bluuebunny/crossref_metadata_2025 huggingface dataset:
Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism
Authors: Choi Ashley , Smith Jennifer , Wang Yingqi , Shin Hyunsoo , Kim Bowon , Wiest Alyssa , Jin Xi , An Isabella , Hong Jiso , Antila Hanna , Thomas Steven , Bhattarai Janardhan P. , Beier Kevin , Ma Minghong , Weber Franz , Chung Shinjae
Published: December 2023

Sleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep disturbances in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings demonstrate that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.
Ventilation does not affect influenza virus transmission efficiency in a ferret playpen setup
Authors: Rockey Nicole C. , Sage Valerie Le , Shephard Meredith , Vargas-Maldonado Nahara , French Andrea J. , Walter Sydney , Ferreri Lucas M. , Holmes Katie E. , VanInsberghe David , Clack Herek , Prussin Aaron J. , Lowen Anice C. , Marr Linsey C. , Lakdawala Seema S.
Published: December 2023

Sustained community spread of influenza viruses relies on efficient person-to-person transmission. Current experimental transmission systems do not mimic environmental conditions (e.g., air exchange rates, flow patterns), host behaviors or exposure durations relevant to real-world settings. Therefore, results from these traditional systems may not be representative of influenza virus transmission in humans. To address this pitfall, we developed a modified, more realistic transmission setup and used it to investigate the impact of ventilation rates on transmission in a close-range, play-based scenario. In this setup, four immunologically naïve recipient ferrets were exposed to a donor ferret infected with a genetically barcoded 2009 H1N1 virus (H1N1pdm09) for four hours. The ferrets interacted in a shared space that included toys, similar to a child care setting. The transmission efficiency was determined under conditions of low and high ventilation rates; air exchange rates of ∼ 1.3 hr-1and 23 hr-1, respectively. Despite the large difference in ventilation rate, transmission efficiency was the same, 50% in two independent replicate studies. The presence of infectious virus or viral RNA on surfaces and in air throughout the exposure area was similar regardless of ventilation rate. While high viral genetic diversity in donor ferret nasal washes was maintained during infection, recipient ferret nasal washes displayed low diversity, revealing a narrow transmission bottleneck regardless of ventilation rate. Our findings indicate that in exposures characterized by frequent close-range, play-based interactions and the presence of fomites, ventilation does not significantly impact transmission efficiency.

Significance

Improved ventilation in building has the potential to reduce transmission of respiratory viruses, but its effect in different settings is not well understood. We developed a novel system to study influenza virus transmission in the ferret animal model in an environment that mimics a child care center. We demonstrate that increased ventilation is not effective at disrupting transmission in this setting, suggesting that transmission occurs mainly at close-range or via fomites. Multiple interventions are needed to reduce the spread of influenza virus in this type of setting.
Can tourists get used to the threat? A comparative study of tourists' behavioral intention during the COVID-19 pandemic
Authors: Młynkowiak-Stawarz Anna , Bęben Robert , Kraus Zuzanna
Published: December 2023

Purpose

The purpose of this paper is to present a model depicting the relationship between the behavioral intention of tourists in the conditions prevailing during a pandemic and other variables.

Design/methodology/approach

In constructing the research procedure, two measurements of tourist behavioral intention were taken into account, which were taken far apart in time. In verifying the developed model, the results of surveys of 1,615 people carried out in June 2021 and 917 people carried out in December 2021 were considered.

Findings

As a result of the habituation process, tourists show greater acceptance of the restrictions.

Practical implications

Information on the basis of which companies make management decisions plays a significant role in the creation of company value. In the tourism sector, the information concerns primarily consumer behavior.

Originality/value

Changes over time in risk perception, health protection motivation, and reactance due to perceived pandemic-related restrictions were taken into account in the context of behavioral intention towards tourism.
Does Critical HRD really exist outside academia?: An interview study with nine Critical HRD scholars
Authors: Kwon Chang-kyu , Archer Matthew
Published: December 2023

Purpose

The complex world in which we reside is calling for more critical approaches to address the precarity experienced by the most marginalized in social systems. However, human resource development (HRD) lacks empirical data to describe, define and project the objectives and future directions of Critical HRD in today’s turbulent and volatile times. Therefore, the purpose of this study is to examine the historical and contemporary progression of Critical HRD, as described by nine of its most well-known scholars.

Design/methodology/approach

Data were collected through semistructured interviews, and a constructivist grounded theory coding approach was applied during analysis to identify themes and patterns.

