bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pivotal trial of low-intensity pulsed ultrasound therapy for early Alzheimer's disease: Rationale and design
Authors: Shimokawa Hiroaki , Akishita Masahiro , Ihara Masafumi , Teramukai Satoshi , Ishiki Aiko , Nagai Yoji , Fukushima Masanori 
Published: January 2025

Background There are lines of evidence suggesting that cerebral microcirculatory dysfunction is involved in the pathogenesis of Alzheimer's disease (AD). We have developed a low-intensity pulsed ultrasound (LIPUS) therapy that upregulates endothelial NO synthase with therapeutic angiogenesis. We demonstrated that the LIPUS therapy ameliorates cognitive declines in mouse models of AD and tended to do so in patients with early AD (mild AD and mild cognitive impairment due to AD) in the pilot trial. Thus, the Japanese government has designated our LIPUS device as the first breakthrough medical device in Japan. Objective We are performing a pivotal clinical trial (LIPUS-AD) to finally address the efficacy and safety of our LIPUS therapy in patients with early AD in Japan. Methods LIPUS-AD is a randomized, double-blind, placebo-controlled trial, in which a total of 220 patients with early AD, who are positive for amyloid-β (Aβ) PET, will be randomized in a 1:1 fashion. The LIPUS therapy is performed for the whole brain for one hour 3 times a week as one session under the special conditions (32 cycles, 0.5 MHz, 0.25 W/cm2). It is performed for 6 sessions with 3-month intervals in the LIPUS group for 72 weeks, while the placebo group receives placebo therapy. Before and at 72 weeks of the trial, all subjects undergo brain Aβ PET and MRI and 9 cognitive functions tests. The primary efficacy endpoint is the changes in ADAS-J-cog-14 scores from baseline to 72 weeks. Conclusions LIPUS-AD addresses efficacy and safety of the LIPUS therapy in patients with early AD. Clinical Trial Gov. No.: NCT05983575
From Intent to Inaction: Factors Conditioning Cultural Institutions From Embracing Crowdfunding as a Fundraising Tool
Authors: Rykkja Anders , Bonet Lluís 
Published: January 2025

Purpose The article explores factors explaining cultural institutions’ intentions to adopt and circumstances that lead to inaction in terms of launching a crowdfunding campaign. Study Design The study is a single-case study of a Norwegian museum consortium. It combines thematic analysis of qualitative data from interviews and non-parametric tests of quantitative survey data to examine differences between four categories of employees: leadership, curators, technical staff, and support staff. Findings The study identifies three key factors contributing to the inaction and failure to launch the crowdfunding campaign: (1) the added value of funding and non-monetary benefits; (2) legitimacy concerns surrounding crowdfunding; and (3) the leadership and management of implementing what proved to be a non-routine activity. Contributions The paper provides insights into the drivers and barriers that influence the intention to use institutional cultural crowdfunding. It adds to the literature by demonstrating that cultural institutions’ internal organisational dynamics influence decision-making. The derived propositions provide a basis for further empirical research into how cultural institutions approach crowdfunding. Implications The findings hold practical implications for cultural institutions, policymakers, and scholars. They underscore the importance of leadership in navigating legitimacy concerns, fostering intra-organisational collaboration, and supporting institutional cultural crowdfunding efforts from intent to action.
A systemic approach to identifying sustainable community-based interventions for improving adolescent mental health: a participatory group model building and design protocol
Authors: Keenan Megan , Freeman Leanne , Santana de Lima Ediane , Potter Katie , Hobbs Tim , Ballard Ellis , Fonagy Peter 
Published: January 2025

Abstract

Background
The deteriorating mental health of children and young people in the United Kingdom poses a challenge that services and policy makers have found difficult to tackle. Kailo responds to this issue with a community-based participatory and systemically informed strategy, perceiving mental health and well-being as a dynamic state shaped by the interplay of broader health determinants. The initiative works to explore, define and implement locally relevant solutions to challenges shaping the mental health and well-being of young people. Kailo unfolds in three stages within each locale. These stages encompass: “early discovery”, “deeper discovery and co-design” and “implementation”. This document delves into the participatory group model building and design protocol occurring in the “deeper discovery and co-design” stage of the project.

