J. , Barker Rachel E. , Apa Anthony D. , Oliva‐Aviles Cristian , Walsh Daniel P.
Published: January 2023

Integrating ecological theory with empirical methods is ubiquitous in ecology using hierarchical Bayesian models. However, there has been little development focused on integration of ecological theory into models for survival analysis. Survival is a fundamental process, linking individual fitness with population dynamics, but incorporating life history strategies to inform survival estimation can be challenging because mortality processes occur at multiple scales.

We develop an approach to survival analysis, incorporating model constraints based on a species' life history strategy using functional analytical tools. Specifically, we structurally separate intrinsic patterns of mortality that arise from age‐specific processes (e.g. increasing survival during early life stages due to growth or maturation, versus senescence) from extrinsic mortality patterns that arise over different periods of time (e.g. seasonal temporal shifts). We use shape constrained generalized additive models (CGAMs) to obtain age‐specific hazard functions that incorporate theoretical information based on classical survivorship curves into the age component of the model and capture extrinsic factors in the time component.

We compare the performance of our modelling approach to standard survival modelling tools that do not explicitly incorporate species life history strategy in the model structure, using metrics of predictive power, accuracy, efficiency and computation time. We applied these models to two case studies that reflect different functional shapes for the underlying survivorship curves, examining age‐period survival for white‐tailed deerOdocoileus virginianusin Wisconsin, USA and Columbian sharp‐tailed grouseTympanuchus phasianellus columbianusin Colorado, USA.

We found that models that included shape constraints for the age effects in the hazard curves using CGAMs outperformed models that did not include explicit functional constraints. We demonstrate a data‐driven and easily extendable approach to survival analysis by showing its utility to obtain hazard rates and survival probabilities, accounting for heterogeneity across ages and over time, for two very different species. We show how integration of ecological theory using constrained generalized additive models, with empirical statistical methods, enhances survival analyses.
Striatal dopamine D2 receptor availability as a predictor of subsequent alcohol use in social drinkers
Authors: Jangard Simon , Jayaram‐Lindström Nitya , Isacsson Nils Hentati , Matheson Granville James , Plavén‐Sigray Pontus , Franck Johan , Borg Jacqueline , Farde Lars , Cervenka Simon
Published: January 2023

Background and aims

Whereas striatal dopamine D2 receptor (D2R) availability has shown to be altered in individuals with alcohol use disorder (AUD) and in healthy individuals with a family history of AUD, the role of D2R in the development of AUD is unknown. In this positron emission tomography (PET) study, we measured whether D2R availability is associated with subsequent alcohol use and alcohol‐related factors, at a follow‐up 8 to 16 years post‐PET scan, in social drinkers.

Design

Longitudinal study investigating the association between PET data and later self‐report measures in healthy individuals.

Setting

Academic research imaging centre in Stockholm, Sweden.

Participants

There were 71 individuals (68 of whom had evaluable PET data, 5 females, 42.0 years mean age) from a series of previous PET studies.

Measurements

One PET examination with the D2R antagonist radioligand [11C]raclopride at baseline and self‐report measures assessing alcohol use, drug use, impulsivity, reward sensitivity and family history of alcohol or substance use disorder at follow‐up.

Findings

We found no evidence for an association between D2R availability and later alcohol use (B = −0.019, B 95% CI = −0.043 to −0.006, P = 0.147) nor for the majority of the alcohol‐related factors (B 95% CI = −0.034 to 0.004, P = 0.273–0.288). A negative association with a small effect size was found between D2R availability and later impulsivity (B = −0.017, B 95% CI = −0.034 to −0.001, P = 0.046).

Conclusions

Low striatal dopamine D2 receptor availability may not be a strong predictor in the development of alcohol use disorder.
Comparing taxes on alcoholic beverages in the Region of the Americas
Authors: Roche Maxime , Sandoval Rosa Carolina , Monteiro Maristela G.
Published: January 2023

Background and Aims

Excise taxes represent one of the most cost‐effective policies to reduce the harmful use of alcohol. Existing information about their design is limited and no standardized metric has been used to compare tax levels in the Region of the Americas. This study aimed to compare alcohol excise tax policies throughout the Americas, compare tax levels and consider opportunities to improve the impact of excise taxes on alcohol consumption and health.

