bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel adaptive guidance network for image inpainting
Authors: Jiang Jinyang , Dong Xiucheng , Li Tao , Zhang Fan , Qian Hongjiang , Chen Guifang
Published: April 2022

Motivated by human behavior, dividing inpainting tasks into structure reconstruction and texture generation helps to simplify restoration process and avoid distorted structures and blurry textures. However, most of tasks are ineffective for dealing with large continuous holes. In this paper, we devise a parallel adaptive guidance network(PAGN), which repairs structures and enriches textures through parallel branches, and several intermediate-level representations in different branches guide each other via the vertical skip connection and the guidance filter, ensuring that each branch only leverages the desirable features of another and outputs high-quality contents. Considering that the larger the missing regions are, less information is available. We promote the joint-contextual attention mechanism(Joint-CAM), which explores the connection between unknown and known patches by measuring their similarity at the same scale and at different scales, to utilize the existing messages fully. Since strong feature representation is essential for generating visually realistic and semantically reasonable contents in the missing regions, we further design attention-based multiscale perceptual res2blcok(AMPR) in the bottleneck that extracts features of various sizes at granular levels and obtains relatively precise object locations. Experiments on the public datasets CelebA-HQ, Places2, and Paris show that our proposed model is superior to state-of-the-art models, especially for filling large holes.
Field application of Bacillus subtilis and Aureobasidium pullulans to reduce Monilinia laxa post-harvest rot on cherry
Authors: Bellamy Sophia , Shaw Michael , Xu Xiangming
Published: April 2022

Brown rot caused by Monilinia spp. is one of the most important diseases in stone fruits worldwide. Latent infections of fruit by the pathogen often manifest once the fruit is ripe, leading to post-harvest rots. Two microbial strains (Bacillus subtilis -B91 and Aureobasidium pullulans - Y126) have shown antagonistic properties against M. laxa in previous studies. This study assessed the reduction in post-harvest rot of cherry by M. laxa when the two biocontrol (BCAs) strains were applied pre-harvest under field conditions to fruit artificially inoculated with M. laxa. The experiment was carried out for two consecutive years in cherry orchards in Kent. When applied pre-harvest, both strains (B91 and Y126) reduced the incidence of post-harvest rots by 30% - 60%. This promising result helps towards the commercialisation of the two strains, which would reduce reliance on fungicides in commercial cherry production.
Complexity and aesthetics in generative and evolutionary art
Authors: McCormack Jon , Cruz Gambardella Camilo
Published: April 2022

In this paper we examine the concept of complexity as it applies to generative and evolutionary art and design. Complexity has many different, discipline specific definitions, such as complexity in physical systems (entropy), algorithmic measures of information complexity and the field of “complex systems”. We apply a series of different complexity measures to three different evolutionary art datasets and look at the correlations between complexity and individual aesthetic judgement by the artist (in the case of two datasets) or the physically measured complexity of generative 3D forms. Our results show that the degree of correlation is different for each set and measure, indicating that there is no overall “better” measure. However, specific measures do perform well on individual datasets, indicating that careful choice can increase the value of using such measures. We then assess the value of complexity measures for the audience by undertaking a large-scale survey on the perception of complexity and aesthetics. We conclude by discussing the value of direct measures in generative and evolutionary art, reinforcing recent findings from neuroimaging and psychology which suggest human aesthetic judgement is informed by many extrinsic factors beyond the measurable properties of the object being judged.
Novel mtDNA haplotypes represented in the European captive population of the Endangered François’ langur (Trachypithecus francoisi)
Authors: Farré Marta , Johnstone Cameron , Hopper Jane , Kitchener Andrew C. , Roos Christian , King Tony
Published: April 2022

Assessing the genetic diversity of captive populations of endangered species is key to the successful management of conservation-breeding programs. In this study, we sequenced a 393-bp fragment of the mitochondrial DNA (mtDNA) control region of 23 captive individuals of the Endangered François’ langur (Trachypithecus francoisi) to assess the mtDNA diversity of the European captive population and to identify the possible geographical origins of the population founders. Combined with 42 sequences previously published from 29 wild François’ langurs, we identified a total of 40 haplotypes in T. francoisi, including 12 haplotypes in the 23 samples from the European captive population. Only one of the haplotypes from captive animals has previously been reported from wild populations; the remaining 11 haplotypes are newly reported here. Our results suggest that the captive T. francoisi population currently holds a relatively good genetic diversity compared with many other captive populations, that this diversity originates from a fairly broad range across the species’ distribution in the wild, and that the captive population could play a significant role in increasing genetic diversity of isolated wild populations. However, the European captive population is currently quite small, and genetic diversity could be lost rapidly, which has been demonstrated in other captive populations. We recommend further investigation of the genetic diversity of captive and wild T. francoisi populations, as well as the effective conservation of this diversity.
How to deal with negative preferences in recommender systems: a theoretical framework
Authors: Cena Federica , Console Luca , Vernero Fabiana
Published: April 2022

