bluuebunny/crossref_metadata_2025 huggingface dataset:
The periastron advance in curvature based Extended Gravity and Dark Energy
Authors: Capolupo Antonio , Lambiase Gaetano , Tedesco Antonio
Published: June 2023

In the context of the periastron advance as a fundamental test for gravity theories, we show an approach to deduce constraints on the sizes of the new forces arising in the weak field limit of the Extended Theories of Gravity (ETG). It is also studied the force motivated by Quintessence Fields deforming the Schwarzschild geometry and associated to the Dark Energy, responsible of the acceleration of the Universe. As for the ETG, we consider the more general Scalar-Tensor Fourth Order Gravity (STFOG) and the NonCommutative Spectral Gravity (NCSG) as a special case. The solutions of the linearized field equations provide corrections to the Newtonian potential in the Yukawa-like form

V
(
r
)
=
α

e

−
β
r

r

, where α is the parameter related to the strength of the potential and β to the range of the force. Quintessence Fields lead to a power-law correction with parameters related to the Dark Energy. By analysing the periastron advance with the use of the current data, we find improvements on the parameters of the gravitational models as well as on the bounds of the parameter β by several orders of magnitude.
Quantum-gravitational corrections to the power spectrum for a closed universe
Authors: Vardanyan Tatevik , Kiefer Claus
Published: June 2023

We study the quantum-gravitational corrections to the power spectrum of a gauge-invariant inflationary scalar perturbations in a closed model of a universe. We consider canonical quantum gravity as an approach to quantizing gravity. This leads to the Wheeler-DeWitt equation, which has been studied by applying a semiclassical Born–Oppenheimer type of approximation. At the corresponding orders of approximation, we recover both the uncorrected and quantum-gravitationally corrected Schrödinger equations for the perturbation modes from which we calculate the quantum-gravitational corrections to the power spectrum in the slow-roll regime. The results are compared to the power spectra for the flat model of the universe.
On a Reformulation of Bohmian Mechanics Including Open Dissipative Systems
Authors: Schuch Dieter , Bonilla–Licea Moise
Published: June 2023

In Bohmian mechanics it is assumed that quantum objects are particles that follow real physical paths. These Bohmian trajectories are obtained by integrating the velocity field that occurs in the continuity equation. However, in the course of deriving these trajectories, the independent position variable x, appearing in the velocity field, is arbtirarily replaced by the time-dependent trajectory q(t). We show under which restrictions such a replacement can be justified, leading to a totally different interpretation of the Bohmian trajectories. They are not real paths of physical particles but borders of regions of constant probability, so-called quantiles, and therefore must be seen in the context of descriptive statistics. Thus they provide a tool complementary to the conventional statistical formulation of quantum mechanics. A possible extension to include open dissipative systems is also discussed, showing that the inclusion of an environment does not change our interpretation of the Bohmian trajectories.
Axion like particles, fifth force and neutron interferometry
Authors: Capolupo Antonio , Giampaolo Salvatore Marco , Quaranta Aniello
Published: June 2023

We report on recent result according to which the fermion-fermion interaction mediated by axions and axion–like particles can be revealed by means of neutron interferometry. We assume that the initial neutron beam is split in two beams which are affected by differently oriented magnetic fields, in order that the phase difference depends only by the axion–induced interaction. In this way, the phase difference is directly related to the presence of axions.
Outdoor I-V characterization of tilted and vertical bifacial PV modules
Authors: García M A , Quispe G R , Zamudio M A , Conde L A , Angulo J R , Berastain A E , Töfflinger J A
Published: June 2023

This work proposes an experimental method to characterize bifacial photovoltaic modules through outdoor current-voltage (I-V) measurements. This characterization is an extension of methods developed for monofacial modules by considering the IEC TS 60904-1-2 standard for bifacial modules, particularly the introduction of the equivalent irradiance that accounts for albedo and bifaciality. We extract the short-circuit current, open-circuit voltage, and maximum power from the module I-V characteristic curve under outdoor conditions. We extrapolate these parameters to standard test conditions using the measured equivalent irradiance and module temperature. This method is applied on bifacial modules in two mounting orientations: 15° tilt north-oriented and vertical east-west orientation. Characterizing the bifacial modules’ electrical parameters using the proposed approach yields results with similar accuracy as applying the equivalent characterization of a tilted monofacial module.
Implementation of a monitoring system for a photovoltaic installation based on IoT technology
Authors: Supo J F , Puma P Y , Ramos J M , Beltrán N J
Published: June 2023

In the present work, the monitoring of a grid-connected photovoltaic system of 3.7kW of installed power based on an Internet of Things (IoT) solution is designed and implemented, the monitoring system is implemented in a real facility located in Juliaca, Peru. IoT-based monitoring integrates the data acquisition system (DAQ) of the photovoltaic system, complementing the existing local monitoring with a flexible architecture capable of connecting to different devices and communication environments. The DAQ connects to the IoT-based monitoring system via open-source software, and Microsoft cloud services are also used to visualize the data in real time, as well as to store it. The proposed solution overcomes the challenges faced by a monitoring system of a conventional photovoltaic installation at a low cost.
A Reinforcement Learning approach to the Optimal Torque MPPT problem in wind turbines
Authors: Choquehuanca E , Ortega A
Published: June 2023