Design and Setting

Descriptive analysis using a method developed by the Pan American Health Organization and adapted from the World Health Organization's tobacco tax monitoring. Data were collected by surveying ministries of finance and reviewing tax legislation in effect as of November 2020 in the Region of the Americas.

Measurements

Tax policy design indicators, taxes as a percentage of the retail price of the most‐sold brand of beer, wine and spirits, including a weighted average indicator across beverage types, and tax levels per standard drink (10 g ethanol) in international dollars at purchasing power parity.

Findings

Thirty‐three countries in the Americas (94%) apply excise taxes on alcoholic beverages, with Argentina and Uruguay not applying them to wine. There is significant heterogeneity in excise tax design across countries and beverage types. Only a third of amount‐specific excise taxes are regularly adjusted to avoid erosion. Regional median excise taxes represent the highest share of the price for spirits (21.4%) and the lowest for wine (11.0%). The regional median consumption‐weighted average excise tax share across all beverage types is 12.0%. Excise tax shares are generally higher in Latin America than in the Caribbean and Canada. Excise tax levels per standard drink are generally lower for spirits than for other beverages.

Conclusions

Alcohol excise tax policies vary significantly across the Americas, often reflecting national consumption patterns. To maximize their public health impact, tax rates could be increased and tax designs improved, particularly to ensure higher tax burdens on high‐strength drinks.
Redefining and categorizing emergency medical service opioid‐related incidents in Massachusetts
Authors: Jones Katarina , Bernson Dana , Fillo Katherine T. , Bettano Amy L.
Published: January 2023

Aims

To create a novel emergency medical service (EMS) opioid‐related incident (ORI) tiering framework to describe more accurately the opioid epidemic in Massachusetts. By classifying the data, we could more accurately detail differing trends among the new categories.

Design

Free‐text fields of Massachusetts EMS reports, from 2013 through 2020, were analyzed to identify ORIs and then categorized into a five‐tier severity cascade based on symptom presentation: ‘dead on arrival,’ ‘acute overdose,’ ‘intoxication,’ ‘withdrawal’ and ‘other ORI.’ As a validation of the new classification, an emergency medical technician, paramedic and emergency medical physician reviewed clinical reports and assigned a severity category to 100 randomly selected cases. The algorithm then assessed the same 100 cases to determine if it could accurately identify the severity category for each case.

Findings

Validation of the algorithm by clinical review indicated a substantial level of agreement between the algorithm and the reviewers. Over half of all ORIs were acute overdose (55%), 21% were intoxication, 20% were other ORI, 3% were withdrawal, and 1% were dead on arrival. Overall ORIs decreased in 2020, but the number of ‘dead on arrival’ increased 32% from 2019. Administration of naloxone also differed between the categories, with 95% of acute overdose and 29% of intoxication receiving naloxone.

Conclusions

This novel categorization of emergency medical service opioid‐related incidents in Massachusetts, United States, reveals new trend details and strains on the emergency medical service system. Using these categories also improves dataset linkage within the state and interstate rate comparisons.
Editorial: the burden of alcohol‐related liver disease emergency admissions in England may be twice as high as previously thought—authorsʼ reply
Authors: Bodger Keith , Dhanda Ashwin ,   all co‐authors
Published: January 2023

LINKED CONTENT

This article is linked to Dhanda et al papers. To view these articles, visit https://doi.org/10.1111/apt.17307 and https://doi.org/10.1111/apt.17335
Dose of ibrutinib in Waldenström macroglobulinaemia: Less can be more
Authors: Tohidi‐Esfahani Ibrahim , Trotman Judith
Published: January 2023