Findings

The findings of this study highlight the persistent scholarship versus practice divide among Critical HRD scholars, suggesting that Critical HRD may merely be an academic undertaking and something not practiced within the public domain. The authors call for an evolution of Critical HRD toward more practice- and action-oriented approaches to scholarship and teaching so that meaningful changes can take place in actual organizations and workplaces.

Originality/value

To the best of the authors’ knowledge, this study was the first to empirically show that there is a real research–practice gap, particularly among Critical HRD scholars. Critical HRD scholars need to take these findings seriously as an opportunity to reflect on how they can take Critical HRD to the next level beyond academic discourse.
Bond market development and economic growth nexus in developing countries: a GMM approach
Authors: Ugbam Charles Ogechukwu , Ngong Chi Aloysius , Abner Ishaku Prince , Ibe Godwin Imo
Published: December 2023

Purpose

This study examines the nexus of bond market development and economic growth from 2015 to 2022.

Design/methodology/approach

The system-generalized method of moments (GMM) is employed on economic growth, government market capitalization, corporate market capitalization, bond yield, interest rate spread, trade openness and investment level.

Findings

The findings show that the government bond market, corporate bond capitalization and bond yield positively impact the gross domestic product (GDP). The results equally reveal a causal link between the corporate bond market, bond yield and GDP.

Research limitations/implications

Governments should emphasize creating, developing and sustaining bond markets in the economies of developing countries to boost economic activity by promoting structural transformation. Policymakers should improve the implementation of existing rules and regulations while complementing them with new ones since well-developed bond markets provide alternative sources of financing that make economies financially resilient. Policymakers should encourage the issuance of corporate bonds to enhance the efficiency of the capital markets and mobilize funds for economic growth stimulation. Governments and corporations should diversify their sources of funding into the bond markets since the bond yields are favorable to economic growth.

Originality/value

Earlier studies presented arguable results on the bond market development and economic growth nexus. Several findings indicate a positive link; others give a negative link between bond market development and economic growth. Some show causal directions, while other reveal none. The contradictory results motivate research. This research results contribute to the literature in that the government bond market, corporate bond capitalization and bond yield positively impact the GDP of developing nations.
Activity focus groups – a discursive, practical and social method for studying consumption practices
Authors: Weckroth Katri , Närvänen Elina
Published: December 2023

Purpose

The purpose of this paper is to present a novel qualitative activity focus group (AFG) method for studying consumption practices. This participatory method, which is inspired by practice-theoretical thinking, combines focus group discussions with activities that represent the practices at the centre of the research.

Design/methodology/approach

The application of the AFG method is demonstrated with an empirical study of the transition to plant-based food consumption practices in Finland, involving four group sessions of 13 participants.

Findings

The findings from the empirical application of the AFG method illustrate that its key strength is the ability to foster fruitful and natural discussions on routine consumption practices that connect with discursive and practical dimensions and thus generate multidimensional data in resource-efficient ways.

Originality/value

The AFG method extends the methodological approaches in practice theory–oriented research, responding to the call for creative, real-life-reflecting methods that are able to grasp the discursive and embodied dimensions of practices. The method is proposed to be particularly suitable for research on mundane consumption practices.
What determines behavioural intention in health services? A four-stage loyalty model
Authors: George Ajimon , Sahadevan Jobin
Published: December 2023

Purpose

This study aims to deal with the paucity of studies in the stages of the development of loyalty behaviour of customers in the healthcare context by incorporating three crucial service quality dimensions (physical environment, personnel quality and technical quality) and also investigating trust and commitment as mediating factors.

Design/methodology/approach

Survey data were obtained from 420 respondents admitted to government hospitals in Kerala employing a convenience sampling method. The formulated hypotheses were tested using partial least square structural equation modelling.

Findings

Results indicate that patient satisfaction, trust and commitment can create favourable behavioural intentions amongst patients. When patients reveal higher trust, they are more inclined to value healthcare services and willing to commit to a long-term relationship, resulting in increased patient loyalty.

Practical implications

Organisational efforts should improve trust and commitment and build a good relationship between service providers and patients. Efforts should be taken to raise the standard of technical and personnel aspects, and a focus on physical infrastructure should also be considered to build a favourable behavioural intention to revisit and positive referrals.

