bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz
Authors: Jones Dakota L. , Hallström Grey F. , Jiang Xi , Locke Ryan C. , Evans Mary Kate , Bonnevie Edward D. , Srikumar Anjana , Leahy Thomas P. , Nijsure Madhura P. , Boerckel Joel D. , Mauck Robert L. , Dyment Nathaniel A.
Published: May 2023

Cells integrate mechanical cues to direct fate specification to maintain tissue function and homeostasis. While disruption of these cues is known to lead to aberrant cell behavior and chronic diseases, such as tendinopathies, the underlying mechanisms by which mechanical signals maintain cell function are not well understood. Here, we show using a model of tendon de-tensioning that loss of tensile cues in vivo acutely changes nuclear morphology, positioning, and expression of catabolic gene programs, resulting in subsequent weakening of the tendon. In vitro studies using paired ATAC/RNAseq demonstrate that the loss of cellular tension rapidly reduces chromatin accessibility in the vicinity of Yap/Taz genomic targets while also increasing expression of genes involved in matrix catabolism. Concordantly, the depletion of Yap/Taz elevates matrix catabolic expression. Conversely, overexpression of Yap results in a reduction of chromatin accessibility at matrix catabolic gene loci, while also reducing transcriptional levels. The overexpression of Yap not only prevents the induction of this broad catabolic program following a loss of cellular tension, but also preserves the underlying chromatin state from force-induced alterations. Taken together, these results provide novel mechanistic details by which mechanoepigenetic signals regulate tendon cell function through a Yap/Taz axis.
Paf1 complex subunit Rtf1 stimulates H2B ubiquitylation by interacting with the highly conserved N-terminal helix of Rad6
Authors: Fetian Tasniem , McShane Brendan M. , Horan Nicole L. , Shodja Donya N. , True Jason D. , Mosley Amber L. , Arndt Karen M.
Published: May 2023

Histone modifications coupled to transcription elongation play important roles in regulating the accuracy and efficiency of gene expression. The monoubiquitylation of a conserved lysine in H2B (K123 in
Saccharomyces cerevisiae
; K120 in humans) occurs cotranscriptionally and is required for initiating a histone modification cascade on active genes. H2BK123 ubiquitylation (H2BK123ub) requires the RNA polymerase II (RNAPII)-associated Paf1 transcription elongation complex (Paf1C). Through its histone modification domain (HMD), the Rtf1 subunit of Paf1C directly interacts with the ubiquitin conjugase Rad6, leading to the stimulation of H2BK123ub in vivo and in vitro. To understand the molecular mechanisms that target Rad6 to its histone substrate, we identified the site of interaction for the HMD on Rad6. Using in vitro cross-linking followed by mass spectrometry, we localized the primary contact surface for the HMD to the highly conserved N-terminal helix of Rad6. Using a combination of genetic, biochemical, and in vivo protein cross-linking experiments, we characterized separation-of-function mutations in
S. cerevisiae RAD6
that greatly impair the Rad6–HMD interaction and H2BK123 ubiquitylation but not other Rad6 functions. By employing RNA-sequencing as a sensitive approach for comparing mutant phenotypes, we show that mutating either side of the proposed Rad6–HMD interface yields strikingly similar transcriptome profiles that extensively overlap with those of a mutant that lacks the site of ubiquitylation in H2B. Our results fit a model in which a specific interface between a transcription elongation factor and a ubiquitin conjugase guides substrate selection toward a highly conserved chromatin target during active gene expression.
Reproductive inequality in humans and other mammals
Authors: Ross Cody T. , Hooper Paul L. , Smith Jennifer E. , Jaeggi Adrian V. , Smith Eric Alden , Gavrilets Sergey , Zohora Fatema tuz , Ziker John , Xygalatas Dimitris , Wroblewski Emily E. , Wood Brian , Winterhalder Bruce , Willführ Kai P. , Willard Aiyana K. , Walker Kara , von Rueden Christopher , Voland Eckart , Valeggia Claudia , Vaitla Bapu , Urlacher Samuel , Towner Mary , Sum Chun-Yi , Sugiyama Lawrence S. , Strier Karen B. , Starkweather Kathrine , Major-Smith Daniel , Shenk Mary , Sear Rebecca , Seabright Edmond , Schacht Ryan , Scelza Brooke , Scaggs Shane , Salerno Jonathan , Revilla-Minaya Caissa , Redhead Daniel , Pusey Anne , Purzycki Benjamin Grant , Power Eleanor A. , Pisor Anne , Pettay Jenni , Perry Susan , Page Abigail E. , Pacheco-Cobos Luis , Oths Kathryn , Oh Seung-Yun , Nolin David , Nettle Daniel , Moya Cristina , Migliano Andrea Bamberg , Mertens Karl J. , McNamara Rita A. , McElreath Richard , Mattison Siobhan , Massengill Eric , Marlowe Frank , Madimenos Felicia , Macfarlan Shane , Lummaa Virpi , Lizarralde Roberto , Liu Ruizhe , Liebert Melissa A. , Lew-Levy Sheina , Leslie Paul , Lanning Joseph , Kramer Karen , Koster Jeremy , Kaplan Hillard S. , Jamsranjav Bayarsaikhan , Hurtado A. Magdalena , Hill Kim , Hewlett Barry , Helle Samuli , Headland Thomas , Headland Janet , Gurven Michael , Grimalda Gianluca , Greaves Russell , Golden Christopher D. , Godoy Irene , Gibson Mhairi , Mouden Claire El , Dyble Mark , Draper Patricia , Downey Sean , DeMarco Angelina L. , Davis Helen Elizabeth , Crabtree Stefani , Cortez Carmen , Colleran Heidi , Cohen Emma , Clark Gregory , Clark Julia , Caudell Mark A. , Carminito Chelsea E. , Bunce John , Boyette Adam , Bowles Samuel , Blumenfield Tami , Beheim Bret , Beckerman Stephen , Atkinson Quentin , Apicella Coren , Alam Nurul , Mulder Monique Borgerhoff
Published: May 2023

