bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetrabenazine, a vesicular monoamine transporter 2 inhibitor, inhibits vesicular storage capacity and release of monoamine transmitters in mouse brain tissue
Authors: Tod Pál , Varga Anita , Román Viktor , Lendvai Balázs , Pálkovács Roland , Sperlágh Beáta , Vizi E. Sylvester
Published: September 2024

Background and Purpose

Tetrabenazine (TBZ), used for treating hyperkinetic disorders, inhibits vesicular monoamine transporter‐2 (VMAT‐2), which sequesters monoamines into vesicles for exocytosis. However, our knowledge of the effect of TBZ on monoaminergic transmission is limited. Herein, we provide neurochemical evidence regarding the effect of VMAT‐2 inhibition on vesicular neurotransmitter release from the prefrontal cortex (PFC) and striatum (STR) (brain regions involved in characteristic TBZ treatment side effects). The interaction between TBZ and MDMA was also assessed regarding motor behaviour in mice.

Experimental Approach

Vesicular storage capacity and release of [3H]‐noradrenaline ([3H]‐NA), [3H]‐dopamine ([3H]‐DA), [3H]‐serotonin ([3H]‐5‐HT), and [3H]‐acetylcholine ([3H]‐ACh) was studied in mouse PFC and STR ex vivo slice preparations using electrical field stimulation. Additionally, locomotor activity was assessed in vehicle‐treated mice and compared with that of MDMA, TBZ, and co‐administered animals (n = 6) using the LABORAS system.

Key Results

TBZ lowered the storage capacity and inhibited the vesicular release of [3H]‐NA and [3H]‐DA from the PFC, and [3H]‐DA and [3H]‐5‐HT from the STR in a concentration‐dependent manner. Unlike vesamicol (vesicular ACh uptake inhibitor), TBZ failed to inhibit the vesicular release of [3H]‐ACh from the PFC. When the vesicular storage of the investigated monoamines was inhibited by TBZ in the PFC and STR, MDMA induced the release of transmitters through transporter reversal; MDMA dose dependently increased locomotor activity in vivo.

Conclusion and Implications

Our observations provide neurochemical evidence explaining the mechanism of VMAT‐2 inhibitors in the brain and support the involvement of dopaminergic and noradrenergic transmission in hyperkinetic movement disorders.
Examining the relationship between channel disintermediation and chemical fertilizer application: Empirical evidence from smallholder farmers in central China
Authors: Zhou Chunchi , Ruiz‐Menjivar Jorge , Zhang Lu
Published: September 2024

Digital advancements have reshaped the sales channels for industrial products like chemical fertilizers, allowing for the elimination of certain intermediaries. Utilizing survey data from 1374 rice‐growing smallholder farmers across counties in central China, this study explored the impact of disintermediation in chemical fertilizer sales channels on application rates among smallholder farmers. Benchmark regression analyses indicated that channel disintermediation significantly decreased chemical fertilizer application across various scenarios. Additionally, the alignment of contractual factors and technical services between chemical suppliers and farmers, facilitated by disintermediation, reduced chemical fertilizer application. Heterogeneity analysis revealed that the reduction in chemical fertilizer application due to channel disintermediation was more pronounced among farmers with higher digital literacy or lower production capacity. These findings highlighted the importance of encouraging chemical suppliers with direct‐to‐consumer channels to enhance their technical services and increase supervision over the quality of their products and services, thereby building trust among farmers and facilitating their adaptation to changes in the sales channel structure.
How Do Chinese Exporting Firms Respond to Environment‐related Notifications? A Green Innovation Perspective
Authors: Chen Wen , Fan Yinzi
Published: September 2024

Environment‐related notifications play an important role in the coordinated development of trade and environment protection. In this paper, we examine how Chinese exporting enterprises responded to environment‐related notifications implemented by the US through green innovation practices. These notifications significantly encouraged exporting firms to increase green innovation, as evidenced particularly by the number of green utility model patents granted. This effect was most pronounced in non‐foreign‐invested enterprises, high‐total‐factor‐productivity firms, technology‐intensive industries, and nongreen industries. These notifications also increased the probability of enterprises exiting the market while reducing the probability of new enterprises entering it. The innovation motivation of surviving firms was higher than that of the new entrants. Our analysis also suggests that environment‐related notifications had a crowding‐out effect on other innovation rather than a leverage effect. This study offers important empirical evidence that helps enterprises to respond to green non‐tariff measures effectively, enrich the existing literature, and provide practical guidance for both policymaking and corporate development.
Does Structural Matching between Finance and Law Promote Economic Development?
Authors: Wang Baifang
Published: September 2024

Financial systems generally operate under two different models: one where capital markets play a primary role in financial transactions and resource allocation (market‐oriented model), and another where banks are the central institutions for these activities (bank‐oriented model). The degree of investor protection afforded by the legal system varies across these systems. What is the most efficient alignment between financial structure and investor protection? This paper attempts to quantify the structural matching relationship between the financial structure and investor protection in various countries, and examines empirically the impact of this relationship on economic development. Using a sample of cross‐country panel data, it finds that the degree of structural matching was positively related to economic development. Both the combination of a securities market and strong investor protection and the combination of a banking system and weak investor protection can contribute to promoting economic development. It extends the law and finance theory framework, enhances the analysis of scenarios with weak alignment between financial structure and investor protection, explains the growth path of developing countries, and highlights the diversity and the dynamic nature of the optimal financial structure.
The Frontiers in Manufacturing Technologies Initiative and University Innovation
Authors: Leng Xuan , Zhang Yichuan
Published: September 2024

