bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring therapeutic strategies for Infantile Neuronal Axonal Dystrophy (INAD/PARK14)
Authors: Lin Guang , Tepe Burak , McGrane Geoff , Tipon Regine C. , Croft Gist , Panwala Leena , Hope Amanda , Liang Agnes J.H. , Zuo Zongyuan , Wang Lily , Bellen Hugo J.
Published: August 2022

Infantile Neuroaxonal Dystrophy (INAD) is caused by recessive variants in PLA2G6 and is a lethal pediatric neurodegenerative disorder. Loss of the Drosophila homolog of PLA2G6, leads to ceramide accumulation, lysosome expansion, and mitochondrial defects. Here, we report that ceramide metabolism, the endolysosomal pathway, and mitochondrial morphology are affected in INAD patient-derived neurons. We show that in INAD mouse models the same features are affected and that glucosylceramides are elevated in dopaminergic neurons and Purkinje cells, arguing that the neuropathological mechanisms are evolutionary conserved and that ceramides can be used as biomarkers. We tested 20 drugs that target these pathways and found that Ambroxol, Desipramine, Azoramide, and Genistein alleviate neurodegenerative phenotypes in INAD flies and INAD patient-derived NPCs. We also develop an AAV-based gene therapy approach that delays neurodegeneration and prolongs lifespan in an INAD mouse model.

One Sentence Summary

Ceramide accumulation, lysosomal expansion and mitochondrial defects are a root cause of INAD/PARK14.
ENGRAILED-1 transcription factor has a paracrine neurotrophic activity on adult spinal α-motoneurons
Authors: Lebœuf Mélanie , Vargas-Abonce Stephanie E. , Pezé-Hedsieck Eugénie , Dupont Edmond , Jimenez-Alonso Lucia , Moya Kenneth L. , Prochiantz Alain
Published: August 2022

Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED-1 is one such homeoprotein expressed in spinal V1 interneurons synapsing on α-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in α-motoneurons loss and limb weakness. A similar but stronger phenotype is observed in theEngrailed-1heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord α-motoneurons. Intrathecal injection of ENGRAILED-1 leads to its specific internalization by spinal motoneurons and has long-lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons expressEngrailed-1and, similarly to spinal cord α-motoneurons, degenerate in the heterozygote. By identifying genes expressed in spinal cord motoneurons also showing modified expression in mouseEngrailed-1heterozygote midbrain neurons, we identified p62/SQTSM1 as an age marker in spinal cord motoneurons with increased expression during aging, in theEngrailed-1heterozygote and upon extracellular ENGRAILED-1 neutralization. We conclude that ENGRAILED-1 is a regulator of motoneuron ageing with non-cell autonomous neurotrophic activity.
Using Machine Learning to identify microRNA biomarkers for predisposition to Huntington’s Disease
Authors: Patel K , Sheridan C , Shanley DP
Published: August 2022

Background

Huntington’s disease (HD) is an autosomal dominant disease which is triggered by a large expansion of CAG nucleotides in theHTTgene. While the CAG expansion linearly correlates with the age of disease onset in HD, twin-studies and cohorts of Juvenile Onset HD (JOHD) patients have shown other factors influence the progression of HD. Thus, it would be of interest to identify molecular biomarkers which indicate predisposition to the development of HD, and as microRNAs (miRNAs) circulate in bio-fluids they would be particularly useful biomarkers. We explored a large HD miRNA-mRNA expression dataset (GSE65776) to establish appropriate questions that could be addressed using Machine Learning (ML). We sought sets of features (mRNAs or miRNAs) to predict HD or WT samples from aged or young mouse cortex samples, and we asked if a set of features could predict predisposition to HD or WT genotypes by training models on aged samples and testing the models on young samples. Several models were created using ADAboost, ExtraTrees, GaussianNB and Random Forest, and the best performing models were further analysed using AUC curves and PCA plots. Finally, genes used to train our miRNA-based predisposition model were mined from HD patient bio-fluid samples.

Results

Our testing accuracies were between 66-100% and AUC scores were between 31-100%. We generated several excellent models with testing accuracies >80% and AUC scores >90%. We also identified homologues ofmmu-miR-154-5p,mmu-miR-181a-5p,mmu-miR-212-3p, mmu-miR-378b, mmu-miR-382-5pandmmu-miR-770-5pfrom our miRNA-based predisposition model to be circulating in HD patient blood samples at p.values of <0.05.