To address claims of human exceptionalism, we determine where humans fit within the greater mammalian distribution of reproductive inequality. We show that humans exhibit lower reproductive skew (i.e., inequality in the number of surviving offspring) among males and smaller sex differences in reproductive skew than most other mammals, while nevertheless falling within the mammalian range. Additionally, female reproductive skew is higher in polygynous human populations than in polygynous nonhumans mammals on average. This patterning of skew can be attributed in part to the prevalence of monogamy in humans compared to the predominance of polygyny in nonhuman mammals, to the limited degree of polygyny in the human societies that practice it, and to the importance of unequally held rival resources to women’s fitness. The muted reproductive inequality observed in humans appears to be linked to several unusual characteristics of our species—including high levels of cooperation among males, high dependence on unequally held rival resources, complementarities between maternal and paternal investment, as well as social and legal institutions that enforce monogamous norms.
Cryo-EM structure of the Mon1–Ccz1–RMC1 complex reveals molecular basis of metazoan RAB7A activation
Authors: Yong Xin , Jia Guowen , Liu Zhe , Zhou Chunzhuang , Yi Jiamin , Tang Yingying , Chen Li , Chen Lu , Wang Yuan , Sun Qingxiang , Billadeau Daniel D. , Su Zhaoming , Jia Da
Published: May 2023

Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1–Ccz1 dimeric complex to activate the small GTPase RAB7A, metazoans rely on the Mon1–Ccz1–RMC1 trimeric complex. Here, we report a near-atomic resolution cryogenic-electron microscopy structure of the
Drosophila
Mon1–Ccz1–RMC1 complex. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1 on the surface opposite to the RAB7A-binding site, with many of the RMC1-contacting residues from Mon1 and Ccz1 unique to metazoans, explaining the binding specificity. Significantly, the assembly of RMC1 with Mon1–Ccz1 is required for cellular RAB7A activation, autophagic functions and organismal development in zebrafish. Our studies offer a molecular explanation for the different degree of subunit conservation across species, and provide an excellent example of how metazoan-specific proteins take over existing functions in unicellular organisms.
Mutation rates and adaptive variation among the clinically dominant clusters of
Mycobacterium abscessus
Authors: Commins Nicoletta , Sullivan Mark R. , McGowen Kerry , Koch Evan M. , Rubin Eric J. , Farhat Maha
Published: May 2023

Mycobacterium abscessus
(
Mab
) is a multidrug-resistant pathogen increasingly responsible for severe pulmonary infections. Analysis of whole-genome sequences (WGS) of
Mab
demonstrates dense genetic clustering of clinical isolates collected from disparate geographic locations. This has been interpreted as supporting patient-to-patient transmission, but epidemiological studies have contradicted this interpretation. Here, we present evidence for a slowing of the
Mab
molecular clock rate coincident with the emergence of phylogenetic clusters. We performed phylogenetic inference using publicly available WGS from 483
Mab
patient isolates. We implement a subsampling approach in combination with coalescent analysis to estimate the molecular clock rate along the long internal branches of the tree, indicating a faster long-term molecular clock rate compared to branches within phylogenetic clusters. We used ancestry simulation to predict the effects of clock rate variation on phylogenetic clustering and found that the degree of clustering in the observed phylogeny is more easily explained by a clock rate slowdown than by transmission. We also find that phylogenetic clusters are enriched in mutations affecting DNA repair machinery and report that clustered isolates have lower spontaneous mutation rates in vitro. We propose that
Mab
adaptation to the host environment through variation in DNA repair genes affects the organism’s mutation rate and that this manifests as phylogenetic clustering. These results challenge the model that phylogenetic clustering in
Mab
is explained by person-to-person transmission and inform our understanding of transmission inference in emerging, facultative pathogens.
TRPV1 activation in human Langerhans cells and T cells inhibits mucosal HIV-1 infection via CGRP-dependent and independent mechanisms
Authors: Mariotton Jammy , Cohen Emmanuel , Zhu Aiwei , Auffray Cédric , Barbosa Bomfim Caio César , Barry Delongchamps Nicolas , Zerbib Marc , Bomsel Morgane , Ganor Yonatan
Published: May 2023