Basic innovation, with universities as a key driver, is essential for advancing core technologies in the manufacturing industry. This study used a manufacturing technologies initiative as a natural experiment, combining funding and its outcomes data from the National Natural Science Foundation of China to construct a difference‐in‐differences model. It found that the Frontiers in Manufacturing Technologies Initiative had a positive effect on university innovation, particularly by increasing the number of university patents. Mechanism analysis showed that the policy mainly encouraged university innovation through university‐industry collaboration. The effect was more salient in universities with stronger basic research capabilities and those whose research fields matched strategic emerging industries covered by the initiative. This study underscores the crucial role of the Frontiers in Manufacturing Technologies Initiative in enhancing university‐led innovation. It highlights the effectiveness of industry‐academia partnerships in advancing technology, particularly in emerging strategic industries.
Establishment and characterization of mouse lines useful for endogenous protein degradation via an improved auxin‐inducible degron system (AID2)
Authors: Makino‐Itou Hatsune , Yamatani Noriko , Okubo Akemi , Kiso Makoto , Ajima Rieko , Kanemaki Masato T. , Saga Yumiko
Published: September 2024

The development of new technologies opens new avenues in the research field. Gene knockout is a key method for analyzing gene function in mice. Currently, conditional gene knockout strategies are employed to examine temporal and spatial gene function. However, phenotypes are sometimes not observed because of the time required for depletion due to the long half‐life of the target proteins. Protein knockdown using an improved auxin‐inducible degron system, AID2, overcomes such difficulties owing to rapid and efficient target depletion. We observed depletion of AID‐tagged proteins within a few to several hours by a simple intraperitoneal injection of the auxin analog, 5‐Ph‐IAA, which is much shorter than the time required for target depletion using conditional gene knockout. Importantly, the loss of protein is reversible, making protein knockdown useful to measure the effects of transient loss of protein function. Here, we also established several mouse lines useful for AID2‐medicated protein knockdown, which include knock‐in mouse lines in the ROSA26 locus; one expresses TIR1(F74G), and the other is the reporter expressing AID‐mCherry. We also established a germ‐cell‐specific TIR1 line and confirmed the protein knockdown specificity. In addition, we introduced an AID tag to an endogenous protein, DCP2 via the CAS9‐mediated gene editing method. We confirmed that the protein was effectively eliminated by TIR1(F74G), which resulted in the similar phenotype observed in knockout mouse within 20 h.
Relevance, Risks, and Benefits of Early‐Phases Clinical Trials Participations for Patients With Hematological Malignancies From 2008 to 2023
Authors: Guerra Matteo , Alouani Emily , Hueso Thomas , Ouali Kaissa , Danu Alina , Hollebecque Antoine , Bahleda Rastislav , Willekens Christophe , Gazzah Anas , Baldini Capucine , Postel‐Vinay Sophie , Micol Jean‐Baptiste , Massard Christophe , De Botton Stéphane , Ribrag Vincent , Michot Jean‐Marie
Published: September 2024

Background

Early‐phases clinical trials (Phases 1 and 2) have evolved from a traditional assessment of toxicity to an adaptive approach based on patients' medical needs and access to effective new therapies. The global risks, benefits, and relevance of early‐phases clinical trials participation for patients with hematological malignancies remain poorly evaluated.

Patients and Methods

All early‐phases clinical trials participations for patients with hematological malignancies, from 2008 to 2023, in a tertiary academic center in Europe, were reviewed. Patient's demographics, tumor type categories, therapeutic responses, mortality, overall survival (OS), and investigational product (IP) were assessed.

Results

Over the period 2008–2023, 736 patients participating in 92 different early‐phases clinical trials, were analyzed. The most common tumor categories were diffuse large B‐cell lymphoma (n = 253; 34.4%), acute myeloid leukemia/myelodysplastic syndrome (n = 164; 22.3%) and multiple myeloma (n = 100; 13.6%). The median OS was 14.8 (95% CI: 12.4–17.9) months and response rate 31.9%, including complete responses in 13.5% of patients. By tumor categories, the highest and lowest median duration of OS were observed for patients with Hodgkin lymphoma (99.8; [95% CI: 47.0‐not reached] months) and peripheral T‐cell lymphoma (8.9 [95% CI: 5.3–12.0] months), respectively. The on‐protocol and treatment‐related mortality rates were 5.43% and 0.54%, respectively. Overall response rate was 29.1% including 13.5% of complete response. Overall, 202 (27.5%) patients received an IP later approved by the health authorities, and those patients had better OS (18.2 months vs. 12.1 months HR: 1.160 [95% CI; 0.6977–1.391], p = 0.0283).