Negative information plays an important role in the way we express our preferences and desires. However, it has not received the same attention as positive feedback in recommender systems. Here we show how negative user preferences can be exploited to generate recommendations. We rely on a logical semantics for the recommendation process introduced in a previous paper and this allows us to single out three main conceptual approaches, as well as a set of variations, for dealing with negative user preferences. The formal framework provides a common ground for analysis and comparison. In addition, we show how existing approaches to recommendation correspond to alternatives in our framework.
The influence of parent austenite characteristics on the intervariant boundary network in a lath martensitic steel
Authors: Mirzaei Ahmad , Ghaderi Razieh , Hodgson Peter D. , Ma Xiang , Rohrer Gregory S. , Beladi Hossein
Published: April 2022

The influence of the parent austenite deformation state on the intervariant boundary network (i.e., population, plane orientation, and connectivity) of a lath martensitic microstructure was investigated using conventional EBSD mapping and five-parameter boundary analysis approach along with quantification of boundary connectivity using homology metrics. The lath martensite largely revealed a bimodal misorientation angle distribution, closely matched with the Kurdjumov–Sachs (K–S) orientation relationship. The application of deformation significantly changed the distribution, gradually reducing the intensity of the 60° misorientation angle peak. This was largely ascribed to substructure development within the parent austenite upon deformation, which stimulates particular variant/s having a habit plane (011)α′ closely parallel to the primary (111)γ and/or secondary (1$$\overline{1 }$$

1
¯

1)γ slip plane. The interaction of these variants eventually promoted specific intervariant boundaries (e.g., 60°/[111], 10.5°/[011], and 49.5°/[110]) at the expense of 60°/[011]. The application of deformation in the parent austenite did not change the intervariant boundary plane character distribution, which mostly exhibited an anisotropic character terminated on {110} planes because of the displacive nature of the martensitic transformation. However, the extent of anisotropy progressively decreased with increasing strain in the austenite prior to transformation. The grain boundary network connectivity was markedly altered due to the local variant selection induced by the deformation. Deformation in the austenite regime generally decreased the connectivity of boundaries having a {110} plane orientation. The intervariant boundaries with the {110} twist character also displayed a similar trend, though the connectivity of {110} tilt boundaries progressively enhanced with increasing strain. The former was closely matched with a decrease in the population of 60°/[110] intervariant boundaries with the strain. The current findings suggest that the intervariant boundary network of lath martensite can be manipulated through changes in the parent austenite deformation state which, in turn, can be used to enhance key final product properties such as toughness.

Graphical abstract
Modulating Drug Release from Short Poly(ethylene glycol) Block Initiated Poly(L-lactide) Di-block Copolymers
Authors: Azhari Zein , Smith Patricia , McMahon Sean , Wang Wenxin , Cameron Ruth E.
Published: April 2022

This paper investigates drug release from a novel series of mPEG-functionalised PLLA polymers whose individual components (PEG and PLLA) have regulatory FDA approval. Two processing methods were explored to understand their effect on the morphology and drug release profiles of the polymers, with and without mPEG functionalisation. In the first method the polymer and Propranolol.HCl drug powders were mixed together before injection moulding. In the second method, supercritical CO2 was used to mix the polymer and drug before injection moulding. When non-functionalised PLLA was processed through injection moulding alone, there were no signs of polymer-drug interaction, and the drug was confined to crystals on the surface. This resulted in up to 85 wt% burst release of propranolol.HCl after one day of incubation. By contrast, injection moulding of mPEG-functionalised polymers resulted in the partial dissolution of drug in the polymer matrix and a smaller burst (50 wt% drug) followed by sustained release. This initial burst release was completely eliminated from the profile of mPEG-functionalised polymers processed via supercritical CO2. The addition of mPEG facilitated the distribution of the drug into the bulk matrix of the polymer. Paired with supercritical CO2 processing, the drug release profile showed a slow, sustained release throughout the 4 months of the study.
Role of Tissue Hydraulic Permeability in Convection-Enhanced Delivery of Nanoparticle-Encapsulated Chemotherapy Drugs to Brain Tumour
Authors: Yang Yi , Zhan Wenbo
Published: April 2022

Purpose

Tissue hydraulic permeability of brain tumours can vary considerably depending on the tissue microstructure, compositions in interstitium and tumour cells. Its effects on drug transport and accumulation remain poorly understood.

Methods

Mathematical modelling is applied to predict the drug delivery outcomes in tumours with different tissue permeability upon convection-enhanced delivery. The modelling is based on a 3-D realistic tumour model that is extracted from patient magnetic resonance images.

Results

Modelling results show that infusing drugs into a permeable tumour can facilitate a more favourable hydraulic environment for drug transport. The infused drugs will exhibit a relatively uniform distribution and cover a larger tumour volume for effective cell killing. Cross-comparisons show the delivery outcomes are more sensitive to the changes in tissue hydraulic permeability and blood pressure than the fluid flow from the brain ventricle. Quantitative analyses demonstrate that increasing the fluid gain from both the blood and brain ventricle can further improve the interstitial fluid flow, and thereby enhance the delivery outcomes. Furthermore, similar responses to the changes in tissue hydraulic permeability can be found for different types of drugs.

