bluuebunny/crossref_metadata_2025_split huggingface dataset:
(117) Interrater Agreement and Feasibility of Three-Dimensional Photography for Curvature Assessment in Peyronie's Disease
Authors: Thorogood SL , Novaes LF , Furtado TP , Flores JM , Mulhall JP 
Published: February 2024

Abstract

Introduction
Curvature assessment is an iterative aspect of the evaluation of Peyronie’s Disease (PD); its accuracy is subject to patient erection quality and clinician technique. Prior studies have shown promising results when using 3D modeling software in curvature assessment, yet none have applied the technology to human subjects with complex PD in an authentic clinical scenario.

Objective
To evaluate the feasibility of using 3D modeling to assess penile deformity in PD patients.

Methods
MirrorMe3D is a HIPPA-compliant iOS mobile and web-based platform designed for 3D anatomical modeling. 2 trained urology fellows (coders 1 and 2) were trained to create models using the app by acquiring ≥ 12 images of the target obtained in a multiplanar, 360-degree fashion. Participants verbally consented to deidentified penile photography during their clinic visit for penile curvature assessment with Doppler ultrasound (CADUS). Photographs were obtained prior to performing DUS with the patient in the supine position and using a commercially available clip-on ring light and custom 3D-printed holder device placed over the penis base for stabilization. 3D models were generated upon completion of the visit and screened for quality. Curvature assessment on the 3D images included curvature direction, location, degrees, and other defects identified via visual inspection of the digital model.

Results
7 unique, quality 3D images were generated using 15-20 photos per participant (Figure 1). The time required to obtain images was 1-2 minutes. Once the 3D image was developed, the curvature assessment took about 5 minutes. Quantitative results are summarized in Table 1. We observed a high rate of agreement in terms of primary direction of curvature and an acceptable variance rate when evaluating degrees of curvature within a margin of 10°; of note, coders were in agreement with each other to within a 10° margin 100% of the time (7/7 patients). We also observed a high agreement rate when evaluating the presence of absence of tapering but low agreement when assessing for the presence of indentation and hourglass deformity. Regarding the penis stabilizer, our experience suggests that it may alter the base of the penis anatomy, but it improves capture of the organ with diminished interference from surrounding anatomy (scrotum, abdomen). Factors influencing the quality of the image were exam room set-up, patient anxiety about losing an erection, lighting, and body hair.

Conclusions
3D image-based PD assessment can be implemented with minimal impact to visit efficiency. The 3D technique does not appear to reproduce complex PD measurements obtained by CADUS; however, future studies will evaluate the utility of employing this technology to a larger cohort and also to monitor treatment effect in complex PD patients.

Disclosure
No.
(127) Sexual Health Implications Associated with Psychotropic Medication Use Among Adolescents During the COVID-19 Pandemic
Authors: Ghomeshi A , White J , Rivero M , Thomas J , Petrella F , Miller D , Ramasamy R 
Published: February 2024

Abstract

Introduction
The use of psychotropic medications has a notable effect on sexual well-being. Prolonged use is closely linked to dyspareunia, reduced sexual desire, hypogonadism, and erectile dysfunction. We hypothesized that there was an increase in the prescription rates of psychotropic medications among adolescent patients during the COVID-19 pandemic due to the unprecedented stress experienced by isolated youth.

Objective
We examined the prescription rates of psychotropic medications and the simultaneous usage of PDE5 inhibitors in adolescent patients during the COVID-19 pandemic in order to compare usage of these medications prior to the pandemic.

Methods
To conduct our retrospective matched cohort study, we utilized data obtained from the TriNetX Research Network. The study focused on adolescent patients aged 10-19 presenting for outpatient evaluation, and were placed into two cohorts: 1) those evaluated before the COVID-19 pandemic, and 2) those evaluated during the pandemic. Patients with previous psychiatric diagnoses or prior use of psychotropic medications were excluded from the study. Our primary interest was to examine new prescription patterns within 90 days of the outpatient evaluation. To ensure balanced cohorts, propensity score matching was conducted using logistic regression, resulting in cohorts of equal size.

