bluuebunny/crossref_metadata_2025 huggingface dataset:
Should we stop referring to the pandemic of antimicrobial resistance as silent?
Authors: Sirota Miroslav
Published: February 2024

Background

Referring to the ongoing antimicrobial resistance crisis as a ‘silent’ pandemic has gained popularity, but there are mixed views on whether such a phrase should be used in public health communication. Some researchers have argued that using the term ‘silent pandemic’ may lower the perceived threat and hinder mobilization efforts to tackle the problem.

Objectives

I investigated the impact of the phrase ‘silent pandemic’ on perceived threat levels and mobilization intentions.

Methods

In three experiments (n = 1677), participants from the UK’s general adult population were randomly allocated to either a ‘pandemic’ or ‘silent pandemic’ condition, where the different terms were embedded in statements (Experiment 1) or brief information materials (Experiments 2 and 3). The term ‘silent pandemic’ was also presented with a brief description of its intended meaning (Experiment 3). The participants expressed their perception of the threat and their mobilization intentions.

Results

In Experiments 1 and 2, referring to the pandemic as silent did not significantly affect the perceived threat (Cohen’s d = −0.06; Cohen’s d = 0.08, respectively) or mobilization intentions (Cohen’s d = −0.07; Cohen’s d = 0.11, respectively). However, in Experiment 3, the term ‘silent pandemic’ decreased the perceived threat and mobilization intentions (Cohen’s d = 0.27; Cohen’s d = 0.35, respectively).

Conclusions

Describing the pandemic as ‘silent’ yielded no measurable effects on perceived threat and mobilization intentions but it showed depreciating effects when accompanied by its intended meaning. Taken together, it is advisable to avoid the term.
The impact of arthritogenic viruses in oral tissues
Authors: Anestino Thales Augusto , Queiroz-Junior Celso Martins , Cruz Amanda Medeiros Frota , Souza Daniele G , Madeira Mila Fernandes Moreira
Published: February 2024

Arthritis and periodontitis are inflammatory diseases that share several immunopathogenic features. The expansion in the study of virus-induced arthritis has shed light on how this condition could impact other parts of the human body, including the mouth. Viral arthritis is an inflammatory joint disease caused by several viruses, most notably the alphaviruses Chikungunya virus (CHIKV), Sindbis virus (SINV), Ross River virus (RRV), Mayaro virus (MAYV), and O'nyong'nyong virus (ONNV). These viruses can induce an upsurge of matrix metalloproteinases and immune-inflammatory mediators such as Interleukin-6 (IL6), IL-1β, tumor necrosis factor, chemokine ligand 2, and receptor activator of nuclear factor kappa-B ligand in the joint and serum of infected individuals. This can lead to the influx of inflammatory cells to the joints and associated muscles as well as osteoclast activation and differentiation, culminating in clinical signs of swelling, pain, and bone resorption. Moreover, several data indicate that these viral infections can affect other sites of the body, including the mouth. The human oral cavity is a rich and diverse microbial ecosystem, and viral infection can disrupt the balance of microbial species, causing local dysbiosis. Such events can result in oral mucosal damage and gingival bleeding, which are indicative of periodontitis. Additionally, infection by RRV, CHIKV, SINV, MAYV, or ONNV can trigger the formation of osteoclasts and upregulate pro-osteoclastogenic inflammatory mediators, interfering with osteoclast activation. As a result, these viruses may be linked to systemic conditions, including oral manifestations. Therefore, this review focuses on the involvement of alphavirus infections in joint and oral health, acting as potential agents associated with oral mucosal inflammation and alveolar bone loss. The findings of this review demonstrate how alphavirus infections could be linked to the comorbidity between arthritis and periodontitis and may provide a better understanding of potential therapeutic management for both conditions.
Screening for the production of polyunsaturated fatty acids and cerebrosides in fungi
Authors: Calarnou Laurie , Vigouroux Estelle , Thollas Bertrand , Le Grand Fabienne , Mounier Jérôme
Published: February 2024

Aims

To investigate fatty acid, including polyunsaturated fatty acids (PUFA), and cerebroside production of a large diversity of fungi from the Ascomycota, Basidiomycota, and Mucoromycota phyla.