In this work, a torque controller for a variable rotational speed wind turbine has been modelled using Reinforcement Learning and considering the Optimal Torque - Maximum Power Point Tracking problem as one of optimization. The reward optimization function is designed as a non-linear function depending mainly on the rotor power variation. Based on this, an optimal action (electromagnetic torque variation) regulates the turbine rotational speed. A simulated 1.5 MW three bladed wind turbine operation is managed by the torque controller. It keeps the turbine working at optimal operational conditions after a successful training process, which is carried out using the Proximal Policy Optimization algorithm. For the controller training, the turbine confronts constant and then randomly staggered wind speed behaviour. Time series of rotor angular speed, torque and power are presented. Our results show that the modelled controller is able to reach and maintain the wind turbine operation at its optimal power generation conditions. This methodology avoids using some empirical parameter characteristic of the Optimal Torque - Maximum Power Point Tracking algorithm widely used in wind turbine control systems.
Dynamic response assessment of an offshore wind turbine under Peruvian environmental conditions
Authors: Barreto D , Ortega A
Published: June 2023

This paper presents a dynamic response analysis of an offshore monopile wind turbine to be deployed at a near-shore area in the south-centre part of the Peruvian coast (Marcona). It is a 5 MW three bladed wind turbine that operates in an aggressive offshore environment described by its stochastic behaviour. Thus it is necessary to use a statistical approach for its characterization. The operating wind turbine is simulated using an aero-hydro-servo-elastic computational tool (FAST) that allows the simulation of coupled systems. After the simulation, this work analyses relevant dynamic responses (thrust, torque, shear forces, and bending moments). Time series of these responses at critical zones of the wind turbine are presented. The results indicate high variability of the responses and critical fluctuations located at the mudline. It is found that this variability is due to the additional dynamic loads coming from the ocean waves. This is a big issue to consider when designing a monopile offshore wind turbine operating under the Peruvian environmental conditions.
Adaptation as Emancipation in Edward Albee’s Lolita
Authors: Holtz Martin
Published: June 2023

Edward Albee’s stage adaptation (1981) of Vladimir Nabokov’s Lolita (1955) is universally regarded as an unqualified failure. This contribution seeks to recover the play from critical neglect by arguing that it not just productively interprets and transforms the source text but also critically comments on its implications regarding the relationship between artist and creation, audience and art, and ethics and aesthetics. The play features an anthropomorphised equivalent to the novel’s implied author in the character of ‘A Certain Gentleman’ (ACG), a figure uniting features of (imagined) Nabokov and Albee, who introduces himself to the audience as the creator of Humbert and guides them through the plot while commenting on the action, alternatively trying to distance himself from his creation, trying to teach him moral values, or admonishing the audience to show empathy. In the interplay of Humbert, Lolita, and ACG, the play stages an emancipatory dialogue between artist and creation, using the presentational character of (epic) theatre to level diegetic hierarchies. Just as Lolita emancipates itself from Nabokov in the act of adaptation, so Humbert emancipates himself from ACG and Lolita from Humbert. In the same way, the play encourages an emancipation on the part of the audience from a position of passive spectatorship by cultivating a critical engagement with the discordant discourses of theatrical narration, presentation, and spectatorship in a dialogic of identification and distance.
Guide to the Diagnosis of Myeloid Neoplasms: A Bone Marrow Pathology Group Approach
Authors: Foucar Kathryn , Bagg Adam , Bueso-Ramos Carlos E , George Tracy , Hasserjian Robert P , Hsi Eric D , Orazi Attilio , Tam Wayne , Wang Sa A , Weinberg Olga K , Arber Daniel A
Published: June 2023

Objectives

The practicing pathologist is challenged by the ever-increasing diagnostic complexity of myeloid neoplasms. This guide is intended to provide a general roadmap from initial case detection, often triggered by complete blood count results with subsequent blood smear review, to final diagnosis.

Methods

The integration of hematologic, morphologic, immunophenotypic, and genetic features into routine practice is standard of care. The requirement for molecular genetic testing has increased along with the complexity of test types, the utility of different testing modalities in identifying key gene mutations, and the sensitivity and turnaround time for various assays.

Results

Classification systems for myeloid neoplasms have evolved to achieve the goal of providing a pathology diagnosis that enhances patient care, outcome prediction, and treatment options for individual patients and is formulated, endorsed, and adopted by hematologists/oncologists.