Originality/value

This is the first empirical study to analyse technical quality, personnel quality and physical environment along with the mediating effect of trust, and commitment in a four-stage loyalty development model in the healthcare context of Kerala, India.
Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster‐associated pain: A placebo‐controlled randomized trial
Authors: Iseki Masako , Yamamoto Takenobu , Ogawa Youichi , Majima Yuta , Abe Yoichiro , Watanabe Daisuke , Amaya Fumimasa , Hasegawa Toshio , Inafuku Kazuhiro , Kosugi Toshifumi , Nomura Yukiko , Deguchi Tokiko , Hamada Toshihisa , Shimizu Kenji , Arai Saori , Takahashi Morito , Hamada Izumi , Ishikawa Yuko , Kawashima Makoto
Published: December 2023

Acute zoster‐associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster‐associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster‐associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double‐blind, placebo‐controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster‐associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low‐dose fosphenytoin group (n = 6, median age 62.5 years, range 39–75 years), high‐dose fosphenytoin group (n = 5, median age 69.0 years, range 22–75 years), and placebo group (n = 5, median age 52.0 years, range 38–72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high‐ and low‐dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2‐point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10–15 μg/mL. Treatment‐emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster‐associated pain.

Trial Registration: ClinicalTrials.gov NCT04139330.
Occupational Therapy Observation Tool–Adjustment Support Details for autistic children: Investigation of content validity and clinical utility
Authors: Kwok WingKwan Michelle , Bourke‐Taylor Helen , Carey Stuart , McKenzie Maria
Published: December 2023

Introduction

Standardised testing is crucial for autistic children to receive appropriate interventions, necessary services, and funding. Behaviours associated with autism can hinder children's test performance and participation. The 18‐item, two‐page Occupational Therapy Observation Tool–Adjustment Support Details (OTOT‐ASD) is used in conjunction with standardised assessments. The OTOT‐ASD enables the recording of autism‐related behaviours and the reasonable assessment accommodations made to support participation in testing. The current study aims to investigate the content validity and clinical utility of the OTOT‐ASD from occupational therapists' perspectives.

Method

A specifically designed online questionnaire was distributed Victoria‐wide to occupational therapists with clinical experience with autistic children. The questionnaire was designed in line with the COnsensus‐based Standards for selection of health Measurement INstruments (COSMIN), including relevance, comprehensiveness, and comprehensibility of items evaluated for content validity. Applicability and clinical usefulness were also investigated. Quantitative data were analysed using descriptive statistics.

Results

Seventy‐one occupational therapists responded to the questionnaire and 46 provided a full dataset. Over 96% of the respondents considered documenting behaviours and testing accommodations as important, yet less than 45% reported having resources to record this information. Ninety‐five percent of the respondents perceived the OTOT‐ASD to be useful in clinical practice. Over 70% agreed that OTOT‐ASD items were significantly relevant to practice and comprehensive. To improve comprehensibility, identified items were altered following feedback.

Conclusion

The findings suggest that the OTOT‐ASD is clinically useful and content validity is sound. Further research on other psychometric properties of the OTOT‐ASD and users' qualitative experiences in utilising the tool is recommended.
Anthropogenic and natural disturbances increase local genetic diversity in an early spring geophyte (Ficaria verna Huds)
Authors: Guicking Daniela , Keßler Sarah , Störmer Eliza , Bersch Maggie , Duchoslav Martin
Published: December 2023

The tetraploid Ficaria verna is a common spring geophyte in central Europe and is considered invasive in the USA and Canada. It is considered an almost seed‐sterile taxon, relying on vegetative reproduction by underground tubers and aerial bulbils. Recent studies have revealed high levels of population genetic diversity in F. verna, raising the question of how genetic diversity is maintained and which factors may be responsible for the observed patterns. Polymorphic nuclear microsatellite markers were established to define multi‐locus genotypes (MLGs), to analyze fine‐scale spatial genetic structure (SGS) using grid and cross‐sampling schemes, and to quantify genetic diversity within and between nine populations with different disturbance regimes in central Germany. In total, 115 MLGs were identified among a total of 347 samples. The G/N ratio varied between 0.16 and 0.70 among populations, and in each population several unique MLGs occurred. Genotypes were highly intermingled within populations, suggesting a “guerrilla” dispersal strategy. Significant SGS (negative regression slope of kinship coefficients against inter‐individual distances) was found in four out of nine populations in fine‐scale cross‐sampling (up to 4 m) and in only one population in grid sampling (up to 14.6 m). No single MLG was found in more than one population, while many alleles were shared between populations. Within‐population clonal and allelic diversity increased with greater exposure to both anthropogenic and natural disturbances. Regular gap openings, facilitated propagule establishment, and propagule dispersal by water and mowing machines are likely important factors explaining the positive effects of disturbance on local genetic diversity of F. verna.
How Green Banks can create multiple types of value in the transition to net zero emissions
Authors: Lyons Michelle , White Lee Victoria
Published: December 2023

