bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trazodone rescues dysregulated synaptic and mitochondrial nascent proteomes in prion neurodegeneration
Authors: Albert-Gasco Hector , Smith Heather L , Alvarez-Castelao Beatriz , Swinden Dean , Halliday Mark , Janaki-Raman Sudha , Butcher Adrian J , Mallucci Giovanna R 
Published: September 2023

Abstract
The unfolded protein response (UPR) is rapidly gaining momentum as a therapeutic target for protein misfolding neurodegenerative diseases, in which its overactivation results in sustained translational repression leading to synapse loss and neurodegeneration. In mouse models of these disorders, from Alzheimer’s to prion disease, modulation of the pathway—including by the licensed drug, trazodone—restores global protein synthesis rates with profound neuroprotective effects. However, the precise nature of the translational impairment, in particular the specific proteins affected in disease, and their response to therapeutic UPR modulation are poorly understood. We used non-canonical amino acid tagging (NCAT) to measure de novo protein synthesis in the brains of prion-diseased mice with and without trazodone treatment, in both whole hippocampus and cell-specifically.
During disease the predominant nascent proteome changes occur in synaptic, cytoskeletal and mitochondrial proteins in both hippocampal neurons and astrocytes. Remarkably, trazodone treatment for just 2 weeks largely restored the whole disease nascent proteome in the hippocampus to that of healthy, uninfected mice, predominantly with recovery of proteins involved in synaptic and mitochondrial function. In parallel, trazodone treatment restored the disease-associated decline in synapses and mitochondria and their function to wild-type levels.
In conclusion, this study increases our understanding of how translational repression contributes to neurodegeneration through synaptic and mitochondrial toxicity via depletion of key proteins essential for their function. Further, it provides new insights into the neuroprotective mechanisms of trazodone through reversal of this toxicity, relevant for the treatment of neurodegenerative diseases via translational modulation.
Theoretical Study of Non-Isothermal Gradient Elution Liquid Chromatography
Authors: Rehman Nazia , Parveen Ayesha , Qamar Shamsul 
Published: September 2023

Abstract
A two-component model of gradient elution chromatography is investigated to theoretically study the effects of simultaneous variations in temperature and solvent strength on the retention behaviors of elution profiles in thermally insulated liquid chromatographic columns. The gradient elution technique is based on the gradual increase or decrease in eluent strength during the chromatographic operation by varying the composition of the mobile phase. The enthalpy of adsorption is primarily responsible for internal temperature variations inside the column, as heat adsorbs during the adsorption process and releases in the desorption phase. Both types of variations change the propagation speeds of moving pulses inside the column which can lead to better separation of the components and a reduction in the recycling time for the next injection. The equilibrium dispersive model (EDM) coupled with the energy balance equation for temperature and transport equation for the volume fraction of the solvent is utilized to simulate this complex process. The resulting nonlinear model equations are approximated by applying a semi-discrete second-order finite volume scheme. The numerical solutions are used to study the impact of a gradient starting and ending times, volume-fraction of the solvent, solvent strength parameter, the slope of gradient, enthalpy of adsorption, injection temperature, and the ratio of specific heats on the concentration profiles.
Prospective Observational Evaluation of the Time-Dependency of Adalimumab Immunogenicity and Drug Concentration in Ulcerative Colitis Patients: the POETIC II Study
Authors: Harnik Sivan , Abitbol Chaya M , Haj Natour Ola , Yavzori Miri , Fudim Ella , Picard Orit , Naftali Timna , Broide Efrat , Hirsch Ayal , Selinger Limor , Shachar Eyal , Yablecovitch Doron , Albshesh Ahmad , Coscas Daniel , Kopylov Uri , Eliakim Rami , Ben-Horin Shomron , Ungar Bella 
Published: September 2023

Abstract

Background and Aims
Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn’s disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking.

Methods
A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1].

Results
Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p = 0.35]. There was no difference in low drug levels [&lt;3 µg/mL] between the two cohorts [OR = 0.87, p = 0.83].

Conclusions
Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters.
A case report of upgrading to cardiac resynchronization therapy in a patient with congenitally corrected transposition of great arteries and dextrocardia
Authors: Šimka Jakub , Sedláček Kamil , Praus Rudolf , Pařízek Petr 
Published: September 2023

Abstract

Background
Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart anomaly. Physiological correction may be associated with a long pre-symptomatic period in many patients and delayed accidental diagnosis. Additional related congenital malformations may increase the complexity of cardiac interventions.