Conclusions

This guide provides diagnostic strategies for all myeloid neoplasm subtypes. Special considerations are provided for each category of testing and neoplasm category, along with classification information, genetic testing requirements, interpretation information, and case reporting recommendations based on the experience of 11 Bone Marrow Pathology Group members.
Immortal Time Bias With Time-Varying Exposures in Environmental Epidemiology: A Case Study in Lung Cancer Survival
Authors: Sheridan Paige , Chen Chen , Thompson Caroline A , Benmarhnia Tarik
Published: June 2023

Immortal time bias is a well-recognized bias in clinical epidemiology but is rarely discussed in environmental epidemiology. Under the target trial framework, this bias is formally conceptualized as a misalignment between the start of study follow-up (time 0) and treatment assignment. This misalignment can occur when attained duration of follow-up is encoded into treatment assignment using minimums, maximums, or averages. The bias can be exacerbated in the presence of time trends commonly found in environmental exposures. Using lung cancer cases from the California Cancer Registry (2000–2010) linked with estimated concentrations of particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5), we replicated previous studies that averaged PM2.5 exposure over follow-up in a time-to-event model. We compared this approach with one that ensures alignment between time 0 and treatment assignment, a discrete-time approach. In the former approach, the estimated overall hazard ratio for a 5-μg/m3 increase in PM2.5 was 1.38 (95% confidence interval: 1.36, 1.40). Under the discrete-time approach, the estimated pooled odds ratio was 0.99 (95% confidence interval: 0.98, 1.00). We conclude that the strong estimated effect in the former approach was likely driven by immortal time bias, due to misalignment at time 0. Our findings highlight the importance of appropriately conceptualizing a time-varying environmental exposure under the target trial framework to avoid introducing preventable systematic errors.
Sustained mangrove reproduction despite major turnover in pollinator community composition at expanding range edge
Authors: Nathan Mayda , Gruner Daniel S
Published: June 2023

Background and Aims

How well plants reproduce near their geographic range edge can determine whether distributions will shift in response to changing climate. Reproduction at the range edge can be limiting if pollinator scarcity leads to pollen limitation, or if abiotic stressors affect allocation to reproduction. For many animal-pollinated plants with expanding ranges, the mechanisms by which they have overcome these barriers are poorly understood.

Methods

In this study, we examined plant–pollinator interactions hypothesized to impact reproduction of the black mangrove, Avicennia germinans, which is expanding northward in coastal Florida, USA. We monitored insects visiting A. germinans populations varying in proximity to the geographic range edge, measured the pollen loads of the most common insect taxa and pollen receipt by A. germinans stigmas, and quantified flower and propagule production.

Key Results

We found that despite an 84 % decline in median floral visits by insects at northernmost versus southernmost sites, range-edge pollen receipt remained high. Notably, local floral visitor assemblages exhibited substantial turnover along the study’s latitudinal gradient, with large-bodied bees and hover flies increasingly common at northern sites. We also observed elevated flower production in northern populations and higher per capita reproductive output at the range edge. Furthermore, mean propagule mass in northern populations was 18 % larger than that from the southernmost populations.

Conclusions

These findings reveal no erosion of fecundity in A. germinans populations at range limits, allowing rapid expansion of mangrove cover in the region. These results also illustrate that substantial turnover in the assemblage of flower-visiting insects can occur at an expanding range edge without altering pollen receipt.
Determinants of interspecific variation in season length of perennial herbs
Authors: Koubek Tomáš , Mašková Tereza , Herben Tomáš
Published: June 2023

Background and aims

Perennial plants in seasonal climates need to optimize their carbon balance by adjusting their active season length to avoid risks of tissue loss under adverse conditions. As season length is determined by two processes, namely spring growth and senescence, it is likely to vary in response to several potentially contrasting selective forces. Here we aim to disentangle the cascade of ecological determinants of interspecific differences in season length.

Methods

We measured size trajectories in 231 species in a botanical garden. We examined correlations between their spring and autumn size changes and determined how they make up season length. We used structural equation models (SEMs) to determine how niche parameters and species traits combine in their effect on species-specific season length.

Key results

Interspecific differences in season length were mainly controlled by senescence, while spring growth was highly synchronized across species. SEMs showed that niche parameters (light and moisture) had stronger, and often trait-independent, effects compared to species traits. Several niche (light) and trait variables (plant height, clonal spreading) had opposing effects on spring growth and senescence.

Conclusions

The findings indicate different drivers and potential risks in growth and senescence. The strong role of niche-based predictors implies that shifts in season length due to global change are likely to differ among habitats and will not be uniform across the whole flora.
Molecular and cellular insights into auxin-regulated primary root growth: a comparative study of Arabidopsis and rice
Authors: Nakamura Ayako , Hirota Yuna , Shigihara Masaru , Watanabe Mayu , Sato Akiko , Tsuji Hiroyuki , Shimada Yukihisa
Published: June 2023

Auxin regulation of primary root growth in Arabidopsis and rice was compared by analyzing root growth in response to changes in auxin levels. A bell-shaped root-growth curve was identified in both Arabidopsis and rice in response to change in auxin levels. In Arabidopsis, cell division was the main regulator of root growth in response to auxin; in rice, auxin promoted root growth by regulating cell division and cell length. The expression levels of PLETHORA (PLT) genes in response to change in auxin level followed a bell-shaped curve and closely correlated with cell division in Arabidopsis but not in rice, implying that PLT gene expression plays key role to control root growth in Arabidopsis. The level of auxin in Arabidopsis was optimal for primary root elongation, while in rice it was higher than optimal. These differences may explain the species-dependent development of root systems.
Reference panel-guided super-resolution inference of Hi-C data
Authors: Zhang Yanlin , Blanchette Mathieu
Published: June 2023

Motivation

Accurately assessing contacts between DNA fragments inside the nucleus with Hi-C experiment is crucial for understanding the role of 3D genome organization in gene regulation. This challenging task is due in part to the high sequencing depth of Hi-C libraries required to support high-resolution analyses. Most existing Hi-C data are collected with limited sequencing coverage, leading to poor chromatin interaction frequency estimation. Current computational approaches to enhance Hi-C signals focus on the analysis of individual Hi-C datasets of interest, without taking advantage of the facts that (i) several hundred Hi-C contact maps are publicly available and (ii) the vast majority of local spatial organizations are conserved across multiple cell types.