Results
A total of 1,612,283 adolescents pre-COVID-19 and 1,008,161 adolescents presenting during the COVID-19 pandemic for outpatient evaluations were identified. After propensity matching, a total of 1,005,408 adolescents were included in each cohort each with an average age of 14.7 ± 2.84 and 52% female and 48% male. Prescribing of antipsychotics and benzodiazepines were more frequent during the pandemic for adolescents (RR: 1.58, 95% CI 1.01-2.2). However, they were less likely to receive antidepressants (Risk Ratio (RR): 0.6, 95% Confidence Interval (CI) 0.57-0.63), anxiolytics (RR: 0.78, 95% CI 0.75-0.81), stimulants (RR: 0.26, 95% CI 0.25-0.27), as well as mood stabilizers (RR: 0.44, 95% CI 0.39-0.49). Erectile dysfunction requiring oral PDE5i in this cohort was more frequent during the pandemic for adolescents (RR: 1.53, 95% CI 1.05-2.01).

Conclusions
During the global COVID-19 pandemic, there was a notable rise in the prescription rates of antipsychotic and benzodiazepine medications compared to previous years. Interestingly, this increase aligned with a statistically significant rise in the prescription of PDE5 inhibitors (PDE5i) for treating erectile dysfunction. These findings indicate that clinicians need to be aware of the potential increased risk of medication-related sexual dysfunction among adolescents.

Disclosure
Yes, this is sponsored by industry/sponsor: NIH health grant RO1 DK130991 and Clinician Scientist Development Grant from the American Cancer Society.
Clarification: Industry funding only - investigator initiated and executed study.
(176) Prior Intracavernosal Injection Therapy and Prostate Cancer Treatment are Both Independently Associated with Increased Risks of Complications in Men Undergoing Inflatable Penile Prosthesis Placement
Authors: Jones JM , Barham DW , Gross MS , Chang C , Hammad MAM , Swerdloff D , Miller J , Andrianne R , Burnett AL , Gross K , Hatzichristodoulou G , Hotaling JM , Hsieh TC , Jones A , Lentz A , Modgil V , Osmonov D , Park SH , Pearce I , Perito P , Sadeghi-Nejad H , Sempels M , Suarez-Sarmiento Jr. A , Simhan J , van Renterghem K , Warner JN , Ziegelmann M , Yafi FA ,   on behalf of the PUMP (Prosthetic Urology Multi-institutional Partnership) collaborators
Published: February 2024

Abstract

Introduction
Intracavernosal injection (ICI) therapy for erectile dysfunction (ED) carries a risk of corporal fibrosis, potentially making placement of an inflatable penile prosthesis more difficult. Prostate cancer treatment may also induce corporal fibrosis.

Objective
To assess whether a history of ICI or prostate cancer treatment is associated with complications following IPP placement.

Methods
A retrospective cohort study of primary IPP cases from 2016-2021 across 16 institutions. Patients were stratified by history of ICI and between-group differences in risk factors were assessed. Multivariable logistic regression was used to assess for predictors of intraoperative complications, postoperative non-infectious complications and postoperative infection.

Results
A total of 2540 patients met inclusion criteria of which 781 (30.8%) had a history of ICI. Patients with a history of ICI tended to be older (mean 63 vs 64 years, p=0.002) and were more likely to have history of radical prostatectomy (21.0% vs. 32.1%, p&lt;0.001) and/or radiation (5.51% vs 10.9%, p&lt;0.001). On multivariable regression, a history of ICI, prostatectomy, and radiation were all significant predictors of intraoperative complications (OR 2.11, p=0.03; OR 2.27, p=0.03; OR 2.40, p=0.04, respectively). A history of ICI and patient age were predictors of non-infectious postoperative complications (OR 1.44, p=0.02, OR 1.02, p=0.004 respectively)). None of the variables were significant predictors of infection.

Conclusions
In men undergoing IPP placement, a history of ICI is associated with an increased risk of both intraoperative and postoperative, non-infectious complications. Prostate cancer treatment with radiation or surgery is independently associated with increased risk of intraoperative complications.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: D.O. has served as a consultant for Coloplast, Intuitive Surgical, and Fidelis. P.P. has served as a consultant for Coloplast, Boston Scientific, and Urofill. M.S. has served as a consultant for Boston Scientific and Coloplast. J.S. has served as a consultant for Boston Scientific and Coloplast. F.A.Y. has served as a consultant for Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, and Acerus Pharma. M.S.G. has served as a consultant for Coloplast. The other authors disclose no conflicts.
(228) Cell-Based Therapy Can Restore Erectile Function in Men with Type 2 Diabetes and Metabolic Syndrome by Promoting Angiogenesis and Endothelial Repair
Authors: Saltzman R , Firdaus F , Arora H , Khan A , Hare J , Ramasamy R 
Published: February 2024

Abstract

Introduction
Although there has been a growing interest in restorative therapies for erectile dysfunction (ED) in recent years, there is still limited mechanistic evidence to support their effectiveness in the clinical setting.