Upon its mucosal transmission, HIV type 1 (HIV-1) rapidly targets genital antigen-presenting Langerhans cells (LCs), which subsequently transfer infectious virus to CD4
+
T cells. We previously described an inhibitory neuroimmune cross talk, whereby calcitonin gene-related peptide (CGRP), a neuropeptide secreted by peripheral pain-sensing nociceptor neurons innervating all mucosal epithelia and associating with LCs, strongly inhibits HIV-1 transfer. As nociceptors secret CGRP following the activation of their Ca
2+
ion channel transient receptor potential vanilloid 1 (TRPV1), and as we reported that LCs secret low levels of CGRP, we investigated whether LCs express functional TRPV1. We found that human LCs expressed mRNA and protein of TRPV1, which was functional and induced Ca
2+
influx following activation with TRPV1 agonists, including capsaicin (CP). The treatment of LCs with TRPV1 agonists also increased CGRP secretion, reaching its anti-HIV-1 inhibitory concentrations. Accordingly, CP pretreatment significantly inhibited LCs-mediated HIV-1 transfer to CD4
+
T cells, which was abrogated by both TRPV1 and CGRP receptor antagonists. Like CGRP, CP-induced inhibition of HIV-1 transfer was mediated via increased CCL3 secretion and HIV-1 degradation. CP also inhibited direct CD4
+
T cells HIV-1 infection, but in CGRP-independent manners. Finally, pretreatment of inner foreskin tissue explants with CP markedly increased CGRP and CCL3 secretion, and upon subsequent polarized exposure to HIV-1, inhibited an increase in LC–T cell conjugate formation and consequently T cell infection. Our results reveal that TRPV1 activation in human LCs and CD4
+
T cells inhibits mucosal HIV-1 infection, via CGRP-dependent/independent mechanisms. Formulations containing TRPV1 agonists, already approved for pain relief, could hence be useful against HIV-1.
Self-organizing actin networks drive sequential endocytic protein recruitment and vesicle release on synthetic lipid bilayers
Authors: Stoops Emily H. , Ferrin Michael A. , Jorgens Danielle M. , Drubin David G.
Published: May 2023

Forces generated by actin assembly assist membrane invagination during clathrin-mediated endocytosis (CME). The sequential recruitment of core endocytic proteins and regulatory proteins, and assembly of the actin network, are well documented in live cells and are highly conserved from yeasts to humans. However, understanding of CME protein self-organization, as well as the biochemical and mechanical principles that underlie actin’s role in CME, is lacking. Here, we show that supported lipid bilayers coated with purified yeast Wiskott Aldrich Syndrome Protein (WASP), an endocytic actin assembly regulator, and incubated in cytoplasmic yeast extracts, recruit downstream endocytic proteins and assemble actin networks. Time-lapse imaging of WASP-coated bilayers revealed sequential recruitment of proteins from different endocytic modules, faithfully replicating in vivo behavior. Reconstituted actin networks assemble in a WASP-dependent manner and deform lipid bilayers, as seen by electron microscopy. Time-lapse imaging revealed that vesicles are released from the lipid bilayers with a burst of actin assembly. Actin networks pushing on membranes have previously been reconstituted; here, we have reconstituted a biologically important variation of these actin networks that self-organize on bilayers and produce pulling forces sufficient to bud off membrane vesicles. We propose that actin-driven vesicle generation may represent an ancient evolutionary precursor to diverse vesicle forming processes adapted for a wide array of cellular environments and applications.
Wetting transition and fluid trapping in a microfluidic fracture
Authors: Qiu Yu , Xu Ke , Pahlavan Amir A. , Juanes Ruben
Published: May 2023

Immiscible fluid–fluid displacement in confined geometries is a fundamental process occurring in many natural phenomena and technological applications, from geological CO
2
sequestration to microfluidics. Due to the interactions between the fluids and the solid walls, fluid invasion undergoes a wetting transition from complete displacement at low displacement rates to leaving a film of the defending fluid on the confining surfaces at high displacement rates. While most real surfaces are rough, fundamental questions remain about the type of fluid–fluid displacement that can emerge in a confined, rough geometry. Here, we study immiscible displacement in a microfluidic device with a precisely controlled structured surface as an analogue for a rough fracture. We analyze the influence of the degree of surface roughness on the wetting transition and the formation of thin films of the defending liquid. We show experimentally, and rationalize theoretically, that roughness affects both the stability and dewetting dynamics of thin films, leading to distinct late-time morphologies of the undisplaced (trapped) fluid. Finally, we discuss the implications of our observations for geologic and technological applications.
‘Help is on the way’
Authors: Skinner Robert , Napier Jemina
Published: May 2023

In the UK, police reforms to meet needs of a diverse society have been limited in the case of deaf signers to an
increase in sign language interpreting services (SLIS). This article explores the consequences of this dependence on SLIS by the
UK police. We consider how deaf signers’ contact with the police may be inaccessible, despite national frameworks that ‘guarantee’
accessibility through the provision of BSL-English interpreting. We draw on qualitative data from focus groups and interviews with
police officers and custody sergeants who describe their experiences of having contact with deaf signers (or other minority
language users) through interpreters. We examine and contrast their perceptions and experiences concerning if, when, and how SLIS
provided access, as well as its impact on their contact with deaf signers. We compare these findings with UK police reform
policies to identify the current state of these provisions along with potential divergences.
Temperature compensation of MEMS resonant accelerometers with an on-chip platinum film thermometer
Authors: Wang Shaohang , Ma Yukun , Xu Wenyi , Liu Yunfeng , Han Fengtian
Published: May 2023