Results

Here, we present RefHiC-SR, an attention-based deep learning framework that uses a reference panel of Hi-C datasets to facilitate the enhancement of Hi-C data resolution of a given study sample. We compare RefHiC-SR against tools that do not use reference samples and find that RefHiC-SR outperforms other programs across different cell types, and sequencing depths. It also enables high-accuracy mapping of structures such as loops and topologically associating domains.

Availability and implementation

https://github.com/BlanchetteLab/RefHiC.
Ghost Criminology: A Framework for the Discipline’s Spectral Turn
Authors: Fiddler Michael , Linnemann Travis , Kindynis Theo
Published: June 2023

Drawing upon recent criminological scholarship examining spectrality, as well as Jacques Derrida’s notion of hauntology, this article sets out a framework to explore harms experienced as ‘out of joint’. We propose a new sub-discipline of ‘ghost criminology’ as a means to explore and reckon with these afterlives. We identify three strands of the (in)visible, the (in)corporeal and dead space with which to capture phenomena hovering between presence and absence. In doing so, we provide examples of justice being achieved within this sense of time being ‘off its hinges’. A ‘ghost criminology’ provides a means of listening to the voices of the discipline’s dead, as well as the ghosts of its future.
O009 Differential attainment at the Intercollegiate Membership of the Royal Colleges of Surgeons (MRCS) examination according to gender, ethnicity, age and socioeconomic factors
Authors: Ellis R , Brennan PA , Lee AJ , Scrimgeour DSG , Cleland J
Published: June 2023

Introduction

The lack of diversity at senior and leadership positions in surgery highlights concerns that some groups of individuals face barriers to progression in surgical training. This study aimed to investigate whether there is group-level differential attainment (DA) at MRCS, a mandatory postgraduate examination for UK surgical trainees.

Methods

All UK graduates attempting MRCS Part A (n=5,780) and Part B (n=2,600) between 2013–2019 were identified using the UK Medical Education Database. Univariate associations with MRCS performance were identified using chi-squared tests. Multiple logistic regression identified independent predictors of first-attempt MRCS success, adjusted for medical school performance.

Results

We found statistically significant differences in MRCS pass rates according to gender, ethnicity, graduate status, childhood socioeconomic status and educational background (all P<0.05). After adjusting for prior academic attainment, being a non-graduate (odds ratio [OR] 1.98, 95%CI 1.44–2.74) or male (OR 2.34, 95%CI 1.87–2.92) were independent predictors of MRCS Part A success. Being a non-graduate (OR 1.77, 95%CI 1.15–2.71) or having attended a fee-paying school (OR 1.51, 95%CI 1.08–2.10) were independent predictors of MRCS Part B success. Black candidates were significantly less likely to pass MRCS Part B at their first attempt (OR 0.41, 95%CI 0.18–0.92) as were Asian candidates (OR 0.49, 95%CI 0.35–0.69 for) in comparison to White candidates.

Conclusion

We found significant DA at MRCS that cannot be attributed to learner deficit. Royal Colleges and training institutions now need to identify and address the causes of these attainment differences to facilitate equitable career progression for surgical trainees.

Take-home message

We found significant DA at MRCS that cannot be attributed to learner deficit. Royal Colleges and training institutions now need to identify and address the causes of these attainment differences to facilitate equitable career progression for surgical trainees.
O039 Evaluating the influence of risk factors on the development of defaecatory problems: a Delphi study
Authors: Chaichanavichkij P , Hartmann M , McLachlan S , Scott SM , Fenton N , Knowles CH
Published: June 2023

Introduction

The influence of risk factors on the development of defaecatory problems is difficult to ascertain due to heterogeneity of published evidence. An understanding of the impact of these risk factors is important in selecting targets for disease prevention.

Methods

Risk factors for chronic constipation and faecal incontinence were anonymously evaluated using a Delphi technique with 50 experts from the Pelvic Floor Society between May and December 2021. Each risk factor was rated as an independent risk factor, a co-factor, or not a risk factor. The importance of an independent risk factor was rated between 1 (not important) and 10 (critically important) and the mean (± standard deviation) was calculated.

Result

38 risk factors for chronic constipation were evaluated, of which 18 were classed as independent and 16 as co-factors. Opioid analgesia (7.87 ± 2.05), eating disorders (7.80 ± 1.72), and history of abuse (7.70 ± 1.89) were classed as most important. Female gender (6.60 ± 2.02) was an independent risk factor but increasing age was a co-factor. 33 risk factors for faecal incontinence were evaluated, of which 20 were classed as independent and 8 as co-factors. Third- or fourth-degree tear (8.88 ± 1.57), instrumental delivery (8.47 ± 1.58), and grand-multiparity (8.00 ± 1.63) were classed as most important. Increasing age (7.41 ± 2.14) and female gender (7.58 ± 2.05) were independent risk factors.