Ibrutinib changed the landscape of treatment in Waldenström macroglobulinaemia (WM) with excellent responses; however, there are high rates of dose reduction due to adverse events. The impact of this reduced dosing is unclear with regards to outcomes. Sarosiek and colleagues provide valuable data in a very large retrospective study demonstrating that dose reduction is effective in managing adverse events in the majority, with equivalent, if not better, outcomes than those without dose reductions.
Sex‐ and age‐specific respiratory alterations induced by prenatal exposure to the cannabinoid receptor agonist WIN 55,212‐2 in rats
Authors: Patrone Luis Gustavo A. , Ferrari Gustavo D. , da Silva Rodrigo Moreira , Alberici Luciane C. , Lopes Norberto Peporine , Stabile Angelita M. , Klein Wilfried , Bícego Kênia C. , Gargaglioni Luciane H.
Published: January 2023

Background and Purpose

Cannabis legalization has risen in many countries, and its use during pregnancy has increased. The endocannabinoid system is present in the CNS at early stages of embryonic development, and regulates functional brain maturation including areas responsible for respiratory control, data on the influence of external cannabinoids on the development of the respiratory system and possible consequences during postnatal life are limited.

Experimental Approach

We evaluated the effects of prenatal exposure to synthetic cannabinoid (WIN 55,212‐2 [WIN], 0.5 mg·kg−1·day−1) on the respiratory control system in neonatal (P0, P6–7 and P12–13) and juvenile (P27–28) male and female rats.

Key Results

WIN administration to pregnant rats interfered sex‐specifically with breathing regulation of offspring, promoting a greater sensitivity to CO2 at all ages in males (except P6–7) and in juvenile females. An altered hypoxic chemoreflex was observed in P0 (hyperventilation) and P6–7 (hypoventilation) males, which was absent in females. Along with breathing alterations, brainstem analysis showed an increase in the number of catecholaminergic neurons and cannabinoid receptor type 1 (CB1) and changes in tissue respiration in the early males. A reduction in pulmonary compliance was observed in juvenile male rats. Preexposure to WIN enhanced spontaneous apnoea and reduced the number of serotoninergic (5‐HT) neurons in the raphe magnus nucleus of P0 females.

Conclusions and Implications

These data demonstrate that excess stimulation of the endocannabinoid system during gestation has prolonged and sex‐specific consequences for the respiratory control system.
IFN‐γ–STAT1‐mediated NK2R expression is involved in the induction of antitumor effector CD8+ T cells in vivo
Authors: Shen Weidong , Wang Xiangdong , Xiang Huihui , Shichi Shunsuke , Nakamoto Hiroki , Kimura Saori , Sugiyama Ko , Taketomi Akinobu , Kitamura Hidemitsu
Published: January 2023

The induction of antitumor effector T cells in the tumor microenvironment is a crucial event for cancer immunotherapy. Neurokinin receptor 2 (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), regulates diverse physiological functions. However, the precise role of NKA–NK2R signaling in antitumor immunity is unclear. Here, we found that an IFN‐γ–STAT1 cascade augmented NK2R expression in CD8+ T cells, and NK2R‐mediated NKA signaling was involved in inducing antitumor effector T cells in vivo. The administration of a synthetic analog of double‐stranded RNA, polyinosinic–polycytidylic acid (poly I:C), into a liver cancer mouse model induced type I and type II IFNs and significantly suppressed the tumorigenesis of Hepa1‐6 liver cancer cells in a STAT1‐dependent manner. The reduction in tumor growth was diminished by the depletion of CD8+ T cells. IFN‐γ stimulation significantly induced NK2R and tachykinin precursor 1 (encodes NKA) gene expression in CD8+ T cells. NKA stimulation combined with anti‐CD3 monoclonal antibody (mAb) treatment significantly augmented IFN‐γ and granzyme B production by CD8+ T cells compared with the anti‐CD3 mAb alone in vitro. ERK1/2 phosphorylation and IκBα degradation in activated CD8+ T cells were suppressed under NK2R deficiency. Finally, we confirmed that tumor growth was significantly increased in NK2R‐deficient mice compared with that in wild‐type mice, and the antitumor effects of poly I:C were abolished by NK2R absence. These findings suggest that IFN‐γ–STAT1‐mediated NK2R expression is involved in the induction of antitumor effector T cells in the tumor microenvironment, which contributes to the suppression of cancer cell tumorigenesis in vivo. In this study, we revealed that IFN‐γ–STAT1‐mediated NK2R expression is involved in the induction of antitumor effector CD8+ T cells in the tumor microenvironment, which contributes to suppressing the tumorigenesis of liver cancer cells in vivo.
Formin‐like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6/CKAP4/ERK axis
Authors: He Guoyang , Li Wei , Zhao Wenli , Men Hui , Chen Qingqing , Hu Jinlong , Zhang Jingyu , Zhu Huifang , Wang Wenxin , Deng Meijing , Xu Zishan , Wang Gaoxiang , Zhou Lin , Qian Xinlai , Liang Li
Published: January 2023