Temperature-dominated drift is generally the main error source for high-performance micromachined resonant accelerometers (MRAs) due to inherent thermal stress effect of resonator structure and die-attach process. This paper describes the design and experimental evaluation of a temperature compensation scheme for MEMS resonant accelerometers that demonstrates excellent bias and scale factor stability against temperature variation. An on-chip temperature sensor fabricated by sputtering platinum film on glass substrate is proposed to accurately sense the temperature-induced frequency change of the resonator. A polynomial fitting-based post-compensation model is firstly used to suppress the temperature sensitivity of the MRA over dynamic temperature environment. The temperature drift test and compensation of four accelerometer prototypes in a range from −40 ∘C to 60 ∘C show that the stability of bias and scale factor has been improved greatly with navigation-grade performance. Temperature compensation results with three improved drift models based on polynomial fitting, convolutional neural network and support vector regression respectively are presented and compared to suppress the temperature drift hysteresis in consecutive temperature-varying tests. These experimental results indicate that this resonant accelerometer exhibits excellent temperature stability after compensation, which offers the promise for high-performance inertial navigation applications.
Optical characterization of isothermal spin state switching in an Fe(II) spin crossover molecular and polymer ferroelectric bilayer
Authors: Yazdani Saeed , Collier Kourtney , Yang Grace , Phillips Jared , Dale Ashley , Mosey Aaron , Grocki Samuel , Zhang Jian , Shanahan Anne E , Cheng Ruihua , Dowben Peter A
Published: May 2023

Using optical characterization, it is evident that the spin state of the spin crossover molecular complex [Fe{H2B(pz)2}2(bipy)] (pz = tris(pyrazol-1-1y)-borohydride, bipy = 2,2ʹ-bipyridine) depends on the electric polarization of the adjacent polymer ferroelectric polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) thin film. The role of the PVDF-HFP thin film is significant but complex. The UV–Vis spectroscopy measurements reveals that room temperature switching of the electronic structure of [Fe{H2B(pz)2}2(bipy)] molecules in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] occurs as a function of ferroelectric polarization. The retention of voltage-controlled nonvolatile changes to the electronic structure in bilayers of PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] strongly depends on the thickness of the PVDF-HFP layer. The PVDF-HFP/[Fe{H2B(pz)2}2(bipy)] interface may affect PVDF-HFP ferroelectric polarization retention in the thin film limit.
Exploration of low field magnetic states in Nd 1−x
Ce
x
CrO3
Authors: Gupta Pragya , Pal D
Published: May 2023

We report the structural and magnetic properties of Nd

1
−
x

Ce
x
CrO3 (

x
=
0.05
−
0.175

) single-phase samples to classify the influence of Ce substitution on the Nd-site. The electron density profile indicates the possible covalent nature of Cr–O bonds. The x-ray photoelectron spectroscopy confirms a mixed Ce valency with a constant ratio of Ce3+/Ce4+ ions in all substituted compounds and the charge neutralization through the oxygen vacancies. The magnetization measurements reveal an increase in antiferromagnetic ordering temperature (

T

N

) and spin-reorientation transition temperature (

T

S
R

) and unfold soft spin-reorientation attributed to diluted superexchange interactions upon Ce incorporation. The presence of mixed Ce ions induces the merging of the hysteresis loop with a significant exchange bias (EB) field. We demonstrate for the first time that the magnitude of the magnetization is different for the same applied field in positive and negative directions, indicating the existence of two different magnetic states. The difference between these two magnetic states possibly arises from the pinning of Cr3+ spins, which requires an additional Zeeman energy for it to rotate. This maximum Zeeman energy from the normalized magnetic susceptibility vs. temperature curves correlates with the maximum EB field, validating unusual EB in these compounds.
Comparative study and multi-parameter analysis to optimize device structure of triboelectric nanogenerators
Authors: Wajahat Muhammad , Kouzani Abbas Z , Khoo Sui Yang , Mahmud M A Parvez
Published: May 2023

Triboelectric nanogenerator is becoming one of the most efficient energy harvesting device among all mechanical energy harvesters. This device consists of dielectric friction layers and metal electrode which generates electrical charges using electrostatic induction effect. There are several factors influencing the performance of this generator which needs to be evaluated prior to experiment. The absence of a universal technique for TENG simulation makes the device design and optimization hard before practical fabrication, which also lengthens the exploration and advancement cycle and hinders the arrival of practical applications. In order to deepen the understanding the core physic behind the working process of this device, this work will provide comparative analysis on different modes of TENG. Systematic investigation on different material combination, effect of material thickness, dielectric constant and impact of surface patterning is evaluated to shortlist the best material combination. COMSOL Multiphysics simulating environment is used to design, model and analyze factor affecting the overall output performance of TENG. The stationary study in this simulator is performed using 2D geometry structure with higher mesh density. During this study short circuit and open circuit condition were applied to observe the behavior of charge and electric potential produced. This observation is analyzed by plotting charge transfer/electric potential against various displacement distances of dielectric friction layers. The ouput is then provided to load ciruitary to measure the maximum output power of the models. Overall, this study provides an excellent understanding and multi-parameter analysis on basic theoretical and simulation modeling of TENG device.
A systematic review and meta-analysis of the measurement properties of concerns-about-falling instruments in older people and people at increased risk of falls
Authors: McGarrigle Lisa , Yang Yang , Lasrado Reena , Gittins Matthew , Todd Chris
Published: May 2023

Background

The 16-item Falls Efficacy Scale International (FES-I) is widely used to assess concerns-about-falling. Variants include 7-item Short FES-I, 30-item Iconographical Falls Efficacy Scale (Icon FES) and 10-item short Icon FES. No comprehensive systematic review and meta-analysis has been conducted to synthesise evidence regarding the measurement properties of these tools.

Objectives

To conduct a systematic review and meta-analysis of the measurement properties of four FES-I variants.