Conclusions

Tissue hydraulic permeability as an intrinsic property can influence drug accumulation and distribution. Results from this study can deepen the understanding of the interplays between drug and tissues that are involved in the drug delivery processes in chemotherapy.
Glucocorticoid Withdrawal Syndrome following treatment of endogenous Cushing Syndrome
Authors: He Xin , Findling James W. , Auchus Richard J.
Published: April 2022

Purpose:

Literature regarding endogenous Cushing syndrome (CS) largely focuses on the challenges of diagnosis, subtyping, and treatment. The enigmatic phenomenon of glucocorticoid withdrawal syndrome (GWS), due to rapid reduction in cortisol exposure following treatment of CS, is less commonly discussed but also difficult to manage. We highlight the clinical approach to navigating patients from GWS and adrenal insufficiency to full hypothalamic-pituitary-adrenal (HPA) axis recovery.

Methods:

We review the literature on the pathogenesis of GWS and its clinical presentation. We provide strategies for glucocorticoid dosing and tapering, HPA axis testing, as well as pharmacotherapy and ancillary treatments for GWS symptom management.

Results:

GWS can be difficult to differentiate from adrenal insufficiency and CS recurrence, which complicates glucocorticoid dosing and tapering regimens. Monitoring for HPA axis recovery requires both clinical and biochemical assessments. The most important intervention is reassurance to patients that GWS symptoms portend a favorable prognosis of sustained remission from CS, and GWS typically resolves as the HPA axis recovers. GWS also occurs during medical management of CS, and gradual dose titration based primarily on symptoms is essential to maintain adherence and to eventually achieve disease control. Myopathy and neurocognitive dysfunction can be chronic complications of CS that do not completely recover.

Conclusions:

Due to limited data, no guidelines have been developed for management of GWS. Nevertheless, this article provides overarching themes derived from published literature plus expert opinion and experience. Future studies are needed to better understand the pathophysiology of GWS to guide more targeted and optimal treatments.
Absence of a home-field advantage within a short-rotation arable cropping system
Authors: Struijk Marijke , Whitmore Andrew P. , Mortimer Simon , Shu Xin , Sizmur Tom
Published: April 2022

Aims

The home-field advantage (HFA) hypothesis predicts faster decomposition of plant residues in home soil compared to soils with different plants (away), and has been demonstrated in forest and grassland ecosystems. It remains unclear if this legacy effect applies to crop residue decomposition in arable crop rotations. Such knowledge could improve our understanding of decomposition dynamics in arable soils and may allow optimisation of crop residue amendments in arable systems by cleverly combining crop-residue rotations with crop rotations to increase the amount of residue-derived C persisting in soil.

Methods

We tested the HFA hypothesis in a reciprocal transplant experiment with mesh bags containing wheat and oilseed rape residues in soils at three stages of a short-rotation cropping system. Subsets of mesh bags were retrieved monthly for six months to determine residue decomposition rates, concomitantly measuring soil available N, microbial community structure (phospholipid fatty acid analysis), and microbial activity (Tea Bag Index protocol) to assess how plants may influence litter decomposition rates via alterations to soil biochemical properties and microbial communities.

Results

The residues decomposed at similar rates at all rotational stages. Thorough data investigation using several statistical approaches revealed no HFA within the crop rotation. Soil microbial community structures were similar at all rotational stages.

Conclusions

We attribute the absence of an HFA to the shortness of the rotation and soil disturbance involved in intensive agricultural practices. It is therefore unlikely that appreciable benefits could be obtained in short conventionally managed arable rotations by introducing a crop-residue rotation.
Trying to make race science the “civil” science: charisma in the race and intelligence debates
Authors: Dasgupta Kushan , Panofsky Aaron , Iturriaga Nicole
Published: April 2022

When studying science contexts, scholars typically position charismatic authority as an adjunct or something that provides a meaning-laden boost to rational authority. In this paper, we re-theorize these relationships. We re-center charismatic authority as an interpretive resource that allows scientists and onlookers to recast a professional conflict in terms of a public drama. In this mode, both professionals and lay enthusiasts portray involvement in the scientific process as a story of suppression and persecution, in which only a few remarkable figures can withstand scrutiny and take on challengers with dignity. Description and elaboration of these figures and the folklore surrounding them sets in motion the interpretive processes by which some actors become charismatic leaders and others charismatic followers within science, ultimately providing alternative symbolic resources for an embattled research agenda to accrue legitimacy. To illustrate, we use the case of Arthur Jensen – a deceased intelligence researcher and the intellectual father to contemporary texts like The Bell Curve – and the circles of hero worship that admirers inside and outside academia have created to praise him. Using this perspective to study Jensen and his admirers demonstrates how the perennial race and intelligence debates gain a kind of symbolic power, unrelated to their scientific merit or racist appeal, which enables such debates to thrive and persist in the public sphere. More generally, our approach identifies contemporary processes by which scientific ideas can gain public authority even when their intellectual merit has been deemed dubious.
The Role of Civil Society Organisations in the Integration of Migrants, Refugees and Asylum Seekers in the Italian Labour Market
Authors: Collini Mattia
Published: April 2022