Objective
The goal of this research was to investigate the mechanistic impact of cell-based therapy in men with ED secondary to Type 2 Diabetes Mellitus (DM2) and Metabolic Syndrome (MetS) through analysis of plasma biomarkers.

Methods
International Index of Erectile Function (IIEF) was completed by all men in the ACESO (NCT02886884) and CERES (NCT03059355) clinical trials. ACESO and CERES were both randomized, blinded, pilot phase clinical trials in which all participants received cellular therapy at varying doses and sources to treat endothelial dysfunction secondary to either DM2 or MetS, respectively. The intervention in both trials was peripheral intravenous infusion of allogeneic Mesenchymal Stem Cells (MSCs) of either 20 or 100 million cells derived from either bone marrow (BM) or umbilical cord tissue (UC). Follow-up was for 1 year. Endothelial function was measured via Brachial Artery Flow Mediated Vasodilation (FMD) and Endothelial Progenitor Cell-Colony Forming Units (EPC-CFU) assay. Plasma aliquots were isolated from blood samples and subjected to multiplex ELISA assay for analysis of angiogenic biomarkers.

Results
Data was pooled from all 20 men in the ACESO and CERES clinical trials. Overall, 7 received 20 million BM-MSCs, 9 received 100 million BM-MSCs, 2 received 20 million UC-MSCs, and 2 received 100 million UC-MSCs. There were no treatment emergent serious adverse effects (TE-SAEs) within 30 days following infusion in any of the participants. Among men with ED (IIEF-EF&lt;25), 31.25% achieved MCID in erectile function. Participants with mild or moderate ED at baseline showed greater improvements in erectile function and endothelial function compared to those with severe ED. Participants who achieved MCID following cell therapy also experienced statistically significant improvements in FMD (P=0.05), whereas those who did not achieve MCID or had normal erectile function at baseline did not experience an improvement in FMD. Furthermore, men with Metabolic Syndrome who met MCID criteria were found to have increased Angiopoietin 1 and decreased Angiopoietin 2 following cell therapy.

Conclusions
The findings of this study demonstrate the potential of cell-based therapies in improving erectile function, angiogenic, and endothelial function. Future studies should aim to identify the causative mechanisms underlying these restorative effects in humans, paving the way for enhanced understanding and optimization of such therapies.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Longeveron LLC.
(313) Low-Intensity Extracorporeal Shockwave Therapy May Result in Improvements in Flaccid Cavernosal Artery Peak Systolic Velocity
Authors: Coffey S , Matthew A , Klaunser A , Smith R , Krzastek S 
Published: February 2024

Abstract

Introduction
Low-intensity extracorporeal shockwave therapy (LiESWT) is thought to treat erectile dysfunction (ED) by stimulating neovascularization and nerve regeneration. Studies suggest subjective improvements following treatment, but objective measures are sparse.

Objective
We aimed to objectively assess the efficacy of LiESWT in the treatment of ED using penile Doppler in men with ED following LiESWT therapy. We hypothesized that LiESWT results in demonstrable increases in penile blood flow.

Methods
Patients were prospectively enrolled in a clinical trial examining objective and subjective changes in erectile function following LiESWT. Patients underwent baseline examination with penile Duplex ultrasound in both the flaccid and rigid states following intracavernosal injection of alprostadil. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment, with follow up Duplex at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Highest peak systolic velocity (PSV) and lowest end diastolic velocity (EDV) were reported.

Results
Twenty-five patients completed all five study visits. The mean highest PSV in the flaccid state prior to treatment was 7.86 cm/s (± 1.47), which significantly increased to 11.31 cm/s (± 1.81, p &lt; 0.05) immediately following completion of treatments. This increase was sustained at 4-6 weeks with a mean PSV of 12.74 cm/s (± 1.80, p &lt; 0.05), followed by 10.74 cm/s (± 1.43, p &lt; 0.05) at 3 months, and 9.87 cm/s (± 1.14, p=0.11) at 6 months (Figure 1). No significant improvements were noted in flaccid lowest EDV or rigid peak PSV/lowest EDV.