Methods

MEDLINE, Embase, CINAHL Plus, PsycINFO and Web of Science were searched systematically and articles were assessed for eligibility independently. The methodological quality of eligible studies was assessed using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) Risk of Bias checklist. The quality of measurement properties was assessed using COSMIN criteria for good measurement properties. Where possible, meta-analysis was conducted; otherwise, narrative synthesis was performed. Overall certainty of evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation system approach.

Results

The review included 58 studies investigating measurement properties of the four instruments. There was high-quality evidence to support internal consistency, reliability and construct validity of all instruments. Moderate- to high-certainty evidence suggests one-factor structure of FES-I with two underlying dimensions, one-factor structure of Short FES-I and two-factor structure of Icon FES. There was high-certainty evidence to support the responsiveness of FES-I, with further research needed for the other instruments.

Conclusion

There is evidence for excellent measurement properties of all four instruments. We recommend the use of these tools with healthy older people and people at a greater risk of falls due to conditions that might affect mobility and balance.
A phase IV, randomised, double-blind, controlled, parallel group trial to evaluate the effectiveness and safety of Balneum Plus versus emollient in the treatment of chronic kidney disease–associated pruritus in haemodialysis patients
Authors: Nevols Jacqueline , Watkins Lynn , Lewis Robert
Published: May 2023

Background

Chronic kidney disease–associated pruritus (CKD-aP) is a common, distressing complaint in patients with advanced renal disease that is frequently overlooked. Treatment is often unsatisfactory. Balneum Plus (Almirall, Barcelona, Spain) is a cream containing 3% lauromacrogols and 5% urea, commonly used to treat atopic dermatitis. It has not been studied in CKD-aP to date.

Methods

Adult haemodialysis patients were randomised 1:1 to apply Balneum Plus or E45 (Reckitt Beckiser, Slough, UK) to compare the active ingredients of lauromacrogol and urea with a control cream. Itch was defined as three episodes of itching during the last 2 weeks, appearing a few times a day, lasting a few minutes and troubling the patient [1]. Patients with other causes of itch, e.g. eczema and liver disease, were excluded. The primary outcome was a reduction in itch as measured by the visual analogue scale (VAS) score at 4 weeks and analysed using an analysis of covariance approach.

Results

A total of 314 patients were screened and 58 patients were randomised, 29 in each group. Three patients dropped out in each group. The median baseline VAS scores were 6.5 [interquartile range (IQR) 4.4–8.0] in the Balneum Plus group and 6.3 (IQR 5.1–7.3) in the E45 group. After 4 weeks, VAS scores decreased to 2.6 (IQR 0.9–4.5) and 2.0 (IQR 0.5–4.8) in the Balneum Plus and E45 groups respectively (P = 0.64 for the difference). Using a validated questionnaire to assess secondary outcomes, we found that the Balneum Plus group had longer itching episodes, more difficulty staying asleep and itching was more annoying than in the E45 group. There was no significant difference in adverse events between the two groups. One patient reported inflamed spots on the abdominal skin in the Balneum Plus group.

Conclusion

This is the first randomised controlled study of two different emollients for the treatment of CKD-aP and is a negative study. We found no significant difference in itch scores between Balneum Plus and E45.
Comparative effectiveness of exercise electrocardiography versus exercise echocardiography in women presenting with suspected coronary artery disease: a randomized study
Authors: Gurunathan Sothinathan , Shanmuganathan Mayooran , Chopra Ankur , Pradhan Jiwan , Aboud Lily , Hampson Reinette , Yakupoglu Haci Yakup , Bioh Gabriel , Banfield Ann , Gage Heather , Khattar Raj , Senior Roxy
Published: May 2023

Aims

There is a paucity of randomized diagnostic studies in women with suspected coronary artery disease (CAD). This study sought to assess the relative value of exercise stress echocardiography (ESE) compared with exercise electrocardiography (Ex-ECG) in women with CAD.

Methods and results

Accordingly, 416 women with no prior CAD and intermediate probability of CAD (mean pre-test probability 41%), were randomized to undergo either Ex-ECG or ESE. The primary endpoints were the positive predictive value (PPV) for the detection of significant CAD and downstream resource utilization. The PPV of ESE and Ex-ECG were 33% and 30% (P = 0.87), respectively for the detection of CAD. There were similar clinic visits (36 vs. 29, P = 0.44) and emergency visits with chest pain (28 vs. 25, P = 0.55) in the Ex-ECG and ESE arms, respectively. At 2.9 years, cardiac events were 6 Ex-ECG vs. 3 ESE, P = 0.31. Although initial diagnosis costs were higher for ESE, more women underwent further CAD testing in the Ex-ECG arm compared to the ESE arm (37 vs. 17, P = 0.003). Overall, there was higher downstream resource utilization (hospital attendances and investigations) in the Ex-ECG arm (P = 0.002). Using National Health Service tariffs 2020/21 (British pounds) the cumulative diagnostic costs were 7.4% lower for Ex-ECG compared with ESE, but this finding is sensitive to the cost differential between ESE and Ex-ECG.

Conclusion

In intermediate-risk women who are able to exercise, Ex-ECG had similar efficacy to an ESE strategy, with higher resource utilization whilst providing cost savings.
Time Required for Nanopore Whole-Genome Sequencing of Neisseria gonorrhoeae for Identification of Phylogenetic Relationships
Authors: Phillips Laura T , Witney Adam A , Furegato Martina , Laing Ken G , Zhou Liqing , Sadiq S Tariq
Published: May 2023

Background

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global health challenge. Limitations to AMR surveillance reporting, alongside reduction in culture-based susceptibility testing, has resulted in a need for rapid diagnostics and strain detection. We investigated Nanopore sequencing time, and depth, to accurately identify closely related N. gonorrhoeae isolates, compared to Illumina sequencing.