Conclusions

We generated several age-based models which could differentiate between HD and WT samples, including an aged mRNA-based model with a 100% AUC score, an aged miRNA-based model with a 92% AUC score and an aged miRNA-based model with a 96% AUC score. We also identified several miRNAs used to train our miRNA-based predisposition model which were detectable in HD patient blood samples, which suggests they could be potential candidates for use as non-invasive biomarkers for HD research.
Plasma membrane nanodeformations promote actin polymerisation through CIP4/CDC42 recruitment and regulate type II IFN signaling
Authors: Benjamin Ledoux , Natacha Zanin , Jinsung Yang , Charlotte Coster , Christine Dupont-Gillain , David Alsteens , Pierre Morsomme , Henri-François Renard
Published: August 2022

In their environment, cells have to cope with mechanical stresses constantly. Among those, nanoscale deformations of plasma membrane induced by substrate nanotopography are now largely accepted as a biophysical stimulus influencing cell behaviour and function. However, the mechanotransduction cascades involved and their precise molecular effects on cellular physiology are still poorly understood. Here, using homemade fluorescent nanostructured cell culture surfaces, we explored the role ofBin/Amphiphysin/Rvs (BAR) domain proteins as mechanosensors of plasma membrane geometry. Our data reveal that distinct subsets of BAR proteins bind to plasma membrane deformations in a membrane curvature radius-dependent manner. Furthermore, we show that membrane curvature promotes the formation of dynamic actin structures mediated by the Rho GTPase CDC42, the F-BAR protein CIP4 and the presence of PI(4,5)P2, independently of clathrin. In addition, these actin-enriched nanodomains can serve as platforms to regulate receptor signaling as they appear to contain Interferon γreceptor (IFNγ-R) and to lead to the partial inhibition of IFNγ-induced Janus-activated tyrosinekinase/signal transducer andactivator of transcription (JAK/STAT) signaling.
Evolution of quality assurance practices in enhancing the quality of open and distance education in a developing nation: a case study
Authors: Ferdousi Farhana , Ahmed Amir , Momen Md Abdul
Published: August 2022

Purpose

The purpose of this study is to look at the challenges and successes that the case institution has had in implementing and maintaining quality assurance (QA) processes. The study also looks into the role of QA techniques in improving an institution's performance in a developing country.

Design/methodology/approach

The research is qualitative. Nine significant persons were interviewed, including the institution's top administration, faculty members and related staff. Data were gathered to learn more about the background, incremental changes and numerous internal and external elements that influenced how QA was approached over time.

Findings

The findings revealed the challenges and experiences of the evolution of QA practices in the case institution. The results show the changes in QA practices regarding three aspects, including people, place and program of case institutions under three phases. During phases I and II, the adoption and upgradation of QA practices were very slow; phase III showed significant improvement in all three aspects. In addition, the positive impact of QA practices is evident in improving the performance of students and teaching and nonteaching staff of the case institution.

Practical implications

The findings of this research could aid open and distance learning (ODL) providers in other developing nations in understanding the challenges of such a system. It may also make it easier for other ODL providers to comprehend the QA-led success in stakeholder confidence, employability and reputation.

Originality/value

The research will give insights into how QA procedures are used and valued in ODL in developing nations.
Community-led guerrilla drug checking in response to deaths from adulterated MDMA in Victoria, Australia
Authors: Barratt Monica J. , Bright Stephen J. , Blackwell Ash R.
Published: August 2022

Purpose

Following deaths and hospitalisations in Melbourne, Victoria, Australia, related to the unwitting consumption of a combination of 25C-NBOMe and 4-FA, a community-led unauthorised drug checking service was rapidly established at a subsequent music festival. We aim to demonstrate the value of community-led drug checking, even when conducted in less-than-ideal conditions, by describing this service and reporting on its outcomes.

Design/methodology/approach

In all, 131 samples were tested with between 1 and 4 (M = 2.24 and SD = 0.61) reagents (Mandelin, Marquis, Mecke and Simons), and behavioural intentions of service users were reported.

Findings

People whose results indicated that the drug tested was what they expected, or was a drug familiar to them, were more likely to report an intention to take the drug compared to those whose results indicated that the drug was not what they had expected. For example, in 11 cases where the expected substance was not identified and novel substances including 2 C-X (including the NBOMe series), methylone, mephedrone, PMA and MXE were indicated, most reported an intention to discard (8/11).

Practical implications

The guerrilla service appeared to dissuade some people from consuming substances with higher risk profiles. It was also quick to identify substances of concern consistent with the NBOMe/4-FA combination for broader community action. The authors urge governments in Australia and elsewhere to reconsider their opposition to drug checking services, given their utility as vital health services during times of volatile drug market shifts.

Originality/value

While these data are five years old, it has only been in the past year that the Coroners Court of Victoria finalised their report on the deaths associated with this drug outbreak, providing context for the rapid peer response.
BIM implementation: an empirical validation for a four-wheel model
Authors: Olugboyega Oluseye , Windapo Abimbola , Aigbavboa Clinton , Oseghale Godwin Ehis
Published: August 2022

Purpose

Because BIM adoption is still afflicted by various types of hurdles, a complete BIM implementation model is required to provide the necessary methods for driving BIM adoption. As a result, this study looked into the parts of the BIM implementation model that had the most impact on increasing the percentage of BIM adoption in South Africa.