Case summary
A 59-year-old man with known dextrocardia, situs viscerum inversus, and CCTGA was scheduled for upgrading of a dual-chamber pacemaker to cardiac resynchronization therapy to treat heart failure related to a progressive systolic dysfunction of the systemic right ventricle (RV). Because of the specific anatomy of this patient, the therapeutic procedure was complicated by the cannulation of the Marshall vein. Nevertheless, the left ventricular lead was successfully implanted into the coronary sinus lateral branch. At the 3-month follow-up, the patient remarkably reported a significant functional improvement, despite no favourable reverse remodelling of the systemic RV.

Discussion
Upgrade of a pacemaker to biventricular pacing was feasible in this patient, who had CCTGA and dextrocardia, which resulted in symptomatic improvement at follow-up. Pre-implant contrast cardiac computed tomography angiography was essential for visualizing the venous-specific anatomy in this patient, who suffered from congenital heart disease. Conduction system pacing represents a potential alternative for the patient to prevent or treat pacing-related heart failure.
Unicentric Castleman’s disease associated with malignant cardiac Amyloid-A amyloidosis: a case report
Authors: Schuetz Thomas , Schiller Dietmar , Klingel Karin , Gattermeier Martin , Poelzl Gerhard 
Published: September 2023

Abstract

Background
Unicentric Castleman’s disease (UCD), a lymphoproliferative disorder characterized by enlargement of the lymph nodes, is a rare cause of Amyloid-A amyloidosis. While patients usually present with impaired kidney function and proteinuria, heart involvement is neither common nor the main cause of signs and symptoms.

Case summary
We present a patient who was admitted to the hospital for impaired exercise capacity. Diagnostic work-up revealed severe left ventricular hypertrophy suggestive of cardiac amyloidosis. Although Congo red staining of endomyocardial biopsies was initially negative, subsequent immunohistochemical staining against serum amyloid A finally confirmed the diagnosis of cardiac amyloidosis. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed a tumour located in dorsal of the duodenum. Fine-needle aspiration biopsy of the tumour was suggestive but could not confirm the presence of UCD beyond reasonable doubt. Rapid worsening of heart failure symptoms warranted urgent surgical tumourectomy, which resulted in immediate post-operative lowering of serum amyloid protein. However, post-operative cardiogenic shock could not be stabilized even with veno-arterial extracorporeal membrane oxygenation, and the patient eventually died. The UCD of the hyaline vascular (HV) subtype was confirmed by pathologic work-up of the excised tumour.

Discussion
This case report presents for the first time a patient with malignant cardiac Amyloid-A amyloidosis caused by unicentric Castleman’s disease of the HV subtype. Since the disease progresses swiftly, rapid diagnosis is essential for potential curative treatment.
Extensive cardiovascular involvement in a young boy with Gaucher’s disease: a case report
Authors: Naderian Mohammadreza , Khederlou Hamid , Hosseinsabet Ali , Salarifar Mojtaba 
Published: September 2023

Abstract

Background
Lysosomal storage diseases (LSDs) are rare, progressive, multi-organ disorders caused by inherited enzyme deficiencies. Gaucher’s disease (GD) is the most prevalent form of LSDs.

Case summary
A 19-year-old Caucasian male presented with exertional dyspnoea. Physical examination revealed a Grade III/VI systolic diamond murmur at the heart base and a Grade IV/VI systolic murmur at the apex. Electrocardiogram showed signs of left ventricular hypertrophy (LVH). Trans-thoracic echocardiography (TTE) and trans-oesophageal echocardiography (TEE) demonstrated moderate LVH, severe aortic valve stenosis, severe supra-valvular aortic stenosis, and moderate mitral stenosis with severe degenerative mitral valve regurgitation. Bone marrow biopsy and aspiration confirmed the presence of characteristic Gaucher's cells. The patient underwent the Bentall procedure and mitral valve replacement and was discharged in good condition.