Methods

N. gonorrhoeae strains collected from a London sexual health clinic were cultured and sequenced with MiSeq and MinION sequencing platforms. Accuracy was determined by comparing variant calls at 68 nucleotide positions (37 resistance-associated markers). Accuracy at varying MinION sequencing depths was determined through retrospective time-stamped read analysis.

Results

Of 22 MinION-MiSeq pairs reaching sufficient sequencing depth, agreement of variant call positions passing quality control criteria was 185/185 (100%; 95% confidence interval [CI], 98.0%–100.0%), 502/503 (99.8%; 95% CI, 98.9%–99.9%), and 564/565 (99.8%; 95% CI, 99.0%–100.0%) at 10x, 30x, and 40x MinION depth, respectively. Isolates identified as closely related by MiSeq, within one yearly evolutionary distance of ≤5 single nucleotide polymorphisms, were accurately identified via MinION.

Conclusions

Nanopore sequencing shows utility as a rapid surveillance tool, identifying closely related N. gonorrhoeae strains, with just 10x sequencing depth, taking a median time of 29 minutes. This highlights its potential for tracking local transmission and AMR markers.
(004) Are Endogenous Androgens Linked to Female Sexual Function? A Systemic Review and Meta-Analysis
Authors: Maseroli E , Cipriani S , Vignozzi L
Published: May 2023

Introduction

The benefits of treatment with testosterone (T) in women with loss of desire suggest that low androgens may distinguish women with sexual dysfunction (SD) from others; however, evidence on this point is lacking.

Objective

Our aim was to answer the question: is there an association between endogenous levels of androgens and sexual function in women?

Methods

An extensive search was performed in MEDLINE, Embase and PsycInfo. Four separate meta-analyses were conducted for total T, free T, Free Androgen Index (FAI), and Dehydroepiandrosterone sulphate (DHEAS). Cohort, cross-sectional, and prospective studies were included. The main outcome was the association between endogenous androgens and sexual desire. Global sexual function was considered as a secondary outcome. The effect measure was expressed as standardized mean difference (SMD).

Results

The meta-analysis on total T included 34 studies involving 3,268 women, mean age 36.5 years. In 11 studies, a significant association was found between sexual desire, measured by validated psychometric instruments, and total T (SMD = 0.59 [0.29;0.88], P < 0.0001), with a moderate effect. The association with global sexual function (n = 12 studies) was also significant (SMD = 0.44 [0.21;0.67], P <0.0001). Overall, total T was associated with a better sexual function (SMD = 0.55 [0.28,0.82)], P < 0.0001), with similar results obtained when poor quality studies were removed. Age showed a negative relationship with the overall outcome. No differences were found when stratifying the studies according to menopausal status, type of menopause, age at menopause, use of hormonal replacement therapy, relationship status, method for T measurement, phase of the menstrual cycle or use of hormonal contraception. The meta-analysis of T derivatives (free T and FAI) also showed a significant, moderate association with sexual desire. In contrast, DHEAS seems not to exert any significant influence on desire, whilst showing a positive association with global sexual function.

Conclusions

There appears to be a moderate association between total T and sexual desire/global sexual function, which is confirmed, although weak, in studies employing liquid chromatography-mass spectrometry (LC-MS). Similar results on desire were obtained for free T and FAI. DHEAS only showed a positive association with global sexual function. A significant publication bias was found for total T. Our results suggest that endogenous androgens show a moderate association with a better sexual function in women; however, the role of psychological, relational and other hormonal factors should not be overlooked. More research is needed.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: LV received scientific research grants, advisory board attendance and speaker honoraria from Therascience, Theramex, Bayer Schering Pharma, Intercept, Lipocine, Ibsa.
(009) An Anatomic Map-Based Study: Erogenous and Aversive Sensation in the Vulva, Vagina, and Breasts
Authors: Stelmar J , Garcia M , Zaliznyak M , Isaacson D , Duralde E , Gaither T , Smith S , Yuan N , Topp K
Published: May 2023

Introduction

Erogenous zones (EZs) of the body elicit sexual arousal in response to touch. While previous studies have attempted to map erogeneity throughout the body, they did not assess internal surfaces or individual genital structures/sub-areas. Furthermore, previous work did not query how important specific EZs were to subjects’ sexual pleasure, nor did it assess what body areas people specifically dislike having touched during sex.

Objective

To develop detailed, topographic maps of erogenous and aversive sensation throughout the vulva, vagina, and breasts.

Methods

A sample of 441 sexually active cisgender women (mean age 48.9 ± 15.6 years) completed our anonymous, online questionnaire via Qualtrics®. Respondents selected predefined areas from anatomic illustrations that bring them pleasure when touched during sex, and areas that they dislike having touched during sex. For each EZ, respondents rated its importance to their sexual pleasure on a 10-point Likert scale, and/or indicated why they dislike having a specific area touched. Maps of erogeneity and aversion were generated based on the percent of respondents that selected each zone.