Conclusion

Several risk factors for chronic constipation and faecal incontinence could be determined by Delphi approach. These factors will feed into Bayesian models of disease development.

Take-home message

Important risk factors for chronic constipation and faecal incontinence could be determined by Delphi approach.
544 Improvement of Skin Quality in Patients Undergoing Nasal Fat Grafting: A Systematic Review Protocol
Authors: Neves P , Ramjeeawon A , Quong W , Bulstrode N , Pitombo V
Published: June 2023

Aim

Primary aims: to understand the effects of adipose tissue or its derivatives on nasal skin quality, and whether lipofilling may improve nasal skin quality. Secondary aims: to understand whether post-lipofilling nasal skin improvement can be observed and quantified in both good quality and scarred nasal skin, to investigate if changes are related to the differing levels of preoperative skin quality (unscarred vs scarred), to review outcomes for different types of fat harvesting and processing techniques prior to grafting and identify complications following nasal lipofilling.

Method

A search strategy will be developed to search MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials, followed by a grey literature search, to identify relevant publications. Two researchers will review titles, abstracts, and full-texts of the resulting publications, against the inclusion and exclusion criteria (a third researcher will decide where there are disagreements), as part of an independent two-person three-stage assessment strategy. Non-English/ Portuguese/ French articles, abstracts, letters, editorials, and expert opinions will be excluded.

Results

This systematic review has been registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD 42021290198).

Conclusion

Adipose tissue has regenerative potential; it has been suggested there may be improvement in nasal skin quality following fat tissue grafting into the nasal region. Primary and secondary rhinoplasty procedures are being increasingly performed and multiple procedures may result in nasal skin damage, which should be addressed during secondary reconstruction. Understanding whether lipofilling improves nasal skin quality in nasal reconstruction could support its use in appropriate patients undergoing rhinoplasty.
Single-cell profiling reveals age-associated immunity in atherosclerosis
Authors: Smit Virginia , de Mol Jill , Schaftenaar Frank H , Depuydt Marie A C , Postel Rimke J , Smeets Diede , Verheijen Fenne W M , Bogers Laurens , van Duijn Janine , Verwilligen Robin A F , Grievink Hendrika W , Bernabé Kleijn Mireia N A , van Ingen Eva , de Jong Maaike J M , Goncalves Lauren , Peeters Judith A H M , Smeets Harm J , Wezel Anouk , Polansky Julia K , de Winther Menno P J , Binder Christoph J , Tsiantoulas Dimitrios , Bot Ilze , Kuiper Johan , Foks Amanda C
Published: June 2023

Aims

Aging is a dominant driver of atherosclerosis and induces a series of immunological alterations, called immunosenescence. Given the demographic shift towards elderly, elucidating the unknown impact of aging on the immunological landscape in atherosclerosis is highly relevant. While the young Western diet-fed Ldlr-deficient (Ldlr−/−) mouse is a widely used model to study atherosclerosis, it does not reflect the gradual plaque progression in the context of an aging immune system as occurs in humans.

Methods and results

Here, we show that aging promotes advanced atherosclerosis in chow diet-fed Ldlr−/− mice, with increased incidence of calcification and cholesterol crystals. We observed systemic immunosenescence, including myeloid skewing and T-cells with more extreme effector phenotypes. Using a combination of single-cell RNA-sequencing and flow cytometry on aortic leucocytes of young vs. aged Ldlr−/− mice, we show age-related shifts in expression of genes involved in atherogenic processes, such as cellular activation and cytokine production. We identified age-associated cells with pro-inflammatory features, including GzmK+CD8+ T-cells and previously in atherosclerosis undefined CD11b+CD11c+T-bet+ age-associated B-cells (ABCs). ABCs of Ldlr−/− mice showed high expression of genes involved in plasma cell differentiation, co-stimulation, and antigen presentation. In vitro studies supported that ABCs are highly potent antigen-presenting cells. In cardiovascular disease patients, we confirmed the presence of these age-associated T- and B-cells in atherosclerotic plaques and blood.

Conclusions

Collectively, we are the first to provide comprehensive profiling of aged immunity in atherosclerotic mice and reveal the emergence of age-associated T- and B-cells in the atherosclerotic aorta. Further research into age-associated immunity may contribute to novel diagnostic and therapeutic tools to combat cardiovascular disease.
Tissue-specific differences in the assembly of mitochondrial Complex I are revealed by a novel ENU mutation in ECSIT
Authors: Nicol Thomas , Falcone Sara , Blease Andrew , Vikhe Pratik , Civiletto Gabriele , Omairi Saleh Salman , Viscomi Carlo , Patel Ketan , Potter Paul K
Published: June 2023

Aims

Mitochondrial Complex I assembly (MCIA) is a multi-step process that necessitates the involvement of a variety of assembly factors and chaperones to ensure that the final active enzyme is correctly assembled. The role of the assembly factor evolutionarily conserved signalling intermediate in the toll (ECSIT) pathway was studied across various murine tissues to determine its role in this process and how this varied between tissues of varying energetic demands. We hypothesized that many of the known functions of ECSIT were unhindered by the introduction of an ENU-induced mutation, while its role in Complex I assembly was affected on a tissue-specific basis.