Current levels of investment are insufficient to meet the goals of the Paris Agreement, and private sector funding shortfalls are acute. Despite this, little research has been undertaken into Green Banks, a new form of institution which mixes public and private institutional logics to mobilise additional private investment in the net zero transition. This paper examines how hybridity manifests in Green Banks and the ways these institutions create value through their investments. We adopt a mixed method, case study approach, combining primary document study with interviews, to elicit information on different forms of hybrid governance and value creation in four Green Banks (located in Australia, New Zealand, and the United States). We find some commonalities in how hybridity manifests between cases (e.g. combining public knowledge sharing logics with private investment logics), but also significant differences (e.g. in investment focus), as policymakers adapt organisational governance to suit jurisdictional circumstances. Green Banks are perceived to create value beyond their core financial roles, including knowledge spillovers, social equity benefits, and enhanced energy security. Current evaluation approaches focus on financial metrics and often exclude these broader areas of value creation. Development of additional value capture metrics could make Green Bank contributions more visible.

Points for practitioners

Green Banks are hybrid organisations that seek to accelerate investments in low carbon infrastructure.

Green Banks aim to mobilise additional private finance to investments which would otherwise not occur, due to economic, social, or political barriers.

Green Banks demonstrate different forms of organisational hybridity and value creation at national, state, and local levels.

At present, the value created by Green Banks, particularly investments in disadvantaged communities, is not fully captured through investment evaluation processes.

The net zero transition is an opportunity to develop new forms of investment governance and evaluation which moves beyond capturing financial value to capture the value of investments more effectively.
Characteristics and outcome of systemic treatment for metastatic or unresectable thymic carcinoma: A single institution experience
Authors: Ho I‐Wei , Pan Yu‐Ling , Lai Jiun‐I , Liu Chun‐Yu
Published: December 2023

Background

Thymic carcinoma is a rare disease with an incidence of around 0.5 cases per million with a poor prognosis. The aim of this study was to assess patient outcomes with advanced thymic carcinoma receiving first‐line chemotherapy.

Methods

In our retrospective cohort study, we included patients who underwent treatment for metastatic thymic carcinoma between January 2013 to December 2019 in our hospital. Overall survival, progression‐free survival (PFS), objective response rates (ORR) and chemotherapy regimens were assessed and analyzed.

Results

A total of 27 patients were retrospectively analyzed. All patients received a platinum (cisplatin or carboplatin) based regimen as first‐line chemotherapy (29.6% received ADOC, 11.1% received PE, 40.7% received CP, 14.8% received CAP). The median PFS on first‐line chemotherapy was 199 days. The response rate was 40.7%. Median overall survival (OS) was 585 days. Positive CD5 staining was associated with better PFS.

Conclusion

We highlight the critical role of platinum‐based chemotherapy agents as a primary treatment modality in advanced thymic carcinoma, underscoring the efficacy of platinum as a first‐line option for recurrent disease, even in cases previously treated with platinum. Additionally, our findings indicate that CD5 positivity could be associated with improved PFS, suggesting its potential as a prognostic marker.
The indirect effects of self‐regulation on the association of social support with increased protective drinking behavior and decreased alcohol problems in a predominantly Hispanic college student sample
Authors: Sanchez‐Garciaguirre Aitiana I. , Najera Sarah N. , Portillo Erin M. , Field Craig A.
Published: December 2023

Background

Research suggests that self‐regulation, which refers to one's ability to manage a behavior, and social support are related to alcohol use. Other research suggests that social support may serve as a precursor to self‐regulation and health‐promoting behaviors. We examined whether self‐regulation has an indirect effect on the association between social support and both protective drinking behaviors and alcohol problems.

Methods

A random sample of students at a Hispanic Serving Institution completed an online survey, which included sociodemographic questions, the Multidimensional Perceived Social Support Scale, the Short Self‐Regulation Questionnaire, the Protective Behavioral Strategies (PBS) Scale, and the Rutgers Alcohol Problem Index. Undergraduate students (n = 192) who reported drinking in the last month were included in the analysis. A path analysis using Mplus8 was conducted to investigate the relationships among social support, self‐regulation, PBS, and alcohol‐related problems.

