bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a small animal model replicating core characteristics of takotsubo syndrome in humans
Authors: Zulfaj Ermir , Nejat Amirali , Espinosa Aaron Shekka , Hussain Shafaat , Haamid Abdulhussain , Soliman Ahmed Elmahdy , Kakaei Yalda , Jha Abhishek , Redfors Björn , Omerovic Elmir 
Published: June 2024

Abstract

Aims
Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models.

Methods and results
We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7–8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia (P &lt; 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48–72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning.

Conclusion
This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation.
Body mass index and pulmonary vein isolation: real-world data on outcomes and quality of life
Authors: Vermeer Jasper , Houterman Saskia , Medendorp Niki , van der Voort Pepijn , Dekker Lukas ,   Ablation Registration Committee of the Netherlands Heart Registration, Kuijt W , Driessen A H G , Kemme M J B , van der Voort P H , Bhagwandien R E , van der Heijden J , Adiyaman A , Trines S A I P , Luermans J G L M , Schoonderwoerd B A , van Dessel P F H M , de Jong J S S G , Westra S W , Balt J C , Hassink R J , Blaauw Y 
Published: June 2024

Abstract

Aims
Increasing numbers of overweight and obese patients undergo pulmonary vein isolation (PVI), despite the association between higher body mass index (BMI) and adverse PVI outcomes. Evidence on complications and quality of life in different bodyweight groups is limited. This study aims to clarify the impact of BMI on repeat ablations, periprocedural complications, and changes in quality of life.

Methods and results
This multi-centre study analysed prospectively collected data from 15 ablation centres, covering all first-time PVI patients in the Netherlands from 2015 to 2021. Patients were categorized by BMI: normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (≥30 kg/m2). Quality of life was assessed using the Atrial Fibrillation Effect on QualiTy-of-life questionnaire at baseline and 1-year post-PVI. Among 20 725 patients, 30% were of normal weight, 47% overweight, and 23% obese. Within the first year after PVI, obese patients had a higher incidence of repeat ablations than normal-weighing and overweight patients (17.8 vs. 15.6 and 16.1%, P &lt; 0.05). Obesity was independently associated with repeat ablations (odds ratio 1.15; 95% confidence interval 1.01–1.31, P = 0.03). This association remained apparent after 3 years. Complication rates were 3.8% in normal weight, 3.0% in overweight, and 4.6% in obese, with weight class not being an independent predictor. Quality of life improved in all weight groups post-PVI but remained lowest in obese patients.

Conclusion
Obesity is independently associated with a higher rate of repeat ablations. Pulmonary vein isolation is equally safe in all weight classes. Despite lower quality of life among obese individuals, substantial improvements occur for all weight groups after PVI.
Mathematical modelling, selection and hierarchical inference to determine the minimal dose in IFNα therapy against myeloproliferative neoplasms
Authors: Hermange Gurvan , Vainchenker William , Plo Isabelle , Cournède Paul-Henry 
Published: June 2024

Abstract
Myeloproliferative neoplasms (MPN) are blood cancers that appear after acquiring a driver mutation in a hematopoietic stem cell. These hematological malignancies result in the overproduction of mature blood cells and, if not treated, induce a risk of cardiovascular events and thrombosis. Pegylated IFN$\alpha $ is commonly used to treat MPN, but no clear guidelines exist concerning the dose prescribed to patients. We applied a model selection procedure and ran a hierarchical Bayesian inference method to decipher how dose variations impact the response to the therapy. We inferred that IFN$\alpha $ acts on mutated stem cells by inducing their differentiation into progenitor cells; the higher the dose, the higher the effect. We found that the treatment can induce long-term remission when a sufficient (patient-dependent) dose is reached. We determined this minimal dose for individuals in a cohort of patients and estimated the most suitable starting dose to give to a new patient to increase the chances of being cured.
Phenotypic and genomic analysis of bacteria from war wounds in Dnipro, Ukraine
Authors: Stepanskyi Dmytro , Ishchenko Oksana , Luo Ting , Lebreton Francois , Bennett Jason W , Kovalenko Iryna , McGann Patrick 
Published: June 2024

Abstract

Objectives
To better understand the source and potential transmission routes of antibiotic-resistant bacteria infecting injured service members in Ukraine.