Methods and results

Here, we describe a mutation in the MCIA factor ECSIT that reveals tissue-specific requirements for ECSIT in Complex I assembly. MCIA is a multi-step process dependent on assembly factors that organize and arrange the individual subunits, allowing for their incorporation into the complete enzyme complex. We have identified an ENU-induced mutation in ECSIT (N209I) that exhibits a profound effect on Complex I component expression and assembly in heart tissue, resulting in hypertrophic cardiomyopathy in the absence of other phenotypes. The dysfunction of Complex I appears to be cardiac specific, leading to a loss of mitochondrial output as measured by Seahorse extracellular flux and various biochemical assays in heart tissue, while mitochondria from other tissues were unaffected.

Conclusions

These data suggest that the mechanisms underlying Complex I assembly and activity may have tissue-specific elements tailored to the specific demands of cells and tissues. Our data suggest that tissues with high-energy demands, such as the heart, may utilize assembly factors in different ways to low-energy tissues in order to improve mitochondrial output. These data have implications for the diagnosis and treatment of various disorders of mitochondrial function as well as cardiac hypertrophy with no identifiable underlying genetic cause.
Evolution of interventional endoscopic ultrasound
Authors: Radlinski Mark J , Strand Daniel S , Shami Vanessa M
Published: June 2023

Endoscopic ultrasound (EUS) has become an indispensable modality for the assessment of the gastrointestinal tract and adjacent structures since its origin in the 1980s. Following the development of the linear echoendoscope, EUS has evolved from a purely diagnostic modality to a sophisticated tool for intervention, with numerous luminal, pancreaticobiliary, and hepatic applications. Broadly, these applications may be subdivided into three categories: transluminal drainage or access procedures, injection therapy, and EUS-guided liver interventions. Transluminal drainage or access procedures include management of pancreatic fluid collection, EUS-guided biliary drainage, EUS-guided bile duct drainage, EUS-guided pancreatic duct drainage, and enteral anastomosis formation. Injection therapies include therapeutic EUS-guided injections for management of malignancies accessible by EUS. EUS-guided liver applications include EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, and EUS-guided vascular therapies. In this review, we discuss the origins of each of these EUS applications, evolution of techniques leading to the current status, and future directions of EUS-guided interventional therapy.
Transfer Trauma Among Nursing Home Residents: Development of a Composite Measure
Authors: Montoya Ana , Park Pil , Bynum Julie , Chang Chiang-Hua
Published: June 2023

Background and Objectives

Nursing home (NH)-to-NH transfers place NH residents at risk for developing transfer trauma. We aimed to develop a composite measure of transfer trauma and apply it among those transferring before and during the pandemic.

Research Design and Methods

Cross-sectional cohort analysis of long-stay NH residents with a NH-to-NH transfer. Minimum Data Set data (2018–2020) were used to create the cohorts. A composite measure of transfer trauma was developed (2018 cohort) and applied to the 2019 and 2020 cohorts. We analyzed resident characteristics and conducted logistic regression analyses to compare rates of transfer trauma between periods.

Results

In 2018, 794 residents were transferred; 242 (30.5%) met the criteria for transfer trauma. In the 2019 and 2020, 750 residents (2019) and 795 (2020) were transferred. In 2019 cohort, 30.7% met the criteria for transfer trauma, and 21.9% in 2020 cohort. During the pandemic, a higher proportion of transferred residents left the facility before the first quarterly assessment. Among residents who stayed in NH for their quarterly assessment, after adjusting for demographic characteristics, residents in the 2020 cohort were less likely to experience transfer trauma than those in the 2019 cohort (adjusted odds ratio [AOR] = 0.64, 95% confidence interval [CI]: 0.51, 0.81). However, residents in 2020 cohort were two times more likely to die (AOR = 1.94, 95% CI: 1.15, 3.26) and 3 times more likely to discharge within 90 days after transfer (AOR = 2.86, 95% CI: 2.30, 3.56) compared with those in 2019 cohort.

Discussion and Implications

These findings highlight how common transfer trauma is after NH-to-NH transfer and the need for further research to mitigate negative outcomes associated with the transfer in this vulnerable population.
Characterization of an optrA-harbouring unconventional circularizable structure located on a novel ICESa2603 family-like integrative and conjugative element ICESsuHN38 in Streptococcus suis
Authors: Yang Qin , Zhu Yao , Schwarz Stefan , Zhang Wanjiang , Wang Xiumei
Published: June 2023

Objectives

To identify the novel genetic elements involved in the horizontal transfer of the oxazolidinone/phenicol resistance gene optrA in Streptococcus suis.

Methods

Whole-genome DNA of the optrA-positive isolate S. suis HN38 was subjected to WGS via both Illumina HiSeq and Oxford Nanopore platforms. MICs of several antimicrobial agents (erythromycin, linezolid, chloramphenicol, florfenicol, rifampicin and tetracycline) were determined by broth microdilution. PCR assays were performed to identify the circular forms of the novel integrative and conjugative element (ICE) ICESsuHN38, but also the unconventional circularizable structure (UCS) excised from this ICE. The transferability of ICESsuHN38 was evaluated by conjugation assays.