In this paper, we address the role of civil society organisations (CSOs) in Italy with regard to the integration of migrants, asylum seekers and refugees (MRAs) in the labour market. The paper analyses the role played by CSOs in practice, looking at the dynamics of demand and offer of services through the perspective of both the CSOs and MRAs. To achieve this, we combine qualitative data from semi-structured interviews to CSO representatives as well as MRAs. Our findings point out that the fragmentation of the policy framework in terms of employment and integration, and an unfavourable legislation (above all, migration law) shape the kind of prevalent activities of CSOs and negatively impact the potential for integration of MRAs in the labour market. In general, much is left to the single CSO to fill in the needs of MRAs beyond minimal provisions established by law, with just asylum seekers and refugees having better opportunities and support. Furthermore, we can also observe how economic migrants generally tend to be less supported.
Burnstock oration — purinergic signalling in kidney transplantation
Authors: Dwyer Karen M.
Published: April 2022

Kidney transplantation is the preferred treatment for individuals with kidney failure offering improved quality and quantity of life. Despite significant advancements in short term graft survival, longer term survival rates have not improved greatly mediated in large by chronic antibody mediated rejection. Strategies to reduce the donor kidney antigenic load may translate to improved transplant survival. CD39 on the vascular endothelium and on circulating cells, in particular regulatory T cells (Treg), is upregulated in response to hypoxic stimuli and plays a critical role in regulating the immune response removing proinflammatory ATP and generating anti-inflammatory adenosine. Herein, the role of CD39 in reducing ischaemia–reperfusion injury (IRI) and on Treg within the context of kidney transplantation is reviewed.
Inclusion Engineering in Medium Mn Steels: Effect of Hot-Rolling Process on the Deformation Behaviors of Oxide and Sulfide Inclusions
Authors: Wang Yong , Yang Yonggang , Dong Zhihua , Park Joo Hyun , Mi Zhenli , Mao Xinping , Mu Wangzhong
Published: April 2022

Medium Mn steel (MMS) is a new category of the third-generation advanced high strength steel (3rd AHSS) which is developed in the recent 1-2 decades due to a unique trade-off of strength and ductility. Thus, this steel grade has a wide application potential in different fields of industry. The current work provides a fundamental study of the effect of hot-rolling on the inclusion deformation in MMS including a varied 7 to 9 mass pct Mn. Specifically, the deformation behavior of different types of inclusions (i.e., Mn(S,Se), liquid oxide (MnSiO3), MnAl2O4, and complex oxy-sulfide) was investigated. The results show that both MnSiO3 and Mn(S,Se) are soft inclusions which are able to be deformed during the hot-rolling process but MnAl2O4 does not. The aspect ratio of soft inclusions increases significantly from as-cast to hot-rolling conditions. When the maximum size of different inclusions is similar, Mn(S,Se) deforms more than MnSiO3 does. This is due to a joint influence of physical parameters including Young’s modulus, coefficient of thermal expansion (α), etc. However, when the maximum size of one type of inclusion (e.g., MnSiO3) is much larger than another one (e.g., Mn(S,Se)), this maximum size of soft inclusions plays a dominant role than other factors. In addition, the deformation behavior of dual-phase inclusion depends on the major phase, i.e., either oxide or sulfide. Last but not least, empirical correlations between the reduction ratio of the thickness of plate, grain size, and aspect ratio of oxide and sulfide inclusions after hot-rolling are provided quantitatively. This work aims to contribute to the ‘inclusion engineering’ concept in the manufacturing of new generation AHSS.
On the Same Wavelength? Differing Geopolitical Positionalities and Voluntary Return and Reintegration in Ghana
Authors: Serra-Mingot Ester , Rudolf Markus
Published: April 2022

This paper explores the range of experiences of “voluntary” return to Ghana, based on the different positionalities of migrants set against migration and return regimes and broader socio-economic inequalities. The cases illustrate how geopolitical relations shape migrants’ mobilities, highlighting the unequal relations between different actors in the countries of origin and destination; primarily these are the migrants, their relatives, and communities of origin. Conflicting interests and expectations of these actors, as much as differing return policies, create unequal options and expectations of mobility. Migrant journeys, regardless the age, gender, legal status or social class, are always geopolitical journeys. The diverging experiences of return, thus, depend not only on the individual situations, but also on the broader politicized relations and interests between stakeholders in the migration and return processes.
Technical layout and fabrication of a compact all-glass four-channel beam splitter based on a Kösters design
Authors: Rothhardt Carolin , Klose Sylvio , Satzer Britta , Schmidl Sebastian , Grabowski Kevin , Birckigt Pascal , Hilpert Enrico , Lippmann Uwe , Schlegel Ralph , Shestaeva Svetlana , Schwinde Stefan , Risse Stefan
Published: April 2022