Methods
Participatory methods, such as group model building, are effective in articulating and building consensus on complex issues like the social determinants of adolescent mental health. This paper describes the protocol for application of group model building within the Kailo design process to develop causal loop diagrams and pinpoint leverage points for improving adolescent mental health. It also suggests a method for considering modifications to delivery within a unique project context and in alignment with participants’ needs. This paper sets out to define the approach and clarify the objectives these engagements aim to fulfil. The method adapts existing group model building (GMB) protocols for use in a community setting. The engagements will involve groups of local young people and existing community members. To assess the success of the session’s implementation post-delivery, the study utilizes existing frameworks for fidelity evaluations, which define a core and flex model.

Discussion
The method described enables an integration of diverse local understandings of complex processes which provides a platform for creating co-designed interventions. This protocol can be used to further strengthen research and design through incorporating complexity and participation into the formulation of contextually relevant policies and practices. The strengths and limitations of the approach are discussed.
SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients
Authors: Khemiri Haifa , Ben Fraj Ilhem , Lorusso Alessio , Mekki Najla , Mangone Iolanda , Gdoura Mariem , Di Pasqual Adriano , Cammà Cesare , Di Lollo Valeria , Cherni Asma , Touzi Henda , Sadraoui Amel , Meddeb Zina , Hogga Nahed , Ben Mustapha Imen , Barbouche Mohamed-Ridha , Ouederni Monia , Triki Henda , Haddad-Boubaker Sondes 
Published: January 2025

Abstract

Background
Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.

Materials and methods
A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.

Results
In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).

Conclusion
Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.
Optical coherence tomography angiography reveals abnormal retinal vascular density and perfusion in patients with X-linked adrenoleukodystrophy: a cross-sectional study
Authors: Zhang Lujie , Yu Yongqiu , Liu Ting , Li Chongyi , Tan Liang , Wen Shuiqian 
Published: January 2025

Abstract

Purpose
X-linked adrenoleukodystrophy (XALD) can affect the eyes. Existing therapies are hampered by early quantitative examination methods. This study used an optical coherence tomography angiography system (OCTA) to investigate retinal microvascular density and perfusion in XALD patients.

Methods
Fifty-two patients and 47 age-matched controls were included in this cross-sectional study. The patients were divided into three groups (symptomatic, less symptomatic, and controls). We compared the foveal avascular zone area, vascular density and perfusion area at the superficial vascular complex (SVC) and deep vascular complex (DVC) of the peripapillary and macular between the groups. We correlated these measurements with scale scores.

Results
Compared with the controls, the symptomatic group had significantly lower vascular density in the superior nasal sector of the peripapillary SVC (MD − 4.940884; 95% CI − 9.655061 to − 0.226707; p = 0.036), lower vascular density (MD − 4.259225; 95% CI − 8.248627  to  − 0.269823; p = 0.032) and lower perfusion area (MD − 0.180304; 95% CI − 0.337135  to  − 0.023472; p = 0.018) in the peripheral ring superior quadrant of the macular SVC. Compared with the less symptomatic group, the symptomatic group exhibited a significantly lower vascular density (MD − 5.635483; 95% CI − 10.450009  to  − 0.820957; p = 0.015) and perfusion area (MD − 0.063351; 95% CI − 0.116611  to  − 0.010091; p = 0.013) in the superior nasal sector of the peripapillary SVC; lower vascular density (MD − 4.817846; 95% CI − 8.924294  to  − 0.711399; p = 0.015) and perfusion area (MD − 0.202707; 95% CI − 0.369499  to  − 0.035915; p = 0.011) in the peripheral ring superior quadrant of the macular SVC; and greater vascular density (MD 7.209401; 95% CI 0.818716–13.600086; p = 0.021) and perfusion area (MD 0.047320; 95% CI 0.001685–0.092956; p = 0.039) in the inferior nasal sector of the peripapillary DVC. Among the 52 patients, the expanded disability status score (EDSS) was moderately negatively correlated with the vascular density (p = 0.001) and perfusion area (p = 0.002) in the peripheral ring superior quadrant of the macular SVC.

Conclusion
Changes in retinal vascular density and perfusion exist in XALD patients and are correlated with disease severity. OCTA has the potential to monitor the progression of XALD.
Validity, reliability and clinical utility of ASSIST-Y in assessing risk of substance-related harm and dependence in Spanish male adolescents
Authors: Ibáñez-Martínez Núria , Stevens Matthew William Richard , Civit-Bel Núria , Moreno-Ferrer Noemí , Lopez-Ferré Sandra , Olivares-Casado Ana , Claramunt-Mendoza Juame , Holmwood Chris , Ali Robert 
Published: January 2025

Abstract

Background
Substance use among adolescents is strongly associated with adverse physical, mental health, and social outcomes. Prevention and early intervention can reduce the likelihood of future problems, but requires valid and reliable screening tools capable of assessing risk across a range of substances. This study assessed the validity, reliability, and clinical utility of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST-Y) for adolescents aged 15–17 years.