Results

S. suis isolate HN38 harboured the oxazolidinone/phenicol resistance gene optrA. The optrA gene was flanked by two copies of erm(B) genes in the same orientation, located on a novel ICESa2603 family-like ICE, designated ICESsuHN38. PCR assays revealed that a novel UCS carrying the optrA and one copy of erm(B) could be excised from ICESsuHN38. Conjugation assays confirmed that ICESsuHN38 was able to successfully transfer into the recipient strain S. suis BAA.

Conclusions

In this work, a novel optrA-carrying mobile genetic element, a UCS, was identified in S. suis. The optrA gene was flanked by copies of erm(B) and its location on the novel ICESsuHN38 will aid its horizontal dissemination.
Seroepidemiology of the Seasonal Human Coronaviruses NL63, 229E, OC43 and HKU1 in France
Authors: De Thoisy Alix , Woudenberg Tom , Pelleau Stéphane , Donnadieu Françoise , Garcia Laura , Pinaud Laurie , Tondeur Laura , Meola Annalisa , Arowas Laurence , Clement Nathalie , Backovic Marija , Ungeheuer Marie-Noëlle , Fontanet Arnaud , White Michael ,   COVID-Oise and SeroPed study teams, Woudenberg Tom , Pelleau Stéphane , Pinaud Laurie , Tondeur Laura , Ungeheuer Marie-Noëlle , Fontanet Arnaud , White Michael , Pellerin Sandrine Fernandes , Guiheneuf Raphaël , Delamare Catherine , Marlet Karl Stefic and Julien , Brochot Etienne , Castelain Sandrine , Augereau Olivier , Sibilia Jean , Dubos François , Guen Christéle Gras-Le , Coste-Burel Marianne , Imbert-Marcille Berthe-Marie , Schweitzer Cyril , Gatin Amélie , Joulié Aline , Haas Hervé , Cantais Aymeric , Bertholon Frederique , Chinazzo-Vigouroux Marie-France , Duru Cécile , Koffi Aymar Davy
Published: June 2023

Background

The seasonal human coronaviruses (HCoV) NL63, 229E, OC43, and HKU1 are globally endemic, yet the majority of HCoV infections remain undiagnosed.

Methods

In a cross-sectional study, 2389 serum samples were collected from children and adults in France in 2020. In a longitudinal cohort study, 2520 samples were collected from 898 French individuals followed up between 2020 and 2021. Antibodies to HCoVs were measured using a bead-based multiplex assay.

Results

The rate of waning of anti-HCoV spike immunoglobulin G antibodies was estimated as 0.22–0.47 year−1 for children, and 0.13–0.27 year−1 for adults. Seroreversion was estimated as 0.31–1.37 year−1 in children and 0.19–0.72 year−1 in adults. The estimated seroconversion rate in children was consistent with 20%–39% of children being infected every year with each HCoV.

Conclusions

The high force of infection in children indicates that HCoVs may be responsible for a substantial proportion of fever episodes experienced by children.
Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability
Authors: Zhang Jian , Wu Qiao , Hu Xiao , Wang Yadong , Lu Jun , Chakraborty Raja , Martin Kathleen A , Guo Shangqin
Published: June 2023

The role of serum response factor (Srf), a central mediator of actin dynamics and mechanical signaling, in cell identity regulation is debated to be either a stabilizer or a destabilizer. We investigated the role of Srf in cell fate stability using mouse pluripotent stem cells. Despite the fact that serum-containing cultures yield heterogeneous gene expression, deletion of Srf in mouse pluripotent stem cells leads to further exacerbated cell state heterogeneity. The exaggerated heterogeneity is detectible not only as increased lineage priming but also as the developmentally earlier 2C-like cell state. Thus, pluripotent cells explore more variety of cellular states in both directions of development surrounding naïve pluripotency, a behavior that is constrained by Srf. These results support that Srf functions as a cell state stabilizer, providing rationale for its functional modulation in cell fate intervention and engineering.
Sphingosine 1‐phosphate elicits a ROS‐mediated proinflammatory response in human endometrial stromal cells via ERK5 activation
Authors: Seidita Isabelle , Tusa Ignazia , Prisinzano Matteo , Menconi Alessio , Cencetti Francesca , Vannuccini Silvia , Castiglione Francesca , Bruni Paola , Petraglia Felice , Bernacchioni Caterina , Rovida Elisabetta , Donati Chiara
Published: June 2023