Methods
Phenotypic and genomic characterizations were performed on 11 Gram-negative pathogens cultured from war wounds at an intermediate evacuation hospital in Dnipro.

Results
The analysis revealed both susceptible and extensively drug-resistant strains present in cultures, including high-risk global clones carrying carbapenemases.

Conclusions
Globally distributed carbapenemase-producing lineages are being acquired early in the medical evacuation process.
Evaluation of a Rapid Drug Test Device for Urine Fentanyl Compared to Mass Spectrometry and 2 Urine Fentanyl Assays
Authors: Laryea Erving T , Nichols James H 
Published: June 2024

Abstract

Background
A new Rapid Drug Test Device (RDTD) is available for analysis of urine fentanyl. With the rise in fentanyl abuse in the United States, we evaluated the analytical performance of the RDTD test strip compared to mass spectrometry and 2 urine fentanyl immunoassays.

Methods
Leftover, deidentified urine samples collected from inpatients and outpatients from our psychiatric hospital and other clinics were frozen at &lt;−70°C, thawed at room temperature, and centrifuged. Aliquots were tested with the RDTD (CLIA Waived, Inc.) test strips and 2 urine fentanyl immunoassays: the ARK Fentanyl II assay (ARK Diagnostics Inc.) and the Immunalysis SEFRIA Fentanyl assay (Immunalysis Corporation). Both assays were conducted on the Abbott Alinity c chemistry analyzer (Abbott Laboratories). Mass spectrometry analysis was performed at ARUP Laboratories. All assays had a 1 ng/mL positive cutoff.

Results
A total of 142 urine samples included 70 positive and 72 negative samples. The RDTD strips had lower sensitivity (84.3%) and efficiency (85.9%) and showed a specificity of 87.5% compared to the other assays. The ARK Fentanyl II assay showed identical sensitivity (95.7%) to the Immunalysis SEFRIA Fentanyl assay but had higher specificity (94.4% vs 81.9%) and overall efficiency (95.1% vs 88.7%).

Conclusions
Differences were noted in the number of false negatives and positives among the assays. The RDTD demonstrated acceptable performance in detecting urine fentanyl in our patient population and would provide faster test results at point-of-care testing sites in our healthcare enterprise.
Collagen structures of demineralized bone paper direct mineral metabolism
Authors: Yoon Hyejin , Park Yongkuk , Kwak Jun-Goo , Lee Jungwoo 
Published: June 2024

Abstract
Bone is a dynamic mineralized tissue that undergoes continuous turnover throughout life. While the general mechanism of bone mineral metabolism is documented, the role of underlying collagen structures in regulating osteoblastic mineral deposition and osteoclastic mineral resorption remains an active research area, partly due to the lack of biomaterial platforms supporting accurate and analytical investigation. The recently introduced osteoid-inspired demineralized bone paper (DBP), prepared by 20-μm thin sectioning of demineralized bovine compact bone, holds promise in addressing this challenge as it preserves the intrinsic bony collagen structure and retains semi-transparency. Here, we report on the impact of collagen structures on modulating osteoblast and osteoclast-driven bone mineral metabolism using vertical and transversal DBPs that exhibit a uniaxially aligned and a concentric ring collagen structure, respectively. Translucent DBP reveals these collagen structures and facilitates longitudinal tracking of mineral deposition and resorption under brightfield microscopy for at least 3 wk. Genetically labeled primary osteogenic cells allow fluorescent monitoring of these cellular processes. Osteoblasts adhere and proliferate following the underlying collagen structures of DBPs. Osteoblastic mineral deposition is significantly higher in vertical DBP than in transversal DBP. Spatiotemporal analysis reveals notably more osteoblast adhesion and faster mineral deposition in vascular regions than in bone regions. Subsequent osteoclastic resorption follows these mineralized collagen structures, directing distinct trench and pit-type resorption patterns. In vertical DBP, trench-type resorption occurs at an 80% frequency, whereas transversal DBP shows 35% trench-type and 65% pit-type resorption. Our studies substantiate the importance of collagen structures in regulating mineral metabolism by osteogenic cells. DBP is expected to serve as an enabling biomaterial platform for studying various aspects of cellular and extracellular bone remodeling biology.
Carboxylesterase 1 directs the metabolic profile of dendritic cells to a reduced inflammatory phenotype
Authors: Elfiky Ahmed M I , Canñizares Jessica López , Li Jiarong , Li Yim Andrew Y F , Verhoeven Arthur J , Ghiboub Mohammed , de Jonge Wouter J 
Published: June 2024