Conclusion

In conclusion, patients with hematologic malignancies who have participated in early‐phases clinical trials over the past 15 years have achieved variable therapeutic response rates, acceptable risk/benefit ratio and potentially significant therapeutic advantages. This study provides framework material for hematologists to further discuss clinical trial participation with their patients.
Exploring the role of help‐seeking behavior, family financial socialization, and capability on financial well‐being
Authors: Zhang Yu , Qi Jia , Chatterjee Swarn
Published: September 2024

Objective

This study develops a conceptual framework for examining the associations between family financial socialization and financial capability on individuals' financial well‐being and explores the mediating role of financial help‐seeking when determining financial well‐being.

Background

Individuals' family financial socialization and financial capability are associated with their financial well‐being. This study extends the literature by examining whether seeking financial help can indirectly mediate the association between these factors and individuals' financial well‐being.

Method

This study used the 2016 National Financial Well‐Being Survey data set, consisting of 6,394 adults, and employed structural equation modeling with full information maximum likelihood and bootstrap estimation for empirical analyses.

Results

Financial knowledge and perceived financial capability were positive contributors to financial well‐being. Family financial socialization showed positive direct and mixed indirect effects on help‐seeking behaviors. When mediated by help‐seeking behaviors, family financial socialization had significantly positive total and indirect associations and a negative direct association with financial well‐being.

Conclusion

This study found that financial help‐seeking behavior was a significant factor in the indirect association between family financial socialization, financial knowledge, and well‐being.

Implications

Providing access to professional advice and encouraging family finance discussions can enhance people's financial well‐being.
Mainstreaming sustainability through sustainability offices: Modes and mechanisms in Swiss cantonal administrations
Authors: Bornemann Basil , Christen Marius
Published: September 2024

Public administrations must change toward sustainability to play a meaningful role in sustainable policy‐making. However, little is known about how and why sustainability‐oriented change unfolds in public administrations. This article aims to advance conceptual and empirical knowledge by examining sustainability mainstreaming through sustainability offices (SO) as a specific type of sustainability‐oriented administrative change. Based on a framework that distinguishes modes and mechanisms of mainstreaming, the article provides qualitative insights into how SO in five Swiss cantons shape the work of their respective administrations toward sustainability. The case comparison suggests that sustainability mainstreaming is most transformative when committed SO address a combination of institutional, ideational, and agency‐related factors through their activities. These findings highlight the critical role of SO in sustainability‐oriented administrative change and lay the groundwork for developing targeted strategies to enhance their effectiveness in mainstreaming sustainability.
What Australia must do to create a climate‐responsive health system
Authors: Smith Carolynn L. , Rojas Christina , Zurynski Yvonne , Partington Andrew , Braithwaite Jeffrey
Published: September 2024

COP‐28, the United Nations' Climate Change Conference, hosted by the United Arab Emirates, ended on 12 December 2023. At the convention, Australia released its National Health and Climate Strategy, committing to low‐carbon, climate‐responsive care. The Strategy will need new policies, projects and investments and a fit‐for‐purpose health workforce. This is a tall order considering healthcare's challenges. Everyone has a role, including clinicians, healthcare agencies, policymakers, politicians, patients and the providers and manufacturers in the supply chain. Clinicians' groups, policymakers and federal and state departments of health have an opportunity to lead climate change reform by considering climate change impacts across clinical practice and health policy.
Selection of Wheat (Triticum aestivum L.) Genotypes Using Yield Components, Water Use Efficiency and Major Metabolites Under Drought Stress
Authors: Mutanda Maltase , Figlan Sandiswa , Chaplot Vincent , Madala Ntakadzeni Edwin , Shimelis Hussein
Published: September 2024

Integrating grain yield, component traits and metabolite profiles aids in selecting drought‐adapted and climate‐smart crop varieties preferred by end users. Understanding the trends and magnitude of grain‐based metabolites is vital for selecting wheat genotypes with higher grain yield, drought tolerance, water use efficiency and product profiles. The aim of this study was to determine the response of newly developed wheat genotypes for grain yield and component traits and metabolites under drought stress to guide selection. One hundred wheat genotypes were preliminarily evaluated for agro‐morphological traits and water use efficiency under drought‐stressed and non‐stressed conditions during the 2022 and 2023 growing seasons using a 5 × 20 alpha lattice design with two replications. Ten high‐yielding genotypes were selected based on grain yield and were validated for agronomic traits and water use efficiency (WUE), and grain samples were assayed to profile their key metabolites under drought‐stressed conditions. Significant differences existed (p < 0.05) among the tested wheat genotypes for yield and yield components, WUE, drought tolerance and major metabolites to discern trait associations. The grain yield of the 10 genotypes ranged from 590.00 g m−2 (genotype LM70 × BW140) to 800.00 g m−2 (BW141 × LM71) under drought‐stressed treatment, whilst under non‐stressed it ranged from 760.06 g m −2 (LM70 × BW140) to 908.33 g m−2 (LM71 × BW162). Grain yield‐based water use efficiency of the assessed genotypes was higher under non‐stressed (0.18 g mm−1) than drought‐stressed (0.17 g mm−1) conditions. The highest drought tolerance index (211.67) and stress susceptibility index (0.77) were recorded for BW162 × LM71, whilst the lowest tolerance index (23.33) and stress susceptibility index (0.09) were recorded in BW141 × LM71. Grain metabolites, including the apigenin‐8‐C‐glucoside (log2Fold = 3.00) and malate (log2Fold = 3.60) were present in higher proportions in the high‐yielding genotypes (BW141 × LM71 and LM71 × BW162) under drought‐stressed conditions, whilst fructose (log2Fold = −0.50) and cellulose (log2Fold = −3.90) showed marked decline in the two genotypes. Based on phenotypic and metabolite profile analyses, genotypes BW141 × LM71 and LM71 × BW162 were selected for being drought‐tolerant, water‐use efficient and recommended for production or breeding. The findings revealed associations between yield components, water use efficiency and grain metabolites to guide the selection of best‐performing and drought‐tolerant wheat varieties.
Multikernel similarity‐based clustering of amorphous systems and machine‐learned interatomic potentials by active learning
Authors: Shuaib Firas , Ori Guido , Thomas Philippe , Masson Olivier , Bouzid Assil
Published: September 2024