Methods and results

Seventy-nine fungal strains were grown in Kavadia medium using a microcultivation system, i.e. Duetz microtiter plates. Following cultivation, fatty acid and cerebroside contents were analyzed by gas chromatography-flame ionization detection (GC-FID) and high performance thin-layer chromatography (HPTLC), respectively.

Mucoromycota fungi appeared as the most promising candidates for omega-6 PUFA production. The best omega-6 producer, including γ-linolenic acid (GLA, 18:3n-6), was Mucor fragilis UBOCC-A109196 with a concentration of 647 mg L−1 total omega-6 PUFA (representing 35% of total fatty acids) and 225 mg L−1 GLA (representing 12% of total fatty acids). Arachidonic acid concentration (20:4n-6) was the highest in Mortierella alpina UBOCC-A-112046, reaching 255 mg L−1 and 18.56% of total fatty acids. Interestingly, several fungal strains were shown to produce omega-7 monounsaturated fatty acids. Indeed, Torulaspora delbrueckii strains accumulated palmitoleic acid (16:1n-7) up to 20% of total fatty acids, reaching 114 mg L−1 in T. delbrueckii UBOCC-A-214128, while C. elegans UBOCC-A-102008 produced mainly paullinic acid (20:1n-7) with concentrations up to 100 mg L−1. Concerning cerebroside production, HPTLC appeared as a relevant approach for their detection and quantification. Promising candidates belonging to the Mucoromycota phylum were found, especially in the Absidia genus with A. spinosa UBOCC-A-101332 as the best producer (12.7 mg L−1).

Conclusions

The present study highlighted PUFA and cerebroside production in a large diversity of fungi and the fact that members of the Mucoromycota phylum are good producers of PUFA as well as cerebrosides.
Diurnal variation in genetic parameters for locomotor activity in Drosophila melanogaster assessed under natural thermal conditions
Authors: Noer Natasja Krog , Rohde Palle Duun , Sørensen Peter , Bahrndorff Simon , Kristensen Torsten Nygaard
Published: February 2024

In nature, organisms are exposed to variable and occasionally stressful environmental conditions. Responses to diurnal and seasonal fluctuations, such as temperature and food accessibility, involve adaptive behavioural and physiological changes. While much work has been done on understanding the genetic architecture and evolutionary potential of stress tolerance traits under constant thermal conditions, there has been less focus on the quantitative genetic background in variable environments. In this study, we use the Drosophila Genetic Reference Panel (DGRP) to investigate the locomotor activity, a key behavioural trait, under variable natural thermal conditions during the summer in a temperate environment. Male flies from 100 DGRP lines were exposed to natural thermal and light conditions in Drosophila activity monitors across three experimental days. We found that activity was highly temperature and time dependent and varied between lines both within and between days. Furthermore, we observed variation in genetic and environmental variance components, with low to moderate estimates of the heritability for locomotor activity, consistently peaking in the afternoons. Moreover, we showed that the estimated genetic correlations of locomotor activity between two time points decreased, as the absolute differences in ambient temperature increased. In conclusion, we find that the genetic background for locomotor activity is environment specific, and we conclude that more variable and unpredictable future temperatures will likely have a strong impact on the evolutionary trajectories of behavioural traits in ectotherms.
Automatic thrust/fault and edge location with gravity data across the Shillong plateau and Mikir hill complex in northeastern India using the most positive and most negative curvature interpretation
Authors: Ghosh Gopal K
Published: February 2024

Northeast India encompasses numerous thrusts, faults, and lineaments with undulated surface topography and is one of the utmost tectonically active regions in the world. Owing to the results of the collision of the Indian Plate under the Tibetan Plate and Burmese Plate, respectively, this area has affected the highest seismic potential zone-V, triggering many earthquakes. The current study area is located in and around the Shillong plateau, Mikir Hills, Naga Hills, Arakan-Yoma fold belt, Bengal basin, and Mishmi hills of the Himalayan foothills and that fall under the northeast of India. The thrusts and faults information available in this area are very scanty due to limited availability of geoscientific data and revealing seismic survey. Henceforth, it is necessary to get enhanced geoscientific learning for a better understanding of thrusts, faults, and lineaments information, the most positive and most negative curvature attribute analyses have been carried out using ground gravity data in this area. The significant derived results from this study encourage supplementary findings of thrust, fault, and lineament information, which also correlate well with the previously found results of 3D Euler deconvolution and source edge detection. Although, gravity data interpretation has its own limitations, however, the current derived results using the latest curvature analysis approach utilizing gravity data show realistic invigorated solutions for a better understanding of the thrust, fault, and lineament locations in this area.
Does administrative burden create racialized policy feedback? How losing access to public benefits impacts beliefs about government
Authors: Bell Elizabeth , Wright James E , Oh Jeongmin
Published: February 2024