Design/methodology/approach

This study developed a four-wheel model of BIM implementation based on implementation process theory, which includes BIM inspiration, BIM capacity development, BIM use and BIM commitment. To assess BIM capacity development, two sub-constructs (BIM learning process and BIM learning methodologies) were used. Two sub-constructs were used to assess BIM utilisation (efficient BIM application and effective BIM application). The sub-constructs employed to quantify BIM motivation were organisational competitiveness, societal conformity and contractual obligations. Incentives, investments and obligations were used to assess BIM commitment. The model was validated using four assumptions and maximum likelihood estimation – structural equation modelling (MLE-SEM).

Findings

The MLE-SEM results demonstrated unequivocally that all of the constructions are critical components of the BIM deployment paradigm in the South African construction industry. BIM motivation, as characterised by organisational competitiveness and social compliance, has the greatest impact. The findings on BIM motivation also revealed that the desire for technological sophistication, competitiveness and social acceptance by clients are encouraging construction organisations and professionals to embrace BIM adoption.

Research limitations/implications

This study's findings have contributed to the increasing body of literature on BIM deployment. The study has significant implications for achieving BIM implementation in underdeveloped nations where BIM deployment is either non-existent or in its early stages. The theoretical component of the study serves as the foundation for further analysis of BIM deployment.

Practical implications

This research is important for identifying BIM goals, developing a BIM implementation framework, allocating resources for BIM implementation and defining key performance indicators for BIM implementation. The BIM implementation aspects outlined in this study will be effective in lowering BIM adoption hurdles.

Originality/value

This study makes a unique contribution to BIM research by providing theoretical and empirical analysis into the elements of the BIM implementation model in a developing country. The study offers an excellent opportunity to further our understanding of BIM application in underdeveloped nations.
Pandemic transitions: impact on business school campus recruitments
Authors: Gupta Anupama , Haldar Arunima , Srivastava Sushmita
Published: August 2022

Purpose

This study aims to examine the transitions in hiring criteria by recruiting companies in top ten Quacquarelli Symonds ranked business schools in India during the pandemic.

Design/methodology/approach

Using an exploratory lens, an in-depth semistructured interview was conducted with 20 recruiting companies across industries and roles.

Findings

Content analysis suggests the changing preferences in hiring criteria and identifies six themes that have assumed importance during the pandemic period.

Research limitations/implications

This study has implications for business school participants who need to change their preparation strategy during the placement season.

Practical implications

There is an opportunity for business schools to focus on these two soft skills, namely, self-management with self-discipline and oral and written communication across the platform. However, in the depth and diversity of soft skills training, there is often a shallow coverage of multiple skills. The rather focused approach to developing these two skills may go a long way in preparing work-delivery graduates who could hit the proverbial ground running as the first step into their careers.

Originality/value

This study contributes to hiring managers by suggesting the traits that may assume importance in the new normal where remote or hybrid working context is a necessity.
Configuring problems of economics in Islamic perspective: moral nexus, realities and its unification
Authors: Furqani Hafas , Haneef Mohamed Aslam
Published: August 2022

Purpose

This paper aims to investigate the subject matter of Islamic economics that will be the object of a study as a discipline by classifying and unifying different approaches proposed by Islamic economists.

Design/methodology/approach

The paper is a conceptual paper using discursive analysis analysing the perspective and approaches proposed by Islamic economists in defining economic problems from an Islamic perspective. The perspective and approaches proposed are classified and analysed for their implications in constructing the subject matter of discipline.

Findings

Islamic economics, as a new body of knowledge, needs to clarify the economic problems that will be its subject matter. The paper brings an insight into the subject matter of Islamic economics as conceived by scholars in two approaches, namely, economic problems “as they are” and economic problems “as they should be”. The paper also proposes a unified perspective in defining the subject matter of Islamic economics for further development of the discipline.

Research limitations/implications

This paper only provides philosophical guidance for researchers in mapping the problems and the goals of the policy being studied, although it does not offer any practical use for policymaking as each policy is faced with different and specific cases. This paper may be used to assist future researchers in shaping other unexplored fields in Islamic economics as a body of knowledge.

Practical implications

Islamic economics as a discipline will be strengthened if it has a clear subject matter that will be the object of study. However, the conception of economic problems proposed by Islamic economists is based on life-reality, i.e. of what human beings face in their life (practical-type economic problems as they are) and based on life guidance from the Qur’an on how human beings should live as well as life-objectives, i.e. of what goals he should strive for (ideal-type economic problems as they ought to be) brings implication that there are differences in determining the object of study of Islamic economics.