Abstract
The metabolic profile of dendritic cells (DCs) shapes their phenotype and functions. The carboxylesterase 1 (CES1) enzyme is highly expressed in mononuclear myeloid cells; however, its exact role in DCs is elusive. We used a CES1 inhibitor (WWL113) and genetic overexpression to explore the role of CES1 in DC differentiation in inflammatory models. CES1 expression was analyzed during CD14+ monocytes differentiation to DCs (MoDCs) using quantitative polymerase chain reaction. A CES1 inhibitor (WWL113) was applied during MoDC differentiation. Surface markers, secreted cytokines, lactic acid production, and phagocytic and T cell polarization capacity were analyzed. The transcriptomic and metabolic profiles were assessed with RNA sequencing and mass spectrometry, respectively. Cellular respiration was assessed using seahorse respirometry. Transgenic mice were used to assess the effect of CES1 overexpression in DCs in inflammatory models. CES1 expression peaked early during MoDC differentiation. Pharmacological inhibition of CES1 led to higher expression of CD209, CD86 and MHCII. WWL113 treated MoDCs secreted higher quantities of interleukin (IL)-6, IL-8, tumor necrosis factor, and IL-10 and demonstrated stronger phagocytic ability and a higher capacity to polarize T helper 17 differentiation in an autologous DC-T cell coculture model. Transcriptomic profiling revealed enrichment of multiple inflammatory and metabolic pathways. Functional metabolic analysis showed impaired maximal mitochondrial respiration capacity, increased lactate production, and decreased intracellular amino acids and tricarboxylic acid cycle intermediates. Transgenic human CES1 overexpression in murine DCs generated a less inflammatory phenotype and increased resistance to T cell–mediated colitis. In conclusion, CES1 inhibition directs DC differentiation toward a more inflammatory phenotype that shows a stronger phagocytic capacity and supports T helper 17 skewing. This is associated with a disrupted mitochondrial respiration and amino acid depletion.
(273) PIEZO TYPE-ESWT ALLEVIATES INFLAMMATION IN THE RAT MODEL OF CHRONIC PROSTATITIS
Authors: Shin Dongho , Piao JunJie , Oh Jin Sik , Kim Sae Woong 
Published: June 2024

Abstract

Objectives
To evaluate the anti-inflammatory effect of piezo type extracorporeal shock wave therapy (ESWT) in the rat model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods
For the in vivo experiments, SD male rats were randomly divided into 3 groups: (1) normal group, (2) CP/CPPS group, and (3) ESWT group (n=6 for each group). Prostatitis was induced with 17 beta-estradiol. After 4 weeks of piezo type ESWT, prostate tissues were harvested for histopathological analysis and western blotting assay.

Results
A previous study in our laboratory found that the optimal energy flux density of ESWT is 0.2 mJ/mm2, so we used this energy flux in this in vivo experiment and found that piezo type ESWT improved the inflammatory symptoms of prostatitis masters. H&E staining of prostate tissues revealed that the inflammatory symptoms of piezo type ESWT were significantly improved relative to the CP/CPPS group. Inflammation-related cytokines such as TNF-α, IL-6 and IL-8 were significantly reduced after piezo type ESWT as derived by western blotting.

Conclusions
In a rat model, piezo type ESWT effectively reduced the inflammatory factors TNF-α, IL-6 and IL-8, and also showed significant improvement in histopathology, and we found that piezo type ESWT may be a potential in the treatment of CP/CPPS.

Conflicts of Interest
None.
(234) TEMPORAL EVOLUTION IN TESTOSTERONE MEASUREMENTS AND DOSES OF TESTOSTERONE REPLACEMENT THERAPY REIMBURSED BY THE BELGIAN HEALTHCARE SYSTEM BETWEEN 2013 AND 2019
Authors: Narinx Nick , Walravens Joeri , Fiers Tom , Lapauw Prof Bruno , Antonio Prof Leen 
Published: June 2024

Abstract

Objectives
There are large regional and international differences in prescription patterns of testosterone replacement therapy (TRT) and testosterone measurements, with increases in testosterone prescriptions reported in several countries. We investigated temporal changes in testosterone testing and reimbursed doses of TRT covered by the Belgian healthcare system.