Methods
A sample of adolescent males (N = 101), aged 15–17 years, held in a juvenile detention facility on substance-related offences in Barcelona, Spain were eligible. Participants were administered a battery of standardized substance-use screening tools by a clinical psychologist, and underwent a diagnostic interview assessing DSM-IV-TR substance abuse and dependence by an addiction medicine specialist. Scores on the various assessments were compared to establish validity (concurrent with interview, convergent with other measures), reliability, and clinical utility of ASSIST-Y.

Results
Majority of participants (n = 77) completed assessments. While tobacco was not assessed as part of the interview, concurrent validity in detecting substance abuse was established for all remaining substances. Concurrent validity for detecting dependence was established for alcohol, cannabis, cocaine, stimulants and sedatives. Fewer numbers in higher-risk groups for inhalants, opioids and hallucinogen use limited confirmation of validity for those substances. ASSIST-Y also demonstrated good convergent validity with the other screening tools for all substances, except hallucinogens. Reliability for each subscale was established, except for tobacco (too few items), sedatives, and hallucinogens. Finally, clinical utility indices were significant for most substances (except sedatives and opioids); whilst clinical utility indices were significant for ruling out cases of non-dependence (all substances).

Conclusions
As a screening tool, the purpose of ASSIST-Y is designed to help identify adolescents who may be at-risk of substance-related harm. While the instrument was found to be valid and reliable in identifying risky use across a variety of substances, further research is needed to validate the instrument in other population groups, and for other substances. Future research should investigate the effect of the linked brief intervention to reduce risk of harm, especially for non-specialist clinicians.
Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage
Authors: Dogan Alan B. , Marsh Spencer R. , Tschetter Rachel J. , E. Beard Claire , Amin Md R. , Jane Jourdan L. , Gourdie Robert G. 
Published: January 2025

Abstract
Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature. Herein, we aim to characterize and engineer a freeze-dried, mEV formulation that can be stored at room temperature without sacrificing structure/bioactivity and can be reconstituted before delivery. In addition to undertaking established mEV assays of structure and function on our preparations, we introduce a novel, efficient, high throughput assay of mEV bioactivity based on Electric Cell Substrate Impedance Sensing (ECIS) in Human dermal fibroblast monolayers. By adding appropriate excipients, such as trehalose and tryptophan, we describe a protective formulation that preserves mEV bioactivity during long-term, room temperature storage. Our identification of the efficacy of tryptophan as a novel additive to mEV lyophilization solutions could represent a significant advancement in stabilizing small extracellular vesicles outside of cold storage conditions.
Inter-rater agreement and characterization of pleural line and subpleural fields in canine lung ultrasound: a comparative pilot study between high-frequency linear and curvilinear transducers using B- and M-mode ultrasonographic profiles
Authors: Granger Kyle L. , Guieu Liz , Boysen Søren R. 
Published: January 2025

Abstract

Background
Lung ultrasound (LUS) is increasingly utilized in veterinary medicine to assess pulmonary conditions. However, the characterization of pleural line and subpleural fields using different ultrasound transducers, specifically high-frequency linear ultrasound transducers (HFLUT) and curvilinear transducers (CUT), remains underexplored in canine patients. This study aimed to evaluate inter-rater agreement in the characterization of pleural line and subpleural fields using B- and M-mode ultrasonography in dogs with and without respiratory distress.

Results
Eighty-eight ultrasound clips from nine dogs were analyzed. HFLUT demonstrated strong inter-rater agreement in B-mode (κ = 0.89) and near-perfect agreement in M-mode (κ = 1.00) for pleural line homogeneity. In contrast, CUT showed minimal agreement in both B-mode (κ = 0.34) and M-mode (κ = 0.37). Homogeneous pleural lines were predominantly observed in control dogs or those with cardiogenic pulmonary edema (CPE), while non-homogeneous pleural lines were more common in dogs with non-cardiogenic alveolar-interstitial syndrome (NCAIS). Vertical subpleural fields identified in M-mode were associated with both CPE and NCAIS, whereas horizontal fields were more often observed in control dogs.