We report on the design and fabrication of a novel all-glass four-channel beam splitter based on a Kösters prism for use in space. The Kösters prism, which consists of three pairs of individual prisms, is used to separate an incoming telescope beam into four spectral channels (λ = 800–1700 nm) with the goal to obtain a multi-band photometry of cosmic sources in the optical/near-infrared bands. We performed optical design studies to evaluate the influence of geometrical tolerances of the six individual prisms on the image quality. A stray light analysis revealed the impact of the composition on the overall optical performance. Mechanical design studies benchmarked possible mounting strategies. We considered optical adhesives, soldering and clamping. The influence of the mechanical loads during a rocket launch as well as thermal loads at 140 K (the operation temperature of the optical element) were studied. We optimized the coating properties of the prisms by considering the results from the optical design study as well as the technological requirements for the direct bonding of the prisms. Bonding strategies to realize the prism pairs were developed and successfully tested. A demonstrator Kösters prism was manufactured and is ready to validate its optical performance.
A greater yellowstone ecosystem grizzly bear case study: genetic reassessment for managers
Authors: Shafer Craig L.
Published: April 2022

There are five grizzly bear (Ursus arctos horribilis) populations in the lower 48 states of the United States. My goal in this Commentary was to ascertain whether genetic diversity is being lost from the isolated GYE grizzly bear population and to better understand any viability implications. I reviewed the scientific literature, including two key genetic studies that the US Fish and Wildlife Service (USFWS) relied upon for their 2007 and current 2017 GYE grizzly bear genetics policy. I discovered that some studies reveal a loss of heterozygosity in the GYE bear population, both historically and in recent decades. Some had a statistically significant depletion rate. My review took place periodically between 2010 and 2021 and indicates that the genome of the GYE grizzly bear population is too small for long-term adaptation. The paper includes a discussion about evolutionary adaptation which invokes time frames rarely considered by nature conservation planners. I also examined genetic statements in the USFWS’s 2017 GYE grizzly bear delisting regulations and highlighted those that seem incongruent with current scientific thought. If this paper is read by some scientists, land managers, administrators, environmentalists, and others with some genetics background, they will better understand some USFWS decisions and policy statements. This case study illustrates that land management agencies can provide a one-sided treatment of some science when writing regulations about genetics.
A new macro-scale volume averaged transport model for diffusive dominated non-Darcian flow problem in multi-scaled naturally fractured reservoirs
Authors: Owusu Richard , Sakyi Adu , Dontwi Isaac Kwame , Amoako-Yirenkyi Peter
Published: April 2022

Diffusive transport in porous media is a complex process in multi-scaled fractured media modeling. This paper presents a diffusive transport model for non-Dacian flow in a naturally fractured reservoir with triple porosity and permeability. To address the non-Darcian flow behavior associated with fluid transport in fractured porous media, the Darcy/Forcheimer equation was used. A point-diffusive equation was obtained from mass conservation and the Darcy–Forcheimer momentum equation; this is used together with interface conditions to incorporate the microscopic properties of the domain. Subsequently, the resulting equation was spatially smoothed to obtain an effective macroscopic average model. The macroscopic model obtained, unlike the existing models, has a cross-diffusive term for mass transport by induced fluxes and a mass transfer term accounting for mass transfer between the matrix and the surrounding fractures via the interface. The numerical simulation displayed a horizontal-linear flow behavior in the fractured network instead of a radial flow in the matrix. The results further suggest that despite the fractures aiding in fluid transport, they enhance fluid production in the reservoir compared to the matrix.
White paper peanut allergy
Authors: Blumchen K. , Fischl A. , Eiwegger T. , Hamelmann E. , Klimek L. , Lange L. , Szepfalusi Z. , Vogelberg C. , Beyer K.
Published: April 2022

The current management of a primary IgE-mediated peanut allergy consists of the two basic pillars “exposure prophylaxis” with avoidance of the allergen and “emergency therapy” with short-term treatment of an acute allergic reaction after accidental ingestion. Accidental reactions are common despite attempted avoidance. The severity of an allergic or even anaphylactic reaction after accidental ingestion is difficult to assess prior to reaction. In addition, reaction thresholds may vary depending on the accompanying augmentation factor. Therefore, every peanut allergic patient should receive individual dietary counseling as well as instructions for the use of the emergency kit and a structured patient education program (anaphylaxis group training), if necessary. For the first time, since fall 2021 a causal treatment option with a drug for oral immunotherapy will now be available for 4‑ to 17-year-old peanut-allergic children and adolescents. The oral immunotherapy with peanut protein as defatted powder of Arachis hypogaea L., semen (peanuts) leads to desensitization with a good efficacy record and an acceptable safety profile. Other treatment options with different therapeutic approaches are also under development and will probably expand the range for treatment in the coming years.
Microbial Dark Matter: From Discovery to Applications
Authors: Zha Yuguo , Chong Hui , Yang Pengshuo , Ning Kang
Published: April 2022