We present a hybrid similarity kernel that exemplifies the integration of short‐ and long‐range descriptors via the use of an average kernel approach. This technique allows for a direct measure of the similarity between amorphous configurations, and when combined with an active learning (AL) spectral clustering approach, it leads to a classification of the amorphous configurations into uncorrelated clusters. Subsequently, a minimum size database is built by considering a small fraction of configurations belonging to each cluster and a machine learning interatomic potential (MLIP), within the Gaussian approximation scheme, is fitted by relying on a Bayesian optimization of the potential hyperparameters. This step is embedded within an AL loop that allows to sequentially increase the size of the learning database whenever the MLIP fails to meet a predefined energy convergence threshold. As such, MLIP are fitted in an almost fully automatized fashion. This approach is tested on two diverse amorphous systems that were previously generated using first‐principles molecular dynamics. Accurate potentials with less than 2 meV/atom root mean square energy error compared to the reference data are obtained. This accuracy is achieved with only 175 configurations sampling the studied systems at various temperatures. The robustness of these potentials is then confirmed by producing models with several thousands of atoms featuring a good agreement with reference ab initio and experimental data.
Emergency clinicians' use of adult and paediatric sepsis pathways: An implementation redesign using the behaviour change wheel
Authors: Munroe Belinda , Hudoba Michelle , Fullick Mary , Couttie Tracey , Makoni Hughes , Butina Ellie , Ghosh Niladri , Kloger Ryan , Balzer Sharyn , Middleton Rebekkah
Published: September 2024

Aims

To identify facilitators and barriers and tailor implementation strategies to optimize emergency clinician's use of adult and paediatric sepsis pathways.

Design

A qualitative descriptive study using focus group methodology.

Methods

Twenty‐two emergency nurses and ten emergency medical officers from four Australian EDs participated in eight virtual focus groups. Participants were asked about their experiences using the New South Wales Clinical Excellence Commission adult and paediatric sepsis pathways using a semi‐structured interview template. Facilitators and barriers to use of the sepsis pathways were categorized using the Theoretical Domains Framework. Tailored interventions were selected to address facilitators and barriers, and a re‐implementation plan was devised guided by the Behaviour Change Wheel.

Results

Thirty‐two facilitators and 58 barriers were identified corresponding to 11 Theoretical Domains Framework domains. Tailored strategies were selected to optimize emergency clinicians' use of the sepsis pathways including refinement of existing education and training programmes, modifications to the electronic medical record system, introduction of an audit and feedback system, staffing strategies and additional resources.

Conclusion

The implementation of sepsis pathways in the Emergency Department setting is complex, impacted by a multitude of factors requiring tailored strategies to address facilitators and barriers and optimize uptake.

Implications for Patient Care

This study presents a theory‐informed systematic approach to successfully implement and embed adult and paediatric sepsis pathways into clinical practice in the Emergency Department.

Impact

Optimizing uptake of sepsis pathways has the potential to improve sepsis recognition and management, subsequently improving the outcome of patients with sepsis.

Reporting Method

The Consolidated Criteria for REporting Qualitative research guided the preparation of this report.

Patient or Public Contribution

Nil.
How the Approaches of Managing Conflict With Patients Affect Nurse Emotional Exhaustion and Life Satisfaction: A Time‐Lagged Three‐Wave Survey
Authors: Luo Weijia , Wang Jessie Lin , Chen Tingting , Zhu Yue , Wang Jie , Zhou Liping , Zhuang Yiyu
Published: September 2024

Aim(s)

To explore whether nurses' use of different approaches to manage patient mistreatment can exert distinctive effects on their emotional exhaustion and life satisfaction, and to examine whether supervisor support can mitigate the negative effects of emotional exhaustion on nurses' life satisfaction.

Design

A time‐lagged three‐wave survey study with a 2‐week time interval was conducted in 2022.

Methods

A total of 257 nurses from a Joint Commission International (JCI) accredited general hospital located in eastern China in 2022 completed three‐wave surveys. Descriptive analyses, confirmatory factor analyses and mediation and moderated mediation analyses were performed.