Results

More respondents selected at least one area of the vulva as erogenous (82.0%), as compared to the breasts (77.4%) and vagina (59.4%). Of the EZs of the vulva (Figure 1a), the vaginal introitus (50.8%), peri urethra (42.6%), and clitoris (41.3%) were the three most frequently selected and highest rated structures for pleasure. Conversely, the anus (34.0%) and perineum (7.9%) were the most disliked areas (Figure 1b) for the primary reason of respondents finding “It’s gross,” followed by “It hurts” and “I’m ashamed/embarrassed.” The five EZs of the vagina (Figure 2a) revealed enhanced erogeneity in the superficial anterior (48.1%) and posterior (32.9%) regions. The cervix (6.8%) and posterior zones (3.4%, 5.0%) of the vagina were the most disliked areas (Figure 2b) due to respondents reporting that “It hurts” and “It’s overly sensitive.” Interestingly, two of the most erogenous zones of the breasts (Figure 3a) were also the most disliked (Figure 3b): fatty breast tissue (57.8% erogenous, 5.4% aversive) and the nipples (42.7%, 6.5%). Respondent reasoning for disliking these areas included “It’s overly sensitive,” “It hurts,” and “It reminds me of a bad experience.”

Conclusions

The vulva and vagina were associated with enhanced erogenous sensation not only at (but also in regions immediately peripheral to) the clitoris. These EZs were also rated as “highly important” to sexual pleasure. The anus was overwhelmingly associated with aversive sensation due to feelings of judgment/shame. Other aversive zones were primarily disliked for objective reasons of pain and sensitivity.

Disclosure

No
(024) Cognitive Behavioral Therapy for Compulsive Sexual Behavior Disorder
Authors: Kolomanska A
Published: May 2023

Introduction

Cognitive Behavioral Therapy (CBT) is often used in the treatment for Compulsive Sexual Behavior Disorder (CSBD). However, no review of the evidence on the clinical efficacy of CBT for CSBD has been conducted. Compulsive Sexual Behavior Disorder (CSBD) is characterized by a lack of control over sexual impulses, thought, phantasies and urges and may have serious negative consequences of a person well-being, families, and functioning in work and education (Kraus et al., 2018). The prevalence of CSBD in the general population ranges from 3% to 6% (Derbyshire & Grant, 2015) with a near 4:1 ratio of male to female (Kuzma & Black, 2008). Due to the negative consequences of CSBD people often seek professional help.

Objective

To provide a systematic review of published studies on the efficacy of CBT for Compulsive Sexual Behavior Disorder.

Methods

The material for the analysis was obtained by searching 4 internet databases: Scopus, PubMed, ResearchGate and the Cochrane Library. Articles describing Cognitive Behavioral Therapy and their efficiency in reducing symptoms of CSBD were required. The search in the selected databased using the keywords identified in 203 records. Screening of abstract excluded 174 records and 29 records were assessed for eligibility. Four studies fulfilled the criteria for eligibility and were included in the study (see table 1). The selection process and reasons for exclusion of studies are shown in the Prisma flowchart (see Figure 1).

Results

4 original research articles were included to the review (Hallberg et al., 2017; Hallberg et al., 2019; Hallberg et al., 2020; Nwokeoma et al., 2019). Articles were devoted to the analysis of the efficiency of Cognitive Behavioral Therapy in reducing symptoms of hypersexual behavior. Studies show that CBT led to a significant reduction in hypersexual as well as symptoms of CSBD. Both RCT and non-controlled studies showed decrease in symptoms of CSBD after CBT. RCTs showed significant intermediate effects between treatment groups and control groups. Means (s.d.) on pre- and post-treatment scores of selected measures from included RCTs are shown in table (see table 2). Result indicate that CBT is a promising treatment for CSBD. However, studies included in the current review suffer from several methodological bias.

Conclusions

CBT show promise as treatment of CSBD. However, future studies should evaluate the treatment program with a larger sample in randomized controlled procedures and investigate the long-term effects; include women and comprise dismantling analysis of the constituting interventions.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Clinic for Sexology and Psychotherapy
(040) Is it Hard Enough? Higher Axial Force is Necessary for Penetrative Anal Intercourse
Authors: Miller J , Loeb C , La J , El Khatib F , Yafi F
Published: May 2023

Introduction

Inflatable penile prosthesis (IPP) remains the gold standard for surgical management of erectile dysfunction. Device buckling and malfunction represent a problem leading to patient dissatisfaction and high cost of care. While prior data suggests that the force needed for vaginal penetration (6.0 – 14.1 N) is typically below that at which prostheses begin to buckle (8.2 – 10.5 N), no data exists detailing the force needed for penetrative anal intercourse.

Objective

To evaluate the safety of IPP use with anal intercourse, especially for the population of men who have sex with men, we aim to determine the maximal axial loading force associated with anal penetration.

Methods

A hand-held force sensor device attached to a silicone rod with a length and girth representative of the average male phallus in the United States was inserted into the anal canal of six participants. The maximal axial loading force during penetration to a depth of six inches was recorded for a total of five measurements per participant. Participants then completed a survey eliciting demographic information and past experience with receptive anal intercourse.

Results

The average maximal force recorded across all participants was 30.3 N (16.1 – 51.7 N) [Figure 1]. By participant, average maximal forces ranged between 21.1 N – 49.4 N. All participants identified as homosexual men and had engaged in anal receptive intercourse within the past year. Participants who engaged in receptive anal intercourse more than once per month were with lesser average maximal forces (25.7 N) than those who less frequently engaged in receptive anal intercourse (42.0 N).