Results

The sample was mostly female (58.9) and of Hispanic ethnicity (89.6). Analyses showed that social support had a significant positive association with PBS and a significant negative association with alcohol‐related problems. When self‐regulation was added to the models, these associations were no longer significant, and self‐regulation had a significant indirect effect on the relationship between social support and both PBS and alcohol‐related problems.

Conclusions

The results of the current cross‐sectional study suggest that a viable hypothesis in future longitudinal studies is that self‐regulation is a mechanism by which social support increases PBS and reduces alcohol problems. Future research should assess longitudinally both the mediating effects of self‐regulation between social support and drinking outcomes and potential moderators, such as ethnicity.
Improving electrotactile communication with a multi‐pad electrode under cognitive load
Authors: Jure Fabricio A. , Spaich Erika G. , Petrini Laura , Malešević Jovana , Kostić Miloš , Štrbac Matija , Došen Strahinja
Published: December 2023

Background

Electrotactile systems are compact interfaces that can be used to convey information through the skin by producing a range of haptic sensations. In many applications, however, the user needs to perceive and interpret haptic stimulation while being engaged in parallel activities. Developing methods that ensure reliable recognition of electrotactile messages despite additional cognitive load is, therefore, an important step for the practical application of electrotactile displays.

Methods

This study investigated if a simple strategy of repeating electrotactile messages can improve message identification during multitasking. Ten participants identified 36 spatiotemporal electrotactile messages delivered through a 3 × 2 pad–matrix electrode placed on the torso while performing a concomitant cognitive task in three conditions: the messages were presented once (No‐REP), and each message was repeated three (REP3) and five (REP5) times. The main outcome measure was the success rate (SR) of message identification.

Results

During multitasking, in the No‐REP condition, the SR (median (IQR)) dropped to 56.25% (22.62%), demonstrating that the cognitive task decreased performance. However, the SR significantly improved with message repetitions, reaching 72.92% (21.87%) and 81.25% (18.66%) in REP3 and REP5 conditions respectively, without a statistically significant difference between REP3 and REP5.

Conclusions

Multitasking affected the efficacy of haptic communication, but message repetition was shown to be an effective strategy for improving performance. Additionally, only three repetitions were enough, as an additional increase in the duration of message transmission (5 repetitions) did not lead to further improvement. This study is an important step toward delivering electrotactile communication that can cope with the demands of real‐world applications.
Effect of changes in metabolic enzymes and transporters on drug metabolism in the context of liver disease: Impact on pharmacokinetics and drug–drug interactions
Authors: Armani Sara , Geier Andreas , Forst Thomas , Merle Uta , Alpers David H. , Lunnon Martin W.
Published: December 2023

Changes in the pharmacokinetic and resulting pharmacodynamic properties of drugs are common in many chronic liver diseases, leading to adverse effects, drug interactions and increased risk of over‐ or underdosing of medications. Structural and functional hepatic impairment can have major effects on drug metabolism and transport. This review summarizes research on the functional changes in phase I and II metabolic enzymes and in transport proteins in patients with metabolic diseases such as type 2 diabetes, metabolic dysfunction‐associated steatotic liver disease, metabolic dysfunction‐associated steatohepatitis and cirrhosis, providing a clinical perspective on how these changes affect drug uptake and metabolism. Generally, a decrease in expression and/or activity of many enzymes of the cytochrome P450 family (e.g. CYP2E1 and CYP3A4), and of influx and efflux transporters (e.g. organic anion‐transporting polypeptide [OATP]1B1, OATP2B1, OAT2 and bile salt export pump), has been recently documented in patients with liver disease. Decreased enzyme levels often correlate with increased severity of chronic liver disease. In subjects with hepatic impairment, there is potential for strong alterations of drug pharmacokinetics due to reduced absorption, increased volume of distribution, metabolism and extraction. Due to the altered pharmacokinetics, specific drug–drug interactions are also a potential issue to consider in patients with liver disease. Given the huge burden of liver disease in western societies, there is a need to improve awareness among all healthcare professionals and patients with liver disease to ensure appropriate drug prescriptions.
Welfare analysis of bank mergers with financial instability
Authors: Ino Akio , Matsuki Yusuke
Published: December 2023