With the rapid increase of the microbiome samples and sequencing data, more and more knowledge about microbial communities has been gained. However, there is still much more to learn about microbial communities, including billions of novel species and genes, as well as countless spatiotemporal dynamic patterns within the microbial communities, which together form the microbial dark matter. In this work, we summarized the dark matter in microbiome research and reviewed current data mining methods, especially artificial intelligence (AI) methods, for different types of knowledge discovery from microbial dark matter. We also provided case studies on using AI methods for microbiome data mining and knowledge discovery. In summary, we view microbial dark matter not as a problem to be solved but as an opportunity for AI methods to explore, with the goal of advancing our understanding of microbial communities, as well as developing better solutions to global concerns about human health and the environment.
7 Prevalence and Severity of Obstructive Sleep Apnea in Men with Polycythemia on Testosterone Therapy
Authors: Salter C , Flores JMF , Schofield E , Tan M , Mulhall J
Published: April 2022

Introduction

Polycythemia is independently associated with both testosterone therapy (TTH) and obstructive sleep apnea (OSA).

Objective

The purpose of this study was to evaluate the prevalence and severity of OSA in men who experience polycythemia while on TTH.

Methods

Study population included men who had polycythemia [hematocrit (HCT) >50%] while on TTH for TD, with total and free T levels within the normal range. Men completed screening questionnaires for OSA and daytime sleepiness, respectively: STOP-BANG (SB, range 0-8) and the Epworth Sleepiness Scale (ESS, range 0-24). Men whose scores demonstrated intermediate to high risk of OSA proceeded to a diagnostic sleep study which recorded the following parameters: apnea hypoxia index (AHI, normal <5 events/h), total duration SpO2 saturation <88% and SpO2 nadir. Descriptive statistics are presented.

Results

73 men had a mean age of 60±11.5 years. Mean HCT pre-TTH and on TTH were 45±3% and 52±1.5%, respectively, for a mean increase of 6.6±3.6%. Mean on-treatment total T level 686±285 ng/dL. Median STOP-BANG score was 4 (IQR 3-5), median ESS score was 5 (IQR 3-9). 63% of patients screened positive for OSA on questionnaires. 81% of sleep studies confirmed OSA; mean AHI of the group was 15.4±13.2 events/hour (range 1.6-54.6 events/hour). 36% of men had AHI≥15 events/hour and 14% ≥30 AHI events/hour. Mean SpO2 nadir was 83±5% (range 69%-93%). 67% of men with OSA had an oxygen nadir in the 80s, 19% in the 70s and 3% in the 60s. Total duration of hypoxia (SpO2 ≤88%) was 32±50 minutes (range 0.1-202 minutes), 46% of men having hypoxia <10 minutes, 8% 10-20 minutes, 19% 70-150 minutes.

Conclusions

Men on TTH who are eugonadal that experience polycythemia have high rates of OSA. 80% of the patients undergoing sleep study had OSA. These data suggest that men with polycythemia on TTH should be screened for OSA.

Disclosure

No
15 Safety of Human Chorionic Gonadotropin Monotherapy for Men with Previous Exogenous Testosterone Use or Replacement Therapy
Authors: Rainer Q , Pai R , Masterson T
Published: April 2022

Introduction

Human chorionic gonadotropin (hCG) is homologous to luteinizing hormone (LH) and stimulates endogenous testosterone (T) production and may be an option for testosterone replacement therapy (TRT). Currently, hCG is recommended for hypogonadal men with fertility concern as it prevents azoospermia seen with exogenous testosterone use. It is unknown if hCG is as efficacious as T in improving symptoms. We hypothesized that hCG is an effective and safe treatment in males with a history of exogenous T use or TRT.

Objective

Our objective was to evaluate for changes in symptoms and side effects to assess hCG monotherapy as a possible method of TRT in adult males with a history of previous exogenous T use or TRT.

Methods

We retrospectively reviewed 50 charts using exogenous T (including testosterone cypionate, clomid, anastrozole, methandienone, and testosterone gel) and were switched to hCG monotherapy for at least 1 month with follow-up labs. We evaluated changes in hormones [T, LH, follicle stimulating hormone (FSH), and estradiol], hematocrit (HCT), glycated hemoglobin (A1c), and prostate specific antigen (PSA). Results presented as means standard deviation. Student t-test was used to compare pre- and post-treatment values, significance was set at p=0.05. We also evaluated for incidence of thromboembolic events, including stroke, deep vein thrombosis, and myocardial infarction.

Results

The average age was 43.3±10.2 years with a BMI of 29.4±3.9 kg/m2. Of the patient's reviewed, 46% had used clomid, 18% T cypionate, 15% anabolic steroids, 13% T gel, 4% T pellets, and 4% methandienone. Average follow-up after starting hCG therapy was 163 days, range 28 to 583 days. Average weekly hCG dosage was 2435 IU. Serum T experienced no significant change, from 402.54±281.34 ng/dL to 404.29 ±259.64 ng/dL (p=0.58, n=50). No change was seen in FSH (4.82±6.21 to 3.71±3.24 mIU/mL, n=25), LH (3.12±4.18 to 1.98±1.86 mIU/mL, n=25), PSA (0.79±0.39 to 0.64±0.25 ng/mL, n=6), estradiol (27.84±14.82 to 27.96±13.18 pg/mL, n=31), or A1c (5.51±0.41 to 5.41±0.0.43 %, n=8). There was a statistically significant decrease of HCT (45.05±4.87 to 43.91±4.48 %, n=15). When evaluated for improvement of erectile dysfunction (ED, n=30), low libido (n=30), and low energy (n=32), 57%, 63%, and 66% of patients reported improvement of each symptom, respectively. Only 41% of patients with ED were noted to be on another medication or therapy specifically for ED. No thromboembolic events were observed.