Methods
Anonymous data on serum total testosterone measurements (number of analyses and amount spent in euro) in men 17 years or older, were requested from the government (RIZIV) for 2012-2022. Data on TRT were requested from the government (Farmanet) from 1-2013 until 11-2019 (requested results for 12-2019 – 12-2022 pending). This covers pharmaceutical preparations reimbursed in Belgium, prescribed by a physician and provided to the patient via public pharmacies. In Belgium, only Sustanon® is reimbursed, so this dataset does not comprise transdermal preparations or testosterone undecanoate. Data were provided as number of delivered packages and amount spent. Since 2012, one package of Sustanon® on the Belgian market contains one dose of 250 mg testosterone esters.

Results
In 2013, total testosterone was measured 105.060 times in Belgian adult men. This increased to 138.570 in 2019 (+32% over a 7-year time period). The amount spent by the healthcare system for testosterone testing increased from €379.394 in 2013 to €487.645 in 2019 (+29%). In 2013, 38.695 doses of Sustanon® were sold. In 2019, this increased to 56.789 doses (+47%), corresponding to a cost of €380.403 in 2013 and €496.390 (+30%). From 2013 till 2019, the population of Belgian adult men increased by 4.3%.

Conclusions
The number of testosterone measurements increased by 32% in Belgium between 2013 and 2019. Remarkably, the number of doses of the only reimbursed testosterone replacement therapy showed an increase of 47% over a 7-year time period, showing a similar trend of prescription pattern increases as reported in other European countries.

Conflicts of Interest
This work was funded by an Applied Biomedical Research with a Primary Societal finality (TBM) project-grant from the Flanders Research Foundation (FWO-TBM T004321N). Leen Antonio participated in advisory boards for Galapagos, Merck and Androlabs.
(257) CYSTOSCOPY AND ITS POTENTIAL ASSOCIATION WITH PEYRONIE’S DISEASE: A RETROSPECTIVE COHORT STUDY
Authors: Durukan Dr Emil , Jensen Christian FS , Østergren Peter B , Frandsen Dr Rasmus , Fode Prof Mikkel 
Published: June 2024

Abstract

Objectives
Patients may present with Peyronie's disease (PD) following cystoscopy. The potential link between the two remains uncertain. We aimed to investigate the potential association.

Methods
We retrospectively analyzed electronic health records from the Capital and Zealand regions of Denmark to study men diagnosed with PD between January 2018 and October 2022. Initially, we identified men diagnosed with PD between January 2018 and October 2022 and calculated their interquartile age range. We then focused on men who underwent cystoscopy within the same time frame and whose age fell within the same interquartile range (IQR). We collected data on PD risk factors (diabetes, hypertension, ischemic heart disease, erectile dysfunction, Dupuytren’s contracture) and determined the number of men diagnosed with PD within a year after their cystoscopy. We included similar-aged men who had scrotal ultrasound or thoracic x-ray for comparison, representing urological and non-urological examinations.

Results
The IQR for PD patients was 52-66 years. During the timeframe, 6,210 men within this age range underwent cystoscopies, 6,691 underwent scrotal ultrasound, and 70,927 underwent thoracic x-ray. Risk factors for PD were present in 23% in the cystoscopy group, 17% of the ultrasound group, and 22% in the x-ray group. Within the following year of their respective procedures, PD were diagnosed in 0.97%, 1.85%, and 0.16% in the three groups, respectively. The adjusted odds ratios for PD were 0.369 (95% CI 0.268 – 0.507, p &lt;0.0001) for cystoscopy vs. ultrasound and 6.258 (95% CI 4.547 – 8.612, p &lt;0.0001) for cystoscopy vs. x-ray.

Conclusions
As there is no plausible mechanism for scrotal ultrasound to cause PD, our analysis implies that having an examination of the male genitals leads to a higher chance of being diagnosed with PD, while cystoscopy is not a specific risk factor. Prospective studies are needed to further address the topic.