In this study, we analyze the effect of a merger between banks by extending a structural model of the banking industry with the possibility of bank runs developed by Egan et al. (2017; American Economic Review, 107, 169–216). We use our framework to analyze whether the 2008 merger between Wells Fargo and Wachovia was beneficial for social welfare. The results suggest that the stability of the financial system is critical for evaluating mergers in the banking industry.
Decision tree‐based identification of important molecular fragments for protein‐ligand binding
Authors: Li Baiyi , Wang Yunsong , Yin Zuode , Xu Lei , Xie Liangxu , Xu Xiaojun
Published: December 2023

Fragment‐based drug design is an emerging technology in pharmaceutical research and development. One of the key aspects of this technology is the identification and quantitative characterization of molecular fragments. This study presents a strategy for identifying important molecular fragments based on molecular fingerprints and decision tree algorithms and verifies its feasibility in predicting protein‐ligand binding affinity. Specifically, the three‐dimensional (3D) structures of protein‐ligand complexes are encoded using extended‐connectivity fingerprints (ECFP), and three decision tree models, namely Random Forest, XGBoost, and LightGBM, are used to quantitatively characterize the feature importance, thereby extracting important molecular fragments with high reliability. Few‐shot learning reveals that the extracted molecular fragments contribute significantly and consistently to the binding affinity even with a small sample size. Despite the absence of location and distance information for molecular fragments in ECFP, 3D visualization, in combination with the reverse ECFP process, shows that the majority of the extracted fragments are located at the binding interface of the protein and the ligand. This alignment with the distance constraints critical for binding affinity further supports the reliability of the strategy for identifying important molecular fragments.
The contribution of metal allergy to the failure of metal alloy implants, with special reference to titanium: Current knowledge and controversies
Authors: Huang Chenghao , Chiang Shu Yu Vanessa , Gawkrodger David J.
Published: December 2023

After almost three‐quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal‐alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily—opinion probably favours the first. Metal‐on‐polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium‐containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium‐containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non‐dermatologists, such that it is now needed for temporo‐mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable.
Relevance and the Role of Labels in Categorization
Authors: Gervits Felix , Johanson Megan , Papafragou Anna
Published: December 2023

Language has been shown to influence the ability to form categories. Nevertheless, in most prior work, the effects of language could have been bolstered by the fact that linguistic labels were introduced by the experimenter prior to the categorization task in ways that could have highlighted their relevance for the task. Here, we compared the potency of labels to that of other non‐linguistic cues on how people categorized novel, perceptually ambiguous natural kinds (e.g., flowers or birds). Importantly, we varied whether these cues were explicitly presented as relevant to the categorization task. In Experiment 1, we compared labels, numbers, and symbols: One group of participants was told to pay attention to these cues because they would be helpful (Relevant condition), a second group was told that the cues were irrelevant and should be ignored (Irrelevant condition), and a third group was told nothing about the cues (Neutral condition). Even though task relevance affected overall reliance on cues during categorization, participants were more likely to use labels to determine category boundaries, compared to numbers or symbols. In Experiments 2 and 3, we replicated and fine‐tuned the advantage of labels in more stringent categorization tasks. These results offer novel evidence for the position that labels offer unique indications of category membership, compared to non‐linguistic cues.
Gel immersion cold polypectomy with a duodenoscope for supra‐ampullary adenoma
Authors: Okamoto Takeshi , Nakagawa Hiroki , Sasahira Naoki
Published: December 2023

Watch a video of this article.
Developing and exploring the validity of a patient reported experience measure for adult inpatient diabetes care
Authors: Kozlowska Olga , Tallett Amy , Bond Samuel , Mansbridge Sarah E. , Aveyard Helen , Jenkinson Crispin , Dudbridge Alexander , McRobert Nicky , Lumb Alistair , Rea Rustam , Tan Garry D. , Walthall Helen
Published: December 2023

Aim

To develop and explore the validity of a Patient Reported Experience Measure (PREM) for adult inpatient diabetes care.

Method

27 in‐depth interviews were conducted to inform the development of the 42‐item PREM which was cognitively tested with 10 people. A refined 38‐item PREM was piloted with 228 respondents completing a paper (n = 198) or online (n = 30) version. The performance of the PREM was evaluated by exploring (i) uptake/number of responses and (ii) survey validity by investigating whether the PREM data were of adequate quality and delivered useful information.