Discussion
Gaucher’s disease exhibits three clinical phenotypes, and cardiovascular involvement is commonly seen in GD Type III. Valvular calcification and ascending aorta involvement are frequent cardiovascular manifestations. Although severe valvular heart involvement is rare in GD, cardiac valve surgery has shown favourable outcomes in previous studies and our case.
Pre-screening for non-diagnostic coronary computed tomography angiography
Authors: Hakimjavadi Ramtin , Lu Juan , Yam Yeung , Dwivedi Girish , Small Gary R , Chow Benjamin J W 
Published: September 2023

Abstract

Aims
Indiscriminate coronary computed tomography angiography (CCTA) referrals for suspected coronary artery disease could result in a higher rate of equivocal and non-diagnostic studies, leading to inappropriate downstream resource utilization or delayed time to diagnosis. We sought to develop a simple clinical tool for predicting the likelihood of a non-diagnostic CCTA to help identify patients who might be better served with a different test.

Methods and results
We developed a clinical scoring system from a cohort of 21 492 consecutive patients who underwent CCTA between February 2006 and May 2021. Coronary computed tomography angiography study results were categorized as normal, abnormal, or non-diagnostic. Multivariable logistic regression analysis was conducted to produce a model that predicted the likelihood of a non-diagnostic test. Machine learning (ML) models were utilized to validate the predictor selection and prediction performance. Both logistic regression and ML models achieved fair discriminate ability with an area under the curve of 0.630 [95% confidence interval (CI) 0.618–0.641] and 0.634 (95% CI 0.612–0.656), respectively. The presence of a cardiac implant and weight &gt;100 kg were among the most influential predictors of a non-diagnostic study.

Conclusion
We developed a model that could be implemented at the ‘point-of-scheduling’ to identify patients who would be best served by another non-invasive diagnostic test.
Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the Swiss cohort
Authors: Herrera Siklody Claudia , Schiappacasse Luis , Jumeau Raphaël , Reichlin Tobias , Saguner Ardan M , Andratschke Nicolaus , Elicin Olgun , Schreiner Frederic , Kovacs Boldizsar , Mayinger Michael , Huber Adrian , Verhoeff Joost J C , Pascale Patrizio , Solana Muñoz Jorge , Luca Adrian , Domenichini Giulia , Moeckli Raphael , Bourhis Jean , Ozsahin Esat M , Pruvot Etienne 
Published: September 2023

Abstract

Aims
Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analysed recurrences in our patients after STAR.

Methods and results
From 09.2017 to 01.2020, 20 patients (68 ± 8 y, LVEF 37 ± 15%) suffering from refractory VT were enrolled, 16/20 with a history of at least one electrical storm. Before STAR, an invasive electroanatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23 ± 2 Gy was delivered to the planning target volume (PTV). The median ablation volume was 26 mL (range 14–115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in the proximity of the treated substrate in nine cases, remote from the PTV in three cases and involved a larger substrate over ≥3 LV segments in two cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR.

Conclusion
STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude.
S1-2 Findings from the children and adolescent working group project on whole systems approaches to whole school physical activity promotion across Europe
Authors: Morris Jade 
Published: September 2023

Abstract

This talk will focus on a working group project investigating the research, policy and practice needs related to co-developing a whole-school system approach to physical activity (PA).
The World Health Organization (2018) calls for all countries to implement a whole-system approach and positions school as an opportune site for increasing PA opportunities for children. Yet, current research reveals that most whole-school approaches fail to create impactful and sustainable changes. Consistent limitations include a focus on short-term initiatives that fail to address the many ingredients required to promote systems change through addressing organisational structure and culture within and beyond school settings. While contemporary guidance provides an in-depth understanding of “what” factors to address within the school, the system still lacks an understanding of “how” to address each factor required to create impactful and sustainable change. It is essential that the implementation of the different ingredients that form the school system are co-developed with multi-stakeholders from within and beyond the school environment.

Project description
To establish the research, policy and practice needs related to co-developing a whole-school systems approach to PA, this project includes three stages.
First, we drew on an extensive European network to identify and categorise stakeholders involved in influencing and/or operationalising whole-school PA across the region.
Second, we will conduct a needs analysis to systematically identify training needs. We will conduct six focus groups across Europe to gain diverse stakeholders perspectives on the required training needs aligned to capabilities, opportunities, and motivation (COM-B). Finally, we will be using the aforementioned insights to create a policy briefing on whole-school systems-based PA training needs. We will conduct two virtual stakeholder events to consult on the findings and gather further insights, offering contextual different within and between countries.