Originality/value

This paper promotes the unification of two conceptions of economic problems proposed by scholars by defining Islamic economics as “a study of resource appropriation to realize human well-being (maslahah)”. This suggests that economic problems as manifested in life reality will be studied within the grand objective of life in Islam (maqasid al-Shariah), and economic problems as perceived in life goals will be studied in the context of life reality. Islamic economic theory will be formulated not only to solve the apparent problem of “what is” but also formulated in a way that refers to goals (ideals) of “what ought to be” that will provide solutions to current economic problems according to certain vision and to take steps to move in that visionary direction.
Electricity consumption and industrial output: fresh evidence from economic community of West African states (ECOWAS)
Authors: Onatunji Olufemi Gbenga
Published: August 2022

Purpose

The current wave of decreasing electricity supply to meet the immediate demand of the populace is influencing not only economic growth but also the industrial productivity of the ECOWAS sub-region. In this context, this paper investigates the long-run and causal relationships between electricity consumption and industrial output in selected ECOWAS countries over the period 1971–2017.

Design/methodology/approach

The Autoregressive Distributed Lag (ARDL) bound testing approach is employed to determine the existence of relationships among the variables. The causal nexus between electricity consumption and industrial output is examined using both the Toda-Yamamoto causality test and the bootstrap-corrected causality technique.

Findings

The long run results indicated that increasing electricity supply enhances industrial output only in Benin, Cote d'Ivoire, Gambia, Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. Furthermore, the causality test results confirmed the presence of all four hypotheses in this study, but the two causality tests agree, particularly in the evidence of growth and neutrality hypotheses. In the cases of Benin, Burkina Faso, Gambia, Ghana, Nigeria, and Sierra Leone, a unilateral causality running from electricity consumption to industrial output is found. However, no evidence of causality between electricity consumption and industrial production has been confirmed in Cote d'Ivoire, Guinea Bissau, Liberia and Niger.

Practical implications

The relevant energy stakeholders in the subregion need to reprioritize their policy framework to focus more on the electricity sector of their economies since electricity consumption is identified as an important driver of industrial growth in the West African countries.

Originality/value

This is the first study to provide a comparative and country-specific investigation of the nexus between electricity consumption and industrial output in Africa, particularly in the West African region.
Compliance cultures and the role of financial incentives
Authors: Teichmann Fabian Maximilian Johannes , Wittmann Chiara
Published: August 2022

Purpose

The concept of compliance is in danger of becoming obsolete as a result of its generalization and overuse. This paper aims to refine the concept of a culture of compliance and its effective implementation in association with financial regulations, in line with the societal expectations of compliance.

Design/methodology/approach

This paper begins by assessing the watershed reconception of compliance in light of the Global Financial Crisis of 2008 (GFC). The influence of financial incentivization and structural weakness is highlighted above all. Recommendations focusing on the significance of the corporate context are made from this and viewed in relation to the growing relevance of compliance in regulating cyberspace.

Findings

Individuals and their decision-making are heavily influenced by the culture of their environment. Clearly, defining the values behind regulations encourages employees to follow the rules based on the principles that underlie them rather than out of fear of punishment, risk aversion or a sense of the “tick-box” duty. This contributes to the longevity of healthy compliance rather than a compliance fatigue.

Originality/value

By casting a look back at the development of compliance, the modern social expectations of compliance can be elucidated and, in turn, translated into mechanisms for corporations to effectively use. The literature on compliance has grown substantially but often limits itself to commentaries on the history of non-compliance or sector-based investigations. Hinged between the past and future of compliance, this study contributes to bridging a considerable gap in the literature by using a wider lens and positive redefinition of compliance.
Application of AHP and G-TOPSIS for prioritizing capabilities and related practices for a mature and resilient supply chain during disruption
Authors: Echefaj Khadija , Charkaoui Abdelkabir , Cherrafi Anass , Kumar Anil , Luthra Sunil
Published: August 2022

Purpose

The purpose of this study is to identify and prioritize capabilities and practices to ensure a resilient supply chain during an unexpected disruption. In addition, this study ranks maturity factors that influence the main capabilities identified.

Design/methodology/approach

This paper is conducted in three stages. First, capabilities and practices are extracted through a literature review. Second, capabilities and practices are ranked using the analytical hierarchical process method. Third, a gray technique for order preference by similarity to ideal solution method is used to rank maturity factors influencing capabilities.

Findings

The findings indicate that responsiveness, readiness, flexibility and adaptability are the most important capabilities for supply chain resilience. Also, commitment and communication are the highest maturity factors influencing resilience capabilities.

Research limitations/implications

The findings provide a hierarchical vision of capabilities and practices for industries to increase resilience. Limitations of the paper are related to capabilities, practices and number of experts consulted.

Practical implications

This paper highlights the importance of high-maturity practices in resilience capability adoption. The findings of this study will encourage decisions-makers to increase maturity practices to build resilience against disruption.

Originality/value

The paper reveals that developing powerful capabilities, good practices and a high level of maturity improve supply chain resilience.
The legality of cryptocurrency from an Islamic perspective: a research note
Authors: Khan Saleh Nawaz
Published: August 2022

Purpose

Islamic scholars are not unanimous on the legality of cryptocurrency. Muslims are confused about the permissibility of cryptocurrency. Thus, this study aims to evaluate the cryptocurrency from Shariah’s perspective.