Conclusions
HFLUT offers superior inter-rater reliability for characterizing pleural and subpleural features in canine LUS compared to CUT, particularly in M-mode. These findings suggest HFLUT may enhance diagnostic accuracy for pulmonary conditions in dogs. Further studies are needed to explore the diagnostic potential of LUS in differentiating vertical artifact (e.g., B-lines) etiologies in veterinary patients.
Real-time ultrasound for umbilical venous catheter insertion in neonates- a systematic review and meta-analysis
Authors: Anne Rajendra Prasad , Rahiman Emine A. , Aradhya Abhishek Somashekara 
Published: January 2025

Abstract

Objective
There has been an increase in real-time ultrasonography use in central venous catheterisation. This systematic review and meta-analysis aimed to assess the role of real-time ultrasound use in umbilical venous catheterisation in neonates.

Data sources
PubMed, Embase, Web of Science and Cochrane Library were searched on July 11, 2024. We followed the Cochrane Handbook for Systematic Reviews of Interventions (for study conduct), GRADE methodology (for certainty of evidence), and PRISMA guidelines (for reporting).

Study selection
All randomised controlled trials/RCTs and non-randomised studies of interventions/NRSIs comparing real-time ultrasound with the conventional technique of umbilical venous catheterisation were included.

Data extraction
The outcomes of interest were malposition rates, procedure duration, mortality, sepsis, and cost. Data extraction and quality assessment were done in duplicate.

Data synthesis
Six studies (three RCTs and three NRSI), including 863 participants, were included. Data were analysed separately for RCTs and NRSIs. The RCTs were at low risk of bias, but NRSIs were at moderate to serious risk. The pooled estimates from RCTs showed a decrease in malposition rates (2 studies, 165 participants, risk ratio/RR 0.45, 95% confidence interval/CI 0.23, 0.90) and procedure duration (3 studies, 196 participants, mean difference −6.1 min, 95% CI −8.4, −3.8 min) with real-time ultrasound use. There was no reduction in sepsis. Mortality was not reported. The certainty of evidence was low for malposition rates and procedure duration. The data from NRSIs showed a reduction in malposition rates (3 studies, 667 participants, risk ratio/RR 0.10, 95% confidence interval/CI 0.07, 0.14) without an impact on procedure duration and sepsis. However, these findings did not improve the evidence.

Conclusions
Low certainty evidence suggests that using real-time ultrasound for umbilical venous catheterisation reduces malposition rates. There is a clinically insignificant reduction in procedure duration. There is no sufficient data to come to a conclusion on the critical outcomes of sepsis and mortality.

PROSPERO registration number: CRD42024567895.
Validation of a tele-robotic ultrasound system for abdomen and thyroid gland explorations: a comparison with standard ultrasound
Authors: Antolin Andreu , Roson Nuria , Planes Marina , Castillo Mar , Alberti Anna , Escobar Manuel 
Published: January 2025

Abstract

Background
Tele-robotic ultrasound (US) is a novel technique that might help overcome the current shortage of radiologists and poor access to radiologists and/or sonographers in remote or rural areas. Despite the promising results of this technology in the past two decades, there is still insufficient data about its advantages and limits, as well as the implementation in routine clinical practice and the learning curve for the user. The purpose of this prospective cohort-based study is to evaluate the performance of a 5G-based tele-robotic US system for abdominal and thyroid gland assessment in a cohort of healthy volunteers and outpatients, as well as assessing the learning curve and patient satisfaction.

Results
64 participants (23 male, 41 female) were consecutively included during the recruitment period, for a total of 51 abdominal and 37 thyroid gland US studies. The mean age was 45.23 ± 18.90 years old, and the body mass index of the abdominal cohort was 22.97 ± 2.95 kg/m2. The learning curve estimated a minimum of 20 patients for abdominal tele-robotic US training, being almost non-existent in the thyroid gland cohort. All the variables showed no-statistical differences between standard US and tele-robotic US in the abdominal post-trained cohort except the visualization of the left kidney short axis and its interpolar length. Thyroid gland variables showed no statistical differences. The mean time of exploration for the tele-robotic US for abdomen and thyroid gland examinations were 18.33 ± 6.26 min and 4.64 ± 0.97 min respectively. Most participants (> 70%) felt comfortable and safe while being examined by the tele-robotic US.

Conclusion
Tele-robotic US achieves equal performance in comparison with the standard US when evaluating abdominal structures in this cohort of patients, as well as a relatively fast learning curve and good patient satisfaction. The performance when assessing the thyroid gland is almost identical to the standard US, which makes it a strong first candidate for a future clinical implementation.