Data Sources

Data were collected by using three‐wave self‐reported questionnaires from 257 nurses from a Joint Commission International (JCI) accredited general hospital located in eastern China in 2022.

Results

Nurses who managed patient mistreatment more cooperatively experienced lower levels of emotional exhaustion, whereas those who managed patient mistreatment more competitively experienced higher levels of emotional exhaustion. Emotional exhaustion was negatively related to life satisfaction. Moreover, emotional exhaustion mediated the positive and negative relationships between cooperative and competitive conflict management approaches and overall life satisfaction. Additionally, supervisor support mitigated the negative impact of emotional exhaustion on life satisfaction and the indirect effects of conflict management approaches on life satisfaction.

Conclusion

To effectively manage the negative impact of patient mistreatment on nurses, both nurses themselves and their supervisors play an important role. Nurses who adopt a cooperative conflict management approach experience lower levels of emotional exhaustion and higher levels of life satisfaction. Supervisor support can alleviate the negative effect of emotional exhaustion on life satisfaction.

Implications for the Profession and/or Patient Care

The findings provide a better understanding for nurses on how to mitigate the detrimental effects of patient mistreatment on nurses and highlight the role of both nurses themselves and their supervisors in protecting nurses' well‐being.

Patient or Public Contribution

No patient or public contributed to the design or conduct of the study, analysis or interpretation of the data, or in the preparation of the manuscript.
Effects of Dignity Therapy on Dignity, Anxiety, Depression and Quality of Life for People With Burns: A Randomised Controlled Trial
Authors: Deng YunYun , Yao YiMing , Wang Chang , Li Ting , Wang Yuan , Kang ChanJuan , Tan HuiYi
Published: September 2024

Aims

To evaluate the effect of dignity therapy on dignity, anxiety, depression and overall quality of life for people with burns.

Design

A single‐blind, double‐arm, parallel randomised controlled study.

Methods

The Patient Dignity Scale, Hospital Anxiety and Depression Scale, and Burn‐Specific Health Scale‐Short were employed to assess the dignity, anxiety, depression and overall quality of life for people with burns. These outcome indicators were measured and analysed at baseline, 2‐, 4‐ and 8‐week follow‐up. The generalised estimating equations were used to analyse the effect of the intervention during each time point.

Results

A total of 99 participants were recruited (50 in the intervention group and 49 in the control group), with a high retention rate of 97 participants (94.95%) completing the 8‐week follow‐up. All outcome measurement tools met the feasibility criteria related to completeness and responsiveness over time. Dignity was the primary outcome measure, with anxiety, depression and quality of life serving as secondary outcome measures. At the 8‐week post‐intervention, participants in the intervention group demonstrated a statistically significant decrease in dignity and anxiety and depression, and a statistically significant increase in burn‐specific health.

Conclusions

Dignity therapy can effectively reduce the loss of dignity, anxiety and depression, and improve the quality of life for people with burns. This study has a positive impact on burn dignity nursing practice and provides healthcare professionals with a novel approach to help people with burns return to normal social life with dignity.

Implications for the Profession

It is important to develop patient‐centred care for burns with dignity. Focusing on developing a rational understanding of non‐discriminatory dignity care practices among clinical providers and to develop dignity‐oriented clinical care practices on the wards.

Impact

This study validated the feasibility of implementing dignity therapy for people with burns. Dignity therapy is effective in reducing the degree of dignity impairment, reducing anxiety and depressive symptoms, and enhancing the quality of life for people with burns. Our findings can help healthcare professionals to provide personalised dignity care throughout the patient's journey to facilitate a dignified reintegration into society and life for people with burns.

Reporting Method

This randomised controlled trial used the CONSORT guidelines.

Patient or Public Contribution

No patients or members of the public participated in the study design, data analysis or interpretation.

Clinical Trials

This study has been registered in the Chinese Clinical Trial Registry registration number: ChiCTR2200065145, 29 October 2022.
Role of the mechanotransductor PIEZO1 in megakaryocyte differentiation
Authors: Demagny Julien , Poirault‐Chassac Sonia , Ilsaint Damtz Nehemie , Marchelli Aurore , Gomila Cathy , Ouled‐Haddou Hakim , Collet Louison , Le Guyader Maïlys , Gaussem Pascale , Garçon Loïc , Bachelot‐Loza Christilla
Published: September 2024