Design/methodology/approach

This study is qualitative and uses a deductive research approach. It drives conceptual and logical deduction from Qur'an and Hadith.

Findings

The cryptocurrency is an intangible currency without any precious metal or commodity backing. It does not possess any intrinsic value, and also its prices are highly volatile. On these grounds, cryptocurrency does not qualify as money in Islam.

Social implications

Cryptocurrency is not compatible with Islamic principles. It is not legal tender and is not backed by any government. Its prices are highly volatile, which opens the door for speculation. Muslims should avoid investing in it.

Originality/value

This study fulfills an identified need to evaluate cryptocurrency as money from Shariah’s perspective.
Culturally tailored substance use interventions for Indigenous people of North America: a systematic review
Authors: Richer Ariel M.S. , Roddy Ariel L.
Published: August 2022

Purpose

The purpose of the current study is to conduct a systematic review of peer-reviewed work on culturally tailored interventions for alcohol and drug use in Indigenous adults in North America. Substance use has been reported as a health concern for many Indigenous communities. Indigenous groups experienced the highest drug overdose death rates in 2015, the largest percentage increase in the number of deaths over time from 1999 to 2015 compared to any other racial group. However, few Indigenous individuals report participating in treatment for alcohol or drug use, which may reflect the limited engagement that Indigenous groups have with treatment options that are accessible, effective and culturally integrative.

Design/methodology/approach

Electronic searches were conducted from 2000 to April 21, 2021, using PsycINFO, Cumulative Index to Nursing and Allied Health Literature, MEDLINE and PubMed. Two reviewers classified abstracts for study inclusion, resulting in 18 studies.

Findings

Most studies were conducted in the USA (89%). Interventions were largely implemented in Tribal/rural settings (61%), with a minority implemented in both Tribal and urban contexts (11%). Study samples ranged from 4 to 742 clients. Interventions were most often conducted in residential treatment settings (39%). Only one (6%) intervention focused on opioid use among Indigenous people. Most interventions addressed the use of both drugs and alcohol (72%), with only three (17%) interventions specifically intended to reduce alcohol use.

Originality/value

The results of this research lend insight into the characteristics of culturally integrative treatment options for Indigenous groups and highlight the need for increased investment in research related to culturally tailored treatment across the diverse landscape of Indigenous populations.
Microstructure and properties of ZnO-Bi2O3-based varistor ceramics via flash sintering
Authors: Jiang Ming , Shi Mengyang , Li Jiamao , Liu Juan , Zhang Lei , Qin Jian , Jiu Yongtao , Tang Bin , Xu Dong
Published: August 2022

Purpose

This paper aims to study the effects of MnO2 on the ZnO–Bi2O3-based varistor prepared via flash sintering (FS)

Design/methodology/approach

MnO2-doped ZnO–Bi2O3-based varistors were successfully prepared by the FS with a step-wise increase of the .current in 60 s at the furnace temperature <750°C under the direct current electric field of 300 V cm−1. The FS process, microstructure and the electrical performance of ZnO–Bi2O3-based varistors were systematically investigated.

Findings

The doping of MnO2 significantly decreased the onset temperature of FS and improved the electrical performance of FS ZnO varistor ceramic. The sample with 0.5 mol% MnO2 doping shows the highest improvement, with the nonlinear coefficient of 18, the leakage current of 16.82 µA, the threshold voltage of 459 V/mm and the dielectric constant of 1,221 at 1 kHz.

Originality/value

FS is a wonderful technology to enhance ZnO varistors for its low energy consumption, and a short sintering time can reduce grain growth and inhabit Bi2O3 volatilize, yet few research studies work on that. In this research, the authors analyzed the FS process and improved the electrical characteristics through MnO2 doping.
Agency problems in the private pension system of Turkey: pension sector employee perspectives
Authors: Aslan Remziye Gül
Published: August 2022

Purpose

This study aims to examine how the governance structure of the private pension system of Turkey affects the extent of agency problems through a qualitative exploratory analysis of the pension sector employees’ perspectives.

Design/methodology/approach

This study is based on qualitative exploratory research, which includes semi-structured interviews with 13 pension sector employees to investigate their perspectives on agency problems within Turkey’s private pension system. Data from interviews are analyzed by using the thematic content analysis method.

Findings

This study shows us that agency problems are prevalent in Turkey's private pension system, especially in the relations between pension company employees and participants. This study highlights four vulnerabilities of governance structure: the incapacity of governance structure to prevent pension companies as institutional agents from risky operations and transactions, the ability of local capital groups to use their controlling power for effecting fund management operations, the incapacity of the governance structure to prevent the employment of agents with inadequate qualifications, the lack of proper legal and regulatory framework for ensuring sufficient information disclosure to participants during contract-making and fund selection processes.