Conclusions
Our results suggest that LiESWT may improve baseline penile vascularity. Overall, the clinical significance of the noted improvement in flaccid PSV after LiESWT remains to be determined and more work needs to be done to define the mechanism of action of LiESWT at a tissue level in human subjects.

Disclosure
No.
(327) Adverse Event Reporting in Testosterone Therapy Randomized Controlled Trials (RCT)
Authors: Novaes LF , Flores JM , Mulhall JP 
Published: February 2024

Abstract

Introduction
Testosterone (T) therapy (TTH) is associated with well recognized adverse events (AEs) such as: polycythemia (PCT), major adverse cardiac events (MACE), gynecomastia (GYN), worsening obstructive sleep apnea (OSA).

Objective
We aimed to critically analyze published TTH RCTs with regard to how well TTH AEs were reported.

Methods
A literature review was performed of all TTH RCTs listed on PUBMED that had been published between 1997-2021. We describe sample size, trial duration, industry funding, T assay used, baseline and on-treatment total and free T, TTH modality, and mean follow-up during the RCTs. We also describe the reporting of PCT, GYN, MACE, OSA and the definitions used in these RCTs.

Results
29 trials were reviewed (Table 1), 55% reported on transdermal T, 41% intramuscular T, 7% enclomiphene, 7% human chorionic gonadotropin and 7% other oral treatments (aromatase inhibitor, tamoxifen). 17% compared two TTH modalities. Median sample size was 73 [41, 189]. Median age was 63 [58, 67] years. Median follow-up in the RCT reported was 8 [6, 12] months. 55% had the support of pharmaceutical companies. The total T (TT) assay used was immunoassay (IA 59%), LCMS (24%), other (10%), while 7% did not report on the assay type, and only 55% reported free T level (79% calculate by Vermeulen formula, and 21% equilibrium dialysis). Median baseline TT level was 248 [227, 320] ng/dL; on TTH it was 528 [460, 621] ng/dL. Median baseline free T level was 5.4 [5, 6.3] ng/dL, on TTH it was 11.1 [9.3, 15.5] ng/dL. 83% measured HCT levels at any point, only 21% reported baseline levels, 24% reported post treatment. Median baseline HCT 43 [42, 46]%, post-TTH median HCT increase of 2.4[-2.5, +3]%. 52% reported on PCT rates (45% defined HCT &gt;52%, 7% HB &gt;17 g/dL). Median PCT rate was 2%, none mentioned phlebotomy. 17% of RCTs reported on GYN, with a median rate of 1.5%, while none mentioned GYN grade or if mammography had been performed. 17% of trials mentioned MACE, but only 2 defined MACE. Median MACE rate was 2%. 10% reported OSA, but none mentioned the type of assessment; the median rate was OSA 2%.

Conclusions
This analysis showed that the majority TTH RCTs have sub-optimal reporting of TTH safety.

Disclosure
No.
Numerical MHD simulations of solar flares and their associated small-scale structures
Authors: González-Servín Mauricio , González-Avilés J J 
Published: February 2024

ABSTRACT
Using numerical simulations, we study the formation and dynamics of solar flares in a local region of the solar atmosphere. The magnetohydrodynamics (MHD) equations describe the dynamic evolution of flares, including space-dependent and anomalous magnetic resistivity and highly anisotropic thermal conduction on a 2.5 D slice. We adopt an initial solar atmospheric model in magnetohydrostatic equilibrium, with a magnetic configuration consisting of a vertical current sheet, which helps trigger the magnetic reconnection process. Specifically, we study three scenarios, two with only resistivity and the third with resistivity plus thermal conduction. The main results of the numerical simulations show differences in the global morphology of the flares, including the post-flare loops and the current sheet in three cases. In particular, localized resistivity produces more substructure around the post-flare loops that could be related to the Ritchmyer–Meshkov Instability (RMI). Furthermore, in the scenario of anomalous resistivity, we identify the formation of a plasmoid and a jet at coronal heights. On the other hand, in the scenario with resistivity plus thermal conduction, the post-flare loops are smooth, and no apparent substructures develop. Besides, in the z-component of the current density for the Res + TC case, we observe the development of multiple magnetic islands generated due to the Tearing instability in the non-linear regime.
The unique dual targeting of AGO1 by two types of PRMT enzymes promotes phasiRNA loading in Arabidopsis thaliana
Authors: Barre-Villeneuve Clément , Laudié Michèle , Carpentier Marie-Christine , Kuhn Lauriane , Lagrange Thierry , Azevedo-Favory Jacinthe 
Published: February 2024