Conclusions

Weekly hCG dosing appears to have no significant effect on T levels in men with a history of exogenous T use or TRT. The majority of patients reported an improvement in their hypogonadal symptoms. No changes were noted in PSA and A1c. HCT was noted to have a small, but statistically significant decrease and no thromboembolic events were recorded.

Disclosure

No
18 Innovative Findings Characterizing the Location and Severity of Postoperative Pain Following Inflatable Penile Prosthesis Surgery Managed With Multimodal Analgesia
Authors: Braun A , Xiang A , Chen M , Gross M , Simhan J
Published: April 2022

Introduction

Adoption of multimodal analgesia (MMA) in inflatable penile prosthesis (IPP) surgery has changed the management landscape by decreasing reliance on opioid usage for postoperative pain. However, there remains a paucity of literature characterizing severity, location and duration of postoperative pain following inflatable penile prosthesis (IPP) placement.

Objective

We rigorously characterized postoperative pain throughout the recovery period following IPP implantation in patients managed with multimodal analgesia (MMA). We aimed to provide an innovative and detailed analysis to better understand the pain profile experienced by implant recipients.

Methods

This is a single-center prospective analysis of 64 patients who underwent penoscrotal approach, primary three-piece IPP surgery from 9/2019 to 8/2020. All revision cases, infrapubic and combination anti-incontinence cases were excluded along with chronic pain patients. Interval follow-up was conducted via telephone with a standardized, validated pain questionnaire, executed on a scheduled timeline. A flow chart of the timeline and survey components are illustrated in Figure 1. Patient pain scores were assessed with the Wong-Baker visual analog scale (VAS).

Results

Pain locations and trends are illustrated in Image 1. Average VAS improved over the entire recovery period from 5.16 on POD2, to 5.28 on POD7, 3.55 on POD14 and 2.31 on POD30 (p=0.039). Patients were most bothered by scrotal pain followed closely by incisional pain (p=0.381) throughout the thirty days at each time interval. 20/27 (74%) patients indicated adequate pain management with MMA while 7/27 (26%) reported poorly controlled pain. No patients required additional narcotics. 27/64 (42.2%) patients had a 100% phone response rate and another 8/64 (12.5%) responded to three of the four postoperative calls. Barriers included no response to voicemail (12/64, 18.7%), full voicemail box (5/64, 7.8%) and wrong/nonfunctioning number (3/64, 4.7%).

Conclusions

This is the first descriptive analysis of the pain profile experienced by IPP patients during the first postoperative month. Although most patients experienced incisional and scrotal pain following penile implantation, multimodal analgesia provides reasonable pain relief for most patients.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast
33 Persistent Testosterone Suppression After Cessation of Androgen Deprivation Therapy for Localized Prostate Cancer
Authors: Delgado J , Ory J , Bitran J , Blachman Braun R , Nackeeran S , Ramasamy R
Published: April 2022

Introduction

ADT plays a fundamental role in the treatment of localized prostate cancer. However, there is limited data regarding testosterone recovery in men who have received ADT for prostate cancer. Identification of T recovery profiles associated with ADTs will facilitate personalization of ADT regimens and guide future treatment strategies to minimize the risk of T deficiency in patients with prostate cancer.

Objective

Temporary use of Androgen Deprivation Therapy (ADT) is a cornerstone in the treatment of localized prostate cancer. However, the ability for testosterone to recover after ADT is not well understood. The aim of this study was to investigate testosterone recovery in men with prostate cancer following varying ADT modalities and treatment durations.

Methods

A global federated health research network (TriNetX) was used to identify men with a diagnosis of prostate cancer who underwent temporary use of ADT. Three cohorts were identified: Men who received LHRH antagonists, LHRH agonists, and men who received combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 or 18 months to compare T recovery profiles at follow up periods of 2 and 5 years.

Results

A total of 17,884 men received LHRH agonists alone, 12,767 men received combined ADT, and 628 men received LHRH antagonist therapy alone. Eugondal mean baseline T level (>300 ng/dL) prior to starting ADT was an inclusion criterion for all men. Five years after ADT cessation, 36% of patients who received LHRH agonists recovered eugondal T levels, 26% recovered after LHRH antagonist therapy, and 36.8% recovered after combined ADT. Overall, more than half of men who received ADT failed to recover eugondal T levels even 5 years after treatment cessation.

Conclusions

Five years after ADT cessation, incomplete testosterone recovery persists in more than 50% of men. Testosterone deficiency will lead to metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and poor quality of life and needs to be evaluated even after cessation of ADT.