Increasing evidence indicates that angiogenesis plays a pivotal role in tumor progression. Formin‐like 2 (FMNL2) is well‐known for promoting metastasis; however, the molecular mechanisms by which FMNL2 promotes angiogenesis in colorectal cancer (CRC) remain unclear. Here, we found that FMNL2 promotes angiogenesis and metastasis of CRC in vitro and in vivo. The GDB/FH3 domain of FMNL2 directly interacts with epidermal growth factor‐like protein 6 (EGFL6). Formin‐like 2 promotes EGFL6 paracrine signaling by exosomes to regulate angiogenesis in CRC. Cytoskeleton associated protein 4 (CKAP4) is a downstream target of EGFL6 and is involved in CRC angiogenesis. Epidermal growth factor‐like protein 6 binds to the N‐terminus of CKAP4 to promote the migration of HUVECs by activating the ERK/MMP pathway. These findings suggest that FMNL2 promotes the migration of HUVECs and enhances angiogenesis and tumorigenesis in CRC by regulating the EGFL6/CKAP4/ERK axis. Therefore, the EGFL6/CKAP4/ERK axis could be a candidate therapeutic target for CRC treatment.
Maturation of consonant perception, but not vowel perception, predicts lexical skills at 12 months
Authors: Schaadt Gesa , Werwach Annika , Obrig Hellmuth , Friederici Angela D. , Männel Claudia
Published: January 2023

Consonants and vowels differentially contribute to lexical acquisition. From 8 months on, infants' preferential reliance on consonants has been shown to predict their lexical outcome. Here, the predictive value of German‐learning infants' (n = 58, 29 girls, 29 boys) trajectories of consonant and vowel perception, indicated by the electrophysiological mismatch response, across 2, 6, and 10 months for later lexical acquisition was studied. The consonant‐perception trajectory from 2 to 6 months (β = −2.95) and 6 to 10 months (β = −.91), but not the vowel‐perception trajectory, significantly predicted receptive vocabulary at 12 months. These results reveal an earlier predictive value of consonant perception for word learning than previously found, and a particular role of the longitudinal maturation of this skill in lexical acquisition.
Koala conservation in South East Queensland: A grey literature review analysis
Authors: Tkaczynski Aaron , Rundle‐Thiele Sharyn
Published: January 2023