Originality/value

Previous research on the agency problems in the private pension schemes mostly investigated the issue from the viewpoint of participants. Thus, exploring agency problems from the agents’ point of view will be a contribution to the literature while illuminating the underlying structural problems within the system.
Effects of 10 add‐on HF‐rTMS treatment sessions on alcohol use and craving among detoxified inpatients with alcohol use disorder: a randomized sham‐controlled clinical trial
Authors: Hoven Monja , Schluter Renée S. , Schellekens Arnt F. , van Holst Ruth J. , Goudriaan Anna E.
Published: August 2022

Background and aims

Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF‐rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add‐on sessions of HF‐rTMS over the right dorsolateral pre‐frontal cortex (DLPFC) on alcohol use and craving.

Design

Single‐center, single blind sham‐controlled parallel‐group RCT (n = 80), with 3 and 6 months follow‐up.

Setting

Clinical treatment center in Amsterdam, the Netherlands.

Participants

Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years).

Intervention

Ten sessions of active or sham HF‐rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work‐days.

Measurements

The primary outcome measure is the number of abstinent days over 6‐month follow‐up (FU). Secondary outcome measures are craving over 6‐month FU (alcohol urge questionnaire and obsessive‐compulsive drinking scale), time to first relapse over 6‐month FU and grams of alcohol consumed over 6‐month FU. Additional outcome measures: full abstinence over 6‐month FU and treatment success over 12‐month FU.

Findings

HF‐rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578–3.547]. Moreover, HF‐rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/−0.53, 95% CI mixed‐effects model = −9.14 to 2.07/−1.44 to 2.40).

Conclusions

There was no clear evidence that high‐frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre‐frontal cortex treatment has a long‐term positive effect on alcohol use or craving as add‐on treatment for alcohol use disorder. High treatment response at 6‐month follow‐up could have limited the possibility to find an effect.
Farm labor supply and fruit and vegetable production
Authors: Rutledge Zachariah , Mérel Pierre
Published: August 2022

This study provides econometric estimates of the effects of reductions in farm labor supply on the production of hand‐harvested fruits and vegetables. Using crop production and employment data from California counties, we estimate panel regressions linking farm employment to crop production outcomes. Because we exploit variation in equilibrium employment, as opposed to exogenous variation in the labor supply curve, we use an equilibrium displacement model to identify the most likely sources of estimation bias and conclude that our regression estimates should be interpreted as upper bounds for the effect of interest. Our results indicate that a 10% decrease in the farm labor supply (in terms of the number of workers) causes at most a 4.2% reduction in production in the top 10 fruit and vegetable producing counties. Production effects are channeled primarily through a reduction in harvested acreage, although we also uncover some effects on yield.
Urine eosinophil‐derived neurotoxin: A potential marker of activity in select eosinophilic disorders
Authors: Makiya Michelle A. , Khoury Paneez , Kuang Fei Li , Mata Alexis Dominique , Mahmood Sana , Bowman Abbie , Espinoza David , Kovacs Nicholas , Brown Thomas , Holland Nicole , Wetzler Lauren , Ware JeanAnne M. , Dyer Anne‐Marie , Akuthota Praveen , Bochner Bruce S. , Chinchilli Vernon M. , Gleich Gerald J. , Langford Carol , Merkel Peter A. , Specks Ulrich , Weller Peter F. , Wechsler Michael E. , Prussin Calman , Fay Michael P. , Klion Amy D.
Published: August 2022

Background

Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil‐derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil‐associated diseases treated with mepolizumab, benralizumab, or dexpramipexole.

Methods

Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay.

Results

Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups.

Conclusions

Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.
Effects of inflammation on voriconazole levels: A systematic review
Authors: Li Xuejuan , Lai Fangyuan , Jiang Zhaohui , Li Meng , Chen Zebin , Cheng Junjie , Cui Hao , Wen Feiqiu
Published: August 2022

Aims

This study aimed to review the studies evaluating the effect of the inflammatory state on voriconazole (VRZ) levels.

Methods

The study included randomized clinical trials, cohort studies, and case–control studies that focused on the influence of the inflammatory state on VRZ levels. Following the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines, relevant articles published until 2021 were searched in several databases, including PubMed, Embase, Web of Science and the Cochrane Library.

Results

Twenty studies were included in this review, of which 15 described adult populations, three described paediatric populations, and two included both adult and paediatric populations. Seventeen studies used C‐reactive protein (CRP) as an indicator of inflammation, six described a dose–response relationship for the effect of inflammation represented by CRP on VRZ concentrations, and four examined the effect of CRP on the metabolic rate of VRZ.

Conclusions

Our findings showed that the level of inflammation can significantly affect VRZ levels. However, the effect of inflammation on VRZ concentrations in children is controversial and must be analysed along with age. Clinicians dosing VRZ should take into account the patient's inflammatory state. The impact of inflammation on genotype‐based dosing decisions requires further study to explain the high pharmacokinetic variability of VRZ.
Lichen planus in Deutschland – Epidemiologie, Behandlung und Komorbidität. Eine retrospektive Krankenkassendatenanalyse
Authors: Schruf Eva , Biermann Mona HC , Jacob Josephine , Häckl Dennis , Reinhardt Maximilian , Hertl Michael , Wohlrab Johannes
Published: August 2022

Hintergrund und Ziele

Lichen planus (LP) ist eine chronisch entzündliche Hauterkrankung, die eine große Belastung für die betroffenen Patienten darstellt. Es liegen jedoch nur wenige Daten zu dieser Erkrankung vor. Ziel dieser Studie ist es, das Wissen über die Epidemiologie und die Behandlungsmuster des LP anhand von Abrechnungsdaten deutscher Krankenkassen zu erweitern.