Disclosure

No
48 Tumor Necrosis Factor- α (TNF-α) and Rho-Associated Kinase 2 (ROCK2) Inhibitors Improve Erectile Function in a Bilateral Cavernous Nerve Injury Rat Model
Authors: Liu J , Lombardo K , Singh A , Karakus S , Praharaj M , Burnett A , Bivalacqua T
Published: April 2022

Introduction

Prior studies suggest Rho-kinase (ROCK) upregulation and pro-inflammatory cytokines such as Tumor Necrosis Factor-α as causative factors of axonal degeneration, neuropathy, and penile fibrosis following peripheral cavernous nerve (CN) injury. We hypothesize, the combination therapy using inhibitors/antagonists of ROCK and TNF-α may prevent end-organ damage and neuroinflammation in the penis. The current study was designed to investigate selective inhibition of ROCK2 (SAR407899) and TNF-α (Infliximab) in a pre-clinical model of post-radical prostatectomy ED to prevent penile neuroinflammation, fibrosis, and preserve penile hemodynamics.

Objective

This study investigates the effect of FDA approved TNF- α inhibitor (Infliximab) in combination with ROCK2 selective inhibitor (SAR407899) on erectile function restoration in the bilateral crush nerve injury (BCNI) rat model.

Methods

Sprague Dawley rats were randomized to undergo either sham (6) or BCNI (28). The BCNI rats were further randomly stratified to receive saline (6), Infliximab (5 mg/kg once weekly) (6), low dose of SAR407899 (1.5 mg/kg QD) (5), high dose of SAR407899 (3 mg/kg QD) (5), or combination treatment SAR407899 (1.5 mg/kg QD) + Infliximab (5 mg/kg once weekly) (6). At 14 days after injury rats underwent cavernous nerve stimulation to determine erectile function. Penes were collected and immune infiltrate analyses were performed using multicolor flow-cytometry.

Results

Erectile response studies demonstrated that rodents treated with combination of Infliximab and SAR407899 had significantly improved (p<0.05) erectile function (ICP/MAP) at all voltages compared to BCNI alone (2V: 0.243 vs 0.051, 4V: 0.321 vs 0.0782, 6V: 0.456 vs 0.091, p <0.05). Peak ICP and total ICP were also significantly (p<0.05) improved compared to BCNI rats. Combination therapy, however, did not show a significant change compared to each treatment alone. Likewise, there was no significant difference between low and high dose SAR407899. Flow cytometry showed that Infliximab and SAR407899 significantly (p<0.05) decreased % of CD11b+ CD45+ monocytes in the penis. While combination therapy had no effect. The percent of CD11b+ MHCII+ CD45+ macrophages were increased (p<0.05) in the penes of rats treated with Infliximab and SAR407899 while combination therapy decreased penile macrophage population. We found no change in TNF- α+ monocytes and macrophages compared in penes from all groups investigated.

Conclusions

Our study suggests that treatment with commercially available TNF-α and ROCK2 inhibitors result in mitigation of erectile dysfunction in a BCNI rat model when administered at the time of nerve injury. The mechanism of the beneficial effects may involve reduction in macrophage population in the penis.

Disclosure

No
51 Differences in the Gut Microbiome Composition Between Men with Erectile Dysfunction and A Matched Cohort: A Pilot Study
Authors: Osman MM , El-Khatib FM , Dianatnejad S , Nguyen J , Choi E , Towe M , Yafi FA
Published: April 2022

Introduction

The gut microbiome (GM) plays an important role in human health, ranging from supplying essential nutrients, synthesizing vitamin K, to promoting angiogenesis and enteric nerve function. It has also been recently associated with a variety of chronic health conditions. To date, however, there have been no studies that have attempted to establish any association between the GM and erectile dysfunction (ED).

Objective

To analyze stool samples from patients with ED and compare them to matched controls for differences in their GM.

Methods

We collected stool samples from 37 patients with ED and matched them with 37 controls. All samples were processed by a third-party company, Viome Inc. The samples were analyzed by metatranscriptome sequencing which allows for data to show both the taxonomy of the microbiome and its KEGG orthology (KO). We compared richness, prevalence and expression of the taxa and KOs between the ED and control groups.

Results

There were 224 species (16.85%) with significantly differential prevalence and 135 species (10.31%) with significantly differential expression. There were 565 KOs (10.42%) with significantly differential prevalence and 653 KOs (12.05%) with significantly differential expression. Richness is the number of microbial species detected in a sample. Diversity assesses the abundance and evenness of a species to assess how diverse an individual sample is. The ED group demonstrated significantly lower taxonomic richness and diversity, p= 1.33 × 10^-5 (see figure below).

Conclusions

This is the first study to look at associations between the GM and ED. Patients with ED have significantly lower taxonomic richness and diversity. Further analyses are needed to better understand the implications of these findings and uncover potential targets for early targeted treatment or prevention of ED.

Disclosure

Yes, this is sponsored by industry/sponsor: Viome Inc.

Clarification

Industry funding only - investigator initiated and executed study

Any of the authors act as a consultant, employee or shareholder of an industry for: Antares. Clarus. Coloplast. Promescent.