Endometriosis is a chronic gynecological disease affecting ~10% women in the reproductive age characterized by the growth of endometrial glands and stroma outside the uterine cavity. The inflammatory process has a key role in the initiation and progression of the disorder. Currently, there are no available early diagnostic tests and therapy relies exclusively on symptomatic drugs, so that elucidation of the complex molecular mechanisms involved in the pathogenesis of endometriosis is an unmet need. The signaling of the bioactive sphingolipid sphingosine 1‐phosphate (S1P) is deeply dysregulated in endometriosis. S1P modulates a variety of fundamental cellular processes, including inflammation, neo‐angiogenesis, and immune responses acting mainly as ligand of a family of G‐protein‐coupled receptors named S1P receptors (S1PR), S1P1–5. Here, we demonstrated that the mitogen‐activated protein kinase ERK5, that is expressed in endometriotic lesions as determined by quantitative PCR, is activated by S1P in human endometrial stromal cells. S1P‐induced ERK5 activation was shown to be triggered by S1P1/3 receptors via a SFK/MEK5‐dependent axis. S1P‐induced ERK5 activation was, in turn, responsible for the increase of reactive oxygen species and proinflammatory cytokine expression in human endometrial stromal cells. The present findings indicate that the S1P signaling, via ERK5 activation, supports a proinflammatory response in the endometrium and establish the rationale for the exploitation of innovative therapeutic targets for endometriosis.
Laser-Assisted and Device-Assisted Filler Delivery: A Histologic Evaluation
Authors: Cervantes Jessica , Chang Yu-Feng , Dover Jeffrey S. , Hernandez Alvarez Angelica , Chung Hye Jin
Published: June 2023

BACKGROUND

Lasers and devices are used to enhance transcutaneous delivery of fillers. However, little has been published on the histologic findings of this form of laser/device-assisted delivery to determine the optimal devices and fillers.

OBJECTIVE

To objectively evaluate the histological effects of laser-assisted and device-assisted filler delivery.

METHODS

Ex vivo human abdominoplasty skin samples were treated with fractional CO2 laser (ECO2, 120 μm tip, 120 mJ), fractional radiofrequency microneedling (FRMN, Genius, 1.5 mm, 20 mJ/pin), and microneedling (2.0 mm). Immediately after poly-l-lactic acid (PLLA), hyaluronic acid gel, calcium hydroxylapatite, and black tissue marking dye were topically applied. After treatment, biopsies were collected for histologic evaluation.

RESULTS

Histology revealed that PLLA and black dye were found in greatest abundance, hyaluronic acid was found to a lesser extent, and calcium hydroxylapatite was least found within channels created by fractional CO2 laser. Microneedling was effective only at delivering black dye, whereas FRMN failed to show significant channel formation or delivery of the studied products.

CONCLUSION

Among the devices and fillers studied, fractional CO2 laser and PLLA proved to be the most effective combination for laser/device-assisted filler delivery. Neither microneedling nor FRMN was effective as devices to enhance filler delivery.
Gastrointestinal failure, big data and intensive care
Authors: Singer Pierre , Robinson Eyal , Raphaeli Orit
Published: June 2023

Purpose of review

Enteral feeding is the main route of administration of medical nutritional therapy in the critically ill. However, its failure is associated with increased complications. Machine learning and artificial intelligence have been used in intensive care to predict complications. The aim of this review is to explore the ability of machine learning to support decision making to ensure successful nutritional therapy.

Recent findings

Numerous conditions such as sepsis, acute kidney injury or indication for mechanical ventilation can be predicted using machine learning. Recently, machine learning has been applied to explore how gastrointestinal symptoms in addition to demographic parameters and severity scores, can accurately predict outcomes and successful administration of medical nutritional therapy.

With the rise of precision and personalized medicine for support of medical decisions, machine learning is gaining popularity in the field of intensive care, first not only to predict acute renal failure or indication for intubation but also to define the best parameters for recognizing gastrointestinal intolerance and to recognize patients intolerant to enteral feeding. Large data availability and improvement in data science will make machine learning an important tool to improve medical nutritional therapy.
Sex-based Disparities in Access to Liver Transplantation for Waitlisted Patients With Model for end-stage Liver Disease Score of 40
Authors: Cron David C. , Braun Hillary J. , Ascher Nancy L. , Yeh Heidi , Chang David C. , Adler Joel T.
Published: June 2023

Objective:

To determine the association of sex with access to liver transplant among candidates with the highest possible model for end-stage liver disease score (MELD 40).

Background:

Women with end-stage liver disease are less likely than men to receive a liver transplant, due in part to MELD’s underestimation of renal dysfunction in women. The extent of the sex-based disparity among patients with high disease severity and equally high MELD scores is unclear.

Methods:

Using national transplant registry data, we compared liver offer acceptance (offers received at match MELD 40) and waitlist outcomes (transplant vs. death/de-listing) by sex for 7,654 waitlisted liver transplant candidates from 2009-2019 who reached MELD 40. Multivariable logistic and competing risks regression was used to estimate the association of sex with outcome and adjust for candidate and donor factors.

Results:

Women (N=3,019, 39.4%) spent equal time active at MELD 40 (median 5 vs. 5 days, P=0.28) but had lower offer acceptance (9.2% vs. 11.0%, P<0.01) compared to men (N=4,635, 60.6%). Adjusting for candidate/donor factors, offers to women were less likely accepted (OR=0.87, P<0.01). Adjusting for candidate factors, once they reached MELD 40, women were less likely transplanted (sub-distribution hazard ratio [SHR]=0.90, P<0.01) and more likely to die or be de-listed (SHR=1.14, P=0.02).

Conclusions:

Even among candidates with high disease severity and equally high MELD scores, women have reduced access to liver transplant and worse outcomes compared to men. Policies addressing this disparity should consider factors beyond MELD score adjustments alone.