Patienten und Methoden

Diese retrospektive Beobachtungsstudie nutzte die InGef‐Forschungsdatenbank. Es wurden prävalente und inzidente LP‐Patienten aus den Jahren 2015 und 2018 identifiziert. Für demografische Charakteristika, Behandlungsmuster und Komorbidität wurden deskriptive Statistiken berechnet.

Ergebnisse

Die Prävalenz des LP lag bei 95,9 und die Inzidenz bei 20,1 pro 100 000 Personen im Jahr 2018, was 79 605 prävalenten LP‐Fällen in Deutschland entspricht. Die erste LP‐Diagnose wurde in der Regel von einem Dermatologen oder Hausarzt gestellt. Drei Viertel der inzidenten und die Hälfte der prävalenten Patienten erhielten eine topische Therapie, meist ohne zusätzliche systemische Therapie. Die Komorbidität des LP stand im Einklang mit bereits bekannten Assoziationen.

Schlussfolgerungen

Die verfügbaren Therapieoptionen sind nach wie vor begrenzt, was den ungedeckten Bedarf an sicheren und wirksamen systemischen Behandlungsmodalitäten unterstreicht. Der LP ist häufig mit klinisch relevanter systemischer Komorbidität verbunden. Zusammengenommen könnten diese Beobachtungen zu einem verbesserten Verständnis der Krankheitslast führen und das diagnostische Bewusstsein für diese Erkrankung unter Klinikern schärfen.
S2k‐Leitlinie: Rosazea
Authors: Clanner‐Engelshofen Benjamin M. , Bernhard Dominik , Dargatz Sonja , Flaig Michael J. , Gieler Uwe , Kinberger Maria , Klövekorn Winfried , Kuna Anne‐Charlotte , Läuchli Severin , Lehmann Percy , Nast Alexander , Pleyer Uwe , Schaller Martin , Schöfer Helmut , Steinhoff Martin , Schwennesen Thomas , Werner Ricardo Niklas , Zierhut Manfred , Reinholz Markus
Published: August 2022

Die vorliegende aktualisierte und auf S2k‐Niveau angehobene Leitlinie befasst sich mit der Diagnostik und der Therapie der Rosazea, bei welcher es sich um eine häufige, chronisch‐entzündliche Hauterkrankung handelt, die meist das Gesicht betrifft. Der Verlauf der Rosazea ist initial durch rezidivierende Erytheme, Teleangiektasien sowie Flushing gekennzeichnet. Später überwiegt die entzündliche Komponente, wobei es zu persistierenden Erythemen mit follikulären Papeln, Papulopusteln und Pusteln kommt. Die Bildung von Phymen, die meist an den Akren auftreten, stellt dabei die schwerste Ausprägung der Erkrankung dar. Zur Behandlung empfiehlt die interdisziplinäre Leitlinienkommission, die aus Vertretern der Deutschen Dermatologischen Gesellschaft (DDG), des Berufsverbandes der Deutschen Dermatologen (BVDD), der Deutschen Ophthalmologischen Gesellschaft (DOG), der Gesellschaft für Dermopharmazie (GD), der Schweizerischen Gesellschaft für Dermatologie und Venerologie (SGDV) und der Deutschen Rosazea Hilfe e. V. besteht, neben der Meidung von Triggerfaktoren, die topische Anwendung der Wirkstoffe Metronidazol, Azelainsäure oder Ivermectin. Zur symptomatischen Behandlung persistierender zentrofazialer Erytheme können zudem die Vasokonstriktoren Brimonidin oder Oxymetazolin topisch angewandt werden. Bei therapieresistenten sowie bei schweren Formen der Rosacea papulopustulosa wird eine systemische Therapie empfohlen. Hierfür ist niedrigdosiertes Doxycyclin das Präparat der 1. Wahl. Alternativ kann niedrigdosiertes Isotretinoin empfohlen werden. Für die okulären Rosazea kann neben einer Lidrandhygiene die topische Behandlung mit Ciclosporin‐haltigen Augentropfen, Azithromycin, Ivermectin oder Metronidazol empfohlen werden.
Dissecting the brain's fear systems responding to snake threats
Authors: Melleu Fernando F. , de Oliveira Amanda R. , Grego Kathleen F. , Blanchard D. Caroline , Canteras Newton S.
Published: August 2022