Abstract
Arginine/R methylation (R-met) of proteins is a widespread post-translational modification (PTM), deposited by a family of protein arginine/R methyl transferase enzymes (PRMT). Regulations by R-met are involved in key biological processes deeply studied in metazoan. Among those, post-transcriptional gene silencing (PTGS) can be regulated by R-met in animals and in plants. It mainly contributes to safeguard processes as protection of genome integrity in germlines through the regulation of piRNA pathway in metazoan, or response to bacterial infection through the control of AGO2 in plants. So far, only PRMT5 has been identified as the AGO/PIWI R-met writer in higher eukaryotes. We uncovered that AGO1, the main PTGS effector regulating plant development, contains unique R-met features among the AGO/PIWI superfamily, and outstanding in eukaryotes. Indeed, AGO1 contains both symmetric (sDMA) and asymmetric (aDMA) R-dimethylations and is dually targeted by PRMT5 and by another type I PRMT in Arabidopsis thaliana. We showed also that loss of sDMA didn’t compromise AtAGO1 subcellular trafficking in planta. Interestingly, we underscored that AtPRMT5 specifically promotes the loading of phasiRNA in AtAGO1. All our observations bring to consider this dual regulation of AtAGO1 in plant development and response to environment, and pinpoint the complexity of AGO1 post-translational regulation.
LSD1 controls a nuclear checkpoint in Wnt/β-Catenin signaling to regulate muscle stem cell self-renewal
Authors: Mouradian Sandrine , Cicciarello Delia , Lacoste Nicolas , Risson Valérie , Berretta Francesca , Le Grand Fabien , Rose Nicolas , Simonet Thomas , Schaeffer Laurent , Scionti Isabella 
Published: February 2024

Abstract
The Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/β-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the lysine demethylase LSD1/KDM1A converge to indicate that this epigenetic regulator is a key regulator of cell fate, although the extracellular cues controlling LSD1 action remain largely unknown. Here we show that β-Catenin is a substrate of LSD1. Demethylation by LSD1 prevents β-Catenin degradation thereby maintaining its nuclear levels. Consistently, in absence of LSD1, β-Catenin transcriptional activity is reduced in both MuSCs and ESCs. Moreover, inactivation of LSD1 in mouse muscle stem cells and embryonic stem cells shows that LSD1 promotes mitotic spindle orientation via β-Catenin protein stabilization. Altogether, by inscribing LSD1 and β-Catenin in the same molecular cascade linking extracellular factors to gene expression, our results provide a mechanistic explanation to the similarity of action of canonical Wnt/β-Catenin signaling and LSD1 on stem cell fate.
Rewiring of the epigenome and chromatin architecture by exogenously induced retinoic acid signaling during zebrafish embryonic development
Authors: Moreno-Oñate Marta , Gallardo-Fuentes Lourdes , Martínez-García Pedro M , Naranjo Silvia , Jiménez-Gancedo Sandra , Tena Juan J , Santos-Pereira José M 
Published: February 2024

Abstract
Retinoic acid (RA) is the ligand of RA receptors (RARs), transcription factors that bind to RA response elements. RA signaling is required for multiple processes during embryonic development, including body axis extension, hindbrain antero-posterior patterning and forelimb bud initiation. Although some RA target genes have been identified, little is known about the genome-wide effects of RA signaling during in vivo embryonic development. Here, we stimulate the RA pathway by treating zebrafish embryos with all-trans-RA (atRA) and use a combination of RNA-seq, ATAC-seq, ChIP-seq and HiChIP to gain insight into the molecular mechanisms by which exogenously induced RA signaling controls gene expression. We find that RA signaling is involved in anterior/posterior patterning, central nervous system development, and the transition from pluripotency to differentiation. AtRA treatment also alters chromatin accessibility during early development and promotes chromatin binding of RARαa and the RA targets Hoxb1b, Meis2b and Sox3, which cooperate in central nervous system development. Finally, we show that exogenous RA induces a rewiring of chromatin architecture, with alterations in chromatin 3D interactions involving target genes. Altogether, our findings identify genome-wide targets of RA signaling and provide a molecular mechanism by which developmental signaling pathways regulate target gene expression by altering chromatin topology.