Public trust and civic predisposition are cornerstones of well-functioning democratic societies, and burdensome citizen-state encounters may undermine positive views of government, especially for racially minoritized clientele. Leveraging insights from policy feedback theory, we argue that administrative burden has the potential to undermine trust in government and civic predisposition through two mechanisms: (1) interpretive effects: burdensome experiences that induce negative emotional responses and (2) resource effects: experiences of losing access to public benefits. In our OLS regression analysis of survey data from applicants for a means-tested public benefit program in the US (n = 2,250), we find that clients who lost access to benefits were significantly less likely to trust government, and these findings were driven by racially minoritized clients rather than White clients. Our findings demonstrate that experiences of administrative burden that result in the loss of public benefits may result in racialized policy feedback, by disproportionately reducing trust in government and civic predisposition for racially minoritized clientele.
Unsupervised Bayesian classification for models with scalar and functional covariates
Authors: Garcia Nancy L , Rodrigues-Motta Mariana , Migon Helio S , Petkova Eva , Tarpey Thaddeus , Ogden R Todd , Giordano Julio O , Perez Martin M
Published: February 2024

We consider unsupervised classification by means of a latent multinomial variable which categorizes a scalar response into one of the L components of a mixture model which incorporates scalar and functional covariates. This process can be thought as a hierarchical model with the first level modelling a scalar response according to a mixture of parametric distributions and the second level modelling the mixture probabilities by means of a generalized linear model with functional and scalar covariates. The traditional approach of treating functional covariates as vectors not only suffers from the curse of dimensionality, since functional covariates can be measured at very small intervals leading to a highly parametrized model, but also does not take into account the nature of the data. We use basis expansions to reduce the dimensionality and a Bayesian approach for estimating the parameters while providing predictions of the latent classification vector. The method is motivated by two data examples that are not easily handled by existing methods. The first example concerns identifying placebo responders on a clinical trial (normal mixture model) and the other predicting illness for milking cows (zero-inflated mixture of the Poisson model).
(015) The Association Between Prostate Volume and Erectile Function Recovery Following Radical Prostatectomy
Authors: Thorogood SL , Liso N , Laudone V , Ehdaie B , Mulhall JP , Flores JM
Published: February 2024

Introduction

The relationship between prostate volume (PV) and erectile function recovery (EFR) after radical prostatectomy (RP) has not been well studied.

Objective

We aimed to evaluate PV as a predictor of EFR 24 months after RP.

Methods

We included men who underwent RP with surgeon-reported nerve-sparing score (NSS) and 2-year follow up who had documentation of pre-RP PV on MRI and baseline functional erections (pre-RP IIEF-EFD scores ≥ 24). Demographics, ED-related comorbidities, pathological features, PDE5i use, and total testosterone (T) levels were recorded. At 12 months post-RP, patients scored PDE5i use 0-3; 0 never, 1 sometimes, 2 regularly, 3 routinely. NSS on each side (R/L) was scored on a 1-4 scale: 1 complete preservation, 2 near-complete preservation, 3 partial resection, 4 complete resection. Scores of 1 or 2 indicate nerve-sparing and scores of 3 or 4 indicate non-nerve-sparing. We then classified overall NS status as bilateral, unilateral, or non-spared. At 24 months post-RP, EFD score ≥ 24 defined functional erections, ≤ 10 severe ED. Multivariable analysis (MVA) evaluated predictors of EFD score ≥ 24 as well as EFD ≤ 10 after RP; patient age, number of comorbidities, baseline EF, NSS, PDE5i use, and PV were analyzed.