This grey literature review documents koala (Phascolarctos cinereus) conservation initiatives applied across 12 local government areas in South East Queensland, Australia. To overcome threats to koalas' survival, the grey literature indicates that local governments in this region focus on wildlife management solutions, wildlife signage, habitat restoration projects and koala awareness campaigns. Despite these measures, land clearing of koala habitat to cater for urban population growth combined with recent bushfires and floods have contributed to the decline of koalas in this region. Recommendations to enhance progress include greater usage of the grey literature in peer review work and further application of social marketing to encourage residents to uptake behaviors that can mitigate threats to koalas, including slowing down when driving in koala zones, participating in citizen science, and leashing dogs when walking in native bush areas. The need for collaborative efforts aimed at conserving the koala from potential extinction is indicated. This paper provides an approach that can be applied to track progress on coordinated efforts to conserve koalas.
MR imaging biomarkers in HCC: outcomes correlation in liver transplant listed patients
Authors: Wibulpolprasert Pornphan , Agopian Vatche , Dumronggittigule Wethit , Lee Yong Seok , Yuen Alexander , Raman Steven S. , Markovic Daniela , Lu David S.
Published: January 2023

Purpose

To determine hepatocellular carcinoma (HCC) magnetic resonance imaging (MRI) biomarkers that enable the prediction of delisting from tumor progression versus successful transplantation in patients listed for orthotopic liver transplantation (OLT).

Methods

With IRB approval and HIPPA compliance, patients with HCC awaiting OLT who were delisted due to HCC progression from 2006 to 2015 were identified. Patients with adequate MR images for review were subsequently matched with a cohort of patients successfully bridged to OLT in the same time period. Matching considered the tumor stage and the dominant treatment strategy adopted to bridge the patient to OLT. Potential MRI features were evaluated by univariable and multivariable analysis using a conditional logistic model.

Results

There were 53 patients included in each cohort. On uni‐variable analysis, significant unfavorable MR imaging features included T2 hyperintensity (odds ratio [OR], 19.0), infiltrative border (OR, 7.50), lobulated shape (OR, 4.5), T1 hypointensity (OR, 3.0), heterogeneous arterial enhancement (OR, 7.0), and corona venous enhancement (OR, 4.0). A significant favorable MR imaging feature was the presence of intralesional fat (OR = .36). The best multivariable logistic prediction model derived from the above notable features included only T1 and T2 signal intensity, border definition, and absence of intra‐lesional fat as significant variables, with an area under the receiver operating characteristic curve (AUC) of .86 in the prediction of delisting.

Conclusion

Select MR imaging features of HCC at presentation before any treatment are significantly associated with the risk of tumor progression regardless of tumor stage and treatment strategy in patients awaiting liver transplantation.
Autonomy: How it has become problematic for medicine
Authors: Wispe Jonathan
Published: January 2023

This essay arises from the current state of the American medical system. Neither patients nor practitioners are satisfied. This essay focuses on an important source of discontent, the dependence on ethical principlism which is unsupported by a moral virtue. This ethical system is bounded by no recognition of telos of medicine and no articulation of how medicine can advance human flourishing. This essay explores how principlism, and autonomy in particular, attained a dominant stature, and how it damaged patient–practitioner relationships. This essay will conclude with a brief description about the potential benefits of covenantal relationships in medicine.
Current treatment and prevention of orthopaedic infections in the horse
Authors: Crosby Corinne E. , Redding Laurel E. , Ortved Kyla F.
Published: January 2023

Orthopaedic infections, including synovial sepsis, osteomyelitis and infection of orthopaedic implants are common in equine medicine. Infections can be caused by haematogenous spread of pathogens, trauma or penetrating injuries, extension of local infections and iatrogenic causes such as surgery and synovial injections. Horses with orthopaedic infections are generally markedly lame and often require aggressive and prolonged therapy. Early diagnosis can greatly impact treatment outcomes and can be facilitated by careful physical examinations, haematology, diagnostic imaging and timely synovial fluid sampling. Concerted efforts should always be made to obtain a positive bacterial culture and sensitivity. Treatment is focused on antimicrobial therapy with local therapy, including intravenous regional limb perfusion and intrasynovial injections, being employed whenever possible; lavage and debridement; and analgesia and supportive care. Responsible use of antimicrobials and antimicrobial stewardship are critical when treating orthopaedic infections. Prognosis will depend on the source and severity of the infection, the causative agent and the time to intervention. Foals and horses can respond well to treatment and return to soundness with early, aggressive and targeted treatment.