Conflicts of Interest
No conflict of interests.
(210) EXPRESSION OF POTENTIAL FUNCTIONAL SIGNIFICANCE OF ARGINASE ISOENZYMES (L-ARGININE-AMINIDOHYDROLASES) IN THE HUMAN PROSTATE
Authors: Ückert Prof Stefan , Kedia Priv-Doz George T , Tsikas Prof Dimitrios , Märker Dr Viktoria , Kuczyk Prof Markus A 
Published: June 2024

Abstract

Objectives
There is evidence that the nitric oxide (NO)/cyclic GMP pathway contributes mainly to the control of the normal function of smooth musculature in the human prostate. The activity of nitric oxide synthases (NOS) is in part regulated by arginase enzymes (L-arginine-aminidohydrolases, Arg), known to hydrolyse the amino acid L-arginine (the common substrate of NOS and Arg) to L-ornithineand urea. We have investigated in the transition zone of the human prostate the expression and potential functional significance of arginase enzymes type I and type II (Arg I, Arg II).

Methods
Human prostate tissue was obtained from male subjects who had undergone pelvic surgery (prostatectomy/cystectomy). The expression of Arg I and Arg II was investigated by means of Western blot analysis. Using the tissue bath technique, the effects were assessed of the cumulative administration of arginase inhibitors (DFMO, H-Orn-OH.HCl, H-Ile-OH, nor-NOHA, 1 nM - 10 μM each) on the tension induced by the alpha-adrenergic agonist norepinephrine (NE) of isolated prostate tissue. The production of cyclic GMP in the tissue strips in response to exposure to the compounds was measured also.

Results
Western blot analysis revealed the expression of Arg I and Arg II in the transition zone of the prostate. The tension induced by NE was antagonized by the arginase inhibitors with the following rank order of efficacy: H-Orn-OH.HCl ≥ H-Ile-OH ≥ DFMO &gt; nor-NOHA (in a range from -13% to -25%). The enhancement in cyclic GMP production registered in the presence of the arginase inhibitors was 4-fold to 14-fold.

Conclusions
Arg I and Arg II are expressed in the human prostate. Isometric tension studies and measurement of cyclic GMP showed that inhibition of arginase can reverse, to a certain degree, the tension of prostate smooth muscle induced by the activation of alpha-adrenoceptors and enhance the accumulation of cyclic GMP.

Conflicts of Interest
The authors have no conflicts of interest to declare.
(299) THE ROLE OF ATTACHMENT IN PORNOGRAPHY USE AND PROBLEMATIC PORNOGRAPHY USE: A SYSTEMATIC REVIEW
Authors: Ghinassi Simon , Fioravanti Giulia , Casale Silva , Benucci Sara Bocci 
Published: June 2024

Abstract

Objectives
Pornography Use (PU) is a widespread and socially accepted behavior in most parts of the world. However, its uncontrolled use, i.e., Problematic Pornography Use (PPU), can have negative consequences for the health of the individual. Among the factors associated with such behavior, attachment appears to play a significant role. However, the evidence on the association between attachment-related phenomena and PU/PPU has not yet been systematized in the literature. Therefore, the present systematic review aims to fill this gap.

Methods
Following the updated PRISMA 2020 guidelines, the research process of the studies through four electronic scientific databases (Scopus, PubMed, ScienceDirect and Web of Science) has led to the identification of 160 records. Subsequently, duplicates (n = 83) were removed, and the titles and abstracts of the remaining 77 were screened. After this preliminary screening, 37 full-text records were examined for eligibility assessment, and 10 articles met the eligibility criteria and were selected for the present systematic review.

Results
Findings from these studies have shown the significant role played by attachment-related phenomena in PU and PPU, highlighting some differences according to the type of attachment considered. While anxious attachment has emerged to be associated with both PU and PPU, the results regarding avoidant attachment were mixed. Moreover, the secure attachment indicators were considered only in PU, and the results obtained were not consistent.

Conclusions
Overall, the results suggest that individuals with insecure attachment are more likely to use pornography, also in a problematic way. Specifically, the findings suggest that people with high levels of attachment anxiety may tend to use pornography to cope with their fear of being abandoned and rejected by significant others, such as their romantic or sexual partner. Limitations, strengths, and implications of the present systematic review will be discussed.

Conflicts of Interest
No conflicts of interest to declare.