From haematopoietic stem cells to megakaryocytes (Mks), cells undergo various mechanical forces that affect Mk differentiation, maturation and proplatelet formation. The mechanotransductor PIEZO1 appears to be a natural candidate for sensing these mechanical forces and regulating megakaryopoiesis and thrombopoiesis. Gain‐of‐function mutations of PIEZO1 cause hereditary xerocytosis, a haemolytic anaemia associated with thrombotic events. If some functions of PIEZO1 have been reported in platelets, few data exist on PIEZO1 role in megakaryopoiesis. To address this subject, we used an in vitro model of Mk differentiation from CD34+ cells and studied step‐by‐step the effects of PIEZO1 activation by the chemical activator YODA1 during Mk differentiation and maturation. We report that PIEZO1 activation by 4 μM YODA1 at early stages of culture induced cytosolic calcium ion influx and reduced cell maturation. Indeed, CD41+CD42+ numbers were reduced by around 1.5‐fold, with no effects on proliferation. At later stages of Mk differentiation, PIEZO1 activation promoted endomitosis and proplatelet formation that was reversed by PIEZO1 gene invalidation with a shRNA‐PIEZO1. Same observations on endomitosis were reproduced in HEL cells induced into Mks by PMA and treated with YODA1. We provide for the first time results suggesting a dual role of PIEZO1 mechanotransductor during megakaryopoiesis.
Beyond biomarkers: Exploring the diverse potential of a novel phosphoprotein in lung cancer management
Authors: Rostami Amirabbas , Ranjbar Ehsan , Amiri Somayeh , Ezzatifar Fatemeh
Published: September 2024

In addressing the challenges of lung cancer, attention has increasingly turned to molecular diagnostics and targeted therapies, with nucleolin (NCL) assuming a pivotal role, especially in non‐small cell lung cancer. The aberrant activity and cellular distribution of NCL act as crucial biomarkers for early detection and treatment monitoring, showing a strong correlation with disease progression and patient prognosis. Elevated NCL levels signal advanced disease and poorer outcomes, underscoring its significance in evaluating disease severity and therapeutic response. Strategies targeting the molecular interactions of NCL have spurred innovative approaches to inhibit tumour growth, overcome drug resistance and improve treatment efficacy. These advancements are paving the way for personalized therapies tailored to the unique molecular profiles of patients' tumours. Consequently, NCL stands at the forefront of lung cancer management, symbolizing the move towards more precise and individualized oncology care, and marking substantial progress in therapeutic development.
Temperature‐dependent alterations in the proteome of the emergent fish pathogen Edwardsiella piscicida
Authors: Jacobsen Kim L. , Griffin Matt , Phinney Brett S. , Salemi Michelle , Yazdi Zeinab , Balami Sujita , Older Caitlin E. , Soto Esteban
Published: September 2024

Edwardsiella piscicida is an emerging bacterial pathogen and the aetiological agent of edwardsiellosis among cultured and wild fish species globally. The increased frequency of outbreaks of this Gram‐negative, facultative intracellular pathogen pose not only a threat to the aquaculture industry but also a possible foodborne/waterborne public health risk due to the ill‐defined zoonotic potential. Thus, understanding the role of temperature on the virulence of this emerging pathogen is essential for comprehending the pathogenesis of piscine edwardsiellosis in the context of current warming trends associated with climate change, as well as providing insight into its zoonotic potential. In this study, significant temperature‐dependent alterations in bacterial growth patterns were observed, with bacterial isolates grown at 17°C displaying higher peak growth sizes, extended lag times, and slower maximal growth rates than isolates grown at 27or 37°C. When E. piscicida isolates were grown at 37°C compared to 27 and 17°C, mass spectrometry analysis of the E. piscicida proteome revealed significant downregulation of crucial virulence proteins, such as Type VI secretion system proteins and flagellar proteins. Although in vivo models of infection are warranted, this in vitro data suggests possible temperature‐associated alterations in the virulence and pathogenic potential of E. piscicida in poikilotherms and homeotherms.
Identifying and quantifying potentially problematic prescribing cascades in clinical practice: A mixed‐methods study
Authors: Mohammad Atiya K. , Hugtenburg Jacqueline G. , Vanhommerig Joost W. , van den Bemt Patricia M. L. A. , Denig Petra , Karapinar‐Carkıt Fatma
Published: September 2024

Background

A prescribing cascade occurs when medication causes an adverse drug reaction (ADR) that leads to the prescription of additional medication. Prescribing cascades can cause excess medication burden, which is of particular concern in older adults. This study aims to identify and quantify potentially problematic prescribing cascades relevant for clinical practice.

Methods

A mixed‐methods study was conducted. First, prescribing cascades were identified through literature search. An expert panel (n = 16) of pharmacists and physicians assessed whether these prescribing cascades were potentially problematic. Next, a cohort study quantified potentially problematic prescribing cascades in adults using Dutch community pharmacy data for the period 2015–2020. Additionally, the influence of multiple medications potentially causing the same ADR was evaluated. Prescription sequence symmetry analysis was used to calculate adjusted sequence ratios (aSRs), adjusting for temporal prescribing trends. An aSR >1.0 indicates the occurrence of a prescribing cascade. In a subgroup analysis, aSRs were calculated for older adults.

Results

Seventy‐six prescribing cascades were identified in literature and three were provided by experts. Of these, 66 (83.5%) were considered potentially problematic. A significant positive aSR for the medication sequence was found for 41 (62.1%) of these prescribing cascades. The highest aSR was found for amiodarone potentially causing hypothyroidism treated with thyroid hormones (4.63 [95% confidence interval 4.40–4.85]), based on 565 incident users. The biggest population (n = 34,645) was found for angiotensin converting enzyme‐inhibitors potentially causing urinary tract infections treated with antibiotics. Regarding four potential ADRs, the aSRs were higher for people using multiple medications that cause the same ADR as compared to people using only one of those medications. Among older adults the aSRs remained significant for 37 prescribing cascades.