We examined the behavioural responses and Fos expression pattern of rats that were exposed to snake threats from shed snakeskin and a live snake. We differentiated the behavioural responses and the pattern of Fos expression in response to the odour cues and mild threat from a live snake. Animals exposed to the snake odour alone or to the confined snake showed a great deal of risk assessment. Conversely, the intensification of odour during exposure to the live snake decreased the threat ambiguity, and the animals froze for a significantly longer period. Our Fos analysis showed that a pathway formed by the posteroventral part of the medial amygdalar nucleus to the central part of the ventromedial hypothalamic nucleus appeared to be solely responsive to odour cues. In addition, we showed increased Fos expression in a parallel circuit comprising the lateral amygdalar nucleus, ventral subiculum, lateral septum, and juxtadorsomedial region of the lateral hypothalamic area that is responsive to both the odour and mild threat from a live snake. This path is likely to process the environmental boundaries of the threat to be avoided. Both paths merge into the dorsal premammillary nucleus and periaqueductal grey sites, which all increase Fos expression in response to the snake threats and are likely to organize the defensive responses. Moreover, we found that the snake threat mobilized the Edinger–Westphal and supraoculomotor nuclei, which are involved in stress adaptation and attentional mechanisms.
Helicobacter pylori infection prevalence in ambulatory settings in 2017–2019 in RUSSIA: The data of real‐world national multicenter trial
Authors: Bordin Dmitry , Morozov Sergey , Plavnik Roman , Bakulina Natalia , Voynovan Irina , Skibo Irina , Isakov Vasily , Bakulin Igor , Andreev Dmitrii , Maev Igor
Published: August 2022

Background

The recent data on the prevalence of Helicobacter pylori (H. pylori) infection in Russia are limited. The aim of the study was to compare Helicobacter pylori infection prevalence in ambulatory settings in Russia in 2017 and 2019 years.

Materials and Methods

Subjects visiting primary care centers were invited to take part in the study. H. pylori status was assessed by 13C‐urea breath test (UBT). Data on subjects' demography, previous treatment exposure, and place of residence were collected in all federal districts of Russia in 2017 and in 2019 calendar years and processed centrally.

Results

The data of 19,875 subjects were available for analysis. The prevalence of H. pylori infection assessed by positive UBT in treatment‐naive subjects was highest in the Southern (54.9%) and the North Caucasian (45.1%) federal districts. A significant difference (p < 0.05) in H. pylori prevalence between two testing periods was found only in a half of federal districts: the Central (46.2% in 2017 vs. 36.2% in 2019), the Northwestern (38.6% vs. 35.5% accordingly), the Volga (40.6% vs. 33.0%, accordingly), and the Ural (40.4% vs. 32.7%, accordingly). The lowest prevalence of H. pylori infection was revealed in the age group <18 years old (20.2%), while the highest in the age group of 41–50 years old (43.9%). In 2017, the prevalence of H. pylori was significantly (p < 0.05) higher than in 2019 in all age groups but younger than 18 and older than 70 y.o., where similar rates were found during both study periods.

Conclusions

The prevalence of H. pylori according to 13C‐UBT testing of primary care visitors in Russia is lower than expected (38.8%). The highest prevalence of H. pylori infection found in the Southern and the North Caucasian federal districts of Russia and in the age group of 41–50 years old.

This study was registered at clinicaltrials.gov (NCT04892238).
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment‐naïve (AMBER) and virologically suppressed (EMERALD) participants with neurological and/or psychiatric comorbidities: Week 96 subgroup analysis
Authors: Dunn Keith , Bushen Jennifer , Luo Donghan , Cai Jiyun , Simonson Richard Bruce , Anderson David
Published: August 2022

Objective

Our objective was to evaluate the prevalence of pre‐existing neurological and/or psychiatric comorbidities (NPCs) and efficacy/safety outcomes for participants with versus without baseline NPCs in AMBER and EMERALD.

Methods

AMBER (treatment‐naïve population) and EMERALD (virologically suppressed population) were phase III randomized studies of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg. The primary objective of this post hoc analysis was to assess virological response (HIV‐1 RNA <50 copies/mL) at week 48 by intent‐to‐treat US Food and Drug Administration snapshot analysis comparing participants with and without baseline NPCs.

Results

Among participants in AMBER, 88/362 (24%) in the D/C/F/TAF arm and 99/363 (27%) in the control arm had baseline NPCs; in EMERALD, 294/763 (39%; D/C/F/TAF) and 166/378 (44%; control) participants had baseline NPCs. At baseline, psychiatric NPCs were more common than neurological NPCs in both studies; the most common of each type were depression and headache, respectively. High virological response rates were achieved with D/C/F/TAF across studies regardless of baseline NPCs at weeks 48 (range 86%–95%) and 96 (range 80%–91%). No participants in either study with a baseline NPC prematurely discontinued because of a study drug–related neurological or psychiatric adverse event.

Conclusion

D/C/F/TAF may be a suitable treatment option for individuals with HIV‐1 and NPCs.