Conclusions

The average maximal force recorded during anal penetration exceeded the historically reported force required for vaginal penetration by a factor of 3.2 times, and that at which IPP buckling has been noted by a factor of 2.9 to 3.7 times [Table 1]. While the axial force required for anal penetration was lesser in those who more frequently engaged in receptive anal intercourse, this force still exceeded that at which IPP buckling can be seen. This study, while limited by sample size, highlights the necessity for further research investigating the efficacy and satisfaction associated with IPP implantation in those who engage in penetrative anal intercourse.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Antares Pharma; Clarus Therapeutics; Coloplast; Cynosure; Promescent; Sprout; Viome.
(137) Surgical Outcomes at a Single Institution of Infrapubic insertion of Malleable Penile Prosthesis in Transmen after Phalloplasty
Authors: Sun H , Isali I , Mishra K , Callegari M , Sellke N , Tay K , Gupta S , Chen M
Published: May 2023

Introduction

Penile reconstruction has allowed transmasculine individuals to attain the aesthetic appearance of male genitalia, however a penile prosthesis is needed to achieve the ridigity and bulk for penetration. High complication rates have been reported with penile prosthesis placement after phalloplasty, with the rate of reoperation exceeding 40% following both inflatable penile prosthesis (IPP) and malleable penile prosthesis (MPP). We describe the experience of a single surgeon with the infrapubic approach for MPP placement after phalloplasty.

Objective

To review the surgical outcomes of the infrapubic approach to the insertion of the MPP after phalloplasty in transgender men.

Methods

The infrapubic prosthesis insertion after phalloplasty technique involves a horizontal incision anterior to the pubic symphysis, which allows dissection of the neophallus channel and the anchor site on the pubic symphysis. Surgical outcomes using the Spectra (Boston Scientific, Marlborough, MA) and Genesis (Coloplast, Minneapolis, MN) MPP were analyzed between October 2017 and May 2022. Complications were reviewed and categorized into erosions, infections, device malposition and malfunction, and less common events like necrosis.

Results

The infrapubic MPP technique was performed on 40 patients by a single surgeon; 35 patients had a prior radial forearm free flap (RFFF) phalloplasty, and 5 had a prior anterolateral thigh flap (ALT) phalloplasty. Of the 30 patients who have continued to follow-up, mean follow-up was 34.9 months. Complications were not mutually exclusive, with 7 implant detachments from the anchor site, 3 malpositions, 2 with pain/activity limitation, and 1 infection. Surgical revision was required in 12 patients (40.0%). There were no neophallus erosions, flap loss, seromas, nor urethral injuries. More complications occurred with the Spectra MPP (9/17 or 52.9%) compared to the Genesis MPP (3/13 or 23.1%).

Conclusions

Infrapubic MPP insertion in transmen after phalloplasty is associated with high prosthetic surgical revision rates. Fewer complications were identified in the Genesis cohort. Longer term studies with patient reported outcome measures are required for further evaluation.

Disclosure

No
(155) Peyronie's Disease in Young Adults: Symptomatic Burden and Clinical Characteristics
Authors: Fallara G , Capogrosso P , Boeri L , Cazzaniga W , Candela L , Schifano N , Costa A , Pozzi E , Belladelli F , Cignoli D , Lanzaro F , Bertini A , Raffo M , Matloob R , Cornelius J , Ventimiglia E , Abbate C , Mattei A , Montorsi F , Salonia A
Published: May 2023

Introduction

Peyronie's disease is a common yet poorly understood condition occurring in teenagers as well as in men in their late 70s.

Objective

The aim of the study is to investigate whether patients’ age has an impact in terms of Peyronie’s disease (PD) clinical characteristics at presentation.

Methods

Data from a group of 125 consecutive patients aged >18 and with PD and seeking first medical attention at a single andrological tertiary-referral centre, with a complete clinical assessment and who completed the IIEF-15 and PDQ questionnaires were included in the study. Descriptive statistics was used to compare categorical and continuous variables, between young (≤45 years) and old (>45 years) patients at presentation. Linear and logistic regression analyses tested the association between age and PDQ subscales (Pain, Bother and Symptoms) or IIEF-erectile function domain scores (IIEF-EF ≤26), after adjusting for Charlson Comorbidity Index (CCI), Body Mass Index (BMI), duration of PD (as self-reported by the patient), smoking habit and penile curvature. LOWESS curve was used to graphically investigate the association between age and PDQ pain score.

Results

Of 125, 33 (26%) patients were ≤45 years old. Young patients had lower BMI [median (IQR) 23.6 (21.4-25.1) vs. 25.5 (23.7-27.8); p=0.01] and CCI [CCI≥1 in 1 patient (3%) vs. 25 (27%); p=0.007) compared to older patients. No differences were found between groups in terms of PD duration and plaque size, however curvature was lower among younger patients (20° [15-50] vs 47 [40-75]; p=0.045). PDQ pain score was 6 (2.0-10.0) for younger and 3 (0-8) for older patients (p=0.049). No differences were found in terms of PDQ-symptoms and bother scores, and for IIEF domain scores. At multivariable regression analysis, younger age was associated with significant higher PDQ-pain scores at presentation (Coeff 4.39; 95%CI 2.64:6.16; p<0.011). No further associations were observed between age and the other questionnaires. The figure depicts the higher PDQ-pain scores in young compared to older age.

Conclusions

Younger PD patients are at higher risk of complaining penile pain at presentation despite having a lower penile curvature. No difference in terms of symptoms, PD-associated bother, erectile function and other clinical and morphometric characteristics were found between younger and older patients at first assessment.

Disclosure

No