Results

1741 men were included. Median age was 60 (55, 65) years. 36% had ≥ 2 comorbidities. Median PV was 33 (26, 44) mL with 12% having PV ≥ 60 mL. Median pre-RP IIEF-EFD score was 29 (27, 30). Grade group 1, 2, 3, 4 and 5 comprised 12%, 68%, 15%, 2%, and 3% of the cohort, respectively. NSS: bilateral (82%), unilateral (15%), non-spared (3%). Median PDE5i use score within 4 weeks of the 12 month post-RP visit was 1 (0, 1); reported PDE5i use was 44% never, 39% sometimes, 13% regularly, and 4% routinely. At 24 months post-RP, median EFD was 22 (9, 28), and 56% had EFD < 24. Men with post-RP EFD < 24 had greater PV (41 ± 26 mL) vs men with EFD ≥ 24 (36 ± 17 mL, p<0.001). 67% of the men with EFD < 24 had a PV ≥ 60 mL vs 33% of men with EFD ≥ 24 (p=0.02). On MVA, predictors of EFD ≥ 24 included bilateral NS, age and PV. Predictors of EFD ≤ 10 included bilateral NS and age. At 24 months post-RP, neither routine PDE5i use nor a higher comorbidity index were predictive of EF outcome.

Conclusions

Among men with functional erections pre-RP, larger PV is associated with a poorer EFR at 24m post-RP independent of degree of nerve-sparing, age, and PDE5i use.

Disclosure

No.
(027) Assessment of Sexual Medicine Curriculum Across Northeast Medical Schools
Authors: Milazzo M , Parwatkar K , Perelmuter S , Blackman C , Tomaszewski A , Williams A , Lufler R , Rubin R
Published: February 2024

Introduction

Sexual health is an imperative area of study in medical school education. However, many medical schools do not offer a comprehensive curriculum nor is it standardized across the US. The history of sexual health as an academic area was introduced in the 1970s but minimal work has been done to assess the validity and accuracy of teachings. While previous work has evaluated the full, mandatory, sexual health course in year 1 medicine at a large state university, the relationship between curricula across different institutions has not been considered (Ross, Bayer, 2021).

Objective

The sexual medicine curriculum across U.S. medical schools has not been well documented or standardized. This study aims to assess the current guidelines and recommendations for sexual health curriculums in medical schools across the northeast region and compare the current teachings to suggested standards.

Methods

A compilation of academic resources including lecture material and syllabus will be systematically reviewed utilizing a standardized and validated rubric. The variables assessed include: biological and psychological aspects of human sexual development, anatomy and physiology of the human sexual response cycle, sexual health in relation to human reproduction, and contraceptive options.

Results

Statistical analyses will include a chi-squared to determine whether rubric ratings differ by region, type of school and degree awarded as well as a four-way ANOVA to explore whether geographic region, school control, degree awarded, and research activity levels influence the quantity and quality of sexual health curricula.

Conclusions

The goal of this study is to determine the areas of discrepancies between guidelines of sexual health curricula and the current teachings with the aim to improve sexual medicine education in U.S. medical schools.

Disclosure

No.
(090) The Relationship Between C-Reactive Protein and Total Testosterone in Aging Men: Findings from the Baltimore Longitudinal Study of Aging
Authors: Grewal MR , Gurayah AA , Weber AR , Ramasamy R
Published: February 2024

Introduction

Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, diabetes, and cardiovascular disease. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome are considered. We hypothesized that men with testosterone deficiency will have high levels of CRP.

Objective

We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging and specifically attempted to determine if low androgen status is associated with a high inflammatory profile independent of comorbidities.

Methods

Male participants with serum TT level measured during two separate visits >3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL) and Triglyceride levels were collected via blood specimens. Comorbidity data were documented at each visit. Panel regression was used to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable for modeling.

Results

A total of 347 patients were included in this study (mean age = 69 ± 15, average follow up time = 6.7 ± 3.2 years). Participants had a median CRP level of 1.0 mg/dL and a median TT level of 446 ng/dL. On univariable analysis TT and HDL levels were associated with a decline in CRP, while BMI, congestive heart failure (CHF), Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP. On multivariable analysis, we found that increasing TT level was associated with a decline in CRP levels, independent of comorbidities (p = 0.018; Table 1). BMI was associated with a significant increase in CRP (p = 0.001, Table 1). Age, CHF, Diabetes, HDL, and Triglycerides were not significant predictors of CRP on multivariable analysis.