Conclusion

An overview was generated of potentially problematic prescribing cascades relevant for clinical practice. These results can support healthcare providers to intervene and reduce medication burden for older adults.
Memory problems in elderly people with traumatic brain injury
Authors: Monov Dimitar , Lilyanov Nikolay
Published: September 2024

The aim of this study is to assess the effectiveness of various therapy methods in elderly individuals with traumatic brain injury (TBI), taking into account the degree of memory loss and the severity of the injury. The study was conducted in 2022 in Moscow, Russia, and Sofia, Bulgaria, involving six clinics. A total of 200 elderly patients with TBI participated in the study, with a mean age of 72 years. Patients were categorized into groups based on the degree of memory loss and severity of the injury. Standardized tests, including the Mini‐Mental State Examination (MMSE), Clock Drawing Test, Digit Symbol Substitution Test, and Free, and Cued Selective Reminding Test, were used to assess cognitive functions. The Progressive Learning Test evaluated patients' ability to memorize and reproduce information over time. Groups receiving physical therapy and cognitive rehabilitation showed statistically significant improvement in cognitive functions compared to other therapy methods. Specifically, the mean score of the MMSE in these groups increased by 7 points (p < .001). Patients with more severe memory loss demonstrated more pronounced improvement in cognitive functions following the integrated therapy approach. The mean MMSE score increased by 10 points (p < .001), whereas in patients with milder memory loss, the growth was less significant (mean increase of 5 points, p < .05). Groups receiving physical therapy and cognitive rehabilitation consistently demonstrated significantly better results compared to speech therapy and psychological support throughout the study period.
Combination Therapy With CGF and Microneedling‐Assisted Compound Betamethasone for Resistant Alopecia Areata: A Pilot Study
Authors: Jia Lingling , Zhao Changjiang , Zhang Hongyi , Jiang Hua , Xiong Jiachao , Li Yufei
Published: September 2024

Background

Alopecia areata (AA), an autoimmune disorder characterized by hair loss, can be particularly difficult to manage when patients do not respond to standard therapeutic approaches such as topical or injectable corticosteroids, contact immunotherapy, and systemic treatments. In instances where these conventional therapies prove ineffective, alternative or adjunctive treatments are sought. Concentrated growth factor (CGF) and microneedling (MN)‐assisted drug delivery are promising methods for the treatment of different dermatological diseases.

Objective

This study aimed to assess the practical benefits and the safety aspects of utilizing a dual treatment approach involving CGF and MN‐assisted compound betamethasone for patients suffering from resistant AA that are unresponsive to conventional medical interventions.

Material and Methods

This retrospective study was based on evaluations of seven patients with refractory AA treated with CGF and MN‐assisted compound betamethasone from July 2021 to December 2023. The efficacy of treatment was assessed by extents of hair regrowth percentages of involved areas.

Results

Among the seven enrolled patients with refractory AA, a notable outcome was observed where one patient (14.3%) achieved a regrowth of hair by over 50%, while six patients (85.7%) exhibited complete recovery without any systemic or local adverse effects. Furthermore, the difference in SALT scores between baseline, and the final visit for all patients was found to be statistically significant, substantiating the therapeutic efficacy of the intervention employed.

Conclusion

The present study demonstrated that the synergistic application of CGF in conjunction with MN‐assisted compound betamethasone may constitute a promising and well‐tolerated therapeutic modality for refractory AA, offering a potentially efficacious and safe treatment alternative.
The effect of intratesticular autologous platelet‐rich plasma injection on sperm retrieval rates and in vitro fertilization outcomes in couples with non‐obstructive azoospermia
Authors: Gudelci Tansu , Cakiroglu Yigit , Yuceturk Aysen , Batır Sevil , Karaosmanoglu Ozge , Korun Zeynep Ece Utkan , Tufek Ilter , Kural Ali Riza , Tiras Bulent
Published: September 2024

Aim

To assess the efficacy of intratesticular injection of autologous platelet‐rich plasma (PRP) in men with non‐obstructive azoospermia (NOA) and a history of failed microdissection‐testicular sperm extraction (mTESE) procedures.

Methods

A prospective case series of a cohort study was conducted involving couples diagnosed with NOA. Patients with at least one failed mTESE procedure were included. Intratesticular PRP injection was performed using a standardized protocol. Follow‐up assessments included sperm analysis, hormonal evaluation, and in vitro fertilization (IVF) outcomes.

Results

Data from 177 men with NOA were analyzed, with 135 patients meeting eligibility criteria. PRP treatment resulted in positive sperm retrieval rates of 27.5% in patients with one prior failed mTESE procedure and 16.4% in patients with two or more failed attempts. IVF outcomes showed fertilization rates of 86.4% and 100.0% in respective groups, with pregnancy rates of 36.8% and 22.2% per embryo transfer. Histopathological examination post‐mTESE revealed varied patterns, including Sertoli cell‐only syndrome and maturation arrest.