Results

The PREM had low drop‐out or missing data rates suggesting it was appropriately constructed. Analysis of item frequencies and variances, and problem score calculations concluded that questions provided sufficient score differentiation.

Conclusions

This new PREM allows for experiences of inpatient diabetes care to be measured, understood and reported on to help identify priority areas for improving care quality.
A preliminary study on the association of single nucleotide polymorphisms and methylation of dopamine system‐related genes with psychotic symptoms in patients with methamphetamine use disorder
Authors: Fang Ting , Liu Meng‐Nan , Liu Meng‐Qi , Tian Xiao‐Yu , Zhang Xiao‐Jie , Liu Feng , Hao Wei , Wu Ning , Li Hong , Li Jin
Published: December 2023

Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high‐risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol‐O‐methyltransferase (COMT) genes, and paranoid and motor‐impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor‐impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor‐impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high‐risk psychotic symptoms in MAUD patients.
Eosinophilic oesophagitis: a common cause of food bolus obstruction
Authors: Collins Kate , Lu Irene , Ng Jer Fuu , Stevenson Connor , Dowling Damian
Published: December 2023

Background

Eosinophilic oesophagitis (EOE) is a known cause of food bolus obstruction (FBO) with rising incidence and prevalence.

Aims

To assess the rates of EOE in adult cases presenting with an FBO via prospective biopsy collection during index endoscopy.

Methods

Oesophageal FBO cases requiring gastroscopy between February 2014 and January 2021 at a single institution with a unified policy to perform biopsies on FBO cases were analysed using medical records, endoscopy and histology. Statistical analysis was undertaken to compare those with and without EOE as their final diagnosis, including the timing of oesophageal biopsy and the season that cases presented.

Results

One hundred ninety FBO presentations were analysed, 15 patients presented twice and one patient presented four times within the 7‐year study period. Men represented 72% of cases. A total of 78% of cases had biopsies collected at an index or scheduled follow‐up endoscopy. EOE was the cause of the FBO in 28% (53/190) of presentations. FBO secondary to EOE was more likely to occur in the spring and summer months (Australian September to March), with 39% (19 of 49) of cases presenting in spring attributable to EOE.

Conclusion

EOE affects a significant proportion of patients presenting with FBO (28%); a high biopsy rate of 78% in FBO cases provides an opportunity for prompt diagnosis and treatment.
TLR7 enhancing follicular helper T (Tfh) cells response in C57BL/6 mice infected with Plasmodium yoeliiNSM TLR7 mediated Tfh cells in P. yoelii infected mice
Authors: Yang Quan , Zhou Lu , Tan Zhengrong , Zhu Yiqiang , Mo Lengshan , Fang Chao , Li Jiajie , Chen Chen , Luo Ying , Wei Haixia , Yin Weiguo , Huang Jun
Published: December 2023

Toll‐like receptors (TLRs) play an important role in inducing innate and acquired immune responses against infection. However, the effect of Toll‐like receptor 7 (TLR7) on follicular helper T (Tfh) cells in mice infected with Plasmodium is still not clear. The results showed that the splenic CD4+CXCR5+PD‐1+ Tfh cells were accumulated after Plasmodium yoelii NSM infection, the content of splenic Tfh cells was correlated to parasitemia and/or the red blood cells (RBCs) counts in the blood. Moreover, the expression of TLR7 was found higher than TLR2, TLR3 and TLR4 in splenic Tfh cells of the WT mice. TLR7 agonist R848 and the lysate of red blood cells of infected mice (iRBCs) could induce the activation and differentiation of splenic Tfh cells. Knockout of TLR7 leads to a decrease in the proportion of Tfh cells, down‐regulated expression of functional molecules CD40L, IFN‐γ, IL‐21 and IL‐10 in Tfh cells; decreased the proportion of plasma cells and antibody production and reduces the expression of STAT3 and Ikzf2 in Tfh cells. Administration of R848 could inhibit parasitemia, enhance splenic Tfh cell activation and increase STAT3 and Ikzf2 expression in Tfh cells. In summary, this study shows that TLR7 could regulate the function of Tfh cells, affecting the immune response in the spleen of Plasmodium yoelii NSM‐infected mice.
High TSLP responses in the human infant airways are associated with pre‐activated airway epithelial IFN antiviral immunity
Authors: Welham Allison , Chorvinsky Elizabeth , Bhattacharya Surajit , Bera Betelehem Solomon , Salka Kyle , Weinstock Jered , Chen Xilei Xu , Perez Geovanny F. , Pillai Dinesh K. , Gutierrez Maria J. , Morizono Hiroki , Jaiswal Jyoti , Nino Gustavo
Published: December 2023