Conclusion
The policy briefing will provide recommendations for working across national contexts relating to school-based PA, providing guidance for policymakers and practitioners. We anticipate these insights will promote the development of bottom-up and top-down approaches to create ‘systems’ change within the school context.

Funding
This project is supported by the WHO European Office for Prevention and Control of Noncommunicable Diseases.
S5-5 Developing an individual-based advice for sports participation and physical activity in children using the concept of Physical Literacy
Authors: Singh Amika , Veldman Sanne 
Published: September 2023

Abstract

Purpose
Practitioners, researchers and policy makers have been looking for ways to change the negative trend observed in physical activity (PA) behaviour in children. An individual PA advice for children, based on the concept of physical literacy (PL), might offer an important avenue to support and motivate children to be physically active in a way that fits their needs and skills. Due to the holistic approach of PL, this concept is suitable for the development of an individual PA advice to motivate children to be physically active for life. Therefore, we aim to develop a feasible tool to provide children aged 4 to 12 years with an individual PA advice in the Dutch school setting.

Method
In this project, experts on the different areas of PL collaborate to create a tool feasible for implementation in the Dutch primary school setting. Experts will comprise children, parents, practitioners, researchers and policy makers.
First, available measurement instruments on (elements of) PL will be reviewed. This will help us determine what instruments are best suitable to be used in the Dutch setting to create ‘input’ for a tool. Secondly, we will examine how data from these instruments can be harmonized to create an individual PA advice. This step will involve close collaborations with ICT while adhering to privacy rules and regulations. During this step we will also examine how the translation from ‘input’ to ‘output’, an individual PA advice, might have to differ for different age groups. Thirdly, we will develop a plan for the implementation in the Dutch setting and educational context. This involves feasibility in terms of finances as well as feasibility from a practical point of view.

Conclusion
By creating a tool to develop an individual PA advice, we hope to support and motivate children and parents to engage in PA that will last a life time. Throughout the process, relevant stakeholders will be involved in any step needed to ensure acceptability, feasibility and sustainability.

Funding
This project is funded by the Dutch Ministery of Health, Welfare, and Sports.
S7-4 Active transport to physical exercise places among older adults living in different urban zones
Authors: Keskinen Kirsi E , Tuomola Essi-Mari , Rantanen Taina , Portegijs Erja 
Published: September 2023

Abstract

Purpose
Motorized transport to and from places of physical exercise (PE) causes considerable amounts of carbon emissions. We study how locations of home and PE place on urban zones (UZs), reflecting options for transport modes, relate to use of active transport (AT) among older adults. No previous knowledge on the topic exists.

Methods
Data of AGNES study participants reporting at least one regular PE place &lt;10 km from home (n = 819, mean 79 years, 58% women, Jyväskylä Finland) were combined with geospatial data on UZ. Using digital mapping, participants located their PE places (N = 2171) and reported transport mode (active/passive) used. Type of UZ (pedestrian/public transport/car) of participants’ home and PE places and distance from home to PE place were defined in GIS. For analyses, participants were grouped according to home UZ, shares of PE places in each UZ defined, and differences in total number of PE places and median distance tested with Kruskal-Wallis test. In each group, use of AT (vs. passive) to PE place was regressed for PE place’s UZ and distance, and adjusted for car availability, difficulty walking 2 km, age, sex, and years of education using a mixed model nested in participants.

Results
In all groups, participants had more PE places in their home UZ than in other UZs. Median distance to and number of PE places did not differ across groups (for both p&gt;.05). Overall, between-participant differences explained 22 % of total variance in AT. Compared to AT to PE place in home UZ, odds for AT were higher to PE place in car zones among those living in pedestrian (OR 5.1 95%CI 1.7-15.4) and public transport zones (OR 3.6 95%CI 1.3-8.4).
The odds for AT were lower to PE place in pedestrian zones among those living in public transport (OR 0.2 95%CI 0.1-0.4) or car zones (OR 0.02 95%CI 0.001-0.3). In all groups, longer distance was negatively associated with AT.

Conclusions
Older adults’ transport mode choices cannot be concluded from the UZ of home or PE place. Proximity to PE places is important to facilitate AT use.

Funding Source
Ministry of Education and Culture.