Conclusions

Lower levels of serum total testosterone are associated with an increased CRP in older men. Given the importance of CRP in pathogenesis of chronic disease, we highlight the potential benefits of restoring testosterone levels in older, hypogonadal men via TRT.

Disclosure

No.
(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

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

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

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<0.001) and/or radiation (5.51% vs 10.9%, p<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

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<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

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 < 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 < 0.05), followed by 10.74 cm/s (± 1.43, p < 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

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 >52%, 7% HB >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

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

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

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

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.
Molecular basis of an atypical dsDNA 5mC/6mA bifunctional dioxygenase CcTet from Coprinopsis cinerea in catalyzing dsDNA 5mC demethylation
Authors: Zhang Lin , Mu Yajuan , Li Tingting , Hu Jingyan , Lin Houwen , Zhang Liang
Published: February 2024

The eukaryotic epigenetic modifications 5-methyldeoxycytosine (5mC) and N6-methyldeoxyadenine (6mA) have indispensable regulatory roles in gene expression and embryonic development. We recently identified an atypical bifunctional dioxygenase CcTet from Coprinopsis cinerea that works on both 5mC and 6mA demethylation. The nonconserved residues Gly331 and Asp337 of CcTet facilitate 6mA accommodation, while D337F unexpectedly abolishes 5mC oxidation activity without interfering 6mA demethylation, indicating a prominent distinct but unclear 5mC oxidation mechanism to the conventional Tet enzymes. Here, we assessed the molecular mechanism of CcTet in catalyzing 5mC oxidation by representing the crystal structure of CcTet–5mC-dsDNA complex. We identified the distinct mechanism by which CcTet recognizes 5mC-dsDNA compared to 6mA-dsDNA substrate. Moreover, Asp337 was found to have a central role in compensating for the loss of a critical 5mC-stablizing H-bond observed in conventional Tet enzymes, and stabilizes 5mC and subsequent intermediates through an H-bond with the N4 atom of the substrates. These findings improve our understanding of Tet enzyme functions in the dsDNA 5mC and 6mA demethylation pathways, and provide useful information for future discovery of small molecular probes targeting Tet enzymes in DNA active demethylation processes.
Differential expression of paralog RNA binding proteins establishes a dynamic splicing program required for normal cerebral cortex development
Authors: Cesari Eleonora , Farini Donatella , Medici Vanessa , Ehrmann Ingrid , Guerra Marika , Testa Erika , Naro Chiara , Geloso Maria Concetta , Pagliarini Vittoria , La Barbera Livia , D’Amelio Marcello , Orsini Tiziana , Vecchioli Stefano Farioli , Tamagnone Luca , Fort Philippe , Viscomi Maria Teresa , Elliott David J , Sette Claudio
Published: February 2024

Sam68 and SLM2 are paralog RNA binding proteins (RBPs) expressed in the cerebral cortex and display similar splicing activities. However, their relative functions during cortical development are unknown. We found that these RBPs exhibit an opposite expression pattern during development. Sam68 expression declines postnatally while SLM2 increases after birth, and this developmental pattern is reinforced by hierarchical control of Sam68 expression by SLM2. Analysis of Sam68:Slm2 double knockout (Sam68:Slm2dko) mice revealed hundreds of exons that respond to joint depletion of these proteins. Moreover, parallel analysis of single and double knockout cortices indicated that exons regulated mainly by SLM2 are characterized by a dynamic splicing pattern during development, whereas Sam68-dependent exons are spliced at relatively constant rates. Dynamic splicing of SLM2-sensitive exons is completely suppressed in the Sam68:Slm2dko developing cortex. Sam68:Slm2dko mice die perinatally with defects in neurogenesis and in neuronal differentiation, and develop a hydrocephalus, consistent with splicing alterations in genes related to these biological processes. Thus, our study reveals that developmental control of separate Sam68 and Slm2 paralog genes encoding homologous RBPs enables the orchestration of a dynamic splicing program needed for brain development and viability, while ensuring a robust redundant mechanism that supports proper cortical development.