Thymic stromal lymphopoietin (TSLP) is a primarily epithelial‐derived cytokine that drives type 2 allergic immune responses. Early life viral respiratory infections elicit high TSLP production, which leads to the development of type 2 inflammation and airway hyperreactivity. The goal of this study was to examine in vivo and in vitro the human airway epithelial responses leading to high TSLP production during viral respiratory infections in early infancy. A total of 129 infants (<1–24 m, median age 10 m) with severe viral respiratory infections were enrolled for in vivo (n = 113), and in vitro studies (n = 16). Infants were classified as ‘high TSLP’ or ‘low TSLP’ for values above or below the 50th percentile. High versus low TSLP groups were compared in terms of type I–III IFN responses and production of chemokines promoting antiviral (CXCL10), neutrophilic (CXCL1, CXCL5, CXCL8), and type 2 responses (CCL11, CCL17, CCL22). Human infant airway epithelial cell (AEC) cultures were used to define the transcriptomic (RNAseq) profile leading to high versus low TSLP responses in vitro in the absence (baseline) or presence (stimulated) of a viral mimic (poly I:C). Infants in the high TSLP group had greater in vivo type III IFN airway production (median type III IFN in high TSLP 183.2 pg/mL vs. 63.4 pg/mL in low TSLP group, p = 0.007) and increased in vitro type I–III IFN AEC responses after stimulation with a viral mimic (poly I:C). At baseline, our RNAseq data showed that infants in the high TSLP group had significant upregulation of IFN signature genes (e.g., IFIT2, IFI6, MX1) and pro‐inflammatory chemokine genes before stimulation. Infants in the high TSLP group also showed a baseline AEC pro‐inflammatory state characterized by increased production of all the chemokines assayed (e.g., CXCL10, CXCL8). High TSLP responses in the human infant airways are associated with pre‐activated airway epithelial IFN antiviral immunity and increased baseline AEC production of pro‐inflammatory chemokines. These findings present a new paradigm underlying the production of TSLP in the human infant airway epithelium following early life viral exposure and shed light on the long‐term impact of viral respiratory illnesses during early infancy and beyond childhood.
Considering biotic interactions exacerbates the predicted impacts of climate change on coral‐dwelling species
Authors: Zhang Zhixin , Ma Shaobo , Bede‐Fazekas Ákos , Mammola Stefano , Qu Meng , Zhou Jinxin , Feng Ellias Yuming , Qin Geng , Lin Qiang
Published: December 2023

Aim

Climate change is affecting the geographic distributions of many species and researchers are increasingly relying on species distribution models (SDMs) to forecast species' redistributions under climate change. Such modelling studies, however, often ignore biotic interactions that shape species' geographic ranges. This is especially problematic for coral reefs, which host a high diversity of species and interactions. We tested how biotic interactions affect the distribution patterns of obligate coral‐dwelling Trapezia crabs.

Location

Global coastal ocean.

Time Period

2000–2014, 2040–2050, 2090–2100.

Major Taxa Studied

Corals and coral‐dwelling Trapezia crabs.

Methods

We determined the symbiotic relationships between 22 crab species in the genus Trapezia and corals via field survey and extensive literature review. We first developed SDMs for coral and crab species using exclusively abiotic variables (abiotic‐only models for corals and crabs). Then we constructed a second set of models where we accounted for coral distributions into crab predictions by combining model predictions for the two taxa a posteriori (abiotic‐plus‐biotic models for crabs only).

Results

We obtained 30 commonly accepted coral‐crab symbiotic relationships from nine Trapezia crab and six stony coral species. The abiotic‐only model predictions showed that six corals may lose approximately one‐sixth of suitable ranges under RCP 8.5 in 2040–2050. The two types of models for crabs yielded largely different habitat suitability predictions and accounting for biotic interactions into SDM predictions exacerbates the predicted impacts of climate change on coral‐dwelling crabs.

Main Conclusions

Our results show large discrepancies in crab spatial distribution patterns with and without accounting for symbiotic interactions. Our findings highlight the important role of modeller's decision on accounting for biotic interactions when predicting the geographical ranges of coral‐dwelling species, with important implications for designing future conservation and management strategies for marine species.