Conclusions

Intratesticular PRP injection shows promise as a potential therapeutic approach for NOA patients with prior failed mTESE procedures, demonstrating improved sperm retrieval rates and favorable IVF outcomes. Further randomized controlled trials are warranted to validate these findings and refine the technique's efficacy in male infertility management to answer the question of whether PRP could significantly improve the second attempt retrieval rate.
Temporomandibular Joint Discectomy in Patients With Disc Displacement: Assessment of Osteoarthritis at 10‐ and 30‐Year Follow‐Up
Authors: Hol Caroline , Mork‐Knutsen Peer , Larheim Tore A. , Bjørnland Tore , Arvidsson Linda Z.
Published: September 2024

Background

Few ≥ 10‐year follow‐up studies of temporomandibular joint (TMJ) discectomy without replacement in patients with disc displacement (DD) analyse the relationship between the surgery and osteoarthritis (OA) exist.

Objectives

To radiologically evaluate bony joint changes and OA development 10 and 30 years after TMJ discectomy as well as 30‐year clinical outcome.

Methods

Twenty‐two discectomy patients at the University of Oslo, Norway, with records confirming initial TMJ diagnosis and attendance of 10‐year radiological follow‐up were evaluated and eligible for 30‐year follow‐up. Primary variables: discectomy and CT‐/CBCT‐diagnosed OA at follow‐ups. Secondary variables: perioperative TMJ diagnoses and remodelling at follow‐up. Unoperated TMJs (Unop‐TMJs) in unilaterally operated patients were controls. Statistical association and correlation analyses were performed for the 10‐year follow‐up (significance level p < 0.05).

Results

Twenty‐two patients attended the 10‐year follow‐up (mean follow‐up 11 years) with 27 operated TMJs (Op‐TMJs) and 17 Unop‐TMJs. OA perioperatively was associated with DD without reduction (p = 0.001) and additional disc abnormalities (p = 0.016). Although statistically non‐significant, the number of TMJs with OA had increased at 10‐year follow‐up (p = 0.114, Op‐TMJs: 14 to 20 joints; Unop‐TMJs: 2 to 5 joints). Remodelling was correlated with discectomy (p = 0.003) and to OA (p = 0.006). Nine patients attended the 30‐year follow‐up (mean follow‐up 32 years, 11 Op‐TMJs). All TMJs with OA at 30‐year follow‐up had OA at 10‐year follow‐up. Mean maximal interincisal opening was 39 mm. No DC‐TMD‐diagnosed arthralgia was found.

Conclusion

Osteoarthritis developed similarly between Op‐ and Unop‐TMJs. Only remodelling, not OA, was correlated to the surgery. The clinical results were still favourable at final follow‐up.
Correlation Between Swallowing and Cognitive Brain Networks in Older Adults via Functional MRI
Authors: Wang Jie , Zhang Mengqing , Wen Hongmei , Yang Cheng , Wei Xiaomei , Wang Yonghui , Dou Zulin
Published: September 2024

Background

Clinical evidence supports that swallowing function is correlated with cognition, but the neurobiological mechanism associated with cognitive impairment and dysphagia remains unclear.

Objectives

To compare the brain activation patterns of the swallowing and the cognitive tasks and explore neural associations between swallowing and cognitive function via task‐related functional magnetic resonance imaging (fMRI).

Methods

A total of 13 healthy older adults (aged > 60 years) were recruited. Participants underwent the clinical dementia rating (CDR) test and the Montreal Cognitive Assessment (MoCA). A block‐designed task‐related fMRI study was conducted where each participant completed both swallowing and cognitive tasks within a single session. During the swallowing task, participants swallowed 2 mL of thickened water, while the Stroop Colour Word Test (SCWT) served as the cognitive task. First‐level analysis of swallowing time‐series images utilised the general linear model (GLM) with Statistical Parametric Mapping (SPM), applying a voxel threshold of p < 0.001 for significance. Common activations in brain regions during swallowing and cognitive tasks were extracted at the group level, with significance set at p < 0.05, corrected for multiple comparisons using the false discovery rate (FDR), with a minimum cluster size of 20 voxels. Correlation analysis between behavioural measurements and imaging signals was also conducted.

Results

Some regions were commonly activated in both task networks; these regions were the bilateral occipital lobe, cerebellum, lingual gyrus, fusiform, middle frontal gyrus, precentral and postcentral gyrus, right supramarginal and inferior parietal lobe. Most importantly, the average beta value of cognitive and swallowing tasks in these areas are both significantly negative related to the MoCA score. Furthermore, opposite signal changes were seen in the bilateral prefrontal lobes during the swallowing task, while positive activation in the bilateral prefrontal lobes was observed during the SCWT. Postcentral gyrus activation was more extensive than precentral gyrus activation in the swallowing task.

Conclusion

The common activation of swallowing and cognitive tasks had multiple foci. The activity of cognitive and swallowing task in these areas is significantly negative correlated with the MoCA score. These findings may help to illustrate the association between dysphagia and cognitive impairment due to the common brain regions involved in cognition and swallowing and may provide a reference for further rehabilitation of dysphagia.

Trial Registration

Clinical Trial: (Chinese Clinical Trial Registry): ChiCTR1900021795